bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Biofeedback-Guided Pelvic Floor Muscle Training With and Without Extracorporeal Magnetic Innervation Therapy on Stress Incontinence
Authors: Gumussoy Sureyya , Kavlak Oya , Yeniel Ahmet Ozgur 
Published: March 2021

PURPOSE:
We evaluated the effects of biofeedback-guided pelvic floor muscle training (EMG-BF), with and without extracorporeal magnetic innervation (EMG-BF+ExMI) therapy on lower urinary tract symptoms based on frequency of stress urinary incontinence (SUI) and grams of urine loss, health-related quality of life, and sexual function in women with SUI.

DESIGN:
This was a randomized controlled trial.

SUBJECTS AND SETTING:
The sample comprised 51 adult women with SUI. Their mean age was 50.92 years (SD 8.88). Twenty-six were randomly allocated to EMG-BF alone and 25 were allocated to undergo EMG-BF+ExMI.

METHODS:
This study's main outcome was lower urinary tract symptoms measured via the 1-hour pad test (grams of urine loss) and a 3-day bladder diary (frequency of stress incontinence episodes). Additional outcome measures were health-related quality of life measured with the Incontinence Quality of Life (I-QOL) questionnaire, sexual function evaluated via the Female Sexual Function Index (FSFI), and pelvic floor muscle contraction force measured via a perineometer and Modified Oxford Scale (MOS). All participants underwent biofeedback-enhanced pelvic floor muscle training using EMG during 20-minute sessions twice weekly for a period of 8 weeks. In addition to the EMG-BF+ExMI group, ExMI was applied during 20-minute sessions twice weekly for a period of 8 weeks. Participants from both groups were asked to perform pelvic floor muscle exercises at home (60 pelvic floor muscle contractions daily, divided into 3 sessions of 20 contractions each). Outcome measures were made at baseline and repeated at the end of treatment.

RESULTS:
Fifteen (57.7%) in the EMG-BF group and 13 (52.0%) in the EMG-BF+ExMI group achieved dryness. Four participants (15.4%) in the EMG-BF group and 5 (20%) in the EMG-BF+ExMI group experienced improvement. Seven patients (26.9%) in the EMG-BF group and 7 (28%) in the EMG-BF+ExMI group did not benefit from the treatments. There was no statistically significant difference between the groups in terms of cure and improvement (P = .895).

CONCLUSIONS:
Findings indicate that use of magnetic innervation does not improve lower urinary tract symptoms, health-related quality of life, sexual function, and pelvic floor muscle strength when compared to pelvic floor muscle training alone.
COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19
Authors: Menestrina Luca , Cabrelle Chiara , Recanatini Maurizio 
Published: March 2021

AbstractThe COVID-19 pandemic poses a huge problem of public health that requires the implementation of all available means to contrast it, and drugs are one of them. In this context, we observed an unmet need of depicting the continuously evolving scenario of the ongoing drug clinical trials through an easy-to-use, freely accessible online tool. Starting from this consideration, we developed COVIDrugNet (http://compmedchem.unibo.it/covidrugnet), a web application that allows users to capture a holistic view and keep up to date on how the clinical drug research is responding to the SARS-CoV-2 infection.Here, we describe the web app and show through some examples how one can explore the whole landscape of medicines in clinical trial for the treatment of COVID-19 and try to probe the consistency of the current approaches with the available biological and pharmacological evidence. We conclude that careful analyses of the COVID-19 drug-target system based on COVIDrugNet can help to understand the biological implications of the proposed drug options, and eventually improve the search for more effective therapies.
COVID-19 is associated with multiple sclerosis exacerbations that are prevented by disease modifying therapies
Authors: Garjani Afagh , Middleton Rodden M , Hunter Rachael , Tuite-Dalton Katherine A , Coles Alasdair , Dobson Ruth , Duddy Martin , Hughes Stella , Pearson Owen R , Rog David , Tallantyre Emma C , Nair Roshan das , Nicholas Richard , Evangelou Nikos 
Published: March 2021

ABSTRACTBackgroundInfections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS.MethodsThe COVID-19 and MS study is an ongoing community-based, prospective cohort study conducted as part of the United Kingdom MS Register. People with MS and COVID-19 were invited by email to complete a questionnaire about their MS symptoms during the infection. An MS exacerbation was defined as developing new MS symptoms and/or worsening of pre-existing MS symptoms.ResultsFifty-seven percent (230/404) of participants had an MS exacerbation during their infection; 82 developed new MS symptoms, 207 experienced worsened pre-existing MS symptoms, and 59 reported both. Disease modifying therapies (DMTs) reduced the likelihood of developing new MS symptoms during the infection (OR 0.556, 95%CI 0.316-0.978). Participants with a higher pre-COVID-19 webEDSS (web-based Expanded Disability Status Scale) score (OR 1.251, 95%CI 1.060-1.478) and longer MS duration (OR 1.042, 95%CI 1.009-1.076) were more likely to experience worsening of their pre-existing MS symptoms during the infection.ConclusionCOVID-19 infection was associated with exacerbation of MS. DMTs reduced the chance of developing new MS symptoms during the infection.
Sodium valproate increases activity of the sirtuin pathway resulting in beneficial effects for spinocerebellar ataxia-3in vivo
Authors: Watchon Maxinne , Luu Luan , Robinson Katherine J. , Yuan Kristy C. , De Luca Alana , Suddull Hannah J. , Tym Madelaine C. , Guillemin Gilles J. , Cole Nicholas J. , Nicholson Garth A. , Chung Roger S. , Lee Albert , Laird Angela S. 
Published: March 2021

AbstractMachado-Joseph disease (MJD, also known as spinocerebellar ataxia-3) is a fatal neurodegenerative disease that impairs control and coordination of movement. Here we tested whether treatment with the histone deacetylase inhibitor sodium valproate (SV) prevented a movement phenotype that develops in larvae of a transgenic zebrafish model of the disease. We found that treatment with SV improved the swimming of the MJD zebrafish, increased levels of acetylated histones 3 and 4, but also increased expression of polyglutamine expanded human ataxin-3. Proteomic analysis of protein lysates generated from the treated and untreated MJD zebrafish also predicted that SV treatment had activated the sirtuin longevity signaling pathway and this was confirmed by findings of increased SIRT1 protein levels and sirtuin activity in SV treated MJD zebrafish and HEK293 cells expressing ataxin-3-84Q, respectively. Treatment with resveratrol (another compound known to activate the sirtuin pathway), also improved swimming in the MJD zebrafish. Co-treatment with SV alongside EX527, a SIRT1 activity inhibitor, prevented induction of autophagy by SV and the beneficial effects of SV on the movement in the MJD zebrafish, indicating that they were both dependent on sirtuin activity. These findings provide the first evidence of sodium valproate inducing activation of the sirtuin pathway. Further, they indicate that drugs that target the sirtuin pathway, including sodium valproate and resveratrol, warrant further investigation for the treatment of MJD and related neurodegenerative diseases.
A simple method to separate birds and insects in single-pol weather radar data
Authors: Nussbaumer Raphaël , Schmid Baptiste , Bauer Silke , Liechti Felix 
Published: March 2021

AbstractRecent and archived data from weather radar networks are extensively used for quantification of continent-wide bird migration pattern. While discriminating birds from weather signals is well established, insect contamination is still a problem. We present a simple method combining two doppler radar products within a single Gaussian-mixture model to estimate the proportions of birds and insects within a single measurement, as well as the density and speed of birds and insects. The method can be applied to any existing archives of vertical bird profiles, such as the ENRAM repository (enram.eu) with no need to recalculate the huge amount of original polar volume data, which often are not available.
Two different cell-cycle processes determine the timing of cell division inEscherichia coli
Authors: Colin Alexandra , Micali Gabriele , Faure Louis , Lagomarsino Marco Cosentino , van Teeffelen Sven 
Published: March 2021

AbstractCells must control the cell cycle to ensure that key processes are brought to completion. InEscherichia coli, it is controversial whether cell division is tied to chromosome replication or to a replication-independent inter-division process. A recent model suggests instead thatbothprocesses may limit cell division with comparable odds in single cells. Here, we tested this possibility experimentally by monitoring single-cell division and replication over multiple generations at slow growth. We then perturbed cell width, causing an increase of the time between replication termination and division. As a consequence, replication became decreasingly limiting for cell division, while correlations between birth and division and between subsequent replication-initiation events were maintained. Our experiments support the hypothesis that both chromosome replication and a replication-independent inter-division process can limit cell division: the two processes have balanced contributions in non-perturbed cells, while our width perturbations increase the odds of the replication-independent process being limiting.
Differential condensation of sister chromatids coordinates with Cdc6 to ensure distinct cell cycle progression inDrosophilamale germline stem cell lineage
Authors: Ranjan Rajesh , Snedeker Jonathan , Wooten Matthew , Chu Carolina , Bracero Sabrina , Mouton Taylar , Chen Xin 
Published: March 2021

AbstractStem cells undergo asymmetric division to produce both a self-renewing stem cell and a differentiating daughter cell. DuringDrosophilamale germline stem cell (GSC) asymmetric division, preexisting old histones H3 and H4 are enriched in the self-renewed stem daughter cell, whereas the newly synthesized H3 and H4 are enriched in the differentiating daughter cell. However, the biological consequences in the two daughter cells resulting from asymmetric histone inheritance remained to be elucidated. In this work, we track both old and new histones throughout GSC cell cycle using high spatial and temporal resolution microscopy. We find several unique features differentiating old versus new histone-enriched sister chromatids, including nucleosome density, chromosomal condensation, and H3 Ser10 phosphorylation. These distinct chromosomal features lead to their differential association with Cdc6, an essential component of the pre-replication complex, which subsequently contributes to asynchronous initiation of DNA replication in the two resulting daughter cells. Disruption of asymmetric histone inheritance abolishes both differential Cdc6 association and asynchronous S-phase entry, demonstrating that asymmetric histone acts upstream of these critical events during cell cycle progression. Furthermore, GSC defects are detected under these conditions, indicating a connection between histone inheritance, cell cycle progression and cell fate decision. Together, these studies reveal that cell cycle remodeling as a crucial biological ‘readout’ of asymmetric histone inheritance, which precedes and could lead to other well-known readouts such as differential gene expression. This work also enhances our understanding of asymmetric histone inheritance and epigenetic regulation in other stem cells or asymmetrically dividing cells in multicellular organisms.
Explainable machine learning models of major crop traits from satellite-monitored continent-wide field trial data
Authors: Newman Saul Justin , Furbank Robert T 
Published: March 2021

AbstractFour species of grass generate half of all human-consumed calories1. However, abundant biological data on species that produce our food remains largely inaccessible, imposing direct barriers to understanding crop yield and fitness traits. Here, we assemble and analyse a continent-wide database of field experiments spanning ten years and hundreds of thousands of machine-phenotyped populations of ten major crop species. Training an ensemble of machine learning models, using thousands of variables capturing weather, ground-sensor, soil, chemical and fertiliser dosage, management, and satellite data, produces robust cross-continent yield models exceeding R2= 0.8 prediction accuracy. In contrast to ‘black box’ analytics, detailed interrogation of these models reveals fundamental drivers of crop behaviour and complex interactions predicting yield and agronomic traits. These results demonstrate the capacity of machine learning models to build unified, interpretable, and explainable models of crop behaviour, and highlight the powerful role of data in the future of food.
Recurrent chromosome reshuffling and the evolution of neo-sex chromosomes in parrots
Authors: Huang Zhen , Furo Ivanete , Peona Valentina , Liu Jing , Gomes Anderson J. B. , Cen Wan , Huang Hao , Zhang Yanding , Chen Duo , Ting Xue , Chen Youling , Zhang Qiujin , Yue Zhicao , Suh Alexander , de Oliveira Edivaldo H. C. , Xu Luohao 
Published: March 2021

AbstractThe karyotype of most birds has remained considerably stable during more than 100 million years’ evolution, except for some groups, such as parrots. The evolutionary processes and underlying genetic mechanism of chromosomal rearrangements in parrots, however, are poorly understood. Here, using chromosome-level assemblies of three parrot genomes (monk parakeet, blue-fronted amazon, budgerigar), we uncovered frequent chromosome fusions and fissions among parrots, with most of them being lineage-specific. In particular, at least 12 chromosomes recurrently experienced inter-chromosomal fusions in different parrot lineages. Two conserved vertebrate genes,ALC1andPARP3,with known functions in the repair of double-strand breaks and maintenance of genome stability, were specifically lost in parrots. The loss ofALC1was associated with multiple deletions and an accumulation of CR1-psi, a novel subfamily of transposable elements (TEs) that recently amplified in parrots, while the loss ofPARP3was associated with an inversion. Additionally, the fusion of the ZW sex chromosomes and chromosome 11 has created a pair of neo-sex chromosomes in the ancestor of parrots, and the chromosome 25 has been further added to the sex chromosomes in monk parakeet. The newly formed neo-sex chromosomes were validated by our chromosomal painting, genomic and phylogenetic analyses. Transcriptome profiling for multiple tissues of males and females did not reveal signals of female-specific selection driving the formation of neo-sex chromosomes. Finally, we identified one W-specific satellite repeat that contributed to the unusual enlargement of the W chromosome in monk parakeet. Together, the combination of our genomic and cytogenetic analyses highlight the role of TEs and genetic drift in promoting chromosome rearrangements, gene loss and the evolution of neo-sex chromosome in parrots.
The N501Y spike substitution enhances SARS-CoV-2 transmission
Authors: Liu Yang , Liu Jianying , Plante Kenneth S. , Plante Jessica A. , Xie Xuping , Zhang Xianwen , Ku Zhiqiang , An Zhiqiang , Scharton Dionna , Schindewolf Craig , Menachery Vineet D. , Shi Pei-Yong , Weaver Scott C. 
Published: March 2021

SummaryBeginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1.1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 UK spike mutations, suggesting it is a major determinant responsible for increased transmission of this variant. Mechanistically, the N501Y substitution improved the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil and South Africa, our results indicate that N501Y substitution is a major adaptive spike mutation of major concern.
Topographical overlapping of the Aβ and Tau pathologies in the Default mode networks predicts Alzheimer’s Disease with higher specificity
Authors: Hojjati Seyed Hani , Feiz Farnia , Ozoria Sindy , Razlighi Qolamreza R. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2021

AbstractWhile Amyloid-plaques and Tau-tangles are the well-recognized pathologies of Alzheimer’s disease (AD), they are more often observed in healthy individuals than in AD patients. This discrepancy makes it extremely challenging to utilize these two proteinopathies as reliable biomarkers for the early detection as well as later diagnosis of AD. Using the recent advancements in the imaging technology, our newly developed quantification methods, and publicly available neuroimaging data from 303 individuals, we hypothesize and provide preliminary evidence that topographically overlapping Aβ and Tau within the DMN play more critical roles in the underlying pathophysiology of AD than the Tau and/or Aβ pathologies. We first showed that the probability of observing overlapping Aβ and Tau is significantly higher within the DMN than outside DMN. Then we showed evidence that using Aβ and Tau overlap can increase the reliability of the prediction of healthy individuals converting to MCI and a lesser degree converting from MCI to AD. These findings shed some light on the complex pathophysiology of AD and suggest that overlapping Aβ and Tau pathologies within DMN might be a more reliable biomarker of AD for early detection and later diagnosis of the disease.
Efficacy of remdesivir in hospitalised COVID-19 patients in Japan: A large observational study using the COVID-19 Registry Japan
Authors: Tsuzuki Shinya , Hayakawa Kayoko , Uemura Yukari , Shinozaki Tomohiro , Matsunaga Nobuaki , Terada Mari , Suzuki Setsuko , Ohtsu Hiroshi , Asai Yusuke , Kitajima Koji , Saito Sho , Yamada Gen , Shibata Taro , Kondo Masashi , Izumi Kazuo , Hojo Masayuki , Mizoue Tetsuya , Yokota Kazuhisa , Nakamura-Uchiyama Fukumi , Saito Fumitake , Sugiura Wataru , Ohmagari Norio 
Published: March 2021

AbstractObjectivesAlthough several randomised controlled trials have compared the efficacy of remdesivir with that of placebo, there is limited evidence regarding its effect in the early stage of nonsevere COVID-19 cases.MethodsWe evaluated the efficacy of remdesivir on the early stage of nonsevere COVID-19 using the COVID-19 Registry Japan, a nationwide registry of hospitalised COVID-19 patients in Japan. Two regimens (start remdesivir therapy within 4 days from admission vs. no remdesivir during hospitalisation) among patients without the need for supplementary oxygen therapy were compared by a three-step processing (cloning, censoring, and weighting) method. The primary outcome was supplementary oxygen requirement during hospitalisation. Secondary outcomes were 30-day fatality risk and risk of invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO).ResultsThe data of 12,657 cases met our inclusion criteria. The ‘start remdesivir’ regimen showed a lower risk of supplementary oxygen requirement (hazard ratio: 0.861, p < 0.001). Both 30-day fatality risk and risk of IMV/ECMO introduction were not significantly different between the two regimens (hazard ratios: 1.05 and 0.886, p values: 0.070 and 0.440, respectively).ConclusionsRemdesivir might reduce the risk of oxygen requirement during hospitalisation in the early stage of COVID-19; however, it had no positive effect on the clinical outcome and reduction of IMV/ECMO requirement.
Niche signals regulate continuous transcriptional states in hematopoietic stem cells
Authors: Fast Eva M , Sporrij Audrey , Manning Margot , da Rocha Edroaldo Lummertz , Yang Song , Zhou Yi , Guo Jimin , Baryawno Ninib , Barkas Nikolaos , Scadden David T , Camargo Fernando , Zon Leonard I 
Published: March 2021

AbstractHematopoietic stem cells (HSCs) must ensure adequate blood cell production following distinct external stressors. A comprehensive understanding ofin vivoheterogeneity and specificity of HSC responses to external stimuli is currently lacking. We performed single-cell RNA sequencing (scRNA-Seq) on functionally validated mouse HSCs and LSK (Lin-, c-Kit+, Sca1+) progenitors afterin vivoperturbation of niche signals interferon, granulocyte-colony stimulating factor (G-CSF), and prostaglandin. We identified six HSC states that are characterized by enrichment but not exclusive expression of marker genes. Niche perturbations induce novel and rapid transitions between these HSC states. Differential expression analysis within each state revealed HSC- and LSK-specific molecular signatures for each perturbation. Chromatin analysis of unperturbed HSCs and LSKs by scATAC-Seq revealed HSC-specific, cell intrinsic predispositions to niche signals. We compiled a comprehensive resource of HSC- and progenitor-specific chromatin and transcriptional features that represent important determinants of regenerative potential during stress hematopoiesis.