Circulating Protein and Metabolite Correlates of Histologically Confirmed Diabetic Kidney Disease.

Rationale & Objective: Diabetic kidney disease (DKD) is one of the leading causes of end-stage kidney disease globally. We aim to identify proteomic and metabolomic correlates of histologically confirmed DKD that may improve our understanding of its pathophysiology.

Study Design: A cross-sectional study.

Brazilian authorship gender trends on academic surgery: a bigdata analysis.

Purpose: To evaluate the gender distribution of first and last authors with Brazilian surgical affiliations in PubMed-indexed surgical journals.

Methods: Data from eligible surgical journals were retrieved using Scimago Journal & Country Rank 2021 and manually reviewed. Manuscripts published from 2018 to 2022 were included if at least one author was affiliated with a Brazilian institution and a surgical specialty.

Artificial Intelligence Algorithms in Cardiovascular Medicine: An Attainable Promise to Improve Patient Outcomes or an Inaccessible Investment?

Purpose Of Review: This opinion paper highlights the advancements in artificial intelligence (AI) technology for cardiovascular disease (CVD), presents best practices and transformative impacts, and addresses current concerns that must be resolved for broader adoption.

Recent Findings: With the evolution of digitization in data collection, large amounts of data have become available, surpassing the human capacity for processing and analysis, thus enabling the application of AI. These models can learn complex spatial and temporal patterns from large amounts of data, providing patient-specific outputs.

Steroid Hormone Biosynthesis and Dietary Related Metabolites Associated with Excessive Daytime Sleepiness.

Background: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep, and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large scale single- and pathway-level metabolomics analyses.

Remodeling p38 signaling in muscle controls locomotor activity via IL-15.

Skeletal muscle has gained recognition as an endocrine organ releasing myokines upon contraction during physical exercise. These myokines exert both local and pleiotropic health benefits, underscoring the crucial role of muscle function in countering obesity and contributing to the overall positive effects of exercise on health. Here, we found that exercise activates muscle p38γ, increasing locomotor activity through the secretion of interleukin-15 (IL-15).

High-throughput discovery of MHC class I- and II-restricted T cell epitopes using synthetic cellular circuits.

Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context.

Brain-wide functional connectivity artifactually inflates throughout functional magnetic resonance imaging scans.

Functional magnetic resonance imaging (fMRI) is a central tool for investigating human brain function, organization and disease. Here, we show that fMRI-based estimates of functional brain connectivity artifactually inflate at spatially heterogeneous rates during resting-state and task-based scans. This produces false positive connection strength changes and spatial distortion of brain connectivity maps.

The infected diabetic foot: Analysis of diabetic and non-diabetic foot infections.

The aim of this study was to compare outcomes of moderate and severe foot infections in people with and without diabetes mellitus (DM). We retrospectively evaluated 382 patients (77% with DM and 23% non-DM). We collected demographic data, co-morbidities and one-year outcomes including healing, surgical interventions, number of surgeries, length of stay, re-infection and re-hospitalisation.

Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia.

Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.

The HLA-II immunopeptidome of SARS-CoV-2.

Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames.

Deletion of FNDC5/Irisin modifies murine osteocyte function in a sex-specific manner.

Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lacking (KO), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet.

Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function.

We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive.

Brain-wide functional connectivity artifactually inflates throughout fMRI scans: a problem and solution.

The fMRI blood oxygen level-dependent (BOLD) signal is a mainstay of neuroimaging assessment of neuronal activity and functional connectivity . Thus, a chief priority is maximizing this signal's reliability and validity. To this end, the fMRI community has invested considerable effort into optimizing both experimental designs and physiological denoising procedures to improve the accuracy, across-scan reproducibility, and subject discriminability of BOLD-derived metrics like functional connectivity.

Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.

Background: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection.

Association Between Cervical Cancer Screening Guidelines and Preterm Delivery Among Females Aged 18 to 24 Years.

Importance: Cervical cancer screening is associated with reduced cervical cancer mortality; however, clinical trials have also shown an association between excisional procedures for cervical neoplasia and an increased risk of preterm delivery (PTD). National screening guidelines must weigh adverse effects on birth outcomes against benefits of cancer prevention.

Objective: To ascertain the population-level association between the number of guideline-recommended cervical cancer screenings and downstream PTD risk among females aged 18 to 24 years.

Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium.

Background: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18.

Methods: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18.

Structural sexism moderates work and occupational risks for alcohol consumption and binge drinking among US women, 1989-2016.

Background: People in the labor force and in high-status careers consume alcohol at high rates. State-level structural sexism (sex inequality in political/economic status) is inversely related to alcohol use among women. We examine whether structural sexism modifies women's labor force characteristics and alcohol consumption.

Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis.

Objective: In retrospective studies, liver stiffness (LS) by vibration-controlled transient elastography (VCTE) is associated with the risk of liver decompensation in patients with non-alcoholic steatohepatitis (NASH), but prospective data in biopsy-confirmed cohorts with advanced fibrosis are limited. We aimed to establish thresholds for LS by VCTE that predict progression to cirrhosis among patients with bridging fibrosis and hepatic decompensation among patients with cirrhosis due to NASH.

Design: We used data from four randomised placebo-controlled trials of selonsertib and simtuzumab in participants with advanced fibrosis (F3-F4).

Bariatric surgeon perceptions of the safety of same-day sleeve gastrectomy in the state of Massachusetts.

Background: During the past 2.5 years, select bariatric surgeons in the Commonwealth of Massachusetts have been implementing same-day sleeve gastrectomy (SDSG). Key reasons for this change have been to reduce risks associated with hospitalization in the context of the COVID-19 pandemic and to comply with third-party payer preference to reduce costs.