Analyses of Human Genetic Data to Identify Clinically Relevant Domains of Neuroligins.

Neuroligins (NLGNs) are postsynaptic adhesion molecules critical for neuronal development that are highly associated with autism spectrum disorder (ASD). Here, we provide an overview of the literature on rare variants. In addition, we introduce a new approach to analyze human variation within genes to identify sensitive regions that have an increased frequency of ASD-associated variants to better understand NLGN function.

The effective multiplicity of infection for HCMV depends on the activity of the cellular 20S proteasome.

Human cytomegalovirus (HCMV) is a betaherpesvirus capable of infecting numerous cell types and persisting throughout an infected individual's life. Disease usually occurs in individuals with compromised or underdeveloped immune systems. Several antivirals exist but have limitations relating to toxicity and resistance.

Setting targets for antibiotic use in general practice in Europe: A scoping review.

Background: National Action Plans (NAPs) aim to address antimicrobial resistance (AMR) understanding and awareness but struggle to translate targets into clinically relevant guidance for general practice.

Objective: To identify and map antibiotic use targets in European general practice and explore if and how these targets are linked to NAPs.

Methods: A systematic search was carried out in MEDLINE (OVID), EMBASE and SCOPUS, with additional manual searches.

Connectivity of toxigenic Pseudo-nitzschia species assemblages between the Northeast U.S. continental shelf and an adjacent estuary.

Pseudo-nitzschia harmful algal blooms have recently caused elevated domoic acid in coastal environments of the Northeast United States. In 2017, the toxigenic species P. australis was observed in Narragansett Bay, Rhode Island, a temperate estuarine ecosystem, for the first time since 2009 when DNA monitoring for Pseudo-nitzschia species began.

Public Perceptions of Individuals Attracted to Children: The Impact of the Person's Gender, Child Gender, and Preferentiality on Stigma and Perceived Risk to Offend.

Stigma-related stress may contribute to increased risk in individuals who are sexually attracted to children. Further, certain subgroups of people attracted to children may be more stigmatized than others; this has important implications for prevention programs. We conducted a vignette study to examine whether public stigma toward people attracted to children differed based on the person's gender (man/woman), the gender of the child to whom the person is attracted (boy/girl), and preferentiality (non-preferentially/preferentially attracted to children).

The effective multiplicity of infection for HCMV depends on activity of the cellular 20S proteasome.

Unlabelled: Human cytomegalovirus (HCMV) is a betaherpesvirus capable of infecting numerous cell types and persisting throughout an infected individual's life. Disease usually occurs in individuals with compromised or underdeveloped immune systems. Several antivirals exist but have limitations relating to toxicity and resistance.

Biochemical Properties of Synaptic Proteins Are Dependent on Tissue Preparation: NMDA Receptor Solubility Is Regulated by the C-Terminal Tail.

Synaptic proteins are essential for neuronal development, synaptic transmission, and synaptic plasticity. The postsynaptic density (PSD) is a membrane-associated structure at excitatory synapses, which is composed of a huge protein complex. To understand the interactions and functions of PSD proteins, researchers have employed a variety of imaging and biochemical approaches including sophisticated mass spectrometry.

A human-serum-free medium can induce more infectious P. falciparum gametocytes than a conventional human-serum-containing medium.

Malaria remains a global health problem, and the standard membrane feeding assay (SMFA) is a key functional assay for development of new interventions to stop malaria transmission from human to mosquito. For SMFA, media with ~ 10% of human serum has been used for infectious gametocyte cultures, however, there are multiple challenges to obtain a suitable human serum. Here we show a human-serum-free culture medium (HSF), which was a mixture of two stem cell culture media and AlbuMAX, supported infectious gametocyte growth.

Thyroid Cancer-Related Fear & Anxiety in Patients With Benign Thyroid Nodules: A Mixed-Methods Study.

Introduction: Thyroid cancer diagnosis often evokes strong negative emotions in patients, yet little is understood about such responses in those with benign thyroid nodules. This study explored the impact of a hypothetical cancer diagnosis, the provision of treatment information, and emotional support from surgeons on patients with benign nodules.

Methods: Patients within 30 d of a thyroid nodule biopsy were asked to imagine their nodule was cancerous and write down their feelings about this diagnosis.

Enhancing radiotherapy response via intratumoral injection of a TLR9 agonist in autochthonous murine sarcomas.

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden.

Social and environmental predictors of gut microbiome age in wild baboons.

Mammalian gut microbiomes are highly dynamic communities that shape and are shaped by host aging, including age-related changes to host immunity, metabolism, and behavior. As such, gut microbial composition may provide valuable information on host biological age. Here we test this idea by creating a microbiome-based age predictor using 13,563 gut microbial profiles from 479 wild baboons collected over 14 years.

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer.

Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity.

FDA, CDC, and NIH Co-sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets.

Pediatric stoma in Zambia: Current ethical challenges and advancement of public policy.

Introduction: Pediatric ostomy creation is becoming increasingly prevalent in Sub-Saharan Africa (SSA). The procedure is associated with both physical and ethical challenges for patients, their families, and medical providers.

Ethical Discussion: Counseling parents of children in need of ostomy creation must address each of their trepidations while seeking to promote the ethical tenets of beneficence, non-maleficence, autonomy, quality of life, and justice.

Relationship between skeletal mitochondrial function and digital markers of free-living physical activity in older adults.

This study examined the association between in vivo skeletal mitochondrial function and digital free-living physical activity patterns-a measure that summarizes biological, phenotypic, functional, and environmental effects on mobility. Among 459 participants (mean age 68 years; 55% women) in the Baltimore Longitudinal Study of Aging, mitochondrial function was quantified as skeletal muscle oxidative capacity via post-exercise phosphocreatine recovery rate (τ) in the vastus lateralis muscle of the left thigh, using 31P magnetic resonance spectroscopy. Accelerometry was collected using a 7-day, 24-h wrist-worn protocol and summarized into activity amount, intensity, endurance, and accumulation patterning metrics.

Evaluating Child Sexual Abuse Perpetration Prevention Efforts: A Systematic Review.

Many child sexual abuse prevention efforts focus on the prevention of victimization, through education of children and parents, bystander training, and policies and practices in youth-serving organizations (e.g. requiring criminal record checks).

US Immigration Policy Stressors and Latinx Youth Mental Health.

Importance: The youth mental health crisis is exacerbated for Latinx adolescents, a group whose families are targets of anti-immigrant rhetoric and policy.

Objective: To investigate how immigration-related stressors are associated with disruptions in parent-child relationships and, in turn, the mental health symptoms of Latinx adolescents.

Design, Setting, And Participants: Data for this prospective cohort study of adolescent-mother dyads were derived from surveys completed at 3 time points spanning 4 years (time 1 [T1] in 2018, time 2 [T2] in 2020, and time 3 [T3] in 2022).

Intratumoral delivery of the chitin-derived C100 adjuvant promotes robust STING, IFNAR, and CD8 T cell-dependent anti-tumor immunity.

Stimulator of IFN genes (STING) is a promising target for adjuvants utilized in in situ cancer vaccination approaches. However, key barriers remain for clinical translation, including low cellular uptake and accessibility, STING variability necessitating personalized STING agonists, and interferon (IFN)-independent signals that can promote tumor growth. Here, we identify C100, a highly deacetylated chitin-derived polymer (HDCP), as an attractive alternative to conventional STING agonists.

Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

Background: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care.

Methods: A multidisciplinary working group was formed.

Antithrombotics in the Fall Patient: Appropriateness and Risk-Benefit Analysis.

Falls are the leading cause of hospitalizations following trauma nationwide, resulting in over 3 million admissions in 2020. This population is typically aged, and many are prescribed antithrombotic (AT) therapy. In this prospective study, we aimed to analyze fall history while assessing appropriateness of AT regimen relative to fall risk.

Application of the Geriatric Trauma Outcome Score in a Rural Setting.

Objective: To retrospectively apply the Geriatric Trauma Outcome (GTO) score to the patient population of a rural South Central Appalachian level 1 trauma center and identify the potential utility of the GTO score in guiding goals of care discussions.

Methods: Trauma registry data was extracted for 5,627 patients aged 65+ from 2017 to 2021. GTO score was calculated for each patient.

Assessing Futile Trauma Transfers in Rural Appalachia Following a Regional Health Care System Consolidation.

This study sought to define and analyze rates of futile trauma transfers (FTTs) after the consolidation of two rural level 1 trauma centers into one. Data was extracted from the regional trauma registry for a period of 5 years (2017-2022) for all trauma patients transferred into our level 1 trauma center (n = 3369). An FTT was defined as a transfer that (1) received no major interventions and (2) died or was discharged to a hospice facility within 72 hours.