tbuckley/cabot-search huggingface dataset:
The Oral Microbiome Bank of China
Authors: Peng Xian, Zhou Xuedong, Xu Xin, Li Yuqing, Li Yan, Li Jiyao, Su Xiaoquan, Huang Shi, Xu Jian, Liao Ga
Journal: International Journal of Oral Science (2018)

Abstract The human microbiome project (HMP) promoted further understanding of human oral microbes. However, research on the human oral microbiota has not made as much progress as research on the gut microbiota. Currently, the causal relationship between the oral microbiota and oral diseases remains unclear, and little is known about the link between the oral microbiota and human systemic diseases. To further understand the contribution of the oral microbiota in oral diseases and systemic diseases, a Human Oral Microbiome Database (HOMD) was established in the US. The HOMD includes 619 taxa in 13 phyla, and most of the microorganisms are from American populations. Due to individual differences in the microbiome, the HOMD does not reflect the Chinese oral microbial status. Herein, we established a new oral microbiome database—the Oral Microbiome Bank of China (OMBC, http://www.sklod.org/ombc ). Currently, the OMBC includes information on 289 bacterial strains and 720 clinical samples from the Chinese population, along with lab and clinical information. The OMBC is the first curated description of a Chinese-associated microbiome; it provides tools for use in investigating the role of the oral microbiome in health and diseases, and will give the community abundant data and strain information for future oral microbial studies.
Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial
Authors: Michel Azizi, Roland E Schmieder, Felix Mahfoud, Michael A Weber, Joost Daemen, Justin Davies, Jan Basile, Ajay J Kirtane, Yale Wang, Melvin D Lobo, Manish Saxena, Lida Feyz, Florian Rader, Philipp Lurz, Jeremy Sayer, Marc Sapoval, Terry Levy, Kintur Sanghvi, Josephine Abraham, Andrew S P Sharp, Naomi D L Fisher, Michael J Bloch, Helen Reeve-Stoffer, Leslie Coleman, Christopher Mullin, Laura Mauri, Yale Wang, Desmond Jay, Nedaa Skeik, Robert Schwartz, Florian Rader, Suhail Dohad, Ronald Victor, Kintur Sanghvi, Josh Costello, Courtney Walsh, Josephine Abraham, Theophilus Owan, Anu Abraham, Naomi D.L. Fisher, Laura Mauri, Piotr Sobieszczky, Jonathan Williams, Michael J. Bloch, Chanwit Roongsritong, Thomas Todoran, Jan Basile, Eric Powers, Emily Hodskins, Pete Fong, Cheryl Laffer, James Gainer, Mark Robbins, John P. Reilly, Michael Cash, Jessie Goldman, Sandeep Aggarwal, Gary Ledley, David Hsi, Scott Martin, Edward Portnay, David Calhoun, Thomas McElderry, William Maddox, Suzanne Oparil, Pei-Hsiu Huang, Powell Jose, Matheen Khuddus, Suzanne Zentko, James O'Meara, Ilie Barb, Joseph Garasic, Doug Drachman, Randy Zusman, Kenneth Rosenfield, Chandan Devireddy, Janice Lea, Bryan Wells, Rick Stouffer, Alan Hinderliter, Eric Pauley, Srinivasa Potluri, Scott Biedermann, Sripal Bangalore, Stephen Williams, David Zidar, Mehdi Shishehbor, Barry Effron, Marco Costa, Ajay J. Kirtane, Jai Radhakrishnan, Melvin D. Lobo, Manish Saxena, Anthony Mathur, Ajay Jain, Jeremy Sayer, Sudha Ganesh Iyer, Nicholas Robinson, Sadat Ali Edroos, Terry Levy, Amit Patel, David Beckett, Clare Bent, Justin Davies, Neil Chapman, Matthew Shun-Shin, James Howard, Andrew S.P. Sharp, Anil Joseph, Richard D'Souza, Robert Gerber, Mohamad Faris, Andrew J. Marshall, Cristina Elorz, Philipp Lurz, Robert Höllriegel, Karl Fengler, Karl-Philipp Rommel, Felix Mahfoud, Michael Böhm, Sebastian Ewen, Jelena Lucic, Roland E. Schmieder, Christian Ott, Axel Schmid, Michael Uder, L. Christian Rump, Johannes Stegbauer, Patric Kröpil, Michel Azizi, Marc Sapoval, Erika Cornu, David Fouassier, Philippe Gosse, Antoine Cremer, Hervé Trillaud, Panteleimon Papadopoulos, Atul Pathak, Benjamin Honton, Pierre Lantelme, Constance Berge, Pierre-Yves Courand, Joost Daemen, Lida Feyz, Peter J. Blankestijn, Michiel Voskuil, Zwaantina Rittersma, A.A. Kroon, W.H. van Zwam, Alexandre Persu, Jean Renkin
Journal: The Lancet (2018)
Survival among older adults with kidney failure is better in the first three years with chronic dialysis treatment than not
Authors: Helen Tam-Tham, Robert R. Quinn, Robert G. Weaver, Jianguo Zhang, Pietro Ravani, Ping Liu, Chandra Thomas, Kathryn King-Shier, Karen Fruetel, Matt T. James, Braden J. Manns, Marcello Tonelli, Fliss E.M. Murtagh, Brenda R. Hemmelgarn
Journal: Kidney International (2018)
A cognitive, non-selectionist account of moral externalism
Authors: Jason Zinser
Journal: Behavioral and Brain Sciences (2018)

Abstract A general feature of our moral psychology is that we feel that some moral demands are motivated externally. Stanford explains this feature with an evolutionary account, such that moral externalism was selected for its ability to facilitate prosocial interactions. Alternatively, I argue that a cognitive, non-selectionist account of moral externalism is a more parsimonious explanation.
Targeting p38α Increases DNA Damage, Chromosome Instability, and the Anti-tumoral Response to Taxanes in Breast Cancer Cells
Authors: Begoña Cánovas, Ana Igea, Alessandro A. Sartori, Roger R. Gomis, Tanya T. Paull, Michitaka Isoda, Héctor Pérez-Montoyo, Violeta Serra, Eva González-Suárez, Travis H. Stracker, Angel R. Nebreda
Journal: Cancer Cell (2018)
Drugs in Development for Malaria
Authors: Elizabeth A. Ashley, Aung Pyae Phyo
Journal: Drugs (2018)

The last two decades have seen a surge in antimalarial drug development with product development partnerships taking a leading role. Resistance of Plasmodium falciparum to the artemisinin derivatives, piperaquine and mefloquine in Southeast Asia means new antimalarials are needed with some urgency. There are at least 13 agents in clinical development. Most of these are blood schizonticides for the treatment of uncomplicated falciparum malaria, under evaluation either singly or as part of two-drug combinations. Leading candidates progressing through the pipeline are artefenomel–ferroquine and lumefantrine-KAF156, both in Phase 2b. Treatment of severe malaria continues to rely on two parenteral drugs with ancient forebears: artesunate and quinine, with sevuparin being evaluated as an adjuvant therapy. Tafenoquine is under review by stringent regulatory authorities for approval as a single-dose treatment for Plasmodium vivax relapse prevention. This represents an advance over standard 14-day primaquine regimens; however, the risk of acute haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency remains. For disease prevention, several of the newer agents show potential but are unlikely to be recommended for use in the main target groups of pregnant women and young children for some years. Latest predictions are that the malaria burden will continue to be high in the coming decades. This fact, coupled with the repeated loss of antimalarials to resistance, indicates that new antimalarials will be needed for years to come. Failure of the artemisinin-based combinations in Southeast Asia has stimulated a reappraisal of current approaches to combination therapy for malaria with incorporation of three or more drugs in a single treatment under consideration.
Abstract 15322: Pacinchagas-crt: A Cohort Study of Cardiac Resynchronization Therapy in Patients With Chronic Chagas Cardiomyopathy
Authors: Martino Martinelli, Giselle L Peixoto, Sérgio Siqueira, Johnny Santos, Sérgio Martins, Silvana Nishioka, Anísio Pedrosa, Ricardo Teixeira, Roberto Costa
Journal: Circulation (2015)

Background: Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure (HF). However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC), an important cause of HF in endemic countries. We aimed to assess the role of CRT in a cohort of patients with CCC. Methods: This was a retrospective study of consecutive CCC patients who underwent CRT between January 2005 and December 2012. We compared the outcomes of CCC patients who underwent CRT (CCC-CRT group) with those of ischemic and dilated cardiomyopathy patients who underwent CRT (CRT-control group) in the same period and with those of CCC patients with induced left bundle branch block (LBBB) who did not undergo CRT (CCC-control group). The primary endpoint was all-cause mortality and the secondary endpoint was echocardiographic changes, at least 24 months after CRT. Results: There were 115 patients in the CCC-CRT group, 311 in the CRT-control group, and 16 in the CCC-control group. The annual mortality rates were 25.4%, 10.9%, and 42.9%, respectively. Multivariate analysis adjusted for potential confounders showed that the CCC-CRT group had a two-fold (hazard ratio [HR] 2.11 [1.56-2.86], P&lt;0.001) higher risk of death compared to the CRT-control group, and that the CCC-control group had an almost three-fold (HR 2.78 [1.09-7.01], P=0.032) higher risk of death compared to the CCC-CRT group. Conclusions: This cohort study showed that CRT has a favorable impact in patients with CCC, despite their worse prognosis compared to patients with other cardiomyopathies who undergo CRT.
Abstract 17313: Impact of Late Onset Worsening Renal Function on Outcomes in Patients With Acute Decompensated Heart Failure
Authors: Kenta Ishibashi, Takafumi Yamane, Ryosuke Murai, Yasuhiro Sasaki, Mitsuhiko Ota, Kitae Kimu, Takeshi Kitai, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Shuichiro Kaji, Yutaka Furukawa
Journal: Circulation (2016)

Background:  Development of worsening renal function (WRF) in acute decompensated heart failure (ADHF) patients was associated with poor clinical outcome in several past studies. In most of these studies, WRF was defined as the occurrence during several days from admission, however we often experience WRF in chronic phase during admission. The purpose of this study was to focus on onset time of WRF and its clinical importance.   Methods:  We evaluated 250 patients admitted our hospital with ADHF between April 2014 to May 2015. We excluded the patients who were on dialysis and died during the admission. WRF was defined as the occurrence, at any time during the hospitalization, of both a ≥25% and a ≥0.3 mg/dL increase in serum creatinine from admission. We divided patients developing WRF into two groups, early WRF (≤ 5 days from admission) and late WRF (≥ 6 days from admission). Outcomes (ADHF readmission and all cause death) were recorded during follow-up (mean 50.3 ± 28.5 weeks).   Results:  A total of 224 patients were included in this study. Among these patients, WRF occurred in 114 (50.9 %) patients, 57 (25.5 %) with early onset of WRF, 57 (25.5 %) with late onset of WRF. Patients with late onset of WRF had a higher rate of readmission with ADHF and all cause death than that in patients without WRF (47.4 % vs. 31.2 %, p=0.041), however not in patients with early onset of WRF (36.8 % vs 31.2 %, p=0.46). Late onset of WRF was an independent predictor of readmission or mortality (hazard ratio: 2.61, 95 % confidence interval: 1.47-4.62, p =0.0012). The most important predictor of developing late onset of WRF was reduction in body weight during admission (7.68 ± 0.63 kg vs. 4.89 ± 0.37 kg, p=0.022).   Conclusion:  Not early but late onset of WRF was independently related to poor prognosis in patients with ADHF. Patients with late onset of WRF showed greater reduction in body weight but worse prognosis, so the goal of decongestion or the way of decongestion might be important.
Assessment of Frontalis Myocutaneous Transposition Flap for Forehead Reconstruction After Mohs Surgery
Authors: Alejandra Tomás-Velázquez, Pedro Redondo
Journal: JAMA Dermatology (2018)

Forehead reconstruction after Mohs surgery has become a challenge for dermatology surgeons, and achieving an excellent cosmetic and functional result is imperative in this location.To highlight the utility of a frontalis myocutaneous transposition flap (FMTF) for forehead reconstruction after Mohs surgery.Surgical technique case series including 12 patients with large forehead defects recruited between January 2010 and June 2017 at the Dermatology Department of the University Clinic of Navarra, Spain. All patients underwent Mohs micrographic surgery for skin cancer (5 basal cell carcinomas, 4 melanomas, 2 squamous cell carcinomas, and 1 adnexal tumor) located on the forehead (8 paramedian, 2 midline, and 2 lateral subunits) resulting in defects ranging from 9 to 28 cm2 in size.Mohs micrographic surgery followed by FMTF. Taking into account the defect's size and location, a lateral lobulated flap is designed with an inferior pedicle and incision lines are made vertically to the hairline containing part of the frontalis muscle or its fascia. The flap swings into the primary defect and direct closure of the donor site is achieved. Additional corrections for removing skin folds or a guitar-string suture can be made.Absence of acute complications and achievement of high aesthetic and functional goals in postoperative follow-up.Satisfactory cosmetic and functional results were achieved for all 12 patients (7 men and 5 women; mean age, 62.7 years [range, 47-86 years]) and there were no postoperative complications. All the myocutaneous flaps survived without any acute complications, such as episodes of local bleeding, infection, flap margin necrosis, or congestion. Postoperative follow-up ranged from 6 months to 3 years. No patient needed scar revision. Six patients presented with paresthesia in areas of the forehead and scalp. Sensory recovery tended to improve over time, and paresthesia gradually decreased, disappearing in 5 of 6 cases after 12 months. In 3 patients there was a minimal hair transposition that required laser treatment.The FMTF provides a simple method for 1-stage reconstruction of large forehead defects as an alternative to classic advancement flaps.
Externalization of moral demands does not motivate exclusion of non-cooperators: A defense of a subjectivist moral psychology
Authors: Armin W. Schulz
Journal: Behavioral and Brain Sciences (2018)

Abstract It is not clear how a moral demand alone can motivate an agent to exclude those who fail to act as the demand states. A more plausible hypothesis for the evolution of human moral cognition is based on seeing moral demands as subjective, but inherently conjunctive. This subjectivist-conjunctive proposal can still account for the apparent externalization of moral demands.
Abstract 284: Elevation of Cardiac NAD+ Levels Improves Mitochondrial Function in Mice Lacking Sirtuin 3
Authors: Matthew A Walker, Rong Tian
Journal: Circulation Research (2017)

The mitochondria rely heavily on the ratio between NAD+ and its reduced form NADH to maintain proper function and generate 95% of cardiac cellular energy. Sirtuin 3 (SIRT3) is the major mitochondrial deacetylase and its activity level has been linked to the NAD+/NADH ratio. Numerous studies have shown that deletion of SIRT3 results in hyperacetylation and impairment of mitochondrial enzymes involved in fatty acid metabolism and in the mitochondrial respiratory chain. Because impairments in these processes have shown to be associated with decreases in the NAD+/NADH ratio and contribute to deficits in energy production, we hypothesized that the SIRT3 knockout mice (SIRT3 -/- ) would have a decreased NAD+/NADH ratio and that normalizing the ratio would improve mitochondrial respiratory function and inner membrane potential. In the present study, we observed increases in both NAD+ (1.1-fold, n=3, p&lt;0.05) and NADH (1.5-fold) in cardiac tissue from 14-week old SIRT3 -/- mice compared to wild-type (WT) controls, resulting in a 26±2.2% reduction in the NAD+/NADH ratio. These changes correlated with decreased Complex I ADP stimulated respiration (173±16 vs 118±14 nmolO 2 /min/mg for WT and SIRT3 -/- , respectively, n=3, p&lt;0.05) and suppressed mitochondrial membrane potential. Intraperitoneal injection (I.P.) of Nicotinamide Riboside (NR) increased NAD+ levels in cardiac tissue lysates (WT 1.5-fold and SIRT3 -/- 1.4-fold, n=5, p&lt;0.05) and in mitochondria isolated (WT 1.9-fold and SIRT3 -/- 1.7-fold) from the mice with no significant changes in NADH levels. Therefore, the NR I.P. injections normalized the NAD+/NADH ratio, partially restored the Complex I supported mitochondrial respiration (123±11 vs 157±8 nmolO 2 /min/mg for vehicle and NR treated SIRT3 -/- mice, respectively, n=3, p&lt;0.05), and improved mitochondrial membrane potential in the SIRT3 -/- mice. These results suggest that increasing cardiac NAD+ levels can rescue mitochondrial dysfunction independent of SIRT3 protein deacetylation and warrants further investigation. The next step will be to test whether increasing cardiac NAD+ levels can improve mitochondrial function and reduce injury in SIRT3 -/- mice subjected to chronic heart stress induced by transverse aortic constriction surgery.
Abstract P237: Cardiovascular Disease Risk Factor Associations with Volume and Density Components of Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Julie O Denenberg
Journal: Circulation (2016)

Introduction: Coronary artery calcium (CAC) strongly predicts incident cardiovascular disease (CVD) beyond traditional risk factors. CAC volume and density can be determined separately. CAC volume is positively associated with CVD risk, whereas CAC density is inversely associated with CVD risk. Hypothesis: We assessed the hypothesis that traditional CVD risk factors would associate differently with CAC volume than with CAC density. Methods: Baseline measurements from 6814 community-dwelling participants free of known CVD were collected for the Multiethnic Study of Atherosclerosis between 2000 and 2002. The 3398 CAC-positive participants were included in these analyses. Multivariable linear regression models were used to evaluate independent risk factors for CAC volume and CAC density separately. Results and Conclusions: Standardized beta coefficients for risk factors significantly associated with increased CAC volume in the multivariable linear regression model included age (β=0.34), male gender (β=0.48), diabetes (β=0.38), current smoking (β=0.27), hypertension medication use (β=0.18), family history of MI (β=0.21), body mass index (β=0.17), total cholesterol (β=0.06), and reduced walking pace (β=0.12). Compared to the non-Hispanic white (NHW) reference group, Chinese (β=-0.62), African-American (β=-0.48), and Hispanic (β=-0.47) race/ethnicities had decreased CAC volume. Risk factors positively associated with increased CAC density in the multivariable linear regression model included HDL (β=0.03), and Chinese (β=0.39), African-American (β=0.16), and Hispanic (β=0.18) race/ethnicities in comparison with NHW. Diabetes (β=-0.10) and body mass index (β=-0.08) were both inversely associated with CAC density. In conclusion, CVD risk factors predicted both increased CAC volume and decreased CAC density, suggesting they could increase atherosclerotic risk both by increasing CAC volume and decreasing CAC density. Ethnic groups other than NHW had lower risk CAC plaques, with lower volume and greater density.
Preventive strategies for mental health
Authors: Celso Arango, Covadonga M Díaz-Caneja, Patrick D McGorry, Judith Rapoport, Iris E Sommer, Jacob A Vorstman, David McDaid, Oscar Marín, Elena Serrano-Drozdowskyj, Robert Freedman, William Carpenter
Journal: The Lancet Psychiatry (2018)
Serial monitoring of ctDNA to highlight mutation profiles in colorectal cancer.
Authors: Jonathan M. Loree, John H. Strickler, Allan Andresson Lima Pereira, Michael Lam, Kanwal Pratap Singh Raghav, Van Karlyle Morris, David Menter, Kimberly Banks, Rebecca J Nagy, Victoria Raymond, Michael J. Overman, AmirAli Talasaz, Richard B. Lanman, Scott Kopetz
Journal: Journal of Clinical Oncology (2018)

641 Background: Circulating tumor DNA (ctDNA) represents an ideal platform to obtain the most current genomic profile of a patient’s tumor. We aimed to investigate how stable these profiles remain during serial ctDNA assays in metastatic colorectal cancer (mCRC). Methods: In 77 patients (pts) with mCRC and serial Guardant360 assays with a detectable mutation (mt), we compared mt stability by assessing whether variants were gained/lost between serial assays and changes in relative mutant allele frequency (rMAF). rMAF of a mt was defined as (mt allele frequency / mt present at the maximum allele frequency in that assay). rMAF results were normalized to detected ctDNA concentration changes between assays to ensure changes in rMAF were not due to changes in ctDNA concentration. MAPK pathway mutations were defined as RAS, BRAF, EGFR, KIT, or MET mutations. Results: Of 77 pts, 64 (83%) had 2 serial assays and 13 (16.9%) had 3 or 4 assays performed. Serial assays occurred an average of 138 days apart (+/- SD of 111 days). Only 13/77 (17%) pts had no change in the number of mts detected between assays. A new mt was detected in 42/77 (55%) pts, while 43/77 (56%) lost a previously detected mt. Of 52 mts detected in patients with &gt; 2 assays, 16 (31%) were gained and subsequently lost. After controlling for ctDNA concentration, mts were equally likely to have an increasing (129/308 – 42%) or decreasing (150/308 – 49%) allele frequency. Potentially clinically relevant MAPK variants were gained/lost in 29% of patients; though MAPK mts developed in a large number of pts (16/77 – 21%), many pts also lost MAPK mts (9/77 – 12%), showing ongoing subclonal dynamics. Median time between assays did not differ between pts with gain/lost mts or stable mt profiles (P = 0.73), however mt rMAF shift of &gt; 25% was more common if assays were &gt; 90 days apart (OR 4.3, P &lt; 0.0001). Conclusions: Serial ctDNA assays demonstrate ongoing mutational changes in mCRC, with emergence/disappearance of MAPK variants being more common than expansion of a pre-existing clone. Our results suggest repeated sampling may be important to optimize selection of targeted therapies at each regimen alteration.
Abstract 18333: Association Between Leukocyte Telomere Length and Peripheral Arterial Disease: Results From NHANES
Authors: Pankaj Malhotra, Nisha Parikh, Iftikhar Kullo, Siddharth Singh
Journal: Circulation (2016)

Introduction: Leukocyte telomere length (LTL), a marker of cellular senescence, may predict susceptibility to cardiovascular disease (CVD). Peripheral arterial disease (PAD) is associated with an i...
Role of Molecular Pathology in the Treatment of Anaplastic Gliomas and Glioblastomas
Authors: Matthias Holdhoff
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1">The 2016 WHO Classification of Tumors of the Central Nervous System integrated molecular biomarkers into the classifications of malignant gliomas. Several markers now play a key role in our understanding of these tumors and are integral for clinical decision-making; these include codeletion of 1p and 19q and <em>IDH1</em> and <em>IDH2</em> mutations. The presentation by Matthias Holdhoff, MD, PhD, at the NCCN 23rd Annual Conference discussed the current understanding of anaplastic gliomas (WHO grade III) in the context of the new classification and its implications on clinical practice. The 2018 NCCN Guidelines for Central Nervous System Cancers incorporate molecular and histologic characteristics in the staging and treatment of both low- and high-grade gliomas (WHO grades II–IV). </section>
The Epigenetic State of PRDM16-Regulated Enhancers in Radial Glia Controls Cortical Neuron Position
Authors: José-Manuel Baizabal, Meeta Mistry, Miguel Turrero García, Nicolás Gómez, Olubusola Olukoya, Diana Tran, Matthew B. Johnson, Christopher A. Walsh, Corey C. Harwell
Journal: Neuron (2018)