tbuckley/cabot-search huggingface dataset:
CKLF1 Enhances Inflammation-Mediated Carcinogenesis and Prevents Doxorubicin-Induced Apoptosis via IL6/STAT3 Signaling in HCC
Authors: Youyi Liu, Lijuan Liu, Yan Zhou, Ping Zhou, Qiujin Yan, Xiaobei Chen, Shuang Ding, Fan Zhu
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Hepatocellular carcinoma (HCC), one of the most common and deadliest malignancies worldwide, has a poor prognosis, owing to its high potential for vascular invasion and metastasis and the lack of biomarkers for early diagnosis. Thus, it must be a crucial factor for investigating therapeutic strategies for HCC to identify the functional molecular targets. Here, we reported a novel chemokine, CKLF1, that might act as a pivotal modulator in the invasion and metastasis of HCC and could serve as an attractive target for cancer therapy. Experimental Design: Bioinformatics analysis, PCR, Western blotting, and IHC were performed to detect the expression of CKLF1 in HCC. The function of CKLF1 was demonstrated by a series of in vitro and in vivo experiments. Pharmacologic treatment, flow cytometry, and Western blotting were carried out to demonstrate the potential mechanisms of CKLF1. Results: We proved that CKLF1 was overexpressed in HCC tissues and was related to tumor stage, vascular invasion, and patient survival. Then, functional assays showed that CKLF1 promoted hepatocellular carcinogenesis and metastatic potential. Finally, the IL6/STAT3 signaling pathway was involved in the mechanistic investigation. The results demonstrated that CKLF1 enhanced the progression of HCC and prevented doxorubicin-induced apoptosis through activating the IL6/STAT3 pathway. Conclusions: These data showed that CKLF1 inhibited apoptosis and promoted malignant transformation through the IL6/STAT3 pathway, and ultimately enhanced the development and metastasis of HCC. Thus, our work revealed that CKLF1 was a significant prognostic factor of HCC and might be a potential molecular therapeutic target for HCC.
Abstract 14809: Comparison Of The Effectiveness And Safety Of Dabigatran Etexilate Versus Acenocoumarol In Patients With Left Ventricular Assist Device
Authors: John Terrovitis, Christos Kapelios, Styliani Vakrou, Nickolaos Diakos, Lampros Katsaros, Argyrios Ntalianis, Elisavet Kaldara, Dimitrios Kontoyannis, Christos Charitos, John Nanas
Journal: Circulation (2011)

Administration of anticoagulation is mandatory in patients with LVAD. Vitamin K antagonists require regular monitoring and dosage adjustment. Dabigatran administered at a standard dose twice daily ...
QIM19-133: Assessing and Reducing FDG PET/CT Radiotracer Infiltrations: Lessons in Quality Improvement Sustainability
Authors: Jackson W. Kiser, James Crowley, Thad Benefield, Ronald Lattanze, Steve Perrin, Kelley Ryan, Josh Knowland
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Oncologic PET/CT studies require a prescribed 18 F-fluorodeoxyglucose (FDG) dose delivered as a bolus prior to imaging; this same dose is used in the standardized uptake value (SUV) calculation. An infiltration is the misadministration of FDG outside the systemic circulation and will result in underestimating the SUV. Interpreting and treating physicians are often unaware of infiltrations when the injection site is outside the imaging field of view. Despite existing quality control (QC) efforts to ensure accuracy of the administered dose, there is no routine QC method that confirms complete delivery of the dose into the patient's circulation. 5 technologists in our center participated in a quality improvement project that reduced infiltration rates from 13.3% to 2.9% ( P -value for difference in rates &lt;.0001). Our objective was to evaluate sustainability of the improvement. Methods: 8 new technologists joined the team during the sustainability period. Infiltration rates in the sustainability period were calculated, controlling for technologist- and patient-level correlations (SAS v. 9.4). Infiltration rates were compared between QI participants and nonparticipants. Results: 13 technologists administered 1,240 injections in the sustainability period (10/7/2017–9/26/2018) with a 3.1% infiltration rate. The Infiltration rate for technologists who did not participate in the QI project was higher (6.08%; SE: 1.31%; 95% CI: 3.19%–8.97%) compared to the QI project technologists (2.05%; SE: 0.0055%; 95% CI: 0.83%–3.26%). This 66% decrease in rates was found to be statistically significant ( P =.017). Conclusions: Although the overall infiltration rate remained low in the sustainability period, rates among new technologists who joined after the QI project were higher, compared to their QI project counterparts. This is especially important given the number of new technologists (n=8) compared to the QI project technologists (n=5). Quality improvement is a continuous process, and dissemination of lessons learned from the QI project should be provided as new technologists are onboarded. Because proper injections are critical to PET/CT images, ongoing monitoring is essential to ensuring that injection quality remains high, as infiltration rates can change over time.
BPI19-012: Differences in Stakeholder Perspectives Regarding Key Components of Shared Decision-Making for Mammography in Breast Cancer Screening for Women Ages 40–50
Authors: Lori L. DuBenske, Sarina B. Schrager, Terry A. Little, Elizabeth S. Burnside
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: National health organizations offer contrasting guidelines for women aged 40–49 regarding when to begin and how often to use mammography screening for breast cancer. The ACS recommends average risk women aged 40–44 receive annual screening “if they wish to do so” and annual screening for women aged 45–54. The United States Preventive Services Task Force recommends individualized screening for average-risk women before age 50 advised by risk assessment and shared decision-making (SDM). Clinicians lack guidance on how to conduct and what elements to include in mammography SDM. Our prior work identified core elements via scoping review applied to a modified Delphi consensus process involving patients, primary care physicians (PCP), and healthcare decision scientists (HDS). This study examines stakeholder group differences in endorsing core SDM elements. Methods: The Delphi consensus included 10 patients, 10 PCP, and 10 HDS and fielded 48 items to codify core elements of mammography SDM. A threshold of 80% agreement across all participants was set to establish consensus for retaining or dropping an item. In this study, separate stakeholder groups’ endorsement rates for each item were calculated. Items were deemed to have stakeholder discrepancy if one group differed from the 2 others in either meeting or not meeting the 80% threshold criteria. Results: 16 items (13 retained, 3 dropped in Delphi) had a discrepant group. For all retained items, the discrepant group fell below 80% criteria for retaining. For 2 of the dropped items, discrepant groups achieved threshold for retaining the item. One item was dropped despite most participants voting to retain it (&gt;80%) due to the discrepant group’s rating &lt;80%. Patients rated less importance to educating women about risks and recommendations. PCPs rated lower importance to training PCPs and women for discussions about mammograms and having discussions on a regular basis. HDSs rated greater importance to considering mammogram procedures and costs in SDM. Discussion: Leading healthcare organizations are increasingly recommending SDM in breast cancer screening, among other decisions. Guidelines enumerating core elements of SDM are needed to effectively direct clinicians. This study, by illuminating differences between stakeholder group perspectives, highlights the importance of eliciting varied perspectives in identifying core elements of SDM when informing healthcare practices and policy.
KLRG1+ natural killer cells exert a novel antifibrotic function in chronic hepatitis B
Authors: Ratna S. Wijaya, Scott A. Read, Stephen Schibeci, Mohammed Eslam, Mahmoud K. Azardaryany, Korri El-Khobar, David van der Poorten, Rita Lin, Lawrence Yuen, Vincent Lam, Jacob George, Mark W. Douglas, Golo Ahlenstiel
Journal: Journal of Hepatology (2019)
Frontiers in Cryo Electron Microscopy of Complex Macromolecular Assemblies
Authors: Jana Ognjenović, Reinhard Grisshammer, Sriram Subramaniam
Journal: Annual Review of Biomedical Engineering (2019)

In recent years, cryo electron microscopy (cryo-EM) technology has been transformed with the development of better instrumentation, direct electron detectors, improved methods for specimen preparation, and improved software for data analysis. Analyses using single-particle cryo-EM methods have enabled determination of structures of proteins with sizes smaller than 100 kDa and resolutions of ∼2 Å in some cases. The use of electron tomography combined with subvolume averaging is beginning to allow the visualization of macromolecular complexes in their native environment in unprecedented detail. As a result of these advances, solutions to many intractable challenges in structural and cell biology, such as analysis of highly dynamic soluble and membrane-embedded protein complexes or partially ordered protein aggregates, are now within reach. Recent reports of structural studies of G protein-coupled receptors, spliceosomes, and fibrillar specimens illustrate the progress that has been made using cryo-EM methods, and are the main focus of this review.
Mucinous Ovarian Carcinoma
Authors: Philippe Morice, Sebastien Gouy, Alexandra Leary
Journal: New England Journal of Medicine (2019)

Mucinous ovarian cancer accounts for 3% of epithelial ovarian cancers and must be distinguished from mucinous carcinomas that have metastasized to the ovary. Most cases manifest as large, localized masses; resection is associated with a good prognosis.
Randomized, Double‐Blind, Placebo‐Controlled Trial of Intraarticular Trans <i>‐</i> Capsaicin for Pain Associated With Osteoarthritis of the Knee
Authors: Randall M. Stevens, John Ervin, Jennifer Nezzer, Yeni Nieves, Kimberly Guedes, Robin Burges, Peter D. Hanson, James N. Campbell
Journal: Arthritis & Rheumatology (2019)

To assess the efficacy and safety of high-purity synthetic trans-capsaicin (CNTX-4975) in patients with chronic moderate-to-severe osteoarthritis (OA)-associated knee pain.In this phase II multicenter double-blind study, patients ages 45-80 years who had stable knee OA were randomized in a 2:1:2 ratio to receive a single intraarticular injection of placebo, CNTX-4975 0.5 mg, or CNTX-4975 1.0 mg. The primary efficacy end point was area under the curve (AUC) for change from baseline in daily Western Ontario and McMaster Universities Osteoarthritis Index pain with walking score (range 0-10, 0 = none and 10 = extreme) through week 12. Secondary efficacy end points included a similar AUC analysis of outcomes in patients treated with CNTX-4975 0.5 mg, and evaluations extending to 24 weeks.Efficacy was evaluated in 172 patients (placebo group, n = 69; CNTX-4975 0.5 mg group, n = 33; CNTX-4975 1.0 mg group, n = 70). At week 12, greater decreases in the AUC for the pain score were observed with CNTX-4975 in the 0.5 mg and 1.0 mg groups versus placebo (0.5 mg group least squares mean difference [LSMD] -0.79, P = 0.0740; 1.0 mg group LSMD -1.6, P < 0.0001). Significant improvements were maintained at week 24 in the 1.0 mg group (LSMD -1.4, P = 0.0002). Treatment-emergent adverse events were similar in the placebo and CNTX-4975 1.0 mg groups.In this study, CNTX-4975 provided dose-dependent improvement in knee OA-associated pain. CNTX-4975 1.0 mg produced a significant decrease in OA knee pain through 24 weeks; CNTX-4975 0.5 mg significantly improved pain at 12 weeks, but the effect was not evident at 24 weeks.
CLO19-024: Risk of Atrial Fibrillation and Pulmonary Toxicities in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Treated With Ibrutinib
Authors: Nimesh Adhikari, Myo H. Zaw, Sriman Swarup, Anita Sultan, Upama Sharma, Wai P. Thi, Nay N. Yee, Khaing K. Htwe, Tun W. Naing, Kyaw Z. Thein
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Bruton’s tyrosine kinase (BTK), a kinase downstream of the B-cell receptor, involves in the B cell survival and proliferation and has become an attractive therapeutic target. Ibrutinib is an oral potent, covalent inhibitor of BTK and hence employed in many hematologic malignancies. We performed a systematic review and pooled analysis of randomized controlled trials (RCTs) to determine the risk of atrial fibrillation (AF) and pulmonary toxicities among patients treated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through September 2018. Phase 3 RCTs that mention AF and pulmonary toxicities as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% CI. Random effects model was applied. Results: 4 phase III RCTs with a total of 1,383 patients with chronic lymphocytic leukemia or small lymphocytic lymphoma were eligible. Studies comparing Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R, and I vs R were included in the analysis. The AF incidence was 41 (5.686%) in the ibrutinib group vs 8 (1.208%) in the control arm. The relative risk (RR) for AF was statistically significant at 3.825 (95% CI: 1.848–7.917; P &lt;.0001) and RD was 0.041 (95% CI: 0.023–0.059; P &lt;.0001). The RR of all-grade side effects was as follows: cough, 1.133 (95% CI: 0.724–1.773; P =.584); edema, 1.375 (95% CI: 0.943–2.006; P =.098); pneumonia, 1.227 (95% CI: 0.884–1.703; P =.221); and upper respiratory infections (URI), 1.075 (95% CI: 0.809–1.429; P =.616). The RR of high-grade side effects was as follows: cough, 0.373 (95% CI: 0.063–2.209; P =.277); edema, 1.232 (95% CI: 0.199–7.649; P =.822); pneumonia, 1.277 (95% CI: 0.847–1.926; P =.243); and URI, 1.555 (95% CI: 0.239–10.127; P =.644). Conclusion: Our meta-analysis demonstrated that patients on ibrutinib noted a significant increase in the risk of atrial fibrillation with a relative risk of 3.825. However, the risk of pulmonary toxicities was not statistically increased in the ibrutinib group.
Open-label, multicenter study of sipuleucel-T in men with metastatic castrate-resistant prostate cancer (mCRPC) previously treated with sipuleucel-T: Evaluation of antigen presenting cell (APC) activation and ELISPOT data.
Authors: Tomasz M. Beer, L. Michael Glode, Raymond S. Lance, Richard H. Greengold, Corazon P. dela Rosa, Robert Brownell Sims, Yang Wang, Nadeem A. Sheikh, John M. Corman
Journal: Journal of Clinical Oncology (2013)

5053^ Background: P10-1 (NCT01338012) is a study of sipuleucel-T, an autologous cellular immunotherapy, in men with mCRPC previously treated with sipuleucel-T in PROTECT (NCT00779402). This preliminary analysis of P10-1 evaluates APC activation (a measure of product potency) and immune responses in men retreated with sipuleucelET. Methods: Men who received ≥1 infusion of sipuleucel-T in PROTECT and progressed to mCRPC were retreated with 3 infusions of sipuleucel-T. APC activation was assessed by CD54 upregulation. T cell responses to prostatic acid phosphatase (PAP) and PA2024 (PAP-GM-CSF) antigens were assessed by IFN-γELISPOT assay. Results: As of October 23, 2012, 7 men were enrolled and received ≥1 infusion. Median time between the third PROTECT infusion and first P10-1 infusion was 9.2 (range: 7.8–10.0) years. APC activation was greater at the first P10-1 treatment vs the last PROTECT treatment (Table). PA2024 and PAP ELISPOT responses were present prior to retreatment, indicating long-term memory (Table 1); based on other studies of sipuleucel-T, ELISPOT responses are not generally present prior to the first treatment (Beer. Clin Cancer Res 2011; Sheikh. Cancer Immunol Immunother 2013). Conclusions: This is the first trial to report the feasibility of sipuleucel-T retreatment following treatment in an earlier stage of prostate cancer. These data indicate the presence of existing immunological memory to the immunizing antigen several years after initial treatment. In addition, retreatment with sipuleucel-T appeared to boost product potency compared with prior treatment. Clinical trial information: NCT01338012. [Table: see text]
YIA19-001: Mechanisms of Diagnostic Delay Among Black women With Endometrial Cancer (EC): Results from Qualitative Interviews and a National Analysis of Healthcare Data
Authors: Kemi M. Doll, Sarah Khor, Bridgette Hempstead, Julianna G. Alson, Liz Kellogg, Erika Wolff, David Flum, Scott Ramsey, Barbara Goff
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: A major contributor to the black-white mortality gap in endometrial cancer (EC) is late stage at diagnosis for black women, which may be driven by delays in diagnosis both prior to and after symptom disclosure. Methods: For phase 1, black women with EC were recruited through oncology clinics and a local cancer support group. In-depth interviews were conducted focused on experiences of menopause, postmenopausal bleeding (PMB), and symptom disclosure, and transcripts coded using directed content analysis. For phase 2, EC cases from 2001–2015 were identified in SEER-Medicare. Location, provider type, and dates of symptom report and diagnosis were defined by claims data. The diagnostic interval was then calculated and step-wise multivariate modeling used to determine factors associated with time to diagnosis. Results: Phase 1 included 11 black women from 4 states (WA, LA, GA, CA), ages 47–70, stages 1––3 at diagnosis, for a total of 147 pages of transcribed interviews. Most were insured, with access to routine medical care. Common themes were a lack of knowledge of normal vs abnormal menopausal symptoms and silencing about bleeding among friends and family. The predominant interpretation of PMB was a resumption of normal menstruation, leading to significant delay in symptom disclosure. Reporting to an MD was largely driven by increased severity of bleeding or the onset of pain. Phase 2 included 3,363 EC cases, with 293 (8%) black women. The median diagnostic interval was 28 days (IQR: 8–110 days). After adjusting for age, region, gynecologic history and other presenting symptoms, provider differences were noted with shorter time for ER MDs (84%; P &lt;.01) and PCPs (16%; P =.05) vs OBGYN. Characterization of bleeding as ‘abnormal’ rather than ‘postmenopausal’ prolonged time to diagnosis by 60% ( P &lt;.001). Black race was associated with a 2.4-fold increased diagnostic time interval ( P =.017). Step-wise modeling showed that this association was explained by differences in diagnostic work-up: Compared to those with a biopsy within 7 days of presentation, women who had an ultrasound or no procedures had longer intervals (42% and 99%, respectively) to diagnosis ( P &lt;.001 for all). Conclusion: Among black women with access to medical care, there are modifiable factors that contribute to delays in diagnosis of EC both prior to and after symptom disclosure to a physician. This is the first study to identify targets for intervention to reduce the mortality rate in this high-risk group.
Cross talk between neutrophils and the microbiota
Authors: Dachuan Zhang, Paul S. Frenette
Journal: Blood (2019)

The microbiota has emerged as an important regulator of the host immunity by the induction, functional modulation, or suppression of local and systemic immune responses. In return, the host immune system restricts translocation and fine tunes the composition and distribution of the microbiota to maintain a beneficial symbiosis. This paradigm applies to neutrophils, a critical component of the innate immunity, allowing their production and function to be influenced by microbial components and metabolites derived from the microbiota, and engaging them in the process of microbiota containment and regulation. The cross talk between neutrophils and the microbiota adjusts the magnitude of neutrophil-mediated inflammation on challenge while preventing neutrophil responses against commensals under steady state. Here, we review the major molecular and cellular mediators of the interactions between neutrophils and the microbiota and discuss their interplay and contribution in chronic inflammatory diseases and cancer.
Corrigendum to “Comparison of different techniques for prostate biopsy: Systematic versus cognitive versus software fusion” [Eur Urol Suppl 2018;17(12);e2637]
Authors: M. Mokrzyś, A. Lewicki, M. Zagrodzka, M. Pyzlak, J. Ostrowska, K. Sklinda, J. Dobruch
Journal: European Urology (2019)
Picosecond Infrared Laser Desorption Mass Spectrometry Identifies Medulloblastoma Subgroups on Intrasurgical Timescales
Authors: Michael Woolman, Claudia M. Kuzan-Fischer, Isabelle Ferry, Taira Kiyota, Betty Luu, Megan Wu, David G. Munoz, Sunit Das, Ahmed Aman, Michael D. Taylor, James T. Rutka, Howard J. Ginsberg, Arash Zarrine-Afsar
Journal: Cancer Research (2019)

Abstract Medulloblastoma (MB) is a pediatric malignant brain tumor composed of four different subgroups (WNT, SHH, Group 3, Group 4), each of which are a unique biological entity with distinct clinico-pathological, molecular, and prognostic characteristics. Although risk stratification of patients with MB based on molecular features may offer personalized therapies, conventional subgroup identification methods take too long and are unable to deliver subgroup information intraoperatively. This limitation prevents subgroup-specific adjustment of the extent or the aggressiveness of the tumor resection by the neurosurgeon. In this study, we investigated the potential of rapid tumor characterization with Picosecond infrared laser desorption mass spectrometry (PIRL-MS) for MB subgroup classification based on small molecule signatures. One hundred and thirteen ex vivo MB tumors from a local tissue bank were subjected to 10- to 15-second PIRL-MS data collection and principal component analysis with linear discriminant analysis (PCA-LDA). The MB subgroup model was established from 72 independent tumors; the remaining 41 de-identified unknown tumors were subjected to multiple, 10-second PIRL-MS samplings and real-time PCA-LDA analysis using the above model. The resultant 124 PIRL-MS spectra from each sampling event, after the application of a 95% PCA-LDA prediction probability threshold, yielded a 98.9% correct classification rate. Post-ablation histopathologic analysis suggested that intratumoral heterogeneity or sample damage prior to PIRL-MS sampling at the site of laser ablation was able to explain failed classifications. Therefore, upon translation, 10-seconds of PIRL-MS sampling is sufficient to allow personalized, subgroup-specific treatment of MB during surgery. Significance: This study demonstrates that laser-extracted lipids allow immediate grading of medulloblastoma tumors into prognostically important subgroups in 10 seconds, providing medulloblastoma pathology in an actionable manner during surgery.