tbuckley/cabot-search huggingface dataset:
Abstract 13913: Comparisons of Nutritional Indices on Mortality in Heart Failure Patients
Authors: Yuki Kanno, Akiomi Yoshihisa, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Shunsuke Watanabe, Makiko Tatsumi, Satoshi Abe, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2017)

Background: Malnutrition is common, and is associated with adverse prognosis in patients with heart failure (HF), especially in elderly patients. The prognostic nutritional index (PNI), geriatric n...
Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Authors: Li Xuan, Qifa Liu
Journal: Journal of Hematology & Oncology (2021)

Abstract Relapse remains the main cause of treatment failure in acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Emerging evidence has demonstrated that AML patients might benefit from maintenance therapy post-transplantation, especially for high-risk AML patients. In this mini-review, we will summarize targeted drugs, such as hypomethylating agents, FLT3 inhibitors and isocitrate dehydrogenase inhibitors, as maintenance therapy post-transplantation in AML patients undergoing allo-HSCT.
Chr15q25 genetic variant (rs16969968) independently confers risk of lung cancer, COPD and smoking intensity in a prospective study of high-risk smokers
Authors: Raewyn J Hopkins, Fenghai Duan, Greg D Gamble, Caroline Chiles, Alana Cavadino, Paul Billings, Denise Aberle, Robert P Young
Journal: Thorax (2021)

While cholinergic receptor nicotinic alpha 5 (CHRNA5) variants have been linked to lung cancer, chronic obstructive pulmonary disease (COPD) and smoking addiction in case-controls studies, their corelationship is not well understood and requires retesting in a cohort study. To re-examine the association between the CHRNA5 variant (rs16969968 AA genotype) and the development of lung cancer, relative to its association with COPD and smoking. In 9270 Non-Hispanic white subjects from the National Lung Screening Trial, a substudy of high-risk smokers were followed for an average of 6.4 years. We compared CHRNA5 genotype according to baseline smoking exposure, lung function and COPD status. We also compared the lung cancer incidence rate, and used multiple logistic regression and mediation analysis to examine the role of the AA genotype of the CHRNA5 variant in smoking exposure, COPD and lung cancer. As previously reported, we found the AA high-risk genotype was associated with lower lung function (p=0.005), greater smoking intensity (p<0.001), the presence of COPD (OR 1.28 (95% CI 1.10 to 1.49) p=0.0015) and the development of lung cancer (HR 1.41, (95% CI 1.03 to 1.93) p=0.03). In a mediation analyses, the AA genotype was independently associated with smoking intensity (OR 1.42 (95% CI 1.25 to 1.60, p<0.0001), COPD (OR 1.25, (95% CI 1.66 to 2.53), p=0.0015) and developing lung cancer (OR 1.37, (95% CI 1.03 to 1.82) p=0.03). In this large-prospective study, we found the CHRNA5 rs 16 969 968 AA genotype to be independently associated with smoking exposure, COPD and lung cancer (triple whammy effect).
Abstract MP50: The Development of Severe Obesity in Urban Girls
Authors: Kathleen M McTigue, Stephanie Stepp, Elan Cohen, Alison Hipwell, Charity Moore, Rolf Loeber, Lewis Kuller
Journal: Circulation (2013)

Introduction: Despite rising prevalence of youth-onset severe obesity, its development is poorly understood. Hypothesis: Girls who are severely obese in early adolescence will show more rapid growth between ages 7-10 and 11-14 compared with those who have normal BMI in early adolescence. The two groups’ BMI trajectories will diverge in late childhood. Methods: To estimate the prevalence and incidence of youth-onset severe obesity (BMI &gt;99 th percentile-for-age) and compare weight development between girls with severe obesity and those with healthy BMI. We examined data from participants in an accelerated longitudinal cohort study of urban girls from a single US city (n=2206; 51% African American). Data were collected annually from 2003-2004 (when participants were aged 7-10) to 2008-2009. Girls were excluded who became pregnant (n=143) or provided no weight data (n=102) in those six years. Prevalence data calculations were compared using the standard severe obesity definition as well as an alternative definition (120% of the 95 th BMI-percentile-for-age). We used unconditional latent growth curve models (LGCM) to compare the BMI development of girls who were severely obese at age 12-15 with those who had normal BMI at age 12-15. Results: Severe obesity prevalence was 4.5% at age 7-10 and 6.3% (3.6% of white girls and 8.2% of African American girls; p&lt;0.001) at age 12-15. Incident severe obesity was 0% to 1.9% annually. The alternative definition of severe obesity yielded slightly higher prevalence estimates (6.2% at age 7-10 and 9.5% age 12-15). When we compared 12-15 year-old girls with severe obesity versus healthy BMI, average body weight was already distinct 5 years earlier [16.5 kg (SD 2.2) versus 27.0 kg (SD 4.7)].The difference in average BMI between the two groups widened with each sample year. Unconditional latent growth curve models between ages 7-10 and 11-14 indicated an average increase of 0.59 kg/m 2 annually in the healthy BMI group and 2.32 kg/m 2 annually in the severe obesity group. Conclusions: Severe obesity was relatively common in urban girls, particularly African American girls, by age 7-10. Girls with severe obesity showed a nearly 4-fold rate of BMI change over 5 years, compared to girls with healthy BMI. Girls with early adolescent severe obesity already showed significantly higher BMI by age 7-10. Prevention is essential prior to age 7, with emphasis on minority populations.
The Mutational Landscape of Metastatic Castration-sensitive Prostate Cancer: The Spectrum Theory Revisited
Authors: Matthew P. Deek, Kim Van der Eecken, Ryan Phillips, Neil R. Parikh, Pedro Isaacsson Velho, Tamara L. Lotan, Amar U. Kishan, Tobias Maurer, Paul C. Boutros, Christopher Hovens, Matthew Abramowtiz, Alan Pollack, Neil Desai, Bradley Stish, Felix Y. Feng, Mario Eisenberger, Michael Carducci, Kenneth J. Pienta, Mark Markowski, Channing J. Paller, Emmanuel S. Antonarakis, Alejandro Berlin, Piet Ost, Phuoc T. Tran
Journal: European Urology (2021)

Emerging data suggest that metastasis is a spectrum of disease burden rather than a binary state, and local therapies, such as radiation, might improve outcomes in oligometastasis. However, current definitions of oligometastasis are solely numerical. To characterize the somatic mutational landscape across the disease spectrum of metastatic castration-sensitive prostate cancer (mCSPC) to elucidate a biological definition of oligometastatic CSPC. This was a retrospective study of men with mCSPC who underwent clinical-grade sequencing of their tumors (269 primary tumor, 25 metastatic sites). Patients were classified as having biochemically recurrent (ie, micrometastatic), metachronous oligometastatic (≤5 lesions), metachronous polymetastatic (>5 lesions), or de novo metastatic (metastasis at diagnosis) disease. We measured the frequency of driver mutations across metastatic classifications and the genomic associations with radiographic progression-free survival (rPFS) and time to castrate-resistant prostate cancer (CRPC). The frequency of driver mutations in TP53 (p = 0.01), WNT (p = 0.08), and cell cycle (p = 0.04) genes increased across the mCSPC spectrum. TP53 mutation was associated with shorter rPFS (26.7 vs 48.6 mo; p = 0.002), and time to CRPC (95.6 vs 155.8 mo; p = 0.02) in men with oligometastasis, and identified men with polymetastasis with better rPFS (TP53 wild-type, 42.7 mo; TP53 mutated, 18.5 mo; p = 0.01). Mutations in TP53 (incidence rate ratio [IRR] 1.45; p = 0.004) and DNA double-strand break repair (IRR 1.61; p < 0.001) were associated with a higher number of metastases. Mutations in TP53 were also independently associated with shorter rPFS (hazard ratio [HR] 1.59; p = 0.03) and the development of CRPC (HR 1.71; p = 0.01) on multivariable analysis. This study was limited by its retrospective nature, sample size, and the use of commercially available sequencing platforms, resulting in a limited predefined set of genes examined. Somatic mutational profiles reveal a spectrum of metastatic biology that helps in redefining oligometastasis beyond a simple binary state of lesion enumeration. Oligometastatic prostate cancer is typically defined as less than three to five metastatic lesions and evidence suggests that using radiation or surgery to treat these sites improves clinical outcomes. As of now, treatment decisions for oligometastasis are solely defined according to the number of lesions. However, this study suggests that tumor mutational profiles can provide a biological definition of oligometastasis and complement currently used numerical definitions.
Integrated Molecular Characterization of Fumarate Hydratase–deficient Renal Cell Carcinoma
Authors: Guangxi Sun, Xingming Zhang, Jiayu Liang, Xiuyi Pan, Sha Zhu, Zhenhua Liu, Cameron M. Armstrong, Jianhui Chen, Wei Lin, Banghua Liao, Tianhai Lin, Rui Huang, Mengni Zhang, Linmao Zheng, Xiaoxue Yin, Ling Nie, Pengfei Shen, Jinge Zhao, Haoran Zhang, Jindong Dai, Yali Shen, Zhiping Li, Jiyan Liu, Junru Chen, Jiandong Liu, Zhipeng Wang, Xudong Zhu, Yuchao Ni, Dan Qin, Ling Yang, Yuntian Chen, Qiang Wei, Xiang Li, Qiao Zhou, Haojie Huang, Jin Yao, Ni Chen, Hao Zeng
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC. Experimental Design: Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded. Results: We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade–based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months; P = 0.03). Conclusions: These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.
Sequential Chemotherapy for Early-Stage, Post–Radical Hysterectomy Cervical Cancer
Authors: Leslie M. Randall, Jyoti Mayadev, Bradley J. Monk
Journal: JAMA Oncology (2021)

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 Oncology 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 2022 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 Oncology journal
Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma
Authors: Ruiping Wang, Minghao Dang, Kazuto Harada, Guangchun Han, Fang Wang, Melissa Pool Pizzi, Meina Zhao, Ghia Tatlonghari, Shaojun Zhang, Dapeng Hao, Yang Lu, Shuangtao Zhao, Brian D. Badgwell, Mariela Blum Murphy, Namita Shanbhag, Jeannelyn S. Estrella, Sinchita Roy-Chowdhuri, Ahmed Adel Fouad Abdelhakeem, Yuanxin Wang, Guang Peng, Samir Hanash, George A. Calin, Xingzhi Song, Yanshuo Chu, Jianhua Zhang, Mingyao Li, Ken Chen, Alexander J. Lazar, Andrew Futreal, Shumei Song, Jaffer A. Ajani, Linghua Wang
Journal: Nature Medicine (2021)
Identification of a novel pathway in immune response towards S.aureus protease like protein D
Authors: Olga Krysko, Andrea Renate Teufelberger, Sharon Van Nevel, Szanne De Graeve, Paco Hulpiau, M. Nordengruen, B. M. Broeker, Dmitri Krysko, Claus Bachert
Journal: Allergy (2020)
Effect of tissue microenvironment on fibrous capsule formation to biomaterial-coated implants
Authors: Jamie L. Hernandez, Jaehyung Park, Shan Yao, Anna K. Blakney, Hienschi V. Nguyen, Bob H. Katz, Jeffrey T. Jensen, Kim A. Woodrow
Journal: Biomaterials (2021)

Within tissue exposed to the systemic immune system, lymphocytes and fibroblasts act against biomaterials via the development of a fibrous capsule, known as the foreign body reaction (FBR). Inspired by the natural tolerance that the uterine cavity has to foreign bodies, our study explores the role of microenvironment across classical (subcutaneous) and immune privileged (uterine) tissues in the development of the FBR. As a model biomaterial, we used electrospun fibers loaded with sclerosing agents to provoke scar tissue growth. Additionally, we integrated these materials onto an intrauterine device as a platform for intrauterine biomaterial studies. Polyester materials in vitro achieved drug release up to 10 days, greater pro-inflammatory and pro-healing cytokine expression, and the addition of gelatin enabled greater fibroblast attachment. We observed the materials that induced the greatest FBR in the mouse, had no effect when inserted at the utero-tubal junction of non-human primates. These results suggest that the FBR varies across different tissue microenvironments, and a dampened fibrotic response exists in the uterine cavity, possibly due to immune privilege. Further study of immune privileged tissue factors on biomaterials could broaden our understanding of the FBR and inform new methods for achieving biocompatibility in vivo.
The Vasculopathy of Juvenile Dermatomyositis: Endothelial Injury, Hypercoagulability, and Increased Arterial Stiffness
Authors: Charalampia Papadopoulou, Ying Hong, Petra Krol, Muthana Al Obaidi, Clarissa Pilkington, Lucy R. Wedderburn, Paul A. Brogan, Despina Eleftheriou
Journal: Arthritis & Rheumatology (2021)

Vasculopathy is considered central to the pathogenesis of juvenile dermatomyositis (DM) and is associated with severe extramuscular manifestations. We undertook this study to investigate the hypothesis that the vasculopathy of juvenile DM can be noninvasively tracked by examining biomarkers of endothelial injury, subclinical inflammation, hypercoagulability, and vascular arterial stiffness.The study population was a UK cohort of children with juvenile DM. Circulating endothelial cells (CECs) and microparticles (MPs) were identified using immunomagnetic bead extraction and flow cytometry, respectively. Plasma thrombin generation was determined using a fluorogenic assay. Cytokine and chemokine levels were measured by electrochemiluminescence. Arterial stiffness was assessed using pulse wave velocity (PWV). Results were expressed as the median and interquartile range (IQR), and statistical significance was assessed using nonparametric analyses.Ninety patients with juvenile DM and 79 healthy control subjects were included. The median age of the patients was 10.21 years (IQR 6.68-13.40), and the median disease duration was 1.63 years (IQR 0.28-4.66). CEC counts were higher in all patients with juvenile DM compared to controls (median 96 cells/ml [IQR (40-192] and 12 cells/ml [IQR 8-24], respectively; P < 0.0001). Circulating MP numbers were also significantly higher in patients with active juvenile DM compared to controls (median 204.7 × 103 /ml [IQR 87.9-412.6] and 44.3 × 103 /ml [IQR 15.0-249.1], respectively; P < 0.0001). MPs were predominantly of platelet and endothelial origin. Enhanced plasma thrombin generation was demonstrated in patients with active juvenile DM compared to those with inactive disease (P = 0.0003) and controls (P < 0.0001). Carotid-radial PWV adjusted for age was increased in patients with juvenile DM compared to controls (P = 0.003).We observed increased endothelial injury and increased levels of proinflammatory cytokines in patients with active juvenile DM. MP profiles reflected distinct disease activity status in juvenile DM and are markers of vascular pathology, platelet activation, and thrombotic propensity. Ongoing long-term vascular injury may result in increased arterial stiffness in patients with juvenile DM.
Current Concepts and Advances in Graft-Versus-Host Disease Immunology
Authors: Geoffrey R. Hill, Brian C. Betts, Victor Tkachev, Leslie S. Kean, Bruce R. Blazar
Journal: Annual Review of Immunology (2021)

Worldwide, each year over 30,000 patients undergo an allogeneic hema-topoietic stem cell transplantation with the intent to cure high-risk hematologic malignancy, immunodeficiency, metabolic disease, or a life-threatening bone marrow failure syndrome. Despite substantial advances in donor selection and conditioning regimens and greater availability of allograft sources, transplant recipients still endure the morbidity and mortality of graft-versus-host disease (GVHD). Herein, we identify key aspects of acute and chronic GVHD pathophysiology, including host/donor cell effectors, gut dysbiosis, immune system and cytokine imbalance, and the interface between inflammation and tissue fibrosis. In particular, we also summarize the translational application of this heightened understanding of immune dysregulation in the design of novel therapies to prevent and treat GVHD.
PEGylation enables subcutaneously administered nanoparticles to induce antigen-specific immune tolerance
Authors: Peter Y. Li, Frank Bearoff, Pu Zhu, Zhiyuan Fan, Yucheng Zhu, Mingyue Fan, Laura Cort, Taku Kambayashi, Elizabeth P. Blankenhorn, Hao Cheng
Journal: Journal of Controlled Release (2021)
Surgery vs Observation for Patients With Small Pancreatic Neuroendocrine Tumors
Authors: Hassan Aziz, James R. Howe, Timothy M. Pawlik
Journal: JAMA Surgery (2021)

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
Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Authors: Ruijuan Gao, Xueyan Peng, Carrighan Perry, Huanxing Sun, Aglaia Ntokou, Changwan Ryu, Jose L. Gomez, Benjamin C. Reeves, Anjali Walia, Naftali Kaminski, Nir Neumark, Genta Ishikawa, Katharine E. Black, Lida P. Hariri, Meagan W. Moore, Mridu Gulati, Robert J. Homer, Daniel M. Greif, Holger K. Eltzschig, Erica L. Herzog
Journal: Journal of Clinical Investigation (2021)

Fibrosis is a macrophage-driven process of uncontrolled extracellular matrix accumulation. Neuronal guidance proteins such as netrin-1 promote inflammatory scarring. We found that macrophage-derived netrin-1 stimulates fibrosis through its neuronal guidance functions. In mice, fibrosis due to inhaled bleomycin engendered netrin-1-expressing macrophages and fibroblasts, remodeled adrenergic nerves, and augmented noradrenaline. Cell-specific knockout mice showed that collagen accumulation, fibrotic histology, and nerve-associated endpoints required netrin-1 of macrophage but not fibroblast origin. Adrenergic denervation; haploinsufficiency of netrin-1's receptor, deleted in colorectal carcinoma; and therapeutic α1 adrenoreceptor antagonism improved collagen content and histology. An idiopathic pulmonary fibrosis (IPF) lung microarray data set showed increased netrin-1 expression. IPF lung tissues were enriched for netrin-1+ macrophages and noradrenaline. A longitudinal IPF cohort showed improved survival in patients prescribed α1 adrenoreceptor blockade. This work showed that macrophages stimulate lung fibrosis via netrin-1-driven adrenergic processes and introduced α1 blockers as a potentially new fibrotic therapy.
Pursuing Sinus Rhythm in Patients With Persistent Atrial Fibrillation: When Is It Too Late?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: David J. Wilber
Journal: Journal of the American College of Cardiology (2009)