bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of MELD3.0 in 2 centers from different continents
Authors: Tejedor Marta , Bellón José María , Fernández de la Varga Margarita , Peralta Peregrina , Montalvá Eva , Selzner Nazia , Berenguer Marina 
Published: July 2024

Background:
MELD3.0 has been proposed to stratify patients on the liver transplant waiting list (WL) to reduce the historical disadvantage of women in accessing liver transplant. Our aim was to validate MELD3.0 in 2 unique populations.

Methods:
This study is a 2-center retrospective cohort study from Toronto, Canada, and Valencia, Spain, of all adults added to the liver transplant WL between 2015 and 2019. Listing indications whose short-term survival outcome is not adequately captured by the MELD score were excluded. All patients analyzed had a minimum follow-up of 3 months after inclusion in the WL.

Results:
Six hundred nineteen patients were included; 61% were male, with a mean age of 56 years. Mean MELD at inclusion was 18.00 ± 6.88, Model for End-Stage Liver Disease Sodium (MELDNa) 19.78 ± 7.00, and MELD3.0 20.25 ± 7.22. AUC to predict 90-day mortality on the WL was 0.879 (95% CI: 0.820, 0.939) for MELD, 0.921 (95% CI: 0.876, 0.967) for MELDNa, and 0.930 (95% CI: 0.888, 0.973) for MELD3.0. MELDNa and MELD3.0 were better predictors than MELD (p = 0.055 and p = 0.024, respectively), but MELD3.0 was not statistically superior to MELDNa (p = 0.144). The same was true when stratified by sex, although the difference between MELD3.0 and MELD was only significant for women (p = 0.032), while no statistical significance was found in either sex when compared with MELDNa. In women, AUC was 0.835 (95% CI: 0.744, 0.926) for MELD, 0.873 (95% CI: 0.785, 0.961) for MELDNa, and 0.886 (95% CI: 0.803, 0.970) for MELD3.0; differences for the comparison between AUC in women versus men for all 3 scores were nonsignificant. Compared to MELD, MELD3.0 was able to reclassify 146 patients (24%), the majority of whom belonged to the MELD 10–19 interval. Compared to MELDNa, it reclassified 68 patients (11%), most of them in the MELDNa 20–29 category.

Conclusions:
MELD3.0 has been validated in centers with significant heterogeneity and offers the highest mortality prediction for women on the WL without disadvantaging men. However, in these cohorts, it was not superior to MELDNa.
A plasma peptidomic signature reveals extracellular matrix remodeling and predicts prognosis in alcohol-associated hepatitis
Authors: Sayed Khaled , Dolin Christine E. , Wilkey Daniel W. , Li Jiang , Sato Toshifumi , Beier Juliane I. , Argemi Josepmaria , Vatsalya Vatsalya , McClain Craig J. , Bataller Ramon , Wahed Abdus S. , Merchant Michael L. , Benos Panayiotis V. , Arteel Gavin E. 
Published: July 2024

Background:
Alcohol-associated hepatitis (AH) is plagued with high mortality and difficulty in identifying at-risk patients. The extracellular matrix undergoes significant remodeling during inflammatory liver injury and could potentially be used for mortality prediction.

Methods:
EDTA plasma samples were collected from patients with AH (n = 62); Model for End-Stage Liver Disease score defined AH severity as moderate (12–20; n = 28) and severe (>20; n = 34). The peptidome data were collected by high resolution, high mass accuracy UPLC-MS. Univariate and multivariate analyses identified differentially abundant peptides, which were used for Gene Ontology, parent protein matrisomal composition, and protease involvement. Machine-learning methods were used to develop mortality predictors.

Results:
Analysis of plasma peptides from patients with AH and healthy controls identified over 1600 significant peptide features corresponding to 130 proteins. These were enriched for extracellular matrix fragments in AH samples, likely related to the turnover of hepatic-derived proteins. Analysis of moderate versus severe AH peptidomes was dominated by changes in peptides from collagen 1A1 and fibrinogen A proteins. The dominant proteases for the AH peptidome spectrum appear to be CAPN1 and MMP12. Causal graphical modeling identified 3 peptides directly linked to 90-day mortality in >90% of the learned graphs. These peptides improved the accuracy of mortality prediction over the Model for End-Stage Liver Disease score and were used to create a clinically applicable mortality prediction assay.

Conclusions:
A signature based on plasma peptidome is a novel, noninvasive method for prognosis stratification in patients with AH. Our results could also lead to new mechanistic and/or surrogate biomarkers to identify new AH mechanisms.
Intraocular Lens Opacification After Descemet's Membrane Endothelial Keratoplasty—Risk Factors and Outcomes After Intraocular Lens Exchange
Authors: Moura-Coelho Nuno , Papa-Vettorazzi Renato , Reyes Alonso , Cunha João Paulo , Dutra-Medeiros Marco , Manero Felicidad , Güell José Luis 
Published: July 2024

Purpose:
To determine risk factors for intraocular lens opacification (IOLop) after Descemet membrane endothelial keratoplasty (DMEK) and to analyze clinical outcomes after IOL exchange.

Methods:

Cross-Sectional Study: Analysis of all cases of IOL exchange because of post-DMEK IOLop with a minimum of 6-month postoperative follow-up observed in clinic between November 2021 and April 2022. Main outcomes analyzed at the study visit were change in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity after IOL exchange, endothelial cell loss (ECL), and graft survival. An historical cohort of 232 pseudophakic DMEK eyes was retrospectively analyzed to determine risk factors for post-DMEK IOLop.

Results:

Cross-Sectional Study: Four eyes were observed (median follow-up = 45 (35.5–86.8) months). IOL materials were hydrophilic acrylic IOLs in 2 eyes and hydrophobic–hydrophilic in the other 2. At the study visit, improvement in median best-corrected visual acuity after IOL exchange was statistically significant (0.25 (0.19–0.41) logMAR to 0.00 (0–0.10) logMAR; P = 0.041). ECL ranged between 57.7% and 85.3%, without cases of graft failure. In the historical cohort, 21 eyes (9.05%) had some IOLop. In multivariate logistic regression model (105 eyes where IOL material data was available), IOLs with high water content material (odds ratio = 65.5, P = 0.0005) and rebubbling (odds ratio = 9.51, P = 0.0138) were independent risk factors for post-DMEK IOLop.

Conclusions:
Post-DMEK IOLop is infrequent, but a non-neglectable proportion of cases may require IOL explantation. IOL exchange is safe and effective in these eyes but may pose a risk for increased ECL. This study confirms that IOL material and number of rebubblings are major risk factors for post-DMEK IOLop.
New Insights Into Infections’ Risk of Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia
Authors: Trimbour Camille , Balsat Marie , Olivier Laura , Mihalcea Ana-Raluca , Garnier Nathalie , Kebaili Kamila , Sirvent Nicolas , Dupont Damien , Fuhrmann Christine , Theron Alexandre , Domenech Carine 
Published: July 2024

Background:
This study aims to compare the infections’ risk between adolescents and young adults (AYAs), treated for acute lymphoblastic leukemia, and pediatric population. We also focused on their bacterial and fungal infection specificities.

Methods:
This case–control study investigated the occurrence of bacterial bloodstream infection (BSI) and proven and probable invasive fungal infection (IFI) in AYAs (15–25 years old) and children (1–14 years old) treated for acute lymphoblastic leukemia between January 2013 and December 2020 in 2 French tertiary pediatric and 2 referral adult hematological centers, independent of their treatment protocol. We also evaluated the impact of these infections on morbidity (necessity of intensive care) and mortality.

Results:
We analyzed 83 AYAs and 230 children and found that AYAs developed significantly more IFI than the pediatric population (22% vs. 10%, P = 0.007), regardless of their care center (adult or pediatric). Furthermore, the occurrence of BSI was similar between the 2 populations (48% vs. 51%, P = 0.66). Moreover, the occurrence of infection increased with the AYAs’ risk group of treatment: standard, medium or high risk (P = 0.021 for BSI and P = 0.029 for IFI). Finally, the mortality rate is only 1.3% after a BSI whereas it increases to 4.9% after IFI.

Conclusion:
AYAs have their own specificity with an increased risk of fungal infection compared to children, independent of the care center. Antifungal prophylaxis should be contemplated, especially for patients classified in high-risk groups.
Performance of formulas included in the ESCRS intraocular lens power calculator
Authors: Skrzypecki Janusz , Koch Douglas D. , Wang Li 
Published: July 2024

Purpose:
To compare the refractive prediction errors (PEs) of formulas included in the ESCRS intraocular lens (IOL) power calculator to aid in informed decisions on IOL power selection based on the output of this tool.

Setting:
Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.

Design:
Retrospective case-series.

Methods:
748 eyes of 748 patients after implantation of 1 of 3 lenses were included, single-piece: the SN60WF, PCB00/ZCB00 and 3-piece: MA60MA. IOL constants recommended by the calculator were used for the study. We performed analysis for the whole dataset, short (<22 mm) and long eyes (>25 mm) as well as in subgroups based on the type of the implanted IOL. SD and root mean square absolute error (RMSAE) were selected as the primary endpoints.

Results:
Cooke K6 had the lowest SD of PEs in the whole dataset (P < .05) when compared with Barrett, EVO, and Hoffer QST. In the subgroup of long eyes, the Kane formula had the lowest RMSAE (P < .05) when compared with Barrett and EVO. No significant differences in primary endpoints for implantation of the 3 types of IOLs were found. However, the median absolute error after implantation of the MA60MA was significantly higher for Hoffer QST than for all other formulas except for Pearl-DGS.

Conclusions:
Significant differences in the performance of formulas included in the calculator were found. In the whole dataset, Cooke K6 had the lowest SD of PEs among the analyzed formulas.
Metastasis to the External Auditory Canal: A Systematic Review
Authors: Epperson Madison V. , Mahajan Arushi , Welch Christopher M. 
Published: July 2024

Objective
To systematically review the literature and understand the behavior, diagnosis, management, and mortality of metastasis to the external auditory canal (EAC).

Databases Reviewed
PubMed/Medline, EMBASE, Web of Science.

Methods
Studies from 1948 to June 2023 describing metastasis to the EAC were included. Non-English literature was excluded. Data extraction: Study design, age, sex, pathology, primary site, staging, additional sites of metastasis, time to EAC metastasis from diagnosis, time from diagnosis of EAC metastasis to death, symptoms, exam and imaging findings, and management.

Results
Data were synthesized qualitatively with means calculated. Thirty-two studies met the criteria, totaling 37 patients with EAC metastasis. Mean age was 58 years; 73% were male. The most common pathologies were adenocarcinoma (37.8%), acute myelogenous leukemia (8.1%), and renal cell carcinoma (8.1%). Sites of primary malignancy were hematologic (10.8%), breast (8.1%), esophagus (8.1%), renal (8.1%), and prostate (8.1%). Within the temporal bone, 73% had isolated EAC metastasis. Median time to EAC metastasis from the diagnosis of primary malignancy was 18 months. Metastasis to the EAC was the first presentation of malignancy in 21.6% of patients. Median time to death was 4.5 months. Symptoms included hearing loss (59.5%), otalgia (27.0%), otorrhagia (24.3%), facial paralysis (21.6%), otorrhea (16.2%), and aural fullness (13.5%). On imaging, bony erosion was present in 50% of cases. Treatment was primarily palliative with excision and radiation.

Conclusions
EAC metastasis has a distinct presentation from other temporal bone subsites. Early biopsy to establish a diagnosis and intervene is critical.
Revision of the Essential Core Competencies: Domains of Competence and Associated Competencies for Pediatric Physical Therapy Professional Education
Authors: Schreiber Joe , Rapport Mary Jane , Anderson Deborah , Lundeen Heather , Moore James , Furze Jennifer 
Published: July 2024

Purpose:
The purpose of this Special Communication is to describe the processes of Education Summit III, sponsored by the Academy of Pediatric Physical Therapy, with an emphasis on the review, update, and integration of contemporary language and the Competency-Based Education framework into a revision of the Essential Core Competencies (ECCs).

Summary of Key Points:
The Academy of Pediatric Physical Therapy has consistently supported pediatric professional education, including sponsoring 3 Education Summits in 2012, 2016, and 2023. The most recent summit focused on a revision of the ECCs and the development of materials to support their implementation.

Recommendations for Practice:
These revised domains of competence and associated competencies will support and guide pediatric physical therapy education for professional students. Educators are encouraged to use their creativity and resources to integrate these into teaching and learning activities.
Ultra-high dose methylcobalamin and other emerging therapies for amyotrophic lateral sclerosis
Authors: Kaji Ryuji , Izumi Yuishin , Oki Ryosuke 
Published: July 2024

Purpose of review
Recent development in understanding the pathophysiology of amyotrophic lateral sclerosis (ALS) has led to increasing number of promising test drugs in the pipeline along with the existing ones. We will review these agents focusing on ultra-high dose methylcobalamin, which is pending approval in Japan. Clinical trial design best suited for ALS will also be discussed.

Recent findings
The most recent phase 3 trial (JETALS) of ultra-high dose methylcobalamin demonstrated significant slowing of ALSFRSR changes (0.5/month), with marked reduction of serum homocysteine levels in the initial double-blind period. The post hoc analysis of the previous phase 2/3 study (E761 trial; Eisai) showed that it prolonged survival of ALS patients, if started within 1 year of onset, but the previous studies suggested its efficacy even in later stages, depending upon the rate of progression. Phase 3 trial of AMX0035 or Relyvrio on the other hand showed negative results despite the promising phase 2 data. The latter did not adjust the disease progression rate before entry.

Summary
Ultra-high dose methylcobalamin is not a vitamin supplement but a novel disease-modifying therapy for ALS, and it emphasizes homocysteine as a key factor in the disease process. Clinical trial design must include entering patients early and with similar rates of progression using pretrial observation periods for meaningful results, since ALS is a chronologically heterogenous condition with similar phenotypes.
A One Health Investigation into H5N1 Avian Influenza Virus Epizootics on Two Dairy Farms
Authors: Shittu Ismaila , Silva Diego , Oguzie Judith U. , Marushchak Lyudmyla V. , Olinger Gene G. , Lednicky John A. , Trujillo-Vargas Claudia M. , Schneider Nicholas E. , Hao Haiping , Gray Gregory C. 
Published: July 2024

AbstractBackgroundIn early April 2024 we studied two Texas dairy farms which had suffered incursions of H5N1 highly pathogenic avian influenza virus (HPAIV) the previous month.MethodsWe employed molecular assays, cell and egg culture, Sanger and next generation sequencing to isolate and characterize viruses from multiple farm specimens (cow nasal swab, milk specimens, fecal slurry, and a dead bird).ResultsWe detected H5N1 HPAIV in 64% (9/14) of milk specimens, 2.6% (1/39) of cattle nasal swab specimens, and none of 17 cattle worker nasopharyngeal swab specimens. We cultured and characterized virus from eight H5N1-positive specimens. Sanger and next-generation sequencing revealed the viruses were closely related into other recent Texas epizootic H5N1 strains of clade 2.3.4.4b. Our isolates had multiple mutations associated with increased spillover potential. Surprisingly, we detected SARS-CoV-2 in a nasal swab from a sick cow. Additionally, 14.3% (2/14) of the farm workers who donated sera were recently symptomatic and had elevated neutralizing antibodies against a related H5N1 strain.ConclusionsWhile our sampling was limited, these data offer additional insight into the large H5N1 HPAIV epizootic which thus far has impacted at least 96 cattle farms in twelve US states. Due to fears that research might damage dairy businesses, studies like this one have been few. We need to find ways to work with dairy farms in collecting more comprehensive epidemiological data that are necessary for the design of future interventions against H5N1 HPAIV on cattle farms.
Perspective on Harnessing Large Language Models to Uncover Insights in Diabetes Wearable Data
Authors: Alavi Arash , Cha Kexin , Esfarjani Delara P , Patel Bhavesh , Than Jennifer Li Pook , Lee Aaron Y. , Nebeker Camille , Snyder Michael , Bahmani Amir 
Published: July 2024

AbstractLarge Language Models (LLMs) have gained significant attention and are increasingly used by researchers. Concurrently, publicly accessible datasets containing individual-level health information are becoming more available. Some of these datasets, such as the recently released Artificial Intelligence Ready and Equitable Atlas for Diabetes Insights (AI-READI) dataset, include individual-level data from digital wearable technologies. The application of LLMs to gain insights about health from wearable sensor data specific to diabetes is underexplored. This study presents a comprehensive evaluation of multiple LLMs, including GPT-3.5, GPT-4, GPT-4o, Gemini, Gemini 1.5 Pro, and Claude 3 Sonnet, on various diabetes research tasks using diverse prompting methods to evaluate their performance and gain new insights into diabetes and glucose dysregulation. Notably, GPT-4o showed promising performance across tasks with a chain-of-thought prompt design (aggregate performance score of 95.5%). Moreover, using this model, we identified new insights from the dataset, such as the heightened sensitivity to stress among diabetic participants during glucose level fluctuations, which underscores the complex interplay between metabolic and psychological factors. These results demonstrate that LLMs can enhance the pace of discovery and also enable automated interpretation of data for users of wearable devices, including both the research team and the individual wearing the device. Meanwhile, we also emphasize the critical limitations, such as privacy and ethical risks and dataset biases, that must be resolved for real-world application in diabetes health settings. This study highlights the potential and challenges of integrating LLMs into diabetes research and, more broadly, wearables, paving the way for future healthcare advancements, particularly in disadvantaged communities.
Social Determinants of Health and Lifestyle Risk Factors Modulate Genetic Susceptibility for Women’s Health Outcomes
Authors: Guare Lindsay A , Das Jagyashila , Caruth Lannawill , Setia-Verma Shefali 
Published: July 2024

AbstractWomen’s health conditions are influenced by both genetic and environmental factors. Understanding these factors individually and their interactions is crucial for implementing preventative, personalized medicine. However, since genetics and environmental exposures, particularly social determinants of health (SDoH), are correlated with race and ancestry, risk models without careful consideration of these measures can exacerbate health disparities. We focused on seven women’s health disorders in the All of Us Research Program: breast cancer, cervical cancer, endometriosis, ovarian cancer, preeclampsia, uterine cancer, and uterine fibroids. We computed polygenic risk scores (PRSs) from publicly available weights and tested the effect of the PRSs on their respective phenotypes as well as any effects of genetic risk on age at diagnosis. We next tested the effects of environmental risk factors (BMI, lifestyle measures, and SDoH) on age at diagnosis. Finally, we examined the impact of environmental exposures in modulating genetic risk by stratified logistic regressions for different tertiles of the environment variables, comparing the effect size of the PRS. Of the twelve sets of weights for the seven conditions, nine were significantly and positively associated with their respective phenotypes. None of the PRSs was associated with different age at diagnoses in the time-to-event analyses. The highest environmental risk group tended to be diagnosed earlier than the low and medium-risk groups. For example, the cases of breast cancer, ovarian cancer, uterine cancer, and uterine fibroids in highest BMI tertile were diagnosed significantly earlier than the low and medium BMI groups, respectively). PRS regression coefficients were often the largest in the highest environment risk groups, showing increased susceptibility to genetic risk. This study’s strengths include the diversity of the All of Us study cohort, the consideration of SDoH themes, and the examination of key risk factors and their interrelationships. These elements collectively underscore the importance of integrating genetic and environmental data to develop more precise risk models, enhance personalized medicine, and ultimately reduce health disparities.