tbuckley/cabot-search huggingface dataset:
Bevacizumab in progressive disseminated atypical choroid plexus papilloma in adults
Authors: Francesca Colò, Louis Larrouquere, Romain Rivoirard, Hugues Loiseau, Augustin Mervoyer, Alain Lortholary, Isabelle Catry-Thomas, Didier Frappaz
Journal: Neuro-Oncology (2020)
Mechanisms and rejuvenation strategies for aged hematopoietic stem cells
Authors: Xia Li, Xiangjun Zeng, Yulin Xu, Binsheng Wang, Yanmin Zhao, Xiaoyu Lai, Pengxu Qian, He Huang
Journal: Journal of Hematology & Oncology (2020)

Abstract Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.
慢性骨髄性白血病においてキナーゼ不活性でありチロシンキナーゼ阻害剤耐性の一因とはならないBCR-ABL 35INS 挿入/切断型変異体
Authors: O’Hare Thomas, S Zabriskie Matthew, A Eide Christopher, Agarwal Anupriya, T Adrian Lauren, You Huihong, S Corbin Amie, Yang Fei, D Press Richard, M Rivera Victor, Toplin Julie, Wong Stephane, W Deininger Michael, J Druker Brian
Journal: Blood (2011)
Leprosy: Treatment and management of complications
Authors: Mayra B.C. Maymone, Samantha Venkatesh, Melissa Laughter, Rana Abdat, Jeremy Hugh, Mara M. Dacso, P. Narasimha Rao, Barbara M. Stryjewska, Cory A. Dunnick, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2020)
Junctional and somatic hypermutation-induced CX4C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody
Authors: Chunyan Yi, Jing Xia, Lan He, Zhiyang Ling, Xuesong Wang, Yu Yan, Jiangjun Wang, Xinhao Zhao, Weiguo Fan, Xiaoyu Sun, Ronghua Zhang, Sheng Ye, Rongguang Zhang, Yongfen Xu, Liyan Ma, Yaguang Zhang, Honglin Zhou, Zhong Huang, Junqi Niu, Gang Long, Junxia Lu, Jin Zhong, Bing Sun
Journal: Cellular and Molecular Immunology (2020)

Induction of broadly neutralizing monoclonal antibodies (bNAbs) that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus (HCV) vaccine research. The study of bNAbs arising in natural infection is essential in this endeavor. We generated a human antibody, 8D6, recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient. This antibody shows broadly neutralizing activity, which covers a pan-genotypic panel of cell culture-derived HCV virions (HCVcc). Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2. We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization. We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge (C-C) motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6. This motif is conserved among a series of broadly neutralizing HCV antibodies, indicating a common binding model. Next, the 8D6 inferred germline (iGL) was reconstructed and tested for its binding affinity and neutralization activity. Interestingly, 8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain, suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs. Overall, our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3, while its iGL can serve as a probe to identify potential HCV vaccine strains.
Abstract 15069: Novel Approach to Arrhythmia Risk Stratification in Patients With Cardiac Sarcoidosis Incorporating Machine Learning and a MRI-PET-Fusion Computational Model
Authors: Julie K Shade, Adityo Prakosa, David R Okada, Jonathan Chrispin, Natalia Trayanova
Journal: Circulation (2018)

Introduction: Clinical measures fail to correctly identify cardiac sarcoidosis (CS) patients at high risk for VT. This limits life-saving treatments, including ICDs, in high-risk patients and subje...
Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study
Authors: Zhi-Hao Li, Xiang Gao, Vincent CH Chung, Wen-Fang Zhong, Qi Fu, Yue-Bin Lv, Zheng-He Wang, Dong Shen, Xi-Ru Zhang, Pei-Dong Zhang, Fu-Rong Li, Qing-Mei Huang, Qing Chen, Wei-Qi Song, Xian-Bo Wu, Xiao-Ming Shi, Virginia Byers Kraus, Xingfen Yang, Chen Mao
Journal: Annals of the Rheumatic Diseases (2020)

To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.
Early gastric cancer detection in high-risk patients: a multicentre randomised controlled trial on the effect of second-generation narrow band imaging
Authors: Naohiro Yoshida, Hisashi Doyama, Tomonori Yano, Takahiro Horimatsu, Noriya Uedo, Yoshinobu Yamamoto, Naomi Kakushima, Hiromitsu Kanzaki, Shinichiro Hori, Kenshi Yao, Ichiro Oda, Chikatoshi Katada, Chizu Yokoi, Ken Ohata, Kenichi Yoshimura, Hideki Ishikawa, Manabu Muto
Journal: Gut (2020)

Early detection of gastric cancer has been the topic of major efforts in high prevalence areas. Whether advanced imaging methods, such as second-generation narrow band imaging (2G-NBI) can improve early detection, is unknown.This open-label, randomised, controlled tandem trial was conducted in 13 hospitals. Patients at increased risk for gastric cancer were randomly assigned to primary white light imaging (WLI) followed by secondary 2G-NBI (WLI group: n=2258) and primary 2G-NBI followed by secondary WLI (2G-NBI group: n=2265) performed by the same examiner. Suspected early gastric cancer (EGC) lesions in both groups were biopsied. Primary endpoint was the rate of EGC patients in the primary examination. The main secondary endpoint was the positive predictive value (PPV) for EGC in suspicious lesions detected (primary examination).EGCs were found in 44 (1.9%) and 53 (2.3%; p=0.412) patients in the WLI and 2G-NBI groups, respectively, during primary EGD. In a post hoc analysis, the overall rate of lesions detected at the second examination was 25% (n=36/145), with no significant differences between groups. PPV for EGC in suspicious lesions was 13.5% and 20.9% in the WLI (50/371 target lesions) and 2G-NBI groups (59/282 target lesions), respectively (p=0.015).The overall sensitivity of primary endoscopy for the detection of EGC in high-risk patients was only 75% and should be improved. 2G-NBI did not increase EGC detection rate over conventional WLI. The impact of a slightly better PPV of 2G-NBI has to be evaluated further.UMIN000014503.
Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China
Authors: Qiurong Ruan, Kun Yang, Wenxia Wang, Lingyu Jiang, Jianxin Song
Journal: Intensive Care Medicine (2020)

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.
Many people in UK underestimate their weight
Authors: J. Wise
Journal: BMJ (2015)

More than a third of UK residents who think of themselves as overweight are actually clinically obese, a European survey has shown.1

The survey, carried out for the European Association for the Study of Obesity, also found that a fifth of UK adults who consider themselves to be of a normal weight are in fact overweight. This compares with 16% in France and 10% in Italy.

The online survey of …
Detection of SARS-CoV-2 Among Residents and Staff Members of an Independent and Assisted Living Community for Older Adults — Seattle, Washington, 2020
Authors: Alison C. Roxby, Alexander L. Greninger, Kelly M. Hatfield, John B. Lynch, Timothy H. Dellit, Allison James, Joanne Taylor, Libby C. Page, Anne Kimball, Melissa Arons, Laura A. Schieve, Albert Munanga, Nimalie Stone, John A. Jernigan, Sujan C. Reddy, James Lewis, Seth A. Cohen, Keith R. Jerome, Jeffrey S. Duchin, Santiago Neme
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In the Seattle, Washington metropolitan area, where the first case of novel coronavirus 2019 disease (COVID-19) in the United States was reported (1), a community-level outbreak is ongoing with evidence of rapid spread and high morbidity and mortality among older adults in long-term care skilled nursing facilities (SNFs) (2,3). However, COVID-19 morbidity among residents of senior independent and assisted living communities, in which residents do not live as closely together as do residents in SNFs and do not require skilled nursing services, has not been described. During March 5-9, 2020, two residents of a senior independent and assisted living community in Seattle (facility 1) were hospitalized with confirmed COVID-19 infection; on March 6, social distancing and other preventive measures were implemented in the community. UW Medicine (the health system linked to the University of Washington), Public Health - Seattle & King County, and CDC conducted an investigation at the facility. On March 10, all residents and staff members at facility 1 were tested for SARS-CoV-2, the virus that causes COVID-19, and asked to complete a questionnaire about their symptoms; all residents were tested again 7 days later. Among 142 residents and staff members tested during the initial phase, three of 80 residents (3.8%) and two of 62 staff members (3.2%) had positive test results. The three residents had no symptoms at the time of testing, although one reported an earlier cough that had resolved. A fourth resident, who had negative test results in the initial phase, had positive test results 7 days later. This resident was asymptomatic on both days. Possible explanations for so few cases of COVID-19 in this residential community compared with those in several Seattle SNFs with high morbidity and mortality include more social distancing among residents and less contact with health care providers. In addition, early implementation of stringent isolation and protective measures after identification of two COVID-19 cases might have been effective in minimizing spread of the virus in this type of setting. When investigating a potential outbreak of COVID-19 in senior independent and assisted living communities, symptom screening is unlikely to be sufficient to identify all persons infected with SARS-CoV-2. Adherence to CDC guidance to prevent COVID-19 transmission in senior independent and assisted living communities (4) could be instrumental in preventing a facility outbreak.
Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers
Authors: Myriam Chalabi, Lorenzo F. Fanchi, Krijn K. Dijkstra, José G. Van den Berg, Arend G. Aalbers, Karolina Sikorska, Marta Lopez-Yurda, Cecile Grootscholten, Geerard L. Beets, Petur Snaebjornsson, Monique Maas, Marjolijn Mertz, Vivien Veninga, Gergana Bounova, Annegien Broeks, Regina G. Beets-Tan, Thomas R. de Wijkerslooth, Anja U. van Lent, Hendrik A. Marsman, Elvira Nuijten, Niels F. Kok, Maria Kuiper, Wieke H. Verbeek, Marleen Kok, Monique E. Van Leerdam, Ton N. Schumacher, Emile E. Voest, John B. Haanen
Journal: Nature Medicine (2020)
Imaging in immune checkpoint inhibitor-induced polymyalgia rheumatica
Authors: Kornelis S M van der Geest, Maria Sandovici, Abraham Rutgers, T Jeroen N Hiltermann, Sjoukje F Oosting, Riemer H J A Slart, Elisabeth Brouwer
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article ‘Addressing immune-related adverse events of cancer immunotherapy: how prepared are rheumatologists?’ by Kostine et al .1 The introduction of immune checkpoint inhibitor (ICI) therapy has been a major breakthrough in the management of metastatic cancer. On the downside, ICI therapy may induce unwanted autoimmune effects, the so-called immune-related adverse effects (irAEs). Various irAEs have been described that resemble a regular rheumatic disease, including polymyalgia rheumatica (ICI-PMR).2 3 The authors report that rheumatologists may lack confidence in diagnosing irAEs. Therefore, recommendations for the diagnosis of rheumatic irAEs are needed. Based on our experience with ICI-PMR, we propose that imaging could be an important part of such recommendations.

We investigated six consecutive patients with ICI-PMR by ultrasonography, and five of these patients also by [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan. Five patients fulfilled the provisional American College of Rheumatology/European League Against Rheumatism classification criteria for PMR.4 A normal C-reactive protein level in the absence of an erythrocyte sedimentation rate (ESR) test precluded PMR classification in one patient. However, this patient fulfilled both the clinical and ultrasound criteria for PMR,4 and showed findings suggestive of PMR on the FDG-PET/CT scan.5 The median age was 73 years (range 59–83; online supplementary table 1). Patients received anti-programmed cell death protein 1 (PD-1) treatment, that …
Covid-19 worldwide: we need precise data by age group and sex urgently
Authors: Raj Bhopal
Journal: BMJ (2020)

<h3>Objective</h3> The aim of this study was to characterize the indication, outcomes and adverse effects of rituximab treatment in a large single-center cohort of patients with systemic rheumatoid vasculitis (RV). <h3>Methods</h3> We retrospectively reviewed the medical charts of 17 patients treated with rituximab for systemic RV from 2000 to 2017. Clinical characteristics, outcomes and adverse effects were analyzed. <h3>Results</h3> At RV diagnosis, mean age was 59 years, 59% were female, 94% were Caucasian and 82% had positive rheumatoid factor. At time of initiating rituximab, median BVAS/RA was 4.0 (IQR, 2.0-7.5). RV presented in the skin in 8 patients (47%), as mononeuritis multiplex in 2 (12%), inflammatory ocular disease in 2 (12%), and affected multiple organ systems in 5 (29%). Rituximab was used for induction in 8 (47%) patients, relapsing RV in 4 (24%), second-line in 2 (12%), and salvage therapy or in combination with another agent in 3 (18%). At 3 months, 2 (13%) of 15 patients with available follow up information achieved complete remission (CR), and 10 (67%) achieved partial response (PR). At 6 months, 6 patients (40%) achieved CR, 8 (53%) achieved PR, and one had no response. At 12 months, 8 of 13 patients with available records (62%) had CR and 5 patients (38%) had PR. <h3>Conclusion</h3> Systemic RV is difficult to treat effectively. Complete remission of RV was achieved in 62% and partial response in 38% of patients within 12 months of rituximab use. Further evidence is needed to inform treatment for patients with RV.
A novel synthetic hTERT-Mini-CMV chimera promoter-driven tumor-selective and high-efficiency expression of transgene for systemic cancer gene therapy
Authors: Guanglin Wu, Wuguo Deng, Vikas Kundra, Bingliang Fang, Jack A. Roth, Lin Ji
Journal: Cancer Research (2005)

3358  One of the major obstacles to a successful cancer gene therapy is the lack of an effective systemic delivery system that can be specifically targeted to primary and metastatic tumors. The hTERT promoter has been cloned and showed to be capable of targeting transgene expression in tumors but not in the normal cells. However, the weak transcription-promoting strength of hTERT promoter, like most other intrinsic mammalian promoters, has hampered its direct use for cancer gene therapy. To circumvent these problems, we have developed a novel chimera hTERT-mini-CMV (hTMC) promoter that was engineered by optimally fusing essential hTERT regulatory sequence with minimal CMV promoter elements. We transfected various human cancers and normal cells with various EGFP-constructs, in which EGFP expression is driven by either the original CMV and hTERT promoters or by the hTMC promoter in vitro. Expression of EGFP in the transfectants was visualized by a fluorescence imaging (FI) under a fluorescence microscope and the population of EGFP-positive cells and fluorescence intensity were quantified by FACS analysis. A high level of EGFP expression driven by the hTMC promoter was detected in all tumor cells but not in normal cells. While a similar tumor-selectivity of EGFP expression driven by hTERT promoter could be seen but the level of expression was several hundred-fold lower than that driven by hTMC promoter under the same transfection efficiency. We also evaluated the effectiveness of hTMC promoter in vivo by systemic injection of DOTAP:cholesterol-complexed hTMC-EGFP-nanoparticles into nude mice that bear intrathoracic human N417 lung tumor xenografts. Consistently, a high level of EGFP expression could be detected only in the tumor cells in animals treated with hTMC-EGFP but not in any other normal tissues. Furthermore, we used the above N417 tumor mouse model to evaluate the therapeutic efficacy of systemic treatment with a novel hTMC-FUS1-nanoparticle by a non-invasive and quantitative MR imaging analysis. A significant inhibition (P
Novel findings obtained by single chain Fv antibody library establishment from tumor infiltrating B lymphocytes of human breast carcinomas and melanomas
Authors: Beatrix Kotlan, Michael McKnight, Andrea Ladanyi, Erzsebet Raso, Jozsef Toth, Mepur Ravindranath, Jozsef Timar, Mark Glassy
Journal: Cancer Research (2007)

3328  Introduction : Human monoclonal antibodies against tumor-associated ganglioside antigens have the potential for tumor therapeutic reagents. We report here a novel strategy to obtain such antibodies. We aimed to investigate and compare B cells infiltrating breast carcinomas and melanomas (TIL-B), in terms of tumor antigen specific binding potential. We questioned the characteristics of these different tumor types and how the immunoglobuline repertoire of their TIL-B parallels the distinguished features.Description of the work: Different types of breast carcinoma and melanoma tumor tissues were processed for further cellular and molecular studies. Heavy (VH) and light chain (Vκ, Vλ) immunoglobulin variable region genes were amplified. Single chain Fv (scFv) antibody fragments were constructed and phage display libraries generated. We compared our previously developed method to other techniques. The effectiveness of the selection process in respect of tumor associated ganglioside specific antibody fragments was tested against various tumor cell membranes. Selected tumor binder antibody fragments of breast cancer and melanoma TIL-B libraries were investigated in cell ELISA, immunofluorescence FACS analysis, confocal microscopy. DNA sequence analysis and biochemical investigations were done to define the targeted tumor associated antigens. Summary of results: Heavy and light chain immunoglobulin variable region genes could be amplified from any of the investigated tissues. This way single chain Fv antibody fragment phage libraries could be generated and specific tumor binders could be selected.With our technique we obtained human antibody fragmenst with unique GD3 ganglioside specificities on breast carcinomas and melanomas. The anti-GD3 antibody pattern was selective for the cancerous tissues and showed apoptotic effects in different tumor cell cultures. Conclusion: Our results suggest that B cells accumulated in breast carcinomas or melanomas have the potential to reveal key tumor associated antigens. Acknowledgements:Supporting grants (Fulbright Research Scholarship 26.0911, OTKA T048933, OTKA T030380, NATO CLG 978639, Rajko Medenica Research Foundation).  Key words: antibody fragments, breast carcinomas, ganglioside, melanoma
A durable protective immune response to wild-type measles virus infection of macaques is due to viral replication and spread in lymphoid tissues
Authors: Wen-Hsuan W. Lin, Eileen Moran, Robert J. Adams, Robert E. Sievers, Debra Hauer, Steven Godin, Diane E. Griffin
Journal: Science Translational Medicine (2020)

Wild-type measles virus replicates better in immune cells and induces more durable antibody responses in macaques than the live-attenuated measles virus vaccine.
Mechanistic Insights for Optimizing PSMA Radioligand Therapy
Authors: Aravind S. Ravi Kumar, Michael S. Hofman
Journal: Clinical Cancer Research (2020)

Abstract PSMA radioligand therapy is a promising new class of therapy for prostate cancer. Heterogeneity of PSMA expression is an important factor explaining variability in clinical results. The ability to visualize the target with theranostics provides unique mechanistic insights. Potential clinically applicable strategies to improve patient selection and optimize therapeutic efficacy are discussed. See related article by Current et al., p. 2946
Design of a novel vaccine nanotechnology-based delivery system comprising CpGODN-protein conjugate anchored to liposomes
Authors: Despo Chatzikleanthous, Signe Tandrup Schmidt, Giada Buffi, Ida Paciello, Robert Cunliffe, Filippo Carboni, Maria Rosaria Romano, Derek T. O'Hagan, Ugo D'Oro, Stuart Woods, Craig W. Roberts, Yvonne Perrie, Roberto Adamo
Journal: Journal of Controlled Release (2020)