bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to luspatercept can be predicted and improves overall survival in the real‐life treatment of LR‐MDS
Authors: Consagra Angela , Lanino Luca , Al Ali Najla H. , Aguirre Luis , Xie Zhuoer , Chan Onyee , Andreossi Gloria , Raddi Marco G. , Rigodanza Luca , Sanna Alessandro , Mattiuz Giorgio , Tofacchi Elena , Amato Cristina , Tanturli Michele , De Pourcq Sven , Walker Alison , Kuykendall Andrew , Lancet Jeffrey , Padron Eric , Sallman David A. , Restuccia Francesco , Perego Alessandra , Ubezio Marta , Fattizzo Bruno , Riva Marta , Maggioni Giulia , Campagna Alessia , Della Porta Matteo G. , Santini Valeria , Komrokji Rami S. 
Published: February 2025

AbstractWe explored the impact of luspatercept therapy on overall survival (OS) and possible predictors of response in low‐risk (LR) myelodysplastic syndrome (MDS) patients. We evaluated 331 anemic patients treated with luspatercept. Hematological response (HI) was defined as (i) hemoglobin (Hb) increase of ≥1.5 g/dL in nontransfusion‐dependent (NTD) patients, and (ii) red blood cell (RBC) transfusion independence (TI) with a concomitant Hb increase of ≥1.5 g/dL, or RBC‐TI without an Hb increase of 1.5 g/dL, or >50% reduction in RBC transfusion burden (TB) for TD patients. Response was observed in 166 patients (50.2%), with significantly higher response in NTD and low TB versus high TB patients (p < 0.001). A significant correlation between lower Molecular International Prognostic Scoring System (IPSS‐M) risk scores and response was observed. No statistically significant difference in HI was found in SF3B1‐mutated versus wild‐type MDS patients (53.8% vs. 40.1%, respectively). SF3B1mut hotspots (K700E vs. others) and variant allele frequencies (VAFs; <38% VAF vs. ≥38% VAF) did not impact on HI. SF3B1‐mutated MDS with del5q showed inferior HI compared to other LR‐MDS (p = 0.046). The median treatment duration overall was 35 weeks (20.86–90.29), the median time to response was 11 weeks (8.71–21.86), and the median duration of response was 65 weeks (26.5–114). After a median follow‐up of 13 months, median OS was not reached (NR) for responders and 24 months for nonresponders (hazard ratio [HR] 0.25, 95% confidence interval 0.14–0.44, p < 0.001). This analysis of 331 luspatercept real‐life‐treated LR‐MDS patients demonstrated a significant OS benefit upon luspatercept response. Low baseline RBC‐TB and lower risk IPSS‐M scores correlated with higher HI and could constitute predictive markers of response.
Does Long‐Term Care Insurance Release the Unmet Long‐Term Care Needs and Promote Long‐Term Care Services? A Quasi‐Experimental Study in China
Authors: Zhang Liangwen , Li Sicheng , Fang Ya 
Published: February 2025

ABSTRACTObjectiveLong‐term care insurance (LTCI) is a widely adopted approach to address the growing long‐term care (LTC) needs associated with ageing. Little is known about its effect on unmet LTC needs among different LTC populations in China. This study explored the effect of LTCI pilot programs on unmet LTC needs and their pathways among different LTC need populations in China.MethodsData were derived from the China Health and Retirement Longitudinal Study 2013, 2015, and 2018. Difference‐in‐Difference methods were used to estimate the impact of LTCI on unmet LTC needs and informal LTC services. According to the degree of ADL or IADL needs, participants were categorised into broad, intermediate, and narrow LTC need populations.ResultsThe unmet LTC needs increased in both broad, intermediate, and narrow LTC need populations, while informal LTC hours received decreased for the intermediate and narrow LTC need populations. Informal LTC was identified as a mediator, contributing to increased unmet LTC needs. With LTCI coverage, heterogeneity analysis showed a direct effect, resulting in a 72.1% reduction in informal LTC hours without an increase in unmet LTC needs. Additionally, a spillover effect led to a 35.7% reduction in informal LTC hours and an average increase of 0.133 unmet needs.ConclusionsWith the inadequate formal LTC services, the LTCI implementation decreased the informal LTC provision and further increased the unmet LTC needs in almost all LTC need populations. Only for individuals with severe disabilities LTCI effectively substituted the informal LTC provided by families. The government needs to improve the quality of formal LTC services to avoid increasing unmet LTC needs.
DNA methylation and copy number alterations in the progression of HPV‐associated high‐grade vulvar intraepithelial lesion
Authors: Runello Flavia , Jary Aude , Duin Sylvia , Kim Yongsoo , van Eer Kahren , Voss Féline O. , Thuijs Nikki B. , Bleeker Maaike C. G. , Steenbergen Renske D. M. 
Published: February 2025

AbstractHuman papillomavirus (HPV)‐associated high‐grade vulvar intraepithelial lesion (HSIL) is a precursor of vulvar squamous cell carcinoma (VSCC). Because of the 8% cancer risk, many vulvar HSIL patients undergo aggressive and mutilating treatments. Characterizing HSIL by their progression risk can help individualize treatment strategies. Accordingly, copy number alterations (CNAs) and DNA methylation have been identified as biomarkers for cancer risk stratification of HSIL. Here, we assessed their potential correlation, and relation to HPV16 (sub)lineages and progression to vulvar cancer. Eighty‐two vulvar formalin‐fixed paraffin‐embedded (FFPE) samples, including controls, HSIL, HSIL adjacent to VSCC and VSCC, with previously determined DNA methylation profiles, were analysed for CNAs using mFAST‐SeqS. Genome‐wide z‐scores were calculated to determine overall aneuploidy (aneuploidy scores), and compared to the methylation levels and status of marker panel ZNF582/SST/miR124‐2. For 52 HPV16‐positive cases, HPV (sub)lineages were determined by Sanger sequencing. HPV16 lineage A was predominant (86.4%), followed equally by lineages B, C, and D. Frequent chromosomal alterations included chr1pq, chr3q, chr9q gains, and chr2q, chr4q losses. Median aneuploidy scores increased across disease categories, from 0 in controls, to 3 in HSIL, 16 in HSIL adjacent to VSCC and 29 in VSCC. A positive relationship between aneuploidy scores and DNA methylation levels was found (ρ = 0.61, Spearman's rank correlation test). Aneuploidy scores were significantly higher in methylation‐positive samples (p < .001). In conclusion, we showed that DNA methylation and CNAs both rise with increasing severity of disease, indicating their prognostic value for cancer risk stratification of HSIL, while no relation to HPV16 (sub)lineages was found.
Development of a rubric to assess pharmacy regulatory models
Authors: Vernon Veronica P. , O'Connor Shanna , Seignemartin Brandy , Shipman Allie Jo , Akers Julie M. , Adams Jennifer L. 
Published: February 2025

AbstractIntroductionLicensure of pharmacy personnel and facilities is overseen by state boards of pharmacy, which varies from state to state. Two broad approaches to the regulation of health care professions are bright line and standard of care. States in which pharmacists are able to deliver the broadest range of services to patients regulate pharmacy personnel using a standard of care regulatory model.ObjectivesThe objective of this project was to build upon the previous benchmark published in 2021, the Pharmacy Regulatory Innovation Index, which focused on pharmacy personnel, to develop and validate an expanded rubric for assessing innovation in pharmacy regulation including personnel and facilities.MethodsThe Pharmacy Regulatory Innovation Index was expanded by the study team. After an initial validation of the rubric by analyzing four of the original states, a modified Delphi process was used. The rubric categories were converted to a web‐based survey, which was sent to executive directors or members of boards of pharmacy in western states. These individuals were then invited to participate in a panel session about their perceptions of pharmacy regulations and the approaches used by their boards of pharmacy to regulate pharmacy personnel and facilities.ResultsAn initial rubric was developed using the Pharmacy Regulatory Innovation Index as a baseline. Four changes were made to the rubric based on the results of the Delphi Process and weighting was increased for two categories and decreased for two categories as a result of panel feedback.ConclusionThe completed Pharmacy Regulatory Assessment Rubric can be used as a tool to evaluate pharmacy regulatory innovation in the United States. It can also be used to support advocacy efforts.
Population Pharmacokinetics of Caffeine in Infants with Hypoxic‐Ischemic Encephalopathy: A Phase I, Dose‐Escalating Trial
Authors: Thompson Elizabeth J , Gonzalez Daniel , Dumond Julie , Hornik Christoph P , Kilborn Alison , Laughon Matthew M , Jackson Wesley M 
Published: February 2025

AbstractThe mainstay of treatment for infants with hypoxic‐ischemic encephalopathy (HIE) is cooling. Caffeine may be an important adjunct to cooling and provide neuroprotection via its anti‐inflammatory and anti‐oxidative properties. This study aimed to characterize caffeine pharmacokinetics in term infants with HIE receiving cooling.In this phase 1, dose‐escalating study, enrolled infants received IV caffeine 20 mg/kg followed by up to two daily doses of 5 or 10 mg/kg. A population pharmacokinetic analysis was performed using NONMEM (v7.5). The effects of clinical covariates, including cooling, on pharmacokinetic parameters were evaluated. Dosing simulations were performed to evaluate the percentage of plasma exposures in the reference range (15–25 mg/L).Seventeen infants were included in model development. A one‐compartment model best fit the data. Population clearance was 0.445 L/h/70 kg and volume of distribution was 87.1 L/70 kg. Current dosing regimens (20 mg/kg followed by 5 mg/kg) resulted in 89.5% of infants having at least one simulated exposure below the reference range across the dosing interval. Dosing regimens of 30 mg/kg followed by 5 or 10 mg/kg were predicted to result in more than half of infants achieving simulated exposures in the reference range, with ≤20% of infants having simulated exposures in the toxic range (>46 mg/L).Term infants with HIE had similar weight‐normalized clearance but higher weight‐normalized volume of distribution compared to prior studies in preterm infants without HIE or cooling. While exposure targets for neuroprotection in HIE are unknown, this phase 1 study suggests alternate dosing strategies should be considered in future studies.
Treatment of Myeloproliferative Neoplasms With Janus Kinase Inhibitors: A Meta‐Analysis of Cardiovascular Safety
Authors: Dunn Roberta , Long Edouard , Gagnon Laura Li , Harrison Claire , Yang Yunfan , O'Sullivan Jennifer 
Published: February 2025

ABSTRACTBackgroundJanus kinase inhibitors (JAKis) are an integral aspect of the management of myeloproliferative neoplasms (MPNs). Part of the clinical benefit derived from JAKis may be due to reductions in thrombosis, a potentially life‐threatening complication of MPNs. However, evidence has emerged of adverse cardiovascular effects secondary to JAKis. We conducted a first‐of‐a‐kind meta‐analysis of the cardiovascular safety of JAKis in the treatment of MPNs.MethodsThis study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA). Systematic searches for studies comparing JAKi treatment to a control group were conducted. Studies reporting hypertension, major adverse cardiovascular events (MACE) and thromboembolic events were included in a meta‐analysis using a random‐effects model for the primary analysis, and fixed‐effects model for any subgroup analyses performed.ResultsA total of 23 publications, consisting of nine clinical trials and one retrospective analysis, met the inclusion criteria. This resulted in a pooled population of 2198 patients (JAKi n = 1145, Control n = 1053). In studies reporting thromboembolic events (n = 9), pooled analysis revealed a significantly lower rate of thromboembolic events in the JAKi group (incidence rate ratio (IRR): 0.52, 95% CI: 0.28–0.98, p = 0.04). This was primarily driven by ruxolitinib studies in myelofibrosis (MF) and polycythemia vera (PV) as when a subgroup analysis of these trials was performed (n = 7), an even more significant reduction in thromboembolic events with JAKi treatment was found (IRR: 0.41, 95%CI: 0.26–0.64, p < 0.001). There was no significant difference in MACE or hypertension between JAKi and control groups.ConclusionThis meta‐analysis suggests that JAKi treatment of MPN was associated with a reduced risk of thromboembolic events; primarily driven by studies of ruxolitinib in PV and MF. Further prospective clinical trials are warranted to confirm these findings and characterise the cardiovascular profile of other JAKis and other types of MPNs.
Hodgkin Lymphoma Treatment With Brentuximab Vedotin in a Patient With HIV, Liver Failure, and Anemia Without Transfusion
Authors: Marin Ellen , Abousaud Aseala , Davis Kathleen , Sumrall Bradley , Li Shiyong , Langston Amelia A. , Chang Andres 
Published: February 2025

ABSTRACTBrentuximab vedotin (BV) is a drug that has improved outcomes in classical Hodgkin lymphoma (cHL). However, its safety and efficacy in patients living with HIV who present with severe liver failure and life‐threating cytopenias is unclear. Here, we describe the case of a woman living with HIV diagnosed with cHL and how she recovered from a hemoglobin nadir of 24 g/L despite declining transfusion support and a bilirubin peak of 417.24 µmol/L, eventually achieving a complete response with a BV‐based therapy. Studies are needed to determine the safety and efficacy of BV in patients excluded from the pivotal trials.Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.
Unveiling the Threat of Disease X: Preparing for the Next Global Pandemic
Authors: Zhao Mengyuan , Lei Luping , Jiang Yinghan , Tian Yuxin , Huang Yuanyu , Yang Minghui 
Published: February 2025

ABSTRACTThe term “Disease X”, first introduced by the World Health Organization (WHO) in 2018, symbolizes the threat of an unknown pathogen capable of causing a global pandemic. Classified as a “priority pathogens,” Disease X stands alongside well‐known threats like SARS, Ebola, and ZIKV due to its potential for widespread outbreaks. SARS‐CoV‐2 is considered the first “Disease X” to fulfill this prediction, demonstrating the devastating impact such pathogens can have. A future pathogen X could pose an even greater threat, with catastrophic consequences. This paper examines the potential origins of such pathogens, drawing lessons from outbreaks like SARS, MERS, and SARS‐CoV‐2. It also highlights strategic approaches to detect, prevent, and respond effectively to mitigate the risk of future pandemics.
Questionnaire to assess immunosuppressant knowledge among kidney transplant recipients: item generation and content validation
Authors: Nik Mustaffa Shapri Nik Aisyah Najwa , Samsudin Nurul Syazfeeza , Abd Wahab Mohd Shahezwan , Ibrahim Norkasihan 
Published: February 2025

AbstractBackgroundSeveral questionnaires are available to evaluate immunosuppressant knowledge among kidney transplant recipients (KTRs). However, most contain a mixture of questions about different aspects of health management before and after kidney transplantation and do not specifically assess immunosuppressant knowledge.AimThis study aimed to generate preliminary items for a questionnaire to assess immunosuppressant knowledge among KTRs, validate the items, and translate the items into Malay.MethodPreliminary items were generated from domains and subdomains identified through a review of previous questionnaires. Then, the item content was validated in a three‐round Delphi study by an expert panel of 11 renal pharmacists. The experts rated the relevance of the items and provided feedback on their comprehensibility and comprehensiveness. Items that attained ≥75% expert agreement on their relevance were considered relevant. Finally, the relevant items were translated into Malay through a forward–backward translation process by three external translators and two researchers. Ethical approval was granted by the Universiti Teknologi Malaysia Research Ethics Committee (Reference no: REC (PH)PG/027/2022) and the study conforms with the Declaration of Helsinki. Participants were approached electronically, and informed consent was obtained from all participants via distribution of a project information sheet, explaining their participation was voluntary and a gift card would be provided as an incentive upon completion of all three rounds of the Delphi study and completion of a written consent form.ResultsA total of 24 preliminary items were generated. In Round 1 of the Delphi study, four items needed revision, and nine new items were suggested for Round 2 (n = 13). In Round 2, only five of the 13 items were carried forward to Round 3. In the final round, only one of the five items was relevant. The final experts' revision produced 27 items. A Malay‐language questionnaire equivalent to the English version was produced.ConclusionA content‐validated questionnaire consisting of 27 items in English and Malay was produced. This questionnaire serves as a reliable tool to identify immunosuppressant knowledge gaps and evaluate the impacts of educational interventions.
Supramolecular Assembly of Organic Cu(I) Halides with Efficient Broad Emission for Real‐Time Dynamic High‐Resolution White Light and X‐Ray Image Fusion and 3D Image Reconstruction
Authors: Peng Hui , Yuan Shengji , Wei Qilin , Kong Linghang , Huang Wenjie , Wang Fei , Zhao Jialong , Zou Bingsuo 
Published: February 2025

Abstract0D organic Cu(I) halides have gained much attention for their fascinating optical properties. However, the narrow excitation in the UV region, strong afterglow, and poor stability severely limit their applications. Herein, three 0D organic Cu(I) halides of [Ba2(18‐crown‐6)2]Cu4Cl8·H3PO3·6H2O (Compound‐Cl), [Ba(18‐crown‐6)2]Cu4Br6·CH3OH·H2O (Compound‐Br), and [Ba(18‐crown‐6)2]Cu4I6·H3PO2·H2O (Compound‐I) are synthesized via supramolecular assembly. Compared to Compound‐Cl with poor stability and Compound‐Br with feeble photoluminescence quantum yield (PLQY), Compound‐I exhibits broadband blue light excitation characteristics, excellent stability, and efficient yellow emission with a PLQY of 99.4%. A high‐performance single‐component white light emitting diode is fabricated by coating Compound‐I powders on a 460 nm chip, which shows ultra‐high luminous efficiency of 106 lm W−1. Under X‐ray irradiation, Compound‐I has a high light yield of 87 100 photons MeV−1 and a low detection limit of 45.9 nGairy s−1. Moreover, the Compound‐I scintillation screen is made using a cold pressing method, which shows a spatial resolution of 20.6 lp mm−1. Based on the remarkable optical properties and short decay lifetime of 1.9 µs of Compound‐I, the 3D image reconstruction of screws wrapped in capsule by combining real‐time dynamic white light and X‐ray image fusion, as well as multi‐angle imaging is successfully demonstrated.
Activate Reconstruction from Sb3+/Ho3+ Synergistic Doping Nanofibers for Interactive Information Encryption and Customized Display
Authors: Dong Xiaolong , Zhao Xin , Zhang Yuhang , Hu Maosen , Shen Lifan , Pun Edwin Yue Bun , Lin Hai 
Published: February 2025

AbstractDriven by the escalating demand for cutting‐edge materials in interactive encryption and customized display, the optimization of excitonic coupling mechanisms in perovskite‐based luminescent systems has emerged as a pivotal focus in advanced materials research. Inspired by synergistic doping (SD), a photoswitchable energy transfer channel is realized utilizing the UV‐responsive Cs2NaInCl6: Sb3+‐Ho3+ (CNIC: Sb‐Ho) phosphor. Benefiting from the self‐trapped exciton of Sb3+, the visible blue luminescence of Ho3+ achieves excitation reconstruction through SD, with a sensitization coefficient from Sb3+ to Ho3+ in CNIC reaching two orders of magnitude. Notably, CNIC: Sb‐Ho quantum dot is embedded into polyacrylonitrile (PAN) and polymethyl methacrylate (PMMA) fibers, respectively, and distinct color coordinate channels are created by altering the doping concentration and fiber matrix, thereby enabling the personalization and the customization of the desired colors with enhanced precision. Furthermore, excellent read‐in performance under UV irradiation is achieved by screen‐printing CNIC: Sb‐Ho microcrystal on nanofibers and combining it with ACSII code, which endows nanofibers with UV‐induced controllable shape programming behavior for interactive multidimensional information encryption. This work establishes an enhanced visual interaction framework through effectively integrating perovskite fluorescence tunability and nanofiber adaptive structures, thus opening new possibilities for the smart application of next‐generation optical encryption technology.
A Silibinin‐Poly(ε‐Caprolactone) Conjugate as an Enhanced Anticancer Agent
Authors: Vento Fabiana , Privitera Anna , Caruso Giuseppe , Nicosia Angelo 
Published: February 2025

AbstractPoly(ε‐caprolactone) (PCL) is a hydrolytically degradable biopolyester used in drug delivery to enhance drug solubility and bioavailability, where drugs are typically incorporated physically within the biopolymeric matrix rather than covalently bonded, due to the limited availability of functional groups required for covalent attachment. In pursuit of developing a facile method for the production of a biopolyester‐drug covalent conjugate with effective drug loading capacity, this study reports the synthesis of a covalent Silibinin‐PCL conjugate (Sil‐PCLHyd) through a two‐step approach. This involves the controlled hydrolysis of a high molecular weight PCL to increase the concentration of carboxylic end groups, which are subsequently used for the catalyzed esterification with Silibinin. The Sil‐PCLHyd is characterized with mass spectrometry, gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetry, and NMR and UV–vis spectroscopies. The cytotoxic effects of Sil‐PCLHyd against colorectal adenocarcinoma cells (Caco‐2) are measured through the MTT assay. The results of the Sil‐PCLHyd characterization revealed a Silibinin loading of ≈9.8 wt.%. The MTT assay demonstrated that Sil‐PCLHyd induced cytotoxic effects at concentrations a hundred times lower than those required for free Silibinin. The proposed approach might represent a reliable pathway for the development of biopolyester‐based covalent conjugates with a high drug loading capacity.
On the Lyapunov exponents of triangular discrete time‐varying systems
Authors: Czornik Adam , Doan Thai Son 
Published: February 2025

AbstractIn this paper, we present upper and lower estimates for the Lyapunov exponents of discrete linear systems with triangular time‐varying coefficients. These estimates are expressed by the diagonal elements of the coefficient matrix. As a conclusion from these estimates, we also obtain bounds for the Grobman regularity coefficient.
A nonlinear characterization of stochastic completeness of graphs
Authors: Schmidt Marcel , Zimmermann Ian 
Published: February 2025

AbstractWe study nonlinear Schrödinger operators on graphs. We construct minimal nonnegative solutions to corresponding semilinear elliptic equations and use them to introduce the notion of stochastic completeness at infinity in a nonlinear setting. We provide characterizations for this property in terms of a semilinear Liouville theorem. It is employed to establish a nonlinear characterization for stochastic completeness, which is a graph version of a recent result on Riemannian manifolds.