Tetraspanins are an evolutionary conserved family of proteins involved in multiple aspects of cell physiology, including proliferation, migration and invasion, protein trafficking, and signal transduction; yet their detailed mechanism of action is unknown. Tetraspanins have no known natural ligands, but their engagement by antibodies has begun to reveal their role in cell biology. Studies of tetraspanin knockout mice and of germline mutations in humans have highlighted their role under normal and pathological conditions. Previously, we have shown that mice deficient in the tetraspanin CD81 developed fewer breast cancer metastases compared to their wild-type (WT) counterparts. Here, we show that a unique anti-human CD81 antibody (5A6) effectively halts invasion of triple-negative breast cancer (TNBC) cell lines. We demonstrate that 5A6 induces CD81 clustering at the cell membrane and we implicate JAM-A protein in the ability of this antibody to inhibit tumor cell invasion and migration. Furthermore, in a series of in vivo studies we demonstrate that this antibody inhibits metastases in xenograft models, as well as in syngeneic mice bearing a mouse tumor into which we knocked in the human CD81 epitope recognized by the 5A6 antibody.

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The State of Climate Action 2022 provides a comprehensive assessment of the global gap in climate action across the world’s highest-emitting systems, highlighting where recent progress made in reducing GHG emissions, scaling up carbon removal, and increasing climate finance must accelerate over the next decade to keep the Paris Agreement’s goal to limit warming to 1.5°C within reach.

Introduction Stereotactic radiation therapy is a highly specialised technique which requires careful and structured implementation. As part of a national stereotactic programme implementation, protocols were developed and a national stereotactic chart round was formed, which strongly recommended attendance and presentation of all cases before treatment. Herein, we describe our experiences launching a national chart round and its importance in a stereotactic programme. Method Stereotactic chart rounds were held via videoconference between July 2018 and July 2019. Data collected included attendances, patient‐related information including, diagnosis, clinical background, treatment intent, prescribed dose and fractionation and technical approach. Consensus recommendations regarding changes to treatment approaches were also recorded. Results For the 12 months recorded, there were 1126 attendances, from 144 individual attendees, across 21 locations. In total, 285 cases (237 new cases, and 48 re‐presentations) were presented by 27 radiation oncologists (ROs) from 13 different locations. From the cases presented, 65 changes were recommended from 53 patients (22.3%), including 27 (11.4%) changes to contours, 18 (7.6%) changes to dose prescription/fractionation, 9 (3.8%) changes to plan dosimetry, 1 (0.4%) changes to treatment technique and 10 (4.2%) recommendations for which stereotactic radiation therapy was not advised. A significant inverse relationship was found between frequency of recommended changes and the individual RO’s stereotactic case load (P < 0.002). Conclusion The implementation of a national stereotactic chart held via videoconference has ensured national protocol compliance across the network of locations. Furthermore, the chart rounds have allowed the entire multidisciplinary team to be provided with mentorship and guidance. Increasing number of cases presented was associated with lower rates of recommended changes highlighting the impact of experience and the need for continued mentorship.

Background: The authors analyzed the distribution of medical student debt and identified demographic features that placed students at high risk for increased debt and financial stress. Methods: From April to May 2019, a cross-sectional, anonymous, web-based survey was administered to first-year (M1) to fourth-year (M4) medical students at the University of Michigan to assess financial literacy, debt burden, financial stress, and demographic factors. A total of 216 of 680 (32%) students completed the survey. Respondents voluntarily answered 15 multiple-choice questions on personal finance and 30 questions on their demographics, current financial situation, and debt burden. To quantify debt burden, students estimated anticipated education-related debt in one of four categories: no debt, $1–99,999; $100,000–$199,999; and $200,000 or more. A chi-square test was used to identify associations between categorical variables and logistic regression was used to identify risk factors for debt and worry. Results: Fifty-four respondents (25%) reported $0 in education related debt, while 44 (16%) had $200,000 or more. Race (p=0.006), first-generation college student status (p=0.004), first-generation medical student status (p<0.001), household income (p<0.001), and parental education (p=0.008) were associated with higher levels of debt. Students who were underrepresented in medicine (URiM) had higher odds of higher debt compared to Arab and Asian students (p=0.02). URiM students (p=0.02), first-generation college students (p=0.009), and parental education (p=0.01) were associated with increased financial stress. Additionally, female students had higher odds of increased financial stress (OR=1.85, p=0.045) on logistic regression. Conclusions: URiM and socioeconomically disadvantaged students feel the burden of the high cost of medical school disproportionately more, suggesting that our current systems are not adequately supporting these students. Reducing this burden may serve to further promote diversity in medicine.