bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidental Mucinous Neoplasms of the Pancreas: Performance of the AGA, European, and IAP Guidelines in Advising Further Management after Endoscopic ultrasound-guided fine-needle Aspiration Biopsy
Authors: Pacheco Débora , Micelli-Neto Otávio , Taglieri Eloy , Issamu Tabushi Fernando , Malafaia Osvaldo , Cañada Trofo Surjan Rodrigo , Machado Marcel Autran , Venco Filadélfio Euclides , Kemp Rafael , dos Santos José Sebastião , Ardengh José Celso 
Published: January 2025

Objectives:
We compared the performance of AGA-2015, ESG-2018, and IAP-2024 guidelines in referring patients for surgery versus surveillance when applied to incidental after diagnosis by EUS-FNA.

Methods:
Single-center, retrospective study with prospective data collection. PLs identified incidentally on CT or MRI/MRCP performed for other diseases with inconclusive imaging results were eligible for analysis. After EUS-FNA and microhistological diagnosis, each of the guidelines was applied; sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were compared.

Results:
140 asymptomatic patients (mean age 64.7 y, 61% female) had a confirmed diagnosis of MN. Of these, 42 (30%) had “high rik stigmata” and 16 (11.4%) were malignant. AGA-2015, ESG-2018, and IAP-2024, criteria would have advised surgery unnecessarily in 66%, 15%, and 46%, respectively (P<0.001). AGA-2015, ESG-2018, and IAP-2024, and criteria failed to identify 59%, 46.1%, and 33.3% of HGD/IC, respectively (P=1.00).

Conclusion:
The AGA-2015 criteria were highly specific, while IAP-2024 had superior sensitivity. All had moderate sensitivity to indicate surgery, and all missed similar numbers of malignant lesions. Performing EUS-FNA before application of guidelines seems appropriate to guide further management of asymptomatic PLs, preventing unnecessary surgery and referring patients appropriately for surveillance. The ESG-2018 guideline proved most accurate for this purpose.
Mpox primer for clinicians: what makes the difference in 2024?
Authors: Abdel-Rahman Sama Mahmoud , Bayici Büşra Zeynep , Keske Şiran , Kuşkucu Mert , Özsürekçi Yasemin , Rimoin Anne W. , Rodriguez-Morales Alfonso J. , Ergönül Önder 
Published: January 2025

Purpose of review
The 2024 mpox outbreak, primarily driven by the possibly more virulent clade Ib strain, prompted the WHO declaring it a public health emergency of international concern (PHEIC) on August 14, 2024. This review provides essential guidance for clinicians managing mpox cases, as it contrasts the features of the 2024 outbreak with those of the 2022 epidemic to support better clinical decision-making.

Recent findings
The review highlights significant differences between the 2024 and 2022 outbreaks, including total case numbers, demographic distribution, and fatality rates. It also examines the increased severity associated with clade Ib. The article reviews the differential diagnosis of mpox, diagnostic tools, updates on Tecovirimat treatment, and infection control practices, particularly among healthcare workers. Vaccination strategies, including the role of smallpox vaccines and at-risk groups, are also discussed, along with recommendations for countries outside Africa.

Summary
The findings underscore the importance of early diagnosis and appropriate treatment for mpox in light of the 2024 outbreak's unique characteristics. Clinicians are advised to stay informed about updated diagnostic and therapeutic strategies, including vaccine recommendations, to mitigate the spread of the disease.
Performance of an Algorithm Grading Surgery-Related Adverse Events According to the Clavien-Dindo Classification
Authors: Båverud Olsson Lisen , Parkan Dennis , Sjövall Annika , Nauclér Pontus , van der Werff Suzanne D. , Buchli Christian 
Published: January 2025

Objective:
To assess performance of an algorithm for automated grading of surgery-related adverse events (AEs) according to Clavien-Dindo (C-D) classification.

Summary Background Data:
Surgery-related AEs are common, lead to increased morbidity for patients, and raise healthcare costs. Resource-intensive manual chart review is still standard and to our knowledge algorithms using electronic health record (EHR) data to grade AEs according to C-D classification have not been explored.

Method:
The algorithm was developed in a research database containing all EHR data of Karolinska University Hospital Stockholm and returns a C-D grade for each AE within 30 days. This raw score was used to grade postoperative recovery of 1,379 elective colorectal procedures according to C-D classification and Comprehensive Complication Index® (CCI). Agreement with manual annotation of colorectal surgeon (gold standard) and research nurse (current practice) was assessed in a random sample of 399 procedures.

Results:
For the C-D classification, kappa was 0.77 (95%CI 0.71-0.84) for algorithm vs surgeon and 0.74 (95%CI 0.67-0.82) for algorithm vs nurse. The kappa value increased to 0.89 (95%CI 0.84-0.95) after correction of misclassified annotations of surgeon. The intraclass correlation for CCI between algorithm and surgeon was 0.89 (95%CI 0.87-0.91) after correction and 0.76 (95%CI 0.71-0.80) for algorithm vs nurse.

Conclusion:
The performance of the algorithm motivates in our opinion implementation to real-time data under continuous scientific evaluation of the impact on AEs in different types of surgery. In the future, local EHR data could be used to enhance risk prediction with machine learning techniques.
Not all branches are equal: Branch Length Evaluation for Phylogenetic Diversity analysis
Authors: Miranda-Esquivel Daniel Rafael 
Published: January 2025

AbstractPhylogenetic Diversity (PD) is a crucial metric in evolutionary and conservation studies; however, its dependence on branch-length information can be a source of uncertainty. Branch Length Evaluation for Phylogenetic Diversity analysis (BLEPD) is a free and open-source R program used to quantify the uncertainty in PD calculations caused by varying branch length information. It offers two main approaches: resampling branch lengths within the phylogenetic tree, and modifying individual branch lengths. By comparing the initial and selected areas after resampling or modification, BLEPD allows researchers to assess the sensitivity of PD to these variations. This analysis of branch length sensitivity provides valuable insights into the robustness of PD results and their dependence on this information. BLEPD may improve the interpretation of PD analyses in evolutionary, conservation, and ecological studies.
OVEREXPRESSION OF TEMPRANILLO-LIKE PROTEINS PROMOTES ENDORMANCY RELEASE IN POPLAR
Authors: Gómez-Soto D. , Triozzi P. M. , Conde D. , del Barrio C. , Allona I. , Perales M. 
Published: January 2025

ABSTRACTTrees in temperate and boreal latitudes synchronize their growth-dormancy cycles with seasonal environmental variations to ensure their survival over the years. Dormancy control is crucial during winter when plants cease growth and establish buds to protect their apical meristems from cold temperatures. To overcome endormancy, initiate bud break, and restore growth, plants must be exposed to a specific duration of chilling, referred to as the chilling requirement, which is species- and ecotype-dependent. In this work, we study the novel roles of twoTEMPRANILLO-like genes (TEML1andTEML2) in the annual cycle of poplar. We demonstrated thatPopulus TEMLgenes are regulated by photoperiod, cold temperatures and the circadian clock, and they play a role in the control of endodormancy. Notably, their function diverges from the role of its Arabidopsis orthologAtTEM, which regulatesFLOWERING LOCUS T (FT)transcription and the photoperiodic flowering transcription. Transcriptomic analysis of endodormant buds during winter revealed that the activation ofTEML1andTEML2promotes endodormancy release by modulating the expression of endodormancy regulators and growth-promoting genes.
Diacylglycerol kinase ζ dictates CD40-mediated immune synapse formation, mTORC1 signaling and plasma cell fate in B lymphocytes
Authors: Fernández-Barrecheguren Ana , Fernández-Rego Adrián , Fuentes-Cantos Lucía , Pons Tirso , Estrada Belén S. , Iborra-Pernichi Marta , Ebrahimi Tahmineh , Sagrega-Aparisi Ana , Cogliati Sara , Martínez-Martín Nuria , Jiménez-Saiz Rodrigo , Carrasco Yolanda R. 
Published: January 2025

ABSTRACTTo mount a robust T-dependent immune response, antigen-specific B lymphocytes require CD40 stimulation through immune synapse formation with CD4+T follicular helper cells. CD40 triggers the activation of mammalian target of rapamycin complex-1 (mTORC1) and remodels the mitochondria to meet increased bioenergetic and anabolic demands. We show that diacylglycerol-kinase-ζ (DGKζ) has a crucial role in activating the mTORC1 pathway and remodeling mitochondria downstream of CD40 signaling in B cells. DGKζ governs organelle translocation to the CD40-mediated immune synapse and the recruitment of mTORC1 to lysosomes. DGKζ−/−B cells exhibited impaired mitochondria function, protein biosynthesis, metabolite transporter expression and cell cycle progression, accompanied by dysregulation of the transcriptional network governing B cell fate. These defects lead to a blockage in the progression of the germinal center response and plasma cell differentiationin vivo. Our findings establish DGKζ as a key mediator of CD40 functions in the B cell response.
Joint single-cell measurements of surface proteins, intracellular proteins and gene expression with icCITE-seq
Authors: Chen Kelvin Y. , Takeshima Yusuke , Zorzetto-Fernandes Andre L. , Makino Katsuhiro , Kibayashi Tatsuya , Hata Mayu , Ichiyama Kenji , Croteau Josh , Taylor Kevin , Sakaguchi Shimon 
Published: January 2025

AbstractThe development of single-cell RNA-sequencing assays has transformed our understanding of cellular and tissue heterogeneity, yielding significant insights into disease biology and its underlying mechanisms. In this work, we describe icCITE-seq (intracellular cellular indexing of transcriptomes and epitopes), a scalable method that simultaneously measures surface and intracellular protein levels alongside gene expression across thousands of cells. We validate the specificity of intracellular staining and demonstrate the utility of this multi-omic approach in interrogating phenotypic cellular states through targeted genetic perturbations in primary human T cells. icCITE-seq enables systematic profiling of gene expression, coupled with cytoplasmic, nuclear and PTM epitopes, providing an integrated approach towards understanding cellular identity, complexity and disease regulatory mechanisms.
CellSP: Module discovery and visualization for subcellular spatial transcriptomics data
Authors: Aggarwal Bhavay , Sinha Saurabh 
Published: January 2025

ABSTRACTSpatial transcriptomics has enabled the study of mRNA distributions within cells, a key aspect of cellular function. However, there is a dearth of tools that can identify and interpret functionally relevant spatial patterns of subcellular transcript distribution. To address this, we present CellSP, a computational framework for identifying, visualizing, and characterizing consistent subcellular spatial patterns of mRNA. CellSP introduces the concept of “gene-cell modules”, which are gene sets with non-random subcellular transcript distributions in many cells. It provides intuitive visualizations of the captured patterns and offers functional insights into each discovered module. We demonstrate that CellSP reliably identifies functionally significant modules across diverse tissues and technologies. We use the tool to discover subcellular spatial phenomena related to myelination, axonogenesis and synapse formation in the mouse brain. We find immune response-related modules that change between kidney cancer and healthy samples, and myelination-related modules specific to mouse models of Alzheimer’s Disease.
Differentiation of human T follicular helper cellsin vitrorequires co-operation between STAT3 and SMAD signaling cytokines that is restrained by IL-2
Authors: Foster William S. , Labeur-Iurman Lucía , Williams Geoffrey S. , Robinson Matthew J. , Carlesso Gianluca , Lloyd Clare M. , Harker James A. 
Published: January 2025

AbstractT follicular helper cells (TFH) are a CD4 T cell subset required for effective humoral immunity; promoting antibody responses to vaccines and natural infections. The mechanisms by which human TFH differentiate are not fully understood, and given the anatomical localization to the secondary lymphoid tissues, and asynchronous nature ofin vivoTFH populations, studying TFH differentiationin vitrorepresents an attractive alternative, through which the mechanisms which govern TFH differentiation can be explored. Here we demonstrate reliable differentiation ofin vitroTFH from naïve human CD4 T cells in a STAT3 dependent fashion. Cooperation between STAT3 and SMAD signaling cytokines led to expression of the lineage defining transcriptional regulator BCL6, multiple downstream proteins required for TFH function and localization (including PD1 and CXCR5), and potent IL-21 production capacity by thesein vitroTFH. Critically we found that autocrine production of IL-2 acted as an intrinsic brake on TFH differentiationin vitro; promoting proliferation but limiting the acquisition of a TFH phenotype resembling that found in germinal centersin vivo; neutralization of IL-2 resulting in the emergence of this phenotype. Overall, we show that human TFH expansion, differentiation and function relies on careful regulation of pro- and anti-TFH cytokine signaling.
Structural Basis for the Assembly of Amyloid Fibrils by the Master Cell-Signaling Regulator Human Receptor-Interacting Protein Kinase 1
Authors: Polonio Paula , López-Alonso Jorge Pedro , Jiang Hanxing , Escobedo Fátima , Titaux Gustavo , Ubarretxena-Belandia Iban , Mompeán Miguel 
Published: January 2025

AbstractAmyloid fibrils, typically associated with neurodegenerative diseases, also play critical roles as functional assemblies in biological processes. The RIP homotypic interaction motifs (RHIMs) in receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) are essential for necroptosis, orchestrating the formation of amyloid-like fibrils that assemble into necrosomes. These supramolecular complexes propagate cell death signals and activate effectors like MLKL. While the structures of human RIPK3 (hRIPK3) homomeric fibrils and RIPK1-RIPK3 heteromeric fibrils have been resolved, the atomic structure of human RIPK1 (hRIPK1) homomeric fibrils has remained elusive.Here, we present a high-resolution structure of hRIPK1 RHIM-mediated amyloid fibrils, determined using an integrative approach combining cryoprobe-detected solid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy. The fibrils adopt an N-shaped amyloid fold consisting of three β-sheets stabilized by the conserved IQIG RHIM motif through hydrophobic interactions and hydrogen bonding. A key hydrogen bond between N545 and G542 closes the β2-β3 loop, resulting in denser side-chain packing compared to hRIPK3 homomeric fibrils. This structural feature likely contributes to the compact architecture of hRIPK1 fibrils, in contrast to the more relaxed S-shaped fold observed in hRIPK3.These findings provide structural insights into how hRIPK1 homomeric fibrils nucleate hRIPK3 recruitment and fibrillization during necroptosis, offering broader perspectives on the molecular principles governing RHIM-mediated amyloid assembly and functional amyloids.
Novel Insights into T-Cell Exhaustion and Cancer Biomarkers in PDAC Using ScRNA-Seq
Authors: Saleem Muhammad Usman , Sajid Hammad Ali , Shabbir Muhammad Imran 
Published: January 2025

AbstractOne of the aggressive and lethal cancers, pancreatic ductal adenocarcinoma (PDAC) is characterised by poor prognosis and resistance to conventional treatments. Moreover, tumor immune microenvironment (TIME) plays a crucial role in the progression and therapeutic resistance of PDAC. It is associated with T-cells exhaustion, leading to the progressive loss of T-cell functions with impaired ability to kill tumor cells. Therefore, this study employed single cell RNA sequencing (scRNA-seq) analysis and identified upregulated genes of cancer cells in two groups (“cancer cells_vs_all-PDAC” and “cancer-PDAC_vs_all-normal”), while of T-cells, including CD8+ NKT-like cells, memory CD4+ T-cells, and naive CD4+ T-cells were identified between conditions (PDAC_vs_Normal) with their respective cell types. Subsequently, common and unique markers of cancer cells from both groups were identified, resulting in three sub-groups (common in both groups, unique to “cancer cells_vs_all-PDAC” and unique to “cancer-PDAC_vs_all-normal” group). Moreover, the top-10 enriched Reactome pathways of cancer cells (common and unique) and T-cells were identified; and the genes implicated in those pathways were selected to perform PPI analysis, eventually revealing the top-10 hub-genes of each group (common and unique) of cancer cells (GAPDH, AKT1, EGFR, CS, RHOA, TPI1, SDHA, TFRC, FASN, HIF1A, H4C6, MYC, H3C12, DDX21, USP7, RFC4, APEX1, CDK9, H2BC9, NOP2, FN1, COL1A1, COL1A2, COL3A1, COL5A2, COL6A1, COL5A1, BGN, COL6A2,andFBN1) and T-cells (ACTB, AKT1, CD4, CTNNB1, FN1, H3-3B, HIF1A, HSP90AA1, HSP90AB1, HSPA8, IFNG, ITGB1, JUN, MAPK3, MMP9, NFKB1, TP53, UBB,andUBC). Furthermore, the gene expression validation of cancer cell and T-cells hub-genes was performed using GEPIA2 and TISCH2, while overall survival analysis of cancer cell hub-genes was performed using GEPIA2. Conclusively, this study unravelled a total of 16 novel markers (CS, H4C6, H3C12, H2BC9, TP53, FN1, MMP9, ITGB1, HSP90AB1, AKT1, ACTB, MAPK3, UBC, UBB, CTNNB1, and H3-3B) of cancer and T-cells, indicating that these might be implicated in the pathways leading to T-cell exhaustion, rendering growth, proliferation, and survival of cancer cells. This study provides the groundwork for future research into the immune landscape of PDAC, particularly T-cell exhaustion. However, further clinical studies are needed to validate these novel markers as potential therapeutic targets in PDAC patients.
Where were the Caribbean mangroves during the Last Glacial Maximum? A microtopographical approach
Authors: Rull Valentí 
Published: January 2025

AbstractDuring the Last Glacial Maximum (LGM), when global sea levels dropped by ∼132 m, the Caribbean continental shelf was fully exposed, which drastically reduced the flat topographical habitat necessary for mangrove growth. It has been proposed that mangroves survived in flat microsites beyond the shelf break and later expanded from these microrefugia to their current distribution after the LGM. However, this hypothesis remains untested. This study aims to identify potential refugia by locating flat areas around the −132 m isobath using Global Multiresolution Topography (GMRT) images. A significant ∼200-km-long potential refugium was identified on the northern Trinidad (NT) shelf, along with several scattered kilometer-scale microrefugia near the Cariaco Basin (CB) in northeastern Venezuela. Additionally, two isolated prospective microrefugia were detected in northern Colombia (NC) and western Hispaniola (WH). The remaining LGM Caribbean coasts were considered unsuitable for mangrove growth. The NT refugium, along with the CB microrefugia, may have served as the primary sources for subsequent mangrove expansion. This expansion was likely facilitated by postglacial sea-level rise and the SE-NE Caribbean Current (CC), which would have acted as a major agent for propagule dispersal. This microtopographical survey not only supports the microrefugial hypothesis but also narrows the focus to the most promising areas, significantly reducing the time, effort and resources required for future seismic and coring campaigns.
Asparagine endopeptidase promotes radioresistance in breast cancer through ATR pathway modulation
Authors: Morillo-Huesca Macarena , Tomé Mercedes , Watts Colin , Huertas Pablo , Moreno-Bueno Gema , Durán Raúl V. , Martinez-Fabregas Jonathan 
Published: January 2025

AbstractBackgroundTumor resistance represents a major challenge in the current oncology landscape. Asparagine endopeptidase (AEP) overexpression correlates with worse prognosis and reduced overall survival in most human solid tumors. However, the underlying mechanisms of the connection between AEP and reduced overall survival in cancer patients remain unclear.MethodsHigh-throughput proteomics, cellular and molecular biology approaches and clinical data from breast cancer (BC) patients were used to identify novel, biologically relevant AEP targets. Immunoblotting and qPCR analyses were used to quantify mRNA and protein levels. Flow cytometry, confocal microscopy, chemical inhibitors, siRNA- and shRNA-silencing and DNA repair assays were used as functional assays. In-silico analyses using the TCGA BC dataset and immunofluorescence assays in an independent cohort of invasive ductal (ID) BC patients were used to validate the clinical relevance of our findings.ResultsHere we showed a dual role for AEP in genomic stability and radiotherapy resistance in BC patients by suppressing ATR and PPP1R10 levels. Reduced ATR and PPP1R10 levels were found in BC patients expressing high AEP levels and correlated with worst prognosis. Mechanistically, AEP suppresses ATR levels, reducing DNA damage-induced cell death, and PPP1R10 levels, promoting Chek1/P53 cell cycle checkpoint activation, allowing BC cells to efficiently repair DNA. Functional studies revealed AEP-deficiency results in genomic instability, increased DNA damage signaling, reduced Chek1/P53 activation, impaired DNA repair and cell death, with phosphatase inhibitors restoring the DNA damage response in AEP-deficient BC cells. Furthermore, AEP inhibition sensitized BC cells to the chemotherapeutic reagents cisplatin and etoposide. Immunofluorescence assays in an independent cohort of IDBC patients showed increased AEP levels in ductal cells. These analyses showed that higher AEP levels in radioresistant IDBC patients result in ATR nuclear eviction, revealing AEPhigh/ATRlowprotein levels as an efficient predictive biomarker for the stratification of radioresistant patients.ConclusionThe newly identified AEP/ATR/PPP1R10 axis plays a dual role in genomic stability and radiotherapy resistance in BC. Our work provides new clues to the underlying mechanisms of tumor resistance and strong evidence validating the AEP/ATR axis as a novel predictive biomarker and therapeutic target for the stratification and treatment of radioresistant BC patients.