tbuckley/cabot-search huggingface dataset:
The Nietzschean precedent for anti-reflective, dialogical agency
Authors: Mark Alfano
Journal: Behavioral and Brain Sciences (2018)

Abstract Nietzsche anticipates both the anti-reflective and the dialogical aspects of Doris's theory of agency. Nietzsche's doctrine of will to power presupposes that agency does not require reflection but emerges from interacting drives, affects, and emotions. Furthermore, Nietzsche identifies two channels through which dialogical processes of person-formation flow: sometimes a person announces what she is and meets with social acceptance of that claim; sometimes someone else announces what the person is, and she accepts the attribution.
T-cell Dysfunction in Glioblastoma: Applying a New Framework
Authors: Karolina I. Woroniecka, Kristen E. Rhodin, Pakawat Chongsathidkiet, Kristin A. Keith, Peter E. Fecci
Journal: Clinical Cancer Research (2018)

Abstract A functional, replete T-cell repertoire is an integral component to adequate immune surveillance and to the initiation and maintenance of productive antitumor immune responses. Glioblastoma (GBM), however, is particularly adept at sabotaging antitumor immunity, eliciting severe T-cell dysfunction that is both qualitative and quantitative. Understanding and countering such dysfunction are among the keys to harnessing the otherwise stark potential of anticancer immune-based therapies. Although T-cell dysfunction in GBM has been long described, newer immunologic frameworks now exist for reclassifying T-cell deficits in a manner that better permits their study and reversal. Herein, we divide and discuss the various T-cell deficits elicited by GBM within the context of the five relevant categories: senescence, tolerance, anergy, exhaustion, and ignorance. Categorization is appropriately made according to the molecular bases of dysfunction. Likewise, we review the mechanisms by which GBM elicits each mode of T-cell dysfunction and discuss the emerging immunotherapeutic strategies designed to overcome them. Clin Cancer Res; 24(16); 3792–802. ©2018 AACR.
Intérêt de l'entéroscope double-ballon pour explorer l'estomac, après chirurgie bariatrique
Authors: M Frédéric, G Gay, I Fassler, M Delvaux
Journal: Endoscopy (2009)

Introduction: L'exploration endoscopique des patients opérés d'un by-pass gastrique ou ayant une anastomose hépatico-jéjunale sur une anse en Y est souvent difficile du fait de la longueur de l'anse afférente et de l'angle fixé au niveau de l'anastomose jéjuno-jéjunale. L'entéroscopie double ballon permet d'explorer ces patients, en tirant parti de la technique du double ballon et du surtube pour raccourcir l'anse jéjunale en Y et ainsi accéder de manière rétrograde à l'estomac exclu. De plus, l'utilisation du surtube rend la progression de l'endoscope plus sûre puisque les forces exercées par l'opérateur pour avancer l'endoscope sont constamment transmises à la partie distale de l'endoscope.
Next-Generation Sequencing Assisted in Establishing the Diagnosis and Treatment for a Chinese Patient With Breast and Lung Multiple Primary Malignancies
Authors: Chunqing Song, Zhengxing Gao, Jiabao Zong, Junping Shi, Ming Yao, Guilong Lu, Xiaoliang Liu, Kai Wang, Lei Han
Journal: Journal of Thoracic Oncology (2018)

Multiple primary malignancies (MPMs) are malignancies in the same patient with two or more different tissue origins.1 MPMs are easily confused with tumor metastases. Here we report a dual primary cancer initially misdiagnosed as breast cancer metastasis to the lung. With the application of next-generation sequencing (NGS), the specific driver mutations were identified, which corrected the diagnosis and resulted in clinical benefit for the patient.
MANAGEMENT OF SCARRED POLYPS: THE USE OF A NOVEL NON-DIATHERMIC ENDOSCOPIC MUCOSAL RESECTION DEVICE
Authors: K Kandiah, P Bhandari, S Subramaniam
Journal: Endoscopy (2018)

Benign colonic polyps are traditionally resected via endoscopic mucosal resection (EMR). This technique is safe but carries risk of recurrence of 10 – 15% in polyps larger than 20 mm. Post-EMR recurrences are often scarred making endoscopic management of these polyps challenging with a high risk of complications. EndoRotor is a novel non-diathermic EMR device designed to reduce diathermy related complications (eg. perforation and delayed bleeding). We present a video demonstrating the use of this device in the management of scarred polyps.
RECTAL DICLOFENAC DOES NOT PREVENT POST-ERCP PANCREATITIS IN HIGH AND LOW RISK CONSECUTIVE PATIENTS
Authors: L Del Olmo Martinez, B Velayos, A Almaraz
Journal: Endoscopy (2018)

Rectal diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), is used to prevent pancreatitis in high-risk patients during an endoscopic retrogade cholangiopancreatography (ERCP). The European Society of Gastrointestinal Endoscopy (ESGE) recommends prophylaxis with indometacin or diclofenac in all patients undergoing an ERCP, even those with medium-risk and low-risk pancreatitis. We have conducted a study to research the effectiveness of this recommendation.
The RNA binding protein SORBS2 suppresses metastatic colonization of ovarian cancer by stabilizing tumor-suppressive immunomodulatory transcripts
Authors: Linjie Zhao, Wei Wang, Shuang Huang, Zhengnan Yang, Lian Xu, Qilian Yang, Xiu Zhou, Jinjin Wang, Qiuhong Shen, Chenlu Wang, Xiaobing Le, Min Feng, Nianxin Zhou, Wayne Bond Lau, Bonnie Lau, Shaohua Yao, Tao Yi, Xin Wang, Xia Zhao, Yuquan Wei, Shengtao Zhou
Journal: Genome biology (2018)

Ovarian cancer constitutes one of the most lethal gynecologic malignancies for females. Currently, early detection strategies and therapeutic options for ovarian cancer are far from satisfactory, leading to high diagnosis rates at late stages and disease relapses. New avenues of therapy are needed that target key processes in ovarian cancer progression. While a variety of non-coding RNAs have been proven to regulate ovarian cancer metastatic progression, the functional roles of RNA-binding proteins (RBPs) in this process are less well defined.In this study, we identify that the RBP sorbin and SH3 domain containing 2 (SORBS2) is a potent suppressor of ovarian cancer metastatic colonization. Mechanistic studies show that SORBS2 binds the 3' untranslated regions (UTRs) of WFDC1 (WAP four-disulfide core domain 1) and IL-17D (Interleukin-17D), two secreted molecules that are shown to act as metastasis suppressors. Enhanced expression of either WFDC1 or IL-17D potently represses SORBS2 depletion-mediated cancer metastasis promotion. By enhancing the stability of these gene transcripts, SORBS2 suppresses ovarian cancer invasiveness and affects monocyte to myeloid-derived suppressor cell and M2-like macrophage polarization, eliciting a tumor-suppressive immune microenvironment.Our data illustrate a novel post-transcriptional network that links cancer progression and immunomodulation within the tumor microenvironment through SORBS2-mediated transcript stabilization.
Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation
Authors: Fan Liao, Aimin Li, Monica Xiong, Nga Bien-Ly, Hong Jiang, Yin Zhang, Mary Beth Finn, Rosa Hoyle, Jennifer Keyser, Katheryn B. Lefton, Grace O. Robinson, Javier Remolina Serrano, Adam P. Silverman, Jing L. Guo, Jennifer Getz, Kirk Henne, Cheryl E.G. Leyns, Gilbert Gallardo, Jason D. Ulrich, Patrick M. Sullivan, Eli Paul Lerner, Eloise Hudry, Zachary K. Sweeney, Mark S. Dennis, Bradley T. Hyman, Ryan J. Watts, David M. Holtzman
Journal: Journal of Clinical Investigation (2018)

The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE influences Alzheimer disease (AD) in large part by affecting amyloid β (Aβ) aggregation and clearance; however, the molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti–human apoE antibodies can decrease Aβ pathology in mice producing both human Aβ and apoE4, and investigated the mechanism underlying these effects. We utilized APPPS1-21 mice crossed to apoE4-knockin mice expressing human apoE4 (APPPS1-21/APOE4). We discovered an anti–human apoE antibody, anti–human apoE 4 (HAE-4), that specifically recognizes human apoE4 and apoE3 and preferentially binds nonlipidated, aggregated apoE over the lipidated apoE found in circulation. HAE-4 also binds to apoE in amyloid plaques in unfixed brain sections and in living APPPS1-21/APOE4 mice. When delivered centrally or by peripheral injection, HAE-4 reduced Aβ deposition in APPPS1-21/APOE4 mice. Using adeno-associated virus to express 2 different full-length anti–apoE antibodies in the brain, we found that HAE antibodies decreased amyloid accumulation, which was dependent on Fcγ receptor function. These data support the hypothesis that a primary mechanism for apoE-mediated plaque formation may be a result of apoE aggregation, as preferentially targeting apoE aggregates with therapeutic antibodies reduces Aβ pathology and may represent a selective approach to treat AD.
Abstract MP63: Fine-mapping and Characterization of Adiponectin Gwas Loci Harboring Extensive Allelic Heterogeneity
Authors: Cassandra N Spracklen, Anne U Jackson, Apoorva Iyengar, Swarooparani Vadlamudi, Heather Stringham, Chelsea K Raulerson, Maren E Cannon, Kevin W Currin, Ying Wu, Christian Fuchsberger, Ryan Welch, Peter Chines, Narisu Narisu, Johanna Kuusisto, Paivi Pajukanta, Francis Collins, Michael Boehnke, Markku Laakso, Karen Mohlke
Journal: Circulation (2018)

Background: Elevated levels of adiponectin, an adipose-tissue derived hormone, are associated with a decreased risk for development of obesity, cardiovascular disease, and type 2 diabetes. We sought to fine-map and characterize loci from an adiponectin genome-wide association study (GWAS) to better understand the genes, variants, and mechanisms that contribute to adiponectin levels. Methods: We performed a GWAS of plasma adiponectin levels in 9,262 nondiabetic Finnish men from the Metabolic Syndrome in Men (METSIM) study using an efficient mixed model (EPACTS) to account for cryptic relatedness among the subjects. To identify multiple association signals within 1 Mb of each other, we used stepwise conditional analyses and Genome-wide Complex Trait Analysis (GCTA). We annotated association signals using regulatory elements based on chromatin marks from adipocyte nuclei (Epigenomic Roadmap) and ATAC-seq data from adipose tissue (METSIM) and SGBS preadipocyte cells. We also evaluated expression quantitative trait loci (eQTL) in subcutaneous adipose RNA-seq data from 387 METSIM samples. To test for allele-specific effects on transcriptional activity, we performed transcriptional reporter assays in HeLa cells. Results: We identified 5 loci associated with adiponectin ( P &lt;5x10 -8 ): CDH13, ADIPOQ , IRS1, PBRM1, and EPHA3. Two loci ( CDH13 and ADIPOQ ) contained 2 and 7 association signals ( P &lt;1x10 -5 ), respectively. At CDH13 , the first signal contained the lead adipose eQTL variant for CDH13 . At the novel second signal at CDH13 , rs4782722 is located in a regulatory element and the G-allele showed increased transcriptional activity compared to the T-allele, suggesting a functional role for this variant. At ADIPOQ , the first association signal also contained the lead adipose eQTL variant for ADIPOQ. All signals at ADIPOQ contained ≥1 variant in a putative enhancer, and the 7th signal includes rs62625753, a coding variant (G90S; P init =3x10 -3 , P cond =6x10 -4 ) predicted to be deleterious (SIFT) and probably damaging (PolyPhen). Accounting for multiple signals resulted in a 1.6-fold increase in variance explained over the lead signals alone (5.9 vs 9.4%). Conclusions: Fine-mapping, annotation, and experimental validation of GWAS signals and variants provide novel insight into the molecular mechanisms underlying genetic association signals, leading to a clearer biological basis for disease.
Hyperamylasemia after Endoscopic Ultrasound-guided Fine Needle Aspiration (EUS-FNA) of pancreatic lesions: incidence and clinical impact
Authors: G Fernández-Esparrach, P Garcia, O Trujillo, M Pellisé, O Sendino, P Cortés, L Sampaio, I Grilo, A Mata, J Llach, JM Bordas, A Ginès
Journal: Endoscopy (2006)

Background: Acute pancreatitis as a complication of EUS-FNA of pancreatic lesions is rarely observed. However, there is no information about the incidence of hyperamylasemia and to assess its clinical impact. Aim: To evaluate the incidence of hyperamylasemia after EUS-FNA of pancreatic lesion and its clinical impact. Patients and methods: Patients who underwent an EUS-FNA of a pancreatic lesion between october 2004 and october 2005 were prospectively included. Exclusion criteria were: 1. Platelet count under 50,000 and/or protrombine time <50%; 2. Surgery, ERCP or another invasive procedure seven days prior to EUS-FNA; 3. Not informed consent. Procedures were carried out with the patient under conscious sedation. A radial echoendoscope (Olympus GF-UM160), linear echoendoscope for FNA (Olympus UCT-140) and a 22 G needle (Wilson-Cook) were used. An on site cytologist evaluated the EUS-FNA samples at the time of the procedure. Patients were treated with antibiotic when cystic lesions were found. Serum amylasa levels were determinated before, and 8 and 24 hours after the procedure. Hyperamylasemia was defined as amylasa levels 8 hours after the procedure >104 UI/L (and higher than baseline levels). Results: A total of 100 patients underwent EUS-FNA of pancreatic lesions (58 m/42 w, mean age 60 + 14 y). Main indications were diagnosis of a pancreatic mass (66 cases, 66%) and pancreatic cysts (24 cases; 24%) and the FNA was performed from the duodenum (53 cases, 53%) or the stomach (47 cases, 47%). Mean number of passes was 2 + 1. Twelve patients (12%) showed hyperamylasemia at 8 hours after puncture (288 + 283 UI/Ll, range 105–1044), and two of them developed acute pancreatitis after EUS-FNA defined using clasical criteria. Hyperamylasemia was not related to the type of lesion (cystic or solid), its location, the duration of the procedure or the number of passes. There was no relationship between baseline amylasa levels and the development of hyperamylasemia after EUS-FNA. Conclusions: 1.- The incidence of hyperamylasemia after pancreatic EUS-FNA is low and has no clinical impact in the majority of cases. 2.- EUS-FNA of the pancreas is a safe procedure.
In-depth haemodynamic phenotyping of pulmonary hypertension due to left heart disease
Authors: Christian Gerges, Mario Gerges, Pierre Fesler, Anna Maria Pistritto, Nicholas P. Konowitz, Johannes Jakowitsch, David S. Celermajer, Irene M. Lang
Journal: European Respiratory Journal (2018)

The commonest cause of pulmonary hypertension (PH) is left heart disease (LHD). The current classification system for definitions of PH-LHD is under review. We therefore performed prospective in-depth invasive haemodynamic phenotyping in order to assess the site of increased pulmonary vascular resistance (PVR) in PH-LHD subsets. Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned PVR in larger arterial ( R up , upstream resistance) and small arterial plus venous components ( R ds , downstream resistance). In the case of small vessel disease, R up decreases and R ds increases. Inhaled nitric oxide (NO) testing was used to assess acute vasoreactivity. Right ventricular afterload (PVR, pulmonary arterial compliance and effective arterial elastance) was significantly higher in combined post- and pre-capillary PH (Cpc-PH, n=35) than in isolated post-capillary PH (Ipc-PH, n=20). Right ventricular afterload decreased during inhalation of NO in Cpc-PH and idiopathic pulmonary arterial hypertension (n=31), but remained unchanged in Ipc-PH. R up was similar in Cpc-PH (66.8±10.8%) and idiopathic pulmonary arterial hypertension (65.0±12.2%; p=0.530) suggesting small vessel disease, but significantly higher in Ipc-PH (96.5±4.5%; p&lt;0.001) suggesting upstream transmission of elevated left atrial pressure. Right ventricular afterload is driven by elevated left atrial pressure in Ipc-PH and is further increased by elevated small vessel resistance in Cpc-PH. Cpc-PH is responsive to inhaled NO. Our data support current definitions of PH-LHD subsets.
Multidisciplinary Taiwan Consensus Recommendations for the Use of DEBDOX-TACE in Hepatocellular Carcinoma Treatment
Authors: Pi-Yi Chang, Chun-Chieh Huang, Chao-Hung Hung, Chih-Yung Yu, Ding-Kwo Wu, Jen-I Hwang, Po-Chin Liang, Reng-Hong Wu, Wei-Lun Tsai, Yih-Jyh Lin, Yi-Sheng Liu, Huei-Lung Liang, Rheun-Chuan Lee, Chien-Hung Chen
Journal: Liver Cancer (2018)

Transarterial chemoembolization (TACE) is the first-line treatment in patients with unresectable hepatocellular carcinoma (HCC). In recent years, there has been increasing clinical evidence that drug-eluting beads provide a combined ischemic and cytotoxic effect that may be superior to conventional TACE, with low systemic toxicity. The therapeutic value of TACE performed using the embolic microsphere DC Bead loaded with doxorubicin (drug-eluting bead doxorubicin [DEBDOX]) has been shown by several randomized controlled trials. Since Lencioni et al. [Cardiovasc Intervent Radiol 2012; 35: 980–985] published the first widely accepted technical recommendations on HCC embolization with DEBDOX-TACE in 2012, new studies have contributed to a better understanding of when and how to apply this new therapeutic modality, and they have yet to be incorporated into an updated guideline. Additionally, differences in the underlying liver pathology and practice of transcatheter embolization between Asian and Western populations have not been adequately addressed, and there remain significant variations in the TACE protocols adopted in different parts of the world. These mainly revolve around the number and type of chemotherapeutic agents used, type of embolic material, reliance on Lipiodol, and selectivity of catheter positioning. As a result of these issues, it has been difficult to interpret and compare results obtained from different centers in a systematic fashion. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to craft an updated set of recommendations that better reflect recent clinical experiences and are tailored to the use of DEBDOX-TACE in Taiwan. The conclusions of this expert panel are described in the following article.
UTILITY OF TRANSPAPILLARY CHOLECYSTODUODENAL DRAINAGE AS A METHOD FOR PREVENTION OF NEW COMPLICATIONS IN PATIENTS WITH CHOLELITHIASIS ASSOCIATED WITH CHOLEDOCHOLITHIASIS AND HIGH SURGICAL RISK
Authors: B Silva, L Pérez, F Santos, S Maestro, R Madrigal, J Barcenilla, A Pérez, F Igea
Journal: Endoscopy (2018)

Surgery for biliary disease has changed with the progress of endoscopic techniques. To date, the treatment of choice for symptomatic cholelithiasis and acute cholecystitis is surgical, whereas choledocholithiasis is ERCP. However, in older patients with high surgical risk, cholecystectomy, implies high morbidity and mortality, so other alternatives should be studied.
Simulating target lesion for endoscopic submucosal dissection training in a live pig model
Authors: M.-J. Chen, C.-Y. Liu, C.-J. Chen, S.-C. Shih, H.-Y. Wang
Journal: Endoscopy (2012)

Endoscopic submucosal dissection (ESD) is a operator-dependent technique for performing en bloc resection of early digestive neoplasms [1]. A panel of experts from Europe reached a consensus that hands-on experience in a model of harvested pig stomach and in live pigs should be a major part of structured training [2]. In the previous training protocol, only a flat target lesion could be considered in the normal mucosa [3]. Then we developed a method of simulating target lesions in ex vivo systems [4], but this still cannot simulate a setting that provides the opportunity to respond to the potential complication of bleeding.
Precision medicine becomes reality-tumor type-agnostic therapy
Authors: Li Yan, Wei Zhang
Journal: Cancer Communications (2018)

Abstract Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti‐programmed cell death‐1 (PD‐1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability‐high (MSI‐H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol‐Myers Squibb's anti‐PD‐1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI‐H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy. These regulatory approvals marked an important milestone that a cancer treatment may be approved based on a common biomarker rather than the anatomic location in the body where the tumor originated, and therefore established a precedent for tumor type‐agnostic therapy. In the 2017 American Society for Clinical Oncology annual meeting, larotrectinib (LOXO‐101), Loxooncology's oral, potent, and selective inhibitor of tropomyosin receptor kinases (TRK), demonstrated unprecedented efficacy on unresectable or metastatic solid tumors with neurotrophic tropomyosin receptor kinase (NTRK)‐fusion proteins in adult and pediatric patients. Both the anti‐PD‐1 mAbs and the TRK‐targeting therapies share some basic features: (a) biomarker‐based, well‐defined rare patient population; (b) exceptionally high clinical efficacy, e.g., near 40% overall response rate (ORR) for pembrolizumab across 15 tumor types with MSI‐H/dMMR and 75% ORR for larotrectinib across more than 12 tumor types with NTRK‐fusion proteins; (c) durable responses lasting at least 6 months with complete responses observed; and (d) parallel development in adult and pediatric populations. With increasing accessibility to genetic analysis tools such as next‐generation sequencing, tumor type‐agnostic therapy has become a reality, both during clinical development and in clinical practice. Adjustments in our approaches to developing new anti‐cancer drugs and to adopting these new cancer treatments in clinical practice need to occur in order to prepare ourselves for the new era of precision medicine.
Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate
Authors: Morgan E. Grams, Yingying Sang, Shoshana H. Ballew, Juan Jesus Carrero, Ognjenka Djurdjev, Hiddo J.L. Heerspink, Kevin Ho, Sadayoshi Ito, Angharad Marks, David Naimark, Danielle M. Nash, Sankar D. Navaneethan, Mark Sarnak, Benedicte Stengel, Frank L.J. Visseren, Angela Yee-Moon Wang, Anna Köttgen, Andrew S. Levey, Mark Woodward, Kai-Uwe Eckardt, Brenda Hemmelgarn, Josef Coresh
Journal: Kidney International (2018)
Evaluation prospective multicentrique de la qualité de la préparation colique en coloscopie chez 1019 patients
Authors: J Lapuelle, E Abdini, JM Canard, P Coulom, B Croguennec, JC Letard, C Boustière, J Cassigneul, JB Cazals, P Dalbies, N Gimbert, T Helbert, P Houcke, P Pienkowski, R Systchenko, C Chaussier, F Kohler, F Vicari
Journal: Endoscopy (2009)

Introduction: La qualité de la préparation colique reste l'élément essentiel pour la détection et la résection des polypes. Le but de ce travail était d'évaluer à l'aide d'enregistrements systématiques des coloscopies, les facteurs influençant la qualité de la préparation colique et ses modalités d'examen, indépendamment du type de produit utilisé.