bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome sequencing of three mesorhizobia isolated from northern Canada to identify genomic adaptations promoting nodulation in cold climates
Authors: Duan Yi Fan , Grogan Paul , Walker Virginia K , diCenzo George C 
Published: May 2022

ABSTRACTThe N2-fixing symbiosis between rhizobia and legumes is negatively impacted by numerous stresses, including low temperatures. To identify genomic features and biochemical pathways of rhizobia that could foster improved symbiotic function under low temperatures, we isolated and characterized three Mesorhizobium strains from legume nodules collected at two distant northern Canadian sites. Whereas the classical determinants of nodulation and nitrogen fixation are located on the chromosome of most mesorhizobia, whole genome sequencing revealed that these genes are on a large symbiotic megaplasmid in all three of the newly isolated strains. A pangenome-wide association study identified 25 genes putatively associated with mesorhizobia isolated from arctic or subarctic environments, with the genomic location of many of these genes implying a relationship with legume symbiosis. Phylogenetic and sequence analyses of the common nodulation genes revealed alleles that are highly conserved amongst mesorhizobia isolated from northern climates but uncommon in mesorhizobia isolated from similar plant hosts in other climatic regions, suggesting potential functional adaptive differences and the horizontal transfer of these alleles between northern rhizobia. We speculate that nod sequence divergence was driven by climatic factors, and that the encoded proteins may be particularly stable and/or active at low temperatures.
A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice
Authors: Gamble Mackenzie C. , Chuan Byron , Gallego-Martin Teresa , Shelton Micah A. , Puig Stephanie , O’Donnell Christopher P. , Logan Ryan W. 
Published: May 2022

AbstractRationaleSynthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations.ObjectivesTo determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes.MethodsElectroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice.ResultsAcute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice.ConclusionsChronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.
RT-RPA-Cas12a-based discrimination of SARS-CoV-2 variants of concern
Authors: Tang Guiyue , Zhang Zilong , Tan Wei , Long Fei , Sun Jingxian , Li Yingying , Zou Siwei , Yang Yujiao , Cai Kezhu , Li Shenwei , Wang Zhiyi , Liu Jiakun , Mao Guobing , Ma Yingxin , Zhao Guo-Ping , Tian Zhen-Gan , Zhao Wei 
Published: May 2022

AbstractTimely and accurate detection of SARS-CoV-2 variants of concern (VOCs) is urgently needed for pandemic surveillance and control. However, current methods are limited by the low sensitivity, long turn-around time or high cost. Here, we report a nucleic acid testing-based method aiming to detect and discriminate SARS-CoV-2 VOCs by combining RT-RPA and CRISPR-Cas12a detecting assays (RRCd). With a detection limit of 10 copies RNA/reaction, RRCd was validated in 204 clinical samples, showing 99% positive predictive agreement and 100% negative predictive agreement, respectively. Critically, using specific crRNAs, representatives of single nucleotide polymorphisms and small deletions in SARS-CoV-2 VOCs including N501Y, T478K and ΔH69-V70 were discriminated by RRCd, demonstrating 100% accuracy in clinical samples with Ct < 33. The method completes within 65 min and could offer visible results without using any electrical devices, which may facilitate point-of-care testing of SARS-CoV-2 and its variants.
Application of aptamer technology in enterobacteria and non-fermenters: literature review
Authors: Bes Taniela Marli , Cortês Farrel Marina , Santos Carlos , Sabino Ester Cerdeira , Costa Silvia Figueiredo 
Published: May 2022

AbstractAntimicrobial resistance has grown exponentially in the last decade and become a global health threat. The antibiotic resistance crisis has guided the scientific community to explore non-conventional interventions to target resistant bacteria. Development of new technologies, such as aptamers-based treatment and diagnosis, has shown to be promising with remarkable advantages over the past five years. This narrative review aims on what is already known regarding application of aptamer technology in enterobacteria and non-fermenters, and the prospects for future achievements. A systematic search of the English literature was performed on the 7th of December 2021 to identify papers on aptamer discovery, with a focus on gram negative isolates, published from January 01, 1993, to December 07, 2021, under the topics: (aptamer OR aptamers OR SELEX) AND (bacteria OR sepsis OR non-fermenter OR Enterobacteriaceae OR infection)). The reference lists of included articles were also searched, in addition to hand-searching of various relevant high-impact journals. Out of 2,474 articles, 30 experimental studies were recruited for review, and are chronologically described. Although the number of publications regarding development of aptamers to target these pathogenic agents has increased over the years, the recent publications are mostly around diagnostic devices manufactured using previously described aptamers. There have been less than one-third of the studies describing new and specific aptamers. From the 30 selected papers, 18 are regarding non-fermenters, seven approaching multi-species of bacteria and only five regarding a single enterobacteria. Even for the newly described aptamers, most of the published papers pertain to diagnostic aptamers and only seven focus on aptamers for therapeutics. The number of aptamers with strong and specific binding capacity are still limited. Improving the current SELEX and developing more APT remains the major hurdle for aptamer related studies.
Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing
Authors: Sahajpal Nikhil Shri , Mondal Ashis K , Fee Timothy , Hilton Benjamin , Layman Lawrence , Hastie Alex R , Chaubey Alka , DuPont Barbara R. , Kolhe Ravindra 
Published: May 2022

AbstractThe standard-of-care (SOC) diagnostic prenatal testing includes a combination of cytogenetic methods such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA) using either direct or cultured amniocytes or chorionic villi sampling (CVS). However, each technology has its limitations: karyotyping has a low resolution (>5Mb), FISH is targeted, and CMA does not detect balanced structural variants (SVs) or decipher complex rearrangements in the genome. These limitations necessitate the use of multiple tests, either simultaneously or sequentially to reach a genetic diagnosis. This long-standing prenatal testing workflow demonstrates the need for an alternative technology that can provide high-resolution results in a cost and time-effective manner. Optical genome mapping (OGM) is an emerging technology that has demonstrated its ability to detect all classes of SVs, including copy number variations (CNVs) and balanced abnormalities in a single assay, but has not been evaluated in the prenatal setting. This retrospective validation study analyzed 114 samples (including replicates), representing 94 unique and well-characterized samples that were received in our laboratory for traditional cytogenetic analysis with karyotyping, FISH, and/or CMA. Samples comprised 84 cultured amniocytes, and 10 phenotypically normal and cytogenetically negative controls. Six samples were run in triplicate to evaluate intra-run, inter-run, and inter-instrument reproducibility. Clinically relevant SVs and CNVs were reported using the Bionano Access software with standardized and built-in filtration criteria and phenotype-specific analysis. OGM was 100% concordant in identifying the 101 aberrations that included 29 interstitial/terminal deletions, 28 duplications, 26 aneuploidies, 6 absence of heterozygosity (AOH), 3 triploid genomes, 4 Isochromosomes, 1 translocation, and revealed the identity of 3 marker chromosomes, and 1 chromosome with additional material not determined by karyotyping. Additionally, OGM detected 64 additional clinically reportable SVs in 43 samples. OGM demonstrated high technical and analytical robustness and a limit of detection of 5% allele fraction for interstitial deletions and duplications, and 10% allele fraction for translocation and aneuploidy. This study demonstrates that OGM has the potential to identify unique genomic abnormalities such as CNVs, AOHs, and several classes of SVs including complex structural rearrangements. OGM has a standardized laboratory workflow and reporting solution that can be adopted in routine clinical laboratories and demonstrates the potential to replace the current SOC methods for prenatal diagnostic testing. We recommend its use as a first-tier genetic diagnostic test in a prenatal setting.
JBrowse Jupyter: A Python interface to JBrowse 2
Authors: Martinez Teresa De Jesus , Hershberg Elliot A. , Guo Emma , Stevens Garrett J , Diesh Colin , Xie Peter , Bridge Caroline , Cain Scott , Haw Robin , Buels Robert M. , Stein Lincoln D. , Holmes Ian H. 
Published: May 2022

AbstractMotivationJBrowse Jupyter is a package that aims to close the gap between Python programming and genomic visualization. Web-based genome browsers are routinely used for publishing and inspecting genome annotations. Historically they have been deployed at the end of bioinformatics pipelines, typically decoupled from the analysis itself. However, emerging technologies such as Jupyter notebooks enable a more rapid iterative cycle of development, analysis and visualization.ResultsWe have developed a package that provides a python interface to JBrowse 2’s suite of embeddable components, including the primary Linear Genome View. The package enables users to quickly set up, launch and customize JBrowse views from Jupyter notebooks. In addition, users can share their data via Google’s Colab notebooks, providing reproducible interactive views.AvailabilityJBrowse Jupyter is released under the Apache License and is available for download on PyPI. Source code and demos are available on GitHub at https://github.com/GMOD/jbrowse-jupyter.Contactihh@berkeley.edu
Analysis of the All of Us Research Program Researcher Workbench Workspaces
Authors: Kerawala Rhea P. , King Paula F. , Mayo Kelsey Ross , Vogel Julia Moore ,   the All of Us Research Program
Published: May 2022

ABSTRACTThe All of Us Research Program, through the All of Us Research Hub platform’s Researcher Workbench, provides researchers and citizen scientists with access to a broad dataset of surveys, electronic health records, physical measurements, genetic data, and Fitbit device wearable data. All of Us has a goal of recruiting a minimum of one million participants and aims to capture the diversity of individuals in the United States. The All of Us Research Hub platform includes a Research Projects Directory on its website, displaying researcher-provided descriptions of each active workspace on the Researcher Workbench. Inspired by the initial work completed by All of Us investigators in 2019, these workspace descriptions were analyzed with a new methodology. Genetic, methods and validation studies, and educational research purposes were associated with disease-focused research, as compared to non-disease focused research. Of all the population categories of interest, only race and ethnicity were associated with disease-focused research. Further categorization of the disease-focused workspaces revealed the top five disease categories: cardiovascular disease, brain and mental health disorders, cancer and benign tumors, diabetes, and immunology-related conditions. Athena OHDSI catalog terms were sorted and helped classify the workspaces by each disease category. Subcategory distribution for the cancer, genetic, and cardiovascular disease-related conditions was examined as well. This framework has the potential to be used for continued longitudinal analysis of the workspaces and continued learnings regarding the importance of disease-focused research in public health. Additionally, as workspace descriptions are created at project initiation, this can provide us with a leading-edge indication of researcher interest in the All of Us Research Program data.
“Puberty age gap”: New method of assessing pubertal timing and its association with mental health problems
Authors: Dehestani Niousha , Vijayakumar Nandita , Ball Gareth , Sina Mansour L. , Whittle Sarah , Silk Timothy J. 
Published: May 2022

AbstractPuberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed a new measure of pubertal timing using multiple pubertal features and nonlinear associations with age and investigated its association with mental health problems. Using the Adolescent Brain Cognitive Development (ABCD) cohort, we implemented three models of pubertal timing by predicting chronological age from i) observed physical development, ii) hormones (testosterone and dehydroepiandrosterone [DHEA]), and iii) a combination of the two, using a supervised machine learning method (n ∼9,900). Accuracy of the new models, and their associations with mental health problems were evaluated. The new pubertal timing measure performed better in capturing age variance compared to a commonly used method, and the physical measure accounted for more variance in mental health, such that earlier pubertal timing was associated with higher symptoms. This study demonstrates the utility for a new model of pubertal timing and suggests that physical maturation may play a predominant role in predicting mental health problems in early adolescence.
AI-based search for convergently expanding, advantageous mutations in SARS-CoV-2 by focusing on oligonucleotide frequencies
Authors: Ikemura Toshimichi , Iwasaki Yuki , Wada Kennosuke , Wada Yoshiko , Abe Takashi 
Published: May 2022

AbstractAmong mutations that occur in SARS-CoV-2, efficient identification of mutations advantageous for viral replication and transmission is important to characterize and defeat this rampant virus. Mutations rapidly expanding frequency in a viral population are candidates for advantageous mutations, but neutral mutations hitchhiking with advantageous mutations are also likely to be included. To distinguish these, we focus on mutations that appear to occur independently in different lineages and expand in frequency in a convergent evolutionary manner. Batch-learning SOM (BLSOM) can separate SARS-CoV-2 genome sequences according by lineage from only providing the oligonucleotide composition. Focusing on remarkably expanding 20-mers, each of which is only represented by one copy in the viral genome, allows us to correlate the expanding 20-mers to mutations. Using visualization functions in BLSOM, we can efficiently identify mutations that have expanded remarkably both in the Omicron lineage, which is phylogenetically distinct from other lineages, and in other lineages. Most of these mutations involved changes in amino acids, but there were a few that did not, such as an intergenic mutation.
Identifying the modification factors of exercise therapy on biomechanical load in patients with knee osteoarthritis: A systematic review and meta-analysis
Authors: Yokoyama Moeka , Iijima Hirotaka , Kubota Keisuke , Kanemura Naohiko 
Published: May 2022

AbstractObjectiveAs the progression of knee osteoarthritis (OA) is associated with large biomechanical loads, an optimally designed intervention is needed to prevent disease progression and symptoms. We aimed to investigate the effect of exercise therapy—the gold standard intervention—on biomechanical loads in patients with knee OA and identify its modification factors.DesignSystematic review and meta-analysisData sourcesPubMed, PEDro, and CINAHL; from study inception to May 2021Eligibility criteriaStudies evaluating the first peak knee adduction moment (KAM), peak knee flexion moment (KFM), maximal knee joint compression force (KCF), or co-contraction during walking before and after exercise therapy in patients with knee OARisk of BiasPEDro scale and NIH scale.ResultsAmong 11 RCTs and nine non-RCTs, 1100 patients with knee OA were included. First peak KAM (SMD 0.11; 95% CI: -0.03–0.24), peak KFM (SMD 0.13; 95% CI: -0.03–0.29), and maximal KCF (SMD 0.09; 95% CI -0.05–0.22) tended to increase. An increased first peak KAM was significantly associated with a larger improvement in knee muscle strength and WOMAC pain. The quality of evidence regarding the biomechanical loads was low-to-moderate according to the GRADE approach.ConclusionsExercise therapy tends to increase biomechanical loads. The improvement in pain and knee muscle strength may mediate the increase in first peak KAM, suggesting difficulty in balancing symptom relief and biomechanical load reduction. Therefore, exercise therapy may satisfy both aspects simultaneously when combined with biomechanical interventions, such as a valgus knee brace or insoles.FundingGrant-in-Aid for JSPS Research Fellows, 19J23020.RegistrationPROSPERO (CRD42021230966)
Questioning the axiom: Is hyperflexed scaphoid a common occurrence in South Indian population? - An observational study
Authors: Ashik Mohamed Nazir , Sethu Maithreyi , Rajappa Srinivasan 
Published: May 2022

AbstractBackgroundScapholunate angle SLA greater than 80° is one of the indicators of surgery for carpal instability. The normal SLA is between 30-60°. This is based on studies which were conducted several decades ago in the western part of the world. The SLA of Indian population has never been measured before. The knowledge of normal SLA in each population becomes imperative because it lays down the guidelines for surgical and non-surgical management of wrist fractures and instability in that population. In this study, we aim to measure the SLAs in asymptomatic volunteers of South Indian origin and compare the results with existing data.MethodsAn observational study was done in a tertiary care hospital in South India. Lateral radiographs of the wrist of asymptomatic volunteers were taken. The SLA was measured using a software in the PACS system. The relation of SLA to gender, age, left and right sides and handedness was compared. These were compared to pre-existing global data available on SLAs.ResultsThe SLA of the 202 radiographs with 47 males and 54 females were studied.The average SLA was 51.33° and the range was between 29° and 74°.The average SLA of males was 51.8° and females 50.8°. There was no significant difference between the two.Similarly, there was no significant difference between the SLA of right and left sides in right handed and left handed subgroups.However, there was an increasing trend in SLA among females with age. But no similar pattern was seen among males.Interestingly, 39 out of the 202 radiographs (19.3%) had a SLA above 60°.ConclusionThis study suggests the normal SLA in South Indians may be higher than the previously established reference values and serves as a pilot project and a reference for further studies on SLA.
Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development
Authors: Kaspi Antony , Hildebrand Michael S. , Jackson Victoria E. , Braden Ruth , van Reyk Olivia , Howell Tegan , Debono Simone , Lauretta Mariana , Morison Lottie , Coleman Matthew , Webster Richard , Coman David , Goel Himanshu , Wallis Mathew , Dabscheck Gabriel , Downie Lilian , Baker Emma K. , Parry-Fielder Bronwyn , Ballard Kirrie , Harrold Eva , Ziegenfusz Shaun , Bennett Mark F. , Robertson Erandee , Wang Longfei , Boys Amber , Fisher Simon E. , Amor David J. , Scheffer Ingrid E. , Bahlo Melanie , Morgan Angela T. 
Published: May 2022

AbstractChildhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we ascertained 70 unrelated probands with a clinical diagnosis of CAS and performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials.