tbuckley/cabot-search huggingface dataset:
Empagliflozin in Patients With Heart Failure, Reduced Ejection Fraction, and Volume Overload
Authors: Milton Packer, Stefan D. Anker, Javed Butler, Gerasimos Filippatos, Joao Pedro Ferreira, Stuart J. Pocock, Naveed Sattar, Martina Brueckmann, Waheed Jamal, Daniel Cotton, Tomoko Iwata, Faiez Zannad
Journal: Journal of the American College of Cardiology (2021)

Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention. This study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload. This double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Approximately 40% of the patients had volume overload in the 4 weeks before study enrollment. Patients with recent volume overload were more likely to have been hospitalized for heart failure and to have received an intravenous diuretic agent in an outpatient setting in the previous 12 months, and to experience a heart failure event following randomization, even though they were more likely to be treated with high doses of a loop diuretic agent as an outpatient (all p < 0.001). When compared with placebo, empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure, decreased total hospitalizations for heart failure, and improved health status and functional class. Yet despite the predisposition of patients with recent volume overload to fluid retention, the magnitude of these benefits (even after 1 month of treatment) was not more marked in patients with recent volume overload (interaction p values > 0.05). Changes in body weight, hematocrit, and natriuretic peptides (each potentially indicative of a diuretic action of SGLT2 inhibitors) did not track each other closely in their time course or in individual patients. Taken together, study findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)
Abstract 14120: Impact of Incidental Non-Coronary Artery Calcification in Cardiovascular System on Prognosis in Patients With Acute Coronary Syndrome
Authors: Yukio Mizuguchi, Sho Hashimoto, Takeshi Yamada, Norimasa Taniguchi, Tetsuya Hata, Shunsuke Nakajima, Akihiko Takahashi
Journal: Circulation (2017)

Introduction: The presence of severe calcium deposits in the coronary artery is known to carry poor prognosis in patients after percutaneous coronary intervention. However, the clinical significanc...
Camrelizumab Combined with Chemotherapy Followed by Camrelizumab plus Apatinib as First-line Therapy for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Authors: Zhi Peng, Jia Wei, Feng Wang, Jieer Ying, Yanhong Deng, Kangsheng Gu, Ying Cheng, Xianglin Yuan, Juxiang Xiao, Yanfei Tai, Linna Wang, Jianjun Zou, Yanqiao Zhang, Lin Shen
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for unresectable, advanced, or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Camrelizumab shows promising antitumor activity in advanced or metastatic G/GEJ adenocarcinoma in a phase I study. We reported the outcomes of cohort 1 in a multicenter, open-label, phase II trial, which assessed camrelizumab in combination with CAPOX followed by camrelizumab plus apatinib as a first-line combination regimen for advanced or metastatic G/GEJ adenocarcinoma. Patients and Methods: Systemic treatment-naïve patients with EGFR2-negative advanced or metastatic G/GEJ adenocarcinoma received initial camrelizumab plus CAPOX for 4–6 cycles, and patients without progressive disease were administrated subsequent camrelizumab plus apatinib. Primary endpoint was objective response rate (ORR). Results: All 48 enrolled patients comprised the efficacy and safety analysis population. The ORR was 58.3% [95% confidence interval (CI), 43.2–72.4] with this combination regimen. Median duration of response was 5.7 months (95% CI, 4.4–8.3). Median overall survival was 14.9 months (95% CI, 13.0–18.6), and median progression-free survival was 6.8 months (95% CI, 5.6–9.5), respectively. The most common grade ≥3 treatment-related adverse events (&amp;gt;10%) were decreased platelet count (20.8%), decreased neutrophil count (18.8%), and hypertension (14.6%). Treatment-related death occurred in 1 patient (2.1%) due to abnormal hepatic function and interstitial lung disease. Conclusions: Camrelizumab combined with CAPOX followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as first-line therapy for patients with advanced or metastatic G/GEJ adenocarcinoma.
Endoscopic transgastric cholecystectomy during direct endoscopic necrosectomy for walled-off necrosis of the pancreas
Authors: Marcos Eduardo Lera dos Santos, Igor Braga Ribeiro, Igor Mendonça Proença, Gabriel Mayo Vieira de Souza, Diogo Turiani Hourneaux de Moura, Sergio Eiji Matuguma, Eduardo Guimarães Hourneaux de Moura
Journal: Endoscopy (2021)

Pancreatic fluid collections may occur as a result of acute pancreatitis, although many spontaneously resolve. However, a subset of patients with necrotizing pancreatitis may develop symptomatic well-defined necrotic collections, classified as walled-off necrosis (WON) [1] [2]
MA04.07 Comparative Clinical Outcomes for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations
Authors: N. Girard, L. Bazhenova, A. Minchom, S. Ou, S. Gadgeel, J. Trigo, S. Viteri, G. Li, P. Mahadevia, A. Londhe, D. Backenroth, T. Li, J.M. Bauml
Journal: Journal of Thoracic Oncology (2021)
FP05.04 Outcomes of Resected Thymic Epithelial Tumors (TET), insights from RYTHMIC
Authors: J.C. Benitez, M.E. Boucher, E. Dansin, M. Kerjouan, L. Bigay-Game, E. Pichon, F. Thillays, P.E. Falcoz, S. Lyubimova, Y. Oulkhouir, F. Calcagno, L. Thiberville, C. Clément-Duchêne, F. Morin, P. Missy, P.A. Thomas, J. Maury, T. Molina, N. Girard, B. Besse
Journal: Journal of Thoracic Oncology (2021)
FunHoP: Enhanced Visualization and Analysis of Functionally Homologous Proteins in Complex Metabolic Networks
Authors: Kjersti Rise, May-Britt Tessem, Finn Drabløs, Morten B. Rye
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Cytoscape is often used for visualization and analysis of metabolic pathways. For example, based on KEGG data, a reader for KEGG Markup Language (KGML) is used to load files into Cytoscape. However, although multiple genes can be responsible for the same reaction, the KGML-reader KEGGScape only presents the first listed gene in a network node for a given reaction. This can lead to incorrect interpretations of the pathways. Our new method, FunHoP, shows all possible genes in each node, making the pathways more complete. FunHoP collapses all genes in a node into one measurement using read counts from RNA-seq. Assuming that activity for an enzymatic reaction mainly depends upon the gene with the highest number of reads, and weighting the reads on gene length and ratio, a new expression value is calculated for the node as a whole. Differential expression at node level is then applied to the networks. Using prostate cancer as model, we integrate RNA-seq data from two patient cohorts with metabolism data from literature. Here we show that FunHoP gives more consistent pathways that are easier to interpret biologically. Code and documentation for running FunHoP can be found at https://github.com/kjerstirise/FunHoP.
Analysis and Validation of Human Targets and Treatments Using a Hepatocellular Carcinoma–Immune Humanized Mouse Model
Authors: Yue Zhao, Jiaxu Wang, Wai Nam Liu, Shin Yie Fong, Timothy Wai Ho Shuen, Min Liu, Sarah Harden, Sue Yee Tan, Jia Ying Cheng, Wilson Wei Sheng Tan, Jerry Kok Yen Chan, Cheng Ean Chee, Guan Huei Lee, Han Chong Toh, Seng Gee Lim, Yue Wan, Qingfeng Chen
Journal: Hepatology (2021)

Recent development of multiple treatments for human hepatocellular carcinoma (HCC) has allowed for the selection of combination therapy to enhance the effectiveness of monotherapy. Optimal selection of therapies is based on both HCC and its microenvironment. Therefore, it is critical to develop and validate preclinical animal models for testing clinical therapeutic solutions.We established cell line-based or patient-derived xenograft-based humanized-immune-system mouse models with subcutaneous and orthotopic HCC. Mice were injected with human-specific antibodies (Abs) to deplete human immune cells. We analyzed the transcription profiles of HCC cells and human immune cells by using real-time PCR and RNA sequencing. The protein level of HCC tumor cells/tissues or human immune cells was determined by using flow cytometry, western blotting, and immunohistochemistry. The HCC tumor size was measured after single, dual-combination, and triple-combination treatment using N-(1',2-Dihydroxy-1,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide (C188-9), bevacizumab, and pembrolizumab. In this study, human immune cells in the tumor microenvironment were strongly selected and modulated by HCC, which promoted the activation of the IL-6/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in tumor cells and led to augmented HCC proliferation and angiogenesis by releasing angiogenic cytokines in humanized-immune-system mice with HCC. In particular, intratumor human cluster of differentiation-positive (hCD14+ ) cells could produce IL-33 through damage-associated molecular pattern/Toll-like receptor 4/activator protein 1, which up-regulated IL-6 in other intratumor immune cells and activated the JAK2/STAT3 pathway in HCC. Specific knockdown of the CD14 gene in human monocytes could impair IL-33 production induced by cell lysates. Subsequently, we evaluated the in vivo anti-HCC effect of C188-9, bevacizumab, and pembrolizumab. The results showed that the anti-HCC effect of triple-combination therapy was superior to that of single or dual treatments.Humanized-immune-system HCC mouse models are suitable for identifying targets from cancer and immune components and for testing combinational therapies.
P50.04 Real-World Survival Outcomes with Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Tumors of Lung
Authors: E. Dudnik, S. Kareff, M. Moskovitz, A. Lobachov, C. Kim, S. Liu, S. Sherman, D. Urban, A. Zer, O. Rotem, M. Wollner, J. Bar
Journal: Journal of Thoracic Oncology (2021)
A Survey on Mathematical, Machine Learning and Deep Learning Models for COVID-19 Transmission and Diagnosis
Authors: Christopher Clement John, VijayaKumar Ponnusamy, Sriharipriya Krishnan Chandrasekaran, Nandakumar R
Journal: IEEE Reviews in Biomedical Engineering (2021)

COVID-19 is a life threatening disease which has a enormous global impact. As the cause of the disease is a novel coronavirus whose gene information is unknown, drugs and vaccines are yet to be found. For the present situation, disease spread analysis and prediction with the help of mathematical and data driven model will be of great help to initiate prevention and control action, namely lockdown and qurantine. There are various mathematical and machine-learning models proposed for analyzing the spread and prediction. Each model has its own limitations and advantages for a particluar scenario. This article reviews the state-of-the art mathematical models for COVID-19, including compartment models, statistical models and machine learning models to provide more insight, so that an appropriate model can be well adopted for the disease spread analysis. Furthermore, accurate diagnose of COVID-19 is another essential process to identify the infected person and control further spreading. As the spreading is fast, there is a need for quick auotomated diagnosis mechanism to handle large population. Deep-learning and machine-learning based diagnostic mechanism will be more appropriate for this purpose. In this aspect, a comprehensive review on the deep learning models for the diagnosis of the disease is also provided in this article.
Breathe—Your immune system is counting on it
Authors: Nael A. McCarty
Journal: The Journal of Experimental Medicine (2021)

Always, but especially in these times of COVID pandemic, we know the dangers of breathing into our lungs a deadly pathogen. Fortunately, healthy lungs are equipped with an innate immune system that works to clear those pathogens. A study in this issue (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201831) shows, for the first time, that breathing-induced changes in the pH of the airway surface contribute to bacterial killing, pointing to new therapeutic strategies for maintaining pulmonary health.
P76.23 A Retrospective Study of Non-Small Cell Lung Cancer Treated with Second- and Third-Generation EGFR Tyrosine Kinase Inhibitors
Authors: S. Mitsuya, K. Tsuruoka, K. Kanaoka, T. Funamoto, H. Tsuji, N. Matsunaga, T. Nakamura, Y. Tamura, M. Imanishi, S. Ikeda, Y. Fujisaka, I. Goto
Journal: Journal of Thoracic Oncology (2021)
IgE‐cross‐blocking antibodies to <i>Fagales</i> following sublingual immunotherapy with recombinant Bet v 1
Authors: João Rodrigues Grilo, Claudia Kitzmüller, Lorenz Aglas, Gabriela Sánchez Acosta, Ute Vollmann, Christof Ebner, Fritz Horak, Tamar Kinaciyan, Christian Radauer, Fatima Ferreira, Beatrice Jahn‐Schmid, Barbara Bohle
Journal: Allergy (2021)

Evidence has accumulated that birch pollen immunotherapy reduces rhinoconjunctivitis to pollen of birch homologous trees. Therapeutic efficacy has been associated with IgE-blocking IgG antibodies. We have recently shown that sera collected after 16 weeks of sublingual immunotherapy with recombinant Bet v 1 (rBet v 1-SLIT) display strong IgE-blocking bioactivity for Bet v 1. Here, we assessed whether rBet v 1-SLIT-induced IgG antibodies display cross-blocking activity to related allergens in Fagales pollen.IgE, IgG1 and IgG4 reactivity to recombinant Bet v 1, Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1 and Que a 1 were assessed in pre- and post-SLIT samples of 17 individuals by ELISA. A basophil inhibition assay using stripped basophils re-sensitized with a serum pool containing high Bet v 1-specific IgE levels was established and used to assess CD63 expression in response to allergens after incubation with pre-SLIT or post-SLIT samples. IgG1 and IgG4 were depleted from post-SLIT samples to assess its contribution to IgE-cross-blocking.Sublingual immunotherapy with recombinant Bet v 1 boosted cross-reactive IgE antibodies and induced IgG1 and IgG4 antibodies with inter- and intra-individually differing reactivity to the homologs. Highly variable cross-blocking activities of post-SLIT samples to the different allergens were found. IgG1 and IgG4 antibodies displayed cross-blocking activity with individual variance.Our mechanistic approach suggested that immunotherapy with the reference allergen Bet v 1 induces individual repertoires of cross-reactive IgG1 and IgG4 antibodies. The cross-blocking bioactivity of these antibodies was also highly variable and neither predictable from protein homology nor IgE-cross-reactivity.
MYC oncogene is associated with suppression of tumor immunity and targeting Myc induces tumor cell immunogenicity for therapeutic whole cell vaccination
Authors: Xiaofang Wu, Marie Nelson, Mousumi Basu, Priya Srinivasan, Christopher Lazarski, Peng Zhang, Pan Zheng, Anthony David Sandler
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background MYC oncogene is deregulated in 70% of all human cancers and is associated with multiple oncogenic functions including immunosuppression in the tumor microenvironment. The role of MYC in the immune microenvironment of neuroblastoma and melanoma is investigated and the effect of targeting Myc on immunogenicity of cancer cells is evaluated. Methods Immune cell infiltrates and immunogenic pathway signatures in the context of MYCN amplification were analyzed in human neuroblastoma tumors and in metastatic melanoma. Dose response and cell susceptibility to MYC inhibitors (I-BET726 and JQ1) were determined in mouse cell lines. The influence of downregulating Myc in tumor cells was characterized by immunogenic pathway signatures and functional assays. Myc-suppressed tumor cells were used as whole cell vaccines in preclinical neuroblastoma and melanoma models. Results Analysis of immune phenotype in human neuroblastoma and melanoma tumors revealed that MYCN or c-MYC amplified tumors respectively are associated with suppressed immune cell infiltrates and functional pathways. Targeting Myc in cancer cells with I-BET726 and JQ1 results in cell cycle arrest and induces cell immunogenicity. Combining vaccination of Myc-inhibited tumor cells with checkpoint inhibition induced robust antitumor immunity and resulted in therapeutic cancer vaccine therapy in mouse neuroblastoma tumors. Despite vigorous antitumor immunity in the mouse melanoma model, upregulation of immunosuppressive pathways enabled tumor escape. Conclusions This study demonstrates that the Myc oncogene is an appropriate target for inducing tumor cell immunogenicity and suggests that Myc-suppressed whole tumor cells combined with checkpoint therapy could be used for formulating a personalized therapeutic tumor vaccine.
Cytomegaloviral determinants of CD8 <sup>+</sup> T cell programming and RhCMV/SIV vaccine efficacy
Authors: Daniel Malouli, Scott G. Hansen, Meaghan H. Hancock, Colette M. Hughes, Julia C. Ford, Roxanne M. Gilbride, Abigail B. Ventura, David Morrow, Kurt T. Randall, Husam Taher, Luke S. Uebelhoer, Matthew R. McArdle, Courtney R. Papen, Renee Espinosa Trethewy, Kelli Oswald, Rebecca Shoemaker, Brian Berkemeier, William J. Bosche, Michael Hull, Justin M. Greene, Michael K. Axthelm, Jason Shao, Paul T. Edlefsen, Finn Grey, Jay A. Nelson, Jeffrey D. Lifson, Daniel Streblow, Jonah B. Sacha, Klaus Früh, Louis J. Picker
Journal: Science Immunology (2021)

Eight RhCMV gene products control induction of unconventionally restricted CD8 + T cells and RhCMV/SIV vaccine efficacy.
Single-cell transcriptomics dissects hematopoietic cell destruction and T-cell engagement in aplastic anemia
Authors: Caiying Zhu, Yu Lian, Chenchen Wang, Peng Wu, Xuan Li, Yan Gao, Sibin Fan, Lanlan Ai, Liwei Fang, Hong Pan, Tao Cheng, Jun Shi, Ping Zhu
Journal: Blood (2021)
Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial
Authors: A. Bardia, W.A. Messersmith, E.A. Kio, J.D. Berlin, L. Vahdat, G.A. Masters, R. Moroose, A.D. Santin, K. Kalinsky, V. Picozzi, J. O'Shaughnessy, J.E. Gray, T. Komiya, J.M. Lang, J.C. Chang, A. Starodub, D.M. Goldenberg, R.M. Sharkey, P. Maliakal, Q. Hong, W.A. Wegener, T. Goswami, A.J. Ocean
Journal: Annals of Oncology (2021)

Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously.Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer.In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR).SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.
P40.04 Knowledge, Attitudes and Perception of Lung Cancer Screening Among Smoking Soft-Ware Professionals in India
Authors: V.P.B. Koyyala, A. Jajodia, S. Pasricha, U. Batra, K. Domadia, A. Bp, S. Soni, S. Singla, S. Bothra, S. Joga, P. Medisetty, M. La Mantia, H. Prosch, A. Mehta
Journal: Journal of Thoracic Oncology (2021)
Comment on Samara et al. Metformin Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes: The Sydney Memory and Ageing Study. Diabetes Care 2020;43:2691–2701
Authors: Jorge Rafael Violante-Cumpa, Luis Alberto Pérez-Arredondo, José Gerardo González-González, Leonardo Guadalupe Mancillas-Adame
Journal: Diabetes Care (2021)

We have read with great interest the article published by Samaras et al. (1); the authors found an association of metformin use with slowed cognitive decline and lower risk of incident dementia in older adults with type 2 diabetes. In this work, the authors reported an impressive 81% risk reduction in the incidence of dementia between patients with diabetes and metformin (DM+MF) compared with the group with diabetes without metformin (DM-noMF).

We found some aspects of the study worth further discussion. First, there is high contrast …
QIM21-080: Patterns of Patient Portal Use in Patients With Cancer Who Utilized the Portal Frequently: Results From the UWCCC Survivorship Program
Authors: Hamid Emamekhoo, Rebecca P. Luoh, Thevaa Chandereng, Amye J. Tevaarwerk, Elena M. Smith, Cibele B. Carroll, Mary E. Sesto
Journal: Journal of the National Comprehensive Cancer Network (2021)

"QIM21-080: Patterns of Patient Portal Use in Patients With Cancer Who Utilized the Portal Frequently: Results From the UWCCC Survivorship Program" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Pediatric MDS and bone marrow failure-associated germline mutations in SAMD9 and SAMD9L impair multiple pathways in primary hematopoietic cells
Authors: Melvin E. Thomas, Sherif Abdelhamed, Ryan Hiltenbrand, Jason R. Schwartz, Sadie Miki Sakurada, Michael Walsh, Guangchun Song, Jing Ma, Shondra M. Pruett-Miller, Jeffery M. Klco
Journal: Leukemia (2021)
FP14.12 Quality of Life and Subgroup Analysis in a Phase 3 Randomized Study of Ensartinib vs Crizotinib in ALK–Positive NSCLC Patients: eXalt3.
Authors: G. Selvaggi, Y. Wu, Z. Wang, G. Wu, E. Poddubskaya, M. Reck, T. Mok, A. Chiappori, D.H. Lee, V. Breder, S. Orlov, I. Cicin, Y. Cheng, Y. Liu, Y. Fan, J. Zhou, C. Liang, L. Mao, L. Horn, H.A. Wakelee
Journal: Journal of Thoracic Oncology (2021)