Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L.

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings.

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease.

Background: Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction.

Methods: In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure.

Investigation of hypertension and type 2 diabetes as risk factors for dementia in the All of Us cohort.

The World Health Organization recently defined hypertension and type 2 diabetes (T2D) as modifiable comorbidities leading to dementia and Alzheimer's disease. In the United States (US), hypertension and T2D are health disparities, with higher prevalence seen for Black and Hispanic minority groups compared to the majority White population. We hypothesized that elevated prevalence of hypertension and T2D risk factors in Black and Hispanic groups may be associated with dementia disparities.

Radiofrequency Ablation Remodels the Tumor Microenvironment and Promotes Neutrophil-Mediated Abscopal Immunomodulation in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents a 5-year overall survival rate of 11%, despite efforts to improve clinical outcomes in the past two decades. Therapeutic resistance is a hallmark of this disease, due to its dense and suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising local ablative and potential immunomodulatory therapy for PDAC.

The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses.

Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to the infection. Among metabolic changes, the most prominent is the upregulated glycolysis process as the main pathway of glucose utilization. Glycolysis activation is a common mechanism of cell adaptation to several viral infections, including noroviruses, rhinoviruses, influenza virus, Zika virus, cytomegalovirus, coronaviruses and others.

Longitudinal Associations of Plasma TMAO and Related Metabolites with Cognitive Impairment and Dementia in Older Adults: The Cardiovascular Health Study.

Background: Animal studies suggest that gut microbiome metabolites such as trimethylamine N-oxide (TMAO) may influence cognitive function and dementia risk. However potential health effects of TMAO and related metabolites remain unclear.

Objective: We examined prospective associations of TMAO, γ-butyrobetaine, crotonobetaine, carnitine, choline, and betaine with risk of cognitive impairment and dementia among older adults aged 65 years and older in the Cardiovascular Health Study (CHS).

Alcohol and cannabis co-use and longitudinal gray matter volumetric changes in early and late adolescence.

Background: Previous studies have characterized the impact of substance use on cerebral structure and function in adolescents. Yet, the great majority of prior studies employed a small sample, presented cross-sectional findings, and omitted potential sex differences.

Methods: Using data based on 724 adolescents (370 females) curated from the NCANDA study, we investigated how gray matter volumes (GMVs) decline longitudinally as a result of alcohol and cannabis use.

Natural history, angiographic presentation and outcomes of anterior cranial fossa dural arteriovenous fistulas.

Background: Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins.

Transgenic Mouse Models of Alzheimer's Disease: An Integrative Analysis.

Alzheimer's disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability.

A crosstalk between gut and brain in sepsis-induced cognitive decline.

Background: Sepsis is a potentially fatal disease characterized by acute organ failure that affects more than 30 million people worldwide. Inflammation is strongly associated with sepsis, and patients can experience impairments in memory, concentration, verbal fluency, and executive functioning after being discharged from the hospital. We hypothesize that sepsis disrupts the microbiota-gut-brain axis homeostasis triggering cognitive impairment.

Interaction between the BDNF rs11030101 genotype and job stress on cognitive empathy.

Background: Empathy refers to an individual's ability to experience the emotional and cognitive processes of another person during social interactions. Although many studies have examined the effects of genetic variation on emotional empathy, little is currently known about whether genetic factors may influence cognitive empathy. This study investigated the relationship between BDNF rs11030101 genotype, job stress, and empathy, especially cognitive empathy, in a Chinese Han population.

Social networks, high-risk anal HPV and coinfection with HIV in young sexual minority men.

Objectives: Young sexual minority men (SMM) exhibit a high prevalence and incidence of high-risk genotypes of human papillomavirus (hrHPV) anal infections and a confluence of a high prevalence of HIV and rectal STIs. Social determinants of health (SDOHs) are linked to social network contexts that generate and maintain racial disparities in HIV and STIs. A network perspective was provided to advance our knowledge of drivers of genotype-specific hrHPV infection and coinfection with HIV.

Biomarkers for sepsis: more than just fever and leukocytosis-a narrative review.

A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood-brain barrier (BBB) breakdown, brain injury, and short and long-term mortality.

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs.

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications.

Association between the CLOCK gene polymorphism and depressive symptom mediated by sleep quality among non-clinical Chinese Han population.

Background: Depression is a common mental disorder associated with sleep problems and the circadian clock genes may underlie the relationship between the two in clinical samples. However, little is known about whether poor sleep quality is associated with depressive symptom in healthy individuals and whether is mediated by specific single-nucleotide polymorphisms (SNPs).

Methods: Using a cross-sectional design, 444 university staff members were randomly recruited in Beijing.

Statistical reanalysis of vascular event outcomes in primary and secondary vascular prevention trials.

Background: Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them.

Methods: Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared individual participant data from their trials.

NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain.

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.

A noncoding RNA modulator potentiates phenylalanine metabolism in mice.

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. Here, we demonstrate that the mouse lncRNA and human associate with phenylalanine hydroxylase (PAH). -knockout mice exhibited excessive blood phenylalanine (Phe), musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU.

Behavioral Economic Assessment of Alcohol and Cigarette Demand in Smokers With Alcohol Use Disorder.

Behavioral economic purchase tasks are widely used to assess drug demand in substance use disorder research. Comorbid alcohol use is common among cigarette smokers and associated with greater difficulty in quitting smoking. However, demand for alcohol and cigarettes in this population has not been fully characterized.