bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current status of porcine islet xenotransplantation
Authors: Coe Taylor M. , Markmann James F. , Rickert Charles G. 
Published: August 2020

Purpose of review
Human islet transplantation has proven to be a highly effective treatment for patients with labile type 1 diabetes mellitus, which can free patients from daily glucose monitoring and insulin injections. However, the shortage of islet donors limits its’ broad application. Porcine islet xenotransplantation presents a solution to the donor shortage and recent advances in genetic modification and immunosuppressive regimens provide renewed enthusiasm for the potential of this treatment.

Recent findings
Advances in genetic editing technology are leading to multigene modified porcine islet donors with alterations in expression of known xenoantigens, modifications of their complement and coagulation systems, and modifications to gain improved immunological compatibility. Recent NHP-based trials of costimulation blockade using CD154 blockade show promising improvements in islet survival, whereas results targeting CD40 are less consistent. Furthermore, trials using IL-6 receptor antagonism have yet to demonstrate improvement in glucose control and suffer from poor graft revascularization.

Summary
This review will detail the current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and review barriers to translation of xenoislets to the clinic.
Giardiasis treatment: an update with a focus on refractory disease
Authors: Mørch Kristine , Hanevik Kurt 
Published: August 2020

Purpose of review
Giardiasis remains a common cause of diarrhea and intestinal enteropathy globally. Here we give an overview of clinical treatment studies and discuss potential mechanisms and molecular targets for in-vitro testing of drug resistance.

Recent findings

Giardia is a cause of disease both in diarrheal and nondiarrheal cases. The prevalence of treatment refractory giardiasis is increasing. Recent studies reveal 5-nitroimidazole refractory infection occurs in up to 50% of cases. Mechanisms of drug resistance are not known. Placebo controlled studies of drug efficacy, taking the self-limiting course of giardiasis into account, has not been reported. No randomized controlled trials of treatment of refractory infection have been performed the last 25 years. Based on the clinical studies reported, combination treatment with a 5-nitroimidazole and a benzimidazole is more effective than repeated courses of 5-nitroimidazole or monotherapies in refractory cases. Quinacrine is effective in refractory cases, but potentially severe side effects limit its use.

Summary
A combination of a 5-nitroimidazole and albendazole or mebendazole, and quinacrine monotherapy, are rational choices in nitroimidazole refractory infections, but randomized controlled studies are needed. Further research into more recent clinical isolates is necessary to uncover mechanisms for the increase in metronidazole refractory giardiasis observed during the last decade.
The Development and Natural History of Hiatal Hernias
Authors: Abdelmoaty Walaa , Dunst Christy , Fletcher Reid , Doan Huy , Tugulan Carmen , Walters Jarvis , Davila-Bradley Daniel , Reavis Kevin , Swanstrom Lee , DeMeester Steven 
Published: August 2020

Objective:
The aim of this study was to use barium upper gastrointestinal series (UGI) to evaluate the development and natural history of a hiatal hernia.

Summary of Background Data:
Hiatal hernias are common but the natural history of sliding and paraesophageal type hernias is poorly understood.

Methods:
We reviewed UGI reports from 1987 to 2017 using a word scanning software program to identify individuals that had a hiatal hernia. Only those with at least 2 UGI studies 5 or more years apart were selected. The studies were then reviewed.

Results:
There were 89 individuals that met inclusion criteria. Twenty-one people had no hiatal hernia on initial UGI and over a median of 99 months a sliding hiatal hernia (SHH) developed in 16 and a PEH developed in 5 people. A SHH was present on initial UGI in 55 people and at a median of 84 months subsequent UGI showed the SHH was stable in 11 (20%), increased in size in 30 (55%), and changed to a PEH in 14 people (25%). In 13 people a PEH was present on initial UGI and over a median of 97 months it was stable in 5 and increased in size in 8 people (62%).

Conclusions:
We showed that both SHH and PEH can develop over time and that the majority of both increased in size on follow-up UGI study. Further, 25% of SHH became a PEH over time. Recognizing an increase in size or change in type of a hiatal hernia may be clinically relevant to help understand changing or worsening symptoms in an individual.
Molecular pathogenesis of spinal bulbar muscular atrophy (Kennedy's disease) and avenues for treatment
Authors: Grunseich Christopher , Fischbeck Kenneth H. 
Published: August 2020

Purpose of reviewThe aim of this study was to illustrate the current understanding and avenues for developing treatment in spinal and bulbar muscular atrophy (SBMA), an inherited neuromuscular disorder caused by a CAG trinucleotide repeat expansion in the androgen receptor (AR) gene.Recent findingsImportant advances have been made in characterizing the molecular mechanism of the disease, including the disruption of protein homeostasis, intracellular trafficking and signalling pathways. Biomarkers such as MRI quantification of muscle volume and fat fraction have been used to track disease progression, and will be useful in future clinical studies. Therapies tested and under development have been based on diverse strategies, including targeting mutantARgene expression, stability and activity, and pathways that mitigate disease toxicity.SummaryWe provide an overview of the recent advances in understanding the SBMA disease mechanism and highlight efforts to translate these insights into well tolerated and effective therapy.
Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial
Authors: Zhang Yanjun , Zeng Gang , Pan Hongxing , Li Changgui , Kan Biao , Hu Yaling , Mao Haiyan , Xin Qianqian , Chu Kai , Han Weixiao , Chen Zhen , Tang Rong , Yin Weidong , Chen Xin , Gong Xuejie , Qin Chuan , Hu Yuansheng , Liu Xiaoyong , Cui Guoliang , Jiang Congbing , Zhang Hengming , Li Jingxin , Yang Minnan , Lian Xiaojuan , Song Yan , Lu Jinxing , Wang Xiangxi , Xu Miao , Gao Qiang , Zhu Fengcai 
Published: August 2020

ABSTRACTBACKGROUNDThe top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac).METHODSWe conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 μg/0.5 mL or 6 μg /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay.RESULTSCoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 μg dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules.CONCLUSIONSFavorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.
Newborn Life Support Course: Does it make me more confident when resuscitating a newborn?
Authors: Renesme Laurent , Merched Maria , Tandonnet Olivier , Naud Julien 
Published: August 2020

AbstractObjectiveTo describe the effectiveness of the Neonatal Life Support (NLS) course in terms of attendees’ knowledge, perceived self-efficacy, and clinical applicability.MethodsWe conducted an electronic survey of NLS course attendees (NLS+ group). The survey had six themes: i) demographic characteristics; ii) NLS clinical applicability; iii) attendee’s perceived proficiency at neonatal resuscitation; iv) attendee’s perceived experience of fluency, security, and quality of care during neonatal resuscitation; v) knowledge (multiple-choice questions); and vi) perceived personal and professional impact of the NLS course. A control group (NLS−) was recruited via our regional perinatal network. The survey data were analysed anonymously. Multiple linear regression analysis examined the following: NLS course, job tenure, maternity level, and profession.ResultsThe survey completion rate was 62% (200/323) for the NLS+ group. Among participants, 84% had participated in neonatal resuscitation since their course. The scores for positive perceived experience for neonatal resuscitation (fluency, security, and quality of care delivered) were higher in the NLS+ group than the NLS− group (p < 0.006). After adjustment, the independent factors associated with a higher positive perceived experience were the NLS course, work in tertiary level maternity ward, and job tenure > 5 years. The multiple-choice questions score (n = 10) was 8.2 ± 1.3 (NLS+) vs. 6.7 ± 1.5 (NLS−) (p < 0.0001). NLS course, medical degree, and work in a tertiary level maternity ward were independently associated with higher knowledge scores.ConclusionThe NLS course was associated with better knowledge of, and a positive perceived experience regarding, neonatal resuscitation.
SARS-CoV-2 and the Role of Orofecal Transmission: Systematic Review
Authors: Heneghan C , Spencer EA , Brassey J , Jefferson T 
Published: August 2020

AbstractBackgroundHow SARS-CoV-2 is transmitted is of key public health importance. SARS-CoV-2 has been detected in the feces of some Covid-19 patients which suggests the possibility that the virus could additionally be transmitted via the orofecal route.MethodsThis review is part of an Open Evidence Review on Transmission Dynamics of Covid-19. We conduct ongoing searches using LitCovid, medRxiv, Google Scholar and Google for Covid-19; assess study quality based on five criteria and report important findings on an ongoing basis. Where necessary authors are contacted for further details or clarification on the content of their articles.ResultsWe found 59 studies: nine reviews and 51 primary studies or reports (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Half (n=29) were done in China. Thirty seven studies reported positive fecal samples for SARS-CoV-2 based on RT-PCR results (n=1,034 patients). Six studies reported isolating the virus from fecal samples of nine patients, one study isolated the virus from rectal tissue and one laboratory study found that SARS-CoV-2 productively infected human small intestinal organoids. Eleven studies report on fecal samples found in sewage, and two sampled bathrooms and toilets.ConclusionsVarious observational and mechanistic evidence support the hypothesis that SARS-CoV-2 can infect and be shed from the human gastrointestinal tract. Policy should emphasize the importance of strict personal hygiene measures, and chlorine-based disinfection of surfaces in locations where there is presumed or known SARS-CoV-2 activity.
Mental Health Problems in Nepalese Migrant Workers and their Families
Authors: Mahat Pashupati , Thorley Kevan , Kunwar Karuna , Ghirime Smriti 
Published: August 2020

AbstractBackgroundNepal has an economy increasingly dependent on remittences from migrant wokers. Mental health problems affect a significant number of these workers and the prevalence of mental health problems in the left behind families of migrant workers is high. Facilities for the psychosocial support of migrant workers and their families are scarce. A project to provide such support is described.ObjectiveWe aim to describe the mental health problems of Nepalese migrant workers and their family members remaining at home in Nepal.MethodsFamilies of migrant workers from nine project districts were interviewed and offered appropriate psychosocial counseling. The psychosocial problems experienced by families left behind in Nepal (women, children and elderly parents) were assessed.ResultsSocial isolation, excessive worry, low mood, fearfulness and sleep disturbances were frequently reported. Wives and mothers of migrant workers experienced anxiety, depression and suicidal ideation as well as suicide attempts.. Domestic violence, death of migrant workers, health problems of migrant workers and their families and the difficulties of communication when working overseas were found to be contributing factors for psychosocial and mental health problems.
The windblown: possible explanations for dinophyte DNA in forest soils
Authors: Gottschling Marc , Czech Lucas , Mahé Frédéric , Adl Sina , Dunthorn Micah 
Published: August 2020

ABSTRACTDinophytes are widely distributed in marine- and fresh-waters, but have yet to be conclusively documented in terrestrial environments. Here we evaluated the presence of these protists from an environmental DNA metabarcoding dataset of Neotropical rainforest soils. Using a phylogenetic placement approach with a reference alignment and tree, we showed that the numerous sequencing reads that were assigned to the dinophytes did not associate with taxonomy, environmental preference, nutritional mode, or dormancy. All the dinophytes in the soils are most likely windblown dispersal units of aquatic species, and are not biologically active residents of terrestrial environments.
Screening of yeast display libraries of enzymatically-cyclized peptides to discover macrocyclic peptide ligands
Authors: Bowen John , Schneible John , Labar Collin , Menegatti Stefano , Rao Balaji M. 
Published: August 2020

AbstractWe present the construction and screening of yeast display libraries of cyclic peptides wherein site-selective enzymatic cyclization of linear peptides is achieved using bacterial transglu-taminase. To this end, we developed two alternative routes, namely(i)yeast display of linear peptides followed by treatment with recombinant transglutaminase in solution; or(ii)intracellular co-expression of linear peptides and transglutaminase to achieve cyclization in the endoplasmic reticulum prior to yeast surface display. The cyclization yield was evaluated via orthogonal detection of epitope tags integrated in the yeast-displayed peptides by flow cytometry, and via comparative cleavage of cyclicvs.linear peptides by tobacco etch virus (TEV) protease. Subsequently, yeast display libraries of transglutaminase-cyclized peptides were screened to isolate binders to the N-terminal region of the Yes-Associated Protein (YAP) and its WW domains using magnetic selection and fluorescence activated cell sorting (FACS). The identified cyclic peptide cyclo[E-LYLAYPAH-K] featured a KDof 1.67 µM for YAP and 0.84 µM for WW as well as high binding selectivity against albumin and lysozyme. These results demonstrate the usefulness of yeast surface display for screening transglutaminase-cyclized peptide libraries, and efficient identification of cyclic peptide ligands.
Independent respiratory and locomotor rhythms in running mice
Authors: Hérent Coralie , Diem Séverine , Fortin Gilles , Bouvier Julien 
Published: August 2020

ABSTRACTExamining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea to exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and/or imposed by a synchronization of breaths to strides is still unclear. Here, we examined the specifications of respiratory changes during running in mice, the premier model for investigating, in a standardized manner, complex integrative tasks including adaptive breathing. We show that respiratory rate increases during running to a fixed and stable value, irrespective of trotting velocities and of inclination. Yet, respiratory rate was further enhanced during gallop. We also demonstrate the absence of temporal coordination of breaths to strides at any speed, intensity or gait. Our work thus highlights a hardwired mechanism that sets respiratory frequency independently of limb movements but in relation with the engaged locomotor program.
Rapid discovery of novel prophages using biological feature engineering and machine learning
Authors: Sirén Kimmo , Millard Andrew , Petersen Bent , Gilbert M Thomas P , Clokie Martha RJ , Sicheritz-Pontén Thomas 
Published: August 2020

ABSTRACTProphages are phages that are integrated into bacterial genomes and which are key to understanding many aspects of bacterial biology. Their extreme diversity means they are challenging to detect using sequence similarity, yet this remains the paradigm and thus many phages remain unidentified. We present a novel, fast and generalizing machine learning method based on feature space to facilitate novel prophage discovery. To validate the approach, we reanalyzed publicly available marine viromes and single-cell genomes using our feature-based approaches and found consistently more phages than were detected using current state-of-the-art tools while being notably faster. This demonstrates that our approach significantly enhances bacteriophage discovery and thus provides a new starting point for exploring new biologies.
DEER-PREdict: Software for Efficient Calculation of Spin-Labeling EPR and NMR Data from Conformational Ensembles
Authors: Tesei Giulio , Martins João M. , Kunze Micha B. A. , Wang Yong , Crehuet Ramon , Lindorff-Larsen Kresten 
Published: August 2020

AbstractOwing to their plasticity, intrinsically disordered and multidomain proteins require descriptions based on multiple conformations, thus calling for techniques and analysis tools that are capable of dealing with conformational ensembles rather than a single protein structure. Here, we introduce DEER-PREdict, a software to predict Double Electron-Electron Resonance distance distributions as well as Paramagnetic Relaxation Enhancement rates from ensembles of protein conformations. DEER-PREdict uses an established rotamer library approach to describe the paramagnetic probes which are bound covalently to the protein. DEER-PREdict has been designed to operate efficiently on large conformational ensembles, such as those generated by molecular dynamics simulation, to facilitate the validation or refinement of molecular models as well as the interpretation of experimental data. The performance and accuracy of the software is demonstrated with experimentally characterized protein systems: HIV-1 protease, T4 Lysozyme and Acyl-CoA-binding protein. DEER-PREdict is open source (GPLv3) and available atgithub.com/KULL-Centre/DEERpredictand as a Python PyPI packagepypi.org/project/DEERPREdict.
The lncRNAMARSmodulates the epigenetic reprogramming of the marneral cluster in response to ABA
Authors: Roulé Thomas , Ariel Federico , Hartmann Caroline , Hussain Nosheen , Benhamed Moussa , Gutierrez-Marcos Jose , Crespi Martin , Blein Thomas 
Published: August 2020

ABSTRACTClustered organization of biosynthetic non-homologous genes is emerging as a characteristic feature of plant genomes. The co-regulation of clustered genes seems to largely depend on epigenetic reprogramming and three-dimensional chromatin conformation. Here we identified the long noncoding RNA (lncRNA)MARneral Silencing(MARS), localized inside the Arabidopsis marneral cluster, which controls the local epigenetic activation of its surrounding region in response to ABA.MARSmodulates the POLYCOMB REPRESSIVE COMPLEX 1 (PRC1) component LIKE-HETEROCHROMATIN PROTEIN 1 (LHP1) binding throughout the cluster in a dose-dependent manner, determining H3K27me3 deposition and chromatin condensation. In response to ABA,MARSdecoys LHP1 away from the cluster and promotes the formation of a chromatin loop bringing together theMARNERAL SYNTHASE 1(MRN1) locus and a distal ABA-responsive enhancer. The enrichment of co-regulated lncRNAs in clustered metabolic genes in Arabidopsis suggests that the acquisition of novel noncoding transcriptional units may constitute an additional regulatory layer driving the evolution of biosynthetic pathways.
Computational Tool for Ensemble Averaging of Single-Molecule Data
Authors: Blackwell Thomas , Stump W. Tom , Clippinger Sarah R. , Greenberg Michael J. 
Published: August 2020

AbstractMolecular motors couple chemical transitions to conformational changes that perform mechanical work in a wide variety of biological processes. Disruption of this coupling can lead to diseases, and therefore there is a need to accurately measure mechanochemical coupling in motors in both health and disease. Optical tweezers, with nanometer spatial and millisecond temporal resolution, have provided valuable insights into these processes. However, fluctuations due to Brownian motion can make it difficult to precisely resolve these conformational changes. One powerful analysis technique that has improved our ability to accurately measure mechanochemical coupling in motor proteins is ensemble averaging of individual trajectories. Here, we present a user-friendly computational tool, Software for Precise Analysis of Single Molecules (SPASM), for generating ensemble averages of single-molecule data. This tool utilizes several conceptual advances, including optimized procedures for identifying single-molecule interactions and the implementation of a change point algorithm, to more precisely resolve molecular transitions. Using both simulated and experimental data, we demonstrate that these advances allow for accurate determination of the mechanics and kinetics of the myosin working stroke with a smaller set of data. Importantly, we provide our open source MATLAB-based program with a graphical user interface that enables others to readily apply these advances to the analysis of their own data.Statement of SignificanceSingle molecule optical trapping experiments have given unprecedented insights into the mechanisms of molecular machines. Analysis of these experiments is often challenging because Brownian motion-induced fluctuations introduce noise that can obscure molecular motions. A powerful technique for analyzing these noisy traces is ensemble averaging of individual binding interactions, which can uncover information about the mechanics and kinetics of molecular motions that are typically obscured by Brownian motion. Here, we provide an open source, easy-to-use computational tool, SPASM, with a graphical user interface for ensemble averaging of single molecule data. This computational tool utilizes several conceptual advances that significantly improve the accuracy and resolution of ensemble averages, enabling the generation of high-resolution averages from a smaller number of binding interactions.