Two Examples of Circular Motion for Introductory Courses in Relativity

The circular twin paradox and Thomas Precession are presented in a way that makes both accessible to students in introductory relativity courses. Both are discussed by examining what happens during travel around a polygon and then in the limit as the polygon tends to a circle. Since relativistic predictions based on these examples can be verified in experiments with macroscopic objects such as atomic clocks and the gyroscopes on Gravity Probe B, they are particularly convincing to introductory students.Comment: Accepted by the American Journal of Physics This version includes revision

GITR Activation Induces an Opposite Effect on Alloreactive CD4+ and CD8+ T Cells in Graft-Versus-Host Disease

Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4+ and CD8+ T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8+CD25− T cell proliferation, whereas it decreases alloreactive CD4+CD25− proliferation. Allo-stimulated CD4+CD25− cells show increased apoptosis upon GITR stimulation that is dependent on the Fas–FasL pathway. Recipients of an allograft containing CD8+CD25− donor T cells had increased GVHD morbidity and mortality in the presence of GITR-activating antibody (Ab). Conversely, recipients of an allograft with CD4+CD25− T cells showed a significant decrease in GVHD when treated with a GITR-activating Ab. Our findings indicate that GITR has opposite effects on the regulation of alloreactive CD4+ and CD8+ T cells

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤.05. Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p <.001), hormone receptor–positive (p <.001), and node-positive (p =.003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p <.001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2-low (p =.014) and TN and luminal A-like in HER2-0 (p =.019) showed the worst DFS. Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis

Assessment of Wound Care Products at Major Retailers in Accordance with the American Academy of Dermatology’s Recommendations

Background: Proper wound care is important for improving healing outcomes and minimizing long-term effects of scar formation. Selection of appropriate care may be challenging for individuals due to overabundance of product selection, and conflicting evidence on common wound care products, which may pose a risk for delayed wound healing.   Objective: We aimed to assess whether wound care products sold by major retailers, specifically Walmart, Walgreens, and Target, align with the recommendations on patient support information websites provided by the American Academy of Dermatology. Methods: A unique search inquiry was established for each major retailer, and analysis of their first aid wound care sections was performed. Results: 393 Walgreens, 334 Walmart, and 285 Target products were included. 0% of wound cleansing products available were recommended by the academy. Petroleum-based products were represented in 61% in Walgreens, 76.2% in Walmart, and 78.4% in Target products assessed. In total, 61.6% of products in Walgreens, 57% in Walmart, and 52.7% in Target were consistent with AAD recommendations for providing appropriate wound coverage. Conclusion: Many products sold in retailers are not recommended in managing acute minor wounds; appropriate counseling from the AAD may provide insight to optimizing wound care and scar minimization

High Expression of Interleukin-17A in Cutaneous Sarcoidosis

Increasing evidence of Th17 pathways are implicated in sarcoidosis granulomatous inflammation and maintenance. Our study evaluated the presence of IL-17A, a downstream proinflammatory cytokine, in cutaneous sarcoidosis biopsies. We found that all 26 biopsy samples had increased expression of IL-17A, predominately located in macrophages in granulomas, in cytoplasms of multinucleated histiocytes surrounding the granulomas, and within lymphocytic infiltrates surrounding the inflammation

Evaluating the Risk of Hydrochlorothiazide and ACE Inhibitor Exposure and Cutaneous Malignant Neoplasm

Objective. This study was conducted to assess the effects of using hydrochlorothiazide (HCTZ) and angiotensin-converting enzyme inhibitors (ACEIs) alone and in combination, and the risk of developing cutaneous malignant neoplasm (CMN). Background. HCTZ and ACEIs are known photosensitizers, which cause phototoxicity following exposure to the drug and either UV or visible radiation, posing a future risk for skin cancer. Previous studies have not examined combined ACEI and HCTZ use and increased risk of malignancy. Methods. The study was conducted through a HIPAA compliant national database in the United States between 2010 and 2018, retrospectively reviewed using diagnostic codes for CMN and generic drug codes for ACEIs and HCTZ. Access to the database was granted by Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Standard statistical tests were used. Results. The query yielded 1,375,562 patients, with 436,377 taking these antihypertensives and 939,185 that were not. CMN occurred in the antihypertensive-consuming population with an incidence of 4,327 (0.99%) and occurred in the control population with an incidence of 6,210 (0.66%). The difference was statistically significant with χ² p=2.2x10-16 and logistic regression odds ratio (OR) = 1.48 (95% CI, 1.42-1.55). Patients taking HCTZ and ACEIs together have an increased risk of developing CMN that is statically significant. Conclusion. The study shows a statistically significant correlation between both HCTZ and ACEI consumption and development of CMN. Further investigation is recommended regarding the potential synergistic adverse effects when HCTZ and ACEIs are used together and the development of CMN