The tale of TILs in breast cancer : a report from the International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed deathligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.The National Health and Medical Research Council of Australia; the Cure; the Royal Australasian College of Physicians; the NIH/NCI ; the National Breast Cancer Foundation of Australia Endowed Chair; the Breast Cancer Research Foundation, New York and the Breast Cancer Research Foundation (BCRF).www.nature.com/npjbcanceram2022Immunolog

Effect of holding time, thickness and heat treatment on microstructure and mechanical properties of compacted graphite cast iron

The effect of holding time, thickness and annealing heat treatment on the microstructure and some mechanical properties of compacted graphite iron (CGI) are studied. Samples of CGI are produced in Helwan factory for casting by using GGG 70 as base metal in a medium frequency induction furnace. The mechanical properties (tensile strength, and hardness) of the as-cast and after heat treatment samples are determined and the microstructure of the samples is examined using optical microscope. The results show that the mechanical properties and microstructure of CGI depend on holding time, thickness and annealing heat treatment; it is found that increasing the holding time from 10 min to 17 min results in lowering the Mg content from 0.031% to 0.021% and as a result lower nodularity was obtained. Lowering the thickness from 20 mm to 5 mm increases the tendency of dendritic structure as a result of increasing the cooling rate. The annealed samples with mainly ferritic matrix gave the lowest tensile strength and hardness value compared with the as-cast conditions. Keywords: Compacted graphite iron (CGI), Heat treatment, Microstructures, Mechanical propertie

Medical Student Research: An Integrated Mixed-Methods Systematic Review and Meta-Analysis

<div><p>Importance</p><p>Despite the rapidly declining number of physician-investigators, there is no consistent structure within medical education so far for involving medical students in research.</p><p>Objective</p><p>To conduct an integrated mixed-methods systematic review and meta-analysis of published studies about medical students' participation in research, and to evaluate the evidence in order to guide policy decision-making regarding this issue.</p><p>Evidence Review</p><p>We followed the PRISMA statement guidelines during the preparation of this review and meta-analysis. We searched various databases as well as the bibliographies of the included studies between March 2012 and September 2013. We identified all relevant quantitative and qualitative studies assessing the effect of medical student participation in research, without restrictions regarding study design or publication date. Prespecified outcome-specific quality criteria were used to judge the admission of each quantitative outcome into the meta-analysis. Initial screening of titles and abstracts resulted in the retrieval of 256 articles for full-text assessment. Eventually, 79 articles were included in our study, including eight qualitative studies. An integrated approach was used to combine quantitative and qualitative studies into a single synthesis. Once all included studies were identified, a data-driven thematic analysis was performed.</p><p>Findings and Conclusions</p><p>Medical student participation in research is associated with improved short- and long- term scientific productivity, more informed career choices and improved knowledge about-, interest in- and attitudes towards research. Financial worries, gender, having a higher degree (MSc or PhD) before matriculation and perceived competitiveness of the residency of choice are among the factors that affect the engagement of medical students in research and/or their scientific productivity. Intercalated BSc degrees, mandatory graduation theses and curricular research components may help in standardizing research education during medical school.</p></div

Factors related to- or affecting medical student research (ii)–The effect of financial factors on appeal of research to medical students.

<p>Factors related to- or affecting medical student research (ii)–The effect of financial factors on appeal of research to medical students.</p

Assessing the current situation: Interest in- and exposure- to research among medical students.

<p><b>Forest Plot symbols: *</b> The axis, not the data, is shown in logit scale for aesthetic purposes. <b>Table symbols: *</b> Mandatory exposure (in the form of curricular components or graduation theses) was excluded from this analysis. <b>Abbreviations used: D,</b> developing countries; <b>H,</b> higher commitment to a research career; <b>I,</b> intercalated Bachelor of Science degree (iBSc). Dates are shown beside studies that may be confused with others referenced in this review having the same similar first-author names.</p

The proportion of medical student research resulting in a peer-reviewed journal publication.

<p>Since the duration of research exposure will almost always affect the publication outcome, it has been shown too. <b>Forest Plot symbols: *</b> The axis, not the data, is shown in logit scale for aesthetic purposes. <b>Table symbols: *</b> The duration is probably prolonged (possibly months long); <b>**</b> 20–40 European medical school credits; <b>||</b> For published projects, the average duration was 18 months. <b>D</b>, developing countries; <b>I</b>, intercalated Bachelor of Science degree (iBSc); <b>HQ</b>, relatively high quality publication (indexed in Medline, Scopus or Medic), <b>HF</b>, first-author publication in a relatively high quality journal. Dates are shown beside studies that may be confused with others referenced in this review having the same similar first-author names.</p

Flow diagram of the citation screening and article selection process followed in this systematic review.

<p>Flow diagram of the citation screening and article selection process followed in this systematic review.</p

Factors related to- or affecting medical student research (i)–Effects of previous research experience, academic success and higher degree graduate-entry into medical school.

<p><b>Forest Plot symbols: *</b> The axis, not the data, is shown in log scale for aesthetic purposes. <b>Abbreviations used: D</b>, developing countries; <b>I</b>, intercalated Bachelor of Science degree (iBSc); <b>M</b>, motivation to perform research; <b>K</b>, research knowledge or skills; <b>C</b>, confidence in research competencies; <b>In</b>, interest in research. For some studies, odds ratios and 95% confidence interval values were reported, but not the raw numbers.</p