Long-read RNA sequencing: A transformative technology for exploring transcriptome complexity in human diseases.

Long-read RNA sequencing (RNA-seq) is emerging as a powerful and versatile technology for studying human transcriptomes. By enabling the end-to-end sequencing of full-length transcripts, long-read RNA-seq opens up avenues for investigating various RNA species and features that cannot be reliably interrogated by standard short-read RNA-seq methods. In this review, we present an overview of long-read RNA-seq, delineating its strengths over short-read RNA-seq, as well as summarizing recent advances in experimental and computational approaches to boost the power of long-read-based transcriptomics.

Repurposing colforsin daropate to treat MYC-driven high-grade serous ovarian carcinomas.

High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers for women, with a low survival rate, no early detection biomarkers, a high rate of recurrence, and few therapeutic options. Forskolin, an activator of cyclic AMP signaling, has several anticancer activities, including against HGSOC, but has limited use in vivo. Its water-soluble derivative, colforsin daropate, has the same mechanism of action as forskolin and is used to treat acute heart failure.

A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium.

Behavioural economics to improve and motivate vaccination in primary care using nudges through the electronic health record: rationale and design of the BE IMMUNE randomised clinical trial.

Introduction: Annual influenza vaccination reduces disease burden but vaccination rates are suboptimal, with persistent disparities among subpopulations. The purpose of this trial is to evaluate multicomponent behavioural economic nudge interventions to clinicians and patients to increase influenza vaccination. This trial also includes an intensification nudge to reduce disparities in vaccination among older adult, primary care patients.

Complement C3 knockout protects photoreceptors in the sodium iodate model.

Complement factor 3 (C3) has emerged as a primary therapeutic target in age-related macular degeneration (AMD) supported by genetic, histologic, and clinical trial evidence. Yet, the site(s) of action are unclear. The purpose of this study was to test the effect of C3 knockout on photoreceptors and retinal pigment epithelial cells (RPE) in the sodium iodate (NaIO) model, which mirrors some features of AMD.

TLR priming licenses NAIP inflammasome activation by immunoevasive ligands.

NLR family, apoptosis inhibitory proteins (NAIPs) detect bacterial flagellin and structurally related components of bacterial type III secretion systems (T3SS), and recruit NLR family CARD domain containing protein 4 (NLRC4) and caspase-1 into an inflammasome complex that induces pyroptosis. NAIP/NLRC4 inflammasome assembly is initiated by the binding of a single NAIP to its cognate ligand, but a subset of bacterial flagellins or T3SS structural proteins are thought to evade NAIP/NLRC4 inflammasome sensing by not binding to their cognate NAIPs. Unlike other inflammasome components such as NLRP3, AIM2, or some NAIPs, NLRC4 is constitutively present in resting macrophages and not known to be induced by inflammatory signals.

Associations of pre- and postnatal per- and polyfluoroalkyl substance exposure with adolescents' eating behaviors.

Background: Per- and polyfluoroalkyl substances (PFAS), persistent environmental chemicals, may act as obesogens by interacting with neuroendocrine pathways regulating energy homeostasis and satiety signals influencing adolescent eating behaviors.

Methods: In 211 HOME Study adolescents (Cincinnati, OH; recruited 2003-2006), we measured PFAS concentrations in serum collected during pregnancy, at delivery, and at ages 3, 8, and 12 years. Caregivers completed the Child Eating Behavior Questionnaire (CEBQ) at age 12, and we calculated food approach and food avoidance scores.

Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling.

A cell's ability to respond and adapt to environmental stimuli relies in part on transcriptional programs controlled by histone proteins. Histones affect transcription through numerous mechanisms including through replacement with variant forms that carry out specific functions. We recently identified the first widely expressed H2B histone variant, H2BE and found that it promotes transcription and is critical for neuronal function and long-term memory.

Evaluating Performance and Agreement of Coronary Heart Disease Polygenic Risk Scores.

Importance: Polygenic risk scores (PRSs) for coronary heart disease (CHD) are a growing clinical and commercial reality. Whether existing scores provide similar individual-level assessments of disease susceptibility remains incompletely characterized.

Objective: To characterize the individual-level agreement of CHD PRSs that perform similarly at the population level.

Economic Analysis of Catheter-Directed Thrombolysis for Intermediate-Risk Pulmonary Embolism.

Background: Pulmonary embolism is associated with a significant burden of morbidity, mortality, and health care costs. Catheter-directed thrombolysis has emerged as a promising option for patients with intermediate-risk pulmonary embolism which aims to improve outcomes over standard anticoagulation.

Methods: We constructed a decision-analytic model comparing the cost-effectiveness of catheter-directed thrombolysis to anticoagulation alone for the management of intermediate-risk pulmonary embolism.

FMRP regulates MFF translation to locally direct mitochondrial fission in neurons.

Fragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile X syndrome. FMRP dysfunction disrupts mitochondrial health in neurons, but it is unclear how FMRP supports mitochondrial homoeostasis. Here we demonstrate that FMRP granules are recruited to the mitochondrial midzone, where they mark mitochondrial fission sites in axons and dendrites.

Allogeneic chimeric antigen receptor cell therapies for cancer: progress made and remaining roadblocks.

Chimeric antigen receptor (CAR) T cells are revolutionizing cancer therapy, particularly for haematological malignancies, conferring durable and sometimes curative responses in patients with advanced-stage disease. The CAR T cell products currently approved for clinical use are all autologous and are often effective; however, in patients who are lymphopenic and/or heavily pretreated with chemotherapy, autologous T cells can be difficult to harvest in sufficient numbers or have functional impairments that might ultimately render them less efficacious. Moreover, autologous products take several weeks to produce, and each product can be used in only one patient.

Pediatric Post-Intensive Care Syndrome and Current Therapeutic Options.

Post-intensive care syndrome (PICS) impacts most pediatric critical care survivors. PICS spans physical, cognitive, emotional, and social health domains and is increasingly recognized in survivorship literature. Children pose unique challenges in identifying and treating PICS given the inherent population heterogeneity in pediatric samples with biological differences across ages and neurodevelopmental stages, unique disease pathophysiology, strong environmental influences on disease and recovery, and lack of standardized measurements to identify morbidities or track response to intervention.

Evaluating Social Determinants of Health-Based Alternatives to Race-Based Cognitive Normative Models.

Background And Objectives: Race and ethnicity are proxy measures of sociocultural factors that influence cognitive test performance. Our objective was to compare different regression-based cognitive normative models adjusting for demographics and different combinations of easily accessible/commonly used social determinants of health (SDoH) factors, which may help describe cognitive performance variability historically captured by ethnoracial differences.

Methods: We performed cross-sectional analyses on data from Black and White participants without mild cognitive impairment/dementia in the Atherosclerosis Risk in Communities Study who attended visit 5 in 2011-2013.

Interoceptive Awareness Is Associated With Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes.

Objective: To assess the association between impaired awareness of hypoglycemia (IAH) and interoceptive awareness in type 1 diabetes.

Research Design And Methods: A total of 154 adults with type 1 diabetes completed IAH surveys and the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2). Logistic regression was performed for assessment of associations between IAH and MAIA-2, accounting for covariates.

Why Clinicians should Care about YouCare and Other Wearable Health Devices.

In this issue of Journal of Medical Systems, Neri et al. share results from their study in which they compared the YouCare device to a standard Holter monitor. The wearable used in the study incorporates a single electrocardiogram lead in a crop top garment that is customized for each patient.

Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium.

Objectives: To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.

Methods: In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi).

Lysosomal damage triggers a p38 MAPK-dependent phosphorylation cascade to promote lysophagy via the small heat shock protein HSP27.

Maintenance of lysosomal integrity is essential for cell viability. Upon injury, lysosomes may be targeted for degradation via a selective form of autophagy known as lysophagy. The engulfment of a damaged lysosome by an autophagosome is mediated by the recruitment of adaptor proteins, including SQSTM1/p62.