tbuckley/cabot-search huggingface dataset:
Genomic Analysis of Picochlorum Species Reveals How Microalgae May Adapt to Variable Environments
Authors: Fatima Foflonker, Devin Mollegard, Meichin Ong, Hwan Su Yoon, Debashish Bhattacharya
Journal: Molecular Biology and Evolution (2018)

Understanding how microalgae adapt to rapidly changing environments is not only important to science but can help clarify the potential impact of climate change on the biology of primary producers. We sequenced and analyzed the nuclear genome of multiple Picochlorum isolates (Chlorophyta) to elucidate strategies of environmental adaptation. It was previously found that coordinated gene regulation is involved in adaptation to salinity stress, and here we show that gene gain and loss also play key roles in adaptation. We determined the extent of horizontal gene transfer (HGT) from prokaryotes and their role in the origin of novel functions in the Picochlorum clade. HGT is an ongoing and dynamic process in this algal clade with adaptation being driven by transfer, divergence, and loss. One HGT candidate that is differentially expressed under salinity stress is indolepyruvate decarboxylase that is involved in the production of a plant auxin that mediates bacteria-diatom symbiotic interactions. Large differences in levels of heterozygosity were found in diploid haplotypes among Picochlorum isolates. Biallelic divergence was pronounced in P. oklahomensis (salt plains environment) when compared with its closely related sister taxon Picochlorum SENEW3 (brackish water environment), suggesting a role of diverged alleles in response to environmental stress. Our results elucidate how microbial eukaryotes with limited gene inventories expand habitat range from mesophilic to halophilic through allelic diversity, and with minor but important contributions made by HGT. We also explore how the nature and quality of genome data may impact inference of nuclear ploidy.
Abstract 18753: Intra-left Ventricular Pressure Difference During Atrial Contraction is a Useful Parameter to Assess Left Ventricular End-diastolic Pressure
Authors: Kazuaki Wakami, Shinro Saiki, Junki Yamamoto, Keisuke Muto, Shohei Kikuchi, Hiroshi Fujita, Toshihiko Goto, Hidekatsu Fukuta, Nobuyuki Ohte
Journal: Circulation (2017)

Background: Vector Flow Mapping (VFM TM, Hitachi) enables us to obtain intra-left ventricular pressure difference (IVPD) from blood flow velocity data set acquired by color Doppler imaging (CDI). W...
Diagnosis and Pharmacotherapy of Alcohol Use Disorder
Authors: Henry R. Kranzler, Michael Soyka
Journal: JAMA (2018)

<h3>Importance</h3> Alcohol consumption is associated with 88 000 US deaths annually. Although routine screening for heavy alcohol use can identify patients with alcohol use disorder (AUD) and has been recommended, only 1 in 6 US adults report ever having been asked by a health professional about their drinking behavior. Alcohol use disorder, a problematic pattern of alcohol use accompanied by clinically significant impairment or distress, is present in up to 14% of US adults during a 1-year period, although only about 8% of affected individuals are treated in an alcohol treatment facility. <h3>Observations</h3> Four medications are approved by the US Food and Drug Administration to treat AUD: disulfiram, naltrexone (oral and long-acting injectable formulations), and acamprosate. However, patients with AUD most commonly receive counseling. Medications are prescribed to less than 9% of patients who are likely to benefit from them, given evidence that they exert clinically meaningful effects and their inclusion in clinical practice guidelines as first-line treatments for moderate to severe AUD. Naltrexone, which can be given once daily, reduces the likelihood of a return to any drinking by 5% and binge-drinking risk by 10%. Randomized clinical trials also show that some medications approved for other indications, including seizure disorder (eg, topiramate), are efficacious in treating AUD. Currently, there is not sufficient evidence to support the use of pharmacogenetics to personalize AUD treatments. <h3>Conclusions and Relevance</h3> Alcohol consumption is associated with a high rate of morbidity and mortality, and heavy alcohol use is the major risk factor for AUD. Simple, valid screening methods can be used to identify patients with heavy alcohol use, who can then be evaluated for the presence of an AUD. Patients receiving a diagnosis of the disorder should be given brief counseling and prescribed a first-line medication (eg, naltrexone) or referred for a more intensive psychosocial intervention.
Abstract 16794: Electrocardiographic Differentiation of Fascicular Ventricular Tachycardia From Atrial Flutter With Right Bundle Branch Block Aberrant Conduction
Authors: Minsu Kim, Jongmin Hwang, You Mi Hwang, Ji Hyun Lee, Chang Hee Kwon, Jun Kim, Gi-Byoung Nam, Kee-Joon Choi, You-Ho Kim
Journal: Circulation (2016)

Introduction: Atrial fibrillation often converts to atrial flutter (AFL) during management with class IC antiarrhythmic drugs. Differentiation of AFL with right bundle branch block (RBBB) pattern from fascicular ventricular tachycardia (VT) is difficult when R/S ratio in V6 is below 1.0. We sought to investigate the electrocardiographic criterion for distinguishing these arrhythmias. Method: We studied 32 consecutive patients (mean age 40.7±15.8 years, 24 male) who underwent successful catheter ablation for left posterior fascicular VT and 30 consecutive patients (mean age 57.0±17.8 years, 22 male) who were diagnosed with AFL with RBBB aberrancy where R/S raito in V6 was < 1.0. AFL with RBBB pattern was diagnosed based on the following criteria: 1) AV block during adenosine infusion or treadmill test 2) Induced by electrophysiology study 3) Interrogation of cardiac implantable electronic devices The rS/QRS ratio was defined as the ratio of QRS waveform durations as measured from the QRS onset to nadir of ...
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism
Authors: Nolan R. Williams, Boris D. Heifets, Christine Blasey, Keith Sudheimer, Jaspreet Pannu, Heather Pankow, Jessica Hawkins, Justin Birnbaum, David M. Lyons, Carolyn I. Rodriguez, Alan F. Schatzberg
Journal: American Journal of Psychiatry (2018)

Objective: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects. Method: In a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0.5 mg/kg of ketamine. Response was defined as a reduction ≥50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D) score on postinfusion day 1. Results: In the interim analysis, seven of 12 adults with treatment-resistant depression met the response criterion during the ketamine plus placebo condition. Reductions in 6-item and 17-item HAM-D scores among participants in the ketamine plus naltrexone condition were significantly lower than those of participants in the ketamine plus placebo condition on postinfusion days 1 and 3. Secondary analysis of all participants who completed the placebo and naltrexone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis. Conclusions: The findings suggest that ketamine’s acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.
Gain of positively charged amino acids at specific positions of HBsAg C-terminus tightly correlates with HBV-induced hepatocellular carcinoma by altering the structural folding of this domain
Authors: R. Salpini, L. Carioti, M. Aragri, D. Di Carlo, L. Colagrossi, A. Battisti, L. Piermatteo, A. Bertoli, L. Fabeni, A. Ricciardi, R. Longo, S. Romano, G. Cappiello, A. Spanò, P. Trimoulet, H. Fleury, J. Vecchiet, N. Iapadre, A. Barlattani, T. Mari, C. Pasquazzi, I. Lenci, S. Francioso, G. Parruti, L. Sarmati, M. Andreoni, M. Angelico, F. Ceccherini-Silberstein, C.F. Perno, V. Svicher
Journal: Journal of Hepatology (2017)
Comparing Spending on Medical Care in the United States and Other Countries
Authors: Andrew Bazemore, Stephen Petterson, Zachary Levin
Journal: JAMA (2018)

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Abstract 18934: Inhibition of Wnt6 by Sfrp2 Regulates CPC Differentiation by Differential Modulation of Canonical and Non Canonical Wnt Pathways
Authors: Amanda K Verma, Jeffrey Schmeckpeper, Lucy Yin, Lunan Zhang, Farideh Beigi, Alan Payne, Zhiping Zhang, Richard Pratt, Victor J Dzau, Maria Mirotsou
Journal: Circulation (2012)

Introduction: We have previously shown that in vivo administration of Sfrp2, an inhibitor of canonical Wnt signaling, into injured myocardium enhanced cardiac regeneration. In vitro, Sfrp2 selectively bound to Wnt6 expressed in cardiac progenitor cells (CPCs) and induced cell cycle arrest and cardiac differentiation. Here, we explore the role of Wnt6 inhibition by Sfrp2 in modulating Wnt pathways and regulation of CPC proliferation and differentiation. We also employ lineage tracing to investigate the contribution of CPCs to the in vivo effects of Sfrp2. Methods: Sca1+ CPCs were established and treated with recombinant Sfrp2 or Wnt6. Wnt pathway activation was measured by Western blotting. Proliferation was assessed by BrdU. Differentiation was documented by Nkx2.5 and Gata4 staining. Recombinant Sfrp2 protein was injected in Sca1-eGFP mice after ischemia/reperfusion injury. Co-staining of GFP with cardiac markers was assessed by confocal microscopy. Cardiac function was evaluated by echocardiography. Results: Treatment with Wnt6 increased canonical Wnt signaling and induced a 3.9 ± 0.9 fold increase in CPC proliferation. Simultaneous addition of Sfrp2 abolished the effects of Wnt6. Sfrp2 treatment alone inhibited canonical and activated non canonical Wnt signaling through β-catenin and JNK, respectively. JNK inhibitor SP600125 repressed Sfrp2 induced differentiation. To further explore the dual role of Sfrp2 in regulating Wnt signaling, CPCs modified to express constitutive active β-catenin (CA-CPCs) were treated with Sfrp2 and found to be resistant to both cell cycle arrest and differentiation. Interestingly, Sfrp2 treatment of CA-CPCs did not result in JNK activation suggesting Sfrp2 regulates JNK indirectly. Preliminary in vivo data indicate that exogenous Sfrp2 increased CPC differentiation and restored fractional shortening and contractility 2 months post infarction. Conclusion: Inhibition of Wnt6 by Sfrp2 differentially regulates canonical and non canonical Wnt pathways in CPCs, permitting further lineage commitment towards cardiomyocytes. Along with its cytoprotective and antifibrotic effects, Sfrp2 enhances cardiac regeneration in vivo thus highlighting its value as a potential therapeutic agent for cardiac disease.
Cardiorenal Syndrome Revisited
Authors: Faiez Zannad, Patrick Rossignol
Journal: Circulation (2018)

Cardiorenal syndromes have been categorized into 5 clinical subtypes based on which organ is perceived to be the primary precipitant of the vicious and interrelated cycle of declining function in both organs. This clinical classification has broadened interest in cardiorenal interactions, but it is merely descriptive, does not rely on or inform predominant pathophysiology, and has produced little change in either practice or the research agenda. In contrast, recent scientific work identifies common pathophysiological pathways for several categories of cardiorenal syndromes, suggesting a unifying pathogenesis. Fibrosis is a common consequence of inflammation- and oxidative stress–related endothelial dysfunction in aging, hypertension, diabetes mellitus, obesity, ischemia, and organ injury. It is a common feature in heart failure and chronic kidney disease. Therefore, we suggest that fibrosis may be not only a marker but also the primary driver of pathophysiology in several cardiorenal syndromes. Interstitial fibrosis in the heart, large arteries, and kidneys may play a key role in the pathophysiology of the cardiorenal syndrome continuum. Focusing on fibrosis as a disease mediator might enable the identification of fibrosis-related biotargets that could potentially be modulated with renin-angiotensin-aldosterone system inhibitors, mineralocorticoid receptor antagonists, or other novel antifibrotic agents in development. This conceptual approach may be an effective new strategy for the prevention and treatment of fibrosis within the cardiorenal syndrome continuum.
Abstract 20210: Comparison of Infectious Complications Encountered in Heart Transplant Recipients With and Without Pre-Transplant LVAD Therapy
Authors: Sana Arif, Randall Walker, Mark P Wihelm, Michael R Keating, Lisa Brumble, Holenarasipur R Vikram, Shimon Kusne, John M Stulak, Richard C Daly, Daniel Yip, Matthew A Hathcock, Jodi Chen Nienaber, Muhammad Rizwan Sohail
Journal: Circulation (2014)

Background: Due to growing discrepancy between the number of candidates for heart transplant therapy and the available donor organs in the United States, implantable left ventricular assist devices (LVADs) are increasingly being used as a bridge to transplantation and also as destination myocardial surrogate therapy. However, little is known about the impact of pre-heart transplant LVAD therapy on the risk of post-transplant infectious complications. Objective: To assess the differences in the types of infections encountered in heart transplant recipients who receive pre-transplant LVAD therapy compared to those who do not receive any assist device. Methods: We retrospectively reviewed medical records of all patients undergoing heart transplantation at three Mayo Clinic sites in Minnesota, Arizona and Florida, from January 2007 to June 2013. Patients were included in this study if 1) had a heart transplant without any assist device or 2) if they had a Heartmate II device as a bridge to transplant. Patient...
Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer
Authors: A. Kron, C. Alidousty, M. Scheffler, S. Merkelbach-Bruse, D. Seidel, R. Riedel, M.A. Ihle, S. Michels, L. Nogova, J. Fassunke, C. Heydt, F. Kron, F. Ueckeroth, M. Serke, S. Krüger, C. Grohe, D. Koschel, J. Benedikter, B. Kaminsky, B. Schaaf, J. Braess, M. Sebastian, K -O Kambartel, R. Thomas, T. Zander, A.M. Schultheis, R. Büttner, J. Wolf
Journal: Annals of Oncology (2018)

BackgroundWe analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC).Patients and methodsALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders.ResultsAmong 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4–5.6) versus 10.3 months (95% CI: 8.6–12.0), P< 0.001; OS 15.0 months (95% CI: 5.0–24.9) versus 50.0 months (95% CI: 22.9–77.1), P= 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3–4.1) versus 6.2 months (95% CI: 1.8–10.5), P= 0.021; OS 2.0 months (95% CI: 0.0–4.6) versus 9.0 months (95% CI: 6.1–11.9), P= 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9–7.2) versus 14.0 months (95% CI: 8.0–20.1), P< 0.001; OS 17.0 months (95% CI: 6.7–27.3) versus not reached, P= 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1–10.7) versus 9.9 months (95% CI: 6.4–13.5), P= 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P= 0.001).ConclusionsIn ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.
Abstract 19301: Blood Pressure Trajectories From Age 7 To 31 are Associated With Augmentation Index at Age 31 in Young Adults: The Kangwha Study
Authors: Ju-Mi Lee, Norrina B Allen, Yuichiro Yano, Hyeon Chang Kim, Joo Young Lee, Philip Greenland, Il Suh
Journal: Circulation (2015)

Introduction: Longterm blood pressure (BP) trajectories have been associated with subsequent subclinical atherosclerosis in early adulthood. However the association of BP trajectories at earlier age with subsequent arterial stiffness have not been studied. Objectives: Are BP trajectories from early childhood to adulthood associated with augmentation index (AIx) in young adults? Methods: The Kangwha Study is a community-based prospective cohort study that started in 1986 in Kangwha County, South Korea. Study participants were recruited at age 7 years, and 15 follow-up examinations have been conducted until age 31 (every year from age 7 to 18, and at age 20, 26, and 31 years). The current analysis includes 239 (male 110, female 129) participants whose BP were measured at least 3 times (on average 10 times) over 25 years. Augmentation index (AIx) as a measure of arterial stiffness was determined using radial artery tonometry by (Second peak systolic BP- diastolic BP) / (first peak SBP- DBP)*100 at the age 31 examination and adjusted for heart rate 75 were used. Latent mixture modeling was used to identify trajectories in mid-BP ((SBP+DBP)/2) over time. The associations of BP trajectories with AIx were assessed by linear regression. Results: We identified 5 mid-BP trajectories: low-stable (Group 1; 18.9%), continuously increasing (Group 2; 27.3%), increased slow and remain lower (Group 3; 29.9%), increasing moderately and remain lower (Group 4; 18.6%), and increasing fast and remain (Group 5; 5.3%). When we adjusted for sex and age, group 2 (β=6.05, p=0.01) and group 4 (β=6.72, p&lt;0.01) showed higher AIx than group 1. With additional adjustment for obesity, high fasting glucose, high cholesterol, cigarette smoking, alcoholic drinks, and exercise, group 2 (β=6.53, p=0.01), and group 4 (β=7.47, p&lt;0.01) showed higher AIx than group1. Conclusions: Longterm BP trajectories from early childhood had increased associations with arterial stiffness in early adulthood.
Biochemical profile in an infant with neonatal hemochromatosis shows evidence of impairment of mitochondrial long-chain fatty acid oxidation
Authors: Karina Lucio de Medeiros Bastos, Caio Robledo Quaio, Fabiana Roberto Lima, Iana Manuelle Araújo, Candice Alves Tavares Araújo, Flávia Balbo Piazzon, Ismael Dale Cotrim Guerreiro da Silva, Gabriel Nuncio Benevides, Ana Cristina Tannuri, Uenis Tannuri, Ramiro Anthero Azevedo, Chong Ae Kim
Journal: Clinical and Molecular Hepatology (2018)

2][3][4][5][6][7] Although its exact etiology remains to be better clarified, it has been hypothesized that maternal alloimmunity 1 and mitochondrial dysfunction 2 might play important roles in this disease.This condition differs from the main disorders that present with liver iron deposits, such as HFE-related hemochromatosis (autosomal recessive disorder caused by biallelic mutations in HFE gene in which iron deposits lead to adult-onset liver, heart, testicular and pancreatic involvement; OMIM#235200), juvenile hereditary hemochromatosis (autosomal recessive condition associated with biallelic mutations in HJV and HAMP genes and clinically similar to HFE-related hemochromatosis, but earlier onset and fast progression; OMIM#602390 and 613313), TFR2-related hereditary hemochromatosis (autosomal recessive condition associated with biallelic mutations in TFR2 gene and clinically similar to HFE-related hemochromatosis, but earlier onset and slow progression; OMIM#604250) and ferroportin (SLC40A1)-related iron overload (autosomal dominant condition associated with monoallelic mutations in SLC40A1 gene; OMIM#606069).Our male infant was born at term (39 weeks of gestation, birth weight: 2,615 g), after an uneventful pregnancy.His parents were healthy, caucasian, non-consanguineous and have not reported any familial history of liver, genetic, metabolic or syndromic conditions.His general conditions deteriorated after delivery and he required intensive care unit admission for anemia, bleeding, hypoglycemia, hypoactivity and unconjugated hyperbilirubinemia.During the following days, he developed recurrent hypoglycemia, cholestatic jaundice, hepatomegaly and hepatic dysfunction.He was then transferred to our tertiary-care unit at the 33rd day of life.Laboratory tests demonstrated anemia (hemoglobin 9.1 g/dL; hematocrit 26.3%), thrombocytopenia (platelet count: 49,000/μL), abnormal synthetic liver function (International Normalised Ratio