tbuckley/cabot-search huggingface dataset:
A Reduced Incretin Effect Mediated by the rs7903146 Variant in the <i>TCF7L2</i> Gene Is an Early Marker of β-Cell Dysfunction in Obese Youth
Authors: Alfonso Galderisi, Domenico Tricò, Bridget Pierpont, Veronika Shabanova, Stephanie Samuels, Chiara Dalla Man, Brittany Galuppo, Nicola Santoro, Sonia Caprio
Journal: Diabetes Care (2020)

OBJECTIVE The risk genotype for the common variant rs7903146 of the transcription factor 7-like-2 (TCF7L2) gene has been found to affect the incretin response in healthy and obese adults; however, whether a similar functional defect is also present in obese adolescents remains unexplored. Herein, we examined the functional effect of the rs7903146 variant in the TCF7L2 gene on the incretin effect and determined its translational metabolic manifestation by performing deep phenotyping of the incretin system, β-cell function relative to insulin sensitivity, the gastrointestinal-induced glucose disposal (GIGD) in obese youth with normal and impaired glucose tolerance. RESEARCH DESIGN AND METHODS Thirty-nine obese adolescents without diabetes (median age 15 [25th, 75th percentile 14, 18] years; BMI 37 [33, 43] kg/m2) were genotyped for the rs7903146 variant of TCF7L2 and underwent a 3-h oral glucose tolerance test (OGTT) followed by an isoglycemic intravenous glucose infusion (iso-intravenous glucose tolerance test [IVGTT]) to match the plasma glucose concentrations during the OGTT and a hyperglycemic clamp with arginine stimulation. The incretin effect was measured as 100 * (AUC-SROGTT − AUC-SRiso-IVGTT) / AUC-SROGTT, where AUC-SR = area under the curve of C-peptide secretion rate. Participants were grouped into tertiles according to the percentage incretin effect (high, moderate, and low) to describe their metabolic phenotype. RESULTS The presence of T risk allele for TCF7L2 was associated with a markedly reduced incretin effect compared with the wild-type genotype (0.3% [−7.2, 14] vs. 37.8% [12.5, 52.4], P &amp;lt; 0.002). When the cohort was stratified by incretin effect, the high, moderate, and low incretin effect groups did not differ with respect to anthropometric features, while the low incretin effect group exhibited higher 1-h glucose (P = 0.015) and a reduced disposition index, insulin sensitivity, and insulin clearance compared with the high incretin effect group. GIGD was reduced in the low incretin effect group (P = 0.001). The three groups did not differ with respect to intravenous glucose-induced insulin secretion and arginine response during the hyperglycemic clamp. CONCLUSIONS A reduced incretin effect and its association with the TCF7L2 variant rs7903146 identify an early metabolic phenotype in obese youth without diabetes, featuring a higher plasma glucose peak at 1 h; lower insulin secretion, sensitivity, and clearance; and GIGD.
Plans of US Parents Regarding School Attendance for Their Children in the Fall of 2020
Authors: Emily Kroshus, Matt Hawrilenko, Pooja S. Tandon, Dimitri A. Christakis
Journal: JAMA Pediatrics (2020)

As schools consider reopening for in-person instruction prior to availability of a coronavirus disease 2019 (COVID-19) vaccine, families may be weighing their priorities regarding school attendance.
Prediction of clinically relevant Pancreatico-enteric Anastomotic Fistulas after Pancreatoduodenectomy using deep learning of Preoperative Computed Tomography
Authors: Wei Mu, Chang Liu, Feng Gao, Yafei Qi, Hong Lu, Zaiyi Liu, Xianyi Zhang, Xiaoli Cai, Ruo Yun Ji, Yang Hou, Jie Tian, Yu Shi
Journal: Theranostics (2020)

Rationale: Clinically relevant postoperative pancreatic fistula (CR-POPF) is among the most formidable complications after pancreatoduodenectomy (PD), heightening morbidity/mortality rates. Fistula Risk Score (FRS) is a well-developed predictor, but it is an intraoperative predictor and quantifies >50% patients as intermediate risk. Therefore, an accurate and easy-to-use preoperative index is desired. Herein, we test the hypothesis that quantitative analysis of contrast-enhanced computed tomography (CE-CT) with deep learning could predict CR-POPFs. Methods: A group of 513 patients underwent pancreatico-enteric anastomosis after PD at three institutions between 2006 and 2019 was retrospectively collected, and formed a training (70%) and a validation dataset (30%) randomly. A convolutional neural network was trained and generated a deep-learning score (DLS) to identify the patients with higher risk of CR-POPF preoperatively using CE-CT images, which was further externally tested in a prospective cohort collected from August 2018 to June 2019 at the fourth institution. The biological underpinnings of DLS were assessed using histomorphological data by multivariate linear regression analysis. Results: CR-POPFs developed in 95 patients (16.3%) in total. Compared to FRS, the DLS offered significantly greater predictability in training (AUC:0.85 [95% CI, 0.80-0.90] vs. 0.78 [95% CI, 0.72-0.84]; P = 0.03), validation (0.81 [95% CI, 0.72-0.89] vs. 0.76 [95% CI, 0.66-0.84], P = 0.05) and test (0.89 [95% CI, 0.79-0.96] vs. 0.73 [95% CI, 0.61-0.83], P < 0.001) cohorts. Especially in the challenging patients of intermediate risk (FRS: 3-6), the DLS showed significantly higher accuracy (training: 79.9% vs. 61.5% [P = 0.005]; validation: 70.3% vs. 56.3% [P = 0.04]; test: 92.1% vs. 65.8% [P = 0.013]). Additionally, DLS was independently associated with pancreatic fibrosis (coefficients: -0.167), main pancreatic duct (coefficients: -0.445) and remnant volume (coefficients: 0.138) in multivariate linear regression analysis (r2 = 0.512, P < 0.001). The user satisfaction score in the test cohort was 4 out of 5. Conclusions: Preoperative CT based deep-learning model provides a promising novel method for predicting CR-POPF occurrences after PD, especially at intermediate FRS risk level. This has a potential to be integrated into radiologic reporting system or incorporated into surgical planning software to accommodate the preferences of surgeons to optimize preoperative strategies, intraoperative decision-making, and even postoperative care.
Clinical Guidelines Synopsis of Groin Hernia Management
Authors: David C. Chen, Benjamin K. Poulose
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
A brief introduction to climate change and health
Authors: Victoria Fairweather, Elke Hertig, Claudia Traidl‐Hoffmann
Journal: Allergy (2020)

Dr Hertig reports grants and personal fees from German Research Foundation, during the conduct of the study. Dr Traidl-Hoffmann reports grants and personal fees from Töpfer, personal fees from Sanofi, personal fees from Lilly, grants and personal fees from Sebapharma, personal fees from La Roche Posay, personal fees from Lancome and personal fees from Novartis, during the conduct of the study. Dr Fairweather has nothing to disclose.
Targeting immune checkpoints in hematological malignancies
Authors: Basit Salik, Mark J. Smyth, Kyohei Nakamura
Journal: Journal of Hematology & Oncology (2020)

Immune checkpoint blockade (ICB) therapies such as anti-programmed death 1 (PD-1) and anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) have dramatically transformed treatment in solid tumor oncology. While immunotherapeutic approaches such as stem cell transplantation and anti-cancer monoclonal antibodies have made critical contributions to improve outcomes in hematological malignancies, clinical benefits of ICB are observed in only limited tumor types that are particularly characterized by a high infiltration of immune cells. Importantly, even patients that initially respond to ICB are unable to achieve long-term disease control using these therapies. Indeed, primary and acquired resistance mechanisms are differentially orchestrated in hematological malignancies depending on tumor types and/or genotypes, and thus, an in-depth understanding of the disease-specific immune microenvironments will be essential in improving efficacy. In addition to PD-1 and CTLA-4, various T cell immune checkpoint molecules have been characterized that regulate T cell responses in a non-redundant manner. Several lines of evidence suggest that these T cell checkpoint molecules might play unique roles in hematological malignancies, highlighting their potential as therapeutic targets. Targeting innate checkpoint molecules on natural killer cells and/or macrophages has also emerged as a rational approach against tumors that are resistant to T cell-mediated immunity. Given that various monoclonal antibodies against tumor surface proteins have been clinically approved in hematological malignancies, innate checkpoint blockade might play a key role to augment antibody-mediated cellular cytotoxicity and phagocytosis. In this review, we discuss recent advances and emerging roles of immune checkpoint blockade in hematological malignancies.
Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment
Authors: Hao Cai, Yufan Xiang, Yujun Zeng, Zhiqian Li, Xiuli Zheng, Qiang Luo, Hongyan Zhu, Qiyong Gong, Zhongwei Gu, Yanhui Liu, Hu Zhang, Kui Luo
Journal: Acta Pharmaceutica Sinica B (2020)

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.
Comparison of <i>International Classification of Diseases and Related Health Problems, Tenth Revision</i> Codes With Electronic Medical Records Among Patients With Symptoms of Coronavirus Disease 2019
Authors: Brendan T. Crabb, Ann Lyons, Margaret Bale, Valerie Martin, Ben Berger, Sara Mann, William B. West, Alyssa Brown, Jordan B. Peacock, Daniel T. Leung, Rashmee U. Shah
Journal: JAMA Network Open (2020)

<h3>Importance</h3> <i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision </i>(<i>ICD-10</i>) codes are used to characterize coronavirus disease 2019 (COVID-19)–related symptoms. Their accuracy is unknown, which could affect downstream analyses. <h3>Objective</h3> To compare the performance of fever-, cough-, and dyspnea-specific<i>ICD-10</i>codes with medical record review among patients tested for COVID-19. <h3>Design, Setting, and Participants</h3> This cohort study included patients who underwent quantitative reverse transcriptase–polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 at University of Utah Health from March 10 to April 6, 2020. Data analysis was performed in April 2020. <h3>Main Outcomes and Measures</h3> The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of<i>ICD-10</i>codes for fever (R50*), cough (R05*), and dyspnea (R06.0*) were compared with manual medical record review. Performance was calculated overall and stratified by COVID-19 test result, sex, age group (&lt;50, 50-64, and &gt;64 years), and inpatient status. Bootstrapping was used to generate 95% CIs, and Pearson χ<sup>2</sup>tests were used to compare different subgroups. <h3>Results</h3> Among 2201 patients tested for COVD-19, the mean (SD) age was 42 (17) years; 1201 (55%) were female, 1569 (71%) were White, and 282 (13%) were Hispanic or Latino. The prevalence of fever was 66% (1444 patients), that of cough was 88% (1930 patients), and that of dyspnea was 64% (1399 patients). For fever, the sensitivity of<i>ICD-10</i>codes was 0.26 (95% CI, 0.24-0.29), specificity was 0.98 (95% CI, 0.96-0.99), PPV was 0.96 (95% CI, 0.93-0.97), and NPV was 0.41 (95% CI, 0.39-0.43). For cough, the sensitivity of<i>ICD-10</i>codes was 0.44 (95% CI, 0.42-0.46), specificity was 0.88 (95% CI, 0.84-0.92), PPV was 0.96 (95% CI, 0.95-0.97), and NPV was 0.18 (95% CI, 0.16-0.20). For dyspnea, the sensitivity of<i>ICD-10</i>codes was 0.24 (95% CI, 0.22-0.26), specificity was 0.97 (95% CI, 0.96-0.98), PPV was 0.93 (95% CI, 0.90-0.96), and NPV was 0.42 (95% CI, 0.40-0.44).<i>ICD-10</i>code performance was better for inpatients than for outpatients for fever (χ<sup>2</sup> = 41.30;<i>P</i> &lt; .001) and dyspnea (χ<sup>2</sup> = 14.25;<i>P</i> = .003) but not for cough (χ<sup>2</sup> = 5.13;<i>P</i> = .16). <h3>Conclusions and Relevance</h3> These findings suggest that<i>ICD-10</i>codes lack sensitivity and have poor NPV for symptoms associated with COVID-19. This inaccuracy has implications for any downstream data model, scientific discovery, or surveillance that relies on these codes.
FRI0039 An assessment of leflunomide for patients with rheumatoid arthritis treated in routine clinical practice
Authors: JA Teir, AD Woolf, MJ Davis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Phase 3 clinical trails used for licensing of new agents are not always reflective of ‘day to day’ clinical practice. <h3>Objectives</h3> We have examined the use and effect of Leflunomide in the routine clinic situation. <h3>Methods</h3> From December 1999 until May 2000 20 patients with rheumatoid arthritis commenced on Leflunomide had a full clinical assessment in a general rheumatology clinic. All had joint scores (28 swelling and tenderness), health assessment questionnaire (HAQ), VAS pain, patient and physician global and C-reactive protein (CRP) measured at initiation of treatment and follow up visit. joint scores were performed by clinic nurses,5 in total, given basic training in the technique. the mean follow up was 6 months (2–9 months) with the above the American College of rheumatology (ACR) criteria for response was calculated. <h3>Results</h3> At final assessment the mean SJC had reduced from 14.5 to 11.0 (p &lt; 0.02), mean TJC 14.1 to 10.0 (p &lt; 0.02), mean CRP 55.3 to 30 (p &lt; 0.01) and mean HAQ from 2.3 to 2.2(p &lt; 0.9). Only 5(25%) however achieved an ACR20 of which 2 were ACR50. At mean follow up of 6 months 7(35%) had discontinued treatment because of adverse reaction. 6 were as a result of bowel disturbance and 1 because of headache. in this small group no patients had serious abnormalities in either their liver function or full blood counts. 13(65%) were continuing with therapy content with its efficacy. <h3>Conclusion</h3> The ACR 20 response is clearly less than the published trails (52%) yet the perceived patient efficacy is similar. The difference related to the difficulty in performing, reliably, the joint scores in routine clinical practice. this ought to considered when suggesting these measures should be performed outside of the research setting. The incidence of bowel upset is higher than the phase 3 study (13%). This may be attributable to different patient populations with fewer exclusion criteria in clinical practice. <h3>Reference</h3> Smolen JS, <i>et al</i>. Lancet 1999;353:259–66
Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management
Authors: Sandy Feng, John C. Bucuvalas, George V. Mazariegos, John C. Magee, Alberto Sanchez‐Fueyo, Katharine M. Spain, Andrew Lesniak, Sai Kanaparthi, Emily Perito, Veena L. Venkat, Bryna E. Burrell, Estella M. Alonso, Nancy D. Bridges, Edward Doo, Nitika A. Gupta, Ryan W. Himes, David Ikle, Annette M. Jackson, Steven J. Lobritto, Juan Jose Lozano, Mercedes Martinez, Vicky L. Ng, Elizabeth B. Rand, Averell H. Sherker, Shikha S. Sundaram, Yumirle P. Turmelle, Michele Wood‐Trageser, Anthony J. Demetris
Journal: Hepatology (2020)

Background and Aims Tolerance is transplantation’s holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long‐term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance. Approach and Results We conducted a multicenter, single‐arm trial of immunosuppression withdrawal over 36‐48 weeks. Liver tests were monitored biweekly (year 1), monthly (year 2), and bimonthly (years 3‐4). For‐cause biopsies were done at investigators’ discretion but mandated when alanine aminotransferase or gamma glutamyltransferase exceeded 100 U/L. All subjects underwent final liver biopsy at trial end. The primary efficacy endpoint was operational tolerance, defined by strict biochemical and histological criteria 1 year after stopping immunosuppression. Among 88 subjects (median age 11 years; 39 boys; 57 deceased donor grafts), 33 (37.5%; 95% confidence interval [CI] 27.4%, 48.5%) were operationally tolerant, 16 were nontolerant by histology (met biochemical but failed histological criteria), and 39 were nontolerant by rejection. Rejection, predicted by subtle liver inflammation in trial entry biopsies, typically (n = 32) occurred at ≤32% of the trial‐entry immunosuppression dose and was treated with corticosteroids (n = 32) and/or tacrolimus (n = 38) with resolution (liver tests within 1.5 times the baseline) for all but 1 subject. No death, graft loss, or chronic, severe, or refractory rejection occurred. Neither fibrosis stage nor the expression level of a rejection gene set increased over 4 years for either tolerant or nontolerant subjects. Conclusions Immunosuppression withdrawal showed that 37.5% of selected pediatric liver‐transplant recipients were operationally tolerant. Allograft histology did not deteriorate for either tolerant or nontolerant subjects. The timing and reversibility of failed withdrawal justifies future trials exploring the efficacy, safety, and potential benefits of immunosuppression minimization.
Tools as “petrified memes”: A duality
Authors: Carsten Korth
Journal: Behavioral and Brain Sciences (2020)

Abstract Tools are generated by defined steps, fulfill distinct uses, and elicit affordances or mental representations. When the latter are recombined, they are perceived as “technical reasoning,” resulting in novel tools when executed. They can be exchanged, varied, and selected between individuals in a cumulative social process. Tools are materialized, “petrified” memes forming a duality within the framework of active externalism.
Where does the elephant come from? The evolution of causal cognition is the key
Authors: Peter Gärdenfors, Anders Högberg, Marlize Lombard
Journal: Behavioral and Brain Sciences (2020)

Abstract Osiurak and Reynaud do not explain the evolutionary emergence and development of the elephant in the room, that is, technical cognition. We first argue that there is a tight correlation between the evolution of cumulative technological culture (CTC) and the evolution of reasoning about abstract forces. Second, intentional teaching plays a greater role in CTC evolution than acknowledged in the target article.
Pregnancy in lymphangioleiomyomatosis: clinical and lung function outcomes in two national cohorts
Authors: Angelo M Taveira-DaSilva, Simon R Johnson, Patricia Julien-Williams, Jan Johnson, Mario Stylianou, Joel Moss
Journal: Thorax (2020)

Pregnancy in women with lymphangioleiomyomatosis (LAM) has been associated with increased complications and worsening lung function although objective data to advise patients are not available. We assessed lung function and CT scans before and after pregnancy in 16 women with LAM. During the pregnancy, pneumothorax was frequent and mean forced expiratory volume in 1 s (FEV1) fell from 77%±19% prepregnancy to 64%±25% predicted and DLCO from 66±26 to 57±26 (both p<0.01). After pregnancy, rates of FEV1 decline were high and 10 patients required sirolimus. Women with LAM, especially with moderate or advanced disease should be counselled regarding adverse events and loss of lung function during the pregnancy.
Characteristics and Outcomes of COVID-19 Patients During Initial Peak and Resurgence in the Houston Metropolitan Area
Authors: Farhaan S. Vahidy, Ashley L. Drews, Faisal N. Masud, Roberta L. Schwartz, Belimat “Billy” Askary, Marc L. Boom, Robert A. Phillips
Journal: JAMA (2020)

Matt Arentz, MD; Eric Yim, MD; Lindy Klaff, MD; Sharukh Lokhandwala, MD, MSc; Francis X. Riedo, MD; Maria Chong, MD; Melissa Lee, MD
Severe asthma in adults does not significantly affect the outcome of COVID‐19 disease: Results from the Italian Severe Asthma Registry
Authors: Leonardo Antonicelli, Chiara Tontini, Giuseppina Manzotti, Luca Ronchi, Adriano Vaghi, Francesco Bini, Alessandro Scartabellati, Francesco Menzella, Fausto De Michele, Antonino Musarra, Claudio Micheletto, Maria Beatrice Bilò
Journal: Allergy (2020)
4D-bioprinted silk hydrogels for tissue engineering
Authors: Soon Hee Kim, Ye Been Seo, Yeung Kyu Yeon, Young Jin Lee, Hae Sang Park, Md. Tipu Sultan, Jung Min Lee, Ji Seung Lee, Ok Joo Lee, Heesun Hong, Hanna Lee, Olatunji Ajiteru, Ye Ji Suh, Sung-Hyuk Song, Kwang-Ho Lee, Chan Hum Park
Journal: Biomaterials (2020)