bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex hormones and white matter hyperintensities in midlife women in the MsBrain study
Authors: Thurston Rebecca C , Wu Minjie , Chang YueFang , Aizenstein Howard J , Derby Carol A. , Maki Pauline M 
Published: January 2025

AbstractBackgroundSex hormones are frequently implicated in the development of cerebral small vessel disease among midlife women. However, few studies directly measure endogenous sex hormones and consider them in relation to white matter hyperintensities (WMH), indicators of cerebral small vessel disease. Further, existing work on hormones, menopause, and the brain typically focuses on ovarian estradiol (E2), with limited consideration of estrone (E1), the primary postmenopausal estrogen, or follicle stimulating hormone (FSH), an indicator of ovarian age. We tested the associations of E2, E1, and FSH in relation to WMH volume (WMHV) among late midlife women. We considered both whole brain WMHV and the spatial distribution of WMHV.Methods222 women ages 45‐67 (mean = 59.29 years, 99% postmenopausal), not taking hormone therapy, and free of a history of cardiovascular disease were recruited for the MsBrain study. Procedures included physical measures; phlebotomy for sex hormones (E1, E2, FSH; estrogens assessed via LC‐MS/MS), glucose, insulin, and lipids; and 3T magnetic resonance imaging. Associations of E1, E2, and FSH with WMHV were tested in linear regression models with covariates age, race/ethnicity, education, and in a separate step, adjusted for cardiovascular disease (CVD) risk factors [body mass index, smoking, blood pressure level and medications, insulin resistance, lipids]. Additional models considered regional WMHV (deep, periventricular, frontal, temporal, parietal, occipital).ResultsIn age, race, and education‐adjusted models, lower E2 [B(SE) = ‐.12(0.05), p = .02], lower E1 [B(SE) = ‐0.26(0.10), p = 0.007], and higher FSH [B(SE) = 0.26(0.07, p = 0.0005] were each associated with greater whole brain WMHV. When further controlling for CVD risk factors, associations of E1 [B(SE) = ‐.21(.10), p = .04] and FSH [B(SE) = .18(.09), p = .04] (but not E2) to whole brain WMHV remained (Figure 1). Considering the spatial distribution of WMHV, lower E1 was associated with more frontal, deep, and temporal WMHV; and higher FSH with more frontal and periventricular WMHV.ConclusionsFindings indicate the importance of endogenous sex hormones to late midlife women’s cerebrovascular health. They underscore the value, when investigating aging women’s brain health, of moving beyond a sole focus on E2 to also consider E1 and FSH, hormones particularly relevant in the postmenopause.
Phenotype Spectrum of TRPM3‐Associated Disorders
Authors: Jolitz Laura , Helbig Ingo , Fitzgerald Mark P. , McKeown Ruggiero Sarah , Cohen Stacey , Angelini Chloe , Vallespin Elena , Michaud Vincent , Gerasimenko Anna , Cogne Benjamin , Isidor Bertrand , Keren Boris , Dyment David , Heron Delphine , Karstensen Helena Gásdal , Cuppen Inge , Christodoulou John , Wilson Meredith , Lake Nicole J. , Biskup Saskia , Syrbe Steffen , Mori Takayasu , Becker Lena‐Luise , Kaindl Angela M. 
Published: January 2025

ObjectiveMonoallelic variants in the transient receptor potential melastatin‐related type 3 gene (TRPM3) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.MethodsWe analyzed retrospectively the phenotypes and genotypes of 43 individuals with TRPM3 variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22). We included all patients with a pathogenic TRPM3 variant.ResultsThe median age at the time of the study was 10 years, with a preponderance of girls (60%) versus boys (40%). Frequent findings were developmental delay and/or intellectual disability (93%), global or axial hypotonia (77%), ocular involvement (70%), musculoskeletal anomalies (65%), and dysmorphic features (58%). Epilepsy was diagnosed in 31 patients (72%), classified in all as developmental and epileptic encephalopathy with or without spike wave activation in sleep (DEE/DEE‐SWAS). Patients with the variant p.Val1002Met (n = 24) significantly more often had developmental delay and epilepsy. The most effective anti‐seizure medication was primidone. All treated patients showed an improvement in seizure frequency, motor and speech development, and/or learning capability with this drug.InterpretationDevelopmental delay/intellectual disability and epilepsy are dominant phenotypic features in patients with TRPM3 variants. Given that epilepsy can negatively impact development, screening for awake and sleep electroencephalogram abnormalities and other manifestations are essential to offer early intervention. The TRPM3 channel blocker primidone has shown promising effects and should be considered in every child with a TRPM3 gain‐of‐function variant. ANN NEUROL 2025;97:561–570
Entwicklung Konformationsbeschränkter Makrozyklen als Verbesserte FKBP51‐Inhibitoren durch Systematische Linker‐Derivatisierung
Authors: Spiske Moritz , Meyners Christian , Bauder Michael , Repity Maximilian , Brudy Christian , Sugiarto Wisely Oki , Achaq Hanaa , Geiger Thomas M. , Hausch Felix 
Published: January 2025

AbstractMakrozyklen werden zunehmend als vielversprechende Strukturklasse zur Bindung für mit herkömmlichen Arzneistoffen schwer erreichbare intrazelluläre Proteine angesehen. Jedoch sind Strategien, bioaktive azyklische Moleküle zu Makrozyklen mit verbesserten Eigenschaften zu entwickeln in der aktuellen Forschung unterrepräsentiert. In der vorliegenden Studie wurde die Derivatisierung des Linkers als Ansatz zur Optimierung des pharmakologischen Profils von Makrozyklen untersucht. Unter Verwendung des FK506‐bindenden Proteins 51 (FKBP51) als Modellsystem wurden über 140 Makrozyklen mit systematisch derivatisierten Linkern hergestellt. Zwei Grundgerüste wurden als vielversprechende für die anschließende Optimierung identifiziert. Überraschenderweise zeigte die Analyse von Co‐Kristallstrukturen, dass diese identifizierten Grundgerüste eine Vielfalt von dreidimensionalen (3D) Konformationen einnehmen können, die die Basis für unterschiedliche 3D‐Gerüste darstellen. Dies führte zu einer Reihe von Makrozyklen mit durchweg verbesserter Affinität, Plasmastabilität und Wasserlöslichkeit im Vergleich zu den linearen Vorläufern oder den Makrozyklen mit unfunktionalisierten Linker‐Strukturen. Diese Ergebnisse machen deutlich, dass die Linkeroptimierung und ‐derivatisierung großes Potential für die Entwicklung makrozyklischer Arzneistoffe darstellt. Außerdem unterstreicht die Studie die Notwendigkeit, die Entwicklung makrozyklischer Gerüste auch auf dreidimensionaler Ebene zu betrachten.
Construction of Linear Tetramer‐Type Acceptors for High‐Efficiency and High‐Stability Organic Solar Cells
Authors: Zeng Rui , Deng Jiawei , Xue Xiaonan , Tan Sengke , Kan Lixuan , Lin Yi , Zhong Wenkai , Zhu Lei , Han Fei , Zhou Yuhao , Gao Xingyu , Zhang Ming , Zhang Yongming , Xu Shengjie , Liu Feng 
Published: January 2025

AbstractThanks to the development of non‐fullerene acceptor (NFA) materials, the photovoltaic conversion efficiency (PCE) of organic solar cells (OSCs) has exceeded 20 %, which has met the requirements for commercialisation. In the current stage, the main focus is to balance the performance and stability. It has been shown that all‐polymer formulation can improve device stability, however, PCE is not in satifsfaction, and the batch‐to‐batch variation leads to quality control issues. In this work, we constructed monodispersed tetramer NFA materials named G‐1 and G‐2, to best integrate the merits of small molecule and polymer. Density functional theory (DFT) calculations and experimental results showed that different connecting units at the centre could significantly affect the molecular planarity and thin film morphology. The alkene‐bonded tetramer G‐1 had a more regioregular structure, which leads to better molecular planarity, and more ordered packing in thin film. More importantly, the oligomeration induced a favourable face‐on orientation, achieved a lower binding energy and exhibited a higher photoluminescence yield. As a result, the exciton and charge carrier kinetics was optimized with reduced non‐radiative energy loss. The OSC based on PM6 : G‐1 achieved a PCE of 19.6 %, which is the highest PCE reported so far for oligomer‐based binary OSC. In addition, the device stability was largely improved, showing a lifetime over 10000 hours in the inverted OSC device.
Efficient and Robust Europium(III)‐Based Hybrid Lanthanide Scintillators for Advanced X‐Ray Imaging
Authors: Zhang Yimei , Du Tingli , Duan Han , Chen Binqi , Zhang Jiahui , Xiao Qin , Chen Geng , Guo Dongxin , Liao Hong , Zhou Si , Zheng Kezhi 
Published: January 2025

AbstractScintillators that convert ionizing radiation into low‐energy photons are essential for medical diagnostics and industrial inspections. Despite advances in X‐ray scintillators, challenges remain in achieving high efficiency, environmental compatibility, stability, and flexibility. Here, we present experimental investigations of a new type of europium(III)‐based hybrid ternary complex scintillators for improved X‐ray detection and imaging. Benefiting from the synergistic interaction between dual organic ligands and lanthanide ions, the Eu(TTA)3Phen complex demonstrates exceptional radioluminescence and light yield under X‐ray excitation, with a detection limit of 19.97 nGy s−1, well below typical radiation doses used in medical diagnostics. Moreover, lanthanide complex Eu(TTA)3Phen exhibited excellent thermal and photostability, showing minimal degradation even after extended X‐ray exposure. By integrating with flexible polymer matrices, a high‐transmission Eu(TTA)3Phen‐PMMA composite film was fabricated for X‐ray radiography, demonstrating high spatial resolution (<10 um) and superior image quality across various target samples. These findings hold substantial promise for next‐generation X‐ray imaging applications, offering high sensitivity, stability, flexibility, and versatility, making them ideally suited for advanced radiographic systems.
Conformationally Restricted Macrocycles as Improved FKBP51 Inhibitors Enabled by Systematic Linker Derivatization
Authors: Spiske Moritz , Meyners Christian , Bauder Michael , Repity Maximilian , Brudy Christian , Sugiarto Wisely Oki , Achaq Hanaa , Geiger Thomas M. , Hausch Felix 
Published: January 2025

AbstractMacrocycles are increasingly considered as promising modalities to target challenging intracellular proteins. However, strategies for transitioning from active linear starting points to improved macrocycles are still underdeveloped. Here we explored the derivatization of linkers as an approach for macrocycle optimization. Using the FK506‐binding protein 51 (FKBP51) as a model system we prepared >140 macrocycles with systematically derivatized linkers. Two backbones were identified as promising frameworks for subsequent optimization. Surprisingly, co‐crystal structure analyses revealed that these chemical templates represent an ensemble of three‐dimensional (3D) conformations that can give rise to several distinct 3D‐scaffolds. This resulted in a set of macrocycles with consistently improved affinity, plasma stability, and aqueous solubility compared to the linear precursors or the non‐functionalized macrocycles. Our results highlight linkers as an opportunity for macrocyclic drug development, show how linker derivatization can improve the performance of macrocycles, and emphasizes the need to track macrocyclic scaffold evolution at a three‐dimensional level.
Preparation and Performance of Shear‐Resistant and Fast‐Dissolving Drag Reduction With Multiple Cross‐Linking Effects
Authors: Dai Huimin , Lan Jian , He Zou , Zhang Liyin , Xiong Ying , Dai Shanshan 
Published: January 2025

ABSTRACTThe development of shear‐resistant drag reducer agent (DRA) is crucial for enhancing oil recovery, especially during high‐speed pumping and fracturing processes where polymer networks are prone to damage, leading to the reduction of the drag reduction (DR) performance. To address this issue, the introduction of nano‐silica into the polymer structure, while maintaining good DR, endows the DRA with better shear resistance and salt resistance through its unique cross‐linking mode. In this study, a novel shear‐resistant and fast‐dissolving drag reducer was synthesized through free‐radical polymerization using acrylamide (AM), acrylic acid (AA), 2‐acrylamide‐2‐methylpropyl sulfonic acid (AMPS) and KH570 modified nano‐silica. The comprehensive properties of drag reducer were studied using conductivity and dissolution time test, microscopic morphology analysis, thermogravimetric analysis, and rheological test. The results suggestion that the PAPO‐10@SiO2 exhibits outstanding characteristics, including rapid dissolution (4 min), excellent salt resistance (DR rate up to 80.41% at a polymer concentration of 500 mg/L) and nano‐silica concentration of 1.5 wt%. Moreover, the mechanism of drag reduction was proposed that nano‐silica connects the molecular chains through multiple cross‐linking effects of chemical cross‐linking and physical adsorption, which enhances the stability of the network structure and prevents the destruction of the molecular chain structure by shear force effectively (viscosity retention of 76.9% after shearing for 40 min at 90°C and 170 s−1). In summary, this study provides valuable insights for developing polymers with both shear resistance and dissolution properties in aqueous solutions.
A Simple and Sensitive LC‐MS/MS Method for the Determination of Mobocertinib and Its Metabolite Desmethyl‐Mobocertinib in Human Plasma and Its Application to Clinical Pharmacokinetic Study
Authors: Tang Fan , Hou Xiaoli , Chen Jiajie , Cao Yasen , Wang Yixia , Cheng Hong 
Published: January 2025

ABSTRACTMobocertinib is a potent selective tyrosine kinase inhibitor approved for the treatment of non–small cell lung cancer with activating EGFR exon 20 insertions. The aim of this study was to develop a procedure for liquid chromatography tandem mass spectrometry (LC‐MS/MS) for the determination of mobocertinib and its metabolite desmethyl‐mobocertinib in human plasma. The human plasma samples were precipitated with acetonitrile and analyzed using a Waters ACQUITY BEH C18 column coupled to a triple quadrupole mass spectrometer. Separation was executed using the acetonitrile–0.1% formic acid solution with gradient elution, at a flow rate of 0.4 mL/min. Mobocertinib and desmethyl‐mobocertinib were monitored by multiple reaction monitoring (MRM) with m/z 586.5  >  72.2 and 572.4  >  473.2, respectively. The procedure demonstrated excellent linearity (r > 0.997) within the concentration range of 0.1–200 ng/mL for both analytes. Precision in relative standard deviation was <  9.37% for mobocertinib and <  12.03% for desmethyl‐mobocertinib. Accuracy in relative error was within −7.23% to 9.18% for mobocertinib and −2.78% to 9.87% for desmethyl‐mobocertinib. Extraction recovery was >  80% for both analytes. The validated LC‐MS/MS method was successfully applied to the pharmacokinetic study of mobocertinib and desmethyl‐mobocertinib in healthy human volunteers with K2EDTA as anticoagulant after a single dose of mobocertinib (160 mg).
Integrating Plasma Metabolomics, Network Pharmacology, and Experimental Validation to Investigate the Action Mechanism of Qiangxin Lishui Prescription in Chronic Heart Failure
Authors: Jiang Yong , Ji Wenjun , Lu Ying , Wang Qin , Chen Linwei 
Published: January 2025

ABSTRACTThe high mortality rate of chronic heart failure (CHF) makes it a primary battlefield in the field of cardiovascular diseases. Qiangxin Lishui Prescription (QLP) is a traditional Chinese medicine (TCM) prescription used clinically for treating CHF, but its underlying mechanism remains unclear. This study integrated plasma metabolomics, network pharmacology, and experimental validation to reveal the pharmacological effects of QLP and its potential mechanism of anti‐CHF. Using ultra‐high‐performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q/TOF‐MS/MS), 119 absorbed prototype compounds of QLP were identified from rat plasma. By applying network pharmacology and molecular docking techniques, a QLP absorption components–target–CHF network was constructed. The IL6/JAK/STAT3 signaling pathway is likely critical to QLP's therapeutic effect on CHF. A CHF mouse model was established using aortic ligation surgery to investigate the regulation of the IL6/JAK/STAT3 pathway by QLP in CHF mice. Network pharmacology analysis and in vivo experimental data indicate that QLP alleviates myocardial injury and inflammatory response in CHF mice by modulating the IL6/JAK/STAT3 pathway, significantly improving cardiac function. This presents a promising therapeutic strategy for CHF treatment.
Characterization and Analytical Method Validation for Potential Impurities of a Merchantability Drug Substance Fluoxetine HCl
Authors: Reddy Rajani Reddy Janna , Kolli Sunder Kumar , Salakolusu Suresh , Kallam Sudha Divya Madhuri , Raghupathi Jayaprakash Kanijam , Katari Naresh Kumar 
Published: January 2025

ABSTRACTA new selective and sensitive high‐performance liquid chromatography (HPLC) method was developed for the quantification of potential impurities in fluoxetine hydrochloride. Chromatographic separation was achieved on an end‐capped octadecylsilyl silica gel (Gemini‐C18 150 mm × 4.6 mm, 3.0 μm) using a gradient program with triethylamine, methanol, and water as the mobile phase at a flow rate of 1.0 mL/min and monitored at 215 nm. The run time was 60 min. The method was validated to fulfill International Conference on Harmonization (ICH Q2(R2)) requirements, and this validation included specificity, precision, linearity, limit of detection (LOD), limit of quantification (LOQ), and accuracy. The calibration curve was linear over the concentration range from LOQ to 120% with respect to sample concentration. The accuracy of the method is within the acceptable limit of 80%–120%. The results obtained for all parameters were within the acceptance criteria. So, this method can be employed for the regular analysis of potential impurities in the fluoxetine hydrochloride API.
The Impact of Corporate Digital Transformation on Sustainable Development in China
Authors: Chen Wanyi , Ren Hao , Shu Yanyu 
Published: January 2025

ABSTRACTThis study examines the relationship between corporate digital transformation (CDT) and environmental, social, and governance (ESG) performance. Based on resource‐based theory, the findings indicate that CDT contributes to ESG performance through six channels: energy saving, discouragement of greenwashing behavior, improvement of technological innovation and social responsibility, alleviation of information asymmetry, and enhancement of risk management. This relationship was more significant under fierce market competition without cyberattacks. This study enriches the literature on the economic impacts of CDT from the perspective of sustainable development and expands the literature on the factors influencing sustainable performance from the perspective of digital technology. It directs the government to advance digital technology, foster a competitive market environment, and enhance cybersecurity, while also serving as a crucial reference for society in driving the reform of CDT, ensuring the sustainable development of the economy and promoting high‐quality and sustainable CDT in developing countries, including China.
Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies
Authors: Mbous Yves Paul Vincent , Mohamed Rowida , Sambamoorthi Usha , Bharmal Murtuza , Kamal Khalid M. , LeMasters Traci , Kolodney Joanna , Kelley George A. 
Published: January 2025

ABSTRACTObjectiveThe lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early‐stage MCC, prompted this study.MethodsA systematic review and meta‐analysis of randomized and non‐randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease‐specific survival (DSS), and/or disease‐free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.ResultsForty‐nine studies representing 46,215 participants were included in the meta‐analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62–0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I2 = 94%, 95% CI, 93.0–95.5). Both LR (HR = 1.52, 95% CI, 0.37–6.19) and RR (HR = 0.41, 95% CI, 0.09–1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24–1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13–0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E‐value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.ConclusionsAlthough adjuvant RTx improves survival and recurrence outcomes among early‐stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.
Transcatheter Aortic Valve Replacement in Hypertrophic Cardiomyopathy: A Systematic Review and Meta‐Analysis
Authors: Ahmed Ashraf , Kaddoura Rasha , Aggarwal Abhinav , Zinyandu Tawanda , Webber Fabricio , Davila Carlos , Zarich Stuart 
Published: January 2025

ABSTRACTBackgroundThe co‐existence of severe aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM) is not uncommon. Surgical intervention is the gold standard management. Patients with high surgical risk might undergo transcatheter aortic valve replacement (TAVR). However, TAVR outcomes are unclear in this population. We aimed to investigate the impact of HCM on the outcomes of TAVR.AimWe aim to investigate the outcomes of TAVR in patients with HCM.MethodsWe systematically searched PubMed, EMBASE, and Scopus for studies that compared outcomes of TAVR procedure between patients with HCM and those without it. Using the random‐effects model, the odds ratios (OR) with 95% confidence interval (CI) were reported.ResultsWe screened 102 articles and identified three observational cohort studies. Compared to patients who underwent TAVR without underlying HCM, TAVR for AS co‐existed with HCM was associated with higher rates of mortality (OR 5.79; 95% CI: 3.38; 9.91, p < 0.0001), cardiogenic shock (OR 4.55; 95% CI: 3.40; 6.08, p < 0.0001), aortic dissection (OR 4.95; 95% CI: 3.17; 7.74, p < 0.0001), vascular complications (OR 2.10; 95% CI: 1.27; 3.47, p = 0.004), and renal impairment (OR 1.80; 95% CI: 1.36; 2.40, p < 0.0001). There was no difference between the comparison groups in terms of complete heart block, new permanent pacemaker implantation, or bleeding.ConclusionIn patients with severe AS and HCM, TAVR was associated with significantly higher occurrence of mortality, cardiogenic shock, aortic dissection, vascular complications, and renal impairment as well as the need for mechanical ventilation than patients who did not have HCM.