Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Thymic and T-cell intrinsic critical roles associated with Severe Combined Immunodeficiency and Omenn syndrome due to a heterozygous variant (G201R) in PSMB10.

Background: Heterozygous immunoproteasome subunit beta-type 10 (PSMB10) mutations can cause severe combined immunodeficiency (SCID) and Omenn syndrome (OS). Hematopoietic stem cell transplantation in these patients is associated with severe complications and poor immune reconstitution, often resulting in death.

Objective: To perform immunological and molecular characterization of an infant with a PSMB10 heterozygous variant.

Machine Learning for Mental Health: Applications, Challenges, and the Clinician's Role.

Purpose Of Review: This review aims to evaluate the current psychiatric applications and limitations of machine learning (ML), defined as techniques used to train algorithms to improve performance at a task based on data. The review emphasizes the clinician's role in ensuring equitable and effective patient care and seeks to inform mental health providers about the importance of clinician involvement in these technologies.

Recent Findings: ML in psychiatry has advanced through electronic health record integration, disease phenotyping, and remote monitoring through mobile applications.

Flow cytometry-based diagnostic approach for inborn errors of immunity: experience from Algeria.

Purpose: In this study, we retrospectively reviewed the use of flow cytometry (FCM) in the diagnosis of inborn errors of immunity (IEIs) at a single center in Algeria. Sharing insights into our practical experience, we present FCM based diagnostic approaches adapted to different clinical scenarios.

Methods: Between May 2017 and February 2024, pediatric and adult patients presenting with clinical features suggestive of immunodeficiency were subjected to FCM evaluation, including lymphocyte subset analysis, detection of specific surface or intracellular proteins, and functional analysis of immune cells.

Chronotype and emotion processing: a pilot study testing timing of online cognitive bias modification training.

Background: Circadian rhythms influence cognitive performance which peaks in the morning for early chronotypes and evening for late chronotypes. It is unknown whether cognitive interventions are susceptible to such synchrony effects and could be optimised at certain times-of-day.

Objective: A pilot study testing whether the effectiveness of cognitive bias modification (CBM) for facial emotion processing was improved when delivered at a time-of-day that was synchronised to chronotype.

Differentiating neural sensitivity and bias during face-emotion processing in youth: a computational approach.

The ability to interpret face-emotion displays is critical for the development of adaptive social interactions. Using a novel variant of a computational model and fMRI data, we examined behavioral and neural associations between two metrics of face-emotion labeling (sensitivity and bias) and age in youth. Youth and adults (n = 44, M age = 20.

Preformed Vesicle Approach to LNP Manufacturing Enhances Retinal mRNA Delivery.

Complete encapsulation of nucleic acids by lipid-based nanoparticles (LNPs) is often thought to be one of the main prerequisites for successful nucleic acid delivery, as the lipid environment protects mRNA from degradation by external nucleases and assists in initiating delivery processes. However, delivery of mRNA via a preformed vesicle approach (PFV-LNPs) defies this precondition. Unlike traditional LNPs, PFV-LNPs are formed via a solvent-free mixing process, leading to a superficial mRNA localization.

Weight gained during treatment predicts 6-month body mass index in a large sample of patients with anorexia nervosa using ensemble machine learning.

Objective: This study used machine learning methods to analyze data on treatment outcomes from individuals with anorexia nervosa admitted to a specialized eating disorders treatment program.

Methods: Of 368 individuals with anorexia nervosa (209 adolescents and 159 adults), 160 individuals had data available for a 6-month follow-up analysis. Participants were treated in a 6-day-per-week partial-hospital program.

Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization.

Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients.

Thiophene-based lipids for mRNA delivery to pulmonary and retinal tissues.

Lipid nanoparticles (LNPs) largely rely on ionizable lipids to yield successful nucleic acid delivery via electrostatic disruption of the endosomal membrane. Here, we report the identification and evaluation of ionizable lipids containing a thiophene moiety (Thio-lipids). The Thio-lipids can be readily synthesized via the Gewald reaction, allowing for modular lipid design with functional constituents at various positions of the thiophene ring.

Irritability in Youths: A Critical Integrative Review.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps.

IKAROS gain of function disease: Allogeneic hematopoietic cell transplantation experience and expanded clinical phenotypes.

IKAROS, encoded by IKZF1, is a tumor suppressor and a key hematopoietic transcription factor responsible for lymphoid and myeloid differentiation. IKZF1 mutations result in inborn errors of immunity presenting with increased susceptibility to infections, immune dysregulation, and malignancies. In particular, patients carrying IKZF1 gain-of-function (GOF) mutations mostly exhibit symptoms of immune dysregulation and polyclonal plasma cell proliferation.

The changing nitrogen landscape of United States streams: Declining deposition and increasing organic nitrogen.

Air quality regulations have led to decreased nitrogen (N) and sulfur deposition across the conterminous United States (CONUS) during the last several decades, particularly in the eastern parts. But it is unclear if declining deposition has altered stream N at large scales. We compared watershed N inputs with N chemistry from over 2,000 CONUS streams where deposition was the largest N input to the watershed.

Mulibrey nanism and immunological complications: a comprehensive case report and literature review.

Introduction: Mulibrey nanism (MUL) is a rare disorder caused by gene variants characterized by growth failure, dysmorphic features, congestive heart failure (CHF), and an increased risk of Wilms' tumor. Although immune system impairment has been documented in MUL, the underlying mechanisms remain poorly understood.

Methods: We present a case of MUL with progressive lymphopenia and review similar cases from the literature.

Can peripheral psychophysiological markers predict response to exposure-based cognitive behavioral therapy in youth with severely impairing irritability? A study protocol.

Background: Irritability, an increased proneness to anger, is a primary reason youth present for psychiatric care. While initial evidence supports the efficacy of exposure-based cognitive behavioral therapy (CBT) for youth with clinically impairing irritability, treatment mechanisms remain unclear. Here, we propose to measure peripheral psychophysiological indicators of arousal-heart rate (HR)/electrodermal activity (EDA)-and regulation-heart rate variability (HRV)-during exposures to anger-inducing stimuli as potential predictors of treatment efficacy.

An Introduction to Generative Artificial Intelligence in Mental Health Care: Considerations and Guidance.

Purpose Of Review: This paper provides an overview of generative artificial intelligence (AI) and the possible implications in the delivery of mental health care.

Recent Findings: Generative AI is a powerful technology that is changing rapidly. As psychiatrists, it is important for us to understand generative AI technology and how it may impact our patients and our practice of medicine.

Sources of Information Utilized by Active Duty Service Members for Nutritional Supplement Safety and Efficacy.

Introduction: The increasing prevalence of nutritional supplement use in the United States, combined with the risk of adverse effects from these largely unregulated products, poses a significant challenge to health care professionals. The purpose of our study is to evaluate the use of nutritional supplements in an active duty military population, particularly those supplements with increased adverse effect profiles, and the sources of information that service members use to make decisions regarding the safety and efficacy of supplements.

Materials And Methods: The investigators distributed a voluntary, anonymous, self-report survey to a battalion of active duty service members to collect demographic data and information pertaining to the use of, adverse effects from, and sources of information utilized regarding the safety and efficacy of nutritional supplements.