Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular typing of conjunctivitis‐causing adenoviruses in Hanoi, Vietnam from 2017 to 2019 and complete genome analysis of the most prevalent type (HAdV‐8)

Adenoviral conjunctivitis is a common epidemic worldwide. In Vietnam, up to 80,000 patients are infected with adenoviral conjunctivitis annually. However, there are few investigations on the pathogenic adenoviruses that cause conjunctivitis. In total, 120 eye‐swab samples were collected from patients with viral conjunctivitis symptoms in Hanoi, Vietnam from 2017 to 2019. Human adenoviruse (HAdV) was detected in 67 samples (55.83%) using polymerase chain reaction amplification of at least one of three HAdV‐specific marker genes (hexon, penton, and fiber). Of the 67 HAdV samples, 46 samples could be analyzed by all three marker genes. DNA sequence analysis and phylogenetic tree building based on the three marker genes from the 46 HAdV samples revealed five different HAdV types associated with conjunctivitis in Hanoi, including HAdV‐3 (4.3%), HAdV‐4 (2.2%), HAdV‐8 (89.1%), HAdV‐37 (2.2%), and a potential recombinant type between types HAdV‐8 and HAdV‐3 (2.2%). This showed that HAdV‐8 was the most common type identified in Hanoi. Complete genome analysis of HAdV‐8 isolated from a Vietnamese patient (VN2017) using Sanger sequencing revealed 34 unique nucleotide changes, indicating that the adenovirus continuously accumulates new mutations. Hence, continuous surveillance of HAdV‐8 changes in Vietnam is necessary in the future.
Pathogenesis of Mucopolysaccharidoses, an Update

The recent advancements in the knowledge of lysosomal biology and function have translated into an improved understanding of the pathophysiology of mucopolysaccharidoses (MPSs). The concept that MPS manifestations are direct consequences of lysosomal engorgement with undegraded glycosaminoglycans (GAGs) has been challenged by new information on the multiple biological roles of GAGs and by a new vision of the lysosome as a signaling hub involved in many critical cellular functions. MPS pathophysiology is now seen as the result of a complex cascade of secondary events that lead to dysfunction of several cellular processes and pathways, such as abnormal composition of membranes and its impact on vesicle fusion and trafficking; secondary storage of substrates; impairment of autophagy; impaired mitochondrial function and oxidative stress; dysregulation of signaling pathways. The characterization of this cascade of secondary cellular events is critical to better understand the pathophysiology of MPS clinical manifestations. In addition, some of these pathways may represent novel therapeutic targets and allow for the development of new therapies for these disorders.
Prevalence and Risk Factors of Total Parenteral Nutrition Induced Hyperglycemia at a Single Institution: Retrospective Study

Background: Total parenteral nutrition (TPN) provides full nutrition support to critically ill patients with an impaired digestive tract. Patients who receive TPN support are at higher risk for complications such as hyperglycemia. In our study, we aim to assess the prevalence of hyperglycemia induced by TPN and identify its risk factors in hospitalized adult patients. Methods: Patients who received TPN between January 2012 and December 2017 at University of Pittsburgh Medical Center—St. Margaret hospital were retrospectively screened. TPN-induced hyperglycemia was confirmed whether blood glucose was ≥180 mg/dL at any point, from the time of TPN initiation until 1-day post TPN termination. Characteristics of the hyperglycemia and the nonhyperglycemia groups were analyzed to predict potential risk factors. Results: A total of 197 patients were screened, 55 were excluded (1 died, 37 diabetic, and 17 had elevated blood glucose before TPN), and 142 patients were included, 42 of them (29.6%) developed hyperglycemia following TPN administration. Duration of TPN, surgical indications, and obesity were significantly higher in the hyperglycemia group. Additionally, age and steroids use were independent predictors of hyperglycemia in TPN patients after applying multivariable logistic regression model on our sample. Conclusions: Hyperglycemia is common after TPN. Risk factors assessment may help optimizing glycemic control in higher risk individuals to improve their outcomes. These include patients with obesity, surgical indication of TPN, and longer duration of TPN.
Increasing incidence of type 1 diabetes among Hong Kong children and adolescents: The Hong Kong Childhood Diabetes Registry 2008 to 2017

The incidence of childhood‐onset type 1 diabetes (T1D) has been reported to be rising but there is also evidence that it has been attenuated in recent years. We described the time trends and the incidence of T1D in children in Hong Kong from 2008 to 2017 and compared with the previous local registry in 1997 to 2007.
Improvements in Clinical Outcomes for BRAFV600E-Mutant Metastatic Colorectal Cancer

Although the last two decades have seen a broad improvement in overall survival, colorectal cancer is still the second leading cause of cancer deaths worldwide. Patient populations continue to face poor disease prognoses due to the challenges of early detection and the molecular subtypes driving their colorectal cancer. Consequently, many patients present with metastatic colorectal cancer, which often limits options and shifts treatment focus away from curative interventions. BRAFV600E mutations are present in approximately 10% of colorectal cancer tumors and are associated with uninhibited cell proliferation, reduced apoptosis, and resistance to standard therapeutic options. In colorectal cancer, BRAFV600E mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type BRAF. Success in treating other BRAFV600E-mutant cancers with BRAF inhibitors as monotherapy has not translated into efficacious treatment of metastatic colorectal cancer. Consequently, combination therapy with inhibitors of BRAF, MEK, and EGFR, which overcomes the innate treatment-resistant characteristics of BRAFV600E-mutant colorectal cancer, is now recommended by treatment guidelines.
Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective

An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in Wuhan, China, now known as coronavirus disease 2019 (COVID‐19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID‐19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal‐oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID‐19; (b) microbiological and virological investigations; (c) the role of fecal‐oral transmission; and (d) prevention and control of SARS‐CoV‐2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.
Are White Matter Tract Integrities Different in Multiple Sclerosis Women With Voiding Dysfunction?

Supplemental digital content is available in the text. Objectives Two white matter tracts (WMTs) are proposed to be involved in bladder function: anterior thalamic radiation and superior longitudinal fasciculus. Multiple sclerosis (MS) patients with voiding dysfunction (VD) may have distinct changes in these 2 WMTs. This study aims to compare the fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging of MS females with and without VD versus healthy controls (HCs). Methods Prospective observational cohorts of 28 female MS patients and 11 HCs were recruited. Multiple sclerosis patients were divided into 2 groups: voiders (patients without VD, n = 14) and VD (patients with VD, n = 14). Diffusion tensor imaging of each subject was obtained, from which FA and MD maps were generated. The mean FA and MD of each WMT on both sides were analyzed using one-way analysis of variance and pairwise comparison with adjusted P values. Results Overall MS patients had significantly lower mean FA (loss of coherence) and significantly higher mean MD (increased free diffusion) than HCs in both WMTs, indicating more damage. Furthermore, VD showed a trend of loss of integrity in both WMTs when compared with voiders with lower FA and higher MD. Conclusions There is damage reflected by lower FA and higher MD values in the proposed WMTs involved in bladder function in MS women. Voiding dysfunction in this patient population can be attributed to these damages considering women with VD demonstrated a trend of deterioration in these WMTs compared with women without VD. Future studies with larger sample sizes should be done to further confirm this correlation.
A Potent Host Defense Peptide Triggers DNA Damage and is Active against Multi-Drug Resistant Gram-Negative Pathogens.

Gram negative bacteria are some of the biggest threats to public health, with a large prevalence of antibiotic resistance. The difficulty in treating bacterial infections, stemming from their double membrane structure combined with efflux pumps in the outer membrane, has resulted in a much greater need for antimicrobials with activity against these pathogens. Tunicate host defense peptide (HDP), Clavanin A, is capable not only of inhibiting gram negative growth, but also potentiated activity in the presence of Zn(II). Here, we provide evidence that the improvements of Clavanin A activity in the presence of Zn(II) are due to its novel mechanism of action. We employed E. coli TD172 (ΔrecA::kan) and the TUNEL assay to show in cellulae that DNA damage occurs upon treatment with Clavanin A. In vitro assays demonstrated that Zn(II) ions are required for the nuclease activity of the peptide. The QM/MM calculations were used to investigate the mechanism of DNA damage. In the rate-determining step of the proposed mechanism, due to its Lewis acidity the Zn(II) ion activates the scissile P-O bond of DNA and creates a hydroxyl nucleophile from a water molecule. A subsequent attack by this group to the electrophilic phosphorus cleaves the scissile phosphoester bond. Additionally, we utilized bacterial cytological profiling (BCP), circular dichroism (CD) spectroscopy in the presence of lipid vesicles, and surface plasmon resonance combined with electrical impedance spectroscopy in order to address the apparent discrepancies between our results and the previous studies regarding the mechanism of action of Clavanin A. Finally, our approach may lead to the identification of additional Clavanin A like HDPs and promote the development of antimicrobial peptides based therapeutics.
DNA sequence symmetries from randomness: the origin of the Chargaff’s second parity rule

Abstract Most living organisms rely on double-stranded DNA (dsDNA) to store their genetic information and perpetuate themselves. This biological information has been considered as the main target of evolution. However, here we show that symmetries and patterns in the dsDNA sequence can emerge from the physical peculiarities of the dsDNA molecule itself and the maximum entropy principle alone, rather than from biological or environmental evolutionary pressure. The randomness justifies the human codon biases and context-dependent mutation patterns in human populations. Thus, the DNA ‘exceptional symmetries,’ emerged from the randomness, have to be taken into account when looking for the DNA encoded information. Our results suggest that the double helix energy constraints and, more generally, the physical properties of the dsDNA are the hard drivers of the overall DNA sequence architecture, whereas the selective biological processes act as soft drivers, which only under extraordinary circumstances overtake the overall entropy content of the genome.
Characterization of cold stress responses in different rapeseed ecotypes based on metabolomics and transcriptomics analyses

The winter oilseed ecotype is more tolerant to low temperature than the spring ecotype. Transcriptome and metabolome analyses of leaf samples of five spring Brassica napus L. (B. napus) ecotype lines and five winter B. napus ecotype lines treated at 4 °C and 28 °C were performed. A total of 25,460 differentially expressed genes (DEGs) of the spring oilseed ecotype and 28,512 DEGs of the winter oilseed ecotype were identified after cold stress; there were 41 differentially expressed metabolites (DEMs) in the spring and 47 in the winter oilseed ecotypes. Moreover, more than 46.2% DEGs were commonly detected in both ecotypes, and the extent of the changes were much more pronounced in the winter than spring ecotype. By contrast, only six DEMs were detected in both the spring and winter oilseed ecotypes. Eighty-one DEMs mainly belonged to primary metabolites, including amino acids, organic acids and sugars. The large number of specific genes and metabolites emphasizes the complex regulatory mechanisms involved in the cold stress response in oilseed rape. Furthermore, these data suggest that lipid, ABA, secondary metabolism, signal transduction and transcription factors may play distinct roles in the spring and winter ecotypes in response to cold stress. Differences in gene expression and metabolite levels after cold stress treatment may have contributed to the cold tolerance of the different oilseed ecotypes.
Basigin Associates with Integrin in Order to Regulate Perineurial Glia and Drosophila Nervous System Morphology

The Drosophila nervous system is ensheathed by a layer of outer glial cells, the perineurial glia, and a specialized extracellular matrix, the neural lamella. The function of perineurial glial cells and how they interact with the extracellular matrix are just beginning to be elucidated. Integrin-based focal adhesion complexes link the glial membrane to the extracellular matrix, but little is known about integrin's regulators in the glia. The transmembrane Ig domain protein Basigin/CD147/EMMPRIN is highly expressed in the perineurial glia surrounding the Drosophila larval nervous system. Here we show that Basigin associates with integrin at the focal adhesions to uphold the structure of the glia-extracellular matrix sheath. Knockdown of Basigin in perineurial glia using RNAi results in significant shortening of the ventral nerve cord, compression of the glia and extracellular matrix in the peripheral nerves, and reduction in larval locomotion. We determined that Basigin is expressed in close proximity to integrin at the glial membrane, and that expression of the extracellular integrin-binding domain of Basigin is sufficient to rescue peripheral glial compression. We also found that a reduction in expression of integrin at the membrane rescues the ventral nerve cord shortening, peripheral glial compression, and locomotor phenotypes, and that reduction in the integrin-binding protein Talin can partially rescue glial compression. These results identify Basigin as a potential negative regulator of integrin in the glia, supporting proper glial and extracellular matrix ensheathment of the nervous system. SIGNIFICANCE STATEMENT The glial cells and extracellular matrix play important roles in supporting and protecting the nervous system, but the interactions between these components have not been well characterized. Our study identified expression of a conserved Ig superfamily protein, Basigin, at the glial membrane of Drosophila where it associates with the integrin-based focal adhesion complexes to ensure proper ensheathment of the CNS and PNS. Loss of Basigin in the glia results in an overall compression of the nervous system due to integrin dysregulation, which causes locomotor defects in the animals. This underlies the importance of glia-matrix communication for structural and functional support of the nervous system.
Factors associated with overweight and abdominal obesity in Brazilian school-aged children: a comprehensive approach

ABSTRACT Objective We investigated the association between demographic, socio-economic, perinatal, parental and lifestyle-related factors with general and abdominal obesity among prepubertal children aged 6 to 8 years in a Southeastern city of Brazil. Subjects and methods A total of 486 children were randomly selected from public schools in the city of Patos de Minas, and examined to determine body mass index (BMI) and waist circumference (WC). Demographic, socio-economic, perinatal, parental and lifestyle-related data were obtained and assessed as independent risk factors for overweight/obesity and abdominal obesity, using multiple regression analysis. Results Obesity/overweight (BMI percentile ≥ 85), seen in 19% of the children, was positively associated with low maternal education, being born small for gestational age, maternal BMI and screen time, whereas abdominal obesity (WC percentile > 90), seen in 9.9% of the children, was positively associated with maternal age and maternal BMI. When BMI and WC percentile were analyzed as continuous variables, birth by cesarean section, parental BMI, and lower sleep time were positively associated with BMI percentile, and birth by cesarean section, being born small for gestational age, and parental BMI were positively associated with WC percentile. Conclusion Our findings suggest that the frequency of overweight and obesity in a city in the Southeastern region of Brazil is similar to the global frequency reported by the World Health Organization. We also found that many modifiable risk factors were associated with general and abdominal obesity, and these may possibly substantiate future strategies to prevent childhood obesity and its consequences in adult life.
Slow and steady wins the race: The behaviour and welfare of commercial faster growing broiler breeds compared to a commercial slower growing breed

Broilers have been bred for fast growth which has led to welfare problems such as high mortality, lameness and skin lesions. Slower growing breeds are thought to have better welfare but are not as efficient in production. This study investigated welfare, behaviour, production and meat quality of faster growing broilers from three main commercial broiler companies (breeds FA, FB and FC) with a commercially available slower growing breed (Hubbard JA757, S). Four hundred birds of each breed (total 1600 birds) were reared in pens of 50 birds, 8 per breed (total 32 pens). Home pen behaviour was recorded once a week in hourly scan samples to get behavioural time budgets. Welfare Assessments (WA) were done when the average bird weight per breed was 2.2 and 2.5kg. Birds and feed supplied were regularly weighed by pen and Feed Conversion Ratio (FCR) and Average Daily Gain (ADG) were calculated at 2.2kg. Birds were then slaughtered and meat quality measures were taken. S and FC had lower mortality and culls due to lameness (P<0.05 for both). Breeds FA, FB and FC grew faster, ate less feed and had better FCR and ADG (P<0.05 for all). S had scores indicating higher welfare for the majority of WA measures and spent more time active and less time sitting, feeding and drinking than the other breeds (P<0.05 for all). Faster growing breeds had more breast meat and S had more leg meat; although S had better meat quality scores (P<0.05). Overall, S birds have improved welfare in terms of activity and welfare measure scores compared to the other breeds but take longer to reach slaughter weight and are not as efficient in production measures. However if lower mortality and improved meat quality are taken into account, as well as the premium price paid for these birds, slower growing broilers may be a viable commercial option.
Pulmonary artery hemodynamics are associated with duration of nocturnal desaturation but not apnea-hypopnea index.

STUDY OBJECTIVES Sleep-disordered breathing (SDB) and nocturnal hypoxia are prevalent among patients with precapillary pulmonary hypertension (PAH). The rationale for these associations remains unclear and these relationships have not been well studied in other forms of pulmonary hypertension (PH). We hypothesized that severity of SDB and nocturnal hypoxia are associated with worsening pulmonary hemodynamics, regardless of hemodynamic profile. METHODS 493 Patients were divided into 4 groups: 1) no PH, 2) postcapillary pulmonary hypertension (PVH), 3) PAH, and 4) mixed PAH/PVH. The relationship between RHC measurements and apnea-hypopnea index (AHI) or the percentage of sleep time spent with oxygen saturation <90% (T90) was calculated using multiple linear regression. ANOVA was used for between-group comparisons. Statistical models were adjusted for known confounders. RESULTS AHI did not differ between hemodynamic subgroups (p=0.27) and was not associated with right atrial pressure (RAP) (0.11 ± 0.19, p=0.55), Cardiac index (CI) (0.25 ± 1.64, p=0.88)), mean pulmonary artery pressure (mPAP) (-0.004 ± 0.09, p=0.97) or pulmonary artery occlusion pressure (PAOP) (0.16 ± 0.14, p=0.26). While patients with PH had a higher T90 than those without (mean 24.2% vs. 11.7%, p<0.001), there was no difference in T90 between individual PH subgroups (p=0.70). T90 was associated with mPAP (0.55 ± 0.10, p<0.0001), PVR (1.61 ± 0.49, p=0.001) and RAP (0.50 ± 0.20, p=0.01), but not CI (-0.76 ± 1.73, p=0.66) or PAOP (0.23 ± 0.15, p=0.13). CONCLUSIONS Increased PH severity was associated with longer duration of nocturnal hypoxia regardless of hemodynamic subgroup.
Factors Associated With the Choice of Oral Anticoagulant Class in the Older Patients: An Observational Study

Aim: Oral anticoagulants are the first-line drugs for treating thrombotic disorders related to nonvalvular atrial fibrillation and for treating deep vein thrombosis, diseases that increase in prevalence with age. Older patients have a greater risk of thrombotic and hemorrhagic events and are more prone to drug interactions. Given this backdrop, we wanted to determine the factors associated with the prescription of direct oral anticoagulants and vitamin K antagonists in older patients. Methods: We performed a cross-sectional observational study using a hospital prescription database. The study population consists of 405 older patients who were given oral anticoagulants. The 2 variables of interest were the prescription of 1 of the 2 classes of oral anticoagulants (direct oral anticoagulants vs vitamin K antagonists) and appropriateness of oral anticoagulant prescribing according to Summary of Product Characteristics (potentially inappropriate vs appropriate). Results: The factors associated with direct oral anticoagulant prescribing were the female gender (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.22-2.88) and initiation during hospital stay (OR: 2.56, 95% CI: [1.52-4.32]). Stage 4 and 5 chronic kidney diseases (OR: 0.39, 95% CI: [0.19-0.79] and OR: 0.07, 95% CI: [0.01-0.53]) were factors favoring vitamin K antagonist prescription. Being 90 years of age or more (OR: 2.05, 95% CI: [1.06-3.98]) was a factor for potentially inappropriate anticoagulant prescribing. The gastroenterology department (OR: 2.91, 95% CI: [1.05-8.11]) was associated with potentially inappropriate anticoagulant prescribing. Conclusions: Direct oral anticoagulants are the drugs of choice for anticoagulant treatment, including in older adults. The female gender and the initiation during hospital stay increased the chances of being prescribed a direct oral anticoagulant in older adults. Stage 4 and 5 chronic kidney disease increased the likelihood of having a vitamin K antagonist prescribed. Our study also revealed a persistence of potentially inappropriate oral anticoagulant prescriptions in older patients.