CaRLO

Description: Background: Acute symptomatic seizures (ASS) are a common manifestation of autoimmune encephalitis (AE), but the risk of developing epilepsy as a sequela of AE remains unknown, and factors predisposing the development of epilepsy have not been fully identified. Objective: To assess the risk of developing epilepsy in AE and study related risk factors. Materials and methods: This was a retrospective single centre study including patients diagnosed with AE according to criteria described by Graus et al., with a minimum follow-up of 12 months after AE resolution. The sample was divided according to whether patients developed epilepsy or not. Results: A total of 19 patients were included; 3 (15.8%) had AE with intracellular antibodies, 9 (47.4%) with extracellular antibodies, and 7 (36.8%) were seronegative. During follow-up, 3 patients (15.8%) died, 4 (21.1%) presented relapses of AE, and 11 (57.89%) developed epilepsy. There was a significant association between the development of epilepsy and the presence of hippocampal atrophy in control brain magnetic resonance imaging (MRI) (p = 0.037), interictal epileptiform discharges (IED) on control electroencephalogram (EEG) (p = 0.045), and immunotherapy delay (p = 0.016). Conclusions: Hippocampal atrophy in neuroimaging, IED on EEG during follow-up, and immunotherapy delay could be predictors of the development of epilepsy in patients with AE.

Description: Whey proteins and oligomeric proanthocyanidins have nutritional value and are widely used in combination as food supplements. However, the effect of the interactions between proanthocyanidins and whey proteins on their stability has not been studied in depth. In this work, we aimed to characterize the interactions between β-Lactoglobulin (β-LG) and α-lactalbumin (α-LA) and oligomeric proanthocyanidins, including A1, A2, B1, B2, B3, and C1, using multi-spectroscopic and molecular docking methods. Fluorescence spectroscopic data revealed that all of the oligomeric proanthocyanidins quenched the intrinsic fluorescence of β-LG or α-LA by binding-related fluorescence quenching. Among the six oligomeric proanthocyanidins, A1 showed the strongest affinity for β-LG (Ka = 2.951 (±0.447) × 104 L∙mol−1) and α-LA (Ka = 1.472 (±0.236) × 105 L∙mol−1) at 297 K. β-LG/α-LA and proanthocyanidins can spontaneously form complexes, which are mainly induced by hydrophobic interactions, hydrogen bonds, and van der Waals forces. Fourier-transform infrared spectroscopy (FTIR) and circular dichroism spectroscopy showed that the secondary structures of the proteins were rearranged after binding to oligomeric proanthocyanidins. During in vitro gastrointestinal digestion, the recovery rate of A1 and A2 increased with the addition of WPI by 11.90% and 38.43%, respectively. The addition of WPI (molar ratio of 1:1) increased the retention rate of proanthocyanidins A1, A2, B1, B2, B3, and C1 during storage at room temperature by 14.01%, 23.14%, 30.09%, 62.67%, 47.92%, and 60.56%, respectively. These results are helpful for the promotion of protein–proanthocyanidin complexes as functional food ingredients in the food industry.

Description: Watermelon is an important commercial crop in the Southeastern United States and around the world. However, production is significantly limited by biotic factors including fusarium wilt caused by the hemibiotrophic fungus Fusarium oxysporum forma specialis niveum (Fon). Unfortunately, this disease has increased significantly in its presence over the last several decades as races have emerged which can overcome the available commercial resistance. Management strategies include rotation, improved crop resistance, and chemical control, but early and accurate diagnostics are required for appropriate management. Accurate diagnostics require molecular and genomic strategies due to the near identical genomic sequences of the various races. Bioassays exist for evaluating both the pathogenicity and virulence of an isolate but are limited by the time and resources required. Molecular strategies are still imperfect but greatly reduce the time to complete the diagnosis. This article presents the current state of the research surrounding races, both how races have been detected and diagnosed in the past and future prospects for improving the system of differentiation. Additionally, the available Fon genomes were analyzed using a strategy previously described in separate formae speciales avirulence gene association studies in Fusarium oxysporum races.

Description: The paper presents studies on biometric identification methods based on the eye movement signal. New signal features were investigated for this purpose. They included its representation in the frequency domain and the largest Lyapunov exponent, which characterizes the dynamics of the eye movement signal seen as a nonlinear time series. These features, along with the velocities and accelerations used in the previously conducted works, were determined for 100-ms eye movement segments. 24 participants took part in the experiment, composed of two sessions. The users’ task was to observe a point appearing on the screen in 29 locations. The eye movement recordings for each point were used to create a feature vector in two variants: one vector for one point and one vector including signal for three consecutive locations. Two approaches for defining the training and test sets were applied. In the first one, 75% of randomly selected vectors were used as the training set, under a condition of equal proportions for each participant in both sets and the disjointness of the training and test sets. Among four classifiers: kNN (k = 5), decision tree, naïve Bayes, and random forest, good classification performance was obtained for decision tree and random forest. The efficiency of the last method reached 100%. The outcomes were much worse in the second scenario when the training and testing sets when defined based on recordings from different sessions; the possible reasons are discussed in the paper.

Description: All dating studies involving SARS-CoV-2 are problematic. Previous studies have dated the most recent common ancestor (MRCA) between SARS-CoV-2 and its close relatives from bats and pangolins. However, the evolutionary rate thus derived is expected to differ from the rate estimated from sequence divergence of SARS-CoV-2 lineages. Here, I present dating results for the first time from a large phylogenetic tree with 86,582 high-quality full-length SARS-CoV-2 genomes. The tree contains 83,688 genomes with full specification of collection time. Such a large tree spanning a period of about 1.5 years offers an excellent opportunity for dating the MRCA of the sampled SARS-CoV-2 genomes. The MRCA is dated 16 August 2019, with the evolutionary rate estimated to be 0.05526 mutations/genome/day. The Pearson correlation coefficient (r) between the root-to-tip distance (D) and the collection time (T) is 0.86295. The NCBI tree also includes 10 SARS-CoV-2 genomes isolated from cats, collected over roughly the same time span as human COVID-19 infection. The MRCA from these cat-derived SARS-CoV-2 is dated 30 July 2019, with r = 0.98464. While the dating method is well known, I have included detailed illustrations so that anyone can repeat the analysis and obtain the same dating results. With 16 August 2019 as the date of the MRCA of sampled SARS-CoV-2 genomes, archived samples from respiratory or digestive tracts collected around or before 16 August 2019, or those that are not descendants of the existing SARS-CoV-2 lineages, should be particularly valuable for tracing the origin of SARS-CoV-2.

Description: Peritoneal carcinomatosis frequently occurs in advanced gastrointestinal and gynecological cancers. As factors such as poor drug uptake and distribution cause chemotherapy to be less effective, alternative therapies have been explored. Introduced in 2013, PIPAC (pressurized intraperitoneal aerosol chemotherapy) uses aerosolized chemotherapeutics sprayed into the patient’s peritoneal cavity using a laparoscopic approach. Despite the literature showing encouraging data regarding the tolerability and efficacy of PIPAC, there is a lack of articles on the role that imaging plays in selecting patients suitable for PIPAC. The aim of this study is to combine literature-based evidence and clinical experience to provide information able to support training radiologists, as well as experienced radiologists interested in innovative therapies.

Description: Photoplethysmography (PPG) as an additional biosignal for a seizure detector has been underutilized so far, which is possibly due to its susceptibility to motion artifacts. We investigated 62 focal seizures from 28 patients with electrocardiography-based evidence of ictal tachycardia (IT). Seizures were divided into subgroups: those without epileptic movements and those with epileptic movements not affecting and affecting the extremities. PPG-based heart rate (HR) derived from a wrist-worn device was calculated for sections with high signal quality, which were identified using spectral entropy. Overall, IT based on PPG was identified in 37 of 62 (60%) seizures (9/19, 7/8, and 21/35 in the three groups, respectively) and could be found prior to the onset of epileptic movements affecting the extremities in 14/21 seizures. In 30/37 seizures, PPG-based IT was in good temporal agreement (

Description: In this paper, we proposed an approach to study the strain response of polymer film samples under various temperature effects and note their corresponding effects. The advantages of the developed approach are determined by the fact that thin films of material are used as samples where it is possible to generate a sufficiently uniform temperature field in a wide range of temperature change rates. A dynamic mechanical analyzer was used for the experimental implementation of the above approach for two UV-curable polymers and one type of epoxy resin. Experimental results have shown that the thermal expansion coefficients for these polymers depend significantly not only on the temperature but also on its change rate. The strain response of the polymer to heating and cooling, with the same absolute values of the rate of temperature change, differs significantly, and this dissimilarity becomes stronger with its increasing. The results of thermomechanical experiments for massive samples on traditional dilatometer are shown to compare with the results for film samples. The discovered dependences of the temperature expansion coefficient on the temperature and its change rate can be used for mathematical modeling of thermomechanical processes arising during the operation of products made of polymers.

Description: Prolonged or excessive microglial activation may lead to disturbances in the resolution of inflammation (RoI). The importance of specialized pro-resolving lipid mediators (SPMs) in RoI has been highlighted. Among them, lipoxins (LXA4) and aspirin-triggered lipoxin A4 (AT-LXA4) mediate beneficial responses through the activation of N-formyl peptide receptor-2 (FPR2). We aimed to shed more light on the time-dependent protective and anti-inflammatory impact of the endogenous SPMs, LXA4, and AT-LXA4, and of a new synthetic FPR2 agonist MR-39, in lipopolysaccharide (LPS)-exposed rat microglial cells. Our results showed that LXA4, AT-LXA4, and MR-39 exhibit a protective and pro-resolving potential in LPS-stimulated microglia, even if marked differences were apparent regarding the time dependency and efficacy of inhibiting particular biomarkers. The LXA4 action was found mainly after 3 h of LPS stimulation, and the AT-LXA4 effect was varied in time, while MR-39′s effect was mainly observed after 24 h of stimulation by endotoxin. MR-39 was the only FPR2 ligand that attenuated LPS-evoked changes in the mitochondrial membrane potential and diminished the ROS and NO release. Moreover, the LPS-induced alterations in the microglial phenotype were modulated by LXA4, AT-LXA4, and MR-39. The anti-inflammatory effect of MR-39 on the IL-1β release was mediated through FPR2. All tested ligands inhibited TNF-α production, while AT-LXA4 and MR-39 also diminished IL-6 levels in LPS-stimulated microglia. The favorable action of LXA4 and MR-39 was mediated through the inhibition of ERK1/2 phosphorylation. AT-LXA4 and MR39 diminished the phosphorylation of the transcription factor NF-κB, while AT-LXA4 also affected p38 kinase phosphorylation. Our results suggest that new pro-resolving synthetic mediators can represent an attractive treatment option for the enhancement of RoI, and that FPR2 can provide a perspective as a target in immune-related brain disorders.

Description: In previous studies, a below-average, average, or above-average intelligence quotient (IQ) in children with SMA was detected but, aside from a severe physical disability, the cognitive performance of adult SMA patients has not yet been evaluated. The intelligence test used in this study, the Wechsler Adult Intelligence Scale, fourth edition (WAIS-IV), was used to measure major intelligence components of adult SMA patients. The WAIS-IV determines four index scores representing verbal comprehension, perceptual reasoning, working memory, and processing speed. Due to time-dependent demands on motor function, the processing speed index score was excluded. IQ index scores of 33 adult SMA patients did not differ from IQ index scores of the normal population. In SMA type-3 patients, the index scores for verbal comprehension, perceptual reasoning, and working memory did not differ from the normal population but showed a trend of IQ scores towards lower points. Patients with SMA type 2 had lower IQ index scores for working memory (90.33 ± 12.95; p = 0.012) and perceptual reasoning (90.73 ± 12.58; p = 0.013) than the normal population. This study provided further evidence that SMA is a multi-systemic disease and may refute the widespread hypothesis that SMA patients might improve their cognitive skills to compensate for their physical impairment.

Description: Concurrent chemoradiotherapy is recommended for locally advanced and unresectable non-small-cell lung cancer (NSCLC), but radiotherapy alone may be used in patients that are ineligible for combined-modality therapy due to poor performance status or comorbidities, which may concern elderly patients in particular. The best candidates for sequential chemoradiotherapy remain undefined. The purpose of the study was to determine the importance of a patients’ age during qualification for sequential chemoradiotherapy. The study enrolled 196 patients. Older patients (age 〉 65years) more often had above the median Charlson Comorbidity Index CCI 〉 4 (p 〈 0.01) and Simplified Charlson Comorbidity Index SCCI 〉 8 (p = 0.03), and less frequently the optimal Karnofsky Performance Score KPS = 100 (p 〈 0.01). There were no significant differences in histological diagnoses, frequency of stage IIIA/IIIB, weight loss, or severity of smoking between older and younger patients. Older patients experienced complete response more often (p = 0.01) and distant metastases less frequently (p = 0.03). Univariable analysis revealed as significant for overall survival: age 〉 65years (HR = 0.66; p = 0.02), stage IIIA (HR = 0.68; p = 0.01), weight loss 〉 10% (HR = 1.61; p = 0.04). Multivariable analysis confirmed age 〉 65years as a uniquely favorable prognostic factor (HR = 0.54; p 〈 0.01) independent of lung cancer disease characteristics, KPS = 100, CCI 〉 4, SCCI 〉 8. Sequential chemoradiotherapy may be considered as favorable in elderly populations.

Description: The use of the plasticizer bis(2-ethylhexyl)phthalate (DEHP) and other plasticizers in the manufacture of plastic products has been restricted due to adverse health outcomes such as obesity, metabolic syndrome, and asthma, for which inflammation has been described to be a driving factor. The emerging alternative plasticizer 1,2-cyclohexanedioic acid diisononyl ester (DINCH) still lacks information regarding its potential effects on the immune system. Here, we investigated the effects of DINCH and its naturally occurring metabolite monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) on the innate immune response. Human THP-1 macrophages were exposed to 10 nM–10 μM DINCH or MINCH for 4 h, 16 h, and 24 h. To decipher the underlying mechanism of action, we applied an untargeted proteomic approach that revealed xenobiotic-induced activation of immune-related pathways such as the nuclear factor κB (NF-κB) signaling pathway. Key drivers were associated with oxidative stress, mitochondrial dysfunction, DNA damage repair, apoptosis, and autophagy. We verified increased reactive oxygen species (ROS) leading to cellular damage, NF-κB activation, and subsequent TNF and IL-1β release, even at low nM concentrations. Taken together, DINCH and MINCH induced cellular stress and pro-inflammatory effects in macrophages, which may lead to adverse health effects.

Description: Microbial lipid production with cost effectiveness is a prerequisite for the oleochemical sector. In this work, genome-wide transcriptional responses on the utilization of xylose and glucose in oleaginous Aspergillus oryzae were studied with relation to growth and lipid phenotypic traits. Comparative analysis of the active growth (t1) and lipid-accumulating (t2) stages showed that the C5 cultures efficiently consumed carbon sources for biomass and lipid production comparable to the C6 cultures. By pairwise comparison, 599 and 917 differentially expressed genes (DEGs) were identified in the t1 and t2 groups, respectively, in which the consensus DEGs were categorized into polysaccharide-degrading enzymes, membrane transports, and cellular processes. A discrimination in transcriptional responses of DEGs set was also found in various metabolic genes, mostly in carbohydrate, amino acid, lipid, cofactors, and vitamin metabolisms. Although central carbohydrate metabolism was shared among the C5 and C6 cultures, the metabolic functions in acetyl-CoA and NADPH generation, and biosynthesis of terpenoid backbone, fatty acid, sterol, and amino acids were allocated for leveraging biomass and lipid production through at least transcriptional control. This study revealed robust metabolic networks in the oleaginicity of A. oryzae governing glucose/xylose flux toward lipid biosynthesis that provides meaningful hints for further process developments of microbial lipid production using cellulosic sugar feedstocks.

Description: In order to support a massive number of resource-constrained Internet-of-Things (IoT) devices and machine-type devices, it is crucial to design a future beyond 5G/6G wireless networks in an energy-efficient manner while incorporating suitable network coverage expansion methodologies. To this end, this paper proposes a novel two-hop hybrid active-and-passive relaying scheme to facilitate simultaneous wireless information and power transfer (SWIPT) considering both time-switching (TS) and power-splitting (PS) receiver architectures, while dynamically modelling the involved dual-hop time-period (TP) metric. An optimization problem is formulated to jointly optimize the throughput, harvested energy, and transmit power of a SWIPT-enabled system with the proposed hybrid scheme. In this regard, we provide two distinct ways to obtain suitable solutions based on the Lagrange dual technique and Dinkelbach method assisted convex programming, respectively, where both the approaches yield an appreciable solution within polynomial computational time. The experimental results are obtained by directly solving the primal problem using a non-linear optimizer. Our numerical results in terms of weighted utility function show the superior performance of the proposed hybrid scheme over passive repeater-only and active relay-only schemes, while also depicting their individual performance benefits over the corresponding benchmark SWIPT systems with the fixed-TP.

Description: Cheese whey (CW) constitutes a dairy industry by-product, with considerable polluting impact, related mostly with lactose. Numerous bioprocessing approaches have been suggested for lactose utilization, however, full exploitation is hindered by strain specificity for lactose consumption, entailing a confined range of end-products. Thus, we developed a CW valorization process generating high added-value products (crude enzymes, nutrient supplements, biopolymers). First, the ability of Aspergillus awamori to secrete β-galactosidase was studied under several conditions during solid-state fermentation (SSF). Maximum enzyme activity (148 U/g) was obtained at 70% initial moisture content after three days. Crude enzymatic extracts were further implemented to hydrolyze CW lactose, assessing the effect of hydrolysis time, temperature and initial enzymatic activity. Complete lactose hydrolysis was obtained after 36 h, using 15 U/mL initial enzymatic activity. Subsequently, submerged fermentations were performed with the produced hydrolysates as onset feedstocks to produce bacterial cellulose (5.6–7 g/L). Our findings indicate a novel approach to valorize CW via the production of crude enzymes and lactose hydrolysis, aiming to unfold the output potential of intermediate product formation and end-product applications. Likewise, this study generated a bio-based material to be further introduced in novel food formulations, elaborating and conforming with the basic pillars of circular economy.

Description: Continuous and emerging advances in Information and Communication Technology (ICT) have enabled Internet-of-Things (IoT)-to-Cloud applications to be induced by data pipelines and Edge Intelligence-based architectures. Advanced vehicular networks greatly benefit from these architectures due to the implicit functionalities that are focused on realizing the Internet of Vehicle (IoV) vision. However, IoV is susceptible to attacks, where adversaries can easily exploit existing vulnerabilities. Several attacks may succeed due to inadequate or ineffective authentication techniques. Hence, there is a timely need for hardening the authentication process through cutting-edge access control mechanisms. This paper proposes a Blockchain-based Multi-Factor authentication model that uses an embedded Digital Signature (MFBC_eDS) for vehicular clouds and Cloud-enabled IoV. Our proposed MFBC_eDS model consists of a scheme that integrates the Security Assertion Mark-up Language (SAML) to the Single Sign-On (SSO) capabilities for a connected edge to cloud ecosystem. MFBC_eDS draws an essential comparison with the baseline authentication scheme suggested by Karla and Sood. Based on the foundations of Karla and Sood’s scheme, an embedded Probabilistic Polynomial-Time Algorithm (ePPTA) and an additional Hash function for the Pi generated during Karla and Sood’s authentication were proposed and discussed. The preliminary analysis of the proposition shows that the approach is more suitable to counter major adversarial attacks in an IoV-centered environment based on the Dolev–Yao adversarial model while satisfying aspects of the Confidentiality, Integrity, and Availability (CIA) triad.

Description: In this paper, we used an EEG system to monitor and analyze the cortical activity of children and adults at a sensor level during cognitive tasks in the form of a Schulte table. This complex cognitive task simultaneously involves several cognitive processes and systems: visual search, working memory, and mental arithmetic. We revealed that adults found numbers on average two times faster than children in the beginning. However, this difference diminished at the end of table completion to 1.8 times. In children, the EEG analysis revealed high parietal alpha-band power at the end of the task. This indicates the shift from procedural strategy to less demanding fact-retrieval. In adults, the frontal beta-band power increased at the end of the task. It reflects enhanced reliance on the top–down mechanisms, cognitive control, or attentional modulation rather than a change in arithmetic strategy. Finally, the alpha-band power of adults exceeded one of the children in the left hemisphere, providing potential evidence for the fact-retrieval strategy. Since the completion of the Schulte table involves a whole set of elementary cognitive functions, the obtained results were essential for developing passive brain–computer interfaces for monitoring and adjusting a human state in the process of learning and solving cognitive tasks of various types.

Description: Selective arterial embolization (SAE) for renal angiomyolipoma (rAML) is effective to treat or prevent bleeding. We report our experience using a cyanoacrylate–Lipiodol mixture. We performed a single-center retrospective review of all rAMLs embolized with cyanoacrylate glue between July 2014 and June 2020. Demographics, tuberous sclerosis complex (TSC) status, clinical presentation, angiography features, and follow-up data were recorded. Pre- and post-procedure rAML sizes and volumes were estimated from computed tomography (CT) or magnetic resonance imaging (MRI) studies. Kidney function was assessed before and after the procedure. We identified 24 patients (22 females and 2 males, mean age 51 years) treated for 27 AMLs, either prophylactically (n = 20) or as an emergency (n = 4). Technical success was achieved for 25/27 AMLs; two patients, each with a single AML, required nephrectomy and repeated embolization, respectively. Major complications occurred in three patients and minor complications such as postembolization syndrome in 15 patients. AML volume reduction after embolization was 55.1% after a mean follow-up of 15 months (range, 1–72 months). Factors associated with greater volume reduction were a smaller percentage of fat (p = 0.001), larger initial rAML volume (p = 0.014), and longer follow-up (p = 0.0001). The mean creatinine level did not change after SAE. Embolization of rAMLs with a mixture of cyanoacrylate and Lipiodol is feasible, safe, and effective in significantly decreasing tumor volume.

Description: Di-2-ethylhexyl phthalate (DEHP) is a plasticizer commonly found in polyvinyl chloride, medical equipment, and food packaging. DEHP has been shown to target the reproductive system and alter the gut microbiome in humans and experimental animals. However, very little is known about the impact of DEHP-induced microbiome changes and its effects during pregnancy. Thus, the objective of this study was to investigate the effects of DEHP exposure during pregnancy on the cecal microbiome and pregnancy outcomes. Specifically, this study tested the hypothesis that subacute exposure to DEHP during pregnancy alters the cecal microbiome in pregnant mice, leading to changes in birth outcomes. To test this hypothesis, pregnant dams were orally exposed to corn oil vehicle or 20 µg/kg/day DEHP for 10 days and euthanized 21 days after their last dose. Cecal contents were collected for 16S Illumina and shotgun metagenomic sequencing. Fertility studies were also conducted to examine whether DEHP exposure impacted birth outcomes. Subacute exposure to environmentally relevant doses of DEHP in pregnant dams significantly increased alpha diversity and significantly altered beta diversity. Furthermore, DEHP exposure during pregnancy significantly increased the relative abundance of Bacteroidetes and decreased the relative abundance of Firmicutes and Deferribacteres compared with controls. The affected taxonomic families included Deferribacteraceae, Lachnospiraceae, and Mucisprillum. In addition to changes in the gut microbiota, DEHP exposure significantly altered 14 functional pathways compared with the control. Finally, DEHP exposure did not significantly impact the fertility and birth outcomes compared with the control. Collectively, these data indicate that DEHP exposure during pregnancy shifts the cecal microbiome, but the shifts do not impact fertility and birth outcomes.

Description: Objective: Alcohol affects many human systems and is involved in the pathogenesis of other diseases. Particular attention must be paid to alcohol consumption among young people. It has been shown that 25% of young people’s deaths are attributable to alcohol, and around 35 million people aged over 11 had consumed at least one alcoholic beverage in 2015. Study Design: Young people aged 18–24 were the most vulnerable to binge drinking in Italy, and 50.6% of teenagers drunk alcohol. Only a few studies in the literature have investigated those habits in university students. This study aims to examine alcohol use habits in a population of university students in Italy. Methods: Between 2018 and 2019, an anonymous online questionnaire was randomly sent to university students from 17 different universities in a network of research centres to study alcohol use disorders. The survey included socio-demographic information, questions about alcohol use, knowledge about alcohol consumption, and related risks. Used questionnaires were the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and the Drinking Motive Questionnaire-Revised (DMQ-R). Results: the AUDIT-C revealed that 53.3% of students were high-risk drinkers. Regarding binge drinking habits, 13.1% of students admitted to binge drinking behavior at least once a month. In our sample, male students are more likely to be low-risk drinkers than female peers (p 〈 0.008). Students from northern Italy are more likely to be high-risk drinkers (p = 0.003). Beer (65.9%) and wine (60.9%) were the most consumed alcoholic beverages. The most common places to drink alcohol were pubs (85.5%). The most likely motivations to drink alcohol were enhancement (40.43%), social (38.39%), coping (15.63%), and social pressure or conformity (5.55%). Only 43.8% of participants reported having attended an educational course on alcohol. Conclusions: University students were not fully aware of the implications of alcohol misuse and will be part of the adult society as critical figures and future leaders. It is imperative to inform students about alcohol consumption risks and investigate the motivations to drink. Stress, anxiety, and social pressure are only a few issues young people are exposed to. Special attention must be paid to young people and their coping strategies that involve substance abuse by using educative, preventive, and motivational approaches.

Description: Light-scattering spectroscopy (LSS) is an established optical approach for characterization of biological tissues. Here, we investigated the capabilities of LSS and convolutional neural networks (CNNs) to quantitatively characterize the composition and arrangement of cardiac tissues. We assembled tissue constructs from fixed myocardium and the aortic wall with a thickness similar to that of the atrial free wall. The aortic sections represented fibrotic tissue. Depth, volume fraction, and arrangement of these fibrotic insets were varied. We gathered spectra with wavelengths from 500–1100 nm from the constructs at multiple locations relative to a light source. We used single and combinations of two spectra for training of CNNs. With independently measured spectra, we assessed the accuracy of the CNNs for the classification of tissue constructs from single spectra and combined spectra. Combined spectra, including the spectra from fibers distal from the illumination fiber, typically yielded the highest accuracy. The maximal classification accuracy of the depth detection, volume fraction, and permutated arrangements was (mean ± standard deviation (stddev)) 88.97 ± 2.49%, 76.33 ± 1.51%, and 84.25 ± 1.88%, respectively. Our studies demonstrate the reliability of quantitative characterization of tissue composition and arrangements using a combination of LSS and CNNs. The potential clinical applications of the developed approach include intraoperative quantification and mapping of atrial fibrosis, as well as the assessment of ablation lesions.

Description: Pasta is a product that requires culinary processing which can affect the content of minerals in the finished product. The study aimed to examine how cooking pasta (1) in salted water (1 teaspoon—16 g of salt per 1 litre of water) or unsalted water and (2) rinsing cooked pasta with running water affects the content of minerals. Thirty-five samples of six types of pasta were analysed. The content of minerals was determined using the ICP-OES method. Retention of minerals in the cooked pasta was calculated. Taking the culinary treatment into account, the intake of minerals with pasta was assessed for children, adolescents, and adults, and the values were compared with the recommendations for the population of Poland. The analysed culinary factors had a statistically significant influence on the content of minerals. Adding salt to water when cooking pasta significantly increased the content of Na in the product, which in turn was negatively correlated with the content of other minerals. When pasta was cooked in unsalted water, it contained less Na and more other minerals than pasta cooked in salted water. Rinsing of pasta reduced the content of all minerals. Pasta is an important source of Mg, Cu, and Mn in the diet of Poles. These ingredients are particularly important to ensure correct development and functioning of the human body. The best method of culinary treatment of pasta is cooking in unsalted water without rinsing.

Description: Autoimmune pancreatitis (AIP) is an increasingly recognized disease classified into two different subtypes based on histology. According to the International Diagnostic Criteria (ICDC), the diagnosis is achieved using a combination of different criteria. In patients presenting with a typical imaging appearance, the diagnosis may be straightforward, and steroid treatment is recommended, even without histological confirmation. In patients with atypical imaging or mass-forming appearance, the differential diagnosis with pancreatic cancer is challenging and crucial for treatment strategy. Endoscopic ultrasound (EUS)-guided tissue acquisition has been proposed to achieve a histological diagnosis. Fine-needle aspiration (FNA) was first proposed to aspirate cells from pancreatic lesions. Despite excellent results in terms of sensitivity for pancreatic cancer, the data are disappointing regarding the diagnosis of AIP. The recent development of new needles allowing fine-needle biopsy (FNB) has been associated with improved diagnostic accuracy based on preserving the tissue architecture, which is necessary to detect the typical histological features of AIP. However, the published literature on the role of EUS-guided FNA and FNB is limited and mainly focused on type 1 AIP. The present study aimed to review the available literature on the role of EUS-guided FNA and FNB in the diagnosis of AIP.

Description: Glioblastoma is the most aggressive and frequent glioma in the adult population. Because current therapy regimens confer only minimal survival benefit, molecular subgrouping to stratify patient prognosis and therapy design is warranted. This study presents a multi-platform classification of glioblastoma by analyzing a large, ethnicity-inclusive 101-adult-patient cohort. It defines seven non-redundant IDH-wild-type glioblastoma molecular subgroups, G1–G7, corresponding to the upstream receptor tyrosine kinase (RTK) and RAS-RAF segment of the ERK/MAPK signal transduction pathway. These glioblastoma molecular subgroups are classified as G1/EGFR, G2/FGFR3, G3/NF1, G4/RAF, G5/PDGFRA, G6/Multi-RTK, and G7/Other. The comprehensive genomic analysis was refined by expression landscaping of all RTK genes, as well as of the major associated growth pathway mediators, and used to hierarchically cluster the subgroups. Parallel demographic, clinical, and histologic pattern analyses were merged with the molecular subgrouping to yield the first inclusive multi-platform classification for IDH-wild-type glioblastoma. This straightforward classification with diagnostic and prognostic significance may be readily used in neuro-oncological practice and lays the foundation for personalized targeted therapy approaches.

Description: The present study aimed to evaluate the health-promoting potential of breadfruit (Artocarpus altilis (Parkinson) Fosberg, Moraceae family), a traditional Comorian food, considering the sample variability according to geographic localisation. Moreover, the main aims of this research were also to promote its consumption in the Comoros Islands as potential health-promoting food and evaluate it as a source of bioactive molecules for the food industry thanks to its antioxidant and antibacterial properties. Investigations on biologically active substances were carried out on the extracts obtained from breadfruit flours from five regions of Grande Comore (Ngazidja), the main island in Comoros. Phytochemical screening revealed the presence of tannins and polyphenols, flavonoids, leucoanthocyanins, steroids, and triterpenes. The considered secondary metabolites were phenolic compounds, vitamin C, monoterpenes, and organic acids. The contents of total phenolic compounds (mgGAE/100 g of dry weight—DW) in the extracts ranged from 29.69 ± 1.40 (breadfruit from Mbadjini—ExMBA) to 96.14 ± 2.07 (breadfruit from Itsandra—ExITS). These compounds included flavanols, flavonols, cinnamic acid and benzoic acid derivatives, and tannins which were detected at different levels in the different extracts. Chlorogenic acid presented the highest levels between 26.57 ± 0.31 mg/100 g DW (ExMIT) and 43.80 ± 5.43 mg/100 g DW (ExMBA). Quercetin was by far the most quantitatively important flavonol with levels ranging from 14.68 ± 0.19 mg/100 g DW (ExMIT) to 29.60 ± 0.28 mg/100 g DW (ExITS). The extracts were also rich in organic acids and monoterpenes. Quinic acid with contents ranging from 77.25 ± 6.04 mg/100 g DW (ExMBA) to 658.56 ± 0.25 mg/100 g DW of ExHAM was the most important organic acid in all the breadfruit extracts, while limonene was quantitatively the main monoterpene with contents between 85.86 ± 0.23 mg/100 g DW (ExMIT) and 565.45 ± 0.24 mg/100 g DW (ExITS). The antibacterial activity of the extracts was evaluated on twelve pathogens including six Gram (+) bacteria and six Gram (−) bacteria. By the solid medium disc method, except for Escherichia coli and Pseudomonas aeruginosa, all the bacteria were sensitive to one or more extracts. Inhibitory Halo Diameters (IHDs) ranged from 8 mm to 16 mm. Salmonella enterica, Clostridium perfringens, and Vibrio fischeri were the most sensitive with IHD 〉 14 mm for ExITS. By the liquid microdilution method, MICs ranged from 3.12 mg/mL to 50 mg/mL and varied depending on the extract. Bacillus megaterium was the most sensitive with MICs ≤ 12.5 mg/mL. Pseudomonas aeruginosa, Shigella flexneri, and Vibrio fischeri were the least sensitive with all MICs ≥ 12.5 mg/mL. ExHAM was most effective with a MIC of 3.12 mg/mL on Staphylococcus aureus and 6.25 mg/mL on Salmonella enterica. The antioxidant power of the extracts was evaluated by the FRAP method. The activity ranged from 5.44 ± 0.35 (ExMBA) to 14.83 ± 0.11 mmol Fe2+/kg DW (ExHAM). Breadfruit from different regions of Comoros contained different classes of secondary metabolites well known for their important pharmacological properties. The results of this study on phenolics, monoterpenes, and organic acids have provided new data on these fruits. The obtained results showed that breadfruit from the biggest island of the Union of Comoros also presented antimicrobial and antioxidant properties, even if some differences in effectiveness existed between fruits from different regions.

Description: The miniaturization of gas chromatography (GC) systems has made it possible to utilize the analytical technique in various on-site applications to rapidly analyze complex gas samples. Various types of miniaturized sensors have been developed for micro-gas chromatography (µGC). However, the integration of an appropriate detector in µGC systems still faces a significant challenge. We present a solution to the problem through integration of µGC with photonic crystal slab (PCS) sensors using transfer printing technology. This integration offers an opportunity to utilize the advantages of optical sensors, such as high sensitivity and rapid response time, and at the same time, compensate for the lack of detection specificity from which label-free optical sensors suffer. We transfer printed a 2D defect free PCS on a borofloat glass, bonded it to a silicon microfluidic gas cell or directly to a microfabricated GC column, and then coated it with a gas responsive polymer. Realtime spectral shift in Fano resonance of the PCS sensor was used to quantitatively detect analytes over a mass range of three orders. The integrated µGC–PCS system was used to demonstrate separation and detection of a complex mixture of 10 chemicals. Fast separation and detection (4 min) and a low detection limit (ng) was demonstrated.

Description: The authors of this study evaluated the potential benefit on visual performance of a novel 3 week visual rehabilitation program based on the use of Gabor patches in patients undergoing bilateral cataract surgery with the implantation of two models of trifocal diffractive intraocular lens (IOL). A total of 30 patients were randomly assigned to two groups: a study group (15 patients) that used a videogame based on Gabor patches and a placebo group (15 patients) that used a videogame without specific stimuli for improving visual performance. No statistically significant differences between groups were found in distance, intermediate, and near post-training visual acuity (p ≥ 0.15). Significantly better distance contrast sensitivity (CS) was found for the spatial frequencies of 6 (p = 0.02) and 12 cpd (p = 0.01) in the study group. Likewise, significantly better values of near CS were found in the study group compared to the placebo group for the spatial frequency of 1.5 cpd (p = 0.02). In conclusion, a 3 week visual rehabilitation program based on the use of Gabor patches in the immediate postoperative period after the bilateral implantation of trifocal diffractive IOLs seems to be beneficial for improving both distance and near visual performance achieved with the implant.

Description: Introduction: Angiogenesis in the central nervous system is visible in animal models of neuroinflammation and bone cancer pain. However, whether spinal angiogenesis exists and contributes to central sensitization in neuropathic pain remains unclear. This study analyzes the impact of angiogenesis on spinal neuroinflammation in neuropathic pain. Methods: Rats with chronic constriction injury (CCI) to the sciatic nerve underwent the implantation of an intrathecal catheter. Fumagillin or vascular endothelial growth factor-A antibody (anti-VEGF-A) was administered intrathecally. Nociceptive behaviors, cytokine immunoassay, Western blot, and immunohistochemical analysis assessed the effect of angiogenesis inhibition on CCI-induced neuropathic pain. Results: VEGF, cluster of differentiation 31 (CD31), and von Willebrand factor (vWF) expressions increased after CCI in the ipsilateral lumbar spinal cord compared to that in the contralateral side of CCI and control rats from post-operative day (POD) 7 to 28, with a peak at POD 14. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 concentrations, but not IL-10 levels, also increased in the ipsilateral spinal cord after CCI. Fumagillin and anti-VEGF-A reduced CCI-induced thermal hyperalgesia from POD 5 to 14 and mechanical allodynia from POD 3 to 14. Fumagillin reduced CCI-upregulated expressions of angiogenic factors and astrocytes. Furthermore, fumagillin decreased TNF-α and IL-6 amounts and increased IL-10 levels at POD 7 and 14, but not IL-1β concentrations. Conclusions: Fumagillin significantly ameliorates CCI-induced nociceptive sensitization, spinal angiogenesis, and astrocyte activation. Our results suggest that angiogenesis inhibitor treatment suppresses peripheral neuropathy-induced central angiogenesis, neuroinflammation, astrocyte activation, and neuropathic pain.

Description: Meiotic defects derived from incorrect DNA repair during gametogenesis can lead to mutations, aneuploidies and infertility. The coordinated resolution of meiotic recombination intermediates is required for crossover formation, ultimately necessary for the accurate completion of both rounds of chromosome segregation. Numerous master kinases orchestrate the correct assembly and activity of the repair machinery. Although much less is known, the reversal of phosphorylation events in meiosis must also be key to coordinate the timing and functionality of repair enzymes. Cdc14 is a crucial phosphatase required for the dephosphorylation of multiple CDK1 targets in many eukaryotes. Mutations that inactivate this phosphatase lead to meiotic failure, but until now it was unknown if Cdc14 plays a direct role in meiotic recombination. Here, we show that the elimination of Cdc14 leads to severe defects in the processing and resolution of recombination intermediates, causing a drastic depletion in crossovers when other repair pathways are compromised. We also show that Cdc14 is required for the correct activity and localization of the Holliday Junction resolvase Yen1/GEN1. We reveal that Cdc14 regulates Yen1 activity from meiosis I onwards, and this function is essential for crossover resolution in the absence of other repair pathways. We also demonstrate that Cdc14 and Yen1 are required to safeguard sister chromatid segregation during the second meiotic division, a late action that is independent of the earlier role in crossover formation. Thus, this work uncovers previously undescribed functions of the evolutionary conserved Cdc14 phosphatase in the regulation of meiotic recombination.

Description: Due to the prevailing pandemic of the coronavirus disease COVID-19, we are experiencing emotional and social isolation, which negatively affects mental and physical health, particularly among the elderly population. In this study, we performed a cross-sectional analysis based on computer-assisted telephone interviews of 500 Polish adults aged 60 years or older in order to determine the impact of the SARS-CoV-2 pandemic on the older population’s behavior, life activity, and delivery of healthcare services. According to our study, COVID-19 infection entailed a substantial change in older people’s behavior. Over 50%, nearly 80%, and more than 25% of the surveyed participants reduced their social, recreational, and professional activities, respectively. The most significant change in senior’s behavior due to the fear of COVID-19 infection was observed in patients (1) with cardiac and pulmonary problems, (2) being on multi-drug therapy, (3) vaccinated against influenza, and (4) with several mental difficulties including loneliness, social isolation, and depression. Furthermore, we demonstrated that 10% of participants canceled planned hospitalization due to the fear of COVID-19 infection. This was observed primarily in patients suffering from chronic heart and lung diseases, vaccinated against influenza, exhibiting the reluctance to carry out more complex daily activities, and with a higher level of anxiety, social loneliness, and malnutrition. Thus, these groups of seniors require more attention; hence, we propose telemedicine as a strategy directed to them that provides clinical healthcare and information regarding measurements, control, and protection against SARS-CoV-2 during the prevailing COVID-19 pandemic. We believe this strategy may improve treatment outcomes, reduce comorbidities-related complications and unnecessary hospitalizations.

Description: Face processing relies on a network of occipito-temporal and frontal brain regions. Temporal regions are heavily involved in looking at and processing emotional faces; however, the contribution of each hemisphere to this process remains under debate. Semantic dementia (SD) is a rare neurodegenerative brain condition characterized by anterior temporal lobe atrophy, which is either predominantly left- (left-SD) or right-lateralised (right-SD). This syndrome therefore provides a unique lesion model to understand the role of laterality in emotional face processing. Here, we investigated facial scanning patterns in 10 left-SD and 6 right-SD patients, compared to 22 healthy controls. Eye tracking was recorded via a remote EyeLink 1000 system, while participants passively viewed fearful, happy, and neutral faces over 72 trials. Analyses revealed that right-SD patients had more fixations to the eyes than controls in the Fear (p = 0.04) condition only. Right-SD patients also showed more fixations to the eyes than left-SD patients in all conditions: Fear (p = 0.01), Happy (p = 0.008), and Neutral (p = 0.04). In contrast, no differences between controls and left-SD patients were observed for any emotion. No group differences were observed for fixations to the mouth, or the whole face. This study is the first to examine patterns of facial scanning in left- versus right- SD, demonstrating more of a focus on the eyes in right-SD. Neuroimaging analyses showed that degradation of the right superior temporal sulcus was associated with increased fixations to the eyes. Together these results suggest that right lateralised brain regions of the face processing network are involved in the ability to efficiently utilise changeable cues from the face.

Description: Chinese hamster ovary (CHO) cells are the most important host system used for monoclonal antibody (mAb) expression. Moreover, the fed-batch culture mode is the most widely used method to increase mAb expression in CHO cells by increasing the amount of feed. However, a high amount of culture feed results in the production of metabolic byproducts. In this work, we used a continuous feeding strategy to reduce metabolic byproducts and improve mouse–human chimeric anti-epidermal growth factor receptor vIII (EGFRvIII) antibody C12 expression in Chinese hamster ovary-K1 cells. Moreover, the effects of the feeding strategy on the cell culture and monoclonal antibody production were evaluated in chemically defined suspension cultures of recombinant CHO-K1 cells. Compared with bolus feeding methods, the continuous feeding method did not have any advantages when the feeding amount was low, but with a high feeding amount, the continuous feeding method significantly reduced the concentrations of lactate and NH4+ in the later culture stage. At the end of the culture stage, compared with bolus feeding methods, the lactate and NH4+ concentrations under the continuous feeding mode were reduced by approximately 45% and 80%, respectively. In addition, the antibody C12 expression level was also increased by almost 10%. Compared to the bolus feeding method, the antibody C12 produced by the continuous feeding method had a lower content of high-mannose glycoforms. Further analysis found that the osmolality of the continuous feeding method was lower than that of the typical fed-batch bolus feeding method. Conclusively, these results indicate that the continuous feeding method is very useful for reducing metabolic byproducts and achieving higher levels of mAb production.

Description: Radiation damages many cellular components and disrupts cellular functions, and was previously reported to impair locomotion in the model organism Caenorhabditis elegans. However, the response to even higher doses is not clear. First, to investigate the effects of high-dose radiation on the locomotion of C. elegans, we investigated the dose range that reduces whole-body locomotion or leads to death. Irradiation was performed in the range of 0–6 kGy. In the crawling analysis, motility decreased after irradiation in a dose-dependent manner. Exposure to 6 kGy of radiation affected crawling on agar immediately and caused the complete loss of motility. Both γ-rays and carbon-ion beams significantly reduced crawling motility at 3 kGy. Next, swimming in buffer was measured as a motility index to assess the response over time after irradiation and motility similarly decreased. However, swimming partially recovered 6 h after irradiation with 3 kGy of γ-rays. To examine the possibility of a recovery mechanism, in situ GFP reporter assay of the autophagy-related gene lgg-1 was performed. The fluorescence intensity was stronger in the anterior half of the body 7 h after irradiation with 3 kGy of γ-rays. GFP::LGG-1 induction was observed in the pharynx, neurons along the body, and the intestine. Furthermore, worms were exposed to region-specific radiation with carbon-ion microbeams and the trajectory of crawling was measured by image processing. Motility was lower after anterior-half body irradiation than after posterior-half body irradiation. This further supported that the anterior half of the body is important in the locomotory response to radiation.

Description: Actively involved in tumor maintenance, cAMP-dependent protein kinase A (PKA) has been proposed as a putative biomarker in cancer. Recently, an active PKA form has been identified in human sera and PKA autoantibodies have been detected in cancer patients. However, their serum functions, as well as diagnostic significance, remain largely unknown. Although several PKA detection assays have been developed, none refer to a laboratory diagnostic procedure. Among these, ELISA and Western blotting (WB) assays have been employed in PKA detection. Since, to the best of our knowledge, there are no data showing its presence in human urine samples, herein, we explore the possibility of PKA’s existence in this biological specimen. Interestingly, among the 30 screened urines by quantitative sandwich ELISA, we recognized detectable PKA levels in 5 different samples, and of those two exhibited a considerable high concentration. To corroborate these results, we also evaluated PKA’s presence in both positive and negative ELISA urines by WB. Remarkably, immunoblotting analysis confirmed PKA’s existence in certain, but not in all, human urine specimens. Despite being quite preliminary, these findings firstly identify PKA in urine samples and provide evidence for its potential clinic usage as a diagnostic analyte in laboratory medicine.

Description: (1) Background: This study investigated the miscibility of carbon-based fillers within industrial scale polymers for the preparation of superior quality polymer composites. It focuses on finding the light distribution in gamma irradiated ultra-high molecular weight polyethylene (UHMWPE). (2) Methods: The Kubleka–Munk model (KMM) was used to extract the optical properties, i.e., absorption coefficients (μa) and scattering coefficients (μs). Samples amounting to 30 kGy and 100 kGy of irradiated (in the open air) UHMWPE from 630 nm to 800 nm were used for this purpose. Moreover, theoretical validation of experimental results was performed while using extracted optical properties as inputs for the Monte Carlo model of light transport (MCML) code. (3) Conclusions: The investigations revealed that there was a significant decrease in absorption and scattering coefficient (μa & μs) values with irradiation, and 30 kGy irradiated samples suffered more compared to 100 kGy irradiated samples. Furthermore, the simulation of light transport for 800 nm showed an increase in penetration depth for UHMWPE after gamma irradiation. The decrease in dimensionless transport albedo  μs(μa+μs) from 0.95 to 0.93 was considered responsible for this increase in photon absorption per unit area with irradiation. The report results are of particular importance when considering the light radiation (from 600 nm to 899 nm) for polyethylene modification and/or stabilization via enhancing the polyethylene chain mobility.

Description: Porcine Circovirus 2 (PCV2) vaccines are based on either inactivated whole virion, or recombinant ORF2 capsid protein assembled into Virus-like Particles (VLPs). No data are available about the immunizing properties of free, non-assembled capsid protein. To investigate this issue, ORF2 of a reference PCV2b strain was expressed in a Baculovirus-based expression system without assembly into VLPs. The free purified protein was formulated into an oil vaccine at three distinct Ag payloads: 10.8/3.6/1.2 micrograms/dose. Each dose was injected intramuscularly into five, 37-day old piglets, carefully matched for maternally-derived antibody. Five control piglets were injected with sterile PBS in oil adjuvant. Twenty-eight days later, all the pigs were challenged intranasally with 105.3 TCID50 of PCV2b strain DV6503. After challenge infection, all the pigs remained in good clinical conditions. The recombinant vaccine did not induce significant antibody and PCV2-specific IFN-γ responses. ELISPOT and lymphocyte proliferation data confirmed poor induction of cell-mediated immunity. In terms of PCV2 viremia, there was no significant difference between vaccinated and control animals. The histological data indicated the absence of a detectable viral load and of PCVAD lesions in both vaccinated and control animals, as well as of histiocytes and multi-nucleated giant cells. We conclude that free, non-assembled ORF2 capsid protein does not induce protective immunity.

Description: Background: In our previous study regarding infection prevention after COVID-19, many Japanese citizen respondents had not received education/training on infection prevention. However, a total of 47.7% (n = 143) of these respondents wanted to receive education from healthcare professionals regarding the methods and effects of infection prevention. Therefore, changes in recognition of the roles of Japanese pharmacists before and after COVID-19 were investigated. Methods: We conducted a survey to determine whether recognition of Japanese pharmacists’ roles, especially their role in public health in the community, changed after COVID-19. Results: A total of 93.9% (n = 307) of the pharmacist respondents showed an increased awareness of infection prevention. Before COVID-19, the hospital pharmacists (67.2%; n = 80) were more aware of infection prevention than were pharmacy pharmacists (51.7%; n = 74) and drugstore pharmacists (47.7%; n = 31). The number of pharmacists who felt that the role of pharmacists in the community had changed after the pandemic increased, but the numbers of community pharmacy pharmacists (51.8%; n = 74) and drugstore pharmacists (55.4%; n = 36) were found to be slightly higher than those of hospital pharmacists (47.9%; n = 57). Conclusions: In a society in which swift responses and changes are required, for individuals to work as medical personnel their ability to respond while always being aware of the needs of society is required now more than ever.

Description: Early care and education (ECE) settings are important avenues for reaching young children and their families with food and nutrition resources, including through the U.S. federally funded Child and Adult Care Food Program (CACFP). Researchers conducted a cross-sectional survey of ECE providers in two U.S. states in November 2020 to identify approaches used to connect families with food and nutrition resources amid the COVID-19 pandemic. Logistic regression models were used to estimate odds of sites reporting no approaches and adjusted Poisson models were used to estimate the incidence rate ratio of the mean number of approaches, comparing sites that participate in CACFP to those that did not. A total of 589 ECE sites provided responses. Of those, 43% (n = 255) participated in CACFP. CACFP participating sites were more likely to report using any approaches to connecting families to food resources and significantly more likely to report offering “grab and go” meals, providing meal delivery, distributing food boxes to families, and recommending community food resources than non-CACFP sites. This study suggests that CACFP sites may have greater capacity to connect families to food resources amid emergencies than non-CACFP participating sites.

Description: The human genome includes four cytochrome P450 2C subfamily enzymes, and CYP2C8 has generated research interest because it is subject to drug–drug interactions and various polymorphic outcomes. To address the structure-functional complexity of CYP2C8, its catalytic activity was studied using a directed evolution analysis. Consecutive rounds of random mutagenesis and screening using 6-methoxy-luciferin produced two mutants, which displayed highly increased luciferase activity. Wild-type and selected mutants were expressed on a large scale and purified. The expression levels of the D349Y and D349Y/V237A mutants were ~310 and 460 nmol per liter of culture, respectively. The steady-state kinetic analysis of paclitaxel 6α-hydroxylation showed that the mutants exhibited a 5–7-fold increase in kcat values and a 3–5-fold increase in catalytic efficiencies (kcat/KM). In arachidonic acid epoxidation, two mutants exhibited a 30–150-fold increase in kcat values and a 40–110-fold increase in catalytic efficiencies. The binding titration analyses of paclitaxel and arachidonic acid showed that the V237A mutation had a lower Kd value, indicating a tighter substrate-binding affinity. The structural analysis of CYP2C8 indicated that the D349Y mutation was close enough to the putative binding domain of the redox partner; the increase in catalytic activity could be partially attributed to the enhancement of the P450 coupling efficiency or electron transfer.

Description: Background: Nonalcoholic fatty liver disease (NAFLD) is associated with decreased insulin sensitivity. However, the association between NAFLD and pancreatic β-cell function is still ambiguous. Here, we assessed whether pancreatic β-cell function is associated with NAFLD. Method: The data of NHANES III from 1988 to 1994 were used. NAFLD was diagnosed when subjects had ultrasonographically hepatic steatosis without other liver diseases. Disposition index (DI) was employed to assess pancreatic β-cell function. A total of 6168 participants were included in this study. Results: NAFLD participants had much higher HOMA2-%B (weighted mean, 124.1; standard error, 1.8) than the non-NAFLD participants (weighted mean, 100.7; standard error, 0.9). However, when evaluating the β-cell function in the context of insulin resistance by using DI index, DI levels were much lower in NAFLD subjects (weighted mean, 79.5; standard error, 1.0) compared to non-NAFLD (weighted mean, 95.0; standard error, 0.8). Multivariate logistic regression analyses showed that DI was inversely associated with NAFLD prevalence. The adjusted OR (95% CI) for quartile 1 versus quartile 4 was 1.81 (1.31–2.50) (p 〈 0.001 for trend). Moreover, DI was also inversely associated with the presence of moderate to severe hepatic steatosis. The multivariable-adjusted ORs across quartiles of DI were 2.47, 1.44, 0.96 and 1.00 for the presence of moderate to severe hepatic steatosis (p 〈 0.001 for trend). Conclusions: Pancreatic β-cell function might be a new predictor for the presence of NAFLD, and insufficient compensatory β-cell function is associated with NAFLD.

Description: Vitamin D deficiency is a serious public health issue in the United Kingdom. Those at increased risk, such as pregnant women, children under 5 years and people from ethnic groups with dark skin, are not all achieving their recommended vitamin D. Effective vitamin D education is warranted. A qualitative study was undertaken to evaluate the acceptability and understanding of a vitamin D infographic, developed using recommendations from previous research. Fifteen parents/carers, recruited through local playgroups and adverts on popular parent websites, participated in focus groups and telephone interviews. The majority were female, White British and educated to degree level. A thematic analysis methodology was applied. The findings indicated that understanding and acceptability of the infographic were satisfactory, but improvements were recommended to aid interpretation and create more accessible information. These included additional content (what vitamin D is; other sources; its health benefits; methods/doses for administration and scientific symbols used) and improved presentation (eye-catching, less text, simpler language, more images and a logo). Once finalized, the infographic could be a useful tool to educate families around vitamin D supplementation guidelines, support the UK Healthy Start vitamins scheme and help improve vitamin D status for pregnant and lactating women and young children.

Description: Soil bacteria play a key role in the plant–soil system and can regulate the growth of Phoebe bournei seedlings under fertilization. However, there are few reports on how soil bacteria respond to fertilization and regulate seedling growth. This study adopted the “3414” field fertilization experiment, combined with soil microbial sequencing, nutrient contents, and biomass measurement, to explore the changes of soil chemical properties and bacterial structure under different NPK fertilization conditions and to establish the coupling relationship between soil bacteria, soil nutrients, and plant growth. The results showed that NPK fertilization decreased soil pH; increased soil N, P, and K content; reduced bacterial diversity and abundance; promoted the growth of dominant bacterial species; and enhanced Phoebe bournei seedlings’ soil N, P, and K elements. NPK fertilization promoted Proteobacteria growth, especially of three genera (Methylobacterium, Sphingobium, and Acinetobacter) and Actinobacteria, while it decreased Acidobacteria and Chloroflexi. By reducing the ratio of N to K and increasing P, NPK fertilization can slow soil acidification, promote bacterial reproduction, maintain P. bournei seedlings’ soil ecological stability, and balance the seedlings’ growth and sustainable soil utilization. AD3, Pseudomonas, and Rhodanobacter can be used as the marker species for N, P, and K fertilization, respectively, while Methylobacterium, Brevundimonas, Acinetobacter, and Sphingobium can be used as indicator species for soil pH and soil N, P, and K content changes, respectively. These results provided a theoretical basis and technical guidance for the effective fertilization and cultivation of robust P. bournei seedlings.

Description: Enteric tuft cells are chemosensory epithelial cells gaining attention in the field of host-parasite interactions. Expressing a repertoire of chemosensing receptors and mediators, these cells have the potential to detect lumen-dwelling helminth and protozoan parasites and coordinate epithelial, immune, and neuronal cell defenses against them. This review highlights the versatility of enteric tuft cells and sub-types thereof, showcasing nuances of tuft cell responses to different parasites, with a focus on helminths reflecting the current state of the field. The role of enteric tuft cells in irritable bowel syndrome, inflammatory bowel disease and intestinal viral infection is assessed in the context of concomitant infection with parasites. Finally, the review presents pertinent questions germane to understanding the enteric tuft cell and its role in enteric parasitic infections. There is much to be done to fully elucidate the response of this intriguing cell type to parasitic-infection and there is negligible data on the biology of the human enteric tuft cell—a glaring gap in knowledge that must be filled.

Description: Bispecific antibodies (BsAbs) for T cell engagement have shown great promise in cancer immunotherapy, and their clinical applications have been proven in treating hematological malignance. Bispecific antibody binding fragment (BiFab) represents a promising platform for generating non-Fc bispecific antibodies. However, the generation of BiFab is still challenging, especially by means of chemical conjugation. More conjugation strategies, e.g., enzymatic conjugation and modular BiFab preparation, are needed to improve the robustness and flexibility of BiFab preparation. We successfully used chemo-enzymatic conjugation approach to generate bispecific antibody (i.e., BiFab) with Fabs from full-length antibodies. Paired click handles (e.g., N3 and DBCO) was introduced to the C-terminal LPETG tag of Fabs via sortase A mediated transpeptidation, followed by site-specific conjugation between two click handle-modified Fabs for BiFab generation. Both BiFabCD20/CD3 (EC50 = 0.26 ng/mL) and BiFabHer2/CD3 exhibited superior efficacy in mediating T cells, from either PBMC or ATC, to kill target tumor cell lines while spared antigen-negative tumor cells in vitro. The BiFabCD20/CD3 also efficiently inhibited CD20-positive tumor growth in mouse xenograft model. We have established a facile sortase A-mediated click handle installation to generate homogeneous and functional BiFabs. The exemplary BiFabs against different targets showed superior efficacy in redirecting and activating T cells to specifically kill target tumor cells, demonstrating the robustness of sortase A-mediated “bio-click” chemistry in generating various potent BiFabs. This approach also holds promise for further efficient construction of a Fab derivative library for personalized tumor immunotherapy in the future.

Description: This study evaluates the modulation of phasic pain and empathy for pain induced by placebo analgesia during pain and empathy for pain tasks. Because pain can be conceptualized as a dangerous stimulus that generates avoidance, we evaluated how approach and avoidance personality traits modulate pain and empathy for pain responses. We induced placebo analgesia to test whether this also reduces self-pain and other pain. Amplitude measures of the N1, P2, and P3 ERPs components, elicited by electric stimulations, were obtained during a painful control, as well as during a placebo treatment expected to induce placebo analgesia. The placebo treatment produced a reduction in pain and unpleasantness perceived, whereas we observed a decrease in the empathy unpleasantness alone during the empathy pain condition. The moderator effects of the fight-flight-freeze system (FFFS) in the relationships linking P2 and P3 amplitude changes with pain reduction were both significant among low to moderate FFFS values. These observations are consistent with the idea that lower FFFS (active avoidance) scores can predict placebo-induced pain reduction. Finally, in line with the revised Reinforcement Sensitivity Theory (r-RST), we can assume that phasic pain is an aversive stimulus activating the active-avoidance behavior to bring the system back to homeostasis.

Description: Background: Sepsis is still the main etiology of mortality in pediatric intensive care units (PICUs). Therefore, we performed this study to evaluate the value of procollagen Type III amino-terminal propeptide (PIIINP) as a biomarker for sepsis severity diagnosis and mortality. Method: A prospective study was carried out on 170 critically ill children admitted into the PICU and 100 controls. The performed clinical examinations included calculation of the pediatric risk of mortality. Serum PIIINP was withdrawn from patients at admission and from the controls. Results: PIIINP level was significantly more increased in sepsis, severe sepsis, and septic shock than among the controls (p 〈 0.001). PIIINP was significantly higher in severe sepsis and septic shock (568.3 (32.5–1304.7) and 926.2 (460.6–1370), respectively) versus sepsis (149.5 (29.6–272.9)) (p 〈 0.001). PIIINP was significantly increased in non-survivors (935.4 (104.6–1370)) compared to survivors (586.5 (29.6–1169)) (p 〈 0.016). ROC curve analysis exhibited an area under the curve (AUC) of 0.833 for PIIINP, which is predictive for sepsis, while the cut-off point of 103.3 ng/mL had a sensitivity of 88% and specificity of 82%. The prognosis of the AUC curve for PIIINP to predict mortality was 0.651; the cut-off of 490.4 ng/mL had a sensitivity of 87.5% and specificity of 51.6%. Conclusions: PIIINP levels are increased in sepsis, with significantly higher levels in severe sepsis, septic shock, and non-survivors, thus representing a promising biomarker for pediatric sepsis severity and mortality.

Description: Belyaev’s concept of destabilizing selection during domestication was a major achievement in the XX century. Its practical value has been realized in commercial colors of the domesticated fox that never occur in the wild and has been confirmed in a wide variety of pet breeds. Many human disease models involving animals allow to test drugs before human testing. Perhaps this is why investigators doing transcriptomic profiling of domestic versus wild animals have searched for breed-specific patterns. Here we sequenced hypothalamic transcriptomes of tame and aggressive rats, identified their differentially expressed genes (DEGs), and, for the first time, applied principal component analysis to compare them with all the known DEGs of domestic versus wild animals that we could find. Two principal components, PC1 and PC2, respectively explained 67% and 33% of differential-gene-expression variance (hereinafter: log2 value) between domestic and wild animals. PC1 corresponded to multiple orthologous DEGs supported by homologs; these DEGs kept the log2 value sign from species to species and from tissue to tissue (i.e., a common domestication pattern). PC2 represented stand-alone homologous DEG pairs reversing the log2 value sign from one species to another and from tissue to tissue (i.e., representing intraspecific and interspecific variation).

Description: Among the most rapidly declining birds in continental North America, grassland birds evolved with American bison (Bison bison) until bison nearly became extinct due to overhunting. Bison populations have subsequently rebounded due to reintroductions on conservation lands, but the impacts of bison on grassland nesting birds remain largely unknown. We investigated how bison reintroduction, together with other land management and climate factors, affected breeding populations of a grassland bird species of conservation concern, the Bobolink (Dolichonyx oryzivorus). We quantified population changes in Bobolinks over an 18-year period in conservation grasslands where bison were reintroduced, compared with adjacent grasslands grazed by cattle and where hay was harvested after the bird breeding season. Four years after bison reintroduction, the bison population in the study area had doubled, while Bobolink abundance declined 62% and productivity declined 84%. Our findings suggest that bison reintroduction as a conservation strategy may be counterproductive in grassland fragments where overgrazing, trampling, and other negative impacts drive declines in grassland breeding birds. Where bird conservation is an objective, small grassland reserves may therefore be inappropriate sites for bison reintroduction. To maximize conservation benefits to birds, land managers should prioritize protecting grassland birds from disturbance during the bird breeding season.

Description: Background: Recent studies have shown an association between CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex category) score and outcome of acute myocardial infarction, stroke, and chest pain. As pneumonia can affect the cardiovascular system, this study aimed to investigate the performance of the CHA2DS2-VASc score for major adverse cardiovascular events (MACEs) risk stratification in patients with pneumonia. Methods: A retrospective population-based cohort study including 61,843 patients with pneumonia. These patients were divided into two cohorts that were stratified based on the presence or absence of underlying atrial fibrillation (AF). We calculated the CHA2DS2-VASc score and incidence density rates of MACEs in each cohort. Cox regression was conducted to calculate hazard ratio of MACEs in pneumonia patients. The diagnostic performance of CHA2DS2-VASc with regard to MACEs was tested using the receiver operator characteristic curve. Results: Pneumonia patients with higher CHA2DS2-VASc score were more likely develop MACEs in both the AF and non-AF groups. In the AF group, the areas under the curve (AUC), sensitivity, and specificity were 0.824 (0.7773–0.8708), 0.7, and 0.84 respectively. In the non-AF group, the AUC, sensitivity, and specificity were 0.8185 (0.8152–0.8217), 0.75, and 0.83 respectively. Conclusions: The CHA2DS2-VASc score showed good performance in the prediction of MACE in patients with pneumonia.

Description: Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice.

Description: Alzheimer’s disease (AD) is marked by chronic neurodegeneration associated with the occurrence of plaques containing amyloid β (Aβ) proteins in various parts of the human brain. An increase in several Aβ fragments is well documented in patients with AD and anti-amyloid targeting is an emerging area of therapy. Soluble Aβ can bind to various cell surface and intracellular molecules with the pathogenic Aβ42 fragment leading to neurotoxicity. Here we examined the effect of Aβ42 on network adaptations in the proteome of nerve growth factor (NGF) differentiated PC12 cells using liquid-chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS) proteomics. Whole-cell peptide mass fingerprinting was coupled to bioinformatic gene set enrichment analysis (GSEA) in order to identify differentially represented proteins and related gene ontology (GO) pathways within Aβ42 treated cells. Our results underscore a role for Aβ42 in disrupting proteome responses for signaling, bioenergetics, and morphology in mitochondria. These findings highlight the specific components of the mitochondrial response during Aβ42 neurotoxicity and suggest several new biomarkers for detection and surveillance of amyloid disease.

Description: Colorectal cancer (CRC) is an aggressive cancer that remains a challenge to diagnose and treat. Photodynamic diagnosis (PDD) and therapy (PDT) are novel alternative techniques, which can enhance early diagnosis, as well as elicit tumor cell death. This is accomplished through photosensitizer (PS) mediated fluorescence and cytotoxic reactive oxygen species activation upon laser light irradiation excitation at specific low and high range wavelengths, respectively. However, the lack of PS target tumor tissue specificity often hampers these techniques. This study successfully fabricated a bioactive nanoconjugate, ZnPcS4-AuNP-S-PEG5000-NH2-Anti-GCC mAb (BNC), based upon a polyethylene glycol-gold nanoparticle, which was multi-functionalized with a fluorescent PDT metalated zinc phthalocyanine PS, and specific anti-GCC targeting antibodies, to overcome CRC PDD and PDT challenges. The BNC was found to be stable and showed selectively improved subcellular accumulation within targeted CRC for improved PDD and PDT outcomes in comparison to healthy in vitro cultured cells. Additionally, the BNC reported significantly higher late apoptotic PDT-induced CRC cell death rates (34% ***) when compared to PDT PS administration alone (15% *). These results indicated that the improved PDD and PDT outcomes were due to the specific PS accumulation in CRC cells through nanoparticle carriage and bioactive anti-GCC targeting.

Description: Expandable metallic stent placement is often the only way to treat airway obstructions. Such treatment with an uncoated stent causes granulation proliferation and subsequent restenosis, resulting in the procedure’s adverse complications. Systemic administration of steroids drugs in high dosages slows down granulation tissue overgrowth but leads to long-term side effects. Drug-eluting coatings have been used widely in cardiology for many years to suppress local granulation and reduce the organism’s systemic load. Still, so far, there are no available analogs for the trachea. Here, we demonstrate that PLA-, PCL- and PLGA-based films with arrays of microchambers to accommodate therapeutic substances can be used as a drug-eluting coating through securely fixing on the surface of an expandable nitinol stent. PCL and PLA were most resistant to mechanical damage associated with packing in delivery devices and making it possible to keep high-molecular-weight cargo. Low-molecular-weight methylprednisolone sodium succinate is poorly retained in PCL- and PLGA-based microchambers after immersion in deionized water (only 9.5% and 15.7% are left, respectively). In comparison, PLA-based microchambers retain 96.3% after the same procedure. In vivo studies on rabbits have shown that effective granulation tissue suppression is achieved when PLA and PLGA are used for coatings. PLGA-based microchamber coating almost completely degrades in 10 days in the trachea, while PLA-based microchamber films partially preserve their structure. The PCL-based film coating is most stable over time, which probably causes blocking the outflow of fluid from the tracheal mucosa and the aggravation of the inflammatory process against the background of low drug concentration. Combination and variability of polymers in the fabrication of films with microchambers to retain therapeutic compounds are suggested as a novel type of drug-eluting coating.

Description: Biochar (BC) recently gained attention as an additive for anaerobic digestion (AD). This work aims at a critical analysis of the effect of six BCs, with different physical and chemical properties, on the AD of mixed wastewater sludge at 37 °C, comparing their influence on methane production and AD kinetics. AD batch tests were performed at the laboratory scale operating 48 reactors (0.25 L working volume) for 28 days with the addition of 10 g L−1 of BC. Most reactors supplemented with BCs exhibited higher (up to 22%) methane yields than the control reactors (0.15 Nm3 kgVS−1). The modified Gompertz model provided maximum methane production rate values, and in all reactors the lag-phase was equal to zero days, indicating a good adaptation of the inoculum to the substrate. The potential correlations between BCs’ properties and AD performance were assessed using principal component analysis (PCA). The PCA results showed a reasonable correlation between methane production and the BCs’ O–C and H–C molar ratios, and volatile matter, and between biogas production and BCs’ pore volume, specific surface area, and fixed and total carbon. In conclusion, the physic-chemical properties of BC (specifically, hydrophobicity and morphology) showed a key role in improving the AD of mixed wastewater sludge.

Description: The aim of this study is to elucidate the mechanism of micropollutants’ removal in drinking water by the application of catalytic ozonation, using transition metals as appropriate catalysts. For that purpose, the degradation of 500 μg/L of p-chlorobenzoic acid (p-CBA) and benzotriazole with the addition of 2 mg/L of ozone in the presence of 1 mg/L of Co(II) or Fe(II) and at pH 7.8 were examined. It was found that in distilled water experiments, both metal ions can be characterized as catalysts, enhancing the ozonation process; however, in the natural water matrix, only iron presented higher removal rates of examined organic pollutants, when compared to single ozonation. The metal ions present catalytic activity, when they can form precipitates, hence converting the initially homogeneous process of catalytic ozonation towards a heterogeneous one. However, when 2 mg/L of ozone was applied in natural water experiments, Co(II)—unlike Fe(II)—could not be oxidized into its trivalent form, hence it cannot precipitate as Co(OH)3. Therefore, under these experimental conditions, this metal was not found to present any catalytic activity. Nevertheless, the addition of phosphates (PO43−) in concentrations higher than 100 mg/L can increase the oxidation ability of the Co(II)/O3 system, due to the resulting sufficient formation of Co3(PO4)2 precipitates. Although cobalt can enhance the •OH production (and therefore, the ozonation procedure) under these conditions, the relatively highly added concentration of phosphate ions makes the treated water non-potable, resulting in the application of further treatment to remove the excess phosphates. Therefore, only Fe(II) can be considered as a sufficient catalyst to enhance the ozonation processes.

Description: Human-induced pluripotent stem cells (hiPSCs) offer numerous possibilities in science and medicine, particularly when combined with precise genome editing methods. hiPSCs are artificially generated equivalents of human embryonic stem cells (hESCs), which possess an unlimited ability to self-renew and the potential to differentiate into any cell type of the human body. Importantly, generating patient-specific hiPSCs enables personalized drug testing or autologous cell therapy upon differentiation into a desired cell line. However, to ensure the highest standard of hiPSC-based biomedical products, their safety and reliability need to be proved. One of the key factors influencing human pluripotent stem cell (hPSC) characteristics and function is oxygen concentration in their microenvironment. In recent years, emerging data have pointed toward the beneficial effect of low oxygen pressure (hypoxia) on both hiPSCs and hESCs. In this review, we examine the state-of-the-art research on the oxygen impact on hiPSC functions and activity with an emphasis on their niche, metabolic state, reprogramming efficiency, and differentiation potential. We also discuss the similarities and differences between PSCs and cancer stem cells (CSCs) with respect to the role of oxygen in both cell types.

Description: We aim to evaluate whether the first National Emergency Medical Service (NEMS) improved access to hospital care for the people of Sierra Leone. We performed an interrupted time-series analysis to assess the effects of NEMS implementation on hospital admissions in 25 facilities. The analysis was also replicated separately for the area of Freetown and the rest of the country. The study population was stratified by the main Free Health Care Initiative (FHCI) categories of pregnant women, children under 5 years of age, and populations excluded from the FHCI. Finally, we calculated direct costs of the service. We report a 43% overall increase in hospital admissions immediately after NEMS inception (RR 1.43; 95% CI 1.2–1.61). Analyses stratified by FHCI categories showed a significant increase among pregnant women (RR 1.54; 95% CI 1.33–1.77) and among individuals excluded from the FHCI (RR 2.95; 95% CI 2.47–3.53). The observed effect was mainly due to the impact of NEMS on the rural districts. The estimated recurrent cost per ambulance ride and NEMS yearly cost per inhabitant were 124 and 0.45 USD, respectively. To our knowledge, this is the first nationwide study documenting the increase in access to healthcare services following the implementation of an ambulance-based medical service in a low-income country. Based on our results, NEMS was able to overcome the existing barriers of geographical accessibility and transport availability, especially in the rural areas of Sierra Leone.

Description: The organic anion transporter (OAT) family is the subfamily of the solute carrier (SLC) superfamily, which plays a vital role in regulating essential nutrients in milk. However, little is known about the members’ identification, evolutionary basis, and function characteristics of OAT genes associated with milk performance in buffalo. Comparative genomic analyses were performed to identify the potential role of buffalo OAT genes in milk performance in this study. The results showed that a total of 10 and 7 OAT genes were identified in river buffalo and swamp buffalo, respectively. These sequences clustered into three groups based on their phylogenetic relationship and had similar motif patterns and gene structures in the same groups. Moreover, the river-specific expansions and homologous loss of OAT genes occurred in the two buffalo subspecies during the evolutionary process. Notably, the duplicated SLCO3A1 gene specific to river buffalo showed higher expression level in mammary gland tissue than that of swamp buffalo. These findings highlight some promising candidate genes that could be potentially utilized to accelerate the genetic progress in buffalo breeding programs. However, the identified candidate genes require further validation in a larger cohort for use in the genomic selection of buffalo for milk production.

Description: In this study, density functional theory (DFT) calculations have been performed to investigate the adsorption mechanisms of toluene and water onto various cationic forms of Y zeolite (LiY, NaY, KY, CsY, CuY and AgY). Our computational investigation revealed that toluene is mainly adsorbed via π–interactions on alkalis exchanged Y zeolites, where the adsorbed toluene moiety interacts with a single cation for all cases with the exception of CsY, where two cations can simultaneously contribute to the adsorption of the toluene, hence leading to the highest interaction observed among the series. Furthermore, we find that the interaction energies of toluene increase while moving down in the alkaline series where interaction energies are 87.8, 105.5, 97.8, and 114.4 kJ/mol for LiY, NaY, KY and CsY, respectively. For zeolites based on transition metals (CuY and AgY), our calculations reveal a different adsorption mode where only one cation interacts with toluene through two carbon atoms of the aromatic ring with interaction energies of 147.0 and 131.5 kJ/mol for CuY and AgY, respectively. More importantly, we show that water presents no inhibitory effect on the adsorption of toluene, where interaction energies of this latter were 10 kJ/mol (LiY) to 47 kJ/mol (CsY) higher than those of water. Our results point out that LiY would be less efficient for the toluene/water separation while CuY, AgY and CsY would be the ideal candidates for this application.

Description: An extensive survey conducted in the Saïss plain of Morocco during the 2017–2018 growing season revealed that 35 out of 50 apple and pear orchards were infested with a pathogen that causes the decline disease. Morphological and phylogenetic tree analyses using the cox II gene allowed us to identify the pathogen as Phytopythium vexans. Interestingly, no Phytophthora and Pythium species were isolated. The occurrence and prevalence of the disease varied between locations; the most infested locations were Meknes (100%), Imouzzer (83%), and Sefrou (80%). To fulfill Koch’s postulate, a greenhouse pathogenicity test was performed on the stem and collar of one-year-old healthy seedlings of apple rootstock M115. Symptoms similar to those observed in the field were reproduced in less than 4 months post-inoculation with root rot disease severity ranging from 70 to 100%. The survey results evidenced that apple rootstocks, soil type, and irrigation procedure may contribute significantly to the occurrence of the disease. The disease was most prevalent in drip water irrigation and sandy-clay soil on wild apple rootstock. Accordingly, a rational drip advanced watering system and good sanitation practices could eliminate water stagnation and help prevent the onset of this disease. It was concluded that Pp. vexans occurrence may be strongly influenced by irrigation mode and type of soil. Therefore, the obtained findings of this study could help to better understand the recurrence of this disease and to develop a reliable integrated strategy for its management.

Description: Epithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master regulator of oncogenes or tumor suppressors. To investigate novel miR-200c-3p target genes involved in EOC tumorigenesis, we evaluated the association between this miRNA and the mRNA expression of several potential target genes by RNA-seq data of both 46 EOC cell lines from Cancer Cell line Encyclopedia (CCLE) and 456 EOC patient bio-specimens from The Cancer Genome Atlas (TCGA). Both analyses showed a significant anticorrelation between miR-200c-3p and the protein phosphatase 3 catalytic subunit γ of calcineurin (PPP3CC) levels involved in the apoptosis pathway. Quantitative mRNA expression analysis in patient biopsies confirmed the inverse correlation between miR-200c-3p and PPP3CC levels. In vitro regulation of PPP3CC expression through miR-200c-3p and RNA interference technology led to a concomitant modulation of BCL2- and p-AKT-related pathways, suggesting the tumor suppressive role of PPP3CC in EOC. Our results suggest that inhibition of high expression of miR-200c-3p in EOC might lead to overexpression of the tumor suppressor PPP3CC and subsequent induction of apoptosis in EOC patients.

Description: As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC is following debulking surgery. Accumulating evidence shows that T cells are important in OC; thus, cancer vaccines capable of eliciting antitumor T cells will be effective in OC treatment. In this review, we discuss different cancer vaccines and propose strategies for their incorporation into the OC standard-of-care regimens. Using the murine ID8 ovarian tumor model, we provide evidence that a cancer vaccine can be effectively combined with OC standard-of-care to achieve greater overall efficacy. We demonstrate several important similarities between the ID8 model and OC patients, in terms of response to immunotherapies, and the ID8 model can be an important tool for evaluating combinatorial regimens and clinical trial designs in OC. Other emerging models, including patient-derived xenograft and genetically engineered mouse models, are continuing to improve and can be useful for evaluating cancer vaccination therapies in the near future. Here, we provide a comprehensive review of the completed and current clinical trials evaluating cancer vaccines in OC.

Description: Renal cell carcinoma (RCC) is a malignancy of the kidney originating from the tubular epithelium. Inactivation of the von Hippel–Lindau tumor-suppressor gene (VHL) is found in most clear cell renal cell carcinomas (ccRCCs). The VHL–HIF–VEGF/VEGFR pathway, which involves the von Hippel–Lindau tumor suppressor protein (VHL), hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), and its receptor (VEGFR), is a well-studied therapeutic target for metastatic ccRCC. Therefore, over the past decade, anti-angiogenic agents targeting VEGFR have served as the standard treatment for metastatic RCC. Recently, based on the immunomodulatory effect of anti-VEGFR therapy, anti-angiogenic agents and immune checkpoint inhibitor combination strategies have also emerged as therapeutic strategies. These advances were made possible by the improved understanding of the VHL–HIF pathway. In this review, we summarize the historical evolution of ccRCC treatments, with a focus on the involvement of the VHL–HIF pathway.

Description: Carnivores social organization varies widely, from strongly social to solitary predators. European badgers are facultative social carnivores that also shows a geographical variation in social structure. These patterns derive mainly from central/west European regions, with an under-representation of Mediterranean populations that face different conservation challenges, especially regarding group composition, sett use patterns and breeding phenology. We addressed these traits topics for a population inhabiting a Portuguese agro-silvo-pastoral system. Based on monthly monitoring of 34 setts and continuous camera-trapping surveys of 12, we showed that setts surrounded by diversified vegetation and located in sandy sites are more used, a pattern probably linked to food availability and ease of sett excavation and maintenance, respectively. Badgers followed a general pattern regarding group size (2–4 adults), but showed an intermediate population density (0.49–0.73 badgers/km2), with values higher than those estimated for other Mediterranean environments, but lower than for central-western populations. This, together with the breeding (November/January) and cub emergence (1.8 cubs/sett; March/April) periods, indicates an ecological adaptation to the landscape context, where human-related resources and mild environmental conditions allow badger to reach higher densities than in many southern populations, and to reproduce earlier than their northern counterparts.

Description: The Dictyostelium centrosome is a nucleus-associated body with a diameter of approx. 500 nm. It contains no centrioles but consists of a cylindrical layered core structure surrounded by a microtubule-nucleating corona. At the onset of mitosis, the corona disassembles and the core structure duplicates through growth, splitting, and reorganization of the outer core layers. During the last decades our research group has characterized the majority of the 42 known centrosomal proteins. In this work we focus on the conserved, previously uncharacterized Cep192 protein. We use superresolution expansion microscopy (ExM) to show that Cep192 is a component of the outer core layers. Furthermore, ExM with centrosomal marker proteins nicely mirrored all ultrastructurally known centrosomal substructures. Furthermore, we improved the proximity-dependent biotin identification assay (BioID) by adapting the biotinylase BioID2 for expression in Dictyostelium and applying a knock-in strategy for the expression of BioID2-tagged centrosomal fusion proteins. Thus, we were able to identify various centrosomal Cep192 interaction partners, including CDK5RAP2, which was previously allocated to the inner corona structure, and several core components. Studies employing overexpression of GFP-Cep192 as well as depletion of endogenous Cep192 revealed that Cep192 is a key protein for the recruitment of corona components during centrosome biogenesis and is required to maintain a stable corona structure.

Description: Given the differing mechanisms thought to underlie therapeutic sub- and supra-perception-based neurostimulative modalities, Spinal Cord Stimulation (SCS) systems designed for combined delivery of these approaches may help improve analgesic outcomes and quality of life, and reduce treatment failures. This multicenter, observational case-series evaluated 188 patients with chronic back and/or leg pain implanted with an SCS device capable of sequential or simultaneous delivery of sub-perception and supra-perception stimulation programming (i.e., combination therapy) at 16 sites in Europe. Following implantation, patients were provided with an array of advanced supra-perception programs (e.g., paresthesia-based SCS using multiple independent current sources), and a custom set of sub-perception programs optimized with specific waveforms and/or field shapes. A mean overall pain score of 7.9 ± 1.7 (Standard Deviation (SD)) was reported pre-trial (Baseline). Overall pain was reduced by 4.4 ± 2.8 points (NRS) at 3-months (n = 117) and at 12 months post-implant (n = 90), respectively (p 〈 0.0001). Substantial quality-of-life (EQ-5D-5L) improvement as assessed at last follow-up was also observed (n = 60). These results suggest that an implanted SCS device capable of combination therapy, while also enabled with patient-specific waveform optimization and stimulation field targeting capabilities, can enable highly effective pain relief and improve quality of life in patients suffering with chronic pain.

Description: We analysed the effects of Swiss national lockdown due to the COVID-19 pandemic on the glycaemic control in patients with diabetes mellitus. In a retrospective observational cohort study with observation period 16 December 2018–27 July 2020, we included tertiary care patients with diabetes and at least one glycated haemoglobin A1c (HbA1c) measurement before and after the lockdown beginning. Main outcome measure was change in HbA1c after the lockdown. We included 1078 patients (86% diabetes type 2) with a mean HbA1c of 55.63 mmol/mol (7.24%). Glycaemic control was susceptible to seasonal changes with higher mean HbA1c in winter as compared to spring (57.49 mmol/mol (7.41%) vs. 55.52 mmol/mol (7.23%), p = 0.013). The lockdown did not affect the mean HbA1c values of all patients. However, we found a higher proportion of type 2 diabetes patients with a worsening HbA1c after the lockdown as compared to the year before (32% vs. 22.9%, p = 0.02). In a mixed-model regression multivariable analysis, inappropriate alcohol intake and hypothyroidism were associated with an increase in HbA1c after the lockdown. In conclusion, the national lockdown had no effect on overall mean HbA1c values but affected a proportion of type 2 diabetes patients with worsening HbA1c, whose individual risk factors were identified.

Description: Background: The declaration of the first state of alarm for COVID-19 in March 2020 provoked changes in ophthalmological care. The objective of this study was to assess its impact on reorganising care activities, the mental health of ophthalmologists and the training of residents. Methods: We sent an anonymous online questionnaire between August and October 2020 to consultant ophthalmologists and residents who were active during the state of alarm in Spain. We used Google Forms® software for data collection. We analysed responses according to the degree of regional impact. Results: We received a total of 328 responses from the 17 Autonomous Communities. We saw that 99.4% of respondents changed their work activities with 50% reductions in surgery (94.5%) and consultations (93.0%). Furthermore, 58.8% of respondents reported increased anxiety, and 29.9% transferred to support other services, with this number reaching 49.6% in the hardest-hit regions. Training programs were greatly reduced in external consultations (90.7%), and surgical training was completely cancelled (100%). Additionally, 56.5% of trainees wanted to prolong their residence periods. Conclusions: The first wave of the pandemic produced significant changes in ophthalmology services, and these changes were more pronounced in the most affected regions. It caused a negative psychological impact on a high rate of respondents and an interruption of the training of ophthalmology residents. Predictably, the negative consequences of this delay in ophthalmological care on patients will be uneven between regions.

Description: Epoxy/silica thermosets with tunable matrix (vitrimers) were prepared by thermal curing of diglycidyl ether of bisphenol A (DGEBA) in the presence of a hardener—4-methylhexahydrophthalic anhydride (MHHPA), a transesterification catalyst—zinc acetylacetonate (ZAA), and 10–15 nm spherical silica nanoparticles. The properties of the resulting material were studied by tensile testing, thermomechanical and dynamic mechanical analysis. It is shown that at room temperature the introduction of 5–10 wt% of silica nanoparticles in the vitrimer matrix strengthens the material leading to the increase of the elastic modulus by 44% and the tensile stress by 25%. Simultaneously, nanoparticles enhance the dimensional stability of the material since they reduce the coefficient of thermal expansion. At the same time, the transesterification catalyst provides the thermoset with the welding ability at heating, when the chain exchange reactions are accelerated. For the first time, it was shown that the silica nanoparticles strengthen welding joints in vitrimers, which is extremely important, since it allows to repeatedly use products made of thermosets and heal defects in them. Such materials hold great promise for use in durable protective coatings, adhesives, sealants and many other applications.

Description: In this work, a novel approach is demonstrated for 3D-printing of bacterial cellulose (BC) reinforced UV-curable ion gels using two-component solvents based on 1-butyl-3-methylimidazolium chloride or choline chloride combined with acrylic acid. Preservation of cellulose’s crystalline and nanofibrous structure is demonstrated using wide-angle X-ray diffraction (WAXD) and atomic force microscopy (AFM). Rheological measurements reveal that cholinium-based systems, in comparison with imidazolium-based ones, are characterised with lower viscosity at low shear rates and improved stability against phase separation at high shear rates. Grafting of poly(acrylic acid) onto the surfaces of cellulose nanofibers during UV-induced polymerization of acrylic acid results in higher elongation at break for choline chloride-based compositions: 175% in comparison with 94% for imidazolium-based systems as well as enhanced mechanical properties in compression mode. As a result, cholinium-based BC ion gels containing acrylic acid can be considered as more suitable for 3D-printing of objects with improved mechanical properties due to increased dispersion stability and filler/matrix interaction.