Planum Temporale Asymmetries in Primates: A Comparative Study in Great Apes and Monkeys.

Objectives: Most human brains exhibit left hemisphere asymmetry for planum temporale (PT) surface area and gray matter volume, which is interpreted as cerebral lateralization for language. Once considered a uniquely human feature, PT asymmetries have now been documented in chimpanzees and olive baboons. The goal of the current study was to further investigate the evolution of PT asymmetries in nonhuman primates.

Implementation of automated cognitive testing systems for socially housed rhesus (Macaca mulatta) and squirrel (Saimiri spp.) monkeys: Age differences in learning.

Utilizing Automated Cognitive Testing Systems (ACTS) with group-housed nonhuman primates offers a number of advantages over manual testing and computerized testing of singly housed subjects. To date, ACTS usage has been limited to great apes or African monkeys. Here, we detail what we have learned while implementing ACTS with socially housed squirrel monkeys and rhesus macaques and provide information about the training process.

Lymphotoxin limits Foxp3 regulatory T cell development from Foxp3 precursors via IL-4 signaling.

Regulatory T cells (T) are critical players of immune tolerance that develop in the thymus via two distinct developmental pathways involving CD25Foxp3 and CD25Foxp3 precursors. However, the mechanisms regulating the recently identified Foxp3 precursor pathway remain unclear. Here, we find that the membrane-bound lymphotoxin αβ (LTαβ) heterocomplex is upregulated during T development upon TCR/CD28 and IL-2 stimulation.

DEPDC5 protects CD8 T cells from ferroptosis by limiting mTORC1-mediated purine catabolism.

Peripheral CD8 T cell number is tightly controlled but the precise molecular mechanism regulating this process is still not fully understood. In this study, we found that epilepsy patients with loss of function mutation of DEPDC5 had reduced peripheral CD8 T cells, and DEPDC5 expression positively correlated with tumor-infiltrating CD8 T cells as well as overall cancer patient survival, indicating that DEPDC5 may control peripheral CD8 T cell homeostasis. Significantly, mice with T cell-specific Depdc5 deletion also had reduced peripheral CD8 T cells and impaired anti-tumor immunity.

Prioritizing Mental Health within HIV and Tuberculosis Services in PEPFAR.

Underprioritization of mental health is a global problem and threatens the decades-long progress of the US President's Emergency Plan for AIDS Relief (PEPFAR) program. In recent years, mental health has become globally recognized as a part of universal healthcare, making this an opportune moment for the global community to integrate mental health services into routine programming. PEPFAR is well positioned to lead by example.

Tuberculosis Preventive Treatment Update - U.S. President's Emergency Plan for AIDS Relief, 36 Countries, 2016-2023.

Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV.

Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response.

Gain-of-function mutations in stimulator of interferon gene 1 (STING1) result in STING-associated vasculopathy with onset in infancy (SAVI), a severe autoinflammatory disease. Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, which have roles in the onset and severity of SAVI and remain to be elucidated. To this end, we performed a multi-omics comparative analysis of peripheral blood mononuclear cells (PBMCs) and plasma from SAVI patients and healthy controls, combined with a dataset of healthy PBMCs treated with IFN-β.

Behavioral and Cognitive Outcomes of Rhesus Macaques Following Neonatal Exposure to Antiseizure Medications.

Objective: Exposure of neonatal macaques to the antiseizure medications phenobarbital and midazolam (PbM) causes widespread apoptotic death of neurons and oligodendrocytes. We studied behavior and neurocognitive performance in 12 to 24 month-old macaques treated as neonates with PbM.

Methods: A total of 14 monkeys received phenobarbital and midazolam over 24 hours under normothermia (n = 8) or mild hypothermia (n = 6).

RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes.

Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the presence of a C-terminal FYVE domain and by their affinity for phosphatidylinositol 3-phosphate on endosomal membranes. The FYVE domain-bearing isoform (iRUFY3) is preferentially expressed in primary immune cells and up-regulated upon activation by microbes and Interferons.

Interpositional scaffold anchor rotator cuff footprint tear repair: excellent survival, healing, and early outcomes.

Purpose: Shoulder function limitation duration after a full-thickness rotator cuff tendon (RCT) tear may influence post-repair healing and outcomes. A suture anchor was developed to improve footprint repair fixation and healing through biological fluid delivery and scaffold augmentation. The primary multicenter study objective was to evaluate RCT repair failure rate based on 6-month MRI examination, and device survival at 1-year follow-up.

Gray matter network properties show distinct associations with CSF p-tau 181 levels and amyloid status in individuals without dementia.

Gray matter networks are altered with amyloid accumulation in the earliest stage of AD, and are associated with decline throughout the AD spectrum. It remains unclear to what extent gray matter network abnormalities are associated with hyperphosphorylated-tau (p-tau). We studied the relationship of cerebrospinal fluid (CSF) p-tau181 with gray matter networks in non-demented participants from the European Prevention of Alzheimer's Dementia (EPAD) cohort, and studied dependencies on amyloid and cognitive status.

Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells.

Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic cell biology and their ability to orchestrate immune responses is poorly developed. Here, we map single-cell metabolic states and immune profiles of inflammatory and tolerogenic monocytic dendritic cells using recently developed multiparametric approaches. Single-cell metabolic pathway activation scores reveal simultaneous engagement of multiple metabolic pathways in distinct monocytic dendritic cell differentiation stages.

Improving transparency-A call to include social housing information in biomedical research articles involving nonhuman primates.

The social setting of animal subjects in the research environment has known effects on a variety of dependent measures used in biomedical research. Proper evaluation of the robustness of published research is dependent upon transparent, detailed, and accurate reporting of research methods, including the animals' social housing conditions. However, to date, most research articles utilizing nonhuman primates (NHPs) provide only partial data on this topic, hampering transparency, and reproducibility.

RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages.

We report here that RUFY4, a newly characterized member of the 'RUN and FYVE domain-containing' family of proteins previously associated with autophagy enhancement, is highly expressed in alveolar macrophages (AM). We show that RUFY4 interacts with mitochondria upon stimulation by microbial-associated molecular patterns of AM and dendritic cells. RUFY4 interaction with mitochondria and other organelles is dependent on a previously uncharacterized OmpH domain located immediately upstream of its C-terminal FYVE domain.

Predicting their past: Machine language learning can discriminate the brains of chimpanzees with different early-life social rearing experiences.

Early life experiences, including separation from caregivers, can result in substantial, persistent effects on neural, behavioral, and physiological systems as is evidenced in a long-standing literature and consistent findings across species, populations, and experimental models. In humans and other animals, differential rearing conditions can affect brain structure and function. We tested for whole brain patterns of morphological difference between 108 chimpanzees reared typically with their mothers (MR; N = 54) and those reared decades ago in a nursery with peers, human caregivers, and environmental enrichment (NR; N = 54).

Expansion of telehealth in primary care during the COVID-19 pandemic: benefits and barriers.

The novel coronavirus disease 2019 (COVID-19) pandemic remarkably accelerated the adoption of telemedicine in outpatient settings. Out of necessity, virtual care became a preferred and default modality of extending primary care services to health care consumers. Although telemedicine is not a new concept and had been used in many organizations and health systems, the COVID-19 pandemic scaled up its use in a variety of health care settings.

Fortnightly or fractionated weekly docetaxel-cisplatin-5-FU as first-line treatment in advanced gastric and gastroesophageal junction adenocarcinoma: The randomized phase II DoGE study.

Background: While docetaxel/cisplatin/5-fluorouracil (DCF) outperforms CF in first-line gastric adenocarcinoma, toxicity remains an issue.

Methods: This multicenter phase II trial randomized chemonaïve metastatic gastric adenocarcinoma patients to fractionated weekly DCF (D 40 mg/m , C 35 mg/m², F 1800 mg/m² over 24 h, on days 1 and 8 every 3 weeks, arm (1) or fortnightly DCF (D 50 mg/m , C 50 mg/m², F 2000 mg/m² over 48 h every 2 weeks, arm (2). Prophylactic granulocyte colony-stimulating factor (G-CSF) was not allowed.

LAMP-5 is an essential inflammatory-signaling regulator and novel immunotherapy target for mixed lineage leukemia-rearranged acute leukemia.

Although great advances have been made in understanding the pathobiology of mixed lineage leukemia-rearranged (MLL-r) leukemias, therapies for this leukemia have remained limited, and clinical outcomes remain bleak. In order to identify novel targets for immunotherapy treatments, we compiled a lineage-independent MLL-r leukemia gene signature using publicly available data sets. Data from large leukemia repositories were filtered through the in silico human surfaceome, providing a list of highly predicted cell surface proteins overexpressed in MLL-r leukemias.

Recurrence-Free Survival Analysis in Locally Advanced Pheochromocytoma: First Appraisal.

Context: The behavior of locally advanced pheochromocytoma (LAP) remains unknown.

Objective: We characterized the population with LAP and recurrence-free survival (RFS).

Methods: This retrospective multicentric study was run within the ENDOCAN-COMETE network and French Group of Endocrine Tumors (GTE) from 2003 to 2018, including patients from 11 French referral centers with LAP as defined by capsular invasion, vascular invasion, adipose tissue invasion, and/or positive locoregional lymph nodes at diagnosis without evidence of distant metastasis.

Zdhhc2 Is Essential for Plasmacytoid Dendritic Cells Mediated Inflammatory Response in Psoriasis.

Zdhhc family genes are composed of 24 members that regulate palmitoylation, a post-translational modification process for proteins. Mutations in genes that alter palmitoylation or de-palmitoylation could result in neurodegenerative diseases and inflammatory disorders. In this study, we found that Zdhhc2 was robustly induced in psoriatic skin and loss of Zdhhc2 in mice by CRISPR/Cas9 dramatically inhibited pathology of the ear skin following imiquimod treatment.