Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic and Micro-Evolutionary Features of Mammalian 2 orthobornavirus (Variegated Squirrel Bornavirus 1, VSBV-1)

Mammalian 2 orthobornavirus (VSBV-1) is an emerging zoonotic pathogen discovered in several exotic squirrel species and associated with fatal human encephalitis. The dynamics of VSBV-1 spread and evolution in its presumed natural hosts are unknown. Here, we present the phylogeny, micro-evolution, cross-species transmission and spread of VSBV-1 at a temporal and spatial resolution within the limits of animal husbandry. The results showed that VSBV-1 can be classified into six distinct groups and that the most recent common ancestor of the known German strains emerged at least 20 years ago. We here demonstrate that the genetic diversity of the VSBV-1 groups is shaped primarily by in situ evolution and most of the amino acid changes are deleterious polymorphisms removed by purifying selection. Evidence of adaptive evolution has been found in the G and L genes which might have an influence on transmission fitness. Furthermore, there was also evidence for some form of adaptive changes in the glycoprotein which suggests that many sites might be subjected to positive pressure evolving under episodic directional selection, indicating past occurrence of positive selection. Host switching events were detected as dominant evolutionary mechanisms driving the virus-host associations. Virus spread by animal trade followed by subsequent local micro-evolution in zoos and holdings is responsible for diversifying strains. Time-resolved phylogeny indicated that Prevost’s squirrels might be the original squirrel species carrying and seeding the virus in Germany. This study provides the first insight into the ecology and micro-evolutionary dynamics of this novel viral pathogen in the captive exotic squirrel population under artificial ecological conditions (zoos and animal husbandry) and co-housing of different squirrel species.
Porous Polymers from High Internal Phase Emulsions as Scaffolds for Biological Applications

High internal phase emulsions (HIPEs), with densely packed droplets of internal phase and monomers dispersed in the continuous phase, are now an established medium for porous polymer preparation (polyHIPEs). The ability to influence the pore size and interconnectivity, together with the process scalability and a wide spectrum of possible chemistries are important advantages of polyHIPEs. In this review, the focus on the biomedical applications of polyHIPEs is emphasised, in particular the applications of polyHIPEs as scaffolds/supports for biological cell growth, proliferation and tissue (re)generation. An overview of the polyHIPE preparation methodology is given and possibilities of morphology tuning are outlined. In the continuation, polyHIPEs with different chemistries and their interaction with biological systems are described. A further focus is given to combined techniques and advanced applications.
Molecular Characterization of Chitin Synthase Gene in Tetranychus cinnabarinus (Boisduval) and Its Response to Sublethal Concentrations of an Insecticide

Simple Summary In this study, we identified chitin synthase 1 gene (TcCHS1) from Tetranychus cinnabarinus (Boisduval) and then explored the gene expression levels of TcCHS1 at different developmental stages of T. cinnabarinus. We also investigated the effects of sublethal concentrations of diflubenzuron on the toxicities and survivals of T. cinnabarinus eggs and larvae as well as TcCHS1 expression levels. Our results demonstrated that TcCHS1 was essential for growth and development, and diflubenzuron exposure affected chitin metabolism. This work was undertaken to establish a foundation for further research on the functions of chitin synthase. It will provide a new target for controlling of T. cinnabarinus in the agricultural ecosystem. Abstract The carmine spider mite, Tetranychus cinnabarinus (Boisduval), is one of the most important acarine pest species. At present, its control remains primarily dependent on using various chemical insecticides/acaricides in agricultural crops worldwide. To clarify the mechanism whereby T. cinnabarinus responds to insecticide exposure, we identified the chitin synthase 1 gene (TcCHS1) and then explored the gene expression levels of TcCHS1 at different developmental stages of T. cinnabarinus. We also investigated the effects of sublethal concentrations of diflubenzuron on the toxicities and survivals of T. cinnabarinus eggs and larvae as well as TcCHS1 expression levels. The full-length cDNA sequence contains an open reading frame (ORF) of 4881 nucleotides that encoded for a 1474 amino acid residues protein. The predicted TcCHS1 protein had a molecular mass of 168.35 kDa and an isoelectric point of 6.26, and its amino acid sequence contained all the signature motifs (EDR, QRRRW and TWGTR) of chitin synthases. The results of phylogenetic analyses demonstrated that the putative CHS1 amino acid sequence of T. cinnabarinus revealed high similarities with chitin synthases in other insects and mites. Additionally, at the molecular level, transcriptional analysis by real-time quantitative PCR in different developmental stages of T. cinnabarinus revealed that TcCHS1 mRNA was expressed in all stages, and highest in eggs and female adults, but lowest in deutonymphs. Furthermore, the results of toxicity bioassays indicated that diflubenzuron treatment resulted in high mortality rates in eggs and larvae of T. cinnabarinus. The mRNA expression levels of TcCHS1 from the eggs and larvae of T. cinnabarinus were up-regulated in response to sublethal concentrations of diflubenzuron exposures. Together, all these results demonstrate that diflubenzuron has ovicidal and larvicidal effects and TcCHS1 may play an important role in the growth and development of T. cinnabarinus and may disrupt the chitin biosynthesis, thereby controlling T. cinnabarinus populations.
Examining the Determinants of Healthcare Workers’ Performance: A Configurational Analysis during COVID-19 Times

The evaluation of the work performance of health professionals has focused the interest of scientific research in recent decades as a basis for improving the quality of health services. The global COVID-19 pandemic has pushed countries’ health systems to the limit and had previously unknown consequences on the job performance of health professionals. In this context, what are the determinants of performance? There are numerous studies that link job performance with other variables that directly affect it, such as leadership, job satisfaction, organizational commitment, and work environment. However, there are no studies that jointly relate all these variables, and even less in the field of health. The main objective of this work is to analyse how these variables are configured together to generate a good level of performance of health professionals during the times of COVID-19. To do this, a fuzzy set qualitative comparative analysis (fsQCA) is carried out, an appropriate method that will allow finding the joint causal effects of key variables in human resources to ensure a good level of job performance in health organizations. The study reveals that leadership and commitment are the two key drivers of performance. The data confirm that the “recipe” to achieve a good level of performance consists of the combination of leadership, commitment, and a good work environment. Additionally, in the case of less satisfied workers, linking leadership and commitment is a sufficient condition.
Smoking Cessation after Diagnosis of New-Onset Atrial Fibrillation and the Risk of Stroke and Death

Limited data are available regarding the impact of smoking cessation after atrial fibrillation (AF) diagnosis on clinical outcomes. Using the Korean National Health Insurance Service database, we included patients newly diagnosed with AF and categorized them into four groups as follows: (i) never smokers, (ii) ex-smokers, (iii) smoking cessation after AF diagnosis (“quitters”), and (iv) current smokers. The primary outcomes were incident ischemic stroke and all-cause death during follow-up. Fatal ischemic stroke and death from cerebrovascular events were evaluated as secondary outcomes. Among 97,637 patients (mean age, 61 years; mean CHA2DS2-VASc score, 2.3), 6.9% stopped smoking after AF diagnosis. The mean follow-up duration was 3.2 ± 2.0 years. After multivariable adjustment, quitters had lower risks of ischemic stroke (hazard ratio (HR), 0.702; 95% confidence interval (CI), 0.595–0.827) and all-cause death (HR, 0.842; 95% CI, 0.748–0.948) than current smokers. Quitters after AF diagnosis were associated with lower risks of fatal ischemic stroke (HR, 0.454; 95% CI, 0.287–0.718) and death from cerebrovascular events (HR, 0.664; 95% CI, 0.465–0.949) compared with current smokers. Quitting smoking may reduce the risk of ischemic stroke, the severity of ischemic stroke, and the incidence of cerebrovascular events in patients with new-onset AF.
External Validation of the Briganti Nomogram to Predict Lymph Node Invasion in Prostate Cancer—Setting a New Threshold Value

(1) Introduction: The study aimed to test and validate the performance of the 2012 Briganti nomogram as a predictor for pelvic lymph node invasion (LNI) in men who underwent radical prostatectomy (RP) with extended pelvic lymph node dissection (PLND) to examine their performance and to analyse the therapeutic impact of using a different nomogram cut-off. (2) Material and Methods: The study group consisted of 222 men with clinically localized prostate cancer (PCa) who underwent RP with ePLND between 01/2012 and 10/2018. Measurements included: preoperative PSA, clinical stage (CS), primary and secondary biopsy Gleason pattern, and the percentage of positive cores. The area under the curve (AUC) of the receiver operator characteristic analysis was appointed to quantify the accuracy of the primary nomogram model to predict LNI. The extent of estimation associated with the use of this model was graphically depicted using calibration plots. (3) Results: The median number of removed lymph nodes was 16 (IQR 12–21). A total of 53 of 222 patients (23.9%) had LNI. Preoperative clinical and biopsy characteristics differed significantly (all p < 0.005) between men with and without LNI. A nomogram-derived cut-off of 7% could lead to a reduction of 43% (95/222) of lymph node dissection while omitting 19% (10/53) of patients with LNI. The sensitivity, specificity, and negative predictive value associated with the 7% cut-off were 81.1%, 50.3%, and 96.3%, respectively. (4) Conclusions: The analysed nomogram demonstrated high accuracy for LNI prediction. A nomogram-derived cut-off of 7% confirmed good performance characteristics within the first external validation cohort from Poland.
Suboptimal Tongue Pressure Is Associated with Risk of Malnutrition in Community-Dwelling Older Individuals

The tongue plays an important role in swallowing, and its dysfunction theoretically leads to inadequate oral intake and subsequent malnutrition. This study aimed to explore how different levels of tongue pressure are related to malnutrition among community-dwelling older individuals. The target population was community-dwelling adults aged ≥ 65 years. Tongue pressure was measured using the Iowa Oral Performance Instrument, whereas the mini nutrition assessment (MNA) test was administered to determine the nutritional status. A full MNA score of less than 24 points was defined as risk of malnutrition. Multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) of risk of malnutrition among different quartiles of tongue pressure. Among the 362 participants, 26 (7.1%) were classified as having risk of malnutrition. Body weight, body mass index, handgrip strength, skeletal muscle mass index, sum MNA score, and serum levels of albumin were lower in the malnutrition risk groups than in the normal nutrition status group. A positive correlation was identified between tongue pressure and the MNA score (r = 0.143, p < 0.01). Treating the subgroup of the highest quartile of tongue pressure as the reference, the crude odds ratio (OR) of having risk of malnutrition was 5.37 (95% CI, 1.14–25.28) in the subgroup at the third quartile, 3.10 (95% CI, 0.60–15.84) in the subgroup at the second quartile, and 3.95 (95% CI, 0.81–19.15) in the subgroup at the lowest quartile. After adjustment for age and sex, the subgroup in the third quartile still presented with a significantly higher risk (OR, 4.85; 95% CI, 1.02–22.99) of risk of malnutrition. Compared with the subgroup at the highest quartile of tongue pressure, the crude OR for all the subgroups in the lower three quartiles was 4.17 (95% CI, 0.96–18.04), showing borderline significance (p = 0.05). In conclusion, we found hints for an association between decreased tongue pressure and an increased risk of malnutrition in community-dwelling older individuals. Older people with suboptimal tongue pressure should undergo a thorough assessment of their nutritional status and swallowing function for the early identification of subclinical malnutrition and dysphagia.
Fundamental and Advanced Therapies, Vaccine Development against SARS-CoV-2

Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus has been affecting the world since the end of 2019. The severity of the disease can range from an asymptomatic or mild course to acute respiratory distress syndrome (ARDS) with respiratory failure, which may lead to death. Since the outbreak of the pandemic, scientists around the world have been studying the genome and molecular mechanisms of SARS-CoV-2 infection to develop effective therapies and prevention. In this review, we summarize the progressive development of various treatments and vaccines as they have emerged, a year after the outbreak of the pandemic. Initially for COVID-19, patients were recommended drugs with presumed antiviral, anti-inflammatory, and antimicrobial effects that were previously used to treat other diseases. Thereafter, therapeutic interventions were supplemented with promising approaches based on antibodies, peptides, and stem cells. However, licensed COVID-19 vaccines remain the most effective weapon in combating the pandemic. While there is an enormous effort to enhance the vaccination rate to increase the entire population immunity, the production and delivery of vaccines is becoming limited in several countries. In this regard, there are new challenges needing to be addressed by combining non-pharmacological intervention with effective therapies until vaccination is accessible to all.
Extensive Comparative Genomic Analysis of Enterococcus faecalis and Enterococcus faecium Reveals a Direct Association between the Absence of CRISPR–Cas Systems, the Presence of Anti-Endonuclease (ardA) and the Acquisition of Vancomycin Resistance in E. faecium

Here, we performed a comparative genomic analysis of all available genomes of E. faecalis (n = 1591) and E. faecium (n = 1981) and investigated the association between the presence or absence of CRISPR-Cas systems, endonuclease/anti-endonuclease systems and the acquisition of antimicrobial resistance, especially vancomycin resistance genes. Most of the analysed Enterococci were isolated from humans and less than 14% of them were from foods and animals. We analysed and detected CRISPR–Cas systems in 75.36% of E. faecalis genomes and only 4.89% of E. faecium genomes with a significant difference (p-value < 10−5). We found a negative correlation between the number of CRISPR–Cas systems and genome size (r = −0.397, p-value < 10−5) and a positive correlation between the genome %GC content and the number of CRISPR–Cas systems (r = 0.215, p-value < 10−5). Our findings showed that the presence of the anti-endonuclease ardA gene may explain the decrease in the number of CRISPR–Cas systems in E. faecium, known to deactivate the endonucleases’ protective activities and enable the E. faecium genome to be versatile in acquiring mobile genetic elements, including carriers of antimicrobial resistance genes, especially vanB. Most importantly, we observed that there was a direct association between the absence of CRISPR–Cas, the presence of the anti-CRISPR ardA gene and the acquisition of vancomycin resistance genes.
Comparison of Simplified Creatinine Index and Systemic Inflammatory Markers for Nutritional Evaluation of Hemodialysis Patients

Protein-energy wasting (PEW) is associated with adverse outcomes in hemodialysis patients. This study compares the simplified creatinine index (SCI) and circulating inflammatory markers as nutritional screening tools for hemodialysis patients. Maintenance hemodialysis patients (230 total patients, 34.8% women, 64.0 ± 14.3 years old) from a tertiary medical center were assessed for demographic data, body composition analysis, biochemistry tests, and circulating inflammatory biomarkers. The SCI was calculated using Canaud’s formula. Reduced fat-free mass index (FFMI), a surrogate of lean body mass, was identified according to the European Society for Clinical Nutrition and Metabolism guidelines. Nutritional status was assessed by the geriatric nutritional risk index (GNRI) and International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Multivariate logistic regression revealed independent risk factors for low FFMI and malnutrition. Of the patients, 47.4% had low FFMI. Patients with a reduction in FFMI tended to be older females with lower body mass index, SCI, and GNRI scores but significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-8. SCI was found to be an independent predictor for reduced FFMI (OR 0.57, 95% CI 0.40–0.81) and presence of PEW according to ISRNM criteria (OR 0.38, 95% CI 0.21–0.68). Although a positive association between systemic inflammatory markers and low FFMI was observed, this association disappeared in multivariate analysis. Moreover, the inflammatory markers examined in this study were not associated with malnutrition after adjusting for potential confounders. Compared with markers of systemic inflammation, SCI achieved better performance in assessing the nutritional status of hemodialysis patients.
Re: Using Robson's Ten‐Group Classification System for comparing caesarean section rates in Europe: an analysis of routine data from the Euro‐Peristat study

evidence-base is interpreted and applied in Europe. One example is that caesarean birth rates for breech presentations are lower in France than in Sweden, despite overall caesarean rates being low in both countries. In general, however, our study found that countries with higher overall caesarean rates had higher rates in all subgroups. We discuss several hypotheses for these differences, including those related to the characteristics of childbearing women. However, population characteristics are unlikely to explain the variation between countries, in part because risk is low for most women, and because the differences are very wide. For instance, despite the elevated risk of caesarean delivery associated with higher maternal age, only modest changes result from adjustment (Figure 1). The figure also shows variation between countries even when proportions of older mothers are similar. Further, while adjusting for population characteristics is informative, comparing unadjusted rates is also valuable. Many population characteristics that raise caesarean risk are modifiable through primary prevention, including obesity and social deprivation and their complications. Documenting the differences in caesarean birth rates between European countries provides a starting point for research on explanatory population and health system factors. Although many have heard of the ecological fallacy (inferences about individuals are made based on aggregated data), the individualist fallacy (population-level exposures cannot be investigated when they do not vary within the study population) is of equal concern. Comparing countries with similar patient populations, but different health systems and societies, extends the scope for learning and change. As articulated by Michael Robson in his editorial to our paper, these comparisons help to identify the ‘unknown unknowns’ needed for effective audit and evaluation of practice. This diversity should therefore not be viewed as a threat, but welcomed as a way to identify best practices for achieving optimal maternal and infant health without unnecessary caesarean deliveries.
A Novel Personalized Systems Nutrition Program Improves Dietary Patterns, Lifestyle Behaviors and Health-Related Outcomes: Results from the Habit Study

Personalized nutrition may be more effective in changing lifestyle behaviors compared to population-based guidelines. This single-arm exploratory study evaluated the impact of a 10-week personalized systems nutrition (PSN) program on lifestyle behavior and health outcomes. Healthy men and women (n = 82) completed the trial. Individuals were grouped into seven diet types, for which phenotypic, genotypic and behavioral data were used to generate personalized recommendations. Behavior change guidance was also provided. The intervention reduced the intake of calories (−256.2 kcal; p < 0.0001), carbohydrates (−22.1 g; p < 0.0039), sugar (−13.0 g; p < 0.0001), total fat (−17.3 g; p < 0.0001), saturated fat (−5.9 g; p = 0.0003) and PUFA (−2.5 g; p = 0.0065). Additionally, BMI (−0.6 kg/m2; p < 0.0001), body fat (−1.2%; p = 0.0192) and hip circumference (−5.8 cm; p < 0.0001) were decreased after the intervention. In the subgroup with the lowest phenotypic flexibility, a measure of the body’s ability to adapt to environmental stressors, LDL (−0.44 mmol/L; p = 0.002) and total cholesterol (−0.49 mmol/L; p < 0.0001) were reduced after the intervention. This study shows that a PSN program in a workforce improves lifestyle habits and reduces body weight, BMI and other health-related outcomes. Health improvement was most pronounced in the compromised phenotypic flexibility subgroup, which indicates that a PSN program may be effective in targeting behavior change in health-compromised target groups.
Insulin-like Growth Factor 2 mRNA-Binding Protein 2—a Potential Link Between Type 2 Diabetes Mellitus and Cancer

Abstract Context Type 2 diabetes mellitus (T2DM) and cancer share a variety of risk factors and pathophysiological features. It is becoming increasingly accepted that the 2 diseases are related, and that T2DM increases the risk of certain malignancies. Objective This review summarizes recent advancements in the elucidation of functions of insulin-like growth factor 2 (IGF-2) messenger RNA (mRNA)-binding protein 2 (IGF2BP2) in T2DM and cancer. Methods A PubMed review of the literature was conducted, and search terms included IGF2BP2, IMP2, or p62 in combination with cancer or T2DM. Additional sources were identified through manual searches of reference lists. The increased risk of multiple malignancies and cancer-associated mortality in patients with T2DM is believed to be driven by insulin resistance, hyperinsulinemia, hyperglycemia, chronic inflammation, and dysregulation of adipokines and sex hormones. Furthermore, IGF-2 is oncogenic, and its loss-of-function splice variant is protective against T2DM, which highlights the pivotal role of this growth factor in the pathogenesis of these 2 diseases. IGF-2 mRNA-binding proteins, particularly IGF2BP2, are also involved in T2DM and cancer, and single-nucleotide variations (formerly single-nucleotide polymorphisms) of IGF2BP2 are associated with both diseases. Deletion of the IGF2BP2 gene in mice improves their glucose tolerance and insulin sensitivity, and mice with transgenic p62, a splice variant of IGF2BP2, are prone to diet-induced fatty liver disease and hepatocellular carcinoma, suggesting the biological significance of IGF2BP2 in T2DM and cancer. Conclusion Accumulating evidence has revealed that IGF2BP2 mediates the pathogenesis of T2DM and cancer by regulating glucose metabolism, insulin sensitivity, and tumorigenesis. This review provides insight into the potential involvement of this RNA binding protein in the link between T2DM and cancer.