tbuckley/cabot-search huggingface dataset:
Abstract P280: Greater Dietary Fiber Consumption is Associated with Lower Insulin Resistance and Blood Pressure in Adolescents
Authors: Yutong Dong, Norman Pollock, Anas Raed, Samip Parikh, Jigar Bhagatwala, Bernard Gutin, Haidong Zhu
Journal: Circulation (2017)

Introduction: Greater dietary fiber intake has shown cardiometabolic benefits in adults. Previously, we have shown that dietary fiber intake is inversely associated with adiposity and inflammation in youth. However, evidence of the relations of fiber intake to insulin resistance and blood pressure in adolescents is lacking. Hypothesis: We hypothesized that greater daily dietary fiber intake would be associated with lower insulin resistance and blood pressure. Additionally, insulin resistance may mediate the relationship between fiber intake and blood pressure. Methods: Seven hundred and sixty-six Southeastern US adolescents from age 14 to 18 were recruited (50.3% females; 49.2% African-Americans). Diet was assessed via four to seven independent 24-hour recalls. Seated systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured five times at 1 minute intervals after 10 minute rest and the last three measurements were averaged. Percent body fat (%BF) was measured by dual-energy x-ray absorptiometry. Fasting blood samples were measured for fasting glucose and fasting insulin. Homeostatic Model Assessment for insulin resistance (HOMA-IR) was then calculated. Results: Multiple linear regressions with bootstrapping, adjusting for age, sex, race, Tanner stage, %BF, and energy intake, revealed that dietary total fiber intake was negatively associated with HOMA-IR, SBP, and DBP (standardized β = -0.22, β = -0.09, and β = -0.12; all p &lt; 0.05). Subcategorizing fiber into soluble and insoluble fiber revealed that both types were negatively associated with HOMA-IR ( p &lt; 0.01). However, only soluble fiber intake was negatively associated with both SBP and DBP (all p &lt; 0.01). No significant race and gender interactions with fiber were identified. Furthermore, a mediation test identified HOMA-IR as a mediator between soluble fiber intake and SBP and DBP (95% CI: -0.34; -0.04; 95% CI: -0.15; -0.01 respectively). Conclusions: Our data suggest that greater consumption of fiber may reduce insulin resistance and blood pressure in adolescents. Furthermore, insulin resistance may mediate the relationship between soluble fiber intake and blood pressure.
Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
Authors: Mona O. Mohsen, Matthew D. Heath, Gustavo Cabral-Miranda, Cyrill Lipp, Andris Zeltins, Marcos Sande, Jens V. Stein, Carsten Riether, Elisa Roesti, Lisha Zha, Paul Engeroff, Aadil El-Turabi, Thomas M. Kundig, Monique Vogel, Murray A. Skinner, Daniel E. Speiser, Alexander Knuth, Matthias F. Kramer, Martin F. Bachmann
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. <h3>Methods</h3> Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMV<sub>TT</sub>-VLPs) incorporating a universal Tetanus toxoid epitope TT830–843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMV<sub>TT</sub>-VLPs using bio-orthogonal Cu-free click chemistry. The CuMV<sub>TT</sub>-p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined&nbsp;with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. <h3>Results</h3> Our results showed that CuMV<sub>TT</sub>-VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 μM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMV<sub>TT</sub>-p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8<sup>+</sup>, specific p33 T cell response or tumour protection were assessed. <h3>Conclusion</h3> The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic.
Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups
Authors: Simon Rothwell, Hector Chinoy, Janine A Lamb, Frederick W Miller, Lisa G Rider, Lucy R Wedderburn, Neil J McHugh, Andrew L Mammen, Zoe E Betteridge, Sarah L Tansley, John Bowes, Jiří Vencovský, Claire T Deakin, Katalin Dankó, Limaye Vidya, Albert Selva-O'Callaghan, Lauren M Pachman, Ann M Reed, Øyvind Molberg, Olivier Benveniste, Pernille R Mathiesen, Timothy R D J Radstake, Andrea Doria, Jan de Bleecker, Annette T Lee, Michael G Hanna, Pedro M Machado, William E Ollier, Peter K Gregersen, Leonid Padyukov, Terrance P O'Hanlon, Robert G Cooper, Ingrid E Lundberg
Journal: Annals of the Rheumatic Diseases (2019)

Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups.We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10-5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10-53 and HLA-DRB1*03:01, p=3.25×10-9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10-26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10-11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10-13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10-6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10-64) and position 9 of HLA-B (p=7.03×10-11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies.These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.
ERCP IN INFANTS, CHILDREN, AND ADOLESCENTS – DIFFERENT ROLES OF THE METHODS IN DIFFERENT AGE GROUPS
Authors: R Keil, J Drábek, J Lochamnnová, J Šťovíček, P Koptová, M Wasserbauer, B Frýbová, J Šnajdauf, M Rygl, R Kotalová, Š Hlava
Journal: Endoscopy (2019)

Endoscopic retrograde cholangiopancreatography (ERCP) is seldom used in children, and published series have limited numbers of pediatric patients. The aim of this retrospective, long-term, observational study was to assess the efficacy and safety of pediatric ERCP in a large group of children.
EFFICACY OF ENDOSCOPIC TREATMENTS FOR ACUTE ESOPHAGEAL VARICEAL BLEEDING IN CIRRHOTICS: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: F Onofrio, J Pereira Lima, A Azeredo, F Valença, A Stein, G Pereira Lima, F Cavalcanti, CE Oliveira dos Santos
Journal: Endoscopy (2019)

Most guidelines recommend and consider the use of ligation and vasoactive drugs as the first line therapy and grade A evidence for acute variceal bleeding (AVB), although Western studies about this issue are lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of endoscopic treatments for AVB.
Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial
Authors: Lior Carmi, Aron Tendler, Alexander Bystritsky, Eric Hollander, Daniel M. Blumberger, Jeff Daskalakis, Herbert Ward, Kyle Lapidus, Wayne Goodman, Leah Casuto, David Feifel, Noam Barnea-Ygael, Yiftach Roth, Abraham Zangen, Joseph Zohar
Journal: American Journal of Psychiatry (2019)

Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study.At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of ≥30% in YBOCS score) at the posttreatment assessment and after another month of follow-up.Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up.High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions.
EVALUATION OF THE COMBINED EFFECTS OF SPLIT VS. DAY BEFORE AND LOW RESIDUE VS. CLEAR FLUID REGIMENS ON THE COLONOSCOPY PREPARATION
Authors: Z Bari, I Maleki, M Hadizadeh, H Fakheri, SM Valizadeh, V Hoseini, T Taghvaei, A Kazemi
Journal: Endoscopy (2019)

Colonoscopy is widely used to diagnose and treat colonic diseases. Its' accuracy and quality depends on the colonoscopy preparation. Split dosage of Polyethylene Glycol (PEG) has been shown to improve the colonoscopy preparation in comparison to the “day before” prescription. Also, using low residue diet can improve the patient's tolerance and satisfaction and therefore, his/her co-operation in preparation steps. In this study we have combined and assessed these two concepts on four groups of patients.
Use of Ventricular Assist Devices and Heart Transplantation for Advanced Heart Failure
Authors: Leslie Miller, Emma Birks, Maya Guglin, Harveen Lamba, O.H. Frazier
Journal: Circulation Research (2019)

There are only 2 treatments for the thousands of patients who progress to the most advanced form of heart failure despite the application of guideline-based medical therapy, use of ventricular assist devices and heart transplantation. There has been a great deal of progress in both of these therapies that have led to improved outcomes including significant improvement in survival and functional capacity. Heart transplantation offers the best short- and long-term survival for patients with end-stage heart failure, and the majority of these recipients achieve relatively limitless functional capacity for their age. However, the chronic shortage of available donors limits the number of recipients in the United States to an only 2500 patients/y or only a fraction of potential candidates. The significant improvement in outcomes now possible with durable ventricular assist devices has led to a significant increase in their use, which now exceeds the volume of heart transplants in the United States, with the greatest growth in use for those not considered to be candidates for heart transplantation, previously referred to as destination therapy. This article will review the substantial progress that has taken place for both of these life-saving treatment options, as well as the future directions.
A man with severe leg pain
Authors: Prateush Singh, Esha Singh, Mo Akhavani
Journal: BMJ (2019)

A 23 year old man presented to the emergency department after being trapped between two cars and suffering a crush injury to his right leg. Radiography revealed no underlying fractures. One hour after the injury he developed progressively worsening pain in his right leg, which he described as 8/10 in severity. It seemed to be out of proportion to his injury and was worse with both passive and active movement. His right leg became very tense and swollen and he developed paraesthesia in his right foot. Pulses remained palpable and, although painful, he could still actively move his leg and foot. Results of tests he underwent are shown in table 1.

View this table:

Table 1 
Results of relevant investigations



1.  What is the diagnosis?

2.  What is the initial …
Prognostic role of microRNA 182 and microRNA 18a in locally advanced triple negative breast cancer
Authors: R. Bajaj, D. Doval, R. Tripathi, T. Sridhar, A. Korlimarla, K.D. Choudhury, M. Suryavanshi, A. Mehta
Journal: Annals of Oncology (2019)

Background: Breast cancer is a heterogeneous disease and triple negative breast cancers (TNBC) have higher histological grade, more aggressive locally along with higher chances of distant visceral metastasis. The present study was undertaken to assess the epigenetic regulation in breast cancer and the role of microRNA 182 and microRNA 18a (MIR 182 and MIR 18a) expression in locally advanced TNBC and comparison with the clinico-pathological variables and survival. Methods: A total of 50 patients of locally advanced TNBC and 19 estrogen/ progesterone receptor positive patients (controls) during the period January 2011 to December 2013 were included in the study. Clinical response evaluation was done post neoadjuvant chemotherapy. The expression level of test genes (MIR 182 and MIR 18a) was determined using Real time polymerase chain reaction from formalin fixed paraffin embedded (FFPE) biopsy blocks. The MIR 182 and MIR 18a expression levels were correlated with the clinico-pathological data including patient outcome and survival. Results: A total of 36% patients had MIR 182 over-expression (value ≥6.32) whereas 40% patients had MIR 18a over-expression (value ≥8.84). The expression levels of MIR 182 and MIR 18a were significantly higher in the TNBC patients as compared to the non-TNBC group (p < 0.0001). Higher MIR 182 and MIR 18a expression was related to bigger tumour size, higher nodal status and poor clinical and pathological complete response. Also, 56.2% patients with MIR 182 levels <6.32 and 11.1% patients with MIR 182 levels ≥6.32 achieved clinical complete response, p-value 0.002. Around 60% patients with MIR 18a levels <8.84 and 10% patients with MIR 18a levels ≥8.84 achieved clinical complete response, p-value <0.0001. A total of 50% patients with MIR 182 levels <6.32 and 11.1% patients with MIR 182 levels ≥6.32 achieved pathological complete response, p-value 0.007. On univariate cox regression analysis, MIR 182 and MIR 18a overexpression were found to correlate significantly with overall survival. Conclusions: MIR 182 and MIR 18a overexpression is correlated with worse clinical and pathological tumour characteristics in locally advanced TNBC. This study may be used to develop future biomarkers for prognostication of locally advanced TNBC. Legal entity responsible for the study: DC Doval. Funding: Rajiv Gandhi Cancer Institute and Research Centre. Disclosure: All authors have declared no conflicts of interest.
RETROFLEXION IN THE ASCENDING COLON IS A COSTLESS ENDOSCOPIC MANEUVER INCREASING ADENOMA DETECTION RATE
Authors: S Michopoulos, G Axiaris, P Baxevanis, M Stoupaki, V Gagari, G Leonidakis, A Karlaftis, E Zampeli, M Sotiropoulou, K Petraki
Journal: Endoscopy (2019)

Missing polyps during colonoscopy is an important factor for the appearance of interval cancers especially in the ascending colon (AscCol). Study aim: Evaluate the contribution of retroflexion to polyp/adenoma detection.
Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non–Small Cell Lung Cancer
Authors: Siwen Hu-Lieskovan, Aaron Lisberg, Jesse M. Zaretsky, Tristan R. Grogan, Hira Rizvi, Daniel K. Wells, James Carroll, Amy Cummings, John Madrigal, Benjamin Jones, Jacklin Gukasyan, I. Peter Shintaku, Dennis Slamon, Steven Dubinett, Jonathan W. Goldman, David Elashoff, Matthew D. Hellmann, Antoni Ribas, Edward B. Garon
Journal: Clinical Cancer Research (2019)

Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit.
ENDOSCOPIC RESECTION OF WIDESPREAD ADENOMATA OF THE PAPILLA AND SMALL-INTESTINE AS ORGAN PRESERVING MINIMALLY INVASIVE INTERVENTION USING ESD OR ESD/EMR.PRELIMINARY RESULTS FROM A EUROPEAN CENTER
Authors: A Farmer, M Hofmeyer, J Hochberger
Journal: Endoscopy (2019)

Most duodenal adenomata can be resected endoscopically using EMR. However, a considerable number of widespread lesions are still removed surgically with a considerable morbidity and mortality. The challenge of endoscopic resection in the duodenum consists in the thin duodenal wall. Lesions distally to the papilla have a high risk of secondary perforation due to aggressive pancreatic and biliary juice.
A four-year study of epidemiological trends of breast cancer in a Haitian cancer program
Authors: J.J. Bernard, L.G. Alexis, V.J. Degennaro
Journal: Annals of Oncology (2019)

Background: According to GLOBOCAN 2018, breast cancer is the most common cancer among women in Haiti. However, its trend throughout the years has not yet been studied. This study aims to present the four-year epidemiological trends of breast cancer managed by a cancer program in Port-au-Prince, Haiti. Methods: A retrospective study was conducted on patients with breast cancer aged 18 years old (y/o) or more of the cancer clinic of Innovating Health International from January 2014 to December 2017. The chart review focused on variables such as age, gender, year of diagnosis, staging, estrogen receptor (ER) status and outcome. A systematic comparison between the years, age and ER status was performed. Overall mortality and loss to follow-up rates were also estimated. Results: Six hundred and sixty-two (662) cases of breast cancer, among them 659 women and 3 men, were selected for the study period, respectively 114 in 2014, 131 in 2015, 159 in 2016 and 258 in 2017 (p < 0.001). The mean age of the cohort was 50.7 years [20 –94], decreasing from 52.3 years in 2014 to 50.2 years in 2017 (p = 0.2). Patients under 40 y/o represented 21.4%% of this cohort, with the proportion increasing from 15.2% in 2014 to 24.5% in 2017 (p = 0.051). 92.3% of the staged patients (n = 595) had advanced breast cancer (stages IIB to IV). 30.8% of the patients had metastatic cancer, and the proportion decreased from 38.9% in 2014 to 25.7% in 2017 (p < 0.001). There was a higher proportion of MBC among Patients ≥ 40 y/o (32.5%) versus those < 40 y/o (24.6%) (p = 0.07). Of the patients with known ER status (n = 325), 56.9% were ER-positive, 52.4% among the < 40 y/o versus 58.1% among the ≥ 40 y/o (p = 0.41). The overall mortality rate was 35.5%, 35.5% among the <40 y/o versus 35.6% among the ≥ 40 y/o (p = 0.98). 14.8% of the patients were lost to follow-up. ER-negative patients were significantly more likely to die than ER-positive ones (Odds Ratio=1.91, p = 0.007). Conclusions: There were a significant increase of breast cancer admissions and a decrease of metastatic cases from 2014 to 2017, due to a combination of increased awareness, incidence and referral. The breast cancer population became younger throughout the years, with more ER-negative cases among the < 40 y/o subgroup. ER-negative status was significantly associated with mortality. Legal entity responsible for the study: Joseph Bernard Jr. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
CLINICAL OUTCOMES AND POST-PROCEDURAL COMPLICATIONS OF ENDOSCOPIC SUBMUCOSAL DISSECTION OF GASTRIC NEOPLASIA INVOLVING THE PYLORIC CHANNEL
Authors: JS Koh, JJ Park, MK Joo, BJ Lee, HJ Chun, SW Lee, CH Yang, EY Kim
Journal: Endoscopy (2019)

Gastric neoplasia involving pyloric channel (GNPC) is technically difficult and post-procedural stenosis is concerned. We evaluated the feasibility and effectiveness of the endoscopic submucosal dissection (ESD) for GNPC, and predictive factors for stenosis during follow-up.