Deletion of murine astrocytic vesicular nucleotide transporter increases anxiety and depressive-like behavior and attenuates motivation for reward.

Astrocytes are multi-functional glial cells in the central nervous system that play critical roles in modulation of metabolism, extracellular ion and neurotransmitter levels, and synaptic plasticity. Astrocyte-derived signaling molecules mediate many of these modulatory functions of astrocytes, including vesicular release of ATP. In the present study, we used a unique genetic mouse model to investigate the functional significance of astrocytic exocytosis of ATP.

Routine postaccess-closure angiography to detect vascular complications following transfemoral TAVR.

Background: Vascular complications following transfemoral TAVR are associated with increased morbidity and mortality. Measures that may mitigate this risk are important.

Aim: To evaluate the utility of routine, access-vessel angiography post sheath-removal in the detection and management of complications in patients undergoing transcatheter aortic valve replacement (TAVR).

A comprehensive AI-driven analysis of large-scale omic datasets reveals novel dual-purpose targets for the treatment of cancer and aging.

As aging and tumorigenesis are tightly interconnected biological processes, targeting their common underlying driving pathways may induce dual-purpose anti-aging and anti-cancer effects. Our transcriptomic analyses of 16,740 healthy samples demonstrated tissue-specific age-associated gene expression, with most tumor suppressor genes downregulated during aging. Furthermore, a large-scale pan-cancer analysis of 11 solid tumor types (11,303 cases and 4431 control samples) revealed that many cellular processes, such as protein localization, DNA replication, DNA repair, cell cycle, and RNA metabolism, were upregulated in cancer but downregulated in healthy aging tissues, whereas pathways regulating cellular senescence were upregulated in both aging and cancer.

What Are the Causes of Death among Patients Admitted to a Contemporary Tertiary-Level Cardiology Department? An Analysis of 10 Years of Morbidity and Mortality Meetings.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We conducted a retrospective evaluation of mortality events from inpatient admissions to the cardiology department between 2010 and 2019. Data were collected from morbidity and mortality meeting presentations that evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex.

PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models.

Resistance mechanisms to immune checkpoint blockade therapy (ICBT) limit its response duration and magnitude. Paradoxically, Interferon γ (IFNγ), a key cytokine for cellular immunity, can promote ICBT resistance. Using syngeneic mouse tumour models, we confirm that chronic IFNγ exposure confers resistance to immunotherapy targeting PD-1 (α-PD-1) in immunocompetent female mice.

The role of IFN-γ-signalling in response to immune checkpoint blockade therapy.

Treatment with immune checkpoint inhibitors, widely known as immune checkpoint blockade therapy (ICBT), is now the fourth pillar in cancer treatment, offering the chance of durable remission for patients with advanced disease. However, ICBT fails to induce objective responses in most cancer patients with still others progressing after an initial response. It is necessary, therefore, to elucidate the primary and acquired resistance mechanisms to ICBT to improve its efficacy.

Insulin and IGF-1 elicit robust transcriptional regulation to modulate autophagy in astrocytes.

Objective: Insulin is a principal metabolic hormone. It regulates a plethora of metabolic pathways in peripheral tissues. The highly homologous insulin-like growth factor 1 (IGF-1), on the other hand, is important for development and growth.

The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer-An Update.

Globally in 2020, an estimated ~600,000 women were diagnosed with and 340,000 women died from cervical cancer. Compared to 2012, the number of cases increased by 7.5% and the number of deaths increased by 17%.

Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached.

Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cancer cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. Excess FAs are toxic to non-transformed cells but surprisingly not to cancer cells.

Misdiagnosis of aortic dissection: A systematic review of the literature.

Background: Aortic dissection is a rare but potentially catastrophic condition. Misdiagnosis of aortic dissection is not uncommon as symptoms can overlap with other diagnoses.

Objective: We conducted a systematic review to better understand the factors contributing to incorrect diagnosis of this condition.

Misdiagnosis of Heart Failure: A Systematic Review of the Literature.

Background: Heart failure (HF) is a chronic disease associated with a significant burden to patients, families, and health services. The diagnosis of HF can be easily missed owing to similar symptoms with other conditions especially respiratory diseases.

Methods And Results: We conducted a systematic review to determine the rates of HF and cardiomyopathy misdiagnosis and explored the potential causes.

The role of the Tei index in assessing for cardiotoxicity from anthracycline chemotherapy: a systematic review.

Background: Anthracycline agents are known to be effective in treating tumors and hematological malignancies. Although these agents improve survival, their use is associated with cardiotoxic effects, which most commonly manifests as left ventricular systolic dysfunction (LVSD). As such, guidelines recommend the periodic assessment of left ventricular ejection fraction (LVEF).

Percutaneous coronary intervention in patients with cancer and readmissions within 90 days for acute myocardial infarction and bleeding in the USA.

Aims: The post-discharge outcomes of patients with cancer who undergo PCI are not well understood. This study evaluates the rates of readmissions within 90 days for acute myocardial infarction (AMI) and bleeding among patients with cancer who undergo percutaneous coronary intervention (PCI).

Methods And Results: Patients treated with PCI in the years from 2010 to 2014 in the US Nationwide Readmission Database were evaluated for the influence of cancer on 90-day readmissions for AMI and bleeding.

Location of death among patients presenting with cardiovascular disease to the emergency department in the United states.

Background: In-hospital deaths are an important outcome and little is known about deaths in the emergency department (ED). Among patients who died of cardiovascular diseases (CVD), we assessed causes of death, temporal trends and the relative distribution of deaths in the ED versus hospital.

Methods: Using the United States Nationwide Emergency Department Sample, we conducted a retrospective study of patients presenting to the ED with a primary diagnosis of CVD between 2006 and 2014.

Deep learning model for prediction of extended-spectrum beta-lactamase (ESBL) production in community-onset Enterobacteriaceae bacteraemia from a high ESBL prevalence multi-centre cohort.

Adequate empirical antimicrobial coverage is instrumental in clinical management of community-onset Enterobacteriaceae bacteraemia in areas with high ESBL prevalence, while balancing the risk of carbapenem overuse and emergence of carbapenem-resistant organisms. It is unknown whether machine learning offers additional advantages to conventional statistical methods in prediction of ESBL production. To develop a validated model to predict ESBL production in Enterobacteriaceae causing community-onset bacteraemia.

The prognostic value of Tei index in acute myocardial infarction: a systematic review.

Background: Echocardiographic evaluation of left ventricular ejection fraction (LVEF) is used in the risk stratification of patients with an acute myocardial infarction (AMI). However, the prognostic value of the Tei index, an alternative measure of global cardiac function, in AMI patients is not well established.

Methods: We conducted a systematic review, using MEDLINE and EMBASE, to evaluate the prognostic value of the Tei index in predicting adverse outcomes in patients presenting with AMI.

Cardiac arrest and related mortality in emergency departments in the United States: Analysis of the nationwide emergency department sample.

Aims: The aim of this study is to analyse the causes of cardiac arrests (CA) in the emergency departments (ED) in the United States and their clinical outcomes according to whether they had a primary or a secondary diagnosis of CA.

Methods: Data from the Nationwide Emergency Department Sample was assessed for episodes of CA in the emergency department (ED) for adults from 2006 to 2014. Primary and secondary diagnoses of CA and mortality outcomes were evaluated in ED, inpatient and the combined in-hospital setting.

Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1.

Oncolytic viruses are potent anticancer agents that replicate within and kill cancer cells rather than normal cells, and their selectivity is largely determined by oncogenic mutations. M1, a novel oncolytic virus strain, has been shown to target cancer cells, but the relationship between its cancer selectivity and oncogenic signaling pathways is poorly understood. Here, we report that RAS mutation promotes the replication and oncolytic effect of M1 in cancer, and we further provide evidence that the inhibition of the RAS/RAF/MEK signaling axis suppresses M1 infection and the subsequent cytopathic effects.

Clinical features and outcomes of adults with coronavirus disease 2019: A systematic review and pooled analysis of the literature.

Background: The 2019 coronavirus disease (COVID-19) has become a global pandemic and the published literature describing the virus has grown exponentially.

Methods: We conducted a systematic review of the literature to identify the symptoms, comorbidities present, radiological features and outcomes for adults testing positive for COVID-19 admitted to hospital. The results across multiple studies were numerically pooled to yield total estimated.

Zinc-finger antiviral protein acts as a tumor suppressor in colorectal cancer.

Avoiding immune destruction is essential for tumorigenesis. Current research into the interaction between tumor and immunological niches complement tumor pathology beyond cancer genetics. Intrinsic host defense immunity is a specialized innate immunity component to restrict viral infection.

Infective endocarditis is associated with worse outcomes in stroke: A Thailand National Database Study.

Background: There is lack of data on the association between infective endocarditis (IE) and outcomes of mortality and complications in stroke. We aimed to compare characteristics and outcomes of stroke patients with and without IE.

Methods: We retrospectively examined the above association using data obtained from an insurance database which covers ~75% of the Thai population.

A systematic review of the studies that evaluate the performance of the DAPT score.

Background: The Dual Antiplatelet Therapy (DAPT) score was derived to determine which patients may benefit from prolonged DAPT therapy after 12 months based on the balance between ischaemic and bleeding events. Several studies have attempted to validate the score with inconsistent findings.

Methods: We conducted a systematic review of the studies that evaluated the DAPT score in PCI populations.

Topical application of Chinese herbal medicine DAEP relieves the osteoarthritic knee pain in rats.

Background: The potential adverse effects of conventional oral pharmacotherapy of osteoarthritis (OA) restrict their long-term use. Topical application of a Chinese herbal paste for relieving OA knee pain can be effective and safe. However, evidence-based scientific research is insufficient to support its application worldwide.