tbuckley/cabot-search huggingface dataset:
Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma
Authors: Jennifer N. Brudno, Norris Lam, Danielle Vanasse, Yueh-wei Shen, Jeremy J. Rose, John Rossi, Allen Xue, Adrian Bot, Nathalie Scholler, Lekha Mikkilineni, Mark Roschewski, Robert Dean, Raul Cachau, Philippe Youkharibache, Rashmika Patel, Brenna Hansen, David F. Stroncek, Steven A. Rosenberg, Ronald E. Gress, James N. Kochenderfer
Journal: Nature Medicine (2020)
P-0128 HIV-Associated Lymphoma of the Gastrointestinal Tract in the Combination Antiretroviral Therapy Era
Authors: Shoichi Nakazuru, Tomoko Uehira, Toshiyuki Yoshio, Hiroko Hasegawa, Yuko Sakakibara, Takashi Toyama, Hisashi Ishida, Yoshinori Kodama, Eiji Mita
Journal: Annals of Oncology (2012)
Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy
Authors: Adam P. Levine, Melanie M.Y. Chan, Omid Sadeghi-Alavijeh, Edwin K.S. Wong, H. Terence Cook, Sofie Ashford, Keren Carss, Martin T. Christian, Matthew Hall, Claire Louise Harris, Paul McAlinden, Kevin J. Marchbank, Stephen D. Marks, Heather Maxwell, Karyn Megy, Christopher J. Penkett, Monika Mozere, Kathleen E. Stirrups, Salih Tuna, Julie Wessels, Deborah Whitehorn, Sally A. Johnson, Daniel P. Gale
Journal: Journal of the American Society of Nephrology (2020)

Primary membranoproliferative GN, including complement 3 (C3) glomerulopathy, is a rare, untreatable kidney disease characterized by glomerular complement deposition. Complement gene mutations can cause familial C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary membranoproliferative GN.We analyzed whole-genome sequence data from 165 primary membranoproliferative GN cases and 10,250 individuals without the condition (controls) as part of the National Institutes of Health Research BioResource-Rare Diseases Study. We examined copy number, rare, and common variants.Our analysis included 146 primary membranoproliferative GN cases and 6442 controls who were unrelated and of European ancestry. We observed no significant enrichment of rare variants in candidate genes (genes encoding components of the complement alternative pathway and other genes associated with the related disease atypical hemolytic uremic syndrome; 6.8% in cases versus 5.9% in controls) or exome-wide. However, a significant common variant locus was identified at 6p21.32 (rs35406322) (P=3.29×10-8; odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.53 to 2.44), overlapping the HLA locus. Imputation of HLA types mapped this signal to a haplotype incorporating DQA1*05:01, DQB1*02:01, and DRB1*03:01 (P=1.21×10-8; OR, 2.19; 95% CI, 1.66 to 2.89). This finding was replicated by analysis of HLA serotypes in 338 individuals with membranoproliferative GN and 15,614 individuals with nonimmune renal failure.We found that HLA type, but not rare complement gene variation, is associated with primary membranoproliferative GN. These findings challenge the paradigm of complement gene mutations typically causing primary membranoproliferative GN and implicate an underlying autoimmune mechanism in most cases.
Efficacy and Safety of Testosterone Treatment in Men: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians
Authors: Susan J. Diem, Nancy L. Greer, Roderick MacDonald, Lauren G. McKenzie, Philipp Dahm, Nacide Ercan-Fang, Allison Estrada, Laura S. Hemmy, Christina E. Rosebush, Howard A. Fink, Timothy J. Wilt
Journal: Annals of Internal Medicine (2020)

Background: Testosterone treatment rates in adult men have increased in the United States over the past 2 decades. Purpose: To assess the benefits and harms of testosterone treatment for men without underlying organic causes of hypogonadism. Data Sources: English-language searches of multiple electronic databases (January 1980 to May 2019) and reference lists from systematic reviews. Study Selection: 38 randomized controlled trials (RCTs) of at least 6 months' duration that evaluated transdermal or intramuscular testosterone therapies versus placebo or no treatment and reported prespecified patient-centered outcomes, as well as 20 long-term observational studies, U.S. Food and Drug Administration review data, and product labels that reported harms information. Data Extraction: Data extraction by a single investigator was confirmed by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus. Data Synthesis: Studies enrolled mostly older men who varied in age, symptoms, and testosterone eligibility criteria. Testosterone therapy improved sexual functioning and quality of life in men with low testosterone levels, although effect sizes were small (low- to moderate-certainty evidence). Testosterone therapy had little to no effect on physical functioning, depressive symptoms, energy and vitality, or cognition. Harms evidence reported in trials was judged to be insufficient or of low certainty for most harm outcomes. No trials were powered to assess cardiovascular events or prostate cancer, and trials often excluded men at increased risk for these conditions. Observational studies were limited by confounding by indication and contraindication. Limitation: Few trials exceeded a 1-year duration, minimum important outcome differences were often not established or reported, RCTs were not powered to assess important harms, few data were available in men aged 18 to 50 years, definitions of low testosterone varied, and study entry criteria varied. Conclusion: In older men with low testosterone levels without well-established medical conditions known to cause hypogonadism, testosterone therapy may provide small improvements in sexual functioning and quality of life but little to no benefit for other common symptoms of aging. Long-term efficacy and safety are unknown. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42018096585)
Magnitude of the Age-Advancement Effect of Comorbidities in Colorectal Cancer Prognosis
Authors: Daniel Boakye, Viola Walter, Lina Jansen, Uwe M. Martens, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Comorbidities and old age independently compromise prognosis of patients with colorectal cancer (CRC). The impact of comorbidities could thus be considered as conveying worse prognosis already at younger ages, but evidence is lacking on how much worsening of prognosis with age is advanced to younger ages in comorbid versus noncomorbid patients. We aimed to quantify, for the first time, the impact of comorbidities on CRC prognosis in “age advancement” of worse prognosis. Methods: A total of 4,602 patients aged ≥30 years who were diagnosed with CRC in 2003 through 2014 were recruited into a population-based study in the Rhine-Neckar region of Germany and observed over a median period of 5.1 years. Overall comorbidity was quantified using the Charlson comorbidity index (CCI). Hazard ratios and age advancement periods (AAPs) for comorbidities were calculated from multivariable Cox proportional hazards models for relevant survival outcomes. Results: Hazard ratios for CCI scores 1, 2, and ≥3 compared with CCI 0 were 1.25, 1.53, and 2.30 ( P &lt;.001) for overall survival and 1.20, 1.48, and 2.03 ( P &lt;.001) for disease-free survival, respectively. Corresponding AAP estimates for CCI scores 1, 2, and ≥3 were 5.0 (95% CI, 1.9–8.1), 9.7 (95% CI, 6.1–13.3), and 18.9 years (95% CI, 14.4–23.3) for overall survival and 5.5 (95% CI, 1.5–9.5), 11.7 (95% CI, 7.0–16.4), and 21.0 years (95% CI, 15.1–26.9) for disease-free survival. Particularly pronounced effects of comorbidity on CRC prognosis were observed in patients with stage I–III CRC. Conclusions: Comorbidities advance the commonly observed deterioration of prognosis with age by many years, meaning that at substantially younger ages, comorbid patients with CRC experience survival rates comparable to those of older patients without comorbidity. This first derivation of AAPs may enhance the empirical basis for treatment decisions in patients with comorbidities and highlight the need to incorporate comorbidities into prognostic nomograms for CRC.
The association of depression with subsequent dementia diagnosis: A Swedish nationwide cohort study from 1964 to 2016
Authors: Sofie Holmquist, Anna Nordström, Peter Nordström
Journal: PLoS Medicine (2020)

Depression is associated with an increased risk of dementia. However, short follow-up times and lack of adjustment for familial factors in previous studies could influence this association. The purpose of the present study was to investigate the association between depression and subsequent dementia, while controlling for familial factors and with a follow-up of over 35 years.Two cohorts were formed from all individuals aged 50 years or older living in Sweden as of 31 December 2005 (n = 3,341,010). The Swedish National Patient Register was searched from 1964 through 2016 to identify diagnosis of depression and dementia. In the first cohort, individuals diagnosed with depression (n = 119,386) were matched 1:1 with controls without depression diagnosis. The second cohort was a sibling cohort (n = 50,644) consisting of same-sex full sibling pairs with discordant depression status. In the population matched cohort study, a total of 9,802 individuals were diagnosed with dementia during a mean follow-up time of 10.41 (range 0-35) years (5.5% of those diagnosed with depression and 2.6% of those without depression diagnosis (adjusted odds ratio [aOR] 2.47, 95% CI 2.35-2.58; p < 0.001), with a stronger association for vascular dementia (aOR 2.68, 95% CI 2.44-2.95; p < 0.001) than for Alzheimer disease (aOR 1.79, 95% CI 1.68-1.92; p < 0.001). The association with dementia diagnosis was strongest in the first 6 months after depression diagnosis (aOR 15.20, 95% CI 11.85-19.50; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 1.58, 95% CI 1.27-1.98; p < 0.001). Also in the sibling cohort, the association was strongest in the first 6 months (aOR 20.85, 95% CI 9.63-45.12; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 2.33, 95% CI 1.32-4.11; p < 0.001). The adjusted models included sex, age at baseline, citizenship, civil status, household income, and diagnoses at baseline. The main limitation of the study methodology is the use of observational data; hence, the associations found are not proof of causal effects.Depression is associated with increased odds of dementia, even more than 20 years after diagnosis of depression, and the association remains after adjustment for familial factors. Further research is needed to investigate whether successful prevention and treatment of depression decrease the risk of dementia.
Association of Radiographic Progression-Free Survival (RPFS) Adapted from Prostate Cancer Working Group 2 (PCWG2) Consensus Criteria (APCWG2) with Overall Survival (OS) in Patients (PTS) with Metastatic Castration-Resistant Prostate Cancer (MCRPC): Results from COU-AA-302
Authors: C.J. Ryan, M. Morris, A. Molina, J.R. Piulats, P. De Souza, J. Li, T. Kheoh, J.S. de Bono, S. Larson, T. Griffin, S. Matheny, V. Naini, H.I. Scher, E. Small
Journal: Annals of Oncology (2012)
Identification of Risk Factors of Relapse after Curative Surgical Resection in Stage I Gastric Cancer
Authors: J. Park, M.H. Ryu, H.J. Kim, B. Ryoo, I. Park, Y.S. Park, S.T. Oh, J.H. Yook, B.S. Kim, Y. Kang
Journal: Annals of Oncology (2012)
PD-0023 Benefit of Adding Panitumumab (pmab) To 1St/2Nd-Line Chemotherapy in Patients with KRAS WT mCRC: A Number-Needed-To-Treat (NNT) Analysis
Authors: Michel Ducreux, Marc Peeters, Salvatore Siena, Jean-Yves Douillard, Cornelis Punt, Stephan Braun, Alan Rong, Roger Sidhu
Journal: Annals of Oncology (2012)
Optimizing β-Lactams against Tuberculosis
Authors: Veronique R. de Jager, Naadira Vanker, Lize van der Merwe, Elana van Brakel, Morris Muliaditan, Andreas H. Diacon
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

distribution and BCG vaccination coverage.New vaccines should also be tested in animal models against different M. tuberculosis strains before progressing to human studies.Finally, vaccine trials in humans should be performed in Asia where the Beijing genotype family predominates.
Insulin Growth Factor Receptor as a Prognostic Marker in Operable Squamous-Cell Laryngeal Cancer
Authors: G. Mountzios, I. Kostopoulos, V. Kotoula, S. Levva, E. Fountzilas, K. Markou, I. Karasmanis, N. Angouridakis, A. Nikolaou, G. Fountzilas
Journal: Annals of Oncology (2012)
Multicenter, Dose-Escalation Study of the Investigational Drug Tak-733, An Oral Mek inhibitor, in Patients (PTS) with Advanced Solid Tumors: Preliminary Phase 1 Results
Authors: A.A. Adjei, P.M. LoRusso, A. Ribas, J.A. Sosman, G.K. Dy, B. Chmielowski, P. Lipman, X. Zhou, E. Gangolli, V. Bozón
Journal: Annals of Oncology (2012)
Pemetrexed (PEM) Combination Therapy with Carboplatin (CB) Followed by Pem Maintenance in Japanese Patients (PTS) with Nonsquamous Non-Small Cell Lung Cancer (NSCLC): Subgroup Analysis of Elderly Pts
Authors: N. Nogami, R. Sekiguchi, S. Enatsu, K. Nakagawa, T. Tamura
Journal: Annals of Oncology (2012)
Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study
Authors: Fiona V Cresswell, Lillian Tugume, Nathan C Bahr, Richard Kwizera, Ananta S Bangdiwala, Abdu K Musubire, Morris Rutakingirwa, Enock Kagimu, Edwin Nuwagira, Edward Mpoza, Joshua Rhein, Darlisha A Williams, Conrad Muzoora, Daniel Grint, Alison M Elliott, David B Meya, David R Boulware
Journal: The Lancet Infectious Diseases (2020)

IntroductionTuberculous meningitis accounts for 1–5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis.MethodsIn this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard.FindingsFrom Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5–87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6–96·2; 153 of 165), compared with 55·6% sensitivity (44·0–70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9–91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5–75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4–91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5–98·5; 39 of 42), higher than Xpert at 65·8% (48·6–80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9–86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture.InterpretationXpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required.FundingWellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases.
Abstract 10006: Expression and Function of Pcsk9 in Human Pancreatic Beta Cells
Authors: Stephane Ramin-Mangata, Gilles Lambert
Journal: Circulation (2019)

Introduction: Like statins, PCSK9 inhibitors (e.g. alirocumab) are hypocholesterolemic agents that increase the abundance of the LDL-receptor (LDLR). While mendelian randomization studies suggest t...
A comparative study of the osteogenic performance between the hierarchical micro/submicro-textured 3D-printed Ti6Al4V surface and the SLA surface
Authors: Jinkai Zhang, Jiaqiang Liu, Chengtao Wang, Fengshan Chen, Xudong Wang, Kaili Lin
Journal: Bioactive Materials (2020)

Three-dimensional (3D) printed titanium and its alloys have broad application prospect in the field of biomedical implant materials, although the biological performance of the original surface should be improved. Learning from the development experience of conventional titanium implants, to construct a hierarchical hybrid topological surface is the future direction of efforts. Since the original 3D-printed (3D hereafter) Ti6Al4V surface inherently has micron-scale features, in the present study, we introduced submicron-scale pits on the original surface by acid etching to obtain a hierarchical micro/submicro-textured surface. The characteristic and biological performance of the 3D-printed and acid-etched (3DA hereafter) surface were evaluated
Bone Turnover Markers and Potential Correlation with Outcomes in Patients with Genitourinary Cancer (Renal and Bladder) and Bone Metastasis (Results of the Tugamo Study)
Authors: J. Bellmunt, C. La De Piedra, E. Esteban, M. Climent, B. González, J.L. Álvarez-Ossorio, I. Chirivella Gonzalez, B. Mellado, P.C. Lara, A. Alcaraz
Journal: Annals of Oncology (2012)
Recent Out-of-Africa Migration of Human Herpes Simplex Viruses
Authors: Diego Forni, Chiara Pontremoli, Mario Clerici, Uberto Pozzoli, Rachele Cagliani, Manuela Sironi
Journal: Molecular Biology and Evolution (2020)

Abstract Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens. Both viruses evolved from simplex viruses infecting African primates and they are thus thought to have left Africa during early human migrations. We analyzed the population structure of HSV-1 and HSV-2 circulating strains. Results indicated that HSV-1 populations have limited geographic structure and the most evident clustering by geography is likely due to recent bottlenecks. For HSV-2, the only level of population structure is accounted for by the so-called “worldwide” and “African” lineages. Analysis of ancestry components and nucleotide diversity, however, did not support the view that the worldwide lineage followed early humans during out-of-Africa dispersal. Although phylogeographic analysis confirmed an African origin for both viruses, molecular dating with a method that corrects for the time-dependent rate phenomenon indicated that HSV-1 and HSV-2 migrated from Africa in relatively recent times. In particular, we estimated that the HSV-2 worldwide lineage left the continent in the 18th century, which corresponds to the height of the transatlantic slave trade, possibly explaining the high prevalence of HSV-2 in the Americas (second highest after Africa). The limited geographic clustering of HSV-1 makes it difficult to date its exit from Africa. The split between the basal clade, containing mostly African sequences, and all other strains was dated at ∼5,000 years ago. Our data do not imply that herpes simplex viruses did not infect early humans but show that the worldwide distribution of circulating strains is the result of relatively recent events.
P-0185 Health Service Research on Patients With Colon Cancer in A Network of Integrative Oncology
Authors: Friedemann Schad, Jan Axtner, Antje Happe, Thomas Breitkreuz, Constantin Paxino, Johannes Gutsch, Burkhard Matthes, Marion Debus, Guenther Spahn, Hartmut Riess, Hans-Broder von Laue, Gero Leneweit, Matthias Kroez, Harald Matthes
Journal: Annals of Oncology (2012)
Pazonet: A Phase II Trial of Pazopanib as a Sequencing Treatment in Progressive Metastatic Neuroendocrine Tumors (NETS) Patients (PTS), On Behalf of The Spanish Task Force for Nets (GETNE)
Authors: E. Grande, D. Castellano, R. García-Carbonero, A. Teulé, I. Durán, J. Fuster, I. Sevilla, P. Escudero, J. Sastre, O. Casanovas, L. Ortega, J. Earl, J.J. Díez, G. de Velasco, F. Longo, A. Navarro, V. Pachón, A. Carrato, R. Salazar, J. Capdevila
Journal: Annals of Oncology (2012)
Effect of Bevacizumab on Tumour 5-Fluorouracil Concentration and Microcirculatory Parameters Obtained by Dynamic Contrast-Enhanced MRI in a Hepatocellular Carcinoma Xenograft Model
Authors: S. Mikulski, L. Wang, S. Hartono, L. Martarello, T.S. Koh, B.C. Goh, C.H. Thng, Q.S. Ng
Journal: Annals of Oncology (2012)
Adenosine Signaling Is Prognostic for Cancer Outcome and Has Predictive Utility for Immunotherapeutic Response
Authors: Ben Sidders, Pei Zhang, Kelly Goodwin, Greg O'Connor, Deanna L. Russell, Alexandra Borodovsky, Joshua Armenia, Robert McEwen, Bolan Linghu, Johanna C. Bendell, Todd M. Bauer, Manish R. Patel, Gerald S. Falchook, Melinda Merchant, Gayle Pouliot, J. Carl Barrett, Jonathan R. Dry, Rich Woessner, Kris Sachsenmeier
Journal: Clinical Cancer Research (2020)

There are several agents in early clinical trials targeting components of the adenosine pathway including A2AR and CD73. The identification of cancers with a significant adenosine drive is critical to understand the potential for these molecules. However, it is challenging to measure tumor adenosine levels at scale, thus novel, clinically tractable biomarkers are needed.We generated a gene expression signature for the adenosine signaling using regulatory networks derived from the literature and validated this in patients. We applied the signature to large cohorts of disease from The Cancer Genome Atlas (TCGA) and cohorts of immune checkpoint inhibitor-treated patients.The signature captures baseline adenosine levels in vivo (r2 = 0.92, P = 0.018), is reduced after small-molecule inhibition of A2AR in mice (r2 = -0.62, P = 0.001) and humans (reduction in 5 of 7 patients, 70%), and is abrogated after A2AR knockout. Analysis of TCGA confirms a negative association between adenosine and overall survival (OS, HR = 0.6, P < 2.2e-16) as well as progression-free survival (PFS, HR = 0.77, P = 0.0000006). Further, adenosine signaling is associated with reduced OS (HR = 0.47, P < 2.2e-16) and PFS (HR = 0.65, P = 0.0000002) in CD8+ T-cell-infiltrated tumors. Mutation of TGFβ superfamily members is associated with enhanced adenosine signaling and worse OS (HR = 0.43, P < 2.2e-16). Finally, adenosine signaling is associated with reduced efficacy of anti-PD1 therapy in published cohorts (HR = 0.29, P = 0.00012).These data support the adenosine pathway as a mediator of a successful antitumor immune response, demonstrate the prognostic potential of the signature for immunotherapy, and inform patient selection strategies for adenosine pathway modulators currently in development.
GTX-758, An Oral ERa Agonist, Increases Sex Hormone Binding Globulin, Reduces Free T and Decreases PSA in Patients with Castration Resistant Prostate Cancer
Authors: M.S. Steiner, R.P. Taylor, R.H. Getzenberg, M.A. Johnston, M. Hancock, J.T. Dalton
Journal: Annals of Oncology (2012)