bluuebunny/crossref_metadata_2025_split huggingface dataset:
A digital brain sampling protocol atlas to simplify and accelerate biorepository tissue requests
Authors: Webster Jason , Shojaie Ali , Shen Yiqin Alicia , Le Tung , MacDonald Christine , Latimer Caitlin S , Keene C Dirk , Grabowski Thomas J 
Published: January 2025

AbstractBackgroundThe structural, cellular, and biomolecular research necessary for a mechanistic understanding of Alzheimer’s Disease (AD) relies on brain tissue collected according to a brain sampling protocol (BSP) and preserved in biorepositories. Such research involves discipline‐specific terminology such as cytoarchitectonic domains, brain network nodes, etc. This specificity can result in iterative, time‐consuming, and error‐prone request processes. The digital BSP atlas will streamline this process and offer resources for reference, visualization, training, and refinement of BSPs.MethodVirtual Neuropathology was performed by a neuropathology technician and Board‐certified neuropathologist in Figma, a collaborative cloud‐based platform with an intuitive dynamic interface, in which metric properties of the brain slices and samples from the University of Washington BioRepository and Integrated Neuropathology (BRaIN) Laboratory BSP were precisely replicated. Virtual brain slices were taken every 4mm from the Montreal Neurological Institute and International Consortium on Brain Mapping 2009b Nonlinear Asymmetric Brain Template, which has 8x higher resolution than typical brain templates. Data were exported in Scalable Vector Graphics and processed in python.ResultsThe Digital BSP Atlas contains volumetric labels in MNI 2009b space for the routinely collected samples in the BRaIN lab BSP and is stored using standard neuroinformatics conventions for use with freely available software such as FMRIB’s Software Library (FSL) and FreeSurfer.For each sample, volume of brain regions defined by anatomical regions, brain areas, white matter pathways, subcortical structure, cytoarchitectonic domains, functional regions, or functional connectivity network nodes was calculated as the overlap with labels from a range of digital atlases which registered to MNI 2009b space.ConclusionThe digital BSP atlas provides a quantitative representation of the BSP in a standard space which will accelerating the process of requesting brain tissue, allows for the refinement of protocols, and the coordination of neuroimaging information with neuropathology sample. Future directions of this work include customizable visualizations, training software, and website backend to identify corresponding samples from free‐form text with arbitrary neuroscience terms. This research is part of a pipeline to facilitate mechanistic understanding of AD by enhancing the precision and accuracy of neuropathology sampling and robust registration to premortem neuroimaging data even for late‐stage AD participants.
Phase‐Separated Spiropyran Coacervates as Dual‐Wavelength‐Switchable Reactive Oxygen Generators
Authors: Kong Hao , Xie Xian , Bao Yishu , Zhang Fang , Bian Liming , Cheng Kai , Zhao Yuan‐Di , Xia Jiang 
Published: January 2025

AbstractLow‐molecular‐weight compounds of certain structural features may form coacervates through liquid‐liquid phase separation (LLPS). These coacervates can enter mammalian cells and affect cellular physiology. Controlling the properties of the coacervates inside cells, however, is a challenge. Here, we report photochemical reactions of spiropyran (SP)‐based coacervates with two wavelengths of light, in vitro, in the cell, and in animals, generating reactive oxygen species (ROS) for photo‐controlled cell killing. We identify an SP‐containing compound, SP‐PEG8‐SP, that forms coacervates (SP‐C) in the aqueous solution. Photo illumination by a UV light triggers the isomerization of SP to merocyanine (MC), switching SP‐C to the fluorescent coacervates MC‐C. A visible light converts MC‐C back to SP‐C and induces ROS generation. Notably, coacervate formation increases the compound's ROS generation efficiency. The SP‐C/MC‐C coacervate system (collectively called spiropyran coacervates) can spontaneously enter cells, and a dual‐wavelength‐controlled reversible on/off switch and spatiotemporal‐resolved ROS production is realized within the cytoplasm. Light‐induced ROS generation leads to cytotoxicity to cancer cells, tumor organoids, and tumors in vivo, supporting spiropyran coacervates’ potential use as coacervate photosensitizers in photodynamic therapies.
P‐Dopant with Spherical Anion for Stable n‐i‐p Perovskite Solar Cells
Authors: Shao Guang , Zhou Zu‐Kun , Wang Dian , Xiao Jing , Yang Shang‐Gen , Yu Hui‐Juan , Qu Jun‐Feng , Wu Zhi‐Zheng , Zhang Jun‐Jie , Peng Lifen , Ain Qurat Ul , Khan Ammar Ahmed , Chen Yu , Yang Hua , Qiu Zeliang , Hu Ruiyuan , Li Xingao , Alamry Khalid A. , Xia Jianxing , Zhang Yi , Nazeeruddin Mohammad Khaja 
Published: January 2025

AbstractLi‐TFSI/t‐BP is the most widely utilized p‐dopant for hole‐transporting materials (HTMs) in state‐of‐the‐art perovskite solar cells (PSCs). However, its nonuniformity of doping, along with the hygroscopicity and migration of dopants, results in the devices exhibiting limited stability and performance. This study reports on the utilization of a spherical anion derived from the p‐dopant, regulated by its radius and shape, as an alternative to the linear TFSI− anion. The theoretical and experimental results reveal that the spherical anion significantly increases the doping effect of HTMs due to an enhanced electron transfer from larger dipole moments. The enhanced transfer leads to a shift in the Pb‐6p defect orbitals, resulting in shallower trap states. Moreover, compared to the linear structure of the TFSI− anion, the anion of sodium tetrakis[3,5‐bis(trifluoro methyl)phenyl]borate (Na‐TFPB) with a larger van der Waals radius and spherical shape offers increased hydrophobicity and migration barriers, which can protect the perovskite crystal and facilitate stable p‐doping of HTMs. The use of Na‐TFPB results in enhanced thermal and ambient stability of PSCs. The devices fabricated with the shape‐ and radius‐regulated p‐dopant achieve remarkable efficiencies of 24.49 % and 24.31 % for CJ‐01 and spiro‐OMeTAD, respectively, representing the highest efficiency values for organic dopants to date. This study underscores the ingenious design of spherical anions of p‐dopants in contrast to the conventional linear anions.
Evaluation of the Impact of HIFU on Peptide Bond Formation: A Study Using SPE‐LC‐MS/MS Methodology
Authors: Liu Jiale , Yuan Rongfei , Wang Qi , Qiao Hai , Yang Yuling , Yang Siyu , Zhang Hua , Chen Chang 
Published: January 2025

ABSTRACTHigh‐intensity focused ultrasound (HIFU) is a noninvasive soft tissue ablation technique, which utilizes ultrasound energy to induce thermal coagulation necrosis in targeted tissues. Whether this high energy causes side effects in vivo, such as the formation of peptide bonds, has not been fully investigated. Glycylglycine is the simplest dipeptide and hence is often used as a model compound for peptide studies. In this study, we developed and validated a sensitive quantification method based on ion‐exchange solid‐phase extraction, liquid chromatography, and tandem mass spectrometry (SPE‐LC‐MS/MS) for the analysis of glycylglycine without derivatization, and then used it to evaluate whether HIFU promoted peptide bond formation in aqueous solution (without enzymes) and plasma (with enzymes). The results showed that strong cation exchange SPE significantly reduced the matrix effect and improved the sensitivity of the LC‐MS/MS method. No formation of glycylglycine in the aqueous solution or plasma was observed following HIFU irradiation.
Liquid Chromatography Combined With Tandem Mass Spectrometry for the Pharmacokinetic and Metabolism Studies of PROTAC ARV‐471 in Rats
Authors: Huang Wenbin , Zhang Hongjian , Zhou Yayun , Liu Xuechao , Zhang Qilei , Ma Xiaopeng 
Published: January 2025

ABSTRACTProteolysis targeting chimera (PROTAC) is emerging as a promising medicinal modality, which has aroused widespread interest among the field of pharmaceutical manufacturing in the recent years. ARV‐471 is an orally active PROTAC estrogen receptor degrader against breast cancer, which leads to the ubiquitylation and subsequent degradation of estrogen receptors via the proteasome. In this study, we developed a highly sensitive liquid chromatography tandem mass spectrometry method (LLOQ = 0.5 ng/mL) for the measurement of ARV‐471 in rat plasma. The acetonitrile precipitated sample was separated on ACQUITY BEH C18 column using acetonitrile‐0.1% formic acid as mobile phased with gradient elution. Multiple reactions monitoring in positive ESI mode was employed for the quantification of ARV‐471 (m/z 724.4 → 396.2). The assay showed good linearity over the concentration range of 0.5–1000 ng/mL with correlation coefficient > 0.996. The assay was validated according to FDA guidance, and all the validation parameters were within the predefined acceptance criteria. After validation, the assay was applied to the pharmacokinetic study of ARV‐471 in rats. Additionally, the metabolites in rat plasma were identified using liquid chromatography–high resolution mass spectrometry. Four metabolites were identified and characterized. Hydrolysis, glucuronidation and deamination were the main metabolic pathways of ARV‐471 in rats.
Validated LC–MS/MS Method for the Determination of Paxalisib on Mouse Dried Blood Spots: An Application to Pharmacokinetic Study in Mice
Authors: Zakkula Ashok , Haque M. Akiful 
Published: January 2025

ABSTRACTPaxalisib is a dual PI3K/mTOR inhibitor, being used in advanced cancer treatment. In this research, we report a validated LC–MS/MS method for quantifying paxalisib from mouse dried blood spot (DBS). We validated the method in‐line with the FDA guidelines. Liquid–liquid extraction technique was used to extract paxalisib from the DBS discs. We used a Chromolith RP‐18 end cap (100 × 4.6 mm) column and isocratic mobile phase for the chromatographic separation of paxalisib and the internal standard (IS, dasatinib). The flow was 0.80 mL/min. In the optimized chromatographic conditions, the retention of paxalisib and the IS was ~2.13 and 2.06 min, respectively. Each injection total run time was 2.50 min. The MS/MS ion transitions monitored were m/z 383.2 → 309.1 and 488.1 → 410.1 for paxalisib and the IS, respectively. We have used a broad calibration range (1.24–3762 ng/mL) with a determination coefficient (r2) of 0.995. All the validation parameters assessed met the acceptance criteria, and hematocrit had no effect on DBS Paxalisib concentrations. We have used the validated method to derive the intravenous and oral pharmacokinetic parameters by quantifying paxalisib in mouse blood and correlated with mice pharmacokinetic data.
Acute Transverse Myelitis as an Uncommon Presentation of Neurobrucellosis: A Case Report
Authors: Karaja Saja , Kazkz Waddah 
Published: January 2025

ABSTRACTBrucellosis mainly affects the musculoskeletal system with neurological manifestations observed in < 5% of all cases. This report outlines a unique case of neurobrucellosis that resulted in acute transverse myelitis (TM) with absent deep reflexes and negative Wright's reaction. In endemic regions, neurobrocellosis should be considered as a potential etiology of acute TM. Timely initiation of treatment is essential for optimizing clinical outcomes.
Effect of sodium content on the electrochemical performance of P2‐Na2Ni2TeO6 layered oxide cathode for sodium‐ion batteries
Authors: Moeez Iqra , Bhatti Ali Hussain Umar , Cho Min‐Kyung , Susanto Dieky , Akbar Muhammad , Ali Ghulam , Chung Kyung Yoon 
Published: January 2025

AbstractSodium‐ion batteries (SIBs) employ P2‐type layered transition metal oxides as promising cathode materials, primarily due to their abundant natural reserves and environmentally friendly characteristics. However, structural instability and complex phase transitions during electrochemical cycling pose significant challenges to their practical applications. Employing cation substitution serves as a straightforward yet effective strategy for stabilizing the structure and improving the kinetics of the active material. In this study, we introduce a Ni‐rich honeycomb‐layered Na2+xNi2TeO6 (NNTO) cathode material with variable sodium content (x = 0, 0.03, 0.05, 0.10). Physicochemical characterizations reveal that excess sodium content at the atomic scale modifies the surface and suppresses phase transitions, while preserving the crystal structure. This results in enhanced cyclic performance and improved electrochemical kinetics at room temperature. Furthermore, we investigate the performance of the NNTO cathode material containing 10% excess sodium at a relatively high temperature of 60°C, where it exhibits 71.6% capacity retention compared to 60% for the pristine. Overall, our results confirm that a preconstructed surface layer (induced by excess sodium) effectively safeguards the Ni‐based cathode material from surface degradation and phase transitions during the electrochemical processes, thus exhibiting superior capacity retention relative to the pristine NNTO cathode. This study of the correlation between structure and performance can potentially be applied to the commercialization of SIBs.
Asymmetric charge distribution boosts hydrogen evolution performance in two‐dimensional MoO2/MoS2 step heterostructure
Authors: Kang Mengke , Zhang Xiang , Wang Jingyi , Li Wen , Xue Tianyu , Zhai Kun , Xiang Jianyong , Nie Anmin , Cheng Yingchun , Liu Zhongyuan 
Published: January 2025

AbstractStep heterostructures are predicted to hold a profound catalytic performance because of the rearranged electronic structure at their interface. However, limitations in the morphology of heterostructures prepared by hydrothermal reactions or molten salt‐assisted strategies make it challenging to directly assess charge distribution and evaluate a single interface's hydrogen evolution reaction (HER) performance. Here, we prepared two‐dimensional MoO2/MoS2 step heterostructures with a large specific surface area by the chemical vapor deposition method. Surface Kelvin probe force microscopy and electrical transport measurement verified the asymmetric charge distribution at a single interface. By fabricating a series of micro on‐chip electrocatalytic devices, we investigate the HER performance for a single interface and confirm that the interface is essential for superior catalytic performance. We experimentally confirmed that the enhancement of the HER performance of step heterostructure is attributed to the asymmetric charge distribution at the interface. This work lays a foundation for designing highly efficient catalytic systems based on step heterostructures.
Stereoselective Synthesis of 2‐Deoxy Glycosides via a Novel 2‐O‐Resided (o‐Alkynyl)benzoate‐Initiated 1,2‐Sulfur Migration/Glycosylation and Desulfurization Protocol as well as Mechanism Elucidation
Authors: Liao Jin‐Xi , Li Zhen‐Qiang , Qiu Yanli , Gao Xiang‐Yang , Lv Xin , Liu Hui , Tu Yuan‐Hong , Sun Jian‐Song 
Published: January 2025

Comprehensive SummaryStereoselective construction of 2‐deoxy‐glycosidic linkages has been achieved by the 1,2‐sulfur migration/glycosylation and desulfurization strategy; however, current protocols suffer from harsh reaction conditions and unsatisfactory stereoselectivity, particularly during the 1,2‐S‐migration/glycosylation step. With 2‐O‐resided (o‐alkynyl)benzoate and anomeric p‐methoxyphenylsulfenyl groups as the initiating and migrating groups, respectively, a novel protocol for the efficient synthesis of 2‐deoxy‐glycosides via the 1,2‐sulfur migration/glycosylation‐desulfurization strategy has been established, which is featured by the mild and catalytic reaction conditions, expanded substrate scope, as well as good to excellent diastereoselectivity. Mechanism studies determined hyperconjugation‐stabilized oxocarbenium ion as the key intermediate, achieving high 1,2‐trans stereocontrol through thermodynamic, steric, as well as electrostatic effects. This provides the fresh insight for the operative mechanism of the 1,2‐sulfur migration/glycosylation and desulfurization strategy, further corroborated by the elaborately designed testing reactions and DFT calculations. Moreover, the synthetic potential of the newly established protocol was examined by the practical synthesis of natural product, culminating in the acquisition of digoxin from acetylated digoxigenin in 25% overall yield through an 8‐step longest linear sequence.
Zanubrutinib plus R‐CHOP for the treatment of newly diagnosed double‐expressor lymphoma: A phase 2 clinical study
Authors: Yin Xia , He Qiang , Liu Dan , Xie Linna , Wang Hui , Chen Chunyan , Zhao Chuanli , Shan Ningning , Shi Shanshan , Wei Haichen , Ma Ji , Lu Ke , Wang Liang , Wang Yan , Xing Lijie , Li Zengjun 
Published: January 2025

AbstractBackgroundDouble‐expressor lymphoma (DEL) has a poorer prognosis than other subtypes of diffuse large B‐cell lymphoma (DLBCL). This study is a multicenter, prospective, single‐arm, phase 2 clinical study initiated by investigators to evaluate the efficacy and safety of combined zanubrutinib with R‐CHOP, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for patients with DEL (stage II or more), as well as to explore factors related to efficacy preliminarily.MethodsFrom November 2020 to July 2022, 48 newly diagnosed patients were enrolled. All patients received twice‐daily oral zanubrutinib (160 mg) for 6 months and standardized R‐CHOP regimen for six to eight cycles.ResultsThe objective response rate (ORR) was 89.6%, with a complete response rate (CRR) of 83.3%. The median follow‐up was 29.3 months. The median progression‐free survival (PFS) and overall survival (OS) were not reached. The PFS and OS were 81.25% and 93.75% at 2 years, respectively. Grade ≥3 adverse events (AEs) were reported in 23 of 48 (47.9%) patients. Next‐generation sequencing (NGS) results of 33 patients showed that TP53, MYD88, and PIM1 were the most common mutated gene. Multivariate analysis revealed that BCL‐6 gene rearrangement was an adverse prognostic factor for both PFS (hazard ratio [HR], 0.247; 95% confidence article [CI], 0.068–0.9; p = .034) and OS (HR, 0.057; 95% CI, 0.006–0.591; p = .016), whereas the number of extranodal involvements also significantly influenced OS (HR, 15.12; 95% CI, 1.07–213.65; p = .044).ConclusionsZanubrutinib in combination with R‐CHOP is an effective option for DEL patients, and the toxicity of zanubrutinib is entirely acceptable for patients.
Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease
Authors: Rolan Paul , Seckl Jonathan , Taylor Jack , Harrison John , Maruff Paul , Woodward Michael , Mills Richard , Jaros Mark , Hilt Dana 
Published: January 2025

AbstractThis review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β‐hydroxysteroid dehydrogenase 1 (11β‐HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β‐HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease. PK modeling suggested that 20 mg daily would be optimal to maintain cerebrospinal fluid concentrations above the brain half maximal inhibitory concentration. However, subsequent PET scanning suggested that emestedastat doses of 10 or even 5 mg daily may be sufficient to adequately inhibit 11β‐HSD1. With once‐daily doses of 5‐20 mg in cognitively normal, older volunteers, a consistent pattern of pro‐cognitive benefit, without dose‐response, was seen as improvement in attention and working memory but not episodic memory. Thus, emestedastat therapeutic activity might be attained at doses lower than those predicted from cerebrospinal fluid drug levels. Doses as low as 5 mg daily may be efficacious and were studied in subsequent trials.
Ethical Considerations for Conducting Community‐Engaged Research with Women Experiencing Homelessness and Incarcerated Women
Authors: Dickins Kirsten 
Published: January 2025

ABSTRACTSince 1979, The Belmont Report has served as a guidebook for ensuring that basic standards for ethical research are upheld. The Belmont Report calls for special protections of vulnerable research participants, such as people who are incarcerated and economically and educationally disadvantaged individuals who are deemed susceptible to exploitation. With a growing focus on health equity and community‐engaged approaches in health equity research, efforts to involve vulnerable participants are increasing. Yet there is little understanding of what matters most to vulnerable populations. This study sought to understand, from participant perspectives, ethical considerations when conducting research with two vulnerable populations: women experiencing homelessness and women who are incarcerated. Health care professionals and staff that work closely with homeless and incarcerated populations were also interviewed. The findings from semistructured interviews with these populations underscore the sustained importance of respect for persons, beneficence, and justice, and further highlight the need for self‐determination; privacy/confidentiality; continuous consent; fair treatment; benefit‐burden balance; nonauthoritarian relationships; and fair access to research participation. Although The Belmont Report durably serves to ethically guide standard conventional research, the Report's original concepts should be extended to include specific considerations when vulnerable populations are involved in community‐engaged research.
Investigating Moral Distress in Clinical Research Professionals—A Deep Dive into Troubled Waters
Authors: Bosack Elena , Bourne Dawn , Epstein Elizabeth , Marshall Mary Faith , Chen Donna T. 
Published: January 2025

ABSTRACTMoral distress occurs when professionals are constrained from taking what they believe to be ethically appropriate actions or are forced to take actions they believe are ethically inappropriate, challenging their professional identities and representing systems‐level issues within organizations. Moral distress has been recognized in a variety of health care‐related fields; however, the phenomenon is still comparatively unexplored among clinical research professionals (CRPs). In this qualitative study, we interviewed ten CRPs to unearth root causes of moral distress in this ethically unique profession. Four themes emerged from the data as contributors to moral distress: commodification of research; concern for research participants; compromised science; and structures of hierarchy. The experience of racism as a source of moral distress is also explored. The findings of this study indicate that the existence of moral distress in clinical research is troubling not only for the welfare of CRPs but also for the greater clinical research enterprise.