tbuckley/cabot-search huggingface dataset:
Association of Long-term Strenuous Physical Activity and Extensive Sitting With Incident Radiographic Knee Osteoarthritis
Authors: Alison H. Chang, Jungwha (Julia) Lee, Joan S. Chmiel, Orit Almagor, Jing Song, Leena Sharma
Journal: JAMA Network Open (2020)

Persons with knee symptoms recognize the health benefits of engaging in physical activity, but uncertainty persists about whether regular strenuous physical activity or exercise can accelerate tissue damage. A sedentary lifestyle of inactivity or underloading may also be associated with deleterious joint health.To establish whether long-term strenuous physical activity participation and extensive sitting behavior are each associated with increased risk of developing radiographic knee osteoarthritis (KOA) in individuals at high risk for the disease.This cohort study analyzed data from the Osteoarthritis Initiative, a prospective longitudinal cohort study of men and women with or at an increased risk of developing symptomatic, radiographic KOA. Community-dwelling adults were recruited from 4 US sites (Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island) and were followed up for up to 10 years. Individuals were included if they had a baseline Kellgren and Lawrence grade of 0 in both knees and completed a PASE (Physical Activity Scale for the Elderly) questionnaire at baseline and at least 2 follow-up visits over an 8-year interval. Data analyses were conducted from May 2018 to November 2018.Baseline to 8-year trajectories of strenuous physical activity participation and extensive sitting behavior were identified using group-based trajectory models.Incident radiographic KOA, defined as Kellgren and Lawrence grade 2 or higher in either knee by the 10-year follow-up visit.A total of 1194 participants were included in the sample (697 women [58.4%]), with a baseline mean (SD) age of 58.4 (8.9) years and mean body mass index (BMI) of 26.8 (4.5). Four distinct trajectories of weekly hours spent in strenuous physical activities and 3 distinct trajectories of extensive sitting were identified. Long-term engagement in low-to-moderate physical activities (adjusted odds ratio [OR], 0.69; 95% CI, 0.48-1.01) or any strenuous physical activities (adjusted OR, 0.75; 95% CI, 0.53-1.07) was not associated with 10-year incident radiographic KOA. Persistent extensive sitting was not associated with incident KOA. Despite relatively mild symptoms and high function in this early-stage sample, 594 participants (49.7%) did not engage in any strenuous physical activities (ie, 0 h/wk) across 8 years, and 507 (42.5%) engaged in persistent moderate-to-high frequency of extensive sitting. Older age, higher BMI, more severe knee pain, non-college graduate educational level, weaker quadriceps, and depression were each associated with a persistent lack of engagement in strenuous physical activities.Results from this study appeared to show no association between long-term strenuous physical activity participation and incident radiographic KOA. The findings raise the possibility of a protective association between incident KOA and a low-to-moderate level of strenuous physical activities.
The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in mice
Authors: Michaela Kuhn, Katharina Völker, Kristine Schwarz, Javier Carbajo-Lozoya, Ulrich Flögel, Christoph Jacoby, Jörg Stypmann, Martin van Eickels, Stepan Gambaryan, Michael Hartmann, Matthias Werner, Thomas Wieland, Jürgen Schrader, Hideo A. Baba
Journal: Journal of Clinical Investigation (2009)

Cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) modulate blood pressure and volume by activation of the receptor guanylyl cyclase-A (GC-A) and subsequent intracellular cGMP formation. Here we report what we believe to be a novel function of these peptides as paracrine regulators of vascular regeneration. In mice with systemic deletion of the GC-A gene, vascular regeneration in response to critical hind limb ischemia was severely impaired. Similar attenuation of ischemic angiogenesis was observed in mice with conditional, endothelial cell-restricted GC-A deletion (here termed EC GC-A KO mice). In contrast, smooth muscle cell-restricted GC-A ablation did not affect ischemic neovascularization. Immunohistochemistry and RT-PCR revealed BNP expression in activated satellite cells within the ischemic muscle, suggesting that local BNP elicits protective endothelial effects. Since within the heart, BNP is mainly induced in cardiomyocytes by mechanical load, we investigated whether the natriuretic peptide/GC-A system also regulates angiogenesis accompanying load-induced cardiac hypertrophy. EC GC-A KO hearts showed diminished angiogenesis, mild fibrosis, and diastolic dysfunction. In vitro BNP/GC-A stimulated proliferation and migration of cultured microvascular endothelia by activating cGMP-dependent protein kinase I and phosphorylating vasodilator-stimulated phosphoprotein and p38 MAPK. We therefore conclude that BNP, produced by activated satellite cells within ischemic skeletal muscle or by cardiomyocytes in response to pressure load, regulates the regeneration of neighboring endothelia via GC-A. This paracrine communication might be critically involved in coordinating muscle regeneration/hypertrophy and angiogenesis.
PWE-097 Pharmacological treatments for primary sclerosing cholangitis: a network meta-analysis
Authors: K Gurusamy, F Saffioti, C Toon, B Davidson, E Tsochatzis, D Thorburn
Journal: Gut (2015)

<h3>Introduction</h3> The optimal pharmaceutical treatment of primary sclerosing cholangitis (PSC) remains controversial. We performed a systematic review and network meta-analysis of different pharmacological interventions for the treatment of patients with PSC. <h3>Method</h3> We included randomised controlled trials (RCTs) of various pharmacological interventions compared with each other or with placebo in patients with PSC. We conducted network meta-analyses following the National Institute for Health and Care Excellence Decision Support Unit guidance to compare multiple interventions simultaneously for each of the primary (mortality, adverse events, health-related quality of life (HRQoL)) and secondary outcomes (decompensated cirrhosis, liver transplantation, malignancies) and only included trials in which participants could receive any of the interventions being assessed (transitivity assumption). We conducted a Bayesian network meta-analysis and calculated the odds ratios (OR), rate ratios, or hazard ratios with 95% credible intervals or Bayesian confidence intervals (CrI) for assessing the effect of treatment. We used three different non-informative priors and ensured that the results converged prior to calculation of posterior probabilities for Bayesian network meta-analysis. <h3>Results</h3> We included 22 RCTs on different treatment regimens for PSC, comprising of 1111 patients. There was no statistically significant difference in the mortality at 1-year, 5-years or at maximal follow-up between any of the treatments and placebo. There was no statistically significant difference in the proportion of patients with any adverse event, serious adverse events, liver decompensation, liver transplant, any malignancy, cholangiocarcinoma, or colorectal cancer at maximal follow-up or in the HRQoL between any of the treatments and placebo. Penicillamine was associated with higher number of total adverse events compared to placebo (rate ratio 1.93; 95% CrI 1.07 to 3.49) and to low-dose ursodeoxycholic acid (rate ratio 2.38; 95% CrI 1.02 to 5.56). There was no statistically significant difference in the total number of serious adverse events between any of the treatments and placebo. <h3>Conclusion</h3> None of the current therapies for primary sclerosing cholangitis are effective. <h3>Disclosure of interest</h3> K. Gurusamy: None Declared, F. Saffioti: None Declared, C. Toon: None Declared, B. Davidson: None Declared, E. Tsochatzis: None Declared, D. Thorburn Grant/Research Support from: Boston Scientific to fund a clinical research fellow.
Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy
Authors: Lisa J Frigati, Wole Ameyan, Mark F Cotton, Celia L Gregson, Jacqueline Hoare, Jennifer Jao, Edith D Majonga, Landon Myer, Martina Penazzato, Ruramayi Rukuni, Sarah Rowland-Jones, Heather J Zar, Rashida A Ferrand
Journal: The Lancet Child & Adolescent Health (2020)
Extraction of Distinct Neuronal Cell Types from within a Genetically Continuous Population
Authors: Euiseok J. Kim, Zhuzhu Zhang, Ling Huang, Tony Ito-Cole, Matthew W. Jacobs, Ashley L. Juavinett, Gokhan Senturk, Mo Hu, Manching Ku, Joseph R. Ecker, Edward M. Callaway
Journal: Neuron (2020)
FBXW7 Triggers Degradation of KMT2D to Favor Growth of Diffuse Large B-cell Lymphoma Cells
Authors: Rizwan Saffie, Nan Zhou, Delphine Rolland, Özlem Önder, Venkatesha Basrur, Sydney Campbell, Kathryn E. Wellen, Kojo S.J. Elenitoba-Johnson, Brian C. Capell, Luca Busino
Journal: Cancer Research (2020)

Abstract Mature B-cell neoplasms are the fifth most common neoplasm. Due to significant heterogeneity at the clinical and genetic levels, current therapies for these cancers fail to provide long-term cures. The clinical success of proteasome inhibition for the treatment of multiple myeloma and B-cell lymphomas has made the ubiquitin pathway an important emerging therapeutic target. In this study, we assessed the role of the E3 ligase FBXW7 in mature B-cell neoplasms. FBXW7 targeted the frequently inactivated tumor suppressor KMT2D for protein degradation, subsequently regulating gene expression signatures related to oxidative phosphorylation (OxPhos). Loss of FBXW7 inhibited diffuse large B-cell lymphoma cell growth and further sensitized cells to OxPhos inhibition. These data elucidate a novel mechanism of regulation of KMT2D levels by the ubiquitin pathway and uncover a role of FBXW7 in regulating oxidative phosphorylation in B-cell malignancies. Significance: These findings characterize FBXW7 as a prosurvival factor in B-cell lymphoma via degradation of the chromatin modifier KMT2D.
Retroviral Vector Integration Deregulates Gene Expression but Has No Consequences on the Biology and Function of Transplanted T Cells.
Authors: Alessandra Recchia, Chiara Bonini, Zulma Magnani, Fabrizia Urbinati, Daniela Sartori, Sara Muraro, Fabio Ciceri, Claudio Bordignon, Fulvio Mavilio
Journal: Blood (2005)
The many faces of obligation
Authors: Michael Tomasello
Journal: Behavioral and Brain Sciences (2020)

My response to the commentaries focuses on four issues: (1) the diversity both within and between cultures of the many different faces of obligation; (2) the possible evolutionary roots of the sense of obligation, including possible sources that I did not consider; (3) the possible ontogenetic roots of the sense of obligation, including especially children's understanding of groups from a third-party perspective (rather than through participation, as in my account); and (4) the relation between philosophical accounts of normative phenomena in general - which are pitched as not totally empirical - and empirical accounts such as my own. I have tried to distinguish comments that argue for extensions of the theory from those that represent genuine disagreement.
The need to research refractory breathlessness (Letter to the Editor)
Authors: David Currow, Amy Abernethy, Peter Allcroft, Robert Banzett, Claudia Bausewein, Sara Booth, Virginia Carrieri-Kohlman, Patricia M. Davidson, Rebecca Disler, Doranne Donesky, Deborah Dudgeon, Magnus Ekstrom, Morag Farquhar, Irene Higginson, Daisy Janssen, Dennis Jensen, Caroline Jolley, Malgorzata Krajnik, Pierantonio Laveneziana, Christine McDonald, Matthew Maddocks, Capucine Morelot-Panzini, John Moxham, Richard A. Mularski, Simon Noble, Denis O'Donnell, Mark B. Parshall, Kyle Pattinson, Jane Phillips, Joy Ross, Richard M. Schwartzstein, Thomas Similowski, Steffen T. Simon, Tracy A. Smith, Athol Wells, Patsy Yates, Janelle Yorke, Miriam J. Johnson
Journal: European Respiratory Journal (2016)

High-quality research is needed to improve quality of life for people with chronic refractory breathlessness in COPD http://ow.ly/Q2GDY
Efficacy of oral tegafur-uracil (UFT) as adjuvant therapy as compared with classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in early breast cancer: A pooled analysis of two randomized controlled trials (N-SAS-BC01 trial and CUBC trial)
Authors: Y. Ohashi, T. Watanabe, M. Sano, H. Koyama, H. Inaji, T. Suzuki
Journal: Journal of Clinical Oncology (2009)

578 Background: It has been reported that adjuvant oral UFT might be more effective in patients with estrogen receptor (ER)-positive breast cancer (Noguchi et al, J Clin Oncol 2005). 2 randomized clinical trials comparing the efficacy of oral UFT (2 years) with that of classical CMF (6 courses) have been conducted in patients with resected early breast cancer. One study was the N-SAS-BC01 trial (Watanabe et al, J Clin Oncol, in press), conducted in patients with node-negative, high-risk breast cancer. The other was the CUBC trial (Inaji et al, ASCO 2004), performed in patients with node-positive breast cancer. We have performed a pooled analysis of these two randomized trials. Methods: A pooled analysis was performed using individual patient data from the two randomized trials. Hazard ratios (HR) were determined with the Cox regression stratified by study and adjusted for the clinical characteristics of age, tumor size, nodal status, histological type, ER and PgR. The hypothesis was that UFT was noninferior to CMF in all patients or ER-positive patients in terms of relapse-free survival (RFS). Non-inferiority of UFT was concluded if the upper limit of two-sided CI for the HR of RFS did not exceed 1.30; the significance level of CI was determined by the Hochberg multiplicity adjustment (alpha=0.05:two sided). Results: A total of 1,057 patients were analyzed (CMF n=528, UFT n=529). Median follow-up time was 6 years. HR was 1.04 (95% CI: 0.78–1.40) for relapse in all patients and 0.79 (97.5% CI: 0.49–1.27) in ER-positive patients. The table shows HR for RFS according to ER status and age. Conclusions: UFT is noninferior to CMF in terms of inhibiting recurrence of ER-positive early breast cancer. In particular, UFT may be more effective in patients with ER-positive tumors who are 50 years or older. [Table: see text] [Table: see text]
Biodegradable Poly(γ-glutamic acid)@glucose oxidase@carbon dot nanoparticles for simultaneous multimodal imaging and synergetic cancer therapy
Authors: Ming Zhang, Wentao Wang, Fan Wu, Tao Zheng, Jon Ashley, Mohsen Mohammadniaei, Qicheng Zhang, Mingqian Wang, Li Li, Jian Shen, Yi Sun
Journal: Biomaterials (2020)
Sweat monitoring beneath garments using passive, wireless resonant sensors interfaced with laser-ablated microfluidics
Authors: Adam R. Carr, Yash H. Patel, Charles R. Neff, Sadaf Charkhabi, Nathaniel E. Kallmyer, Hector F. Angus, Nigel F. Reuel
Journal: npj Digital Medicine (2020)

Sweat loss can help determine hydration status of individuals working in harsh conditions, which is especially relevant to those who wear thick personal protective equipment (PPE) such as firefighters. A wireless, passive, conformable sweat sensor sticker is described here that can be worn under and interrogated through thick clothing to simultaneously measure sweat loss volume and conductivity. The sticker consists of a laser-ablated, microfluidic channel and a resonant sensor transducer. The resonant sensor is wirelessly read with a handheld vector network analyzer coupled to two, co-planar, interrogation antennas that measure the transmission loss. A sweat proxy is used to fill the channels and it is determined that the sensor can orthogonally determine the sweat conductivity and volume filled in the channel via peak transmission loss magnitude and frequency respectively. A four-person study is then used to determine level of sensor variance caused by local tissue dielectric heterogeneity and sensor-reader orientation.
Effect of signet-ring cell carcinoma histology on bladder cancer outcome.
Authors: J. Wang, F. Wang, C. A. Enke
Journal: Journal of Clinical Oncology (2011)

275 Background: Signet-ring cell carcinoma (SRCC) of the urinary bladder is a rare entity. Recent case series of the condition showed inconsistent results. We used a population-based data set to compare the cancer specific survival of patients with signet-ring cell carcinoma vs. transitional cell carcinoma (TCC) of the urinary bladder. Methods: Signet-ring cell carcinoma of the urinary bladder and transitional carcinoma of the urinary bladder were identified in the Surveillance, Epidemiology and End Results program (2001 to 2004). Demographic and pathological characteristics at diagnosis were compared. Differences in cancer specific survival were compared with univariate and multivariate Cox regression analysis. Results: A total of 103 SRCC cases were present in the database from 2001 to 2004. In that time 14,648 cases TCC cases were diagnosed. SRCC was more common in younger than in older patients (p &lt;0.001); more commonly presented with high grade histology (p &lt;0.001) and advanced stage disease (p &lt;0.001). The 3-year cancer specific survival rate was 67.0% and 33.2% for TCC and SRCC, respectively. On multivariate analysis there was an increased mortality risk in patients with SRCC vs TCC (HR 1.42, 95% CI 1.03–1.97, p &lt;0.001). When only high grade cases of SRCC and TCC were compared, the risk was still worse in SRCC (HR 1.430, 95% CI 1.035–1.976, 0.03). When only local stage of SRCC and TCC were compared, the risk was worse in SRCC (HR 4.294, 95% CI 1.035–17.825, 0.045). Limited to patient who underwent cystectomy only, the difference in cancer specific survival disappeared (HR 1.289, 95% CI 0.771–2.155, 0.33). Conclusions: Even after adjusting for demographic, pathological and treatment factors, cancer specific survival is significantly worse in patients with SRCC than TCC. Further research into the biology of this rare tumor is required to explain these results. No significant financial relationships to disclose.
Insulin-stimulated lipogenesis gets an epigenetic makeover
Authors: Clarence R. Manuel, Rebecca A. Haeusler
Journal: Journal of Clinical Investigation (2020)

Hepatic de novo lipogenesis is a major contributor to nonalcoholic fatty liver disease (NAFLD). In this issue of the JCI, Liu and Lin et al. identified Slug as an epigenetic regulator of lipogenesis. Their findings suggest that Slug is stabilized by insulin signaling, and that it promotes lipogenesis by recruiting the histone demethylase Lsd1 to the fatty acid synthase gene promoter. On the other hand, genetic deletion or acute depletion of Slug, or Lsd1 inhibition, reduced lipogenesis and protected against obesity-associated NAFLD and insulin resistance in mice. This study advances our understanding of how lipogenesis is regulated downstream of insulin signaling in health and disease.
TCTAP A-104 Randomized Comparison of Vascular Healing Response Between Self-Expanding Nitinol Stent and Self-Expanding Paclitaxel-Eluting Stent in the Superficial Femoral Artery: An Optical Frequency Domain Imaging Study
Authors: Kojiro Miki, Kenichi Fujii, Masashi Fukunaga, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2015)
Impact of checkpoint blockade on cancer vaccine–activated CD8+ T cell responses
Authors: Patricia M. Santos, Juraj Adamik, Timothy R. Howes, Samuel Du, Lazar Vujanovic, Sarah Warren, Andrea Gambotto, John M. Kirkwood, Lisa H. Butterfield
Journal: The Journal of Experimental Medicine (2020)

Immune and molecular profiling of CD8 T cells of patients receiving DC vaccines expressing three full-length melanoma antigens (MAs) was performed. Antigen expression levels in DCs had no significant impact on T cell or clinical responses. Patients who received checkpoint blockade before DC vaccination had higher baseline MA-specific CD8 T cell responses but no evidence for improved functional responses to the vaccine. Patients who showed the best clinical responses had low PD-1 expression on MA-specific T cells before and after DC vaccination; however, blockade of PD-1 during antigen presentation by DC had minimal functional impact on PD-1high MA-specific T cells. Gene and protein expression analyses in lymphocytes and tumor samples identified critical immunoregulatory pathways, including CTLA-4 and PD-1. High immune checkpoint gene expression networks correlated with inferior clinical outcomes. Soluble serum PD-L2 showed suggestive positive association with improved outcome. These findings show that checkpoint molecular pathways are critical for vaccine outcomes and suggest specific sequencing of vaccine combinations.
Reporting of Immune Checkpoint Inhibitor Therapy–Associated Diabetes, 2015–2019
Authors: Jiaqing Liu, Huaqiang Zhou, Yaxiong Zhang, Wenfeng Fang, Yunpeng Yang, Yan Huang, Li Zhang
Journal: Diabetes Care (2020)

Immune checkpoint inhibitors (ICIs), including cytotoxic T cell–associated protein-4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1) inhibitors, and programmed death-ligand 1 (PD-L1) inhibitors, have greatly improved the clinical outcomes of cancer patients (1). However, immune-related adverse effects involving various organs, including endocrine organs, can occur during ICI therapy (2). Cases of diabetes associated with ICI therapy have also been reported, which can be life-threatening (3–5). However, the incidence and characteristics of ICI-associated diabetes mellitus (ICI-DM) remain unclear. Therefore, we conducted a retrospective study with data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a pharmacovigilance database, to investigate this issue (6).

We used the FAERS to identify all reported cases of new-onset diabetes that were associated with ICIs approved by the FDA (i.e., ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and cemiplimab) between 1 January 2015 and 31 December 2019. Patients with new-onset type 1 diabetes, fulminant type 1 diabetes, diabetic ketoacidosis (DKA), or diabetic ketosis secondary to ICI therapy were considered to have ICI-DM. Those with DKA or diabetic ketosis secondary to type 2 diabetes or diabetes without detailed subtypes were excluded. We then used the χ …
Epidermal growth factor receptor–dependent DNA repair promotes murine and human hematopoietic regeneration
Authors: Tiancheng Fang, Yurun Zhang, Vivian Y. Chang, Martina Roos, Christina M. Termini, Lia Signaevskaia, Mamle Quarmyne, Paulina K. Lin, Amara Pang, Jenny Kan, Xiao Yan, Anna Javier, Katherine Pohl, Liman Zhao, Peter Scott, Heather A. Himburg, John P. Chute
Journal: Blood (2020)
Science Has Not Proven That Screen Use Impacts Children's Brain Development—Reply
Authors: John S. Hutton, Jonathan Dudley, Tzipi Horowitz-Kraus
Journal: JAMA Pediatrics (2020)

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