Dietary Patterns Associated with Breast Cancer in the Middle East: A Scoping Review.

Breast cancer (BC) is the most predominant malignancy in Arab women in the Middle East, and yearly increases in occurrence by 37.5 and mortality rates by 15.2 for every 100,000 in 2019. This review explores the gap in research investigating the role of dietary patterns and BC in Middle Eastern countries. Furthermore, we analyze the evidence connecting these patterns to BC prevalence in the region, discussing implications for public health and preventive strategies. PubMed, ProQuest, and Cochrane databases were searched up to November 2023. Articles published in English from 2000 to 2023 were identified. Our search included dietary patterns (DP), their association with BC and specific to Middle Eastern Regions. The majority of existing research is concentrated in Iran, with limited illustration from Saudi Arabia, Turkey, and Jordan, and a notable absence of studies from other Middle Eastern countries. We found that dietary intervention is closely related to the occurrence, development, and prognosis of BC. Most DPs such as the Dietary Approaches to Stop Hypertension, Mediterranean, Plant-based and Paleolithic diets are identified to decrease the probability of BC by being rich sources of fiber, healthy fats, and vitamins and minerals. However, there are few DPs that increase the risk of BC, because of the existence of foods such as unhealthy fats, low fiber, sugars, and fried foods in those patterns which contribute to increasing the risk factors associated with BC. This review highlights the intricate connection between DPs and the risk of BC in the Middle East, revealing potential protective effects and heightened risks linked to specific dietary elements.

Heath policy guiding the identification, analysis and management of secondary findings for individuals undergoing genomic sequencing: a systematic review protocol.

INTRODUCTION: Genomic sequencing is increasingly enabling precision care across medical specialties; however, the discovery of genomic 'secondary findings' (SFs) unrelated to the patient's primary indication remains a profuse, unintended consequence. Existing practices within the continuum of SF identification, analysis and management are numerous, inconsistent and sometimes contradictory across health conditions and regions. Final decisions are often at the discretion of the genomic sequencing laboratory, bioinformatician or treating physician. This difference in healthcare delivery causes inconsistent information, disclosure and downstream impacts required to manage SFs and patient outcomes. Improving our understanding of the SF health policy landscape can determine components of the SF policy continuum spanning generation through to management that are in conflict, limitations of current guidance and existing needs across clinical settings. METHODS AND ANALYSIS: We will carry out a systematic review to catalogue and appraise current guidance directing the identification, analysis and management of SFs for participants receiving genomic sequencing globally. We will conduct a comprehensive search of Medline (Medline R, Medline Epub Ahead of Print and Medline-In-Process & In-Data-Review Citations), Embase and Cochrane databases (n=5, inception to Feb 2022) and a grey literature search of international genomics websites (n=64; inception to May 2022). Key inclusion criteria include: guidance produced by health organisations, bioethics committees and professional associations, outlining recommendations for: (1) SF identification, (2) SF analysis or (3) SF management. Non-English language articles and conference abstracts will be excluded. Guidance will be critically appraised with the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE) II tool. We will interpret our findings by process and across populations using a qualitative descriptive approach. ETHICS AND DISSEMINATION: Our systematic review evaluates published data and does not require ethics review. Our findings will be disseminated through peer-reviewed publications, conference presentations and workshops with precision medicine stakeholders. PROSPERO REGISTRATION NUMBER: CRD42022316079.

Virtual breakout rooms: an effective approach to offer guidance to medical students on residency applications.

Peer mentorship on residency applications has been difficult due to recent public health measures, prompting a shift from in-person events to virtual platforms. To address gaps in career exploration, we created a virtual, non-recorded space that allowed medical students and residents to discuss the Canadian Resident Matching Service (CaRMS) process meaningfully and transparently. Attendees reported a greater understanding of the match process and reduced anxiety after the event. This model provides a virtual framework that can be adapted for various mentorship opportunities.

Le mentorat par les pairs offert aux étudiants concernant les demandes de résidence a été difficile à mettre en œuvre en raison des récentes mesures de santé publique, entraînant le transfert des activités en personne vers les plateformes virtuelles. Pour combler les lacunes dans l'exploration des carrières, nous avons créé un espace virtuel, sans enregistrement, qui a permis aux étudiants et aux résidents de discuter du processus du Service canadien de jumelage des résidents (CaRMS) de manière approfondie et transparente. Les participants ont indiqué qu'à la suite de la rencontre, ils comprenaient mieux le processus de jumelage et qu'ils étaient moins anxieux. Ce modèle virtuel peut être adapté et utilisé pour diverses activités de mentorat.

Targeting the Ubiquitin-Proteasome System Using the UBA1 Inhibitor TAK-243 is a Potential Therapeutic Strategy for Small-Cell Lung Cancer.

PURPOSE: Small cell lung cancer (SCLC) is an aggressive disease with an overall 5-year survival rate of less than 10%. Treatment for SCLC with cisplatin/etoposide chemotherapy (C/E) ± radiotherapy has changed modestly over several decades. The ubiquitin-proteasome system is an underexplored therapeutic target for SCLC. We preclinically evaluated TAK-243, a first-in-class small molecule E1 inhibitor against UBA1. EXPERIMENTAL DESIGN: We assessed TAK-243 in 26 SCLC cell-lines as monotherapy and combined with C/E, the PARP-inhibitor, olaparib, and with radiation using cell viability assays. We interrogated TAK-243 response with gene expression to identify candidate biomarkers. We evaluated TAK-243 alone and in combination with olaparib or radiotherapy with SCLC patient-derived xenografts (PDX). RESULTS: Most SCLC cell lines were sensitive to TAK-243 monotherapy (EC50 median 15.8 nmol/L; range 10.2 nmol/L-367.3 nmol/L). TAK-243 sensitivity was associated with gene-sets involving the cell cycle, DNA and chromatin organization, and DNA damage repair, while resistance associated with cellular respiration, translation, and neurodevelopment. These associations were also observed in SCLC PDXs. TAK-243 synergized with C/E and olaparib in vitro across sensitive and resistant SCLC cell lines. Considerable TAK-243-olaparib synergy was observed in an SCLC PDX resistant to both drugs individually. TAK-243 radiosensitization was also observed in an SCLC PDX. CONCLUSIONS: TAK-243 displays efficacy in SCLC preclinical models. Enrichment of gene sets is associated with TAK-243 sensitivity and resistance. TAK-243 exhibits synergy when combined with genotoxic therapies in cell lines and PDXs. TAK-243 is a potential therapeutic strategy to improve SCLC patient outcomes, both as a single agent and in combination with existing therapies.

Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial.

BACKGROUND: Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. METHODS: Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. RESULTS: In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. CONCLUSIONS: This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013.

Intravital Imaging for Tracking of Angiogenesis and Cellular Events Around Surgical Bone Implants.

IMPACT STATEMENT: These new experimental methods allow us to image, and quantify, angiogenesis and perivascular cell dynamics in the endosseous healing compartment. As such, the method is capable of providing a new perspective on, and unique information regarding, healing that occurs around orthopedic and dental implants.

Optically-tracked handheld fluorescence imaging platform for monitoring skin response in the management of soft tissue sarcoma.

Standard clinical management of extremity soft tissue sarcomas includes surgery with radiation therapy. Wound complications (WCs) arising from treatment may occur due to bacterial infection and tissue breakdown. The ability to detect changes in these parameters during treatment may lead to earlier interventions that mitigate WCs. We describe the use of a new system composed of an autofluorescence imaging device and an optical three-dimensional tracking system to detect and coregister the presence of bacteria with radiation doses. The imaging device visualized erythema using white light and detected bacterial autofluorescence using 405-nm excitation light. Its position was tracked relative to the patient using IR reflective spheres and registration to the computed tomography coordinates. Image coregistration software was developed to spatially overlay radiation treatment plans and dose distributions on the white light and autofluorescence images of the surgical site. We describe the technology, its use in the operating room, and standard operating procedures, as well as demonstrate technical feasibility and safety intraoperatively. This new clinical tool may help identify patients at greater risk of developing WCs and investigate correlations between radiation dose, skin response, and changes in bacterial load as biomarkers associated with WCs.