Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

PURPOSE: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P \u3c .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P \u3c .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

RNAlysis: analyze your RNA sequencing data without writing a single line of code

Abstract Background Among the major challenges in next-generation sequencing experiments are exploratory data analysis, interpreting trends, identifying potential targets/candidates, and visualizing the results clearly and intuitively. These hurdles are further heightened for researchers who are not experienced in writing computer code since most available analysis tools require programming skills. Even for proficient computational biologists, an efficient and replicable system is warranted to generate standardized results. Results We have developed RNAlysis, a modular Python-based analysis software for RNA sequencing data. RNAlysis allows users to build customized analysis pipelines suiting their specific research questions, going all the way from raw FASTQ files (adapter trimming, alignment, and feature counting), through exploratory data analysis and data visualization, clustering analysis, and gene set enrichment analysis. RNAlysis provides a friendly graphical user interface, allowing researchers to analyze data without writing code. We demonstrate the use of RNAlysis by analyzing RNA sequencing data from different studies using C. elegans nematodes. We note that the software applies equally to data obtained from any organism with an existing reference genome. Conclusions RNAlysis is suitable for investigating various biological questions, allowing researchers to more accurately and reproducibly run comprehensive bioinformatic analyses. It functions as a gateway into RNA sequencing analysis for less computer-savvy researchers, but can also help experienced bioinformaticians make their analyses more robust and efficient, as it offers diverse tools, scalability, automation, and standardization between analyses

Contribution of Risk and Resilience Factors to Suicidality among Mental Health-Help-Seeking Adolescent Outpatients: A Cross-Sectional Study.

BackgroundPeer victimization is an established risk factor for youth suicidal thoughts and behavior (suicidality), yet most peer-victimized youth are not suicidal. More data are needed pertaining to factors that confer resilience to youth suicidality.AimTo identify resilience factors for youth suicidality in a sample of N = 104 (Mean age 13.5 years, 56% female) outpatient mental health help-seeking adolescents.MethodsParticipants completed self-report questionnaires on their first outpatient visit, including the Ask Suicide-Screening Questions, a battery of risk (peer victimization and negative life events) and resilience (self-reliance, emotion regulation, close relationships and neighborhood) measures.Results36.5% of participants screened positive for suicidality. Peer victimization was positively associated with suicidality (odds ratio [OR] = 3.84, 95% confidence interval [95% CI] 1.95-8.62, p p = 0.002). Nevertheless, high peer victimization was found to be associated with a greater chance of suicidality across all levels of resilience (marked by non-significant peer victimization by resilience interaction, p = 0.112).ConclusionsThis study provides evidence for the protective association of resilience factors and suicidality in a psychiatric outpatient population. The findings may suggest that interventions that enhance resilience factors may mitigate suicidality risk

Contribution of Risk and Resilience Factors to Suicidality among Mental Health-Help-Seeking Adolescent Outpatients: A Cross-Sectional Study.

Peer reviewed: TrueFunder: the Gates Cambridge TrustBACKGROUND: Peer victimization is an established risk factor for youth suicidal thoughts and behavior (suicidality), yet most peer-victimized youth are not suicidal. More data are needed pertaining to factors that confer resilience to youth suicidality. AIM: To identify resilience factors for youth suicidality in a sample of N = 104 (Mean age 13.5 years, 56% female) outpatient mental health help-seeking adolescents. METHODS: Participants completed self-report questionnaires on their first outpatient visit, including the Ask Suicide-Screening Questions, a battery of risk (peer victimization and negative life events) and resilience (self-reliance, emotion regulation, close relationships and neighborhood) measures. RESULTS: 36.5% of participants screened positive for suicidality. Peer victimization was positively associated with suicidality (odds ratio [OR] = 3.84, 95% confidence interval [95% CI] 1.95-8.62, p < 0.001), while an overall multi-dimensional measure of resilience factors was inversely associated with suicidality (OR, 95% CI = 0.28, 0.11-0.59, p = 0.002). Nevertheless, high peer victimization was found to be associated with a greater chance of suicidality across all levels of resilience (marked by non-significant peer victimization by resilience interaction, p = 0.112). CONCLUSIONS: This study provides evidence for the protective association of resilience factors and suicidality in a psychiatric outpatient population. The findings may suggest that interventions that enhance resilience factors may mitigate suicidality risk

Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome

This study aimed to retrospectively evaluate an association between stimulant treatment for attention-deficit/hyperactivity disorder (ADHD) in individuals with 22q11.2DS and the development of psychotic disorders, to evaluate long-term effectiveness and safety of stimulant treatment in individuals with 22q11.2DS compared to individuals with idiopathic ADHD, and to explore effects of catechol-O-methyltransferase (COMT) genotype on 22q11.2DS response to stimulants and risk of side effects. Rates of stimulant use and methylphenidate equivalent exposure were compared among individuals with 22q11.2DS, between 51 with psychotic disorders and a control group of 57 22q11.2DS without psychotic disorders, from Tel Aviv and Geneva. In addition, 44 individuals with 22q11.2DS and ADHD from Tel Aviv who initiated stimulants before age 18 years were compared to a control group of 35 age- and sex-matched controls with idiopathic ADHD, for treatment effectiveness (Clinical Global Impression Scale-Improvement), and rates of side effects. Stimulant use history and methylphenidate equivalent exposure did not differ among individuals with 22q11.2DS, between those with and without psychotic disorders. The long-term retrospective follow-up (5.3 ± 4.1 years) of stimulant-treated individuals with 22q11.2DS showed a higher rate of significant clinical improvement of ADHD symptoms, compared to idiopathic ADHD individuals (p = 0.013), and similar side effect rates. There was no effect of the COMT genotype on response to stimulants or on any side effects. This preliminary long-term retrospective analysis suggests that stimulant treatment in 22q11.2DS is apparently safe in terms of psychosis conversion and rates of side effects, and that it is effective in alleviating ADHD symptoms

Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial

Abstract In our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47–0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session

Diagnostic Rechallenge with 18F-FCH PET/CT Often Allows Minimally Invasive Parathyroidectomy While Maintaining Exceptional Cure Rates

International audienc

Second breast cancer: recurrence score results, clinicopathologic characteristics, adjuvant treatments, and outcomes—exploratory analysis of the Clalit registry

Abstract Data on using the 21-gene Recurrence Score (RS) testing on second breast cancer (BC; second primary or local recurrence) are lacking. This cohort study examined patients with first and second BC, who underwent 21-gene testing both times. It included a ‘study-cohort’ (60 N0/N1mi/N1 ER + HER2‒ BC patients with ≥2 RS results >1 year apart) and a ‘general 21-gene-tested BC-cohort’ (2044 previously described N0/N1mi/N1 patients). The median time between the first and second BC was 5.2 (IQR, 3.1–7.1) years; the second BC was ipsilateral in 68%. Patient/tumor characteristics of the first- and second-BC in the ‘study-cohort’ were similar, except for the RS which was higher in the second BC (median [IQR]: 23 [17–30] vs 17 [14–22], p < 0.001). Overall, 56 patients had follow-up data, of whom 5 experienced distant recurrence (2 RS 11–25 patients and 3 RS 26–100 patients). Studies exploring the prognostic utility of the RS in this setting are warranted