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.

Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104.

Neuroactive steroids reduce mortality, decrease edema, and improve functional outcomes in preclinical and clinical traumatic brain injury (TBI) studies. In this study, we tested the efficacy of two related novel neuroactive steroids, NTS-104 and NTS-105, in a rat model of TBI. NTS-104 is a water-soluble prodrug of NTS-105, a partial progesterone receptor agonist.

Volumetric measurement of terminal ileal Crohn's disease by magnetic resonance enterography: a feasibility study.

Objectives: Magnetic resonance enterography (MRE) interpretation of Crohn's disease (CD) is subjective and uses 2D analysis. We evaluated the feasibility of volumetric measurement of terminal ileal CD on MRE compared to endoscopy and sMARIA, and the responsiveness of volumetric changes to biologics.

Methods: CD patients with MRE and contemporaneous CD endoscopic index of severity-scored ileocolonoscopy were included.

A simple, clinically usable whole-body MRI system of joint assessment in adolescents and young people with juvenile idiopathic arthritis.

Objectives: To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice.

Methods: The proposed system utilizes post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0-2) and structural damage (present/absent) at 81 sites.

Ocular Gene Therapy in a Patient with Dystrophic Epidermolysis Bullosa.

Dystrophic epidermolysis bullosa is a rare genetic disease caused by damaging variants in , which encodes type VII collagen. Blistering and scarring of the ocular surface develop, potentially leading to blindness. Beremagene geperpavec (B-VEC) is a replication-deficient herpes simplex virus type 1-based gene therapy engineered to deliver functional human type VII collagen.

Detection of inflammation by whole-body MRI in young people with juvenile idiopathic arthritis.

Objectives: To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings.

Methods: YP aged 14-24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria.

Assessment of the Performances of the Protein Modeling Techniques Participating in CASP15 Using a Structure-Based Functional Site Prediction Approach: ResiRole.

Background: Model quality assessments via computational methods which entail comparisons of the modeled structures to the experimentally determined structures are essential in the field of protein structure prediction. The assessments provide means to benchmark the accuracies of the modeling techniques and to aid with their development. We previously described the ResiRole method to gauge model quality principally based on the preservation of the structural characteristics described in SeqFEATURE functional site prediction models.

Updated systematic review of the effects of exercise on understudied health outcomes in cancer survivors.

Introduction: The American College of Sports Medicine provided guidelines for exercise prescriptions in cancer survivors for specific cancer- and treatment-related health outcomes. However, there was insufficient evidence to generate exercise prescriptions for 10 health outcomes of cancer treatment. We sought to update the state of evidence.

NTS-105 decreased cell death and preserved long-term potentiation in an in vitro model of moderate traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of hospitalization and death. To mitigate these human costs, the search for effective drugs to treat TBI continues. In the current study, we evaluated the efficacy of the novel neurosteroid, NTS-105, to reduce post-traumatic pathobiology in an in vitro model of moderate TBI that utilizes an organotypic hippocampal slice culture.

Prognostic factors to identify resolution of small bowel obstruction without need for operative management: systematic review.

Objectives: To identify imaging, clinical, and laboratory variables potentially prognostic for surgical management of small bowel obstruction.

Methods: Two researchers systematically reviewed indexed literature 2001-2021 inclusive for imaging, clinical, and laboratory variables potentially predictive of surgical management of small bowl obstruction and/or ischaemia at surgery, where performed. Risk of bias was assessed.

The pathophysiology of cancer-mediated cardiac cachexia and novel treatment strategies: A narrative review.

Significance: Two of the leading causes of death worldwide are cancer and cardiovascular diseases. Most cancer patients suffer from a metabolic wasting syndrome known as cancer-induced cardiac cachexia, resulting in death in up to 30% of cancer patients. Main symptoms of this disease are severe cardiac muscle wasting, cardiac remodeling, and cardiac dysfunction.

Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury.

Traumatic brain injury (TBI) triggers wide-ranging pathology that impacts multiple biochemical and physiological systems, both inside and outside the brain. Functional recovery in patients is impeded by early onset brain edema, acute and chronic inflammation, delayed cell death, and neurovascular disruption. Drug treatments that target these deficits are under active development, but it seems likely that fully effective therapy may require interruption of the multiplicity of TBI-induced pathological processes either by a cocktail of drug treatments or a single pleiotropic drug.

Diagnostic performance of sonographic activity scores for adult terminal ileal Crohn's disease compared to magnetic resonance and histological reference standards: experience from the METRIC trial.

Objectives: The simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) are promising intestinal ultrasound (IUS) indices of CD, but studied mainly in small settings with few sonographers. We compared SUS-CD and BUSS against histological and magnetic resonance enterography (MRE) reference standards in a post hoc analysis of a prospective multicentre, multireader trial.

Methods: Participants recruited to the METRIC trial (ISRCTN03982913) were studied, including those with available terminal ileal (TI) biopsies.

Impact of prostate imaging quality (PI-QUAL) score on the detection of clinically significant prostate cancer at biopsy.

Purpose: To investigate the impact of Prostate Imaging Quality (PI-QUAL) scores on the diagnostic performance of multiparametric MRI (mpMRI) in a targeted biopsy cohort.

Patients And Methods: 300 patients who underwent both mpMRI and biopsy were included. PI-QUAL scores were retrospectively assigned by two radiologists in consensus and were correlated to pre-biopsy PI-RADS scores and biopsy outcomes.

Skeletal muscle omics signatures in cancer cachexia: perspectives and opportunities.

Cachexia is a life-threatening complication of cancer that occurs in up to 80% of patients with advanced cancer. Cachexia reflects the systemic consequences of cancer and prominently features unintended weight loss and skeletal muscle wasting. Cachexia impairs cancer treatment tolerance, lowers quality of life, and contributes to cancer-related mortality.

Cardioprotective effects of preconditioning exercise in the female tumor bearing mouse.

Cancer cachexia, a metabolic wasting syndrome, affects up to 80% of cancer patients and leads to the death in up to 20% of cancer patients. While research is growing in the field, there are still no clear diagnostic criteria and cancer cachexia remains an untreated condition. Aerobic exercise has been shown to positively impact cachexia by slowing its development and attenuating muscle loss.

Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa.

Background: Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in , which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering .

Methods: We conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa.

Performance of Plant-Produced Asphalt Containing Cellular Capsules.

This paper aims to assess the influence of encapsulated rejuvenators on plant-produced asphalt's performance. The polymeric capsules are evaluated as cellular materials that deform and absorb energy while they experience a progressive collapse of their porous structure, rather than a simply means to release the rejuvenator. Additionally, variables during asphalt manufacturing that may affect their plastic deformation under loading are assessed too.

The Pharmacorank Search Tool for the Retrieval of Prioritized Protein Drug Targets and Drug Repositioning Candidates According to Selected Diseases.

We present the Pharmacorank search tool as an objective means to obtain prioritized protein drug targets and their associated medications according to user-selected diseases. This tool could be used to obtain prioritized protein targets for the creation of novel medications or to predict novel indications for medications that already exist. To prioritize the proteins associated with each disease, a gene similarity profiling method based on protein functions is implemented.

Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1- C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade.

Background: Three-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa).

Purpose: To validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP C-MRI in patients.

Chest radiograph classification and severity of suspected COVID-19 by different radiologist groups and attending clinicians: multi-reader, multi-case study.

Objectives: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images.

Methods: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems.

Access to statistical support for medical imaging research: questionnaire survey of UK radiology trainees.

Aim: To investigate the level of statistical support available to UK radiology trainees, and to gather opinions regarding how support may affect their current and future research aspirations.

Materials And Methods: An online survey was developed, piloted, and distributed to radiology trainees via the UK Radiology Academic Network for Trainees and training programme directors. Research experience, research aspirations, available and desired statistical support, and attitudes to statistics were surveyed and responses were collated.

Pharmacological Characterization of a Novel Neuroactive Steroid Prodrug, NTS-104, and Its Neuroprotective Activity in Experimental Stroke Models.

Background: Ischemic stroke affects about 700 000 patients per year in the United States, and to date, there are no effective pharmacological agents that promote recovery. Here, we studied the pharmacokinetics, pharmacodynamics, and efficacy of NTS-105, a novel neuroactive steroid, and NTS-104, a prodrug of NTS-105, in 2 models of ischemic stroke.

Methods: The pharmacodynamics and pharmacokinetics of NTS-104/105 were investigated in naive and stroke rats, and models of embolic and transient middle cerebral artery occlusion were used to investigate the dose-related effects of NTS-104.