Finerenone attenuates downregulation of the kidney GLP-1 receptor and glucagon receptor and cardiac GIP receptor in mice with comorbid diabetes.

Background: Several new treatments have recently been shown to have heart and kidney protective benefits in people with diabetes. Because these treatments were developed in parallel, it is unclear how the different molecular pathways affected by the therapies may overlap. Here, we examined the effects of the mineralocorticoid receptor antagonist finerenone in mice with comorbid diabetes, focusing on the regulation of expression of the glucagon-like peptide-1 receptor (GLP-1R), gastric inhibitory polypeptide receptor (GIPR) and glucagon receptor (GCGR), which are targets of approved or investigational therapies in diabetes.

A Rare Presentation of Extrahepatic Biliary Neuroendocrine Tumor Diagnosed using Ga-DOTA-TOC Imaging, But Undetectable on Ga-FAPI Imaging.

Neuroendocrine tumors (NETs) are commonly seen in the small intestine and rarely found within the bile ducts. This low incidence is due to a smaller number of Kulchitsky cells in the extrahepatic biliary tree, which predisposes to the disease. The diagnosis of biliary tree carcinoid preoperatively is very rare, with most cases in the literature being incidentally diagnosed during surgery or being identified on the histopathology report postoperatively.

Transcriptome-Derived Ligand-Receptor Interactome of Major PitNET Subgroups.

 Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors which can impart significant disability owing to their locally invasive potential. To date, the gamut of PitNET subtypes remains ill-understood at the ligand-receptor (LR) interactome level, potentially limiting therapeutic options. Here, we present findings from in silico analysis of LR complexes formed by PitNETs with clinical presentations of acromegaly, Cushing's disease, high prolactin production, and without symptoms of hormone hypersecretion.

Interferons and interferon-related pathways in heart disease.

Interferons (IFNs) and IFN-related pathways play key roles in the defence against microbial infection. However, these processes may also be activated during the pathogenesis of non-infectious diseases, where they may contribute to organ injury, or function in a compensatory manner. In this review, we explore the roles of IFNs and IFN-related pathways in heart disease.

Neglected Tropical Diseases: A Comprehensive Review.

Neglected tropical diseases (NTDs) are a group of diseases caused by diverse organisms, affecting millions of people in tropical and subtropical conditions. NTDs are more prevalent among people who live in poverty, without access to clean water, adequate sanitation, and quality health care. Most NTDs are chronic conditions and are potentially disablers than killers, leaving behind a trail of social consequences.

Hypoxic transcriptomes predict survival and tumor-infiltrating immune cell composition in cutaneous melanoma.

Hypoxia has established associations with aggressive tumor phenotypes in many cancers. However, it is not currently understood whether tumor hypoxia levels map to distinct immune infiltrates in cutaneous melanoma, potentially unveiling novel therapeutic targets. To this end, we leveraged a previously identified seven-gene hypoxia signature to grade hypoxia levels of 460 cutaneous melanomas obtained from the Broad Institute GDAC Firehose portal.

A Decade of Global Skull Base Researchers: Authorship Trends from 3,295 Abstracts in the .

 The North American Skull Base Society (NASBS) multidisciplinary annual conference hosts skull base researchers from across the globe. We hypothesized that the work presented at the NASBS annual conference would reveal diverse authorship teams in terms of specialty and geography.  In this retrospective review, abstracts presented at the NASBS annual meeting and subsequently published in the between 01/01/2011 and 12/31/2020 were collected.

Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution.

Background: Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear.

Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma.

Glioblastoma (GBM) is an aggressive primary CNS malignancy and clinical outcomes have remained stagnant despite introduction of new treatments. Understanding the tumor microenvironment (TME) in which tumor associated macrophages (TAMs) interact with T cells has been of great interest. Although previous studies examining TAMs in GBM have shown that certain TAMs are associated with specific clinical and/or pathologic features, these studies used an outdated M1/M2 paradigm of macrophage polarization and failed to include the continuum of TAM states in GBM.

Disadvantaged Neighborhoods Continue to Bear the Burden of Gun Violence.

Introduction: Gun violence is a pervasive and dynamic public health crisis causing substantial burden on communities and healthcare systems in the United States. Risk factor and outcome analyses are crucial to develop effective interventions. The aim of this study was to assess firearm injury in a diverse community setting as it relates to neighborhood socioeconomic disadvantage and changes over time following large-scale local interventions.

Genomic subtypes of cutaneous melanoma have distinct metabolic profiles: A single-cell transcriptomic analysis.

Objective: Genomic profiling previously classified melanoma into distinct subtypes based on the presence or absence of mutations in driver genes, but metabolic differences between and within these groups have yet to be thoroughly analyzed. Thus, the objective of the present study is to provide the first effort to holistically characterize the metabolic landscape of qualified melanoma genomic subtypes at single-cell resolution.

Methods: Expression data for a total of 1145 malignant cells sourced from NRAS(Q61L), BRAF(V600E), and NRAS/BRAF WT melanomas were retrieved from the Broad Single Cell Portal.

Altered expression, but small contribution, of the histone demethylase KDM6A in obstructive uropathy in mice.

Epigenetic processes have emerged as important modulators of kidney health and disease. Here, we studied the role of KDM6A (a histone demethylase that escapes X-chromosome inactivation) in kidney tubule epithelial cells. We initially observed an increase in tubule cell Kdm6a mRNA in male mice with unilateral ureteral obstruction (UUO).

Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review.

Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting.

Kimma: flexible linear mixed effects modeling with kinship covariance for RNA-seq data.

Motivation: The identification of differentially expressed genes (DEGs) from transcriptomic datasets is a major avenue of research across diverse disciplines. However, current bioinformatic tools do not support covariance matrices in DEG modeling. Here, we introduce kimma (Kinship In Mixed Model Analysis), an open-source R package for flexible linear mixed effects modeling including covariates, weights, random effects, covariance matrices, and fit metrics.

Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure.

Inflammation promotes adverse ventricular remodeling, a common antecedent of heart failure. Here, we set out to determine how inflammatory cells affect cardiomyocytes in the remodeling heart. Pathogenic cardiac macrophages induced an IFN response in cardiomyocytes, characterized by upregulation of the ubiquitin-like protein IFN-stimulated gene 15 (ISG15), which posttranslationally modifies its targets through a process termed ISGylation.

Single cell G-protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21.

Background And Purpose: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G-protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express.

Experimental Approach: RNA sequencing and single cell qRT-PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO).

Trends in Volume and Charges of Retinal Tear Patients in the Emergency Department.

Purpose: To characterize retinal tears (RTs) and calculate the economic burden of RTs that present to the emergency department (ED) in the US.

Methods: We used a large national ED database to retrospectively analyze RTs that presented to the ED from 2006 to 2019. Using extrapolation methods, national of the RT patient ED volume, demographics, comorbidities, disposition, inpatient (IP) charges, and ED charges were calculated.

Spatial metabolic heterogeneity of oligodendrogliomas at single-cell resolution.

Oligodendrogliomas are a type of rare and incurable gliomas whose metabolic profiles have yet to be fully examined. The present study examined the spatial differences in metabolic landscapes underlying oligodendrogliomas and should provide unique insights into the metabolic characteristics of these uncommon tumors. Single-cell RNA-sequencing expression profiles from 4044 oligodendroglioma cells derived from tumors resected from four locations frontal, temporal, parietal, and frontotemporoinsular) and in which 1p/19q co-deletion and IDH1 or IDH2 mutations were confirmed were computationally analyzed through a robust workflow to elucidate relative differences in metabolic pathway activities among the different locations.

Primary and Metastatic Cutaneous Melanomas Discriminately Enrich Several Ligand-Receptor Interactions.

Introduction: Cutaneous melanoma remains a leading cancer with sobering post-metastasis mortality rates. To date, the ligand-receptor interactome of melanomas remains weakly studied despite applicability to anti-cancer drug discovery. Here we leverage established crosstalk methodologies to characterize important ligand-receptor pairs in primary and metastatic cutaneous melanoma.

Predictors of inpatient admission likelihood and prolonged length of stay among cerebrovascular disease patients: A nationwide emergency department sample analysis.

Purpose: To examine the hospital- and patient-related factors associated with increased likelihood of inpatient admission and extended hospitalization.

Methods: We applied multivariate logistic regression to a subset of ED hospital and patient characteristics linearly extrapolated from the 2019 National Emergency Department Sample database (n=626,508). Patient characteristics with 10 or fewer ED visits after national extrapolation were not reported in the current study to maintain patient confidentiality, in accordance with the HCUP Data Use Agreement.

A Decade of Global Skull Base Researchers: Gender Data from over 2,700 Abstract Authors in the .

 The North American Skull Base Society (NASBS) annual conference brings together skull base researchers from surgical and nonsurgical fields. Our objective was to quantify the contributions of the authors by gender, who presented their work at NASBS and were subsequently published in the .  Oral and poster abstracts presented at the NASBS annual meeting from January 1, 2011 to December 31, 2020 were extracted from the The genderize.

Neuro-oncology authorship trends in gender since 1944: a systematic review of 14,020 articles from five top-tier academic journals.

Objective: This study was performed to compare authorship trends, by gender, in the neurosurgical oncology literature.

Methods: Complete author listings for neurosurgical oncology articles published between 1944 and 2021 in five top neuro-oncology journals were extracted from the PubMed database and journal websites on December 2, 2021. Author gender was characterized with the web application programming interface (API) genderize.

Tyrosine kinase inhibitors versus radiation therapy in unresectable dermatofibrosarcoma protuberans (DFSP): A narrative systematic review.

Background: In unresectable dermatofibrosarcoma protuberans (DFSP), no clear guideline exists regarding the use of tyrosine kinase inhibitors (TKI) versus radiotherapy. This study reviews current literature regarding TKI and radiotherapy in unresectable DFSP.

Methods: Following PROSPERO registration (CRD42021232508), a systematic literature search was performed including all studies reporting clinical results of TKI and/or radiotherapy in the treatment of unresectable DFSP.

The SGLT2i Dapagliflozin Reduces RV Mass Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding.

Background: Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class is efficacious in the treatment and prevention of right heart failure has not been explored.

Hypothesis: We hypothesized that SGLT2 inhibition would reduce the structural, functional, and molecular responses to pressure overload of the right ventricle.