An analysis of RNA quality metrics in human brain tissue.

Human brain tissue studies have used a range of metrics to assess RNA quality but there are few large-scale cross-comparisons of presequencing quality metrics with RNA-seq quality. We analyzed how postmortem interval (PMI) and RNA integrity number (RIN) before RNA-seq relate to RNA quality after sequencing (percent of counts in top 10 genes [PTT], 5' bias, and 3' bias), and with individual gene counts across the transcriptome. We analyzed 4 human cerebrocortical tissue sets (1 surgical, 3 autopsy), sequenced with varying protocols.

Pathologic subtyping of Alzheimer's disease brain tissue reveals disease heterogeneity.

In recent years, multiple groups have shown that what is currently thought of as "Alzheimer's Disease" (AD) may be usefully viewed as several related disease subtypes. As these efforts have continued, a related issue is how common co-pathologies and ethnicity intersect with AD subtypes. The goal of this study was to use a dataset constituting 153 pathologic variables recorded on 666 AD brain autopsies to better define how co-pathologies and ethnicity relate to established AD subtypes.

An analysis of RNA quality metrics in human brain tissue.

Human brain tissue studies have historically used a range of metrics to assess RNA quality. However, few large-scale cross-comparisons of pre-sequencing quality metrics with RNA-seq quality have been published. Here, we analyze how well metrics gathered before RNA sequencing (post-mortem interval (PMI) and RNA integrity number RIN) relate to analyses of RNA quality after sequencing (Percent of counts in Top Ten genes (PTT), 5' bias, and 3' bias) as well as with individual gene counts across the transcriptome.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

Introduction: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact.

Methods: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes.

ZCCHC17 knockdown phenocopies Alzheimer's disease-related loss of synaptic proteins and hyperexcitability.

ZCCHC17 is a master regulator of synaptic gene expression and has recently been shown to play a role in splicing of neuronal mRNA. We previously showed that ZCCHC17 protein declines in Alzheimer's disease (AD) brain tissue before there is significant gliosis and neuronal loss, that ZCCHC17 loss partially replicates observed splicing abnormalities in AD brain tissue, and that maintenance of ZCCHC17 levels is predicted to support cognitive resilience in AD. Here, we assessed the functional consequences of reduced ZCCHC17 expression in primary cortical neuronal cultures using siRNA knockdown.

SIRT4 loss reprograms intestinal nucleotide metabolism to support proliferation following perturbation of homeostasis.

The intestine is a highly metabolic tissue, but the metabolic programs that influence intestinal crypt proliferation, differentiation, and regeneration are still emerging. Here, we investigate how mitochondrial sirtuin 4 (SIRT4) affects intestinal homeostasis. Intestinal SIRT4 loss promotes cell proliferation in the intestine following ionizing radiation (IR).

-related congenital myopathy in a Han Chinese patient: A case report and literature review.

mutations have been shown to be associated with myotonia, paramyotonia congenita, and periodic paralyses. More recently, loss-of-function variants in the gene were also noted to be associated with rarer, autosomal recessive forms of congenital myasthenic syndrome and congenital myopathy. Diagnosis is challenging as the initial clinical presentation and histological features on muscle biopsies are non-specific.

ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease.

ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis using data from human autopsy tissue (consisting of males and females) and female human cell lines. Co-immunoprecipitation (co-IP) of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA-splicing proteins.

TIMP1 is an early biomarker for detection and prognosis of lung cancer.

Background: Lung cancer remains the major cause of cancer-related deaths worldwide. Early stages of lung cancer are characterized by long asymptomatic periods that are ineffectively identified with the current screening programs. This deficiency represents a lost opportunity to improve the overall survival of patients.

ZCCHC17 modulates neuronal RNA splicing and supports cognitive resilience in Alzheimer's disease.

ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's Disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis. Co-immunoprecipitation of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA splicing proteins.

The contribution of peer research in evaluating complex public health interventions: examples from two UK community empowerment projects.

Background: Peer-research is steered and conducted by people with lived experience of the issues being researched. This paper explores the value of peer-research in two complex public health intervention evaluations in the UK.

Methods: Reports from 18 peer research projects, completed by residents from 12 communities in the UK taking part in two community empowerment interventions, were analysed using cross-case analysis.

ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development.

Background: Targeting mitochondrial oncoproteins presents a new concept in the development of effective cancer therapeutics. ATAD3A is a nuclear-encoded mitochondrial enzyme contributing to mitochondrial dynamics, cholesterol metabolism, and signal transduction. However, its impact and underlying regulatory mechanisms in cancers remain ill-defined.

Preadmission predictors of severe COVID-19 in patients with diabetes mellitus.

Objective: To explore predictors of severe COVID-19 disease in patients with diabetes hospitalized for COVID-19.

Methods: This is a retrospective observational study of adults with diabetes admitted for COVID-19. Bivariate tests and multivariable Cox regression were used to identify risk factors for severe COVID-19, defined as a composite endpoint of intensive care unit admission/intubation or in-hospital death.

Induction of dormancy by confinement: An agarose-silica biomaterial for isolating and analyzing dormant cancer cells.

The principal cause of cancer deaths is the residual disease, which eventually results in metastases. Certain metastases are induced by disseminated dormancy-capable single cancer cells that can reside within the body undetected for months to years. Awakening of the dormant cells starts a cascade resulting in the patient's demise.

Preoperative sonographic ulnar nerve mapping in the postoperative elbow.

Objective: To describe the technique of sonographic ulnar nerve mapping in the postoperative elbow for surgical planning.

Materials And Methods: A retrospective review of a surgical databank identified 24 patients, all aged 18 years and older with a history of orthopedic elbow surgery, who were referred for preoperative sonographic mapping of the ulnar nerve prior to subsequent surgery. All cases were reviewed for patient demographics, clinical presentation, prior surgical interventions, and ultrasound technique.

Wire Cerclage Versus Cable Closure After Sternotomy for Dehiscence and DSWI: A Systematic Review and Meta-Analysis.

Objective: Cable closure has been introduced as a potential alternative to traditional wire cerclage (WC) for closure of median sternotomy. To evaluate whether cable closure improves patient outcomes, we conducted a systematic review and meta-analysis of the literature.

Methods: Ovid versions of Medline and Embase, and Google Scholar were used for the literature search.

Immobilization rapidly selects for chemoresistant ovarian cancer cells with enhanced ability to enter dormancy.

Around 20-30% of ovarian cancer patients exhibit chemoresistance, but there are currently no methods to predict whether a patient will respond to chemotherapy. Here, we discovered that chemoresistant ovarian cancer cells exhibit enhanced survival in a quiescent state upon experiencing the stress of physical confinement. When immobilized in stiff silica gels, most ovarian cancer cells die within days, but surviving cells exhibit hallmarks of single-cell dormancy.

Optimizing Integrated Electrode Design for Irreversible Electroporation of Implanted Polymer Scaffolds.

Irreversible electroporation (IRE) is an emerging technology for non-thermal ablation of solid tumors. This study sought to integrate electrodes into microporous poly(caprolactone) (PCL) scaffolds previously shown to recruit metastasizing cancer cells in vivo in order to facilitate application of IRE to disseminating cancer cells. As the ideal parallel plate geometry would render much of the porous scaffold surface inaccessible to infiltrating cells, numerical modeling was utilized to predict the spatial profile of electric field strength within the scaffold for alternative electrode designs.

Engineering T cell response to cancer antigens by choice of focal therapeutic conditions.

Focal thermal therapy (Heat), cryosurgery (Cryo) and irreversible electroporation (IRE) are increasingly used to treat cancer. However, local recurrence and systemic spread are persistent negative outcomes. Nevertheless, emerging work with immunotherapies (i.

Reducing contingent self-worth: A defensive response to self-threats.

Previous research shows that people with high self-esteem cope with threats to the self by reducing the extent to which their self-worth is contingent on the threatened domain (Buckingham, Weber, & Sypher, 2012). The present studies tested the hypothesis that this is a defensive process. In support of this hypothesis, Study 1 (N = 160), showed that self-affirmation attenuates the tendency for people with high self-esteem to reduce their contingencies of self-worth following self-threat.

Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq-based resource for pain and sensory neuroscience research.

Molecular neurobiological insight into human nervous tissues is needed to generate next-generation therapeutics for neurological disorders such as chronic pain. We obtained human dorsal root ganglia (hDRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the hDRG transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene coexpression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment.