tbuckley/cabot-search huggingface dataset:
The Pleural Effusion And Symptom Evaluation (PLEASE) study of breathlessness in patients with a symptomatic pleural effusion
Authors: Sanjeevan Muruganandan, Maree Azzopardi, Rajesh Thomas, Deirdre B. Fitzgerald, Yi Jin Kuok, Hui Min Cheah, Catherine A. Read, Charley A. Budgeon, Peter R. Eastwood, Susan Jenkins, Bhajan Singh, Kevin Murray, Y.C. Gary Lee
Journal: European Respiratory Journal (2020)

Pathophysiology changes associated with pleural effusion, its drainage and factors governing symptom response are poorly understood. Our objective was to determine: 1) the effect of pleural effusion (and its drainage) on cardiorespiratory, functional and diaphragmatic parameters; and 2) the proportion as well as characteristics of patients with breathlessness relief post-drainage.Prospectively enrolled patients with symptomatic pleural effusions were assessed at both pre-therapeutic drainage and at 24-36 h post-therapeutic drainage.145 participants completed pre-drainage and post-drainage tests; 93% had effusions ≥25% of hemithorax. The median volume drained was 1.68 L. Breathlessness scores improved post-drainage (mean visual analogue scale (VAS) score by 28.0±24 mm; dyspnoea-12 (D12) score by 10.5±8.8; resting Borg score before 6-min walk test (6-MWT) by 0.6±1.7; all p<0.0001). The 6-min walk distance (6-MWD) increased by 29.7±73.5 m, p<0.0001. Improvements in vital signs and spirometry were modest (forced expiratory volume in 1 s (FEV1) by 0.22 L, 95% CI 0.18-0.27; forced vital capacity (FVC) by 0.30 L, 95% CI 0.24-0.37). The ipsilateral hemi-diaphragm was flattened/everted in 50% of participants pre-drainage and 48% of participants exhibited paradoxical or no diaphragmatic movement. Post-drainage, hemi-diaphragm shape and movement were normal in 94% and 73% of participants, respectively. Drainage provided meaningful breathlessness relief (VAS score improved ≥14 mm) in 73% of participants irrespective of whether the lung expanded (mean difference 0.14, 95% CI 10.02-0.29; p=0.13). Multivariate analyses found that breathlessness relief was associated with significant breathlessness pre-drainage (odds ratio (OR) 5.83 per standard deviation (sd) decrease), baseline abnormal/paralyzed/paradoxical diaphragm movement (OR 4.37), benign aetiology (OR 3.39), higher pleural pH (OR per sd increase 1.92) and higher serum albumin level (OR per sd increase 1.73).Breathlessness and exercise tolerance improved in most patients with only a small mean improvement in spirometry and no change in oxygenation. Breathlessness improvement was similar in participants with and without trapped lung. Abnormal hemi-diaphragm shape and movement were independently associated with relief of breathlessness post-drainage.
Optimal dose for acetylsalicylic acid provocation test for an accurate diagnosis of nonsteroidal anti-inflammatory drugs hypersensitivity
Authors: Natalia Perez-Sanchez, Francisca Gomez Perez, Raquel Jurado Escobar, Maria Auxiliadora Guerrero, Jose Cornejo-Garcia, Cristobalina Mayorga, Maria Torres Jaen, Inmaculada Doña
Journal: Journal of Allergy and Clinical Immunology (2020)
Reciprocal Regulation Between Forkhead Box M1/NF‐κB and Methionine Adenosyltransferase 1A Drives Liver Cancer
Authors: Yuan Li, Liqing Lu, Jian Tu, Jing Zhang, Ting Xiong, Wei Fan, Jiaohong Wang, Meng Li, Yibu Chen, Justin Steggerda, Hui Peng, Yongheng Chen, Tony W.H. Li, Zhi‐Gang Zhou, José M. Mato, Ekihiro Seki, Ting Liu, Heping Yang, Shelly C. Lu
Journal: Hepatology (2020)

Background and Aims Forkhead box M1 (FOXM1) and nuclear factor kappa B (NF‐ĸB) are oncogenic drivers in liver cancer that positively regulate each other. We showed that methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor in the liver and inhibits NF‐ĸB activity. Here, we examined the interplay between FOXM1/NF‐κB and MAT1A in liver cancer. Approach and Results We examined gene and protein expression, effects on promoter activities and binding of proteins to promoter regions, as well as effects of FOXM1 inhibitors T0901317 (T0) and forkhead domain inhibitory‐6 (FDI‐6) in vitro and in xenograft and syngeneic models of liver cancer. We found, in both hepatocellular carcinoma and cholangiocarcinoma, that an induction in FOXM1 and NF‐κB expression is accompanied by a fall in MATα1 (protein encoded by MAT1A). The Cancer Genome Atlas data set confirmed the inverse correlation between FOXM1 and MAT1A. Interestingly, FOXM1 directly interacts with MATα1 and they negatively regulate each other. In contrast, FOXM1 positively regulates p50 and p65 expression through MATα1, given that the effect is lost in its absence. FOXM1, MATα1, and NF‐κB all bind to the FOX binding sites in the FOXM1 and MAT1A promoters. However, binding of FOXM1 and NF‐κB repressed MAT1A promoter activity, but activated the FOXM1 promoter. In contrast, binding of MATα1 repressed the FOXM1 promoter. MATα1 also binds and represses the NF‐κB element in the presence of p65 or p50. Inhibiting FOXM1 with either T0 or FDI‐6 inhibited liver cancer cell growth in vitro and in vivo . However, inhibiting FOXM1 had minimal effects in liver cancer cells that do not express MAT1A. Conclusions We have found a crosstalk between FOXM1/NF‐κB and MAT1A. Up‐regulation in FOXM1 lowers MAT1A, but raises NF‐κB, expression, and this is a feed‐forward loop that enhances tumorigenesis.
Abstract 13360: A Network Meta-Analysis on the Comparative Efficacy of Nutraceuticals on Lipid Profile
Authors: Jakub Morze, Tadeusz Osadnik, Kamila Osadnik, Mateusz Lejawa, Grzegorz Jakubiak, Natalia Pawlas, Mariusz Gasior, Lukas Schwingschackl, Maciej Banach
Journal: Circulation (2019)

Introduction: Despite a large number of meta-analyses confirming the lipid-lowering effect of several nutraceuticals little is known about their comparative efficacy. The aim of this meta-analysis ...
Abstract 16311: The Role of Echocardiography in Patients With Syncope: A Single-Center Experience
Authors: Ali Raza Ghani, Hafez Mohammad Abdullah, Usman Sarwar, Muhammad Arslan Cheema, Waqas Ullah, Shujaul Haq, Asoka Balaratna
Journal: Circulation (2019)

Introduction: Syncope is a symptom complex comprising of a brief loss of consciousness associated with an inability to maintain postural tone, leading to a transient decrease in cerebral blood flow...
Clinical Characteristics of Coronavirus Disease 2019 in China
Authors: Wei-Jie Guan, Zheng-Yi Ni, Yu Hu, Wen-Hua Liang, Chun-Quan Ou, Jian-Xing He, Lei Liu, Hong Shan, Chun-Liang Lei, David S C Hui, Bin Du, Lan-Juan Li, Guang Zeng, Kwok-Yung Yuen, Ru-Chong Chen, Chun-Li Tang, Tao Wang, Ping-Yan Chen, Jie Xiang, Shi-Yue Li, Jin-Lin Wang, Zi-Jing Liang, Yi-Xiang Peng, Li Wei, Yong Liu, Ya-Hua Hu, Peng Peng, Jian-Ming Wang, Ji-Yang Liu, Zhong Chen, Gang Li, Zhi-Jian Zheng, Shao-Qin Qiu, Jie Luo, Chang-Jiang Ye, Shao-Yong Zhu, Nan-Shan Zhong
Journal: New England Journal of Medicine (2020)

BackgroundSince December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.MethodsWe extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.ResultsThe median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.ConclusionsDuring the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.) Quick Take Clinical Characteristics of Covid-19 2m 8s
Novel risk scoring system for metastatic renal cell carcinoma (mRCC) patients (pts) treated with cabozantinib (C).
Authors: Meredith R Kline, Dylan J. Martini, Yuan Liu, Julie M. Shabto, Bradley Curtis Carthon, Elise Hitron, Greta Russler, Sarah Caulfield, Lauren Beth Yantorni, Wayne Harris, Omer Kucuk, Viraj A. Master, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2020)

734 Background: Cabozantinib (C) is an effective treatment for metastatic renal cell carcinoma (mRCC) patients (pts). The international mRCC database consortium (IMDC) criteria is the gold standard for mRCC risk stratification. We created a risk scoring system for mRCC pts treated with C. Methods: We performed a retrospective review of 87 mRCC pts treated with C at Winship Cancer Institute from 2015-19. Overall survival (OS) and progression free survival (PFS) were defined as months from C initiation. The baseline characteristics and inflammation biomarkers included were monocyte, neutrophil, and platelet-to-lymphocyte ratios (MLR, NLR, and PLR respectively), RCC histology, body mass index (BMI), metastatic sites (mets), and Eastern Cooperative Oncology Group performance status (ECOG PS). Upon variable selection in multivariable analysis (MVA), elevated baseline MLR (≥0.71), presence of sarcomatoid histology, ECOG PS &gt; 1, and absence of bone metastases were assigned 1 point. A three-level risk scoring system was created: low (score = 0-1), intermediate (score = 2), and high risk (score = 3-4). The Kaplan-Meier method, Cox proportional hazard model, and Uno’s C-statistics were used to examine performance. Results: The majority of pts were males (71%) with clear-cell RCC (75%). Most pts (67%) received 1+ prior line of therapy. High and intermediate risk pts had significantly shorter OS and PFS compared to low risk pts (Table). The C-statistics for our risk scoring system were higher than IMDC in predicting OS (0.7 vs. 0.62) and PFS (0.65 vs 0.57). Conclusions: Pts treated with C may benefit from risk scoring using RCC histology, ECOG PS, mets, and MLR. These results are hypothesis-generating and should be validated in a larger study.[Table: see text]
Social Determinants and Differences in Mortality by Race/Ethnicity
Authors: Eliseo J. Pérez-Stable, Erik J. Rodriquez
Journal: JAMA Network Open (2020)

Susan Spillane, PhD; Meredith S. Shiels, PhD; Ana F. Best, PhD; Emily A. Haozous, PhD; Diana R. Withrow, PhD; Yingxi Chen, PhD; Amy Berrington de González, DPhil; Neal D. Freedman, PhD
A methodological comparison of mapping algorithms to obtain health utilities derived using cross-sectional and longitudinal data: Secondary analysis of NRG/RTOG 0415.
Authors: Rahul Ramesh Khairnar, Lyudmila DeMora, Howard M. Sandler, W. Robert Lee, Ester Villalonga Olives, C. Daniel Mullins, Deborah Bruner, Amit Shah, Shawn Malone, Jeff Michalski, Ian Dayes, Samantha A. Seaward, Michele Albert, Adam D. Currey, Thomas Michael Pisansky, Yuhchyau Chen, Eric M. Horwitz, Albert S. DeNittis, Felix Y Feng, Mark V. Mishra
Journal: Journal of Clinical Oncology (2020)

55 Background: To compare the predictive ability of health utility mapping algorithms derived using cross-sectional and longitudinal data specific to the Expanded Prostate Cancer Index Composite (EPIC). Methods: This mapping study utilized data from an international, multicenter, randomized controlled trial of patients with low-risk prostate cancer conducted by NRG Oncology (NCT00331773). Health-related quality-of-life (HRQoL) data were collected using EPIC, and health utilities were obtained using EuroQOL-5D (EQ5D) at baseline and 6, 12 and 24 months post-intervention. Data were split into an estimation sample (70%) and a validation sample (30%). Ordinary Least Squares (OLS) regression models were estimated using baseline cross-sectional data as well as pooled data from all assessment periods. Random effects (RE) specifications that explicitly model the longitudinal nature of the data were also estimated. Candidate models were selected based on root mean square error (RMSE). Results: A total of 196 (147) patients in the estimation sample had complete EQ5D and EPIC domain (subdomain) data at all time points. OLS models using combined data outperformed the counter-part RE models as well as OLS models using baseline data in the five-fold cross-validation. Addition of covariates to the models resulted in improved predictive ability. In the external validation, when only EPIC domain/ subdomain data are available, the OLS model using combined data predicted EQ5D utilities better than the counterpart RE model and OLS model using baseline data (RMSE=0.121108 &amp; 0.111345). OLS model using baseline data outperformed other model types for algorithms with EPIC domains and demographics (RMSE=0.121757), while RE models outperformed the other two model types for algorithms with EPIC subdomains and demographic data, (0.112782) and for algorithms with EPIC domains/ subdomains, demographics, and clinical covariates (RMSE=0.123589 &amp; 0.163093). Conclusions: While algorithms using pooled data outperformed other model types in internal validation, RE models showed better predictive ability in external validation for algorithms with covariates. Clinical trial information: NCT00331773.
Erratum: Corrigendum: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity
Authors: Mylène M Maury, Yu-Huan Tsai, Caroline Charlier, Marie Touchon, Viviane Chenal-Francisque, Alexandre Leclercq, Alexis Criscuolo, Charlotte Gaultier, Sophie Roussel, Anne Brisabois, Olivier Disson, Eduardo P C Rocha, Sylvain Brisse, Marc Lecuit
Journal: Nature Genetics (2017)
Daratumumab for systemic AL amyloidosis: prognostic factors and adverse outcome with nephrotic-range albuminuria
Authors: Christoph R. Kimmich, Tobias Terzer, Axel Benner, Tobias Dittrich, Kaya Veelken, Alexander Carpinteiro, Timon Hansen, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose, Anna Jauch, Stefan Wörner, Jörg Beimler, Carsten Müller-Tidow, Ute Hegenbart, Stefan O. Schönland
Journal: Blood (2020)
Improving data accessibility: New strategies towards implementation of a genomic data portal.
Authors: Christopher McNair, Karen E. Knudsen
Journal: Journal of Clinical Oncology (2020)

159 Background: It is now standard practice to utilize genomic profiling as a mechanism to navigate cancer patients to more effective therapies and clinical trials. Despite routine use, there is no single solution to perform these tests at most institutions, neither in-house nor external. As such, a myriad of options continue to be utilized for molecular diagnostic purposes. Significantly, lack of standardization in testing results in difficulty developing consistent mechanisms for ingesting, organizing, and accessing the data resulting from these tests. Ultimately, the result is a substantial gap in the types of studies researchers are able to perform simply due to lack of data accessibility. Methods: Typical workflows for genomic profiling do not involve a data repository such as the EMR or data warehouse for reasons including: lack of EMR ability to store genomic data, no processes for genomic profiling results to be integrated. The SKCC Cancer Informatics team at Jefferson has utilized the open source cBioPortal platform as a means of organizing, visualizing, and increasing overall access to Jefferson patient-specific genomic data at SKCC, termed the Genomic Data Portal (GDP). Results: We have developed processes for ingesting and transforming test results from multiple sources including in-house and external vendors. Once ingested, results are integrated with patient-specific clinical information from the EMR and tumor registry in order to increase the power of the data. The GDP currently houses over 1200 samples, including over 80 samples from advanced prostate cancer patients, with these numbers growing as more patients receive testing. Genomic results for each patient include gene mutation, fusion, and CNV, in addition to TMB and MSI. Clinical information drawn from the EMR and tumor registry includes demographics, overall survival, as well as disease specific information such as Gleason Score. Conclusions: The GDP has shown utility for multiple purposes including translational research studies and clinical trial feasibility and design. Importantly, this workflow can be adopted by institutions with varying technical expertise and resources, further enabling the research community.
A multicenter phase II study of avelumab in patients with locally advanced or metastatic penile cancer (PC) who are unfit for, or have progressed on or after platinum-based chemotherapy: (ALPACA).
Authors: Husam Alqaisi, Eric Winquist, Som Mukherjee, Christina M. Canil, Nazanin Fallah-Rad, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2020)

TPS7 Background: Squamous cell carcinoma of the penis is a rare and highly aggressive malignancy. Combination platinum-based chemotherapy is the standard of care in the metastatic setting. However, it is poorly tolerated and outcomes are dismal, underscoring an urgent unmet need for novel strategies. Since, penile cancers are often HPV-mediated and frequently overexpress PDL1, there is strong rationale to test the PDL1 inhibitor Avelumab, which is a well-tolerated drug in the setting of metastatic PC. Methods: This is a multicenter, single arm, phase 2 study of Avelumab (10mg/kg IV every 2 weeks) in patients with locally advanced or metastatic PC unfit for or progressed on platinum-based chemotherapy. A Simon’s two-stage design will be used where 9 patients will be enrolled in stage 1. If there is at least 1 response defined by iRECIST (complete response [iCR], partial response [iPR], or stable disease [iSD]) the study will proceed to stage 2, where an additional 15 patients will be enrolled. The primary objective is to demonstrate the anti-tumor activity of avelumab by objective response rate (ORR) according to (iRECIST). Secondary endpoints include: PFS, OS in patients determined to have PD-L1 positive tumors (including infiltrating immune cells) by the GMP verified Dako PD-L1 IHC 22C3 pharmDx test with thresholds of &lt;1%, 1-49%, and ≥ 50% to define PD-L1 positivity, and in all enrolled patients. Secondary objectives also include assessing pathologic complete response rate (pCR) for patients undergoing surgery in the treatment time course, evaluation of safety and immunogenicity profile of Avelumab. The study is now open and actively accruing with further centres opening imminently. Funding Source: Pfizer. Clinical trial information: 03391479.
Prognostic value of immune gene’s expression in head and neck squamous cell carcinoma patients
Authors: C. Lecerf, M. Kamal, S. Vacher, W. Chemlali, C. Dubot, E. Jeannot, J. Klijanienko, C. Hoffmann, I. Bieche, C. Le Tourneau
Journal: Annals of Oncology (2018)

Background: Nivolumab and pembrolizumab that target the PD-1 immune check point have recently been approved in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients who have failed platinum therapy. We aimed to evaluate the prognostic value of selected immune genes' expression in a retrospective analysis of 96 untreated HNSCC patients. Methods: We retrieved 96 HNSCC patients who underwent primary surgery at Institut Curie between 1990 and 2006. Real-time quantitative RT-PCR was used to analyze a panel of 46 genes classified in immunity genes and tissue specific genes. Univariate and multivariate analyses were performed to assess the prognostic value of overexpressed genes. This study was approved by the internal review board of Institut Curie. Results: Median age was 56 years [range: 35–78]. 80% of patients were men with a history of alcohol (70%) and/or tobacco consumption (73%). Twelve patients (12%) were HPV-positive. Primary tumor location was oral cavity (45%), oropharynx (21%), larynx (18%), and hypopharynx (17%). Patients had stage I, II, III, and IVa in 10%, 16%, 13%, and 61%, respectively. Median disease-free interval was 23 months [range: 0.7-185]. Most significantly overexpressed genes were OX40L (74%), TNFRSF9 (77%), and TNFRSF18 (74%) immunity genes, and CD80 (80%) and FOXP3 (62%) tissue specific genes. Median disease-free interval was 11 months in high OX40L mRNA level HNSCC patients versus 23 months in low OX40L mRNA level HNSCC patients (p = 0.0009). Conclusions: OX40L overexpression was associated with a poor outcome in HNSCC patients treated with primary surgery. Legal entity responsible for the study: Institut Curie. Funding: Fondation ARC pour la recherche sur le cancer ICGEx. Disclosure: All authors have declared no conflicts of interest.
Insights Into the Origin of Intrahepatic Cholangiocarcinoma From Mouse Models
Authors: Yan Zhu, Lawrence N. Kwong
Journal: Hepatology (2020)

1Department of Translational Molecular PathologyThe University of Texas MD Anderson Cancer CenterHoustonTX *Address Correspondence and Reprint Requests to: Lawrence N. Kwong, Ph.D. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center 1515 University Boulevard Unit 2951 Houston, TX 77030 E‐mail: [email protected] Tel.: +1‐713‐792‐6811
Type, timing, and risk factors associated with immune-related adverse event development in patients with advanced genitourinary cancers treated with immune checkpoint inhibitor.
Authors: Qian Qin, Vaibhav G. Patel, George Mellgard, Anish B. Parikh, Bo Wang, Parissa Alerasool, Philip Garcia, Suraj Jaladanki, Amanda Leiter, Emily Carroll, Danielle Brooks, Jennifer Ben Shimol, Elliot Eisenberg, Emily J. Gallagher, Matt D. Galsky, William K. Oh, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

480 Background: Immune related adverse events (IRAEs) with immune checkpoint inhibitor (ICI) therapy are well recognized, but predictors for IRAEs are not well defined. We aim to characterize the type, timing, and clinical risk factors associated with (w/) IRAEs in ICI-treated, advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC) patients (pts). Methods: We retrospectively reviewed charts of pts w/ advanced UC and RCC who received at least 2 ICI doses at our institution from 1/1/10 to 10/31/18. Patient baseline characteristics, treatment course, and clinical outcomes were collected. IRAEs were identified and graded (GR) based on CTCAE (v.4.0). Fisher’s exact test was used to study the differences between pts w/ versus without IRAE. Results: Of the 71 pts identified (UC n = 53; RCC n = 18), 27 pts (38%) developed IRAEs with 42 total events (38% GR1, 60% GR2, and 2% GR≥3) [table]. The majority of pts with dermatitis (70%) also developed a secondary, systemic IRAE(s). Systemic steroid (SS) was required in 17 events. The median time to any IRAE was 17.5 weeks (w, range 1-93). ECOG ≤ 1 predicted IRAE development (p &lt; 0.05). No other characteristics (demographics, co-morbidities, metastatic sites, ICI type, line of therapy, and duration of ICI &gt; 12w) were associated with IRAE. Conclusions: In our study, good function status is associated with the development of IRAE. Time to IRAE ranged from immediately to 93w after initiating ICI. Clinical validation with additional datasets will be needed to confirm these findings. [Table: see text]
The RNA-Binding Protein RBM3 Negatively Regulates Group 2 Innate Lymphoid Cells (ILC2s) and Lung Eosinophilia
Authors: Jana Badrani, Michael Amadeo, Kellen Cavagnero, Luay Naji, Sean Lund, Rachel Baum, Naseem Khorram, Julie Pilotte, Peter Vanderklish, Taylor Doherty
Journal: Journal of Allergy and Clinical Immunology (2020)