tbuckley/cabot-search huggingface dataset:
Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma
Authors: Ann Esquivel, William W. Busse, Agustin Calatroni, Alkis G. Togias, Kristine G. Grindle, Yury A. Bochkov, Rebecca S. Gruchalla, Meyer Kattan, Carolyn M. Kercsmar, G. Khurana Hershey, Haejin Kim, Petra Lebeau, Andrew H. Liu, Stanley J. Szefler, Stephen J. Teach, Joseph B. West, Jeremy Wildfire, Jaqueline A. Pongracic, James E. Gern
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma.In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression.RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84).In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).
Characterization of MK-4166, a Clinical Agonistic Antibody That Targets Human GITR and Inhibits the Generation and Suppressive Effects of T Regulatory Cells
Authors: Selvakumar Sukumar, Douglas C. Wilson, Ying Yu, Jerelyn Wong, Saraswathi Naravula, Grigori Ermakov, Romina Riener, Bhagyashree Bhagwat, Antoaneta S. Necheva, Jeff Grein, Tatyana Churakova, Ruban Mangadu, Peter Georgiev, Denise Manfra, Elaine M. Pinheiro, Venkataraman Sriram, Wendy J. Bailey, Danuta Herzyk, Terrill K. McClanahan, Aarron Willingham, Amy M. Beebe, Svetlana Sadekova
Journal: Cancer Research (2017)

Abstract GITR is a T-cell costimulatory receptor that enhances cellular and humoral immunity. The agonist anti-mouse GITR antibody DTA-1 has demonstrated efficacy in murine models of cancer primarily by attenuation of Treg-mediated immune suppression, but the translatability to human GITR biology has not been fully explored. Here, we report the potential utility of MK-4166, a humanized GITR mAb selected to bind to an epitope analogous to the DTA-1 epitope, which enhances the proliferation of both naïve and tumor-infiltrating T lymphocytes (TIL). We also investigated the role of GITR agonism in human antitumor immune responses and report here the preclinical characterization and toxicity assessment of MK-4166, which is currently being evaluated in a phase I clinical study. Expression of human GITR was comparable with that of mouse GITR in tumor-infiltrating Tregs despite being drastically lower in other human TILs and in many human peripheral blood populations. MK-4166 decreased induction and suppressive effects of Tregs in vitro. In human TIL cultures, MK-4166 induced phosphorylation of NFκB and increased expression of dual specificity phosphatase 6 (DUSP6), indicating that MK-4166 activated downstream NFκB and Erk signaling pathways. Furthermore, MK-4166 downregulated FOXP3 mRNA in human tumor infiltrating Tregs, suggesting that, in addition to enhancing the activation of TILs, MK-4166 may attenuate the Treg-mediated suppressive tumor microenvironment. Cancer Res; 77(16); 4378–88. ©2017 AACR.
Significance of dysadherin expression in breast cancer metastasis
Authors: Jeong-Seok Nam, Adam Suchar, Setsuo Hirohashi, Lalage M. Wakefield
Journal: Cancer Research (2004)

5040  Dysadherin is a recently-cloned cancer-associated cell membrane glycoprotein (Ino et al., (2002) Proc. Natl. Acad. Sci. USA 99:365-370). Dysadherin has been shown to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism, and to promote the metastasis of carcinoma cells. Here we have investigated a possible role for dysadherin in breast cancer metastasis. In a xenograft model of breast cancer progression based on derivatives of the MCF10A cell line, dysadherin protein is only increased in the high grade metastatic cell line, and not in low-grade tumorigenic or premalignant lines, suggesting an association of dysadherin expression with more advanced disease. A panel of 10 human breast cancer cell lines was then analysed for expression of dysadherin. Dysadherin mRNA was detectable by PCR in all lines. However, by Western blot analysis, a more restricted pattern of dysadherin protein expression was observed. In general, expression of dysadherin protein correlated negatively with expression of the estrogen receptor and of E-cadherin in vitro. To analyze the functional implications of dysadherin expression in breast cancer, we have shown that in MCF10Ca1a and T47D cell lines, where both dysadherin and E-cadherin are coexpressed, suppression of dysadherin with siRNA caused an increase in functional E-cadherin expression, without affecting total E-cadherin protein expression. Unexpectedly however, siRNA knockout of dysadherin not only suppressed invasion potential but also modified TGF-β transcriptional responses in the MDA-MB-231 breast cancer cell line, in the absence of any functional E-cadherin. Therefore, overexpression of dysadherin may contribute to the metastatic phenotype in ER-negative breast cancer. It has pro-metastatic effects that are independent of E-cadherin expression and it can modify responses to TGF-β, a pro-metastatic factor. We are currently addressing underlying molecular mechanisms using cDNA microarray analysis.
Uncovering Key Downstream Effectors of PU.1 Tumor Suppression in Acute Myeloid Leukemia
Authors: Margherita Ghisi, Mark D McKenzie, Ethan P Oxley, Emilia Simankowicz, Cynthia Liu, Aleksandar Dakic, Stephen L Nutt, Matthew E Ritchie, Johannes Zuber, Ross A Dickins
Journal: Blood (2016)
Association Between Glycemic Variability, HbA1c, and Large-for-Gestational-Age Neonates in Women With Type 1 Diabetes
Authors: Rachel T. McGrath, Sarah J. Glastras, Sean K. Seeho, Emma S. Scott, Gregory R. Fulcher, Samantha L. Hocking
Journal: Diabetes Care (2017)

Fetal exposure to hyperglycemia is a major determinant of large-for-gestational-age (LGA; birth weight >90th centile for gender) neonates (1), yet targets for glycemic control beyond the first trimester in type 1 diabetes (T1D) pregnancy remain controversial. As HbA1c represents a summary measure of glycemic control, it might not adequately reflect acute glucose fluctuations or glycemic variability (GV) that contributes to excess fetal growth. Moreover, neonates born to women who attain HbA1c <6% (42 mmol/mol) in the third trimester of pregnancy have an LGA prevalence of 25% (2), with associated adverse perinatal outcomes (3). In contrast to HbA1c, continuous glucose monitoring (CGM) allows precise observation of GV. Several studies have demonstrated an association between higher GV and increased birth weight (1,4,5). The capability of GV compared with HbA1c to identify women likely to have LGA neonates is, however, unclear. We evaluated the association between various measures of GV, HbA1c, and LGA neonates in T1D pregnancy.

Twenty-one pregnant women with T1D were recruited over a 2-year period, and measurements of HbA1c and GV (EasyGV, University …
An open label, phase II trial of continuous low-irradiance photodynamic therapy (CLIPT) using verteporfin for the treatment of cutaneous breast cancer metastases.
Authors: Steven J. Isakoff, Gary S. Rogers, Samuel Hill, Patrick McMullan, Karleen R. Habin, Hanah Park, Diana W. Bartenstein, Steven T Chen, William Thomas Barry, Beth Overmoyer
Journal: Journal of Clinical Oncology (2017)

TPS1121 Background: Cutaneous metastases occur in approximately 20% of patients (pts) with metastatic breast cancer (mBC) and can be highly symptomatic and distressing. Radiation is frequently offered, but progression often occurs quickly. Photodynamic therapy is a promising approach with encouraging results in small studies. Here we will evaluate a novel Continuous Low-Irradiance Photodynamic Therapy (CLIPT) system that emits 690nm LED via a handheld powerpack attached to a single-use sterile light patch to deliver a total energy level of 10J/cm2. Verteporfin (Visudyne) is a photosensitizer approved for ophthalmological use that when combined with CLIPT generates activated oxygen species which can destroy tumor cells with limited normal tissue reaction. Methods: This open label, phase 2 study will evaluate the efficacy and safety of CLIPT with verteporfin in 15 pts with cutaneous lesions from mBC. Pts will receive a single IV injection of verteporfin on day 1. The 9x9cm patch with an adhesive border is placed over the treatment site and attached to the CLIPT portable power pack. The pt turns the device on at home 6 hours after the verteprofin injection and it automatically turns off after 24 hours. The pt will remove the patch and return to clinic on day 3. The primary endpoint is objective response rate (RR) at 3 weeks following CLIPT using a modified RECIST which accounts for nodular or diffuse plaque-like lesions. Secondary endpoints include RR at 2, 8 and 12 weeks, toxicity, and quality of life (using FACT-B, a Participant Symptom Scale, and Brief Pain Inventory). Pts who derive clinical benefit may be retreated up to 3 times to the same or different region. Eligible pts will have: cutaneous metastases from mBC with measurable disease by protocol defined modified RECIST 1.1, ≥ 1 line of prior systemic or local therapy for mBC, ≥ 14 days from prior systemic therapy or 60 days from radiation to target lesion, and no expectation for systemic therapy for ≥ 14 days after CLIPT. RR will be reported with 95% CI. If ≥ 3 responses (RR ≥ 20%) are observed, the null hypothesis of RR ≤ 5% will be rejected. At the time of abstract submission, 1 patient has been accrued. Clinical trial information: NCT02939274.
Genetic–epigenetic interactions in cis: a major focus in the post-GWAS era
Authors: Catherine Do, Alyssa Shearer, Masako Suzuki, Mary Beth Terry, Joel Gelernter, John M. Greally, Benjamin Tycko
Journal: Genome biology (2017)

Studies on genetic–epigenetic interactions, including the mapping of methylation quantitative trait loci (mQTLs) and haplotype-dependent allele-specific DNA methylation (hap-ASM), have become a major focus in the post-genome-wide-association-study (GWAS) era. Such maps can nominate regulatory sequence variants that underlie GWAS signals for common diseases, ranging from neuropsychiatric disorders to cancers. Conversely, mQTLs need to be filtered out when searching for non-genetic effects in epigenome-wide association studies (EWAS). Sequence variants in CCCTC-binding factor (CTCF) and transcription factor binding sites have been mechanistically linked to mQTLs and hap-ASM. Identifying these sites can point to disease-associated transcriptional pathways, with implications for targeted treatment and prevention.
hLL2-Cys-PBD, a New Site-Specifically Conjugated, Pyrrolobenzodiazepine (PBD) Dimer-Based Antibody Drug Conjugate (ADC) Targeting CD22-Expressing B-Cell Malignancies.
Authors: Francesca Zammarchi, Simon Corbett, Lauren Adams, Maria Mellinas-Gomez, Peter Tyrer, Sandamali Dissanayake, Simone Sims, Karin Havenith, Simon Chivers, David G Willimas, Philip W Howard, John A. Hartley, Patrick van Berkel
Journal: Blood (2016)
Brief Report: Terrorism and Emergency Preparedness in State and Territorial Public Health Departments—United States, 2004Brief Report: Terrorism and Emergency Preparedness in State and Territorial Public Health Departments—United States, 2004
Journal: JAMA (2005)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Outcomes of radiation therapy for advanced T3/T4 nonmelanoma cutaneous squamous cell and basal cell carcinoma
Authors: S.K. Kim, C.A. Barker
Journal: British Journal of Dermatology (2017)

Non-melanoma cutaneous squamous and basal cell carcinoma (NMSC) is common, and most patients present with early stage (T1/T2) NMSC, which has an excellent prognosis. However, a minority of NMSC patients present with an advanced stage (T3/T4) primary tumor, which may be surgically unresectable but potentially curable with radiation therapy (RT). Because advanced NMSC is rare, studies1-5 examining the outcomes of RT for patients with T3/T4 tumors are limited. As the outcomes of RT in this patient cohort are unclear, this study was undertaken to examine survival in a large cohort of patients treated at our institution and to explore variables associated with survival outcomes.

This article is protected by copyright. All rights reserved.
Trends in Receipt of Buprenorphine and Naltrexone for Opioid Use Disorder Among Adolescents and Young Adults, 2001-2014
Authors: Scott E. Hadland, J. Frank Wharam, Mark A. Schuster, Fang Zhang, Jeffrey H. Samet, Marc R. Larochelle
Journal: JAMA Pediatrics (2017)

Opioid use disorder (OUD) frequently begins in adolescence and young adulthood. Intervening early with pharmacotherapy is recommended by major professional organizations. No prior national studies have examined the extent to which adolescents and young adults (collectively termed youth) with OUD receive pharmacotherapy.To identify time trends and disparities in receipt of buprenorphine and naltrexone among youth with OUD in the United States.A retrospective cohort study was conducted using deidentified data from a national commercial insurance database. Enrollment and complete health insurance claims of 9.7 million youth, aged 13 to 25 years were analyzed, identifying individuals who received a diagnosis of OUD between January 1, 2001, and June 30, 2014, with final follow-up date December 31, 2014. Analysis was conducted from April 25 to December 31, 2016. Time trends were identified and multivariable logistic regression was used to determine sociodemographic factors associated with medication receipt.Sex, age, race/ethnicity, neighborhood education and poverty levels, geographic region, census region, and year of diagnosis.Dispensing of a medication (buprenorphine or naltrexone) within 6 months of first receiving an OUD diagnosis.Among 20 822 youth diagnosed with OUD (0.2% of the 9.7 million sample), 13 698 (65.8%) were male and 17 119 (82.2%) were non-Hispanic white. Mean (SD) age was 21.0 (2.5) years at the first observed diagnosis. The diagnosis rate of OUD increased nearly 6-fold from 2001 to 2014 (from 0.26 per 100 000 person-years to 1.51 per 100 000 person-years). Overall, 5580 (26.8%) youth were dispensed a medication within 6 months of diagnosis, with 4976 (89.2%) of medication-treated youth receiving buprenorphine and 604 (10.8%) receiving naltrexone. Medication receipt increased more than 10-fold, from 3.0% in 2002 (when buprenorphine was introduced) to 31.8% in 2009, but declined in subsequent years (27.5% in 2014). In multivariable analyses, younger individuals were less likely to receive medications, with adjusted probability for age 13 to 15 years, 1.4% (95% CI, 0.4%-2.3%); 16 to 17 years, 9.7% (95% CI, 8.4%-11.1%); 18 to 20 years, 22.0% (95% CI, 21.0%-23.0%); and 21 to 25 years, 30.5% (95% CI, 30.0%-31.5%) (P < .001 for difference). Females (7124 [20.3%]) were less likely than males (13 698 [24.4%]) to receive medications (P < .001), as were non-Hispanic black (105 [14.8%]) and Hispanic (1165 [20.0%]) youth compared with non-Hispanic white (17 119 [23.1%]) youth (P < .001).In this first national study of buprenorphine and naltrexone receipt among youth, dispensing increased over time. Nonetheless, only 1 in 4 commercially insured youth with OUD received pharmacotherapy, and disparities based on sex, age, and race/ethnicity were observed.
Inhibitory Effects of Midostaurin and Blu-285 on Myeloid Progenitor Cells Derived from Patients with Multi-Mutated KIT D816V+ Advanced Systemic Mastocytosis
Authors: Mohamad Jawhar, Nicole Naumann, Sebastian Kluger, Juliana Schwaab, Georgia Metzgeroth, Erica K. Evans, Alexandra Gardino, Christoph Lengauer, Wolf-Karsten Hofmann, Nicholas C.P. Cross, Alice Fabarius, Andreas Reiter
Journal: Blood (2016)
Quantitative and Qualitative Gender Differences in the Immune System may Contribute to the Mild Progression of HCV Infection in Women
Authors: L Power, L Golden-Mason, L Lynch, JE Hegarty, C O'Farrelly
Journal: Endoscopy (2004)

Background: HCV infection has progressed slowly in the female chort of patients infected through Anti-D. There is evidence to suggest that the disease is more aggressive in males.
Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts
Authors: Ganqiang Liu, Joseph J Locascio, Jean-Christophe Corvol, Brendon Boot, Zhixiang Liao, Kara Page, Daly Franco, Kyle Burke, Iris E Jansen, Ana Trisini-Lipsanopoulos, Sophie Winder-Rhodes, Caroline M Tanner, Anthony E Lang, Shirley Eberly, Alexis Elbaz, Alexis Brice, Graziella Mangone, Bernard Ravina, Ira Shoulson, Florence Cormier-Dequaire, Peter Heutink, Jacobus J van Hilten, Roger A Barker, Caroline H Williams-Gray, Johan Marinus, Clemens R Scherzer, Clemens R. Scherzer, Bradley T. Hyman, Adrian J. Ivinson, Ana Trisini-Lipsanopoulos, Daly Franco, Kyle Burke, Lewis R. Sudarsky, Michael T. Hayes, Chizoba C. Umeh, Reisa Sperling, John H. Growdon, Michael A. Schwarzschild, Albert Y. Hung, Alice W. Flaherty, Deborah Blacker, Anne-Marie Wills, U. Shivraj Sohur, Nicte I. Mejia, Anand Viswanathan, Stephen N. Gomperts, Vikram Khurana, Mark W. Albers, Maria Alora-Palli, Scott McGinnis, Nutan Sharma, Bradford Dickerson, Matthew Frosch, Teresa Gomez-Isla, Steven Greenberg, James Gusella, Trey Hedden, E Tessa Hedley-Whyte, Aaron Koenig, Marta Marquis-Sayagues, Gad Marshall, Olivia Okereke, Anat Stemmer-Rachaminov, Jessica Kloppenburg, Michael G. Schlossmacher, John H. Growdon, Dennis J. Selkoe, Reisa Sperling, Thomas Yi, Joseph J. Locascio, Haining Li, Gabriel Stalberg, Zhixiang Liao, Roger Barker, Tom Foltynie, Caroline Williams-Gray, Trevor Robbins, Carol Brayne, Sarah Mason, Sophie Winder-Rhodes, Roger Barker, Caroline Williams-Gray, David P Breen, Gemma Cummins, Jonathan Evans, Sophie Winder-Rhodes, Jacobus J. van Hilten, Johan Marinus, Jean-Christophe Corvol, Alexis Brice, Jean-Christophe Corvol, Alexis Elbaz, Alain Mallet, Marie Vidailhet, Anne-Marie Bonnet, Cecilia Bonnet, Jean-Christophe Corvol, Alexis Elbaz, David Grabli, Andreas Hartmann, Stephan Klebe, Lucette Lacomblez, Graziella Mangone, Marie Vidailhet, Frédéric Bourdain, Jean-Philippe Brandel, Pascal Derkinderen, Franck Durif, Valérie Mesnage, Fernando Pico, Olivier Rascol, Christine Brefel-Courbon, Fabienne Ory-Magne, Sylvie Forlani, Suzanne Lesage, Graziella Mangone, Khadija Tahiri, Roger Albin, Roy Alcalay, Alberto Ascherio, Dubois Bowman, Alice Chen-Plotkin, Ted Dawson, Richard Dewey, Dwight German, Rachel Saunders-Pullman, Clemens Scherzer, David Vaillancourt, Vladislav Petyuk, Andy West, Jing Zhang
Journal: The Lancet Neurology (2017)
A Prospective Multicenter Study Evaluating Learning Curves and Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography Among Advanced Endoscopy Trainees: The Rapid Assessment of Trainee Endoscopy Skills Study
Authors: Sachin Wani, Rajesh Keswani, Matt Hall, Samuel Han, Meer Akbar Ali, Brian Brauer, Linda Carlin, Amitabh Chak, Dan Collins, Gregory A. Cote, David L. Diehl, Christopher J. DiMaio, Andrew Dries, Ihab El-Hajj, Swan Ellert, Kimberley Fairley, Ashley Faulx, Larissa Fujii-Lau, Srinivas Gaddam, Seng-Ian Gan, Jonathan P. Gaspar, Chitiki Gautamy, Stuart Gordon, Cynthia Harris, Sarah Hyder, Ross Jones, Stephen Kim, Srinadh Komanduri, Ryan Law, Linda Lee, Rawad Mounzer, Daniel Mullady, V. Raman Muthusamy, Mojtaba Olyaee, Patrick Pfau, Shreyas Saligram, Cyrus Piraka, Amit Rastogi, Laura Rosenkranz, Fadi Rzouq, Aditi Saxena, Raj J. Shah, Violette C. Simon, Aaron Small, Jayaprakash Sreenarasimhaiah, Andrew Walker, Andrew Y. Wang, Rabindra R. Watson, Robert H. Wilson, Patrick Yachimski, Dennis Yang, Steven Edmundowicz, Dayna S. Early
Journal: Clinical Gastroenterology and Hepatology (2017)
“Perception <i>v</i> production” of asparagus odour in urine needs to be determined in a controlled study
Authors: Mark Rishniw
Journal: BMJ (2017)

Markt and colleagues conducted a genome-wide association study of asparagus anosmia.1 As they noted in the introduction, the issue of “perception v production” has not been completely resolved. They could not resolve this issue in their comprehensive study because they asked participants whether after eating asparagus …