tbuckley/cabot-search huggingface dataset:
Family History of Gastric Cancer and <i>Helicobacter pylori</i> Treatment
Authors: Il Ju Choi, Chan Gyoo Kim, Jong Yeul Lee, Young-Il Kim, Myeong-Cherl Kook, Boram Park, Jungnam Joo
Journal: New England Journal of Medicine (2020)

Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown.In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period.A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).
GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents
Authors: Gina L.C. Yosten, Caron M. Harada, Chris Haddock, Luigino Antonio Giancotti, Grant R. Kolar, Ryan Patel, Chun Guo, Zhoumou Chen, Jinsong Zhang, Timothy M. Doyle, Anthony H. Dickenson, Willis K. Samson, Daniela Salvemini
Journal: Journal of Clinical Investigation (2020)

Treating neuropathic pain is challenging and novel non-opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.
Sixty seconds on . . . minimum unit pricing
Authors: Ingrid Torjesen
Journal: BMJ (2020)

In a manner of speaking. The policy to control the price of alcohol and stop the sale of very cheap alcoholic drinks was introduced in Scotland in May 2018. As a result, no drink can be sold at less than 50p (€0.60; $0.65) per unit of alcohol. The policy aimed to reduce sale and consumption of high strength, low cost products, that cause the most health harms.

Immediately …
Abstract 11446: Associations of Sleep Patterns With Objectively Measured Sedentary Behavior and Physical Activity Time: Results From the Hispanic Community Health Study/Study of Latinos
Authors: Nour Makarem, Brooke Aggarwal, Marie-Pierre St-Onge, Gregory A Talavera, Sanjay R Patel, Linda C Gallo, Daniela Sotres-Alvarez, Martha L Daviglus, Keith M Diaz, Alberto R Ramos, William K Wohlgemuth, Phyllis C Zee, Sheila F Castañeda
Journal: Circulation (2018)

Introduction: Sleep, sedentary behavior, and physical activity (PA) are modifiable targets for reducing cardiometabolic risk, yet the interplay between these factors is not well understood. Previou...
EZH2 Inhibition Sensitizes CARM1-High, Homologous Recombination Proficient Ovarian Cancers to PARP Inhibition
Authors: Sergey Karakashev, Takeshi Fukumoto, Bo Zhao, Jianhuang Lin, Shuai Wu, Nail Fatkhutdinov, Pyoung-Hwa Park, Galina Semenova, Stephanie Jean, Mark G. Cadungog, Mark E. Borowsky, Andrew V. Kossenkov, Qin Liu, Rugang Zhang
Journal: Cancer Cell (2020)
Complementary and Alternative Medicine Use in Patients With Hidradenitis Suppurativa
Authors: Kyla N. Price, Alyssa M. Thompson, Omar Rizvi, Aleksi J. Hendricks, Afsaneh Alavi, Jennifer L. Hsiao, Vivian Y. Shi
Journal: JAMA Dermatology (2020)

This survey study examines the use and perceptions of complementary and alternative medicine by individuals with hidradenitis suppurativa who completed an anonymous survey.
Abstract 16618: Amplitude Spectrum Area Changes During Cardiopulmonary Resuscitation After Different Durations of Untreated Cardiac Arrest in a Porcine Model of Ventricular Fibrillation With a Concurrent Acute Myocardial Infarction
Authors: Giuseppe Ristagno, Francesca Fumagalli, Weilun Quan, Davide Olivari, Yongqin Li
Journal: Circulation (2017)

Introduction: The effect of high quality CPR on amplitude spectrum area (AMSA) were investigated in relationship with the duration of untreated ventricular fibrillation (VF) in a preclinical porcin...
CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression
Authors: Erika Tissino, Federico Pozzo, Dania Benedetti, Chiara Caldana, Tamara Bittolo, Francesca Maria Rossi, Riccardo Bomben, Paola Nanni, Hillarj Chivilò, Ilaria Cattarossi, Eva Zaina, Kevin Norris, Jerry Polesel, Massimo Gentile, Giovanni Tripepi, Riccardo Moia, Enrico Santinelli, Idanna Innocenti, Jacopo Olivieri, Giovanni D’Arena, Luca Laurenti, Francesco Zaja, Gabriele Pozzato, Annalisa Chiarenza, Francesco Di Raimondo, Davide Rossi, Chris Pepper, Tanja Nicole Hartmann, Gianluca Gaidano, Giovanni Del Poeta, Valter Gattei, Antonella Zucchetto
Journal: Blood (2020)
Endoscopic dissection of an esophageal submucosal tumor using a novel bipolar radiofrequency device
Authors: Zaheer Nabi, Mohan Ramchandani, Radhika Chavan, Santosh Darisetty, Rama Kotla, D. Nageshwar Reddy
Journal: Endoscopy (2020)

A 42-year-old woman was diagnosed with a submucosal lesion at the lower esophagus extending into the fundus ([Fig. 1]). Endosonography showed the tumor arising from the second layer (i. e. muscularis mucosa). Submucosal tunneling endoscopic resection (STER) was performed using a therapeutic channel (3.7 mm) endoscope (GIF-1TH190; Olympus, Tokyo, Japan) ([Video 1]). We used a new multimodality knife for the entire procedure (Speedboat-RS2; Creo Medical Ltd., Chepstow, UK) ([Fig. 2]). This device consists of curved bipolar electrodes on the sides for cutting using radiofrequency energy (400 kHz and 35 W) and microwave for coagulation (frequency 5.8 GHz, power setting 10 W). In brief, the STER procedure involved: a) submucosal injection at about 1 cm proximal to the submucosal tumor ([Fig. 3 a]); b) mucosal incision of about 2 cm in length ([Fig. 3 b]); c) submucosal tunneling and dissection of the tumor from surrounding tissue ([Fig. 3 c]); d) retrieval of the tumor using a polypectomy snare ([Fig. 3 d]); d) closure of the incision using multiple endoclips.
First-Trimester Pregnancy Exposure to Modafinil and Risk of Congenital Malformations
Authors: Per Damkier, Anne Broe
Journal: JAMA (2020)

Discussion | Evidence from this national cohort of publicly insured pregnant women with confounding adjustment suggests that intravenously administered ondansetron was not associated with an increase in the risk of cardiac malformations, oral clefts, or congenital malformations overall.While the point estimate for oral clefts was lower for intravenous ondansetron compared with oral ondansetron (RR, 1.24 [95% CI, 1.03-1.48]),the CI was wide with an upper limit similar to that for oral ondansetron. 1 The strengths and limitations of using large health care databases to evaluate drug safety in pregnancy have been described. 5Limitations of this study include the potential for residual confounding due to unmeasured or poorly measured characteristics, restriction of the cohort to live births and individuals with Medicaid, and availability of data through 2014 only. 1 An advantage of studying intravenous administration of ondansetron is the high specificity for exposure because a claim for reimbursement is generated.Overall, these findings suggest that ondansetron is not a major teratogen.
Cardiobladeを使用した心房細動手術の成績PV isolationとmodified Maze手術の治癒率の比較 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 大沢肇, 藤松利浩, 高井文恵, 櫻井俊平, 有賀雅和, 荻原史明
Journal: Circulation (2007)
Understanding the asthmatic response to an experimental rhinovirus infection: Exploring the effects of blocking IgE
Authors: Peter W. Heymann, Thomas A.E. Platts-Mills, Judith A. Woodfolk, Larry Borish, Deborah D. Murphy, Holliday T. Carper, Mark R. Conaway, John W. Steinke, Lyndsey Muehling, W. Gerald Teague, Joshua L. Kennedy, Anne-Marie Irani, Matthew D. McGraw, Stephen V. Early, Lisa M. Wheatley, Amy P. Adams, Ronald B. Turner
Journal: Journal of Allergy and Clinical Immunology (2020)
AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells
Authors: Maria L. Lotsberg, Katarzyna Wnuk-Lipinska, Stéphane Terry, Tuan Zea Tan, Ning Lu, Laura Trachsel-Moncho, Gro V. Røsland, Muntequa I. Siraji, Monica Hellesøy, Austin Rayford, Kirstine Jacobsen, Henrik J. Ditzel, Olav K. Vintermyr, Trever G. Bivona, John Minna, Rolf A. Brekken, Bruce Baguley, David Micklem, Lars A. Akslen, Gro Gausdal, Anne Simonsen, Jean Paul Thiery, Salem Chouaib, James B. Lorens, Agnete Svendsen Tenfjord Engelsen
Journal: Journal of Thoracic Oncology (2020)

IntroductionAcquired cancer therapy resistance evolves under selection pressure of immune surveillance and favors mechanisms that promote drug resistance through cell survival and immune evasion. AXL receptor tyrosine kinase is a mediator of cancer cell phenotypic plasticity and suppression of tumor immunity, and AXL expression is associated with drug resistance and diminished long-term survival in a wide range of malignancies, including NSCLC.MethodsWe aimed to investigate the mechanisms underlying AXL-mediated acquired resistance to first- and third-generation small molecule EGFR tyrosine kinase inhibitors (EGFRi) in NSCLC.ResultsWe found that EGFRi resistance was mediated by up-regulation of AXL, and targeting AXL reduced reactivation of the MAPK pathway and blocked onset of acquired resistance to long-term EGFRi treatment in vivo. AXL-expressing EGFRi-resistant cells revealed phenotypic and cell signaling heterogeneity incompatible with a simple bypass signaling mechanism, and were characterized by an increased autophagic flux. AXL kinase inhibition by the small molecule inhibitor bemcentinib or siRNA mediated AXL gene silencing was reported to inhibit the autophagic flux in vitro, bemcentinib treatment blocked clonogenicity and induced immunogenic cell death in drug-resistant NSCLC in vitro, and abrogated the transcription of autophagy-associated genes in vivo. Furthermore, we found a positive correlation between AXL expression and autophagy-associated gene signatures in a large cohort of human NSCLC (n = 1018).ConclusionOur results indicate that AXL signaling supports a drug-resistant persister cell phenotype through a novel autophagy-dependent mechanism and reveals a unique immunogenic effect of AXL inhibition on drug-resistant NSCLC cells.
Abstract 14974: GREM1 Improves the Regenerative Potential of Aging Cardiac Progenitor Cells as a Potential Therapy for Ischemic Heart Disease
Authors: Gurleen Kaur, Xiuchun Li, Lei Teng, Neil Devijian, Edward Bennett, Chuanxi Cai
Journal: Circulation (2018)

Introduction: Ischemic heart disease is the leading cause of mortality in the United States. Autologous stem/progenitor cell therapy can restore myocardial structure and function. However, its effi...
MMP inhibitors attenuate doxorubicin cardiotoxicity by preventing intracellular and extracellular matrix remodelling
Authors: Brandon Y H Chan, Andrej Roczkowsky, Woo Jung Cho, Mathieu Poirier, Consolato Sergi, Vic Keschrumrus, Jared M Churko, Henk Granzier, Richard Schulz
Journal: Cardiovascular Research (2020)

Abstract Aims Heart failure is a major complication in cancer treatment due to the cardiotoxic effects of anticancer drugs, especially from the anthracyclines such as doxorubicin (DXR). DXR enhances oxidative stress and stimulates matrix metalloproteinase-2 (MMP-2) in cardiomyocytes. We investigated whether MMP inhibitors protect against DXR cardiotoxicity given the role of MMP-2 in proteolyzing sarcomeric proteins in the heart and remodelling the extracellular matrix. Methods and results Eight-week-old male C57BL/6J mice were treated with DXR weekly with or without MMP inhibitors doxycycline or ONO-4817 by daily oral gavage for 4 weeks. Echocardiography was used to determine cardiac function and left ventricular remodelling before and after treatment. MMP inhibitors ameliorated DXR-induced systolic and diastolic dysfunction by reducing the loss in left ventricular ejection fraction, fractional shortening, and E′/A′. MMP inhibitors attenuated adverse left ventricular remodelling, reduced cardiomyocyte dropout, and prevented myocardial fibrosis. DXR increased myocardial MMP-2 activity in part also by upregulating N-terminal truncated MMP-2. Immunogold transmission electron microscopy showed that DXR elevated MMP-2 levels within the sarcomere and mitochondria which were associated with myofilament lysis, mitochondrial degeneration, and T-tubule distention. DXR-induced myofilament lysis was associated with increased titin proteolysis in the heart which was prevented by ONO-4817. DXR also increased the level and activity of MMP-2 in human embryonic stem cell-derived cardiomyocytes, which was reduced by ONO-4817. Conclusions MMP-2 activation is an early event in DXR cardiotoxicity and contributes to myofilament lysis by proteolyzing cardiac titin. Two orally available MMP inhibitors ameliorated DXR cardiotoxicity by attenuating intracellular and extracellular matrix remodelling, suggesting their use may be a potential prophylactic strategy to prevent heart injury during chemotherapy.
Opioid prescribing patterns among medical providers in the United States, 2003-17: retrospective, observational study
Authors: Mathew V Kiang, Keith Humphreys, Mark R Cullen, Sanjay Basu
Journal: BMJ (2020)

To examine the distribution and patterns of opioid prescribing in the United States.Retrospective, observational study.National private insurer covering all 50 US states and Washington DC.An annual average of 669 495 providers prescribing 8.9 million opioid prescriptions to 3.9 million patients from 2003 through 2017.Standardized doses of opioids in morphine milligram equivalents (MMEs) and number of opioid prescriptions.In 2017, the top 1% of providers accounted for 49% of all opioid doses and 27% of all opioid prescriptions. In absolute terms, the top 1% of providers prescribed an average of 748 000 MMEs-nearly 1000 times more than the middle 1%. At least half of all providers in the top 1% in one year were also in the top 1% in adjacent years. More than two fifths of all prescriptions written by the top 1% of providers were for more than 50 MMEs a day and over four fifths were for longer than seven days. In contrast, prescriptions written by the bottom 99% of providers were below these thresholds, with 86% of prescriptions for less than 50 MMEs a day and 71% for fewer than seven days. Providers prescribing high amounts of opioids and patients receiving high amounts of opioids persisted over time, with over half of both appearing in adjacent years.Most prescriptions written by the majority of providers are under the recommended thresholds, suggesting that most US providers are careful in their prescribing. Interventions focusing on this group of providers are unlikely to effect beneficial change and could induce unnecessary burden. A large proportion of providers have established relationships with their patients over multiple years. Interventions to reduce inappropriate opioid prescribing should be focused on improving patient care, management of patients with complex pain, and reducing comorbidities rather than seeking to enforce a threshold for prescribing.
57P Validation of Three Breast Cancer Nomograms for Predicting the Non-Sentinel Lymph Node Metastases and a New Formula for Predicting Non-Sentinel Lymph Node Status. (Second Study from Turkey-First Unicenter Study)
Authors: S.Z. Derici, A.I. Sevinc, O. Harmancioglu, S. Saydam, M.A. Kocdor, T. Canda
Journal: Annals of Oncology (2012)
Health-related quality of life (HRQL) in a randomized phase III trial of enzalutamide with standard first-line therapy for metastatic, hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led, international, co-operative group trial
Authors: M.R. Stockler, A.J. Martin, H. Dhillon, I.D. Davis, K.N. Chi, S. Chowdhury, L.G. Horvath, N.J. Lawrence, G.M. Marx, J Mc Caffrey, R. McDermott, S.A. North, F. Parnis, D.W. Pook, M.N. Reaume, S.K. Sandhu, T.H. Tan, A. Thomson, R. Zielinski, C.J. Sweeney
Journal: Annals of Oncology (2019)
Prevention of non-communicable disease: best buys, wasted buys, and contestable buys
Authors: Wanrudee Isaranuwatchai, Yot Teerawattananon, Rachel A Archer, Alia Luz, Manushi Sharma, Waranya Rattanavipapong, Thunyarat Anothaisintawee, Rachel L Bacon, Tazeem Bhatia, Jesse Bump, Kalipso Chalkidou, Adam G Elshaug, David D Kim, Sumithra Krishnamurthy Reddiar, Ryota Nakamura, Peter J Neumann, Arisa Shichijo, Peter C Smith, Anthony J Culyer
Journal: BMJ (2020)

Wanrudee Isaranuwatchai and colleagues highlight the importance of local context in making decisions about implementing interventions for preventing non-communicable diseases
TGF-β inhibition combined with cytotoxic nanomedicine normalizes triple negative breast cancer microenvironment towards anti-tumor immunity
Authors: Myrofora Panagi, Chrysovalantis Voutouri, Fotios Mpekris, Panagiotis Papageorgis, Margaret R Martin, John D Martin, Philippos Demetriou, Chryso Pierides, Christiana Polydorou, Andreas Stylianou, Maria Louca, Laura Koumas, Paul Costeas, Kazunori Kataoka, Horacio Cabral, Triantafyllos Stylianopoulos
Journal: Theranostics (2020)

Tumor normalization strategies aim to improve tumor blood vessel functionality (i.e., perfusion) by reducing the hyper-permeability of tumor vessels or restoring compressed vessels.Despite progress in strategies to normalize the tumor microenvironment (TME), their combinatorial antitumor effects with nanomedicine and immunotherapy remain unexplored.Methods: Here, we re-purposed the TGF-β inhibitor tranilast, an approved anti-fibrotic and antihistamine drug, and combined it with Doxil nanomedicine to normalize the TME, increase perfusion and oxygenation, and enhance anti-tumor immunity.Specifically, we employed two triple-negative breast cancer (TNBC) mouse models to primarily evaluate the therapeutic and normalization effects of tranilast combined with doxorubicin and Doxil.We demonstrated the optimized normalization effects of tranilast combined with Doxil and extended our analysis to investigate the effect of TME normalization to the efficacy of immune checkpoint inhibitors.Results: Combination of tranilast with Doxil caused a pronounced reduction in extracellular matrix components and an increase in the intratumoral vessel diameter and pericyte coverage, indicators of TME normalization.These modifications resulted in a significant increase in tumor perfusion and oxygenation and enhanced treatment efficacy as indicated by the notable reduction in tumor size.Tranilast further normalized the immune TME by restoring the infiltration of T cells and increasing the fraction of T cells that migrate away from immunosuppressive cancer-associated fibroblasts.Furthermore, we found that combining tranilast with Doxil nanomedicine, significantly improved immunostimulatory M1 macrophage content in the tumorigenic tissue and improved the efficacy of the immune checkpoint blocking antibodies anti-PD-1/anti-CTLA-4.Conclusion: Combinatorial treatment of tranilast with Doxil optimizes TME normalization, improves immunostimulation and enhances the efficacy of immunotherapy.
Importation and Human-to-Human Transmission of a Novel Coronavirus in Vietnam
Authors: Lan T Phan, Thuong V Nguyen, Quang C Luong, Thinh V Nguyen, Hieu T Nguyen, Hung Q Le, Thuc T Nguyen, Thang M Cao, Quang D Pham
Journal: New England Journal of Medicine (2020)

Human-to-Human Coronavirus Transmission in Vietnam The authors describe transmission of 2019-nCoV from a father, who had flown with his wife from Wuhan to Hanoi, to the son, who met his father and ...
Going with the flow: diagnosing a lymphocyte-rich pleural effusion
Authors: Catherine Hyams, Megan H Jenkins, Richard Daly, Izak C Heys, Nicholas A Maskell
Journal: Thorax (2020)

### Presentation to pleural clinic

A 52-year-old Medical Secretary was seen in Pleural Outpatient Clinic as follow-up after hospital discharge from the Surgical team 3 weeks previously. Since discharge, the patient had progressive breathlessness with an exercise tolerance of 10 m (previously unlimited) and noted a mild dry cough. She was a lifelong non-smoker. Fevers, sweats or weight loss were not reported. She had no relevant medical or travel history, with no known exposure to asbestos or other chemical agents. Clinical examination was consistent with a large left-sided pleural effusion, which was confirmed on chest radiograph (figure 1A) and thoracic ultrasound. The chest radiograph also demonstrated infiltrates in the left upper zone.



Figure 1 
(A) Chest radiograph on presentation to Respiratory Outpatient Clinic showing moderate left-sided pleural effusion and left upper zone infiltrate. (B) CT showing SL and HP. (C) HE SL, splenic laceration.



### Previous surgical history

The patient originally presented with abdominal pain and non-bloody diarrhoea 4 months prior to her clinic appointment. Routine blood tests were unremarkable, and she was diagnosed with probable infective colitis. She was discharged home with a plan for outpatient colonoscopy if her symptoms continued. Two months following this, the patient re-presented to the surgical team; however, her pain was now epigastric. An abdominal ultrasound was unremarkable, and she was discharged home and her colonoscopy expedited.

The patient was readmitted 48 hours following this second discharge and was haemodynamically unstable with an acute abdomen. …