Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Organization and Proposed Megataxonomy of the Virus World

Viruses and mobile genetic elements are molecular parasites or symbionts that coevolve with nearly all forms of cellular life. The route of virus replication and protein expression is determined by the viral genome type. Comparison of these routes led to the classification of viruses into seven “Baltimore classes” (BCs) that define the major features of virus reproduction. However, recent phylogenomic studies identified multiple evolutionary connections among viruses within each of the BCs as well as between different classes. SUMMARY Viruses and mobile genetic elements are molecular parasites or symbionts that coevolve with nearly all forms of cellular life. The route of virus replication and protein expression is determined by the viral genome type. Comparison of these routes led to the classification of viruses into seven “Baltimore classes” (BCs) that define the major features of virus reproduction. However, recent phylogenomic studies identified multiple evolutionary connections among viruses within each of the BCs as well as between different classes. Due to the modular organization of virus genomes, these relationships defy simple representation as lines of descent but rather form complex networks. Phylogenetic analyses of virus hallmark genes combined with analyses of gene-sharing networks show that replication modules of five BCs (three classes of RNA viruses and two classes of reverse-transcribing viruses) evolved from a common ancestor that encoded an RNA-directed RNA polymerase or a reverse transcriptase. Bona fide viruses evolved from this ancestor on multiple, independent occasions via the recruitment of distinct cellular proteins as capsid subunits and other structural components of virions. The single-stranded DNA (ssDNA) viruses are a polyphyletic class, with different groups evolving by recombination between rolling-circle-replicating plasmids, which contributed the replication protein, and positive-sense RNA viruses, which contributed the capsid protein. The double-stranded DNA (dsDNA) viruses are distributed among several large monophyletic groups and arose via the combination of distinct structural modules with equally diverse replication modules. Phylogenomic analyses reveal the finer structure of evolutionary connections among RNA viruses and reverse-transcribing viruses, ssDNA viruses, and large subsets of dsDNA viruses. Taken together, these analyses allow us to outline the global organization of the virus world. Here, we describe the key aspects of this organization and propose a comprehensive hierarchical taxonomy of viruses.
Accounting for population structure reveals ambiguity in the Zaire Ebolavirus reservoir dynamics

Ebolaviruses pose a substantial threat to wildlife populations and to public health in Africa. Evolutionary analyses of virus genome sequences can contribute significantly to elucidate the origin of new outbreaks, which can help guide surveillance efforts. The reconstructed between-outbreak evolutionary history of Zaire ebolavirus so far has been highly consistent. By removing the confounding impact of population growth bursts during local outbreaks on the free mixing assumption that underlies coalescent-based demographic reconstructions, we find—contrary to what previous results indicated—that the circulation dynamics of Ebola virus in its animal reservoir are highly uncertain. Our findings also accentuate the need for a more fine-grained picture of the Ebola virus diversity in its reservoir to reliably infer the reservoir origin of outbreak lineages. In addition, the recent appearance of slower-evolving variants is in line with latency as a survival mechanism and with bats as the natural reservoir host.
Colorectal cancer statistics, 2020

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population‐based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening‐aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non‐Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steepest among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline‐recommended screening and high‐quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle‐aged adults.
The effect of bed rest on balance control in healthy adults: A systematic scoping review

The objective of this study was to determine the effect of bed rest on balance control and the mechanisms responsible for these changes. Searches were conducted in six databases. Studies had to be conducted on healthy adults who were subjected to bed rest (≥5 days), with balance control measures obtained before and after bed rest in order to be included. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. After screening 9,785 articles, 18 were included for qualitative synthesis. Fifteen studies found decrements in at least one balance control measure following bed rest, either compared to baseline or controls, with eight studies observing impairments in >50% of their balance control measures. Of the 14 studies that included an intervention, four (mechanical stimuli, lower-body negative pressure, and training targeting strength, balance and/or aerobic capacity) successfully offset the majority of balance control deficits and targeted the musculoskeletal and cardiovascular systems. The findings of this review support bed rest negatively affecting balance control in healthy individuals. In clinical populations, these deficits may be further accentuated due to various comorbidities that impact balance control systems. PROSPERO Registration: CRD42018098887.
Crystal structure of an Escherichia coli Hfq Core (residues 2–69)–DNA complex reveals multifunctional nucleic acid binding sites

Abstract Hfq regulates bacterial gene expression post-transcriptionally by binding small RNAs and their target mRNAs, facilitating sRNA-mRNA annealing, typically resulting in translation inhibition and RNA turnover. Hfq is also found in the nucleoid and binds double-stranded (ds) DNA with a slight preference for A-tracts. Here, we present the crystal structure of the Escherichia coli Hfq Core bound to a 30 bp DNA, containing three 6 bp A-tracts. Although previously postulated to bind to the ‘distal’ face, three statistically disordered double stranded DNA molecules bind across the proximal face of the Hfq hexamer as parallel, straight rods with B-DNA like conformational properties. One DNA duplex spans the diameter of the hexamer and passes over the uridine-binding proximal-face pore, whereas the remaining DNA duplexes interact with the rims and serve as bridges between adjacent hexamers. Binding is sequence-independent with residues N13, R16, R17 and Q41 interacting exclusively with the DNA backbone. Atomic force microscopy data support the sequence-independent nature of the Hfq-DNA interaction and a role for Hfq in DNA compaction and nucleoid architecture. Our structure and nucleic acid-binding studies also provide insight into the mechanism of sequence-independent binding of Hfq to dsRNA stems, a function that is critical for proper riboregulation.
Progress in extracellular vesicle biology and their application in cancer medicine

Abstract Under the broader category of extracellular vesicles (EVs), exosomes are now well recognized for their contribution and potential for biomedical research. During the last ten years, numerous technologies for purification and characterization of EVs have been developed. This enhanced knowledge has resulted in the development of novel applications of EVs. This review is an attempt to capture the exponential growth observed in EV science in the last decade and discuss the future potential to improve our understanding of EVs, develop technologies to overcome current limitations, and advance their utility for human benefit, especially in cancer medicine. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Evidence of the Importance of Dietary Habits Regarding Depressive Symptoms and Depression

Background: Mental illness is one of the fastest rising threats to public health, of which depression and anxiety disorders are increasing the most. Research shows that diet is associated with depressive symptoms or depression (depression). Aim: This study aimed to investigate the diets impact on depression, by reviewing the scientific evidence for prevention and treatment interventions. Method: A systematic review was conducted, and narrative synthesis analysis was performed. Result: Twenty scientific articles were included in this review. The result showed that high adherence to dietary recommendations; avoiding processed foods; intake of anti-inflammatory diet; magnesium and folic acid; various fatty acids; and fish consumption had a depression. Public health professionals that work to support and motivate healthy eating habits may help prevent and treat depression based on the evidence presented in the results of this study. Further research is needed to strengthen a causal relationship and define evidence-based strategies to implement in prevention and treatment by public healthcare.
Prevalence and Risk Factors for Oral HPV in Healthy Population, in Central Europe

Abstract. Background/Aim: The incidence of oropharyngeal tumours induced by human papillomaviruses (HPV) is ever increasing. Information about oral HPV prevalence and its risk factors are very important for future screening and early diagnosis of the disease. The present study aimed to assess oral HPV prevalence in healthy population and risk factors for HPV infection, since this data is scarce or even missing in Central Europe. Patients and Methods: HPV prevalence in oral rinse and HPV-specific antibodies in peripheral blood were investigated in two groups of healthy participants. Group I consisted of 294 students who reached sexual maturity after the HPV vaccine had been licensed with mean age 23.2 years, and Group II of 215 unvaccinated participants with the mean age 55.7 years. Additionally, the risk factors were evaluated. Results: In Group I, 2% of participants were positive for oral HPV DNA. A statistically significantly higher rate (8.8%) was found in Group II. The seropositivity rates for anamnestic HPV antibodies were comparable in both groups. None of the analysed risk factors was significantly associated with oral HPV positivity. Conclusion: The lower prevalence of oral HPV DNA in younger participants suggests the positive influence of vaccination against oral HPV.
Rôle de la réhabilitation respiratoire dans la prise en charge multidisciplinaire d'un patient avec sténose trachéale post-intubation et BPCO Role of respiratory rehabilitation in multidisciplinary management for patient with post-intubation tracheal stenosis and COPD

Le traitement de premiere intention a ete la dilatation par bronchoscopie interventionnelle avec des resultats favorables immediatement, mais instables au fil du temps, necessitant la resection chirurgicale. L’evolution postoperatoire a ete favorable, soutenue par un traitement bronchodilatateur et l’inclusion du patient dans un programme de rehabilitation respiratoire pour lutter contre les phenomenes de deconditionnement qui peuvent survenir apres des exacerbations severes. Le programme de rehabilitation respiratoire, ambulatoire, avec une duree de 2 mois, a ameliore significativement la dyspnee, la tolerance a l’effort et la qualite de vie.
Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC): overall survival (OS) data from the phase IIb trial LUX-Lung 7 (LL7)

Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naive patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after ∼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases. Results: Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66‒1.12, P = 0.2580]. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58‒1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. Conclusion In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.
Bedaquiline, pretomanid and linezolid for treatment of extensively drug resistant, intolerant or non-responsive multidrug resistant pulmonary tuberculosis

Background Patients with extensively drug resistant tuberculosis (TB) have limited treatment options with historically poor outcomes. We investigated treatment with 3 oral drugs, bedaquiline (B), pretomanid (Pa) and linezolid (L), (B-Pa-L), with TB bactericidal activity and little pre-existing resistance. Methods Nix-TB is an open label single arm study ongoing at three South African sites evaluating the safety and efficacy of B-Pa-L for 26 weeks for extensively drug-resistant TB or treatment intolerant /non-responsive multidrug-resistant TB. We present the efficacy and safety outcomes for all 109 patients enrolled in the trial followed to the predefined primary endpoint, six months after the end of treatment. Results In the intent to treat analysis, 98 patients (90%), (95% CI 82.7-94.9%) had a favourable outcome at 6 months after the end of treatment. Six patients died during the early stages of treatment, one withdrew during treatment, one died during follow-up without evidence of relapse, one relapsed, one relapsed and subsequently died during follow up and one was lost to follow-up. The expected linezolid toxicities of peripheral neuropathy (experienced by 81% of patients) and myelosuppression (48%), while common, were manageable, often requiring reductions of dose and/or interruptions in linezolid. Conclusions These results suggest that B-Pa-L is a viable option for tuberculosis patients with highly resistant forms of TB, provided adequate safety management is available. Trial registration: ClinicalTrials.gov Identifier: NCT02333799 Sponsor: Global Alliance for TB Drug Development (TB Alliance)
Changes in ultrasound uterine morphology and endometrial thickness during ovarian aging and possible associated factors: findings from a prospective study.

OBJECTIVE The aim of the study was to provide reference values for sonographic measurements of uterine morphology, quantify changes in uterine morphology across the menopausal transition, and identify possible factors associated with sonographic findings in uterine morphology. METHODS This is a longitudinal cohort study conducted in middle-aged Chinese women. Using transvaginal ultrasound, we measured morphologic parameters of the uterus (volume and endometrial thickness) under standardized conditions every year for over a decade. RESULTS Uterine volume begins to decrease before the final menstrual period and declines rapidly thereafter. Compared with a baseline measurement taken in the year of the final menstrual period, uterine volume decreased by 20% and 35% at the first year and second year of postmenopause, respectively. The rate of decrease was slower in the third year. Compared with endometrial thickness in the year of the final menstrual period, the figures for 2 and 3 years before the final menstrual period were 5% and 10% higher, while they decreased by 9% and 18% at the first and second year after the final menstrual period. Similarly, the endometrial thickness became relatively stable 3 years after the final menstrual cycle. These observations were fairly consistent across all women without uterine fibroids. Endometrial thickness was significantly positively associated with body mass index (P = 0.049) after adjusting for time and menopausal stage. CONCLUSIONS The figures for uterine volume and endometrial thickness decrease around menopause using ultrasound measurments with large reductions in the first and second year after the final menstrual period. A higher body mass index is associated with increased endometrial thickness.
Small‐molecule inhibition of aging‐associated chromosomal instability delays cellular senescence

Chromosomal instability (CIN) refers to the rate at which cells are unable to properly segregate whole chromosomes, leading to aneuploidy. Besides its prevalence in cancer cells and postulated implications in promoting tumorigenesis, studies in aneuploidy‐prone mouse models uncovered an unanticipated link between CIN and aging. Using young to old‐aged human dermal fibroblasts, we observed a dysfunction of the mitotic machinery arising with age that mildly perturbs chromosome segregation fidelity and contributes to the generation of fully senescent cells. Here, we investigated mitotic mechanisms that contribute to age‐associated CIN. We found that elderly cells have an increased number of stable kinetochore–microtubule (k‐MT) attachments and decreased efficiency in the correction of improper k‐MT interactions. Chromosome mis‐segregation rates in old‐aged cells decreased upon both genetic and small‐molecule enhancement of MT‐depolymerizing kinesin‐13 activity. Notably, restored chromosome segregation accuracy inhibited the phenotypes of cellular senescence. Therefore, we provide mechanistic insight into age‐associated CIN and disclose a strategy for the use of a small‐molecule to inhibit age‐associated CIN and to delay the cellular hallmarks of aging.
The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain

Cellular (also termed ‘natural’) prion protein has been extensively studied for many years for its pathogenic role in prionopathies after misfolding. However, neuroprotective properties of the protein have been demonstrated under various scenarios. In this line, the involvement of the cellular prion protein in neurodegenerative diseases other than prionopathies continues to be widely debated by the scientific community. In fact, studies on knock-out mice show a vast range of physiological functions for the protein that can be supported by its ability as a cell surface scaffold protein. In this review, we first summarize the most commonly described roles of cellular prion protein in neuroprotection, including antioxidant and antiapoptotic activities and modulation of glutamate receptors. Second, in light of recently described interaction between cellular prion protein and some amyloid misfolded proteins, we will also discuss the molecular mechanisms potentially involved in protection against neurodegeneration in pathologies such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.
Effect of increased expression of both ras-related C3 botulinum toxin substrate 1 and p21-activated kinase 1 in patients with N0M0 upper urinary tract urothelial carcinoma and cancer-free surgical margins.

BACKGROUND As a member of the Rho small guanosine triphosphatase family, ras-related C3 botulinum toxin substrate 1 (RAC1) interacts with various specific effectors, and p21-activated kinase 1 (PAK1), which has a role in both carcinogenesis and cellular invasion, binds to RAC1, after which activated PAK1 regulates cellular functions. There have been few reports about the simultaneous analysis of RAC1 and its downstream effector PAK1 in upper urinary tract urothelial carcinoma (UTUC). We assessed the expressions of both RAC1 and PAK1 and evaluated their association with clinicopathological parameters. METHODS Immunohistochemical studies of RAC1 or PAK1 were performed with specimens from 104 patients with N0M0 UTUC and cancer-free surgical margins. Correlation of the positive expression of RAC1 or PAK1 or both with clinicopathological parameters was evaluated. RESULTS A hazard model showed that the presence of mixed histologic features and moderate or strong positive expression of both RAC1 and PAK1 were independent factors for shortened disease-specific survival time (Ps = 0.041 and 0.016, respectively), and another hazard model revealed that only moderate or strong positive expression of both RAC1 and PAK1 was an independent factor for shortened recurrence-free survival time in the multivariate analysis (P = 0.036). Neither moderate or strong positive expression of RAC1 alone nor moderate or strong positive expression of PAK1 alone was an independent factor for a worse rate of disease-specific or recurrence-free survival in multivariate analysis. CONCLUSIONS Patients with N0M0 UTUC, cancer-free surgical margins and moderate or strong positive expression of both RAC1 and PAK1 should be carefully monitored after surgery.