tbuckley/cabot-search huggingface dataset:
Successful closure of a chronic vesicorectal fistula after radical prostatectomy with an over-the-scope clip
Authors: Alexandra Langers, Rob Bevers, Jurjen Boonstra, James Hardwick
Journal: Endoscopy (2018)

A vesicorectal fistula after prostatectomy is a nightmare for the urologist. Treatment is challenging, invasive, and often unsuccessful. Endoscopic treatment using an over-the-scope clip (OTSC) may be an elegant alternative for the closure of such fistulas, even if they persist for several months after initial surgery.
Abstract 1832: Acquired resistance mechanisms to afatinib in lung cancer cells harboring <i>HER2</i> alterations
Authors: Hidejiro Torigoe, Kazuhiko Shien, Tatsuaki Takeda, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Ken Suzawa, Hiromasa Yamamoto, Junichi Soh, Masakiyo Sakaguchi, Shuta Tomida, Shinichiro Miyoshi, Shinichi Toyooka
Journal: Cancer Research (2018)

Abstract Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small cell lung cancer (NSCLC), just as in breast and gastric cancers. We previously reported that the pan-HER inhibitor afatinib could be a useful therapeutic agent as HER2-targeted therapy for patients with NSCLC harboring HER2 alterations. However, acquired resistance to afatinib was observed in the clinical setting, similar to the case for other HER inhibitors. Thus, elucidation of the mechanisms underlying the development of acquired drug resistance and exploring means to overcome acquired drug resistance are important issues in the treatment of NSCLC. In this study, we experimentally established afatinib-resistant cell lines from NSCLC cell lines harboring HER2 alterations (Calu3, H2170, and H1781), by stepwise-escalation or high-concentration exposure methods, and investigated the mechanisms underlying the acquisition of drug resistance. The established cell lines showed several unique afatinib-resistance mechanisms, including MET amplification, loss of HER2 amplification and gene expression, epithelial-to-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. The afatinib-resistant cell lines showing MET amplification were sensitive to the combination of afatinib plus crizotinib (a MET inhibitor), both in vitro and in vivo. The resistant cell lines with the loss of HER2 amplification obtained MEK inhibitors sensitivity in vitro and in vivo. Other resistant cell lines that showed EMT or had acquired CSC-like features remained sensitive to docetaxel, like the parental cells. These findings may provide clues to countering the resistance to afatinib in NSCLC patients with HER2 alterations. Citation Format: Hidejiro Torigoe, Kazuhiko Shien, Tatsuaki Takeda, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Ken Suzawa, Hiromasa Yamamoto, Junichi Soh, Masakiyo Sakaguchi, Shuta Tomida, Shinichiro Miyoshi, Shinichi Toyooka. Acquired resistance mechanisms to afatinib in lung cancer cells harboring HER2 alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1832.
Web-Based Platform vs Genetic Counselors in Educating Patients About Carrier Results From Exome Sequencing
Authors: Yun Yen, Frank Luh
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Associations Between Gun Shows and Firearm Deaths and Injuries
Authors: Michael Xu
Journal: Annals of Internal Medicine (2018)

Letters3 July 2018Associations Between Gun Shows and Firearm Deaths and InjuriesMichael Xu, MDMichael Xu, MDUniversity of Tennessee Health Science Center, Nashville, Tennessee (M.X.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0102 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Matthay and colleagues (1) should note that it is already a federal crime in all states for both private individuals and businesses to sell a firearm across state borders without a background check. A California resident cannot drive to Nevada, buy a firearm, and then travel back to California. He or she must buy the firearm and have the private individual or business transfer it to a California firearm dealer, at which time a background check will be conducted.Reference1. Matthay EC, Galin J, Rudolph KE, Farkas K, Wintemute GJ, Ahern J. In-state and interstate associations between gun shows and firearm deaths and injuries: a quasi-experimental study. Ann Intern Med. 2017;167:837-44. [PMID: 29059689]. doi:10.7326/M17-1792 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Tennessee Health Science Center, Nashville, Tennessee (M.X.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0102. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoIn-State and Interstate Associations Between Gun Shows and Firearm Deaths and Injuries Ellicott C. Matthay , Jessica Galin , Kara E. Rudolph , Kriszta Farkas , Garen J. Wintemute , and Jennifer Ahern Associations Between Gun Shows and Firearm Deaths and Injuries Seth Breitbart Associations Between Gun Shows and Firearm Deaths and Injuries Alan R. Ertle Associations Between Gun Shows and Firearm Deaths and Injuries Ellicott C. Matthay , Jessica Galin , Kriszta Farkas , Kara Rudolph , Garen Wintemute , and Jennifer Ahern Metrics 3 July 2018Volume 169, Issue 1Page: 65KeywordsCrimeDisclosureFirearm injuries ePublished: 3 July 2018 Issue Published: 3 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 2891: Molecular profiling of hormone-resistant prostate cancer cells with TRPV6 oncochannel knockout/knockdown
Authors: Tyler Lutes, Michelle Davey, Christopher Rice, Tyson MacCormack, John M. Stewart, Dominique Dugourd
Journal: Cancer Research (2018)

Abstract TRPV6 calcium channel is a recognized oncochannel over-expressed in a number of epithelial cancers (e.g. breast, ovarian, prostate). TRPV6, a member of one of seven subfamilies of TRP channels, plays an important role in Ca2+ absorption from the intestinal lumen. TRPV6 over-expression is associated with a poor prognosis particularly with breast and prostate cancers. Although some TRPV6 mechanistic work is available and indicates that NFAT is involved, there is a need to better understand pathways involved in its mechanism of action (MOA). These data could allow the identification of clinically relevant biomarkers and identify potential for synergy of TRPV6-targeting therapies with other anti-cancer treatments. To determine which key pathways TRPV6 influences in prostate cancer, two TRPV6 knockouts (KO) were produced in a castration-resistant prostate cancer cell line (PC-3) using the CRISPR-Cas9 approach with two different gRNAs. In addition, knockdowns (KD) were produced by transfecting PC-3 cells with two TRPV6 siRNA targeting different regions of TRPV6 mRNA. The mRNA expression of 184 genes was analyzed using an RT-qPCR TaqMan array. The panel consisted of genes involved in cancer calcium signalling, genes that have been associated with the MOA of TRPV6 and genes directly or indirectly involved in NFAT signalling. Gene profiling results were generally consistent between the TRPV6 KD and KO cells. Results showed a dramatic reduction in expression of TRPV6 mRNA in the KO/KD cells (14 to 166-fold). TRPV6 KO/KD affected multiple genes involved in cancer cell proliferation (e.g. ESR1, CDH1), metastasis (e.g. SNAI1, MUC1/16), resistance to apoptosis (e.g. Bcl-2-type proteins, Fos) and angiogenesis (e.g. VEGFA/B, FLT4), as well as genes involved in the M2 immune tumor microenvironment (e.g. IL6 and VEGFA). The TRPV6 KO/KD data confirm the basic MOA of TRPV6, activating NFAT by increasing cytosolic calcium and provide information on the downstream pathways involved (e.g. NF-kB, estrogen and MAPK). The data allow for the identification of clinical efficacy biomarkers for TRPV6 inhibitors (e.g. a panel of CXCL12, FLT4, MUC16 and IL-6). Furthermore, results indicate TRPV6 inhibitors have the potential to modify the immune composition of the tumor microenvironment from a tumor promoting to a tumor control response, and thus may help trigger an anti-cancer immune defence. This study demonstrates a central role of TRPV6 and calcium signalling in cancer development. Citation Format: Tyler Lutes, Michelle Davey, Christopher Rice, Tyson MacCormack, John M. Stewart, Dominique Dugourd. Molecular profiling of hormone-resistant prostate cancer cells with TRPV6 oncochannel knockout/knockdown [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2891.
BMA votes to oppose Brexit “as a whole” and calls for public final say on deal
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

Doctors at the BMA’s annual representative meeting have voted to oppose Brexit “as a whole” and called for the public to have a final say on the exit deal negotiated by the government.

The backing of all seven parts of the motion means a change in BMA policy on the European Union, as it has adopted a neutral stance until now. After a debate on 27 June some 76% of representatives voted to remain in the single market, and 91% supported free movement of healthcare workers and research staff.

William Sapwell, a junior doctor who proposed the motion, said that the NHS could not afford to lose any doctors from Europe “at a time when our workforce is stretched and rota gaps …
Abstract 1858: EDNRB isoform 3 confers temozolomide resistance in human melanoma cells by modulating membrane potential, reactive oxygen species and mitochondrial Ca2+
Authors: Long Cui, Bo Liang, Xiaoting Chen, Chi Chiu Wang
Journal: Cancer Research (2018)

Abstract Background: The role of Endothelin receptor type B (EDNRB) isoform 3 involved in Temozolomide (TMZ) induced melanoma cell death has not yet been elucidated. Methods: The subcellular localization of EDNRB isoform 3 was determined by confocal and immunoblotting assays. Silencing EDNRB isoform 3 was performed by CRISPR/Cas9. Apoptosis was assessed by Annexin V/PI staining and caspases 3/7/9 activity. Mitochondrial membrane potential, reactive oxygen species and mitochondrial Ca2+ were measured by flow cytometry. Apoptosis protein array was applied. Results: Confocal and immunoblot analyses indicate mitochondrial localization of EDNRB isoform 3 and the first N-terminal (1-22) amino acids are sufficient for its mitochondrial targeting. EDNRB isoform 3 depleted A375 cells significantly inhibit apoptosis. EDNRB isoform 3 mediates chemoresistance appears to be acting via a mitochondrial apoptosis pathway as manifested by the prevention in mitochondrial depolarization, reduced reactive oxygen species, enhanced mitochondrial Ca2+ uptake and decreased caspase 9 activation. Additionally, apoptosis array shows that lack of EDNRB isoform 3 has relatively lower expression of phosphorylation of p53 at S392 and a slightly higher expression of Paraoxonase 2. Conclusion: Our findings raise the possibility of targeting EDNRB isoform 3 as new therapeutic strategy in combination with TMZ for melanoma treatment. Citation Format: Long Cui, Bo Liang, Xiaoting Chen, Chi Chiu Wang. EDNRB isoform 3 confers temozolomide resistance in human melanoma cells by modulating membrane potential, reactive oxygen species and mitochondrial Ca2+ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1858.
Abstract 5099: Evaluating Ago2 as an oncogene in Kras-dependent lung carcinoma
Authors: Andrew E. Goodrum, Lisha Wang, Alice Xu, Kristin M. Juckette, Arul M. Chinnaiyan, Jean C. Tien
Journal: Cancer Research (2018)

Abstract Background: Lung cancer is the deadliest malignancy in the United States. Non-small cell lung cancer (NSCLC) accounts for 85% of cases, and is frequently driven by activating mutations in the gene encoding the KRAS GTPase (e.g. KRASG12D). Our previous work demonstrated that Argonaute 2 (AGO2)—a component of the RNA induced silencing complex (RISC)—physically interacts with KRAS and stabilizes it at the protein level. In NSCLC cell lines, AGO2 knockdown reduces KRAS protein level and attenuates cell proliferation. We hypothesized that AGO2 acts as an oncogene in KRASG12D-dependent NSCLC in vivo. Methods: To test the hypothesis, we generated a NSCLC model by intercrossing mice harboring a stop-floxed KRASG12D allele with animals containing a tamoxifen-responsive Cre recombinase gene driven by the (clara cell-specific) CCSP promoter. These animals, which frequently die within 10 weeks of tamoxifen treatment, display pulmonary lesions including hyperplasia, adenoma and frank adenocarcinoma. We evaluated whether concomitant ablation of one or both copies of (floxed) AGO2 influenced the NSCLC phenotype. After tamoxifen administration, we monitored mice daily and harvested tissues when mice were clinically moribund or reached 16 weeks of post-treatment. We harvested lungs for gross/ pathological examination and gene/ protein expression analysis. Results: While pathologically discernable adenocarcinoma was detectable in AGO2+/+ and AGO2f/+ animals, AGO2f/f mice were free of these lesions. Despite this, deletion of AGO2 had no impact on frequency or extent of hyperplastic or adenomatous lesions. Immunohistochemistry demonstrated absence of AGO2 in tumor tissue of AGO2f/f mice. Conclusion: AGO2 promotes progression but not initiation of cancerous lesions in a mouse model of KRASG12D-dependent NSCLC. Citation Format: Andrew E. Goodrum, Lisha Wang, Alice Xu, Kristin M. Juckette, Arul M. Chinnaiyan, Jean C. Tien. Evaluating Ago2 as an oncogene in Kras-dependent lung carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5099.
PPM1D-truncating mutations confer resistance to chemotherapy and sensitivity to PPM1D inhibition in hematopoietic cells
Authors: Josephine D. Kahn, Peter G. Miller, Alexander J. Silver, Rob S. Sellar, Shruti Bhatt, Christopher Gibson, Marie McConkey, Dylan Adams, Brenton Mar, Philipp Mertins, Shaunt Fereshetian, Karsten Krug, Haoling Zhu, Anthony Letai, Steven A. Carr, John Doench, Siddhartha Jaiswal, Benjamin L. Ebert
Journal: Blood (2018)
Abstract 20768: Racial Differences in Circulating miRNA and Metabolomic Profiles of Participants in the Morehouse and Emory Team Up to Eliminate Health Disparities Study
Authors: Amanda Marie James, Karan Uppal, Sheena Thomas, Kimberly Rooney, Yi-An Ko, Herman A Taylor, Arshed A Quyyumi, Dean P Jones, Charles D Searles
Journal: Circulation (2016)

Introduction:  The extracellular detection of miRNAs has sparked interest in their role as paracrine signals and biomarkers for cardiovascular disease (CVD). Metabolomics investigates the metabolic network and specific biochemical pathways. We hypothesized that an integrative analysis of circulating miRNA and metabolomic profiles has the potential to identify novel biomarkers and enable a systems biology approach to understanding disparities in CVD. Little is known about the impact of race on these profiles, which we examined here.   Methods:  The META-Health Study was a cross-sectional study of risk factors for CVD in a group of self-reported black and white residents of Atlanta. Archived plasma samples from 52 black and 52 white participants were match by propensity scores based on CVD risk factors. High-resolution metabolomics profiling was performed on plasma, and levels of select miRNAs (miR-10b, -93, -181a, 182) were assessed by RT-qPCR of RNA extracted from microparticle (MP) fraction of plasma. Paired LIMMA analysis was used to identify differentially expressed metabolites, and Partial Least Squares method in mixOmics R package was used for miRNA-metabolome network analysis at different correlation thresholds.   Results:  Blacks had higher MP counts compared to whites (p   Conclusions:  These data demonstrate racial differences in molecular profiles and provide the basis for studies that examine the impact of CVD on these profiles. An integrative analysis of circulating metabolites and miRNAs can identify biomarkers for metabolic phenotype and provide insight into genetic and environmental influences on CVD disparities.
The Limits and Hazards of Clinical Equipoise on Cardiology Study Design and Conduct
Authors: Franklin G. Miller, Neal W. Dickert
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Right heart catheterisation is still a fundamental part of the follow-up assessment of pulmonary arterial hypertension
Authors: Marc Humbert, Jason Weatherald
Journal: European Respiratory Journal (2018)

For patients with pulmonary arterial hypertension (PAH), the most recent European guidelines state that right heart catheterisation (RHC) is mandatory for confirming the diagnosis of PAH, and that RHC should be considered 3–6 months after therapy changes and in patients who experience clinical deterioration [1, 2]. The guidelines also mention that some centres perform RHC at regular intervals during follow-up [1, 2]. However, many centres across the world do not routinely monitor invasive haemodynamic variables during follow-up, for a variety of potential reasons including the invasive nature of the test, cost or availability. We argue that, based on current data, RHC is still an indispensable component of the clinical management and follow-up of PAH patients in the current treatment era. Right heart catheterisation is still a fundamental part of the follow-up assessment of pulmonary arterial hypertension <http://ow.ly/BUUi30kbbM5>
Antibiotic prophylaxis—Preventing severe infections and saving lives in poor countries with very high mortality risk
Authors: Keith P. Klugman, Rasa Izadnegahdar
Journal: PLoS Medicine (2018)

Improvements in child survival are among the most significant achievements in global health during the 21st century.More progress is required, however, to reach the mortality targets established by the Sustainable Development Goals (SDGs).Compared to the average 2%-4% annual reduction in mortality rate for children under 5 years of age (U5MR) observed in sub-Saharan Africa during the Millennium Development Goal (MDG) era, a substantial acceleration to 6%-9% reduction per year will be required to attain these 2030 targets [1].This kind of progress requires strategic consideration of the evidence for existing tools, such as antibiotic prophylaxis, to reduce deaths in very high mortality settings (U5MR greater than 90 per 1,000 live births), which are disproportionately affected by infectious diseases [2].The top 10 of these are African countries-including Chad, Somalia, and Mali in the meningitis belt-and they include 3 large countries with the largest number of under-5-year-old deaths (Angola, Nigeria, and Democratic Republic of the Congo) [2].There are additional countries with geographic areas of mortality in excess of 90/1,000 live births, such as Niger, where 2 studies of mass antibiotic prophylaxis have recently been published [3,4].Niger is in the meningitis belt just south of the Sahara Desert, where, in addition to very high infant mortality, the population is afflicted by meningitis epidemics, during which up to 1% of the population may be affected [5].Campaigns of a conjugated meningococcal group A vaccine have substantially prevented both meningococcal disease and its transmission for a number of years [6].In high-income countries, targeted vaccination is supplemented by antibiotic prophylaxis among household contacts of cases of nonepidemic meningococcal meningitis.[7].The WHO position for antibiotic prophylaxis in the setting of meningitis epidemics is that "antibiotics are recommended as a prophylactic measure for household contacts of all ages in nonepidemic periods but not during epidemics."The guideline summarizes current data as follows:Antibiotic prophylaxis is currently recommended for household contacts of those with sporadic invasive meningococcal disease, but not for widespread use or administration to household contacts during epidemics.Thus, before an epidemic is declared, this policy should be applied for affected families.The consensus of the Guideline Development Group was that, whereas the benefit of antibiotic prophylaxis in the meningitis belt is uncertain, the cost of giving single-dose ciprofloxacin to household contacts and the risk of adverse effects are both low, such that benefit may outweigh harm even if the absolute benefit is small.However, the group did not find any new information to suggest that, during