Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina.

Over recent years, the retina has been increasingly investigated as a potential biomarker for dementia. A number of studies have looked at the effect of Alzheimer's disease (AD) pathology on the retina and the associations of AD with visual deficits. However, while OCT-A has been explored as a biomarker of cerebral small vessel disease (cSVD), studies identifying the specific retinal changes and mechanisms associated with cSVD are lacking.

Parallel median consensus clustering in complex networks.

We develop an algorithm that finds the consensus among many different clustering solutions of a graph. We formulate the problem as a median set partitioning problem and propose a greedy optimization technique. Unlike other approaches that find median set partitions, our algorithm takes graph structure into account and finds a comparable quality solution much faster than the other approaches.

Chronic kidney disease.

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death.

Comparative efficacy and safety of stent retrievers as a bailout strategy following failed contact aspiration technique in acute stroke thrombectomy.

Background: The contact aspiration (CA) technique is often used to perform endovascular thrombectomy (EVT) for acute ischemic stroke (AIS); however, rescue strategies are necessary if CA fails to achieve recanalization. This study investigates the outcomes of incorporating stent retriever (SR) thrombectomy in the rescue strategy following failed CA.

Methods: EVT patients with failed CA attempts were identified from a large multicenter registry and stratified by rescue technique: CA alone or incorporating SR in the rescue strategy.

Heterotropic allosteric modulation of CYP3A4 in vitro by progesterone: Evidence for improvement in prediction of time-dependent inhibition for macrolides.

Predictions of drug-drug interactions resulting from time-dependent inhibition (TDI) of CYP3A4 have consistently overestimated or mispredicted (ie, false positives) the interaction that is observed in vivo. Recent findings demonstrated that the presence of the allosteric modulator progesterone (PGS) in the in vitro assay could alter the in vitro kinetics of CYP3A4 TDI with inhibitors that interact with the heme moiety, such as metabolic-intermediate complex forming inhibitors. The impact of the presence of 100 μM PGS on the TDI of molecules in the class of macrolides typically associated with metabolic-intermediate complex formation was investigated.

sgRNA Single-Nucleotide Resolution by Ion-Pairing Reversed-Phase Chromatography.

Single-stranded guide RNAs (sgRNAs) are important therapeutic modalities that facilitate selective genome editing by the CRISPR/Cas9 system. While these therapeutic modalities are synthesized through solid phase oligonucleotide synthesis similar to small interfering RNA (siRNAs) and antisense oligonucleotide (ASOs) therapeutics, their sequence length and complex secondary and tertiary structure hinder analytical characterization. The resulting current sgRNA methodologies have limited chromatographic selectivity near the FLP and limited MS compatibility.

Helping Teens Move + Thrive: Adolescents' Preferences for Online Exercise Videos.

Online exercise videos can reach adolescents who lack access to in-person physical activity (PA). Yet, health professionals are wary of recommending online exercise resources because most free videos fail to represent diverse teens and perpetuate harmful norms. Our study had two purposes.

Conflicts of interest in the International Agency for Research on Cancer process of identifying carcinogenic hazards to humans.

Managing conflicts of interest (COIs) in scientific decision-making is important for minimizing bias and fostering public trust in science. Proper management of COIs has added significance when scientists are making decisions that impact public policy, such as assessing substances for carcinogenicity. The International Agency for Research on Cancer (IARC) organizes expert working groups to identify putative carcinogens and determine whether or not the hazard is likely to present significant potential harm to humans.

Caregiver Resilience through the First Two Years after Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

Objective: To examine: (1) the trajectory of caregiver resilience over two years following onset of a care recipient's moderate-to-severe traumatic brain injury (TBI), (2) caregiver-related outcomes associated with resilience, and (3) changes in associations between caregiver resilience, other caregiver characteristics, and care-recipient variables across time.

Design: Prospective cohort.

Setting: TBI Model Systems (TBIMS) centers.

Combined Romosozumab and Raloxifene treatment targets impaired bone quality in a male murine model of diabetic kidney disease.

Comorbid diabetes and chronic kidney disease create a complex disease state with multi-faceted impacts on bone health, primarily reduced bone mass and tissue quality. To reduce fracture risk in this growing population, interventions are needed that target both bone mass and quality. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mass and strength in a murine model of combined diabetes and CKD (DKD), while Raloxifene (RAL) is a mild anti-resorptive used to treat osteoporosis that has also been shown to increase bone mechanical properties by increasing bone bound water content.

Advanced profiling and structural analysis of anencephaly gangliosides by ion mobility tandem mass spectrometry.

Anencephaly, the most severe type of neural tube defects (NTDs) in humans, occurs between the third and fourth gestational weeks (GW), involves the cranial part of the NT and results in the absence of the forebrain and skull. Exposed to amniotic fluid toxicity, neural tissue is degraded and prevented from development. Currently, little is known about the molecular bases of the disease and the possible involvement of glycans.

Associations between Advanced Paternal Age and Adverse Reproductive Outcomes in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b).

Objective:  The association between paternal age and adverse pregnancy outcomes (APOs) has not been well studied. We sought to determine whether advanced paternal age (APA) is associated with adverse maternal or neonatal outcomes.

Study Design:  Secondary analysis of 8,863 pregnancies from the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-Be (nuMoM2b) prospective cohort in which both maternal and paternal age at conception were known.

Reactions of SleC, Its Structure and Inhibition in Mitigation of Spore Germination in .

Spore germination in is initiated by a cascade of activities of several proteins that culminates in the activation of SleC, a cell-wall-processing enzyme. We report herein the details of the enzymatic activities of SleC by the use of synthetic peptidoglycan fragments and of spore sacculi. The reactions include the formation of 1,6-anhydromuramate─a hallmark of lytic transglycosylase activity─as well as a muramate hydrolytic product, both of which proceed through the same transient oxocarbenium species.

Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.

Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis.

Hearing in categories and speech perception at the "cocktail party".

We aimed to test whether hearing speech in phonetic categories (as opposed to a continuous/gradient fashion) affords benefits to "cocktail party" speech perception. We measured speech perception performance (recognition, localization, and source monitoring) in a simulated 3D cocktail party environment. We manipulated task difficulty by varying the number of additional maskers presented at other spatial locations in the horizontal soundfield (1-4 talkers) and via forward vs.

Chemical Reaction Networks from Scratch with Reaction Prediction and Kinetics-Guided Exploration.

Algorithmic reaction explorations based on transition state searches can now routinely predict relatively short reaction sequences involving small molecules. However, applying these algorithms to deeper chemical reaction network (CRN) exploration still requires the development of more efficient and accurate exploration policies. Here, an exploration algorithm, which we name yet another kinetic strategy (YAKS), is demonstrated that uses microkinetic simulations of the nascent network to achieve cost-effective, deep network exploration.

Revised Process for ACNS Guidelines Development.

The development of clinical practice guidelines is an evolving field. In response to the need for consistent, evidence-based medical practice, the American Clinical Neurophysiology Society identified the need to update the Society's guideline development process. The American Clinical Neurophysiology Society Guidelines Committee created an action plan with the goal of improving transparency and rigor for future guidelines and bringing existing guidelines to current standards.

Microplastic pollution in aquatic ecosystems: impacts on diatom communities.

In recent years, heightened concern has emerged regarding the pervasive presence of microplastics in the environment, particularly in aquatic ecosystems. This concern has prompted extensive scientific inquiry into microplastics' ecological and physiological implications, including threats to biodiversity. The robust adsorption capacity of microplastic surfaces facilitates their widespread distribution throughout aquatic ecosystems, acting also as carriers of organic pollutants.

A Qualitative Meta-Synthesis of Women's Experiences of Internalized Sociocultural Sexual Pressure.

Sexual coercion occurs when a person applies pressure to force another person to have unwanted sex. Yet, sociocultural expectations may also impact women's sexual consent/refusal behaviors in the absence of partner pressure. We conducted a qualitative meta-synthesis to investigate factors contributing to incongruent sexual decision-making (i.

Dark-Field Absorbance Circular Dichroism of Oriented Chiral Thin Films.

Dark-field and confocal approaches to circular dichroism (CD) spectroscopy of uniaxial thin films examine the relationship between symmetry and incoherence in the nonreciprocal CD response, or the component that is antisymmetric about the light propagation direction. Modifying a conventional CD spectrometer for low-angle scattering detection isolates incoherent contributions to nonreciprocal CD of drop-cast thin films, boasting 5-to-10-fold enhancements in CD dissymmetry parameters. Conversely, confocal detection suppresses the nonreciprocal CD response.

A high-resolution view of the immune and stromal cell response to infection in human volunteers.

causes the genital ulcer disease chancroid and cutaneous ulcers in children. To study its pathogenesis, we developed a human challenge model in which we infect the skin on the upper arm of human volunteers with to the pustular stage of disease. The model has been used to define lesional architecture, describe the immune infiltrate into the infected sites using flow cytometry, and explore the molecular basis of the immune response using bulk RNA-seq.

Mineralized tissue loss at the femoral ACL enthesis in young male ACL-injured patients.

Purpose: Primary anterior cruciate ligament (ACL) reconstruction graft failure remains a significant health concern in young patients. Despite the high incidence of poor graft integration in these patients and the resulting high failure rate, little consideration has been given to the quality of the bone into which the graft is anchored at reconstruction. Therefore, we investigated post ACL injury mineralized tissue changes in the ACL femoral entheses of young males and compared them to changes previously reported for young females.

Scientific and Regulatory Policy Committee Points to Consider: Proposal and Recommendations to Reduce Euthanasia of Control Nonhuman Primates in Nonclinical Toxicity Studies.

Nonhuman primates (NHPs) have been and remain a highly valuable animal model with an essential role in translational research and pharmaceutical drug development. Based on current regulatory guidelines, the nonclinical safety of novel therapeutics should be evaluated in relevant nonclinical species, which commonly includes NHPs for biotherapeutics. Given the practical and ethical limitations on availability and/or use of NHPs and in line with the widely accepted guiding "3Rs" (replace, reduce, and refine) principles, many approaches have been considered to optimize toxicity study designs to meaningfully reduce the number of NHPs used.

AI-based analysis of fetal growth restriction in a prospective obstetric cohort quantifies compound risks for perinatal morbidity and mortality and identifies previously unrecognized high risk clinical scenarios.

Background: Fetal growth restriction (FGR) is a leading risk factor for stillbirth, yet the diagnosis of FGR confers considerable prognostic uncertainty, as most infants with FGR do not experience any morbidity. Our objective was to use data from a large, deeply phenotyped observational obstetric cohort to develop a probabilistic graphical model (PGM), a type of "explainable artificial intelligence (AI)", as a potential framework to better understand how interrelated variables contribute to perinatal morbidity risk in FGR.

Methods: Using data from 9,558 pregnancies delivered at ≥ 20 weeks with available outcome data, we derived and validated a PGM using randomly selected sub-cohorts of 80% (n = 7645) and 20% (n = 1,912), respectively, to discriminate cases of FGR resulting in composite perinatal morbidity from those that did not.