tbuckley/cabot-search huggingface dataset:
PI3K/PTEN/Akt/mTOR pathway aberrations and co-incidence of hormone receptors and HER2 in 19,784 diverse solid tumors.
Authors: Sherri Z. Millis, Sadakatsu Ikeda, David Arguello, Rebecca Feldman, Robert Todd Maney, Joanne Xiu, Sandeep K. Reddy, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2015)

11042 Background: Molecular aberrations in the phosphatidylinositol 3-kinase (PI3K) pathway have been documented across cancers, especially PIK3CAmutations and mutation or loss of PTEN. These alterations may be relevant to therapies targeting the PI3K/PTEN/Akt/mTOR signaling pathway. Methods: Molecular profiling was performed on 19,784 tumors ( > 40 cancer types) at a CLIA-certified laboratory. Tests included next generation sequencing (NGS), protein expression (immunohistochemistry), and gene amplification (FISH or CISH). Results: Frequency and type of PIK3CA, AKT1 and PTEN mutations were collated across cancers. Aggregate gene mutation rates (47 genes), protein expression rates (18 proteins), and copy number (5 biomarkers) were measured. Comparison of frequencies and correlations across cancers identified lineage-specific differences, and co-incidences of associated biomarkers, which will be described. Of note, endometrial, breast, cervical, anal squamous cell, and bladder cancers had the highest PIK3CA mutation rate (37%, n = 1600; 31%, n = 2282; 29%, n = 284; 28%, n = 67, 22%, n = 303, respectively). Patterns in AKT1 and PTEN mutation rates differed by cancer, as did PTEN loss - hepatocellular, 57%, prostate, 52%, and endometrial 50% loss. Co-mutation of PTEN and PIK3CA occurred in 1.5% of breast, 0% of prostate, and 12% of endometrial cancers. Of interest, PIK3CA mutations and PTEN loss co-occurred frequently, e.g. 31% of PIK3CAmutated patients also have a PTEN loss. PIK3CA mutations across cancers were distributed 43% in exon 9, 33% in exon 20, and 24% in other exons. Distribution of PIK3CA mutations by cancer type varied and occurred more frequently in the absence of HER2 protein expression or copy number increase (p= 0.0001) and more frequently in the presence of hormone receptor overexpression (androgen receptor (AR), progesterone receptor (PR), and estrogen receptor (ER)) (p= 0.0335). PTEN loss was seen in 27% of patients with and 30% without HER2 overexpression or amplification (p= 0.004). Conclusions: Patterns of biomarker co-alterations across cancers may provide new insights relevant to targeted therapy and may be crucial to optimizing combination treatments.
Health Insurance and Mobile Health Devices
Authors: Inbar Raber, Cian P. McCarthy, Robert W. Yeh
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect Of Ribavirin And Interferon On The Outcome Of Critically Ill Patients With Mers
Authors: Y M Arabi, S Shalhoub, A Al Omari, Y Mandourah, F Al-Hameed, A Sindi, B Alraddadi, A Al Motairi, K Al Khatib, A A Mommin, I A Qushmaq, A Mady, O Solaiman, A Al Aithan, H H Balkhy, R Al-Raddadi, A Rajab, G A Al Mekhlafi, A Al Harthy, A Kharaba, A Al-Jabbary, R Pinto, M Sadat, H Al Mutairi, E Al Qasim, J Jose, A M Deeb, L Merson, F G Hayden, R Fowler, A S Aldawood
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Interferon and ribavirin have been used in the treatment of the Middle East Respiratory Syndrome (MERS), but the efficacy of this therapy remains uncertain. Existing data are limited by the lack of adjustment to time-dependent covariates at the time of initiation of therapy. This study objective is to examine the association of ribavirin/interferon in critically ill MERS patients using marginal structural models.
Randomized Phase 3 Trial of Amikacin Liposome Inhalation Suspension (ALIS) for Treatment-Refractory Nontuberculous Mycobacterial (NTM) Lung Disease Caused by Mycobacterium Avium Complex (MAC) in Adult Patients
Authors: D. E. Griffith, G. Eagle, R. M. Thomson, T. R. Aksamit, N. Hasegawa, K. Morimoto, D. J. Addrizzo-Harris, A. E. O'Donnell, T. K. Marras, P. A. Flume, M. R. Loebinger, L. C. Morgan, P. F. Castellotti, A. T. Hill, S. J. Ruoss, J. J. Yim, F. C. Ringshausen, S. K. Field, J. Nezamis, K. L. Winthrop
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Successful treatment of arthritis and rash with tofacitinib in systemic lupus erythematosus: the experience from a single centre
Authors: Hanxiao You, Guizhi Zhang, Qian Wang, Shangzhu Zhang, Jiuliang Zhao, Xinping Tian, Hongbin Li, Mengtao Li, Xiaofeng Zeng
Journal: Annals of the Rheumatic Diseases (2019)

Janus kinases (JAKs) are intracellular tyrosine kinases which play a key role in the signal pathways of many cytokines, such as type l interferons (IFNs), interleukin-6 (IL-6), IL-12 and IL-23.1 All these cytokines participate in the pathogenesis of systemic lupus erythematosus (SLE). Hence, inhibition of JAK signals has provided an attractive therapeutic option in SLE. Tofacitinib can inhibit JAK1/JAK3 and has been proved effective in rheumatoid arthritis (RA),2 psoriatic arthritis and ulcerative colitis. Evidence in murine lupus have shown that tofacitinib can decrease the levels of anti-double-stranded (ds) DNA and proteinuria, remit nephritis and skin rash.3 A case report proved that tofacitinib could decrease anti-dsDNA levels in inactive SLE complicated by RA.4 A phase II randomised controlled trial reported modest efficacy of a JAK1/2 inhibitor, baricitinib, in ameliorating lupus arthritis.5 

To better understand the efficacy of tofacitinib in SLE, we describe, to our knowledge for the first time, the efficacy of tofacitinib 5 mg …
SAT-409-Hepatic vein arrival time assessed by contrast-enhanced ultrasound in the non-invasive evaluation of portal hypertension
Authors: Irene Andaluz, Marta Abadía, Dolores Ponce, María Luisa Montes, Teresa Hernández, Consuelo Froilán, Miriam Romero, Araceli García, Joaquín Poza, Joan Novo, Lucía Fernández, Pilar Castillo, Javier García-Samaniego, José Carlos Erdozaín, Pedro Mora, Antonio Olveira
Journal: Journal of Hepatology (2019)
TCTAP C-092 Retrograde Recanalization of a Left Anterior Descending Artery Chronic Total Occlusion
Authors: Chun-Yuan Chu, Wen-Hsien Lee, Po-Chao Hsu, Cheng-An Chiu, Ho-Ming Su, Tsung-Hsien Lin, Chee-Siong Lee, Heueh-Wei Yen, Wen-Chol Voon, Wen-Ter Lai
Journal: Journal of the American College of Cardiology (2019)
Climate Change, Human Health, and Social Stability: Addressing Interlinkages
Authors: Samuel Sellers, Kristie L. Ebi, Jeremy Hess
Journal: Environmental Health Perspectives (2019)

Abundant historical evidence demonstrates how environmental changes can affect social stability and, in turn, human health. A rapidly growing body of literature, largely from political science and economics, is examining the potential for and consequences associated with social instability related to current climate change. However, comparatively little of this research incorporates the effects on human health or the role of health systems in influencing the magnitude and types of instability that could occur.The objective of this commentary is to articulate a conceptual framework incorporating health outcomes and health systems into theorized and observed linkages between climate change and social instability, illustrating in particular the health effects of natural resource shortages, infectious disease outbreaks, and migration.Although increasing evidence exists that climate change, health, and social instability are related, key questions remain about the pathways linking these factors, as well as the magnitude, causality, and directionality of relationships across spatial and temporal scales. Models seeking to explain and predict climate-related social unrest should incorporate the many linkages between climate change, human health, and social instability. Members of the environmental health research community should work closely with those in the political science and economics communities to help deepen understandings of climate-related stressors and shocks that affect instability and worsen health outcomes. https://doi.org/10.1289/EHP4534.
Prevalence of hypogonadism in patients with previously treated germ cell tumors.
Authors: Trent James Miller, Lawrence H. Einhorn, Nasser H. Hanna, Victoria Champion, Patrick Monahan, Timothy E. Stump, Mary J. Brames, Somer Case-Eads
Journal: Journal of Clinical Oncology (2015)

9576 Background: The vast majority of men with germ cell tumors (GCT) will be cured of their disease and may face long-term risks associated with survivorship. This may include hypogonadism (HG), which can be associated with depression, fatigue, and a lower quality of life (QOL). It is thus important to identify the prevalence of HG and correlation with symptoms in survivors of GCT, both in patients treated with platinum combination chemotherapy (PCC) as well as chemo-naïve patients. Methods: Patients treated with chemotherapy (Group 1) or with orchiectomy and/or other surgery or radiotherapy for GCT (Group 2), were 18-50 yrs of age, and not receiving supplemental testosterone at baseline were eligible. Total testosterone was measured at baseline and at 3, 6, and 12 mos. Either A.M. and P.M. lab draws were done depending upon time of patient follow-up. HG was defined as a serum total testosterone < 300 ng/dl. Cancer diagnosis and treatment variables were obtained from medical records. Patients completed a validated QOL questionnaire at baseline, 3, and 6 mos. Results: We evaluated 172 patients treated for GCT. The overall prevalence of HG at baseline was 49.4% (95% CI 41.9-57.0). In Group 1 (N = 103), prevalence was 51.5% (95% CI 41.7-61.2). In Group 2 (N = 69), prevalence was 46.4 (95% CI 34.5-58.3). Overall prevalence of HG was not statistically different between the two groups (p = 0.5371). Within Group 1, there was no difference in prevalence of HG when patients were divided into those who received < 3 cycles of PCC, 3 cycles of PCC, > 3 cycles of PCC, or salvage chemo (p = 0.8131). Overall, compared to patients with testosterone ≥ 300, patients with baseline testosterone < 300 reported worse perceived general health (p = 0.0003) and worse sleep quality (p = 0.0344), but no statistically significant difference in depression (p = 0.3131) or fatigue (p = 0.0622). Conclusions: The overall prevalence of HG is higher than would be expected in the general population. Testosterone levels are lower in the P.M., so the prevalence may have been artificially high due to P.M. as well as A.M. lab draws. There was no difference between the prevalence of HG between the two groups. HG can be a potential cause of medical and psychological distress if not recognized and treated.
Pathogenesis and biomarkers of natural killer T cell lymphoma (NKTL)
Authors: Nagavalli Somasundaram, Jing Quan Lim, Choon Kiat Ong, Soon Thye Lim
Journal: Journal of Hematology & Oncology (2019)

Natural killer T cell lymphoma (NKTL) is an aggressive disease with very poor treatment outcomes in the advanced stages. With chemotherapy, initial response rates to treatment are high but responses are short lived. A better understanding of the complex molecular pathogenesis of this disease is essential in order to design and develop better therapeutics with improved efficacy. This review aims to summarise the key pathogenic mechanisms in NKTL which may have significant prognostic and therapeutic implications.
Intimate Partner Homicide of Adolescents
Authors: Avanti Adhia, Mary A. Kernic, David Hemenway, Monica S. Vavilala, Frederick P. Rivara
Journal: JAMA Pediatrics (2019)

Intimate partner violence during adolescence is widespread, and consequences can be severe. Intimate partner homicide (IPH) is the most extreme form of intimate partner violence, but literature on IPH has almost exclusively focused on adults.To determine the proportion of adolescent homicides that is perpetrated by intimate partners and to describe the victim, perpetrator, and incident characteristics of these IPHs.Analysis of quantitative and qualitative surveillance data from the National Violent Death Reporting System from 2003 to 2016. Data represent 32 states that contributed to the system for 1 year or longer. There were 8048 homicides of victims aged 11 to 24 years with a known relationship between the victim and perpetrator. For persons aged 11 to 18 years, there were 2188 homicides. Analysis began September 2018.An incident was identified as an IPH if the relationship between the perpetrator and victim was coded as spouse, ex-spouse, girlfriend or boyfriend, ex-girlfriend or ex-boyfriend, or girlfriend or boyfriend (unspecified current or former). Variables of interest included demographic characteristics (age, sex, race/ethnicity) for the victim and perpetrator, relationship status at time of death, homicide-suicide, homicide method, firearm type, and location of homicide. Contextual categories were created from the qualitative narratives.Of adolescent homicides, 150 (6.9%) were classified as IPH. A total of 135 victims (90%) were female (mean [SD] age, 16.8 [1.3] years). Overall, 102 perpetrators (77.9%) were 18 years and older (mean [SD] age, 20.6 [5.0] years), and 94 (62.7%) were current intimate partners of the victim. Firearms, specifically handguns, were the most common mechanism of injury. Compared with IPHs of young adults aged 19 to 24 years, perpetrators of adolescent victims were younger and less likely to be a current intimate partner. The most common categories of adolescent IPH homicides were broken/desired relationship or jealousy and an altercation followed by reckless firearm behavior and pregnancy related.Adolescents, particularly girls, in dating relationships may face risk of homicide, especially in circumstances of a breakup or jealousy and when perpetrators have access to firearms. Understanding homicide in early dating relationships can inform prevention and intervention efforts tailored to adolescents.
Retrospective analysis comparing pulmonary toxicity between S-1 and docetaxel in non-small-cell lung cancer patients with preexisting interstitial lung disease.
Authors: Daisuke Akahori, Yuichi Ozawa, Keigo Kouda, Takefumi Abe, Yasunori Enomoto, Hirotsugu Hasegawa, Masayuki Tanahashi, Takashi Matsui, Hiroshi Niwa, Koshi Yokomura, Takafumi Suda
Journal: Journal of Clinical Oncology (2015)

e19105 Background: Preexisting interstitial lung disease (ILD) is associated with a risk of chemotherapy-related acute lung disease (CRALD), which is similar among anti-cancer agents including docetaxel (DTX), pemetrexed, and amrubicin—20%–30% frequency and fatal results in one-third to one-half although there is no comparative trial before. S-1 is an oral anticancer fluoropyrimidinic agent used against non-small-cell lung cancer in Japan, but its pulmonary toxicity remains unknown. Methods: Clinical and radiological data of non-small-cell lung cancer patients who received S-1 or DTX at Seirei Mikatahara General Hospital from 1/1/2006 to 11/30/2014 were reviewed and cases diagnosed with ILD before S-1 or DTX administration were evaluated. CRALD was diagnosed as newly emerged non-segmental ground-glass or consolidated opacity within 30 days after the final administration of S-1 or DTX with no findings indicating pulmonary infection or heart failure. Results: ILD was diagnosed in 65/251 and 93/359 patients who received S-1 and DTX, respectively. Respective patient demographics were as follows: PS (0–1/2–3) 61/4, 86/7; single/combined with platinum 40/25, 70/23; line of administration (1st/2nd/3rd or later) 17/17/31, 25/43/25; usual interstitial pneumonia compatibility of preexisting ILD (definite/possible/inconsistent) 19/27/19, 38/33/22; and area occupied by preexisting ILD (0–10/10–25/25–40/ > 40%) 28/27/6/4, 42/40/8/3. CRALD was found in two S-1 (3%) and 17 DTX (18%) patients, among whom one S-1 and eight DTX patients died due to respiratory failure. Age- and sex- adjusted multivariate analysis showed significantly less risk with S-1 (vs. DTX) (odds ratio 0.142, p = 0.011). CRALD frequency among patients with ILD occupying < 25% of lung field was 0% (0/55) in S-1 and 18% (15/82) in DTX (p < 0.001), while it was similar among patients with ILD occupying > 25% (20%, 18%; p = 0.916). Conclusions: Based on the less pulmonary toxicity, S-1 could be a favorable alternative to DTX for the patients with ILD, particularly when the ILD occupies < 25% of the lung field. Further clinical trial of S-1 for patients with preexisting ILD is warranted.
Revising Our Standards on Dual-Role Physicians: Proceed, but Proceed With Caution
Authors: Stephen A. Berman, Luciana Garbayo
Journal: The American Journal of Bioethics (2019)

"Revising Our Standards on Dual-Role Physicians: Proceed, but Proceed With Caution." The American Journal of Bioethics, 19(4), pp. 49–50
Abstract 14748: Microalbuminuria, Impaired Glucose Tolerance, and Their Prognostic Implications in Patients With Chronic Heart Failure: Insights From the SUPPlemental Benefit of an Angiotensin Receptor Blocker in Hypertensive Patients With Stable Heart Failure Using OlmesaRTan (SUPPORT) Trial
Authors: Kotaro Nochioka, Yasuhiko Sakata, Takuya Oikawa, Ruri Abe, Shintaro Kasahara, Masayuki Sato, Hajime Aoyanagi, Takashi Shiroto, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2017)

Introduction: Diabetes mellitus (DM) is a strong prognostic factor in patients with chronic heart failure (CHF), especially when complicated by microalbuminuria (MA). However, little is known about...
Efficacy of 150 kHz tumor treating fields (TTFields) and cisplatin or pemetrexed for the treatment of mesothelioma cells in vitro
Authors: U. Weinberg, M. Munster, K. Gotlib, R.S. Schneiderman, Y. Porat, T. Voloshin Sela, S. Davidi, A. Shteingauz, N. Kaynan, E. Zeevi, M. Giladi, E. Kirson, A. Kinzel, Y. Palti
Journal: Annals of Oncology (2019)

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive thoracic cancer that has been strongly linked to asbestos exposure. The standard of care treatment for unresectable mesothelioma is cisplatin plus pemetrexed chemotherapy, which offers modest outcomes. Thus, there is an urgent need to identify more effective treatments for mesothelioma patients. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. We explored the potential use of TTFields alone and in combination with cisplatin or pemetrexed as a treatment for mesothelioma. Methods: NCI-H2052 and MSTO-211H cells were treated at various TTFields frequencies for 72 hours using the inovitro system. Results: The optimal TTFields frequency leading to the highest reduction in cell counts was 150 kHz for both NCI-H2052 and MSTO-211H cells. TTFields application (1.1 V/cm, 72 hours) at 150 kHz led to 45%, 51% reduction in cell counts and 64%, 46% reduction in clonogenic potential in NCI-H2052 and MSTO-211H cells, respectively. Efficacy of the combined treatment of TTFields and cisplatin or pemetrexed was tested by applying TTFields at the optimal frequency together with various drug concentrations. The combined treatment of TTFields and cisplatin or pemetrexed led to a significant reduction in cell count, induction of apoptosis and reduced clonogenic potential as compared to either modality alone (2-way ANOVA, p < 0.0001(. Safety studies did not reveal any adverse event associated with 150 kHz TTFields application to the rat torso. Conclusions: These results demonstrate that TTFields can be an effective treatment against mesothelioma cells and that the combination with cisplatin or pemetrexed may further enhance treatment efficacy. These results are supported by a recent phase 2 study, which reported that MPM patients treated with the combination of TTFields with pemetrexed and platinum experienced improved overall survival as compared to historical control with no increase in systemic toxicity. Legal entity responsible for the study: Novocure Israel. Funding: Novocure Israel. Disclosure: U. Weinberg, M. Munster, R.S. Schneiderman, Y. Porat, T. Voloshin Sela, A. Shteingauz, E. Zeevi, M. Giladi, A. Kinzel, Y. Palti: Full time employee, stock options, stock ownership: Novocure Israel. K. Gotlib, S. Davidi, N. Kaynan: Full time employee, stock options: Novocure Israel. E. Kirson: Full time employee stock options, stock ownership: Novocure Israel; Holds senior leadership position: Novocure Israel.
TCT-455 Angiographic derived Endothelial Shear Stress: a new predictor of atherosclerotic disease progression
Authors: Michalis Hadjiandreou, Lorenz Raber, Ryo Torii, Xiaohui Shen, Alexios Karagiannis, Kyohei Yamaji, Taniwaki Masanori, Antonis Sakellarios, Maria Radu, Aris Moschovitis, Dik Heg, Fanis Kalatzis, Dimitrios Fotiadis, Lampros Michalis, Patrick Serruys, Hector Garcia-Garcia, Christos Bourantas, Stephan Windecker
Journal: Journal of the American College of Cardiology (2017)
THU-090-Non-invasive fibrosis scores (APRI, FIB4 index, BARD): Useful tools for evaluating fatty liver disease
Authors: Alina Popescu, Ioan Sporea, Camelia Foncea, radu cotrau, Alexandra Christa Sima, Adina Braha, Roxana Sirli, Mirela Danila, Nistorescu Silviu, Raluca Lupusoru, Diana Gherhardt, Romulus Timar
Journal: Journal of Hepatology (2019)
Exclusive: Trainees can face fees of £65 a night to stay in hospital during 24 hour non-resident on-call shifts
Authors: Abi Rimmer
Journal: BMJ (2019)

Junior doctors are calling for a change in their contracts to ensure that no one is charged to stay overnight in hospital accommodation, after an investigation found that one in five acute trusts in England asked trainees to pay as much as £65 a night.

The trainees’ section of the British Association of Urological Surgeons conducted a freedom of information investigation into accommodation charges for doctors working a 24 hour non-resident on-call shift as part of its #DontPayToStay campaign.1

It sent the request to 213 trusts in England and received responses from 182 (response rate 93%). Of these, 145 had rooms available for non-resident on-calls, and 30 trusts (20%) charged trainees to use them.

Charges ranged from £65 a night at St George’s University Hospitals NHS Foundation Trust in London to £9.14 at Warrington and Halton Hospitals NHS Foundation Trust. The median charge was …
Retraction notice to "Polyethylenimine Nanoparticles as Efficient Transfecting Agents for Mammalian Cells” [Journal of Controlled Release 110/2 (2005) 457–468]
Authors: Surendra Nimesh, Anita Goyal, Vikas Pawar, Sujatha Jayaraman, Pradeep Kumar, Ramesh Chandra, Yogendra Singh, Kailash C. Gupta
Journal: Journal of Controlled Release (2019)
Intramural esophageal dissection during peroral endoscopic myotomy
Authors: Liansong Ye, Jingsun Jiang, Saowanee Ngamruengphong, Wenjuan Yang, Linjie Guo, Yuhang Zhang, Bing Hu
Journal: Endoscopy (2019)

See also: Tips and tricks for avoiding the dreaded intramural esophageal dissection during peroral endoscopic myotomy: recognize!Endoscopy 2019; 51(10): 996-996DOI: 10.1055/a-0958-2395