Neuroendocrine tumors (NET) research papers

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In vivo multiplexed modeling reveals diverse roles of the TBX2 subfamily and Egr1 in Kr as -driven lung adenocarcinoma. reports: The TBX2 subfamily of T-box transcription factors ( e.g. , Tbx2 , Tbx3 , Tbx4 , Tbx5 ) plays an essential role in lung development. Down-regulation of these genes in human lung adenocarcinoma suggests that these genes may be tumor-suppressive; however, because down-regulation appears to occur primarily via epigenetic change, it remains unclear if these changes causally drive tumor progression or are merely the consequence of upstream events.

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A rare renal neoplasm: Case report of mucinous tubular and spindle cell carcinoma. reports: Mucinous tubular and spindle cell renal cell carcinoma (MTSRCC) is a rare subtype of renal cell carcinoma with distinctive histological features and generally favorable prognosis. We report the case of a 52-year-old woman who presented with right lumbar pain. CT and MRI revealed a well-defined solid renal mass with mild, homogeneous enhancement.

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Living bacterial reactor potently activates tumor immunogenic ferroptosis via cysteine depletion and photothermal therapy. reports: Bacterial combination therapy offers immense promise for treating aggressive "cold" solid tumors, such as triple-negative breast cancer (TNBC). However, the clinical translatability of traditional genetic engineering is often hampered by operational complexity and genetic instability. Here, we developed A-SPB-a non-genetically engineered, multi-functional living bioreactor based on Shewanella oneidensis MR-1 (SO), surface-modified with Prussian blue (PB) nanoparticles and attenuated via deoxycholic acid (DA) treatment.

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Astragalus membranaceus sprouts and their unique constituents regulate reactive oxygen species production, inflammation-related senescence-associated secretory phenotype components, and extracellular matrix in fibroblasts. reports: Aging involves a gradual decline in physiological functions and increased susceptibility to damage and disease. Suppressing reactive oxygen species (ROS) production and inflammatory responses is critical for delaying age-related cellular decline. Astragalus membranaceus is one of the important health functional foods worldwide due to its health benefits, including antioxidant and immunomodulatory properties.

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Philippine marine macroalgae as sources of bioactive natural products and macronutrients for food applications. reports: The coastal waters of the Philippine archipelago harbor a remarkable diversity of macroalgae (seaweeds), representing a valuable yet underexplored resource for food, medicine, and biotechnological applications. Several species are traditionally consumed as fresh salads in the Philippines, offering dietary benefits such as essential minerals, macronutrients, and antioxidants. At the same time, some macroalgae produce bioactive natural products that may serve as pharmaceutical leads, though in certain cases, these compounds could pose toxicological risks to consumers.

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Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma. reports: Immune checkpoint inhibitor (ICI) therapy has significantly improved the treatment of solid tumors such as hepatocellular carcinoma (HCC); however, most patients fail to respond. Here, we examined whether co-administration of the tumor-penetrating internalizing (i)RGD peptide, which selectively increases tumor vascular permeability in a neuropilin-1-dependent manner, enhances intratumoral delivery and therapeutic efficacy of αPD-L1 in mouse models of HCC. αPD-L1, with or without iRGD, was administered intravenously to mice bearing endogenous HCCs (TGFα/c-myc and diethylnitrosamine [DEN]/carbon tetrachloride [CCl 4 ] models).

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Conducting clinical trials in supportive and palliative oncology: challenges and opportunities. reports: High-quality research is essential to enhance the delivery and outcomes of supportive care for patients with cancer. In this review, we discuss key challenges and potential solutions for conducting supportive care clinical trials in oncology. Structural barriers to supportive care research include limited infrastructure and investigators, insufficient funding, a paucity of foundational research, and a lack of standardized terminologies.

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DoBSeqWF: a framework for sensitive detection of individual genetic variation in pooled sequencing data. reports: Population screening for rare genetic diseases has the potential to increase early diagnosis and treatment, but the high cost of next-generation sequencing limits widespread implementation. Double-batched sequencing (DoBSeq) is a cost-effective method that uses two-dimensional overlapping pool sequencing to enable individual-level rare variant detection. However, the resulting high-depth, complex data require a specialized workflow for efficient, sensitive, and reproducible analysis.

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Cancer-associated fibroblasts as a critical driver in tumor metastasis: The mechanisms and future perspectives. reports: Tumor metastasis represents a lethal event for patients due to the lack of effective treatments. Compared with primary tumors, the components of the tumor microenvironment (TME) of metastatic tumors are different. Tumor cells alone are unable to metastasize.

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Gut fungal landscape in colorectal cancer and its cross-kingdom interplay with gut microbial ecology. reports: The gut microbiota is a key hallmark of colorectal cancer (CRC), yet gut fungi remain understudied. We characterized the gut fungal landscape and its associations with bacteria, metabolites, and trace elements in CRC using fecal samples from healthy controls ( n = 401), colorectal polyp patients ( n = 162), and CRC patients ( n = 253). Fungal annotation was performed using genomic data from NCBI (PRJNA833221) as reference.

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KNSTRN knockdown impairs autophagy flux to inhibit bladder cancer progression. reports: Bladder cancer (BLCA) is a common malignant tumor of the urinary system. Kinetochore-localized astrin-binding protein (KNSTRN) has been implicated in the initiation and progression of multiple cancers. Furthermore, abnormal autophagy levels have been shown to significantly impact tumor development.

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Rare RET Variants in a Patient With MEN2A and Multiple Follicular-Derived Thyroid Tumors: A Case Report and Review of the Literature. reports: Multiple endocrine neoplasia (MEN) syndromes are a group of rare autosomal dominant hereditary disorders that are classified into 5 distinct types. MEN2A, the most common type of MEN2, is associated with mutations and variants of RET , which are continually being updated. However, studies regarding RET mutations/variants related to MEN2A in the Chinese population are scarce, and patients involving MEN2A along with other differentiated thyroid tumors are rarer.

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Win statistics (win ratio, win odds, and net benefit): Noncollapsibility and standardization for randomized clinical trials. reports: The win ratio, along with its stratified variant known as the stratified win ratio, has been widely utilized in many disease areas for both design and analysis of clinical trials. It is applied most prominently in cardiovascular diseases, followed by respiratory disease, diabetes, oncology, neurology, and other areas. Additionally, the win odds, which incorporates ties in its calculation, has also garnered attention in both prospective and retrospective analyses, alongside their utilization in study design.

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A nationwide population-based cohort study of hospital academic status and survival following colorectal cancer surgery in Finland 1987-2016. reports: There is a lack of evidence regarding hospital academic status and survival following colorectal cancer surgery and there is a paucity of data from European countries. The aim of this study was to investigate this association between hospital academic status and mortality after colon and rectal cancer surgery. All 49 032 patients who underwent resection for colorectal cancer in years 1987-2016 in Finland were included, with complete follow-up until December 31, 2019.

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Bone health in patients with cancer: a SEOM-SEIOMM consensus review of risk factors, assessment strategies, and management approaches. reports: Anticancer therapies frequently compromise skeletal health and increase fracture risk. This narrative review synthesizes information and provides guidance on assessment, prevention, and management of therapy-related bone loss in adults with cancer. Major contributors to bone loss in this population include aromatase inhibitors, androgen deprivation therapy, systemic glucocorticoids, chemotherapy, and selected targeted or immune agents.

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Cheilanthenetetraol, a sesterterpenoid isolated from Aleuritopteris bicolor with anti-hepatocellular carcinoma and anti-inflammatory activity. reports: The 1 H-NMR, LC-MS, and HPLC guided isolation of n-hexane and ethyl acetate fractions led to the purification of one new sesterterpene cheilanthenetetraol (1) together with thirteen known compounds (2-14) for the first time from Aleuritopteris bicolor Roxb. The structure of the isolated compounds were established by extensive analysis of spectroscopic data, 1D and 2D NMR, HR-ESI-MS, and IR. The isolated compounds (2, 3, 6, and 9-14), as well as the n-hexane, ethyl acetate fractions, and aqueous methanol extract, were evaluated for cytotoxic activity against the HepG2 cancer cell line.

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Effect of carbamazepine on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader, in healthy adults. reports: To evaluate the effects of carbamazepine, a strong cytochrome P450 (CYP)3A4 inducer, on the pharmacokinetics and safety of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader. This was a phase 1, open-label, fixed-sequence, two-period study in healthy adult participants. During Period 1, a single oral dose of vepdegestrant 200 mg was administered (Day 1).

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M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors. reports: Cerebrospinal fluid (CSF) liquid biopsies serve as a rich source of tumor-derived cell-free DNA (cfDNA) for evaluating persons with central nervous system (CNS) tumors. However, challenges stemming from trace cfDNA yields and low mutational burden have hindered sensitivity, whereas first-generation clinical assays have relied on genetic alterations as biomarkers. Leveraging the diagnostic utility of DNA methylation classification in CNS tumors, we developed M-PACT (methylation-based predictive algorithm for CNS tumors), a robust deep neural network that accurately classifies tumors from subnanogram-input cfDNA methylomes.

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MDPNet: a multi-scale difference perception network for esophageal cancer segmentation in CT images. reports: Accurate segmentation of esophageal cancers in CT images is crucial for disease treatment planning but remains difficult due to variable tumor morphology, low contrast with surrounding tissues, and blurred boundaries. We propose MDPNet, a Multi-scale Difference Perception Network for accurate esophageal cancer segmentation in CT images. MDPNet integrates three key modules, a Dynamic Feature Enhancement (DFE) strategy for global and local context fusion, a Cross-level Difference Modeling (CDM) module to highlight foreground-background differences, and a Multi-stage Foreground Enhancement (MFE) mechanism for progressive boundary refinement.

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R-GAT: cancer document classification leveraging graph-based residual network for scenarios with limited data. reports: Accurate classification of cancer-related biomedical abstracts is critical for advancing cancer informatics and supporting decision-making in healthcare research. Yet progress in this domain is often constrained by limited availability of labeled corpora and the high computational demands of transformer-based approaches. To address these challenges, we propose a Residual Graph Attention Network (R-GAT) that integrates multi-head attention with residual connections to capture semantic and relational dependencies in biomedical texts.

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TFAP2C protects against ferroptosis in ovarian cancer through the KEAP1-NRF2 axis by recruiting HDAC1/2. reports: Ferroptosis, a distinct form of programmed cell death characterized by the iron-dependent aberrant buildup of lipid peroxides, has emerged as a promising approach in cancer therapy. The KEAP1-NRF2 axis serves as a critical regulator of ferroptosis, exerting its suppressive effects by preserving cellular redox homeostasis and orchestrating the transcriptional activation of downstream antioxidant genes. NRF2 hyperactivation is frequently observed across multiple cancer types and is associated with tumor progression and therapeutic resistance.

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Tumor cell-intrinsic PD-1 in malignant ascites drives ovarian cancer progression via MAPK/ERK signaling. reports: Programmed cell death protein 1 (PD-1), an immune checkpoint primarily expressed on T cells, plays a critical role in mediating tumor immune evasion. However, the role of PD-1 in non-immune cells remains poorly understood. Here, we report tumor cell-intrinsic PD-1 expression in malignant ascites from ovarian cancer patients.

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Discovery and Preclinical Evaluations of Potent, Selective, and Allosteric Covalent WRN Inhibitors with Improved PK Properties. reports: Werner syndrome helicase (WRN) has received significant interest due to its implication as a synthetic lethal target in microsatellite instability-high (MSI-H) cancers. Here we report the discovery of a novel allosteric covalent WRN inhibitor, compound 22 , via structure-based medicinal design and pharmacokinetic optimization from VVD-214. Compound 22 occupied a new cavity and formed an additional hydrogen bond with K894, thereby improving its activities.

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Precision Control of Transcription and Cell-Cycle Signaling: Emerging Strategies from Epigenetic Degradation to CDK-Targeted Oncology. reports: Recent patent disclosures highlight complementary strategies to modulate transcriptional and cell-cycle control in cancer. Selective and dual p300/CBP degraders introduce emerging epigenetic degradation modalities, while biomarker-guided CDK4 inhibition and a crystalline CDK2 inhibitor exemplify precision oncology and potential late-stage development. Together, these inventions illustrate how mechanistic innovation, patient stratification, and pharmaceutical execution converge to advance targeted anticancer therapies.

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Magnetic graphene-based ferrite nanoparticles: synthesis, characterization, and anti-proliferative activity against some human cancer cells ( in vitro study). reports: This work introduces a novel soft magnetic building block (GCM), based on reduced graphene oxide covalently functionalized with Congo red molecules and incorporated with barium ferrite nanoparticles, creating a promising multifunctional platform for future magnetically controlled nanorobotic systems for potential cancer therapy and diagnosis nanodevices. The sol-gel auto-combustion method was used for the synthesis of pure barium ferrite (M) and in situ synthesis of reduced graphene oxide-barium ferrite nanoconjugate (GM). Physicochemical characterization techniques were used for identification, including infrared spectroscopy, X-ray diffraction, UV-visible spectroscopy, thermogravimetric analysis, scanning electron microscopy, energy-dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, vibrating sample magnetometry, size distribution analysis, and ζ -potential analysis.

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Non-canonically regulated heterochronic expression of Hsp70 drives clonal expansion and invasion in Drosophila epithelial tumors reports: Oncogenic stress responses are critical modulators of tumour cell adaptation to hostile microenvironments and clonal dynamics. The evolutionarily conserved Hsp70 chaperone promotes tumour cell survival by suppressing apoptosis and facilitating metastatic progression. However, the temporal order and regulation of its expression in neoplastic tumours remains ill-defined. This is a preprint and not peer reviewed.

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Cerebrovascular Malformations Associated With Hereditary Hemorrhagic Telangiectasia and HHT-Like Syndromes: A Comparative Overview. reports: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder marked by mucocutaneous telangiectasias, recurrent epistaxis, and visceral arteriovenous malformations (AVMs). Neurologic risks include brain AVMs and hemorrhagic stroke. Several rare genetic and sporadic syndromes ("HHT-like" syndromes) share overlapping vascular features, complicating diagnosis.

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Delayed intracardiac migration of a retained epicardial pacing wire 14 years after coronary artery bypass grafting presenting with high-burden polymorphic ventricular ectopy: a case report. reports: Temporary epicardial pacing wires (TEPWs) are routinely inserted during open-heart surgery and are usually removed before discharge. When retained, most remain clinically silent; however, late complications, including migration, erosion, infection, and arrhythmia, have been reported. An 84-year-old man, 14 years after coronary artery bypass grafting, had an incidental metallic density on computed tomography.

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Primary synovial sarcoma of the pericardium diagnosed after multiple biopsies following recurrent episodes of haemorrhagic pericardial effusion following infection: a case report. reports: Primary malignant pericardial tumours are extremely rare, and synovial sarcoma arising from the pericardium is an exceptionally uncommon entity with poor survival. Diagnosis is often delayed because initial pericardial biopsies can be non-diagnostic, and distinguishing between inflammatory disease and malignancy may be challenging. An 11-year-old boy developed recurrent fever and chest pain 15 days after Coronavirus disease 2019 infection.

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The uncoordinated-5 homologue A is a key receptor in netrin-ligand-mediated fast-twitch myotube formation in male mice. reports: Myoblasts autonomously govern myofiber-type specification of newly formed myotubes through autocrine-paracrine-dependent manners mediated by multipotent modulators. Netrin-1, which is particularly produced in myoblasts isolated from the extensor digitorum longus (EDL; fast-twitch myofiber-abundant) rather than the soleus (slow-twitch myofiber-abundant), and netrin-4, which is abundantly expressed during myogenic differentiation initiation, stimulate the synthesis of fast-type myosin heavy chain (MyHC) isoforms. However, the mechanisms by which netrin-1 and netrin-4 promote fast-twitch myotube formation remain unclear.

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Transfer Learning Strategies for Pathological Foundation Models: A Systematic Evaluation in Brain Tumor Classification. reports: Deploying pathology AI at individual hospitals faces challenges including limited cases and adapting pretrained models to local data. Brain tumor classification, with diverse diagnostic categories but few cases per institution, represents this challenge. Foundation models may offer a solution, but optimal transfer learning strategies remain unclear.

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Deriving genetic codes for molecular phenotypes from first principles reports: The genetic code is a formal principle that determines which proteins an organism can produce from only its genome sequence, without mechanistic modeling. Whether similar formal principles govern the relationship between genome sequence and phenotype across scales - from molecules to cells to tissues - is unknown. Here, we show that a single formal principle - structural correspondence -- underlies the relationship between phenotype and genome sequence across scales. This is a preprint and not peer reviewed.

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A Decade of Oncolytic Virotherapy in Pediatric Cancers: A Systematic Review of Safety, Immune Awakening, and Emerging Efficacy. reports: Oncolytic virotherapy employs genetically modified viruses to selectively lyse tumor cells while activating antitumor immune responses. In pediatric oncology, where outcomes for high-grade gliomas and refractory solid tumors remain poor, oncolytic viruses represent a promising therapeutic strategy. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, including searches of PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov for studies published between 2015 and 2025 that evaluated oncolytic virotherapy in patients aged 18 years or younger.

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A Mandibular Metastasis as the Initial Presentation of Hepatoid Adenocarcinoma of the Lung: A Case Report. reports: Hepatoid adenocarcinoma of the lung is a rare primary pulmonary malignancy that exhibits morphological traits resembling those seen in hepatocellular carcinoma and is associated with high alpha-fetoprotein expression. It follows a very aggressive course and is often diagnosed in advanced oncologic stages. We present our experience with this malignancy and report on a case with mandibular metastasis, an uncommon metastatic site.

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Bronchial sleeve anastomosis in children: a single-center experience demonstrating safety and efficacy. reports: To evaluate the technical feasibility, safety, and clinical outcomes of bronchial sleeve anastomosis in a pediatric case series encompassing two main etiologies (trauma and tumor). A retrospective analysis was conducted on 8 pediatric patients who underwent bronchial sleeve resection at our center between May 2018 and May 2025. Preoperative diagnosis was confirmed by computed tomography, magnetic resonance imaging, and bronchoscopy.

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Evaluating the Relationship Between Programmed Death Ligand-1 (Clone: 22C3), Anaplastic Lymphoma Kinase (D5F3), and C-ros Oncogene 1 (OT11A1) Expression in Lung Adenocarcinoma. reports: Objective This study investigates the relationship between programmed death ligand-1 (PD-L1), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) expression in lung adenocarcinoma (ADC). Methods Sixty-two cases were analyzed for ALK, ROS1, and PD-L1 expression using immunohistochemistry. Statistical evaluations were performed using chi-square and Fisher's exact tests.

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Evaluation of Ginsenosides and Their Derivatives From Panax ginseng as Aromatase Inhibitors for Breast Cancer Treatment-An in silico study. reports: Breast cancer, particularly estrogen receptor-positive subtypes, is a leading cause of cancer-related mortality worldwide. Aromatase inhibitors, which target estrogen biosynthesis, are a cornerstone of therapeutic intervention. Panax ginseng , a widely recognized medicinal herb, contains bioactive compounds known as ginsenosides, which possess various pharmacological activities, including anticancer properties.

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Gastrointestinal adverse events following brentuximab vedotin and polatuzumab vedotin therapy. reports: Brentuximab vedotin (BV) and polatuzumab vedotin (PV), CD30-specific and CD79b-specific monoclonal antibody conjugates, respectively, are used in the treatment of hematologic cancers. Both have been observed to cause gastrointestinal adverse events (GI AEs). We aimed to assess the clinical characteristics, disease course, treatment, and outcomes of patients who developed GI AEs following treatment with BV or PV.

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Macrophage-Mediated Cellular Communication Networks in Lung Squamous Cell Carcinoma and Adenocarcinoma Revealed by Single-Cell Sequencing. reports: Lung cancer, particularly the non-small cell lung cancer (NSCLC) subtypes lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), exhibits high heterogeneity and high mortality. This study aimed to explore their tumor microenvironment (TME) features, cellular interactions, and potential therapeutic targets. Using scRNA-seq datasets (GSE200972, GSE117570, and GSE127465) and TCGA bulk RNA-seq data, we performed cell clustering, pseudotime trajectory, cell-cell communication, and survival analyses.

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Magnetic resonance imaging differentiating benign from malignant bone and soft tissue tumors and assessing Ki-67 expression using APT and DWI tools. reports: Conventional MRI mainly provides the morphologic information of tumors with low specificity, but its ability to distinguish between benign and malignant bone lesions is limited. Amide proton transfer (APT) is a novel MRI tool for detecting amide protons in free proteins and peptides. A few studies have reported on APT in tumors; however, studies on qualitative diagnosis of bone and soft tissue tumors are lacking.

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Multifaceted roles of fibronectin type III domain containing 3B (FNDC3B) in cell biology and signaling. reports: FNDC3B is an endoplasmic reticulum (ER)-anchored transmembrane protein with diverse roles in cell adhesion, migration, and growth signaling. Recognized as multifunctional, it contributes to key cellular processes such as adhesion, proliferation, differentiation, and migration, yet its molecular functions remain largely unannotated in the Gene Ontology database. Initially identified as a regulator of adipogenesis, promoting fat cell differentiation, FNDC3B also facilitates lung cell maturation, which is essential for neonatal survival.

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Multimodal management of hormonal and oncological progression in PTHrP-secreting pancreatic neuroendocrine tumours. reports: Parathyroid hormone-related peptide (PTHrP)-secreting pancreatic neuroendocrine tumours (Pan-NETs) are a rare cause of humoural hypercalcaemia of malignancy (HCM). We report two contrasting cases of metastatic well-differentiated PTHrP-secreting Pan-NETs (WHO grade 2; Ki-67: 7 and 8%, respectively), highlighting the variability in disease progression, response to multiple treatment modalities, and long-term outcomes. The first patient, a 55-year-old woman with mild hypercalcaemia who was largely asymptomatic except for a persistent dry cough at presentation, achieved stable disease control following eight years of treatment with somatostatin analogues (SSAs), peptide receptor radionuclide therapy (PRRT), and chemotherapy.

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Nonmetastatic Pulmonary Carcinoid Presenting With Carcinoid Syndrome Despite Negative 5-HIAA: A Case Report. reports: Carcinoid syndrome from pulmonary carcinoids without hepatic metastases is rare and diagnostically challenging when biochemical markers are normal. A woman in her mid-60 s presented with an incidental right adrenal mass during evaluation for dyspnea and elevated D-dimer. She reported a 20-year history of paroxysmal tachycardia and 5 years of episodic flushing, profuse sweating, exertional dyspnea, and fine tremors triggered by minimal physical activity.

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Oxidative stress-mediated responses in endometrial cancer cells: contrasting effects of doxorubicin and menadione. reports: Oxidative stress plays a crucial role in the development and treatment response of endometrial cancer, yet the antioxidant defense mechanisms in different tumor subtypes remain unclear. We investigated the cellular response to oxidative (menadione) and genotoxic (doxorubicin) stress in two TP53-mutated endometrial cancer cell lines, AN3CA and KLE. Cell viability, reactive oxygen species (ROS) levels, and the expression of antioxidant-related genes (SESN2, SESN3, SOD1) were assessed using qPCR and In-Cell Western assays.

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Procalcitonin as a potential tumor marker for fibrolamellar hepatocellular carcinoma: Insights from three patients and a literature review. reports: Fibrolamellar hepatocellular carcinoma (fHCC) was diagnosed through magnetic resonance imaging in three young patients (with biopsies confirming the diagnosis in two of them prior to referral) aged 17, 22, and 24&#x202f;years. All had normal or near-normal standard biochemistry results, except for increased levels of procalcitonin (PCT) and C-reactive protein (CRP) in the absence of any infectious source: PCT: 41, 5.8, and 1.2&#x202f;ng/mL, respectively (normal range&#x202f;<&#x202f;0.05&#x202f;ng/mL) and CRP: 127, 21, and 14&#x202f;mg/L, respectively (normal range: 0-5&#x202f;mg/L). Right hepatectomy with negative surgical margins resulted in the eventual normalization of CRP levels in all patients, and PCT levels normalized in the latter two patients.

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Rates of colorectal surgery in patients with non-malignant colorectal polyps: Results from a nationwide study. reports: Despite advances in endoscopic techniques, many colorectal surgeries in the United States are still performed for non-malignant colorectal polyps (NMCRPs). This study evaluated trends, demographic variations, and outcomes of surgeries for NMCRPs among all colorectal surgeries over the past decade. Using the TriNetX nationwide database, we identified adults (&#x2265; 18 years of age) who underwent colectomy or proctectomy for NMCRPs or colorectal cancer between 2013 and 2023.

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ROS1 -positive non-small cell lung cancer: from genomics to treatment decisions. reports: ROS1 rearrangements define a distinct, targetable subset of non-small cell lung cancer (NSCLC), representing ~2% of non-squamous cases and frequently presenting with metastatic disease and CNS involvement. Multiple ROS1 tyrosine kinase inhibitors (TKIs)-from crizotinib to newer agents such as entrectinib, lorlatinib, repotrectinib, taletrectinib, and the highly selective zidesamtinib-have improved systemic and intracranial outcomes, although resistance remains inevitable and biologically diverse, involving both on-target kinase mutations and off-target mechanisms. This review synthesizes current knowledge on ROS1 biology, diagnostic strategies, therapeutic options, and resistance mechanisms.

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Single-cell RNA sequencing and spatial transcriptomic analysis reveal a distinct population of G6PD + cells with aberrant bile acid metabolism in hepatocellular carcinoma. reports: Metabolic reprogramming is a hallmark of hepatocellular carcinoma (HCC). Among various metabolic pathways, bile acids act not only as crucial metabolites but also as key signaling molecules that regulate diverse physiological and pathological processes in the liver. However, the biological functions and clinical implications of bile acid metabolism in HCC progression remain largely unclear.

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Spectral discrimination of pediatric SF188 and adult glioblastoma stem cells by deep learning-enhanced Raman profiling. reports: Pediatric and adult glioblastomas (GBM) represent biologically distinct entities requiring age-tailored therapeutic strategies. However, rapid and non-invasive methods to distinguish these molecular subtypes remain an unmet clinical need. This study evaluates the potential of confocal Raman spectroscopy combined with deep learning as a label-free diagnostic tool to differentiate pediatric from adult GBM based on intrinsic biochemical fingerprints.

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Sulfasalazine-Induced Urinary Normetanephrine Elevation Mimicking Recurrent Phaeochromocytoma-A Case Report. reports: Phaeochromocytomas and paragangliomas (PPGLs) are catecholamine-secreting neuroendocrine tumours (NETs) of the adrenal medulla and autonomic nervous system. Early recognition and management is critical given their potential morbidity and mortality. For this reason, stand-alone screening investigations rely on a low diagnostic threshold, achieving high sensitivity at the relative cost of specificity.

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Systemic sclerosis-associated pulmonary arterial hypertension and pulmonary fibrosis: exploring biomarker discriminators with advanced omics in a Caucasian cohort. reports: Systemic sclerosis (Scleroderma; SSc) is associated with high morbidity and mortality, particularly in patients with pulmonary arterial hypertension (SSc-PAH) and pulmonary fibrosis (SSc-PF). Effective risk stratification and treatment of SSc remains a significant challenge. This proof-of-concept study aimed to identify potential biomarkers capable of distinguishing between three SSc patient groups, defined by no pulmonary involvement (SSc-NLD; n=30), SSc-PAH (n=30), SSc-PF (n=30) compared to healthy controls (HC; n=30).

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TCN-5mC: a predictor of 5-methylcytosine sites based on multi-feature fusion and TCN-inspired block networks. reports: Accurate identification of 5-methylcytosine (5&#xa0;mC) sites in promoter regions is crucial for understanding epigenetic regulation, but experimental methods remain costly and time-consuming, highlighting the need for reliable computational prediction tools. While existing deep learning approaches, such as BiLSTM-based, Transformer-based, and pretrained language models, have advanced the field, opportunities remain for further improvements in capturing long-range dependencies and handling imbalanced genomic data. Here, we present TCN-5mC, a deep learning model that integrates Temporal Convolutional Networks (TCN) inspired block with Bidirectional Gated Recurrent Units (BiGRU) and employs hybrid One-Hot and Nucleotide Chemical Property feature encoding.

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The dysregulation of the immune microenvironment during endometrial intraepithelial neoplasia serves as a marker of endometrial carcinogenesis. reports: The development of endometrial cancer is a gradual malignant transformation process driven by multiple factors, and the immune microenvironment is closely related to clinical outcomes and immunotherapy responses. Under physiological conditions, the immune microenvironment of the normal endometrium undergoes periodic reshaping under the regulation of estrogen and progesterone, maintaining the balance between immune defense and reproductive capacity. However, continuous exposure to risk factors, such as non-antagonistic estrogen, may trigger endometrial intraepithelial neoplasia.

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Tumor-associated neutrophils in renal cell carcinoma. reports: Renal cell carcinoma (RCC) is an immunogenic tumor in which tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs) represent a functionally important component of the tumor microenvironment. Recent studies have revealed pronounced phenotypic heterogeneity of RCC-infiltrating neutrophils, including interferon-responsive, immunosuppressive PMN-MDSC-like, pro-angiogenic, and NET-forming subsets that cannot be adequately described by the classical N1/N2 model. Their polarization is shaped by ELR + CXC chemokines (CXCL1, CXCL8), cytokine signals, systemic inflammation, hypoxia driven by VHL/HIF pathways, and tumor-intrinsic oncogenic alterations such as PTEN loss, ER&#x3b2;- and c-Myc-dependent programs, as well as epigenetic remodeling.

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Systematic Analysis of Network-driven Adaptive Resistance to CDK4/6 and Estrogen Receptor Inhibition using Meta-Dynamic Network Modelling reports: Drug resistance inevitably emerges during the treatment of cancer by targeted therapy. Adaptive resistance is a major form of drug resistance, wherein the rewiring of protein signalling networks in response to drug perturbation allows drug-targeted protein activity to recover. This can occur in the continuous presence of the drug and enables cells to survive/grow. This is a preprint and not peer reviewed.

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Nuclear biocondensate-forming lncRNA and cellular stress surveillance shape host cancer susceptibility reports: Host genetics is known to influence cancer susceptibility. However, the specific candidate genes and molecular mechanisms that confer resistance remain poorly understood. Here, we demonstrate the power of haploinsufficiency screen to uncover host genetic regulators of cancer in Drosophila and identify the long noncoding RNA (lncRNA) hsr{omega}, a structural component of nuclear biomolecular condensate known as omega speckles, as a key host cancer susceptibility locus. This is a preprint and not peer reviewed.

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Ddx3x regulates B-cell development and immunoglobulin rearrangement in mice reports: The X chromosome gene, DDX3X, is an ATP-dependent RNA helicase with roles in transcription, splicing, nuclear export, and translation. Loss of function mutations in DDX3X are linked to a variety of neoplasms, including B-cell lymphoma. We find that conditional homozygous deletion (Mb1-Cre) of Ddx3x in developing mouse B cells in female mice results in a complete absence of mature peripheral B cells associated with an absolute block at the pro-B cell stage of development in the bone marrow. This is a preprint and not peer reviewed.

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Current diagnosis and treatment of pancreatic cancer. reports: Pancreatic ductal adenocarcinoma (PDAC) is a tumor characterized by a very poor prognosis and increasing global incidence. Environmental factors have been identified among the various causes of pancreatic cancer, while about 10-15% of presenting patients show a genetic predisposition towards the disease. This paper presents the current insight into the etiology and pathogenesis of cancer, as well as the principles of diagnosis and treatment of the disease.

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Atlas-Guided Discovery of Transcription Factors for T Cell Programming reports: CD8+ T cells differentiate into diverse states that shape immune outcomes in cancer and chronic infection1-4. To systematically define the transcription factors (TFs) driving these states, we built a comprehensive atlas integrating transcriptional and epigenetic data across nine CD8+ T cell states and inferred TF activity profiles. Our analysis catalogued TF activity fingerprints, uncovering regulatory mechanisms governing selective cell state differentiation. This is a preprint and not peer reviewed.

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Circadian regulation of Homologous Recombination by Cryptochrome1-mediated dampening of DNA end resection reports: Genomic stability maintenance requires the repair of DNA breaks in the most accurate fashion. So, an exquisite regulatory network controls the choice between different repair mechanisms to maximize genome integrity. This relies mostly at the level of DNA end resection, the initial steps of the homologous recombination. This is a preprint and not peer reviewed.

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Identification of GTF2IRD1 as a novel transcription factor essential for acute myeloid leukemia reports: Acute myeloid leukemia (AML) is an aggressive blood malignancy characterized by clonal accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Transcription factors are the most frequently mutated and dysregulated genes in AML, and they have critical roles in AML pathogenesis and progression. In this study, we performed large-scale RNA interference screens in MLL-AF9-transformed AML cells and identified GTF2IRD1 as a novel transcription factor essential for the survival of various types of myeloid leukemic cells in vitro and in vivo, but not for primary normal hematopoietic cells. This is a preprint and not peer reviewed.

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Differential migration mechanics and immune responses of glioblastoma subtypes reports: Glioblastoma remains a deadly cancer driven in part by invasion of tumor cells into the brain. Transcriptomic analyses have identified distinct molecular subtypes, but mechanistic differences that account for clinical differences are not clear. Here, we show that, as predicted by the motor-clutch model of cell migration, mesenchymal glioma cells are more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. This is a preprint and not peer reviewed.

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Domain-adaptive matching bridges synthetic and in vivo neural dynamics for neural circuit connectivity inference reports: Accurately inferring neural circuit connectivity from in vivo recordings is essential for understanding the computations that support behavior and cognition. However, current deep learning approaches are limited by incomplete observability and the lack of ground-truth labels in real experiments. Consequently, models are often trained on synthetic data, which leads to the well-known "model mismatch" problem when simulated dynamics diverge from true neural activity. This is a preprint and not peer reviewed.

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Loss of long-range co-expression is a common feature in cancer reports: Cancer cells display common features and enabling characteristics collectively known as the Hallmarks of Cancer, which occur alongside alterations in the regulatory mechanisms controlling gene transcription. Gene co-expression networks (GCNs) provide a framework to identify correlated gene sets that may share these regulatory mechanisms. Previously, we reported the loss of long-range co-expression in breast, lung, kidney, and hematopoietic cancer GCNs. This is a preprint and not peer reviewed.

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Yeast with elevated chromosome numbers are addicted to high levels of Mps1 reports: Tumor cell lines with elevated chromosome numbers frequently exhibit elevated expression of Mps1. These tumors are also dependent on high Mps1 activity for their survival. Mps1 is a conserved kinase involved in controlling aspects of chromosome segregation in mitosis and meiosis. This is a preprint and not peer reviewed.

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Identifying the genetic basis and molecular mechanismsunderlying phenotypic correlation between complex humantraits using a gene-based approach reports: Phenotypic correlations between complex human traits have long been observed based on epidemiological studies. However, the genetic basis and underlying mechanisms are largely unknown. Here we developed a gene-based approach to measure genetic overlap between a pair of traits and to delineate the shared genes/pathways, through three steps: 1) translating SNP-phenotype association profile to gene-phenotype association profile by integrating GWAS with eQTL data using a newly developed algorithm called Sherlock-II; 2) measuring the genetic overlap between a pair of traits by a normalized distance and the associated p value between the two gene-phenotype association profiles; 3) delineating genes/pathways involved. This is a preprint and not peer reviewed.

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Genome-wide annotation of gene regulatory elements linked to cell fitness reports: Noncoding regulatory elements control gene expression and thus govern nearly all biological processes. Epigenomic profiling assays have identified millions of putative regulatory elements, but systematically determining the function of those regulatory elements remains a substantial challenge. Here we adapt CRISPR screening by epigenetic repression to screen all 111,619 putative non-coding regulatory elements defined by open chromatin sites in human K562 leukemia cells for their role in regulating essential cellular processes and proliferation. This is a preprint and not peer reviewed.

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Sex differences in bile acid homeostasis and excretion underlie the disparity in liver cancer incidence between males and females. reports: Hepatocellular carcinoma (HCC), the most common liver cancer, exhibits a higher incidence in males. Here, we report that mice lacking the bile acid regulators, Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. This is a preprint and not peer reviewed.

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Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial transcriptomics reports: While advances in single cell genomics have helped to chart the cellular components of tumor ecosystems, it has been more challenging to characterize their specific spatial organization and functional interactions. Here, we combine single cell RNA-seq, spatial transcriptomics by Slide-seq, and in situ multiplex RNA analysis, to create a detailed spatial map of healthy and dysplastic colon cellular ecosystems and their association with disease progression. We profiled inducible genetic CRC mouse models that recapitulate key features of human CRC, assigned cell types and epithelial expression programs to spatial tissue locations in tumors, and computationally used them to identify the regional features spanning different cells in the same spatial niche. This is a preprint and not peer reviewed.

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Extra-cellular matrix remodeling as a unique mechanism of expansion of periprostatic adipose tissue: a potential driver of prostate cancer aggressiveness reports: One of the most striking features of the adipose depot surrounding the prostate (periprostatic adipose tissue, PPAT) is that its accumulation is independent of body mass index. Its volume varies considerably between individual with some patients exhibiting abundant PPATs that have been correlated to occurrence of aggressive prostate cancer (PCa). However, abundant PPAT are not defined at biological levels. This is a preprint and not peer reviewed.

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Crosstalk between Proline Hydroxylation and Histidine Methylation Regulates Actin-Dependent Cell Mobility Control reports: Actin filaments generate intrinsic forces that are essential for cell motility. This process is tightly regulated by various posttranslational modifications (PTMs), including acetylation, arginylation, and oxidation. However, the role of actin hydroxylation in regulating its dynamics remains poorly understood. This is a preprint and not peer reviewed.

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Adaptive fitness in APC-mutant cells requires chromosome rearrangements reports: Cancer cells tolerate copy number alterations (CNAs) of genomic regions that are lethal to non-cancer cells. Certain CNAs are preferentially associated with specific cancer types and lineages, but the mechanisms underlying the emergence and selection of specific CNAs remain unclear. Adenomatous polyposis coli (APC) mutations induce mitotic errors, but their impact on tumor evolution remains elusive. This is a preprint and not peer reviewed.

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KSR2 promotes self-renewal and clonogenicity of small-cell lung carcinoma reports: Small-cell lung carcinoma (SCLC) tumors are heterogeneous, with a subpopulation of cells primed for tumor initiation. Here, we show that Kinase Suppressor of Ras 2 (KSR2) promotes the self-renewal and clonogenicity of SCLC cells. KSR2 is a molecular scaffold that promotes Raf/MEK/ERK signaling. This is a preprint and not peer reviewed.

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Genome-wide association study provides novel insight into the genetic architecture of severe obesity. reports: Severe obesity (SevO) is a primary driver of cardiovascular diseases (CVD), cardiometabolic diseases (CMD) and several cancers, with a disproportionate impact on marginalized populations. SevO is an understudied global health disease, limiting knowledge about its mechanisms and impacts. In genome-wide association study (GWAS) meta-analyses of the tail end of the BMI distribution ([&ge;]95th percentile BMI) and two SevO phenotypes [Obesity Class III BMI [&ge;]40 kg/m2 and Obesity Class IV BMI [&ge;]50 kg/m2] in 159,359 individuals across eleven ancestrally diverse population-based studies followed by replication in 480,897 individuals across six ancestrally diverse studies, we identified and replicated one novel signal in an unknown locus [BHLHE40-AS1] and three novel signals in known loci of BMI [TENM2, PLCL2, ZNF184], associated with SevO traits. This is a preprint and not peer reviewed.

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A large-scale genome-wide association meta-analysis for nevus count provides direct insights into the genetics of melanoma reports: A greater understanding of the biology of nevi will provide insights into the etiology of melanoma. Our large-scale meta-analysis of 14 nevus genome-wide association study (GWAS) included 85,967 individuals of European ancestry. We identified 29 nevus-associated loci (p < 5x10-8), of which 24 were not previously reported in a GWAS conducted for nevus count alone. This is a preprint and not peer reviewed.

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Breast cancer multigene germline panel testing in mainstream oncology based on clinical-public health utility (cancer mortality benefit): ESMO Precision Oncology Working Group recommendations reports: BackgroundWith widening therapeutic indications, germline genetic testing is offered to an increasing proportion of patients with breast cancer (BC) via mainstream oncology services. However, the gene set tested varies widely from just BRCA1/BRCA2 through to pan-cancer panels of near 100 genes. If a germline pathogenic variant (GPV) is detected, the BC proband and other family GPV-carriers may be offered interventions such as risk-reducing surgery and decades of intensive surveillance for the various cancers linked to that gene. This is a preprint and not peer reviewed.

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DUNE: a versatile neuroimaging encoder captures brain complexity across three major diseases: cancer, dementia and schizophrenia reports: Magnetic resonance images (MRI) of the brain exhibit high dimensionality that pose significant challenges for computational analysis. While models proposed for brain MRIs analyses yield encouraging results, the high complexity of neuroimaging data hinders generalizability and clinical application. We introduce DUNE, a neuroimaging-oriented encoder designed to extract deep-features from multisequence brain MRIs, thereby enabling their processing by basic machine learning algorithms. This is a preprint and not peer reviewed.

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Integration of CA attention and KAN algorithm to predict EGFR mutation status in lung cancer reports: Epidermal Growth Factor Receptor (EGFR) mutations are critical biomarkers for targeted therapies in non-small cell lung cancer (NSCLC). However, conventional diagnostic methods rely on invasive tissue biopsies, which are costly, time-consuming, and pose significant limitations. As an alternative, non-invasive approaches using lung CT imaging to predict EGFR mutation status have gained attention for their rapid and user-friendly nature. This is a preprint and not peer reviewed.

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Robust Medical Crowdfunding Predictions: Leveraging Large Language Models and Machine Learning for Success Analysis reports: BackgroundIn the field of medical crowdfunding prediction, traditional statistical methods have long been the standard. Machine learning algorithms are popular because they can model complex relationships between variables, capture interactions, and provide more accurate predictions, even when input variables are highly correlated. Furthermore, previous research has largely overlooked the quantitative assessment of success levels and the selection of key predictors. This is a preprint and not peer reviewed.

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Ethnicity-specific molecular alterations in MAPK and JAK/STAT pathways in early-onset colorectal cancer reports: Background/ObjectivesEarly-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed before the age of 50, has been increasing in incidence, particularly among Hispanic/Latino (H/L) populations. Despite this trend, the underlying molecular mechanisms driving EOCRC disparities remain poorly understood. The MAPK and JAK/STAT pathways play critical roles in tumor progression, proliferation, and treatment response; however, their involvement in ethnicity-specific differences in EOCRC remains unclear. This is a preprint and not peer reviewed.

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Molecular alterations in TP53, WNT, PI3K, TGF-Beta and RTK/RAS pathways in gastric cancer among ethnically heterogeneous cohorts reports: Background/ObjectivesGastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with significant racial and ethnic disparities in incidence, molecular characteristics, and patient outcomes. However, genomic studies focusing on Hispanic/Latino (H/L) populations remain scarce, limiting our understanding of ethnicity-specific molecular alterations. This study aims to characterize pathway-specific mutations in TP53, WNT, PI3K, TGF-Beta and RTK/RAS signaling pathways in GC and compare mutation frequencies between H/L and Non-Hispanic White (NHW) patients. This is a preprint and not peer reviewed.

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Cancer and Post-therapy Cardiotoxicity Risk in Adolescents, Young Adults, and Adults with Down Syndrome reports: The median life expectancy of people with Down syndrome has increased substantially over the past several decades, from 4 years in 1970 to 53 years in 2010. Despite the recent improvement in survival, there is little data about the prevalence of age-related diseases, including age-related malignancies, and the impact of standard cancer treatments on cardiovascular health. We retrospectively reviewed medical records for age- and sex-matched patients [&ge;]15 years old with and without Down syndrome using the TriNetX platform to identify the prevalence of malignancies and explore cardiovascular outcomes after treatment with anthracyclines. This is a preprint and not peer reviewed.

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DINASTY in NSCLC - a multicenter retrospective study on real-world data using federated analysis reports: Real-world data is an important complement to randomized controlled trials and can be used to assess whether study results translate well to routine clinical practice and to groups of patients that are often excluded from clinical trials. The aim of this disease natural history and care quality assessment (DINASTY) study is to describe treatments, outcomes and care quality for patients with metastatic non-small cell lung cancer using real-world data. The study is a retrospective observational multicenter study conducted within DIGICORE, a non-profit European Economic Interest Grouping, formed to facilitate real-world evidence studies. This is a preprint and not peer reviewed.

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Polygenic susceptibility to dilated cardiomyopathy underlies peripartum, alcohol-induced, and cancer therapy-related cardiomyopathies reports: BackgroundRare (monogenic) variants linked to non-ischemic dilated cardiomyopathy (DCM) are enriched among individuals with peripartum (PPCM), alcohol-induced (ALCM), and cancer therapy-related (CCM) cardiomyopathies, but are present in less than 15% of cases. Whether a common variant (polygenic) predisposition to DCM also pervades these secondary cardiomyopathies remains unclear. MethodsWe evaluated the association of a DCM polygenic score with PPCM, ALCM, and CCM in the Mass General Brigham (MGB) Biobank (n = 42,137), with replication in the UK Biobank (n = 295,160) and FinnGen (n = 417,950). This is a preprint and not peer reviewed.

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Assessment of MYC Gene and WNT Pathway Alterations in Early-Onset Colorectal Cancer Among Hispanic/Latino Patients Using Integrated Multi-Omics Approaches reports: Colorectal cancer (CRC) has increased at an alarming rate amongst younger (< 50 years) individuals. Such early-onset colorectal cancer (EOCRC) has been particularly notable within the Hispanic/Latino population. Yet, this population has not been sufficiently profiled in terms of two critical elements of CRC -- the MYC proto-oncogene and WNT signaling pathway. This is a preprint and not peer reviewed.

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VOYAGER: an international consortium investigating the role of human papilloma virus and genetics in oral and oropharyngeal cancer risk and survival reports: Head and neck cancer (HNC) is the sixth most common cancer globally. Incidence and survival rates vary significantly across geographic regions and tumor subsites. This is partly due to differences in risk factor exposure, which includes tobacco smoking, alcohol consumption and human papillomavirus (HPV) infection, alongside detection and treatment strategies. This is a preprint and not peer reviewed.

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Risk Stratification for Endometrial Cancer Reveals Independent Contributions of Polygenic Risk and Body Mass Index reports: BackgroundObesity is a major risk factor for endometrial cancer, but it is unknown whether it impacts the association between genetic risk and endometrial cancer. We incorporated polygenic risk score and epidemiological risk factors in the prediction of and investigated associations of BMI and polygenic risk score with endometrial cancer risk MethodsWe generated polygenic risk score for endometrial cancer in 129,829 unrelated female participants of European ancestry (including 956 incident cases with endometrial cancer) in the UK Biobank and predicted endometrial cancer using endometrial cancer polygenic risk score and established epidemiological risk factors, including BMI. We evaluated the performance of endometrial cancer prediction models by odds ratios and area under the receiver operating characteristic curves (AUCs) to using logistic regression. This is a preprint and not peer reviewed.

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YAP controls cell migration and invasion through a Rho-GTPase switch reports: Delineating the mechanisms controlling the invasive spread of non-diseased and transformed cells is central to understanding diverse processes including cancer progression. Here, we found that Yes-associated protein (YAP), a central transcriptional regulator implicated in controlling organ and body size, modulated a Rho-GTPase switch that drives cellular migration by transactivating the Rac1-GEF protein TRIO through direct modulation of its intronic enhancer. Additionally, YAP and TRIO may promote invasive behavior through putative crosstalk with STAT3 signaling, a potential downstream target. This is a preprint and not peer reviewed.

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Causal associations between gut microbiota and cancers reports: BackgroundEmerging evidence suggests that the gut microbiota is associated with various cancer-related outcomes. Recent studies using Mendelian randomization (MR) have indicated a causal relationship between gut microbiota and several types of cancer. However, these conclusions remain controversial. This is a preprint and not peer reviewed.

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Investigating the relationship between breast cancer risk factors and an AI-generated mammographic texture feature in the Nurses' Health Study II reports: IntroductionThe mammogram risk score (MRS), an AI-driven texture feature derived from digital mammograms, strongly predicts breast cancer risk independently of breast density, though underlying mechanisms remain unclear. This study investigated relationships between established breast cancer risk factors, covering anthropometrics, reproductive factors, family history, and mammographic density metrics, and MRS. MethodsUsing data from the Nurses Health Study II (292 cases, 561 controls), we validated MRSs association with breast cancer using logistic regression and evaluated its relationships with risk factors through: linear regressions of MRS on observed risk factors and polygenic scores associated with risk factors, and Mendelian randomization (MR) analysis via two-stage least squares regression. This is a preprint and not peer reviewed.

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Analysis of Multiple Myeloma Drug Efficacy reports: IntroductionMultiple myeloma (MM) is an incurable plasma cell neoplasm. MM-specific alterations in methylation status cause gradual epigenetic changes and lead to pre-MM disease states, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering MM (SMM). The communication between MM cells and the bone marrow (BM) stromal cells serves a pivotal role in MM development by supporting transformed cell growth and proliferation. This is a preprint and not peer reviewed.

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Phase I study on the pharmacokinetics of intravaginal, self-administered artesunate vaginal pessaries among women in Kenya. reports: Cervical cancer remains a significant global health issue, especially in low- and middle-income countries (LMICs), where access to prevention and treatment is limited and women are at a higher risk of cervical cancer. Artesunate, a widely available drug used to treat malaria, has shown promise in treating human papillomavirus (HPV)-associated anogenital lesions including high-grade cervical precancer, in a recent Phase I studies in the United States. Data on the pharmacokinetics of artesunate following intravaginal use, and its implications on malaria resistance, are lacking. This is a preprint and not peer reviewed.

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Tumors with mutations in chromatin regulators are associated with higher mutational burden and improved response to checkpoint immunotherapy reports: In recent years, it has been demonstrated that many of the pervasive genetic defects throughout cancerogenesis occur in genes encoding chromatin regulators (CRs). We analyzed the distribution and characteristics of well-studied CRs across tens of thousands of tumor samples. Our analysis revealed that tumors with mutations in CRs are associated with high tumor mutational burden (TMB). This is a preprint and not peer reviewed.

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Adapting the BOADICEA breast and ovarian cancer risk models for the ethnically diverse UK population reports: BackgroundBOADICEA is a widely used algorithm for predicting breast and ovarian cancer risks, using a combination of genetic and lifestyle/environmental risk factors. However, it has largely been developed using data from individuals of White ethnicity. MethodsWe utilised data from multiple sources to derive estimates for the distributions of risk factors and their effect sizes in major UK ethnic groups (White, Black, South Asian, East Asian, and Mixed). This is a preprint and not peer reviewed.

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Cancer risks for MSH6 pathogenic variant carriers reports: IntroductionLynch syndrome (LS) is a hereditary cancer syndrome caused by (likely) pathogenic variants (LP/P) in DNA mismatch repair genes, including MSH6. It is associated with elevated lifetime risks for colorectal cancer (CRC), endometrial cancer (EC), and other malignancies. However, cancer risks specific to MSH6-associated LS, particularly for non-colorectal cancers, remain poorly defined. This is a preprint and not peer reviewed.

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Detecting papilloedema as a marker of raised intracranial pressure using artificial intelligence: a systematic review reports: IntroductionAutomated detection of papilloedema using artificial intelligence (AI) and retinal images acquired through an ophthalmoscope for triage of patients with potential intracranial pathology could prove to be beneficial, particularly in resource-limited settings where access to neuroimaging may be limited. However, a comprehensive overview of the current literature on this field is lacking. MethodsWe conducted a systematic review on the use of AI for papilloedema detection by searching four databases: Ovid MEDLINE, Embase, Web of Science, and IEEE Xplore. This is a preprint and not peer reviewed.

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Neurology Training in Italy: A Survey on Italian Residency Programmes and Compliance with European Training Standards reports: BackgroundSince 2005, the European Union of Medical Specialists - Section of Neurology and the European Board of Neurology have outlined a comprehensive curriculum, the European Training Requirements in Neurology (ETRN), which defines the essential clinical knowledge, practical skills, and research competencies that European neurology training programmes should encompass. Despite these standards, notable differences in training quality and resources persist among Italian residency programmes. This survey, conducted by the Italian Section of Young Neurologists, aimed to assess the alignment of Italian neurology residency programmes with ETRN standards and to evaluate residents and early-career neurologists self-reported knowledge, practical skills, and access to specialised training opportunities. This is a preprint and not peer reviewed.

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SCellBOW: AI-Driven Tumor Risk Stratification from Single-Cell Transcriptomics Using Phenotype Algebra reports: Single-cell RNA-sequencing (scRNA-seq) coupled with robust computational analysis facilitates the characterization of phenotypic heterogeneity within tumors. Current scRNA-seq analysis pipelines are capable of identifying a myriad of malignant and non-malignant cell subtypes from single-cell profiling of tumors. However, given the extent of intra-tumoral heterogeneity, it is challenging to assess the risk associated with individual cell subpopulations, primarily due to the complexity of the cancer phenotype space and the lack of clinical annotations associated with tumor scRNA-seq studies. This is a preprint and not peer reviewed.

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Automated segmentation of trunk musculature with a deep CNN trained from sparse annotations in radiation therapy patients with metastatic spine disease: an observational study. reports: Given the high prevalence of vertebral fractures following radiotherapy in patients with metastatic spine disease, torso muscle segmentation is necessary for biomechanical modeling of vertebral loading, permitting individualized evaluation of fracture risk. In this study, we developed and validated a deep-learning model for full volumetric segmentation of the thoracic and abdominal spinal musculature in cancer patients with metastatic spine disease from sparsely annotated clinical CT image data. We obtained CT data for 148 metastatic spine disease patients undergoing radiotherapy treatment, and an external set of randomly selected 30 subjects from the National Lung Screening Trial.

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From genetic risk to early detection - clinical outcomes of a person-centered screening program for women with a high genetic risk of breast cancer. reports: There is little evidence on breast cancer (BC) diagnosed in women with a high genetic risk, before and after their inclusion in a long-term risk management program based on genetic risk assessment. We analyzed clinical outcomes in women enrolled in the Phare Grand Ouest (PGO) program. The PGO includes carriers of the BRCA1 and BRCA2 pathogenic variants (PV) and women at high risk without BRCA PV , enrolled in eight cancer genetics units.

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M2 macrophage infiltration drives tumor progression and identifies a multigene prognostic signature in esophageal cancer. reports: This study aimed to elucidate the mechanistic role of M2 tumor-associated macrophages in esophageal cancer (EC) progression and to construct an M2 macrophage-related gene signature for prognostic prediction. Integrated analyses of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of EC were performed. scRNA-seq data were processed with Seurat and annotated using SingleR.

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Modulation of gut microbiota and short-chain fatty acids by probiotics attenuates inflammation in endometriosis. reports: This study investigated whether probiotics alleviate Endometriosis (EMs)-related inflammation by modulating the gut microbiota and short-chain fatty acids (SCFAs). An endometriosis model was established in SD rats, which were randomly divided into a normal diet group (NCD) and a probiotic group (NCD_Pro), with four rats per group. After a 4-week dietary intervention, serum and fecal samples were collected.

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Unveiling the tumor microenvironment in colorectal cancer therapeutic resistance. reports: Therapeutic resistance remains a major barrier to effective treatment in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a pivotal role in modulating responses to chemotherapy, immunotherapy, and targeted therapies. This review synthesizes current evidence on how cellular and non-cellular TME components contribute to resistance mechanisms in CRC. Key immune cells, including T cells, macrophages, neutrophils, natural killer cells, dendritic cells, and myeloid-derived suppressor cells, orchestrate immunosuppressive networks that impair drug efficacy.

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