tbuckley/cabot-search huggingface dataset:
Stent placement for benign esophageal leaks, perforations, and fistulae: a clinical prediction rule for successful leakage control
Authors: Emo van Halsema, Wouter Kappelle, Bas Weusten, Robert Lindeboom, Mark van Berge Henegouwen, Paul Fockens, Frank Vleggaar, Manon Spaander, Jeanin van Hooft
Journal: Endoscopy (2017)

Abstract Background and study aims Sealing esophageal leaks by stent placement allows healing in 44 % – 94 % of patients. We aimed to develop a prediction rule to predict the chance of successful stent therapy. Patients and methods In this multicenter retrospective cohort study, patients with benign upper gastrointestinal leakage treated with stent placement were included. We used logistic regression analysis including four known clinical predictors of stent therapy outcome. The model performance to predict successful stent therapy was evaluated in an independent validation sample. Results We included etiology, location, C-reactive protein, and size of the leak as clinical predictors. The model was estimated from 145 patients (derivation sample), and 59 patients were included in the validation sample. Stent therapy was successful in 55.9 % and 67.8 % of cases, respectively. The predicted probability of successful stent therapy was significantly higher in success patients compared with failure patients in both the derivation (P &lt; 0.001) and validation (P &lt; 0.001) samples. The area under the receiver operating characteristic curve was 74.1 % in the derivation sample and 84.7 % in the validation sample. When the model predicted ≥ 70 % chance of success, the positive predictive value was 79 % in the derivation sample and 87 % in the validation sample. When the model predicted ≤ 50 % chance of success, the negative predictive value was 64 % and 86 %, respectively. Conclusions This prediction rule, consisting of four clinical predictors, could identify patients with esophageal leaks who were likely to benefit from or fail on stent therapy. The prediction rule can support clinical decision-making when the predicted probability of success is ≥ 70 % or ≤ 50 %.
Fabrication of self-assembling nanofibers with optimal cell uptake and therapeutic delivery efficacy
Authors: Dawei Xu, Damien S.K. Samways, He Dong
Journal: Bioactive Materials (2017)

Effective strategies to fabricate finite organic nanoparticles and understanding their structure-dependent cell interaction is highly important for the development of long circulating nanocarriers in cancer therapy. In this contribution, we will capitalize on our recent development of finite supramolecular nanofibers based on the self-assembly of modularly designed cationic multidomain peptides (MDPs) and use them as a model system to investigate structure-dependent cell penetrating activity. MDPs self-assembled into nanofibers with high density of cationic charges at the fiber-solvent interface to interact with the cell membrane. However, despite the multivalent charge presentation, not all fibers led to high levels of membrane activity and cellular uptake. The flexibility of the cationic charge domains on self-assembled nanofibers plays a key role in effective membrane perturbation. Nanofibers were found to sacrifice their dimension, thermodynamic and kinetic stability for a more flexible charge domain in order to achieve effective membrane interaction. The increased membrane activity led to improved cell uptake of membrane-impermeable chemotherapeutics through membrane pore formation. In vitro cytotoxicity study showed co-administering of water-soluble doxorubicin with membrane-active peptide nanofibers dramatically reduced the IC50 by eight folds compared to drug alone. Through these detailed structure and activity studies, the acquired knowledge will provide important guidelines for the design of a variety of supramolecular cell penetrating nanomaterials not limited to peptide assembly which can be used to probe various complex biological processes.
Nanolayered hybrid mediates synergistic co-delivery of ligand and ligation activator for inducing stem cell differentiation and tissue healing
Authors: Heemin Kang, Minkyu Kim, Qian Feng, Sien Lin, Kongchang Wei, Rui Li, Chan Ju Choi, Tae-Hyun Kim, Gang Li, Jae-Min Oh, Liming Bian
Journal: Biomaterials (2017)
Abstract 88: Cardiac-specific Deletion of Protein Tyrosine Phosphatase 1B Exacerbates Pressure Overload-induced Hypertrophy and Heart Failure in Mice
Authors: Gerald Coulis, Alexandre Bergeron, Yanfen Shi, David Labbe, Michel Tremblay, Gerard Karsenty, Benoit Boivin
Journal: Circulation Research (2016)

Cardiac hypertrophy involves the re-expression of a foetal gene program that occurs when cardiomyocytes are continuously exposed to stresses. The enlargement initially improves cardiac function, however, this compensatory hypertrophy predisposes individuals to arrhythmias, pathological hypertrophy and heart failure. Given the importance of reactive oxygen species (ROS) in the transition from cardiac hypertrophy to heart failure and the documented inhibition of PTPs by ROS, we hypothesized and explored whether specific PTPs could act as checkpoints in this process. We have identified PTP1B as a target of ROS in hearts undergoing hypertrophy. To better understand the role of PTP1B inhibition in cardiac hypertrophy, we generated cardiomyocyte-specific PTP1B knockout (PTP1B cKO) mice. Subjecting PTP1B cKO mice to pressure overload (PO) caused a dramatic left ventricular dilation and several distinctive features of heart failure when compared to control mice subjected to PO for the same period. Characterization of the mRNAs expressed in the hypertrophy-associated foetal gene program revealed that although PO led to increased mRNA levels of ANF and BNP, the increased expression of β-MHC observed in control mice subjected to PO was compromised in PTP1B cKO-PO mice. Since PTP1B inactivation can lead to the inactivation of AGO2 and compromise miRNA-mediated mRNAs repression, we investigated whether PTP1B regulated AGO2 phosphorylation and association with mRNAs in this context. We observed that AGO2 phosphotyrosine-393 levels were elevated and that AGO2 was a substrate of PTP1B in myocytes and in hearts undergoing hypertrophy. We also found changes in AGO2-mRNA associations between control- and PTP1B cKO-PO hearts and identified MED13 as a regulator of β-MHC expression that was differentially regulated by AGO2 in PTP1B cKO-PO hearts. Since increased expression of β-MHC contributes to the compensatory response that initially improves cardiac function, we will propose a model in which PTP1B inhibition regulates AGO2 activity and contributes to heart failure.
The quantitaive assessment of WT1 gene expression as a method to predict response to STI571 therapy in CML patients
Authors: D. Cilloni, F. Messa, E. Gottardi, A. Morotti, E. Giugliano, E. Messa, G. Rege-Cambrin, F. Pane, M. Martinelli, M. Baccarani, G Saglio
Journal: Blood (2002)
A randomized phase III trial of 1-year adjuvant chemotherapy with oral tegafur-uracil (UFT) vs. surgery alone in stage II colon cancer: SACURA trial.
Authors: Yoshiki Kajiwara, Megumi Ishiguro, Satoshi Teramukai, Chu Matsuda, Shoichi Fujii, Yusuke Kinugasa, Yoshihiko Nakamoto, Masanori Kotake, Yoshiyuki Sakamoto, Kiyotaka Kurachi, Atsuyuki Maeda, Koji Komori, Naohiro Tomita, Yasuhiro Shimada, Keiichi Takahashi, Kenjiro Kotake, Masahiko Watanabe, Hidetaka Mochizuki, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2016)

3617 Background: Efficacy of adjuvant chemotherapy in stage II colon cancer patients is still controversial. The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer in a large population. Methods: 20-80 aged patients with curatively resected stage II colon cancer were randomly assigned to the surgery alone group or UFT group (UFT at 500-600 mg/day as tegafur in 2 divided doses for 5 days, followed by 2-day rest, then repeated for 1 year). Primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS), recurrence-free survival (RFS), and safety. Sample size was 2000 determined with an assumed hazard ratio (HR) 0.729, respectively, a two-sided significance level of 5%, and a power of 90%. Results: A total of 1982 patients (997 in the surgery alone group and 985 in the UFT group) were included in the efficacy analysis. Median follow-up was 69.5 months, the median age at enrollment was 66 years, and stage IIA/IIB/IIC were 84%/13%/3%, respectively. The 5-year DFS rate was 78.4% in the surgery alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95%CI, 0.75-1.10; p = 0.307), and superiority of the UFT group was not demonstrated. Approximately 9% of patients in the both groups experienced second cancers, which consist 41.7% of the DFS events. The 5-year RFS rate was 84.6% and 87.2% (HR, 0.82; 95%CI, 0.65-1.04), and the 5-year OS rate was 94.3% and 94.5% (HR, 0.93; 95%CI, 0.66-1.31) in the surgery alone group and the UFT group, respectively. The completion rate of the 1-year UFT was 60.8%. The Incidence of grade 3/4 adverse events in the UFT group was 3.7% for ALT elevation, 3.3% for AST elevation, 1.4% for hyperbilirubinemia, 2.6% for anorexia, 1.9% for nausea, 1.4% for diarrhea, and < 1% for hematologic toxicities. Conclusions: Superiority of 1-year adjuvant treatment with UFT to surgery alone was not demonstrated in patients with stage II colon cancer. Clinical trial information: NCT00392899.
In-depth Genetic Analysis of Sclerosing Epithelioid Fibrosarcoma Reveals Recurrent Genomic Alterations and Potential Treatment Targets
Authors: Elsa Arbajian, Florian Puls, Cristina R. Antonescu, Fernanda Amary, Raf Sciot, Maria Debiec-Rychter, Vaiyapuri P. Sumathi, Marcus Järås, Linda Magnusson, Jenny Nilsson, Jakob Hofvander, Fredrik Mertens
Journal: Clinical Cancer Research (2017)

Purpose: Sclerosing epithelioid fibrosarcoma (SEF) is a highly aggressive soft tissue sarcoma closely related to low-grade fibromyxoid sarcoma (LGFMS). Some tumors display morphologic characteristics of both SEF and LGFMS, hence they are known as hybrid SEF/LGFMS. Despite the overlap of gene fusion variants between these two tumor types, SEF is much more aggressive. The current study aimed to further characterize SEF and hybrid SEF/LGFMS genetically to better understand the role of the characteristic fusion genes and possible additional genetic alterations in tumorigenesis.Experimental Design: We performed whole-exome sequencing, SNP array analysis, RNA sequencing (RNA-seq), global gene expression analyses, and/or IHC on a series of 13 SEFs and 6 hybrid SEF/LGFMS. We also expressed the FUS-CREB3L2 and EWSR1-CREB3L1 fusion genes conditionally in a fibroblast cell line; these cells were subsequently analyzed by RNA-seq, and expression of the CD24 protein was assessed by FACS analysis.Results: The SNP array analysis detected a large number of structural aberrations in SEF and SEF/LGFMS, many of which were recurrent, notably DMD microdeletions. RNA-seq identified FUS-CREM and PAX5-CREB3L1 as alternative fusion genes in one SEF each. CD24 was strongly upregulated, presumably a direct target of the fusion proteins. This was further confirmed by the gene expression analysis and FACS analysis on Tet-On 3G cells expressing EWSR1-CREB3L1Conclusions: Although gene fusions are the primary tumorigenic events in both SEF and LGFMS, additional genomic changes explain the differences in aggressiveness and clinical outcome between the two types. CD24 and DMD constitute potential therapeutic targets. Clin Cancer Res; 23(23); 7426-34. ©2017 AACR.
Developing and validating the Cutaneous WARTS (CWARTS) diagnostic tool: a novel clinical assessment and classification system for cutaneous warts
Authors: G.K. Hogendoorn, S.C. Bruggink, K.E. Hermans, S.T.P. Kouwenhoven, K.D. Quint, R. Wolterbeek, J.A.H. Eekhof, M.N.C. de Koning, R. Rissmann, J. Burggraaf, J.N. Bouwes Bavinck
Journal: British Journal of Dermatology (2017)

The clinical appearance of cutaneous warts is highly variable and not standardized. To develop and validate a reproducible clinical tool for the standardized assessment of cutaneous warts to distinguish these lesions accurately. Nine morphological characteristics were defined and validated regarding intra‐ and interobserver agreement. Based on literature and semistructured interviews, a systematic dichotomous assessment tool, the Cutaneous WARTS (CWARTS) diagnostic tool was developed. The validation consisted of two independent parts performed with photographs from the recent WARTS‐2 trial. In part A, the CWARTS diagnostic tool was tested by 28 experienced physicians who assessed photographs of 10 different warts to investigate interobserver concordance. In part B, morphological characteristics were validated by masked and independent scoring of 299 photographs by six different observers. Part B also entailed reassessment of the photographs after at least 1 week. The primary outcome measurement was the intraclass correlation coefficient (ICC). Presence of black dots (capillary thrombosis) had the greatest ICC (0·85) for interobserver agreement in part A, followed by arrangement (0·65), presence of border erythema (0·64) and sharpness of the border (0·60). In part B, results were similar for interobserver agreement with presence of black dots having the highest ICC (0·68), followed by border erythema (0·64), arrangement (0·58) and colour (0·55). For intraobserver agreement, presence of black dots had the highest agreement (0·70), followed by presence of border erythema (0·694) and colour (0·59). Wart phenotype can be reliably assessed using the CWARTS diagnostic tool.
Saving Primary Care
Authors: Laura L. Sessums, Patrick H. Conway
Journal: JAMA Internal Medicine (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 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
The WPA- Lancet Psychiatry Commission on the Future of Psychiatry
Authors: Dinesh Bhugra, Allan Tasman, Soumitra Pathare, Stefan Priebe, Shubulade Smith, John Torous, Melissa R Arbuckle, Alex Langford, Renato D Alarcón, Helen Fung Kum Chiu, Michael B First, Jerald Kay, Charlene Sunkel, Anita Thapar, Pichet Udomratn, Florence K Baingana, Dévora Kestel, Roger Man Kin Ng, Anita Patel, Livia De Picker, Kwame Julius McKenzie, Driss Moussaoui, Matt Muijen, Peter Bartlett, Sophie Davison, Tim Exworthy, Nasser Loza, Diana Rose, Julio Torales, Mark Brown, Helen Christensen, Joseph Firth, Matcheri Keshavan, Ang Li, Jukka-Pekka Onnela, Til Wykes, Hussien Elkholy, Gurvinder Kalra, Kate F Lovett, Michael J Travis, Antonio Ventriglio
Journal: The Lancet Psychiatry (2017)
Met Receptor Tyrosine Kinase and Chemoprevention of Oral Cancer
Authors: Pierre Saintigny, William N William, Jean-Philippe Foy, Vassiliki Papadimitrakopoulou, Wenhua Lang, Li Zhang, You Hong Fan, Lei Feng, Edward S Kim, Adel K El-Naggar, J Jack Lee, Li Mao, Waun Ki Hong, Mark W Lingen, Scott M Lippman
Journal: JNCI Journal of the National Cancer Institute (2017)

We have previously shown that gene expression profiles of oral leukoplakia (OL) may improve the prediction of oral cancer (OC) risk. To identify new targets for prevention, we performed a systematic survey of transcripts associated with an increased risk of oral cancer and overexpressed in OC vs normal mucosa (NM).
Trends and Patterns of Differences in Chronic Respiratory Disease Mortality Among US Counties, 1980-2014
Authors: Laura Dwyer-Lindgren, Amelia Bertozzi-Villa, Rebecca W. Stubbs, Chloe Morozoff, Shreya Shirude, Mohsen Naghavi, Ali H. Mokdad, Christopher J. L. Murray
Journal: JAMA (2017)

Chronic respiratory diseases are an important cause of death and disability in the United States.To estimate age-standardized mortality rates by county from chronic respiratory diseases.Validated small area estimation models were applied to deidentified death records from the National Center for Health Statistics and population counts from the US Census Bureau, National Center for Health Statistics, and Human Mortality Database to estimate county-level mortality rates from 1980 to 2014 for chronic respiratory diseases.County of residence.Age-standardized mortality rates by county, year, sex, and cause.A total of 4 616 711 deaths due to chronic respiratory diseases were recorded in the United States from January 1, 1980, through December 31, 2014. Nationally, the mortality rate from chronic respiratory diseases increased from 40.8 (95% uncertainty interval [UI], 39.8-41.8) deaths per 100 000 population in 1980 to a peak of 55.4 (95% UI, 54.1-56.5) deaths per 100 000 population in 2002 and then declined to 52.9 (95% UI, 51.6-54.4) deaths per 100 000 population in 2014. This overall 29.7% (95% UI, 25.5%-33.8%) increase in chronic respiratory disease mortality from 1980 to 2014 reflected increases in the mortality rate from chronic obstructive pulmonary disease (by 30.8% [95% UI, 25.2%-39.0%], from 34.5 [95% UI, 33.0-35.5] to 45.1 [95% UI, 43.7-46.9] deaths per 100 000 population), interstitial lung disease and pulmonary sarcoidosis (by 100.5% [95% UI, 5.8%-155.2%], from 2.7 [95% UI, 2.3-4.2] to 5.5 [95% UI, 3.5-6.1] deaths per 100 000 population), and all other chronic respiratory diseases (by 42.3% [95% UI, 32.4%-63.8%], from 0.51 [95% UI, 0.48-0.54] to 0.73 [95% UI, 0.69-0.78] deaths per 100 000 population). There were substantial differences in mortality rates and changes in mortality rates over time among counties, and geographic patterns differed by cause. Counties with the highest mortality rates were found primarily in central Appalachia for chronic obstructive pulmonary disease and pneumoconiosis; widely dispersed throughout the Southwest, northern Great Plains, New England, and South Atlantic for interstitial lung disease; along the southern half of the Mississippi River and in Georgia and South Carolina for asthma; and in southern states from Mississippi to South Carolina for other chronic respiratory diseases.Despite recent declines in mortality from chronic respiratory diseases, mortality rates in 2014 remained significantly higher than in 1980. Between 1980 and 2014, there were important differences in mortality rates and changes in mortality by county, sex, and particular chronic respiratory disease type. These estimates may be helpful for informing efforts to improve prevention, diagnosis, and treatment.
Immune-related adverse events (IRAEs) in metastatic lung cancer patients receiving PD-1/PD-L1 inhibitors and thoracic radiotherapy.
Authors: William L. Hwang, Andrzej Niemierko, Henning Willers, Florence K. Keane, Justin F. Gainor
Journal: Journal of Clinical Oncology (2017)

9079 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with unique IRAEs, including pneumonitis (PNS). Thoracic radiotherapy (TRT) is also associated with PNS but it is unknown whether TRT+ICI increases the risk of PNS or other IRAEs. Furthermore, low serum LDH levels are associated with better response/survival to ICI but its potential role as a biomarker for IRAEs is unexplored. Methods: We retrospectively reviewed 164 pts with metastatic lung cancer (95% NSCLC, 5% SCLC) consecutively treated at our institution from 2013-2016 with PD-1/PD-L1 inhibitors and a minimum of one month follow-up, except in cases of rapid death from an IRAE ( n =4). Pts were grouped according to TRT received (+ vs -). IRAE grades were assigned using NCI CTCAE v4.0. Outcomes were compared using Fisher’s exact test and two-sided Student’s t-test. Results: Baseline characteristics such as age, gender, smoking status, supplemental oxygen requirement, median number of chemotherapy lines prior to ICI (1 vs 1), median ICI cycles (5 vs 3), and median follow-up after ICI initiation (8 vs 7 months) were similar in the +TRT ( n = 73) and -TRT ( n =91) groups. Rates of grade ≥ 2 IRAEs (18.1 vs 14.4%, p = 0.67), all-grade PNS (8.2 vs 5.5%, p= 0.54), and grade ≥ 2 PNS (4.1 vs 3.3%, p = 1) were not significantly different between the +TRT and -TRT cohorts. Mean TRT dose was similar between those pts who developed PNS and those who did not (55.8 vs 55.9 Gy). In the +TRT group, 85% received TRT a median of 8.6 months before ICI. Among 7 pts (10%) who had concurrent TRT+ICI, none developed symptomatic PNS. Patients who developed grade ≥ 2 IRAEs ( n= 26) had significantly higher mean serum LDH before initiation of ICI than patients who did not (283 vs 214, ref 98-192 IU/L, p= 0.03). Conclusions: TRT in lung cancer pts receiving ICI was not associated with increased risk of PNS in this series. LDH may be a negative predictive biomarker as pts who suffered grade ≥ 2 IRAEs had significantly higher baseline LDH than those who did not. Larger cohorts and prospective studies would be helpful to validate these findings.
Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria
Authors: Shannon I. Ohlemacher, Daryl E. Giblin, D. André d’Avignon, Ann E. Stapleton, Barbara W. Trautner, Jeffrey P. Henderson
Journal: Journal of Clinical Investigation (2017)

Escherichia coli and other Enterobacteriaceae are among the most common pathogens of the human urinary tract. Among the genetic gains of function associated with urinary E. coli isolates is the Yersinia high pathogenicity island (HPI), which directs the biosynthesis of yersiniabactin (Ybt), a virulence-associated metallophore. Using a metabolomics approach, we found that E. coli and other Enterobacteriaceae expressing the Yersinia HPI also secrete escherichelin, a second metallophore whose chemical structure matches a known synthetic inhibitor of the virulence-associated pyochelin siderophore system in Pseudomonas aeruginosa. We detected escherichelin during clinical E. coli urinary tract infection (UTI) and experimental human colonization with a commensal, potentially probiotic E. coli bacteriuria strain. Escherichelin production by colonizing enterobacteria may help human hosts resist opportunistic infections by Pseudomonas and other pyochelin-expressing bacteria. This siderophore-based mechanism of microbial antagonism may be one of many elements contributing to the protective effects of the human microbiome. Future UTI-preventive probiotic strains may benefit by retaining the escherichelin biosynthetic capacity of the Yersinia HPI while eliminating the Ybt biosynthetic capacity.