tbuckley/cabot-search huggingface dataset:
CAR T Cell Therapy Targeting G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D), a Novel Target for the Immunotherapy of Multiple Myeloma
Authors: Eric L. Smith, Kimberly Harrington, Mette Staehr, Reed Masakayan, Jon Jones, Thomas Long, Majid Ghoddusi, Terence J Purdon, Trevor Do, Xiuyan Wang, Minh Pham, Jessica M Brown, Elizabeth Peguero, Carlos Fernández De Larrea, Pei Wang, Hong Liu, Yiyang Xu, Sarah Garrett, Steven Almo, Isabelle Riviere, Cheng Liu, Blythe Duke Sather, Renier J. Brentjens
Journal: Blood (2018)
Abstract 17144: Architecture of Atrial Fibrosis is Associated With Increased Risk of Recurrence Post Af Treatment
Authors: Pim Gal, Christina F Pacchia, Robert White, Alan Morris, Joshua Cates, Gagandeep Kaur, arif elvan, Nassir Marrouche
Journal: Circulation (2015)

Background: Previous studies reported the association between left atrial (LA) fibrosis as assessed by delayed enhancement (DE)-MRI and arrhythmia recurrence post AF ablation. In this study we report the significance of atrial fibrotic infiltrations architecture in predicting treatment failure. Methods: 271 patients (mean age was 59 years, 64% had paroxysmal AF) from the multicenter prospective DECAAF study were included in this sub-analysis. We assessed the location and size of patchy fibrotic atrial tissue infiltrations (figure 1) in all patients who underwent ablation of AF. Due to the strong correlation between LA fibrosis and the largest patch(r=0.875, P&lt;0.001), a Z-transformation of LA fibrosis and the sum of LA fibrosis and largest patch was performed. This allowed direct comparison of hazard ratios (HR) in a Cox proportional hazard model. Results: Mean LA fibrosis score was 18%, the mean largest patch was 21.5 cm2. AF recurrences were associated with the largest patch size per quartile: Q1: 15%, Q2: 28%, Q3: 34%, Q4: 45%, P&lt;0.001. The HR for the standardized LA fibrosis was 1.317, P=0.009.compared to 1.437 for the standardized sum of LA fibrosis and largest patch size, demonstrating that the addition of largest patch to the LA fibrosis score improved the predictive properties of the model. In a multivariate model with age, AF type and LA volume, the standardized sum of LA fibrosis and largest patch size was significantly associated with AF recurrences post-ablation (HR 1.404, P=0.001). Conclusion: From our preliminary data not only the quantity but also the architectural presentation of atrial tissue fibrotic infiltrations was significantly associated with AF treatment failure. This finding would help better understand the severity of AF in addition to improving patient selection undergoing various treatments of AF.
Reply to Parker: Implications of Tuberculosis Sputum Culture Test Sensitivity on Accuracy of Other Diagnostic Modalities
Authors: Christina Yoon, Fred C. Semitala, Adithya Cattamanchi
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

We welcome the interest shown by Dr. Parker in our recent publication that described the yield and efficiency of novel intensified tuberculosis (TB) case-finding algorithms for people living with HIV (1).We agree that sputum mycobacterial culture has imperfect sensitivity for active pulmonary TB.Nonetheless, culture is the best available microbiological reference standard for evaluation of novel TB diagnostics.The addition of clinical follow-up can be helpful but also has limitations.For example, in the context of our study, initiation of antiretroviral therapy complicates assessment of whether clinical and radiological improvements are a result of TB treatment.Furthermore, in most TB-endemic areas, culture is not routinely available for TB diagnosis, and Xpert MTB/RIF (Xpert) is used as the confirmatory TB test.In such settings, all patients with a positive Xpert result are in fact regarded as a TB case and initiated on TB treatment.If we consider all Xpert-positive patients to be true positives, as suggested by Dr. Parker and as occurs in routine clinical practice, our study conclusions would remain unchanged: 1) CRP (C-reactive protein)-based TB screening followed by Xpert confirmatory testing would identify a similar proportion of TB cases as the current intensified case-finding (ICF) algorithm (54% [95% confidence interval (CI), 45-63] vs. 58% [95% CI, 49-66]; difference in yield 4% [95% CI, 29% to 116%]; P = 0.57); 2) CRPbased ICF would use less than half as many Xpert assays (9 vs. 4); and 3) the addition of a single culture would substantially increase ICF yield, detecting >77% of all TB cases, regardless of the screening strategy used.Thus, we believe HIV programs should first consider implementation of CRP-based TB screening, which may then enable the routine use of more sensitive confirmatory tests, such as culture, to improve ICF yield.
The Burden of Chronic Hepatitis C in China From 2004 to 2050: An Individual‐Based Modeling Study
Authors: Jie Wu, Yuqing Zhou, Xiaofang Fu, Min Deng, Yang Zheng, Guo Tian, Yiping Li, Chencheng Wang, Cheng Ding, Bing Ruan, Shigui Yang, Lanjuan Li
Journal: Hepatology (2018)

The launch of new direct‐acting antivirals (DAAs) is expected to substantially reduce the burden of hepatitis C virus (HCV) in China. However, the effect of these changes has not yet been modeled in China. Therefore, we aim to predict the burden of HCV‐related diseases in China by simulating different scenarios that incorporate recent therapeutic advances of HCV and China’s current screening strategy. We developed an individual‐based microsimulation Markov model that simulated disease progression of HCV‐infected patients in China from 2004 to 2050. We simulated four scenarios with different assumptions about treatment, including a natural history scenario, a pre‐DAAs scenario, a DAA treatment for all patients with a METAVIR fibrosis score ≥F3 (DAAs [≥F3]) scenario, and a DAAs (≥F0) scenario. The introduction of DAAs is predicted to have great impacts on the burden of HCV in China, particularly under the DAAs (≥F0) scenario in which we rapidly expand DAAs to all HCV‐infected patients (≥F0) in 2021. Under this scenario, prevalence of chronic HCV is expected to peak at 10.75 million (95% confidence interval [CI], 8.30‐12.85) around 2020 and then decrease to 7.92 million (95% CI, 5.41‐10.08) in 2050. Conclusion: If the future increasing burden of HCV‐related diseases is to be averted, China needs to start launching the new DAA treatment and rapidly increase the number of patients treated. However, to maximize the benefits of new DAAs, expanded screening is necessary to identify more cases that require treatment in the short term. Without these changes, the HCV burden in China will remain high in the future.
Pathologic Complete Response in a Large Gastric GIST: Using Molecular Markers to Achieve Maximal Response to Neoadjuvant Imatinib
Authors: Joshua B. Brown, Reetesh K. Pai, Melissa A. Burgess, Jennifer Chennat, Amer H. Zureikat
Journal: Journal of the National Comprehensive Cancer Network (2018)

Gastrointestinal stromal tumors (GISTs) represent 1% of alimentary tract neoplasms. Up to 90% of GISTs are driven by activating mutations in tyrosine kinase KIT or PDGFRα genes. Imatinib mesylate is a tyrosine kinase inhibitor that has recently been used in a neoadjuvant role for locally advanced GIST. Pathologic complete response (pCR) to imatinib, however, is rare and may be limited to patients with certain mutations. We report on a 71-year-old woman with a large advanced gastric GIST near the gastroesophageal junction initially involving the pancreas, spleen, adrenal, and aortic wall. The tumor harbored a KIT exon 11 deletion mutation in codon 558, which predicts a favorable response to imatinib. After 6 months of neoadjuvant imatinib therapy, the tumor was downstaged to allow partial gastric resection without the need for total gastrectomy reconstruction. The patient underwent partial gastrectomy, distal pancreatectomy, and splenectomy, and histologic examination showed a margin-negative resection with a near-pCR, with <5% viable tumor. Prolonged neoadjuvant therapy was undertaken based on the prognostic significance of a KIT exon 11 deletion mutation in codon 558, which facilitated an R0 resection while minimizing the surgical extent of the resection. A near-pCR of a large gastric GIST after neoadjuvant imatinib therapy remains a rare occurrence. Molecular testing should be undertaken before neoadjuvant therapy, because specific mutations can identify patients who will respond to imatinib and those likely to achieve significant downstaging and pCR.
Hand, Foot, and Mouth Disease
Authors: Brittany Cox, Fatma Levent
Journal: JAMA (2018)

Hand, Foot, and Mouth DiseaseHand, foot, and mouth disease is a common viral infection in children.Hand, foot, and mouth disease can be very concerning to parents and caretakers.Most commonly, hand, foot, and mouth disease affects children younger than 5 years, but it can sometimes affect older children, adolescents, and adults.Most people are exposed to the virus that causes hand, foot, and mouth disease during their lives.The virus is commonly spread by coughing or personal contact with a sick person or their belongings.This makes schools, day care centers, and sports teams common environments for a child to pick up the virus. SymptomsHand, foot, and mouth disease typically begins with feeling ill and having a low-grade fever.A child may also experience feeling tired and wanting to eat less.This progresses to flat, red spots that appear a few days later on the hands and the bottoms of the feet and sometimes elsewhere, which may turn into blisters.Painful spots appear in the mouth and throat that may also turn into blisters.The illness usually runs its course in 7 to 10 days.Hand, foot, and mouth disease is often seen during the summer months.If your child experiences repeated high fevers, a stiff and painful neck, or a headache that will not go away, call your child's doctor.
Integrative Genomic Analyses Identifies GGA2 as a Cooperative Driver of EGFR-Mediated Lung Tumorigenesis
Authors: Hannah O’Farrell, Bryant Harbourne, Zimple Kurlawala, Yusuke Inoue, Amy L. Nagelberg, Victor D. Martinez, Daniel Lu, Min Hee Oh, Bradley P. Coe, Kelsie L. Thu, Romel Somwar, Stephen Lam, Wan L. Lam, Arun M. Unni, Levi Beverly, William W. Lockwood
Journal: Journal of Thoracic Oncology (2018)
Redox-responsive biocompatible nanocarriers based on novel heparosan polysaccharides for intracellular anticancer drug delivery
Authors: Lipeng Qiu, Lu Ge, Miaomiao Long, Jing Mao, Kamel S. Ahmed, Xiaotian Shan, Huijie Zhang, Li Qin, Guozhong Lv, Jinghua Chen
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Heparosan is a natural precursor of heparin biosynthesis in mammals. It is stable in blood circulation but can be degraded in lysosomes, showing good biocompatibility and long circulation features. So heparosan can be designed as anticancer drug carriers to increase tumor selectivity and improve the therapeutic effect. A novel redox-sensitive heparosan-cystamine-vitamin E succinate (KSV) micelle system was constructed for intracellular delivery of doxorubicin (DOX). Simultaneously, the redox-insensitive heparosan-adipic acid dihydrazide-vitamin E succinate copolymer (KV) was synthesized as control. DOX-loaded micelles (DOX/KSV) with an average particle size of 90-120 nm had good serum stability and redox-triggered depolymerization.
Six US doctors are charged in $464m opioid and fake treatment scheme
Authors: Owen Dyer
Journal: BMJ (2018)

A group of Michigan doctors prescribed opioids to addicts who in return submitted to painful back injections and other unnecessary treatments so that the doctors could bill the US government for over $450m (£359m; €397m), charges in federal court have asserted.

The alleged mastermind of the scheme was Rajendra Bothra, 77, who amassed $35m and bought his own private island, US prosecutors said. Bothra’s arrest brought news coverage in his native India, where in 1999 he was awarded one of the country’s highest civil honours, the Padma Shri.

His wealth was the subject of a bail hearing on 7 December, shortly after his arrest. He sat on a courtroom bench with five other charged doctors, all of whom were his employees. The doctors, described by the Detroit News as “rumpled” and …
Is the current healthcare system ready to treat all eligible patients using car t-cell therapies? An analysis of the NHL situation in France
Authors: T. Verrier, T. Sejourne, M. Rose, L.M. Mitrofan
Journal: Annals of Oncology (2018)

Background: CAR T-cell therapies (CART) hold out the potential for a paradigm shift in cancer treatment. However, underlying regulatory and manufacturing processes delay hospitals from offering an optimal patient coverage. This study provides an overview of French hospitals regarding CAR T implementation potential and addresses the unmet requirements for a coverage of all French CAR T eligible NHL (Non-Hodgkins Lymphoma) patients. Methods: This study used the PMSI French claim database, which exhaustively lists hospital stays and associated diagnosis, along with a scoring approach applied to main criteria for CAR T hospital eligibility. NHL patient volume was assessed for each hospital and CAR T eligibility was then defined as confirmed NHL with a relapse/refractory disease and non-eligiblility to a Stem Cell Transplantation. The inclusion period was 2015 to 2016. Based on the CAR T implementation guidelines, a score was then attributed to each hospital based on four eligibility criteria: accreditation by the European JACIE committee (score 2); accreditation by the regional health agency for the collection of peripheral Hematopoietic Stem Cells (HSC) (score 1); whether the hospital was referenced by the French Society of Hematology for HSC collection (score 0.5) and for the presence of a leukapheresis unit (score 0.5). "Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)" Yakoub-Agha I. et al. (2017). DOI: 10.1016/j.bulcan.2017.10.017. Results: 33 out of 948 hospitals with NHL patients have at least one of the eligibility criteria. Eight hospitals cumulate a score ≥ 2.5, considered as the minimum to be able to integrate CAR T technology within the next 2 years. Seven are University Public Hospitals, one is a Public/Private Oncology center. These eight centers cover only 11% from the calculated CAR T-eligible population. Conclusions: The current gap between the centers qualified to perform CAR T and the actual size of the population eligible for this therapy suggests that significant adaptations might be necessary, which could directly impact the healthcare structure. Legal entity responsible for the study: IQVIA. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Non-Invasive Flexible and Stretchable Wearable Sensors With Nano-Based Enhancement for Chronic Disease Care
Authors: Geng Yang, Gaoyang Pang, Zhibo Pang, Ying Gu, Matti Mantysalo, Huayong Yang
Journal: IEEE Reviews in Biomedical Engineering (2018)

Advances in flexible and stretchable electronics, functional nanomaterials, and micro/nano manufacturing have been made in recent years. These advances have accelerated the development of wearable sensors. Wearable sensors, with excellent flexibility, stretchability, durability, and sensitivity, have attractive application prospects in the next generation of personal devices for chronic disease care. Flexible and stretchable wearable sensors play an important role in endowing chronic disease care systems with the capability of long-term and real-time tracking of biomedical signals. These signals are closely associated with human body chronic conditions, such as heart rate, wrist/neck pulse, blood pressure, body temperature, and biofluids information. Monitoring these signals with wearable sensors provides a convenient and non-invasive way for chronic disease diagnoses and health monitoring. In this review, the applications of wearable sensors in chronic disease care are introduced. In addition, this review exploits a comprehensive investigation of requirements for flexibility and stretchability, and methods of nano-based enhancement. Furthermore, recent progress in wearable sensors-including pressure, strain, electrophysiological, electrochemical, temperature, and multifunctional sensors-is presented. Finally, opening research challenges and future directions of flexible and stretchable sensors are discussed.
Abstract 18000: Cumulative Psychological Stress and Type II Diabetes Mellitus in Women
Authors: Jonathan Z Butler, Alan Zaslavsky, David R Williams, Natalie Slopen, Aruna Pradhan, Julie Buring, Michelle A Albert
Journal: Circulation (2016)

Background: Data support an association between psychological stress and cardiovascular disease (CVD) risk. However, the relationship between psychological stress and type II diabetes (diabetes), a...
FDG PET/CT Imaging of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus
Authors: Wei Zhang, Cheng Fang, Huipan Liu, Yue Chen
Journal: Clinical Nuclear Medicine (2018)

Hepatocellular carcinoma rarely involves the major bile duct. Here, we reported a 46-year-old man with liver cancer who underwent FDG PET/CT for staging. The images showed abnormal FDG uptake in the left lobe and hilum of the liver, which was confirmed as hepatocellular carcinoma and hepatic portal bile duct tumor thrombus, respectively, by the pathology.
Abstract 19820: 18F-FDG Uptake is Increased in Abdominal Aortic Aneurysms: Localization of Metabolic Activity within Aneurysmal Transition Zones.
Authors: Sharath Subramanian, Sadia Qadir, Kenneth M Fifer, Jayanthi Vijayakumar, Sara I Fontanez, Noeen Sarfraz, Amparo L Figueroa, Suhny Abbara, Thomas J Brady, Ahmed Tawakol
Journal: Circulation (2010)

Introduction: Inflammation plays an important role in the pathobiology of abdominal aortic aneurysms (AAA). Here we compared vascular inflammation in the aortic wall between patients with AAA and age and gender-matched subjects without AAA, using 18-fluorodeoxyglucose-positron emission tomography (FDG-PET). Methods and Materials: Thirty-three patients (Median [IQR] 71[7] years, 82% male), 11 with AAA and 22 age/gender-matched controls without AAA, underwent PET and CT imaging. FDG uptake within the aortic wall was assessed in axial images, from the celiac artery to the iliac bifurcation. Mean target-to-Background ratio (TBR) was determined by dividing aortic wall activity by vena caval blood activity. Additionally, within AAA, TBR was measured in transitional zones of the AAA (the shoulders of the aneurysm) as well as in the opposite wall (figure 1). Results: Vessel wall inflammation (TBR) was higher in AAA vs. controls (2.82 [1.81] vs. 1.84 [0.59], P<0.001), a difference which remained significant after ...
TELS: A Novel Computational Framework for Identifying Motif Signatures of Transcribed Enhancers
Authors: Dimitrios Kleftogiannis, Haitham Ashoor, Vladimir B. Bajic
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract In mammalian cells, transcribed enhancers (TrEns) play important roles in the initiation of gene expression and maintenance of gene expression levels in a spatiotemporal manner. One of the most challenging questions is how the genomic characteristics of enhancers relate to enhancer activities. To date, only a limited number of enhancer sequence characteristics have been investigated, leaving space for exploring the enhancers’ DNA code in a more systematic way. To address this problem, we developed a novel computational framework, Transcribed Enhancer Landscape Search (TELS), aimed at identifying predictive cell type/tissue-specific motif signatures of TrEns. As a case study, we used TELS to compile a comprehensive catalog of motif signatures for all known TrEns identified by the FANTOM5 consortium across 112 human primary cells and tissues. Our results confirm that combinations of different short motifs characterize in an optimized manner cell type/tissue-specific TrEns. Our study is the first to report combinations of motifs that maximize classification performance of TrEns exclusively transcribed in one cell type/tissue from TrEns exclusively transcribed in different cell types/tissues. Moreover, we also report 31 motif signatures predictive of enhancers’ broad activity. TELS codes and material are publicly available at http://www.cbrc.kaust.edu.sa/TELS.
Vitamin D Receptor Agonists for Patients Undergoing Hemodialysis
Authors: Rasheeda K. Hall, Julia J. Scialla
Journal: JAMA (2018)

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AB0783 Clinical characteristics of a cohort of patients with anti-jo1 antibodies
Authors: M.C. Carrasco Cubero, S.M. Rojas Herrera, M.L. Vargas Pérez, M.I. Alcalá Peña, M. Espárrago Rodilla, E. Chamizo Carmona
Journal: Annals of the Rheumatic Diseases (2018)

Table 1.Characteristics of 16 patients with Scleroderma renal crisis SRC: Scleroderma renal crisis,
Role of linoleic acid in autoimmune disorders: a Mendelian randomisation study
Authors: Young Ho Lee
Journal: Annals of the Rheumatic Diseases (2018)

I read with great interest the article by Zhao and Schooling1 regarding the role of linoleic acid in autoimmune disorders. This Mendelian randomisation (MR) analysis suggests that linoleic acid protects against rheumatoid arthritis (RA). However, it has a methodological issue. The choice of the genetic instrumental variables (IV) is essential for a successful MR study. MR analyses using multiple genetic variants can be viewed as a meta-analysis of the causal estimates from each variant.2 The availability of estimates of both the gene-risk factor and the gene-outcome …