bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histone demethylase KDM6B links obstructive sleep apnea to idiopathic pulmonary fibrosis
Authors: Han Shuangyu , Huang Jie , Yang Changqing , Feng Jing , Wang Yubao 
Published: January 2025

AbstractObstructive sleep apnea (OSA) is increasingly recognized for its link to idiopathic pulmonary fibrosis (IPF), though the underlying mechanisms remain poorly understood. Histone lysine demethylase 6B (KDM6B) may either prevent or promote organ fibrosis, but its specific role in IPF is yet to be clarified. This study aimed to investigate the function and mechanisms of KDM6B in IPF and the exacerbating effects of OSA. We assessed KDM6B levels in lung tissues from IPF patients, IPF mouse models, and a dual‐hit model combining OSA‐associated intermittent hypoxia (IH) with bleomycin (BLM) or TGF‐β1. We evaluated pulmonary fibrosis, myofibroblast activation, and oxidative stress. KDM6B levels were elevated in lung tissues from IPF patients and BLM‐treated mice, as well as in TGF‐β1‐stimulated myofibroblasts. Importantly, IH significantly worsened BLM‐induced pulmonary fibrosis and TGF‐β1‐induced myofibroblast activation, further amplifying KDM6B expression both in vivo and in vitro. Inhibition of KDM6B reduced pulmonary fibrosis and decreased fibroblast activation and migration in IPF and dual‐hit models. Mechanistically, KDM6B inhibition led to decreased NOX4 expression and reduced oxidative stress. KDM6B plays a critical role in promoting pulmonary fibrosis and mediating the exacerbating effects of OSA on this condition. Our findings identify KDM6B as a novel potential therapeutic target for IPF.
Budget Impact Analysis of Integrative Medicine Practices for Pediatric Patients With Chronic Pain
Authors: Gong Cynthia L. , Okoro Chelsea C. , Wan Ruihan , Lopez Cristal , Ngo Nhat H. , Gold Jeffrey I. 
Published: January 2025

Objectives:
Chronic pain is a leading cause of morbidity in children and adolescents globally but can be managed with a combination of traditional Western medicine and integrative medicine (IM) practices. This combination has improved various critical health outcomes, such as quality of life, sleep, pain, anxiety, and health care utilization. These IM practices include acupuncture, yoga, biofeedback, massage, mindfulness, or any combination of these modalities. The current article﻿ developed a budget impact model to estimate the institutional costs of implementing these practices among adolescents.

Methods:
A decision tree was used to estimate the reduction in hospitalizations and emergency department (ED) use based on a previously published retrospective analysis of children receiving IM practices comparing utilization rates 1-year pre-implementation and post-implementation of IM services (Figure 1). Costs associated with implementing each modality were based on hourly compensation rates for licensed professionals administering each service and equipment associated with delivery (eg, acupuncture needles, biofeedback equipment, and sensors). The cost of each hospitalization and ED visit was derived from the literature. In addition, cost savings were estimated based on government-contracted and commercial-contracted reimbursement rates for each service.

Results:
Cost savings were approximated to range from $1344 to $3439 per patient, with even greater cost savings of up to $6000 and $4132 when accounting for governmental and commercial payer reimbursement, respectively.

Discussion:
IM leads to improved pain relief when combined with traditional medicine and yields significant cost savings, thus supporting the routine implementation of IM alongside traditional medicine in health care settings.
Protein alterations in patients with delirium after cardiac surgery: An exploratory case-control sub-study of the VISION Cardiac Surgery Biobank
Authors: Spence Jessica , Devereaux PJ , Bashir Shaheena , Brady Katheryn , Sun Tao , Chan Matthew T.V. , Wang Chew Yin , Lamy Andre , Whitlock Richard P. , McIntyre William F. , Belley-Côté Emilie , Paré Guillaume , Chong Michael 
Published: January 2025

Background:
Delirium is an acute state of confusion associated with adverse postoperative outcomes. Delirium is diagnosed clinically using screening tools; most cases go undetected. Identifying a delirium biomarker would allow for accurate diagnosis, application of therapies, and insight into causal pathways. To agnostically discover novel biomarkers of delirium, we conducted a case-control sub-study using the VISION-Cardiac Surgery biobank. Our objective was to identify candidate biomarkers to investigate in future studies.

Methods:
We obtained a convenience sample of 30 patients with delirium on postoperative day 1 matched to 30 matched controls by age, sex, ethnicity, center and cardiopulmonary bypass time. The Olink Explore 3K platform was used to identify blood protein alterations on postoperative day 3. Protein concentrations were expressed as normalized protein expression (NPx) units (log2 fold scale). We compared protein expression between cases and controls using a paired t-test and reported significantly different biomarkers based on a False Discovery Rate (FDR)-adjusted p-value<0.05.

Results:
Of 2,865 unique serum proteins, 26 (0.9%) were significantly associated with delirium status; all were elevated in cases versus controls at an FDR<0.05. Pathway analysis identified “calcium-release channel activity” (Padj=0.02) and “Guanosine 5’ triphosphate (GTP)-binding” (Padj=0.005) functions as characteristic of proteins associated with delirium. The top three differentially expressed biomarkers were FKBP1B (Padj=0.003), C2CD2L (Padj=0.004), and RAB6B (Padj=0.004). The inflammatory biomarker IL-8 (CXCL8) (mean difference = 2.36; P=3.6x10-4) was also associated with delirium.

Discussion:
We identified 26 biomarkers significantly associated with delirium; all are novel except for IL-8. We did not identify an association between delirium and recognized neuro-inflammatory proteins and markers of brain injury, which supports using biomarkers to differentiate between delirium and other neurological conditions. While exploratory, our findings support using biomarkers to diagnose postoperative delirium and validate using agnostic screens to identify potential delirium biomarkers.
A scoping review and thematic analysis of the effects of tropical cyclones on diarrheal diseases
Authors: Lin Szu Yu , Chua Paul L. C. , Yuan Lei , Hossain Nasif , He Jinyu , Yamasaki Lisa , Madaniyazi Lina , Ng Chris Fook Sheng , Tobias Aurelio , Hashizume Masahiro 
Published: January 2025

Background:
Tropical cyclones pose significant health risks and can trigger outbreaks of diarrheal diseases in affected populations. Although the effects of individual hazards, such as rainfall and flooding, on diarrheal diseases are well-documented, the complex multihazard nature of tropical cyclones is less thoroughly explored. To date, no dedicated review comprehensively examines the current evidence and research on the association between tropical cyclones and diarrheal diseases.

Methods:
We performed a scoping review to map the literature on tropical cyclones and diarrheal diseases. A comprehensive literature search was performed across multiple online databases, including PubMed/MEDLINE, Web of Science, Scopus, Google Scholar, and ProQuest. We then performed a thematic analysis on the specific transmission pathways between tropical cyclones and diarrheal diseases as described in the literature.

Results:
A total of 96 studies were included and categorized in this scoping review. Of these, 23 studies quantitatively assessed the association between tropical cyclones and diarrheal diseases, with more than half reporting a positive association. Additionally, we identified 30 studies that detailed transmission pathways, which we used for thematic analysis. Significant variability was observed in the definition of tropical cyclone exposure, with studies using different criteria such as an event, wind speed, or rainfall. Most studies used pre-post comparison designs without concurrent control groups, which can introduce limitations affecting internal validity by not accounting for temporal confounders. Diarrheal diseases can either increase or decrease during and after tropical cyclones, depending on the specific pathogens and the different strengths of tropical cyclones.

Conclusion:
The variability in exposure definitions and study designs impedes the ability to quantitatively pool evidence. To improve the comparability and reliability of future research, we recommend that studies explore how different tropical cyclone exposure definitions impact results to identify the most appropriate metrics. We also suggest adopting more robust study designs, such as difference-in-difference or controlled interrupted time series for studying single tropical cyclone events, and case-crossover designs for studying multiple events. Additionally, studies examining specific causal pathways, such as integrating environmental sampling with health outcomes, should be explored to identify effective prevention strategies.
Surgical and multimodal approaches to right-sided cardiac tumours
Authors: Patel Shubh K. , Dhingra Nitish K. , Cusimano Robert J. 
Published: January 2025

Purpose of review
Cardiac tumours present significant clinical challenges due to their wide differential, complex anatomical and physiological implications, as well as the potential for widespread invasion in the case of malignancies. This review synthesizes recent findings surrounding the diagnosis and management of specifically right-sided cardiac tumours, with a particular focus on surgical resection and reconstructive techniques.

Recent findings
Management of cardiac tumours can be categorized into three key phases. First: early and accurate diagnosis is critical for improving outcomes, especially in malignancies. Advances in imaging modalities like MRI, CT, PET-CT, and biopsy techniques enhance diagnostic accuracy. Second: surgical resection is a cornerstone treatment for both benign and malignant right-sided cardiac tumours. Surgery is often curative for benign tumours, while for malignant tumours, R0 resection (complete microscopic removal) in appropriate candidates correlates with better survival. Third: managing cardiac malignancies necessitates a multidisciplinary approach, integrating additional therapies such as chemotherapy, radiation, and emerging immunotherapies tailored to patient and tumour characteristics.

Summary
Managing right-sided cardiac tumours demands interdisciplinary expertise. Standardized protocols are limited by the rarity of cases and insufficient high-quality data. International collaboration and sharing of experiences through prospective registries and clinical studies are essential to advancing knowledge and improving patient outcomes.
Role of preoperative biliary stents, bile contamination and antibiotic therapy in patients undergoing pancreaticoduodenectomy: A Retrospective Cohort Study
Authors: Fontani Giovanni , Nelli Tommaso , Canonico Giuseppe , Fratarcangeli Riccardo , Gabellini Linda , Damigella Andrea , Anastasi Alessandro 
Published: January 2025

Background:
The use of preoperative biliary drainage before pancreaticoduodenectomy (PD) remains controversial. The correlation between antibiotic prophylaxis and intraoperative biliary swab is a matter of further investigation to reduce postsurgical complications.

Methods:
The operative series of PD performed at the Pancreatic Surgery reference center for the USL Toscana Centro between January 1, 2021 and August 2023 were retrospectively analyzed. This study compared stented and nonstented patients undergoing PD to assess any differences in postoperative morbidity and mortality. In addition, intraoperative bile and abdominal drain fluid cultures were microbiologically assessed, and the susceptibility of bacterial isolates to antibiotics currently used for preoperative short-term prophylaxis was evaluated.

Results:
Almost 47/90 underwent preoperative stenting, 30/47 had jaundice above 12 mg/dl and went to upfront surgery, and 12/47 underwent neoadjuvant chemotherapy. Biliary microbial cultures were positive in 38/90 patients, among them 28 showed a polymicrobial flora. The most frequent postoperative complications detected were: abdominal abscess 9/90, pancreatic fistula type B-C 8/90, and delayed gastric emptying 7/90. From the statistical analysis, a P value = 0.0215 was obtained for the correlation between the preoperative stent group and P = 0.0285 with positive bile culture.

Conclusion:
There is no statistically significant correlation between the result of rectal and biliary swabs and the development of postoperative complications. Instead, biliary stent placement and positive biliary culture examination are two statistically significant risk factors for the development of postoperative complications. In relation to the increased rate of complications in patients subjected to preoperative stenting, careful presurgical evaluation is necessary to define who will have to undergo this procedure.
SNHG16 alleviates pulmonary ischemia-reperfusion injury by promoting the Warburg effect through regulating MTCH2 expression: experimental studies
Authors: Zhou Wenyong , Wang Shaohua , Yang Jichun , Shi Qi , Feng Nana , Gao Kaiheng , Posum Wan , Shi Mengkun , Xiang Meng , Shi Meng 
Published: January 2025

Background:
Pulmonary ischemia-reperfusion injury (PIRI) is a major cause of fatality post-lung transplantation. Though some long non-coding RNAs (lncRNAs) have been studied in acute lung injury (ALI), their effects on PIRI remain undefined. The present study aims to explore the underlying mechanism of small nucleolar RNA host gene 16 (SNHG16) in PIRI.

Methods:
PIR mouse and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established. Exosomes were extracted from human pulmonary microvascular endothelial cells (HPMECs). Functional and rescue experiments were conducted in OGD/R-exposed HPMECs, OGD/R-exposed pulmonary alveolar epithelial type II cells (AECs), and I/R model mice. The relationships among SNHG16, miR-372-3p/miR-373-3p, and MTCH2 were also verified using dual luciferase reporter assay, RNA pull-down and RIP assay.

Results:
SNHG16 was downregulated in OGD/R-exposed HPMECs, and SNHG16 overexpression accelerated proliferation, angiogenesis, and ameliorated mitochondrial respiration in OGD/R-exposed HPMECs. HPMEC-derived exosomal SNHG16 suppressed OGD/R-induced type II AEC injury. SNHG16 ameliorated lung injury in PIR mice. Mechanistically, SNHG16 targeted and negatively regulated miR-372-3p and miR-373-3p expression, and MTCH2, a target gene of miR-372-3p/miR-373-3p. SNHG16 was found to upregulate MTCH2 expression not only in a miR-372-3p and miR-373-3p-dependent manner but also suppress ubiquitination induced MTCH2 degradation.

Conclusions:
Our findings revealed that SNHG16 overexpression suppressed OGD/R-induced HPMEC apoptosis by promoting Warburg effect, and HPMEC-derived exosomal SNHG16 alleviated PIRI through the miR-372-3p/miR-373-3p/MTCH2 axis, suggesting that SNHG16 as a therapeutic target for PIRI.
The impact of deep response to ursodeoxycholic acid in primary biliary cholangitis – should it be the new clinical standard?
Authors: Martins Adrielly , Levy Cynthia 
Published: January 2025

Purpose of review
This review explores the emerging concept of “deep response” in primary biliary cholangitis (PBC), defined by the normalization of biochemical markers, particularly alkaline phosphatase and bilirubin. It examines its potential as a new standard for disease management and its implications for long-term patient outcomes, health policies, and clinical decision-making.

Recent findings
Recent studies suggest that achieving a deep response significantly improves long-term outcomes in some patients with PBC. In particular, a significant complication-free survival gain was observed among patients who at baseline were at high risk for disease progression. However, limitations in data and the variability in patient populations pose challenges for universal adoption of this standard.

Summary
Deep biochemical response represents a promising new standard for optimizing PBC management, offering measurable goals for clinicians and potentially improved long-term outcomes for patients. However, further research is necessary to better define the appropriate biochemical thresholds, understand the risks of overprescribing, and identify patient subgroups that are most likely to benefit from this strategy. A balanced, patient-centered approach incorporating deep response into comprehensive management could improve care for high-risk PBC patients.
Using Implementation Science to Assess Barriers to Agreement on Sedation Goal Setting and Assessment
Authors: Yang Youyang , Becla Kate , Kennedy Heather , Eder Katrina , Akhondi-Asl Alireza , Mehta Nilesh M. , Geva Alon 
Published: January 2025

OBJECTIVES:
Sedation assessment and goal setting using a validated assessment tool are key components of the ICU Liberation bundle. Appropriate integration of these bundle elements into daily practice remains challenging. Understanding barriers is an important step toward implementation of these best practice bundle elements.

DESIGN:
Two-phased explanatory mixed methods assessment carried out 2022–2023.

SETTING:
Forty-bed quaternary PICU.

SUBJECTS:
Bedside nurses and prescribers caring for mechanically ventilated patients on sedative infusions.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Forty-one nurses and 32 prescribers participated in the phase 1 pre-education assessments (2022). We identified lack of correlation between the providers’ stated State Behavioral Scale (SBS) numerical goal and descriptive goal and hypothesized that this discrepancy was either due to a knowledge gap or disagreement on sedation goals. To investigate this hypothesis, we performed a phase 2 assessment (2022–2023), starting with a multipronged educational activity, followed by a repeat survey that included a qualitative interview. One hundred ninety nurses and 45 prescribers received the educational activity. Twenty-eight nurses and 22 prescribers participated in the phase 2 assessments with the qualitative interview. Although correlation of the sedation goal between providers improved, it remained poor. Subsequent qualitative interview data indicated that the reasons for persistent disagreement in the sedation goal for a given patient were related to individual providers’ beliefs and attitudes toward sedation, rather than lack of understanding about using the SBS to set a target sedation goal.

CONCLUSIONS:
Barriers to setting and managing daily patient sedation goal in the PICU extend beyond providers’ knowledge gaps. An improved understanding of underlying barriers is essential for successful implementation of evidence-based sedation guidelines.
Impact of Social Determinants of Health on Pre-exposure Prophylaxis Care for HIV Prevention
Authors: Chan Philip A. , Goedel William C. , Li Yu , Mena Leandro , Patel Rupa R. , Marshall Brandon D. L. , Yelena Malyuta , Ward Lori , Underwood Ashley , Johnson Catrell J. , Gomillia Courtney E. , Almonte Alexi , Tao Jun , Curoe Kate , Villalobos Jesus , Nunn Amy S. 
Published: January 2025

Background:
HIV continues to disproportionately impact men who have sex with men (MSM) in the United States (US). Pre-exposure prophylaxis (PrEP) is effective, but disparities persist. Limited studies have conducted systematic evaluations of social determinants of health (SDOH) and their effects on PrEP persistence among MSM.

Setting:
We enrolled MSM into a prospective observational cohort to assess progression through the PrEP care continuum. We enrolled patients from three diverse US settings from 2018-2022.

Methods:
We explored the impact of SDOH on PrEP persistence (defined as successfully obtaining PrEP prescriptions and/or clinical documentation of retention in PrEP care) at 6- and 12-months using multilevel, mixed-effects logistic models.

Results:
A total of N=300 MSM were enrolled. Median age was 28 years; 40% were Black/African American (B/AA), and 11% were Hispanic/Latino (H/L). PrEP persistence was 84.7% and 49.3% at 6- and 12-months, respectively. In the unadjusted analysis, B/AA and H/L individuals were 56% and 54%, respectively, less likely to demonstrate PrEP persistence at 6- and 12-months compared to white/non-H/L individuals. Findings were no longer significant after adjusting for economic stability and educational attainment. Individuals with higher levels of internalized homophobia were less likely to persist on PrEP. Every 1-unit increase on a validated measure of internalized homophobia was independently and negatively associated with PrEP persistence (adjusted odds ratio = 0.95, 95% CI: 0.93-0.98).

Conclusion:
SDOH are important predictors of racial and ethnic disparities in PrEP persistence among MSM. Addressing these factors could help mitigate racial disparities in PrEP persistence in the US.
False-Positive Uptake of 123I-MIBG in the Basal Ganglion in a Pediatric Neuroblastoma Patient
Authors: Xu Yanfeng , Li Siqi , Lu Xia , Wang Wei , Yang Jigang 
Published: January 2025

Abstract
A 7-year-old boy with high-risk neuroblastoma underwent 123I-MIBG SPECT/CT to evaluate the therapy response. The scan revealed abnormal 123I-MIBG uptake in the left basal ganglion, indicating the possibility of brain metastasis. Subsequent contrast-enhanced brain MRI, however, did not show any abnormal signal intensity in the left basal ganglion. Follow-up 123I-MIBG SPECT/CT scans at 3-month and 9-month also did not show abnormal MIBG uptake in the same area. The case highlights the possibility of false-positive uptake of 123I-MIBG in the basal ganglion.
Serial Changes in Cranial Asymmetry During Helmet Therapy for Deformational Plagiocephaly
Authors: Tsugu Wataru , Hikosaka Makoto , Takamatsu Ako , Kaneko Tsuyoshi 
Published: January 2025

Background:
To analyze the serial changes in cranial asymmetry (CA) during helmet therapy for deformational plagiocephaly (DP).

Methods:
The subjects were 159 patients with DP who visited National Center for Child Health and Development between October 2011 and March 2014 and completed helmet therapy. The authors retrospectively collected information from medical records and analyzed the rate of improvement of deformation.

Results:
The average age at the start of the helmet was 24.1 weeks old [standard deviation (SD): 5.0], and the average treatment period was 21.2 weeks (SD: 5.3). The average CA before the start of helmet therapy was 16.3 mm (SD: 4.2), and it improved to 7.7 mm (SD: 3.5) after therapy. The analysis in the present article was limited to 16 weeks after initiation of helmet therapy when 1/4 of patients completed the therapy. In general, improvement of CA occurred inverse proportionally to the enlargement of head circumference. In subgroup analysis, for those who started earlier than 24 weeks of age or those with the severity of Argenta 1 or 2, improvement occurred rapidly and reached nearly a plateau at 12 weeks of treatment. For those started later or those with more severe deformity, improvement occurred slower and it continued even after 12 weeks of treatment.

Conclusion:
The rate of improvement was rapid at the early stage of treatment for those started earlier or with milder severity. This rapid improvement was obtained when the cranial enlargement was rapid. By understanding the course of improvement, evaluation of treatment responsiveness and ideal timing to finish therapy is possible.