Miracle-dz/UniFAR-FTUs huggingface dataset:
Resistance exercise as a treatment for sarcopenia: prescription and delivery

Abstract Sarcopenia is a generalised skeletal muscle disorder characterised by reduced muscle strength and mass and associated with a range of negative health outcomes. Currently, resistance exercise (RE) is recommended as the first-line treatment for counteracting the deleterious consequences of sarcopenia in older adults. However, whilst there is considerable evidence demonstrating that RE is an effective intervention for improving muscle strength and function in healthy older adults, much less is known about its benefits in older people living with sarcopenia. Furthermore, evidence for its optimal prescription and delivery is very limited and any potential benefits of RE are unlikely to be realised in the absence of an appropriate exercise dose. We provide a summary of the underlying principles of effective RE prescription (specificity, overload and progression) and discuss the main variables (training frequency, exercise selection, exercise intensity, exercise volume and rest periods) that can be manipulated when designing RE programmes. Following this, we propose that an RE programme that consists of two exercise sessions per week and involves a combination of upper- and lower-body exercises performed with a relatively high degree of effort for 1–3 sets of 6–12 repetitions is appropriate as a treatment for sarcopenia. The principles of RE prescription outlined here and the proposed RE programme presented in this paper provide a useful resource for clinicians and exercise practitioners treating older adults with sarcopenia and will also be of value to researchers for standardising approaches to RE interventions in future sarcopenia studies.
Whole Genome Sequence Analyses-Based Assessment of Virulence Potential and Antimicrobial Susceptibilities and Resistance of Enterococcus faecium Strains Isolated from Commercial Swine and Cattle Probiotic Products.

Enterococcus faecium is one of the more commonly used bacterial species as a probiotic in animals. The organism, a common inhabitant of the gut of animals and humans, is a major nosocomial pathogen responsible for a variety infections in humans and sporadic infections in animals. In swine and cattle, E. faecium-based probiotic products are used for growth promotion and gut functional and health benefits. The objective of this study was to utilize whole genome sequence-based analysis to assess virulence potential, detect antimicrobial resistance genes and analyze phylogenetic relationships of E. faecium strains from commercial swine and cattle probiotics. Genomic DNA extracted from E. faecium strains, isolated from commercial probiotic products of swine (n=9) and cattle (n=13), were sequenced in an Illumina MiSeq platform and analyzed. Seven of the nine swine strains and seven of the 13 cattle strains were identified as E. lactis, and not as E. faecium. None of the 22 probiotic strains carried major virulence genes required to initiate infections, but many carried genes involved in adhesion to host cells, which may benefit the probiotic strains to colonize and persist in the gut. Strains also carried genes encoding resistance to a few medically important antibiotics, which included aminoglycosides (aac(6')-Ii, aph(3')-III, ant(6)-Ia), macrolide, lincosamide and streptogramin B (msrC,), tetracyclines (tet(L) and tet(M)), and phenicols (cat-(pc194)). The comparison of the genotypic to phentypic AMR data showed presence of both related and unrelated genes in the probiotic strains. Swine and cattle probiotic E. faecium strains belonged to diverse sequence types. Phylogenetic analysis of the probiotic strains, and strains of human (n=29), swine (n=4) and cattle (n=4) origin, downloaded from GenBank, indicated close clustering of strains belonging to the same species and source, but a few swine and cattle probiotic strains clustered closely with other cattle and human fecal strains. In conclusion, the absence of major virulence genes characteristic of the clinical E. faecium strains suggests that these probiotic strains are unlikely to initiate opportunistic infection. However, the carriage of AMR genes to medically important antibiotics and close clustering of the probiotic strains with other human and cattle fecal strains, suggests that probiotic strains may pose risk to serve as a source of transmitting AMR genes to other gut bacteria.
The DNA dioxygenase Tet1 regulates H3K27 modification and embryonic stem cell biology independent of its catalytic activity

Abstract Tet enzymes (Tet1/2/3) oxidize 5-methylcytosine to promote DNA demethylation and partner with chromatin modifiers to regulate gene expression. Tet1 is highly expressed in embryonic stem cells (ESCs), but its enzymatic and non-enzymatic roles in gene regulation are not dissected. We have generated Tet1 catalytically inactive (Tet1m/m) and knockout (Tet1−/−) ESCs and mice to study these functions. Loss of Tet1, but not loss of its catalytic activity, caused aberrant upregulation of bivalent (H3K4me3+; H3K27me3+) developmental genes, leading to defects in differentiation. Wild-type and catalytic-mutant Tet1 occupied similar genomic loci which overlapped with H3K27 tri-methyltransferase PRC2 and the deacetylase complex Sin3a at promoters of bivalent genes and with the helicase Chd4 at active genes. Loss of Tet1, but not loss of its catalytic activity, impaired enrichment of PRC2 and Sin3a at bivalent promoters leading to reduced H3K27 trimethylation and deacetylation, respectively, in absence of any changes in DNA methylation. Tet1−/−, but not Tet1m/m, embryos expressed higher levels of Gata6 and were developmentally delayed. Thus, the critical functions of Tet1 in ESCs and early development are mediated through its non-catalytic roles in regulating H3K27 modifications to silence developmental genes, and are more important than its catalytic functions in DNA demethylation.
A Case Report with a Mini-Review of the Literature on the Overeating and Weight Gain Due to Propranolol.

As a non-blocker propranolol, which is widely used in many branches, is one of the first/most preferred drugs among the treatments for extrapyramidal system side effects such as akathisia and tremor secondary to psychotropic use in psychiatry. Commonly known side -blockers include bradycardia, hypotension, hypoglycemia, weakness, and feeling of depression, while increased appetite or weight gain are not among the noticeable side effects.
Neurobehavioral Morbidity of Pediatric Mild Sleep-Disordered Breathing and Obstructive Sleep Apnea.

STUDY OBJECTIVES Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea. METHODS Children 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index<3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis. RESULTS The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing. CONCLUSIONS Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.
Phonological characteristics of novel gesture production in children with developmental language disorder: Longitudinal findings

Abstract Children with developmental language disorder (DLD; aka specific language impairment) are characterized based on deficits in language, especially morphosyntax, in the absence of other explanatory conditions. However, deficits in speech production, as well as fine and gross motor skill, have also been observed, implicating both the linguistic and motor systems. Situated at the intersection of these domains, and providing insight into both, is manual gesture. In the current work, we asked whether children with DLD showed phonological deficits in the production of novel gestures and whether gesture production at 4 years of age is related to language and motor outcomes two years later. Twenty-eight children (14 with DLD) participated in a two-year longitudinal novel gesture production study. At the first and final time points, language and fine motor skills were measured and gestures were analyzed for phonological feature accuracy, including handshape, path, and orientation. Results indicated that, while early deficits in phonological accuracy did not persist for children with DLD, all children struggled with orientation while handshape was the most accurate. Early handshape and orientation accuracy were also predictive of later language skill, but only for the children with DLD. Theoretical and clinical implications of these findings are discussed.
Transferring Performance between Distinct Configurable Systems : A Case Study

Many research studies predict the performance of configurable software using machine learning techniques, thus requiring large amounts of data. Transfer learning aims to reduce the amount of data needed to train these models and has been successfully applied on different executing environments (hardware) or software versions. In this paper we investigate for the first time the idea of applying transfer learning between distinct configurable systems. We design a study involving two video encoders (namely x264 and x265) coming from different code bases. Our results are encouraging since transfer learning outperforms traditional learning for two performance properties (out of three). We discuss the open challenges to overcome for a more general application.
Determinant Factors Affecting the Information System Success of Community-Based Application to Fight Covid-19 Pandemic

National governments around the world have made every effort to fight Covid-19. One of which is by building mobile applications that can be used to trace and monitor the citizens’ health during this pandemic. These applications are expensive. It requires a significant amount of time and effort to develop and maintain the information systems. Therefore, there is a continuous struggle to identify the key factors influencing the information systems’ adoption, utilization, and success. This study was performed to address the problem by identifying parameters that affect the information system success of ”10 Rumah Aman (10 Safe Houses)”, a community-based application in fighting the Covid-19 pandemic, using the DeLone and McLean (D&M) model. As a result, system quality positively affected the use and user satisfaction. Furthermore, service quality positively influenced use but not user satisfaction. Meanwhile, information quality had no significant effect either on use or satisfaction. Both use and user satisfaction had a significant effect on net benefits.
Reproducible Science and Deep Software Variability

Biology, medicine, physics, astrophysics, chemistry: all these scientific domains need to process large amount of data with more and more complex software systems. For achieving reproducible science, there are several challenges ahead involving multi-disciplinary collaboration and socio-technical innovation with software at the center of the problem. Despite the availability of data and code, several studies report that the same data analyzed with different software can lead to different results. I am seeing this problem as a manifestation of deep software variability: many factors (operating system, third-party libraries, versions, workloads, compile-time options and flags, etc.) themselves subject to variability can alter the results, up to the point it can dramatically change the conclusions of some scientific studies. In this keynote, I argue that deep software variability is a threat and also an opportunity for reproducible science. I first outline some works about (deep) software variability, reporting on preliminary evidence of complex interactions between variability layers. I then link the ongoing works on variability modelling and deep software variability in the quest for reproducible science.
Activity modulation of anti‐sigma factor via cysteine alkylation in Actinobacteria

σR (SigR) is an alternative sigma factor that enables gene expression in Streptomyces coelicolor to cope with thiol oxidation and antibiotic stresses. Its activity is repressed by a zinc‐containing anti‐sigma (ZAS) factor RsrA that senses thiol oxidants and electrophiles. Inactivation of RsrA by disulfide formation has been well studied. Here we investigated another pathway of RsrA inactivation by electrophiles. Mass spectrometry revealed alkylation of RsrA in vivo by N‐ethylmaleimide (NEM) at C61 and C62 located in the C‐terminal loop. Substitution mutation (C61S/C62S) in RsrA decreased the induction of σR target genes by electrophiles and made cells more sensitive to electrophiles. In contrast to stable protein of oxidized RsrA, alkylated RsrA is subjected to degradation partly mediated by ClpP proteases. RsrA2, a redox‐sensitive homolog of RsrA in S. coelicolor lacking cysteine in the terminal loop, did not respond to electrophiles. However, redox‐sensitive RsrA homologs in other Actinobacteria also harboring terminal loop cysteines all responded to electrophiles. These results indicate that the activity of RsrA can be modulated via cysteine alkylation, apart from disulfide formation of zinc‐coordinating cysteines. This pathway expands the spectrum of signals that the σR‐RsrA system can sense and reveals another intricate regulatory layer for optimal survival of Actinobacteria.
Multi-ancestry fine-mapping improves precision to identify causal genes in transcriptome-wide association studies

Transcriptome-wide association studies (TWAS) are a powerful approach to identify genes whose expression associates with complex disease risk. However, non-causal genes can exhibit association signals due to confounding by linkage disequilibrium patterns (LD) and eQTL pleiotropy at genomic risk regions which necessitates fine-mapping of TWAS signals. Here, we present MA-FOCUS, a multi-ancestry framework for the improved identification of genes underlying traits of interest. We demonstrate that by leveraging differences in ancestry-specific patterns of LD and eQTL signals, MA-FOCUS consistently outperforms single-ancestry fine-mapping approaches with equivalent total sample size across multiple metrics. We perform 15 blood trait TWAS using genome-wide summary statistics (average NEA=511k, NAA=13k) and lymphoblastoid cell line eQTL data from cohorts of primarily European and African continental ancestries. We recapitulate evidence demonstrating shared genetic architectures for eQTL and blood traits between the two ancestry groups and observe that gene-level effects correlate 20% more strongly across ancestries compared with SNP-level effects. We perform fine-mapping using MA-FOCUS and find evidence that genes at TWAS risk regions are more likely to be shared across ancestries rather than ancestry-specific. Using multiple lines of evidence to validate our findings, we find gene sets produced by MA-FOCUS are more enriched in hematopoietic categories compared to alternative approaches (P = 1.73 × 10−16). Our work demonstrates that including, and appropriately accounting for, genetic diversity can drive deeper insights into the genetic architecture of complex traits.
Mitochondrial ATP Synthase is a Target of Oxidative Stress in Neurodegenerative Diseases

The mitochondrial ATP synthase is responsible for the production of cellular ATP, and it does so by harnessing the membrane potential of the mitochondria that is produced by the sequential oxidation of select cellular metabolites. Since the structural features of ATP synthase were first resolved nearly three decades ago, significant progress has been made in understanding its role in health and disease. Mitochondrial dysfunction is common to neurodegeneration, with elevated oxidative stress a hallmark of this dysfunction. The patterns of this oxidative stress, including molecular targets and the form of oxidative modification, can vary widely. In this mini review we discuss the oxidative modifications of ATP synthase that have been observed in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Oxidative modifications of ATP synthase in Alzheimer’s disease are well-documented, and there is a growing body of knowledge on the subject in Parkinson’s disease. The consideration of ATP synthase as a pharmacological target in a variety of diseases underlines the importance of understanding these modifications, both as a potential target, and also as inhibitors of any pharmacological intervention.
PHLDA1 Suppresses TLR4-Triggered Proinflammatory Cytokine Production by Interaction With Tollip

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) has been reported to be expressed in many mammalian tissues and cells. However, the functions and exact mechanisms of PHLDA1 remain unclear. In this study, we found that PHLDA1 expression was significantly altered in macrophages after exposure to lipopolysaccharide (LPS) in vitro, suggesting that PHLDA1 may be involved in the regulation of TLR4 signaling pathway activated by LPS. PHLDA1 attenuated the production of LPS-stimulated proinflammatory cytokines (TNF-α, IL-6, and IL-1β). Further research showed that the phosphorylation levels of some important signal molecules in TLR4/MyD88-mediated MAPK and NF-κB signaling pathways were reduced by PHLDA1, which in turn impaired the transcription factors NF-κB and AP1 nuclear translocation and their responsive element activities. Furthermore, we found that PHLDA1 repressed LPS-induced proinflammatory cytokine production via binding to Tollip which restrained TLR4 signaling pathway. A mouse model of endotoxemia was established to confirm the above similar results. In brief, our findings demonstrate that PHLDA1 is a negative regulator of LPS-induced proinflammatory cytokine production by Tollip, suggesting that PHLDA1 plays an anti-inflammatory role through inhibiting the TLR4/MyD88 signaling pathway with the help of Tollip. PHLDA1 may be a novel therapeutic target in treating endotoxemia.
Biological Characterization of Yellow Fever Viruses Isolated From Non-human Primates in Brazil With Distinct Genomic Landscapes

Since the beginning of the XXI Century, the yellow fever virus (YFV) has been cyclically spreading from the Amazon basin to Brazil’s South and Southeast regions, culminating in an unprecedented outbreak that started in 2016. In this work, we studied four YFV isolated from non-human primates obtained during outbreaks in the states of Rio Grande do Sul in 2008 (PR4408), Goiás (GO05), and Espírito Santo (ES-504) in 2017, and Rio de Janeiro (RJ 155) in 2019. These isolates have genomic differences mainly distributed in non-structural proteins. We compared the isolates’ rates of infection in mammal and mosquito cells and neurovirulence in adult mice. RJ 155 and PR4408 YFV isolates exhibited higher infectivity in mammalian cells and neurovirulence in mice. In mosquito Aag2 cells, GO05 and PR4408 displayed the lowest proliferation rates. These results suggest that RJ 155 and PR4408 YFV isolates carry some genomic markers that increase infectivity in mammal hosts. From this characterization, it is possible to contribute to discovering new molecular markers for the virulence of YFV.
The Phylosymbiosis Pattern Between the Fig Wasps of the Same Genus and Their Associated Microbiota

Microbial communities can be critical for many metazoans, which can lead to the observation of phylosymbiosis with phylogenetically related species sharing similar microbial communities. Most of the previous studies on phylosymbiosis were conducted across the host families or genera. However, it is unclear whether the phylosymbiosis signal is still prevalent at lower taxonomic levels. In this study, 54 individuals from six species of the fig wasp genus Ceratosolen (Hymenoptera: Agaonidae) collected from nine natural populations and their associated microbiota were investigated. The fig wasp species were morphologically identified and further determined by mitochondrial CO1 gene fragments and nuclear ITS2 sequences, and the V4 region of 16S rRNA gene was sequenced to analyze the bacterial communities. The results suggest a significant positive correlation between host genetic characteristics and microbial diversity characteristics, indicating the phylosymbiosis signal between the phylogeny of insect hosts and the associated microbiota in the lower classification level within a genus. Moreover, we found that the endosymbiotic Wolbachia carried by fig wasps led to a decrease in bacterial diversity of host-associated microbial communities. This study contributes to our understanding of the role of host phylogeny, as well as the role of endosymbionts in shaping the host-associated microbial community.