bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relation of neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume with idiopathic acute anterior uveitis
Authors: Demir Ulku 
Published: January 2024

Objective In this study leukocyte, lymphocyte, neutrophil, platelet count, mean platelet volume (MPV), neutrophil/lymphocyte (NLR) ratio and platelet/lymphocyte ratio (PLR) were retrospectively evaluated in patients with idiopathic acute anterior uveitis. Materials and methods Medical records were retrospectively reviewed from March 2016 to February 2020. Fifty patients (25 men and 25 women) and as the control group, 50 healthy volunteers (25 males and 25 females) were included in this study. Blood samples of the patients were taken before starting treatment. A complete ophthalmological examination, including corrected visual acuity, tonometry, slit lamp and fundus examination, was performed in all patients. Gender, age, leukocyte, neutrophil, lymphocyte, platelet, MPV, PLR, and NLR values of the patients were recorded. Results In this study, a statistically significant difference was found in leukocyte ( p < .001), neutrophil ( p < .001), platelet ( p < .001), NLR ( p < .001) and PLR ( p < .001) values. No significant difference was found between the two groups in terms of lymphocyte count ( p = .063) and in the MPV value ( p = .051). Leukocyte, neutrophil, platelet count, NLR, and PLR values were higher in the uveitis group compared to the control group. In the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for NLR was 0.805, with a sensitivity of 56.0% and a specificity of 98.0%. The AUC for PLR was 0.657, with a sensitivity of 52.0% and a specificity of 98.0%. Conclusion In this retrospective study, leukocyte, neutrophil, platelet count, PLR, and NLR levels were significantly higher in patients with idiopathic acute anterior uveitis compared to the control group. These blood parameters are useful as diagnostic markers and can be used in early diagnosis.
What Matters for Students’ Learning? The Roles of Social and Emotional Skills and the Factors Affecting These Skills
Authors: Huang (黄忠敬) Zhongjing , Zhang (张静) Jing , Yuan (袁振国) Zhenguo 
Published: January 2024

Purpose This study employs a multi-cohort and multi-informant design to assess how the social and emotional skills of Chinese youth vary according to age and gender, as well as the home, school, and community environment factors that promote or hinder the development of such skills. This study also investigates the relevance of these skills for students’ educational, social, and psychological outcomes. Design/Approach/Methods The survey sample consisted of two cohorts comprising a total of 7,268 students. In terms of age, 3,647 respondents (50.2%) were 10-year-olds, while 3,621 (49.8%) were 15-year-olds. In terms of gender, 3,824 (52.8%) respondents were male, 3,417 (47%) were female, and 13 (0.2%) respondents did not identify their gender. Multiple group confirmatory factor analyses were conducted to test for measurement invariance across age and gender. Moreover, correlation and relative weight analyses were conducted to examine the degree and relative contributions of self-, parent-, and teacher-rated social and emotional skills in predicting various important life outcomes. Findings The results revealed that the 10-year-old respondents scored higher in all 15 social and emotional skills than the 15-year-old respondents. Among the younger cohort, girls score higher in cooperation, empathy, sociability, persistence, and tolerance. In general, a sense of school belonging was related to engaging with others (sociability), collaboration (cooperation and trust), and emotion regulation (optimism and stress resistance). The School Bullying Index was closely related to stress resistance, trust, and cooperation. Optimism was the strongest factor related to life satisfaction and psychological well-being, followed by energy and trust. Stress resistance and optimism were closely related to test anxiety. Originality/Value This study makes a significant contribution to the literature because it is the first large-scale assessment of adolescents’ social and emotional skills worldwide and in China. This original study explores the importance of social and emotional skills in predicting educational, social, and psychological outcomes and identifies potential factors that drive the development of such skills.
Healing of Venous Leg Ulcers Influenced by Individual Aspects: Cluster Analysis in a Specialist Wound Management Clinic
Authors: Jacinto Maria Angélica Gomes , Oliveira Adriana Catarina de Souza , Martínez Carmelo Sergio Gómez , Schlosser Thalyta Cristina Mansano , Dantas Bruno Araújo da Silva , Torres Gilson de Vasconcelos 
Published: January 2024

Introduction/Objective: Venous Leg Ulcers (VLU) present a challenging healing process. Attaining healing is a primary treatment objective, commonly pursued in Primary Health Care (PHC) or Specialist Wound Management Clinics. Our objective was to examine the association and interplay between sociodemographic, health, clinical, and care factors with the outcomes of VLU treatment in patients undergoing care at a Specialist Wound Management Clinic. Methods: Longitudinal, observational study took place in a center for the treatment of chronic injuries linked to PHC. The sociodemographic aspects, health status and habits, clinical and care aspects of patients with VLU were scrutinized over a 1-year period. Results: The sample comprised 103 participants, with some still under treatment (Treatment Group—TG/ n = 60) and others having achieved VLU healing (Healing Group—HG/ n = 43). An association between sociodemographic, health, clinical, and care factors and the healing outcome (HG) was identified. A moderate correlation was observed between factors predisposing to healing in the sociodemographic group and health habits. Notably, among sociodemographic factors, the older age group and improvements in health, particularly the reduced use of alcohol/smoking, appeared to exert the most significant influence on healing. Additionally, specialized service monitoring and the application of compression therapy were contributory factors. Conclusions: These findings substantiate the hypothesis that sociodemographic, health, clinical, and care-related aspects are intertwined with VLU healing. Protective factors associated with healing interacted synergistically, fostering a positive outcome over one year of treatment.
Prevalence of Cognitive Impairment and Associated Factors Among Diabetes Mellitus Patients Attending Follow-up Treatment at Fiche General Hospital, North Ethiopia
Authors: Ashebir Nimona , Hailesilassie Hailemariam , Girma Shimelis , Nigusu Elias , Ezo Elias 
Published: January 2024

Introduction Cognitive impairment is having trouble remembering, learning new things, concentrating, or making decisions that affect the daily life of diabetic patients. The worldwide prevalence of diabetes mellitus (DM) was 2.8% in 2000 and is estimated to be 4.4% by 2030. Objective To assess the prevalence of cognitive impairment and associated factors among DM patients attending follow-up treatment at Fiche General Hospital, North Ethiopia, 2022. Methods A hospital-based cross-sectional study was conducted from July 15 to September 15, 2022. The total sample size was 421 and a systematic random sampling technique was used. Data were collected through a face-to-face interview. Data were entered using EpiData Version 3.1 and exported to SPSS Version 24 for analysis. Statistically significant was declared at a P-value of less than .05 with an adjusted odds ratio (AOR) and 95% confidence interval (CI). Result The prevalence of cognitive impairment in the current study was 56.3% with (95% CI: 51.5–60.8). Primary educational status (AOR 6.73, 95% CI: 2.92–15.51), having Type II DM (AOR 4.93, 95% CI: 2.84–8.56), uncontrolled blood sugar (AOR 6.24, 95% CI: 3.84–10.17), and current alcohol use (AOR 1.94, 95% CI: 1.11–3.36) were significantly associated. Conclusion About three in 5 DM patients attending follow-up treatment at Fiche General Hospital were suffering from cognitive impairment. Educational status, type of DM, status of fasting blood sugar, and current alcohol use were associated with cognitive impairment among DM patients. Therefore, improving educational status, controlling blood sugar, and avoiding alcohol use may reduce the risk of cognitive impairment in DM patients.
Association of covert brain infarct phenotype with stroke recurrence in first-ever manifest ischemic stroke according to etiology
Authors: Meinel Thomas Raphael , Leber Stefan L. , Janisch Michael , Vynckier Jan , Mujanovic Adnan , Boronylo Anna , Kaesmacher Johannes , Seiffge David Julian , Roten Laurent , Arnold Marcel , Enzinger Christian , Gattringer Thomas , Fischer Urs , Kneihsl Markus 
Published: January 2024

Introduction: Covert brain infarcts (CBI) are frequent incidental findings on MRI and associated with future stroke risk in patients without a history of clinically evident cerebrovascular events. However, the prognostic value of CBI in first-ever ischemic stroke patients is unclear and previous studies did not report on different etiological stroke subtypes. We aimed to test CBI phenotypes and their association with stroke recurrence in first-ever ischemic stroke patients according to stroke etiology. Patients and methods: This study is a pooled data analysis of two prospectively collected cohorts of consecutive first-ever ischemic stroke patients admitted to the comprehensive stroke centers of Bern (Switzerland) and Graz (Austria). CBI phenotypes were identified on brain MRI within 72 h after admission. All patients underwent a routine follow-up (median: 12 months) to identify stroke recurrence. Results: Of 1577 consecutive ischemic stroke patients (median age: 71 years), 691 patients showed CBI on brain MRI (44%) and 88 patients had a recurrent ischemic stroke (6%). Baseline CBI were associated with stroke recurrence in multivariable analysis (HR 1.9, 95% CI 1.1–3.3). CBI phenotypes with the highest risk for stroke recurrence were cavitatory CBI in small vessel disease (SVD)-related stroke (HR 7.1, 95% CI 1.6–12.6) and cortical CBI in patients with atrial fibrillation (HR 3.0, 95% CI 1.1–8.1). Discussion and conclusion: This study reports a ≈ 2-fold increased risk for stroke recurrence in first-ever ischemic stroke patients with CBI. The risk of recurrent stroke was highest in patients with cavitatory CBI in SVD-related stroke and cortical CBI in patients with atrial fibrillation. Subject terms: Covert brain infarcts, stroke
Open Reduction Internal Fixation vs Primary Arthrodesis for Lisfranc Fracture-Dislocations: A Cost Analysis
Authors: Ochuba Arinze , Murdock Christopher J. , Xu Amy L. , Snow Morgan , Schmerler Jessica , Leland Christopher R. , McDaniel Claire , Thompson John , Aiyer Amiethab A. 
Published: January 2024

Background: Lisfranc fracture-dislocation is an uncommon but serious injury that currently lacks universal consensus on optimal operative treatment. Two common fixation methods are open reduction and internal fixation (ORIF) and primary arthrodesis (PA). The objective of this study is to analyze the cost difference between ORIF and PA of Lisfranc injuries, along with the contribution of medical services to overall costs. Methods: This was a retrospective cost analysis of the MarketScan database from 2010 to 2020. MarketScan is an insurance and commercial claims database that integrates deidentified patient information. It captures person-specific clinical utilization, expenditures, and enrollment across inpatient and outpatient services. Patients undergoing primary ORIF ( CPT code 28615) vs PA (28730 and 28740) for Lisfranc fracture-dislocation were identified. The primary independent variable was ORIF vs PA of Lisfranc injury. Total costs due to operative management was the primary objective. The utilization of and costs contributed by medical services was a secondary outcome. Results: From 2010 to 2020, a total of 7268 patients underwent operative management of Lisfranc injuries, with 5689 (78.3%) ORIF and 1579 (21.7%) PA. PA was independently associated with increased net and total payment and coinsurance, clinic visits, and imaging, and patients attended significantly more PT sessions. Conclusion: Using this large database that does not characterize severity or extent of injury, we found that treatment of Lisfranc fracture-dislocation with ORIF was associated with substantially lower initial episode of treatment costs compared with PA. Specific excessive cost drivers for PA were clinic visits, PT sessions, and imaging. Level of Evidence: Level III, retrospective cohort study.
Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results
Authors: Yacoub Abdulraheem , Borate Uma , Rampal Raajit K. , Ali Haris , Wang Eunice S. , Gerds Aaron T. , Hobbs Gabriela , Kremyanskaya Marina , Winton Elliott , O’Connell Casey , Goel Swati , Oh Stephen T. , Schiller Gary , McCloskey James , Palmer Jeanne , Holmes Houston , Hager Steven , Assad Albert , Erickson-Viitanen Susan , Zhou Feng , Daver Naval 
Published: January 2024

Abstract
Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib. Eligible patients remained on a stable ruxolitinib dose and received add-on parsaclisib 10 or 20 mg, once daily for 8 weeks, and once weekly thereafter (daily-to-weekly dosing; n = 32); or parsaclisib 5 or 20 mg, once daily for 8 weeks, then 5 mg once daily thereafter (all-daily dosing; n = 42). Proportion of patients achieving a ≥10% decrease in spleen volume at 12 weeks was 28% for daily-to-weekly dosing and 59.5% for all-daily dosing. Proportions of patients achieving ≥50% decrease at week 12 in Myelofibrosis Symptom Assessment Form and Myeloproliferative Neoplasms Symptom Assessment Form symptom scores were 14% and 18% for daily-to-weekly dosing, and 28% and 32% for all-daily dosing, respectively. Most common nonhematologic treatment-emergent adverse events were nausea (23%), diarrhea (22%), abdominal pain and fatigue (each 19%), and cough and dyspnea (each 18%). New-onset grade 3 and 4 thrombocytopenia were observed in 19% of patients, each dosed daily-to-weekly, and in 26% and 7% of patients dosed all-daily, respectively, managed with dose interruptions. Hemoglobin levels remained steady. The addition of parsaclisib to stable-dose ruxolitinib can reduce splenomegaly and improve symptoms, with manageable toxicity in patients with myelofibrosis with suboptimal response to ruxolitinib. This trial was registered at www.clinicaltrials.gov as #NCT02718300.
Modeling primitive and definitive erythropoiesis with induced pluripotent stem cells
Authors: Pavani Giulia , Klein Joshua G. , Nations Catriana C. , Sussman Jonathan H. , Tan Kai , An Hyun Hyung , Abdulmalik Osheiza , Thom Christopher S. , Gearhart Peter A. , Willett Camryn M. , Maguire Jean Ann , Chou Stella T. , French Deborah L. , Gadue Paul 
Published: January 2024

Abstract
During development, erythroid cells are produced through at least 2 distinct hematopoietic waves (primitive and definitive), generating erythroblasts with different functional characteristics. Human induced pluripotent stem cells (iPSCs) can be used as a model platform to study the development of red blood cells (RBCs) with many of the differentiation protocols after the primitive wave of hematopoiesis. Recent advances have established that definitive hematopoietic progenitors can be generated from iPSCs, creating a unique situation for comparing primitive and definitive erythrocytes derived from cell sources of identical genetic background. We generated iPSCs from healthy fetal liver (FL) cells and produced isogenic primitive or definitive RBCs which were compared directly to the FL-derived RBCs. Functional assays confirmed differences between the 2 programs, with primitive RBCs showing a reduced proliferation potential, larger cell size, lack of Duffy RBC antigen expression, and higher expression of embryonic globins. Transcriptome profiling by scRNA-seq demonstrated high similarity between FL- and iPSC-derived definitive RBCs along with very different gene expression and regulatory network patterns for primitive RBCs. In addition, iPSC lines harboring a known pathogenic mutation in the erythroid master regulator KLF1 demonstrated phenotypic changes specific to definitive RBCs. Our studies provide new insights into differences between primitive and definitive erythropoiesis and highlight the importance of ontology when using iPSCs to model genetic hematologic diseases. Beyond disease modeling, the similarity between FL- and iPSC-derived definitive RBCs expands potential applications of definitive RBCs for diagnostic and transfusion products.
Six-year follow-up and subgroup analyses of a phase 2 trial of venetoclax for del(17p) chronic lymphocytic leukemia
Authors: Stilgenbauer Stephan , Tausch Eugen , Roberts Andrew W. , Davids Matthew S. , Eichhorst Barbara , Hallek Michael , Hillmen Peter , Schneider Christof , Schetelig Johannes , Böttcher Sebastian , Kater Arnon P. , Jiang Yanwen , Boyer Michelle , Popovic Relja , Ghanim Majd T. , Moran Michael , Sinai Wendy J. , Wang Xifeng , Mukherjee Nabanita , Chyla Brenda , Wierda William G. , Seymour John F. 
Published: January 2024

Abstract
Chromosome 17p deletion (del[17p]) is associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL). Venetoclax is approved for treatment of previously untreated and relapsed/refractory (R/R) CLL, including patients with del(17p), based on the open-label, multicenter, phase 2 M13-982 trial (NCT01889186). Here, we detail the 6-year follow-up analysis for M13-982. A total of 158 patients with previously untreated (n = 5) or R/R (n = 153) del(17p) CLL received 400 mg venetoclax daily after initial ramp-up until progressive disease. After a median follow-up of 70 months, the best objective response rate (ORR) was 77% (21% complete remission [CR] and 49% partial remission [PR]), with a median duration of response (DOR) of 39.3 months (95% confidence interval [CI], 31.1-50.5). The median progression-free survival (PFS) was 28.2 months (95% CI, 23.4-37.6), and median overall survival (OS) was 62.5 months (95% CI, 51.7-not reached), with 16% of patients remaining on treatment after 6 years. Multivariable analysis did not identify statistically significant correlation between patient subgroups defined by clinical or laboratory variables and ORR or PFS. The most common grade ≥3 adverse events were neutropenia (42%), infections (33%), anemia (16%), and thrombocytopenia (16%). Post hoc comparative analyses of PFS and OS from treatment initiation, from a 24-month landmark, and by minimal residual disease status were performed between patients with del(17p) in the M13-982 and MURANO studies in the interest of understanding these data in another context. These long-term data show the continued benefits of venetoclax in patients with del(17p) CLL. The trial was registered at www.clinicaltrials.gov as #NCT01889186.
Learning self-supervised molecular representations for drug–drug interaction prediction
Authors: Kpanou Rogia , Dallaire Patrick , Rousseau Elsa , Corbeil Jacques 
Published: January 2024

AbstractDrug–drug interactions (DDI) are a critical concern in healthcare due to their potential to cause adverse effects and compromise patient safety. Supervised machine learning models for DDI prediction need to be optimized to learn abstract, transferable features, and generalize to larger chemical spaces, primarily due to the scarcity of high-quality labeled DDI data. Inspired by recent advances in computer vision, we present SMR–DDI, a self-supervised framework that leverages contrastive learning to embed drugs into a scaffold-based feature space. Molecular scaffolds represent the core structural motifs that drive pharmacological activities, making them valuable for learning informative representations. Specifically, we pre-trained SMR–DDI on a large-scale unlabeled molecular dataset. We generated augmented views for each molecule via SMILES enumeration and optimized the embedding process through contrastive loss minimization between views. This enables the model to capture relevant and robust molecular features while reducing noise. We then transfer the learned representations for the downstream prediction of DDI. Experiments show that the new feature space has comparable expressivity to state-of-the-art molecular representations and achieved competitive DDI prediction results while training on less data. Additional investigations also revealed that pre-training on more extensive and diverse unlabeled molecular datasets improved the model’s capability to embed molecules more effectively. Our results highlight contrastive learning as a promising approach for DDI prediction that can identify potentially hazardous drug combinations using only structural information.
Bioprocessing of Epothilone B from Aspergillus fumigatus under solid state fermentation: Antiproliferative activity, tubulin polymerization and cell cycle analysis
Authors: El-Sayed Ashraf S. A. , Shindia Ahmed , Ammar Hala , Seadawy Mohamed G. , Khashana Samar A. 
Published: January 2024

AbstractEpothilone derivatives have been recognized as one of the most powerful anticancer drugs towards solid tumors, for their unique affinity to bind with β-tubulin microtubule arrays, stabilizing their disassembly, causing cell death. Sornagium cellulosum is the main source for Epothilone, however, the fermentation bioprocessing of this myxobacteria is the main challenge for commercial production of Epothilone. The metabolic biosynthetic potency of epothilone by Aspergillus fumigatus, an endophyte of Catharanthus roseus, raises the hope for commercial epothilone production, for their fast growth rate and feasibility of manipulating their secondary metabolites. Thus, nutritional optimization of A. fumigatus for maximizing their epothilone productivity under solid state fermentation process is the objective. The highest yield of epothilone was obtained by growing A. fumigatus on orange peels under solid state fermentation (2.2 μg/g), bioprocessed by the Plackett-Burman design. The chemical structure of the extracted epothilone was resolved from the HPLC and LC-MS/MS analysis, with molecular mass 507.2 m/z and identical molecular fragmentation pattern of epothilone B of S. cellulosum. The purified A. fumigatus epothilone had a significant activity towards HepG2 (IC50 0.98 μg/ml), Pancl (IC50 1.5 μg/ml), MCF7 (IC50 3.7 μg/ml) and WI38 (IC50 4.6 μg/ml), as well as a strong anti-tubulin polymerization activity (IC50 0.52 μg/ml) compared to Paclitaxel (2.0 μg/ml). The effect of A. fumigatus epothilone on the immigration ability of HepG2 cells was assessed, as revealed from the wound closure of the monolayer cells that was estimated by ~ 63.7 and 72.5%, in response to the sample and doxorubicin, respectively, compared to negative control. From the Annexin V-PI flow cytometry results, a significant shift of the normal cells to the apoptosis was observed in response to A. fumigatus epothilone by ~ 20 folds compared to control cells, with the highest growth arrest of the HepG2 cells at the G0-G1 stage.