tbuckley/cabot-search huggingface dataset:
OC-050 A national survey on prevalence, diagnosis, management and service provision for narcotic bowel syndromein the u.k
Authors: E Kilgallon, DH Vasant, PL Shields, PA Paine
Journal: Gut (2017)

Introduction  Narcotic bowel syndrome (NBS) is characterised by chronic abdominal pain that worsens or fails to respond to increasing opioid doses. Limited benefit and harmful effects of long-term opiates, with resultant morbidity, mortality and healthcare use are well documented. We aimed to evaluate current UK clinical practice and services for diagnosis and management of NBS.  Method  A 27 item electronic questionnaire (surveymonkey) was developed to establish clinicians’ perspectives on demographics, clinical phenotype and management of NBS patients. After a regional pilot study this was circulated nationally via the BSG.  Results  47 responses were received (96% gastroenterologists, 57% at teaching hospitals (TH), 30% at district general hospitals (DGH)) with almost all respondents (94%) having made a prior NBS diagnosis.  Demographics  Reported NBS prevalence was low (57% of clinicians with   Diagnosis  The most popular criteria used to make a NBS diagnosis were ‘chronic abdominal pain’ (91%) and ‘long term opiate use’ (91%), whereas presence of a ‘soar and crash response’ (34%) and ‘pain that is progressing over time’ (30%) were least frequently used. Only 3/47 (6%) respondents use Rome IV criteria.  Management  70% offer opiate withdrawal as either inpatient or outpatient. Surprisingly, only 51% prescribe non-opioid analgesia in NBS. Of these Amitriptyline (64%), Gabapentin (55%) and Pregabalin (53%) were reported to be the most useful. Clinicians at TH were more likely to prescribe non-opioid analgesia than at DGH (p=0.006). Up to 1/4 of NBS patients require nutritional support according to a majority (62%) of respondents. The most common form of nutritional support was oral (83%), then nasogastric (45%) and jejunal tube (43%). 33% had used parenteral nutrition in a NBS patient.   Referral to additional services:  77% refer to a chronic pain team, 36% to clinical psychology and 21% to tertiary services. In most centres (87%) there is no designated service to manage NBS and no access to clinical psychology (56%). In centres without access to NBS services, 76% believed their hospital would benefit from the development of a service.  Conclusion  This survey has identified wide variation in clinical practice when diagnosing and managing NBS, and a national demand for improving and developing access to specialist services in the UK.  Disclosure of Interest  None Declared
Selective factor VIII activation by the tissue factor–factor VIIa–factor Xa complex
Authors: Yuichi Kamikubo, G. Loredana Mendolicchio, Antonella Zampolli, Patrizia Marchese, Andrea S. Rothmeier, Jennifer Nagrampa Orje, Andrew J. Gale, Sriram Krishnaswamy, András Gruber, Henrik Østergaard, Lars C. Petersen, Wolfram Ruf, Zaverio M. Ruggeri
Journal: Blood (2017)
Increases in Thyroid Cancer Incidence and Mortality—Reply
Authors: Cari M. Kitahara, Susan S. Devesa, Julie A. Sosa
Journal: JAMA (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 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
Antiproliferative effects of Hypericum Perforatum L. extract involve induction of p21CIP1 and inhibition of Rb expression in human bladder cancer cells.
Authors: Kathleen Shiverick, Ono Nseyo, Theresa Medrano, Maria Mejia, Unyime Nseyo
Journal: Cancer Research (2007)

3392  Bladder cancer is the fourth most common malignant disease in the United States. Hypericum perforatum L., also known as St. John’s wort, is an herb used to alleviate inflammation and infections, as well as pain in urinary interstitial cystitis. The polar methanolic fraction (PMF) of Hypericum perforatum L. (HPL) extract has recently been evaluated as a novel, natural photosensitizer for use in photodynamic therapy in cancer cells. The present study investigated mechanisms of growth-inhibitory effects of PMF on the human T24 human bladder cancer cell line that is derived from a high-grade metastatic cancer.  Methods: PMF was prepared from dry HPL herb brewed in methanol, followed by extraction with ether and methanol (polar methanolic fraction, PMF). Stock solutions of the PMF extract were made in DMSO for cell culture use and stored in the dark. PMF contained 0.57 % hypericin and 2.52 % hyperforin. The T24 cell line was obtained from ATCC. DNA synthesis was measured by [3H]-thymidine incorporation, and cell cycle phase distribution by flow cytometry. Cell cycle regulatory proteins were assayed by Western immunoblot, and apoptosis detected by PARP cleavage as a measure of caspase-3 activation.  Results: PMF inhibited DNA synthesis in a dose-dependent manner with a 90% inhibitory concentration (IC90) = 25 ug/ml. Flow cytometry analysis showed that PMF results in G0/G1 cell cycle arrest, with a 2-fold increase in G0/G1 cells concomitant with 50 % decrease in cells in both S and G2/M phases. Western blot analysis showed that PMF extract markedly increased levels of p21CIP1 , the major cell cycle inhibitory protein. In contrast, PMF significantly decreased levels of cyclins A, B and D, with an IC50 of 25 ug/ml for each protein. In addition, PMF produced parallel dose-related decreases in both Rb and phospho-Rb proteins. The inverse relationship between p21CIP1 and Cyclins A, B and D levels are evidence of a significant interference with cell cycle progression. While only a cystostatic effect was observed with PMF at 25 ug/ml, higher PMF concentrations and longer treatment times markedly decreased cell viability. Interestingly, no sub G0/G1 peak was detected by flow cytometry, nor was PARP cleavage observed with PMF 50 ug/ml for 3 days. Thus, apoptosis does not appear to be the mechanism of cell death promoted by PMF treatment.  Conclusions: Low concentrations of a polar methanolic fraction of Hypericum Perforatum L. extract produced dose-dependent inhibition of DNA synthesis associated with G0/G1 cell cycle arrest and coordinate changes in key cell cycle regulatory proteins in human bladder cancer cells. Thus, PMF may be a potent and effective anti-proliferative agent for inhibition of urothelial carcinoma cells. (NIH Minority Research Program)
Hepatocyte Nuclear Factor-1β Controls Mitochondrial Respiration in Renal Tubular Cells
Authors: Audrey Casemayou, Audren Fournel, Alessia Bagattin, Joost Schanstra, Julie Belliere, Stéphane Decramer, Dimitri Marsal, Marion Gillet, Nicolas Chassaing, Antoine Huart, Marco Pontoglio, Claude Knauf, Jean-Loup Bascands, Dominique Chauveau, Stanislas Faguer
Journal: Journal of the American Society of Nephrology (2017)

AKI is a frequent condition that involves renal microcirculation impairment, infiltration of inflammatory cells with local production of proinflammatory cytokines, and subsequent epithelial disorders and mitochondrial dysfunction. Peroxisome proliferator-activated receptor γ coactivator 1- α (PPARGC1A), a coactivator of the transcription factor PPAR- γ that controls mitochondrial biogenesis and function, has a pivotal role in the early dysfunction of the proximal tubule and the subsequent renal repair. Here, we evaluated the potential role of hepatocyte nuclear factor–1 β (HNF-1 β ) in regulating PPARGC1A expression in AKI. In mice, endotoxin injection to induce AKI also induced early and transient inflammation and PPARGC1A inhibition, which overlapped with downregulation of the HNF-1 β transcriptional network. In vitro , exposure of proximal tubule cells to the inflammatory cytokines IFN- γ and TNF- α led to inhibition of HNF-1 β transcriptional activity. Moreover, inhibition of HNF-1 β significantly reduced PPARGC1A expression and altered mitochondrial morphology and respiration in proximal tubule cells. Chromatin immunoprecipitation assays and PCR analysis confirmed HNF-1 β binding to the Ppargc1a promoter in mouse kidneys. We also demonstrated downregulation of renal PPARGC1A expression in a patient with an HNF1B germinal mutation. Thus, we propose that HNF-1 β links extracellular inflammatory signals to mitochondrial dysfunction during AKI partly via PPARGC1A signaling. Our findings further strengthen the view of HNF1B -related nephropathy as a mitochondrial disorder in adulthood.
Virtual proteomics of pathology specimens: Mass spectrometric detection of multiple proteins in formalin-fixed paraffin-embedded tissue.
Authors: Elzbieta Izbicka, Robert Streeper, I-Tien Yeh
Journal: Clinical Cancer Research (2007)

A9  The goal of personalized medicine is to deliver the best treatment to the patient. In clinical oncology, proteomics can evaluate differential expression and post-translational modifications of proteins in healthy and diseased states. Given that many novel anticancer therapies are designed to target tumor proteins, proteomic analysis of tumor tissue should complement conventional genomic or immunohistochemical (IHC) analyses in delivering information relevant for diagnosis, prognosis and predicting tumor response to treatment.  Formalin fixation and paraffin embedding (FFPE) of diagnostic specimens is the preparation method of choice for pathological assessment. We undertook this study to identify differentially expressed proteins in FFPE specimens from various pathological states of breast tissue and to compare expression of select known tumor biomarkers in normal and diseased states. Tissue was extracted using an improved protocol that results in enhanced protein yields. We examined FFPE archival breast tissue specimens including 23 normal samples from reduction mammoplasties (control group), 21 fibroadenomas, 25 node negative breast cancers, and 22 node positive breast cancers (test group). Histological subtype and the expression status of estrogen and progesterone receptors, HER2, p53, and Ki-67 were evaluated in the breast cancer specimens. Ten micron FFPE sections were microdissected, de-paraffinized, digested with trypsin, and analyzed by liquid chromatography electrospray ionization mass spectrometry (LC-ESI MS).  We developed a novel strategy for MS data mining referred to as “virtual proteomics”, which encompassed diverse mathematical operations on data sets. First, we identified differentially expressed mass/time signals, which were subjected to on- and off-line MS analysis. Data were searched against on-line protein data libraries for the identifications of likely target proteins based on the observed peptide sequences (discovery mode). In parallel, we interrogated the MS data with virtual probes derived from theoretical tryptic digests of known cancer biomarkers (hypothesis testing mode). In the discovery mode, we identified over 5 proteins that were present in >50% specimens in >1 test groups with >10-fold relative differences in expression in comparison with the controls, Mowse scores of >70 (p
Abstract 212: Inhibition of Protein Phosphatase 2A (PP2A) Leads to Beta-adrenergic Receptor Dysfunction With Cardiac Stress Following Pressure-overload Hypertrophy
Authors: Arunachal Chatterjee, Neelakantan Vasudevan, Maradumane Mohan, Elizabeth Martelli, John George, Sathyamangla Naga Prasad
Journal: Circulation Research (2015)

Beta-Adrenergic receptors (bARs) play a key role in regulating cardiac function. Loss of surface receptors and desensitization (impaired G-protein coupling) of bARs are hallmarks of a failing heart. Desensitization occurs by phosphorylation of bARs. The bARs are resensitized by protein phosphatase 2A (PP2A) mediated dephosphorylation in the endosomes before recycling to the plasma membrane. While mechanisms of desensitization are well understood, little is known about mechanisms regulating resensitization. Our previous work has shown that PI3Kg phosphorylates an endogenous inhibitor of PP2A (I2PP2A) on serine 9 &amp; 93, which then robustly binds to PP2A inhibiting bAR resensitization. Since it is not known whether resensitization is altered in response to cardiac stress or whether altered bAR resensitization contributes to cardiac hypertrophy and failure, we generated transgenic mice with cardiomyocyte specific overexpression of wild type I2PP2A (WT I2PP2A Tg), I2PP2A phospho-mimetic mutants S9, 93D and mutants with constitutively dephosphorylated S9, 93A state. To test whether resensitization is critical in the development of bAR dysfunction during cardiac hypertrophy, WT I2PP2A Tg mice were subjected to transverse aortic constriction (TAC) for 8 weeks. Echocardiographic analysis post-TAC showed that WT I2PP2A Tg mice had accelerated cardiac dysfunction compared to their littermate controls [HW (mg)/BW(g): Sham: WT - 4.83, WT I2PP2A Tg - 4.82, TAC: WT- 6.47, WT I2PP2A Tg - 7.61; %EF: Sham: WT - 83.53, WT I2PP2A Tg - 74.72, TAC: WT - 70.47, WT I2PP2A Tg - 49.62]. To directly test whether resensitization mechanisms are altered, plasma membranes and endosomes were isolated and in vitro Adenylyl Cyclase activity assessed. Our studies show that compared to littermate controls, WT I2PP2A Tg had altered in vitro adenylyl cyclase activity showing that resensitization mechanisms in the endosomes may in part, contribute to cardiac dysfunction. Mechanistic underpinnings of the resensitization pathways using the I2PP2A S9, 93A and S9, 93D will be presented showing that bAR resensitization a process considered passive is altered in conditions of cardiac stress that in part may contribute to bAR dysfunction leading to cardiac hypertrophy and heart failure.
Serum albumin to globulin ratio as an indicator for the prognosis for cholangiocarcinoma.
Authors: Qu Lin, Zhi-Huan Lin, Jie Chen, Mingsheng Huang, Xing Li, Jun-rong Jiang, Min Dong, Tian-tian Wang, Dong-hao Wu, Xiao-kun Ma
Journal: Journal of Clinical Oncology (2016)

e15605 Background: Cholangiocarcinoma is a highly malignance with poor prognosis. To date,the prognostic factors remained unclear. Prior studies have demonstrated the prognostic value of pretreatment serum albumin to globulin ratio(AGR) in different types of cancer.This study was aimed to assess the predictive value of AGR on progression free survival (PFS) and overall survival(OS) in cholangiocarcinoma patients. Methods: We retrospectively studied 87 patients with cholangiocarcinoma who had documented pretreatment serum albumin and globulin levels from June 2003 to June 2007 in the Third Affiliated Hospital of Sun Yat-senUniversity.The primarystudyendpoint was OS.The predictive accuracy and discriminative ability of the AGR and other laboratoryindexes as well as tumor parameters for 1year survival after diagnosis were determined by ROC curves and the area under the ROC curve (AUC).The associations of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Univariate analysis and multivariate analyses using Cox regression models were performed to determine the independent prognostic value of AGR. Results: Univariate analysis by Cox regression reviewed that globulin, AGR,tumor size and TNM stage reached statistical significance when predicting OS with serum albumin presenting P > 0.05. Multivariate analyses showed that AGR was an independent prognostic factor for OS regardless of TNM stages and tumor size with serumglobulin failed to achieve positive results. However AGR did not present prognostic value for PFS. Next, the optimal cutoff point of AGR was determined to be 1.51 according to the ROC analysis. High AGR was significantly positively associated with ECOG and 1 year survival ratebut negatively correlated withage, alkaline phosphatase, gamma-glutamyl transpeptidase andtotal bilirubin . Moreover, Kaplan-Meier analysis showed that patients with low AGR displayed significantly poorer OS compared to the high AGR group. Conclusions: Preoperative AGR can act as an effective biomarker with easy accessibility for evaluating the prognosis of patients with cholangiocarcinoma. Patients with higher AGR levels may have better survival than those with lower AGR.
ARAMIS trial: Efficacy and safety of ODM-201 in men with high-risk nonmetastatic castration-resistant prostate cancer.
Authors: Karim Fizazi, Neal D. Shore, Teuvo L. J. Tammela, Toni Sarapohja, Annamari Vuorela, Iris Kuss, Amir Snapir, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2016)

TPS5094 Background: Treatment for nonmetastatic castration-resistant prostate cancer (nmCRPC) other than continuing androgen deprivation therapy (ADT) remains an unmet need. There are no approved therapies for preventing metastatic disease in nmCRPC. Pts with nmCRPC who have shorter prostate-specific antigen doubling time (PSADT) are at higher risk for metastatic disease or death. ODM-201, a novel second-generation oral androgen receptor inhibitor, has demonstrated a tolerable safety profile and antineoplastic activity in progressive CRPC. The ARAMIS trial will evaluate the efficacy and safety of ODM-201 in high-risk nmCRPC pts. Methods: This randomized, double-blind, placebo-controlled phase 3 trial (NCT02200614) involves > 450 sites in > 33 countries. 1500 pts on ADT will be randomized 2:1 to ODM-201 600 mg or placebo BID. Pts will be stratified by PSADT and baseline bone-targeting agent use. Eligibility criteria include nmCRPC, PSADT ≤ 10 months, and screening PSA ≥ 2 ng/mL. 90% power to detect a target hazard ratio of 0.75 is based on a 2-sided log-rank test at an overall significance level of 0.05. The primary endpoint is metastasis-free survival based on central independent review of bone scan and CT/MRI every 16 weeks. Secondary endpoints are overall survival, time to first symptomatic skeletal event, initiation of first cytotoxic chemotherapy for PC, pain progression, and first opioid use. Additional endpoints are progression-free survival, time to first PC–related invasive procedure, initiation of subsequent antineoplastic therapy, PSA progression, change in ECOG status, and changes in health-related quality of life. Time to event endpoints will be analyzed using a stratified log-rank test, and Kaplan-Meier estimates will be produced for both treatment groups. The ARAMIS trial is open and recruiting, the first pt was randomized in October 2014. Clinical trial information: NCT02200614.
BAG3 (Bcl-2–Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy
Authors: Joseph M. McClung, Timothy J. McCord, Terence E. Ryan, Cameron A. Schmidt, Tom D. Green, Kevin W. Southerland, Jessica L. Reinardy, Sarah B. Mueller, Talaignair N. Venkatraman, Christopher D. Lascola, Sehoon Keum, Douglas A. Marchuk, Espen E. Spangenburg, Ayotunde Dokun, Brian H. Annex, Christopher D. Kontos
Journal: Circulation (2017)

Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1, that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia.We treated mice with either adeno-associated viruses encoding a control (green fluorescent protein) or 2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and subjected the mice to hind-limb ischemia.We found that the BAG3 Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6-Lsq1-3). BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29) expressing animals. BAG3Ile81, but not BAG3Met81, improved ischemic muscle myopathy and muscle precursor cell differentiation and improved muscle regeneration in a separate, toxin-induced model of injury. Systemic injection of adeno-associated virus-BAG3Ile81 (n=9), but not BAG3Met81 (n=10) or green fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle histology and restored muscle function (force production). Compared with BAG3Met81, BAG3Ile81 displayed improved binding to the small heat shock protein (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic flux.Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle function in the setting of ischemia.
Dissecting the Role of PCDH7, an Oncogenic Cell Surface Receptor, in Non–Small Cell Lung Cancer
Authors: X. Zhou, B.L. Updegraff, Y. Guo, M. Peyton, L. Girard, J.E. Larsen, X.-J. Xie, Y. Zhou, T.H. Hwang, Y. Xie, J. Rodriguez-Canales, P. Villalobos, C. Behrens, I.I. Wistuba, J.D. Minna, K.A. O’Donnell
Journal: Journal of Thoracic Oncology (2017)
Synthesising ‘best evidence<i>’</i> in systematic reviews when randomised controlled trials are absent: three tips for authors to add value for clinician readers
Authors: Clare L Ardern, Marinus Winters
Journal: British Journal of Sports Medicine (2017)

‘More research is needed’ is a most unhelpful conclusion for the clinician reader of a systematic review. Clinicians look to researchers for the ‘research evidence’ part of Professor Sackett’s ‘three circles’ of evidence-based practice.1 The clinician can not ignore the patient in front of him or her just because there is no evidence from systematic reviews or randomised controlled trials (RCTs): ‘Kindly forget about your shoulder problem, until we have better research to tell me what to do’? This will not do! In this editorial, we share three practical tips for authors synthesising lower level evidence in systematic reviews, when high-quality RCTs are absent. Our goal is to help authors help clinicians help patients.

Consider the patient who plays tennis and presents with shoulder pain. Right now, the clinician who is seeking RCT evidence on how to progress from impairment-focused tasks in neutral shoulder positions to high-level, sport-specific tasks will be disappointed. Being able to function in shoulder elevation positions above …