tbuckley/cabot-search huggingface dataset:
Association of <i>KRAS</i> Variant Subtypes With Survival and Recurrence in Patients With Surgically Treated Intrahepatic Cholangiocarcinoma
Authors: Shao-Lai Zhou, Hao-Yang Xin, Rong-Qi Sun, Zheng-Jun Zhou, Zhi-Qiang Hu, Chu-Bin Luo, Peng-Cheng Wang, Jia Li, Jia Fan, Jian Zhou
Journal: JAMA Surgery (2021)

<h3>Importance</h3> <i>KRAS</i>variants are associated with tumor progression; however, the prevalence of<i>KRAS</i>variant subtypes and their association with survival and recurrence in patients with intrahepatic cholangiocarcinoma (ICC) after curative resection are largely unknown. <h3>Objective</h3> To explore the prognostic association of<i>KRAS</i>variant subtypes with survival and recurrence in patients with ICC. <h3>Design, Setting, and Participants</h3> In this cohort study, patients who underwent curative resection for ICC from January 2009 through December 2016 at a single hospital in China were recruited, and whole-exome sequencing, targeted sequencing, and Sanger sequencing were performed to identify<i>KRAS</i>variants. Kaplan-Meier and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Data were analyzed from April 2020 to January 2021. <h3>Interventions</h3> Hepatectomy in patients with ICC. <h3>Main Outcomes and Measures</h3> The association of<i>KRAS</i>variant subtypes with OS and DFS. <h3>Results</h3> Of 1024 included patients with ICC, 621 (60.6%) were male, and the mean (SD) age was 59.2 (10.2) years. A total of 14 different subtypes of<i>KRAS</i>somatic variants affecting 127 patients (12.4%) were identified. G12D was the most frequent allele in this cohort, accounting for 55 of 127 identified<i>KRAS</i>variants (43.3%), followed by G12V (25 [19.7%]), G12C (9 [7.1%]), and G13D (8 [6.3%]). Compared with patients with wild-type<i>KRAS</i>, patients with variant<i>KRAS</i>were more likely to have high levels of carbohydrate antigen 19-9 (92 of 127 [72.4%] vs 546 of 897 [60.9%];<i>P</i> = .01) and γ-glutamyltransferase (72 of 127 [56.7%] vs 420 of 897 [46.8%];<i>P</i> = .04). Multivariable analysis revealed that G12<i>KRAS</i>variants but not non-G12<i>KRAS</i>variants were independently associated with worse OS (hazard ratio [HR], 1.69; 95% CI, 1.31-2.18;<i>P</i> &lt; .001) and DFS (HR, 1.47; 95% CI, 1.16-1.88;<i>P</i> = .002). Among the patients with G12<i>KRAS</i>variants, the G12V<i>KRAS</i>variant was the strongest prognostic determinant for the worst OS (HR, 3.05; 95% CI, 1.94-4.79;<i>P</i> &lt; .001) and DFS (HR, 1.79; 95% CI, 1.13-2.85;<i>P</i> = .01). <h3>Conclusions and Relevance</h3> In this cohort study, the distribution of<i>KRAS</i>variant subtypes was characterized in a large cohort of patients with ICC from China. The presence of G12<i>KRAS</i>variants but not non-G12<i>KRAS</i>variants was associated with worse survival and increased risk of recurrence. Patients with the G12V variant exhibited the worst outcomes in the whole cohort.
Integrating Supported Decision-Making into the Clinical Research Process
Authors: Barbara E. Bierer, Ari Ne’eman, Willyanne DeCormier Plosky, David H. Strauss, Benjamin C. Silverman, Michael Ashley Stein
Journal: The American Journal of Bioethics (2021)

This article is referred to by:Supported Decision Making with People at the Margins of Autonomy: Response to Commentaries
Synergistic antitumor activity of pan-PI3K inhibition and immune checkpoint blockade in bladder cancer
Authors: Shaoming Zhu, A-Hong Ma, Zheng Zhu, Elio Adib, Ting Rao, Na Li, Kaiyuan Ni, Veera Chandra Sekhar Reddy Chittepu, Rao Prabhala, Juan Garisto Risco, David Kwiatkowski, Kent Mouw, Guru Sonpavde, Fan Cheng, Chong-xian Pan
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune checkpoint blockade (ICB) induces durable response in approximately 20% of patients with advanced bladder urothelial cancer (aUC). Over 50% of aUCs harbor genomic alterations along the phosphoinositide 3-kinase (PI3K) pathway. The goal of this project was to determine the synergistic effects and mechanisms of action of PI3K inhibition and ICB combination in aUC.Alterations affecting the PI3K pathway were examined in The Cancer Genome Atlas (TCGA) and the Cancer Dependency Map databases. Human and mouse cells with Pten deletion were used for in vitro studies. C57BL/6 mice carrying syngeneic tumors were used to determine in vivo activity, mechanisms of action and secondary resistance of pan-PI3K inhibition, ICB and combination.Alterations along the PI3K pathway occurred in 57% of aUCs in TCGA. CRISPR (clustered regularly interspaced short palindromic repeats) knockout of PIK3CA induced pronounced inhibition of cell proliferation (p=0.0046). PI3K inhibition suppressed cancer cell growth, migration and colony formation in vitro. Pan-PI3K inhibition, antiprogrammed death 1 (aPD1) therapy and combination improved the overall survival (OS) of syngeneic mice with PTEN-deleted tumors from 27 days of the control to 48, 37, and 65 days, respectively. In mice with tumors not containing a PI3K pathway alteration, OS was prolonged by the combination but not single treatments. Pan-PI3K inhibition significantly upregulated CD80, CD86, MHC-I, and MHC-II in dendritic cells, and downregulated the transforming growth factor beta pathway with a false discovery rate-adjusted q value of 0.001. Interferon alpha response was significantly upregulated with aPD1 therapy (q value: <0.001) and combination (q value: 0.027). Compared with the control, combination treatment increased CD8+ T-cell infiltration (p=0.005), decreased Treg-cell infiltration (p=0.036), and upregulated the expression of multiple immunostimulatory cytokines and granzyme B (p<0.01). Secondary resistance was associated with upregulation of the mammalian target of rapamycin (mTOR) pathway and multiple Sprr family genes.The combination Pan-PI3K inhibition and ICB has significant antitumor effects in aUC with or without activated PI3K pathway and warrants further clinical investigation. This combination creates an immunostimulatory tumor milieu. Secondary resistance is associated with upregulation of the mTOR pathway and Sprr family genes.
Soluble CD89 is a critical factor for mesangial proliferation in childhood IgA nephropathy
Authors: Alexandra Cambier, Patrick J Gleeson, Lilia Abbad, Fanny Canesi, Jennifer da Silva, Julie Bex-Coudrat, Georges Deschênes, Olivia Boyer, Marion Rabant, Tim Ulinski, Julien Hogan, Michel Peuchmaur, Laureline Berthelot, Renato C Monteiro
Journal: Kidney International (2021)
Injectable AuNP-HA matrix with localized stiffness enhances the formation of gap junction in engrafted human induced pluripotent stem cell-derived cardiomyocytes and promotes cardiac repair
Authors: Hekai Li, Bin Yu, Pingzhen Yang, Jie Zhan, Xianglin Fan, Peier Chen, Xu Liao, Caiwen Ou, Yanbin Cai, Minsheng Chen
Journal: Biomaterials (2021)
Abstract 13694: Developing a Veterans Affairs Women Atherosclerotic Cardiovascular Risk Assessment Model From Veterans Affairs National Electronic Health Records Data
Authors: Haekyung Jeon-Slaughter, Xiaofei Chen, Bala Ramanan, Shirling Tsai
Journal: Circulation (2019)

Introduction: Current prediction models for atherosclerotic cardiovascular disease (ASCVD) risk demonstrate poor fit for minority groups and do not account for non-traditional risk factors that may...
Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
Authors: Irene Talon, Adrian Janiszewski, Bart Theeuwes, Thomas Lefevre, Juan Song, Greet Bervoets, Lotte Vanheer, Natalie De Geest, Suresh Poovathingal, Ryan Allsop, Jean-Christophe Marine, Florian Rambow, Thierry Voet, Vincent Pasque
Journal: Genome biology (2021)

Abstract Background Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear. Results Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency. Conclusions Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.
Adding carbon nanoparticles to dual-tracers for the sentinel node evaluation after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers: The TT-SLNB trial.
Authors: Jie Chen, Jiqiao Yang, Tao He, Yunhao Wu, Xian Jiang, Zhoukai Fu, Qing Lv, Shan Lu, Xiaodong Wang, Hongjiang Li, Jing Wang
Journal: Journal of Clinical Oncology (2021)

566 Background: This study measures the feasibility and accuracy of sentinel lymph node biopsy (SLNB) with triple-tracers (TT-SLNB) which combines carbon nanoparticles (CNS) with dual tracers of radioisotope and blue dye, hoping to achieve an optimized method of SLNB after neoadjuvant chemotherapy (NAC) in ycN0 breast cancer patients with pretreatment positive axillary lymph nodes. Methods: Clinically node-negative invasive breast cancer patients with pre-NAC positive axillary lymph nodes who received surgeries from November 2020 to January 2021 were included. CNS was injected at the peritumoral site the day before surgery. Standard dual-tracer (SD)-SLNs were defined as blue-colored and/or hot nodes, and TT-SLNs were defined as lymph nodes detected by any of hot, blue-stained, black-stained, and/or palpated SLNs. All patients received subsequent axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were calculated. Results: Seventy-six of 121 (62.8%) breast cancer patients converted to cN0 after NAC and received TT-SLNB. After NAC, 28.95% (22/76) achieved overall (breast and axilla) pCR. The DR was 94.74% (72/76), 88.16% (67/76) and 96.05% (73/76) for SLNB with single-tracer of CNS (CNS-SLNB), SD-SLNB, and TT-SLNB, respectively. The FNR was 22.86% (8/35) for CNS-SLNB and 10% (3/30) for SD-SLNB. The FNR of TT-SLNB was 5.71% (2/35), which was significantly lower than those of CNS-SLNB and SD-SLNB. The NPV and accuracy was 95.0% and 97.3% for TT-SLNB, respectively. Moreover, a significant relation was seen between the pretreatment clinical T classification and the DR of TT-SLNB (Fisher’s exact test, p= 0.010). Conclusions: TT-SLNB revealed ideal performance in post-NAC ycN0 patients with pretreatment node-positive breast cancers. The application of TT-SLNB reached a better balance between more accurate axillary evaluation and less intervention. Clinical trial information: ChiCTR2000039814. [Table: see text]
In Vivo Micro‐Computerized Tomography Tracking of Human Periodontal Ligament Stem Cells Labeled with Gold Nanocomplexes
Authors: Chen Zong, Annelies Bronckaers, Greetje Vande Velde, Guy Willems, Maria Cadenas de Llano‐Pérula
Journal: Advanced Healthcare Materials (2021)

Abstract Gold nanocomplexes have been proposed as contrast agents for computerized tomography (CT) and cell tracking, which is especially useful in stem cell therapy. However, their potential for long‐term in vivo cell detection is still unknown. This study proposes an optimized approach to labeling human periodontal ligament stem cells (hPDLSCs) with gold nanocomplexes to evaluate their detection with micro‐CT after transplantation at four different rat tissues. The gold nanocomplexes of 0.05 mg mL −1 do not affect cell viability nor osteogenic differentiation capacity, but render fluorescent and radiopaque hPDLSCs. Excellent linear correlation with the number of labeled cells is shown over a wide range ( r = 0.99, P &lt; 0.01), with a detection limit of ≈1.2 × 10 3 cells/µL. In vivo, strong, and durable detection of transplanted labeled cells within 5 days at all investigated areas is seen by micro‐CT and immunohistochemical assay. This approach confirms the potential of gold nanocomplexes in longitudinal in vivo cell tracking, which may facilitate their application in CT image‐guided interventions commonly used in oromaxillofacial or systemic applications of stem cell therapy.
Association of Inherited Mutations in DNA Repair Genes with Localized Prostate Cancer
Authors: Daniel J. Lee, Ryan Hausler, Anh N. Le, Gregory Kelly, Jacquelyn Powers, James Ding, Emily Feld, Heena Desai, Casey Morrison, Abigail Doucette, Peter Gabriel, Regeneron Genetics Center, Renae L. Judy, Joellen Weaver, Rachel Kember, Scott M. Damrauer, Daniel J. Rader, Susan M. Domchek, Vivek Narayan, Lauren E. Schwartz, Kara N. Maxwell
Journal: European Urology (2021)

Identification of germline mutations in DNA repair genes has significant implications for the personalized treatment of individuals with prostate cancer (PrCa). To determine DNA repair genes associated with localized PrCa in a diverse academic biobank and to determine genetic testing burden. A cross-sectional study of 2391 localized PrCa patients was carried out. Genetic ancestry and mutation rates (excluding somatic interference) in 17 DNA repair genes were determined in 1588 localized PrCa patients and 3273 cancer-free males. Burden testing within individuals of genetically determined European (EUR) and African (AFR) ancestry was performed between biobank PrCa cases and cancer-free biobank and gnomAD males. AFR individuals with localized PrCa had lower DNA repair gene mutation rates than EUR individuals (1.4% vs 4.0%, p = 0.02). Mutation rates in localized PrCa patients were similar to those in biobank and gnomAD controls (EUR: 4.0% vs 2.8%, p = 0.15, vs 3.1%, p = 0.04; AFR: 1.4% vs 1.8%, p = 0.8, vs 2.1%, p = 0.5). Gene-based rare variant association testing revealed that only BRCA2 mutations were significantly enriched compared with gnomAD controls of EUR ancestry (1.0% vs 0.28%, p = 0.03). Of the participants, 21% and 11% met high-risk and very-high-risk criteria; of them, 3.7% and 6.2% had any germline genetic mutation and 1.0% and 2.5% had a BRCA2 mutation, respectively. Limitations of this study include an analysis of a relatively small, single-institution cohort. DNA repair gene germline mutation rates are low in an academic biobank cohort of localized PrCa patients, particularly among individuals of AFR genetic ancestry. Mutation rates in genes with published evidence of association with PrCa exceed 2.5% only in high-risk, very-high-risk localized, and node-positive PrCa patients. These findings highlight the importance of risk stratification in localized PrCa patients to identify appropriate patients for germline genetic testing. In the majority of patients who develop localized prostate cancer, germline genetic testing is unlikely to reveal an inherited DNA repair mutation, regardless of race. High-risk features increase the possibility of a germline DNA repair mutation.
TCT-209 In-Hospital Outcomes of Patients Undergoing Transcatheter Aortic Valve Implantation Based on Obesity: Nationwide Inpatient Sample Database Analysis
Authors: Neel Patel, Birendra Amgai, Adrija Hajra, Sandipan Chakraborty, Dhrubajyoti Bandyopadhyay, Natasha Srinivas, Zeel Patel, Wilbert Aronow
Journal: Journal of the American College of Cardiology (2021)
TCT-190 Transcatheter Closure of Secundum Atrial Septal Defects With the Use of Cocoon Septal Occluders: Immediate and Long-Term Outcomes
Authors: Santosh Sinha, Umeshwar Pandey, Puneet Aggarwal, Mahmadula Razi, Awadesh Sharma, Mohit Sachan, Mukesh Jha, Praveen Shukla, Ramesh Thakur
Journal: Journal of the American College of Cardiology (2021)
Rapid attenuation of anti–<scp>SARS</scp>–<scp>CoV</scp>‐2 antibodies in patients with musculoskeletal diseases in whom intensive immunosuppressive therapies were reinitiated after <scp>COVID</scp>‐19: comment on the article by Curtis et al
Authors: Masashi Okamoto, Shoji Kawada, Hiroshi Shimagami, Naoko Fujii, Kazuki Matsukawa, Nachi Ishikawa, Keisuke Kawamoto, Shinji Higa, Yutaka Ishida, Atsushi Ogata, Yuta Yamaguchi, Takayoshi Morita, Yasuhiro Kato, Atsushi Kumanogoh
Journal: Arthritis & Rheumatology (2021)

Disclosure Form Figure S1 Supplementary Figure Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
TCT-63 North American COVID-19 Myocardial Infarction (NACMI) Risk Score for Prediction of In-Hospital Mortality
Authors: Payam Dehghani, Christian Schmidt, Ross Garberich, Santiago Garcia, Cindy Grines, Rajan Patel, Cristina Sanina, Wah Wah Htun, Keshav Nayak, M Chadi Alraies, Nima Ghasemzadeh, Laura Davidson, Deepak Acharya, Jay Stone, Tareq Alyousef, Brian Case, Xuming Dai, Abdul Moiz Hafiz, Mina Madan, Farouc Amin Jaffer, Jay Shavadia, Timothy Henry
Journal: Journal of the American College of Cardiology (2021)
Hierarchical Nanostructured Electrospun Membrane with Periosteum‐Mimic Microenvironment for Enhanced Bone Regeneration (Adv. Healthcare Mater. 21/2021)
Authors: Laijun Liu, Yuna Shang, Chaojing Li, Yongjie Jiao, Yanchen Qiu, Chengyi Wang, Yuge Wu, Qiuyun Zhang, Fujun Wang, Zhimou Yang, Lu Wang
Journal: Advanced Healthcare Materials (2021)
スフェロイド組み込みヒト皮膚線維芽細胞シートの送達は創傷治癒のための血管新生とM2分極を増加させる【JST・京大機械翻訳】
Authors: Kim Sung-Won, Im Gwang-Bum, Jeong Gun-Jae, Baik Sangyul, Hyun Jiyu, Kim Yu-Jin, Pang Changhyun, Jang Young Charles, Bhang Suk Ho
Journal: Biomaterials (2021)
Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes
Authors: Detlef Schuppan, Markku Maki, Knut E. A. Lundin, Jorma Isola, Tina Friesing-Sosnik, Juha Taavela, Alina Popp, Jari Koskenpato, Jost Langhorst, Oistein Hovde, Marja-Leena Lahdeaho, Stefano Fusco, Michael Schumann, Helga P. Toeroek, Juozas Kupcinskas, Yurdagul Zopf, Ansgar W. Lohse, Mika Scheinin, Karin Kull, Luc Biedermann, Valerie Byrnes, Andreas Stallmach, Jorgen Jahnsen, Jonas Zeitz, Ralf Mohrbacher, Roland Greinwald
Journal: New England Journal of Medicine (2021)
Anaphylactic reactions to polyethylene glycol-containing bowel cleansing preparations after Moderna COVID-19 vaccination
Authors: Maximilian Schreiner, Christian Zobel, Ulrich Baumgarten, Tina Uhlmann, Staffan Vandersee
Journal: Endoscopy (2021)

Shortly after emergency use authorization of COVID-19 mRNA vaccines was given, the first reports of anaphylactic reactions emerged. While the causative agent is still a matter of debate, allergy to the excipient polyethylene glycol (PEG) is a possible explanation [1]. PEG is a hydrophilic polymer with variable molecular weight and also the main constituent of many bowel cleansing agents used prior to colonoscopy. Anaphylaxis to PEG-containing bowel cleansing preparations is exceedingly rare, with an estimated average of four cases per year in the USA [2].
Assessing a Veterinary Sedative’s Role in Drug Overdose Deaths
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

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Preventing overdiagnosis: how to stop harming the healthy Evidence is mounting that medicine is harming healthy people through ever earlier detection and ever wider definition of disease. With the announcement of an international conference to improve understanding of the problem of overdiagnosis, Ray Moynihan, Jenny Doust, and David Henry examine its causes and explore solutions
Authors: Moynihan Ray, Doust Jenny, Hanry David
Journal: BMJ (2012)