Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2.

Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.

Methods: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies.

Specific human leucocyte antigen-DQ risk epitope mismatches are associated with chronic lung allograft dysfunction after lung transplantation.

A high-risk epitope mismatch (REM) (found in DQA1∗05 + DQB1∗02/DQB1∗03:01) is associated with de novo donor specific antibodies after lung transplantation (LTx). Chronic lung allograft dysfunction (CLAD) remains a barrier to LTx survival. This study aimed to measure the association between DQ REM and the risk of CLAD and death after LTx.

Structural and functional characterization of capsid binding by anti-AAV9 monoclonal antibodies from infants after SMA gene therapy.

Success in the treatment of infants with spinal muscular atrophy (SMA) underscores the potential of vectors based on adeno-associated virus (AAV). However, a major obstacle to the full realization of this potential is pre-existing natural and therapy-induced anti-capsid humoral immunity. Structure-guided capsid engineering is one possible approach to surmounting this challenge but necessitates an understanding of capsid-antibody interactions at high molecular resolution.

International Survey of Pediatric Oncologists' Beliefs and Communication Practices Regarding Symptom Self-Monitoring by Childhood Cancer Survivors.

Purpose: Childhood cancer survivors report self-monitoring for and worrying about symptoms of disease recurrence and secondary cancers, although symptom-related worry is associated with poorer health-related quality of life. This survey captured pediatric oncologists' beliefs and communication practices regarding symptom self-monitoring for childhood cancer survivors.

Methods: Using a closed-loop snowball sampling technique, pediatric oncologists completed an online survey regarding the importance of symptom self-monitoring for off-therapy patients, the degree to which symptom self-monitoring was perceived to cause stress and worry, and communication practices.

Complete Horizontal Gaze Paresis Due to Medial Pontine Haemorrhage.

We report a case of bilateral horizontal conjugate gaze palsy due to a dorsal median pontine haemorrhage. The development of horizontal gaze palsy has been attributed to lesions in the pontine tegmentum, and in this case, has occurred in conjunction with other features as part of Foville's syndrome. Complete horizontal gaze palsy is a rare clinical manifestation as bilateral involvement is unusual.

Surgical management of clavicle fractures in Australia: an analysis of Australian Medicare Benefits Schedule database from 2001 to 2020.

Background: There is no consensus on the optimal management of clavicle fractures, with advocates of both operative and non-operative management. The objective of this study is to assess the trends in the management of clavicle fractures in Australia over the past two decades.

Methods: The incidence of surgical fixation of clavicle fractures from 2001 to 2020 was analysed using the Australian Medicare Benefits Schedule database, reflective of operations performed on privately insured patients, thus excluding public patients and compensable cases.

Increased Resting-State Functional Connectivity as a Compensatory Mechanism for Reduced Brain Volume in Prediabetes and Type 2 Diabetes.

Objective: To investigate the contribution of alterations in brain structure and function to cognitive function and their interactions in individuals with diabetes and patients with type 2 diabetes mellitus (T2DM).

Research Design And Methods: This population-based study included 2,483 participants who underwent structural MRI (n = 569 with normal glucose metabolism [NGM], n = 1,353 with prediabetes, and n = 561 with T2DM) and cognitive testing. Of these, 2145 participants also underwent functional MRI (n = 496 NGM, n = 1,170 prediabetes, and n = 479 T2DM).

Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.

Background: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.

Goal-Directed Action Is Initially Impaired in a hAPP-J20 Mouse Model of Alzheimer's Disease.

Cognitive-behavioral testing in preclinical models of Alzheimer's disease has failed to capture deficits in goal-directed action control. Here, we provide the first comprehensive investigation of goal-directed action in a transgenic mouse model of Alzheimer's disease. Specifically, we tested outcome devaluation performance in male and female human amyloid precursor protein (hAPP)-J20 mice.

Clinically significant anxiety as a risk factor for Alzheimer's disease: Results from a 10-year follow-up community study.

Objective: There is growing evidence for an association between anxiety and an increased risk of dementia, but it is not clear whether anxiety is a risk factor or a prodromic symptom. In this study, we investigated if clinically significant anxiety increases the risk of developing Alzheimer's disease (AD) up to 10 years later.

Methods: We used data from the longitudinal Zaragoza Dementia and Depression (ZARADEMP) Project.

Minimum 5-Year Follow-up Results: CROSSBAT (Combined Randomised and Observational Study of Surgery vs No Surgery for Type B Ankle Fracture Treatment).

Background: Isolated Weber B, AO (Association for the Study of Internal Fixation) type 44B ankle fractures with no fracture to the medial side are the most common type of ankle fracture and may be treated with internal fixation or without surgery.This study aimed to determine if surgery is superior to nonsurgical management for the treatment of these fractures after a minimum 5-year follow-up.

Methods: A pragmatic, multicenter, single-masked, randomized controlled trial with minimum 5-year follow-up.

Screening for unmet social needs in paediatric speech-language pathology to achieve the Sustainable Development Goals.

Purpose: To examine the need, feasibility and acceptability of speech-language pathologists (SLPs) implementing a systematic, routine, unmet social needs identification and referral pathway, as a means of promoting health equity and addressing Sustainable Development Goals (SDGs).

Method: Quality Improvement methodologies were used to adapt and pilot an unmet social needs identification and referral pathway for use with parents/carers of children with communication disabilities referred to an urban Australian speech-language pathology service. SLPs were surveyed about the acceptability and feasibility of this practice.

Australasian paediatric gastroenterologist practices of coeliac disease diagnosis before and during the COVID-19 pandemic.

Aim: To explore the perceptions and practices of Australasian paediatric gastroenterologists in diagnosing coeliac disease (CD) before and during the COVID-19 pandemic.

Methods: Paediatric gastroenterologists in Australasia were invited via email to complete an anonymous online questionnaire over a 2-week period in 2021.

Results: The questionnaire was completed by 39 respondents: 33 from Australia and six from New Zealand (NZ) equating to a 66% response rate.

Proxy-reported sensory measures for children and adolescents with neurodevelopmental disorders: A systematic review.

Aim: To determine the quality and utility of proxy-reported sensory measures for children and adolescents with neurodevelopmental disorders (such as autism spectrum disorder, attention-deficit/hyperactivity disorder, movement disorders, and intellectual disability).

Method: We systematically searched 11 databases. We applied the updated Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist and criteria for good measurement properties to evaluate instrument development and psychometric properties.

Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial.

Background: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy).

Methods: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial.

Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials.

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer's disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed "practice effects").

Adverse roles of mast cell chymase-1 in COPD.

Background: COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed.

High temporal resolution RNA-seq time course data reveals widespread synchronous activation between mammalian lncRNAs and neighboring protein-coding genes.

The advent of massively parallel sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long noncoding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Expression of lncRNAs is strongly linked with adjacent protein-coding gene expression, suggesting potential -regulatory functions.

Circulation of enterovirus D68 (EV-D68) causing respiratory illness in New South Wales, Australia, between August 2018 and November 2019.

The incidence of enterovirus D68 (EV-D68) in New South Wales, Australia, is unknown. As part of a state-wide surveillance program, enterovirus positive diagnostic specimens were assessed from patients presenting to hospitals with respiratory and meningitis syndromes from August 2018 to November 2019. Diagnostic enterovirus positive samples were collected from 339 patients and re-extracted followed by targeted PCR across the whole EV-D68 genome (7.

Impact of Obesity Phenotype on Central Aortic Hemodynamics and Arterial Stiffness in a Chinese Health Assessment Population.

Background: This study aimed to explore the association between BMI and/or central obesity parameters and measures of arterial hemodynamics to assess the effect of obesity on function of large arteries.

Methods: Data was obtained from 634 subjects undergoing health assessment at Ruijin Hospital, Shanghai. Subjects were divided into 3 groups according to their Body Mass Index (BMI (kg/ ) 24 normal, 24-28 overweight, 28 obese).

Early Reduction of MRI Activity During 6 Months of Treatment With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS.

Background And Objectives: The onset of action for high-efficacy immunotherapies in multiple sclerosis (MS) is an important parameter. This study (MAGNIFY-MS) evaluates the onset of action of cladribine tablets by observing changes in combined unique active (CUA) MRI lesion counts during the first 6 months of treatment in patients with highly active relapsing MS.

Methods: MRI was performed at screening, baseline, and at months 1, 2, 3, and 6 after initiating treatment with cladribine tablets 3.