Electronic Phenotyping of Urinary Tract Infections as a Silver Standard Label for Machine Learning.

This study explored the efficacy of electronic phenotyping in data labeling for machine learning with a focus on urinary tract infections (UTIs). We contrasted labels from electronic phenotyping against previously published labels such as urine culture positivity. In comparison, electronic phenotyping showed the potential to enhance specificity in UTI labeling while maintaining similar sensitivity and was easily scaled for application to a large dataset suitable for machine learning, which we used to train and validate a machine learning model. Electronic phenotyping offers a valuable method for machine learning label generation in healthcare, with potential benefits for patient care and antimicrobial stewardship. Further research will expand its application and optimize techniques for increased performance.

Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities.

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

No differences in outcomes with stopping or continuing antibiotic suppression in periprosthetic joint infections.

The data on long-term antibiotic use following debridement, antibiotics, and implant retention (DAIR) for treatment of periprosthetic joint infections are limited. In this single-center retrospective study, we show that patients with eventual cessation of antibiotic suppression after DAIR had similar outcomes to those who remained on chronic antibiotic suppression.

Cholinergic signaling via muscarinic M1 receptor confers resistance to docetaxel in prostate cancer.

Docetaxel is the most commonly used chemotherapy for advanced prostate cancer (PC), including castration-resistant disease (CRPC), but the eventual development of docetaxel resistance constitutes a major clinical challenge. Here, we demonstrate activation of the cholinergic muscarinic M1 receptor (CHRM1) in CRPC cells upon acquiring resistance to docetaxel, which is manifested in tumor tissues from PC patients post- vs. pre-docetaxel. Genetic and pharmacological inactivation of CHRM1 restores the efficacy of docetaxel in resistant cells. Mechanistically, CHRM1, via its first and third extracellular loops, interacts with the SEMA domain of cMET and forms a heteroreceptor complex with cMET, stimulating a downstream mitogen-activated protein polykinase program to confer docetaxel resistance. Dicyclomine, a clinically available CHRM1-selective antagonist, reverts resistance and restricts the growth of multiple docetaxel-resistant CRPC cell lines and patient-derived xenografts. Our study reveals a CHRM1-dictated mechanism for docetaxel resistance and identifies a CHRM1-targeted combinatorial strategy for overcoming docetaxel resistance in PC.

Compact CRISPR genetic screens enabled by improved guide RNA library cloning.

CRISPR genome editing approaches theoretically enable researchers to define the function of each human gene in specific cell types, but challenges remain to efficiently perform genetic perturbations in relevant models. In this work, we develop a library cloning protocol that increases sgRNA uniformity and greatly reduces bias in existing genome-wide libraries. We demonstrate that our libraries can achieve equivalent or better statistical power compared to previously reported screens using an order of magnitude fewer cells. This improved cloning protocol enables genome-scale CRISPR screens in technically challenging cell models and screen formats.

Fibrous Dysplasia With Atypical Bilateral Upper Extremity Pattern.

ABSTRACT: Fibrous dysplasia (FD) typically presents unilaterally in the lower limbs, or in the skull, mandible, or pelvis. Bilateral presentation is rarely reported. Most cases are diagnosed in the teens with 75% of patients diagnosed before the age of 30 years. In this case, a 63-year-old woman with suspected diagnosis of malignancy was referred to 99mTc-MDP scan and found to have polyostotic FD in bilateral upper extremities. Nuclear medicine can play an important role in diagnosing FD cases with atypical presentation and help risk stratification for more aggressive transformation.

An integrative review of assessments used in occupational therapy interventions for children with cerebral palsy / Revisão integrativa de avaliações utilizadas em intervenções de terapia ocupacional para crianças com paralisia cerebral

Abstract Introduction: Children with cerebral palsy (CP) experience a wide range of deficits and symptoms. When undergoing occupational therapy (OT) interventions, it is essential that the OT select assessments that can accurately reflect the outcome measures of the targeted domains. Objective: To identify the assessment tools most frequently reported in research studies as measures for OT interventions when treating children with CP. Method: Pubmed and Ovid databases were systematically searched by using key terms "cerebral palsy," "assessments," and "occupational therapy". Assessment tools were explored and extracted from articles contingent on the following inclusion criteria: (1) children birth to 18 years diagnosed with cerebral palsy; (2) use of assessment(s) as a measure of OT intervention; (3) published in English between 2007 and 2017. In the preliminary search, Pubmed yielded 151 records and Ovid yielded 571. Out of these, only 76 met the inclusion criteria. From the remaining 76 articles, a total of 88 assessment tools were retrieved and included in this literature review. Results: Ten assessments were found to be of importance based on frequency of use. The Assisting Hand Assessment (AHA) and Pediatric Evaluation of Disability Inventory (PEDI) were the most commonly used. Conclusion: This study helps to determine which assessments are frequently used in OT practice with children with CP. The findings of this study play an important role in addressing the challenge of assessment selection faced by occupational therapists and provide a basis for future research to expand on with regards to treating children with CP.

Resumo Introdução: Crianças com Paralisia Cerebral (PC) apresentam uma ampla gama de déficits e sintomas. Quando submetidos a intervenções de terapia ocupacional (OT), é essencial que as avaliações utilizadas reflitam com precisão as medidas de resultados dos domínios visados. Objetivo: Identificar os instrumentos de avaliação mais utilizados como medidas para intervenções no TO no tratamento de crianças com PC. Método: Bancos de dados Pubmed e Ovid foram sistematicamente pesquisados ​​usando os termos-chave "paralisia cerebral", "avaliações" e "terapia ocupacional". Avaliaçoes foram exploradas e extraídas de artigos contingentes aos seguintes critérios de inclusão: (1) crianças de até 18 anos com diagnóstico de paralisia cerebral; (2) uso da(s) avaliação (ões) como medida de intervenção do TO; (3) publicado em inglês entre 2007 e 2017. Na pesquisa preliminar, foram encontrados 151 artigos em Pubmed e 571 em Ovid. Destes, apenas 76 foram inlcuidos devido aos critérios de inclusão. Dos 76 artigos restantes, um total de 89 avaliaçoes foram encontradas e incluídas nesta revisão da literatura. Resultados: Dez avaliações foram consideradas importantes com base na frequência de uso. A "Assisting Hand Assessment" (AHA) e o Inventário de Avaliação Pediátrica de Incapacidade (PEDI) foram os mais utilizados. Conclusão: Os achados deste estudo desempenham um papel importante no e do desafio de seleção de avaliação enfrentado pelos terapeutas ocupacionais e fornecem uma base para futuras pesquisas para expandir no que diz respeito ao tratamento de crianças com PC.