bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning enables reliable and comprehensive profiling of invertible promoters in microbes
Authors: Wen Jiejie , Zhang Haobo , Chu Dongliang , Chen Xiaoke , Li Yuxue , Liu Guanxi , Zhang Yuhao , Ning Kang 
Published: October 2023

AbstractInvertible promoters (invertons) are regulatory elements found in bacteria, with inverted repeat sequences at both ends, leading to alternating changes in the expression of the regulated genes. Since invertons were present in more than 20% of bacterial genomes, while they regulated more than 5% of genes in these genomes, they are of pivotal importance for microbial functional dynamics especially when under stress. However, the prevalence of invertons, as well as the full spectrum of gene functions regulated by them, remain poorly understood. In this study, we developed DeepInverton, a deep learning model capable of accurately identifying novel inverton sequences without sequencing reads, which could profile inverton sequences from large genomic and metagenomic datasets. We conducted a pan-genomic and pan-metagenomic analysis of invertons on 68,969 bacterial genomes and 8,516 metagenome samples, resulting in a comprehensive overview of more than 200,000 nonredundant invertons and their regulated gene functional patterns. This result suggests that invertons, as a key player for bacterial adaptation to environmental stresses, are prevalent in bacterial genomes. Among the genomes analyzed, we observed a profound enrichment of invertons in pathogen such asBordetella pertussis, and discovered a significant increase of inverton enrichment rates in strains associated with recent pertussis outbreaks, as well as novel evolving strains, unveiling a hidden link between the evolution ofBordetella pertussisand its inverton enrichment. We also utilized DeepInverton to explore inverton profiles mong human and marine metagenomes. Results revealed an unprecedented diversity of functional genes regulated by invertons, including antimicrobial resistance, biofilm formation and flagella, indicating their potential role in facilitating environmental adaptation. Thein vitroexperiments have confirmed the functions of tens of novel invertons that we have identified. Overall, we developed the DeepInverton model for exploration of invertons at unprecedented scale, which enabled our comprehensive profiling of invertons and their regulated genes. The comprehensive inverton profiles have deepen our understanding of invertons at pan-genome and metagenome scale, and could enabled a broad spectrum of inverton-related applications in microbial ecology and synthetic biology.
Complement dysregulation is a predictive and therapeutically amenable feature of long COVID
Authors: Baillie Kirsten , Davies Helen E , Keat Samuel B K , Ladell Kristin , Miners Kelly L , Jones Samantha A , Mellou Ermioni , Toonen Erik J M , Price David A , Morgan B Paul , Zelek Wioleta M 
Published: October 2023

ABSTRACTBackgroundLong COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID.MethodsWe quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/gender/infection/vaccine-matched patients with long COVID.FindingsMarkers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785.ConclusionsThese findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID.FundingThis work was funded by the National Institute for Health Research (COV-LT2-0041), the PolyBio Research Foundation, and the UK Dementia Research Institute.
A calibration protocol for soil-crop models
Authors: Wallach Daniel , Buis Samuel , Seserman Diana-Maria , Palosuo Taru , Thorburn Peter , Mielenz Henrike , Justes Eric , Kersebaum Kurt-Christian , Dumont Benjamin , Launay Marie , Seidel Sabine Julia 
Published: October 2023

AbstractProcess-based soil-crop models are widely used in agronomic research. They are major tools for evaluating climate change impact on crop production. Multi-model simulation studies show a wide diversity of results among models, implying that simulation results are very uncertain. A major path to improving simulation results is to propose improved calibration practices that are widely applicable. This study proposes an innovative generic calibration protocol. The two major innovations concern the treatment of multiple output variables and the choice of parameters to estimate, both of which are based on standard statistical procedure adapted to the particularities of soil-crop models. The protocol performed well in a challenging artificial-data test. The protocol is formulated so as to be applicable to a wide range of models and data sets. If widely adopted, it could substantially reduce model error and inter-model variability, and thus increase confidence in soil-crop model simulations.
A genetic screen for dominant chloroplast reactive oxygen species signaling mutants reveals life stage-specific singlet oxygen signaling networks
Authors: Lemke Matthew D. , Woodson Jesse D. 
Published: October 2023

AbstractPlants employ intricate molecular mechanisms to respond to abiotic stresses, which often lead to the accumulation of reactive oxygen species (ROS) within organelles such as chloroplasts. Such ROS can produce stress signals that regulate cellular response mechanisms. One ROS, singlet oxygen (1O2), is predominantly produced in the chloroplast during photosynthesis and can trigger chloroplast degradation, programmed cell death (PCD), and retrograde (organelle-to-nucleus) signaling. However, little is known about the molecular mechanisms involved in these signaling pathways or how many different signaling1O2pathways may exist. TheArabidopsis thaliana plastid ferrochelatase two(fc2) mutant conditionally accumulates chloroplast1O2, makingfc2a valuable genetic system for studying chloroplast1O2-initiated signaling. Here, we have used activation tagging in a new forward genetic screen to identify eight dominantfc2activation-tagged (fas) mutations that suppress chloroplast1O2-initiated PCD. Whilefc2 fasmutants all block1O2-triggered PCD in the adult stage, only twofc2 fasmutants block such cellular degradation at the seedling stage, suggesting that life-stage-specific1O2-response pathways exist. In addition to PCD,fasmutations generally reduce1O2-induced retrograde signals. Furthermore,fasmutants have enhanced tolerance to excess light, a natural mechanism to produce chloroplast1O2. However, general abiotic stress tolerance was only observed in onefc2 fasmutant (fc2 fas2). Together, this suggests that plants can employ general stress tolerance mechanisms to overcome1O2production but that this screen was mostly specific to1O2signaling. We also observed that salicylic acid (SA) and jasmonate (JA) stress hormone response marker genes were induced in1O2-stressedfc2and generally reduced byfasmutations, suggesting that SA and JA signaling is correlated with active1O2signaling and PCD. Together, this work highlights the complexity of1O2signaling by demonstrating that multiple pathways may exist and introduces a suite of new1O2signaling mutants to investigate the mechanisms controlling chloroplast-initiated degradation, PCD, and retrograde signaling.
White matter integrity and its association with amyloid-PET and serum NfL in healthyAPOE4homozygotes, heterozygotes and non-carries
Authors: Tato-Fernández Claudia , Ekblad Laura L. , Pietilä Elina , Saunavaara Virva , Helin Semi , Parkkola Riitta , Zetterberg Henrik , Blennow Kaj , Rinne Juha O. , Snellman Anniina 
Published: October 2023

AbstractExcept for aging,APOE ε4allele (APOE4) is the most important risk factor for sporadic Alzheimer’s disease.APOE4carriers may have reduced capacity to recycle lipids, resulting in reduced white matter integrity. Here, we evaluated if white matter impairment measured by diffusion tensor imaging (DTI) differs between healthy individuals with different number ofAPOE4alleles and if white matter impairment associates with brain beta-amyloid (Aβ) load and serum levels of neurofilament light chain (NfL). We studied 96 participants (APOE4/4,N= 20;APOE4/3,N= 39;APOE3/3,N= 37; mean age 70.7 (SD 5.22) years, 63% females) with brain MRI including a DTI sequence (N = 96), Aβ-PET (N = 89) and a venous blood sample for serum NfL concentration measurement (N = 88). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) in sixa priori-selected white matter regions-of-interest (ROIs) were compared between the groups using ANCOVA, with sex and age as covariates. A voxel-weighted average of FA, MD, RD and AxD was calculated for each subject, and correlations with Aβ-PET and NfL levels were evaluated.APOE4/4carriers exhibited higher MD and higher RD in the body of corpus callosum thanAPOE4/3(p = 0.0053 and p = 0.0049, respectively) andAPOE3/3(p = 0.026 and p = 0.042).APOE4/4carriers had higher AxD thanAPOE4/3(p = 0.012) andAPOE3/3(p = 0.040) in the right cingulum adjacent to cingulate cortex. In the total sample, composite MD, RD and AxD positively correlated with cortical Aβ load (r = 0.26 to 0.33, p < 0.013 for all) and with serum NfL concentrations (r = 0.31 to 0.36, p < 0.0028 for all). In conclusion, reduced white matter integrity was detected in cognitively unimpairedAPOE4/4homozygotes compared toAPOE4/3andAPOE3/3carriers and reduced white matter integrity correlated with biomarkers of Alzheimer’s disease and neurodegeneration. White matter impairment seems to be an early phenomenon in the Alzheimer’s disease pathologic process inAPOE4/4homozygotes.HighlightsCognitively normal elderlyAPOE4homozygotes showed impaired white matter integrityAPOE4homozygotes showed higher diffusivity in corpus callosum and right cingulumMD, RD and AxD correlate with amyloid load assessed by PET inAPOE4carriersMD, RD and AxD correlate with serum neurofilament light chain inAPOE4carriersWhite matter impairment may be an early phenomenon in the AD pathologic process
ANALYZING THE PATTERN OF USE OF ANTIBIOTICS IN A GHANAIAN DISTRICT HOSPITAL, ACROSS TWO DIFFERENT YEARS, USING THE WHO AWARE CLASSIFICATION
Authors: Opoku-Agyeman Kwame , Forson David , Acheampong Gerald Anim , Addo Daniel , Akwasi Thomas Afrifa , Asamoah Yaw Asiamah , Prince Ayim Britwum , Baffour Adade-Boateng Kyei , Frimpong Prince Boakye 
Published: October 2023

AbstractBackgroundThere has been an increment in the resistance of microorganisms to various antibiotics used in regional hospitals in the Ashanti region of Ghana and the country. This has led to difficulty in selecting agents to treat patients without the associated increment in side effects, the astronomical increase in the cost of medical care and a longer duration of hospitalization. In this study, we analyze the pattern of antibiotic use in a district hospital using the WHO AWaRe recommendation.ObjectivesTo ascertain the general pattern of antibiotic use with reference to the Access, Watch and Reserve Classes using the selected parameters (year of visit and patient demographics) and to confirm if the standard set by the WHO with respect to Access Class antibiotics is met.MethodFiles of patients, in 2021 and 2022, were systematically sampled from the database of SDA Hospital - Kwadaso (the hospital involved), and data concerning the visits for which antibiotics were administered were extracted to carry out the analysis required. The data extracted included the year of visit, demographics of the patients involved (patient status, age and sex) and the antibiotics that were administered.ResultsThis study seeks to ascertain the distribution of antibiotics used across the two years in the hospital of interest using the 2021 WHO AWaRe (Access, Watch and Reserve Antibiotics) Classification. Ultimately, the value, in percentage, of the distribution of the antibiotics used in the Access class will be compared to the target of at least 60% of the total antibiotic consumption being Access group antibiotics as recommended by WHO.
Early life factors associated with childhood trajectories of violence among the Birth to Twenty-Plus Cohort in Soweto, South Africa
Authors: Muchai Lilian , Naicker Sara , Kagura Juliana 
Published: October 2023

AbstractViolence against children (VAC) has devastating and long-term negative consequences on individuals’ and society’s health, social and economic well-being. There is limited research on the life course experience of VAC, especially in Africa. This study aimed to identify sub-groups of physical & sexual violence victimization patterns separately in childhood, and evaluate early life factors predicting violence trajectories. This study used data from ages 5 to 18 years from the ongoing prospective Birth to Twenty Plus cohort (Bt20+). Children with data on physical and sexual violence in at least 2-time points between 5 and 18 years were included in the analyses. Group-based trajectory modelling was employed to identify groups of children with similar patterns of violence over time, while multivariable logistic regression was used to identify early life factors associated with violence trajectory group membership. Separately, two trajectory groups of physical violence (adolescent limited (65.1%) and chronic increasing (34.9%)) and sexual violence (adolescent limited (74.1%) and late increasing (25.9%)) victimization were identified. Early life factors associated with a higher risk of chronic increasing trajectory group membership, after adjusting for covariates, were being male (aOR 1.67, 95% CI 1.31; 2.10) and having a mother with at least secondary education compared to higher education (aOR 1.73, 95% CI 1.08; 2.76). In addition, residing in middle, compared to low, socioeconomic households (aOR 0.68, 95% CI 0.50; 0.92) was protective against membership in this group. Residing in high compared to low socioeconomic households, was the only early life factor with marginally significant (aOR 0.63, 95% CI 0.42; 0.95) association with membership in the late-increasing sexual violence victimization trajectory group. In conclusion, children follow different violence victimization trajectories over childhood. Identifying early life factors predicting violence trajectories provides key prevention intervention areas that can mitigate children’s violence experience.
Unlocking the Potential of Genetic Research in Pulmonary Arterial Hypertension: Insights from Clinicians, Researchers and Study Team
Authors: Swietlik Emilia M , Fay Michaela , Morrell Nicholas W 
Published: October 2023

AbstractBackgroundWhile genetics has been incorporated into various subspecialties of medicine for some time, the significance of genetic research and testing in understanding the fundamental mechanisms of Pulmonary Arterial Hypertension (PAH) and formulating effective treatment approaches has only recently come to the forefront. We aimed to explore how attitudes toward genetic research among clinical and research teams impacted the engagement in genetic research and the integration of genetic insights into clinical practice.MethodsParticipants were selected from the National Institute for Health Research BioResource Rare Diseases study (NBR) and the Cohort study of idiopathic and heritable PAH (the PAH Cohort), representing a range of roles, ages, genders, and mutation statuses. We conducted a total of 53 semi-structured interviews and focus groups involving a total of 63 patients, clinicians, and researchers from nine UK PH centres. Following the principles of Grounded Theory, interview transcripts were thematically coded by two authors using MAXQDA (2022) software. In this paper, we focus on the researchers’, clinicians’ and study team’s perspectives.ResultsFrom the interview data, several key themes emerged, ranging from study design, recruitment and consent procedures to the return of individual genetic results. Additionally, participants reflected on both the successes of these studies and the future directions of genetic research. The analysis highlighted the critical importance of fostering collaborative networks firmly rooted in existing clinical and research infrastructure in rare disease study setups. Furthermore, the significance of trust-building, personalised communication, and transparency among stakeholders was underscored. The study offered valuable insights into the motivating and hindering factors to participant recruitment and consent procedures. Lastly, the findings gathered from processes surrounding the return of individual genetic results, genetic counselling, and the recruitment of relatives provided invaluable lessons regarding the integration of genetics into clinical practice.ConclusionsThis in-depth analysis yields a crucial understanding of attitudes to genetic research among various stakeholders and sheds light on the complexities of genetic research and the evidence-practice gap.
Outcomes and Management When Using High-sensitivity Versus Conventional Cardiac Troponin in Patients With Chest Pain: A Meta-analysis
Authors: Pilapil John Christopher A. , Cheng Paula Victoria Catherine Y. , Alad Paul Anthony O. , Aherrera Jaime Alfonso M. 
Published: October 2023

ABSTRACTBackgroundCardiac troponin (cTn) measurement is pivotal in diagnosing and managing chest pain. High-sensitivity cTn (hs-cTn) assays are slowly supplanting conventional cardiac troponin (c-cTn) use, allowing earlier identification of high-risk patients and diagnosis of myocardial infarction (MI). This improved sensitivity is said to come at the cost of reduced specificity for MI. However, there is a paucity of data regarding the exact impact of this change in patient management and outcomes.ObjectivesTo compare outcomes and management of patients with chest pain when using hs-cTn versus c-cTn.MethodsWe conducted a systematic search of studies in all languages across various databases. Inclusion criteria for studies were (1) observational or randomized trials, (2) included adult patients presenting with chest pain, (3) use of hs-cTn or c-cTn in diagnosis, (3) reported data on any of the pre-defined outcomes. The primary outcome was all-cause mortality and secondary outcomes were major adverse cardiovascular events (MACE), MI following index admission, coronary angiography, and revascularization. Study quality was appraised using the Cochrane Tool for Assessing Risk of Bias for randomized trials and the Newcastle-Ottawa Quality Assessment scale for observational studies. Outcomes were analyzed using Review Manager (RevMan) 5.3, employing Mantel-Haenszel analysis of random effects to compute for relative risk and odds ratio.ResultsPooled analysis from 5 studies showed that among patients with chest pain, those for whom hs-cTn over c-cTn was used had no difference in all-cause mortality (RR 1.01, 95% CI 0.92-1.12, p=0.82, I2=0%), a significant decrease in MI (RR 0.74, 95% CI 0.63-0.87, p=0.0003) and a trend towards increase in MACE (RR 1.08, 95% CI 1.00-1.16, p=0.04, I2=0%). They were more likely to undergo coronary angiogram (OR 1.52, 95% CI 1.02-2.28, p=0.04) and revascularization (OR 1.34, 95% CI 1.03-1.75, p=0.03).ConclusionUse of hs-cTn over conventional cTn led to higher rates of coronary angiography and revascularization. While there was significant reduction in myocardial infarction, there was no reduction in all-cause mortality and even a trends towards increased MACE.
Factors influencing the delayed presentation of patients with large vessel occlusion in acute ischemic stroke
Authors: Hong Gan-Ji , Zeng Shao-Hui , Yi Ting-Yu , Wu Yan-Min , Lin Ding-Lai , Pan Zhi-Nan , Zheng Xiu-Fen , Lin Xiao-Hui , Chen Rong-Cheng , Zeng Li-San , Ye Jin-hua , Chen Wen-Huo 
Published: October 2023

AbstractObjectiveThe benefit of treatment for patients with large vessel occlusion (LVO) in acute ischemic stroke (AIS) is associated with timely access to reperfusion therapy. This study aimed to analyze the factors associated with delayed access to medical attention among patients with AIS-LVO.MethodsPatients with acute ischemic stroke admitted to the cerebrovascular intervention department of Zhangzhou Hospital, Fujian Province, China, from September 1, 2020 to September 1, 2022, were enrolled in this study. Patients with AIS-LVO were divided into two groups based on whether they visited the hospital for more than 24 hours. Demographic data, NIHSS scores, clinical and radiological data, and in-hospital flow time were collected. Differences between the two groups were analyzed, and univariate and multivariate analyses were performed to identify factors associated with delayed presentation.ResultsA total of 1396 patients were included in the study, with 218 in the delayed group and 1178 in the non-delayed group. There were no significant differences between the two groups in terms of age, gender, or education level. However, the delayed group had a higher proportion of patients living alone (P<0.05). Regarding stroke risk factors, hypertension (83.5% vs 69.9%,P<0.001), diabetes mellitus (35.8% vs 26.1%,P=0.047), and smoking (39.5% vs 28.0%,P=0.020) were more prevalent in the delayed group compared with the non-delayed group. Conversely, the non-delayed group had a higher incidence of atrial fibrillation (37.5% vs 12.8%,P<0.001). After multivariate regression analysis, the independent predictors for the delay group were solitary OR=11.10 (95% CI 5.72-21.5), large artery atherosclerosis OR=2.63 (95% CI 1.40-4.94), presence of atrial fibrillation OR=0.41 (95% CI 0.19-0.87), and involvement of the middle cerebral artery OR=0.51 (95% CI 0.32-0.81).ConclusionsAmong patients with AIS-LVO who delay seeking medical attention for more than 24 hours, large artery atherosclerosis appears to be the predominant pathogenesis.
Landscaping of Urine Proteome: Unlocking Diagnostic Potential and Overcoming Unique Challenges
Authors: Budnik Bogdan , Amirkhani Hossein , Weinberger Klaus , Sargsyan Karine , Forouzanfar Mohammad H. , Afshin Ashkan 
Published: October 2023

AbstractThis study explores the application of deep proteomic profiling to extract disease-specific features from urine. Early detection of cancer and other chronic disorders is crucial for better outcomes, but traditional diagnostics as well as emerging genomic-based diagnostics are expensive and invasive. Our research reveals that a select group of urinary proteins can accurately detect early-stage diseases with high sensitivity, surpassing current tests. While urine-based protein panels could offer cost-effective and accurate alternatives to current screening methods, kidney factors and blood urine barrier pathologies could pose significant challenges. New diagnostic technologies may emerge because of these findings, ushering in an era of early detection for cancer and chronic diseases.One-Sentence SummaryUrine-based protein panels show distinct patterns in early disease detection, promising opportunities for advancing diagnostic tests