tbuckley/cabot-search huggingface dataset:
Association of Modifiable Lifestyle Factors With Cortical Amyloid Burden and Cerebral Glucose Metabolism in Older Adults With Mild Cognitive Impairment
Authors: Noriyuki Kimura, Yasuhiro Aso, Kenichi Yabuuchi, Masato Ishibashi, Daiji Hori, Yuuki Sasaki, Atsuhito Nakamichi, Souhei Uesugi, Mika Jikumaru, Kaori Sumi, Atsuko Eguchi, Hitoshi Obara, Tatsuyuki Kakuma, Etsuro Matsubara
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Understanding the association of lifestyle factors with mild cognitive impairment enables the development of evidence-based interventions for delaying cognitive impairment. <h3>Objective</h3> To explore whether objectively measured lifestyle factors, such as physical activity, conversation, and sleep, are associated with cortical amyloid burden and cerebral glucose metabolism in older adults with mild cognitive impairment. <h3>Design, Setting, and Participants</h3> This cohort study included 855 community-dwelling adults in Usuki, Oita Prefecture, Japan, aged 65 years or older. Data were collected from August 2015 to December 2017. Participants were reviewed to examine risk and protective lifestyle factors for dementia. Data analysis was conducted in June 2019. <h3>Exposures</h3> Wearable sensors, carbon-11 labeled Pittsburgh compound B positron emission tomography images, and fluorine-18 fluorodeoxyglucose positron emission tomography images. <h3>Main Outcomes and Measures</h3> Wearable sensor data, such as walking steps, conversation time, and sleep, were collected from August 2015 to October 2017, and positron emission tomography images were collected from October 2015 to December 2017. A multiple regression model and change-point regression model were used to examine the association of lifestyle factors with mean amyloid or fluorodeoxyglucose uptake, assessed on the basis of a standardized uptake value ratio of the frontal lobes, temporoparietal lobes, and posterior cingulate gyrus with the cerebellar cortex as the reference region. The bootstrap method was used to obtain nonparametric 95% CIs on the associations of lifestyle factors with cognitive decline. <h3>Results</h3> Of the 855 adults in the study, 118 (13.8%) were diagnosed with mild cognitive impairment, with a mean (SD) age of 75.7 (5.8) years and 66 (55.9%) women. Total sleep time was inversely associated with fluorodeoxyglucose uptake after adjusting for covariates (β = −0.287; 95% CI, −0.452 to −0.121,<i>P</i> &lt; .001). Change-point regression showed an inverse association between total sleep time and mean amyloid uptake when sleep duration was longer than 325 minutes (B = −0.0018; 95% CI, −0.0031 to −0.0007). <h3>Conclusions and Relevance</h3> To our knowledge, this is the first study to demonstrate that total sleep time was associated with brain function in older adults with mild cognitive impairment. Sleep duration is a potentially modifiable risk factor for dementia at the mild cognitive impairment stage.
長期宇宙飛行後に宇宙飛行士で観察される視神経乳頭浮腫,眼球の平坦化,脈絡膜ひだ,及び遠視への変化 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: H Mader Thomas, Gibson C. Robert, Tran Duc, Lipsky William, Choi Jung, F Pass Anastas, A Kramer Larry, G Lee Andrew, Fogarty Jennifer, J Tarver William, P Dervay Joseph, D Polk James, R Hamilton Douglas, Sargsyan Ashot, L Phillips John, Stern Claudia, Kuyumjian Raffi
Journal: Ophthalmology (2011)
The looming threat of bedaquiline resistance in tuberculosis
Authors: Chen-Yuan Chiang, Arnaud Trébucq, Alberto Piubello, Hans L. Rieder, Valérie Schwoebel, Armand Van Deun
Journal: European Respiratory Journal (2020)

<b>The first step to reduce the risk of creating an epidemic of bedaquiline-resistant TB entails addressing the lack of access to rapid fluoroquinolone drug susceptibility testing in a high proportion of MDR-/RR-TB in low- and middle-income countries</b>https://bit.ly/2KbtyZ3
Abstract P132: Cardiorespiratory Fitness Has Declined in Individuals Joining a Self-referred Exercise Program Over the Past 45 Years
Authors: Matthew P Harber, Alexander H Montoye, Mitchell H Whaley, Leonard A Kaminsky
Journal: Circulation (2016)

Introduction: Cardiorespiratory fitness (CRF) has emerged as a strong predictor of cardiovascular disease (CVD) and all-cause mortality; however, there are limited data to describe population trends in CRF over time. Thus, the purpose of this investigation was to examine changes in objectively measured CRF over the past four decades. We hypothesized that CRF would be progressively lower, by decade, from 1970 to 2015. Methods: We retrospectively examined 3238 individuals who were tested at enrollment into a self-referred university based exercise program. All participants underwent a CVD risk assessment (including measures of blood pressure, blood lipids, and anthropometrics) and a maximal cardiopulmonary exercise treadmill test with measured CRF (i.e., VO2max). Differences in CRF and risk factor variables were analyzed by sex (n=1467 female, n=1771 male) and group based on when testing was conducted (Group A: 1970-1984, n=872; B: 1985-1994, n=1154; C: 1995-2004, n=670; D: 2005-2015, n=542) using a 2x4 factorial analysis of variance. Results: Mean age of participants was higher (P&lt;0.05) in successive cohorts after group B, regardless of sex (41.1±0.3, 41.7±0.3, 45.4±0.5, 47.1±0.6 years for A, B, C, D, respectively). CRF was lower (P&lt;0.05) in successive cohorts after group B for both men (38.1±0.4, 38.0±0.4, 34.8±0.6, 32.8±0.7 ml/kg/min for A, B, C, D, respectively) and women (28.8±0.4, 29.1±0.4, 26.9±0.4, 25.1±0.5 ml/kg/min for A, B, C, D, respectively). Differences in CRF persisted after controlling for age, body weight, and BMI. BMI increased (P&lt;0.05) with each successive cohort up to C for men (25.8±0.2, 27.4±0.2, 29.3±0.3, 29.3±0.3 kg/m2 for A, B, C, D, respectively) and women (24.9±30.3, 25.7±0.2, 27.9±0.3, 29.0±0.4 kg/m2 for A, B, C, D, respectively) and the increase was greater (P&lt;0.05) in women. Resting diastolic blood pressure was lower (P&lt;0.05) with each successive cohort after B (80.1±0.3, 79.5±0.3, 77.8±0.4, 75.6±0.4 mmHg for A, B, C, D, respectively) regardless of sex while no differences were noted for systolic blood pressure. Total cholesterol decreased (P&lt;0.05) with each successive cohort for men (221±2, 211±2, 205±2, 185±2 mg/dl for A, B, C, D, respectively) and women (210±2, 197±2, 199±2, 196±2 mg/dl for A, B, C, D, respectively) with the decrease being greater (P&lt;0.05) in men. Resting heart rate was higher (P&lt;0.05) in cohort D compared to A, B, C in men only (65±1, 68±1, 67±1, 71±1 bpm for A, B, C, D, respectively). Conclusion: Over the past 20 years, adults making the decision to begin an exercise program are doing so at a later age and with a markedly lower CRF (&gt;1.5 METs) than 20-45 years ago. The change in CRF is not fully explained by increasing obesity trends. These data suggest that greater emphasis be given in exercise prescriptions to aggressively improve CRF.
A dynamic relationship between two regional causes of IgE-mediated anaphylaxis: α-Gal syndrome and imported fire ant
Authors: Jeffrey M. Wilson, Behnam Keshavarz, Maya Retterer, Lisa J. Workman, Alexander J. Schuyler, Emily C. McGowan, Charles Lane, Alaaddin Kandeel, Jane Purser, Eva Rönmark, Joseph LaRussa, Scott P. Commins, Tina Merritt, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2020)
Abstract 13579: Sex and Racial Differences in Acute Myocardial Infarction Treatment and Outcomes
Authors: Erica N Schorr, Bradly Watarai, Stephanie Jarosek
Journal: Circulation (2019)

Introduction: Coronary heart disease treatment has been shown to vary according to race, with large black-white disparities observed after an acute hospitalization. This study used a nationally rep...
Sacubitril/Valsartan in Advanced Heart Failure With Reduced Ejection Fraction
Authors: Douglas L. Mann, Stephen J. Greene, Michael M. Givertz, Justin M. Vader, Randall C. Starling, Andrew P. Ambrosy, Palak Shah, Steven E. McNulty, Claudius Mahr, Divya Gupta, Margaret M. Redfield, Anuradha Lala, Gregory D. Lewis, Selma F. Mohammed, Nisha A. Gilotra, Adam D. DeVore, Eiran Z. Gorodeski, Patrice Desvigne-Nickens, Adrian F. Hernandez, Eugene Braunwald
Journal: JACC Heart Failure (2020)
Abstract A38: A critical role of Wnt5a-Axin2 axis in small-cell lung cancer development
Authors: Kee-Beom Kim, Dong-Wook Kim, Youngchul Kim, Jae-Il Park, Kwon-Sik Park
Journal: Cancer Research (2020)

Abstract The paucity of readily actionable alterations in the small-cell lung cancer (SCLC) genome necessitates exploration of alternative targets for clinical intervention, including reactivated developmental signaling pathways. Despite the widespread implication of deregulated WNT signaling in cancer, its role in the pathogenesis of SCLC remains unknown. In this study, we observe selective induction of Axin2, a target of WNT pathway, and its genetic reporter in the lung tumors developed in genetically engineered mouse models (GEMM) of SCLC. Intriguingly, however, other transcription targets of b-catenin-dependent “canonical” pathway are downregulated in tumors relative to normal lung, and knockout of Ctnnb1 encoding b-catenin does not affect tumor development in the GEMM. On the other hand, Axin2 knockout, which enhances b-catenin level, suppresses the tumor development. These findings suggest not only the dispensability of b-catenin-dependent pathway but also the significant role of Axin2 in SCLC. Meanwhile, we observe that tumors and cell lines express significantly higher levels of ligands for b-catenin-independent “noncanonical” pathway, including Wnt5a, than precancerous cells (preSC) as well as whole lung. Ectopic Wnt5a in preSC enhances cell proliferation in culture and tumorigenic capacity in athymic nude mice while increasing Axin2 expression. Depletion of Wnt5a suppresses cell proliferation and tumor development. Taken together, these results suggest a critical role of the Wnt5a-Axin2 axis in SCLC development. Citation Format: Kee-Beom Kim, Dong-Wook Kim, Youngchul Kim, Jae-Il Park, Kwon-Sik Park. A critical role of Wnt5a-Axin2 axis in small-cell lung cancer development [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A38.
Abstract A27: Heterotypic 3D bioprinted tissues to interrogate tumor-microenvironment crosstalk in cancer
Authors: Ellen M. Langer, Isabel A. English, Megan A. Turnidge, Zinab O. Doha, Rosalie C. Sears
Journal: Cancer Research (2020)

Abstract The tumor microenvironment is composed of multiple cell types (e.g., fibroblast, vascular, and immune cells), extracellular matrix (ECM) proteins, and signaling molecules that critically influence tumor cell phenotypes. The study of isolated tumor cells in culture has contributed to the discovery of oncogenes and tumor suppressors that regulate oncogenic phenotypes. As tumors develop, however, cancer cells secrete factors that functionally reprogram the genetically “normal” stromal cells in their environment. These tumor-associated stromal cells then further alter the microenvironment, providing tumor-stromal cell and tumor-ECM interactions that critically regulate tumor behaviors such as early tumor initiation, metastatic progression, and response to therapies. We recently developed heterotypic, scaffold-free tissue models of advanced cancer using an extrusion-based bioprinter system. Multiple cell types including cancer cells, fibroblasts, bone marrow-derived mesenchymal stem cells, and endothelial cells can be incorporated into bioprinted tissues with defined architecture. We found that cells within these structures exhibit a tissue-like cellular density, proliferate, deposit ECM, migrate, and respond to extrinsic signals. Cells within these tissues self-organize to form complex structures, as indicated by nascent endothelial networks, and respond to extrinsic signals. We assessed intrinsic, extrinsic, and spatial tumorigenic phenotypes including cell survival, cell proliferation, differentiation state, ECM deposition, and cellular migration within these tissues in response to extrinsic signals or therapies. Together, this work demonstrates that bioprinted tumor tissue models recapitulate many aspects of in vivo neoplastic tissues. We are continuing to use 3D bioprinted tumor tissues, leveraging the manipulable nature of these models to interrogate the role of distinct tumor microenvironments on tumor cell phenotypes including proliferation, migration, and response to therapies. In pancreatic cancer models, we have printed tissues containing pancreatic stellate cells with and without knockdown of the prolyl isomerase PIN1, which we show inhibits stellate cell activation. We show that loss of PIN1 in the stellate cells surrounding the tumor has effects not only on activation markers of fibroblasts, but also on tumor, endothelial, and immune phenotypes within the tissues. Further work is focused on characterizing the signals that drive these changes. Citation Format: Ellen M. Langer, Isabel A. English, Megan A. Turnidge, Zinab O. Doha, Rosalie C. Sears. Heterotypic 3D bioprinted tissues to interrogate tumor-microenvironment crosstalk in cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A27.
COVID-19, Health, Conservation, and Shared Wellbeing: Details Matter
Authors: Robert A. Montgomery, David W. Macdonald
Journal: Trends in Ecology & Evolution (2020)

Many have stridently recommended banning markets like the one where coronavirus disease 2019 (COVID-19) originally spread. We highlight that millions of people around the world depend on markets for subsistence and the diverse use of animals globally defies uniform bans. We argue that the immediate and fair priority is critical scrutiny of wildlife trade.
COVID-19
Authors: Partha Sinha, Shyamashree Sinha, Evemarie Schlehr, James M. Schlehr
Journal: Clinical Nuclear Medicine (2020)

Abstract A 73-year-old man with chronic obstructive pulmonary disease and no known malignancies was evaluated for back pain. MR examination showed lumbar spine compression fractures, and an 18 F-FDG PET/CT scan was requested to assess for skeletal metastatic disease and potential detection of a primary neoplasm. The PET/CT examination revealed scattered FDG-avid pulmonary opacities with upper lobe preponderance highly suspicious for COVID-19. Real-time polymerase chain reaction testing of nasopharyngeal swabs confirmed the diagnosis.
FRI0022 THE ANALYSIS OF THE INVOLVEMENT OF TRANSFORMING-GROWTH INTERACTING FACTOR POLYMORPHISMS IN THE BONE METABOLISM OF RHEUMATOID ARTHRITIS
Authors: H. Tan, L. Zhang, B. Yang, L. Zhou
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is an autoimmune disease that mainly invades synovial membranes and further damage to articular cartilage and bone. The abnormal activation of transforming-growth factor β (TGF-β) in the subchondral bone is related to the onset of RA joint cartilage degeneration and transforming-growth interacting factor (TGIF) is a negative regulator of TGF-β signaling, while there is no literature addressing the relationship between TGIF polymorphisms and the bone metabolism of RA. Objectives: The aim of the study was to comprehensively explore the possible association for single nucleotide polymorphisms (SNPs) in the TGIF gene with serum bone metabolism markers and RA susceptibility. Methods: Three SNPs within the TGIF gene were genotyped in 155 RA patients and 168 healthy controls by high resolution melting (HRM) analysis in a case-control study. The serum levels of osteocalcin, bone alkaline phosphatase (BALP) and β type I collagen-crosslinked C telopeptide (β-CTX) were detected by electrochemical luminescence in 108 RA patients randomly selected from RA patients group. Results: Genotypes and alleles frequency analysis showed rs7362020 was associated with bone erosion in RA (P=0.012, P=0.003, respectively) and individuals carrying T allele for rs7362020 showed a decreased RA risk (OR=0.59, 95% CI = 0.42-0.84; P= 0.003). In the gender-specific analysis, rs73620203 polymorphism was associated with bone erosion of female RA patients (P values of the distribution of genotypes and alleles were 0.022 and 0.006, respectively). In addition, RA patients with CC, CT and TT genotypes at rs73620203 locus had statistically significant differences in serum osteocalcin and BALP (P=0.006, P=0.037, respectively) and the serum levels in TT genotype RA patients were significantly lower than CC and CT genotype RA patients. The serum levels of β-CTX in rs85440 AA genotype male RA patients were significantly higher than female RA patients (P=0.001), while the serum levels of osteocalcin and BALP in genotype AA, AG and GG female and male RA patients were not significantly different (P all&gt;0.05). Conclusion: Our study provided the first evidence that rs73620203 is associated with bone erosion of RA and provided new insight into the relationship between three SNPs within TGIF gene and regulation of bone metabolism in RA patients of different genders. Acknowledgments: This work was supported by the National Natural Science Foundation of China (Nos. 81772258) and Science and Technology Agency of Sichuan Province (Nos. 2019YFS0310, 2018FZ0106). Disclosure of Interests: None declared
Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies
Authors: Devikala Gurusamy, Amanda N. Henning, Tori N. Yamamoto, Zhiya Yu, Nikolaos Zacharakis, Sri Krishna, Rigel J. Kishton, Suman K. Vodnala, Arash Eidizadeh, Li Jia, Christine M. Kariya, Mary A. Black, Robert Eil, Douglas C. Palmer, Jenny H. Pan, Madhusudhanan Sukumar, Shashank J. Patel, Nicholas P. Restifo
Journal: Cancer Cell (2020)
Cavernosal Metastasis From Prostate Cancer on 18F-Fluciclovine PET/CT
Authors: Ba D. Nguyen
Journal: Clinical Nuclear Medicine (2020)

Abstract Uncommon penile metastasis from prostate cancer has been reported on PET/CT imaging with 18 F-FDG, 18 F-fluorocholine, 11 C-choline, and 68 Ga-PSMA. The author presents an additional case of 18 F-fluciclovine PET/CT depiction of proximal and distal cavernosal metastases from prostate cancer with corresponding contrast-enhanced CT findings.
The Lymphatic Cell Environment Promotes Kaposi Sarcoma Development by Prox1-Enhanced Productive Lytic Replication of Kaposi Sarcoma Herpes Virus
Authors: Dongwon Choi, Eunkyung Park, Kyu Eui Kim, Eunson Jung, Young Jin Seong, Luping Zhao, Shrimika Madhavan, George Daghlian, Hansuh H. Lee, Patill T. Daghlian, Saren Daghlian, Khoa Bui, Chester J. Koh, Alex K. Wong, Il-Taeg Cho, Young-Kwon Hong
Journal: Cancer Research (2020)

Kaposi sarcoma is the most common cancer in human immunodeficiency virus-positive individuals and is caused by Kaposi sarcoma-associated herpesvirus (KSHV). It is believed that a small number of latently infected Kaposi sarcoma tumor cells undergo spontaneous lytic reactivation to produce viral progeny for infection of new cells. Here, we use matched donor-derived human dermal blood and lymphatic endothelial cells (BEC and LEC, respectively) to show that KSHV-infected BECs progressively lose viral genome as they proliferate. In sharp contrast, KSHV-infected LECs predominantly entered lytic replication, underwent cell lysis, and released new virus. Continuous lytic cell lysis and de novo infection allowed LEC culture to remain infected for a prolonged time. Because of the strong propensity of LECs toward lytic replication, LECs maintained virus as a population, despite the death of individual host cells from lytic lysis. The master regulator of lymphatic development, Prox1, bound the promoter of the RTA gene to upregulate its expression and physically interacted with RTA protein to coregulate lytic genes. Thus, LECs may serve as a proficient viral reservoir that provides viral progeny for continuous de novo infection of tumor origin cells, and potentially BECs and mesenchymal stem cells, which give rise to Kaposi sarcoma tumors. Our study reveals drastically different host cell behaviors between BEC and LEC and defines the underlying mechanisms of the lymphatic cell environment supporting persistent infection in Kaposi sarcoma tumors. SIGNIFICANCE: This study defines the mechanism by which Kaposi's sarcoma could be maintained by virus constantly produced by lymphatic cells in HIV-positive individuals.
Response assessment in diffuse intrinsic pontine glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group
Authors: Tabitha M Cooney, Kenneth J Cohen, Carolina V Guimaraes, Girish Dhall, James Leach, Maura Massimino, Alessandra Erbetta, Luisa Chiapparini, Fatema Malbari, Kim Kramer, Ian F Pollack, Patricia Baxter, Suzanne Laughlin, Zoltán Patay, Tina Young Poussaint, Katherine E Warren
Journal: The Lancet Oncology (2020)
Response by Ma et al to Letter Regarding Article, “miRNA-Mediated Suppression of a Cardioprotective Cardiokine As a Novel Mechanism Exacerbating Post-MI Remodeling by Sleep Breathing Disorders”
Authors: Xin-Liang Ma, Yunhui Du, Yajing Wang, Wayne Bond Lau, Xiao Wang, Shaoping Nie, Yongxiang Wei
Journal: Circulation Research (2020)
Early tumor shrinkage identifies long-term disease control and survival in patients with lung cancer treated with atezolizumab
Authors: Ashley M Hopkins, Ganessan Kichenadasse, Chris S Karapetis, Andrew Rowland, Michael J Sorich
Journal: Journal for ImmunoTherapy of Cancer (2020)

Preliminary evidence indicates that early tumor shrinkage (ETS) following immune checkpoint inhibitor (ICI) initiation may be associated with survival outcomes in patients with advanced melanoma. ETS has not been explored as a biomarker of survival outcomes or patient-reported outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs.The study pooled data from patients with NSCLC in the randomized trials OAK and POPLAR (atezolizumab vs docetaxel; n=1464), and single-arm atezolizumab trials BIRCH and FIR (n=797). The association between ETS (≥10% decrease in pretreatment sum-of-longest diameters of target-lesions at 6 weeks) and overall survival (OS), progression-free survival (PFS), time to deterioration (TDD) in health-related quality-of-life (HRQoL) and physical function (PF) was assessed using Cox proportional hazard analysis.ETS occurred in 20% of atezolizumab-treated patients with NSCLC within OAK and POPLAR and was associated with highly favorable OS (HR 0.33, p<0.001), PFS (HR 0.31, p<0.001), TDD in HRQoL (HR 0.73, p=0.01) and PF (HR 0.52, p<0.001). The results were replicated in the BIRCH and FIR data. Atezolizumab-treated patients achieving ETS had markedly improved OS compared with docetaxel-treated patients achieving ETS (24-month OS 55% vs 32%); PFS was also markedly improved (24-month PFS 31% vs 4%). In contrast, for patients not achieving ETS, atezolizumab-treatment was associated with more modest OS (24-month OS 23% vs 20%) and PFS (24-month PFS 3% vs 1%) improvement compared with docetaxel. Overall, the effect size for ETS within the atezolizumab-treated patients was significantly greater than that in the docetaxel-treated patients (P(interaction)=0.002 for OS and P(interaction)<0.001 for PFS).ETS is an easily measurable biomarker, predictive of highly favorable survival and patient-reported outcomes with atezolizumab treatment for advanced NSCLC. Further, ETS identifies patients with significantly greater treatment benefit for ICI therapy.