bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer of cyclobutane pyrimidine dimer photolyase to chloroplasts forPoaceaesurvival under ultraviolet-B radiation
Authors: Otake Momo , Teranishi Mika , Komatsu Chiharu , Hara Mamoru , Yoshiyama Kaoru Okamoto , Hidema Jun 
Published: September 2023

AbstractCyclobutane pyrimidine dimer (CPD) photolyase (PHR), the primary enzyme for repairing the CPD induced by ultraviolet B (UV-B) radiation, is essential for plants living under sunlight. Rice CPD photolyase (OsPHR), is such a unique triple-targeting protein. The signal sequences required for its translocation to the nucleus or mitochondria are located in the C-terminal region but were yet to be identified for chloroplasts. Here, we identified sequences located in the N-terminal region, including the serine-phosphorylation site at position 7 of OsPHR, and found that OsPHR is transported/localized to chloroplasts via a vesicle transport system under the control of serine phosphorylation. However, the sequence identified in this study is only conserved in somePoaceaespecies and in many other plants, PHR does not localize to chloroplasts Therefore, we reasoned thatPoaceaespecies need the ability to repair CPD in the chloroplast genome to survive under sunlight and have acquired this new mechanism for chloroplast translocation.
Reliability, validity, and sensitivity of Japanese version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument: application to efficacy assessment of intravenous immunoglobulin administration
Authors: Matsuda Kazuki M , Sugimoto Eiki , Ako Yoshiaki , Kitamura Marie , Miyahara Mai , Kotani Hirohito , Norimatsu Yuta , Hisamoto Teruyoshi , Kuzumi Ai , Fukasawa Takemichi , Sato Shinichi , Yoshizaki Ayumi 
Published: September 2023

AbstractObjectiveThis study aimed to develop and assess the reliability, validity, and sensitivity of Japanese version of the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (GIT) Instrument 2.0 (the GIT score), as an evaluation tool for GIT symptoms in systemic sclerosis (SSc).MethodsJapanese version of the GIT score was constructed using the forward-backward method. The reliability and validity of this instrument were evaluated in a cohort of 38 SSc patients. Correlation analysis was conducted to assess the relationship between the GIT score and existing patient-reported outcome measures. Additionally, the sensitivity of the GIT score was examined by comparing GIT scores before and after intravenous immunoglobulin (IVIG) administration in 10 SSc-myositis overlap patients, as IVIG has recently demonstrated effectiveness in alleviating GIT symptoms of SSc.ResultsJapanese version of the GIT score exhibited internal consistency and a significant association with the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease. Furthermore, the total GIT score, as well as the reflux and distention/bloating subscales, displayed moderate correlations with the EQ-5D pain/discomfort subscale, Short Form-36 body pain subscale, and its physical component summary. Notably, following IVIG treatment, there was a statistically significant reduction in the total GIT score and most of the subscales.ConclusionWe firstly validated Japanese version of the GIT score in Japanese SSc patients in real-world clinical settings. This instrument holds promise for application in future clinical trials involving this patient population.Key messagesWhat is already known about this subject?Khanna et al. developed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (GIT) Instrument (the GIT score) to assess patient-reported GIT symptoms in individuals with systemic sclerosis (SSc).What does this study add?We have developed and established the reliability, validity, and sensitivity of the Japanese version of the GIT score in cohorts of Japanese individuals with SSc.How might this impact on clinical practice?This tool can effectively evaluate GIT manifestations in Japanese SSc patients in routine clinical settings, and potentially in clinical trial contexts.
Dimeric immunoglobulin A as a novel diagnostic marker of measles infection
Authors: Hanafiah Khayriyyah Mohd , Hiebert Joanne , Zubach Vanessa , Severini Alberto , Anderson David A. , Drummer Heidi E. 
Published: September 2023

AbstractDespite tremendous measles incidence reduction through universal vaccination, elimination efforts rely on improved surveillance. Detection of anti-measles immunoglobulin M (IgM) by ELISA is the standard laboratory diagnostic method. However, true infection is rare and seroconversion following MMR vaccination also generates IgM, which results in low positive predictive values of assays in elimination settings, thus necessitating confirmatory testing. Improved diagnostic tests for measles infection are a World Health Organization (WHO) research priority. We investigated whether dimeric immunoglobulin A (dIgA), the predominant antibody produced in mucosal immunity, may be a marker of recent or acute measles infection. We examined a serological panel of confirmed measles infection (anti-measles IgM positives, n=50), and non-measles infection with rubella (n=36), roseola (n=40), chikungunya/dengue/zika (n=41), parvovirus (n=35) and other fever-rash illness of unknown cause (n=37). Sera were examined on a Micrommune anti-measles IgM, Euroimmun anti-measles virus lysate (VL) and nucleoprotein (NP) IgM kits. Assays were then modified to detect dIgA using an in-house protocol based on a recombinant chimeric secretory component protein and anti-secretory component monoclonal antibody. We observed significantly higher levels of anti-measles VL dIgA in measles samples than non-measles controls (p<0.001), and there was low correlation with IgM (R2: 0.01, p value:0.487). Unlike IgM, dIgA reactive to measles NP was not detected in most samples. Comparable diagnostic potential of anti-measles dIgA (AUC 0.920 - 0.945) to anti-measles IgM (AUC 0.986 – 0.995), suggests that dIgA may be a new blood-based marker of acute measles, independent of IgM, which merits further investigation and optimization.
A clinical microscopy dataset to develop a deep learning diagnostic test for urinary tract infection
Authors: Liou Natasha , De Trina , Urbanski Adrian , Chieng Catherine , Kong Qingyang , David Anna L , Khasriya Rajvinder , Yakimovich Artur , Horsley Harry 
Published: September 2023

AbstractUrinary tract infection (UTI) is a common disorder. Its diagnosis can be made by microscopic examination of voided urine for cellular markers of infection. This manual technique is technically difficult, time-consuming and prone to inter-observer errors. The application of computer vision to this domain has been slow due to the lack of a clinical image dataset from UTI patients. We present an open dataset containing 300 images and 3,562 manually annotated urinary cells labelled into seven classes of clinically significant cell types. It is an enriched dataset acquired from the unstained and untreated urine of patients with symptomatic UTI using a simple imaging system. We demonstrate that this dataset can be used to train a Patch U-Net, a novel deep learning architecture with a random patch generator to recognise urinary cells. Our hope is that with this dataset UTI diagnosis will be made possible in nearly all clinical settings by using a simple imaging system which leverages advanced machine learning techniques.
Chinese Herbal Medicine Treatment for Alzheimer’s Disease Inpatients in China: Alternative or Complement to Conventional Medicine, a Cross-sectional Study
Authors: Chen Xiaoping , Yan Hao , Nicholas Stephen , Maitland Elizabeth , Huang Zhengwei , Ma Yong , Shi Xuefeng 
Published: September 2023

AbstractObjectivesChinese herbal medicine (CHM), a typical type of complementary and alternative medicine (CAM), has been used to treat Alzheimer’s disease (AD) with costs covered by China’s urban basic medical insurance. Previous studies have demonstrated the treatment effectiveness of CHM for intractable disease and CHM’s ability to reduce medical costs. There has been no research exploring the impact of CHM on AD inpatient hospital costs or whether CHM is a complement or alternative to conventional medicine treatments. We compared the medical costs of AD inpatients, CHM users, and non-CHM users to analyze whether CHM has increased or decreased the AD inpatient costs, to assess whether CHM was an alternative or complementary treatment.MethodsOur cross-sectional research was based on a 5% random sample from the 2010 to 2016 Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) claim data, yielding information on 1507 urban AD inpatients. Wilcoxon rank sum test and chi square test were applied to the medical cost data with an abnormal distribution. To control for confounding factors, such as demographic (age and sex) and medical costs, the influence between CHM costs and conventional medicine costs were analyzed by quantile regression.ResultsCHM users accounted for 79.83% (1203/1507) of the total inpatients. The median inpatient cost of CHM users was RMB13293.95 (USD2084.49), which was higher than non-CHM users’ (RMB8428.10/USD1321.53, P<0.001). The median CHM cost was RMB721.00 (USD113.05). Positive correlations between CHM users and CHM costs were found after controlling for confounder variables (Coef.=0.09, P<0.001).ConclusionDuring 2010-2016, nearly 80% of AD inpatients in our sample used CHM. Participation in CHM increased the total inpatient costs, pharmacy costs, and conventional medicine costs of AD inpatients over non-CHM users. CHM mainly plays a complementary or less alternative role to conventional medicine for AD treatment.
Optimal Social Group Size in Spotted Hyaenas (Crocuta crocuta): Insights into a Multilevel Society
Authors: Dunbar R.I.M. 
Published: September 2023

AbstractThe spotted hyaena lives in unusually large social groups for a carnivore. Since the infertility trap normally limits the size of social groups in mammals, it seems likely that this species has evolved some way of mitigating the stresses involved. In primates, this usually takes the form of female-female alliances, often embedded in multilevel social systems. I show (1) that the distribution of hyaena clan sizes is multimodal, with a fractal scaling close to 3 and a base unit of 12-15 individuals (3-5 reproductive females) and (2) that fertility is a trade off between the benefits of having more males in the group and the costs incurred by having more females, with 4-5 as the limit on the number of females that can live together without their reproductive rates falling below the demographic replacement rate. I present evidence that females buffer themselves against the infertility trap by forming matrilineal alliances that in turn create a multilevel structure. In this respect, hyaena resemble cercopithecine primates in using social strategies to enable animals to live in larger groups than they would otherwise be able to do.
Use of CRISPR interference for efficient and rapid gene inactivation inFusobacterium nucleatum
Authors: Zhou Peng , G C Bibek , Stolte Flynn , Wu Chenggang 
Published: September 2023

ABSTRACTGene inactivation via creating in-frame deletion mutations inFusobacterium nucleatumis time-consuming, and most fusobacterial strains are genetically intractable. Addressing these problems, we introduced a riboswitch-based inducible CRISPRi system. This system employs the nuclease-inactiveStreptococcus pyogenesCas9 protein (dCas9), specifically guided to the gene of interest by a constantly expressed single guide RNA (sgRNA). Mechanistically, this dCas9-sgRNA complex serves as an insurmountable roadblock for RNA polymerase, thus repressing the target gene transcription. Leveraging this system, we first examined two non-essential genes,ftsX,andradD, pivotal for fusobacterial cytokinesis and coaggregation. Upon adding the inducer, theophylline,ftsXsuppression caused filamentous cell formation akin to chromosomalftsXdeletion, while targetingradDsignificantly reduced RadD protein levels, abolishing coaggregation. The system was then extended to probe essential genesbamAandftsZ, vital for outer membrane biogenesis and cell division. Impressively,bamAsuppression disrupted membrane integrity and bacterial separation, stalling growth, whileftsZ-targeting yielded elongated cells in broth with compromised agar growth. Further studies onF. nucleatumclinical strain CTI-2 andFusobacterium periodonticumrevealed reduced indole synthesis when targetingtnaA. Moreover, silencingclpBinF. periodonticumdecreased ClpB, increasing thermal sensitivity. In summary, our CRISPRi system streamlines gene inactivation across various fusobacterial strains.IMPORTANCEHow can we effectively investigate the gene functions inFusobacterium nucleatum, given the dual challenges of gene inactivation and the inherent genetic resistance of many strains? Traditional methods have been cumbersome and often inadequate. Addressing this, our work introduces a novel inducible CRISPRi system in which dCas9 expression is controlled at the translation level by a theophylline-responsive riboswitch unit, and sgRNA expression is driven by the robust, constitutiverpsJpromoter. This approach simplifies gene inactivation in the model organism (ATCC 23726) and extends its application to previously considered resistant strains like CTI-2 andFusobacterium periodontium. With CRISPRi’s potential, it is a pivotal tool for in-depth genetic studies into fusobacterial pathogenesis, potentially unlocking targeted therapeutic strategies.
Biofoundry-scale DNA assembly validation using cost-effective high-throughput long read sequencing
Authors: Vegh Peter , Donovan Sophie , Rosser Susan , Stracquadanio Giovanni , Fragkoudis Rennos 
Published: September 2023

AbstractBiofoundries are automated high-throughput facilities specialising in the design, construction and testing of engineered/synthetic DNA constructs (plasmids), often from genetic parts. A critical step of this process is assessing the fidelity of the assembled DNA construct to the desired design. Current methods utilised for this purpose are restriction digest or PCR followed by fragment analysis, and sequencing. The Edinburgh Genome Foundry (EGF) has recently established a single-molecule sequencing quality control step using the Oxford Nanopore sequencing technology, along with a companion Nextflow pipeline and a Python package to perform in-depth analysis and generate a detailed report. Our software enables biofoundry scientists and end-users to rapidly analyse sequencing data, without specialised bioinformatics knowledge. In conclusion, we have created a laboratory and software protocol that validates assembled, cloned or edited plasmids, using Nanopore long reads, which can serve as a useful resource for the genetics, synthetic biology and sequencing communities.Author informationAll authors contributed to the design of the sequencing quality control step and pipeline, and the preparation of the manuscript. P.V. wrote the manuscript, designed and implemented the bioinformatics pipeline and interpreted results. S.D. wrote the manuscript, implemented the laboratory protocol and interpreted results. G.S. designed the bioinformatics pipeline. R.F. wrote the manuscript and contributed to the design of the laboratory protocol and pipeline.Address: Edinburgh Genome Foundry (University of Edinburgh), Michael Swann Building, Max Born Crescent, Edinburgh, EH9 3BF, United KingdomGraphical abstract
Site-Specific Crosslinking Reveals Phosphofructokinase-L Inhibition Drives Self-Assembly and Attenuation of Protein Interactions
Authors: Sivadas Athira , McDonald Eli Fritz , Shuster Sydney O. , Davis Caitlin M. , Plate Lars 
Published: September 2023

ABSTRACTPhosphofructokinase is the central enzyme in glycolysis and constitutes a highly regulated step. The liver isoform (PFKL) compartmentalizes during activation and inhibitionin vitroandin vivorespectively. Compartmentalized PFKL is hypothesized to modulate metabolic flux consistent with its central role as the rate limiting step in glycolysis. PFKL tetramers self-assemble at two interfaces in the monomer (interface 1 and 2), yet how these interfaces contribute to PFKL compartmentalization and drive protein interactions remains unclear. Here, we used site-specific incorporation of noncanonical photocrosslinking amino acids to identify PFKL interactors at interface 1, 2, and the active site. Tandem mass tag-based quantitative interactomics reveals interface 2 as a hotspot for PFKL interactions, particularly with cytoskeletal, glycolytic, and carbohydrate derivative metabolic proteins. Furthermore, PFKL compartmentalization into puncta was observed in human cells using citrate inhibition. Puncta formation attenuated crosslinked protein-protein interactions with the cytoskeleton at interface 2. This result suggests that PFKL compartmentalization sequesters interface 2, but not interface 1, and may modulate associated protein assemblies with the cytoskeleton.
Systematic Perturbation of Thousands of Retroviral LTRs in Mouse Embryos
Authors: Yang Jian , Cook Lauryn , Chen Zhiyuan 
Published: September 2023

AbstractIn mammals, many retrotransposons are de-repressed during zygotic genome activation (ZGA). However, their functions in early development remain elusive largely due to the challenge to simultaneously manipulate thousands of retrotransposon insertions in embryos. Here, we employed epigenome editing to perturb the long terminal repeat (LTR) MT2_Mm, a well-known ZGA and totipotency marker that exists in ∼2667 insertions throughout the mouse genome. CRISPRi robustly repressed 2485 (∼ 93%) MT2_Mm insertions and 1090 (∼55%) insertions of the closely related MT2C_Mm in 2-cell embryos. Remarkably, such perturbation caused down-regulation of hundreds of ZGA genes at the 2-cell stage and embryonic arrest mostly at the morula stage. Mechanistically, MT2_Mm/MT2C_Mm primarily served as alternative ZGA promoters activated by OBOX proteins. Thus, through unprecedented large-scale epigenome editing, we addressed to what extent MT2_Mm/MT2C_Mm regulates ZGA and preimplantation development. Our approach could be adapted to systematically perturb retrotransposons in other mammalian embryos as it doesn’t require transgenic animals.
A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N=221,127)
Authors: Pan Qi , Cai Tengda , Veluchamy Abi , Hebert Harry L , Zhu Peixi , Haque Mainul , Dottorini Tania , Colvin Lesley A , Smith Blair H , Meng Weihua 
Published: September 2023

AbstractHip pain is a common musculoskeletal complaint that leads many people to seek medical attention. Approximately 14.3% of the population aged 60 and above have reported substantial hip pain persisting for most days over a six-week period. Our research aimed to identify the genetic variants associated with hip pain by conducting a genome-wide association study (GWAS) on the hip pain phenotype, utilizing data from 221,127 participants from the UK Biobank cohort. We found 7 different loci associated with hip pain, with the most significant SNP being rs77641763, which is situated within theEXD3gene (pvalue = 2.20 x 10-13). We utilized publicly available summary statistics from a previous GWAS meta-analysis on hip osteoarthritis as a replication cohort. Two loci (rs12042579 and rs9597759) were suggestively replicated. Further analysis of tissue expression revealed significant associations between brain tissues and hip pain. Additionally, we found strong genetic correlations between hip pain and other pain phenotypes. This research has therefore identified multiple genetic loci associated with hip pain, which may potentially pave the way for medical interventions that can alleviate the burden of hip pain.
Effect of Acute Kidney Injury on In-hospital Mortality in Non-critical Medical Patients in a Sub-Saharan African Country
Authors: Mekonnen Nahom Desalegn , Leulseged Tigist Workneh , Mera Nebiat Adane , Berhe Helen Surafeal , Beyene Anteneh Abera , Yemaneberhan Kidus Haile , Hassen Buure Ayderuss , Abriha Feven Negasi , Getachew Lidiya Zenebe , Habtezgi Birukti Gebreyohannes 
Published: September 2023

ABSTRACTBackgroundAKI is a major global public health problem that affects millions of people each year and has been linked to poor prognosis in critically ill patients. As being a common complication in hospitalized patients, understanding its effect on non-critical patients is equally crucial, but there is a paucity of knowledge in this area, particularly in Africa. Therefore, the aim of this study was to assess the effect of AKI on in-hospital morality in non-critical medical patients admitted to a large tertiary hospital in Ethiopia.MethodsA retrospective cohort study of 319 non-critical medical patients (113 with AKI and 206 without AKI) admitted between July 2019 and January 2022 was conducted. The in-hospital mortality rate was estimated using incidence density with a 95% CI. The two groups’ comparability was assessed using chi-square and Fisher’s exact tests. The effect of AKI on in-hospital mortality was analyzed using a log binomial regression model with a p-value of ≤ 0.05 determining a significant effect, and the effect was measured using adjusted relative risk (ARR) and its 95% CI.ResultsThe in-hospital mortality rate was 6.8 per 1000 person-days of observation (95% CI=4.9-9.4). AKI did not show a significant effect on in-hospital mortality (ARR = 0.72, 95% CI=0.30-1.71, p=0.450). On the other hand, sepsis was found to be a significant predictor, with over a threefold increase in risk of in-hospital mortality (ARR=3.47, 95% CI=1.60-7.52, p=0.002).ConclusionWith early detection and proper management, non-critical patients with AKI can have a similar prognosis as those without AKI, unlike the critical setting. However, sepsis was found to be a significant predictor of in-hospital mortality implying the need to pay special attention to the management of these cases.
Comparative single-cell regulome reveals evolutionary innovations in neural progenitor cells during primate corticogenesis
Authors: Liu Yuting , Luo Xin , Sun Yiming , Chen Kaimin , Hu Ting , You Benhui , Xu Jiahao , Zhang Fengyun , Meng Xiaoyu , Li Xiang , He Xiechao , Li Cheng , Su Bing 
Published: September 2023

AbstractThe cellular and genetic mechanism underlying the human-specific features of cortex development remains unclear. We generated a cell-type resolved atlas of transcriptome and regulome of the developing macaque and mouse prefrontal cortex, and conducted evolutionary analyses with the published complementary human data. We discovered a primate-specific expansion of two neural progenitor subclasses, glia-committed radial glia (RG) and truncated RG. Specifically, the human neural progenitors show extensive transcriptional rewiring in the growth factor and extracellular matrix pathways. Expression of the human-specific progenitor markerITGA2in the cortex of fetal mouse promotes progenitor proliferation and an increased upper-layer neuron proportion. We demonstrate that these transcriptional divergences are primarily driven by the activity changes of the distal regulatory elements in the genome. Markedly, the chromatin regions with human-gained accessibility enrich the human-fixed sequence changes, as well as sequence polymorphisms associated with intelligence and neuropsychiatric disorders. Our results uncover evolutionary innovations in neural progenitors and gene regulatory mechanism during primate cortex evolution.