bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short Horizon for Audit Partner and Audit Quality: Evidence From a Dual-Rotation Regime
Authors: Mazza Tatiana , Azzali Stefano , Reichelt Kenneth J. , Fornaciari Luca 
Published: February 2025

Our study examines how a short audit partner horizon affects audit quality. A short audit partner horizon originates from the joint requirement of mandatory audit firm rotation and mandatory audit partner rotation. We study a unique setting in Italy where a 9-year mandatory firm rotation term and a 7-year mandatory partner rotation term are jointly imposed. The outcome is at least two partner horizons, where one partner horizon is shorter than the other. We predict that the partner with the shorter horizon will likely invest less effort in acquiring client knowledge. Namely, the expected payoffs are fewer, tacit knowledge is not sufficiently transferred from the previous partner, and monitoring by the successor partner is insufficient. We find that clients whose auditors have a shorter partner horizon are associated with lower audit quality. Our findings provide insights for academics, audit firms, and regulators in evaluating auditor rotation strategies in their countries, especially in the European Union, where member states have mandatory audit partner and audit firm rotation. JEL codes: M42 and M48
A Mendelian randomization approach for advancing healthcare innovation: From pregnancy hypertension to schizophrenia
Authors: Peng Wenjie , Ran Qingqi , Wu Fang , Hu Zhangxue 
Published: February 2025

Background Schizophrenia, a severe mental disorder, is strongly associated with perinatal factors, including pregnancy hypertension, which affects fetal neurodevelopment. The causal relationship between pregnancy hypertension and schizophrenia remains unclear. Objective To investigate the causal relationship between pregnancy hypertension and schizophrenia using a two-sample Mendelian randomization (MR) study. Methods Pregnancy hypertension (cases/controls: 7686/115,8993) was considered as exposure and schizophrenia (cases/controls: 76755/243,649) as outcome. A two-sample MR study genetically estimated associations, with the inverse variance-weighted method as primary analysis. A two-step MR study explored potential mediators. Sensitivity tests assessed pleiotropy, heterogeneity, and stability. Results Four single nucleotide polymorphisms (SNPs) were identified as genetic instruments for pregnancy hypertension (P < 5 × 10-8, r² < 0.001). Pregnancy hypertension increased the risk of schizophrenia (odds ratio = 1.098, 95% CI = 1.025–1.173, P = 0.007), while reverse MR analysis found no significant link (odds ratio = 1.03, 95% CI = 0.980–1.082, P = 0.235). The two-step study revealed pregnancy hypertension elevated levels of 1,4-Dihydroxy-2-naphthoic acid (odds ratio = 1.351, 95% CI = 1.097–1.664, P = 0.004), which decreased schizophrenia risk (odds ratio = 0.97, 95% CI = 0.942–0.998, P = 0.040). Conclusion Pregnancy hypertension is a high-risk factor for schizophrenia, with 1,4-Dihydroxy-2-naphthoic acid potentially mitigating this effect. These findings offer insights for the prophylaxis of schizophrenia and highlight the need for further research into underlying mechanisms.
Assessment of the quality and reliability of Turkish YouTube videos on frozen shoulder exercises
Authors: Tuna Mustafa , Ay Bilgehan Kolutek 
Published: February 2025

Purpose This study aimed to evaluate the reliability and quality of Turkish videos about frozen shoulder exercises published on the Youtube platform. Material-Method 54 videos were included in the study as a result of searches and evaluations made on the YouTube platform using the keywords “frozen shoulder exercises” and “adhesive capsulitis exercises”. The included videos were evaluated by two independent observers and a final independent 3rd observer, and the given modified DISCERN (mDISCERN), Global Quality Scale (GQS) and JAMA scores were compared with other video parameters. Differences between groups were examined. Result Exercises were detected in 10 different categories in the 54 videos included in the study. In the examination made according to GQS scoring, a statistically significant relationship was found between the viewing rate, mDISCERN and JAMA scores, the number of exercise types included in the video and the GQS quality grouping (p < 0.05). In the examination conducted in terms of reliability, a statistically significant relationship was found between mDISCERN scores and the number of exercise types included in the videos, JAMA and GQS scores (p < 0.05). Conclusion In our study, more than half of the frozen shoulder exercise videos on the Youtube platform were found to be low in reliability and quality. Due to the variety of content in the videos and the lack of individualized exercises, YouTube does not appear to be a suitable resource for frozen shoulder exercises. Considering all these, we believe that videos with informative content should be created by physicians or should be audited.
Radiation symptoms resemble laminopathies and the physical underlying cause may sit at the lamin A C-terminus
Authors: Waldherr Alexandra , Fogtman Anna 
Published: February 2025

Abstract
Ionizing radiation causes three divergent effects in the human body: On one side, tissue death (= deterministic effects) sets on, on the other side, mutations and cancer growth (= stochastic effects) can occur. In recent years, the additional phenomenon of accelerated aging has come to light. In the following, we argue that these seemingly contradictory radiation responses namely: (i) increased cancer growth, (ii) ablation of cancer tissue or (iii) deterministic senescence, share an underlying cause from damage at the lamin A C-terminus. In other words, besides the typically described genomic radiation impact, we propose an additional destabilization pathway via oxidation at the nuclear envelope. We propose five concrete hypotheses that draw a direct mechanistic model from radiation damage and cellular oxidative stress, to micronuclei and clinical symptoms. In conjunction with lamin B compensation, we might be able to explain why deterministic or stochastic responses dominate. If our model holds true, a novel target for radiotherapeutics and radiooncology arises, and a rationale to closer connect laminopathy and radioprotection research.

Graphical Abstract
Profiling conserved transcription factor binding motifs in Phaseolus vulgaris through comparative genomics
Authors: Kondratova Liudmyla , Vallejos C. Eduardo , Conesa Ana 
Published: February 2025

Abstract
Common bean (Phaseolus vulgaris), a staple food in Latin America and Africa, serves as a vital source of energy, protein, and essential minerals for millions of people. However, genomics knowledge that breeders could leverage for improvement of this crop is scarce. We have developed and validated a comparative genomics approach to predict conserved transcription factor binding sites (TFBS) in common bean and studied gene regulatory networks. We analyzed promoter regions and identified TFBS for 12,631 bean genes with an average of 6 conserved motifs per gene. Moreover, we discovered a statistically significant relationship between the number of conserved motifs and amount of available experimental evidence of gene regulation. Notably, ERF, MYB, and bHLH transcription factor families dominated conserved motifs, with implications for starch biosynthesis regulation. Furthermore, we provide gene regulatory data as a resource that can be interrogated for the regulatory landscape of any set of genes. Our results underscore the significance of TFBS conservation in legumes and aligns with the notion that core genes often exhibit a more conserved regulatory makeup. The study demonstrates the effectiveness of a comparative genomics approach for addressing genome information gaps in non-model organisms and provides valuable insights into the regulatory networks governing starch biosynthesis genes that can support crop improvement programs.
Additive effect of a single intravenous dose of acetaminophen administered at the end of laparoscopic hysterectomy on postoperative pain control with nefopam and fentanyl-based patient-controlled analgesia: a double-blind, randomized controlled trial
Authors: Nam Seungpyo , Yoo Seokha , Park Sun-Kyung , Kim Jin-Tae 
Published: February 2025

Abstract

Background
Acetaminophen is a widely used analgesic for postoperative pain management. However, data on its combined use with nefopam for managing postoperative pain following laparoscopic hysterectomy are limited. This study evaluated the effects of a single intravenous dose of acetaminophen combined with fentanyl- and nefopam-based patient-controlled analgesia (PCA) in patients undergoing laparoscopic hysterectomy.

Methods
In this prospective, double-blind, randomized controlled trial, 84 patients were randomized to receive either 1 g of intravenous acetaminophen (treatment group, n = 42) or normal saline (control group, n = 42) at the end of surgery. All patients received fentanyl and nefopam via PCA, postoperatively. PCA consumption, pain scores at rest, and postoperative nausea and vomiting (PONV) scores were assessed at 1, 6, and 24 h postoperatively. Patient satisfaction and opioid-related side effects were also evaluated. The primary outcome was the total PCA consumption within the first 24 h.

Results
No significant difference in 24-h PCA consumption was observed between the control and treatment groups (27.9 ± 16.6 vs. 26.4 ± 11.2, P = 0.623). The pain scores at rest measured at 1, 6, and 24 h after surgery were also not significantly different between the two groups. There were no differences in the satisfaction scores, PONV scores, rescue analgesic use, adverse effects, or length of hospital stay between the groups.

Conclusions
A single intraoperative dose of intravenous acetaminophen, combined with nefopam- and fentanyl-based PCA, did not significantly reduce analgesic requirements, pain scores at rest, or opioid-related side effects compared with placebo in laparoscopic hysterectomy patients.

Trial registration
ClinicalTrials.gov (Identifier: NCT03644147 | August 21, 2018).
Association between glycation gap and impaired cardiorespiratory fitness: evidence from American adults
Authors: Fei Min , Wu Bo , Tu Jiabin , Chen Hongkui , Guo Yansong 
Published: February 2025

Abstract

Background
Cardiorespiratory fitness (CRF) is a critical indicator of overall health, while the glycation gap (G-Gap) emerges as a potential novel biomarker for metabolic and cardiovascular risk assessment. However, the relationship between G-Gap and CRF remains incompletely understood.

Objective
To investigate the association between glycation gap and impaired CRF, and evaluate its potential as an early health risk indicator.

Methods
Using data from the National Health and Nutrition Examination Survey (NHANES, 1999–2004), we conducted a comprehensive analysis of 3,818 adult participants. G-Gap was calculated by standardizing glycated albumin (GA) and glycated hemoglobin (HbA1c) levels, comparing actual and predicted HbA1c values. Cardiorespiratory fitness was assessed through maximal oxygen uptake (VO2 max), with impaired CRF defined as performance below the 20th percentile for gender and age-specific thresholds. Multivariate logistic regression models were employed, adjusting for demographic characteristics, laboratory parameters, and potential confounding factors.

Results
In unadjusted models, For every 1 increase in G-Gap as a continuous variable, the chance of CRF damage increased by 65% (OR 1.65, 95% CI 1.29–2.11). After comprehensive covariate adjustment, the association remained statistically significant, with odds ratios of 1.87 (95% CI 1.41–2.49) in partially adjusted and 1.41 (95% CI 1.01–1.98) in fully adjusted models. Quartile analysis revealed significantly higher risks of impaired CRF in the third and fourth G-Gap quartiles compared to the first quartile.

Conclusions
This study demonstrates an association between higher G-Gap values and an increased likelihood of impaired CRF.
Perceived discrimination and coping with substance use among Asian Americans during the COVID-19 pandemic: a cross-sectional analysis
Authors: Bacong Adrian Matias , Maglalang Dale Dagar , Tsoh Janice Y. , Saw Anne 
Published: February 2025

Abstract

Background
Race/ethnicity-related discrimination against Asian Americans increased during the COVID-19 pandemic. Previous studies have found an association between discrimination and use of alcohol and other drugs (AOD) as a form of coping. In this study, we evaluate the association of stress from race/ethnicity-related discrimination and coping with tobacco, alcohol, or cannabis (marijuana or cannabidiol) among Asian Americans during the pandemic.

Methods
We used data from Asian American participants of the Asian American and Native Hawaiian/Pacific Islander (AA & NH/PI) COVID-19 Needs Assessment Project (n = 3,159). We measured COVID-19 discrimination by racial/ethnic discrimination perceived as the greatest stressor, whether racial/ethnic discrimination impacted participants’ families, and perceived racial bias. Binary logistic regression examined the association between each AOD outcome, discrimination variables, and other COVID-19 stressors accounting for sociodemographic factors, physical and mental health, and survey medium.

Results
Asian Americans used alcohol to cope with COVID-19 pandemic stressors (13.0%) followed by tobacco (4.3%) and cannabis (4.1%). About 24% of Asian Americans reported that racial/ethnic discrimination was the greatest source of stress. Racial/ethnic discrimination was only associated with cannabis use. However, COVID-19 stressors (aside from discrimination) were positively associated with all the AOD outcomes.

Conclusions
Asian Americans’ AOD use for stress coping during the pandemic was prevalent. Perceived racial bias was associated with cannabis use, however other pandemic-induced stressors, not discriminatory in nature, were consistently associated with AOD use. Targeted research and policy efforts are warranted to address impacts from diverse stressors while tackling racism and substance use within Asian American communities to facilitate post-pandemic recovery.
miR-193b-3p suppresses lung cancer cell migration and invasion through PRNP targeting
Authors: Ho Hsiang-Ling , Lin Shin-Chih , Chiang Chao-Wei , Lin Ching , Liu Che-Wei , Yeh Yi-Chen , Chen Mei-Yu , Chou Teh-Ying 
Published: February 2025

Abstract

Background
Tumor metastasis is responsible for approximately 90% of mortality in lung cancer. Understanding the molecular mechanisms of lung cancer metastasis is crucial for developing new treatment strategies. Cellular prion protein (PrPc), encoded by PRNP gene, was previously found to enhance lung cancer invasiveness. However, research on the post-transcriptional regulation of PRNP remains limited.

Methods
Dual-luciferase reporter assays identified miRNAs targeting the PRNP 3'-UTR, and RNA immunoprecipitation (RIP) confirmed the interaction between miR-193b-3p and PRNP mRNA. Promoter deletions and chromatin immunoprecipitation (ChIP) assays established c-Jun as a transcriptional repressor of miR-193b-3p. Functional validation of the c-Jun-miR-193b-3p-PrPc axis was conducted using transwell assays, LNA-in situ hybridization, RT-PCR, Western blot, and immunohistochemistry. Subcutaneous mouse xenograft models assessed the anti-tumor effects of miR-193b-3p in vivo.

Results
We demonstrated that miR-193b-3p downregulates PrPc expression by directly targeting the 3'-UTR of PRNP. Overexpression of miR-193b-3p significantly suppressed PRNP expression at both mRNA and protein levels, and reduced lung cancer cell migration, invasion and proliferation, which was reversed by PrPc overexpression. Conversely, miR-193b-3p silencing enhanced PRNP expression as well as those oncogenic properties, which were mitigated by PRNP knockdown. Spearman correlation analysis revealed a significant negative association between miR-193b-3p and PrPc expression in lung cancer tissues (p = 0.017), and Kaplan–Meier survival analysis demonstrated that high PrPc (p = 0.039) or low miR-193b-3p (p = 0.027) expression correlated with poorer overall survival. Intra-tumoral injection of the miR-193b-3p mimic in mouse xenograft models significantly reduced tumor volume. In addition, c-Jun was identified as a transcriptional repressor of miR-193b-3p. Functional studies revealed that c-Jun knockdown inhibited lung cancer cell migration, invasion, and proliferation, effects that were reversed by either PrPc overexpression or miR-193b-3p inhibitor treatment. A significant association between PrPc and c-Jun expression in lung cancer tissues (p = 0.004) was observed. High expression of PrPc and/or c-Jun was found to be associated with poor overall survival of patients (p < 0.05).

Conclusions
This study is the first to uncover a novel regulatory pathway where c-Jun acts as a transcriptional repressor of miR-193b-3p, leading to PRNP upregulation, which promotes lung cancer migration and invasion. This previously unrecognized c-Jun-miR-193b-3p-PrPc axis also provides valuable insights for the potential development of new therapeutic strategies against lung cancer metastasis through RNA-targeting technology.
MGMT epimutations and risk of incident cancer of the colon, glioblastoma multiforme, and diffuse large B cell lymphomas
Authors: Nikolaienko Oleksii , Anderson Garnet L. , Chlebowski Rowan T. , Jung Su Yon , Harris Holly R. , Knappskog Stian , Lønning Per E. 
Published: February 2025

Abstract

Background
Constitutional BRCA1 epimutations (promoter hypermethylation) are associated with an elevated risk of triple-negative breast cancer and high-grade serous ovarian cancer. While MGMT epimutations are frequent in colon cancer, glioblastoma, and B-cell lymphoma, it remains unknown whether constitutional MGMT epimutations are associated with risk of any of these malignancies.

Methods
We designed a nested case–control study, assessing potential associations between MGMT epimutations in blood from healthy individuals and subsequent risk of incident cancer. The study cohort was drawn from postmenopausal women, participating in the Women’s Health Initiative (WHI) study, who had not been diagnosed with either colon cancer, glioblastoma, or B-cell lymphoma prior to study entry. The protocol included n = 400 women developing incident left-sided and n = 400 women developing right-sided colon cancer, n = 400 women developing diffuse large B-cell lymphomas, all matched on a 1:2 basis with cancer-free controls, and n = 195 women developing incident glioblastoma multiforme, matched on a 1:4 basis. All cancers were confirmed in centralized medical record review. Blood samples, collected at entry, were analyzed for MGMT epimutations by massive parallel sequencing. Associations between MGMT methylation and incident cancers were analyzed by Cox proportional hazards regression.

Results
Analyzing epimutations affecting the key regulatory area of the MGMT promoter, the hazard ratio (HR) was 1.07 (95% CI 0.79–1.45) and 0.80 (0.59–1.08) for right- and left-sided colon cancer, respectively, 1.13 (0.78–1.64) for glioblastoma, and 1.11 (0.83–1.48) for diffuse large B-cell lymphomas. Sensitivity analyses limited to subregions of the MGMT promoter and to individuals with different genotypes of a functional SNP in the MGMT promoter (rs16906252), revealed no significant effect on HR for any of the cancer forms. Neither did we observe any effect of rs16906252 status on HR for any of the cancer forms among individuals methylated or non-methylated at the MGMT promoter.

Conclusions
Constitutional MGMT promoter methylation in normal tissue is not associated with an increased risk of developing colon cancer, glioblastoma, or B-cell lymphoma.
Low apolipoprotein A-II levels causally contribute to increased mortality in septic shock
Authors: Takahashi Nozomi , Campbell Kyle R. , Shimada Tadanaga , Nakada Taka-aki , Russell James A. , Walley Keith R. 
Published: February 2025

Abstract

Background
Lipoproteins and their component apolipoproteins play an important role in sepsis. However, little is known with regard to the association and causal contribution of these proteins to mortality in patients of different ancestries following septic shock. The objective of this study was to determine whether lipoprotein and apolipoprotein levels, and related genetic variants, are associated with clinical outcomes in septic shock.

Methods
We investigated the association between lipoprotein and apolipoprotein levels at the point of admission to the intensive care unit and in-hospital mortality in 687 Japan patients diagnosed with septic shock. For each clinically significant candidate protein, we extracted haplotype tag single nucleotide polymorphisms (SNPs) of the corresponding gene and examined the association of the candidate gene variants with 28-day mortality and organ dysfunction. We tested for replication in a Caucasian septic shock cohort (Vasopressin and Septic Shock Trial, VASST, n = 474). To determine whether the candidate lipoprotein causally contributed to septic shock outcome, we used a Mendelian randomization analysis based on polygenic scores generated from a genome-wide association study (GWAS) in the Japan cohort.

Results
In the Japan cohort, low apolipoprotein A-II levels were associated with increased septic shock mortality (adjusted odds ratio, 1.05; 95%CI, 1.02–1.09; P < 0.001). For a haplotype tag SNP of the corresponding ApoA2 gene, rs6413453 GG carriers had significantly higher 28-day mortality (adjusted hazard ratio [aHR], 1.79; 95% confidence interval [CI], 1.06–3.04; P = 0.029) and significantly fewer days free of cardiovascular, respiratory, renal and neurologic dysfunction than AG/AA carriers. This result was replicated in the Caucasian septic shock cohort (28-day mortality: aHR, 1.65; 95% CI, 1.02–2.68; P = 0.041). Mendelian randomization using 9 SNPs from an apolipoprotein A-II GWAS suggested that genetically decreased levels of apolipoprotein A-II were a causal factor for increased mortality in septic shock (odds ratio for mortality due to a 1 mg/dL decrease in apolipoprotein A-II is 1.05 [95% CI; 1.01–1.03, P = 0.0022]).

Conclusions
In septic shock, apolipoprotein A-II levels and ApoA2 genetic variations are important factors associated with outcome.
Intermittent Echocardiographic Monitoring During Superior Vena Cava Recanalization: A Protocol for Early Recognition and Management of Hemopericardium
Authors: Fitzgerald Kara M. , Shin David S. , Monroe Eric J. , Abad Santos Matthew , Hua Ethan , Chick Jeffrey Forris Beecham 
Published: February 2025

Abstract

Purpose
Endovascular recanalization and stent reconstruction constitute an effective and safe treatment option for symptomatic thoracic central venous obstruction (TCVO). Rare life-threatening adverse events are possible during or immediately following the procedure, with the most feared one being hemopericardium with cardiac tamponade. A technique to improve efficiency in detection and treatment of cardiac tamponade is described.

Materials and methods
An institutional protocol was established for intraprocedural transthoracic echocardiographic monitoring during the TCVO recanalization procedures. The lower chest and upper abdomen were prepared within the sterile field. A separate stand was set up with unopened supplies needed for pericardial drain placement. Intermittent echocardiographic monitoring was performed throughout the TCVO procedure using a dedicated curvilinear probe prepared on the field. If indicated, an image guided pericardial drain was placed expeditiously.

Results
Four cases of cardiac tamponade were encountered during or immediately post-procedure. All cases demonstrated technically successful and prompt pericardial drain placement with immediate reversal of the tamponade physiology.

Conclusion
Echocardiographic monitoring during TCVO reconstruction by interventional radiologists is a useful technique which may aid in early diagnosis and management of cardiac tamponade.