MDA-9/Syntenin as a therapeutic cancer metastasis target: current molecular and preclinical understanding.

Introduction: Metastasis is a principal cause of patient morbidity and death from solid cancers with current therapies being inadequate.

Areas Covered: Detailed genomic analyses document mutational differences between the initial tumor and metastatic clones, posing a challenge to current targeted therapies, which focus predominantly on the phenotype of primary tumors. Considering the diverse signaling cascades and numerous compensatory pathways in metastasis, designing broad-spectrum anti-metastatic therapies remains challenging.

Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study.

Background: Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects of a single dose have not been investigated.

Aims: To investigate the pharmacokinetics, feasibility, safety and efficacy of single-dose psilocybin therapy in AUD.

Acute psilocybin and ketanserin effects on cerebral blood flow: 5-HT2AR neuromodulation in healthy humans.

Psilocin, the active metabolite of psilocybin, is a psychedelic and agonist at the serotonin 2A receptor (5-HT2AR) that has shown positive therapeutic effects for brain disorders such as depression. To elucidate the brain effects of psilocybin, we directly compared the acute effects of 5-HT2AR agonist (psilocybin) and antagonist (ketanserin) on cerebral blood flow (CBF) using pseudo-continuous arterial spin labeling magnetic resonance imaging (MRI) in a single-blind, cross-over study in 28 healthy participants. We evaluated associations between plasma psilocin level (PPL) or subjective drug intensity (SDI) and CBF.

Solar Modulation of Cosmic Nuclei over a Solar Cycle: Results from the Alpha Magnetic Spectrometer.

We report the properties of precision time structures of cosmic nuclei He, Li, Be, B, C, N, and O fluxes over an 11-year solar cycle from May 2011 to November 2022 in the rigidity range from 1.92 to 60.3 GV.

Antiprotons and Elementary Particles over a Solar Cycle: Results from the Alpha Magnetic Spectrometer.

We present results over an 11-year Solar cycle of cosmic antiprotons based on 1.1×10^{6} events in the rigidity range from 1.00 to 41.

Relation Between Brain Morphological Features and Psychiatric Hospitalization Risk in Major Depressive and Bipolar Disorders.

Introduction: Patients with mood disorders, especially, major depressive disorder (MDD) and bipolar disorder (BD), are at heightened risk of relapse and psychiatric rehospitalizations. Therefore, there is an urgent need to identify modifiable biomarkers to inform personalized and intensified prevention strategies for those at the greatest risk of relapse and hospital readmissions. Brain structural measures subserving cognitive function hold particular promise among potential predictive biomarkers.

Midwives experience of working with maternity assistants: A qualitative study.

Introduction: The midwifery workforce is essential for delivering safe, high-quality maternity care, however, global staffing shortages pose significant challenges. To address these issues, incorporating midwifery assistants, including undergraduate midwifery students into the model of care has been proposed as a strategy to support midwives and maintain effective service delivery.

Aim: This study explores the Registered Midwives' experiences working with Midwifery Assistants (MAs) in an Australian tertiary maternity service.

Allogeneic CAR T Cell Products Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Experience From the ALPHA2/ALPHA Clinical Studies.

Purpose: Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T cell products may improve access to treatment versus autologous ones. We report the phase 1 experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naive patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).

Patients And Methods: In the ALPHA2/ALPHA studies, safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naive patients with R/R LBCL.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Report of a Work Group on Nonverbal Learning Disability: Consensus Criteria for Developmental Visual-Spatial Disorder: Reconceptualizing Nonverbal Learning Disability for DSM Consideration.

Objective: Although extant research points to nonverbal learning disability (NVLD) as a distinct disorder, it is not included in the diagnostic nomenclatures, and there is heterogeneity in how it is defined. A working group was formed to gain consensus on a standard DSM-type definition for NVLD, a necessary first step for proposing its inclusion in future DSM editions, and the disorder was renamed to better reflect the core deficit-visual-spatial problems.

Method: An iterative process was used to reach consensus on a DSM-style criteria set that reconceptualizes NVLD as developmental visual-spatial disorder (DVSD).

Psychological impact of an intensive care admission for COVID-19 on patients in the United Kingdom.

Background: The psychological impact of surviving an admission to an intensive care unit (ICU) with COVID-19 is uncertain. The objective of the study was to assess the prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) symptoms in ICU survivors treated for COVID-19 infection, and identify risk factors for psychological distress.

Methods: This observational study was conducted at 52 ICUs in the United Kingdom.

Bridging Them and Us Divisions: A Focus Group Study of Identities in Clinical Psychology Training.

Background: The training of clinical psychologists is conducted by staff, trainees, service users and carers. Often those working in clinical psychology do so due to their own lived experiences. These stakeholders may require having to navigate both personal and professional identities.

Taking a step back: Parents' experiences of the decision-making process for elective orthognathic surgery in cleft lip and palate (IPA).

Objective: This study explored parents' experiences of the transition of responsibility to their child for healthcare decisions relating to their cleft lip and/or palate (CL/P).

Methods: Online semi-structured interviews were conducted with 11 participants (six females and five males, aged 41 to 60 years). They were parents of young people who had decided whether to undergo orthognathic surgery.

T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions.

The continuous rise in skin cancer incidence highlights an imperative for improved skin cancer prevention. Topical calcipotriol-plus-5-fluorouracil (calcipotriol-plus-5-FU) immunotherapy effectively eliminates precancerous skin lesions and prevents squamous cell carcinoma (SCC) in patients. However, its mechanism of action remains unclear.

A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals.

Introduction: Long COVID is a debilitating condition that lasts for more than three months post-infection by SARS-CoV-2. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and biomarkers that could be associated with Long COVID.

Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression.

Background: Using [F]altanserin, a serotonin 2A receptor (5-HTR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HTR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HTR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HTR and neuroticism are both modulated by HPA axis function.

Global analysis of endogenous protein disorder in cells.

Disorder and flexibility in protein structures are essential for biological function but can also contribute to diseases, such as neurodegenerative disorders. However, characterizing protein folding on a proteome-wide scale within biological matrices remains challenging. Here we present a method using a bifunctional chemical probe, named TME, to capture in situ, enrich and quantify endogenous protein disorder in cells.

Intravenous and intracranial GD2-CAR T cells for H3K27M diffuse midline gliomas.

H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the disialoganglioside GD2 (ref. ). Chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) eradicated DMGs in preclinical models.

Optimizing generalized anxiety disorder screening in young adults perinatally affected by HIV: A psychometric analysis.

Background: Generalized Anxiety Disorder (GAD) is prevalent among people with HIV and is associated with adverse health outcomes. This study investigates the suitability of the Generalized Anxiety Disorder Scale-7 item (GAD-7) screening tool and its 2-item (GAD-2) version for use in young adults with perinatally-acquired HIV (YAPHIV) and young adults perinatally exposed to HIV but uninfected (YAPHEU).

Methods: Data come from the 7th follow-up interview (FU7) from a longitudinal study of youth with PHIV and PHEU, first recruited when 9-16 years.

Design and Synthesis of Small Molecule Probes of MDA-9/Syntenin.

MDA-9/Syntenin, a key scaffolding protein and a molecular hub involved in a diverse range of cell signaling responses, has proved to be a challenging target for the design and discovery of small molecule probes. In this paper, we report on the design and synthesis of small molecule ligands of this key protein. Genetic algorithm-based computational design and the five-eight step synthesis of three molecules led to ligands with affinities in the range of 1-3 µM, a 20-60-fold improvement over literature reports.