bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic disease markers in primary sclerosing cholangitis and primary biliary cholangitis—methylomics of cholestatic liver disease
Authors: Juran Brian D. , McCauley Bryan M. , Atkinson Elizabeth J. , Schlicht Erik M. , Bianchi Jackie K. , Vollenweider Jason M. , Ye Hong , LaRusso Nicholas F. , Gores Gregory J. , Sun Zhifu , Lazaridis Konstantinos N. 
Published: July 2024

Background:
The epigenome, the set of modifications to DNA and associated molecules that control gene expression, cellular identity, and function, plays a major role in mediating cellular responses to outside factors. Thus, evaluation of the epigenetic state can provide insights into cellular adaptions occurring over the course of disease.

Methods:
We performed epigenome-wide association studies of primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) using the Illumina MethylationEPIC Bead Chip.

Results:
We found evidence of increased epigenetic age acceleration and differences in predicted immune cell composition in patients with PSC and PBC. Epigenetic profiles demonstrated differences in predicted protein levels including increased levels of tumor necrosis factor receptor superfamily member 1B in patients with cirrhotic compared to noncirrhotic PSC and PBC. Epigenome-wide association studies of PSC discovered strongly associated 5′-C-phosphate-G-3′ sites in genes including vacuole membrane protein 1 and SOCS3, and epigenome-wide association studies of PBC found strong 5′-C-phosphate-G-3′ associations in genes including NOD-like receptor family CARD domain containing 5, human leukocyte antigen-E, and PSMB8. Analyses identified disease-associated canonical pathways and upstream regulators involved with immune signaling and activation of macrophages and T-cells. A comparison of PSC and PBC data found relatively little overlap at the 5′-C-phosphate-G-3′ and gene levels with slightly more overlap at the level of pathways and upstream regulators.

Conclusions:
This study provides insights into methylation profiles of patients that support current concepts of disease mechanisms and provide novel data to inspire future research. Studies to corroborate our findings and expand into other -omics layers will be invaluable to further our understanding of these rare diseases with the goal to improve and individualize prognosis and treatment.
Drug interaction with UDP-Glucuronosyltransferase (UGT) enzymes is a predictor of drug-induced liver injury
Authors: Olubamiwa AyoOluwa O. , Liao Tsung-Jen , Zhao Jinwen , Dehanne Patrice , Noban Catherine , Angin Yeliz , Barberan Olivier , Chen Minjun 
Published: July 2024

Background and Aims:
DILI frequently contributes to the attrition of new drug candidates and is a common cause for the withdrawal of approved drugs from the market. Although some noncytochrome P450 (non-CYP) metabolism enzymes have been implicated in DILI development, their association with DILI outcomes has not been systematically evaluated.

Approach and Results:
In this study, we analyzed a large data set comprising 317 drugs and their interactions in vitro with 42 non-CYP enzymes as substrates, inducers, and/or inhibitors retrieved from historical regulatory documents using multivariate logistic regression. We examined how these in vitro drug-enzyme interactions are correlated with the drugs’ potential for DILI concern, as classified in the Liver Toxicity Knowledge Base database. Our study revealed that drugs that inhibit non-CYP enzymes are significantly associated with high DILI concern. Particularly, interaction with UDP-glucuronosyltransferases (UGT) enzymes is an important predictor of DILI outcomes. Further analysis indicated that only pure UGT inhibitors and dual substrate inhibitors, but not pure UGT substrates, are significantly associated with high DILI concern.

Conclusions:
Drug interactions with UGT enzymes may independently predict DILI, and their combined use with the rule-of-two model further improves overall predictive performance. These findings could expand the currently available tools for assessing the potential for DILI in humans.
Development and validation of pFIB scores for exclusion of significant liver fibrosis in pediatric MASLD
Authors: Lefere Sander , Mosca Antonella , Hudert Christian , Dupont Ellen , Fitzpatrick Emer , Kyrana Eirini , Dhawan Anil , Kalveram Laura , Pietrobattista Andrea , Geerts Anja , De Bruyne Ruth 
Published: July 2024

Background and Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most prevalent pediatric liver disease, yet accurate risk scores for referral of children/adolescents with suspected clinically significant liver fibrosis are currently lacking.

Approach and Results:
Clinical and biochemical variables were collected in a prospective cohort of 327 children and adolescents with severe obesity, in whom liver fibrosis was evaluated by transient elastography. Logistic regression was performed to establish continuous (pFIB-c) and simplified (pFIB-6) diagnostic scores that accurately exclude significant (≥F2) fibrosis. Performance for each was compared to established noninvve fibrosis scores. These scores were validated in elastography (n=504) and multiple biopsy-proven MASLD (n=261) cohorts. Patient sex, ethnicity, weight z-score, homeostatic model assessment of insulin resistance index, ALT, and presence of hypertension were included in the scores. The pFIB-c and pFIB-6 exhibited good discriminatory capacity (c-statistic of 0.839 and 0.826), outperforming existing indices. Negative predictive values were >90% for both scores in the derivation and elastography validation cohorts. Performance in the histological cohorts varied (AUROCs for the pFIB-c between 0.710 and 0.770), as the scores were less accurate when applied to populations in tertiary referral centers characterized by a high prevalence of significant fibrosis and high ALT levels.

Conclusions:
Analyzing several cohorts totaling approximately 1100 children and adolescents, we developed novel risk scores incorporating readily available clinical variables. In accordance with the aim of excluding pediatric MASLD-associated fibrosis, the scores performed better in nonselected cohorts of children and adolescents living with obesity than in patients referred to tertiary liver units.
Descemet Membrane Endothelial Keratoplasty in Aphakic, Aniridic, and Vitrectomized Eyes: A Review
Authors: Romano Davide , Shimizu Toshiki , Kobayashi Akira , Yamagami Satoru , Romano Vito , Hayashi Takahiko 
Published: July 2024

Purpose:
The aim of this review is to examine the techniques, complications, and outcomes of Descemet membrane endothelial keratoplasty (DMEK) in aphakic, aniridic, and vitrectomized eyes.

Methods:
A literature search was conducted in the MEDLINE database (via PubMed), using as keywords “(DMEK) AND (aphakia OR aniridia OR vitrectomy OR vitrectomized).” The research was limited to 10 years (January 2014–March 2024), in view of lack of literature before 2014. Articles, including case reports and case series, were included.

Results:
Twenty articles were included. No randomized controlled trials were found nor comparative studies with more than 1 technique used. Mean rebubbling rate in complex eyes was 29%, whereas mean endothelial cell loss at 6 months was 37%. The mean postoperative visual acuity improved from 1.47 logarithm of the minimal angle of resolution to 0.7 logarithm of the minimal angle of resolution.

Conclusions:
Despite being more challenging, compared with the techniques reported in literature, DMEK can be considered a valid option for the management of endothelial decompensation in complex eyes, with rebubbling rate and endothelial cell loss at 6 months, which are similar to non-complex eyes.
Mycoplasma hominis Pneumonia Presented as a Cavitary Mass with a Halo Sign in an Immunocompetent Adult Male: A Case Report
Authors: Xie Pan-Pan , Yao Yao , Yang Ning , Niu Wen-Kai , Yuan Xin 
Published: July 2024

Abstract

Mycoplasma hominis is an opportunistic microorganism that colonizes the genitourinary tract and causes genitourinary infections. However, pulmonary infections caused by M. hominis have rarely been reported in immunocompetent individuals. Herein, we report a rare case of an immunocompetent adult male with M. hominis pneumonia who presented with multiple pulmonary nodules that progressed to a cavitary mass with a halo sign. The presence of M. hominis infection was confirmed using multiplex polymerase chain reaction (mPCR) of the bronchoalveolar lavage fluid. The patient demonstrated no response to the initial levofloxacin therapy; however, the symptoms subsequently improved after the administration of moxifloxacin. M. hominis may be an underestimated causative agent of community-acquired pneumonia of unknown etiology in immunocompetent adults, and the involvement of the organism should be especially suspected in sexually active patients. Molecular diagnostic methods, such as mPCR, can be used to identify the etiology of atypical pneumonia. Appropriate antibiotics are crucial for effective treatment.
Monkeypox: A Viral Zoonotic Disease of Rising Global Concern
Authors: Anil Sukumaran , Joseph Betsy , Thomas Mary , Sweety Vishnupriya K. , Suresh Nandita , Waltimo Tumos 
Published: July 2024

AbstractMonkeypox (mpox) is a rare viral zoonotic disease, endemic to Central and West Africa, caused by the monkeypox virus, an orthopoxvirus similar to the variola virus (smallpox). Although sporadic travel-associated cases have historically occurred outside Africa, in May 2022, mpox began spreading globally in multiple nonendemic countries across several continents. In 2024, there has been an increase in globally reported confirmed cases of mpox and deaths from mpox, making it a public health emergency of international concern. The reasons for the unusual global spread are under investigation but likely relate to increased travel and waning population immunity to orthopoxviruses. Transmission now appears to be mainly through close, intimate contact, especially among men who have sex with men. Mpox is usually a self-limited disease. Although limited approved antiviral treatments are available, such as tecovirimat, which the European Medicines Agency approved in January 2022 for the treatment of mpox, their widespread availability and effectiveness in the current outbreak remain to be investigated. Public health control measures include surveillance, case identification/isolation, contact tracing, and targeted vaccination of contacts at high risk of exposure. However, challenges remain in curtailing the current unprecedented outbreak. Critical knowledge gaps include animal reservoir(s) responsible for initial spillover events, viral mutations that may enhance transmissibility, optimal diagnostics for noninvasive specimens, effective antiviral therapies, next-generation vaccines providing longer-term immunity, and building global capacity for outbreak response. This review summarizes the current literature on mpox virology, epidemiology, pathogenesis, clinical manifestations, diagnostics, treatment, prevention, and public health control measures. Ongoing investigation and research are needed to better understand mpox’s evolving epidemiology, pathogenicity, transmissibility, and ecology to guide strategies for containing the outbreak and preventing future global emergence.
Citrobacter Causing Septic Arthritis: A Case Report
Authors: Levine Kimberly K. , Dahl Mary , Tauseef Abubakar , Thirumalareddy Joseph 
Published: July 2024

Abstract
The genus Citrobacter commonly found in water and soil as well as the intestinal and urinary tracts of animals and humans. Although Citrobacter infections are infrequently diagnosed in environmental contexts, the rising incidence of nosocomial manifestations underscores the importance of considering this organism in the differential diagnosis of hospital-acquired infections. We present a case of patient with septic arthritis of the shoulder who had been originally admitted for the management of acute-on-chronic congestive heart failure exacerbation and severe sepsis. On hospital day 1, joint aspiration cultures and Gram stain confirmed the presence of Citrobacter koseri, a pathogen not commonly associated with septic arthritis, and ceftriaxone was administered to target it. On hospital day 7, antibiotic was transitioned to levofloxacin, every other day for 4 weeks. The patient was discharged to an acute rehabilitation facility after a 14-day hospital stay. This case stresses the importance of maintaining a broad differential diagnosis for any patients who present with fever and joint inflammation or swelling, especially in a postoperative setting.
Power profile and optical performance of two extended range-of-vision intraocular lens designs
Authors: Vega Fidel , Garzón Nuria , García-Montero María , Millán María S. 
Published: July 2024

Purpose:
To assess the power profile and optical performance of 2 extended range-of-vision (ERV) intraocular lenses (IOLs), TECNIS Eyhance (ICB00) and LuxSmart, and compare them with their monofocal counterpart lenses with similar platforms and materials: TECNIS 1-piece (ZCB00) and LuxGood, respectively.

Setting:
Optics and Optometry Faculties of Complutense University (Madrid) and Universitat Politècnica de Catalunya BarcelonaTech (Terrassa) in Spain.

Design:
Laboratory investigation on optical bench.

Methods:
For each design, the power distribution and (fourth and sixth-order) spherical aberration (SA) across the lens aperture were measured as well as the optical performance using modulation transfer function–based metrics with through-focus evaluation. 3 nominal powers (+10.00 diopters [D], +20.00 D, and +30.00 D) and 3 pupil sizes (2.0 mm, 3.0 mm, and 4.5 mm) were considered to assess whether the base power of the lens and pupillary dynamics have an influence on the depth-of-focus extension.

Results:
TECNIS Eyhance and LuxSmart IOLs had different power and SA profiles, but both designs shared a positive add power in their central region in comparison with their monofocal counterparts. LuxSmart had a greater add power while TECNIS Eyhance showed higher peak optical quality but smaller depth of focus.

Conclusions:
Differences of focus extension between the 2 ERV IOL designs are related to differences of power and SA profile. The nominal base power of the IOLs has little effect on their optical quality. However, pupil dynamics plays a key role since it determines the effective add power and optical performance of the ERV IOLs.
Norepinephrine versus phenylephrine affects prethrombotic response in patients undergoing cesarean section under spinal anesthesia: a randomized, double-blind, controlled study
Authors: Tao Wenhui , Bao Jinfeng , Xie Yufang , Ding Wei , Wu Yule , Zhang Ye , Hu Xianwen 
Published: July 2024

Background:
Venous thromboembolism is one of the most common and serious complications of cesarean section in parturients. Norepinephrine (NE) has been shown to activate coagulation. The aim of this study was to compare the effect of a fixed-rate prophylactic NE infusion and a fixed-rate prophylactic phenylephrine (PHE) infusion under spinal anesthesia for cesarean section on the prethrombotic response.

Materials and methods:
Sixty-six women undergoing cesarean section under spinal anesthesia were randomly assigned to the NE group or PHE group, starting simultaneously with the administration of the subarachnoid solution, a ‘study drug’ solution containing either NE or PHE was pumped intravenously at a constant rate of 15 ml/h until the end of the operation. Plasma coagulation factor VIII activity (FVIII: C), Fibrinogen, and D-dimer levels were measured in blood samples obtained on admission to the operating theater and at the end of the procedure.

Results:
Compared with preoperative levels, there were no significant differences in postoperative fibrinogen and D-dimer levels in the NE group, except for a decrease in FVIII: C levels (P=0.003). However, postoperative levels of FVIII: C (P=0.009), fibrinogen (P=0.035), and D-dimer (P=0.025) were increased in the NE group compared with postoperative levels in the PHE group.

Conclusions:
NE does not affect the maternal prethrombotic response and can be safely used in cesarean sections. Compared with PHE infusion, NE infusion increased the level of coagulation molecules, suggesting that NE maybe more beneficial for women with high intraoperative bleeding requiring hemostasis.
Inclusion, Participation, Belonging = Surviving, Thriving, Flourishing
Authors: Long Toby 
Published: July 2024

Purpose:
To share my perspectives on how pediatric physical therapists support children with disabilities and their families to maximize their potential to flourish.

Key Points:
Best practice supports the inclusion of people with disabilities in all aspects of society. Policy statements from governmental agencies, research universities, advocacy, and non-governmental organizations all support inclusion. The concept of belonging and how pediatric physical therapists can promote belonging is less familiar to pediatric physical therapists than inclusion and participation. Essential elements necessary to bring about a sense of belonging in young children will be presented, leading to a discussion on the role of the pediatric physical therapist and key implications for the early childhood system of care.

Conclusions:
Pediatric physical therapists support children with disabilities and their families to maximize the potential of every child. I propose that to do this, we must focus our interventions to promote a child’s active participation in community life and build programs and relationships that promote belonging.

Clinical Relevance:
Interventions for children with disabilities will be successful by focusing on the outcomes that promote inclusion, participation, and belonging.
Building Partnerships Out of Barriers: Lessons Learned From Partnerships Between Centers for Independent Living and Health Departments During the COVID-19 Pandemic
Authors: Bednar Hailey , Callis LaTasha , Whitton Alaina , Lyons Sara , Tissot Kimberly 
Published: July 2024

Introduction
People with disabilities were left behind in the beginning of the COVID-19 vaccination rollout. More work needs to be done to connect people with disabilities to public health initiatives. Centers for Independent Living (CILs) are an important and under-utilized community partner for health departments and should be engaged as a trusted source when working to reach people with disabilities and improve access to public health programs and services.

Methods
The National Foundation for the Centers for Disease Control and Prevention (CDC Foundation), through funding from the CDC, launched the Leveraging CILs to Increase Vaccine Access for People with Disabilities project. The primary goal was to increase accessibility of the COVID-19 vaccination among people with disabilities through (1) outreach and education, (2) service linkage and barrier removal through increasing accessible, (3) widespread education about the vaccine, and (4) improved partnerships between disability-led organizations and local health care providers.

Outputs
A grant program resulted in 39 awards distributed to CILs across the United States totaling $2 955 294.00 between November 2021 and March 2023. The project successfully resulted in reported improvements in partnerships between funded CILs and local health providers and a reported reduction in barriers to accessing vaccinations faced by people with disabilities. A suite of resources was also created to address targeted needs identified throughout partner implementation. Successful outreach to the targeted population resulted in 27 044 consumers being directly reached by CILs and 3 675 655 people reached through communication and outreach activities.

Discussion
Catalytic funding to disability-led organizations during public health emergency response and including people with disabilities as subject matter experts in program design can successfully strengthen access to care via trust building, message dissemination, and partnership. Building the capacity of community-based and consumer-led partners to implement evidence-based public health programming can provide a foundation for improved care for people with disabilities, particularly during an emergency response.
An Emergency Department Quality Improvement Project to Decrease Lumbar Puncture Rates in Febrile Infants 22 to 28 Days Old
Authors: Kelly Jessica M. , Ku Brandon C. , Gala Payal , Hawkins Bobbie , Lee Brian , Corso Salvatore , Green Rebecca , Scarfone Richard , Lavelle Jane M. , Kane Emily R. , Sartori Laura F. 
Published: July 2024

Introduction:
Most providers have routinely performed universal lumbar puncture (LP) on well-appearing, febrile infants 22 to 28 days old. In 2021, the American Academy of Pediatrics recommended clinicians should perform an LP in this age group if inflammatory markers are abnormal. This quality improvement project aimed to decrease LP rates in febrile infants 22 to 28 days old in the emergency department (ED) within 1 year, regardless of race/ethnicity, from a baseline of 87%.

Methods:
We used our institution’s quality improvement framework to perform multiple Plan-Do-Study-Act cycles. A multidisciplinary team reviewed the febrile infant literature, local epidemiology, and identified key drivers. We provided departmental education, updated our clinical pathway, and used clinical decision support. We analyzed baseline (January 2017–March 2022) and intervention data (April 2022–March 2024) and tracked data using statistical process control charts. Our primary outcome measure was rates of LP in the ED for this cohort. Process measures included rates of infants with procalcitonin results. ED length of stay, rates of first LP attempt after hospitalization, and missed bacterial meningitis were balancing measures.

Results:
The baseline LP rate of 87% decreased to 44% during the intervention period, resulting in a downward centerline shift. There were no significant differences when LP rates were analyzed by race/ethnicity. There was an upward centerline shift in the process measure of infants with procalcitonin results. There was no observed special cause variation in our balancing measures.

Conclusion:
Quality improvement efforts, including education, clinical pathway updates, and clinical decision support, safely reduced rates of LPs in febrile infants 22 to 28 days old.