bluuebunny/crossref_metadata_2025_split huggingface dataset:
T‐Wave Alternans Measured by 24‐Hour Ambulatory Recordings Rather Than Exercise Stress Tests as a Risk Stratification Marker in Patients With Long QT Syndrome
Authors: Yang Jing , Luo Jiangying , Li Kun , Li Dan , Lv Tingting , Liu Fulan , Liu Yuanwei , She Fei , He Rong , Zhang Ping 
Published: July 2024

Background
Few small‐sample studies have quantified the T‐wave alternans (TWA) value by 24‐hour ambulatory recordings or exercise stress tests in patients with long QT syndrome (LQTS). The cutoff point of TWA ≥47 μV was based on patients with myocardial infarction. In our study, we aimed to (1) evaluate the association of TWA with life‐threatening arrhythmic events (LAEs); (2) compare the predictive model of LAEs according to the TWA value measured by 24‐hour ambulatory recordings and exercise stress tests; and (3) propose a cutoff point for the high risk of LAEs in patients with LQTS.

Methods and Results

The study cohort included 110 patients with LQTS referred to our hospital, and the primary outcome was LAEs. Thirty‐one patients with LQTS (31/110 [28.2%]) developed LAEs during the following 24 (12–47) months. Peak TWA value quantified from 12 leads by 24‐hour ambulatory recordings in patients with LQTS with LAEs (LQTS–LAEs group) was significantly higher than LQTS without LAEs (LQTS–non‐LAEs group) (64.0 [42.0–86.0] μV versus 43.0 [36.0–53.0] μV;
P
<0.01). There was no statistical difference in TWA value measured by exercise stress tests between the 2 groups (69.0 [54.5–127.5] μV versus 68.5 [53.3–99.8] μV;
P
=0.871). The new cutoff point of the peak TWA value measured by 24‐hour ambulatory recordings was 55.5 μV, with a sensitivity of 75.0% and a specificity of 78.6%. A univariate Cox regression analysis revealed that TWA value ≥55.5 μV was a strong predictor of LAEs (hazard ratio [HR], 4.5 [2.1–9.6];
P
<0.001]. A multivariate Cox regression analysis indicated that TWA value ≥55.5 μV remained significant (HR, 2.7 [1.1–6.8];
P
=0.034).

Conclusions
Peak TWA measured by 24‐hour ambulatory recordings was a more favorable risk stratification marker than exercise stress tests for patients with LQTS.
Pulmonary Hypertension Induced by Right Pulmonary Artery Occlusion: Hemodynamic Consequences of
Bmpr2
Mutation
Authors: Todesco Alban , Grynblat Julien , Akoumia Kouamé Kan Firmin , Bonnet Damien , Mendes‐Ferreira Pedro , Morisset Stéphane , Chemla Denis , Levy Marilyne , Méot Mathilde , Malekzadeh‐Milani Sophie‐Guiti , Tielemans Birger , Decante Benoit , Vastel‐Amzallag Carine , Habert Paul , Ghigna Maria‐Rosa , Humbert Marc , Montani David , Boulate David , Perros Frédéric 
Published: July 2024

Background

The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the
BMPR2
gene. The incomplete penetrance of
BMPR2
mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers pulmonary hypertension (PH) in rats with
Bmpr2
mutations.

Methods and Results

Male and female rats with a 71 bp monoallelic deletion in exon 1 of
Bmpr2
and their wild‐type siblings underwent acute and chronic RPAO. They were subjected to full high‐fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced precapillary PH in male and female rats, both acutely and chronically.
Bmpr2
mutant and male rats manifested more severe PH compared with their counterparts. Although wild‐type rats adapted to RPAO,
Bmpr2
mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male
Bmpr2
rats. Chronic RPAO resulted in elevated pulmonary IL‐6 (interleukin‐6) expression and decreased
Gdf2
expression (corrected
P
value<0.05 and log2 fold change>1). In this context, male rats expressed higher pulmonary levels of endothelin‐1 and IL‐6 than females.

Conclusions
Our novel 2‐hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex‐ and gene‐related effects.
Patient‐Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta‐Analysis
Authors: Hu Xin‐Ru , Liao Guang‐Zhi , Wang Jun‐Wen , Ye Yu‐Yang , Chen Xue‐Feng , Bai Lin , Shi Fan‐Fan , Liu Kai , Peng Yong 
Published: July 2024

Background
The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient‐specific factors predicting the RDN response.

Methods and Results
We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta‐analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24‐hour systolic BP reduction (weighted mean difference, −4.05 [95% CI, −7.33 to −0.77]; weighted mean difference, −7.20 [95% CI, −9.79 to −4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN.

Conclusions
In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.
Cerebrovascular Disease Detected on Preprocedural Computed Tomography in Patients With Severe Aortic Stenosis Undergoing Aortic Valve Replacement
Authors: Yamamoto Ko , Ueda Hiroyuki , Uchiyama Daiji , Takeji Yasuaki , Taniguchi Tomohiko , Morimoto Takeshi , Tabata Hiroyuki , Ishizu Kenichi , Morofuji Toru , Hayashi Masaomi , Isotani Akihiro , Shirai Shinichi , Ohno Nobuhisa , Kakumoto Shinichi , Ando Kenji , Minatoya Kenji , Kimura Takeshi 
Published: July 2024

Background
There is a scarcity of data on the prevalence and clinical impact of cerebrovascular disease detected on preprocedural computed tomography (CT) before aortic valve replacement (AVR) in patients with severe aortic stenosis.

Methods and Results

Among patients with severe aortic stenosis undergoing AVR, the authors compared clinical outcomes between patients with and without cerebrovascular disease detected on preprocedural CT, which was defined as chronic brain infarction or hemorrhage. The primary outcome measure in this study was a composite of all‐cause death or stroke. Among 567 study patients, 200 patients (35.3%) had cerebrovascular disease on preprocedural CT. Among 200 patients with cerebrovascular disease on preprocedural CT, only 28.5% of patients had a clinical history of symptomatic stroke. The cumulative 3‐year incidence of death or stroke was higher in patients with cerebrovascular disease on preprocedural CT than in those without cerebrovascular disease on preprocedural CT (40.7% versus 24.1%, log‐rank
P
<0.001). After adjusting for confounders, the higher risk of patients with cerebrovascular disease on preprocedural CT relative to those without remained significant for death or stroke (hazard ratio [HR], 1.42 [95% CI, 1.02–1.98];
P
=0.04). Among 200 patients with cerebrovascular disease on preprocedural CT, patients with prior symptomatic stroke compared with those without were not associated with higher adjusted risk for death or stroke (HR, 1.18 [95% CI, 0.72–1.94];
P
=0.52).

Conclusions
Among patients with severe aortic stenosis undergoing AVR, a substantial proportion had cerebrovascular disease on preprocedural CT, with a clinical history of symptomatic stroke in one‐fourth of patients. Regardless of history of symptomatic stroke, patients with cerebrovascular disease on preprocedural CT had worse clinical outcomes compared with those without cerebrovascular disease on preprocedural CT.
Probabilistic Neural Networks for Ensemble Postprocessing
Authors: Liu Pu , Dabernig Markus , Atencia Aitor , Wang Yong , Zhao Yuchu 
Published: July 2024

Abstract
Accurate temperature forecasts are critical for various industries and sectors. We propose a probabilistic neural network (PNN), an extension of the distributional regression network (DRN), for 2-m temperature forecasts, consisting of three variants with different inputs and target variables. The first variant, standardized anomaly probabilistic neural network (SAPNN), employs a two-step approach involving standardized anomalies and global PNN modeling to effectively capture underlying features and anomalies. The second variant, PNN with geographical predictors (PNNGE), incorporates raw and static geographical predictors to enhance predictive performance. The third variant, PNN with station one-hot encoding (PNNEN), utilizes raw with station one-hot encoding predictors to represent geographical information effectively. We compare three PNN variants with two benchmarks: 1) standardized anomaly model output statistics (SAMOS) and 2) three DRN variants identical to those applied to PNN. These evaluations utilize ECMWF data from 2019 to 2020 at 6-h intervals up to 72 h over Hebei, China. Results show that SAPNN and PNNGE are better than SAMOS, while PNNEN notably exhibits a significant 14% improvement in the continuous ranked probability skill score (CRPSS). Moreover, the PNN variants exhibit comparable or superior performance to DRN regarding forecast accuracy, CRPSS, and reliability, showcasing a better-calibrated spread–error relationship. This study highlights the value of the proposed PNN variants with a distribution output in capturing nonlinear relationships within different sources of predictors and improving temperature forecast skills.

Significance Statement
This study aims to improve the accuracy, skills, and reliability of 2-m temperature forecasts, which are crucial in agriculture and energy management. To achieve this, we extend a popular artificial intelligence framework and explore four data sources with two schemes to systematically compare the predictive performances in making temperature forecasts. The findings of this research are vital as they offer novel ways to improve forecast skills. Imagine having a weather app that is significantly more accurate, enabling you to plan your day better. This study is about discovering innovative approaches to enhance forecast skills and reliability, which could benefit various aspects of our daily lives. One of the new methods even exhibits a 14% improvement in forecast skills.
Exploring NWS Forecasters’ Assessment of AI Guidance Trustworthiness
Authors: Cains Mariana G. , Wirz Christopher D. , Demuth Julie L. , Bostrom Ann , Gagne David John , McGovern Amy , Sobash Ryan A. , Madlambayan Deianna 
Published: July 2024

Abstract
As artificial intelligence (AI) methods are increasingly used to develop new guidance intended for operational use by forecasters, it is critical to evaluate whether forecasters deem the guidance trustworthy. Past trust-related AI research suggests that certain attributes (e.g., understanding how the AI was trained, interactivity, and performance) contribute to users perceiving the AI as trustworthy. However, little research has been done to examine the role of these and other attributes for weather forecasters. In this study, we conducted 16 online interviews with National Weather Service (NWS) forecasters to examine (i) how they make guidance use decisions and (ii) how the AI model technique used, training, input variables, performance, and developers as well as interacting with the model output influenced their assessments of trustworthiness of new guidance. The interviews pertained to either a random forest model predicting the probability of severe hail or a 2D convolutional neural network model predicting the probability of storm mode. When taken as a whole, our findings illustrate how forecasters’ assessment of AI guidance trustworthiness is a process that occurs over time rather than automatically or at first introduction. We recommend developers center end users when creating new AI guidance tools, making end users integral to their thinking and efforts. This approach is essential for the development of useful and used tools. The details of these findings can help AI developers understand how forecasters perceive AI guidance and inform AI development and refinement efforts.

Significance Statement
We used a mixed-methods quantitative and qualitative approach to understand how National Weather Service (NWS) forecasters 1) make guidance use decisions within their operational forecasting process and 2) assess the trustworthiness of prototype guidance developed using artificial intelligence (AI). When taken as a whole, our findings illustrate that forecasters’ assessment of AI guidance trustworthiness is a process that occurs over time rather than automatically and suggest that developers must center the end user when creating new AI guidance tools to ensure that the developed tools are useful and used.
Deletion of GPR81 activates CREB/Smad7 pathway and alleviates liver fibrosis in mice
Authors: Zhi Ying , Fan Kerui , Liu Shuang , Hu Kai , Zan Xinyan , Lin Ling , Yang Yongqiang , Gong Xianqiong , Chen Kun , Tang Li , Li Longjiang , Huang Jiayi , Zhang Shujun , Zhang Li 
Published: July 2024

Abstract
Background
Enhanced glycolysis is a crucial metabolic event that drives the development of liver fibrosis, but the molecular mechanisms have not been fully understood. Lactate is the endproduct of glycolysis, which has recently been identified as a bioactive metabolite binding to G-protein-coupled receptor 81 (GPR81). We then questioned whether GPR81 is implicated in the development of liver fibrosis.

Methods
The level of GPR81 was determined in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and in transforming growth factor beta 1 (TGF-β1)-activated hepatic stellate cells (HSCs) LX-2. To investigate the significance of GPR81 in liver fibrosis, wild-type (WT) and GPR81 knockout (KO) mice were exposed to CCl4, and then the degree of liver fibrosis was determined. In addition, the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) was supplemented in CCl4-challenged mice and TGF-β1-activated LX-2 cells to further investigate the pathological roles of GPR81 on HSCs activation.

Results
CCl4 exposure or TGF-β1 stimulation significantly upregulated the expression of GPR81, while deletion of GPR81 alleviated CCl4-induced elevation of aminotransferase, production of pro-inflammatory cytokines, and deposition of collagen. Consistently, the production of TGF-β1, the expression of alpha-smooth muscle actin (α-SMA) and collagen I (COL1A1), as well as the elevation of hydroxyproline were suppressed in GPR81 deficient mice. Supplementation with DHBA enhanced CCl4-induced liver fibrogenesis in WT mice but not in GPR81 KO mice. DHBA also promoted TGF-β1-induced LX-2 activation. Mechanistically, GPR81 suppressed cAMP/CREB and then inhibited the expression of Smad7, a negative regulator of Smad3, which resulted in increased phosphorylation of Smad3 and enhanced activation of HSCs.

Conclusion
GPR81 might be a detrimental factor that promotes the development of liver fibrosis by regulating CREB/Smad7 pathway.
gcplyr: an R package for microbial growth curve data analysis
Authors: Blazanin Michael 
Published: July 2024

Abstract
Background
Characterization of microbial growth is of both fundamental and applied interest. Modern platforms can automate collection of high-throughput microbial growth curves, necessitating the development of computational tools to handle and analyze these data to produce insights.

Results
To address this need, here I present a newly-developed R package: gcplyr. gcplyr can flexibly import growth curve data in common tabular formats, and reshapes it under a tidy framework that is flexible and extendable, enabling users to design custom analyses or plot data with popular visualization packages. gcplyr can also incorporate metadata and generate or import experimental designs to merge with data. Finally, gcplyr carries out model-free (non-parametric) analyses. These analyses do not require mathematical assumptions about microbial growth dynamics, and gcplyr is able to extract a broad range of important traits, including growth rate, doubling time, lag time, maximum density and carrying capacity, diauxie, area under the curve, extinction time, and more.

Conclusions
gcplyr makes scripted analyses of growth curve data in R straightforward, streamlines common data wrangling and analysis steps, and easily integrates with common visualization and statistical analyses.
Comparative proteomics in tall fescue to reveal underlying mechanisms for improving Photosystem II thermotolerance during heat stress memory
Authors: Wang Guangyang , Wang Xiulei , Li Dongli , Yang Xuehe , Hu Tao , Fu Jinmin 
Published: July 2024

Abstract
Background
The escalating impacts of global warming intensify the detrimental effects of heat stress on crop growth and yield. Among the earliest and most vulnerable sites of damage is Photosystem II (PSII). Plants exposed to recurring high temperatures develop heat stress memory, a phenomenon that enables them to retain information from previous stress events to better cope with subsequent one. Understanding the components and regulatory networks associated with heat stress memory is crucial for the development of heat-resistant crops.

Results
Physiological assays revealed that heat priming (HP) enabled tall fescue to possess higher Photosystem II photochemical activity when subjected to trigger stress. To investigate the underlying mechanisms of heat stress memory, we performed comparative proteomic analyses on tall fescue leaves at S0 (control), R4 (primed), and S5 (triggering), using an integrated approach of Tandem Mass Tag (TMT) labeling and Liquid Chromatography-Mass Spectrometry. A total of 3,851 proteins were detected, with quantitative information available for 3,835 proteins. Among these, we identified 1,423 differentially abundant proteins (DAPs), including 526 proteins that were classified as Heat Stress Memory Proteins (HSMPs). GO and KEGG enrichment analyses revealed that the HSMPs were primarily associated with the “autophagy” in R4 and with “PSII repair”, “HSP binding”, and “peptidase activity” in S5. Notably, we identified 7 chloroplast-localized HSMPs (HSP21, DJC77, EGY3, LHCA4, LQY1, PSBR and DEGP8, R4/S0 > 1.2, S5/S0 > 1.2), which were considered to be effectors linked to PSII heat stress memory, predominantly in cluster 4. Protein-protein interaction (PPI) analysis indicated that the ubiquitin-proteasome system, with key nodes at UPL3, RAD23b, and UCH3, might play a role in the selective retention of memory effectors in the R4 stage. Furthermore, we conducted RT-qPCR validation on 12 genes, and the results showed that in comparison to the S5 stage, the R4 stage exhibited reduced consistency between transcript and protein levels, providing additional evidence for post-transcriptional regulation in R4.

Conclusions
These findings provide valuable insights into the establishment of heat stress memory under recurring high-temperature episodes and offer a conceptual framework for breeding thermotolerant crops with improved PSII functionality.
Prior emergency medical services utilization is a risk factor for in-hospital death among patients with substance misuse: a retrospective cohort study
Authors: Gupta Preeti , Mayampurath Anoop , Gruenloh Tim , Oguss Madeline , Afshar Askar Safipour , Spigner Michael , Gussick Megan , Churpek Matthew , Lee Todd , Afshar Majid 
Published: July 2024

Abstract
Background
Substance misuse poses a significant public health challenge, characterized by premature morbidity and mortality, and heightened healthcare utilization. While studies have demonstrated that previous hospitalizations and emergency department visits are associated with increased mortality in patients with substance misuse, it is unknown whether prior utilization of emergency medical service (EMS) is similarly associated with poor outcomes among this population. The objective of this study is to determine the association between EMS utilization in the 30 days before a hospitalization or emergency department visit and in-hospital outcomes among patients with substance misuse.

Methods
We conducted a retrospective analysis of adult emergency department visits and hospitalizations (referred to as a hospital encounter) between 2017 and 2021 within the Substance Misuse Data Commons, which maintains electronic health records from substance misuse patients seen at two University of Wisconsin hospitals, linked with state agency, claims, and socioeconomic datasets. Using regression models, we examined the association between EMS use and the outcomes of in-hospital death, hospital length of stay, intensive care unit (ICU) admission, and critical illness events, defined by invasive mechanical ventilation or vasoactive drug administration. Models were adjusted for age, comorbidities, initial severity of illness, substance misuse type, and socioeconomic status.

Results
Among 19,402 encounters, individuals with substance misuse who had at least one EMS incident within 30 days of a hospital encounter experienced a higher likelihood of in-hospital mortality (OR 1.52, 95% CI [1.05 – 2.14]) compared to those without prior EMS use, after adjusting for confounders. Using EMS in the 30 days prior to an encounter was associated with a small increase in hospital length of stay but was not associated with ICU admission or critical illness events.

Conclusions
Individuals with substance misuse who have used EMS in the month preceding a hospital encounter are at an increased risk of in-hospital mortality. Enhanced monitoring of EMS users in this population could improve overall patient outcomes.