tbuckley/cabot-search huggingface dataset:
Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust
Authors: Mercy Adetoye
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build TrustFREEMercy Adetoye, MDMercy Adetoye, MDUniversity of Michigan, Ann Arbor, Michigan (M.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0009 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust "Voices of Medical Students and Residents: What Can Be Done to Build Trust," by Mercy Adetoye, MD (Duration 4:20)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Michigan, Ann Arbor, Michigan (M.A.)Current Author Address: Mercy Adetoye, MD; e-mail, [email protected]umich.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Abstract P5-03-10: The spectrum of BRCA1 and BRCA2 mutations and clinicopathologic characteristics of young-onset breast cancer in BRCA-carriers and non-carriers
Authors: Lili Chen, Fangmeng Fu, Jinxing Lv, Chuan Wang
Journal: Cancer Research (2020)

Abstract Background: For now, Seldom studies have reported that relationship between BRCA1/2 mutation and their clinical characteristics in young-onset breast cancers. This study is the first article which characterizes the risk factor profiles in Chinese patients selected by the age of onset (&amp;lt;40 years old).Patient and method:A total of 1371 consecutive unselected Chinese young-onset breast cancer patients were collected form Fujian Union hospital, China, screened for germline BRCA1/2 mutation. The full-exome sequencing in the next generation sequencing technology was performed in all patients to examine the BRCA1/2 mutation.Result: In our study, 25 (1.8%) and 61 (4.4%) patients were identified with BRCA1 and BRCA2 mutation among the unselected early-onset breast cancer patients, respectively. BRCA1 mutations were associated with pregnancies (p=0.026), BRCA1-carriers had a higher likelihood of HR positive(p&amp;lt;0.001), or HER-2 negative(p&amp;lt;0.001), or high grade(p=0.002) than non-carriers. Among BRCA2 mutations, the age of onset was younger than non-carriers(P=0.017), BRCA2-carriers were more likely to have lymph node metastasis(P=0.004). with HR positive or HER-2 negative were likely to detected positive for BRCA2(p&amp;lt;0.001). Citation Format: Lili Chen, Fangmeng Fu, Jinxing Lv, Chuan Wang. The spectrum of BRCA1 and BRCA2 mutations and clinicopathologic characteristics of young-onset breast cancer in BRCA-carriers and non-carriers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-10.
A validated novel continuous prognostic index to deliver stratified medicine in pediatric acute lymphoblastic leukemia
Authors: Amir Enshaei, David O’Connor, Jack Bartram, Jeremy Hancock, Christine J. Harrison, Rachael Hough, Sujith Samarasinghe, Monique L. den Boer, Judith M. Boer, Hester A. de Groot-Kruseman, Hanne V. Marquart, Ulrika Noren-Nystrom, Kjeld Schmiegelow, Claire Schwab, Martin A. Horstmann, Gabriele Escherich, Mats Heyman, Rob Pieters, Ajay Vora, John Moppett, Anthony V. Moorman
Journal: Blood (2020)
ATM Paradoxically Promotes Oncogenic Transformation via Transcriptional Reprogramming
Authors: Xinjian Liu, Mengjie Hu, Pei Liu, Meng Jiao, Min Zhou, Andrew K. Lee, Fang Li, Chuan-Yuan Li
Journal: Cancer Research (2020)

Abstract The role of the ataxia-telangiectasia-mutated (ATM) gene in human malignancies, especially in solid tumors, remains poorly understood. In the present study, we explored the involvement of ATM in transforming primary human cells into cancer stem cells. We show that ATM plays an unexpected role in facilitating oncogene-induced malignant transformation through transcriptional reprogramming. Exogenous expression of an oncogene cocktail induced a significant amount of DNA double-strand breaks in human fibroblasts that caused persistent activation of ATM, which in turn enabled global transcriptional reprogramming through chromatin relaxation, allowing oncogenic transcription factors to access chromatin. Consistently, deficiencies in ATM significantly attenuated oncogene-induced transformation of human cells. In addition, ATM inhibition significantly reduced tumorigenesis in a mouse model of mammary cancer. ATM and cellular DNA damage response therefore play a previously unknown role in facilitating rather than suppressing oncogene-induced malignant transformation of mammalian cells. Significance: These findings uncover a novel pro-oncogenic role for ATM and show that contrary to established theory, ATM does not always function as a tumor suppressor; its function is however dependent on cell type.
Efficacy and safety of topical sofpironium bromide gel for the treatment of axillary hyperhidrosis: A phase II, randomized, controlled, double-blinded trial
Authors: Brandon Kirsch, Stacy Smith, Joel Cohen, Janet DuBois, Lawrence Green, Leslie Baumann, Neal Bhatia, David Pariser, Ping-Yu Liu, Deepak Chadha, Patricia Walker
Journal: Journal of the American Academy of Dermatology (2020)
Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study
Authors: Johan Burisch, Hillel Vardi, Doron Schwartz, Michael Friger, Gediminas Kiudelis, Juozas Kupčinskas, Mathurin Fumery, Corinne Gower-Rousseau, Laszlo Lakatos, Peter L Lakatos, Renata D'Incà, Alessandro Sartini, Daniela Valpiani, Martina Giannotta, Naila Arebi, Dana Duricova, Martin Bortlik, Stefania Chetcuti Zammit, Pierre Ellul, Natalia Pedersen, Jens Kjeldsen, Jóngerð Maria Miné Midjord, Kári Rubek Nielsen, Karina Winther Andersen, Vibeke Andersen, Konstantinos H Katsanos, Dimitrios K Christodoulou, Viktor Domislovic, Zeljko Krznaric, Shaji Sebastian, Pia Oksanen, Pekka Collin, Luisa Barros, Fernando Magro, Riina Salupere, Hendrika Adriana Linda Kievit, Adrian Goldis, Ioannis P Kaimakliotis, Jens F Dahlerup, Carl Eriksson, Jonas Halfvarson, Alberto Fernandez, Vicent Hernandez, Svetlana Turcan, Elena Belousova, Ebbe Langholz, Pia Munkholm, Selwyn Odes, Niksa Turk, Silvija Cukovic-Cavka, Anastasia Nicolaou, Milan Lukas, Olga Shonová, Birgitte Blichfeldt, Dorte Marker, Katrine Carlsen, Petra Weimers, Clays Aalykke, Karen Kudsk, Ida Vind, Niels Thorsgaard, Alexandros Skamnelos, Dimitrios Politis, Zsuzsanna Vegh, Peterne Demenyi, Szabina Nemethne Kramli, Giualia Dal Piaz, Alessia Santini, Giulia Girardin, Limas Kupcinskas, Laimas Jonaitis, Irena Valantiene, Romanas Zykus, Ruta Kucinskiene, Daniela Lazar, Inna Nikulina, Luisa de Castro, Juan-Ramon Pineda, Santos Pereira, Jesus Martinez-Cadilla, Luciano Sanroman, Montserrat Figueira, David Martinez Ares, Jose-Ignacio Rodriguez-Prada, Amalia Carmona, Carlos Gonzalez-Portela, Ulla-Britt Widen, Sally Myers, Katherine Ashton, Emma Whitehead
Journal: The Lancet. Gastroenterology & hepatology (2020)
Abstract P6-16-05: Clinical outcomes achieved with brachytherapy vs whole breast irradiation for ductal carcinoma in situ
Authors: Katarina T Nguyen, David Francis, Thevaa Chandering, Kelli Pointer, Bethany Anderson
Journal: Cancer Research (2020)

Abstract Purpose: To compare the locoregional control achieved with whole breast irradiation (WBI) and accelerated partial breast irradiation (APBI) in women with ductal carcinoma in situ (DCIS). Methods: We used an institutional, IRB-approved database to retrospectively identify women with primary DCIS lesions less than 3 cm from 1995 to 2014, who underwent negative-margin breast conserving surgery (BCS) followed by either WBI or APBI. Cox-proportional hazard analysis was performed to estimate risks of in-breast tumor recurrence (IBTR) and regional nodal recurrence (RNR), adjusting for age of patient at diagnosis. Results: Three-hundred and eighty women were identified. Seventy-nine percent received WBI and 21% underwent APBI. Among women receiving WBI, 15.4% received a sequential lumpectomy cavity boost. APBI was delivered via high-dose-rate (HDR) brachytherapy technique, utilizing either a multi-catheter interstitial or single-entry intracavitary approach. The median follow-up time was 6 years for women who received WBI, and 8.9 years for women who received APBI. The actuarial 10-year IBTR rate was 9.0% for WBI and 8.75% for APBI (p = 0.94). The actuarial 10-year isolated regional nodal recurrence (RNR) rate was 0% for WBI and 2.5% for APBI. Among women who received WBI, the 10-year IBTR rate was 10.0% without lumpectomy cavity boost and 6.36% with boost (p = 0.40). Increasing age correlated with a lower risk of recurrence, regardless of treatment modality (p = 0.005). Conclusions: No differences in locoregional control was detected for women with DCIS measuring &amp;lt;3 cm, treated with BCS followed by APBI vs WBI. Citation Format: Katarina T Nguyen, David Francis, Thevaa Chandering, Kelli Pointer, Bethany Anderson. Clinical outcomes achieved with brachytherapy vs whole breast irradiation for ductal carcinoma in situ [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-05.
Mutational signatures: experimental design and analytical framework
Authors: Gene Koh, Xueqing Zou, Serena Nik-Zainal
Journal: Genome biology (2020)

Abstract Mutational signatures provide a powerful alternative for understanding the pathophysiology of cancer. Currently, experimental efforts aimed at validating and understanding the etiologies of cancer-derived mutational signatures are underway. In this review, we highlight key aspects of mutational signature experimental design and describe the analytical framework. We suggest guidelines and quality control measures for handling whole-genome sequencing data for mutational signature analyses and discuss pitfalls in interpretation. We envision that improved next-generation sequencing technologies and molecular cell biology approaches will usher in the next generation of studies into the etiologies and mechanisms of mutational patterns uncovered in cancers.
Quality of Life in Patients With Skin of Color and Chronic Graft-vs-Host Disease
Authors: Zoë I. Smith, Rachel K. Rosenstein, Srikanta Banerjee, Dominique C. Pichard, Steven Z. Pavletic, Edward W. Cowen
Journal: JAMA Dermatology (2020)

This survey study explores the scope of chronic graft-vs-host disease among a cohort of patients with skin of color.
PS1085 ORAL CHOP LIKE CHEMOTHERAPY IN ELDERLY PATIENTS WITH HIGH‐GRADE NON HODGKIN B CELL LYMPHOMA
Authors: S. Guidez, C. Tomowiak, I. Princet, C. Motard, A. Corby, A. Machet, C. Debiais, J. Guilhot, V. Delwail
Journal: HemaSphere (2019)

Background: The Doxorubicin based R‐CHOP regimen remains the standard of care for the upfront treatment of DLBCL. The advent of oral idarubicin permitted to develop an all‐oral ambulatory oro‐CIEP regimen. Aims: We hypothesized this regimen would improve the treatment of elderly DLBCL. Methods: We have performed a phase 1/2 study to determine the MTD[CA1] of idarubicin in the oro‐CIEP regimen. Idarubicin was orally administrated on day 1 with starting dose at 20 mg/m 2 and escalated per 10 mg/m 2 increment. Results: Twenty‐six newly diagnosed patients were enrolled, median age of 71 years (range, 62–80). All first 3 patients developed a DLT at level 3 (40 mg/m2), and 14 patients were then enrolled at RP2D 30 mg/m 2 in the phase 2. The most significant hematological toxicities were thrombocytopenia grade 3 or 4 (3.3%) and neutropenia grade 3 or 4 (26%); and extra‐hematological toxicities were infectious disease (5% grade 3 or 4). Second primary malignancies were reported in three patients. No toxic related death was observed. ORR and CR rates were 85% and 77%, respectively. The 5‐year overall survival and event free survival were 65% (95%CI 41;81) and 65% (95%CI 42;81), respectively. Summary/Conclusion: This analysis shows that oral idarubicin at the MTD of 30 mg/m 2 is safe and active in elderly DLBCL. The results we have observed, particularly overall survival seemed to be superimposable to previous publications with the regular CHOP‐like regimens for this population. Further improvements in the protocol will be introduced with the subcutaneous anti‐CD20 immunotherapy approach. This data needs to be confirmed in the context of a larger study.
Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP
Authors: Yi Zhou, Mingjian Fei, Gu Zhang, Wei-Ching Liang, WeiYu Lin, Yan Wu, Robert Piskol, John Ridgway, Erin McNamara, Haochu Huang, Juan Zhang, Jaehak Oh, Jaina M. Patel, Diana Jakubiak, Jeff Lau, Beth Blackwood, Daniel D. Bravo, Yongchang Shi, Jianyong Wang, Hong-Ming Hu, Wyne P. Lee, Rajiv Jesudason, Dewakar Sangaraju, Zora Modrusan, Keith R. Anderson, Søren Warming, Merone Roose-Girma, Minhong Yan
Journal: Immunity (2020)
Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust
Authors: Alyse Wheelock
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build TrustFREEAlyse WheelockAlyse WheelockBoston Medical Center, Boston, Massachusetts (A.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0015 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust "Voices of Medical Students and Residents: What Can Be Done to Build Trust," by Alyse Wheelock (Duration 3:22)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Boston Medical Center, Boston, Massachusetts (A.W.)Current Author Address: Alyse Wheelock; e-mail, alyse.[email protected]org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Creativity and Bipolar Disorder: A Shared Genetic Vulnerability
Authors: Tiffany A. Greenwood
Journal: Annual Review of Clinical Psychology (2020)

Bipolar disorder is a lifelong mood disorder characterized by extreme mood swings between mania and depression. Despite fitness costs associated with increased mortality and significant impairment, bipolar disorder has persisted in the population with a high heritability and a stable prevalence. Creativity and other positive traits have repeatedly been associated with the bipolar spectrum, particularly among unaffected first-degree relatives and those with milder expressions of bipolar traits. This suggests a model in which large doses of risk variants cause illness, but mild to moderate doses confer advantages, which serve to maintain bipolar disorder in the population. Bipolar disorder may thus be better conceptualized as a dimensional trait existing at the extreme of normal population variation in positive temperament, personality, and cognitive traits, aspects of which may reflect a shared vulnerability with creativity. Investigations of this shared vulnerability may provide insight into the genetic mechanisms underlying illness and suggest novel treatments.
Targeting GRP78-dependent AR-V7 protein degradation overcomes castration-resistance in prostate cancer therapy
Authors: Yuning Liao, Yuan Liu, Xiaohong Xia, Zhenlong Shao, Chuyi Huang, Jinchan He, Lili Jiang, Daolin Tang, Jinbao Liu, Hongbiao Huang
Journal: Theranostics (2020)

Rationale: Androgen receptor splice variant 7 (AR-V7) is a leading cause of the development of castration-resistant prostate cancer (CRPC).However, the regulation and function of AR-V7 at levels of post-translational modifications in prostate cancer therapy remain poorly understood.Here, we conducted a library screen of natural products to identify potential small molecules responsible for AR-V7 protein degradation in human prostate cancer cell lines.Methods: A natural product library was used to screen the inhibitor of AR-V7.Co-IP and biomass spectrum assays were used to identify the AR-V7-interacting proteins, whereas western blot, confocal microscopy, RNA interfering, and gene transfection were used to validate these interactions.Cell viability, EDU staining, and colony formation assays were employed to detect cell growth and proliferation.Flowcytometry assays were used to detect the distribution of cell cycle.Mouse xenograft models were used to study the anti-CRPC effects in vivo.Results: This screen identified rutaecarpine, one of the major components of the Chinese medicine Evodia rutaecarpa, as a novel chemical that selectively induces AR-V7 protein degradation via K48-linked ubiquitination.Mechanically, this effect relies on rutaecarpine inducing the formation of a GRP78-AR-V7 protein complex, which further recruits the E3 ligase SIAH2 to directly promote the ubiquitination of AR-V7.Consequently, the genetic and pharmacological activation of the GRP78-dependent AR-V7 protein degradation restores the sensitivity of castration-resistant prostate cancer to anti-androgen therapy in cell culture and animal models.Conclusions: These findings not only provide a new approach for overcoming castration-resistance in prostate cancer therapy, but also increase our understanding about the interplay between molecular chaperones and ubiquitin ligase in shaping protein stability.
Radiotherapy and Immunotherapy for Cancer: From “Systemic” to “Multisite”
Authors: Ainhoa Arina, Stanley I. Gutiontov, Ralph R. Weichselbaum
Journal: Clinical Cancer Research (2020)

Abstract In the era of cancer immunotherapy, there is significant interest in combining conventional cancer therapies, such as radiotherapy, with drugs that stimulate the immune system. The observation that ionizing radiation applied to murine tumors delays the growth of distant tumors (“abscopal effect”) and that this effect is potentiated by immunostimulatory drugs, led to clinical trials in which often only one lesion is irradiated in combination with immunotherapy drugs. The results of these initial clinical trials combining radio therapy and immunotherapy show that a meaningful abscopal effect is still infrequent. Recent preclinical data suggest that preexistent intratumoral T cells can survive radiation and contribute to its therapeutic effect. In this review, we discuss possible mechanisms underlying the preclinical/clinical discrepancies regarding the abscopal effect, and we propose the irradiation of multiple or all tumor sites in combination with systemic immunotherapy as a possible avenue to increase the efficacy of radio-immunotherapy.
Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird
Authors: Hila Levy, Steven R Fiddaman, Juliana A Vianna, Daly Noll, Gemma V Clucas, Jasmine K H Sidhu, Michael J Polito, Charles A Bost, Richard A Phillips, Sarah Crofts, Gary D Miller, Pierre Pistorius, Francesco Bonnadonna, Céline Le Bohec, Andrés Barbosa, Phil Trathan, Andrea Raya Rey, Laurent A F Frantz, Tom Hart, Adrian L Smith
Journal: Molecular Biology and Evolution (2020)

Over evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes-the Toll-like receptors (TLRs)-across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world's most rapidly changing environments.
Patient gender bias on the diagnosis of idiopathic pulmonary fibrosis
Authors: Deborah Assayag, Julie Morisset, Kerri A Johannson, Athol U Wells, Simon L F Walsh
Journal: Thorax (2020)

Background Patient sex has clinical and prognostic implications in idiopathic pulmonary fibrosis (IPF). It is not known if sex-related and gender-related discrepancies exist when establishing a diagnosis of IPF. The aim was to determine how patient gender influences the diagnosis of IPF and the physician’s diagnostic confidence. Methods This study was performed using clinical cases compiled from a single centre, then scored by respiratory physicians for a prior study. Using clinical information, physicians were asked to provide up to five diagnoses, together with their diagnostic confidence. Logistic regression was used to assess the odds of receiving a diagnosis of IPF based on patient gender. Prognostic discrimination between IPF and non-IPF was used to assess diagnostic accuracy with Cox proportional hazards modelling. Results Sixty cases were scored by 404 physicians. IPF was diagnosed more frequently in men compared with women (37.8% vs 10.6%; p&lt;0.0001), and with greater mean diagnostic confidence (p&lt;0.001). The odds of a male patient receiving an IPF diagnosis was greater than that of female patients, after adjusting for confounders (OR=3.05, 95% CI: 2.81 to 3.31), especially if the scan was not definite for the usual interstitial pneumonia pattern. Mortality was higher in women (HR=2.21, 95% CI: 2.02 to 2.41) than in men with an IPF diagnosis (HR=1.26, 95% CI: 1.20 to 1.33), suggesting that men were more often misclassified as having IPF. Conclusion Patient gender influences diagnosis of IPF: women may be underdiagnosed and men overdiagnosed with IPF.