bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients’ suggestions for improvements to text-based e-consultations. An online survey of users of the national health portal in Norway
Authors: Kristiansen Eli , Atherton Helen , Bergmo Trine Strand , Zanaboni Paolo 
Published: December 2024

BackgroundIn recent years, text-based e-consultations have been widely implemented in general practice and are appreciated by patients for their convenience and efficiency. Policymakers aim to enhance patient access to clinical services with the general practitioner (GP) through text-based e-consultations. However, concerns are raised about their efficiency and security. We aimed to investigate users’ perceptions of potential improvements in the text-based e-consultation service provided by the national health portal in Norway.MethodWe conducted an online survey among users of text-based e-consultations with the GP on the national health portal Helsenorge. The survey was available from January-February 2023 and consisted of 20 questions. This study focused on the free-text answers to the question “Do you have any suggestions to improve the service?” The framework method was used for a thematic analysis of the answers.ResultsThe analysis of 2,954 free-text answers from users of the national e-consultation service resulted in six areas where suggestions for improvement were expressed. According to users, the service would benefit from: (1) a better set-up to facilitate the formulation of the patient's problem, (2) better value for money (in regards to both price and quality), (3) faster response time, (4) improved information and predictability about the status of the e-consultation (e.g., if it is received and when to expect an answer), (5) improvement in technical issues, and (6) improvement of access to dialogue-based services to replace or complement e-consultations.ConclusionThe analysis of users’ suggestions for improvements to the e-consultation service emphasised the need to customise the service to address individual patient needs. Users found a one-size-fits-all approach with mandatory questions, fixed pricing, and inflexible response times less appreciated. Some also felt forced to rely on e-consultations due to the perceived poor availability of other GP services. This highlights the importance of perceiving e-consultations not as a replacement for dialogue-enabled services, but rather as a potentially efficient addition, ensuring a well-tailored setup for appropriate patient use.
Intraspecific phenotypic differentiation by habitat depth in deep demersal fish species
Authors: Steeds Natasha , Zulqurnain Zulqurnain , Regnier Thomas , Gibb Fiona , Stirling David , Hoelzel A. Rus 
Published: December 2024

IntroductionOcean habitat characteristics change with depth. This is due to physical properties such as light, temperature and hydrostatic pressure, but also species community. In some cases, this generates a boundary (e.g. when light is lost in the bathypelagic), and in others it varies continuously (e.g. for hydrostatic pressure). Various studies have noted general morphometric adaptations to living at different depths seen among species, even though vertical migration can cause their ranges to overlap. However, few have looked at intraspecific changes.MethodsHere we investigate intraspecific variation for four species of demersal fish that inhabit a broad range of depths (200 m to over 2000 m). We test the hypothesis that intraspecific morphological variation will be similar to that seen among species.ResultsWe find that there are significant phenotypic differences between fish taken at different habitat depths, especially associated with mouth gape size, eye size, body shape and organ mass, despite the potential for vertical migration. However, we find that these patterns vary among species.DiscussionWe consider the possible drivers and implications for maintaining intraspecific phenotypic differences.
Conjunctival ultraviolet autofluorescence as a biomarker of outdoor time in myopic children
Authors: de la Puente Miriam , Bilbao-Malavé Valentina , González-Zamora Jorge , Claici Aura Ortega , Bezunartea Jaione , Gomez-Arteta Leire , Alonso Elena , Hernández María , Fernández-Robredo Patricia , de Viteri Manuel Sáenz , Calvo Nerea Martín , García-Layana Alfredo , Barrio-Barrio Jesús , Recalde Sergio 
Published: December 2024

IntroductionThe prevalence of myopia has increased significantly in recent years including an earlier onset of myopia development on the pediatric population. The main objective of the study is to compare CUVAF (Conjunctival Ultraviolet Autofluorescence) in children with and without myopia to validate its usefulness as an outdoor protective biomarker.MethodsA case–control observational study was conducted in a child cohort from subjects that attended to the Ophthalmology Department of Clínica Universidad de Navarra for an ophthalmological examination. The general exclusion criteria were (among others): amblyopia, congenital myopia, general ophthalmic disease, and any conjunctival alteration that might difficult the measurement of the CUVAF area. All participants underwent an automatic objective refraction under cycloplegic effect, biometry to measure axial length (AL) and central corneal radius (CCR), and completed a questionnaire about their lifestyle habits. A total of 4 images of the bulbar conjunctiva were taken with blue light in order to quantify the CUVAF area.ResultsA total of 263 subjects (6 to 17 years old) were analyzed with no significant differences in demographic data between case group and control group. There were 50 non-myopic subjects (19%) and 213 myopic subjects (81%). In relation to the outdoor activities (OA), myopic subjects spent significantly fewer hours per week outdoors than the control-group (p = 0.03). About the CUVAF area, the differences between groups were statistically significant, showing that the myopic group has a significantly smaller CUVAF area than the control-group (0.33 ± 0.72 mm2 vs. 0.78 ± 1.22 mm2; p = 0.0023), likewise, the frequency of CUVAF area absence between both groups showed an odds ratio (OR) of 2.52 (CI95% 1.33–4.74). A Pearson correlation test was done, obtaining a strong significant inverse correlation between myopia degree-CUVAF area (r = 0.1877; IC95% 0.068–0.302), and also ratio (AL/CCR)-CUVAF area (p = 0.002 and p = 0.04) respectively.ConclusionCUVAF is a useful biomarker for OA and it has an inverse relationship with myopia degree also in pediatric age, especially after the age of 12, so it could be useful to differentiate the risk of developing myopia. Having a CUVAF area greater than that corresponding to age, protect to myopia 2.5 times, being almost 5 times the protection in case of high myopia.
High activity and specificity of bacteriophage cocktails against carbapenem-resistant Klebsiella pneumoniae belonging to the high-risk clones CG258 and ST307
Authors: Tellez-Carrasquilla Sara , Salazar-Ospina Lorena , Jiménez J. Natalia 
Published: December 2024

IntroductionThe widespread clinical and environmental dissemination of successful clones of carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a serious global public health threat. In this context, lytic bacteriophages have emerged as a promising alternative for controlling these pathogens. This study describes the biological, structural, and genomic characteristics of lytic bacteriophages against the high-risk CRKP clones CG258 and ST307 and describes their performance in combination.MethodsAn experimental study was carried out. Bacteriophages were isolated from hospital wastewater and from wastewater treatment plants (WWTP). Bacteriophages were isolated using the double layer agar technique and their characterization included host range (individual and cocktail), plating efficiency (EOP), infection or bacterial killing curve, one-step curve, bacteriophage stability at pH and temperature conditions, transmission electron microscopy (TEM) and whole genome sequencing.ResultsAfter purification, five active bacteriophages against CRKP were obtained, three bacteriophages (FKP3, FKP4 and FKP14) had targeted activities against CG258 CRKP and two (FKP10 and FKP12) against ST307 isolates. Seven cocktails were prepared, of which Cocktail 2, made up of the bacteriophages FKP3, FKP10, and FKP14, showed the best activity against 85.7% (n = 36/42) of CRKP isolates belonging to both clones, CG258 (80.8%; n = 21/26) and ST307 (93.8%, n = 15/16). The efficiency of the plating (EOP), infection curve, and one-step growth curve showed that the cocktail phages efficiently infected other CRKP isolates (EOP ≥ 0.5), controlled bacterial growth up to 73.5%, and had short latency periods, respectively, (5–10 min). In addition, they were stable at temperatures between 4°C and 50°C and pH between 4 and 10. All bacteriophages belonged to the Caudoviricetes class, and no genes associated with virulence factors or antibiotic resistance were detected.ConclusionThese findings showed bacteriophages and phage cocktails with high specificity against CRKP belonging to the successful clones CG258 and ST307 with promising characteristics, making them an alternative for controlling these clones in different environmental or health settings, biocontrol agents, or disinfectants in industry and in the field of diagnosis.
Efficacy and safety of hypomethylating agents in the treatment of AML/MDS patients relapsed post allogenetic hematopoietic stem cell transplantation
Authors: Wang Yaxin , Wang Qingyun , Ren Hanyun , Dong Yujun , Wang Qingya , Liang Zeyin , Yin Yue , Liu Wei , Xu Weilin , Han Na , Li Yuan 
Published: December 2024

IntroductionAcute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) constitute myeloid malignancies, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a potentially optimal approach for achieving a long term cure. However, post-allo-HSCT relapse remains a leading cause of mortality and therapeutic failure.MethodsTo evaluate the efficacy and safety of combining hypomethylating agents (HMAs) with Bcl-2 inhibitors in the treatment of AML/MDS relapse following allo-HSCT, we retrospectively collected data from 42 patients who experienced relapse between April 2012 and March 2022 at Peking University First Hospital. Among these patients, 21 underwent intensive chemotherapy (IC) alone, while the other 21 received treatment with HMAs after IC treatment, either alone or in combination with the Bcl-2 inhibitor venetoclax (VEN).ResultsThe median overall survival (OS) was 9 ± 2.153 months, and the one-year OS rate was 41.5%. The overall response rate (ORR) in the chemotherapy group and the IC+HMAs ± VEN group was 52.38% (11/21) and 76.19% (16/21), respectively, with no significant difference found (P=0.107). Kaplan-Meier analysis revealed a significant difference in OS between the chemotherapy group and the IC+HMAs ± VEN group in our retrospective cohort study (P=0.041, χ2= 4.016). Additionally, a significant difference in overall survival (OS) rates was observed between the two groups for patients categorized as intermediate/high risk (P=0.008). The secondary relapse rate was 45.45% (5/11) in the IC cohort and 25% (4/16) in the IC+HMAs ± VEN group, respectively, with no significant difference identified between the two cohorts (P=0.268). Furthermore, upon assessing the risk of graft-versus-host disease (GvHD), infection, and agranulocytosis, no notable differences were observed with the use of HMAs, suggesting that HMAs did not increase the risk. In the IC+HMAs ± VEN group, 7 patients received VEN in addition to HMAs, and no significant statistical difference was found in OS when comparing patients who received HMAs alone and those who received HMA+VEN (P=0.183), also, a statistically significant difference in OS was noted between the two groups whenaccounting for competing risks (P=0.028).ConclusionsThis retrospective study highlights the efficacy of IC+HMAs ± VEN in treating AML/MDS patients experiencing relapse post allo-HSCT, improving survival rates, especially for those classified as intermediate/high risk, with favorable tolerability.
Comprehensive analysis of IRF8-related genes and immune characteristics in lupus nephritis
Authors: Yu Zhibin , Zheng Chenghui , Wang Yilun 
Published: December 2024

BackgroundThere are currently no reliable diagnostic biomarkers or treatments for lupus nephritis (LN), a complication of systemic lupus erythematosus. Objective: We aimed to explore gene networks and potential biomarkers for LN by analyzing the GSE32591 and GSE113342 datasets from the Gene Expression Omnibus database, focusing on IRF8 and IRF8-related genes.MethodsWe used differential expression analysis, functional enrichment, protein-protein interaction (PPI) network construction, and the CIBERSORT algorithm for immune infiltration assessment. To validate the expression levels of the IRF8 gene in the kidneys of lupus mice models, we used quantitative real-time PCR (qRT-PCR) and Western blotting (WB). A diagnostic classifier was built using the RandomForest method to evaluate the diagnostic potential of selected key genes. To bridge our findings with potential therapeutic implications, we used the drug-gene interaction database to predict drugs targeting the identified genes.ResultsTwenty co-differentially expressed genes (DEGs) were identified, with IRF8 exhibiting significant expression differences and potential as a biomarker. Functional enrichment analysis revealed pathways associated with immune response. Validation through qRT-PCR and WB confirmed that the IRF8 gene and its protein exhibited elevated expression levels in the kidneys of lupus mice compared to control groups. The diagnostic classifier revealed impressive accuracy in differentiating LN from control samples, achieving a notable area under the curve values across various datasets. Additionally, immune infiltration analysis indicated significant differences in the immune cell profiles between the LN and control groups.ConclusionIRF8 and its related genes show promise as biomarkers and therapeutic targets for LN. These findings contribute to a deeper understanding of the molecular mechanisms involved in LN and may support the development of precision medicine strategies for improved patient outcomes.
Quercetin alleviates ulcerative colitis through inhibiting CXCL8-CXCR1/2 axis: a network and transcriptome analysis
Authors: Jiang Zhangyu , Yan Mingjuan , Qin Yanmi , Liu Zhenglin , Duan Yilin , Wang Yingju , Zhang Ruisen , Lin Wenjia , Li Yanwu , Xie Tian , Ke Junyu 
Published: December 2024

IntroductionUlcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract in which mucosal healing is a crucial measure of therapeutic efficacy. Quercetin, a flavonoid prevalent in various foods and traditional Chinese medicines, exhibits notable pharmacological properties, including antioxidant and anti-inflammatory activities. Consequently, it warrants investigation to determine its potential therapeutic effects on UC. The objective of this study was to investigate the effects and underlying mechanisms of quercetin in a murine model of UC.MethodsA comprehensive approach integrating network predictions with transcriptomic analyses was employed to identify the potential targets and enriched pathways associated with quercetin in UC. Subsequently, the effects of quercetin on pathological morphology, inflammatory mediators, and mucosal barrier-associated proteins, as well as the identified potential targets and enriched pathways, were systematically investigated in a murine model of dextran sulfate sodium (DSS)-induced UC.ResultsNetwork analyses identified CXCL8 and its receptors, CXCR1 and CXCR2, as primary target genes for therapeutic intervention in UC. Further validation through transcriptomic analysis and immunofluorescence staining demonstrated significant upregulation of the CXCL8-CXCR1/2 axis in the intestinal tissues of patients with UC. Experimental investigations in animal models have shown that quercetin markedly alleviates DSS-induced symptoms in mice. This effect includes the restoration of colonic crypt architecture, normalization of goblet cell structure and density, reduction of inflammatory cell infiltration, and decreased concentrations of inflammatory mediators. Quercetin enhanced the expression of tight junction (TJ) proteins, including ZO-1, MUC2 (Mucin 2), and occludin, thereby preserving the integrity of the intestinal mucosal barrier. Additionally, it significantly diminished the levels of IL-17A, NF-κB, CXCL8, CXCR1, and CXCR2 in the colonic tissues of mice with UC.DiscussionThe ameliorative effects of quercetin on colon tissue damage in DSS-induced UC mice were significant, possibly due to its ability to inhibit the CXCL8-CXCR1/2 signaling axis. These findings provide a solid foundation for the clinical application and pharmaceutical advancement of quercetin.
A prospective, self-controlled study of sub-plateau heart rate variability in healthy adults
Authors: Ye Xianglin , Liu Hao , Yang Haixia , Zhang Hongyang , Gong Meiting , Duan Zhen , Fu Yan , Xiong Shiqiang , Dan Xiaoping , Pei Haifeng 
Published: December 2024

BackgroundThe low-pressure, hypoxic environment characteristic of high-altitude regions significantly affects the cardiovascular and autonomic nervous system functions of individuals, consequently impairing their sleep quality. Heart rate variability, a non-invasive indicator of autonomic nervous system activity and balance within the cardiovascular system, has not been thoroughly investigated in terms of its patterns during acclimatization and de-acclimatization phases for individuals traveling to and residing in high-altitude areas and its relationship with sleep stability.MethodsData was collected from 22 medical staff members who traveled from Chengdu to Yecheng, with measurements taken before leaving Chengdu, 1 week in Yecheng, 3 months in Yecheng, and 1 week after returning to Chengdu. The study analyzed changes in heart rate variability during acclimatization and de-acclimatization at 1,400 m above sea level. It also examined arrhythmia and sleep disorders based on circadian groups.Results1. Following 1 week of acclimatization to the sub-plateau environment of Yecheng, significant decreases were observed in SDANN, SDNN and SD2 indices compared to departure from Chengdu (P &lt; 0.05). After 3 months of sub-plateau acclimatization, these indices significantly increased (P &lt; 0.05). Upon returning to Chengdu and undergoing de-acclimatization for 1 week, these indices further significantly increased (P &lt; 0.05). 2. During the period of sub-plateau acclimatization and de-acclimatization, significant changes were noted in average heart rate and minimum heart rate (P &lt; 0.05), with the average heart rate showing a continuous decrease and the minimum heart rate exhibiting an initial increase followed by a decrease. No significant changes were observed in maximum heart rate or the incidence of arrhythmias (P &gt; 0.05). 3. When stratified by day and night, the trends for SDANN, RMSSD, and TP were consistent with the overall trend at night (P &lt; 0.05), but opposite during the day (P &lt; 0.05). 4. During the sub-plateau acclimatization period, stable sleep duration was significantly reduced, and increased markedly after de-acclimatization, although it did not return to pre-acclimatization levels (P &lt; 0.05).ConclusionAcclimatization to the sub-plateau environment of Yecheng affects the autonomic nervous system, heart rate, and sleep in healthy adults. De-acclimatization can ameliorate these effects. Furthermore, the impact of sub-plateau acclimatization on the autonomic nervous system exhibits a distinct circadian rhythmicity.
Alinéa suicide postvention program: a codesigned early proactive intervention for survivors
Authors: Coquelin Mélanie , Kopp-Bigault Céline , Barinoil Canelle , Berrouiguet Sofian , Guarnaccia Cinzia 
Published: December 2024

BackgroundBereavement following suicide is a risk factor for major depression, post-traumatic stress disorder, suicidal behavior, the emergence of bipolar disorders and prolonged mourning. The scientific literature agrees on the need to deploy support services tailored to the specificities of post-suicide bereavement. Alinéa responds to these specificities with an early and proactive individual postvention program.MethodThis article presents the process of co-designing Alinéa by involving participants who have been exposed to suicide either through the loss of a loved one or in the course of their work. This co-design led to the creation of a collaborative system for early, proactive professional intervention. The Alinéa program, design intervention objectives and protocol, are presented in this article.DiscussionThe Alinéa system is committed to research and is developing different types of research: evaluative research, fundamental research and action research.
The use of combined cognitive training and non-invasive brain stimulation to modulate impulsivity in adult populations: a systematic review and meta-analysis of existing studies
Authors: Khalifa Najat R. , Alabdulhadi Yousef , Vazquez Pilar , Wun Charlotte , Zhang Peng 
Published: December 2024

IntroductionImpulsivity, a tendency to act rashly and without forethought, is a core feature of many mental disorders that has been implicated in suicidality and offending behaviours. While research supports the use of non-invasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS), to modulate brain functions, no studies specifically reviewed the use of combined cognitive training and NIBS to modulate impulsivity.MethodsWe aimed to conduct a systematic review and meta-analysis to synthesise the literature on the use of combined cognitive training and NIBS to modulate impulsivity and its subdomains (motor, delay discounting, reflection). We searched Scopus, PsychInfo, Medline, and Cinahl electronic databases, dissertations database, and Google scholar up to September 2024.ResultsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, four randomised controlled studies involving the use of combined cognitive training and tDCS in 127 subjects were included in the study. These studies included subjects with substance use disorders, obesity, and Parkinson’s disease. Meta-analysis showed that combined cognitive training and tDCS had no statistically significant effects on motor impulsivity as measured using reaction times on the Stop Signal Task and Go/No Go tasks. One study that measured impulsiveness scores on a delay discounting task also showed no significant results. No studies measured reflection or cognitive impulsivity.DiscussionThere is a dearth of literature on the use of combined cognitive training and NIBS for impulsivity. This in conjunction of clinical heterogeneity across studies makes it difficult to draw definitive conclusions about the neuromodulation of impulsivity and its subdomains using combined cognitive training and NIBS. The findings of this study highlight the need to conduct more studies in the field.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD 42024511576.