Medicines

Chemotherapeutics, radiation, targeted therapeutics and immunotherapeutics each demonstrate clinical benefits for a small subset of patients with solid malignancies. Immune cells infiltrating the tumor and the surrounding stroma play a critical role in shaping cancer progression and modulating therapy response. They do this by interacting with the other cellular and molecular components of the tumor microenvironment (TME). Spatial multi-OMICs technologies are rapidly evolving. Currently, such technologies allow high-throughput RNA and protein profiling and retain geographical information about the TME cellular architecture and the functional phenotype of tumor, immune and stromal cells...

Metallaphotoredox cross-coupling is a well-established strategy for generating clinically privileged aliphatic scaffolds via single-electron reactivity. Correspondingly, expanding metallaphotoredox to encompass new C( sp 3 )-coupling partners could provide entry to a novel, medicinally relevant chemical space. In particular, alkenes are abundant, bench-stable, and capable of versatile C( sp 3 )-radical reactivity via metal-hydride hydrogen atom transfer (MHAT), although metallaphotoredox methodologies invoking this strategy remain underdeveloped...

BACKGROUND: Even among minors, the use of psychotropic substances is widespread in Europe. Data on the use of tobacco, alcohol and cannabis are regularly reported in Germany, but data on problematic use are lacking. In the present study, established screening instruments were used to investigate the prevalence of problematic use of cigarettes, alcohol and cannabis among children and adolescents. METHODS: A survey that was designed to be representative was conducted across Germany in a sample of 4001 persons aged 12-17...

BACKGROUND: Psoriasis was long regarded as an inflammatory disease limited to the skin. Data from dermatologic, rheumatologic and cardiologic research now show it to be a systemic disease, for which the term psoriatic disease is used. METHODS: This paper is based on a selective literature search with special attention to the findings of clinical trials and other current publications, as well as the recommendations of international guidelines. RESULTS: Immunologically mediated inflammation of the skin, arteries, bones, and joints is a central feature of psoriatic disease...

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, causing a substantive threat to the public, which receives global concern. However, there are limited drugs targeting the treatment of DN. Owing to this, it is highly crucial to investigate the pathogenesis and potential therapeutic targets of DN. The process of ferroptosis is a type of regulated cell death (RCD) involving the presence of iron, distinct from autophagy, apoptosis, and pyroptosis. A primary mechanism of ferroptosis is associated with iron metabolism, lipid metabolism, and the accumulation of ROS...

No abstract text is available yet for this article.

OBJECTIVES: The aim of the present study was to assess the accuracy of weight estimation in cats provided by pet owners, veterinary technicians, house officers (interns and residents) and attending clinicians in an emergency room (ER). An additional objective was to determine whether carrying the cat contributed to a more accurate weight estimate. METHODS: A total of 72 cats presented to an ER and were enrolled in the study. Pet owners, veterinary technicians, house officers and attending clinicians were asked to record the cats' estimated weights on individual data collection cards...

No abstract text is available yet for this article.

OBJECTIVE: Alzheimer's disease, an irreversible neurological condition, demands timely diagnosis for effective clinical intervention. This study employs radiomics analysis to assess image features in default mode network cerebral perfusion imaging among individuals with cognitive impairment. METHODS: A radiomics analysis of cerebral perfusion imaging was conducted on 117 patients with cognitive impairment. They were divided into training and validation sets in a 7:3 ratio...

Tumor mutation burden (TMB) has profound implications for personalized cancer therapy, particularly immunotherapy. However, the size of the panel and the cutoff values for an accurate determination of TMB are still controversial. In this study, a pan-cancer analysis was performed on 22 cancer types from The Cancer Genome Atlas. The efficiency of gene panels of different sizes and the effect of cutoff values in accurate TMB determination was assessed on a large cohort using Whole Exome Sequencing data ( n  = 9929 patients) as the gold standard...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection even in previously exposed individuals. In addition, for some pathogens, such as dengue virus, poorly targeted immunity is associated with increased risk of severe disease through a mechanism known as antibody-dependent enhancement. However, it remains unclear whether the antigenic distances between an individual's first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalizations across years...

Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids...

The Fontan operation is the current standard of care for single-ventricle congenital heart disease. Individuals with a Fontan circulation (FC) exhibit central venous hypertension and face life-threatening complications of hepatic fibrosis, known as Fontan-associated liver disease (FALD). The fundamental biology and mechanisms of FALD are little understood. Here, we generated a transcriptomic and epigenomic atlas of human FALD at single-cell resolution using multiomic snRNA-ATAC-seq. We found profound cell type-specific transcriptomic and epigenomic changes in FC livers...

Sepsis is a life-threatening disease caused by a dysregulated host response to infection, resulting in 11 million deaths globally each year. Vascular endothelial cell dysfunction results in the loss of endothelial barrier integrity, which contributes to sepsis-induced multiple organ failure and mortality. Erythropoietin-producing hepatocellular carcinoma (Eph) receptors and their ephrin ligands play a key role in vascular endothelial barrier disruption but are currently not a therapeutic target in sepsis. Using a cecal ligation and puncture (CLP) mouse model of sepsis, we showed that prophylactic or therapeutic treatment of mice with EphA4-Fc, a decoy receptor and pan-ephrin inhibitor, resulted in improved survival and a reduction in vascular leak, lung injury, and endothelial cell dysfunction...

Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon...

Domestic rabbits (Oryctolagus cuniculus) are the fourth most common species admitted to the British Columbia Society for the Prevention of Cruelty to Animals (BC SPCA) shelter system. However, shelter data analysis has largely focused on cats and dogs and little is known about the population dynamics of rabbits in shelters. We analyzed five years of rabbit records (n = 1567) at the BC SPCA to identify trends in intake and predictors of length of stay (LOS) of rabbits. The majority of rabbits were surrendered by their owners (40...