Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids.

Importance: Current evidence of the association between prenatal exposure to glucocorticoids and long-term mental disorders is scarce and has limitations.

Objective: To investigate the association between prenatal exposure to systemic glucocorticoids and mental disorders in offspring at the age of 15 years, comparing exposed vs unexposed offspring born to mothers with the same underlying disease (risk of preterm delivery and autoimmune or inflammatory disorders).

Design, Setting, And Participants: This nationwide population-based cohort study used data from registries in Denmark with follow-up until December 31, 2018.

Molecular Pathway and Immune Profile Analysis of IPMN-Derived Versus PanIN-Derived Pancreatic Ductal Adenocarcinomas.

Intraductal papillary mucinous neoplasms (IPMN) are commonly detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need.

: Integrative Module Analysis for Multi-omics Data.

Summary: The integration of metabolomics with other omics ("multi-omics") offers complementary insights into disease biology. However, this integration remains challenging due to the fragmented landscape of current methodologies, which often require programming experience or bioinformatics expertise. Moreover, existing approaches are limited in their ability to accommodate unidentified metabolites, resulting in the exclusion of a significant portion of data from untargeted metabolomics experiments.

The peri-operative implications of sodium-glucose co-transporter 2 inhibitors: a narrative review.

Introduction: Sodium-glucose co-transporter 2 inhibitors are a novel class of antihyperglycaemic drugs used in the management of type 2 diabetes, that improve glycaemic control, cardiovascular outcomes and promote weight loss. They are also approved for the treatment of heart failure and chronic kidney disease in patients with or without diabetes. This narrative review discusses the peri-operative effects and implications of sodium-glucose co-transporter 2 inhibitors and gives an overview of current evidence and existing peri-operative guidelines.

Multimodal data integration for oncology in the era of deep neural networks: a review.

Cancer research encompasses data across various scales, modalities, and resolutions, from screening and diagnostic imaging to digitized histopathology slides to various types of molecular data and clinical records. The integration of these diverse data types for personalized cancer care and predictive modeling holds the promise of enhancing the accuracy and reliability of cancer screening, diagnosis, and treatment. Traditional analytical methods, which often focus on isolated or unimodal information, fall short of capturing the complex and heterogeneous nature of cancer data.

Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management.

Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria.

Defining and Addressing Research Priorities in Cancer Cachexia through Transdisciplinary Collaboration.

For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects.

Impact of deprivation and preferential usage on functional connectivity between early visual cortex and category selective visual regions.

Unlabelled: Human behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how the removal of input changes brain function. However, an important question has yet to be answered: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details.

Implementation of a High-Accuracy Targeted Gene Expression Panel for Clinical Care.

This study describes the validation of a clinical RNA expression panel with evaluation of concordance between gene copy gain by a next-generation sequencing (NGS) assay and high gene expression by an RNA expression panel. The RNA Salah Targeted Expression Panel (RNA STEP) was designed with input from oncologists to include 204 genes with utility for clinical trial prescreening and therapy selection. RNA STEP was validated with the nanoString platform using remnant formalin-fixed, paraffin-embedded-derived RNA from 102 patients previously tested with a validated clinical NGS panel.

Structure-independent machine-learning predictions of the CDK12 interactome.

Cyclin-dependent kinase 12 (CDK12) is a critical regulatory protein involved in transcription and DNA repair processes. Dysregulation of CDK12 has been implicated in various diseases, including cancer. Understanding the CDK12 interactome is pivotal for elucidating its functional roles and potential therapeutic targets.

Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma.

A specific splicing isoform of RNASET2 is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment.

Branched-chain keto acids promote an immune-suppressive and neurodegenerative microenvironment in leptomeningeal disease.

Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD.

RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing.

RNA splicing is an important biological process associated with cancer initiation and progression. However, the contribution of alternative splicing to pancreatic cancer (PDAC) development is not well understood. Here, we identify an enrichment of RNA binding proteins (RBPs) involved in splicing regulation linked to PDAC progression from a forward genetic screen using Sleeping Beauty insertional mutagenesis in a mouse model of pancreatic cancer.

Clinical Presentation and Genomic Analysis of HPV-Related Squamous Cell Carcinoma of the Larynx in Two Young Female Patients.

Laryngeal cancer most frequently develops in males aged 60-70 years with a history of tobacco and/or alcohol use, while fewer cases occur in young patients in which tobacco and alcohol are often absent or less significant, highlighting the importance of other etiologies. We present cases of human papillomavirus (HPV)-associated laryngeal cancer in two previously healthy young women. A retrospective case review was carried out for both patients.

Increased spatial coupling of integrin and collagen IV in the immunoresistant clear cell renal cell carcinoma tumor microenvironment.

Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples.

Brain metastasis-associated fibroblasts secrete fucosylated PVR/CD155 that induces breast cancer invasion.

Brain metastasis cancer-associated fibroblasts (bmCAFs) are emerging as crucial players in the development of breast cancer brain metastasis (BCBM), but our understanding of the underlying molecular mechanisms is limited. In this study, we aim to elucidate the pathological contributions of fucosylation (the post-translational modification of proteins by the dietary sugar L-fucose) to tumor-stromal interactions that drive the development of BCBM. Here, we report that patient-derived bmCAFs secrete high levels of polio virus receptor (PVR), which enhance the invasive capacity of BC cells.