tbuckley/cabot-search huggingface dataset:
Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study
Authors: Helene Moustgaard, Gemma L Clayton, Hayley E Jones, Isabelle Boutron, Lars Jørgensen, David R T Laursen, Mette F Olsen, Asger Paludan-Müller, Philippe Ravaud, Jelena Savović, Jonathan A C Sterne, Julian P T Higgins, Asbjørn Hróbjartsson
Journal: BMJ (2020)

Abstract Objectives To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study). Design Meta-epidemiological study. Data source Cochrane Database of Systematic Reviews (2013-14). Eligibility criteria for selecting studies Meta-analyses with both blinded and non-blinded trials on any topic. Review methods Blinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding. Results The study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses. Conclusion No evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.
Outcomes of Gamma Knife radiosurgery, bimodality, and trimodality treatment regimens for patients with one or multiple brain metastases: The Columbia University Medical Center experience.
Authors: Tony J. Wang, Shumaila Saad, Yasir H. Qureshi, Steven R. Isaacson, Michael B. Sisti, Jeffrey N. Bruce, Guy M. McKhann, Jeraldine L. Lesser, Simon Cheng, K.S. Clifford Chao, Andrew B. Lassman
Journal: Journal of Clinical Oncology (2014)

e13032 Background: To report our Gamma Knife Radiosurgery (GKRS) outcomes for brain metastases (BM) based on different treatment modalities and number of BM. Methods: We reviewed all patients treated with GKRS at a single institution for BM from 1998 to 2013. We evaluated outcome according to number of BM, treatment modalities, and other prognostic factors. Results: There were 541 patients (231 men) with median age 62 years (range, 21-94). Histology included 264 (48.8%) lung, 99 (18.4%) breast, 69 (12.8%) melanoma, 42 (7.8%) renal cell carcinoma, 28 (5.2%) gastrointestinal, and 39 (7.2%) other primary cancers. 206 (38.1%) patients received GKRS alone, 114 (21.1%) GKRS plus whole brain radiotherapy (WBRT), 108 (20.0%) underwent GKRS plus neurosurgical resection (NSG), and 113 (20.9%) all three modalities. The median overall survival (OS) correlated with RPA Class (16.3, 10.8, and 6.05 months for classes I, II, and III, respectively (p<0.001) and GPA score (8.9, 11.7, 10.3, and 17.3 months for scores 0-1, 1.5-2, 3, 3.5-4, respectively (p=.010)). For patients with one BM, the median OS for following GKRS alone, GKRS plus WBRT, GKRS plus NSG, and all three modalities were 8.2, 16.6, 18.7, and 22.7 months, respectively. For patients with multiple BM, the median OS for patients who received GKRS alone, GKRS plus WBRT, GKRS plus NSG, and all three modalities were 7.7, 14.8, 16.8, 19.8 months, respectively. On multivariate analysis, there was no difference in OS between GKRS plus WBRT, GKRS plus NSG, and trimodality; however, all three were superior to GKRS alone (p<0.05). One versus multiple BM was not significant for OS (HR:0.92 95% CI: 0.74-1.15; p=0.464). Primary controlled disease (HR: 2.026; 95%CI 1.603-2.560; p<0.05) and age at time of GKRS (HR: 1.019; 95%CI 1.011-1.028; p<0.001) were strong independent predictors of survival. Extracranial metastases, primary disease type, gender, race, and marital status were not significant predictors. Conclusions: Patients treated with GKRS plus NSG, GKRS plus WBRT, and trimodality had improved OS vs. GKRS alone. In our analysis, resection and GKRS allowed avoidance of WBRT without shortening survival.
B32 Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations
Authors: J.H. Starrett, A. Guernet, M.E. Cuomo, K. Poels, I.K. van Alderwerelt van Rosenburgh, A. Nagelberg, D. Farnsworth, K. Price, H. Khan, K.D. Ashtekar, M. Gaefele, D. Ayeni, T.F. Stewart, A. Kuhlmann, S.M. Kaech, A.M. Unni, R. Homer, W.W. Lockwood, F. Michor, S.B. Goldberg, M.A. Lemmon, P. Smith, D. Cross, K. Politi
Journal: Journal of Thoracic Oncology (2020)
Intense FAPI Uptake in Inflammation May Mask the Tumor Activity of Pancreatic Cancer in 68Ga-FAPI PET/CT
Authors: Yaping Luo, Qingqing Pan, Wen Zhang, Fang Li
Journal: Clinical Nuclear Medicine (2020)

Abstract Contrast CT revealed diffuse enlargement of the pancreas with a suspicious lesion in the uncinate process in a 57-year-old man who presented with jaundice. 18 F-FDG PET/CT showed increased radioactivity in the enlarged pancreas with a nodular lesion with even higher uptake in the uncinate process. To differentiate autoimmune pancreatitis and pancreatic cancer, 68 Ga-FAPI PET/CT was performed. It revealed intense 68 Ga-FAPI uptake in the pancreas, but the FDG-avid lesion in the uncinate process was not shown. The patient was finally diagnosed with pancreatic cancer with tumor-induced pancreatitis with endoscopic ultrasonography–guided biopsy.
Predictors of left ventricular remodelling in patients with dilated cardiomyopathy – a cardiovascular magnetic resonance study
Authors: Upasana Tayal, Ricardo Wage, Simon Newsome, Ramasamy Manivarmane, Cemil Izgi, Amal Muthumala, Jason N. Dungu, Ravi Assomull, Suzan Hatipoglu, Brian P. Halliday, Amrit S. Lota, James S. Ware, John Gregson, Michael Frenneaux, Stuart A. Cook, Dudley J. Pennell, Andrew D. Scott, John G.F. Cleland, Sanjay K. Prasad
Journal: European Journal of Heart Failure (2020)
Short-Term Hemodynamic and Electrophysiological Effects of Cardiac Resynchronization by Left Ventricular Septal Pacing
Authors: Floor C.W.M. Salden, Justin G.L.M. Luermans, Sjoerd W. Westra, Bob Weijs, Elien B. Engels, Luuk I.B. Heckman, Léon J.M. Lamerichs, Michel H.G. Janssen, Kristof J.H. Clerx, Richard Cornelussen, Subham Ghosh, Frits W. Prinzen, Kevin Vernooy
Journal: Journal of the American College of Cardiology (2020)
Abstract 11317: “High Risk” Features of Mitral Annular Calcification on Echocardiography Are Associated With Cerebral Infarction
Authors: Aaron A Smith, Joseph D Steffens, Alexander J Baxa, Jorge Reyes-Castro, Holly Rodin, Mengistu A Simegn, Richard W Asinger
Journal: Circulation (2019)

Introduction: Echocardiographic features of mitral annular calcification (MAC) have been associated with embolic stroke in previous studies and case reports as MAC is thought to be a source of embo...
Wildervanck症候群(頸-眼-聴覚症候群),眼瞼下垂小人症を有するバルサルバ洞の破裂した動脈瘤 症例報告 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: OE Kotaro, Mori Kiyoo, Konno Tetsuo, Yoneda Takashi, Ueyama Katsushi, Yamagishi Masakazu
Journal: Circulation (2007)
Breast Cancer Cell–Derived Soluble CD44 Promotes Tumor Progression by Triggering Macrophage IL1β Production
Authors: Jeong-Hoon Jang, Do-Hee Kim, Jae Min Lim, Joon Won Lee, Su Jin Jeong, Kwang Pyo Kim, Young-Joon Surh
Journal: Cancer Research (2020)

IL1β is a central regulator of systemic inflammatory response in breast cancer, but the precise regulatory mechanisms that dictate the overproduction of IL1β are largely unsolved. Here, we show that IL1β secretion is increased by the coculture of human monocyte-like cells and triple-negative breast cancer (TNBC) cells. In addition, macrophages robustly produced IL1β when exposed to the conditioned media of TNBC cells. Consistent with these observations, macrophage depletion decreased serum IL1β and reduced breast cancer progression in an orthotopic breast cancer mouse model. Profiling the secretome of human breast cancer cells revealed that the CD44 antigen was the most differentially released protein in basal conditions of TNBC cells. Antibody-mediated neutralization of CD44 abrogated IL1β production in macrophages and inhibited the growth of primary tumors. These results suggest IL1β-mediated oncogenic signaling is triggered by breast cancer cell membrane-derived soluble CD44 (sCD44) antigen, and targeting sCD44 antigen may provide an alternative therapeutic strategy for breast cancer treatment by modulating inflammatory tumor microenvironment. SIGNIFICANCE: A novel positive feedback loop between IL1β and CD44 promotes TNBC malignant progression.
Efficacy of primary liver organoid culture from different stages of non-alcoholic steatohepatitis (NASH) mouse model
Authors: Mohamed Elbadawy, Megumi Yamanaka, Yuta Goto, Kimika Hayashi, Ryouichi Tsunedomi, Shoichi Hazama, Hiroaki Nagano, Toshinori Yoshida, Makoto Shibutani, Ryo Ichikawa, Junta Nakahara, Tsutomu Omatsu, Tetsuya Mizutani, Yukie Katayama, Yuta Shinohara, Amira Abugomaa, Masahiro Kaneda, Hideyuki Yamawaki, Tatsuya Usui, Kazuaki Sasaki
Journal: Biomaterials (2020)
Pan-viral protection against arboviruses by activating skin macrophages at the inoculation site
Authors: Steven R. Bryden, Marieke Pingen, Daniella A. Lefteri, Janne Miltenburg, Leen Delang, Sofie Jacobs, Rana Abdelnabi, Johan Neyts, Emilie Pondeville, Jack Major, Marietta Müller, Henna Khalid, Andrew Tuplin, Margus Varjak, Andres Merits, Julia Edgar, Gerard J. Graham, Kave Shams, Clive S. McKimmie
Journal: Science Translational Medicine (2020)

Arthropod-borne viruses (arboviruses) are important human pathogens for which there are no specific antiviral medicines. The abundance of genetically distinct arbovirus species, coupled with the unpredictable nature of their outbreaks, has made the development of virus-specific treatments challenging. Instead, we have defined and targeted a key aspect of the host innate immune response to virus at the arthropod bite that is common to all arbovirus infections, potentially circumventing the need for virus-specific therapies. Using mouse models and human skin explants, we identify innate immune responses by dermal macrophages in the skin as a key determinant of disease severity. Post-exposure treatment of the inoculation site by a topical TLR7 agonist suppressed both the local and subsequent systemic course of infection with a variety of arboviruses from the Alphavirus, Flavivirus, and Orthobunyavirus genera. Clinical outcome was improved in mice after infection with a model alphavirus. In the absence of treatment, antiviral interferon expression to virus in the skin was restricted to dermal dendritic cells. In contrast, stimulating the more populous skin-resident macrophages with a TLR7 agonist elicited protective responses in key cellular targets of virus that otherwise proficiently replicated virus. By defining and targeting a key aspect of the innate immune response to virus at the mosquito bite site, we have identified a putative new strategy for limiting disease after infection with a variety of genetically distinct arboviruses.
Re: Cutaneous Manifestation of Sarcoidosis in Lower-Back Tattoo With Increased Uptake of 18F-FDG
Authors: Nicolas Kluger
Journal: Clinical Nuclear Medicine (2020)

Department of Dermatology, Allergology and Venereology, Helsinki University Central Hospital, Helsinki, Finland; “Tattoo” Consultation, Department of Dermatology, Bichat-Claude Bernard Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France [email protected] Conflict of interest and sources of funding: none declared.
Detection of colorectal adenomas with a real-time computer-aided system (ENDOANGEL): a randomised controlled study
Authors: Dexin Gong, Lianlian Wu, Jun Zhang, Ganggang Mu, Lei Shen, Jun Liu, Zhengqiang Wang, Wei Zhou, Ping An, Xu Huang, Xiaoda Jiang, Yanxia Li, Xinyue Wan, Shan Hu, Yiyun Chen, Xiao Hu, Youming Xu, Xiaoyun Zhu, Suqin Li, Liwen Yao, Xinqi He, Di Chen, Li Huang, Xiao Wei, Xuemei Wang, Honggang Yu
Journal: The Lancet. Gastroenterology & hepatology (2020)
The complicated dialogue between <i>Helicobacter pylori</i> and p53
Authors: Zhi-Hang Tao, Jing-Yuan Fang
Journal: Gut (2020)

We recently read the interesting paper published in GUT elucidating the role of upstream stimulatory factor 1 (USF1) in Helicobacter pylori (Hp )-induced p53 degradation.1 The work greatly broadens our knowledge of the interplay between Hp and p53 during gastric carcinogenesis. Here we propose some additional exploration, if incorporated in study design, can further deepen our understanding.

The significance of USF1 in gastric carcinogenesis should be acknowledged as the study showed that loss of USF1, on its own, exacerbated the severity of …
Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth
Authors: Miao Liu, Yuanyuan Wang, Chuanzhen Yang, Yuxia Ruan, Changsen Bai, Qiaoyun Chu, Yanfen Cui, Ceshi Chen, Guoguang Ying, Binghui Li
Journal: The Journal of Experimental Medicine (2020)

Cancer cells often proliferate under hypoxia and reprogram their metabolism. However, how to find targets to effectively block the hypoxia-associated metabolic pathways remains unclear. Here, we developed a tool to conveniently calculate electrons dissipated in metabolic transformations. Based on the law of conservation of electrons in chemical reactions, we further built up an electron balance model for central carbon metabolism, and it can accurately outline metabolic plasticity under hypoxia. Our model specifies that glutamine metabolism reprogrammed for biosynthesis of lipid and/or proline actually acts as the alternative electron bin to enable electron transfer in proliferating cells under hypoxia. Inhibition of both proline biosynthesis and lipogenesis can synergistically suppress cancer cell growth under hypoxia and in vivo tumor onset. Therefore, our model helps to reveal combinations of potential targets to inhibit tumor growth by blocking hypoxia-rewired metabolism and provides a useful tool for future studies on cancer metabolism.
High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy
Authors: Xiangyu Zhang, Ismail Sergin, Trent D. Evans, Se-Jin Jeong, Astrid Rodriguez-Velez, Divya Kapoor, Sunny Chen, Eric Song, Karyn B. Holloway, Jan R. Crowley, Slava Epelman, Conrad C. Weihl, Abhinav Diwan, Daping Fan, Bettina Mittendorfer, Nathan O. Stitziel, Joel D. Schilling, Irfan J. Lodhi, Babak Razani
Journal: Nature Metabolism (2020)
Establishment of a scalable microfluidic assay for characterization of population‐based neutrophil chemotaxis
Authors: Fulvio Grigolato, Cecilie Egholm, Daniela Impellizzieri, Paolo Arosio, Onur Boyman
Journal: Allergy (2020)

Regulation of neutrophil chemotaxis and activation plays crucial roles in immunity, and dysregulated neutrophil responses can lead to pathology as seen in neutrophilic asthma. Neutrophil recruitment is key for initiating immune defense and inflammation, and its modulation is a promising therapeutic target. Microfluidic technology is an attractive tool for characterization of neutrophil migration. Compared to transwell assays, microfluidic approaches could offer several advantages, including precis e control of defined chemokine gradients in space and time, automated quantitative analysis of chemotaxis, and high throughput.We established a microfluidic device for fully automated, quantitative assessment of neutrophil chemotaxis. Freshly isolated mouse neutrophils from bone marrow or human neutrophils from peripheral blood were assessed in real time using an epifluorescence microscope for their migration toward the potent chemoattractants C-X-C-motif ligand 2 (CXCL2) and CXCL8, without or with interleukin-4 (IL-4) pre-incubation.Our microfluidic device allowed the precise and reproducible determination of the optimal CXCL2 and CXCL8 concentrations for mouse and human neutrophil chemotaxis, respectively. Furthermore, our microfluidic assay was able to measure the equilibrium and real-time dynamic effects of specific modulators of neutrophil chemotaxis. We demonstrated this concept by showing that IL-4 receptor signaling in mouse and human neutrophils inhibited their migration toward CXCL2 and CXCL8, respectively, and this inhibition was time-dependent.Collectively, our microfluidic device shows several advantages over traditional transwell migration assays and its design is amenable to future integration into multiplexed high-throughput platforms for screening of molecules that modulate the chemotaxis of different immune cells.
Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside in prevention of oxaliplatin-induced neurotoxicity in stage II/III colorectal cancer patients.
Authors: Yu-hong Li, De-Shen Wang, Zhiqiang Wang, Jie-wen Peng, Wei Wang, Fen Feng, Yanhong Deng, Jianwei Zhang, Fenghua Wang, Chao Ren, Feng Wang, Ying Jin, Chuanbo Xie, Qiong Tan, Gong Chen, Rui-hua Xu
Journal: Journal of Clinical Oncology (2019)

674 Background: Monosialotetrahexosylganglioside (GM1) is a glycosphingolipid, which has antioxidant and neuroprotective properties. Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy. This study was designed to assess the efficacy of GM1 for preventing oxaliplatin-induced neurotoxicity in colorectal cancer (CRC) patients. Methods: A total of 186 patients with stage II/III CRC undergoing adjuvant chemotherapy with modified FOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to intravenous GM1 80mg per day or placebo from day 0 to day 4 during chemotherapy. The primary end point was the rate of grade 2 or worse cumulative neurotoxicity, measured by investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. The secondary end point were the chronic cumulative neurotoxicity measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity by using the NCI-CTCAE or the oxaliplatin-specific neuropathy scale, the rates of acute neurotoxicity measured by a numerical analog scale ranging from 0 to 10, and the rates of dose reduction or withdrawal of both arms. Results: There were no statistically significant differences in the rate of NCI-CTCAE grade 2 or worse neurotoxicity between the study arms (GM1: 33.7% vs. placebo: 31.6%; P= 0.76). Similarly, there were no significant differences measured by EORTC QLQ-CIPN20 neuropathy scale ( P= 0.89) or additional measures of neuropathy, including measurement of the time to grade 2 neurotoxicity by using the NCI-CTCAE ( P= 0.99) or an oxaliplatin-specific neuropathy scale ( P= 0.98). In addition, GM1 did not substantially decrease oxaliplatin-induced acute neuropathy. The rates of dose reduction or withdrawal of both arms were not significantly different (GM1: 64.6% vs. placebo: 54.6%, P= 0.15). Conclusions: This study does not support using GM1 to prevent oxaliplatin-induced neurotoxicity. (NCT02251977) Clinical trial information: NCT02251977.
Eosinophilic Fasciitis Triggered by Nivolumab: A Remarkable Efficacy of the mTOR Inhibitor Sirolimus
Authors: Erwan Le Tallec, Alain Lescoat, Alice Ballerie, Bérengère Cador, Hervé Lena, Charles Ricordel, Sène Damien, Céleste Lebbe, Patrick Jego, Nicolas Belhomme
Journal: Journal of Thoracic Oncology (2020)
Assessing coverage of interventions for reproductive, maternal, newborn, child, and adolescent health and nutrition
Authors: Jennifer Requejo, Theresa Diaz, Lois Park, Doris Chou, Allysha Choudhury, Regina Guthold, Debra Jackson, Ann-Beth Moller, Jean-Pierre Monet, Allisyn C Moran, Lale Say, Kathleen L Strong, Anshu Banerjee
Journal: BMJ (2020)

Progress has been made in priority interventions, but we need new measurement systems that include the whole life course and give better assessment of equity of coverage, argue <b>Jennifer Requejo and colleagues</b>
Corrigendum to: “Central metal-derived co-assembly of biomimetic GdTPP/ZnTPP porphyrin nanocomposites for enhanced dual-modal imaging-guided photodynamic therapy” [Biomaterials 229 (2020) 119576]
Authors: Jiefei Wang, Zhongjie Wang, Yong Zhong, Yan Zou, Chong Wang, Haigang Wu, Albert Lee, Weitao Yang, Xiao Wang, Yanjie Liu, Dongya Zhang, Jiliang Yan, Mingcong Hao, Meng Zheng, Roger Chung, Feng Bai, Bingyang Shi
Journal: Biomaterials (2020)
Robotic fluidic coupling and interrogation of multiple vascularized organ chips
Authors: Richard Novak, Miles Ingram, Susan Marquez, Debarun Das, Aaron Delahanty, Anna Herland, Ben M. Maoz, Sauveur S. F. Jeanty, Mahadevabharath R. Somayaji, Morgan Burt, Elizabeth Calamari, Angeliki Chalkiadaki, Alexander Cho, Youngjae Choe, David Benson Chou, Michael Cronce, Stephanie Dauth, Toni Divic, Jose Fernandez-Alcon, Thomas Ferrante, John Ferrier, Edward A. FitzGerald, Rachel Fleming, Sasan Jalili-Firoozinezhad, Thomas Grevesse, Josue A. Goss, Tiama Hamkins-Indik, Olivier Henry, Chris Hinojosa, Tessa Huffstater, Kyung-Jin Jang, Ville Kujala, Lian Leng, Robert Mannix, Yuka Milton, Janna Nawroth, Bret A. Nestor, Carlos F. Ng, Blakely O’Connor, Tae-Eun Park, Henry Sanchez, Josiah Sliz, Alexandra Sontheimer-Phelps, Ben Swenor, Guy Thompson, George J. Touloumes, Zachary Tranchemontagne, Norman Wen, Moran Yadid, Anthony Bahinski, Geraldine A. Hamilton, Daniel Levner, Oren Levy, Andrzej Przekwas, Rachelle Prantil-Baun, Kevin K. Parker, Donald E. Ingber
Journal: Nature Biomedical Engineering (2020)
A23 A Genomically Adjusted Clinicopathologic Model Predicts Recurrence in Resected Early-Stage Lung Squamous Cell Carcinoma
Authors: J.G. Connolly, K.S. Tan, F. Sanchez-Vega, G.D. Jones, Y. Liu, R. Caso, G. Rocco, B.J. Park, P.S. Adusumilli, D. Molena, D.R. Jones
Journal: Journal of Thoracic Oncology (2020)