bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIGIT expression in extrahepatic cholangiocarcinoma and its impact on CD8 + T cell exhaustion: implications for immunotherapy
Authors: Tang Tengqian , Wang Wenhao , Gan Lang , Bai Jie , Tan Dehong , Jiang Yan , Zheng Ping , Zhang Weijun , He Yu , Zuo Qianfei , Zhang Leida 
Published: February 2025

Abstract
Extrahepatic cholangiocarcinoma (ECCA) is a malignant tumor. The precise role of T-cell immunoreceptor with Ig and ITIM domains (TIGIT), an emerging immunosuppressive receptor, in ECCA, and its impact on CD8+ T cell exhaustion (Tex) remains unclear. We performed single-cell RNA sequencing (scRNA-seq) to characterize tumor-infiltrating lymphocytes (TILs) isolated from ECCA. We found that TIGIT was significantly overexpressed in TOX+CD8 T cells. Tissue microarray and immunohistochemistry staining demonstrated that increased TIGIT expression was associated with poorer patient survival. Flow cytometry analysis revealed that TIGIT+CD8+ T cells exhibited decreased TNF-α, IFN-γ, and TCF-1 expression, accompanied by elevated PD-1 and TIM-3 expression compared to TIGIT−CD8+ T cells. In the patient-derived xenograft (PDX) model, the anti-TIGIT treatment group demonstrated reduced tumor weight, enhanced CD8 frequency, and an increased IFN-γ proportion compared to the PBS treatment group. The TIGIT antibody-treated group exhibited a notably higher fraction of GRZB, and anti-TIGIT treatment led to elevated TCF-1 protein levels and decreased protein levels of TOX1 and NR4A1. Moreover, TIGIT+CD8 T cells from TILs appear to be in a state of exhaustion with low potential killing capacity in ECCA, as shown by scRNA-seq. Taken together, the present study underscores the significant role of TIGIT in ECCA, contributing to T cell exhaustion and a compromised CD8+ T cell immune response. Targeting TIGIT presents a promising therapeutic avenue to enhance the CD8+ T-cell response, thereby potentially improving ECCA therapeutic benefits.
HIF2α drives ccRCC metastasis through transcriptional activation of methylation-controlled J protein and enhanced prolegumain secretion
Authors: Shen Tianyu , Su Yu , Wang Dekun , Li Gang , Liu Xuan , Sun Chuangxin , Hu Taoyu , Pang Haoxiang , Mi Xue , Zhang Yuying , Yue Shijing , Zhang Zhujun , Tan Xiaoyue 
Published: February 2025

Abstract
The role of hypoxia-inducible factor 2α (HIF2α) in clear cell Renal Cell Carcinoma (ccRCC) is still not fully understood. In this study, we identified that urinary prolegumain levels positively correlated with the malignant characteristics of ccRCC. In cultured 786-O and OSRC-2 cells, HIF2α downregulation reduced prolegumain secretion. RNA sequencing assay revealed that HIF2α induces methylation-controlled J (MCJ), a negative regulator on the mitochondrial respiratory chain. Silencing MCJ reduced prolegumain secretion, and MCJ overexpression restored prolegumain secretion inhibited by HIF2α downregulation. Chromatin immunoprecipitation and luciferase assay confirmed MCJ as a transcription target of HIF2α. Furthermore, we showed the ectopic MCJ overexpression reversed the improved mitochondrial damage resulting from HIF2α downregulation, as evidenced by electron microscope, ATP level, GSSG/GSH ratio, MitoSOX, and DHE staining. Through mass spectrometry analysis, we identified oxidation site His343 on the legumain sequence as contributing to the prolegumain secretion. Therapeutically, silencing MCJ or HIF2α or using ROS scavengers Vitamin C or MitoQ alleviated MMP2 activation as well as cell migration and tube formation. In a mouse orthotopic xenograft model of ccRCC, silencing MCJ or administration of MitoQ significantly protected against mitochondrial damage and subsequently reduced the lung metastasis of tumors. Overall, our study identified MCJ as a target molecule of HIF2α in ccRCC. Silencing MCJ or using ROS scavengers like MitoQ can suppress oxidation site His343 in legumain, preventing prolegumain secretion and subsequently reducing metastasis of ccRCC.
An optimised faecal microRNA sequencing pipeline reveals fibrosis in Trichuris muris infection
Authors: Layton Emma , Goldsworthy Sian , Yang EnJun , Ong Wei Yee , Sutherland Tara E. , Bancroft Allison J. , Thompson Seona , Au Veonice Bijin , Griffiths-Jones Sam , Grencis Richard K. , Fairhurst Anna-Marie , Roberts Ian S. 
Published: February 2025

Abstract
The intestine is a site of diverse functions including digestion, nutrient absorption, immune surveillance, and microbial symbiosis. Intestinal microRNAs (miRNAs) are detectable in faeces and regulate barrier integrity, host-microbe interactions and the immune response, potentially offering valuable non-invasive tools to study intestinal health. However, current experimental methods are suboptimal and heterogeneity in study design limits the utility of faecal miRNA data. Here, we develop an optimised protocol for faecal miRNA detection and report a reproducible murine faecal miRNA profile in healthy mice. We use this pipeline to study faecal miRNAs during infection with the gastrointestinal helminth, Trichuris muris, revealing roles for miRNAs in fibrosis and wound healing. Intestinal fibrosis was confirmed in vivo using Hyperion® imaging mass cytometry, demonstrating the efficacy of this approach. Further applications of this optimised pipeline to study host-microbe interactions and intestinal disease will enable the generation of hypotheses and therapeutic strategies in diverse contexts.
UM171 glues asymmetric CRL3–HDAC1/2 assembly to degrade CoREST corepressors
Authors: Yeo Megan J. R. , Zhang Olivia , Xie Xiaowen , Nam Eunju , Payne N. Connor , Gosavi Pallavi M. , Kwok Hui Si , Iram Irtiza , Lee Ceejay , Li Jiaming , Chen Nicholas J. , Nguyen Khanh , Jiang Hanjie , Wang Zhipeng A. , Lee Kwangwoon , Mao Haibin , Harry Stefan A. , Barakat Idris A. , Takahashi Mariko , Waterbury Amanda L. , Barone Marco , Mattevi Andrea , Carr Steven A. , Udeshi Namrata D. , Bar-Peled Liron , Cole Philip A. , Mazitschek Ralph , Liau Brian B. , Zheng Ning 
Published: February 2025

Abstract
UM171 is a potent agonist of ex vivo human haematopoietic stem cell self-renewal1. By co-opting KBTBD4, a substrate receptor of the CUL3–RING E3 ubiquitin ligase (CRL3) complex, UM171 promotes the degradation of the LSD1–CoREST corepressor complex, thereby limiting haematopoietic stem cell attrition2,3. However, the direct target and mechanism of action of UM171 remain unclear. Here we show that UM171 acts as a molecular glue to induce high-affinity interactions between KBTBD4 and HDAC1/2 to promote corepressor degradation. Through proteomics and chemical inhibitor studies, we identify the principal target of UM171 as HDAC1/2. Cryo-electron microscopy analysis of dimeric KBTBD4 bound to UM171 and the LSD1–HDAC1–CoREST complex identifies an asymmetric assembly in which a single UM171 molecule enables a pair of KELCH-repeat propeller domains to recruit the HDAC1 catalytic domain. One KBTBD4 propeller partially masks the rim of the HDAC1 active site, which is exploited by UM171 to extend the E3–neosubstrate interface. The other propeller cooperatively strengthens HDAC1 binding through a distinct interface. The overall CoREST–HDAC1/2–KBTBD4 interaction is further buttressed by the endogenous cofactor inositol hexakisphosphate, which acts as a second molecular glue. The functional relevance of the quaternary complex interaction surfaces is demonstrated by base editor scanning of KBTBD4 and HDAC1. By delineating the direct target of UM171 and its mechanism of action, we reveal how the cooperativity offered by a dimeric CRL3 E3 can be leveraged by a small molecule degrader.
fruit-SALAD: A Style Aligned Artwork Dataset to reveal similarity perception in image embeddings
Authors: Ohm Tillmann , Karjus Andres , Tamm Mikhail V. , Schich Maximilian 
Published: February 2025

Abstract
The notion of visual similarity is essential for computer vision, and in applications and studies revolving around vector embeddings of images. However, the scarcity of benchmark datasets poses a significant hurdle in exploring how these models perceive similarity. Here we introduce Style Aligned Artwork Datasets (SALAD), and an example of fruit-SALAD with 10,000 images of fruit depictions. This combined semantic category and style benchmark comprises 100 instances each of 10 easy-to-recognize fruit categories, across 10 easy distinguishable styles. Leveraging a systematic pipeline of generative image synthesis, this visually diverse yet balanced benchmark demonstrates salient differences in semantic category and style similarity weights across various computational models, including machine learning models, feature extraction algorithms, and complexity measures, as well as conceptual models for reference. This meticulously designed dataset offers a controlled and balanced platform for the comparative analysis of similarity perception. The SALAD framework allows the comparison of how these models perform semantic category and style recognition task to go beyond the level of anecdotal knowledge, making it robustly quantifiable and qualitatively interpretable.
Improving landslide susceptibility prediction through ensemble recursive feature elimination and meta-learning framework
Authors: Halder Krishnagopal , Srivastava Amit Kumar , Ghosh Anitabha , Das Subhabrata , Banerjee Santanu , Pal Subodh Chandra , Chatterjee Uday , Bisai Dipak , Ewert Frank , Gaiser Thomas 
Published: February 2025

Abstract
Landslides pose significant threats to ecosystems, lives, and economies, particularly in the geologically fragile Sub-Himalayan region of West Bengal, India. This study enhances landslide susceptibility prediction by developing an ensemble framework integrating Recursive Feature Elimination (RFE) with meta-learning techniques. Seven advanced machine learning models- Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Extremely Randomized Trees (ET), Gradient Boosting (GB), Extreme Gradient Boosting (XGBoost), and a Meta Classifier (MC) were applied using Remote Sensing and GIS tools to identify key landslide-conditioning factors and classify susceptibility zones. Model performance was assessed through metrics such as accuracy, precision, recall, F1 score, and AUC of the ROC curve. Among the models, the Meta Classifier (MC) achieved the highest accuracy (0.956) and AUC (0.987), demonstrating superior predictive ability. Gradient Boosting (GB), XGBoost, and RF also performed well, with accuracies of 0.943 and AUC values of 0.987 (GB and XGBoost) and 0.983 (RF). Extremely Randomized Trees (ET) exhibited the highest accuracy (0.946) among individual models and an AUC of 0.985. SVM and LR, while slightly less accurate (0.941 and 0.860, respectively), provided valuable insights, with SVM achieving an AUC of 0.972 and LR achieving 0.935. The models effectively delineated landslide susceptibility into five zones (very low, low, moderate, high, and very high), with high and very high susceptibility zones concentrated in Darjeeling and Kalimpong subdivisions. These zones are influenced by intense rainfall, unstable geological structures, and anthropogenic activities like deforestation and urbanization. Notably, ET, RF, GB, and XGBoost demonstrated efficiency in feature selection, requiring fewer input variables while maintaining high performance. This study establishes a benchmark for landslide susceptibility mapping, providing a scalable and adaptable framework for geospatial hazard prediction. The findings hold significant implications for land-use planning, disaster management, and environmental conservation in vulnerable regions worldwide.
Crystal structure of the plasmid-encoded R67 dihydrofolate reductase complexed with Congo red an amyloid binding dye
Authors: Narendra Akshay N. , Howell Elizabeth E. , Narayana Narendra 
Published: February 2025

Abstract
Plasmid-encoded bacterial R67 dihydrofolate reductase (DHFR) catalyzes the same reaction as the chromosomal counterpart but is highly resistant to the widely used antibiotic Trimethoprim (TMP) unlike the chromosomal enzyme. The structure of Q67H mutant of R67 DHFR complexed with a non-specific inhibitor Congo red (CGR) has been determined at 1.15 Å resolution. In the F

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-F

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map, one of the two naphthalene moieties in CGR is clearly observed, however, the biphenyl linker and the other naphthalene moiety are not seen owing to flexibility. CGR does not utilize its twofold axis to align with any of the three crystallographic twofold axes of the tetrameric protein instead, it binds like the asymmetrical folate and NADP+ at any one of the four symmetry-related positions in the active site pore. The naphthalene moiety with exocyclic sulphonate ion and amino group, interacts with residues 66–68 from all four protomers via metal-based ionic, van der Waals, stacking, and hydrogen bonding interactions. Preliminary modeling studies suggest variant fragments of CGR targeting one or both Lys32 residues at the site of enlarging pore may yield specific and potent inhibitors. Based on the CGR – protein interactions in the present work, we propose a putative model for the binding of CGR to cross-β amyloid.
Controlling mildew of tobacco leaf by Bacillus amyloliquefaciens ZH-2 and its effect on storage quality of tobacco leaf
Authors: Zhou Hang , Yang Yongfeng , Jia Tao , Yu Yangyang , Chen Siyuan , Qiu Yao , Zhang Ruina , Chen Hongli 
Published: February 2025

Abstract
Tobacco mildew is a common fungal disease that reduces tobacco quality, resulting in serious economic losses in the tobacco industry. In this study, the pathogens Aspergillus niger, Aspergillus flavus, and Rhizopus arrhizus were isolated from infected leaves. Furthermore, five plant endophytic bacteria isolated from healthy tobacco leaves were found to possess strong antifungal activity against these pathogens. Among these strains, Bacillus amyloliquefaciens ZH-2 exerted the strongest antagonistic effect against all mildew types (bacteriosphere diameter > 22 mm). The antagonistic action of ZH-2 was further observed using scanning electron microscopy, which revealed signs of contraction, deformation, and dissolution of the treated mycelia compared with that seen in the control group. The ZH-2 strain was found to produce high levels of proteases, chitinases, and β-1,3-glucanase, contributing to its antifungal activity via fungal cell wall rupture. The antifungal activity of ZH-2 was also demonstrated in the application test, as indicated by the significant reduction in mildew disease severity in tobacco leaves treated with this strain. Fermentation tests showed that the quality of ZH-2–treated, solid-state fermented tobacco leaves was superior to that of the control. Specifically, the alkaloid content significantly decreased by 10.62%, whereas the total and reduced sugar contents increased by 12.9 and 55.75%, respectively. Furthermore, macromolecular starch, cellulose, and protein contents significantly decreased by 25.85, 12.77, and 10.04%, respectively. These results indicate that the Bacillus amyloliquefaciens ZH-2 strain is effective against tobacco mildew and can improve tobacco quality upon solid-state fermentation.
Decreasing aerosols increase the European summer diurnal temperature range
Authors: Roesch Carla M. , Fons Emilie , Ballinger Andrew P. , Runge Jakob , Hegerl Gabriele C. 
Published: February 2025

Abstract
The diurnal temperature range (DTR), the difference between daily maximum and minimum temperature, is important for the impact of extreme temperatures, but despite physical links to aerosol forcing previous studies have struggled to attribute observed DTR changes to aerosols. Using causal inference, we can clearly identify aerosols as a driver of European DTR change since 1940. Following a decrease from the 1940s, since the 1980s the European DTR has increased by about 0.5K due to a reduction in European aerosol emissions leading to cooler nights relative to days. Agreement between causal effects estimated from observations with those estimated for two CMIP6 models evaluates the models’ microphysical and radiative parameterizations. From causal effects, we also derive effective radiative forcing estimates of aerosols on surface shortwave during European summer, which amount to [−1.7; −1.5] Wm−2 in observations and one model, while it is less negative in the other model ([−0.9; −0.8] Wm−2).
Multiple planetary boundaries preclude biomass crops for carbon capture and storage outside of agricultural areas
Authors: Braun Johanna , Werner Constanze , Gerten Dieter , Stenzel Fabian , Schaphoff Sibyll , Lucht Wolfgang 
Published: February 2025

Abstract
Six of nine planetary boundaries are currently transgressed, many related to human land use. Conversion of sizeable land areas to biomass plantations for Bioenergy with Carbon Capture and Storage (BECCS) – often assumed in climate mitigation scenarios to meet the Paris Agreement – may exert additional pressure on terrestrial planetary boundaries. Using spatially-explicit, process-based global biogeochemical modelling, we systematically compute feedstock production potentials for BECCS under individual and joint constraints of the planetary boundaries for nitrogen flows, freshwater change, land system change and biosphere integrity (including protection of remaining forests), while reserving current agricultural areas for meeting the growing global demand for food, fodder and fibre. We find that the constrained BECCS potential from dedicated Miscanthus plantations is close to zero (0.1 gigatons of carbon dioxide equivalents per year under mid-century climate for Representative Concentration Pathway (RCP) 4.5). The planetary boundary for biosphere integrity has the largest individual effect, highlighting a particularly severe trade-off between climate change mitigation with BECCS and ecosystem preservation. Ultimately however, the overall limitation results from the joint effect of all four planetary boundaries, emphasizing the importance of a holistic consideration of Earth system stability in the context of climate change mitigation.
Early Intervention Providers' Perspectives on the Use of Telepractice During the COVID-19 Pandemic
Authors: Mahurin-Smith Jamie , Lorio Ciera M. 
Published: February 2025

Purpose:
The COVID-19 pandemic precipitated an abrupt transition to telepractice for many early intervention (EI) service providers; often, they had little previous experience with remote service provision. This study was designed to investigate their experiences with telepractice.

Method:
This qualitative study used interpretative phenomenological analysis to evaluate semistructured phone interviews with eight Illinois EI providers, recruited through EI agencies, social media, and word of mouth. In their interviews, they described the challenges and benefits of the transition to telepractice in 2020–2021.

Results:
These participants described a difficult adjustment period due to the unprecedented effects of the COVID-19 pandemic and a number of technological and interpersonal challenges. After this adjustment, they found telepractice offered a surprising and welcome degree of flexibility and spurred them to place new emphasis on caregiver coaching.

Conclusions:
Telepractice presents unique challenges and offers unique benefits to EI service providers due to the age of their clients and their emphasis on caregiver coaching. Clinical implications are discussed.
Kausale Immunmodulation
Authors: Grafen Keren , Blume Ralf , Zhang Zheng , Vigl Sebastian 
Published: February 2025

SummaryVier Experten stellen Behandlungsansätze für eine kausale Immunmodulation mithilfe von der Förderung der Darmgesundheit, Homöopathie, Traditioneller Chinesischer Medizin und Phytotherapie dar.
Tendon Anatomy and Tendon Disorders of the Wrist
Authors: Marth Thomas , Grob Nadja A. , Jacobson Jon A. , Zechmann Nadja , Guggenberger Roman , Falkowski Anna L. 
Published: February 2025

AbstractWrist pain is common and can be attributed to tendon pathologies.This review aims to give a structured review of tendon anatomy, discuss anatomical pitfalls, and provide an overview of typical tendon pathologies of the wrist based on the current literature.Typical tendon pathologies of the wrist include de Quervain tenosynovitis, proximal and distal intersection syndrome, extensor and flexor pollicis longus tendon ruptures, and extensor carpi ulnaris subsheath injury. Typical pitfalls are multiple bundles of the abductor pollicis longus tendon or the centrally increased signal of the extensor carpi ulnaris tendon.Both ultrasound and MRI are appropriate modalities for assessing the tendons of the wrist. Knowledge of normal anatomy, variants, pathologies, as well as appropriate imaging is crucial to determine the diagnosis.
Alternativa cirúrgica para leiomioma cutâneo pilar múltiplo de membro inferior: Relato de caso e revisão da literatura
Authors: Soares Igor Moura , Cunha Armando dos Santos , Aquino Lucas Albuquerque , Dalbosco Lucas Vargas , Vilela Marcela Santos , Gomes Saulo Francisco de Assis 
Published: February 2025

ResumoO leiomioma pilar, ou neoplasia benigna do músculo eretor do pelo, é uma patologia incomum, apesar de ser o tipo mais frequente de leiomioma cutâneo. Ocorre entre adultos jovens, acometendo igualmente ambos os sexos. Sua apresentação se dá em lesões dolorosas, isoladas ou múltiplas, papulonodulares vermelhas e castanhas. Apesar de não ter sido relatada nenhuma malignização dos tumores, é importante incluir essa patologia no diagnóstico diferencial de lesões cutâneas papulonodulares. O tratamento cirúrgico geralmente é reservado a casos extensos e sintomáticos, com relatos de recidiva. Nesse artigo, relatamos o caso de um paciente de 28 anos, do sexo masculino, com diagnóstico de leiomioma pilar em face lateral de coxa e perna direita submetido à ressecção de pele tangencial.
Pressure-induced metallization and semiconductor PN transition in InAs
Authors: Gao Yang , Gu Yushi , Zhuang Teng , Tian Lianhua , Gu Guangrui , Piao Hongguang , Wu Baojia , Han Yonghao 
Published: February 2025

Employing a diamond anvil cell, we measured resistivity and the Hall effect of InAs under pressures of 25 GPa, identifying key structural and electronic phase transitions at 3.8, 7.2, 10.3, and 14.7 GPa. The resistivity minima at 7.2 and 14.7 GPa coincide with structural shifts, while changes between 3.8 and 10.3 GPa indicate electronic transitions, including metallization and semiconductor type inversion. First-principles calculations validate these observations, highlighting the role of pressure in tailoring semiconductor properties, with implications for developing high-performance devices.