tbuckley/cabot-search huggingface dataset:
Sarcomatoid Renal Cell Carcinoma Has a Distinct Molecular Pathogenesis, Driver Mutation Profile, and Transcriptional Landscape
Authors: Zixing Wang, Tae Beom Kim, Bo Peng, Jose Karam, Chad Creighton, Aron Joon, Fumi Kawakami, Patricia Trevisan, Eric Jonasch, Chi-Wan Chow, Jaime Rodriguez Canales, Pheroze Tamboli, Nizar Tannir, Christopher Wood, Federico Monzon, Keith Baggerly, Marileila Varella-Garcia, Bogdan Czerniak, Ignacio Wistuba, Gordon Mills, Kenna Shaw, Ken Chen, Kanishka Sircar
Journal: Clinical Cancer Research (2017)

Purpose: Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity.Experimental Design: We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of nonsarcomatoid RCC (RCC). We evaluated whole-exome sequencing, single-nucleotide polymorphism, and RNA sequencing data from patients with SRCC (n = 65) and RCC (n = 598) across different parent RCC subtypes, including clear-cell RCC, papillary RCC, and chromophobe RCC subtypes.Results: SRCC was molecularly discrete from RCC and clustered according to its parent RCC subtype, though with upregulation of TGFβ signaling across all subtypes. The epithelioid (E-) and spindled (S-) histologic components of SRCC did not show differences in mutational load among cancer-related genes despite a higher mutational burden in S-. Notably, sarcomatoid clear-cell RCC (SccRCC) showed significantly fewer deletions at 3p21-25, a lower rate of two-hit loss for VHL and PBRM1, and more mutations in PTEN, TP53, and RELN compared with ccRCC. A two-hit loss involving VHL predicted for ccRCC and a better prognosis, whereas mutations in PTEN, TP53, or RELN predicted for SccRCC and worse prognosis.Conclusions: SRCC segregates by parent subtype, and SccRCC has a fundamentally different early molecular pathogenesis, usually lacking the classic 3p21-25 deletion and showing distinctive mutational and transcriptional profiles. These features prompt a more precise molecular classification of RCC, with diagnostic, prognostic, and therapeutic implications. Clin Cancer Res; 23(21); 6686-96. ©2017 AACRSee related commentary by Bergerot et al., p. 6381.
New law will force hospitals to charge foreign patients for non-urgent care
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The UK government is to press ahead with plans to make it a legal requirement for NHS hospitals to charge foreign visitors and migrants upfront for any non-urgent care received as part of its crackdown on so called health tourism.

New regulations—to be laid out in parliament “in due course,” a Department of Health spokesperson said—will kick start the government’s bid to recover £500m (€570m; $640m) a year in costs of treatment of patients from countries inside and outside the European Economic Area by the end of 2017-18, a target that the National Audit Office has said ministers will struggle to meet.1

The plans, initially set to be implemented on 1 April 2017,2 seemed to have …
Mu opioid receptor stimulates a growth promoting and pro-angiogenic tumor microenvironment
Authors: Mariya Farooqui, Tasneem Poonawala, Robert W. Griffin, Julia Nguyen, Robert P. Hebbel, Kalpna Gupta
Journal: Cancer Research (2005)

4650   We observed that morphine stimulates MAPK/ERK and PKB/Akt signaling in endothelial cells and promotes proliferation, migration and survival leading to increased angiogenesis and tumor growth in mice (Gupta et al 2002, Cancer Res). Morphine and other opioid analgesics are mu opioid receptor (MOR) agonists, which act centrally as well as peripherally directly and by modulating the secretion of cytokines. Therefore, we examined the role of MOR in endothelium and cancer progression using MOR deleted (MOR-KO) and wild type (wt) mice. We isolated and cultured blood outgrowth endothelial cells (BOEC) and implanted T241 fibrosarcoma tumor cells for in vitro and in vivo studies, respectively. MOR-KO derived BOEC assume round shape after 3 days in culture at P1 and undergo significant apoptosis Vs the wild type BOEC (p
The disappointments of the double helix: a master theory
Authors: James Le Fanu
Journal: Journal of the Royal Society of Medicine (2010)

For James Watson, ‘A structure this pretty just had to exist’.1 For Maurice Wilkins, ‘The structure was too perfect to be wrong’.2 Horace Judson, in his magisterial history of molecular biology The Eighth Day of Creation, described it as ‘flawlessly beautiful … truly for the first time at the ultimate biological level structure had become one with function’.3 And, ever since Watson and Crick's letter to Nature of April 25 1953 – with its famous throwaway line ‘it has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material’ – science has been seduced by the elegant simplicity of the double helix into supposing that if we could only decode its genetic instructions, we would understand the programme that makes an organism.4
Ketamine for the Treatment of Depression
Authors: Samad E. J. Golzari, Ata Mahmoodpoor
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
Abstract 45: Systemic Illness in Ece1 Ablated Adult Mice
Authors: Jasmin Kristianto, Michael Johnson, Abigail Radcliff, Jill Koch, Timothy Hacker, Forum Patel, Ryley Zastrow, Xiaohu Wang, Baozhi Yuan, Robert Blank
Journal: Circulation Research (2015)

Endothelin converting enzyme-1 (ECE1) catalyzes the conversion of inactive big endothelin 1 (ET1) to active ET1. Homozygous Ece1 knock out (KO) mice die in utero or at birth, displaying multiple abnormalities including mandibular hypoplasia and cardiac outflow tract malformations, in spite of the presence of ample tissue ET1. However, increased ECE1 activity and circulating and/or tissue ET1 are associated with many adult cardiovascular diseases, including idiopathic pulmonary fibrosis (IPF), a chronic and fatal lung disease. There is an apparent paradox between the need for ET1 in development and its harmful effects in adult disease. Therefore, our lab developed a conditional Ece1 KO mouse, in which Ece1 is ablated following tamoxifen (tam) treatment. We hypothesized that ECE1 serves to localize ET1 signals to specific cell populations and is essential in normal adult physiology. We studied the following groups: mice given vehicle rather than tam, mice lacking tam-inducible Cre recombinase, mice harboring a normal Ece1 allele ( Ece1 +/flox ), and the experimental animals (Cre Ece1 -/flox ). Mice were treated with vehicle or tam at 8-9 weeks of age. Cre Ece1 -/flox mice showed 85-100% mRNA knock-down efficiency 8 weeks after tam treatment. By 17 weeks of age, Cre Ece1 -/flox mice have tachypnea, decreased activity, and weight loss, requiring euthanasia for humane considerations. They display depleted adipose tissue mass compared to controls. By two weeks after treatment, Cre Ece1 -/flox mice had lower blood pressure relative to controls, which persisted until euthanasia at 17-20 weeks old (p=0.004). Between 17-20 weeks of age, most of Cre Ece1 -/flox mice develop pectus excavatum, enlarged right hearts and have reduced stroke volume and cardiac output as analyzed by echocardiography. Histological examination revealed eosinophilic crystalline pneumonia and increased collagen in the lung and heart. These findings are consistent with development of IPF in the experimental mice. Our findings show that Ece1 ablation in post-natal animal results in a severe cardiorespiratory disease, suggesting that ectopic activation of ET1 by other tissue proteases is the primary mechanism underlying the association of increased ET1 signaling in disease states.
17 Comparison of low volume polyethylene glycol-electrolyte solution (PEG-ELS) and phosphate enema in flexible sigmoidoscopy: a large retrospective study
Authors: A Yusuf, S Paranahewa, P Mayhead
Journal: Gut (2017)

Background  Flexible sigmoidoscopy is a popular method for examining the left side of the colon, but adequate bowel cleansing is critical for detection of mucosal abnormalities, and for minimising the number of repeat procedures. It has, however, long been debated which method, oral preparation or enema, gives the best results.  Aim  At our unit both oral and phosphate enema preparations are utilised, and we therefore wanted to find out which type of preparation gives best results.  Methods  Patients who underwent flexible sigmoidoscopy from 1 st  February to 31 st  July 2016 were retrospectively reviewed using our endoscopy reporting system. Their demographics and the individually achieved quality of bowel preparation (subjectively graded as: Excellent, Adequate or Inadequate) were analysed. A chi-squared test was used calculate p-values.  Results  1054 patients underwent flexible sigmoidoscopy during the study period, of whom 822 were included in this study, after excluding 232 patients (22.01%) due to: no bowel preparation (n=69), no documentation of quality of bowel preparation (n=151) and other reasons (n=12). 494 (46.87%) patients (males 248 (50.20%), mean age 60.48 years, range 15-94 years) had oral preparation with low volume polyethylene glycol-electrolyte solution (PEG-ELS), and 491 (46.58%) (males 245 (49.90%), mean age 65.49 years, range 18-98 years) had phosphate enema. The outcomes are summarised in the table below.  Conclusions  Our relatively large retrospective study showed that oral preparation with PEG-ELS resulted in significantly better bowel preparation compared to phosphate enema. PEG-ELS is now the preferred option in our unit where there is no contraindication for this.
Serotonergic Modulation Enables Pathway-Specific Plasticity in a Developing Sensory Circuit in Drosophila
Authors: Takuya Kaneko, Ann Marie Macara, Ruonan Li, Yujia Hu, Kenichi Iwasaki, Zane Dunnings, Ethan Firestone, Shawn Horvatic, Ananya Guntur, Orie T. Shafer, Chung-Hui Yang, Jie Zhou, Bing Ye
Journal: Neuron (2017)
DNA hypermethylation phenotypes and one carbon metabolism genetic variants in breast tissues from normal healthy women
Authors: Ramona Dumitrescu, Catalin Marian, Shiva Krishnan, Scott Spear, Bhaskar Kallakury, Francoise Seillier-Moiseiwitsch, Habtom Ressom, Jo Freudenheim, Peter Shields
Journal: Cancer Research (2008)

1   Hypermethylation of tumor suppressor genes promoter region may have important implications in understanding breast cancer etiology. In this study, we examined potential determinants of DNA hypermethylation in normal breast tissue, including genetic variants for genes important to one-carbon metabolism in relation to hypermethylation.   We recruited 141 women without a history of breast or other cancers, who were undergoing reduction mammoplasty. These women underwent a structured interview and donated breast tissue and blood. Hypermethylation phenotypes for  p16  INK4 , BRCA1,  ERα   and  RAR-β  from the normal breast tissues were determined by MSP and Pyrosequencing assays. Genetic variants of  MTHFR  and  MTR  genes were determined by TaqMan assays. Chi-square, t tests and logistic regression model were used to determine the association between promoter hypermethylation of these genes and genotypes and other characteristics of these women.  The mean age of women was 35+/-12 years.  p16  INK4 , BRCA1,  ERα  and  RAR-β  promoter hypermethylation was identified in 31%, 16% 9% and 0% of women respectively. Race was significantly associated with the methylation status (p-value=0.03). When we stratified these women by race we observed that  p16  INK4  hypermethylation was associated with family history of cancer, with the variant allele of the  MTR A2756G  polymorphism and marginally associated with alcohol consumption (p-value=0.01; 0.02 and 0.05)  only in Caucasian women. There were no significant associations for African-American women.  BRCA1  hypermethylation was significantly associated with family history of cancer (p-value=0.03) for African-American women. Family history of cancer in Caucasians and family history of breast cancer for African-American women were weakly associated with  BRCA1  methylation (p-value=0.09; 0.06 respectively).  ERα  methylation phenotype was significantly correlated with the age of both Caucasian and African-American women (p MTR 2756G  were also weakly associated with  ERα  hypermethylation in African-American women (p-value=0.08; 0.08 and 0.09 respectively).  The presence of hypermethylation of important tumor suppressor genes was a common finding in apparently healthy women without history of breast cancer. Several known risk factors for breast cancer were associated with increased risk of hypermethylation, as were genetic variants for  MTR  gene. There were important differences in these associations by race. Understanding the determinants of hypermethylation in normal breast tissues can provide insight into a potentially significant mechanism for breast carcinogenesis.  Supported by: DOD BC022346
FRI0490 Real-life effectiveness of tnf inhibitors in psoriatic arthritis: are changing national policies on choice of tnf inhibitor reflected in response to treatment?
Authors: EK Kristianslund, KM Fagerli, E Lie, A Wierød, S Kalstad, E Rødevand, F Krøll, P Mielnik, TK Kvien, IC Olsen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tumour necrosis factor inhibitors (TNFi) are essential in the treatment of psoriatic arthritis (PsA). Whether the effectiveness of the five different TNFi differs is not known, as they have not been directly compared. In Norway the national authorities consider the TNFi to be equivalent, and since 2009 the least expensive drug in an annual national tender has been preferred in the publicly funded healthcare system. This has led to substantial year-to-year differences in chioce of first TNFi, the system has acted as an unbiased factor distributing patients between different agents across years. <h3>Objectives</h3> Comparing response to TNFi during the first year of treatment of PsA over years with highly varying uptake of different TNFi. <h3>Methods</h3> From the NOR-DMARD register we included the 715 biologics-naïve patients with PsA who started their first TNFi from 2009 through 2015. The preferred TNFi in national recommendations were: 2009 adalimumab, 2010 golimumab, 2011 and 2012 etanercept, 2013 golimumab, 2014 certolizumab, 2015 certolizumab/biosimilar infliximab (CT-P13). The estimated Disease Activity Score 28 joints (DAS28) at 3, 6 and 12 months after treatment start was compared between treatment years using a mixed-model, adjusted for baseline disease activity, age, sex and treatment centre. <h3>Results</h3> Demographics, choice of TNFi and baseline characteristics are listed for each year 2009–2015 in Table 1. The preferred drug was started in 56–91% of patients. There was a trend towards lower disease activity at baseline over time. There were no significant differences in DAS28 at 3 and 6 months between treatment years, but a difference was found at 1 year (figure). <h3>Conclusions</h3> The results from this innovative analytic approach indicate similar effectiveness of different TNFi in PsA, and consequently supports the practice of selecting agent based on cost and feasibility of use. However, there are potential differences after 1 year. The interpretation of this is challenging, especially as there is a marked difference in outcomes between the years 2011 and 2012, where the distribution of type of TNFi was similar. <h3>Disclosure of Interest</h3> E. K. Kristianslund: None declared, K. M. Fagerli: None declared, E. Lie Consultant for: AbbVie, Celgene, Hospira, Pfizer, UCB., A. Wierød: None declared, S. Kalstad: None declared, E. Rødevand: None declared, F. Krøll: None declared, P. Mielnik: None declared, T. K. Kvien Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, UCB, I. C. Olsen: None declared
FRET-enabled monitoring of the thermosensitive nanoscale assembly of polymeric micelles into macroscale hydrogel and sequential cognate micelles release
Authors: Pingsheng Huang, Huijuan Song, Yumin Zhang, Jinjian Liu, Zhen Cheng, Xing-Jie Liang, Weiwei Wang, Deling Kong, Jianfeng Liu
Journal: Biomaterials (2017)
Tubulointerstitial fibrosis can sensitize the kidney to subsequent glomerular injury
Authors: Beom Jin Lim, Jae Won Yang, Jun Zou, Jianyong Zhong, Taiji Matsusaka, Ira Pastan, Ming-Zhi Zhang, Raymond C. Harris, Hai-Chun Yang, Agnes B. Fogo
Journal: Kidney International (2017)
HIV Is Associated with a High Rate of Unexplained Multilineage Cytopenias and Portends a Poor Prognosis in Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
Authors: Justin Kaner, Santiago Thibaud, Ashwin Sridharan, Amer Assal, Rahul Polineni, Barry Zingman, Anjali Sharma, Harold Kunal Elias, Louis Weiss, Murali Janakiram, Ira Braunschweig, Swati Goel, Ulrich Steidl, Kith Pradhan, Aditi Shastri, Britta Will, Ioannis Mantzaris, Mark Chaitowitz, Amit Verma
Journal: Blood (2016)
Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone
Authors: Kristian F. Axelsson, Anna G. Nilsson, Hans Wedel, Dan Lundh, Mattias Lorentzon
Journal: JAMA (2017)

<h3>Importance</h3> Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids. <h3>Objective</h3> To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects. <h3>Design, Setting, and Participants</h3> Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (≥5 mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014. <h3>Exposures</h3> Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation. <h3>Main Outcomes and Measures</h3> The primary outcome was incident hip fracture. <h3>Results</h3> Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of −17.6 (95% CI, −24.8 to −10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years;<i>P</i> = .40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years;<i>P</i> = .86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group. <h3>Conclusions and Relevance</h3> Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.
French comment on article Elipse, the first procedureless gastric balloon for weight loss: a prospective, observational, open-label, multicenter study1 Le ballon intra gastrique ingérable sans endoscopie Elipse: essai ouvert multicentrique observationnel
Journal: Endoscopy (2017)

Les données épidémiologiques estiment à plus de 2 milliards le nombre d’individus en excès de poids ou obèses selon les critères de l’OMS. Si la chirurgie bariatrique a clairement démontré son bénéfice sur la réduction de la morbi-mortalité liée à l’obésité morbide, il existe une place grandissante pour des alternatives mini invasives. Le ballon intra gastrique (BIG), mis en place et retiré sous contrôle endoscopique, est efficace en termes de perte d’excès de poids, avec une efficacité tendant à diminuer à distance de son explantation. Le BIG Elipse® est un nouveau dispositif qui ne requiert aucune endoscopie pour la pose ni la dépose du ballon. Il s’agit d’un BIG qui est ingéré sous contrôle scopique par le malade et gonflé à l’eau (550 ml) via un fin cathéter lorsque son positionnement intra gastrique est satisfaisant. Le BIG reste en place 4 mois avant que son revêtement ne se résorbe: il se dégonfle et les fragments du ballon sont évacués par le transit. Cet article rapporte les résultats d’un essai bicentrique chez 34 malades obèses. 3 malades ne parvinrent pas au terme du suivi: le ballon du premier était défectueux, 2 patients présentaient une intolérance nécessitant sa dépose. Le BIG était ingéré et gonflé sous contrôle médical, en ambulatoire. Un traitement IPP était prescrit pendant la durée de l’étude, associé à un traitement anti émétique les premiers jours. Au cours du suivi, quatre malades ont présenté des vomissements avec expulsion du ballon, vers la seizième semaine de prise en charge. Tous les autres ballons étaient évacués dans les selles. La perte de poids constatée à 4 mois était de 10 % (± 6,6), la diminution d’IMC était de 3,9 (± 3,1), la diminution du taux d’HbA1c était de 0,16 % (± 0,16), toutes ces valeurs étaient significatives. De même, la diminution du tour de taille, l’amélioration des taux de LDL-cholestérol et de triglycérides, la diminution de la pression artérielle étaient significatives.