bluuebunny/crossref_metadata_2025 huggingface dataset:
Service learning and the just community: Complementary pragmatist forms of civic character education
Authors: Jover Gonzalo , Gozálvez Vicent
Published: January 2024

This article investigates the theoretical link between two approaches to civic character education: Service Learning and the Just Community, given that the two share a strong democratic ethical component. Based on historical research and bibliographical review, we show that John Dewey’s pragmatism forms a theoretical foundation of both approaches. Our revision combines the search for a normative foundation of democratic life with the need for contextual agreements: universal principles of justice with conversation and action in specific situations, moral autonomy with social commitment in real circumstances. By merging the two educational approaches to civic character education, we conclude that social and democratic progress does not mean renouncing ethical principles, but drawing them in a different way: revisably, creatively, dialectically, practically, and intersubjectively.
Novel reed development for width-variable fabrics on wide weaving machines
Authors: Nuss Dominik , Cornelia Sennewald , Chokri Cherif
Published: January 2024

Technical fabrics find extensive use as reinforcement in plastic components across various applications. Traditionally, these fabrics are produced using wide weaving machines with a constant fabric width and are then cut to achieve the desired component geometry, leading to significant waste generation. An effective approach to minimizing waste and conserving resources involves utilizing fabrics with outer contours that match the desired component geometry from the outset. Until now, the production of width-variable fabrics during the weaving process has not been achievable using wide weaving machines. Addressing this limitation, this paper introduces a novel reed design specifically developed for wide weaving machines. The paper presents the design concept of the new reed and elucidates the fabric development process associated with its implementation. Furthermore, the resulting fabric properties and physical relationships are demonstrated based on manufactured samples. By enabling the production of width-variable fabrics, this innovative approach aims to contribute to more sustainable manufacturing practices in the field of technical fabrics—reducing waste and optimizing resource utilization.
Latine Students’ Motivational and Emotional Experiences Related to Their Introductory Statistics Course: Differences by Institution Type Necessitate Tailored Interventions
Authors: Sutter Claudia C. , Givvin Karen B. , Solomon Paige L. , Leandro-Ramos Ana
Published: January 2024

The study compared concerns, anxiety, mindsets, and belonging in introductory statistics among Latine students across three higher education institutions. Students at the Predominantly White Institution voiced more concerns about R-coding and lack of prior knowledge. Students at the Hispanic-Serving Institutions voiced more concerns about math anxiety and social comparison and had more fixed mindsets, yet higher levels of belonging—pointing toward the value of exploring Latine students’ experiences across different contexts and providing tailored interventions.
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.
Independence of the European Public Prosecutor’s Office in the context of the appointment procedures
Authors: Márton Balázs
Published: January 2024

The personal independence of the European Chief Prosecutor and European Prosecutors is a prerequisite of the independence of the European Public Prosecutor's Office. Based on the experience of the first appointment procedures and a combined examination of EU law, areas of vulnerability can be identified which could jeopardise their independence. The definition and doctrinal positioning of prosecutorial independence, such as its separation from autonomy and accountability, is not a simple task in case of a supranational prosecutorial body. However, there are international expert bodies that have drawn attention to the central importance of guarantees in the appointment procedures and transparency in ensuring prosecutorial independence, which also underpins public confidence in the process. Although there are institutional safeguards in the appointment procedures for the European Chief Prosecutor and the European Prosecutors, the shortcomings of the legislation have been exposed by the recent experiences. There is insufficient transparency in the selection of the members of the selection panel and in its functioning. In addition, the legislation does not categorically exclude the possibility that political considerations without a legal basis may be introduced into the appointment procedure. The EU regulation governing the functioning of the European Public Prosecutor's Office and the operating rules of the selection panel should also be amended to ensure full transparency of the criteria used to select the members of the selection panel and the assessment of the selection panel during selection and ranking of the prosecutors. In addition, the relevant EU regulation should be amended to make the decision-making process in the Council of the European Union more transparent and to stipulate that the Council of the European Union and the European Parliament may base their selection decisions only on the criteria set out in the applicable legislation and the opinion of the selection panel.
The platformation and transformation of the digital public sphere: An introduction
Authors: Xie Ming
Published: January 2024

This article introduces the complex landscape of social media platforms and their evolving integration within social and political contexts. Focusing on the concept of platform society, this article discusses the emergence and growth of new platforms as well as the localization trends of mobile communication. This article examines the interplay between technological structures and social, cultural, and political dimensions of mobile communication, focusing on issues such as privacy policies, data protection, and profit-seeking motives of platform owner companies. In addition, this article introduces the six papers chosen for this special issue. The diverse viewpoints presented in this special issue contribute to a deeper understanding of digital communication’s role in advancing democracy, encouraging citizen participation, and transforming public spheres.
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.
Relationship Between Chronotype With Emotional Eating, Eating Disorder Risk and Depression: A Cross-Sectional Study
Authors: Esin Kübra , Ayyıldız Feride
Published: January 2024

Chronotype is defined as individuals’ preferences regarding the timing of their sleep and wake cycle. An individual’s chronotype is associated with many factors such as age, sex, and lifestyle. This study was conducted to evaluate the relationship between chronotype and emotional eating,depression, anxiety, stress, body weight, eating disorder risk, and life satisfaction in university students. This present study included 511 Turkish university students with a mean age of 20.0 ± 1.93 years. The anthropometric measurements (body weight, and height) were recorded. Additionally, the Morningness-Eveningness Questionnaire (MEQ), the Emotional Eater Questionnaire (EEQ), the Sick, Control, One stone, Fat, Food (SCOFF) Questionnaire, the Depression, Anxiety, Stress Scale-21 (DASS-21), and the Contentment with Life Assessment Scale (CLAS) were used to collect data. The evening-type individuals had significantly higher total EEQ and DASS-21 subscale scores than the morning-type individuals. The morning-type individuals had significantly higher total CLAS scores than the evening-type individuals. There was no significant difference between the groups in terms of their SCOFF total scores and BMI values. This showed that chronotype is related to emotional eating, depression, anxiety, stress, and life satisfaction in university students, but there is not related to the risk of eating disorders and BMI. The regulation of the circadian system will be useful for improving eating behavior and mood, as well as weight loss programs. It is thought that further long-term follow-up studies with different samples would contribute to this field.
Overcoming Emotional and Communication Barriers With Performing Arts Strategies: The Case of Puerto Rican Business Students
Authors: Irizarry Quintero Anamari
Published: January 2024

This article discusses interdisciplinary approaches to help students overcome communication barriers by integrating performing arts in Business Communication courses. Companies emphasize a workforce with solid soft skills to succeed. International Business employs English; thus, practical communication skills in English provide access to jobs in international scenarios. However, in Puerto Rico, second-language speakers of English feel intimidated when speaking it. The emotional barriers students endure while developing intercultural and communication skills in English is a topic worth researching. Performing arts provide strategies to raise body awareness and increase self-confidence. These elements will lead to a confident and effective communicator.
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

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

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

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

Drug–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

Epothilone 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.
Dexmedetomidine nasal administration improves perioperative sleep quality and neurocognitive deficits in elderly patients undergoing general anesthesia
Authors: He Jiang , Zhang Xinning , Li Cuicui , Fu Baojun , Huang Yizhou , Li Heng
Published: January 2024

Objective

To investigate the improvement of perioperative sleep quality and neurocognitive impairment in elderly patients under general anesthesia by nasal administration of dexmedetomidine.

Methods

One hundred and twenty patients admitted to our hospital for various laparoscopic elective gynecological surgeries lasting more than 1 h under general anesthesia from July 2021 to March 2023 were selected. All subjects were divided into 3 groups according to the random number table method. From 21:00 to 21:30 every night from one day before to 5 days after surgery, group A was given alprazolam 0.4 mg orally; group B was given dexmedetomidine 1.5ug/kg nasal drip; group C was given saline nasal drip. All subjects were observed for general information, sleep quality, postoperative cognitive function, anxiety status, sleep quality, adverse effects and complication occurrence.

Results

The difference in general information between the three groups was not statistically significant, P > 0.05; the sleep quality scores of the three groups on admission were not statistically significant, P > 0.05. At the Preoperative 1d, postoperative 1d, 3d and 5d, the RCSQ scores of the subjects in group A and group B were higher than those in groups C, and with the postoperative RCSQ scores of subjects in group B were higher as the time increased; the assessment of anxiety status in the three groups 1d before surgery was not statistically significant, P > 0.05. The cognitive function scores of subjects in the three groups were not statistically significant in the preoperative 1d, P > 0.05. The postoperative 1d (24.63 ± 2.23), 3d (25.83 ± 2.53), and 5d (26.15 ± 2.01) scores of the subjects in group B were higher than those in groups A and C (P < 0.05), and the subjects in group B had better recovery of postoperative cognitive function with increasing time; the occurrence of postoperative delirium (POD) in group B (12.5%) were lower on postoperative 5d than those in groups A (37.5%) and C (32.5%) (P < 0.05). There was no statistical significance in the evaluation of anxiety state of the three groups on the first day before operation (P > 0.05). The scores in group B were lower than those in group C on the postoperative 1d, 3d, 5 d (P < 0.05). The overall incidence of adverse reactions and complications in subjects in group B was 17.5% significantly lower than that in groups A and C (P < 0.05).

Conclusion

Dexmedetomidine can effectively improve the sleep disorder of elderly general anesthesia patients, reduce the damage to their neurocognitive function and the occurrence of POD, effectively reduce the anxiety of patients and the occurrence of adverse reactions and complications, and has better sedative, improve postoperative cognitive function and anti-anxiety effects, with a high drug safety, worthy of clinical application and promotion.
Effect of sacubitril valsartan on heart failure with mid-range or preserved ejection fraction in patients on maintenance hemodialysis: real-world experience in a single-center, prospective study
Authors: Huang Xiao-mei , Li Jing-jing , Yin Wang , Fu Hui-ling , Yu Fen , Gu Lian-qing , Zhang Yi , Du Min , Ye Zheng , Xu Li
Published: January 2024

Background

This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF).

Methods

This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day.

Results

Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e’) improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF.

Conclusions

SV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.
Adaptation of a guided low-intensity behavioral activation intervention for people with dementia in Sweden: a qualitative study exploring the needs and preferences of key stakeholders
Authors: Blomberg Oscar , Svedin Frida , Farrand Paul , Brantnell Anders , von Essen Louise , Patriksson Karlsson Johanna , Åberg Anna Cristina , Woodford Joanne
Published: January 2024

Background

Despite depression being prevalent in people with dementia, contributing to negative health outcomes and placing increased burden on individuals and family members, access to psychological interventions is limited. A potential solution is guided low-intensity behavioral activation, supported by informal caregivers and guided by healthcare professionals. However, it is necessary to adapt interventions to meet the needs and preferences of key stakeholders to enhance acceptability and relevance. Study objectives were to: (1) explore needs and preferences concerning the content and delivery model of the guided low-intensity behavioral activation intervention; and (2) adapt the intervention to ensure cultural appropriateness, relevancy, and acceptability to people with dementia and their caregivers in Sweden.

Methods

Semi-structured interviews and focus group discussions were conducted with key stakeholders, including healthcare professionals (n = 18), community stakeholders (n = 7), people with dementia (n = 8), and informal caregivers (n = 19). A draft of the written low-intensity behavioral activation intervention and a description of the proposed intervention delivery model were provided to participants. Open-ended questions explored the perceived relevance of the intervention, alongside needs and preferences concerning content and delivery. A manifest content analysis approach was adopted.

Results

Content analysis resulted in three categories: Content, Delivery procedures, and Illness trajectory. Results highlighted a need to consider the intervention Content via increased cultural adaptation to the Swedish context, and increasing the inclusiveness of intervention content. Delivery procedures were identified as needing to be flexible given the unpredictable nature of caring for people with dementia, with the provision of additional guidance to informal caregivers supporting the intervention. Illness trajectory was viewed as essential to consider, with the intervention regarded as suitable for those early in the dementia trajectory, alongside a need to reduce workbook text to minimize burden given dementia symptomology.

Conclusions

The intervention and proposed delivery model were generally well received by all stakeholders. We were able to identify key adaptations to enhance cultural appropriateness, relevancy, and acceptability for a currently neglected population. Results will inform a feasibility study to explore the feasibility and acceptability of the intervention and study procedures to inform the design of a future superiority randomized controlled trial.

Trial registration/protocol

Not applicable.
Prevalence of iron deficiency in patients admitted to a geriatric unit: a multicenter cross-sectional study
Authors: Fougère Bertrand , Puisieux François , Chevalet Pascal , Annweiler Cédric , Michel Emeline , Joly Laure , Blanc Frédéric , Azouzi Abdelghani EL , Desré-Follet Valérie , Cacoub Patrice ,   on behalf of the CARENFER PA study group*, Billet Anne-Sophie , Fiasson Florent , Garnier-Crussard Antoine , Goidin Isabelle , Paccalin Marc , Parnet Laure , Sarasibar Mikel , Thomas Caroline
Published: January 2024

Background

Iron deficiency (ID) is often associated with other comorbidities in older patients and is a factor of morbimortality. However, the prevalence of ID remains poorly documented in this population.

Methods

The CARENFER PA study was a French multicenter cross-sectional study whose objective was to evaluate ID in patients (> 75 years) admitted to a geriatric unit. The primary endpoint was the ID prevalence defined as: serum ferritin < 100 µg/L and/or transferrin saturation coefficient (TSAT) < 20%. The Short Physical Performance Battery (SPPB) test was used to identify older patients at high risk of adverse events (e.g., disability, falls, hospitalization, death).

Results

A total of 888 patients (mean age, 85.2 years; women, 63.5%) from 16 French centers were included from October 2022 to December 2022. The prevalence of ID was 57.6% (95% CI, 54.3–60.9) in the cohort of older patients (62.6% in anemic and 53.3% in non-anemic patients; p = 0.0062). ID prevalence increased significantly with the presence of more than three comorbidities (65.6% vs. 55.9%; p = 0.0274), CRP ≥ 12 mg/L (73.0% vs. 49.3%; p < 0.001) and treatment that may influence ID/anemia (60.5% vs. 49.6%; p = 0.0042). In multivariate analysis, only CRP ≥ 12 mg/L was an independent predictive factor of ID (odds ratio, 2.78; 95% CI, 1.92–4.08; p < 0.001). SPPB scores were low (0–6) in 60.5% of patients with ID versus 48.6% of patients without ID (p = 0.0076).

Conclusion

More than half of older patients had ID, including non-anemic patients. ID was associated with the presence of inflammation and a low SPPB score.

Trial registration

NCT05514951.
The effect of educational intervention on efficacy of 1% permethrin shampoo and 4% dimeticone lotion to treat head lice infestation using propensity score matching (PSM)
Authors: Moradi-Asl Eslam , Saghafipour Abedin , Hamta Amir , Taheri-Kharameh Zahra , Abazari Malek , Asghari Jajin Shabnam
Published: January 2024

Background

Head lice are a main public health problem and the most important human ectoparasites and the use of pediculicides is the most common way to control it. One of the possible causes of treatment failure is the lack of improper application of pediculicide. The aim of this study was to assess the effect of education on efficacy of 1% permethrin or 4% dimeticone lotion to treat head lice infestation.

Methods

This quasi-experimental study included 100 individuals with head lice infestation from comprehensive urban health centers in Ardabil as the intervention group, and 400 individuals from East Azerbaijan and West Azerbaijan provinces as the control group, from April to March 2019. The data collection tools included a demographic questionnaire and an examination recording sheet, which documented the presence of adult lice or nits. Due to the inability to perform random assignment and control for numerous observed covariates, propensity score matching (PSM) was used.

Results

The outcome of treatment included elimination of head lice infestation on is 7, and in the case of recurrence, it was considered on days 14 and 30 after treatment. The results showed that the educational intervention program had a significant positive effect on the efficacy of both treatments. The likelihood of improvement was approximately three times greater in the intervention group compared to the control group.

Conclusion

Participants who received the training intervention (OR = 3.29; CI 95%: 2.21–4.88) were more likely to have a successful treatment than control group. In the case of providing proper training on the use of pediculicides and observing hygiene tips to patients with pediculosis, could help to successful treatment of pediculosis.
Enhanced systematic delivery of fluconazole-loaded biotin-glutathione functionalized chitosan-g-proline carrier into the infected retinitis treatment
Authors: Guo Qing , Li Zheng , Cao Fang
Published: January 2024

Background

The polymer-based facile and effective drug carrier approach was developed to treat superficial fungal infected retinopathy infections.

Methods

Here, biotin-glutathione (B-GHS) functionalized with chitosan grafted proline (CS-g-P) moieties were fabricated with the loading of fluconazole (FLZ) for the treatment of retinopathy. FT-IR and XRD techniques were used to characterize chemical structural and phase changes of the prepared carriers The SEM results show that the sphere morphology with interconnection particle nature.

Results

The particle diameter was found as ~ 6.5 and ~ 8.6 nm for CS-g-P/B-GHS and FLZ-loaded CS-g-P/B-GHS carriers, respectively. The negative surface charge was found as the values of CS-g-P/B-GHS and FLZ-loaded CS-g-P/B-GHS, such as -20.7 mV and − 32.2 mV, from zeta potential analysis. The in-vitro FLZ releases from the CS-g-P/B-GHS were investigated at pH 7.4 (PBS) as the tear fluid environment, and it was observed at 85.02% of FLZ release in 8 h reaction time. The sustained release was observed, leading to the necessity for prolonged therapeutic effects. The antifungal effect of the carrier was studied by the minimum inhibitory concentration (MIC) and the percentage inhibition of viable fungal count against Candida albicans, and it observed 81.02% of the zone of inhibition by the FLZ carrier.

Conclusion

FLZ-loaded CS-g-P/B-GHS carrier could inhibit the biofilm formation in a concentration-dependent inhibition. Hence, A novel FLZ/B-GHS-CS-g-P carrier is a hopeful approach for effectively treating superficial fungal contaminations of the retina region.