bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Pogostone in an Acetaminophen-induced Liver Injury Rat Model
Authors: Hou Yingkui , Sun Wencong , Yang Jing 
Published: January 2025

Background One of the leading causes of serious liver disease worldwide is drug-induced liver injury, which is brought on by either the direct hepatotoxic effects of a medication or one of its reactive metabolites. One often-used medication over the counter is acetaminophen (APAP). Although APAP is safe in small amounts, an overdose can result in rapid liver damage and even death from acute liver failure. It is common knowledge that the pharmaceutical business has been using more and more plant products in recent years. Traditional Chinese medicine has utilized patchouli, scientifically known as Pogostemon cablin ( P. cablin) Benth, a member of the Lamiaceae family, since the Eastern Han period. Purpose The current study aims to assess pogostone’s (PO) hepatoprotective effects on rats’ APAP-induced toxicity. Materials and Methods APAP was used to produce toxicity after two different dosages of PO were given. Liver function markers and biochemical parameters, bilirubin, and protein profile were used to determine the extent of hepatoprotection. The indicators of oxidative stress in the liver and kidney tissue were examined, including superoxide dismutase, catalase, glutathione, and malondialdehyde along with the histopathological analysis. Results PO has been found to return hepatic and renal antioxidant levels, as well as liver function markers, to normal, compared to the aberrant levels detected in the APAP-treated group. After being observed, it was discovered that the liver weight and liver index were comparable to the positive control. A liver histological examination was also performed, and the results indicated that co-administration with PO significantly reduced the histopathological lesions in the liver caused by APAP. Conclusion As a result, the current study demonstrates that PO has hepatoprotective effects against liver damage brought on by APAP.
Perceptions and experiences of commercial virtual reality games in early postoperative rehabilitation among cardiac surgical patients: A qualitative study
Authors: Wu Zhongkang , Li Xihan , Li Lin , Zhang Yan , Shen Xiao 
Published: January 2025

Background Although numerous studies have focused on the outcomes of virtual reality games for early rehabilitation in postoperative cardiac surgical patients, research on these patients’ perceptions and experiences with virtual reality games has been limited. Objectives The aim of this qualitative study was to provide insights into the perceptions and experiences of postoperative cardiac surgery patients in using commercial virtual reality games during early rehabilitation. Methods A cohort of postoperative cardiac surgery patients ( n = 12) who used the same VR games during the early rehabilitation period at the cardiac surgery intensive care unit (ICU) of a tertiary hospital in Nanjing, China, was enrolled in this study, conducted between January 2023 and December 2023. Data were collected through individual in-depth interviews and analyzed using Colaizzi's phenomenological method. Results Two themes emerged from the interviews: (1) the benefits of virtual reality games for rehabilitation, including (i) enhancing enthusiasm for rehabilitation, (ii) helping patients to focus attention, (iii) increasing individual exercise, (iv) providing enjoyment, and (v) regulating negative emotions; (2) shortcomings in the use of virtual reality games, including (i) producing stress, (ii) insufficient operating space, (iii) discomfort while wearing, (iv) difficulty in mastering the application, and (v) individualized needs. Conclusion Cardiac patients believed that the use of commercial virtual reality games during early postoperative rehabilitation was beneficial to rehabilitation, but they highlighted some shortcomings that require improvement. The results of this study provide a certain theoretical basis for the further promotion and application of commercial virtual reality games in clinical practice in the future.
Protocol for the INFORM ASTHMA Trial: Budesonide-formoterol reliever in adults with asthma on maintenance inhaled corticosteroid
Authors: Noble Jonathan , Bean Orlagh , Bruce Pepa , Black Melissa , Sayers Ross , Cullen Ryan , Black Bianca , Holliday Mark , Kirton Louis , Perry Blake , Eathorne Allie , Pavord Ian , Weatherall Mark , Beasley Richard 
Published: January 2025

BackgroundInternational asthma guidelines recommend inhaled corticosteroid (ICS)/formoterol in preference to short-acting beta2-agonist (SABA) reliever-based regimens as reliever therapy in adults and adolescents of all asthma severities. A major limitation to this recommendation is the absence of randomised controlled trial (RCT) efficacy and safety data for this approach in patients who continue to use maintenance ICS. The anti-inflammatory effect of ICS/formoterol reliever therapy on airway inflammation is also not well characterised.ObjectiveTo determine the anti-inflammatory effect, efficacy and safety of budesonide-formoterol reliever therapyversusterbutaline reliever therapy in adults with asthma on maintenance ICS therapy. Fractional exhaled nitric oxide (FeNO) will specifically be examined to determine the time-course and magnitude of anti-inflammatory effect.MethodsA 26-week, open-label, parallel-group, 2-arm, phase IV, two-sided superiority RCT will recruit 180 adults aged 16–75 with a clinical diagnosis of asthma using reliever only therapy, or SABA reliever therapy with maintenance ICS at baseline, and with baseline FeNO at screening ≥25 ppb. Enrolled participants will be allocated to maintenance budesonide with the dose based on their baseline treatment step and randomised 1:1 to either budesonide-formoterol or terbutaline reliever therapy. All participants will perform at home FeNO measurements at regular intervals for the first 12 weeks of the study. The primary outcome is FeNO at 26 weeks. Key secondary outcomes include FeNO time-course, asthma exacerbations, asthma control and spirometry.ConclusionThis will be the first RCT comparing ICS-formoterolversusSABA reliever therapy in patients who use maintenance ICS therapy.
Lifestyle scores and their potential to estimate the risk of multiple non-communicable disease-related endpoints: a systematic review
Authors: Ding Jie , Fu Ruojin , Yuan Tanwei , Brenner Hermann , Hoffmeister Michael 
Published: January 2025

Abstract

Background
Lifestyle scores have emerged as a practical tool to assess the risk of major non-communicable diseases (NCDs). However, most of them are primarily developed for single NCDs. Given the common risk factors for some of the major NCDs, we conducted a systematic review to evaluate the potential of existing lifestyle scores in predicting the risk of multiple NCD-related endpoints.

Methods
PubMed, Web of Science, the Cochrane Library, Embase, and Google Scholar were searched from inception to October 2024. We included observational studies assessing the association between lifestyle scores and the risk of morbidity or mortality of multiple NCDs, including type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer.

Results
Of 16,138 unique records identified by the search, 56 eligible studies were included in the systematic review, consisting of 48 cohort studies, 5 case-control studies, 2 case-cohort studies, and 1 cross-sectional study from 16 countries. 15 lifestyle scores were identified to estimate the risk of 32 NCDs, with HLIBMI being the most reported score (14/56, 25.0%). Moderate to strong associations were found between the 15 lifestyle scores and the risk of developing and dying from multiple types of cancers, CVDs, and T2D. Healthy lifestyle scores including additional risk factors (i.e., blood pressure, blood glucose, and waist circumference) aside from major risk factors (i.e., Body Mass Index (BMI), smoking, and diet) seemed to have a stronger ability to estimate NCDs risk than scores including only major risk factors.

Conclusion
All 15 simple lifestyle scores were shown to estimate the risk of multiple NCDs endpoints, although some scores were originally developed to estimate the risk of single diseases only. Therefore, further research is required to identify which lifestyle score is most effective for assessing the risk of multiple NCD-related endpoints in a head-to-head comparison.
Differences in influenza testing and treatment in micropolitan versus metropolitan areas in the U.S. using medicare claims data from 2010 to 2016
Authors: Couture Alexia , Dahlgren F. Scott , Izurieta Hector S. , Forshee Richard A. , Lu Yun , Reed Carrie 
Published: January 2025

Abstract

Background
To improve understanding of influenza and rurality, we investigated differences in influenza testing and anti-viral treatment rates between micropolitan (muSAs) and metropolitan statistical areas (MSAs) using national medical claims data over multiple influenza seasons.

Methods
Using billing data from the Centers for Medicare and Medicaid Services for those aged 65 years and older, we estimated weekly rates of ordered rapid influenza diagnostic tests (RIDT) and antivirals (AV) among Medicare enrollees by core-based statistical areas (CBSAs) during 2010–2016. We used Negative Binomial generalized mixed models to estimate adjusted rate ratios (aRR) between MSAs and muSAs, adjusting for clustering by CBSA plus explanatory variables. We ran models for all weeks and only high influenza activity weeks.

Results
For all weeks, the unadjusted rate of RIDTs was 1.97 per 10,000 people in MSAs compared with 2.69 in muSAs (Rate ratio (RR) = 0.73, 95% Confidence Interval (CI): 0.73–0.74) and of AVs was 1.85 in MSAs compared with 1.40 in muSAs (RR = 1.32, CI: 1.31–1.32). From the multivariate model, aRR for RIDTs was 0.82 (0.73–0.94) and for AVs was 1.12 (1.04–1.22) in MSAs versus muSAs. For high influenza activity weeks, aRR for RIDTs was 0.82 (0.73–0.92) and for AVs was 1.15 (1.06–1.24). All models found influenza testing rates higher in muSAs and treatment rates higher in MSAs.

Conclusions
Our study found lower testing and higher treatment in U.S. metropolitan versus micropolitan areas from 2010 to 2016 for those aged 65 years and older in our population. Identifying differences in influenza rates by rurality may improve public health response. Further research into the relationship of rurality and health disparities is needed.
VA physicians intent to leave and correlations to drivers of burnout: a cross-sectional study
Authors: Oh Robert C. , Mohr David C. , Schult Tamara M. 
Published: January 2025

Abstract

Background
Physician well-being and workforce retention within the healthcare system is of critical importance. Understanding physicians’ intent to leave the organization will inform efforts on optimizing the physician workforce. In this study, we examine the association of burnout and specific drivers of burnout on turnover intentions.

Methods
The study was a cross-sectional design using data collected from an organization-wide workforce survey. The sample included 16,363 respondents from the Veterans Health Administration (VA). A multinomial model was run to compare physicians indicating turnover intent because they were: a.) changing internal jobs; b.) leaving the organization for another job; or c.) retiring, against physicians indicating they had no plans to turnover. Explanatory variables in the model included burnout, drivers of burnout, and demographics. We also asked about the primary reason behind turnover intent.

Results
Most physicians responding to the survey (n = 13,083, 80%) indicated they would stay within their current job, while 5.8% indicated they would look for another VA job, 5% indicated planning to retire, and 9.3% said they would leave the VA workforce altogether. Burnout and less favorable senior leadership perceptions were associated with greater odds of turnover intent specific to finding another VA job, leaving VA, or retire. Experiencing discrimination was related to turnover intent for another VA job and leaving VA, while satisfaction with workload and recognition were related to lower odds of finding another VA job or leaving VA. Culture of well-being was associated with lower odds of leaving VA.

Conclusions
The study highlights how burnout is associated with turnover intentions with physicians have differing rationales for leaving. Several drivers of burnout were related to turnover intentions for both finding another VA job and leaving VA altogether. Efforts to improve workforce well-being and drivers of burnout may help address the different rationales physicians may have for considering leaving.
From bench to bedside: elucidating VEGF(R) inhibitor-related heart failure in cancer treatment
Authors: Peng Shengkun , Cai MinHong , Kuang Hongyu , Lin Anqi , Ma Qinghua , Dai Xiaoqin , Luo Peng , Liu Yijun , Zhang Guo , Bai Yifeng 
Published: January 2025

Abstract

Background
Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors play a pivotal role in treating various tumors; however, the clinical characteristics and molecular mechanisms of their associated heart failure (HF) remain incompletely understood.

Methods
We investigated the epidemiological characteristics of VEGF or VEGFR inhibitors [VEGF(R)i]-related heart failure (VirHF) using the global pharmacovigilance database Vigibase. The phenotypic features and molecular mechanisms of VirHF were characterized using VEGF(R)i-treated mouse models through a combination of echocardiography, histopathological analysis, and transcriptome sequencing. Furthermore, we performed a retrospective analysis of cardiac function parameters in patients undergoing VEGF(R)i treatment at local hospitals.

Results
In the analysis of 1871 VirHF cases, elderly patients (≥ 65 years) and female subjects demonstrated an elevated risk of occurrence. Experimental studies in mice revealed that both acute and chronic VEGF(R)i administration resulted in reduced left ventricular EF, cardiomyocyte hypertrophy, and myocardial fibrosis. Transcriptomic analysis identified significant dysregulation of multiple key signaling pathways, including DNA repair (R = 0.46), mitochondrial ATP synthesis (R = 0.39), glycogen metabolism regulation (R = 0.45), and proteasome-mediated protein degradation (R = 0.45). Moreover, significant upregulation was observed in inflammatory pathways, specifically those involving IL-1, IL-6, TNF-α, and IRF3/IRF7-mediated immune responses. Clinical cohort analyses demonstrated significant elevations in both cardiac injury biomarkers (NT-proBNP, CK-MB, cTnT) and inflammatory mediators (CRP) following VEGF(R)i administration.

Conclusions
Our findings present the first comprehensive characterization of VirHF clinical features and elucidate its underlying molecular mechanisms, thereby providing a theoretical framework for optimizing the clinical safety of VEGF(R)i therapy.
Sleep-driven prefrontal cortex coordinates temporal action and multimodal integration
Authors: Ibrahim Ahmed Z. , Abdou Kareem , Nomoto Masanori , Yamada-Nomoto Kaori , Okubo-Suzuki Reiko , Inokuchi Kaoru 
Published: January 2025

Abstract
Cognitive processes such as action planning and decision-making require the integration of multiple sensory modalities in response to temporal cues, yet the underlying mechanism is not fully understood. Sleep has a crucial role for memory consolidation and promoting cognitive flexibility. Our aim is to identify the role of sleep in integrating different modalities to enhance cognitive flexibility and temporal task execution while identifying the specific brain regions that mediate this process. We have designed “Auditory-Gated Patience-to-Action” Task in which mice should process different auditory signals before action execution as well as analyzing the visual inputs for feedback of their action. Mice could learn the task rule and apply it only after sleeping period and could keep the performance constant across sessions. c-fos positive cells showed the involvement of prelimbic cortex (PrL) during task execution. Chemo-genetic inhibition verified that PrL is required for proper signal response and action timing. These findings emphasize that sleep and cortical activity are keys for cognitive flexibility in adapting to different modalities.
DNA copy number variations and craniofacial abnormalities in 1,457 children with neurodevelopmental disorders
Authors: Wu Dandan , Chen Ran , Zhang Jerry , Yan Wu , Chen Mengyin , Xia Dongqing , Li Xiaonan , Dai Yanyan , Chen Yinhua , Li Rong 
Published: January 2025

Abstract

Background
This study aimed to investigate deoxyribonucleic acid (DNA) copy number variations (CNVs) in children with neurodevelopmental disorders and their association with craniofacial abnormalities.

Methods
A total of 1,457 children who visited the Child Health Department of our hospital for unexplained Neurodevelopmental disorders (NDDs) between November 2019 and December 2022 were enrolled. Peripheral venous blood samples (2 mL) were collected from the children and their parents for whole-exome sequencing. Positive results were verified through Sanger sequencing for locus and pedigree validation. Simultaneously, a specific sign-scoring scale was created to evaluate characteristics related to the developments of eyes, nose, ears, eyebrows, head, mouth, face, trunk, limbs, and reproductive, urinary, and cardiovascular systems.

Results
A total of 536 children (36.78%, 536/1,457) were found to have genetic variations, with 379 (70.71%, 379/536) exhibiting pathogenic monogenic mutations. Furthermore, 157 children (29.29%, 157/536) harbored DNA copy number variants, encompassing microdeletions (68.15%, 107/157) and microduplications (31.85%, 50/157). Regarding the pathogenicity of CNVs, 91 (57.96%, 91/157) were identified as pathogenic, 28 (17.83%, 28/157) as variants of uncertain clinical significance (VOUS), and 38 (24.20%, 38/157) as benign according to the American College of Medical Genetics and Genomics (ACMG).Using a specific sign-scoring scale, the proportion of pathogenic CNVs in children graded 1 point or higher (64%, 58/91) was significantly higher than that of non-pathogenic CNVs (43%, 29/66) (P < 0.05). Furthermore, the proportion of microdeletions in children graded 1 point or higher (60.75%, 65/107) was significantly higher than those carrying microduplications (44%, 22/50) (P < 0.05). The proportion of pathogenic microdeletions in children graded 1 point or higher (73.43%,47/64) was significantly higher than those carrying pathogenic microduplications (40.74%, 11/27) (P < 0.05).

Conclusion
The positive rate of whole-exome sequencing for children with combined craniofacial abnormalities and NDDs exceeds the international average in our study cohort. Thus, whole-exome sequencing may be recommended for precise diagnosis of neurogenetic diseases in such cases.
Evolutionary constrained genes associated with autism spectrum disorder across 2,054 nonhuman primate genomes
Authors: Kikuchi Yukiko , Uddin Mohammed , Veltman Joris A. , Wells Sara , Morris Christopher , Woodbury-Smith Marc 
Published: January 2025

Abstract

Background
Significant progress has been made in elucidating the genetic underpinnings of Autism Spectrum Disorder (ASD). However, there are still significant gaps in our understanding of the link between genomics, neurobiology and clinical phenotype in scientific discovery. New models are therefore needed to address these gaps. Rhesus macaques (Macaca mulatta) have been extensively used for preclinical neurobiological research because of remarkable similarities to humans across biology and behaviour that cannot be captured by other experimental animals.

Methods
We used the macaque Genotype and Phenotype (mGAP) resource consisting of 2,054 macaque genomes to examine patterns of evolutionary constraint in known human neurodevelopmental genes. Residual variation intolerance scores (RVIS) were calculated for all annotated autosomal genes (N = 18,168) and Gene Set Enrichment Analysis (GSEA) was used to examine patterns of constraint across ASD genes and related neurodevelopmental genes.

Results
We demonstrated that patterns of constraint across autosomal genes are correlated in humans and macaques, and that ASD-associated genes exhibit significant constraint in macaques (p = 9.4 × 10− 27). Among macaques, many key ASD-implicated genes were observed to harbour predicted damaging mutations. A small number of key ASD-implicated genes that are highly intolerant to mutation in humans, however, showed no evidence of similar intolerance in macaques (CACNA1D, MBD5, AUTS2 and NRXN1). Constraint was also observed across genes associated with intellectual disability (p = 1.1 × 10− 46), epilepsy (p = 2.1 × 10− 33) and schizophrenia (p = 4.2 × 10− 45), and for an overlapping neurodevelopmental gene set (p = 4.0 × 10− 10).

Limitations
The lack of behavioural phenotypes among the macaques whose genotypes were studied means that we are unable to further investigate whether genetic variants have similar phenotypic consequences among nonhuman primates.

Conclusion
The presence of pathological mutations in ASD genes among macaques, along with evidence of similar genetic constraints to those in humans, provides a strong rationale for further investigation of genotype-phenotype relationships in macaques. This highlights the importance of developing primate models of ASD to elucidate the neurobiological underpinnings and advance approaches for precision medicine and therapeutic interventions.