Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base.

Large-scale, pan-cancer analysis is enabled by data driven knowledge bases that link tumor molecular profiles with phenotypes. A debilitating cancer-related phenotype is skeletal muscle loss, or cachexia, which occurs partly from tumor products secreted into circulation. Using the LinkedOmicsKB knowledge base assembled from the Clinical Proteomics Tumor Analysis Consortium proteogenomic analysis, along with catalogs of human secretome proteins, ligand-receptor pairs and molecular signatures, we sought to identify candidate pan-cancer proteins secreted to blood that could regulate skeletal muscle phenotypes in multiple solid cancers.

On the Gaussian modulus of lipid membranes.

The Gaussian modulus is a crucial property that influences topological transformations in lipid membranes. However, unlike the bending modulus, estimating the Gaussian modulus has been particularly challenging due to the constraints imposed by the Gauss-Bonnet theorem. Despite this, various theoretical, computational, and experimental approaches have been developed to estimate the Gaussian modulus, though they are often complex, and analytical estimates remain rare.

Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.

Differential diagnosis in immune checkpoint inhibitors neurotoxicity.

Background: Neurologic symptoms seen in patients receiving immune checkpoint inhibitors (ICI) may not be entirely caused by immunotoxicity. We aim to highlight these confounding conditions through clinical cases to encourage early recognition and management.

Methods: We describe a series of seven cases from our institution that were treated with ICI and presented with Neurologic symptoms and were diagnosed with superimposed conditions beyond immunotoxicity.

Circulating Endocannabinoids and Cognitive Function in Older Adults.

The role of endogenous cannabinoids (endocannabinoids; eCBs) in cognitive-related processes has been demonstrated in preclinical studies. However, observational studies are lacking. We examined the associations of multiple circulating eCBs and eCB-like molecules with cognitive function in a sample of dementia-free older adults.

Economic impact of reduced postoperative visits after inflatable penile prosthesis implantation.

This study assessed the economic impact of reducing one postoperative visit following inflatable penile prosthesis (IPP) implantation. Scenario analyses were used to model the effects of eliminating one 30-min IPP postoperative visit from the expected 2.5 visits accounted for by the American Medical Association resource-based relative value scale data.

Thoracic endovascular repair of a ruptured thoracic aortic aneurysm with in situ laser fenestration of the left subclavian and left common carotid artery.

Most thoracic aortic aneurysms (TAAs) are asymptomatic and often diagnosed at the time of rupture. TAAs involving the proximal arch require adequate coverage with thoracic endovascular aortic repair, which is timely and challenging in emergent ruptures. In situ laser fenestration is a novel method of arch revascularization.

A novel technique for external iliac artery reconstruction in renal transplant patients with extensively atherosclerotic lower limb vasculature.

We describe a 54-year-old man with type 2 diabetes mellitus, ischemic myopathy, pulmonary hypertension, and end-stage renal disease who was admitted for heart failure and listed for a dual cardiac-renal transplantation. Extensive calcification in the iliac arteries prevented clamping. Proximal endovascular balloon control of the left iliac artery was achieved using contralateral access; distal control was established by passing a Fogarty catheter distally through an iliac arteriotomy, later used for anastomosis of the cadaveric conduit.

Directed evolution of an orthogonal transcription engine for programmable gene expression in eukaryotes.

T7 RNA polymerase (RNAP) has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5' methyl guanosine caps on T7 RNAP-derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using .

Light-dark shift promotes colon carcinogenesis through accelerated colon aging.

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC.

Exosomal Galectin-3 promotes peritoneal metastases in gastric adenocarcinoma via microenvironment alterations.

Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear.

Reversal of inflammatory reprogramming by vasodilator agents in pulmonary hypertension.

Background: Pulmonary arterial hypertension (PAH) is a deadly disease without effective non-invasive diagnostic and prognostic testing. It remains unclear whether vasodilators reverse inflammatory activation, a part of PAH pathogenesis. Single-cell profiling of inflammatory cells in blood could clarify these PAH mechanisms.

Inhaled alpha-1 antitrypsin (AAT) restores lower respiratory tract protease-antiprotease homoeostasis and reduces inflammation in AAT-deficient individuals: a randomised phase 2 study.

Background: Alpha-1 antitrypsin (AAT)-deficient individuals have a greater risk for developing COPD than individuals with normal AAT levels.

Methods: This was a double-blind, randomised, parallel group, placebo-controlled trial to examine the safety and tolerability of "Kamada-AAT for Inhalation" (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). 36 patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks.

Effect of the TiCT (T = O, OH, and H) Functionalization on the Formation of (TiO)/TiCT Composites.

First-principles density functional theory calculations are carried out on the (TiO) cluster supported on the TiCT (0001) surface with different chemical terminations, , -H, -O, and -OH, to study the interaction and understand the TiCT functionalization effect on the formation of (TiO)/TiCT composites. Results show an exothermic interaction for all cases, whose strength is driven by the surface termination, promoting weaker bonds when the MXene is functionalized with H atoms. For TiCH and TiC(OH) MXenes, the interaction is accompanied by a charge transfer towards the titania cluster.

TiCT MXene Thin Films and Intercalated Species Characterized by IR-to-UV Broadband Ellipsometry.

MXenes are two-dimensional (2D) materials with versatile applications in optoelectronics, batteries, and catalysis. To unlock their full potential, it is crucial to characterize MXene interfaces and intercalated species in more detail than is currently possible with conventional optical spectroscopies. Here, we combine ultra-broadband ellipsometry and transmission spectroscopy from the mid-infrared (IR) to the deep-ultraviolet (UV) to probe quantitatively the composition, structure, transport, and optical properties of spray-coated TiCT MXene thin films with varying material properties.

Use of Immunoglobulin Replacement Therapy in Clinical Practice: A Review.

Immunoglobulins (Igs) are produced by B lymphocytes and play a key role in humoral immunity. Igs are classified into five isotypes (IgG, IgA, IgM, IgE, and IgD). Their primary function is to recognize and bind to foreign antigens.

A Rare But Fatal Toxicity: Immune Checkpoint Inhibitor-Related Acquired Thrombotic Thrombocytopenic Purpura.

Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombotic microangiopathy resulting from decreased activation of the von Willebrand factor-cleaving protease (ADAMTS13). TTP can cause organ damage and is often fatal if the appropriate treatment is not started immediately. Although primary immune TTP is the most common form of TTP, secondary immune etiologies, including complications from immune checkpoint inhibitors (ICIs), have also been reported.

Durable Remission After Targeted Therapy in Mutant Metastatic Colorectal Cancer: Case Report.

BRAF mutation leads to constitutive activation of the MAPK pathway and is associated with the immune-activating molecular subtype of colorectal cancer. Targeted therapy for mutant metastatic colorectal cancer (CRC) has significantly improved outcomes for these patients when combined with anti-epithelial growth factor receptor (EGFR) therapy. However, most patients ultimately develop disease progression.

Expert Clinical Management of Inflammatory Immune-Related Arthritis in Patients with Cancer Receiving Immune Checkpoint Inhibitors.

Introduction: Treatment guidelines for immune-related inflammatory arthritis (irAE-IA) in patients with cancer receiving immune checkpoint inhibitors (ICIs) are vague with respect to the use of specific agents. Patients are usually referred to rheumatologists for treatment. We conducted a survey of expert rheumatologists to determine current practices.

Retrospective claims data analysis of ASCT characteristics and costs for working-age, multiple myeloma patients in the US, 2017-2019.

Multiple myeloma (MM) is a rare hematologic malignancy with a 5-year survival rate of 52 %. For transplant-eligible MM patients, high-dose chemotherapy followed by autologous stem cell transplant (ASCT) is recommended. Given the complexities of the ASCT procedure, understanding patient-specific factors and their impact on treatment decisions is essential.