Relations of temporoparietal connectivity with neighborhood social fragmentation in youth at clinical high-risk for psychosis.

Temporoparietal brain areas comprise a candidate set of regions for interrogating the brain functional correlates of socioenvironmental factors in people at clinical high-risk for psychosis (CHR-P). Temporal lobe abnormalities have been shown to be common among people with schizophrenia spectrum conditions. Further, temporoparietal brain regions are implicated in tasks relevant to psychosocial outcomes, including coherent autobiographical memory recall and multimodal integration.

Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer.

Background: Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods: Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included.

Emergence and dynamics of delusions and hallucinations across stages in early psychosis.

Background: Hallucinations and delusions are often grouped together within the positive symptoms of psychosis. However, recent evidence suggests they may be driven by distinct computational and neural mechanisms. Examining the time course of their emergence may provide insights into the relationship between these underlying mechanisms.

Predicting conversion to psychosis using machine learning: response to Cannon.

Background: We previously reported that machine learning could be used to predict conversion to psychosis in individuals at clinical high risk (CHR) for psychosis with up to 90% accuracy using the North American Prodrome Longitudinal Study-3 (NAPLS-3) dataset. A definitive test of our predictive model that was trained on the NAPLS-3 data, however, requires further support through implementation in an independent dataset. In this report we tested for model generalization using the previous iteration of NAPLS-3, the NAPLS-2, using the identical machine learning algorithms employed in our previous study.

Patient-Reported Distress in Individuals With Head and Neck Cancer.

Importance: Distress is common among patients with cancer, and evidence of disparities associated with distress has been mixed. Head and neck cancer (HNC) is one of the most emotionally distressing cancers and is also a highly disparate disease. However, it is unknown whether there are disparities associated with patient-reported distress in HNC.

Attention Deficit Hyperactivity Disorder Among Youth at Clinical High Risk of Psychosis.

Background: Attention Deficit Hyperactivity Disorder (ADHD) affects a significant proportion of the population and is associated with numerous adverse outcomes including lower educational attainment, occupational challenges, increased substance use, and various mental health issues including psychosis. This study examined the demographic, clinical, cognitive, social cognitive, and functional differences between youth at clinical high-risk (CHR) for psychosis with and without comorbid ADHD.

Method: Data were drawn from the North American Prodrome Longitudinal Studies (NAPLS2 and NAPLS3), which included 764 and 710 CHR individuals, respectively.

Mismatch Negativity as an Index of Auditory Short-Term Plasticity: Associations with Cortisol, Inflammation, and Gray Matter Volume in Youth at Clinical High Risk for Psychosis.

Mismatch negativity (MMN) event-related potential (ERP) component reduction, indexing N-methyl-D-aspartate receptor (NMDAR)-dependent auditory echoic memory and short-term plasticity, is a well-established biomarker of schizophrenia that is sensitive to psychosis risk among individuals at clinical high-risk (CHR-P). Based on the NMDAR-hypofunction model of schizophrenia, NMDAR-dependent plasticity is predicted to contribute to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia during late adolescence or young adulthood, including gray matter loss. Moreover, stress and inflammation disrupt plasticity.

Convergent Validity of Experimental Cognitive Tests in a Large Community Sample.

Experimental cognitive tests are designed to measure particular cognitive domains, although evidence supporting test validity is often limited. The Consortium for Neuropsychiatric Phenomics test battery administered 23 experimental and traditional neuropsychological tests to a large sample of community volunteers ( = 1,059) and patients with psychiatric diagnoses ( = 137), providing a unique opportunity to examine convergent validity with factor analysis. Traditional tests included subtests from the Wechsler and Delis-Kaplan batteries, while experimental tests included the Attention Networks Test, Balloon Analogue Risk Task, Delay Discounting Task, Remember-Know, Reversal Learning Task, Scene Recognition, Spatial and Verbal Capacity and Manipulation Tasks, Stop-Signal Task, and Task Switching.

Protective Factors Predict Resilient Outcomes in Clinical High-Risk Youth with the Highest Individualized Psychosis Risk Scores.

Background And Hypothesis: Studying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator.

Study Design: CHR participants (N = 572) from NAPLS3 were assessed on the Risk Calculator.

Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of -Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial.

Purpose: This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab for the second-line treatment of -mutant metastatic colorectal cancer (mCRC).

Patients And Methods: This multicenter, open-label, single-arm study enrolled patients with -mutated mCRC previously treated with oxaliplatin and fluorouracil with or without bevacizumab. Patients received onvansertib (15 mg/m once daily on days 1-5 and 15-19 of a 28-day cycle) and FOLFIRI + bevacizumab (days 1 and 15).

Impact of adverse childhood experiences on risk for internalizing psychiatric disorders in youth at clinical high-risk for psychosis.

Introduction: Research has established that adverse childhood experiences (ACEs) confer risk for psychiatric diagnoses, and that protective factors moderate this association. Investigation into the effect of protective factors in the relationship between ACEs and internalizing disorders (e.g.

Proteomics based selection achieves complete response to HER2 therapy in HER2 IHC 0 breast cancer.

Recent trials have shown the efficacy of trastuzumab deruxtecan (T-DXd) in HER2-negative patients, but there is not yet a way to identify which patients will best respond, especially with the inability of current HER2 IHC and FISH assays to accurately determine HER2 expression in the unamplified setting. Here, we present a heavily pre-treated patient with triple-negative breast cancer (HER2 IHC 0 who had a complete response to T-DXd. In this case, we used a CLIA-certified reverse-phase protein array-based proteomic assay (RPPA) to determine that the patient had moderate HER2 protein expression (HER2 2+, 42%) and activation (HER2 1+, 23%).

Beyond the Descriptive: A Comprehensive, Multidomain Validation of Symptom Trajectories for Individuals at Clinical High Risk for Psychosis.

Background: Although the clinical high risk for psychosis (CHR-P) criteria are widely used to ascertain individuals at heightened risk for imminent onset of psychosis, it remains controversial whether CHR-P status defines a diagnostic construct in its own right. In a previous study, CHR-P nonconverters were observed to follow 3 distinct trajectories in symptoms and functioning: remission, partial remission, and maintenance of symptoms and functional impairments at subthreshold levels of intensity.

Methods: Here, we utilized the NAPLS3 (North American Prodrome Longitudinal Study phase 3) sample (N = 806) to determine whether 1) the same trajectory groups can be detected when assessing symptoms at 2-month intervals over an 8-month period and 2) the resulting trajectory groups differ from each other and from healthy control participants and converting CHR-P cases in terms of risk factors, comorbidities, and functional outcomes.

Fetal Gene Regulatory Gene Deletions are Associated with Poor Cognition and Altered Cortical Morphology in Schizophrenia and Community-Based Samples.

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals.

Cognitive subtypes in youth at clinical high risk for psychosis.

Introduction: Schizophrenia is a mental health condition that severely impacts well-being. Cognitive impairment is among its core features, often presenting well before the onset of overt psychosis, underscoring a critical need to study it in the psychosis proneness (clinical high risk; CHR) stage, to maximize the benefits of interventions and to improve clinical outcomes. However, given the heterogeneity of cognitive impairment in this population, a one-size-fits-all approach to therapeutic interventions would likely be insufficient.

Unique Functional Neuroimaging Signatures of Genetic Versus Clinical High Risk for Psychosis.

Background: 22q11.2 deletion syndrome (22qDel) is a copy number variant that is associated with psychosis and other neurodevelopmental disorders. Adolescents who are at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms.

Targeting Non-V600 Mutations in BRAF: A Single Institution Retrospective Analysis and Review of the Literature.

Background And Objective: While successful treatment paradigms for BRAF V600 mutations have been developed, 10% of BRAF mutations are not at V600 and lack a standard treatment regimen. This study summarizes the current body of knowledge on the treatment of non-V600 mutations and reports a single institution experience.

Methods: We conducted a literature review to summarize relevant preclinical and clinical published data on the response of non-V600 mutations to targeted therapies.