bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates
Authors: Kuang Junqi , Li Pengli , Zhai Ziwei , Fan Yixin , Xu HuaiYuan , Zhao Chengchen , Li Wei , Li Xiaoxi , Liang Zechuan , Huang Tao , Qin Yue , Gao Huiru , Ma Zhaoyi , Liu Dong , Zhong Guifa , Wang Bo , Liu Jing , Wang Jin , Tortorella Micky D. , Liao Baojian , Pei Duanqing 
Published: April 2024

AbstractNuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.
Associations between trans fatty acids and systemic immune-inflammation index: a cross-sectional study
Authors: Zhu Xiao-Feng , Hu Yu-Qi , Dai Zhi-Cheng , Li Xiu-Juan , Zhang Jing 
Published: April 2024

Abstract
Background
Previous studies have demonstrated that trans fatty acids (TFAs) intake was linked to an increased risk of chronic diseases. As a novel systemic inflammatory biomarker, the clinical value and efficacy of the systemic immune-inflammation index (SII) have been widely explored. However, the association between TFAs and SII is still unclear. Therefore, the study aims to investigate the connection between TFAs and SII in US adults.

Methods
The study retrieved data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999–2000 and 2009–2010. Following the exclusion of ineligible participants, the study encompassed a total of 3047 individuals. The research employed a multivariate linear regression model to investigate the connection between circulating TFAs and SII. Furthermore, the restricted cubic spline (RCS) model was utilized to evaluate the potential nonlinear association. Subgroup analysis was also conducted to investigate the latent interactive factors.

Results
In this investigation, participants exhibited a mean age of 47.40 years, with 53.91% of them being female. Utilizing a multivariate linear regression model, the independent positive associations between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, and the log2-transformed-total sum of TFAs with the SII (all P < 0.05) were noted. In the RCS analysis, no nonlinear relationship was observed between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, the log2-transformed-total sum of TFAs and the SII (all P for nonlinear > 0.05). For the stratified analysis, the relationship between the circulating TFAs and the SII differed by the obesity status and the smoking status.

Conclusions
A positive association was investigated between three types of TFA, the sum of TFAs, and the SII in the US population. Additional rigorously designed studies are needed to verify the results and explore the potential mechanism.
Implementation opportunities and challenges to piloting a community-based drug-checking intervention for sexual and gender minority men in Vancouver, Canada: a qualitative study
Authors: Coulaud Pierre-julien , Chayama Koharu Loulou , Schwartz Cameron , Purdie Aaron , Lysyshyn Mark , Ti Lianping , Knight Rod 
Published: April 2024

Abstract
Background
In response to the overdose crisis, a collaborative group of two community-based organizations, a health authority and a research institute in Vancouver, Canada, implemented a pilot community-based drug checking (CBDC) intervention for sexual and gender minority (SGM) men. This study identified key factors that influenced the implementation of the CBDC intervention, including opportunities and challenges.

Methods
We conducted semi-structured interviews with seven pertinent parties involved in the CBDC, including policymakers, researchers and representatives from community-based organizations. These interviews were coded and analyzed using domains and constructs of the Consolidated Framework for Implementation Research.

Results
While drug-related stigma was identified as a challenge to deliver drug checking services, participants described the context of the overdose crisis as a key facilitator to engage collaboration between relevant organizations (e.g., health authorities, medical health officers, community organizations) to design, resource and implement the CBDC intervention. The implementation of the CBDC intervention was also influenced by SGM-specific needs and resources (e.g., lack of information about the drug supply). The high level of interest of SGM organizations in providing harm reduction services combined with the need to expand drug checking into community spaces represented two key opportunities for the CBDC intervention. Here, SGM organizations were recognized as valued partners that fostered a broader culture of harm reduction. Participants’ emphasis that knowing the composition of one’s drugs is a “right to know”, particularly in the context of a highly contaminated illicit drug market, emerged as a key implementation factor. Lastly, participants emphasized the importance of involving SGM community groups at all stages of the implementation process to ensure that the CBDC intervention is appropriately tailored to SGM men.

Conclusions
The context of the overdose crisis and the involvement of SGM organizations were key facilitators to the implementation of a drug checking intervention in SGM community spaces. This study offers contextualized understandings about how SGM knowledge and experiences can contribute to implement tailored drug checking interventions.
Obesity-induced blood-brain barrier dysfunction: phenotypes and mechanisms
Authors: Feng Ziying , Fang Cheng , Ma Yinzhong , Chang Junlei 
Published: April 2024

AbstractObesity, a burgeoning global health issue, is increasingly recognized for its detrimental effects on the central nervous system, particularly concerning the integrity of the blood-brain barrier (BBB). This manuscript delves into the intricate relationship between obesity and BBB dysfunction, elucidating the underlying phenotypes and molecular mechanisms. We commence with an overview of the BBB’s critical role in maintaining cerebral homeostasis and the pathological alterations induced by obesity. By employing a comprehensive literature review, we examine the structural and functional modifications of the BBB in the context of obesity, including increased permeability, altered transport mechanisms, and inflammatory responses. The manuscript highlights how obesity-induced systemic inflammation and metabolic dysregulation contribute to BBB disruption, thereby predisposing individuals to various neurological disorders. We further explore the potential pathways, such as oxidative stress and endothelial cell dysfunction, that mediate these changes. Our discussion culminates in the summary of current findings and the identification of knowledge gaps, paving the way for future research directions. This review underscores the significance of understanding BBB dysfunction in obesity, not only for its implications in neurodegenerative diseases but also for developing targeted therapeutic strategies to mitigate these effects.
The impact of anxiety on gait impairments in Parkinson’s disease: insights from sensor-based gait analysis
Authors: Zhang Xiaodan , Jin Yulan , Wang Mateng , Ji Chengcheng , Chen Zhaoying , Fan Weinv , Rainer Timothy Hudson , Guan Qiongfeng , Li Qianyun 
Published: April 2024

Abstract
Background
Sensor-based gait analysis provides a robust quantitative tool for assessing gait impairments and their associated factors in Parkinson’s disease (PD). Anxiety is observed to interfere with gait clinically, but this has been poorly investigated. Our purpose is to utilize gait analysis to uncover the effect of anxiety on gait in patients with PD.

Methods
We enrolled 38 and 106 PD patients with and without anxiety, respectively. Gait parameters were quantitively examined and compared between two groups both in single-task (ST) and dual-task (DT) walking tests. Multiple linear regression was applied to evaluate whether anxiety independently contributed to gait impairments.

Results
During ST, PD patients with anxiety presented significantly shorter stride length, lower gait velocity, longer stride time and stance time, longer stance phase, smaller toe-off (TO) and heel-strike (HS) angles than those without anxiety. While under DT status, the differences were diminished. Multiple linear regression analysis demonstrated that anxiety was an independent factor to a serials of gait parameters, particularly ST-TO (B = -2.599, (-4.82, -0.38)), ST-HS (B = -2.532, (-4.71, -0.35)), ST-TO-CV (B = 4.627, (1.71, 7.64)), ST-HS-CV(B = 4.597, (1.66, 7.53)), ST stance phase (B = 1.4, (0.22, 2.58)), and DT stance phase (B = 1.749, (0.56, 2.94)).

Conclusion
Our study discovered that anxiety has a significant impact on gait impairments in PD patients, especially exacerbating shuffling steps and prolonging stance phase. These findings highlight the importance of addressing anxiety in PD precision therapy to achieve better treatment outcomes.
Combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of a mid-distal adjacent finger defect: a retrospective study
Authors: Ge Meng , Zhang Zhijin , Ren Guohua , Hong Shenghu , chen Cheng , Yang Jun , Hou Qiao , Fu Hongmei 
Published: April 2024

Abstract
Purpose
Assessing the clinical effectiveness of combining with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold to repair mid-distal defects in adjacent fingers.

Methods
From September 2012 to April 2022, 21 patients with 42 mid-distal defects of adjacent fingers underwent treatment using combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold. The flaps size ranged from 2.1 cm * 1.6 to 4.9 cm * 3.2 cm. Follow-up evaluations included assessing function, sensation, and appearance, etc. of the injured fingers and donor areas.

Results
All 42 flaps survived in 21 patients without any vascular crises, and the wounds healed in phase I. The mean follow-up time was 12.2 months (range 7–22 months). During follow-up, in injured fingers, according to the Michigan Hand Outcomes Questionnaire (MHOQ), the functional recovery and appearance were satisfactory; in Dargan Function Evaluation (DFE), the results were both “excellent” in fourteen patients, “excellent” and “good” in five patients, both “good” in one patient, “good” and “general” in one. In static two-point discrimination (2PD), the variation ranges from 4 to 9 mm in injured fingers and 6—10 mm in donor toes. Cold Intolerance Severity Score (CISS) is mild in all patients. The visual analogue score (VAS) showed no pain in the injured fingers and donor toes. No deformities or other complications were noted at the donor toes. According to Chinese Manchester Foot Pain and Disability Index (C-MFPDI), there was no morbidity on foot function in all donor areas.

Conclusion
The surgical procedure of combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of mid-distal adjacent fingers defect is highly satisfactory. This approach helps the injured fingers to achieve good function, sensibility and appearance, while also achieving satisfactory results in the donor toes.
Assessing fragility of statistically significant findings from randomized controlled trials assessing pharmacological therapies for opioid use disorders: a systematic review
Authors: Naji Leen , Dennis Brittany , Rodrigues Myanca , Bawor Monica , Hillmer Alannah , Chawar Caroul , Deck Eve , Worster Andrew , Paul James , Thabane Lehana , Samaan Zainab 
Published: April 2024

Abstract
Background
The fragility index is a statistical measure of the robustness or “stability” of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials’ outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades.

Methods
Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials.

Results
Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52–226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1–26).

Conclusions
Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings.

Trial registration
PROSPERO CRD42013006507. Registered on November 25, 2013.
A nonlinear relationship between the triglycerides to high-density lipoprotein cholesterol ratio and stroke risk: an analysis based on data from the China Health and Retirement Longitudinal Study
Authors: Zhang Shike , Cao Changchun , Han Yong , Hu Haofei , Zheng Xiaodan 
Published: April 2024

Abstract
Objective
The connection between triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and stroke risk is controversial. Our goal was to explore this relationship in individuals aged 45 and older enrolled in the China Health and Retirement Longitudinal Study (CHARLS).

Methods
Our analysis encompassed 10,164 participants from the CHARLS cohorts. We applied the Cox proportional-hazards regression model to evaluate the potential correlation between the TG/HDL-C ratio and stroke incidence. Using a cubic spline function and smooth curve fitting within the Cox model allowed us to unearth a possible non-linear pattern in this relationship. We also conducted thorough sensitivity and subgroup analyses to deepen our understanding of the TG/HDL-C ratio’s impact on stroke risk.

Results
Adjusting for various risk factors, we observed a significant link between the TG/HDL-C ratio and increased stroke risk in individuals aged 45 and above (HR: 1.03, 95% CI 1.00–1.05, P = 0.0426). The relationship appeared non-linear, with an inflection at a TG/HDL-C ratio of 1.85. Ratios below this threshold indicated a heightened stroke risk (HR: 1.28, 95% CI 1.06–1.54, P = 0.0089), while ratios above it did not show a significant risk increase (HR: 1.01, 95% CI 0.98–1.04, P = 0.6738). Sensitivity analysis confirmed the robustness of these findings. Notably, non-smokers exhibited a stronger correlation between the TG/HDL-C ratio and stroke risk compared to past and current smokers.

Conclusion
Our investigation revealed a significant, yet non-linear, association between the TG/HDL-C ratio and the incidence of stroke among individuals aged 45 and above. Specifically, we found that stroke risk increased in correlation with TG/HDL-C ratio below the threshold of 1.85. These insights may guide healthcare providers in advising and developing more effective strategies for stroke prevention in this demographic.
Prevalence of Helicobacter pylori infection and effectiveness of first-line triple eradication therapy among dyspeptic patients at hospitals in Hawassa City, Ethiopia: a cross-sectional follow-up study
Authors: Fekadu Sintayehu , Kibru Seyife , Tesfaye Sisay , Egeno Tariku , Tamiso Alemu , Engiso Hizkel , Deyno Serawit 
Published: April 2024

Abstract
Background
Dyspepsia is a common gastrointestinal illness sometimes associated with Helicobacter pylori (H. pylori) infection. Screening and eradicating the bacterium reduces the risk of infection-related complications. The aim of this study was to determine the magnitude of H. pylori infection among dyspeptic patients and the effectiveness of triple eradication therapy at hospitals in Hawassa city, Ethiopia.

Results
The prevalence of H. pylori infection was 48.5%. The H. pylori eradication rate using first-line triple therapy was 83.8%. Eradication therapy failure is associated with previous exposure compared to no exposure (AOR: 4.8, 95% CI: 1.37–10.97), a regimen for 10-days compared to 14-days (AOR: 4.05, 95% CI: 1.42–11.55), and self-reported side effects compared to no report (AOR: 2.5, 95% CI: 1.12–5.97). Based on Morisky-eight scale 230 (79.0%) patients were adherent to their triple therapy. Participants with no reports of adverse effects showed increased odds of adherence to triple therapy compared to those who had reports (AOR = 2.45, 95% CI: 1.29–4.62).

Conclusions
This study demonstrated that about half of adult dyspeptic patients were infected with H. pylori, and moderate eradication was observed. Factors such as previous history of eradication therapy, duration of the eradication regimen, and perception of potential adverse effects are associated with eradication rate and should be considered during the initiation of eradication therapy.
Utilization of fluid-based biomarkers as endpoints in disease-modifying clinical trials for Alzheimer’s disease: a systematic review
Authors: Oosthoek Marlies , Vermunt Lisa , de Wilde Arno , Bongers Bram , Antwi-Berko Daniel , Scheltens Philip , van Bokhoven Pieter , Vijverberg Everard G. B. , Teunissen Charlotte E. 
Published: April 2024

Abstract
Background
Clinical trials in Alzheimer’s disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development.

Methods
We systematically reviewed 272 trials (clinicaltrials.gov) with disease-modifying therapies starting between 01–01-2017 and 01–01-2024 and identified which CSF and/or blood-based biomarker endpoints were used per purpose and trial type.

Results
We found that 44% (N = 121) of the trials employed fluid-based biomarker endpoints among which the CSF ATN biomarkers (Aβ (42/40), p/tTau) were used most frequently. In blood, inflammatory cytokines, NFL, and pTau were most frequently employed. Blood- and CSF-based biomarkers were used approximately equally. Target engagement biomarkers were used in 26% (N = 72) of the trials, mainly in drugs targeting inflammation and amyloid. Lack of target engagement markers is most prominent in synaptic plasticity/neuroprotection, neurotransmitter receptor, vasculature, epigenetic regulators, proteostasis and, gut-brain axis targeting drugs. Positive biomarker results did not always translate to cognitive effects, most commonly the small significant reductions in CSF tau isoforms that were seen following anti-Tau treatments. On the other hand, the positive anti-amyloid trials results on cognitive function were supported by clear effect in most fluid markers.

Conclusions
As the field moves towards primary prevention, we expect an increase in the use of fluid-based biomarkers to determine disease modification. Use of blood-based biomarkers will rapidly increase, but CSF markers remain important to determine brain-specific treatment effects. With improving techniques, new biomarkers can be found to diversify the possibilities in measuring treatment effects and target engagement. It remains important to interpret biomarker results in the context of the trial and be aware of the performance of the biomarker. Diversifying biomarkers could aid in the development of surrogacy biomarkers for different drug targets.
Factors influencing medical expenditures in patients with unresolved facial palsy and pharmacoeconomic analysis of upper eyelid lid loading with gold and platinum weights compared to tarsorrhaphy
Authors: Nowak-Gospodarowicz Izabela , Gospodarowicz Marcin , Rękas Marek 
Published: April 2024

AbstractThere are no standards in diagnostic and therapeutic approaches to eye care in incomplete eyelid closure due to unresolved facial palsy (FP). Loading of the upper eyelid (UELL) with gold weights (GWs) or platinum chains (PCs) is a highly effective procedure for the correction of lagophthalmos. Despite this, the procedure is used infrequently in our country because of the relatively high price of the implant and the lack of reimbursement. The aim of this research was to assess the factors influencing medical expenditures in this group of patients and to analyze utility costs for the UELL procedure with the use of GW and PC compared to tarsorrhaphy.Material and methods The costs of 88 surgical procedures (40 GWs, 11 PCs and 37 tarsorrhaphies) and medical expenditures before and after surgery were calculated based on reporting of materials, staff salaries and the SF-36 questionnaire. Distribution quartiles of the cost per QALY measure (dependent variable) was assessed via an ordered logistic regression model with eight explanatory variables.Results The calculated total cost of the surgery was US$209 for tarsorrhaphy, US$758 for UELL with a GW and US$1,676 for UELL with a PC. Bootstrapped costs per QALY values (CUI) in 88% of cases were below the US$100,000 cutoff. Etiology and duration of facial palsy and presence of Bell’s phenomenon were factors that significantly influenced the CUI. Patient gender and age, history of previous eyelid surgery, and presence of corneal sensation were found to be not significant (p > 0.1). Calculated ICER for GW was US$1,241.74/1QALY and ICER for PC was US$13,181.05/1QALY compared to tarsorrhaphy.Conclusions Eye protection in patients with FP should be a crucial element of health policy. Findings suggest UELL procedure with a GW or a PC to be a cost-effective procedure with GW being the most cost-effective.