Biomarkers of Auditory-Verbal Hallucinations.

Auditory-verbal hallucinations (AVH) are debilitating symptoms experienced by those diagnosed with psychosis as well as many other neurological and psychiatric disorders. Critical to supporting individuals with AVH is identifying biomarkers that serve to track changes in brain states that put individuals at risk for developing or worsening of symptoms. There has been substantial literature identifying neural areas to track over time that may prove to be effective clinical tools.

Intersectionality of sex and race in COVID-19 mortality and vaccination inequities in Massachusetts.

Background: Inequities in COVID-19 incidence, morbidity, and mortality between racial and ethnic groups in the United States (U.S.) have been documented since the start of the pandemic in early 2020.

Community-led diphtheria vaccination campaign to manage a diphtheria outbreak in a remote Aboriginal community.

In 2022, five cases of diphtheria were identified in and around Wujal Wujal, a discrete Aboriginal community in Far North Queensland. This prompted a mass diphtheria vaccination campaign in the community which increased the proportion of residents aged ≥ 14 years receiving a diphtheria containing vaccine in the prior twelve months from 5% to 74%. No further cases were detected in the subsequent twenty-two months.

Predictive Impact of Tumor Mutational Burden on Real-World Outcomes of First-Line Immune Checkpoint Inhibition in Metastatic Melanoma.

Purpose: The choice of threshold and reliability of high tumor mutational burden (TMB) to predict outcomes and guide treatment choice for patients with metastatic melanoma receiving first-line immune checkpoint inhibitor (ICI) therapy in the real world is not well known.

Methods: Using a deidentified nationwide (US-based) melanoma clinicogenomic database, we identified a real-world cohort of patients with metastatic melanoma (N = 497) who received first-line monotherapy anti-PD-1 (n = 240) or dual anti-PD-1 and anti-CTLA-4 ICI (n = 257) and had a tissue-based comprehensive genomic profiling test TMB score.

Results: TMB-high (TMB-H; ≥10 mutations per megabase [muts/Mb], n = 352, 71%) was independently predictive of superior real-world progression-free survival and overall survival versus TMB-low (<10 mut/Mb, n = 145, 29%) in both mono ICI (hazard ratio [HR], 0.

The mechanisms underlying conditioning of phantom percepts differ between those with hallucinations and synesthesia.

There are many different kinds of 'phantom' percepts but it is unknown whether they are united by common mechanisms. For example, synaesthesia (e.g.

Evidence for Reduced Sensory Precision and Increased Reliance on Priors in Hallucination-Prone Individuals in a General Population Sample.

Background: There is increasing evidence that people with hallucinations overweight perceptual beliefs relative to incoming sensory evidence. Past work demonstrating prior overweighting has used simple, nonlinguistic stimuli. However, auditory hallucinations in psychosis are often complex and linguistic.

Barriers and solutions to the adoption of translational tools for computational psychiatry.

Computational psychiatry is a field aimed at developing formal models of information processing in the human brain, and how alterations in this processing can lead to clinical phenomena. There has been significant progress in the development of tasks and how to model them, presenting an opportunity to incorporate computational psychiatry methodologies into large- scale research projects or into clinical practice. In this viewpoint, we explore some of the barriers to incorporation of computational psychiatry tasks and models into wider mainstream research directions.

Genomic analysis of an outbreak of toxin gene bearing in Northern Queensland, Australia reveals high level of genetic similarity.

Toxigenic diphtheria is rare in Australia with generally fewer than 10 cases reported annually; however, since 2020, there has been an increase in toxin gene-bearing isolates of cases in North Queensland, with an approximately 300% escalation in cases in 2022. Genomic analysis on both toxin gene-bearing and non-toxin gene-bearing isolated from this region between 2017 and 2022 demonstrated that the surge in cases was largely due to one sequence type (ST), ST381, all of which carried the toxin gene. ST381 isolates collected between 2020 and 2022 were highly genetically related to each other, and less closely related to ST381 isolates collected prior to 2020.

Real-world Validation of TMB and Microsatellite Instability as Predictive Biomarkers of Immune Checkpoint Inhibitor Effectiveness in Advanced Gastroesophageal Cancer.

Unlabelled: Patients with advanced gastroesophageal cancer (mEG) and tumor mutational burden ≥10 mut/Mb (TMB ≥ 10) have more favorable outcomes on immune checkpoint inhibitor (ICPI) monotherapy compared with chemotherapy in subgroup analyses of randomized controlled trials. We sought to evaluate the robustness of these associations in real-world settings where patients and practices are more diverse. A total of 362 2 L and 692 1 L patients, respectively received ICPI ( = 99, 33) or chemotherapy ( = 263, 659) across approximately 280 U.

The effectiveness of mindfulness-based stress reduction (MBSR) on the mental health, HbA1C, and mindfulness of diabetes patients: A systematic review and meta-analysis of randomised controlled trials.

The clinically standardised mindfulness-based stress reduction (MBSR) has been utilised as an intervention for improving mental health among diabetes patients The present study aimed to assess the effectiveness of mindfulness-based stress reduction (MBSR) on the mental health, haemoglobin A1c (HbA1C), and mindfulness of diabetes patients. A systematic review and meta-analysis approach was employed to review randomised controlled trials published in the English language between the inception of eight databases to July 2022. Eleven articles from 10 studies, with a combined sample size of 718 participants, were included in the systematic review, and nine studies were included in the meta-analysis.

A novel computational approach to pain perception modelling within a Bayesian framework using quantitative sensory testing.

Pain perception can be studied as an inferential process in which prior information influences the perception of nociceptive input. To date, there are no suitable psychophysical paradigms to measure this at an individual level. We developed a quantitative sensory testing paradigm allowing for quantification of the influence of prior expectations versus current nociceptive input during perception.

The educational value of situational judgement tests (SJTs) when used during undergraduate medical training: A systematic review and narrative synthesis.

Introduction: Situational judgement tests (SJTs) are a recognised assessment method for admission into medical school, selection into postgraduate training programs, and postgraduate competency assessment. More recently, however, SJTs have been used during undergraduate medical training (UMT). This systematic review identifies, describes, and appraises the evidence for SJTs in UMT to determine educational associations and outcomes.

Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy in Patients With Metastatic Colorectal Cancer With Measures of Microsatellite Instability, Mismatch Repair, or Tumor Mutational Burden.

Importance: The KEYNOTE-177 trial demonstrated that patients with metastatic colorectal cancer (MCRC) with high microsatellite instability (MSI-H) and/or mismatch repair deficiency (DMMR) have better outcomes when receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy. Data on performance of ICIs in patients with MCRC in standard practice settings remain limited, and direct MMR vs MSI outcome association comparisons are lacking.

Objective: To validate MSI (determined by next-generation sequencing [NGS]) as a biomarker of ICI effectiveness among patients with MCRC in standard practice settings and examine the association of MSI assessed by NGS, DMMR by immunohistochemistry, and tumor mutational burden (cutoff, 10 mutations/megabase) with ICI outcomes.

Increases in sensory noise predict attentional disruptions to audiovisual speech perception.

We receive information about the world around us from multiple senses which combine in a process known as multisensory integration. Multisensory integration has been shown to be dependent on attention; however, the neural mechanisms underlying this effect are poorly understood. The current study investigates whether changes in sensory noise explain the effect of attention on multisensory integration and whether attentional modulations to multisensory integration occur via modality-specific mechanisms.

Complications After Dental Sedation: A Myotonic Mystery Case Report.

Myotonic dystrophy (dystrophia myotonica; DM) is an uncommon progressive hereditary muscle disorder that can present with variable severity at birth, in early childhood, or most commonly as an adult. Patients with DM, especially type 1 (DM1), are extremely sensitive to the respiratory depressant effects of sedative-hypnotics, anxiolytics, and opioid agonists. This case report describes a 37-year-old male patient with previously undiagnosed DM1 who received dental care under minimal sedation using intravenous midazolam.

Biology and Targetability of the Extended Spectrum of PIK3CA Mutations Detected in Breast Carcinoma.

Purpose: Alpelisib is a PI3K alpha (PI3Kα)-selective inhibitor approved for the treatment of hormone receptor-positive/HER2-negative (HR+/HER2-) PIK3CA-mutated advanced breast cancer (ABC) based on the SOLAR-1 trial, which defined 11 substitutions in exons 7, 9, and 20 in PIK3CA (SOLAR1m). We report alpelisib effectiveness for ABC harboring SOLAR1m, as well as other pathogenic PIK3CA mutations (OTHERm) using comprehensive genomic profiling (CGP).

Experimental Design: A total of 33,977 tissue and 1,587 liquid biopsies were analyzed using hybrid capture-based CGP covering the entire coding sequence of PIK3CA.

Multi-state survival models with treatment effects and biomarkers: Simulations for study design assessment.

Background: Comparative effectiveness studies of cancer therapeutics in observational data face confounding by patterns of clinical treatment over time. The validity of survival analysis in longitudinal health records depends on study design choices including index date definition and model specification for covariate adjustment.

Methods: Overall survival in cancer is a multi-state transition process with mortality and treatment switching as competing risks.

The health of mothers of children with a life-limiting condition: A qualitative interview study.

Background: The number of children with a life-limiting condition is increasing. The mothers of these children commonly provide extensive care at home for their child and are at a higher risk of poor health than other mothers. The impact of this is rarely explored from mothers' perspectives.

SPOP Mutations as a Predictive Biomarker for Androgen Receptor Axis-Targeted Therapy in De Novo Metastatic Castration-Sensitive Prostate Cancer.

Purpose: Intensification of androgen deprivation therapy (ADT) with either docetaxel or androgen receptor axis-targeted therapies (ARAT) are the current standard of care for patients with metastatic castration-sensitive prostate cancer (mCSPC). However, biomarkers guiding treatment selection are lacking. We hypothesized that ADT intensification with ARAT, but not with docetaxel, would be associated with improved outcomes in patients with de novo (dn)-mCSPC harboring SPOP mutations.