tbuckley/cabot-search huggingface dataset:
Abstract P3-03-27: Can we select patients suitable for targeted axillary dissection after neoadjuvant chemotherapy who originally presented with involved axillary nodes?
Authors: ES Nagy, L Whisker, K Asgeirsson
Journal: Cancer Research (2019)

Abstract Introduction: The current recommended management for patients with involved lymph nodes at diagnosis of breast cancer is to perform an axillary node dissection after receiving neoadjuvant chemotherapy (NAC), regardless of response. A number of studies have proposed de-escalation of this practice by performing sentinel node biopsies and targeted axillary dissections in those with response to chemotherapy. We have audited our practice to assess the safety of introducing management change. Methods: Cancer data was collected between 2014 and 2018 for patients who had NAC and further selection criteria for those with lymph node involvement at diagnosis and subsequently underwent NAC. Assessment of radiological response at NAC completion, tumour hormone receptors and HER2 status along with axillary nodal response on final histopathology were reviewed to assess whether patients can be stratified to less extensive axillary management. Results: 290 patients underwent NAC, 60 of whom had nodal involvement at diagnosis: - All had USS axilla, MRI at baseline and completion of NAC - All 60 node positive patients underwent axillary clearance, as per current local protocol - Out of those 60 node positive patients, 39 had breast conserving surgery, whilst 21 patients had mastectomy - 20 (33%) patients showed complete radiological response (CRR) on MRI in both breast and nodes - 23 (38%) patients achieved pathological complete response (PCR) in their nodes - 17 patients showed both CRR and PCR - 4 patients showed CRR but did not achieve PCR: o patient 1: 1 macromet / 7 nodes - NEG/NEG/NEG o patient 2: 1 micromet / 14 nodes - POS/POS/POS o patient 3: 7 macromet / 10 nodes - POS/POS/NEG o patient 4: 5 macromet / 19 nodes - POS/POS/NEG - Large volume of nodal disease remained in 2 patients with POS/POS/NEG despite CRR Conclusion: MRI can be safely and reliably used in patients who show CRR with TNBC and HER2+ cancers to select patients for de-escalating axillary surgery. Caution in those patients with POS/POS/NEG cancers as MRI may show CRR but large volume disease in nodes may still persist. Further prospective audit of de-escalating treatment will be essential to ensure locoregional control and long-term disease-free survival outcomes. Citation Format: Nagy ES, Whisker L, Asgeirsson K. Can we select patients suitable for targeted axillary dissection after neoadjuvant chemotherapy who originally presented with involved axillary nodes? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-27.
Effect of a Single Aspirin Dose Prior to Fecal Immunochemical Testing on Test Sensitivity for Detecting Advanced Colorectal Neoplasms
Authors: Hermann Brenner, Silvia Calderazzo, Thomas Seufferlein, Leopold Ludwig, Nektarios Dikopoulos, Jörg Mangold, Wolfgang Böck, Thomas Stolz, Thomas Eisenbach, Thomas Block, Annette Kopp-Schneider, David Czock, Kaja Tikk
Journal: JAMA (2019)

Fecal immunochemical tests for hemoglobin are widely used for colorectal cancer (CRC) screening. Observational studies suggested that sensitivity of fecal immunochemical tests for detecting advanced neoplasms could be increased by acetylsalicylic acid (aspirin), especially among men.To evaluate the potential to increase sensitivity of fecal immunochemical tests by administering a single 300-mg oral aspirin dose 2 days before stool sampling.A randomized, placebo-controlled, double-blind trial was conducted in 14 gastroenterology practices and 4 hospitals in Germany, and included 2422 men and women aged 40 to 80 years scheduled for colonoscopy, with no recent use of aspirin or other drugs with antithrombotic effects (enrollment from June 2013 to November 2016, and final follow-up January 27, 2017).Administration of a single tablet containing 300 mg of aspirin (n = 1208) or placebo (n = 1214) 2 days before fecal sampling for fecal immunochemical test.The primary outcome was sensitivity of a quantitative fecal immunochemical test at 2 predefined cutoffs (10.2 and 17-μg Hb/g stool) for detecting advanced neoplasms (colorectal cancer or advanced adenoma).Among 2422 randomized patients (mean [SD] age, 59.6 [7.9] years; 1219, 50%, men), 2134 were included in the analysis (78% for primary screening colonoscopy, 22% for diagnostic colonoscopy). Advanced neoplasms were identified in 224 participants (10.5%), including 8 participants (0.4%) with CRC and 216 participants (10.1%) with advanced adenoma. Sensitivity was 40.2% in the aspirin group and 30.4% in the placebo group (difference 9.8%, 95% CI, -3.1% to 22.2%, P = .14) at cutoff 10.2-μg Hb/g stool and 28.6% in the aspirin and 22.5% in the placebo group (difference 6.0%, 95% CI, -5.7% to 17.5%, P = .32) at cutoff 17-μg Hb/g stool.Among adults aged 40 to 80 years not using aspirin or other antithrombotic medications, administration of a single dose of oral aspirin prior to fecal immunochemical testing, compared with placebo, did not significantly increase test sensitivity for detecting advanced colorectal neoplasms at 2 predefined cutoffs of a quantitative fecal immunochemical test.Deutsches Register Klinischer Studien Identifier: DRKS00003252; EudraCT Identifier: 2011-005603-32/DE.
New Year’s resolutions for clinical students
Authors: Peregrine Green, Giles Coverdale
Journal: BMJ (2013)

As every doctor knows, as much as being a medical student is a great time in life, we’ve all had moments that were uncomfortable or downright embarrassing. First experiences on the wards can be intimidating, particularly when you don’t know the etiquette or what to expect. In addition, when you’re old and cynical—about six months into foundation training—then you’ll look back on student days as a golden age that you didn’t properly appreciate or make the most of, and you’ll wish you had known certain things at the time. We present here, in no particular order, a list of New Year’s resolutions for medical students that we hope will help.

1. Develop a swift flicking motion with the wrist to aid the “quick curtain draw.” Practise on the curtains at home so that you can do it with ease and impress everybody. (Take care. Over-enthusiasm can lead to you catching a consultant on the side of the head. This rarely goes down well.)

2. Don’t try and carry all your new equipment (tendon hammer, tourniquet, pen torch, Snellen chart) on your belt. This is a common mistake made by all clinical students. You don’t look like Batman.

3. Never interrupt a nurse during his or her break. You will only make this mistake once. On …
Religion and hypocrisy
Authors: Thomas Riddington
Journal: BMJ (2011)

In my early years of medical school, I was one of the students wide awake in ethics tutorials. I loved the debate—having to think critically and form a coherent argument. But I was amazed by the sometimes shocking, extreme, and rigid views I heard from the mouths of future doctors. People who’ll have the power to cure or kill had opinions in line with the most scaremongering, bigoted tabloid press, or held beliefs they couldn’t detach from their professional judgment. I assumed that every student was inherently liberal, universally tolerant to every kind of lifestyle choice and sexual preference. But I suddenly felt in the minority, …
The “online brain”: how the Internet may be changing our cognition
Authors: Joseph Firth, John Torous, Brendon Stubbs, Josh A. Firth, Genevieve Z. Steiner, Lee Smith, Mario Alvarez‐Jimenez, John Gleeson, Davy Vancampfort, Christopher J. Armitage, Jerome Sarris
Journal: World Psychiatry (2019)

The impact of the Internet across multiple aspects of modern society is clear. However, the influence that it may have on our brain structure and functioning remains a central topic of investigation. Here we draw on recent psychological, psychiatric and neuroimaging findings to examine several key hypotheses on how the Internet may be changing our cognition. Specifically, we explore how unique features of the online world may be influencing: a) attentional capacities, as the constantly evolving stream of online information encourages our divided attention across multiple media sources, at the expense of sustained concentration; b) memory processes, as this vast and ubiquitous source of online information begins to shift the way we retrieve, store, and even value knowledge; and c) social cognition, as the ability for online social settings to resemble and evoke real‐world social processes creates a new interplay between the Internet and our social lives, including our self‐concepts and self‐esteem. Overall, the available evidence indicates that the Internet can produce both acute and sustained alterations in each of these areas of cognition, which may be reflected in changes in the brain. However, an emerging priority for future research is to determine the effects of extensive online media usage on cognitive development in youth, and examine how this may differ from cognitive outcomes and brain impact of uses of Internet in the elderly. We conclude by proposing how Internet research could be integrated into broader research settings to study how this unprecedented new facet of society can affect our cognition and the brain across the life course.
Abstract 2099: Induction of tumor suppressor genes <i>IL24</i> and <i>IL32</i> by microRNA-205 in prostate cancer
Authors: Shahana Majid, Altaf A. Dar, Sharanjot Saini, Yi Chen, Varahram Shahryari, Jan Liu, Saif Zaman, Hiroshi Hirata, Soichiro Yamamura, Koji Ueno, Yuichiro Tanaka, Gaurav Khatri, Peter R. Carroll, Rajvir Dahiya
Journal: Cancer Research (2010)

Abstract Introduction and Objective: MicroRNAs are small noncoding RNAs that regulate the expression of approximately 30% of all human genes, either inhibiting target mRNA translation or inducing its degradation. These genes are abnormally expressed in human malignancies, making their biological importance increasingly apparent. Given the functional complexity of miRNA mediated gene regulation, it is unlikely that miRNAs are limited to gene silencing. The main objective of this study was to investigate the involvement of miRNA-205 in prostate carcinogenesis and whether miR-205 functions as a tumor suppressor by transcriptionally up-regulating tumor suppressor genes IL24 and IL32. Methods: The methods employed in this study include quantitative-real time PCR; western blot; in-situ hybridization; fluorescence-activated cell sorting assays for cell cycle distribution and apoptosis; assays for cell viabiltity, clonability, migration and invasiveness of prostate cancer cells. Luciferase reporter and mutational assays; nuclear run-on, in-vitro transcription and chromatin immunoprecipitation assays were also performed. Results: Our results indicated that miR-205 expression levels are either silenced or significantly lower in prostate cancer cell lines and prostate tumors when compared to non-malignant prostate cell lines or benign prostate hyperplasia tissues respectively. By scanning gene promoters for sequences complementary to miR-205, we identified putative miR-205 target sites in the promoters of IL24 and IL32 tumor suppressor genes. Over-expression of miR-205 in prostate cancer cells (PC-3) induced the expression of both genes by targeting specific sites in their promoters. Transfection of miR-205 impaired cancer cell growth, clonability, migration, invasiveness and induced apoptosis and cell cycle arrest by interfering with the expression of genes involved in these pathways. MicroRNA-205 induced in-vitro transcription and caused enrichment of histone markers indicative of transcriptionally active promoters in IL24 and IL32 genes. Luciferase reporter and mutational assays indicated that IL24 and IL32 are the direct targets of miR-205. Conclusion: For the first time we have shown that microRNA-205 specifically activates tumor suppressor genes IL24 and IL32 by targeting complimentary binding sites in their promoters, corroborating a new function for miRNAs in regulating gene transcription. Such a function of microRNAs may contribute to the novel therapeutic approach in the treatment of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2099.
Abstract 16563: Fibrosis and Hypertrophy Assessed by Magnetic Resonance Imaging (MRI) and Serum Biomarkers in Pediatric Hypertrophic Cardiomyopathy (HCM). A Report From the Pediatric Cardiomyopathy Registry Group
Authors: Sonya Kirmani, Pamela K Woodard, Ling Shi, Charles E Canter, Elfriede Pahl, Steven D Colan, Jeffrey A Towbin, Steven A Webber, Joseph W Rossano, Melanie D Everitt, Kimberly M Molina, Paul F Kantor, John L Jefferies, Brian Feingold, Linda J Addonizio, Stephanie M Ware, Wendy K Chung, Jean Ballweg, Teresa M Lee, Jason D Czachor, Hiedy Razoky, James D Wilkinson, Steven E Lipshultz
Journal: Circulation (2017)

Background: MRI can assess left ventricular (LV) hypertrophy and LV fibrosis as indicated by late gadolinium enhancement (LGE). LGE ≥15% of LV mass has been proposed as a threshold for prophylactic...
Abstract LB-244: A phase 0 trial of riluzole in patients with resectable stage III or IV melanoma.
Authors: Dana Yip, Maithao Le, Jonathan H Lee, Suzie Chen, James S Goydos
Journal: Cancer Research (2008)

Abstract Recently, our group described a murine model of melanoma that is based on ectopic expression of metabotropic glutamate receptor 1 (Grm1). Grm1 is a normally occurring receptor in the central nervous system of mammals that controls excitatory neural impulses. Ectopic expression of this receptor in melanocytes results in transformation of these cells into a murine form of melanoma indistinguishable from human melanoma. We also found that &amp;gt;60% of human melanoma samples tested ectopically to date express Grm1 while normal skin and melanocytes from the same patients fail to express this protein. Furthermore, stimulation of this receptor in vitro results in downstream upregulation of phosphorylated (activated) ERK, demonstrating that this receptor is involved in the regulation of the MAPK pathway, a pathway in the cell important in melanoma formation and growth. Finally, a murine xenograft model of melanoma treated with riluzole, an oral Grm1 blocking agent, showed decreased tumor growth in the treated mice compared to the untreated controls. The goal of this study was to validate Grm1 as a therapeutic target in humans with melanoma. To accomplish this we enrolled patients with resectable stage III and stage IV melanoma on a Phase 0 NCI Quick Trial of oral riluzole. We performed a pre-treatment biopsy, treated the patients with 200 mg of oral riluzole per day for 14 days, and then resected the patients’ remaining tumors. We compared the level of pERK in the pre- and post-treatment tumor samples to determine if treatment with an oral Grm1 blocking agent results in modulation of the Grm1 signaling pathway in human melanoma. We also assessed overall metabolic activity and proliferation of the tumors pre- and post-treatment, using PET scanning, assessement of pre- and post-treatment mitotic rate of the tumors, and pre- and post-treatment Ki-67 staining intensity. We have accrued 10 of the 15 patients we need for this trial and all 10 appear to express Grm1. Preliminary results demonstrate a significant decrease in pERK in post-treatment tumor samples as compared to pre-treatment samples in 50% of the cases so far (P&amp;lt;0.01). We also found a significant decrease in post-treatment Ki-67 staining in one patient. Three patients had a significant decrease in PET intensity post-treatment while all other patients had similar pre- and post-treatment PET scan findings except for one patient whose post-treatment PET scan revealed progressive disease. Our preliminary data demonstrates that glutamate-blockade with riluzole can inhibit signaling through the MAPK pathway and suppress metabolic activity of melanoma in a significant number of patients. The ectopic expression of metabotropic glutamate receptors may be important in the pathogenesis of human melanoma and targeting this pathway may be an effective therapy for patients with melanoma.
Abstract 13820: Upregulation of Cardiac Beta3-Adrenergic Receptor-Activated Inducible Nitric Oxide Synthase Promotes Cardiac Aging
Authors: Heng-Jie Cheng, Peng Zhou, Zhi Zhang, Tiankai Li, Xiaowei Zhang, Qun Shao, Zhe Chen, Dalane Kitzman, Che Ping Cheng
Journal: Circulation (2017)

Background: Aging is accompanied by oxidative stress and cardiac dysfunction; however, the link between the two is unclear. Although β3-adrenergic receptor (AR)-mediated nitric oxide synthases (NOS...
Abstract 16960: Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery
Authors: Santiago Garcia, Thomas Rector, Marina Zakharova, Edward O McFalls
Journal: Circulation (2016)

Introduction: Remote ischemic preconditioning (RIPC) has been shown to reduce infarct size in animal models. Hypothesis: We hypothesized that RIPC prior to an elective vascular operation would redu...
Virtual reality simulation training in endoscopy: a Cochrane review and meta-analysis
Authors: Rishad Khan, Joanne Plahouras, Bradley C. Johnston, Michael A. Scaffidi, Samir C. Grover, Catharine M. Walsh
Journal: Endoscopy (2019)

Abstract Background Endoscopy programs are increasingly integrating simulation training. We conducted a systematic review to determine whether virtual reality (VR) simulation training can supplement and/or replace conventional patient-based endoscopy training for health professional trainees with limited or no prior endoscopic experience. Methods We searched medical, educational, and computer literature databases in July 2017 for trials that compared VR simulation training with no training, conventional training, another form of simulation training, or an alternative method of VR training. We screened, abstracted data, and performed quantitative analysis and quality assessment through Cochrane methodology. Results We included 18 trials with 3817 endoscopic procedures. VR training provided no advantage over no training or conventional training based on the primary outcome of composite score of competency. VR training was advantageous over no training based on independent procedure completion (relative risk [RR] = 1.62, 95 % confidence interval [CI] 1.15 – 2.26, moderate-quality evidence), overall rating of performance (mean difference [MD] 0.45, 95 %CI 0.15 – 0.75, very low-quality evidence), and mucosal visualization (MD 0.60, 95 %CI 0.20 – 1.00, very low-quality evidence). Compared with conventional training, VR training resulted in fewer independent procedure completions (RR = 0.45, 95 %CI 0.27 – 0.74, low-quality evidence). We found no differences between VR training and no training or conventional training for other outcomes. Based on qualitative analysis, we found no significant differences between VR training and other forms of simulation training. VR curricula based in educational theory provided benefit with respect to composite score of competency, compared with unstructured curricula. Conclusions VR simulation training is advantageous over no training and can supplement conventional endoscopy training. There is insufficient evidence that simulation training provides benefit over conventional training.
The Immune Microenvironment in Hormone Receptor–Positive Breast Cancer Before and After Preoperative Chemotherapy
Authors: Adrienne G. Waks, Daniel G. Stover, Jennifer L. Guerriero, Deborah Dillon, William T. Barry, Evisa Gjini, Christina Hartl, Wesley Lo, Jennifer Savoie, Jane Brock, Robert Wesolowski, Zaibo Li, Adrienne Damicis, Anne V. Philips, Yun Wu, Fei Yang, Amy Sullivan, Patrick Danaher, Heather Ann Brauer, Wafa Osmani, Mikel Lipschitz, Katherine A. Hoadley, Michael Goldberg, Charles M. Perou, Scott Rodig, Eric P. Winer, Ian E. Krop, Elizabeth A. Mittendorf, Sara M. Tolaney
Journal: Clinical Cancer Research (2019)

Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR+/HER2- breast tumors.HR+/HER2- breast tumors were analyzed before and after neoadjuvant chemotherapy. sTIL were assessed histologically; CD8+ cells, CD68+ cells, and PD-L1 staining were assessed immunohistochemically; whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed.Ninety-six patients were analyzed from two cohorts (n = 55, Dana-Farber cohort; n = 41, MD Anderson cohort). sTIL, CD8, and PD-L1 on tumor cells were higher in tumors with basal PAM50 intrinsic subtype. Higher levels of tissue-based lymphocyte (sTIL, CD8, PD-L1) and macrophage (CD68) markers, as well as gene expression markers of lymphocyte or macrophage phenotypes (NanoString or CIBERSORT), correlated with favorable response to neoadjuvant chemotherapy, but not with improved distant metastasis-free survival in these cohorts or a large gene expression dataset (N = 302). In paired pre-/postchemotherapy samples, sTIL and CD8+ cells were significantly decreased after treatment, whereas expression analyses (NanoString) demonstrated significant increase of multiple myeloid signatures. Single gene expression implicated increased expression of immunosuppressive (M2-like) macrophage-specific genes after chemotherapy.The immune microenvironment of HR+/HER2- tumors differs according to tumor biology. This cohort of paired pre-/postchemotherapy samples suggests a critical role for immunosuppressive macrophage expansion in residual disease. The role of macrophages in chemoresistance should be explored, and further evaluation of macrophage-targeting therapy is warranted.
Light‐Activated Tissue‐Integrating Sutures as Surgical Nanodevices
Authors: Deepanjan Ghosh, Russell Urie, Andy Chang, Rajeshwar Nitiyanandan, Jung Keun Lee, Jacquelyn Kilbourne, Kaushal Rege
Journal: Advanced Healthcare Materials (2019)

Abstract Sutures are typically the primary means of soft tissue repair in surgery and trauma. Despite their widespread use, sutures do not result in immediate sealing of approximated tissues, which can result in bacterial infection and leakage. Nonabsorbable sutures and staples can be traumatic to tissue, and the trauma can be exacerbated by their subsequent removal. Use of cyanoacrylate glues is limited because of their brittleness and toxicity. In this work, laser‐activated tissue‐integrating sutures (LATIS) are described as novel nanodevices for soft tissue approximation and repair. Incorporation of gold nanorods within fibers generated from collagen result in LATIS fibers which demonstrate robust photothermal responses following irradiation with near infrared laser light. Compared to conventional sutures, LATIS fibers result in greater biomechanical recovery of incised skin in a mouse model of skin closure after spine surgeries. Histopathology analyses show improved repair of the epidermal gap in skin, which indicate faster tissue recovery using LATIS. The studies indicate that LATIS‐facilitated approximation of skin in live mice synergizes the benefits of conventional suturing and laser‐activated tissue integration, resulting in new approaches for faster sealing, tissue repair, and healing.