bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mortality of Adults With Sickle Cell Disease at a Comprehensive Sickle Cell Center
Authors: Afranie‐Sakyi Jennifer A. , Randall Eldrida , Fasano Ross , McLemore Morgan L. , El Rassi Fuad 
Published: January 2025

ABSTRACTIntroductionSickle cell disease (SCD) is the most common hemoglobinopathy in North America. The life expectancy of SCD has extended into adulthood with screenings, preventative care, and hydroxyurea. However, comorbidities arise as adults with SCD age, leading to early mortality.MethodsWe conducted a retrospective chart review of the Georgia Comprehensive Sickle Cell Center at Grady Health System, analyzing records of deceased SCD patients from 2013 to 2020.ResultsAmongst the 72 patients analysed, majority had severe complications from SCD and at least 1 cardiovascular comorbidity. The median age of death was 44 (STD = 15.5) for all genotypes with the median age of death at 39 (STD = 14.26) for SS and Sβ0 genotypes (n = 51). There was no difference in the median age of death for patients who maintained regular clinic visits (a visit in the last 6 months prior to death) compared to those who did not. Despite hydroxyurea's known benefits in reducing SCD morbidity and mortality, less than 50% of patients had a prescription.ConclusionAs new therapies are approved, their impact on SCD‐related morbidity and mortality must be evaluated. Improving access to, and education about, disease‐modifying therapies like hydroxyurea for both patients and clinicians is essential to improving outcomes.
The EU interinstitutional body for ethical standards: A legal and policy analysis
Authors: Alemanno Alberto 
Published: January 2025

AbstractAmid several high‐profile ethical scandals, the EU has been discussing since the early 2000s the establishment of a dedicated EU ethics authority capable of restoring trust in its institutions. This article provides one of the first assessments of the newly adopted EU Interinstitutional Body for Ethical Standards by examining whether and how it can contribute to strengthening the existing EU public integrity system. After tracing its genesis and evolution, it first identifies the major structural limitations of the extant EU ethical framework, ranging from its high fragmentation across EU institutions, weak enforcement of its underlying standards to its limited awareness within both the EU institutional setting and wider public. Second, it assesses whether the newly adopted EU ethical body may address and overcome those structural limitations and how it may do so. It concludes that, despite its limited investigative and sanctioning powers, the first dedicated Interinstitutional Body for Ethical Standards carries the potential to mark a qualitative difference in the development of the EU public integrity system as we know it. Through a combination of its standard‐setting, advisory and awareness‐raising functions, the Body may profoundly alter both the ethical standards and their enforcement for participating institutions' members and beyond.
Soft palate angle and basihyoid depth increase with tongue size and with body condition score in horses
Authors: Talbot Alison M. , Shanks‐Boon Hannah , Baldwin Christopher M. , Barnes Harriet , Maddox Thomas W. 
Published: January 2025

AbstractBackgroundObesity has been associated with human obstructive sleep apnoea and canine brachycephalic obstructive airway syndrome. The effect of body condition score (BCS) on structures of the oropharynx, nasopharynx and upper airway of the horse has not been investigated.ObjectivesTo investigate the effect of BCS on tongue measurements, soft palate angle and basihyoid depth in horses.Study designRetrospective, analytical, cross‐sectional.MethodsComputed tomographic (CT) images of the head of 58 horses were assessed. DICOM viewing software was used to measure head length, basihyoid‐skin depth, soft palate angle (SPA), midline tongue area, dorsoventral height (DVH) of the tongue in two locations and head angle. BCS were assigned during CT examinations. Associations between measurements were tested and following initial calculations, further associations with tongue measurements as a ratio of head length were assessed.ResultsFor initial measurements, 44 horses met the inclusion criteria. Addition of head length ratios to tongue measurements resulted in 24 of 44 horses meeting the inclusion criteria for the second set of calculations. Increased BCS led to an increased mean SPA (mean difference = 2.56; p = 0.02) and increased median basihyoid depth (mean difference = 0.246 cm; p = 0.006). Following adjustments made for the effect of head length on tongue measures, significant correlation was identified between SPA and tongue area (Spearman's r = 0.544; p = 0.007); SPA and DVH of the tongue at the level of the hard palate (Spearman's r = 0.562; p = 0.004) and SPA and DVH of the tongue at the lingual process of the basihyoid bone (Spearman's r = 0.690; p < 0.001). No significant correlation was identified between variables and sex.Main limitationsThe sample size was small and the effect of breed on measures was not studied. Measurements were acquired on a single sagittal CT plane. The investigator collecting CT measures was not blinded to BCS. All horses were sedated for the CT procedure which may have affected measures obtained.ConclusionsIncreased BCS increases SPA and basihyoid bone depth. Increases in tongue size measurements increase SPA. Results from this study warrant further investigation into the clinical significance of the effects of BCS on the upper airways of the horse.
Review of biological variation and its applications in interpretation of equine clinical pathology results
Authors: Fernandes T. , Robin Matthew , Freeman Kathleen P. 
Published: January 2025

AbstractBiological variation in laboratory results refers to physiological fluctuations that occur around a homeostatic setpoint (HSP) for various laboratory measurands. Assessment of biological variation includes determining individual variation (CVI), group variation (CVG), and analytical variation (CVA). Reference change value (RCV) is an objective tool for an evidence‐based approach to interpret data by assessing the significance of consecutive results in an individual for the diagnosis, prognosis, and monitoring of disease. The individualised reference intervals (iRI) are derived from the determination of the HSP for an individual and the RCV. Evaluation of dispersion (DI) of results around any numerical result, reference interval limit, or recommended cut‐off value can help define grey zones in clinical data interpretation. The Index of Individuality (II), which compares the amount of biological variation in a group (CVG) relative to the amount of biological variation in an individual (CVI), is useful to determine if 95% population‐based or iRI would be more valuable to detect a significant change in a measurand. The critical number of specimens provides confidence in a defined probability needed for the estimation of the HSP for laboratory measurands. Biological variation data may help support or disprove empirically derived or consensus‐derived interpretation recommendations. Biological variation data has the potential to improve the diagnostic accuracy of clinical laboratory testing. Examples of these applications are included.
Knockdown of RFC3 enhances the sensitivity of colon cancer cells to oxaliplatin by inducing ferroptosis
Authors: Wu Youyi , Chen Tingting , Wu Songsong , Huang Yiwei , Li Fuyao 
Published: January 2025

AbstractBackgroundThe development of resistance to oxaliplatin is a multifaceted process, often involving modifications in drug transport, DNA repair mechanisms, and the ability of cells to evade drug‐induced apoptosis.ObjectiveTo evaluate whether knocking down RFC3 promotes the sensitivity of colorectal cancer (CRC) cells to oxaliplatin, potentially offering a new approach to combat drug resistance.MethodssiRNA‐mediated knockdown of RFC3 was employed in colorectal cancer cell lines to assess the impact on oxaliplatin responsiveness. Cell viability assays, clonogenic survival assays, and flow cytometry were conducted to evaluate the effects on cell growth and apoptosis. Additionally, immunoblot analysis was used to scrutinize modifications in the expression of pivotal protein expression in the Wnt/β‐catenin/GPX4 axis.ResultsRFC3 is highly expressed in CRC tissues and associated with prognosis. Knocking down RFC3 enhances the sensitivity of CRC cells to oxaliplatin. Additionally, the reduction of RFC3 promotes the susceptibility of chemoresistant tumor cells to oxaliplatin by inducing ferroptosis. Furthermore, the knockdown of RFC3 disrupts the Wnt/β‐catenin/GPX4 axis.ConclusionDepletion of RFC3 enhances the sensitivity of CRC cells to oxaliplatin via inducing ferroptosis.
A novel naphthylchalcone ([E]‐4‐(3‐[naphthalen‐2‐yl]‐3‐oxoprop‐1‐en‐1‐yl) induces intrinsic and extrinsic apoptosis in human acute leukemia cell lines
Authors: Jacques Amanda V. , Stefanes Natália M. , Walter Laura O. , Syracuse Stephanie M. , Bigolin Alisson , Chiaradia‐Delatorre Louise D. , de Souza Luiz F. S. , de Moraes Ana C. R. , Nunes Ricardo J. , Santos‐Silva Maria C. 
Published: January 2025

AbstractBackgroundChalcones have been described in the literature as promising antineoplastic compounds.ObjectivesTherefore, the objective of this study was to analyze the cytotoxic effect of 23 synthetic chalcones on human acute leukemia (AL) cell lines (Jurkat and K562).MethodsCytotoxicity assessment was performed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) method. Cell death was evaluated using fluorescence microscopy, the DNA fragmentation technique, and the assessment of proteins involved in apoptosis by flow cytometry.ResultsThe most cytotoxic chalcone (R32) showed no cytotoxicity towards peripheral blood mononuclear cells (PBMC). It exhibited no hemolytic activity, did not alter platelet aggregation after adenosine diphosphate (ADP) and epinephrine stimulation, and did not affect blood coagulation as measured by prothrombin time (PT) and activated partial thromboplastin time (APTT). R32 demonstrated cytotoxic activity by inducing both intrinsic and extrinsic apoptosis, leading to caspase‐3 activation and DNA fragmentation. In Jurkat and K562 cells, intrinsic apoptosis was associated with changes in mitochondrial membrane potential (MMP). There was a decreased expression of Bcl‐2, increased expression of Bax, decreased expression of survivin, and increased expression of apoptosis‐inducing factor (AIF). Extrinsic apoptosis involvement was also observed in both cell lines, characterized by increased expression of the Fas receptor. Additionally, Jurkat cells exhibited decreased expression of the KI‐67 cell proliferation marker.ConclusionThese findings suggest R32 as a potential compound for the development of novel drugs for the treatment of AL.
Long‐term evaluation of rheumatoid arthritis activity with erythrocyte methotrexate‐polyglutamate 3
Authors: Escal Jean , Poudret Marion , Hodin Sophie , Neel Tiphany , Coman Irina , Locrelle Hervé , Amouzougan Adamah , Thomas Thierry , Delavenne Xavier , Marotte Hubert 
Published: January 2025

AbstractBackgroundMethotrexate (MTX) is the first‐line treatment for Rheumatoid Arthritis (RA), yet 30%–50% of RA patients develop resistance to MTX, which can manifest several years after treatment initiation.ObjectiveThis study investigates the relationship between erythrocyte methotrexate polyglutamates (MTX‐PGs) subtype concentrations and clinical disease activity in RA patients undergoing long‐term MTX treatment.MethodsIn this cross‐sectional study, patients on a stable dose of subcutaneous MTX for several years were included. The study protocol was registered in the European Medicines Agency's clinical trials register (n°2017‐004348‐39). Patients were classified as either in clinical remission (DAS28 <2.6) or having active disease (DAS28 >3.2). Erythrocyte MTX‐PGs concentrations were measured using liquid chromatography coupled with mass spectrometry. Multivariate logistic regression analysis assessed the probability of remission status based on MTX‐PG3 concentrations.ResultsThe study included 34 patients with active RA and 25 in remission. The remission group had a median MTX treatment duration of 6.4 years compared to 2.6 years for the active group (p = 0.001). Patients in remission had a longer median disease duration (p = 0.02) and a lower Body Mass Index (BMI) (p = 0.03) than those with active RA. A positive correlation was found between remission status and high MTX‐PG3 concentrations in patients with a BMI <25 kg/m2.ConclusionErythrocyte MTX‐PG3 concentrations may serve as a marker for RA activity after prolonged treatment. However, BMI could limit their utility as a biomarker.
Transitions in treatment: A systematic review and meta‐aggregation of preferences and barriers in switching from oral to long‐acting injectable antiretroviral therapy among people living with HIV and stakeholders
Authors: Hu Tiantian , Yang Shuqi , Yu Junwen , Yang Zhongfang , Jin Yilin , Zhu Zheng 
Published: January 2025

AbstractIntroductionAntiretroviral treatment (ART) has significantly enhanced health outcomes for people living with HIV (PLWH). With the evolution of treatment options, there is an increasing interest in the development of long‐acting injectable formulations of antiretroviral drugs. These formulations present a promising alternative to oral ART.MethodsThe methodology and reporting of this systematic review followed the guidance of the Joanna Briggs Institute Reviewer's Manual and Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ). The comprehensive searches involved multiple databases, including PubMed, MEDLINE (Ovid), Embase (Ovid), CINHAL (EBSCO), ProQuest Dissertations and Theses, Web of Science, Wanfang (Chinese), CNKI (Chinese), Google Scholar and Baidu Scholar (Chinese).ResultsIn all, 142 studies were identified and 20 eligible studies were included in the meta‐aggregation. A total of 141 findings, 20 categories and nine synthesized findings were extracted from 20 studies. The nine synthesized findings identified from the 20 studies focused on the following topics: benefits, flexibility and practicality of long‐acting injectable (LAI) treatment; scepticism about the use of LAI treatment; management challenges; logistical challenges; potential for protecting marginalized populations; concerns about side effects; financial issue; suggestions for improvement. PLWH's geographical distribution, backgrounds, demographics and clinical characteristics were limited.ConclusionWe recommend considering the needs and experiences of PLWH in the transition from oral ART to LAI treatment. For marginalized populations, it is crucial to maintain regular communication with healthcare providers and institutions. Additionally, at the community level, engaging diverse stakeholders with valuable insights is vital, as is enhancing health education programmes and intensifying efforts to combat discrimination. These measures will play a key role in addressing the needs of PLWH, enhancing public awareness and promoting better understanding of LAI treatment.
The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities
Authors: Kan Winnie L. , Weekley Claire M. , Nero Tracy L. , Hercus Timothy R. , Yip Kwok Ho , Tumes Damon J. , Woodcock Joanna M. , Ross David M. , Thomas Daniel , Terán David , Owczarek Catherine M. , Liu Nora W. , Martelotto Luciano G. , Polo Jose M. , Pant Harshita , Tvorogov Denis , Lopez Angel F. , Parker Michael W. 
Published: January 2025

ABSTRACTCytokines are small proteins that are critical for controlling the growth and activity of hematopoietic cells by binding to cell surface receptors and transmitting signals across membranes. The β common (βc) cytokine receptor family, consisting of the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interleukin (IL)‐3, and IL‐5 cytokine receptors, is an architype of the heterodimeric cytokine receptor systems. We now know that signaling by cytokine receptors is not always an “all or none” phenomenon. Subtle alterations of the cytokine:receptor complex can result in differential or selective signaling and underpin a variety of diseases including chronic inflammatory conditions and cancers. Structural biology techniques, such as X‐ray crystallography and cryo‐electron microscopy alongside cell biology studies, are providing detailed insights into cytokine receptor signaling. Recently, we found that the IL‐3 receptor ternary complex forms higher‐order assemblies, like those found earlier for the GM‐CSF receptor, and demonstrated that functionally distinct biological signals arise from different IL‐3 receptor oligomeric assemblies. As we enhance our understanding of the structural nuances of cytokine–receptor interactions, we foresee a new era of theranostics whereby structurally guided mechanism‐based manipulation of cytokine signaling through rational/targeted protein engineering will harness the full potential of cytokine biology for precision medicine.
Enhanced temperature stability of colossal‐permittivity Ce‐doped SrTiO3 ceramics designed by defect engineering
Authors: Zhu Mingliang , Liu Kang , Meng Yingzhi , Qiang Xuerui , Xia Xiyue , Cao Xueli , Lei Xiuyun , Wang Dawei , Liu Laijun 
Published: January 2025

AbstractCerium‐doped SrTiO3 ceramics (Sr1‐3x/2CexTiO3, x = 0, 0.005, 0.0075, 0.01, 0.0125, and 0.015) were prepared by a burying sintering process. The sample with x = 0.0075 exhibits a colossal permittivity (∼ 21,000) and ultra‐low dielectric loss (∼ 0.0073) at room temperature (at 1 kHz). Furthermore, the x = 0.0075 sample maintains high permittivity (ε′ ≥ 15,000) and low dielectric loss (tanδ ≤ 0.018) in a wide temperature range (−60°C to 250°C). X‐ray photoelectron spectroscopy and electron paramagnetic resonance indicate the coexistence of Ce3+ and Ti3+. According to equation , synergetic effects from defect dipoles and interfacial polarization are responsible for the observed high‐performance giant permittivity behaviors with pronounced temperature stability and ultralow tanδ. The dielectric behaviors under different DC biases evidence the minor contribution from the interfacial polarization and reflect the dominant contribution from defect dipoles. The dielectric properties of dielectric ceramics are mainly influenced by oxygen vacancy clusters and defect dipoles ((Ti3+ − − Ti3+) and ( − )). The excellent thermal stability of permittivity is also attributed to the pinning effect of defect dipoles from the charged defects which prohibit the long‐range movement of free carries. The obtained colossal permittivity and low dielectric loss SrTiO3‐based ceramics with high‐frequency/temperature stabilities are suitable for the application of single‐layer ceramic capacitors.
Analysis of Changes in Home‐ and Community‐Based Service Utilisation Among Chinese Older Adults: A National Cohort Study
Authors: Yu Yushan , Zheng Xiaoying , Petrovic Mirko , Zhang Wei‐Hong 
Published: January 2025

ABSTRACTAimTo explore changes in home‐ and community‐based service utilisation and its associated factors among Chinese older adults between 2016 and 2018.DesignA national cohort study.MethodsThis study included 6924 older adults from the China Longitudinal Aging Social Survey 2016 and 2018 waves, examining the changes in service utilisation among four groups: continuous users, former users, new users and nonusers. Multinomial logistic models were employed to identify the determinants of service utilisation changes, and dominance analysis was performed to compare the relative contribution of the main variables associated with utilisation changes.ResultsOverall, there was an approximate 6% increase in the utilisation of any services among the study population from 2016 to 2018. The changes in service utilisation among four groups were 6.9% as continuing users, 4.2% as former users, 10.1% as new users and 78.8% as nonusers from 2016 to 2018, respectively. Factors associated with utilisation changes, ranked from the most to the least relative contribution, included availability of services, living region, type of pension, activities and instrumental activities of daily living, personal income, age and living alone.ConclusionsDespite an increase in service utilisation, low services utilisation remains a concern. Strengthening policy support and boosting financial investments in home‐ and community‐based services to enhance availability across all regions would be an effective measure to improve service utilisation.Implications for the Profession and/or Patient CareThe study highlights the need for long‐term care professionals and policymakers to increase availability to home‐ and community‐based services, especially in underserved areas.ImpactIdentifying key factors associated with changes in service utilisation, such as service availability and living region, can guide targeted strategies to improve access and equity.Patient or Public ContributionNo patient or public contribution.Reporting MethodSTROBE statement (Table S5).
Intersectional marginalized identities as predictors of time until first reported suicide attempt among preadolescent youth using survival analysis
Authors: Mournet Annabelle M. , Kellerman John K. , Hamilton Jessica L. , Kleiman Evan M. 
Published: January 2025

BackgroundSuicide attempts and deaths among children are increasing in the United States, yet suicide in this preadolescent population remains understudied. A clearer understanding of which youth experience early onset of suicidal behavior is crucial for predicting risk and identifying youth best suited to early intervention. This paper examines how intersectional marginalized identities may predict the onset of suicidal behaviors among preadolescent youth.MethodsThe Adolescent Brain and Cognitive Development (ABCD) Study is a prospective cohort study with annual assessments of youth ages 9 and 10 and their caregivers. Lifetime suicide attempts and preparatory suicidal behaviors were assessed annually. Survival models examined overall trends and demographic differences in the onset of suicidal behaviors.ResultsThe final sample included 11,223 participants (mean age = 9.9 years old, SD = 7.5 months). 5,280 (47%) reported a minoritized racial/ethnic identity, and 1,410 (12.6%) were categorized as sexual or gender minorities. 208 suicide attempts and 143 instances of preparatory suicidal behaviors were reported across the study period. An interaction effect was found such that youth who hold multiple minoritized identities (i.e., sexual and gender minority youth from minoritized racial/ethnic backgrounds) were at elevated risk for onset of both suicide attempts (HR = 2.97, 95% CI = 1.59–5.56, p = .001) and preparatory suicidal behaviors (b = 3.09, 95% CI = 1.38–6.93, p = .006).ConclusionsIntersectional marginalized identities were associated with earlier onset of suicide attempts and preparatory suicidal behaviors. Findings suggest that early interventions for minoritized youth may be important to reduce the rapidly increasing suicide rate among preadolescent youth.