bluuebunny/crossref_metadata_2025_split huggingface dataset:
Runt-related transcription factor-1 ameliorates bile acid–induced hepatic inflammation in cholestasis through JAK/STAT3 signaling
Authors: Zhang Liangjun , Pan Qiong , Zhang Lu , Xia Haihan , Liao Junwei , Zhang Xiaoxun , Zhao Nan , Xie Qiaoling , Liao Min , Tan Ya , Li Qiao , Zhu Jinfei , Li Ling , Fan Shijun , Li Jianwei , Zhang Chengcheng , Cai Shi-Ying , Boyer James L. , Chai Jin 
Published: January 2023

Background and Aims:
Bile acids trigger a hepatic inflammatory response, causing cholestatic liver injury. Runt-related transcription factor-1 (RUNX1), primarily known as a master modulator in hematopoiesis, plays a pivotal role in mediating inflammatory responses. However, RUNX1 in hepatocytes is poorly characterized, and its role in cholestasis is unclear. Herein, we aimed to investigate the role of hepatic RUNX1 and its underlying mechanisms in cholestasis.

Approach and Results:
Hepatic expression of RUNX1 was examined in cholestatic patients and mouse models. Mice with liver-specific ablation of Runx1 were generated. Bile duct ligation and 1% cholic acid diet were used to induce cholestasis in mice. Primary mouse hepatocytes and the human hepatoma PLC/RPF/5-ASBT cell line were used for mechanistic studies. Hepatic RUNX1 mRNA and protein levels were markedly increased in cholestatic patients and mice. Liver-specific deletion of Runx1 aggravated inflammation and liver injury in cholestatic mice induced by bile duct ligation or 1% cholic acid feeding. Mechanistic studies indicated that elevated bile acids stimulated RUNX1 expression by activating the RUNX1-P2 promoter through JAK/STAT3 signaling. Increased RUNX1 is directly bound to the promotor region of inflammatory chemokines, including CCL2 and CXCL2, and transcriptionally repressed their expression in hepatocytes, leading to attenuation of liver inflammatory response. Blocking the JAK signaling or STAT3 phosphorylation completely abolished RUNX1 repression of bile acid–induced CCL2 and CXCL2 in hepatocytes.

Conclusions:
This study has gained initial evidence establishing the functional role of hepatocyte RUNX1 in alleviating liver inflammation during cholestasis through JAK/STAT3 signaling. Modulating hepatic RUNX1 activity could be a new therapeutic target for cholestasis.
Quantifying the Risk for Hospital Readmission When Physical Therapist Discharge Recommendations Are Not Followed
Authors: Wright Jonathan R. , Koch-Hanes Trisha , Cortney Ciera , Lutjens Kathryn , Raines Kristopher , Young Daniel 
Published: January 2023

Purpose:
Studies suggest that implementing physical therapist discharge recommendations decreases 30-day hospital readmissions but may have miscounted readmissions. The purpose of this study was to obtain accurate readmission data and calculate the risk for readmission when therapists' recommendations are not followed.

Methods:
We conducted this prospective cohort study at a hospital in the Northwestern United States. Two hundred sixty-nine hospitalized participants with physical therapy orders consented to medical record data extraction and participated in a follow-up phone call. We compared physical therapist discharge recommendations to the actual discharge setting and services established for participants as documented in their medical record. Thirty days after discharge, we called participants to ask whether they had been readmitted to any hospital. We then analyzed associations between readmissions and the mismatch of therapist recommendations and participants' actual discharge locations and services received.

Results:
Twenty-one percent of discharges did not match the location and/or services recommended by the physical therapist. Sixty-six of the 269 participants were readmitted within 30 days. The odds for readmission were 2.3 times greater among participants who did not discharge to the location with the services recommended by their physical therapist.

Conclusions:
When physical therapist discharge location and services recommendations are not implemented, patients have increased risk of hospital readmission. This finding should inform stakeholders involved in discharge planning on the effect of following recommendations.
Halo Nevi in the Pediatric Population
Authors: So Jodi Y. , Admani Shehla 
Published: January 2023

ABSTRACT
Halo nevi are commonly observed in children and adolescents and may coexist with other disorders including vitiligo and Turner syndrome. This review discusses the epidemiology, pathophysiology, diagnosis, and management of halo nevi, with a particular emphasis on pediatric patients.
Medial and lateral dual plating of native distal femur fractures: a systematic literature review
Authors: O'Neill Dillon C. , Hakim Anne J. , DeKeyser Graham J. , Steffenson Lillia N. , Schlickewei Carsten W. , Marchand Lucas S. , Barg Alexej , Haller Justin M. 
Published: January 2023

Abstract

Introduction:
Lateral locked plating (LLP) development has improved outcomes for distal femur fractures. However, there is still a modest rate of nonunion in fractures treated with LLP alone, with higher nonunion risk in high-energy fractures, intra-articular involvement, poor bone quality, severe comminution, or bone loss. Several recent studies have demonstrated both the safety and the biomechanical advantage of dual medial and lateral plating (DP). The purpose of this study was to evaluate the clinical outcomes of DP for native distal femoral fractures by performing a systematic review of the literature.

Methods:
Studies reporting clinical outcomes for DP of native distal femur fractures were identified and systematically reviewed. Publications without full-text manuscripts, those solely involving periprosthetic fractures, or fractures other than distal femur fractures were excluded. Fracture type, mean follow-up, open versus closed fracture, number of bone grafting procedures, nonunion, reoperation rates, and complication data were collected. Methodologic study quality was assessed using the Coleman methodology score.

Results:
The initial electronic review and reverse inclusion protocol identified 1484 publications. After removal of duplicates and abstract review to exclude studies that did not discuss clinical treatment of femur fractures with dual plating, 101 potential manuscripts were identified and manually reviewed. After final review, 12 studies were included in this study. There were 199 fractures with average follow-up time of 13.72 months. Unplanned reoperations and nonunion occurred in 19 (8.5%) and 9 (4.5%) cases, respectively. The most frequently reported complications were superficial infection (n = 6, 3%) and deep infection (n = 5, 2.5%) postoperatively. Other complications included delayed union (n = 6, 3%) not requiring additional surgical treatment and knee stiffness in four patients (2%) necessitating manipulation under anesthesia or lysis of adhesions. The average Coleman score was 50.5 (range 13.5–72), suggesting that included studies were of moderate-to-poor quality.

Conclusions:
Clinical research interest in DP of distal femoral fractures has markedly increased in the past few decades. The current data suggest that DP of native distal femoral fractures is associated with favorable nonunion and reoperation rates compared with previously published rates associated with LLP alone. In the current review, DP of distal femoral fractures was associated with acceptable rates of complications and generally good functional outcomes. More high-quality, directly comparable research is necessary to validate the conclusions of this review.
Chronic pain concepts of pediatricians: a qualitative survey
Authors: Locher Cosima , Wörner Andreas , Carlander Maria , Kossowsky Joe , Dratva Julia , Koechlin Helen 
Published: January 2023

Abstract

Introduction:
Chronic pain is a prevalent, yet underrecognized, condition in children and adolescents. A biopsychosocial framework has been widely adopted over the past decades and resulted in a new pain classification in the International Classification of Diseases, 11th revision (ICD-11). Nevertheless, little is known about pediatricians' pain concepts.

Objectives:
We explored pain concepts of Swiss pediatricians by means of a qualitative analysis.

Method:
A cross-sectional online survey was sent to clinically active Swiss pediatricians registered with the Swiss Society for Pediatrics. A case vignette of a girl with chronic musculoskeletal pain was presented and pediatricians were asked (1) what they think caused the pain, and (2) how they would explain the pain to the patient and their family. Structuring content analysis was applied to describe major themes within the answers.

Results:
The following main categories emerged: psychological factors, biological factors, unclear etiology, social context, disorder specific, and multifactorial. Most pediatricians reported the belief that psychological factors explained the pain. However, when explaining the pain to the patient, biological factors were reported most often.

Conclusion:
There is a discrepancy between pediatricians' conviction that chronic pain is mostly explained by psychological factors and their exploratory model towards patients that focuses on biological factors. Promoting the biopsychosocial framework of chronic pain is key to ensure timely and effective treatment. The new pain classification in the ICD-11 has the potential to increase the use of the biopsychosocial model.
Clinical Feasibility of Automated Brain Tissue and Myelin Volumetry of Normal Brian Using Synthetic Magnetic Resonance Imaging With Fast Imaging Protocol: A Single-Center Pilot Study
Authors: Zheng Zuofeng , Yang Jiafei , Zhang Dongpo , Ma Jun , Yin Hongxia , Wang Zhenchang 
Published: January 2023

Objective
This study aimed to investigate the clinical feasibility of synthetic magnetic resonance imaging (MRI) with fast imaging protocol for automated brain tissue and myelin volumetry in healthy volunteers at 3.0-T MRI.

Methods
Thirty-four healthy volunteers were scanned using synthetic MRI with 3 sets of scan parameters: groups Fast (FAS; 2 minutes, 29 seconds), Routine (ROU; 4 minutes, 7 seconds), and Research (RES; 7 minutes, 46 seconds). White matter (WM), gray matter (GM), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), brain parenchymal volume (BPV), intracranial volume (ICV), and myelin volume (MYV) were compared between 3 groups. Linear correlation analysis was performed for measured volumes of groups FAS and ROU versus group RES.

Results
Significant differences were found in all the measured brain tissue volumes between groups FAS and ROU (P < 0.001), FAS and RES (P < 0.05), and ROU and RES (P < 0.05), except for NoN between groups ROU and RES (P = 0.0673), ICV between groups FAS and ROU (P = 0.2552), and ICV between groups FAS and RES (P = 0.4898). The intergroup coefficients of variation were 4.36% for WM, 6.39% for GM, 10.14% for CSF, 67.5% for NoN, 1.21% for BPV, 0.08% for ICV, and 5.88% for MYV. Strong linear correlation was demonstrated for WM, GM, CSF, BPV, ICV, and MYV (R = 0.9230–1.131) between FAS versus RES, and ROU versus RES.

Conclusions
Using synthetic MRI with fast imaging protocol can change the measured brain tissue volumes of volunteers. It is necessary to use consistent acquisition protocols for comparing or following up cases quantitatively.
Environmental Impact and Cost Savings of Operating Room Quality Improvement Initiatives: A Scoping Review
Authors: Sullivan Gwyneth A , Petit Hayley J , Reiter Audra J , Westrick Jennifer C , Hu Andrew , Dunn Jennifer B , Gulack Brian C , Shah Ami N , Dsida Richard , Raval Mehul V 
Published: January 2023

BACKGROUND:
Operating rooms are major contributors to a hospital’s carbon footprint due to the large volumes of resources consumed and waste produced. The objective of this study was to identify quality improvement initiatives that aimed to reduce the environmental impact of the operating room while decreasing costs.

STUDY DESIGN:
A literature search was performed using PubMed, Scopus, CINAHL, and Google Scholar and included broad terms for “operating room,” “costs,” and “environment” or “sustainability.” The “triple bottom line” framework, which considers the environmental, financial, and social impacts of interventions to guide decision making, was used to inform data extraction. The studies were then categorized using the 5 “Rs” of sustainability—refuse, reduce, reuse, repurpose, and recycle—and the impacts were discussed using the triple bottom line framework.

RESULTS:
A total of 23 unique quality improvement initiatives describing 28 interventions were included. Interventions were categorized as “refuse” (n = 11; 39.3%), “reduce” (n = 8; 28.6%), “reuse” (n = 3; 10.7%), and “recycle” (n = 6; 21.4%). While methods of measuring environmental impact and cost savings varied greatly among studies, potential annual cost savings ranged from $873 (intervention: education on diverting recyclable materials from sharps containers; environmental impact: 11.4 kg sharps waste diverted per month) to $694,141 (intervention: education to reduce regulated medical waste; environmental impact: 30% reduction in regulated medical waste).

CONCLUSIONS:
Quality improvement initiatives that reduce both cost and environmental impact have been successfully implemented across a variety of centers both nationally and globally. Surgeons, healthcare practitioners, and administrators interested in environmental stewardship and working toward a culture of sustainability may consider similar interventions in their institutions.
Random Forest approach for the identification of relationships between epigenetic marks and its application to robust assignment of chromatin states
Authors: Saavedra Leandro Murgas , Pollastri Gianluca , Riquelme Erick , Sáez Mauricio , Martin Alberto J.M. 
Published: January 2023

AbstractStructural changes of chromatin modulate access to DNA for all proteins involved in transcription. These changes are linked to variations in epigenetic marks that allow to classify chromatin in different functional states depending on the pattern of these marks. Importantly, alterations in chromatin states are known to be linked with various diseases. For example, there are abnormalities in epigenetic patterns in different types of cancer. For most of these diseases, there is not enough epigenomic data available to accurately determine chromatin states for the cells affected in each of them, mainly due to high costs of performing this type of experiments but also because of lack of a sufficient amount of sample or degradation thereof.In this work we describe a cascade method based on a random forest algorithm to infer epigenetic marks, and by doing so, to reduce the number of experimentally determined marks required to assign chromatin states. Our approach identified several relationships between patterns of different marks, which strengthens the evidence in favor of a redundant epigenetic code.
Divergence of alternative sugar preferences through modulation of the expression and activity of the Gal3 sensor in yeast
Authors: Fita-Torró Josep , Swamy Krishna B. S. , Pascual-Ahuir Amparo , Proft Markus 
Published: January 2023

AbstractOptimized nutrient utilization is crucial for the progression of microorganisms in competing communities. Here we investigate how different budding yeast species and ecological isolates have established divergent preferences for two alternative sugar substrates: Glucose, which is fermented preferentially by yeast, and galactose, which is alternatively used upon induction of the relevantGALmetabolic genes. We quantified the dose-dependent induction of theGAL1gene encoding the central galactokinase enzyme, and found that a very large diversification exists between different yeast ecotypes and species. The sensitivity ofGAL1induction correlates with the growth performance of the respective yeasts with the alternative sugar. We further define some of the mechanisms, which have established different glucose/galactose consumption strategies in representative yeast strains by modulating the activity of the Gal3 inducer. (1) Optimal galactose consumers, such asSaccharomyces bayanus, contain a hyperactiveGAL3promoter, sustaining highly sensitiveGAL1expression, which is not further improved upon repetitive galactose encounters. (2) Desensitized galactose consumers, such asS. cerevisiaeY12, contain a less sensitive Gal3 sensor, causing a shift of the galactose response towards higher sugar concentrations even in galactose experienced cells. (3) Galactose insensitive sugar consumers, such asS. cerevisiaeDBVPG6044, contain an interruptedGAL3gene, causing extremely reluctant galactose consumption, which however still is improved upon repeated galactose availability. In summary, different yeast strains and natural isolates have evolved galactose utilization strategies, which cover the whole range of possible sensitivities by modulating the expression and/or activity of the inducible galactose sensor Gal3.
DReAmocracy: A Method to Capitalize on Prior Drug Discovery Efforts to Highlight Candidate Drugs for Repurposing
Authors: Savva Kyriaki , Zachariou Margarita , Bourdakou Marilena , Dietis Nikolas , Spyrou George M. 
Published: January 2023

ABSTRACTIn the area of drug research, several computational drug repurposing studies have highlighted candidate repurposed drugs, as well as drugs from clinical trial studies in different phases. To our knowledge, the aggregation of the proposed lists of drugs by previous studies has not been extensively exploited towards the generation of a dynamic reference matrix regarding the disease-related frequencies of drug features such as the modes of action, the initial indications and the targeted pathways. To fill this knowledge gap, we performed a weight-modulated majority voting of the modes of action, initial indications and targeted pathways of the drugs in a well-known repository, namely the Drug Repurposing Hub. Our method, DReAmocracy, exploits this pile of information and creates frequency tables and finally a disease suitability score for each drug. As a testbed, we applied this method to a group of neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s and Multiple Sclerosis). A super-reference table with drug suitability scores has been created for all four neurodegenerative diseases and can be queried for any drug candidate against them. Top-scored drugs for Alzheimer’s disease includeagomelatineandmirtazapine, for Parkinson’s diseaseapomorphineandpramipexole, for Huntington’sfluphezineandperphezine, and for Multiple Sclerosiszonisamideanddisopyramide. Overall, DReAmocracy is a methodology that leverages the existing experimental and/or computational knowledge (1) to reveal trends in selected tracks of drug discovery research that includes modes of action, targeted pathways and initial indications for the investigated drugs and (2) to score new candidate drugs for repurposing against a selected disease.
Integrative Multiomics to Dissect the Lung Transcriptional Landscape of Pulmonary Arterial Hypertension
Authors: Hong Jason , Wong Brenda , Rhodes Christopher J. , Kurt Zeyneb , Schwantes-An Tae-Hwi , Mickler Elizabeth A. , Gräf Stefan , Eyries Mélanie , Lutz Katie A. , Pauciulo Michael W. , Trembath Richard C. , Montani David , Morrell Nicholas W. , Wilkins Martin R. , Nichols William C. , Trégouët David-Alexandre , Aldred Micheala A. , Desai Ankit A. , Tuder Rubin M. , Geraci Mark W. , Eghbali Mansoureh , Stearman Robert S. , Yang Xia 
Published: January 2023

AbstractPulmonary arterial hypertension (PAH) remains an incurable and often fatal disease despite currently available therapies. Multiomics systems biology analysis can shed new light on PAH pathobiology and inform translational research efforts. Using RNA sequencing on the largest PAH lung biobank to date (96 disease and 52 control), we aim to identify gene co-expression network modules associated with PAH and potential therapeutic targets. Co-expression network analysis was performed to identify modules of co-expressed genes which were then assessed for and prioritized by importance in PAH, regulatory role, and therapeutic potential via integration with clinicopathologic data, human genome-wide association studies (GWAS) of PAH, lung Bayesian regulatory networks, single-cell RNA-sequencing data, and pharmacotranscriptomic profiles. We identified a co-expression module of 266 genes, called the pink module, which may be a response to the underlying disease process to counteract disease progression in PAH. This module was associated not only with PAH severity such as increased PVR and intimal thickness, but also with compensated PAH such as lower number of hospitalizations, WHO functional class and NT-proBNP. GWAS integration demonstrated the pink module is enriched for PAH-associated genetic variation in multiple cohorts. Regulatory network analysis revealed that BMPR2 regulates the main target of FDA-approved riociguat, GUCY1A2, in the pink module. Analysis of pathway enrichment and pink hub genes (i.e. ANTXR1 and SFRP4) suggests the pink module inhibits Wnt signaling and epithelial-mesenchymal transition. Cell type deconvolution showed the pink module correlates with higher vascular cell fractions (i.e. myofibroblasts). A pharmacotranscriptomic screen discovered ubiquitin-specific peptidases (USPs) as potential therapeutic targets to mimic the pink module signature. Our multiomics integrative study uncovered a novel gene subnetwork associated with clinicopathologic severity, genetic risk, specific vascular cell types, and new therapeutic targets in PAH. Future studies are warranted to investigate the role and therapeutic potential of the pink module and targeting USPs in PAH.
Gene Expression and Evolution in the Smalltooth Sawfish,Pristis pectinata
Authors: Jarva Taiya M. , Phillips Nicole M. , Eiff Cory Von , Poulakis Gregg R. , Naylor Gavin , Feldheim Kevin A. , Flynt Alex S. 
Published: January 2023

SummarySawfishes (Pristidae) are large, highly threatened rays named for their tooth-studded rostrum, which is used for prey sensing and capture. Of all five species, the smalltooth sawfish,Pristis pectinata, has experienced the greatest decline in range, currently found in only ∼20% of its historic range. To better understand the genetic underpinnings of these taxonomically and morphologically unique animals, we collected transcriptomic data from several tissue types, mapped them to the recently completed reference genome and contrasted the patterns observed with comparable data from other elasmobranchs. Evidence of positive selection was detected in 79 genes inP. pectinata, several of which are involved in growth factor/receptor tyrosine kinase signaling and specification of organ symmetry, suggesting a role in morphogenesis. Data acquired also allow for examination of the molecular components ofP. pectinataelectrosensory systems, which are highly developed in sawfishes and have likely been influential in their evolutionary success.