Pan-cancer prediction of tumor immune activation and response to immune checkpoint blockade from tumor transcriptomics and histopathology.

Accurately predicting which patients will respond to immune checkpoint blockade (ICB) remains a major challenge. Here, we present TIME_ACT, an unsupervised 66-gene transcriptomic signature of tumor immune activation derived from TCGA melanoma data. First, TIME_ACT scores accurately identify tumors with activated immune microenvironments across cancer types.

Potassium sorbate-enriched chitosan coatings enhance antioxidant stability and preserve postharvest quality of lemons (Citrus limon).

Background: Lemons are widely recognized for their culinary and nutritional value, but their high moisture content and delicate skin make them prone to postharvest quality loss and reduced antioxidant properties. This work explores the application of chitosan (CH) coatings enriched with potassium sorbate (PS) to preserve the quality and antioxidant system of lemons.

Results: The prepared coatings were characterized using Fourier transform infrared (FTIR) spectroscopy and rheology.

Resistance Signatures Manifested in Early Drug Response in Cancer and Across Species.

Therapeutic resistance is a major cause of cancer treatment failure, with increasing evidence suggesting a non-genetic basis. This non-genetic resistance is often due to drug-resistant transcriptional cell states, either induced by treatment or pre-existing in some cells. However, the connection between early cellular drug response and long-term resistance is poorly understood.

Transcriptome-guided GLP-1 receptor therapy rescues metabolic and behavioral disruptions in a Bardet-Biedl syndrome mouse model.

Bardet-Biedl syndrome (BBS), a ciliopathy characterized by obesity, hyperphagia, and learning deficits, arises from mutations in Bbs genes. Exacerbated symptoms occur with mutations in genes encoding the BBSome, a complex regulating primary cilia function. We investigated the mechanisms underlying BBS-induced obesity using a Bbs5-knockout (Bbs5-/-) mouse model.

Prevalence of cognitive dysfunction and associated behavioral changes, lactational failure, and their determinants among postpartum women in South India: A community-based study.

Objectives: To estimate the prevalence of cognitive dysfunction and associated behavioral changes and their prevalence among postpartum women, and also the prevalence of lactational failure and its determinants among postpartum women.

Methods: A cross-sectional study was conducted involving 200 postpartum women (65% rural, 35% urban). Data were collected through structured interviews and assessments using the Indian version of the Montreal Cognitive Assessment and Depression, Anxiety, and Stress Scale-21.

Effects of prone positioning on cerebral oxygenation in patients undergoing spine surgery under general anaesthesia.

Background: Under general anaesthesia, the impact of body positioning on different organs is mostly determined by the subsequent changes in the cardiovascular system, which are monitored with standard monitors. However, there is no objective method of neuromonitoring, therefore impacts on brain homeostasis are mainly conjectural. Near-infrared spectroscopy is a non-invasive method for monitoring tissue cerebral oxygenation.

Characterizing the pan-cancer role of exosomal miRNAs in metastasis across cancers.

Exosomal microRNAs (exomiRs) play a critical role in intercellular communication, especially in cancer, where they regulate key cellular processes like proliferation, angiogenesis, and metastasis, highlighting their significance as potential diagnostic and therapeutic targets. Here, we aimed to characterize the role of exomiRs, derived from seven cancer types (four cell lines and three tumors), in influencing the pre-metastatic niche (PMN). In each cancer type we extracted high confidence exomiRs (LogFC >= 2 in exosomes relative to control), their experimentally validated targets, and the enriched pathways among those targets.

Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation.

The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development.

Pulmonary thromboembolism masquerading as bronchial asthma in a remote medical setup at extreme high altitude.

Pulmonary thromboembolism (PTE) is a life-threatening illness. It is a great masquerader that mimics many respiratory illnesses, warranting a high index of suspicion for diagnosis. It should be suspected when respiratory illnesses do not respond to the expected course of treatment.

Non-coding genetic variants underlying higher prostate cancer risk in men of African ancestry.

Incidence and severity of prostate cancer (PrCa) substantially varies across ancestries. American men of African ancestry (AA) are more likely to be diagnosed with and die from PrCa than the those of European ancestry (EA). Published polygenic risk scores for developing prostate cancer, even those based on multi-ancestry genome-wide association studies, do not address population-specific genetic mechanisms underlying PrCa risk in men of African ancestry.

Characterizing the role of exosomal miRNAs in metastasis.

Background: Exosomal microRNAs (exomiRs), transported via exosomes, play a pivotal role in intercellular communication. In cancer, exomiRs influence tumor progression by regulating key cellular processes such as proliferation, angiogenesis, and metastasis. Their role in mediating communication between cancer cells and the tumor microenvironment highlights their significance as potential diagnostic and therapeutic targets.

Intestinal serotonergic vagal signaling as a mediator of microbiota-induced hypertension.

Hypertension is a pervasive global health challenge, impacting over a billion individuals worldwide. Despite strides in therapeutic strategies, a significant proportion of patients remain resistant to the currently available therapies. While conventional treatments predominantly focus on cardiac, renal, and cerebral targets, emerging research underscores the pivotal role of the gut and its microbiota.

Investigating extrusion impact on functional, textural properties, morphological structure, and molecular interactions in hulless barley-based extruded snacks supplemented with mung bean.

The effect of varying extrusion conditions on the functional properties of hulless barley-mung bean (70:30) extruded snacks was investigated using response surface methodology with feed moisture (FM), barrel temperature (BT), and screw speed (SS) as process variables. Results revealed significant impacts on functional characteristics with varying extrusion conditions. Bulk density (BD) of extruded snacks ranged from 0.

Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in triple negative breast cancer.

Breast cancers (BRCA) exhibit substantial transcriptional heterogeneity, posing a significant clinical challenge. The global transcriptional changes in a disease context, however, are likely mediated by few key genes which reflect disease etiology better than the differentially expressed genes (DEGs). We apply our network-based tool PathExt to 1,059 BRCA tumors across 4 subtypes to identify key mediator genes in each subtype.

Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols.

Amol Patel  Peg-GCSF has similar efficacy at a dose of 60 µg/kg and 100 µg/kg. The conventional 6 mg SC dose was based on the maximum tolerable dose. In Japan, 3.

Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation.

The hippocampus (HPC), traditionally known for its role in learning and memory, has emerged as a controller of food intake. While prior studies primarily associated the HPC with food intake inhibition, recent research suggests a critical role in appetitive processes. We hypothesized that orexigenic HPC neurons differentially respond to fats and/or sugars, potent natural reinforcers that contribute to obesity development.

Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in Triple Negative Breast Cancer.

Breast cancers exhibit substantial transcriptional heterogeneity, posing a significant challenge to the prediction of treatment response and prognostication of outcomes. Especially, translation of TNBC subtypes to the clinic remains a work in progress, in part because of a lack of clear transcriptional signatures distinguishing the subtypes. Our recent network-based approach, PathExt, demonstrates that global transcriptional changes in a disease context are likely mediated by a small number of key genes, and these mediators may better reflect functional or translationally relevant heterogeneity.

Non-Nutritive Sweetened Beverages Impair Therapeutic Benefits of Metformin in Prediabetic Diet-Induced Obese Mice.

Metformin, a frontline therapy for type 2 diabetes and related metabolic diseases, results in variable outcomes. This study aimed to investigate whether sweetened beverages (caloric or non-caloric) affect the therapeutic benefits of metformin on glucose, food intake, and weight loss in diet-induced obesity. Mice were given a high-fat diet and sweetened water for 8 weeks to induce obesity and glucose intolerance.

Effect of extrusion processing on techno-functional properties, textural properties, antioxidant activities, in vitro nutrient digestibility and glycemic index of sorghum-chickpea-based extruded snacks.

Physico-chemical, textural, functional, and nutritional properties of the twin screw extruded whole sorghum-chickpea (8:2) snacks was investigated using in vitro procedures. The extruded snacks were analyzed for the effect of variations in extruded conditions on their properties: barrel BT (BT) (130-170°C) and feed moisture (FM) (14%-18%), keeping screw speed constant (400 rpm). The results revealed that specific mechanical energy (SME) decreased (74.

Asymmetric control of food intake by left and right vagal sensory neurons.

We investigated the lateralization of gut-innervating vagal sensory neurons and their roles in feeding behavior. Using genetic, anatomical, and behavioral analyses, we discovered a subset of highly lateralized vagal sensory neurons with distinct sensory responses to intestinal stimuli. Our results demonstrated that left vagal sensory neurons (LNG) are crucial for distension-induced satiety, while right vagal sensory neurons (RNG) mediate preference for nutritive foods.