bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management and outcomes of myelomeningocele-associated hydrocephalus in low- and middle-income countries: a systematic review and meta-analysis protocol
Authors: Takoutsing Berjo Dongmo , Touzet Alvaro Yanez , Park Jay J. , Lee Seong Hoon , Bligh Emily R. , Egiz Abdullah , Gillespie Conor S. , Figaji Anthony 
Published: June 2022

ABSTRACTIntroductionHydrocephalus and myelomeningocele (MMC) place disproportionate burdens of disease on low and middle-income countries (LMICs). MMC-associated hydrocephalus and its sequelae result in a spectrum of severely devastating clinical manifestations, for which LMICs are disproportionately unprepared in terms of human, capital, and technological resources. This study aims to review and compare the management and outcomes of infant MMC-associated hydrocephalus in LMICs and high-income countries.Methods and analysisThis systematic review and meta-analysis will follow the PRISMA 2020 guidelines. The following databases will be searched without restrictions on language, publication date, or country of origin: EMBASE, MEDLINE, The Cochrane Library, Global Index Medicus, African Journals Online, and SciELO. All peer-reviewed studies of primary data reporting management and outcomes of infant MMC-associated hydrocephalus will be included. Where high-quality homogeneous studies exist, meta-analyses will be conducted to compare the management and outcomes of MMC-associated hydrocephalus across socioeconomic and geographic regions of the world. The primary outcome will be treatment failure of the first-line hydrocephalus treatment, which we defined operationally as the performance of a second intervention for the same reason as the first. Secondary outcomes include time to failure, rates of mortality, and postoperative complications.Ethics and disseminationEthical approval was not applicable because this study does not involve human participants. Dissemination strategies will include publication in a peer-reviewed journal, oral and poster presentations at conferences, and an interactive web application to facilitate interaction with the findings and promote the discussion and sharing of findings on social media.ARTICLE SUMMARYStrengths and limitations of this studyThis review focuses on multiple treatment modes of a well-defined disease population.Six electronic databases that are commonly used across both high- and low-income countries will be searched.No restrictions on language, location, or publication date were placed during screening.Unpublished studies will not be sought.The representativeness of the sample will rely on the quality of reporting of myelomeningocoele-associated hydrocephalus in the literature.Only one operational definition of treatment failure—‘the performance of a second intervention for the same reason as the first’—will be sought.An interactive web application dashboard will be developed to facilitate the transparent interaction with our methods and findings and promote scientific discussion and scrutiny.
A causal role of the human left temporoparietal junction in computing social influence during goal-directed learning
Authors: Zhang Lei , Kandil Farid I. , Zhao Ke , Fu Xiaolan , Lamm Claus , Hilgetag Claus C. , Gläscher Jan 
Published: June 2022

AbstractThe human temporoparietal junction (TPJ) is a brain area crucial for processing social information. Although brain stimulation studies have started to explore the causal function of TPJ under social contexts, few have explicitly considered bilateral TPJ as target regions. Here, leveraging non-invasive continuous theta-burst stimulation (cTBS) and hierarchical Bayesian computational modeling, we tested whether left or right TPJ (with vertex as control) is causally involved in how dissenting choices by others influence individuals’ choice adjustments in goal-directed learning. In our social learning paradigm, participants (N = 31) first made their private decision, and then were allowed to re-adjust their choices after observing choices of four other players. Behaviorally, we show that disruption of the left, but not the right TPJ, weakened participants’ choice adjustment and delayed their response speed when confronted with dissenting information from the other players. Computationally, disrupting activity in the left TPJ attenuated the degree of computing social influence during choice adjustment, whereas the extent to which how observational learning from others’ choices was integrated into direct learning remained intact. Together, our results provide evidence for the causal role of left TPJ in social influence during goal-directed learning and shed light on the relational function (with respect to oneself) of the TPJ in social cognition.
Comparative immune responses toMycobacterium tuberculosisin people with latent infection or sterilizing protection
Authors: Jalbert Emilie , Liu Cuining , Mave Vidya , Lang Nancy , Kagal Anju , Valvi Chhaya , Paradkar Mandar , Gupte Nikhil , Lokhande Rahul , Bharadwaj Renu , Kulkarni Vandana , Gupta Amita , Weinberg Adriana 
Published: June 2022

AbstractTuberculosis (TB) affects 2 billion people worldwide and causes 1.5 million deaths every year. There is great need for new TB vaccines that are more efficacious than the currently licensed BCG vaccine, which provides only limited protection. Our goal was to identify potential targets for new TB vaccines by characterizing the immune responses that distinguish individuals with sterilizing protection against TB (TB-resisters), defined by presence of TB-specific immune responses and absence of latent infection, from individuals with latent TB infection (LTBI-participants).Cryopreserved peripheral blood mononuclear cells (PBMC) from 13 TB-resisters and 10 LTBI-participants were analyzed by high dimensional spectral flow cytometry after overnightM. tuberculosis (Mtb)antigenic stimulation or unstimulated control. Activation of conventional and nonconventional T cells, NK cells, and antigen presenting cells (APC) was compared between the two groups. Compared with LTBI-participants, TB-resisters had significantly higher proportions of conventional and nonconventional T cells expressing granzyme B (GranzB) and PD-1, and of polyfunctional cells in unstimulated andMtb-stimulated conditions. Conversely LTBI-participants had higher expression of CD25, CD69, CD107a, IL10 and IFNγ. An unbiased cluster analysis revealed higher frequency of recently described CD8+GMM+GranzB+ T cells in unstimulated PBMC from TB-resisters than LTBI-participants. APC activation revealed very few differences between TB-resisters and LTBI-participants. An exploratory analysis of responses in 14 BCG-recipients with minimal exposure to TB showed multiple differences with TB-resisters and LTBI-participants in PBMC activation; lower polyfunctionality of T cells and APC inMtb-stimulated PBMC; and absence of CD8+GMM+GranzB+ T cells.We conclude that combined increased T cell expression of GranzB and checkpoint inhibitors may contribute to immune protection against TB and may be targeted by new vaccines.
Structural insights into AT-rich DNA recognition by SALL family proteins
Authors: Ru Wenwen , Koga Tomoyuki , Wang Xiaoyang , Guo Qiong , Gearhart Micha , Zhao Shidong , Murphy Mark , Kawakami Hiroko , Corcoran Dylan , Zhang Jiahai , Zhu Zhongliang , Yao Xuebiao , Kawakami Yasu , Xu Chao 
Published: June 2022

AbstractSpalt-like 4 (SALL4) plays an essential role in controlling the pluripotent property of embryonic stem cells (ESCs) via binding to AT-rich regions of genomic DNA. Here we present crystal structures of the the zinc finger cluster 4 (ZFC4) domain of SALL4 (SALL4ZFC4) bound with different double stranded DNAs containing a conserved AT-rich motif. In the structures, two zinc fingers of SALL4ZFC4 coordinatively recognize an AATA tetranucleotide. We also solved the DNA-bound structures of SALL3ZFC4 and SALL4ZFC1. These structures illuminate a common recognition mode for AT-rich DNA by the SALL family proteins. The DNA binding activity is essential for SALL4 function as DNA-binding defective mutants of mouse Sall4 failed to repress aberrant gene expression in Sall4-/- mESCs. Thus, these analyses provide new insights into the mechanisms of action underlying SALL family in controlling cell fate via preferentially targeted to AT-rich sites within genomic DNAs during cell differentiation.
Novel Genetic Loci Associated with Osteoarthritis in Multi-Ancestry Analyses in 484,374 Participants from MVP and the UK Biobank
Authors: McDonald Merry-Lynn N. , Kumar Preeti Lakshman , Srinivasasainagendra Vinodh , Nair Ashwathy , Rocco Alison , Wilson Ava C. , Chiles Joe , Richman Joshua , Pinson Sarah A. , Dennis Richard , Jagadale Vivek , Brown Cynthia , Pyarajan Saiju , Tiwari Hemant K. , Bamman Marcas M. , Singh Jasvinder A. ,   the VA Million Veteran Program
Published: June 2022

AbstractTo date there have been no large multi ancestry genetic studies of osteoarthritis (OA). We leveraged the unique resources of 484,374 participants in the Million Veteran Program (MVP) and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered OA associated genetic variation in 10 loci and replicated association findings from previous OA studies. We also present evidence some OA-associated regions are robust to population ancestry. Drug repurposing analyses revealed enrichment of targets of several medication classes and provide potential insight to etiology of beneficial effects of antiepileptics on OA pain.
Machine learning aided multiscale modelling of the HIV-1 infection in the presence of NRTI therapy
Authors: Tunc Huseyin , Sari Murat , Kotil Seyfullah 
Published: June 2022

ABSTRACTThe Human Immunodeficiency Virus (HIV) is one of the most common chronic infectious diseases of humans. Increasing the expected lifetime of the patients depends on the use of optimal antiretroviral therapies. The emergence of the drug-resistant strains may decrease the effects of treatments and lead to Acquired Immune Deficiency Syndrome (AIDS) even if the existence of antiretroviral therapy. Investigation of the genotype-phenotype relations is a crucial process to optimize the therapy protocols of the patients. Here we propose a mathematical modelling framework to address the effect of initial strains, initiation timing and adherence levels of nucleotide reverse transcriptase inhibitors (NRTI) on the emergence of a possible AIDS phase. For the first time, we have combined the existing Stanford HIV drug resistance data with a multi-strain within-host ordinary differential equation (ODE) model to track the dynamics of most common NRTI resistant strains. Regardless of the drug choice, the late initiation and poor adherence levels to the NRTI therapy increase the probability of the emergence of the AIDS phase. Overall, the 3TC, D4T-AZT and TDF-D4T drug combinations provide higher success rates. The results are in line with genotype-phenotype data and pharmacokinetic parameters of the NRTI inhibitors, but we show the heavy influence of neighbour viral strains of the initial ones has a considerable effect on the success/failure rates. Improving multiscale models can contribute to understanding the disease progression and treatment options.
Application of machine learning and complex network measures to an EEG dataset from DMT experiments
Authors: Alves Caroline L. , Toutain Thaise G. L. de O. , Porto Joel Augusto Moura , Pineda Aruane M. , de Sena Eduardo Pondé , Rodrigues Francisco A. , Thielemann Christiane , Ciba Manuel 
Published: June 2022

There is a growing interest in the medical use of psychedelic substances as preliminary studies using them for psychiatric disorders have shown positive results. In particularly, one of these substances is N,N-dimethyltryptamine (DMT) an agonist serotonergic psychedelic that can induce profound alterations in state of consciousness.In this work, we propose a computational method based on machine learning as an exploratory tool to reveal DMT-induced changes in brain activity using EEG data and provide new insights into the mechanisms of action of this psychedelic substance. To answer these questions, we propose a two-class classification based on (A) the connectivity matrix or (B) complex network measures derived from it as input to a support vector machine We found that both approaches were able to automatically detect changes in the brain activity, with case (B) showing the highest AUC (89%), indicating that complex network measurements best capture the brain changes that occur due to DMT use. In a second step, we ranked the features that contributed most to this result. For case (A) we found that differences in the high alpha, low beta, and delta frequency band were most important to distinguish between the state before and after DMT inhalation, which is consistent with results described in the literature. Further, the connection between the temporal (TP8) and central cortex (C3) and between the precentral gyrus (FC5) and the lateral occipital cortex (T8) contributed most to the classification result. The connection between regions TP8 and C3 has been found in the literature associated with finger movements that might have occurred during DMT consumption. However, the connection between cortical regions FC5 and P8 has not been found in the literature and is presumably related to emotional, visual, sensory, perceptual, and mystical experiences of the volunteers during DMT consumption. For case (B) closeness centrality was the most important complex network measure. Moreover, we found larger communities and a longer average path length with the use of DMT and the opposite in its absence indicating that the balance between functional segregation and integration was disrupted. This findings supports the idea that cortical brain activity becomes more entropic under psychedelics.Overall, a robust computational workflow has been developed here with an interpretability of how DMT (or other psychedelics) modify brain networks and insights into their mechanism of action. Finally, the same methodology applied here may be useful in interpreting EEG time series from patients who consumed other psychedelic drugs and can help obtain a detailed understanding of functional changes in the neural network of the brain as a result of drug administration.
JASPER: a fast genome polishing tool that improves accuracy and creates population-specific reference genomes
Authors: Guo Alina , Salzberg Steven L. , Zimin Aleksey V. 
Published: June 2022

AbstractAdvances in long-read sequencing technologies have dramatically improved the contiguity and completeness of genome assemblies. Using the latest nanopore-based sequencers, we can generate enough data for the assembly of a human genome from a single flow cell. With the long-read data from these sequences, we can now routinely produce de novo genome assemblies in which half or more of a genome is contained in megabase-scale contigs. Assemblies produced from nanopore data alone, though, have relatively high error rates and can benefit from a process called polishing, in which more-accurate reads are used to correct errors in the consensus sequence. In this manuscript, we present a novel tool for genome polishing called JASPER (Jellyfish-based Assembly Sequence Polisher for Error Reduction). In contrast to other polishing methods, JASPER gains efficiency by avoiding the alignment of reads to the assembly. Instead, JASPER uses a database of k-mer counts that it creates from the reads to detect and correct errors in the consensus. In addition to its use for polishing genomes, JASPER can also create population-specific genomes using an existing reference genome along with sequencing reads from multiple individuals from the population of interest. In this mode, JASPER alters the reference genome so that it contains variants that are common in the target population. In our experiments, we show that after creating a Japanese-specific reference genome, we observed a 27% reduction in homozygous variant calls using whole-genome sequencing reads from an individual from Tokyo.
PICLN modulates alternative splicing and ensures adaptation to light and temperature changes in plants
Authors: Mateos Julieta L. , Sanchez Sabrina E , Legris Martina , Esteve-Bruna David , Torchio Jeanette C. , Petrillo Ezequiel , Goretti Daniela , Blanco-Touriñán Noel , Seymour Danelle K. , Schmid Markus , Weigel Detlef , Alabadí David , Yanovsky Marcelo J. 
Published: June 2022

AbstractPlants undergo transcriptome reprogramming to adapt to daily and seasonal fluctuations in light and temperature conditions. While most efforts have focused on the role of master transcription factors, the importance of splicing factors modulating these processes is now emerging. Efficient pre-mRNA splicing depends on proper spliceosome assembly, which in plants and animals requires the methylosome complex. PICLN is part of the methylosome complex in both humans and Arabidopsis thaliana, and we show here that the human PICLN ortholog rescues phenotypes of A. thaliana picln mutants. Altered photomorphogenic and photoperiodic responses in A. thaliana picln mutants are associated with changes in pre-mRNA splicing, which partially overlap with those in prmt5 mutants. Mammalian PICLN also acts in concert with the Survival Motor Neuron (SMN) complex component GEMIN2 to modulate the late steps of UsnRNP assembly, and many alternative splicing events regulated by PICLN but not PROTEIN-ARGININE METHYL TRANSFERASE 5 (PRMT5), the main protein of the methylosome, are controlled by A. thaliana GEMIN2. As with GEMIN2 and SME1/PCP, low temperature, which increases PICLN expression, aggravates morphological and molecular defects of picln mutants. Taken together, these results establish a key role for PICLN in the regulation of pre-mRNA splicing and in mediating plant adaptation to daily and seasonal fluctuations in environmental conditions.
Participation in a voluntary alcohol abstinence program (Alcohol Free for 40) with tracking of laboratory values and physical metrics improves biometric measures of health; a three-year retrospective analysis
Authors: Feehan Amy K. , Knapp Megan B. , Lockhart Jala , Arceneaux Erin E. , Latimer Savanna , Walter Anna , Craft Brittany N. , Quantz Yvette P. , Frugé Hope , Terry Maria Sylvester , Galarneau David , Kimball Molly 
Published: June 2022

AbstractBackgroundLaboratory and physical metric data were available from participants of Alcohol Free for 40 (AFF40), a 40-day alcohol abstinence program in Louisiana. This study was performed to determine whether biometric changes were detectable after 40 days.Materials and MethodsThis was a retrospective data review of three cohorts of AFF40 program participants. Participant pre- and post-program data were analyzed (n=113, 2019; n=105, 2020; n=344, 2021). The intervention was self-directed, 40-day alcohol abstinence with social support. Changes in liver enzymes, cholesterol, vitamin B12, weight, body fat, and blood pressure were measured. Paired t-tests were used to compare pre- and post-program metrics.ResultsRetention rates for participation were 63% (113/179; 2019), 23% (105/449; 2020), and 86% (344/400; 2021), despite the SARS-CoV-2 pandemic in 2020 and 2021. Maximal average changes were - 9 mmHg in systolic blood pressure, -4.3 mmHg in diastolic blood pressure, and -5.7 pounds of weight (all p<0.0001). Liver enzymes decreased; alanine aminotransferase decreased by 5.6 U/L, aspartate transaminase by 4.8 U/L, and gamma glutamyl transferase by 8.7 U/L (all p<0.0001). Vitamin B12 increased by 54.6 pg/mL (p<0.01). Total cholesterol dropped by 15.8 mg/dL (p<0.0001).ConclusionParticipants in abstinence programming with social support improved liver enzymes, cholesterol, body fat, and other factors during a 40-day challenge.HighlightsPrograms for voluntary abstinence from alcohol have become popular around the world (Dry January, Sober October)Alcohol Free for 40, a post-Mardi Gras abstinence program, revealed significant reductions in blood pressure, weight, fat, liver enzymes, total cholesterol, and increased vitamin B12 in participants after just 40 daysProgram retention was high except in 2020 due to the SARS-CoV-2 pandemicDieticians and other healthcare practitioners can replicate Alcohol Free for 40 for individuals or groups who want to improve metrics described in this study
Cardiopulmonary exercise testing to evaluate post-acute sequelae of COVID-19 (“Long COVID”): a systematic review and meta-analysis
Authors: Durstenfeld Matthew S. , Sun Kaiwen , Tahir Peggy M. , Peluso Michael J. , Deeks Steven G. , Aras Mandar A. , Grandis Donald J. , Long Carlin S. , Beatty Alexis , Hsue Priscilla Y. 
Published: June 2022

AbstractImportanceReduced exercise capacity is commonly reported among individuals with Long COVID (LC). Cardiopulmonary exercise testing (CPET) is the gold-standard to measure exercise capacity to identify causes of exertional intolerance.ObjectivesTo estimate the effect of SARS-CoV-2 infection on exercise capacity including those with and without LC symptoms and to characterize physiologic patterns of limitations to elucidate possible mechanisms of LC.Data SourcesWe searched PubMed, EMBASE, and Web of Science, preprint severs, conference abstracts, and cited references in December 2021 and again in May 2022.Study SelectionWe included studies of adults with SARS-CoV-2 infection at least three months prior that included CPET measured peak VO2. 3,523 studies were screened independently by two blinded reviewers; 72 (2.2%) were selected for full-text review and 36 (1.2%) met the inclusion criteria; we identified 3 additional studies from preprint servers.Data Extraction and SynthesisData extraction was done by two independent reviewers according to PRISMA guidelines. Data were pooled with random-effects models.Main Outcomes and MeasuresA prioriprimary outcomes were differences in peak VO2(in ml/kg/min) among those with and without SARS-CoV-2 infection and LC.ResultsWe identified 39 studies that performed CPET on 2,209 individuals 3-18 months after SARS-CoV-2 infection, including 944 individuals with LC symptoms and 246 SARS-CoV-2 uninfected controls. Most were case-series of individuals with LC or post-hospitalization cohorts. By meta-analysis of 9 studies including 404 infected individuals, peak VO2was 7.4 ml/kg/min (95%CI 3.7 to 11.0) lower among infected versus uninfected individuals. A high degree of heterogeneity was attributable to patient and control selection, and these studies mostly included previously hospitalized, persistently symptomatic individuals. Based on meta-analysis of 9 studies with 464 individuals with LC, peak VO2was 4.9 ml/kg/min (95%CI 3.4 to 6.4) lower compared to those without symptoms. Deconditioning was common, but dysfunctional breathing, chronotropic incompetence, and abnormal oxygen extraction were also described.Conclusions and RelevanceThese studies suggest that exercise capacity is reduced after SARS-CoV-2 infection especially among those hospitalized for acute COVID-19 and individuals with LC. Mechanisms for exertional intolerance besides deconditioning may be multifactorial or related to underlying autonomic dysfunction.