bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsaturated intercellular vapor pressure is relevant for leaf water heavy isotope enrichment
Authors: Angove Charlotte , Lehmann Marco M. , Saurer Matthias , Tang Yu , Kilpeläinen Petri , Kahmen Ansgar , Schiestl-Aalto Pauliina P. , Tikkasalo Olli-Pekka , Bäck Jaana K. , Rinne-Garmston Katja T. 
Published: September 2023

AbstractLeaf intercellular vapor pressure (ei) can be unsaturated, but its effect on leaf water heavy isotope enrichment (LWE) has not yet been quantified. We evaluated the ecological relevance of unsaturatedeifor LWE, i.e., for leaf water oxygen-18 and deuterium enrichment, using data from a boreal forest stand and a large-scale dataset. Unsaturatedeican firstly affect LWE by directly decreasingeiin the Craig Gordon model (Mechanism 1), which leads to an increased influence of atmospheric vapor isotopic enrichment above source water (Δv), and a decreased influence of kinetic fractionation by diffusion through the stomata and boundary layer (εk). Unsaturatedeican secondly affect LWE by changing εk(Mechanism 2). To evaluate the effect of Mechanism 1 to LWE, we employed sensitivity tests on LWE model performance using varying measured intercellular relative humidity (RHcellular), or RHcellularfitted to observed LWE. To explore the effects of Mechanism 2 to LWE, we modified the calculation of εkand observed consequences to LWE predictions. Unsaturatedeiis relevant to LWE by Mechanism 1, since a lowered RHcellularnoticeably changed LWE predictions. It clearly improved deuterium predictions and conditionally improved oxygen-18 predictions. Isotope fractionation by Mechanism 2 is unlikely relevant to oxygen-18 and deuterium enrichment. Unsaturatedeimust now be recognized as a variable that introduces error to heavy isotope enrichment models and reconstructions from organic material, via Mechanism 1. We suggest a correction for unsaturatedeifor both oxygen-18 and deuterium enrichment using a variable RHcellularcalculated from atmospheric relative humidity.
The eSAH Score: A Simple Practical Predictive Model for SAH Mortality & Outcomes
Authors: Sharma Rohan , Mandl Daniel , Foettinger Fabian , Salman Saif , Godasi Raja , Wei Yujia , Tawk Rabih , Freeman W David 
Published: September 2023

AbstractBackgroundWe developed a simple quantifiable scoring system that predicts aneurysmal subarachnoid hemorrhage (aSAH) mortality, delayed cerebral ischemia (DCI) and modified Rankin Scale outcomes using readily available SAH admission clinical data with a new radiographic quantitative volumetric SAH method.MethodsWe analyzed 277 patients with aneurysmal SAH (aSAH) admitted at our Comprehensive Stroke Center (CSC) at Mayo Clinic Florida between 2012 and 2022. We developed a mathematical model that measures aSAH basal cisternal subarachnoid hemorrhage volume (SAHV) using a derivation of the ABC/2 ellipsoid formula, where A = width/thickness, B = length, C = vertical extension) on non-contrast CT (NCCT), which we previously demonstrated comparable to pixel based manual segmentation on NCCT scans. Data was analyzed using t-test, chi-square, receiver operator characteristics (ROC) curve, and area under curve analysis. Multivariate logistic regression analysis with stepwise elimination of variables not contributing to the model (0.05 significance level for entry into the model) was used to develop an enhanced SAH (eSAH) scoring system.ResultsUsing regression and logistic regression, we found that age, GCS score and SAHV were significantly associated with final discharge outcome, prediction on in-hospital DCI, and in-hospital mortality. A weighted eSAH score was developed using these factors that ranged between ‘0-5’ and was strongly predictive of outcome (AUC=0.88), DCI (AUC=0.75) and in-hospital mortality (AUC=0.87).ConclusionsA volumetrically-enhanced SAH (eSAH) score is a simple quantitative model based on SAH volumetrics, GCS and age and appears to predict mortality and outcomes in SAH patients. A larger cohort validation study is planned.
Efficacy of cardioneurablation for vasodepressor vasovagal syncope
Authors: Chen Zhenhuan , Li Ying , Liu Yuan , Shen Guowang , Xiong Ganwei , Wu Bo , Liu Yanfeng , Huang Xiantao , Li Hongyan , Zhou Haiwen , Xu Zhicheng , Zhang Gulao , Tao Yu , Zhang Fanzhi , Lai Hengli 
Published: September 2023

AbstractObjectiveCardioneuroablation (CNA) is effective for cardiac inhibitory and mixed vasovagal syncope (VVS) but not vasodepressor VVS. This study aimed to assess the therapeutic benefits of CNA in vasodepressor VVS.MethodsVVS patients hospitalized in the Department of Cardiology of Jiangxi Provincial People’s Hospital were retrospectively reviewed. Holter monitoring was performed before, during, and 3 months after CNA. Changes in heart rate and Wenckebach point of atrioventricular conduction before and after ablation were compared.ResultsThirty-five patients were enrolled, 18 men and 17 women. Mean age was 47.48 ± 16.49 years. Median duration of syncope was 24.0 months (range, 2.5–66.0). Median number of syncope episodes before treatment was two (range, 2–4). The time domain indexes of heart rate variability, mean heart rate, maximum heart rate, and minimum heart rate were significantly higher 3 months after CNA. Mean follow-up was 11 ± 4.67 months. Recurrent syncope occurred in two patients with vasodepressor VVS, one of them with presyncope symptoms in vasodepressor type; and one patient occurred with mixed VVS, without presyncope symptoms. No serious complications occurred. CNA is safe and effective in the treatment of vasodepressor VVS.ConclusionsCNA is effective for treating vasodepressor VVS. Our study provides a theoretical basis for individualization of treatment in patients with vasodepressor VVS.
Blood-based transcriptomic biomarkers are predictive of neurodegeneration rather than Alzheimer’s disease
Authors: Shvetcov Artur , Thomson Shannon , Spathos Jessica , Cho Ann-Na , Wilkins Heather M. , Andrews Shea J. , Delerue Fabien , Couttas Timothy A. , Issar Jasmeen Kaur , Isik Finula , Kaur Simran , Drummond Eleanor , Dobson-Stone Carol , Duffy Shantel L. , Rogers Natasha M. , Catchpoole Daniel , Gold Wendy A. , Swerdlow Russell H. , Brown David A. , Finney Caitlin A. 
Published: September 2023

AbstractAlzheimer’s disease (AD) is a growing global health crisis, affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis, as well as early detection, of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determine whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Our analyses showed that genes involved in spliceosome assembly, RNA binding, transcription, protein synthesis, mitoribosomes, and NADH dehydrogenase were the best performing genes for identifying AD patients relative to cognitively healthy controls. This transcriptomic signature, however, was not unique to AD and subsequent machine learning showed that this signature could also predict PD and ALS relative to controls without neurodegenerative disease. Combined, our results suggest that mRNA from whole blood can indeed be used to screen for patients with neurodegeneration but may be less effective at diagnosing the specific neurodegenerative disease.
Drug-induced liver injury associated with elexacaftor/tezacaftor/ivacaftor from the FDA Adverse Event Reporting System (FAERS)
Authors: Shi Alan , Nguyen Harold , Kuo C. Benson , Beringer Paul M. 
Published: September 2023

AbstractIntroductionThe efficacy and safety of elexacaftor/tezacaftor/ivacaftor (ETI) have been established in prospective clinical trials. Liver function test elevations were observed in a greater proportion of patients receiving ETI compared with placebo; however, the relatively small number of patients and short duration of study preclude detection of rare but clinically significant associations with drug-induced liver injury (DILI). To address this gap, we assessed the real-world risk of DILI associated with ETI through data mining of the FDA Adverse Event Reporting System (FAERS).MethodsDisproportionality analyses were conducted on FAERS data from the fourth quarter of 2019 through the third quarter of 2022. Comparative patient demographics, onset time and outcomes for ETI-DILI were also obtained.Results452 reports of DILI associated with ETI were found, representing 2.1% of all adverse event reports for ETI. All disproportionality measures were significant for ETI-DILI at p < 0.05; the reporting odds ratio (ROR) was comparable to that of drugs classified by FDA as “Most-DILI concern”. The most notable demographic finding was a male majority for ETI-DILI compared to a female majority for non ETI-DILI. Median ETI-DILI onset time was 50.5 days, and hospitalization was the second most common complication.ConclusionUsing FAERS data, ETI was found to be disproportionality associated with DILI. Future research is needed to investigate the hepatotoxic mechanisms and assess potential mitigation strategies for ETI-induced hepatotoxicity.Article HighlightsUsing the FDA Adverse Event Reporting System database, ETI and DILI were found to be significantly associated (p < 0.05) for all disproportionality measures (PRR, ROR, IC, EGBM, Yates’ chi-squared).The ROR for ETI-DILI is greater than that of many “Most-DILI concern” drugs in the FDA DILIRank dataset but is not within the top 20 drugs associated with DILI.Patient reports for ETI-DILI were predominately male, in contrast to patient reports for other drugs and DILI.“Hospitalization” was the second most common patient outcome for ETI-DILI after “other serious outcomes”.Most patients had onset times within 3 months of initiation, several patients had an onset time greater than 1 year.Onset times indicate that liver function test monitoring should be initiated earlier than 3 months and potentially extend beyond 1 year in some patients.
A systematic review of genome-wide association studies on bladder cancer
Authors: Ahmad Aliyu Adamu , Muhammad Umar , Ibrahim Buhari , Kwairanga Suleiman Hamidu , Garkuwa Usman Adamu , Jabril Murtala Muhammad , Ahmad Umar 
Published: September 2023

AbstractBackgroundBladder cancer (BC) is the most common cancer of the urinary tract worldwide with over 550,000 new cases each year, bladder cancer has drawn relatively limited research attention and healthcare interventions despite the escalating incidence and mortality rates, particularly in Africa. Historically, the clinical handling of bladder cancer remained largely unchanged for many years. However, novel research initiatives have heralded a fresh epoch in its diagnosis and treatment, fueled by detailed probing of molecular changes.AimThis study aimed to identify genetic susceptibility loci associated with bladder cancer by systematically reviewing previous Genome-Wide Association Studies (GWAS).MethodsIn line with this objective, comprehensive literature searches were conducted across PubMed, Google Scholar, and relevant genetic databases, focusing on bladder cancer GWAS studies from 2000 through to November 2022. This systematic review adhered to the robust PRISMA standards. To evaluate the credibility of the studies under scrutiny, the Newcastle-Ottawa Scale was employed, further assessing any potential bias risk.ResultsThe investigation identified chromosome 18q12.3 as the most vulnerable to bladder cancer, revealing four polymorphisms at this locus: rs7238033, rs10775480, rs11082469, and rs17674580. Furthermore, chromosome 5p15.3 emerged as the second most susceptible, with three noted polymorphisms: rs2736098 and two instances of rs401681.ConclusionDespite these findings, our understanding of genetic predisposition to bladder cancer remains rudimentary, with the majority of substantial data deriving from GWAS. No additional genetic association evidence emerged from this systematic review. Given the relatively minor influence of our current knowledge of genetic susceptibility to bladder cancer on public health, a call for larger cohort studies is necessary. These expanded studies can potentially unveil a broader range of significant polymorphisms across the genome, thereby enhancing our understanding and approach to bladder cancer.
Capturing recentMycobacterium tuberculosisinfection by tuberculin skin testvs. interferon-gamma release assay
Authors: Gutierrez Jesús , Nsereko Mary , Malone LaShaunda L. , Mayanja-Kizza Harriet , Kisingo Hussein , Boom W. Henry , Bark Charles M. , Stein Catherine M. 
Published: September 2023

AbstractReductions in tuberculosis (TB) incidence and mortality require identification of individuals at high risk of developing active disease, such as those with recentMycobacterium tuberculosis(Mtb) infection. Current tests used for Mtb infection cannot distinguish recent from remote infection. Using a longitudinal, prospective household contact (HHC) study in Kampala, Uganda, we diagnosed new Mtb infection using both the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) to determine if these tests differentiated or added value as measures of recentMtbinfection. We identified 13 HHCs who only converted the IGRA (QFT-only converters), 39 HHCs who only converted the TST (TST-only converters), and 24 HHCs who converted both tests (QFT/TST converters). Univariate analysis revealed that TST-only converters were older than the other groups. This result was confirmed by our logistic regression model where increased odds of TST-only conversion was associated with age (p=0.02), in addition to crowdedness (p=0.025). The odds of QFT conversion increased with a higher epidemiologic risk score (p=0.038), which suggests it is a better measure of Mtb exposure and infection. QFT/TST converters had higher QFT quantitative values at conversion than QFT-only converters and a bigger change in TST quantitative values at conversion than TST-only converters. Collectively, these data indicate that TST conversion alone likely overestimates Mtb infection. Its correlation to older age suggests boosting of BCG responses and/or longer environmental mycobacterial exposure. This result also suggests that QFT/TST conversion may be associated with a more robust immune response, which should be considered when planning vaccine studies.
Data-Driven Strain Design Towards Mitigating Biomanufacturing Stresses
Authors: Phaneuf PV , Kim SH , Rychel K , Rode C , Beulig F , Palsson BO , Yang L 
Published: September 2023

AbstractMicrobial strains used in large-scale biomanufacturing of melatonin often experience stresses like reactive oxygen species (ROS), SOS response, and acid stress, which can reduce productivity. This study leveraged a data-driven workflow to identify mutations that could improve robustness to these stresses for an industrially important melatonin production strain. This work integrated more than 7000 E. coli adaptive laboratory evolution (ALE) mutations to statistically associate mutated genes to 2 ROS tolerance ALE conditions from 72 available conditions. oxyR, fur, iscR, and ygfZ were significantly associated and hypothesized to contribute to fitness in ROS stress. Across these genes, 259 total mutations were inspected and 10 were chosen for reintroduction based on mutation clustering and transcriptional signals as evidence of fitness impact. Strains engineered with mutations in oxyR, fur, iscR, and ygfZ exhibited increased tolerance to H2O2 and acid stress, and reduced SOS response suggesting improved genetic stability. Additionally, new evidence was generated towards understand the function of ygfZ, a gene of relatively uncertain function. This meta-analysis approach utilized interoperable multi-omics datasets to identify targeted mutations conferring industrially-relevant phenotypes, describing an approach for data-driven strain engineering to optimize microbial cell factories.Visual Abstract
Utilization of Eco-friendly Imidazolium-Based Ionic Liquids for Gluten Extraction: Investigating the Influence of Side Chains and Anions
Authors: Chen Wen-Hao , Hsiao Yu-Cheng 
Published: September 2023

AbstractGluten is a well-known food allergen globally, capable of triggering immune responses in both celiac and non-celiac gluten-sensitive individuals. Gluten comprises two major proteins: glutenin and gliadin. Gliadin, in particular, possesses a unique hydrophobic amino acid sequence. The Food and Drug Administration asserts that the toxicity of gliadin cannot be eliminated through fermentation and hydrolysis processes. A common approach to addressing gluten allergies is to adopt a gluten-free diet. However, the hydrophobic nature of gluten makes its detection challenging. Analysts often resort to using organic solvents or employing multiple procedures to denature gluten for extraction. It’s worth noting that while organic solvents can rapidly extract gluten from a sample, they may also alter antibodies, leading to erroneous bio-test results.Ionic liquid (IL) is a highly adaptable green chemical compound consisting of organic salts. We modified imidazolium, a cationic structure, with various carbon side chain lengths (C=0, 1, 3, 5, 7, 9, and 12), and combined it with organic and inorganic anions (e.g., OMs-, Cl-, F-, NO¬3-, HSO4-, and H2PO4-). We used different IL-to-water ratios to assess gluten solubility. We measured the solubility of gliadin in various imidazolium ILs and conducted kinetic studies on the dissolution of gliadin in 1% [C5DMIM][OMs]aq. Additionally, circular dichroism (CD) spectroscopy and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate the structural changes in gliadin and its interaction with antibodies after treatment with 1% [C5DMIM][OMs]aq. An XTT assay was conducted to assess the cytotoxicity of [C5DMIM][OMs]aq on N2a cells.Our research findings indicate that 1% [C5DMIM][OMs]aq demonstrated excellent gluten solubility, dissolving more than 3000 ppm of gluten within 5 minutes. Importantly, [C5DMIM][OMs]aq did not disrupt the gluten structure, did not impede antibody binding to gluten, and exhibited no cell toxicity. This report highlights [C5DMIM][OMs] as a promising extraction solution for gluten detection.
Noise Propagation in Transcriptional Genetic Cascades
Authors: Marmolejo JD , Pedraza JM 
Published: September 2023

ABSTRACTCellular processes are inherently stochastic, leading to fluctuations in protein concentration quantifiable as noise in gene expression. Precise description of noise propagation in gene networks is essential for designing noise-tolerant gene circuits and understanding signal reliability in biological networks, but current models for noise propagation are primarily system-specific or limited to short gene cascades. Here we present an analytical expression for noise propagation in gene expression that works for long cascades and incorporates global noise. Since modelling all aspect of noise can be prohibitively complicated, in many situations only intrinsic or global noise is considered, but general criteria for when each type is dominant are still lacking. As an example of the possible use of our analytical expression, we examine the role different aspects of the network have on the balance between intrinsic and global noises and their propagation. We show that the type of cascade, cascade length, sensitivity, and basal transcription rates have an effect beyond simple protein abundance. This has practical implications for designing synthetic gene networks in prokaryotes and improving our knowledge on noise propagation in gene networks, and could shed light on how evolution may shape circuit sizes to balance signal fidelity and metabolic cost.
General Transcription Factor fromE. coliwith a Distinct Mechanism of Action
Authors: Vasilyev Nikita , Liu Mengjie MJ , Epshtein Vitaly , Shamovsky Ilya , Nudler Evgeny 
Published: September 2023

AbstractGene expression inE. coliis controlled by well-established mechanisms that activate or repress transcription. Here, we identify CedA as an unconventional transcription factor specifically associated with the RNA polymerase (RNAP) σ70holoenzyme. Structural and biochemical analysis of CedA bound to RNAP reveal that it bridges distant domains of β and σ70subunits to stabilize an open-promoter complex. Remarkably, CedA does so without contacting DNA. We further show thatcedAis strongly induced in response to amino acid starvation, oxidative stress, and aminoglycosides. CedA provides a basal level of tolerance to these clinically relevant antibiotics, as well as to rifampicin and peroxide. Finally, we show that CedA modulates transcription of hundreds of bacterial genes, which explains its pleotropic effect on cell physiology and pathogenesis.One sentence summaryAn integrated structure-function approach uncovers CedA as a general transcription initiation factor inE. coliand elucidates its multifaceted role and unique mechanism.
Bacterial purine metabolism modulatesC. elegansdevelopment and stress tolerance via DAF-16 translocation
Authors: Feng Min , Gao Baizhen , Garcia L. Rene , Sun Qing 
Published: September 2023

AbstractPurine homeostasis is crucial for cellular function and is a conserved metabolic network from prokaryotes to humans. While extensively studied in microorganisms like yeast and bacteria, the impact of perturbed dietary purine levels on animal development and balanced growth remains poorly understood. To investigate the mechanisms underlying this deficiency, we utilizedCaenorhabditis elegansas the metazoan model. Through a high-throughput screening of anE. colimutant library Keio collection, we identified 34E. colimutants that delayC. elegansdevelopment. Among these mutants, we found thatE. coli purEgene is an essential genetic component that promotes host development in a dose-dependent manner. Additionally, we observed increased nuclear accumulation of the FoxO transcription factor DAF-16 when fedE. coli purE-mutants, suggesting the role of DAF-16 in response to nutrient, especially purine deficiency. RNA-seq analysis and phenotype assays revealed that worms fed theE. coli purEmutant exhibited elevated lifespan, thermotolerance, and pathogen resistance. These findings collectively suggest that perturbations in bacterial purine metabolism likely serve as a cue to promote development and activate the defense response in the nematodeC. elegansthrough DAF-16 nuclear translocation.
Encouraging SMEs performance through entrepreneurial intentions, competencies, and leadership: serial mediation model
Authors: Khan Mukaram Ali , Rathore Kashif , Zubair Syed Sohaib , Mukaram Aamna Tariq , Selem Kareem M. 
Published: September 2023

Purpose
The study aims to investigate the effect of entrepreneurial leadership (EL), competencies (ECs) and intentions (EIs) on enterprise performance (EP) via entrepreneurial resilience (ER) and risk-taking propensity (RTP).

Design/methodology/approach
Data were collected from 403 early-stage small and medium enterprise (SME) owners in Pakistan at two-time intervals and were analyzed using AMOS 22.

Findings
All predictors (i.e. EIs, EL and ECs) positively affected EP and ER, except for EL and ER. Furthermore, RTP and ER were serially mediated in linking EIs and ECs with EP but could not establish a link between EL and EP.

Research limitations/implications
The findings reveal that the Pakistani government and business owners must focus on SMEs’ sustained development and prioritize ECs.

Originality/value
This paper is unique in nature, as understanding EIs, EL and ECs in a holistic framework has never been tested before in relation to EP.