bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of YTHDC1 m6A reading function promotes invasiveness in urothelial carcinoma of the bladder
Authors: Xu Jinyun , Koch Jonas , Schmidt Claudia , Nientiedt Malin , Neuberger Manuel , Erben Philipp , Michel Maurice Stephan , Rodríguez-Paredes Manuel , Lyko Frank 
Published: January 2025

Abstract
Bladder cancer poses significant clinical challenges due to its high metastatic potential and poor prognosis, especially when it progresses to muscle-invasive stages. Here, we show that the m6A reader YTHDC1 is downregulated in muscle-invasive bladder cancer and is negatively correlated with the expression of epithelial‒mesenchymal transition genes. The functional inhibition or depletion of YTHDC1 increased the migration and invasion of urothelial cells. Integrative analysis of multimodal sequencing datasets provided detailed insights into the molecular mechanisms mediating YTHDC1-dependent phenotypes and identified SMAD6 as a key transcript involved in the invasiveness of urothelial carcinoma of the bladder. Notably, SMAD6 mRNA colocalized less with YTHDC1 in tumoral tissues than in paratumoral tissues, indicating disrupted binding during cancer progression. Our findings establish YTHDC1-dependent m6A reading as a critical epitranscriptomic mechanism regulating bladder cancer invasiveness and provide a paradigm for the epitranscriptomic deregulation of cancer-associated networks.
SPOCK2 controls the proliferation and function of immature pancreatic β-cells through MMP2
Authors: Blaszczyk Katarzyna , Jedrzejak Anna P. , Ziojla Natalia , Shcheglova Ekaterina , Szarafin Karolina , Jankowski Artur , Beamish Christine A. , Chmielowiec Jolanta , Sabek Omaima M. , Balasubramanyam Ashok , Patel Sanjeet , Borowiak Malgorzata 
Published: January 2025

Abstract
Human pluripotent stem cell-derived β-cells (SC-β-cells) represent an alternative cell source for transplantation in diabetic patients. Although mitogens could in theory be used to expand β-cells, adult β-cells very rarely replicate. In contrast, newly formed β-cells, including SC-β-cells, display higher proliferative capacity and distinct transcriptional and functional profiles. Through bidirectional expression modulation and single-cell RNA-seq, we identified SPOCK2, an ECM protein, as an inhibitor of immature β-cell proliferation. Human β-cells lacking SPOCK2 presented elevated MMP2 expression and activity, leading to β-integrin-FAK-c-JUN pathway activation. Treatment with the MMP2 protein resulted in pronounced short- and long-term SC-β-cell expansion, significantly increasing glucose-stimulated insulin secretion in vitro and in vivo. These findings suggest that SPOCK2 mediates fetal β-cell proliferation and maturation. In summary, we identified a molecular mechanism that specifically regulates SC-β-cell proliferation and function, highlighting a unique signaling milieu of SC-β-cells with promise for the robust derivation of fully functional cells for transplantation.
Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation
Authors: Kim Jeeho , Jeon Young Jin , Chang In-Youb , Lee Jung-Hee , You Ho Jin 
Published: January 2025

Abstract
Wnt signaling is essential for cell growth and tumor formation and is abnormally activated in colorectal cancer (CRC), contributing to tumor progression; however, the specific role and regulatory mechanisms involved in tumor development remain unclear. Here, we show that Ephexin1, a guanine nucleotide exchange factor, is significantly overexpressed in CRC and is correlated with increased Wnt/β-catenin pathway activity. Through comprehensive analysis, including RNA sequencing data from TCGA and functional assays, we observed that Ephexin1 promotes tumor proliferation and migration by activating the Wnt/β-catenin pathway. This effect was mediated by the interaction of Ephexin1 with Axin1, a critical component of the β-catenin destruction complex, which in turn enhanced the stability and activity of β-catenin in signaling pathways critical for tumor development. Importantly, our findings also suggest that targeting Ephexin1 may increase the efficacy of Wnt/β-catenin pathway inhibitors in CRC treatment. These findings highlight the potential of targeting Ephexin1 as a strategy for developing effective treatments for CRC, suggesting a novel and promising approach to therapy aimed at inhibiting cancer progression.
Sub-terahertz transmissive reconfigurable intelligent surface for integrated beam steering and self-OOK-modulation
Authors: Shen Dongfang , Lan Feng , Wang Luyang , Song Tianyang , Yang Munan , Hu Tianyu , Li Yueting , Nie Xiaolei , Yang Jiayao , Liang Shixiong , Zeng Hongxin , Zhang Hui-Fang , Mazumder Pinaki , Yang Ziqiang , Zhang Yaxin , Cui Tie Jun 
Published: January 2025

AbstractBoasting superior flexibility in beam manipulation and a simpler framework than traditional phased arrays, terahertz metasurface-based phased arrays show great promise for 5G-A/6G communication networks. Compared with the reflective reconfigurable intelligent surface (reflective RIS), the transmissive RIS (TRIS) offers more feasibility for transceiver multiplexing systems to meet the growing demand for high-performance beam tracking in terahertz communication and radar systems. However, the terahertz TRIS encounters greater challenges in phase shift, beam efficiency, and complex circuitry. Here, we propose a sub-terahertz TRIS based on the phase shift via Pancharatnam-Berry (PB) metasurface and self-on-off keying (OOK) modulation via Schottky diodes. The electrically reconfigurable unit cell consists of a column-wise phase resonator and a rectangular slot. An experimental retrieved equivalent lumped-element circuit model is implemented in joint field-circuit simulations and is validated by experiments. A fabricated prototype demonstrates excellent performance of TRIS with the minimum insertion loss of 2.8 dB for operational states, large bandwidth nearly covering the entire W-band for 1-bit phase shift, deep OOK amplitude modulation of 12 dB, and wide scanning range of ±60° with low specular transmission. We further implement an integrated platform combining high-speed beam steering and spatial-light modulation, verifying the point-to-point signal transmissions in different directions using the TRIS platform. The proposed TRIS with high-performance and cost-effective fabrication makes it a promising solution to terahertz minimalist communication systems, radar, and satellite communication systems.
High-resolution genomic history of early medieval Europe
Authors: Speidel Leo , Silva Marina , Booth Thomas , Raffield Ben , Anastasiadou Kyriaki , Barrington Christopher , Götherström Anders , Heather Peter , Skoglund Pontus 
Published: January 2025

AbstractMany known and unknown historical events have remained below detection thresholds of genetic studies because subtle ancestry changes are challenging to reconstruct. Methods based on shared haplotypes1,2 and rare variants3,4 improve power but are not explicitly temporal and have not been possible to adopt in unbiased ancestry models. Here we develop Twigstats, an approach of time-stratified ancestry analysis that can improve statistical power by an order of magnitude by focusing on coalescences in recent times, while remaining unbiased by population-specific drift. We apply this framework to 1,556 available ancient whole genomes from Europe in the historical period. We are able to model individual-level ancestry using preceding genomes to provide high resolution. During the first half of the first millennium ce, we observe at least two different streams of Scandinavian-related ancestry expanding across western, central and eastern Europe. By contrast, during the second half of the first millennium ce, ancestry patterns suggest the regional disappearance or substantial admixture of these ancestries. In Scandinavia, we document a major ancestry influx by approximately 800 ce, when a large proportion of Viking Age individuals carried ancestry from groups related to central Europe not seen in individuals from the early Iron Age. Our findings suggest that time-stratified ancestry analysis can provide a higher-resolution lens for genetic history.
Learning the fitness dynamics of pathogens from phylogenies
Authors: Lefrancq Noémie , Duret Loréna , Bouchez Valérie , Brisse Sylvain , Parkhill Julian , Salje Henrik 
Published: January 2025

Abstract
The dynamics of the genetic diversity of pathogens, including the emergence of lineages with increased fitness, is a foundational concept of disease ecology with key public-health implications. However, the identification of such lineages and estimation of associated fitness remain challenging, and is rarely done outside densely sampled systems1,2. Here we present phylowave, a scalable approach that summarizes changes in population composition in phylogenetic trees, enabling the automatic detection of lineages based on shared fitness and evolutionary relationships. We use our approach on a broad set of viruses and bacteria (SARS-CoV-2, influenza A subtype H3N2, Bordetella pertussis and Mycobacterium tuberculosis), which include both well-studied and understudied threats to human health. We show that phylowave recovers the main known circulating lineages for each pathogen and that it can detect specific amino acid changes linked to fitness changes. Furthermore, phylowave identifies previously undetected lineages with increased fitness, including three co-circulating B. pertussis lineages. Inference using phylowave is robust to uneven and limited observations. This widely applicable approach provides an avenue to monitor evolution in real time to support public-health action and explore fundamental drivers of pathogen fitness.
Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial
Authors: Korompoki Eleni , Heuschmann Peter , Harvey Kirsten H. , Fiessler Cornelia , Malzahn Uwe , Hügen Klemens , Ullmann Sabine , Todd Gabriele Putz , Schuhmann Carolin , Montaner Joan , Sibon Igor , Debette Stephanie , Enzinger Christian , Ropele Stefan , Rücker Viktoria , Haas Kirsten , Harvey Emily , Wolfe Charles , Wang Yanzhong , Nielsen Peter B. , Caso Valeria , Lip Gregory Y. H. , Lane Deirdre A. , Halse Omid , Ringleb Peter , Haefeli Walter E. , Foerster Kathrin I. , Wurmbach Viktoria S. , Veltkamp Roland ,   on behalf of PRESTIGE-AF investigators
Published: January 2025

AbstractAdequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug). Randomization occurred in a 1:1 ratio and stratification was based on ICH location and sex. The two co-primary binary endpoints included ischemic stroke and recurrent ICH which will be analyzed hierarchically according to the intention-to-treat principle. Secondary efficacy endpoints encompassed all-stroke and systemic embolism, all-cause and cardiovascular mortality, major adverse cardiac events, and net clinical benefit. Secondary safety endpoints included any major hemorrhage and intracranial hemorrhage. All outcome events were adjudicated by an independent committee. Results of PRESTIGE-AF are expected to support risk-adjusted secondary prevention in ICH survivors with AF and to inform clinical guideline recommendations.
Vacuum-Assisted Excision of B3 Lesions: A District General Hospital Experience
Authors: Sandhya Anu , Tahir Qurat Ul Ain , Veerapatheran Keerthanaa 
Published: January 2025

Abstract
Objective The objective of this study was to evaluate the efficacy of utilizing vacuum-assisted excision (VAE) for the management of B3 lesions and to determine the rate of malignant upgrades.
Materials and Methods This observational study was conducted at Surrey and Sussex NHS Healthcare Redhill. All patients with B3 histology on core biopsy from October 2019 to October 2022 were included in the study. The upgrades in both the B3 group with atypia and the B3 group without atypia were examined in terms of ductal carcinoma in situ (DCIS), invasive status, and grade. The data obtained were analyzed using the SPSS version 21.
Results About 65% of the participants in the present study have B3 lesions in their left breast and 43% of the participants have lesions located in the upper inner area of the breast. The majority of the participants in the study had B3 lesions without atypia (75%). In 70 participants, VAE was performed. Out of 70 participants, only 15 had lesion upgrade after VAE (21.4%). Post-VAE follow-up planning was discussed in multidisciplinary team as per the National Health Service breast screening guidelines.
Conclusion The utilization of VAE is a viable alternative strategy for the treatment of B3 lesions, resulting in a decrease in the necessity for invasive surgical interventions. This observational study shows the efficacy of a less invasive procedure in replacement of a surgical procedure producing optimal long-term benefit and less side effects.
Contemporary Use of ctDNA for the Colorectal Surgeon
Authors: Heit Madilyn , Cohen Stacey A. 
Published: January 2025

AbstractWhile advances in treatment and diagnostics have improved prognosis in colorectal cancer (CRC), room for advancement remains, highlighting the importance of improving tools for early detection and treatment guidance. Current national guidelines rely on stage-based treatment recommendations but fail to identify patients with lower stage disease who have a higher likelihood of recurrence or those for whom additional therapy may not be beneficial. Circulating tumor DNA (ctDNA) is an emerging noninvasive blood-based assay, which can inform cancer status as a single time point and/or longitudinal biomarker. ctDNA can be used for the diagnosis of cancer, detection of minimal/molecular residual disease, molecular profiling, and assessing treatment response. In patients for whom operative management is indicated, detectable ctDNA is associated with worse survival outcomes. This review highlights the expanding field of ctDNA in CRC, underlining pivotal data and areas with the need for more research that are key for colorectal surgeons to understand.
Artificial intelligence–enabled histology exhibits comparable accuracy to pathologists in assessing histological remission in ulcerative colitis: a systematic review, meta-analysis, and meta-regression
Authors: Puga-Tejada Miguel , Majumder Snehali , Maeda Yasuharu , Zammarchi Irene , Ditonno Ilaria , Santacroce Giovanni , Capobianco Ivan , Robles-Medranda Carlos , Ghosh Subrata , Iacucci Marietta 
Published: January 2025

Abstract

Background and Aims
Achieving histological remission is a desirable emerging treatment target in ulcerative colitis (UC), yet its assessment is challenging due to high inter- and intraobserver variability, reliance on experts, and lack of standardization. Artificial intelligence (AI) holds promise in addressing these issues. This systematic review, meta-analysis, and meta-regression evaluated the AI’s performance in assessing histological remission and compared it with that of pathologists.

Methods
We searched Medline/PubMed and Scopus databases from inception to September 2024. We included studies on AI models assessing histological activity in UC, with or without comparison to pathologists. Pooled performance metrics were calculated: sensitivity, specificity, positive and negative predictive value (PPV and NPV), observed agreement, and F1 score. A pairwise meta-analysis compared AI and pathologists, while sub-meta-analysis and meta-regression evaluated heterogeneity and factors influencing AI performance.

Results
Twelve studies met the inclusion criteria. AI models exhibited strong performance with a pooled sensitivity of 0.84 (95% CI, 0.80–0.88), specificity 0.87 (0.84–0.91), PPV 0.90 (0.87–0.92), NPV 0.80 (0.71–0.88), observed agreement 0.85 (0.82–0.89), and F1 score 0.85 (0.82–0.89). AI models demonstrated no significant differences with pathologists for specificity, observed agreement, and F1 score, while they were outperformed by pathologists for sensitivity and NPV. AI models for the adult population were linked to reduced heterogeneity and enhanced AI performance at meta-regression.

Conclusions
AI shows significant potential for assessing histological remission in UC and performs comparably to pathologists. Future research should focus on standardized, large-scale studies to minimize heterogeneity and support widespread AI implementation in clinical practice.
AD BLOOD BIOMARKERS IN DIVERSE COMMUNITY SETTINGS: A LONGITUDINAL PERSPECTIVE FROM THE ARIC STUDY
Authors: Palta Priya , Sullivan Kevin , Merten Natascha 
Published: January 2025

Abstract
Alzheimer’s disease and related dementias (ADRD) feature a prolonged preclinical stage spanning decades, with the transition from mid- to late-life marking the critical period for onset and accumulation of pathological brain changes that may lead to physical and cognitive disability. Identifying individuals at risk for cognitive and physical decline during preclinical stages when interventions or disease modifying treatments are more likely to be effective is needed. Blood biomarkers of ADRD pathology and neurodegeneration are promising cost-effective and non-invasive options to fill this gap. To date, however, there are limited data on temporal changes in blood biomarkers and their associations with cognitive, mobility, and neuroimaging outcomes in diverse community-based cohorts. This symposium will feature 23 years of data from the well-established community-based Atherosclerosis Risk in Communities (ARIC) Study cohort which assayed blood biomarkers of amyloid-β (Aβ)42/40, phosphorylated tau at threonine 181 (p-Tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) using Quanterix Simoa assays on stored specimens at up to 3 timepoints in midlife and late-life in ~1,800 participants. This session will present findings on temporal blood biomarker changes from mid- to late-life and associated risk and protective factors of biomarker changes; mid- to late-life changes in blood biomarkers and associations with late-life neuroimaging measures of neurodegeneration, cerebrovascular disease, and amyloid deposition; and the associations of late-life blood biomarkers with prevalent and incident mobility and cognitive impairment.
CHANGE IN ALZHEIMER’S DISEASE BLOOD-BASED BIOMARKERS AND ASSOCIATIONS WITH BRAIN AMYLOID DEPOSITION
Authors: Pike James , Lu Yifei , Chen Jinyu , Walker Keenan , Sullivan Kevin , Griswold Michael , Mosley Thomas , Palta Priya 
Published: January 2025

Abstract
Blood-based biomarkers show promise as a noninvasive, inexpensive method for measuring Alzheimer’s disease pathology throughout the lifecourse. However, the prospective associations and discriminatory accuracy of these biomarkers at different stages of the lifecourse and among diverse, community-dwelling populations requires further investigation. Between 2014 and 2015, 329 dementia-free participants from the Atherosclerosis Risk in Communities Study underwent brain MRI and PET scans. Amyloid positivity was defined as a standardized uptake value ratio greater than 1.2. Stored plasma samples collected in midlife (1993-95, mean age 58.5 years) and late-life (2011-13, mean age 76.2 years) from a subsample of 259 participants were assayed in 2022. The assay quantified amyloid-β (Aβ)42/40, phosphorylated tau (p-Tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Logistic regression models estimated the association between plasma biomarkers from midlife and late-life and amyloid positivity in late-life. Receiver operating characteristic curves documented the discriminatory accuracy of the biomarkers. Assays from midlife were not associated with amyloid positivity in late-life. However, late-life measurements of Aβ42/40, p-Tau181, and GFAP and change per decade from midlife to late-life in p-Tau181 and GFAP were associated with greater odds of amyloid positivity. The greatest discriminatory accuracy was achieved by using all assays measured in midlife and late-life (AUC = 0.754), although the accuracy when using only late-life measures was comparable (AUC = 0.737). Additional longitudinal research is needed to determine whether changes in plasma biomarkers measured before an individual is amyloid positive can identify older adults at risk of developing Alzheimer’s disease.
SUPPORTIVE HOME FEATURES AS PROACTIVE/REACTIVE ASSOCIATES OF DAILY FUNCTIONING IN OLDER ADULTS
Authors: Barbakoff Daniel , Glennie Kristen , Steinman Bernard A 
Published: January 2025

Abstract
Supportive home features (SHF) include attributes of living spaces meant to help people overcome physical limitations that may be barriers to living independently. Evidence suggests that SHFs, including home modifications (HM), may help older adults to age in place at home. However, real-life implementation of HMs is not fully understood. The purpose of this study was to clarify associations between functioning in daily-living activities and the presence of SHFs. We analyzed two waves (2011 and 2015) of the National Health and Aging Trends Study (NHATS) to examine the directionality of this relationship. SHFs were operationalized using indicators of home accessibility (e.g., presence of a bedroom, kitchen, and full bathroom with a shower or tub on the same floor). HMs were operationalized based on whether bathroom fixtures were modified to accommodate disability with features such as grab bars. Daily activities were assessed using measures of activities of daily living (ADL; e.g., dressing) and instrumental ADLs (IADL; e.g., preparing a meal). Changes in ADL/IADL functioning and SHF/HM variables were assessed over the 5-year period. Regression models also included covariates for sociodemographics, chronic conditions, mobility functioning, and participation. Results show that, whereas ADL limitations statistically predict SHF/HM outcomes, the implementation of SHF/HMs does not predict any ADL/IADL outcomes. These findings suggest that in real life, older adults implement SHF/HMs reactively in response to functional needs, as opposed to planning proactively to meet needs in the future.