Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

Eye movement as a simple, cost-effective tool for people who stutter: A case study.

Background:  Access to services remains the biggest barrier to helping the most vulnerable in the South African Stuttering Community. This novel stuttering therapy, harnessing an unconscious link between eye and tongue movement, may provide a new therapeutic approach, easily communicated and deliverable online.

Objectives:  This study provides both objective and subjective assessments of the feasibility of this intervention.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

Background: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.

Methods: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

Background: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

Study Design And Methods: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Background: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined.

Methods: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

To assess the effects of cross-education on strength and motor function in post stroke rehabilitation: a systematic literature review and meta-analysis.

Background: Cross-education refers to the increase in motor output of the untrained limb following unilateral training of the opposite limb. Cross education has been shown to be beneficial in clinical settings.

Objectives: This systematic literature and meta-analysis aims to assess the effects of cross-education on strength and motor function in post stroke rehabilitation.

What are the effects of pilates in the post stroke population? A systematic literature review & meta-analysis of randomised controlled trials.

Objective: Stroke is a leading cause of death and disability worldwide. Pilates, a programme of mind-body exercises is theorised to have beneficial effects on strength, postural control, balance, proprioception, coordination and gait in people with deficits due to a neurological condition. However, the evidence of pilates in stroke patients has never been systemised.

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues.

Sensory substitution for orthopaedic gait rehabilitation: A systematic review and meta-analysis for clinical practice guideline development.

Introduction: Sensory Substitution is a biofeedback intervention whereby at least sensory system is utilised to supplement environmental information which is traditionally gathered by another sense.

Objective: To present an evidence-based overview of the feasibility and effectiveness of wearable Sensory Substitution devices on gait outcomes in orthopaedic patient populations.

Methods: This Systematic Review and Meta-Analysis was reported according to the PRISMA 2020 statement.

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial.

Background: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma.

Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

Background: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.

Methods: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status.

How do I implement an outpatient program for the administration of convalescent plasma for COVID-19?

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect.

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant.

Exploring Fidelity in School-Based Mindfulness Programs.

A small but growing body of research on school-based mindfulness programs (SBMPs) has demonstrated benefits for students' cognitive and affective functioning and overall wellbeing. Yet, lack of fidelity in SBMP implementation may diminish these programs' purported benefits. This commentary presents 4 current challenges that need to be addressed so that questions of whether and how mindfulness improves student functioning can be clarified and implementation of programs can be strengthened and sustained.

Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma.

Background: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain.

Methods: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day.

Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection.

Background: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma.

A College First-Year Mindfulness Seminar to Enhance Psychological Well-Being and Cognitive Function.

Mindfulness training (MT) has shown promise in improving psychological health among college students, yet has rarely been evaluated as an addition to the college academic curriculum. Here, we demonstrate the feasibility and effectiveness of a first-year MT seminar offered to residential students at a selective private university, evaluating its impact on psychological and cognitive functioning, in relationship to a comparable positive psychology seminar. The results suggest the potential for first-year programs that promote student well-being.

Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study.

Background: We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat.

Methods: Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios.

Learning to BREATHE "Plus": A Multi-Modal Adaptive Supplement to an Evidence-Based Mindfulness Intervention for Adolescents.

Incorporating technological supplements into existing group mindfulness-based interventions (MBIs), particularly for use with adolescents, is an important next step in the implementation of MBIs. Yet there is little available content. Herein we present the development and content of a technological supplement for MBIs, which incorporates multiple technological elements to support (a) skill transfer from the group MBI to daily life, (b) the establishment of a formal mindfulness practice, and (c) the use of mindfulness during periods of high stress.

Genomic landscape of platinum resistant and sensitive testicular cancers.

While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures.

Mindfulness Interventions to Reduce Impact of Interparental Conflict on Adolescents.

Exposure to frequent, intense, and poorly resolved interparental conflict puts adolescents at risk for problems in many domains, including internalizing and externalizing problems, and stress physiological dysfunction. Existing intervention strategies to target these adolescents focus almost solely on improving marital dynamics, for example, through relationship education or couples therapy. However, interventions that aim to enhance marital communication require high levels of parental commitment and motivation for change, and may be expensive and time-consuming.

(M2M) study protocol: testing a mindfulness group plus ecological momentary intervention to decrease stress and anxiety in adolescents from high-conflict homes with a mixed-method longitudinal design.

Introduction: Interparental conflict exposure places adolescents at risk for problems with stress and anxiety; existing prevention/intervention strategies focus on reducing interparental conflict. Mindfulness-based programmes may be a promising treatment strategy for this population, but studies have not yet tested whether they are effective in this high-conflict context. In addition, evidence suggests that extensions to traditional treatments, such as delivering components in daily life that are tailored to moments of need, can increase treatment efficacy, particularly when combined with in-person treatments and particularly for adolescents.

Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk.

There is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.