tbuckley/cabot-search huggingface dataset:
A prospective microbiome‐wide association study of food sensitization and food allergy in early childhood
Authors: Jessica H. Savage, Kathleen A. Lee‐Sarwar, Joanne Sordillo, Supinda Bunyavanich, Yanjiao Zhou, George O'Connor, Megan Sandel, Leonard B. Bacharier, Robert Zeiger, Erica Sodergren, George M. Weinstock, Diane R. Gold, Scott T. Weiss, Augusto A. Litonjua
Journal: Allergy (2017)

Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development.Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high-dose vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; P-values were adjusted for multiple comparisons.Complete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log2 fold change -2.15, P=.003), Dialister (log2 fold change -2.22, P=.009), Dorea (log2 fold change -1.65, P=.02), and Clostridium (log2 fold change -1.47, P=.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log2 fold change -3.41, P=.03), Oscillospira (log2 fold change -2.80, P=.03), Lactococcus (log2 fold change -3.19, P=.05), and Dorea (log2 fold change -3.00, P=.05) were underrepresented among subjects with food allergy.The temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy.
Patterns of failure on Ga PSMA (GaPSMA) and F18 FDG (FDG) PET CT in a prospective phase 2 trial of <sup>177</sup>Lu DKFZ PSMA 617 (LuPSMA) in men with castrate resistant metastatic prostate cancer (mCRPC).
Authors: Anthony M. Joshua, Phillip Stricker, Richard J Epstein, Bao Ho, Quoc Nguyen, Robert Kent, Kathy P Willowson, Michael Hofman, John A Violet, Louise Emmett
Journal: Journal of Clinical Oncology (2017)

2562 Background: LuPSMA is emerging as an effective therapy in mCRPC, with retrospective series reporting high PSA response rates in men undergoing treatment (tx). However, not all men have prolonged tx responses. We report the prospective imaging (GaPSMA/FDG) and PSA response of men who progress biochemically during LuPSMA tx to gain information on characteristics of failure patterns, to determine optimal future tx strategies. Methods: Men with mCRPC, who had failed androgen blockade, failed/ ineligible/refused chemotherapy, with GaPSMA positive disease were enrolled in a prospective phase 2 trial. All men underwent LuPSMA therapy 6-8Gbq, 4 doses at 6 weekly intervals. Imaging with FDG, GaPSMA, bone scan and CT scans was at screening, at subsequent PSA rise, or 3 months post completion of 4 cycles of therapy. Results: 14 men met eligibility criteria and enrolled. 4/14 (28%) men had progressive disease (no PSA response). 10/14 (72%) PSA reduced by a mean 56% .Overall 9/14 (64%) men had &gt;30% decline in PSA, and 5/15(36%) &gt;50% reduction in PSA. 7/15 men were reimaged with GaPSMA, FDG at biochemical failure or 3/12 post tx completion. Imaging revealed 4 distinct patterns (P) of progression. Conclusions: PSMA acts as both target for radionuclide therapy and biomarker for effective tx response. PSMA and FDG imaging at PSA failure following or during LU PSMA therapy identifies phenotypic patterns of failure that have implications for determining next best tx options in men with mCRPC. [Table: see text]
Phase I/II trial of palbociclib in combination with bicalutamide for the treatment of androgen receptor (AR)+ metastatic breast cancer (MBC).
Authors: Ayca Gucalp, Tracy Ann Proverbs-Singh, Adriana Corben, Mary Ellen Moynahan, Sujata Patil, Leigh Ann Boyle, Clifford A. Hudis, Tiffany A. Traina
Journal: Journal of Clinical Oncology (2016)

TPS1103 Background: Patients (pts) with triple negative breast cancer (TNBC) have limited effective therapeutic options and generally experience a more aggressive clinical course. Emerging evidence demonstrates that the androgen-signaling pathway plays a role in BC pathogenesis and may be a valuable therapeutic target. In TBCRC011, we tested the efficacy of the AR antagonist, bicalutamide (B) in pts with AR+/ER/PgR- MBC. B was well-tolerated and demonstrated a clinical benefit rate (CBR) of 19% in this population (Gucalp et al. CCR 2013). Palbociclib (P) is a competitive inhibitor of CDK4/6 and has been shown to reduce growth of AR+/ER/PgR- MDA-MB-453 BC cells via reduced Rb phosphorylation. In postmenopausal pts with luminal ER+ MBC the addition of P to letrozole significantly improved median progression-free survival (PFS) in comparison to letrozole monotherapy. Given the luminal signature of AR+ TNBC and the presence of intact Rb in this ER(-) subtype, we are testing the efficacy of B+P in pts with metastatic AR+ TNBC. NCT02605486. Methods: Pts with MBC consent to central AR testing at MSK. Key eligibility criteria include: Ph I AR+ (IHC ≥ 1%)/ER any/HER2(-) MBC/Ph II AR+ TN MBC, ECOG ≤ 2, postmenopausal (LHRH agonist allowed), measurable/non-measurable disease. Any number of prior regimens is permitted; pts with ER+ BC must have progression on 1 prior endocrine therapy. Treatment consists of B 100 mg orally daily and P 100 mg orally daily 3 weeks on 1 week off for the 1st dose-escalation cohort (cycle = 28 days). Pts are evaluated for toxicity every 2-4 weeks and for response every 8 weeks. Primary endpoint: Ph 1: determine recommended Ph II dose; Ph II: 6 month (mo) PFS. Secondary endpoints: CBR, toxicity, correlative studies to better characterize AR+TNBC. Ph I standard 3+3 design with 3 dose escalations; Ph II Simon two-stage minimax design, if 5/18 pts are alive and progression free at 6 mo then accrual would continue to a total 33 pts in stage 2. If ≥ 11/33 pts alive and progression free at 6 mo then B+P will warrant further study. As of 2/1/16, 3 pts with AR+ MBC are enrolled in the 1st dose-escalation cohort of Ph I. Clinical trial information: NCT02605486.
Diabetic End-Stage Renal Disease
Journal: New England Journal of Medicine (1990)

Background.Four linkage analyses have identified a region on chromosome 18q22-23 that appears to harbour a diabetic nephropathy (DN) susceptibility locus.A trinucleotide repeat sequence in exon 2 of the carnosinase gene (CNDP1) residing on 18q22.3 was subsequently associated with DN in European Caucasians and Arabs.Methods.We evaluated the role of the CNDP1 5 leucine/5 leucine (5-5) polymorphism (CNDP1 Mannheim) in diabetic end-stage renal disease (ESRD) susceptibility in 858 European Americans: 294 with type 2 DN-associated ESRD (DN-ESRD), 258 with diabetes mellitus (DM) lacking nephropathy and 306 healthy controls.Results.Subjects with DM lacking nephropathy were significantly more likely to be homozygous for the 5-leucine repeat CNDP1 genotype (5-5), compared with those with DN-ESRD (P ¼ 0.02).Healthy controls were also more likely to be homozygous for the 5-5 genotype, compared with those with DN-ESRD (P ¼ 0.008).No significant difference in 5-5 genotype frequency was observed between healthy controls and DM cases without nephropathy (P ¼ 0.74).Conclusion.European Americans homozygous for the 5-5 leucine repeat polymorphism in the CNDP1 gene are at significantly reduced risk for developing diabetic ESRD.This replicates the CNDP1 gene association with DN that was initially detected in European Caucasians and in Arabs, and further demonstrates that the CNDP1 gene and carnosine pathway appear to play a role in susceptibility to DN.
Types of Shade Vary in Protection Just Like Sunscreens
Authors: Caroline Opene, Mary-Margaret Chren, Eleni Linos
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
MicroRNA Induced Cardiac Reprogramming In Vivo
Authors: Tilanthi M. Jayawardena, Elizabeth A. Finch, Lunan Zhang, Hengtao Zhang, Conrad P. Hodgkinson, Richard E. Pratt, Paul B. Rosenberg, Maria Mirotsou, Victor J. Dzau
Journal: Circulation Research (2014)

A major goal for the treatment of heart tissue damaged by cardiac injury is to develop strategies for restoring healthy heart muscle through the regeneration and repair of damaged myocardium. We recently demonstrated that administration of a specific combination of microRNAs (miR combo) into the infarcted myocardium leads to direct in vivo reprogramming of noncardiac myocytes to cardiac myocytes. However, the biological and functional consequences of such reprogramming are not yet known.The aim of this study was to determine whether noncardiac myocytes directly reprogrammed using miRNAs in vivo develop into mature functional cardiac myocytes in situ, and whether reprogramming leads to improvement of cardiac function.We subjected fibroblast-specific protein 1-Cre mice/tandem dimer Tomato (tdTomato) mice to cardiac injury by permanent ligation of the left anterior descending coronary artery and injected lentiviruses encoding miR combo or a control nontargeting miRNA. miR combo significantly increased the number of reprogramming events in vivo. Five to 6 weeks after injury, morphological and physiological properties of tdTomato(-) and tdTomato(+) cardiac myocyte-like cells were analyzed ex vivo. tdTomato(+) cells expressed cardiac myocyte markers, sarcomeric organization, excitation-contraction coupling, and action potentials characteristic of mature ventricular cardiac myocytes (tdTomato(-) cells). Reprogramming was associated with improvement of cardiac function, as analyzed by serial echocardiography. There was a time delayed and progressive improvement in fractional shortening and other measures of ventricular function, indicating that miR combo promotes functional recovery of damaged myocardium.The findings from this study further validate the potential use of miRNA-mediated reprogramming as a therapeutic approach to promote cardiac regeneration after myocardial injury.
Germline cancer susceptibility mutations in older women with breast cancer (BC).
Authors: Yanin Chavarri Guerra, Sharon Sand, Sandra Brown, Carolyn B. Hendricks, Mary Hander, Kisa Weeman, Suhasini Nadesan, Zdenka E Segota, Howard Ho Wing Cheng, Arti Hurria, Enrique Soto Perez De Celis, Bita Nehoray, Lily Kuzmich, Ilana Solomon, Christina Rybak, Kathleen Reilly Blazer, Lily Ravel Van Tongeren, Kenneth Bruce Blankstein, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2017)

e13030 Background: Older women with BC are less likely to undergo genetic cancer risk assessment since a hallmark of hereditary BC is younger age at onset. Hence there are limited data regarding genetic risk assessment findings in older women with BC. We analyzed the clinical characteristics and germline variant profiles of women with history of BC referred for genetic counseling at age ≥ 65 years, enrolled in the Clinical Cancer Genomics Community Research Network registry. Methods: Women age ≥ 65 with a history of BC (invasive or ductal carcinoma in situ) who underwent genetic testing from 1997 to 2016 were included. The profile of those found to have BC-related pathogenic variants was analyzed. Demographic and clinical characteristics for those with and without germline variants were compared using Fisher’s test and x 2 statistics. Results: 1372 women age ≥ 65 with BC were identified. Genetic testing was performed in 75% (n = 1035), among whom 10.4% (n = 108) had a germline variant in a BC-associated gene. High risk gene variants accounted for 85.1% (n = 92): BRCA2 (41.6%, n = 45), BRCA1 (37%, n = 40), PALB2 (5.5%, n = 6) and TP53 ( &lt; 1%, n = 1). Moderate risk gene variants were identified in 16.6% (n = 18): CHEK2 (13.8%, n = 15), ATM (1.8%, n = 2) and NF1 ( &lt; 1%, n = 1). Mean age at BC diagnosis was 56.4 (range 29 - 84) for women with variants and 60.9 (range 20 - 90) for those without (p &lt; .001). 25.9% of women with variants (n = 28) had their first BC diagnosed ≥ age 65, of which 60.7% (n = 17) were BRCA2 and 21.4% (n = 6) were BRCA1 mutations ( BRCA2 was significantly higher in women diagnosed with BC age ≥ 65 [p &lt; .001]). There was no difference in the mean number of 1st, 2nd and 3rd degree relatives with BC (2.4 [range 0-10] vs 2.2 [range 0-15]) for women with and without variants, respectively, and no difference in stage at diagnosis (Stage I-II in 95% vs 89.5%, p = .4). Women with variants were less likely to have ER/PR positive tumors than those without (66% vs 81.6%, p = .01). Conclusions: BC related susceptibility variants, particularly in BRCA2, are found in a significant number of older women undergoing genetic testing for a first diagnosis of BC ≥ 65. Older women with a clinical suspicion of hereditary BC should not be excluded from genetic testing and counseling based on chronological age alone.
Putting the US Preventive Services Task Force Recommendation for Childhood Obesity Screening in Context
Authors: Rachel L. J. Thornton, Raquel G. Hernandez, Tina L. Cheng
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
Changes in Coronary Artery Plaque With Testosterone Therapy
Authors: Sandeep Dhindsa, Michael F. Wilson, Paresh Dandona
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
Duration of the anti-androgen in men undergoing six months of an LHRH agonist and radiation therapy for unfavorable-risk prostate cancer and the risk of death.
Authors: Nina Niu Sanford, Ming-Hui Chen, Marian J. Loffredo, Andrew A. Renshaw, Philip W. Kantoff, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2016)

5070 Background: Whether adding an anti-androgen (AA) to a luteinizing hormone-releasing hormone (LHRH) agonist in the radiotherapeutic management of unfavorable-risk prostate cancer (PC) reduces all cause and PC-specific mortality (ACM and PCSM) risk is unknown. We evaluated whether the extent of AA received impacted the risk of ACM and PCSM within comorbidity subgroups. Methods: Between 1995 and 2001, 206 men with localized unfavorable-risk PC were enrolled on a randomized trial comparing radiation with (N = 102) or without (N = 104) 6 months of androgen deprivation therapy (ADT). Partial AA use (median: 4.2 months) occurred in 29 of the 102 men randomized to ADT due to discontinuation for elevated liver function tests or diarrhea. Cox and Fine and Gray's regressions were used to evaluate the impact of full versus partial AA use on PCSM and ACM risk within comorbidity subgroups adjusting for age and PC prognostic factors. Results: After a median follow-up of 16.62 years, 156 men died, 29 from PC (19%) including 25 (86%) and 4 (14%) PC deaths in the 157 and 49 men with no or minimal versus moderate to severe comorbidity, respectively. In men with moderate to severe comorbidity, an increased ACM risk with full as opposed to partial AA use that approached statistical significance was observed (adjusted hazard ratio (AHR), 2.25 [95% confidence interval (CI), 0.94-5.41]; P = 0.07); whereas only 1 and no PC deaths occurred in men receiving a partial versus a full AA course respectively. Among men with no or minimal comorbidity, no decrease in ACM (AHR, 0.97 [95% CI, 0.49-1.91]; P = 0.92) or PCSM risk (AHR 0.73 [95% CI 0.10-5.46]; P = 0.76) was observed for full versus partial AA use. Conclusions: Increasing AA use by 2 months does not appear to impact survival in men with localized unfavorable-risk PC and no or minimal comorbidity but may shorten survival in men with moderate to severe comorbidity raising concern regarding in whom and for how long the AA should be prescribed. Clinical trial information: NCT00116220.
5th International Conference on Concussion in Sport (Berlin)
Authors: Paul McCrory, Willem H Meeuwisse, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Nina Feddermann-Demont, Michael McCrea, Michael Makdissi, Jon Patricios, Kathryn J Schneider, Allen K Sills
Journal: British Journal of Sports Medicine (2017)

Sport-related concussion (SRC) has received much media coverage over the past 5 years. In the face of misinformation about this injury in the minds of parents, coaches and athletes, it is critical that all involved stakeholders receive scientifically sound and up-to-date information regarding SRC and its potential consequences.

One of the most significant developments in SRC over the past two decades has been the establishment of the Concussion In Sport Group (CISG). This group has organised the key consensus meetings in this field and has published assessment tools that have …
Abstract 12028: Deranged Renal Functions Improve After Enhanced External Counter Pulsation Therapy in Patients With Chronic Ischemic Heart Disease
Authors: Sanjay Mittal, Vivek Jain, Manish Bansal, Ravi R Kasliwal, Naresh Trehan
Journal: Circulation (2016)

Introduction: Renal dysfunction frequently occurs in patients with coronary artery disease (CAD) significantly limiting their therapeutic options. Enhanced External Counter Pulsation (EECP) therapy improves symptomatic status and cardiac function in patients with CAD; however it’s impact on concomitant renal dysfunction is not well understood. Hypothesis: EECP therapy could improve renal function by improving LV systolic function and subsequently the renal perfusion. Methods: Patients with CAD referred to our EECP lab having baseline calculated glomerular filtration rate (GFR) less than 60ml/min were included in the study. All patients were subjected to 35 EECP sessions of one hour each. A thorough clinical evaluation, echocardiography, 6 min hall walk test and renal function test were done at the baseline and after completion of therapy. GFR was calculated with the help of MDRD (Modification of Diet in Renal Disease) formula. Statistical comparisons were made in renal parameters before and after EECP therapy. Results: Seventy four patients with GFR &lt;60ml/min, mean age 64.5+/-8.7 yrs, 63(92%) males, completed 35 sessions of EECP therapy. Significant improvement was noted in left ventricular ejection fraction (LVEF) (34.8+/-12.4 to 38.8+/-12.3%, P&lt;0.0001), functional class and 6 min hall walk distance (263.4+/-147.8 meters to 403.1+/-96.2 meters, P&lt;0.0001) from baseline to post EECP therapy. GFR increased significantly from 39.5+/-15.1 ml/min at baseline to 46.5 +/- 21.9 ml/min after EECP. The improvement in GFR was more pronounced in the subgroup of 51 patients having baseline LVEF &lt;40%, where 61% patients showed increase in GFR (from mean 40.6+/-14.8 to 48.1 +/- 20.1 ml/min, p= 0.003) after EECP. Blood urea and creatinine also significantly decreased in this group after EECP therapy. Conclusions: Deranged renal function, including reduced GFR, improve significantly after EECP therapy in patients with CAD, especially in those having baseline low LVEF. This beneficial effect of EECP is likely to be due to improvement in renal perfusion secondary to better LV function. Accordingly, EECP could be a potential therapeutic option for stabilizing ischemic heart failure patients with deranged renal function, prior to cardiac interventions.