bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding experiences of neglected tropical diseases of the skin: a mixed-methods study to inform intervention development in Ethiopia
Authors: Kaba Mirgissa , Hailemichael Yohannes , Alemu Abebaw Yeshambel , Cherkose Teklu , Kebebew Getachew , Kassa Fikregabrail Aberra , Ayana Galana Mamo , Nigusse Tedros , Engedawork Kibur , Begna Zenebu , Waday Abay , Mtuy Tara B , Lambert Saba , Halliday Katherine Elizabeth , Zuurmond Maria , Pullan Rachel L , Walker Stephen L , Pitt Catherine , Gadisa Endalamaw , Marks Michael , Palmer Jennifer 
Published: February 2025

BackgroundThe WHO and Ethiopia’s Ministry of Health have developed strategies to expand and integrate services for co-endemic neglected tropical diseases (NTDs) which manifest in the skin. To inform these strategies, we aimed to understand the social, economic and health system context of skin NTD care in Kalu woreda, Amhara region, Ethiopia, where cutaneous leishmaniasis (CL) and leprosy are endemic.MethodsBetween October 2020 and May 2022, we surveyed and reviewed records of 41 primary healthcare facilities and explored common disease experiences in focus group discussions (n=40) and interviews with people affected by leprosy (n=37) and CL (n=33), health workers (n=23), kebele authorities and opinion leaders (n=33) and traditional healers (n=7). Opportunities for integrated skin NTD service provision were explored through policy document review, interviews with health officials (n=25), and stakeholder meetings.ResultsAvailability of diagnostic supplies and health worker competence to provide skin care was very limited across primary healthcare facilities, particularly for CL. People with leprosy commonly sought care from healthcare facilities, while people with CL administered self-care or sought help from traditional healers. Travel and costs of care at specialised facilities outside the district inhibited timely care-seeking for both diseases. Transmission discourses shaped different understandings of who was affected by leprosy and CL and expectations of behaviour during and after treatment. Many policy actors felt that existing supply chain interventions, decentralised treatment approaches and community engagement initiatives for leprosy could also benefit CL, but others also warned against increasing care-seeking unless CL treatment could be provided on a scale commensurate with the large burden they perceived.ConclusionOur findings demonstrate significant gaps in the provision of care for skin NTDs within primary healthcare, very different health-seeking patterns for leprosy and CL, and a need to develop new models of care, especially for CL.
Hepatic and renal functions of paediatric patients with thalassaemia: a cross-sectional study from two large thalassaemia centres in Sri Lanka
Authors: Wijenayake Wasana , Thennakoon Raveen , Pathiraja Hashan , Bandara Dayananda , De Silva Roshitha , Premawardhena Anuja , Fernando Meranthi , Mettananda Sachith 
Published: February 2025

ObjectivesThalassaemia is a genetic disorder of haemoglobin synthesis characterised by life-long chronic anaemia. Although the endocrine and cardiac complications of thalassaemia are well-studied, hepatic and renal complications are understudied. This study aims to describe the hepatic and renal functions and to understand their determinants among paediatric patients with β-thalassaemia.DesignCross-sectional study.SettingTwo largest thalassaemia centres in Sri Lanka.ParticipantsAll haematologically confirmed patients with β-thalassaemia aged 1–16 years attending the study sites were recruited between 1 January and 31 March 2023. Data were collected by interviewing parents and patients, performing physical examinations and perusing clinical records.Results72 children (girls 52.8%) were recruited. The mean age was 7.3 years (SD 3.8). A majority (44 (61.1%)) had β-thalassaemia major, while 22 (30.6%) had haemoglobin E β-thalassaemia. 55 children (76.4%) were transfusion dependent. Hepatomegaly was found in 47 (65.3%), while 28 (38.9%) had elevations of both alanine and aspartate transaminases. Haemoglobin E β-thalassaemia type (OR 13.6, 95% CI 2.0 to 92, p=0.008) and high ferritin above 1000 ng/mL (OR 6.2, 95% CI 1.0 to 38, p=0.047) were independent factors associated with high transaminases. 11 (15.5%) patients had an estimated glomerular filtration rate (eGFR) below 90 mL/min. The proportion of children with low eGFR was higher in β-thalassaemia major (23.3%), transfusion-dependent (18.5%) and deferasirox treatment (18.5%) groups.ConclusionsElevation of hepatic transaminases is common among children with thalassaemia, especially among the subset of patients with haemoglobin E β-thalassaemia and those with high ferritin. Milder reductions in eGFR are noted in some patients with transfusion-dependent β-thalassaemia major.
YEARS clinical decision rule for diagnosing pulmonary embolism: a prospective diagnostic cohort follow-up study in primary care
Authors: van Maanen Rosanne , la Roi-Teeuw Hannah M , Rutten Frans H , Nierman Melchior , Klok Frederikus A , Huisman Menno V , Egbers Tuur , Blom Jeanet , Moons Karel , Geersing Geert-Jan 
Published: February 2025

ObjectivesThe Wells rule is often used in primary care to rule out pulmonary embolism (PE), but its efficiency is low as many referred patients do not have PE. In this study, we evaluated in primary care an alternative and potentially more efficient diagnostic strategy—the YEARS algorithm; a simplified three-item version of the Wells rule combined with a pretest probability adjusted D-dimer interpretation.DesignIn this comprehensive prospective diagnostic validation study, primary care patients suspected of PE were enrolled by their general practitioner. All three YEARS items were collected in addition to D-dimer results, and patients were followed for 3 months to establish the final diagnosis.SettingPrimary care in the Netherlands.Participants753 patients with suspected acute PE were included. Five patients (0.7%) were lost to follow-up.Main outcome measuresFailure rate (number of PE cases among patients classified by the algorithm as ‘PE ruled-out’) and efficiency (fraction of patients classified as ‘PE probable/further imaging needed’).ResultsPrevalence of PE was 5.5% (41/748 patients). In total, 603 patients were classified as ‘PE ruled-out’ by the YEARS algorithm (532 with zero YEARS items and a D-dimer<1000 ng/mL and 71 with≥1 positive YEARS item and a D-dimer<500 ng/mL), resulting in an efficiency of 80.6% (603/748 patients, 95% CI 77.6% to 83.4%). Of these patients, three patients had a diagnosis of non-fatal PE during 3 months follow-up, all three with zero YEARS items and D-dimer between 500 and 1000 ng/mL, resulting in an overall diagnostic failure rate of 0.50% (3/603 patients, 95% CI 0.13% to 1.57%). In the patients categorised as ‘imaging needed’ (n=145), a total of 38 (26.2%) were indeed diagnosed with PE.ConclusionsOur study suggests that acute PE can be safely ruled out in 80% of patients by the YEARS algorithm in a primary care setting, while only 20% of patients required referral to hospital care for imaging tests. In those classified as ‘imaging needed’, PE was present in about one in every four patients, demonstrating a high detection proportion.
Effect of prenatal multiple micronutrient supplementation on birth weight in Ethiopia: protocol for a pragmatic cluster-randomised trial
Authors: Marchant Tanya , Alemayehu Senait , Asfaw Elias , Daba Alemneh Kabeta , Defar Atkure , Opondo Charles , Persson Lars Ake , Schellenberg Joanna , Taye Girum , Tesfa Anene , Tessema Bedasa , Zenebe Kalkidan , Tessema Masresha 
Published: February 2025

IntroductionThis programme effectiveness study responds to the need for evidence of the effect on birth weight of switching from iron-folic acid supplementation to multiple micronutrient supplementation as part of routine antenatal care in Ethiopia. A 2019 meta-analysis reported a mean increase of 35 g in birth weight among newborns of women who took multiple micronutrient supplements in pregnancy compared with those who took iron-folic acid. Responding to that evidence, the government of Ethiopia decided to implement a 21 district pilot of the use of multiple micronutrient supplementation in routine antenatal care and requested an evaluation of implementation outcomes, including on birth weight.Methods and analysisA pragmatic, facility-based, randomised trial is being conducted in 42 districts over five regions of Ethiopia between January 2023 and December 2024. Districts have been randomised to one of the two arms, either to retain iron-folic acid supplementation as part of routine antenatal care or switch to multiple micronutrient supplementation. During the study period, the birth weights of all eligible babies born in enrolled health facilities in these 42 districts are continuously recorded alongside data on maternal receipt and use of either multiple micronutrient or iron-folic acid supplementation. We hypothesise that newborns of women resident in the 21 multiple micronutrient supplementation districts will have higher mean birth weight than newborns of women resident in the 21 iron-folic acid supplementation districts. Facility surveys involving pregnant women and healthcare workers at baseline, midline and endline contribute to a process evaluation and cost and cost-effectiveness evaluation.Ethics and disseminationThe study received ethical approval from the review boards at the Ethiopian Public Health Institute (EPHI-IRB-455-2022) and the London School of Hygiene & Tropical Medicine (LSHTM ref 28021). Results from this pragmatic trial will be used by the government of Ethiopia in assessing success of the multiple-micronutrient supplements pilot and for decision making about subsequent scale-up. Dissemination of findings will also inform global decision making, particularly in settings where a transition from iron-folic acid to multiple micronutrient supplementation is being contemplated at scale.Trial registration numberNCT05708183.
The REpeated ASSEssment of SurvivorS in intracerebral haemorrhage: protocol for a multicentre, prospective observational study
Authors: Ziai Wendy , Woo Daniel , Sansing Lauren , Hanley Daniel , Ostapkovich Noeleen , Triene Kevin , Gilkerson Lee A , Thompson Richard , Walborn Nathan , Lane Karen , McBee Nichol , Langefeld Carl D , Howard Timothy David , Vagal Achala , Flaherty Matthew L 
Published: February 2025

BackgroundThe REpeated ASSEssment of SurvivorS (REASSESS) study will conduct long-term cognitive, functional and neuropsychiatric performance assessments to determine whether evacuation of spontaneous intracerebral haemorrhage (ICH) reduces the risk of later cognitive decline in the ageing brain.Methods and analysisThis study will compare rates of cognitive decline under two treatment strategies for ICH. The first strategy is the use of minimally invasive surgery (MIS) with similar techniques as performed in (1) the Minimally Invasive Surgery plus rt-PA in the Treatment of Intracerebral haemorrhage Evacuation phase III (MISTIE III) trial, (2) the Early MiNimally-invasive Removal of IntraCerebral Haemorrhage (ENRICH) trial and (3) a single-centre cohort of consecutively treated patients with MIS. The second strategy is the current non-surgical standard of care using data from controls in MISTIE III and ENRICH and comparative data from The Ethnic/Racial Variations of ICH (ERICH) studyextended into the ERICH-Longitudinal study, which followed over 900 of ERICH cases with serial cognitive examinations. If successful, the REASSESS study could demonstrate that reduction of ICH volume is a critical target to reduce the risk of progressive cognitive decline, establish targets for residual haematoma volume reduction and determine if greater residual haematoma volume leads to a long-term inflammatory state.Ethics and disseminationApproval of this study was obtained from the Johns Hopkins University Institutional Review Board (IRB00311985). The findings of the study will be published in academic peer-reviewed journals.Trial registration numberNCT05611918; ClinicalTrials.gov; registered on 23 May 2023.
Clofarabine induces tumor cell apoptosis, GSDME-related pyroptosis, and CD8+T-cell antitumor activity via the non-canonical P53/STING pathway
Authors: Wu Jie , Liu Nian , Chen Jing , Tao Qian , Lu Can , Li Qiuqiu , Chen Xiang , Peng Cong 
Published: February 2025

BackgroundClofarabine (Clo) is a Food and Drug Administration (FDA)-approved drug for the treatment of acute lymphoblastic leukemia; however, its effects on solid tumors remain largely unknown.MethodsIn vitro and in vivo experiments have demonstrated the cytotoxic effects of Clo on melanoma and lung cancer. The molecular mechanisms of Clo-induced tumor cell death were analyzed using western blotting, ELISA, reverse transcription-PCR, immunofluorescence, co-immunoprecipitation (CO-IP), short hairpin RNA, co-culture, chromatin immunoprecipitation, and flow cytometry. Clinical data sets were used to analyze the correlation between stimulator of interferon genes (STING)-NFκB signaling and immune infiltration.ResultsIn this study, Clo significantly reduced the growth of melanoma and lung cancer cells. Furthermore, Clo treatment induced GSDME-mediated pyroptosis. Most importantly, Clo administration dramatically increased the cytotoxic activity of CD8+T cells in vitro and in vivo. Mechanistically, the administration of Clo induced the interaction of P53 with STING, which activated the non-canonical STING-NFκB pathway; consequently, NF-κB directly bound to the promoter regions of its target genes, including CCL5, CXCL10, HLAs and BAX. This resulted in apoptosis, pyroptosis, and immunogenic cell death in tumor cells by Clo. Furthermore, Clo-induced GSDME-mediated pyroptosis partly assists in activating T cell immunity via CCL5 and CXCL10. The non-canonical STING-NF-κB pathway is the crucial signaling pathway that initiates and links apoptosis, pyroptosis, and immunogenic cell death.ConclusionsOur study is the first to show that Clo, an FDA-approved drug, induces tumor cell apoptosis, GSDME-related pyroptosis, and CD8+T-cell antitumor activity via the non-canonical P53-STING-NF-κB signaling pathway, providing a novel strategy for the clinical therapy of melanoma and lung cancer.
Atrial fibrillation outcomes in patients from Asia and non-Asia countries: insights from GARFIELD-AF
Authors: Cheng Chun-Yan , Lian Tian-Yu , Zhu Xi-Jie , Virdone Saverio , Sun Kai , Camm John , Li Xian-Mei , Goto Shinya , Pieper Karen , Kayani Gloria , Fang Xian-Hong , Jing Zhi-Cheng , Kakkar Ajay K 
Published: February 2025

BackgroundDifferences in the clinical outcomes and level of risk among Asian versus non-Asian patients with atrial fibrillation (AF) have been sparsely investigated.ObjectiveTo provide a contemporary prospective comparison of outcomes for newly diagnosed patients with AF, between Asian and non-Asian regions.MethodsSix Asian countries (China, Japan, India, Singapore, South Korea and Thailand) and 29 countries outside Asia participated in the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) study. Newly diagnosed patients with AF, enrolled between 2010 and 2016, were followed up for≥2 years. The outcome studies were all-cause, cardiovascular and non-cardiovascular mortality, non-haemorrhagic stroke/systemic embolism (SE), major bleeding. The association of geographical region with clinical outcomes (event rates per 100 person-years) were estimated using multivariable Cox models.Results13 841/52 057 (26.6%) GARFIELD-AF participants were enrolled in Asia. Average age and prevalence of cardiovascular comorbidities were lower than in non-Asian countries and patients at high risk of stroke (ie, CHA2DS2-VASc≥2 excl. sex) were less frequently anticoagulated (60.1% vs 73.2%). Non-vitamin K oral anticoagulant (NOAC) was similar in both regions (∼28%), though Asian patients were more frequently underdosed. Both Asian and non-Asian patients who received NOAC at enrolment experienced lower all-cause mortality and non-haemorrhagic stroke/SE compared with patients on other treatments or none.All-cause mortality, non-cardiovascular mortality and major bleeding were less frequent in patients from Asia versus non-Asia (HR (95% CI): 0.62 (0.39 to 0.99), 0.52 (0.28 to 0.97), 0.58 (0.36 to 0.96), respectively). Associations of moderate-to-severe chronic kidney disease and vascular disease with increased risk of all-cause mortality were stronger in Asian versus non-Asian patients (interaction p values: 0.0250 and 0.0076, respectively). There was notable heterogeneity in oral anticoagulant (OAC) usage within the Asian countries.ConclusionsPatients in Asian countries had a lower risk of all-cause mortality and major bleeding compared to the rest of the world. NOAC had evident benefits for reducing mortality and stroke across populations. Further studies on sociocultural impacts on OAC outcomes are needed.Trial registration numberClinicalTrials.govNCT01090362.
BrainAgeNeXt: Advancing brain age modeling for individuals with multiple sclerosis
Authors: La Rosa Francesco , Dos Santos Silva Jonadab , Dereskewicz Emma , Invernizzi Azzurra , Cahan Noa , Galasso Julia , Garcia Nadia , Graney Robin , Levy Sarah , Verma Gaurav , Balchandani Priti , Reich Daniel S. , Horton Megan , Greenspan Hayit , Sumowski James , Bach Cuadra Merixtell , Beck Erin S. 
Published: February 2025

Abstract
Aging is associated with structural brain changes, cognitive decline, and neurodegenerative diseases. Brain age, an imaging biomarker sensitive to deviations from healthy aging, offers insights into structural aging variations and is a potential prognostic biomarker in neurodegenerative conditions. This study introduces BrainAgeNeXt, a novel convolutional neural network inspired by the MedNeXt framework, designed to predict brain age from T1-weighted magnetic resonance imaging (MRI) scans. BrainAgeNeXt was trained and validated on 11,574 MRI scans from 33 private and publicly available datasets of healthy volunteers, aged 5 to 95 years, imaged with 3T and 7T MRI. Performance was compared against three state-of-the-art brain age prediction methods. BrainAgeNeXt achieved a mean absolute error (MAE) of 2.78 ± 3.64 years, lower than the compared methods (MAE range 3.55–4.16 years). We also tested all methods across different levels of image quality, and BrainAgeNeXt performed well even with motion artifacts and less common 7T MRI data. In three longitudinal multiple sclerosis (MS) cohorts (273 individuals), brain age was, on average, 4.21 ± 6.51 years greater than chronological age. Longitudinal analysis indicated that brain age increased by 1.15 years per chronological year in individuals with MS (95% CI = [1.05, 1.26]). Moreover, in early MS, individuals with worsening disability had a higher annual increase in brain age compared to those with stable clinical assessments (1.24 vs 0.75, p &lt; 0.01). These findings suggest that brain age is a promising prognostic biomarker for MS progression and potentially a valuable endpoint for clinical trials.
Who Are Midlife Women Family Caregivers With Negative Attitudes Toward Alzheimer’s Disease and Dementia Care?
Authors: Im Eun-Ok , Yang You Lee , Chee Wonshik 
Published: February 2025

Background: Midlife women play a major role as the family caregivers of persons living with Alzheimer’s disease (PLAD). Cultural differences are frequently the major reason for the high risk faced by racial and ethnic minority family caregivers. However, little is known about the characteristics of midlife women family caregivers that are linked to their negative attitudes toward Alzheimer’s disease and dementia care. Objective: This study aimed to determine the characteristics of midlife women who were family caregivers of PLAD that were linked to their negative attitudes toward Alzheimer’s disease and dementia caregiving. Methods: A secondary data analysis was conducted using data from 172 midlife women who were family caregivers of PLAD and participated in a large cross-sectional online survey. Linear multiple regression analyses were used for the data analysis. Results: Participants’ attitude toward Alzheimer’s disease and related dementia scores were significantly associated with employment status, race/ethnicity (Hispanic), and instrumental activities of daily living. Those who were unemployed, Hispanic, and with low instrumental activities of daily living tended to have negative attitudes toward Alzheimer’s disease and dementia care. Conclusions: Additional interventions should be developed to improve attitudes toward caring for persons with Alzheimer’s disease and dementia in this specific group of midlife women who are family caregivers of PLAD.
Ethically challenging situations in eldercare: A cross-sectional study
Authors: Selander Kirsikka , Korkiakangas Eveliina , Nikunlaakso Risto , Koivisto Tiina , Laitinen Jaana 
Published: February 2025

Background Ethically challenging situations are one of the many stressors that strain eldercare employees. Aim The study aimed to examine (1) the mean levels of ethically challenging situations among eldercare employees in different Finnish eldercare service types and (2) the associations between organizational constraints and poor work-unit collaboration with ethically challenging situations. Research design Cross-sectional survey in 2020 including 4,347 Finnish eldercare employees (response rate 67%). These employees provide care and support to older adults, such as assist with daily activities and manage medical needs. Employees were classified into four categories based on the eldercare service type: home care ( n = 1,683), service housing ( n = 1,649), outpatient and ward care ( n = 650), and guidance and activity services ( n = 365). The data was analyzed with variance analysis, t-tests, and linear regression analysis. Ethical considerations The study was approved by the ethical board of the Finnish Institute of Occupational Health. Respondents’ provided informed consent for participation. Findings Analyses showed that the level of ethically challenging situations was highest in service housing, among nurses, and among practical nurses. Organizational constraints—job strain and organizational injustice—had the strongest positive association with ethically challenging situations. Poor work-unit collaboration, instead, had a minor positive association with ethically challenging situations. Conclusions Organizational constraints, especially job strain and organizational injustice, are important to identify to alleviate ethically challenging situations among eldercare workers.
Utilization of Mandibular Occlusal Plane as Vector Guidance Oral Prosthesis in Cleft Maxillary Distraction Osteogenesis: A Technical Note
Authors: Tan Fo Yew , Mohd Nor Nor Adilah Binti , Ahmad Siti Fauzza , Hariri Firdaus 
Published: February 2025

Background Conventionally, vector guidance for internal distractor placement during cleft maxillary distraction osteogenesis (DO) is done using vector guidance splint. Vector guidance splint cannot be fabricated if occlusion is not decompensated for model surgery. Solution Using mandibular occlusal plane as anatomical reference, vector guidance oral prosthesis is fabricated to guide distractor placement and vector determination, in cases where model surgery is not possible. What we do that is new Vector guidance oral prosthesis is a new prototype produced to guide maxillary DO without the need of model surgery.