bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Bispecific Antibody CVL006 Superior to AK112 for Dual Targeting of PD-L1 and VEGF in Cancer Therapy
Authors: Wang Chunyan , Huang Hao , Song Zeng , Li Zhongyuan , Huang Jinwen , Cao Liang , Wu Ziai , Pan Junfang , Shen Xiaokun 
Published: December 2024

AbstractBoth preclinical and clinical studies have shown that combining anti-VEGF/VEGFR drugs with immune checkpoint inhibitors (ICIs) significantly enhances anticancer efficacy. Currently, PDL-1/ VEGF bispecific antibodies demonstrate superior antitumor activity compared to monotherapy or even the combination of PD-L1 inhibitors with anti-VEGF antibodies. This enhanced efficacy results from the simultaneous blockade of the PD-1/PD-L1 pathway and the inhibition of VEGF-driven angiogenesis. In this study, we developed a novel bispecific antibody, CVL006, by fusing an anti-PDL1 VHH domain with a humanized IgG1 anti-VEGF monoclonal antibody while retaining antibody-dependent cellular cytotoxicity (ADCC) functionality. CVL006 demonstrated high affinity and specificity for both human PD-L1 and VEGF, effectively blocking both the VEGF/VEGFR signaling pathway and the PD-L1/PD-1 axis. This dual blockade not only suppressed VEGF-induced angiogenesis but also reactivated T cells, increasing the secretion of cytokines essential for immune response. In vivo studies further indicated that CVL006 achieved superior antitumor efficacy compared to the PD-L1 inhibitor atezolizumab in mouse models, with greater tumor growth inhibition and reduced angiogenesis. To compare with approved bispecific antibody PD-1/VEGF AK112 (ivonescimab), CVL006 showed superior antitumor efficacy in vivo. These findings underscore the therapeutic potential of CVL006, which integrates immune checkpoint inhibition with disruption of tumor vascularization, offering a robust and comprehensive anticancer strategy.
Thesev-GAL4driver inDrosophila melanogasterdoes not express in the eight pairs of dorso-medial and some other neurons in larval ventral ganglia: A correction
Authors: Kaushik Vanshika , Lakhotia Subhash C. 
Published: December 2024

AbstractThesev-Gal4driver is widely used inDrosophilato express the target gene in specific subsets of cells in ommatidial units of developing eye. A 2015 report (Ray & Lakhotia, J Genet 94, 407-416) from our laboratory claimed that besides the eye disc cells, theSev-Gal4(Bloomington stock 5793) also expresses in 8 pairs of dorso-medial neurons and some other cells in larval and early pupal ventral ganglia. The current study reveals that this claim was incorrect since theUAS-GFPtransgene in Bloomington stock 1521 used as reporter in the 2015 study expresses in the 8 pairs of dorso-medial neurons and some other cells in larval and early pupal ventral ganglia even in undriven condition. TheUAS-eGFPreporter in the BL-5431 stock, however, does not express in these ganglia, neither in undriven nor insev-Gal4driven condition. This was also confirmed by the G-TRACE cell lineage study. Present results suggest that only four dorsal-midline cells in ventral ganglia and a cluster of cells in central region of brain hemisphere, besides the earlier known cells in eye disc and optic lobe of brain, express thesev-Gal4transgene in the stock 5793. The essentiality of examining undriven expression of a transgene cannot be under-emphasized.
Rapid kinetics of H+transport by membrane pyrophosphatase: evidence for a “direct-coupling” mechanism
Authors: Anashkin Viktor A. , Bogachev Alexander V. , Serebryakova Marina V. , Zavyalova Elena G. , Bertsova Yulia V. , Baykov Alexander A. 
Published: December 2024

ABSTRACTStress resistance-conferring membrane pyrophosphatase (mPPase) found in microbes and plants couples pyrophosphate hydrolysis with H+transport out of the cytoplasm. There are two opposing views on the energy-coupling mechanism in this transporter: the pumping is associated with either pyrophosphate binding to mPPase or the hydrolysis step. We used our recently developed stopped-flow pyranine assay to measure H+transport into mPPase-containing inverted membrane vesicles on the timescale of a single turnover. The vesicles were prepared fromEscherichia colioverproducing the H+-translocating mPPase ofDesulfitobacterium hafniense. Pyrophosphate induced linear accumulation of H+in the vesicles, without evident lag or burst. In contrast, the binding of three nonhydrolyzable pyrophosphate analogs essentially induced no H+accumulation. These findings are inconsistent with the “pumping-before-hydrolysis” model of mPPase functioning and support the alternative model positing the hydrolysis reaction as the source of the transported H+ions. mPPase is thus a first “directly-coupled” proton pump.
West Nile Virus Neuroinvasive Disease in Patients Treated with anti-CD20 Therapies
Authors: Ardakani Rumyar V. , Crane Paul D. , Pastula Daniel M. , Chauhan Lakshmi , Matthews Elizabeth , Money Kelli M. , Shah Anna A. , Piquet Amanda L. , Gross Robert H. , Carlson Aaron M. , Tyler Kenneth L. , Corboy John R. , Alvarez Enrique , Wolf Andrew B. 
Published: December 2024

ABSTRACTBackground and objectivesThe literature on severe West Nile virus (WNV) neuroinvasive disease (WNND) in patients treated with anti-CD20 therapies is limited to case reports. We systematically characterize cases of WNND in the tertiary academic UCHealth system.MethodsA retrospective cohort (January 2016 to January 2024) of patients with a validated diagnosis of WNND and anti-CD20 medication use was identified with electronic medical record (EMR) query followed by individual chart review.ResultsWe identified 25 patients, of whom multiple sclerosis was the most common indication for anti-CD20 therapy in 13 patients (52%). 21 patients (84%) presented with meningoencephalitis. Cerebrospinal fluid (CSF) WNV IgM was positive in 5/21 patients (24%) who were tested, while 13/14 tested patients (93%) had positive RT-PCR findings in the CSF. MRI demonstrated anomalies associated with WNND in 12/23 patients (52%) with available imaging. ICU admission was required in 8 patients (32%) and 12 patients (48%) were treated with intravenous immunoglobulin. Worsening of ≥1 point from pre-WNV baseline modified Rankin scale (mRS) to the 90-day post-discharge mRS was seen in 18 patients (75%). Two patients (8%) died by 90-days.DiscussionWNND leads to disability accrual in patients on B-cell depleting anti-CD20 therapies. Utilization of RT-PCR is important in optimizing diagnosis due to limited sensitivity of antibody testing.
Comprehensive Genetic Profiling of Sensorineural Hearing Loss Using an Integrative Diagnostic Approach
Authors: Lee Sang-Yeon , Lee Seungbok , Park Seongyeol , Jung Sung Ho , Yun Yejin , Choi Won Hoon , Cha Ju Hyuen , Yun Hongseok , Lee Sangmoon , Suh Myung-Whan , Park Moo Kyun , Song Jae-Jin , Choi Byung Yoon , Lee Jun Ho , Ju Young Seok , Koh June-Young , Chae Jong-Hee 
Published: December 2024

AbstractDespite the advent of Next-Generation Sequencing (NGS), genetic diagnosis of genetic disorders remains challenging, with diagnostic rates plateauing at approximately 50%. We investigated sensorineural hearing loss (SNHL), a prevalent sensory disorder with substantial genetic heterogeneity, through a comprehensive genomic analysis of a homogeneous disease cohort. Leveraging 394 families (750 individuals), we implemented a systematic multi-tiered genomic approach encompassing single-gene analysis to whole-genome sequencing (WGS), integrated with functional assays and bioinformatic analysis. Our methodological framework revealed a cumulative diagnostic yield of 55.6% (219 families), with automated WGS bioinformatics pipeline uncovering an additional 20 families harboring pathogenic variants, predominantly structural variants. Notably, comparative genomic analysis unveiled a higher frequency of single pathogenic alleles in recessive genes within our SNHL cohort relative to control populations. Subsequent deep intronic region interrogation identified three pathogenic variants on the opposite allele, substantiating the diagnostic utility of comprehensive genomic profiling. Through this approach, we delineated a genome-phenome landscape of SNHL, elucidating molecular signatures and establishing genotype-phenotype correlations at the inner ear functional level. This study underscores the transformative potential of WGS as a robust molecular diagnostic modality, advancing precision medicine paradigms in genetic disease research.
An Annotated Multi-Site and Multi-Contrast Magnetic Resonance Imaging Dataset for the study of the Human Tongue Musculature
Authors: Ribeiro Fernanda L. , Zhu Xiangyun , Ye Xincheng , Tu Sicong , Ngo Shyuan T. , Henderson Robert D. , Steyn Frederik J. , Kiernan Matthew C. , Barth Markus , Bollmann Steffen , Shaw Thomas B. 
Published: December 2024

AbstractThis dataset provides the first fully annotated, openly available MRI-based imaging dataset for investigations of tongue musculature, including multi-contrast and multi-site MRI data from non-disease participants. The present dataset includes 47 participants collated from three studies: BeLong (four participants; T2-weighted images), EATT4MND (19 participants; T2-weighted images), and BMC (24 participants; T1-weighted images). We provide automatically generated and manually corrected segmentation of five key tongue muscles: the superior longitudinal, combined transverse/vertical, genioglossus, and inferior longitudinal muscles. Other phenotypic measures, including age, sex, weight, height, and tongue muscle volume, are also available for use. This dataset will benefit researchers across domains interested in the structure and function of the tongue in health and disease. For instance, researchers can use this data to train new machine learning models for tongue segmentation, which can be leveraged for segmentation and tracking of different tongue muscles engaged in speech formation in health and disease. Altogether, this dataset provides the means to the scientific community for investigation of the intricate tongue musculature and its role in physiological processes and speech production in health and disease.
Using Machine Learning and Electronic Health Record (EHR) Data for the Early Prediction of Alzheimer’s Disease and Related Dementias
Authors: Akter Sonia , Liu Zhandi , Simoes Eduardo J. , Rao Praveen 
Published: December 2024

ABSTRACTObjectiveIn the United States, over 6 million patients are affected by Alzheimer’s Disease and Related Dementias (ADRD). The study aims to develop and validate machine learning (ML) models for the early diagnosis and prediction of ADRD using de-identified Electronic Health Record (EHR) data from the University of Missouri (MU) Healthcare for different prediction windows.Materials and MethodsThe study used de-identified EHR data provided by the MU NextGen Biomedical Informatics (BMI). An initial cohort of 380,269 patients aged over 40 with at least two healthcare encounters was narrowed to a final dataset of 4,012 unique patients of ADRD cases and 119,723 unique patients of controls. We trained and evaluated six different ML classifier models: Gradient-Boosted Trees (GBT), Light Gradient-Boosting Machine (LightGBM), Random Forest (RF), eXtreme Gradient-Boosting (XGBoost), Logistic Regression (LR), and Adaptive Boosting (AdaBoost) using metrics such as Area Under the Receiver Operating Characteristic Curve (AUC-ROC) score, accuracy, sensitivity, specificity, and F1 score. SHAP (SHapley Additive exPlanations) analysis was used to interpret predictions.ResultsThe GBT model achieved the best AUC-ROC scores of 0.809, 0.821, 0.822, 0.808, and 0.833 for 1-year, 2-year, 3-year, 4-year, and 5-year prediction windows, respectively. The SHAP analysis highlighted key risk factors for ADRD, including depressive disorder, heart disease, higher age, headache, anxiety, and insomnia.ConclusionThis study demonstrates the potential of ML models using EHR data for early ADRD prediction, enabling timely interventions to delay progression and improve outcomes. These findings offer insights for future research and proactive care strategies.
Z-chromosome dosage compensation and a male-specific lncRNA in octopus
Authors: Papanicolaou Natali , Wettersten Sebastian , Kloosterman Alexander , Reinius Björn 
Published: December 2024

AbstractSex chromosomes typically present as two copies of a large, gene-rich differentiated chromosome in the homogametic sex (e.g. XX in female mammals, ZZ in male birds) but as a single copy in the heterogametic sex (XY in male mammals, ZW in female birds). This creates a significant gene-copy imbalance of the X and Z chromosomes between the sexes as well as between the single sex chromosome and the autosomes in the heterogametic sex, making its resolution essential. Dosage compensation and its molecular mechanisms have primarily been studied in select organisms, such as primates, rodents, birds, fruit flies, andC. elegans, while the extent and mechanisms of dosage compensation remain largely unexplored in the vast majority of animal taxa.Recently, coleoid cephalopods, including octopuses, squids, and cuttlefish, were reported to possess a ZZ/Z0 sex chromosome system1, where males carry two copies of the Z chromosome while females carry only one. However, whether dosage compensation occurs in these species remains unexplored. Here, we present evidence that Z-chromosome dosage compensation is achieved in octopus. In two species (Octopus vulgarisandOctopus sinensis), we observed male-to-female ratios of Z-chromosome expression exceeding 1 but significantly below 2, indicating partial dosage compensation, comparable to that achieved for the Z chromosome in birds. Additionally, Z-to-autosomal expression ratios were close to 1. Furthermore, we identified a Z-linked, male-specific long non-coding RNA (lncRNA) inO. vulgaris(“Zmast”), with conserved sequence in annotated Z-linked loci ofO. sinensis—notably expressed in a male-specific manner also in this species.Our results provide the first evidence of sex chromosome dosage compensation in octopus and introduce the intriguing possibility of a long non-coding RNA playing a sex-specific role in gene regulating.
ATG16L1 WD domain regulates lipid trafficking to maintain plasma membrane integrity to limit influenza virus infection
Authors: Bone Benjamin , Griffith Luke , Jefferson Matthew , Yamauchi Yohei , Wileman Thomas , Powell Penny P. 
Published: December 2024

ABSTRACTThe non-canonical functions of autophagy protein ATG16L1 are dependent on a C-terminal WD domain. Recent studies show that the WD domain is required for conjugation of LC3 to single membranes during endocytosis and phagocytosis, where it is thought to promote fusion with lysosomes. Studies in cells lacking the WD domain suggest additional roles in the regulation of cytokine receptor recycling and plasma membrane repair. The WD domain also protects mice against lethal influenza virusin vivo. Here, analysis of mice lacking the WD domain (ΔWD) shows enrichment of cholesterol in brain tissue suggesting a role for the WD domain in cholesterol transport. Brain tissue and cells from ΔWD mice showed reduced cholesterol and phosphatidylserine (PS) in the plasma membrane. Cells from ΔWD mice also showed an intracellular accumulation of cholesterol predominantly in late endosomes in cell culture. Infection studies using IAV suggest that the loss of cholesterol and PS from the plasma membrane in cells from ΔWD mice results in increased endocytosis and nuclear delivery of IAV, as well as increased IFNβ and ISG expression. Upregulation of IL-6, IFNβ and ISG mRNA were observed inex vivoprecision cut lung slices from ΔWD mice both at rest and in response to IAV infection. Overall, we present evidence that regulation of lipid transport by the WD domain of ATG16L1 may have downstream implications in attenuating viral infection and limiting lethal cytokine signaling.
Spatial organization of multisensory convergence in mouse isocortex
Authors: Patel Kinjal , Ryoo Avery Hee-Woon , Buice Michael , Mihalas Stefan , Tripp Bryan 
Published: December 2024

1AbstractThe diverse functions of different cortical areas are thought to arise from their distinct groups of inputs. However, additional organizing principles may exist in the spatial structure of converging inputs. We investigated spatial convergence patterns of projections from primary sensory areas to other areas throughout the mouse isocortex. We used a large tract tracing dataset to estimate the dimension of the space into which topographical connections from multiple modalities converged within each other cortical area. We call this measure the topography dimension (TD). TD is higher for areas that receive inputs of similar strength from multiple sensory modalities, and lower when multiple inputs terminate in register with one another. Across the isocortex, TD varied by a factor of 4. TD was positively correlated with hierarchy score, an independent measure that is based on laminar connection patterns. Furthermore, TD (an anatomical measure) was significantly related to several measures of neural activity. In particular, higher TD was associated with higher neural activity dimension, lower population sparseness, and lower lifetime sparseness of spontaneous activity, independent of an area’s hierarchical position. Finally, we analyzed factors that limited TD and found that linear correlations among projections from different areas typically had little impact, while diversity of connection strengths, both between different projections onto the same area, and within projections across different parts of an area, limited TD substantially. This analysis revealed additional intricacy of cortical networks, beyond areas’ sets of connections and hierarchical organization. We propose a means of approximating this organization in deep-network models.
A systematic review of training for mainstream mental health professionals working with people with intellectual disabilities and mental health needs
Authors: Hunter Emma , Sunley Jade , Richardson Shauni , Hemm Cahley , Dagnan Dave 
Published: December 2024

Purpose
Policy in the UK and many other countries states that mainstream mental health services should be accessible to people with intellectual disabilities (ID). The purpose of this paper is to systematically review training and development needs assessments and delivered training and development for professionals working in mainstream mental health services who may work with people with IQ.

Design/methodology/approach
A systematic search of four databases (Web of Science; PsychInfo; PubMed; CINAHL) over the period of 2011–2023 was used. Papers were included if they described training or development delivered to, or specific training or development needs analyses of, mainstream qualified staff to support working with adults who have an ID.

Findings
Two papers were found that described training and development initiatives and six that described training and development needs analysis, five of these papers originated from Australia and were part of the development of a comprehensive workforce competency framework.

Research limitations/implications
Training and development approaches for mainstream mental health services to facilitate the support of people with IQ should be systematically developed and trialled.

Originality/value
To the best of the authors’ knowledge, this is the first study to review training and training needs analysis in this area since 2012. The review finds only a small number of papers in what is an important area for service development.
The role of technology in tourist guiding: future career, service quality, marketing and tourist experiences
Authors: Seyitoğlu Faruk , Atsız Ozan , Akyuz Meral 
Published: December 2024

Purpose
This study aims to investigate the perceptions of tourist guides in Türkiye regarding the role of technology in the tourist guiding profession.

Design/methodology/approach
This research adopted an exploratory qualitative case study approach, conducting semi-structured interviews with 29 professional tourist guides actively working in different regions of Türkiye.

Findings
The findings reveal the dual roles of technology in tourist guiding. While it can facilitate service quality and enhance experiences, technologies such as robot tourist guides, augmented reality and virtual reality are perceived as disruptive and potentially damaging service quality and tourist experiences.

Originality/value
The research offers unique insights into the facilitative and disruptive aspects of technological tools in the tourism industry. These findings have direct implications for destination managers, travel agencies and tourist guides worldwide, equipping them with a comprehensive understanding of the role of technology in tourist guiding and guiding their future actions, strategies and policies.
Leader emergence as mediator of the relationship between individual career management and career success: a perspective of implicit leadership theory
Authors: Liu Songbo , Cheng Jinkai , Wang Zhen , Wei Shilong 
Published: December 2024

Purpose
This study aims to investigate how individual career management (ICM) affects career success in Chinese organizations. Leader emergence was examined through the theoretical lens of implicit leadership theory as a mediating mechanism of this relationship. In addition, leadership self-efficacy and organizational warmth were analyzed jointly as boundary conditions strengthening the relationship between ICM and leader emergence.

Design/methodology/approach
To avoid common method bias, the authors adopted a three-wave data collection with a one-month lagged design. A total of 765 questionnaires were distributed and 424 usable questionnaires were collected. Mplus version 8.3 was used to test the hypothesized relationships.

Findings
Findings indicated that ICM is positively related to subjective career success and objective career success via leader emergence. Moreover, leadership self-efficacy and organizational warmth jointly moderate the relationship between ICM and leader emergence.

Originality/value
Based on implicit leadership theory, this study identifies leader emergence as a critical mechanism explaining the positive impact of ICM on career success in the Chinese context. Lastly, results stress the simultaneous need for leadership self-efficacy and organization warmth, which can promote high-ICM employees to emerge as leaders.
FinTech as a digital innovation in microfinance companies – systematic literature review
Authors: Offiong Uwakmfon Promise , Szopik-Depczyńska Katarzyna , Cheba Katarzyna , Ioppolo Giuseppe 
Published: December 2024

PurposeThe main purpose of the paper is to identify the most important directions of research to date and to indicate new, emerging areas of research concerned with application of financial technology (FinTech) solutions in microfinance companies.Design/methodology/approachThis paper systematically reviews the literature on FinTech in microfinance, highlighting its role in enhancing operational efficiency, customer experience and financial inclusion through technologies like blockchain and AI. Despite these advancements, significant gaps remain in understanding the key drivers of FinTech as a digital innovation, most important direction of research to date and emerging areas for future research in microfinance literature. This paper has attempted to systematise the results of the research carried out so far, based on the publications indexed in the Web of Science and Scopus databases, using selected multidimensional statistical methods.FindingsThe findings identify key themes, gaps and future research directions, shedding light on the strategic implications of digital technology in microfinance. This comprehensive analysis significantly advances the understanding of how FinTech enhances microfinance management operations and objectives, contributing to both academic discourse and practical applications.Originality/valueThe research’s novelty lies in its focussed exploration of digital innovation within microfinance, an area that remains relatively underexplored. No similar paper was found during the literature review.