bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: PD-L1-targeted high-affinity natural killer cells and IL-15 superagonist N-803-based therapy extend overall survival of advanced metastatic pancreatic cancer patients
Authors: Seery Tara , Sender Lennie , Jafari Omid , Jones Frank , Spilman Patricia , Reddy Sandeep B. , Soon-Shiong Patrick 
Published: January 2025

BackgroundMetastatic pancreatic cancer (mPC) is an aggressive form of cancer with a poor prognosis and few therapeutic options after failure of the second-line treatment. Induction of immunogenic cell death (ICD) by use of relatively low-dose chemo- or radiation therapy, enhancement of immune responses by the IL-15 superagonist N-803 (Anktiva®), and targeting of programmed death receptor ligand 1 (PD-L1)-expressing cells may offer a therapeutic approach to refractory mPC with the potential to increase overall survival (OS).MethodsFrom late 2019 to 2021, single-patient Investigational New Drug (spIND) protocols for five mPC patients were designed and approved that generally comprised combined Abraxane (nab-paclitaxel) and gemcitabine therapy with experimental therapeutics N-803, PD-L1-targeted high-affinity natural killer (PD-L1 t-haNK) cells, and aldoxorubicin, a serum albumin-binding doxorubicin prodrug. Some patients also received stereotactic body radiation therapy (SBRT), cyclophosphamide, pembrolizumab, nivolumab, and/or experimental ETBX-051 (brachyury) and/or ETBX-061 (MUC1) vaccines. Duration of spIND treatment and responses, for some patients including imaging and carbohydrate antigen 19-9 (CA19-9) levels, and OS from initial diagnosis and the start of spIND therapy were assessed.FindingsThe line/duration of spIND therapy was, for patients 1 through 5, respectively, second line/6.4 months, sixth line/3.5 months, third line/25.4 months, third line/7.4 months, and fourth line/23.2 months. OS from the commencement of spIND therapy was 13, 4.8, 26.9, 9, and 23.2 months, and OS from diagnosis was 22, 21, 42, 13, and 33 months for patients 1 through 5, respectively.ConclusionsThe OS from the initiation of spIND for all patients exceeded the reported OS for the greater-than-second-line mPC patients and, for four of five patients, second-line therapy. The OS of 13, 26.9, and 23.2 months for three patients is particularly notable. The findings here support the ongoing clinical investigations of N-803 and PD-L1 t-haNK cells in combination therapy.
Identification of a pathogenic founder variant in the WFS1 gene that causes Wolfram syndrome in the Druze population
Authors: Halabi Inbal , Tenenbaum-Rakover Yardena , Sagi-Dain Lena , Koren Ilana 
Published: January 2025

ContextWolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder caused by pathogenic variants in the WFS1 gene. It is characterized by central diabetes insipidus, juvenile-onset diabetes mellitus (DM), optic atrophy (OA), and deafness. The natural history of WS is variable, even within the same family and with the same variant.ObjectiveTo report the phenotypes of five patients of Druze origin, all carrying the same autosomal recessive pathogenic variant in the WFS1 gene.Patients &amp; methodsFive patients belonging to three core families were enrolled. Clinical, biochemical, and genetic data were retrieved retrospectively from their medical files.ResultsAll five patients carried the same previously reported homozygous WFS1 pathogenic variant: c.2649del, p.Phe884fs. In all patients, the first presentation was DM at a mean age of 5.2 years (range 4–7), diagnosed initially as type 1 DM with negative anti-pancreatic autoantibodies, and all were treated with insulin by either pump or multiple injections. All five patients had OA that appeared at a mean age of 12.3 years (range 4–30). Three had hearing loss and neurological involvement, and none had diabetes insipidus. One patient was treated with a glucagon-like peptide 1 receptor agonist with a good response.ConclusionsThis is the first report of a founder pathogenic variant in the WFS1 gene in the Druze population in Israel. Our findings imply that molecular analysis is warranted in children presenting with DM and negative pancreatic antibodies. The identified variant should be considered for genetic testing in individuals of Druze ancestry diagnosed with young-onset non-autoimmune diabetes. Early diagnosis of WS is important for therapeutic approaches, especially since novel medications are becoming available.
Challenging the curve: can ChatGPT-generated MCQs reduce grade inflation in pharmacy education
Authors: Almaghaslah Dalia 
Published: January 2025

IntroductionGrade inflation in higher education poses challenges to maintaining academic standards, particularly in pharmacy education, where assessing student competency is crucial. This study investigates the impact of AI-generated multiple-choice questions (MCQs) on exam difficulty and reliability in a pharmacy management course at a Saudi university.MethodsA quasi-experimental design compared the 2024 midterm exam, featuring ChatGPT-generated MCQs, with the 2023 exam that utilized human-generated questions. Both exams covered identical topics. Exam reliability was assessed using the Kuder-Richardson Formula 20 (KR-20), while difficulty and discrimination indices were analyzed. Statistical tests, including t-tests and chi-square tests, were conducted to compare performance metrics.ResultsThe 2024 exam demonstrated higher reliability (KR-20 = 0.83) compared to the 2023 exam (KR-20 = 0.78). The 2024 exam included a greater proportion of moderate questions (30%) and one difficult question (3.3%), whereas the 2023 exam had 93.3% easy questions. The mean student score was significantly lower in 2024 (17.75 vs. 21.53, p &lt; 0.001), and the discrimination index improved (0.35 vs. 0.25, p = 0.007), indicating enhanced differentiation between students.DiscussionThe findings suggest that AI-generated MCQs contribute to improved exam rigor and a potential reduction in grade inflation. However, careful review of AI-generated content remains essential to ensure alignment with course objectives and accuracy.ConclusionAI tools like ChatGPT offer promising opportunities to enhance assessment integrity and support fairer evaluations in pharmacy education.
The CYP4/20-HETE/GPR75 axis in the progression of metabolic dysfunction-associated steatosis liver disease (MASLD) to chronic liver disease
Authors: Hardwick James P. , Song Byoung-Joon , Rote Paul , Leahy Charles , Lee Yoon Kwang , Wolf Alexandra Rudi , Diegisser Danielle , Garcia Victor 
Published: January 2025

IntroductionMetabolic-dysfunction-associated steatosis liver disease (MASLD) is a progressive liver disease from simple steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Chronic liver diseases (CLDs) can lead to portal hypertension, which is a major cause of complications of cirrhosis. CLDs cause structural alterations across the liver through increased contents of extracellular matrix (ECM), driving dysfunction of liver sinusoidal endothelial cells (LSECs) alongside hepatic stellate cells (HSCs) and activated resident or infiltrating immune cells. Bioactive arachidonic metabolites have diverse roles in the progression of MASLD. Both secreted levels of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acid (EET) are elevated in patients with liver cirrhosis.MethodsCLD samples were evaluated for changes in free fatty acids (FFA), cholesterol, bilirubin, bile acid, reactive oxygen species (ROD), lipid peroxidation, myeloperoxidase activity and hydroxyproline levels to evaluate the degrees of liver damage and fibrosis. To address the role of the CYP4/20-HETE/GPR75 axis, we measured the amount and the synthesis of 20-HETE in patients with CLD, specifically during the progression of MASLD. Additionally, we evaluated gene expression and protein levels of GPR75, a high-affinity receptor for 20-HETE across CLD patient samples.ResultsWe observed an increase in 20-HETE levels and synthesis during the progression of MASLD. Increased synthesis of 20-HETE correlated with the expression of CYP4A11 genes but not CYP4F2. These results were confirmed by increased P4504A11 protein levels and decreased P4504F2 protein levels during the development and progression of MASLD. The gene expression and protein levels of GPR75, the major receptor for 20-HETE, increased in the progression of MASLD. Interestingly, the CYP4A11 and GPR75 mRNA levels increased in steatohepatitis but dramatically dropped in cirrhosis and then increased in patients with HCC. Also, protein levels of P4504A11 and GPR75 mirrored their mRNA levels.DiscussionThese results indicate that the CYP4A11 and subsequent GPR75 genes are coordinately regulated in the progression of MASLD and may have multiple roles, including 20-HETE activation of peroxisome proliferator-activated receptor α (PPARα) in steatosis and GPR75 in CLD through either increased cell proliferation or vasoconstriction in portal hypertension during cirrhosis. The abrupt reduction in CYP4A11 and GPR75 in patients with cirrhosis may also be due to increased 20-HETE, serving as a feedback mechanism via GPR75, leading to reduced CYP4A11 and GPR75 gene expression. This work illustrates key correlations associated with the CYP4/20-HETE/GPR75 axis and the progression of liver disease in humans.
Epidemiological characterization of congenital heart disease at different altitudes in Ecuador: a four-year retrospective study in a pediatric referral hospital
Authors: Izquierdo-Condoy Juan S. , Arias-Rodríguez Fabian D. , Díaz-Chamba Walter I. , Mena-Noroña Diego A. , Toaquiza Lizbeth Cueva , Espín-Sambache Beanjuly , Valdivieso-Andrade Emilia J. , Cangas-Isacaz Amanda , García-Cañarte Susana , Rubio-Niera Mario , Ortiz-Prado Esteban 
Published: January 2025

BackgroundCongenital heart disease (CHD) is one of the main causes of hospital admissions and infant mortality, especially in developing regions.ObjectivesThis study aims to describe the epidemiological and clinical features of CHD in pediatric patients, from one of the largest tertiary-level national referral pediatric hospitals in Ecuador.Materials and methodsAn epidemiological, retrospective cohort study was conducted among patients with CHD who were hospitalized at “Hospital Baca Ortiz” between January 2019 to December 2022 in Quito, Ecuador.ResultsA total of 1,000 pediatric patient medical records were reviewed from 2019 to 2022. Among these patients, 56.0% were female, and 65.2% resided at high altitudes (2,500–3,500 m). Most cases (71.4%) were acyanotic CHD, with patent ductus arteriosus being the most prevalent (48.7%). Among cyanotic CHD, Tetralogy of Fallot was predominant (28.1%). Mortality was observed in 5.3% of patients, with a higher rate among acyanotic CHD (p &lt; 0.001).ConclusionMost cases of CHD were of the acyanotic type, predominantly affecting female patients. Although most cases occurred in children living above 2,500 meters, no clear influence of altitude on specific types of CHD was found. While mortality related to CHD was low, the burden of disability from these conditions was significant among patients with acyanotic CHD.
Social activities and different intensities of physical activity among older adults in China: a population-based cohort study
Authors: Yang Song , Zhang Qi , Zhao Anhui , Lyu Dongye 
Published: January 2025

IntroductionPopulation aging is an inevitable consequence of demographic transition and an important issue for human society in the 21st century. Physical activity is widely recognized as a critical factor for improving health, yet the specific impact of different intensities of physical activity on the health of older adults remains underexplored.MethodsThis study addresses this gap by analyzing data from the China Health and Retirement Longitudinal Survey (CHARLS), a nationally representative survey of a cohort of Chinese people (aged ≥45 years) from 150 counties or districts and 450 villages or urban communities across 28 provinces, who were selected by use of multistage stratified probability-proportionate-to-size sampling. The study employed a regression model aiming to analyse the effect of different intensities of physical activity on the health level of the elder adults.ResultsThe results demonstrate that physical activity at all intensity levels—high, moderate, and low—significantly improves the health of older adults, with correlation coefficients of −0.245 (p &lt; 0.01), −0.080 (p &lt; 0.05), and −0.077 (p &lt; 0.10), respectively. Among these, high-intensity physical activity is the most effective in enhancing health outcomes. The result further identifies social activities as a mediating factor in this relationship. Moreover, high-intensity exercise proves to be more beneficial for older adults residing in rural areas compared to their urban counterparts.DiscussionThis study demonstrates that engagement in physical activity at all intensity levels—high, moderate, and low—substantially enhances the health of older adults, with high-intensity physical activity demonstrating the most significant impact on health outcomes. Furthermore, the research identifies social activities as a mediating factor in this relationship, highlighting the importance of social engagement in conjunction with physical activity. This suggests that interventions promoting both physical activity and social interaction can be particularly effective in improving the health and wellbeing of the ageing population.
Associations of Pretransplant Patient-Reported Outcomes Measurement Information System Physical Function Score With Kidney Transplant Outcomes
Authors: Yamauchi Junji , Cizik Amy M. , Fornadi Katalin , Thomas Dominik , Raghavan Divya , Jweehan Duha , Oygen Suayp , Marineci Silviana , Buff Michelle , Selim Motaz , Zimmerman Michael , Mucsi Istvan , Molnar Miklos Z. 
Published: January 2025

Simple and validated physical function measures are needed for kidney transplant candidates because pretransplant low physical function is a common and potentially modifiable risk factor. This single-center retrospective study investigated the associations between pretransplant physical function assessed by the Patient-Reported Outcomes Measurement Information System® Physical Function (PROMIS-PF) computer adaptive testing and early posttransplant outcomes. We analyzed 154 adult kidney-alone transplant recipients. The median pretransplant PROMIS-PF score was 43 (interquartile range, 39–47). Patient characteristics were not significantly different across the score category (normal, score ≥45; mild, score of 40–45; and moderate/severe, score &lt;40). The PROMIS-PF score was not associated with length of transplant hospital stay, delayed graft function, 6-month and 12-month graft function, or 12-month patient and graft survival. However, a lower PROMIS-PF score was significantly associated with a higher risk of emergency room visits [adjusted odds ratios compared to normal: mild, 1.68 (95% confidence interval, 0.76–3.83); moderate/severe, 3.23 (1.34–7.79)] and rehospitalization [adjusted odds ratios: mild, 2.61 (1.16–5.90); moderate/severe, 2.53 (1.07–6.00)] within 1 month posttransplant. Results suggest that PROMIS-PF is a practical tool for assessing physical function in kidney transplant candidates. Larger studies are needed to confirm the utility of PROMIS-PF to identify transplant candidates who would benefit from pretransplant prehabilitation.
Resequencing Composite Kazakh Whiteheaded Cattle: Insights into Ancestral Breed Contributions, Selection Signatures, and Candidate Genetic Variants
Authors: Khamzina Aigerim K. , Igoshin Alexander V. , Muslimova Zhadyra U. , Turgumbekov Asset A. , Khussainov Damir M. , Yudin Nikolay S. , Ussenbekov Yessengali S. , Larkin Denis M. 
Published: January 2025

This study investigates the genetic architecture of the Kazakh Whiteheaded (KWH) cattle, applying population genetics approaches to resequenced genomes. FST analysis of 66 cattle breeds identified breeds for admixture analysis. At K = 19, the composite KWH breed showed contributions from Hereford, Altai, and Kalmyk cattle. Principal component analysis and ancestry inference confirmed these patterns, with KWH genomes comprising 45% Hereford, 30% Altai, and 25% Kalmyk ancestries. Haplotype analysis revealed 73 regions under putative selection in KWH, some shared with Hereford (e.g., with the gene DCUN1D4) and some KWH-specific (e.g., with the gene SCMH1). FST analysis identified 105 putative intervals under selection, with key genes (KITLG, SLC9C1, and SCMH1) involved in coat colour and physiological adaptations. Functional enrichment using The Database for Annotation, Visualization, and Integrated Discovery (DAVID) in selected regions highlighted clusters associated with developmental processes, ubiquitination, and fatty acid metabolism. Point FST identified 42 missense variants in genes enriched in functions related to economically important traits. Local ancestry inference revealed genomic intervals with predominantly non-Hereford ancestry, including high Altai (e.g., SCAPER) and Kalmyk (e.g., SRD5A2) contributions, while Hereford-dominated regions included genes ENO1 and RERE. This work elucidates the genomic contributions and adaptive signatures of selection shaping the KWH breed, providing candidate genetic variants for breeding program improvement and enhanced genome predictions.
Lifestyle interventions for depression in primary care: a qualitative study
Authors: Panjer Jolien Alissa , Alma Manna Albertina , Fokkema Tryntsje , Hendriks Tom , Cath Daniëlle , Kik Jolien , Burger Huibert , Berger Marjolein 
Published: January 2025

BackgroundIn individuals with depression a vicious circle tends to occur in which depressive symptoms cause an unhealthy lifestyle, which reversibly causes an increase in depressive symptoms; both of which are associated with a decreased life expectancy. A potential way to break this circle entails a multicomponent lifestyle intervention (MLI).AimExploring the barriers and facilitators for an MLI in patients with depressive symptoms from the perspective of general practitioners (GP), chronic disease practice nurses (CD-PN), mental health nurses (MHN), lifestyle coaches (LC) and patients (PT).Design & settingQualitative study using semi-structured interviews in Dutch primary care.MethodsWe interviewed 5 GPs, 6 MHNs, 5 CD-PNs, 5 LCs and 7 PTs. Focus was on possible barriers and facilitators for an MLI. Data were analyzed using thematic analysis. A focus group was used as a member check.ResultsFive themes were identified: ‘expectations of effectiveness, ‘motivation’, ‘stigma’, ‘logistics and organization’ and ‘communication by professionals’.ConclusionIdeas on effectiveness were crucial and could be either a facilitator or a barrier for a DT-MLI. Professionals often had high expectations, based on work experience, making this a facilitator. Other facilitators are motivating participants, good logistics and good communication by professionals, thus destigmatizing depression. Patients considered being motivated by the program as a reason for participating, as they did not expect a DT-MLI would give them new information. Support from others was considered a motivator to participate.
Hommes et femmes dans les prisons de la RDA
Authors: Aurenche-Beau Emmanuelle 
Published: January 2025

Ma contribution s’intéresse aux récits d’enfermement publiés par des citoyen.ne.s de l’ex-RDA condamné.e.s à des peines de prison pour raisons politiques. Elle est centrée sur l’observation d’éventuelles différences entre ceux rédigés par des hommes et ceux rédigés par des femmes et se fonde principalement sur deux textes, celui de Birgit Schlicke et celui de Bernd Pieper qui, s’ils présentent certains points communs (structuration globale selon le schéma arrestation-enfermement – libération ; thèmes abordés – espaces et temps de l’enfermement, relations avec les autres détenu.e.s, avec les interrogateur.trice.s, avec les gardien.ne.s…), n’en permettent pas moins de mettre en évidence des différences dans la manière de rendre compte de l’expérience de l’enfermement (expression des sentiments, place accordée au corps, style plus personnel et plus concret/style plus factuel et plus abstrait).
ОРИЕНТИРЫ ИНВЕСТИЦИОННОГО РАЗВИТИЯ СЕЛЬСКОГО ХОЗЯЙСТВА РЕГИОНА
Authors: Алексеева Наталья Анатольевна , Рыжкова Ольга Игоревна , Пименова Надежда Борисовна 
Published: January 2025

Активная инвестиционная деятельность в регионах является главным условием достижения стратегических целей национального развития России до 2030 г. и на более отдаленную перспективу. Сложные условия реализации инвестиций дополняются проблемами, касающимися разбалансированности параметров экономического развития в документах стратегического планирования федерального, регионального и отраслевого уровней, чего нельзя допускать. Проанализированы основные механизмы стимулирования инвестиций на региональном уровне в соответствии с целями развития, поставленными на национальном уровне. В статье рассмотрены основные методические подходы различных исследователей к анализу тенденций и сложившегося уровня развития инвестиций в России и в регионах. В соответствии с имеющимися подходами, проведена оценка уровня развития инвестиционной деятельности в сфере АПК в Удмуртии за 2014-2022 гг. В ходе апробации методик выявлено, что не все негативные тенденции, сложившиеся в инвестиционной сфере в России, нашли отражение в экономике региона. По многим параметрам развития инвестиций Удмуртская Республика может стать образцом современного развития инвестиционной деятельности в регионах: доле сельского хозяйства в структуре валового продукта, финансовому оздоровлению предприятий, динамике налоговых поступлений относительно объема полученных субсидий.
Active investment activity in the regions is the main condition for achieving the strategic goals of Russia's national development until 2030 and beyond. The complex conditions for the implementation of investments are complemented by problems related to the imbalance of economic development parameters in the strategic planning documents of the federal, regional and sectoral levels, which should not be allowed. The main mechanisms for stimulating investment at the regional level in accordance with the development goals set at the national level were analyzed. The article discusses the main methodological approaches of various researchers to the analysis of trends and the current level of investment development in Russia and in the regions. In accordance with the existing approaches, the level of development of investment activities in the agro-industrial complex in Udmurtia for 2014-2022 was assessed. During the testing of the methods, it was revealed that not all negative trends in the investment sector in Russia were reflected in the region's economy. According to many parameters of investment development, the Udmurt Republic can become a model of modern development of investment activities in the regions: the share of agriculture in the structure of the gross product, financial recovery of enterprises, the dynamics of tax revenues relative to the amount of subsidies received.