tbuckley/cabot-search huggingface dataset:
Abstract P070: Risk of All-cause Mortality in Women versus Men With Type 2 Diabetes: A Systematic Review and Meta-analysis
Authors: Jiaying Xu, Guodong Xu, Donghui Duan, Jinshun Zhao, Lina Zhang, Liyuan Han
Journal: Circulation (2018)

Introduction: Previous studies have shown sex differences in the all cause mortality rate associated with type 2 diabetes. Hypothesis: We did a meta-analysis to provide reliable and comprehensive estimates of type 2 diabetes on risk of all-cause mortality in women versus men. Methods: We systematically searched PubMed, Embase, and Web of science for studies published from their starting dates to October 10, 2017. Studies were selected only if they reported sex-specific estimates of the standardized mortality ratio (SMR) or hazard ratios associated with type 2 diabetes for all-cause mortality. We used random effects meta-analyses with inverse-variance weighting to obtain sex-specific SMRs and their pooled ratio (women to men) for all-cause mortality. Study quality was assessed using the Newcastle–Ottawa scale. Results: Data from 30 studies including 2,307,694 individuals and 252,491 deaths occurred were included. The pooled women-to-men ratio of the SMR for all-cause mortality was 1·14 (95% CI 1.09-1.19, p&lt;0.001; I 2 =81.6%). Compared with healthy counterparts, the pooled SMR for all-cause mortality in patients with T2D was 2.30(95%CI 1.97-2.68) in women, and 1.94(95%CI 1.73-2.18) in men, respectively. Sensitivity analysis with omission of one study at a time did not change the results of this meta-analysis. Conclusions: Women with type 2 diabetes have a roughly 14% greater excess risk of all-cause mortality compared with men counterparts. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Prospero) ( http://www.crd.york.ac.uk/PROSPERO ; registration number: CRD42017074187). Figure 1 .Pooled women-to-men ratios of SMRs for all-cause mortality, comparing people with type 2 diabetes versus healthy counterparts.
Lower Cancer Incidence—Warfarin Effect or Immortal Time Bias?—Reply
Authors: Gry S. Haaland, Ragnhild S. Falk, James B. Lorens
Journal: JAMA Internal Medicine (2018)

In Reply Svendsen et al and Li et al suggest that the methods used in our Original Investigation1 misallocate person-time and may be biased by residual immortal time. This is due to a misinterpretation of our defintion of a warfarin user.
Abstract O.16: Comprehensive Genotyping Of The FCGR2/3 Locus Reveals A Novel Association Of FCGR2C-ORF With Susceptibility To Kawasaki Disease
Authors: Taco W Kuijpers, Carline E Tacke, Sietse Q Nagelkerke, Willemijn B Breunis, Long T Hoang, Eileen Png, Judy Geissler, Michael W Tanck, Justine A Ellis, Anne L Ponsonby, Sonia Davila, Chiea C Khor, Martin de Boer, Joris van der Heijden, Karin Fijnvandraat, E. van der Schoot, Timo K van den Berg, Rae S Yeung, Michael L Levin, David Burgner, Chisato Shimizu, Jane C Burns, Martin L Hibberd
Journal: Circulation (2015)

The human FCGR2/3 locus contains highly homologous genes encoding the five major receptors for IgG (Fc-gamma receptors, FcγRs). In two prior GWAS on Kawasaki disease (KD), a SNP in FCGR2A (131H&gt;R; rs1801274) was identified to be associated with disease susceptibility. However, the FCGR2/3 locus contains multiple single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), which were not covered by the detection platforms used in the GWAS. In this study we therefore focused on further fine-mapping of this locus to investigate the association of the different genetic variations with KD susceptibility. A highly accurate and validated multiplex ligation-dependent probe amplification (MLPA) assay was used to analyze all functionally relevant SNPs and CNVs within this locus. In a genetic association study involving case-control and family-based testing with 1028 patients with KD, the previous finding of FCGR2A-131H as a susceptibility marker for KD was confirmed (OR 1.16; 95%CI 1.08-1.32, meta-P = 0.01). In addition, we found a novel significant association of the FCGR2C-ORF haplotype with susceptibility to KD (OR 1.34; 95% confidence interval 1.11-1.62, meta-P = 0.003). FCGR2C-ORF leads to the expression of an extra, functionally activating FcγR (i.e. FcγRIIc) on myeloid cell types and NK cells. Being absent in Asian individuals, the FCGR2C-ORF haplotype only contributed to KD susceptibility in European subjects, independent of the established association with FCGR2A-H131R. We did not find any significant association of CNV of the locus with susceptibility to KD. Our data point to an important role of the activating FcγRs in KD pathology. We hypothesize that the identified functional SNPs might alter the balance between the activating and inhibitory FcγRs leading to unbalanced inflammation and KD.
Abstract 19643: C1q/TNF-Related Protein 5 Promotes Oxidation of Low-Density Lipoprotein During Transcytosis Across Endothelial Monolayers by Increasing 12/15-Lipoxygenase
Authors: Chang Li, Jia Wei Chen, Ying Shen, Zhu Hui Liu, Rui Yan Zhang, Wei Feng Shen, Lin Lu, Xiao Qun Wang
Journal: Circulation (2017)

Background: Increased transcytosis of low-density lipoprotein (LDL) across the endothelium and oxidative modification of LDL by activated endothelial cells (EC) constitute pivotal early events to i...
Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension
Authors: Clara Hjalmarsson, Göran Rådegran, David Kylhammar, Bengt Rundqvist, Jonas Multing, Magnus D. Nisell, Barbro Kjellström
Journal: European Respiratory Journal (2018)

Recent reports from worldwide pulmonary hypertension registries show a new demographic picture for patients with idiopathic pulmonary arterial hypertension (IPAH), with an increasing prevalence among the elderly. We aimed to investigate the effects of age and comorbidity on risk stratification and outcome of patients with incident IPAH. The study population (n=264) was categorised into four age groups: 18–45, 46–64, 65–74 and ≥75 years. Individual risk profiles were determined according to a risk assessment instrument, based on the European Society of Cardiology and the European Respiratory Society guidelines. The change in risk group from baseline to follow-up (median 5 months) and survival were compared across age groups. In the two youngest age groups, a significant number of patients improved (18–45 years, Z= −4.613, p&lt;0.001; 46–64 years, Z= −2.125, p=0.034), but no significant improvement was found in the older patient groups. 5-year survival was highest in patients aged 18–45 years (88%), while the survival rates were 63%, 56% and 36% for patients in the groups 46–64, 65–74 and ≥75 years, respectively (p&lt;0.001). Ischaemic heart disease and kidney dysfunction independently predicted survival. These findings highlight the importance of age and specific comorbidities as prognostic markers of outcome in addition to established risk assessment algorithms.
Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment
Authors: Ganjun Yu, Yanfeng Wu, Wenying Wang, Jia Xu, Xiaoping Lv, Xuetao Cao, Tao Wan
Journal: Cellular and Molecular Immunology (2018)

PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability. However, the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement. Here, we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice. A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone. The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine. The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes, including antigen-processing and antigen-presenting genes, were upregulated, whereas the promoter demethylation was downregulated after decitabine exposure. Therefore, decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade. The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses, which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.
Sodium Glucose Cotransporter 2 Inhibitors and Amputation Risk
Authors: Marc P. Bonaca, Joshua A. Beckman
Journal: Circulation (2018)

Numerous studies have established that patients with type 2 diabetes mellitus are at heightened risk of ischemic cardiovascular events, including myocardial infarction and stroke, and microvascular events, including nephropathy and retinopathy. 1Treatments to lower glucose concentrations have demonstrated consistent benefits for reducing microvascular complications regardless of mechanism.Establishing the link between glucose lowering and reducing cardiovascular risk has been more challenging, particularly over the durations of most clinical trials.3][4] The SGLT2i appear to have particularly profound benefits in patients with established cardiovascular disease for reducing cardiovascular death and heart failure as well as adverse renal outcomes.Benefits have been reported in 2 completed randomized trials with consistent associations in observational studies, 2-5 including those reported by Udell et al 6 in this issue of Circulation.In contrast to the more consistent cardiovascular benefits described across these studies, however, is a finding isolated to the CANVAS trial (Canagliflozin Cardiovascular Assessment Study) showing an excess risk of amputation with canagliflozin. 4 These divergent signals of harm in the limb coupled with general cardiovascular benefit have raised questions, including whether the observation is a result of chance alone as well as the potential mechanisms of harm.[9][10] In this context, the results from Udell et al 6 provide the greatest impact.In the study of >25 000 patients with type 2 diabetes mellitus and established cardiovascular disease, the authors observed a consistent 2-fold risk of below-the-knee amputation, with the greatest absolute risk in patients with established peripheral artery disease (PAD).These findings are strikingly consistent with the results of the CANVAS trial and the US Food and Drug Administration safety datasets. 11These findings suggest that the risk of amputation observed in the CANVAS trial is in fact real.Several questions remain, including whether this is an SGLT2i class effect or isolated to a single compound.Data from the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) reassuringly do not show any imbalance in amputation despite a reasonable number of events; however, broader peripheral vascular outcomes were not prospectively collected. 3,12,13The large outcomes trial evaluating the efficacy and safety
An existential perspective on the psychological function of shamans
Authors: Simon Schindler, Jeff Greenberg, Stefan Pfattheicher
Journal: Behavioral and Brain Sciences (2018)

Abstract Shamans deal with events that involve the threat of death. They help buffer death anxiety because, through their claimed supernatural abilities, they can provide both hope for averting death and evidence for existence of a spirit world offering continuance beyond death. Thus, managing the threat of mortality probably played a major role in the development and maintenance of shamanism.
Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific vSNARE Vamp1
Authors: Celine K. Vuong, Weizheng Wei, Ji-Ann Lee, Chia-Ho Lin, Andrey Damianov, Luis de la Torre-Ubieta, Reem Halabi, Klara Olofsdotter Otis, Kelsey C. Martin, Thomas J. O’Dell, Douglas L. Black
Journal: Neuron (2018)
Clinical Usefulness of Imaging and Blood Cultures in Cellulitis Evaluation
Authors: Lauren N. Ko, Anna C. Garza-Mayers, Jessica St John, Lauren Strazzula, Priyanka Vedak, Allison S. Dobry, Daniela Kroshinsky
Journal: JAMA Internal Medicine (2018)

a shorter course of treatment with azithromycin does not involve a shorter duration of antibiotic exposure. 6ur study has limitations.First, we were not able to account for underlying conditions or other indicators for longer courses of antibiotic therapy.Second, by excluding visits with a diagnosis of unspecified sinusitis from our analysis, we may have excluded some cases of acute sinusitis.However, the findings of a sensitivity analysis that included cases of both acute and unspecified sinusitis were similar (median duration of therapy, 10.0 days; 88.1% [95% CI, 85.1%-91.0%] of nonazithromycin antibiotic courses were 10 days or longer in duration).Outpatient antibiotic stewardship programs can optimize infection management by ensuring guideline-concordant treatment, including the use of minimum effective durations of antibiotic therapy.The durations of most courses of antibiotic therapy for adult outpatients with sinusitis exceed guideline recommendations, which represents an opportunity to reduce the unnecessary use of antibiotics when therapy with antibiotics is indicated.
Safety and efficacy results from two randomized expansions of a phase I study of a tablet formulation of the PARP inhibitor, olaparib, in ovarian and breast cancer patients with <i>BRCA</i>1/2 mutations.
Authors: L Rhoda Molife, Joaquin Mateo, Trevor McGoldrick, Matthew Krebs, Yvette Drew, Susana N. Banerjee, Shibani Nicum, Malcolm Ranson, Gordon J. S. Rustin, Cristiana Sessa, Ruth Plummer, Karin Leunen, Michael Friedlander, Helen Swaisland, Wendy Burke, Peter McCormack, Kristine Pemberton, Ilian Tchakov, Stanley B. Kaye, Charlie Gourley
Journal: Journal of Clinical Oncology (2012)

3048 Background: We previously reported the comparative bioavailability of the capsule (CAP) formulation of olaparib and the more convenient new tablet (TAB) formulation (Molife et al ASCO 2010). We subsequently performed two separate dose expansions (DE1 and DE2) to explore comparative safety and efficacy of the TAB (NCT00777582). Methods: Patients with breast or ovarian cancer and BRCA1/2 mutations, ECOG PS 0–2 and adequate organ function were randomized to receive: DE1: 200 TAB or 400 CAP; DE2: 300 TAB, 400 TAB or 400 CAP (all mg BID). Endpoints included safety, pharmacokinetics and exploratory analysis of efficacy (change in tumor size at 8 weeks by RECIST 1.0). Groups were compared using analysis of covariance, including baseline tumor size and treatment as covariates; results are presented using least square (LS) means. Results: 24 patients (ovarian n=15, breast n=9) entered DE1 and 53 patients (ovarian n=38, breast n=15) entered DE2. Baseline characteristics including age, BRCA mutation status and tumor histology were balanced. The table shows key toxicity-related information and change in tumor size at 8 weeks by cohort. Conclusions: These data suggest a dose-response effect for tolerability and, possibly, efficacy with the new TAB between 200 and 400 mg BID. Further studies will require dosing according to patient tolerability within this dose range. [Table: see text]
Admissions for Infective Endocarditis in Intravenous Drug Users
Authors: Salil V. Deo, Sajjad Raza, Ankur Kalra, Vaishali S. Deo, Salah E. Altarabsheh, Aisha Zia, Muhammad Shahzeb Khan, Alan H. Markowitz, Joseph F. Sabik, Soon J. Park
Journal: Journal of the American College of Cardiology (2018)
Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging
Authors: Brian W. Pogue, Jinchao Feng, Ethan P. LaRochelle, Petr Bruža, Huiyun Lin, Rongxiao Zhang, Jennifer R. Shell, Hamid Dehghani, Scott C. Davis, Sergei A. Vinogradov, David J. Gladstone, Lesley A. Jarvis
Journal: Nature Biomedical Engineering (2018)
A deep Boltzmann machine-driven level set method for heart motion tracking using cine MRI images
Authors: Jian Wu, Thomas R. Mazur, Su Ruan, Chunfeng Lian, Nalini Daniel, Hilary Lashmett, Laura Ochoa, Imran Zoberi, Mark A. Anastasio, H. Michael Gach, Sasa Mutic, Maria Thomas, Hua Li
Journal: Medical Image Analysis (2018)
Cutis laxa associated with monoclonal gammopathy: 14 new cases and review of the literature
Authors: Marie Jachiet, Stéphanie Harel, Anne Saussine, Maxime Battistella, Michel Rybojad, Bouchra Asli, Djaouida Bengoufa, Thibault Mahevas, Didier Bessis, Lionel Galicier, Jean-Luc Schmutz, Smail Hadj-Rabia, David Boutboul, Céleste Lebbé, Martine Bagot, Marion Malphettes, Dan Lipsker, Jean-Paul Fermand, Jean-David Bouaziz, Bertrand Arnulf
Journal: Journal of the American Academy of Dermatology (2018)
Precise genome-wide mapping of single nucleosomes and linkers in vivo
Authors: Răzvan V. Chereji, Srinivas Ramachandran, Terri D. Bryson, Steven Henikoff
Journal: Genome biology (2018)

We developed a chemical cleavage method that releases single nucleosome dyad-containing fragments, allowing us to precisely map both single nucleosomes and linkers with high accuracy genome-wide in yeast. Our single nucleosome positioning data reveal that nucleosomes occupy preferred positions that differ by integral multiples of the DNA helical repeat. By comparing nucleosome dyad positioning maps to existing genomic and transcriptomic data, we evaluated the contributions of sequence, transcription, and histones H1 and H2A.Z in defining the chromatin landscape. We present a biophysical model that neglects DNA sequence and shows that steric occlusion suffices to explain the salient features of nucleosome positioning.
Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection
Authors: Chao Chen, Sulan Zhai, Le Zhang, Jingjing Chen, Xuehui Long, Jun Qin, Jianhua Li, Ran Huo, Xiaoming Wang
Journal: The Journal of Experimental Medicine (2018)

The production of high-affinity antibody is essential for pathogen clearance. Antibody affinity is increased through germinal center (GC) affinity maturation, which relies on BCR somatic hypermutation (SHM) followed by antigen-based selection. GC B cell proliferation is essentially involved in these processes; it provides enough templates for SHM and also serves as a critical mechanism of positive selection. In this study, we show that expression of epigenetic regulator ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) was markedly up-regulated by c-Myc–AP4 in GC B cells, and it was required for GC response. Uhrf1 regulates cell proliferation–associated genes including cdkn1a, slfn1, and slfn2 by DNA methylation, and its deficiency inhibited the GC B cell cycle at G1-S phase. Subsequently, GC B cell SHM and affinity maturation were impaired, and Uhrf1 GC B knockout mice were unable to control chronic virus infection. Collectively, our data suggest that Uhrf1 regulates GC B cell proliferation and affinity maturation, and its expression in GC B cells is required for virus clearance.
Association of LAG-3 expression in tumor infiltrating immune cells with prognosis in patients with microsatellite instability high colon cancer.
Authors: Soo Jung Lee, Jong Gwang Kim, Yee Soo Chae, Byung Woog Kang, In Hee Lee, Ghil Suk Yoon, Sun-Young Jun
Journal: Journal of Clinical Oncology (2017)

e15126 Background: Recent findings demonstrated that microsatellite instability high (MSI-H) colon cancer contains high T-cell infiltration and upregulated expression of multiple immune checkpoints. The aim of this study was to reveal the prognostic impact of MSI-H colon cancer showing immune checkpoint protein expressions, which are good candidates for immunotherapy. Methods: From January 2011 to April 2015, we included 98 patients with MSI-H colon cancer who underwent curative surgery at Kyungpook National University Medical Center. Inhibitory receptors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1) and indolamine 2’3’-dioxygenase (IDO) expression status were retrospectively analyzed using immunohistochemistry (IHC). Positivity in tumor cells (T) and immune cells (I) were separately evaluated. IHC values were determined to be positive when moderate or strong intensity of the membranous to cytoplasmic staining pattern were shown in more than 5% of the tumor cells or immune cells. Results: Among the 93 patients, 22 patients (23.9 %) and 63 (68.5%) were determined as PD-L1(T) positive and PD-L1 (I) positive, while 12 (13.2%) and 42 (45.7%) were determined as LAG-3(I) positive and PD-1 (I) positive. Twenty-seven patients (29.3%) and 66 (71.7%) were determined as CTLA-4 (T) positive and CTLA-4 (I) positive, while 66 (71.7%) and 26 (28.3%) were determined as IDO (T) and IDO (I) positive. During median follow-up duration of 39 months, 16 (17.4%) patients experienced recurrence. LAG-3 (I) positivity was significantly associated shorter relapse-free survival (p = 0.016). Moreover, LAG-3 expression was significantly correlated with PD-L1 (T) expression (p = 0.003). Co-expression of PD-L1 and LAG-3 showed worse prognosis for relapse-free survival (p &lt; 0.001). Conclusions: In conclusion, LAG-3 positivity showed worse prognosis in patients with MSI-H colon cancer. Potential differential therapeutic implications LAG-3 should be further investigated.
Economic analysis of transarterial chemoembolization (TACE) versus stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma (HCC).
Authors: Francis W. Nugent, Amy Packard, Klaudia Hunter, Amir Qamar, Keith E. Stuart, Krishna Gunturu, Sebastian Flacke, Christopher Molgaard, Shams Iqbal, Fredric Gordon
Journal: Journal of Clinical Oncology (2018)

508 Background: For HCC patients undergoing liver transplantation (LT), local treatment as a "bridge" is standard to decrease tumor burden. The most common treatment is TACE, but the best and cheapest bridging modality is unclear. We prospectively compared SBRT to TACE as a bridge for HCC patients undergoing LT. We then compared the cost of the two strategies. Methods: From 9/2014-1/2017, 31 patients within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE vs. SBRT. TACE patients received 2 treatments one month apart utilizing DEBDOX beads (n = 17) and were hospitalized for symptom management. Patients receiving SBRT (n = 14) received outpatient treatment comprising 5 fractions of radiation using fiducials. Using EPSI, the institutional cost accounting and clinical data base, all patients treated were analysed. Financial and cost data was used to calculate the average contribution margin (total payment minus direct cost) for each type of treatment and then multiplied for each patient by the number of treatments involved. Results: See table. Conclusions: SBRT costs less than TACE to treat HCC. Given reduced reimbursement for hospitalizations post-TACE, additional opportunity costs may be available at given institutions depending on bed availability. Clinical trial information: NCT02182687. [Table: see text]