Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

Alterations in newborn metabolite patterns with preterm birth and diabetes in pregnancy.

Background: This study examines the influence of prematurity and diabetes (DM) in pregnancy on metabolite patterns at birth, and associations with adiposity development in a prospective cohort.

Methods: Term and preterm (30-36 weeks gestational age [GA]) infants were enrolled and body composition assessments completed through discharge. Targeted metabolomics was used to assess metabolites in cord or infant blood in the first 2 days.

Inflammatory biomarkers profiles and cognition among older adults.

Inflammation plays a major role in cognitive aging. Most studies on peripheral inflammation and cognitive aging focused on selected major inflammatory biomarkers. However, inflammatory markers are regulated and influenced by each other, and it is therefore important to consider a more comprehensive panel of markers to better capture diverse immune pathways and characterize the overall inflammatory profile of individuals.

Decoding the mA epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach.

Epitranscriptomic modifications, particularly N6-methyladenosine (mA), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting mA from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations.

Inhibition of prefrontal glutamatergic neuron activity during the recovery period following chronic stress disrupts fear memory in male rats: potential role of the infralimbic cortex.

Chronic stress typically leads to deficits in fear extinction. However, when a delay occurs from the end of chronic stress and the start of fear conditioning (a "recovery"), rats show improved context-cue discrimination, compared to recently stressed rats or nonstressed rats. The infralimbic cortex (IL) is important for fear extinction and undergoes neuronal remodeling after chronic stress ends, which could drive improved context-cue discrimination.

Population pharmacokinetics and exposure-response analysis of durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer.

Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.

Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.

Disparities in Alcohol-Associated Liver Disease Hospital Encounters Amongst a Texas-Based Cohort of Patients.

Introduction: Alcohol-associated liver disease (ALD) disproportionately impacts men, racial and ethnic minorities, and individuals of low socioeconomic status; however, it's unclear how recent increases in ALD burden have impacted these disparities. We aimed to describe trends in racial, ethnic and socioeconomic disparities in alcohol-associated hospital encounters.

Methods: We conducted a retrospective cohort study of adult hospital encounters with alcohol-associated diagnoses from three health systems between January 2016 and December 2021.

No QT interval prolongation effect of sepiapterin: a concentration-QTc analysis of pooled data from phase 1 and phase 3 studies in healthy volunteers and patients with phenylketonuria.

Sepiapterin is an exogenously synthesized new chemical entity that is structurally equivalent to endogenous sepiapterin, a biological precursor of tetrahydrobiopterin (BH), which is a cofactor for phenylalanine hydroxylase. Sepiapterin is being developed for the treatment of hyperphenylalaninemia in pediatric and adult patients with phenylketonuria (PKU). This study employed concentration-QT interval analysis to assess QT prolongation risk following sepiapterin treatment.

Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice.

Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury.

Background: Presentations and outcomes of acute myocardial infarction (MI) differ between women and men, with the worst outcomes being reported in younger women. Mental stress induced ischemia and sympathetic activation have been suggested to play a prominent role in the pathogenesis of MI in younger women, however, the impact of sex hormones on these parameters remains unknown.

Methods: The effect of sex hormones and age on myocardial infarct size and myocardial sympathetic activity (MSA) was assessed in male and female, as well as young (4-6 months) and aged (20-22 months) FVB/N mice (n = 106, 60 gonadectomized and 46 sham-operated animals) who underwent in vivo [C]meta-hydroxyephedrine ([C]mHED) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging 24 h after a 30 min myocardial ischemic injury.

Adverse childhood experiences and post-traumatic stress impacts on brain connectivity and alcohol use in adolescence.

The current study investigated the relationship between adverse childhood experiences (ACEs), post-traumatic stress disorder (PTSD) symptoms, within-network resting-state functional connectivity (rs-FC), and alcohol use during adolescence using functional magnetic resonance imaging (fMRI) data from the National Consortium on Alcohol and Neurodevelopment in Adolescence study (NCANDA;  = 687). Significant rs-FC differences emerged that linked participant ACEs, PTSD symptoms, and alcohol use problems. Participants with ACEs compared to those without had diminished rs-FC within the default mode, salience, and medial frontoparietal networks ( ≤ 0.

The (in)dependence of single-cell data inferences on model constructs.

Recent developments in single-cell analysis have revolutionized basic research and have garnered the attention of the forensic domain. Though single-cell analysis is not new to forensics, the ways in which these data can be generated and interpreted are. Modern interpretation strategies report likelihood ratios that rely on a model of the world that is a simplification of it.

A Case Series With Cysteamine-Isobionicamide Complex: Clues for Skin-Rejuvenating Activity.

Background: Skin aging is inevitable. Wrinkles, skin texture abnormalities, senile hyperpigmentation, loss of skin tone, dryness, atrophy, and telangiectasias represent some of the hallmarks of aged skin. Skin rejuvenation can be addressed by topical therapies, such as topical retinoids and antioxidants or physical modalities with energy-based devices, all providing acceptable outcomes.

The Two Sides of Placebo Analgesia: Differential Functional Connectivity Reveals Mechanisms of Placebo Analgesic Response.

Background: Previous research has demonstrated that placebo induction manipulations can reduce an individual's pain through non-specific mechanisms, such as expectancy manipulations. However, despite robust research characterizing these effects, individual differences in predicting placebo analgesic responses are not well understood.

Methods: Fifty-four healthy pain-free adults over 18 (M=22.

Balancing anticancer therapy efficacy and safety in advanced hepatocellular carcinoma: a case report.

Background: Hepatocellular carcinoma (HCC) is a significant health problem associated with several risk factors, increasingly driven by non-alcoholic steatohepatitis and metabolic syndrome. This association poses a challenge for the primary treatments of HCC, which may include immune checkpoint inhibitors and vascular endothelial growth factor inhibitors, due to their potential cardiotoxic effect. Therefore, it is imperative to balance the therapeutic effects of these agents with their potential cardiovascular adverse events.

Exploring the Predictive Role of 11-Oxyandrogens in Diagnosing Polycystic Ovary Syndrome.

Context: Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS), yet the androgen(s) responsible remain ambiguous. Recent studies have suggested that 11-oxygenated C steroids (11-oxyandrogens), specifically 11-ketotestosterone, may be a good marker for hyperandrogenism in PCOS.

Objective: To investigate the utility of 11-oxyandrogens to differentiate women with and without PCOS relative to classical androgens.

Enhancing fine-tuning efficiency and design optimization of an eight-channel 3T transmit array via equivalent circuit modeling and Eigenmode analysis.

Background: Radiofrequency (RF) transmit arrays play a crucial role in various MRI applications, offering enhanced field control and improved imaging capabilities. Designing and optimizing these arrays, particularly in high-field MRI settings, poses challenges related to coupling, resonance, and construction imperfections. Numerical electromagnetic simulation methods effectively aid in the initial design, but discrepancies between simulated and fabricated arrays often necessitate fine-tuning.

Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.

Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.

Orthogonalized human protease control of secreted signals.

Synthetic circuits that regulate protein secretion in human cells could support cell-based therapies by enabling control over local environments. Although protein-level circuits enable such potential clinical applications, featuring orthogonality and compactness, their non-human origin poses a potential immunogenic risk. In this study, we developed Humanized Drug Induced Regulation of Engineered CyTokines (hDIRECT) as a platform to control cytokine activity exclusively using human-derived proteins.

Bilateral hip exoskeleton assistance enables faster walking in individuals with chronic stroke-related gait impairments.

Millions of individuals surviving a stroke have lifelong gait impairments that reduce their personal independence and quality of life. Reduced walking speed is one of the major problems limiting community mobility and reintegration. Previous studies have shown positive effect of robot-assisted gait training utilizing hip exoskeletons for individuals with gait impairments due to a stroke, leading to increased walking speed in post-treatment compared to pre-treatment assessments.

Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.

Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.

Aqueous Angiography Guided Bent Ab Interno Needle Goniectomy in High versus Low Aqueous Humor Outflow Regions in POAG: A Pilot RCT.

Prcis: Trabecular cutting minimally invasive glaucoma surgery like bent ab interno needle goniectomy (BANG) when performed in baseline aqueous angiography identified low aqueous humor outflow regions, results in greater success of intraocular pressure reduction.

Purpose: To study the efficacy of Bent Ab Interno Needle Goniectomy (BANG) in high versus low aqueous humor outflow (AHO) regions as determined by Aqueous Angiography(AA) in patients with primary open angle glaucoma (POAG).

Methods: A prospective, single-centre, pilot, randomized control trial recruited 30 eyes of 30 patients of POAG and visually significant cataract (45-80 y) and were randomised into two groups ("A": BANG performed in the high-flow regions and "B": BANG performed in the low-flow regions) of 15 each.

Opioid Prescriptions for Low Back Pain among Military-Connected Older Adults Across Multiple Care Systems.

Background: Untreated low back pain (LBP) in older adults can lead to disability and development of chronicity. Due to the potential development of medical comorbidities and negative risks associated with pharmacological use, chronic LBP management for older adults requires a responsive approach.

Methods: The objective of this study is to evaluate the probability of (1) opioid prescription receipt and (2) opioid-sedative coprescription, in a sample of military-service-connected patients enrolled in the Veterans Health Administration (VHA) or TRICARE, ages 30-85 years, receiving care in three systems: VHA, Military Health System (MHS), and nonfederal (civilian) healthcare facilities.

Pharmacodynamic characterization and evaluation of oxidative stress effects of digitoxigenin derivatives on HeLa cells.

Cancer is a leading cause of death worldwide and its treatment is hampered by the lack of specificity and side effects of current drugs. Cardiotonic steroids (CTS) interact with Na/K-ATPase (NKA) and induce antineoplastic effects, but their narrow therapeutic window is key limiting factor. The synthesis of digitoxigenin derivatives with glycosidic unit modifications is a promising approach to develop more selective and effective antitumor agents.