tbuckley/cabot-search huggingface dataset:
Humans, fruit flies, and automatons
Authors: Evan Charney
Journal: Behavioral and Brain Sciences (2012)

My response is divided into four sections: (1) is devoted to a potpourri of commentaries that are essentially in agreement with the substance of my target article (with one exception); in (2) I address, in response to one of the commentaries, several issues relating to the use of candidate gene association studies in behavior genetics (in particular those proposing a specific G × E interaction); in (3) I provide a detailed response to several defenses of the twin study methodology; and in (4) I conclude with several reflections on that methodology and the conception of human nature it has fostered.
Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis
Authors: Michelle C.M. Cheung, Alex J. Walker, Benjamin E. Hudson, Suman Verma, John McLauchlan, David J. Mutimer, Ashley Brown, William T.H. Gelson, Douglas C. MacDonald, Kosh Agarwal, Graham R. Foster, William L. Irving
Journal: Journal of Hepatology (2016)
Toward a translational neuropsychiatry of resilience
Authors: David Silbersweig
Journal: Behavioral and Brain Sciences (2015)

Abstract Neuropsychiatry integrates neuroscience and clinical pathophysiology of the human brain-mind interface. Kalisch et al. provide an important advance with a clear, quantitative, unified neuropsychiatric model of resilience, a crucial adaptive response to adversity. They highlight positive appraisal style, describing underlying neural circuitry and mechanisms. This provides a foundation for the development of biomarkers and targeted therapeutics across the range of neuropsychiatric disorders.
All government departments must tackle causes of ill health, say experts
Authors: Matthew Limb
Journal: BMJ (2016)

Politicians and health experts have called for cross government action to tackle the causes of poor health and warned of the impact of myopic funding cuts.

The All-Party Parliamentary Health Group and the Health Foundation said that ministers should make health improvement an urgent objective across sectors including education, leisure, housing, and employment.

The two groups published a collection of essays by more than 20 health experts on 6 July exploring public health issues affecting the UK.1

They said that tackling poverty and improving the wider social and physical environment was vital to enhancing people’s health and wellbeing, reducing preventable ill health, and easing pressure on the NHS.

Jo Bibby, the Health Foundation’s director of strategy, said that the health of the population was more important …
Two new phenylpropanoid glycosides from the aerial parts of Lespedeza cuneata
Authors: Chuangfeng Zhang, Jian Zhou, Jingzhi Yang, Chuangjun Li, Jie Ma, Dan Zhang, Dongming Zhang
Journal: Acta Pharmaceutica Sinica B (2016)

Two new phenylpropanoid glycosides named cuneataside E (1) and cuneataside F (2), were isolated from the aerial parts of Lespedeza cuneata (Dum. Cours.) G. Don, whose structures were E and Z isomer, respectively. Their structures were elucidated on the basis of comprehensive spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR). In in vitro bioassays at 10 μmol/L, compound 1 showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HeG2 cells.
Cosyntropin (ACTH alpha 1-24) stimulation test in depressed patients and healthy subjects
Authors: J D Amsterdam, A Winokur, E Abelman, I Lucki, K Rickels
Journal: American Journal of Psychiatry (1983)

Cosyntropin (ACTH alpha 1-24) infusion caused significantly higher cortisol concentrations, with earlier peak responses, in patients with endogenous depression than in normal subjects. There was no relationship between the cortisol levels after administration of dexamethasone and cosyntropin.
Genome-Wide Survey of Gut Fungi (Harpellales) Reveals the First Horizontally Transferred Ubiquitin Gene from a Mosquito Host
Authors: Yan Wang, Merlin M. White, Sebastian Kvist, Jean-Marc Moncalvo
Journal: Molecular Biology and Evolution (2016)

Harpellales, an early-diverging fungal lineage, is associated with the digestive tracts of aquatic arthropod hosts. Concurrent with the production and annotation of the first four Harpellales genomes, we discovered that Zancudomyces culisetae, one of the most widely distributed Harpellales species, encodes an insect-like polyubiquitin chain. Ubiquitin and ubiquitin-like proteins are universally involved in protein degradation and regulation of immune response in eukaryotic organisms. Phylogenetic analyses inferred that this polyubiquitin variant has a mosquito origin. In addition, its amino acid composition, animal-like secondary structure, as well as the fungal nature of flanking genes all further support this as a horizontal gene transfer event. The single-copy polyubiquitin gene from Z. culisetae has lower GC ratio compared with homologs of insect taxa, which implies homogenization of the gene since its putatively ancient transfer. The acquired polyubiquitin gene may have served to improve important functions within Z. culisetae, by perhaps exploiting the insect hosts' ubiquitin-proteasome systems in the gut environment. Preliminary comparisons among the four Harpellales genomes highlight the reduced genome size of Z. culisetae, which corroborates its distinguishable symbiotic lifestyle. This is the first record of a horizontally transferred ubiquitin gene from disease-bearing insects to the gut-dwelling fungal endobiont and should invite further exploration in an evolutionary context.
Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest
Authors: Laurent Argaud, Martin Cour, Pierre-Yves Dubien, François Giraud, Claire Jossan, Benjamin Riche, Romain Hernu, Michael Darmon, Yves Poncelin, Xavier Tchénio, Jean-Pierre Quenot, Marc Freysz, Cyrille Kamga, Pascal Beuret, Pascal Usseglio, Michel Badet, Bastien Anette, Kevin Chaulier, Emel Alasan, Sonia Sadoune, Xavier Bobbia, Fabrice Zéni, Pierre-Yves Gueugniaud, Dominique Robert, Pascal Roy, Michel Ovize
Journal: JAMA Cardiology (2016)

Experimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response.To determine whether early administration of cyclosporine at the time of resuscitation in patients with out-of-hospital cardiac arrest (OHCA) would prevent multiple organ failure.A multicenter, single-blind, randomized clinical trial was conducted from June 22, 2010, to March 13, 2013 (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation [CYRUS]). Sixteen intensive care units in 7 university-affiliated hospitals and 9 general hospitals in France participated. A total of 6758 patients who experienced nonshockable OHCA (ie, asystole or pulseless electrical activity) were assessed for eligibility. Analyses were performed according to the intention-to-treat analysis.Patients received an intravenous bolus injection of cyclosporine, 2.5 mg/kg, at the onset of advanced cardiovascular life support (cyclosporine group) or no additional intervention (control group).The primary end point was the Sequential Organ Failure Assessment (SOFA) score, assessed 24 hours after hospital admission, which ranges from 0 to 24 (with higher scores indicating more severe organ failure). Secondary end points included survival at 24 hours, hospital discharge, and favorable neurologic outcome at discharge.Of the 6758 patients screened, 794 were included in intention-to-treat analysis (cyclosporine, 400; control, 394). The median (interquartile range [IQR]) ages were 63.0 (54.0-71.8) years for the cyclosporine group and 66.0 (57.0-74.0) years for the control group. The cohorts included 293 men (73.3%) in the treatment group and 288 men (73.1%) in the control group. At 24 hours after hospital admission, the SOFA score was not significantly different between the cyclosporine (median, 10.0; IQR, 7.0-13.0) and the control (median, 11.0; IQR, 7.0-15.0) groups. Survival was not significantly different between the 98 (24.5%) cyclosporine vs 101 (25.6%) control patients at hospital admission (adjusted odds ratio [aOR], 0.94; 95% CI, 0.66-1.34), at 24 hours for 67 (16.8%) vs 62 (15.7%) patients (aOR, 1.08; 95% CI, 0.71-1.63), and at hospital discharge for 10 (2.5%) vs 5 (1.3%) patients (aOR, 2.00; 95% CI, 0.61-6.52). Favorable neurologic outcome at discharge was comparable between the cyclosporine and control groups: 7 (1.8%) vs 5 (1.3%) patients (aOR, 1.39; 95% CI, 0.39-4.91).In patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure.clinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.
P-095 MSCMCC gastric cancer cohort: indirect comparison between adjuvant chemoradiation and perioperative chemotherapy in gastric cancer patients in a referral site
Authors: M. Mydlowska, Z. Guzel-Szczepiorkowska, S. Rybski, J. Krynski, A. Cencelewicz, M. Winiarek, J. Zwolinski, E. Kosakowska, T. Olesinski, L. Wyrwicz
Journal: Annals of Oncology (2016)
Esophageal Cancer in the Transkei: 1955–69 2
Authors: Elizabeth Frances Rose
Journal: JNCI Journal of the National Cancer Institute (1973)

During a 15-year survey (1955–69) of esophageal cancer among the Bantu of the Transkei, 5095 cases were reported to the registry from a population of 1.7 million. Of these, 3281 were confirmed by doctors. The survey was divided into 3 five-year study periods. Tabulations for the first and last periods were presented and showed an incidence rate for all cases at 35 per 100,000 for males and 17–19 per 100,000 for females for the whole area (African standard). Variation in incidence was marked among the 26 districts, ranging from 116 for males and 50 for females in the Butterworth area to 3 and 2, respectively, in Bizana during the first study period (1955–59). In the third period the pattern of variation between the districts followed that of the first period, and high- and low-incidence areas tended to remain as such. There was, however, a slight decrease in reported cases from the high incidence areas and an increase in the low incidence areas. More cases were confirmed in the second period, and the male to female ratio remained 2:1.
Genetically engineered NY-ESO-1 specific T cells in HLA-A201+ patients with advanced cancers.
Authors: Melinda S. Merchant, Mihaela C. Cristea, Edward A. Stadtmauer, William D. Tap, Sandra P. D'Angelo, Stephan A. Grupp, Tom Holdich, Gwendolyn Binder-Scholl, Bent K Jakobsen, Kunle Odunsi, Aaron Rapoport, Crystal Mackall
Journal: Journal of Clinical Oncology (2015)

TPS3102 Background: NY-ESO-1 (CTAG-1B) is a cancer testis antigen associated with spontaneous and vaccine-induced immunity that can lead to improved clinical outcomes. NY-ESO-1 is not expressed in vital tissues, and is expressed in approximately 40% of ovarian, 60% of advanced myeloma, and 70% of synovial sarcoma tumors. Expression is correlated with tumor proliferation and high risk features. A human-derived affinity-optimized TCR that recognizes the NY-ESO-1 derived SLLMWITQC peptide in complex with HLA‐A*0201 (NY-ESOc259) has been generated, and clinically tested as previously described using adoptive T cell transfer with supportive IL-21 Methods: Multiple clinical studies were initiated in HLA-A201+ patients with NY-ESO-1 expressing tumors. NY-ESO-1c259-engineered autologous T-cells are manufactured centrally, using a 12 day commercial-grade closed system, and are administered without supportive IL-2. 40 patients have been infused: 25/26 on a phase I/II study in adults with systemic or multifocal myeloma requiring autologous stem cell transplantation, and who have incompletely responded to prior therapy or have high risk features (NCT01352286); 10/30 on a pilot study in patients ≥4 years old with unresectable, metastatic or recurrent synovial sarcoma (NCT01343043); 5/20 on a phase I study in adults with refractory or platinum resistant ovarian cancer and/or that have received ≥2 lines of chemotherapy (NCT01567891). Pre-infusion lymphodepleting chemotherapy is administered, and varies in intensity across studies. Primary objectives include safety and tolerability. Secondary objectives include evaluation of gene modified cells persistence in blood and tumor biopsies, lineage and functionality of these cells over time, and monitoring for serum cytokine levels and NY-ESO-1 antigen on tumor post infusion. Response assessments are performed using RECIST (sarcoma), IMWR criteria (myeloma), or immune-related response criteria (irRC; ovarian). 1. Robbins PF, Morgan RA, Feldman SA, et al: Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1. Journal of Clinical Oncology 29:917-924, 2011 Clinical trial information: NCT01343043.
Gallbladder Activity on 99mTc-Labeled Red Cell Scintigraphy Confirmed by SPECT/CT Imaging
Authors: Ling Wang, Hongli Jing, Libo Chen, Zhenghua Wang, Fang Li
Journal: Clinical Nuclear Medicine (2016)

Tc-labeled red cell (Tc-RBC) scintigraphy is commonly used to detect gastrointestinal bleeding. Gallbladder visualization on Tc-RBC scintigraphy is not common. We present a case of gallbladder visualization on Tc-RBC scintigraphy confirmed by SPECT/CT imaging in a patient with chronic renal failure and anemia.
Myeloid Chimerism Reflects Engraftment of Donor Hematopoiesis, Whereas T Cell Chimerism Reflects Survival and Expansion of Donor and Recipient Residual Mature T Cells Early After T Cell Depleted Allogeneic Stem Cell Transplantation.
Authors: Jessica C. Harskamp, Esther H.M. van Egmond, Hans L. Vos, Stijn J.M. Halkes, Roel Willemze, J.H. Frederik Falkenburg, Erik W.A. Marijt
Journal: Blood (2009)
A Phase II study of gemcitabine plus zoledronic acid in subjects with Stage IV pancreatic cancer
Authors: J. V. Cox, T. H. Cartwright, M. Neubauer, D. McCollum, J. Sandbach, M. A. Monticelli, K. A. Boehm, D. Ilegbodu, L. Asmar
Journal: Journal of Clinical Oncology (2006)

14002 Background: Gemcitabine, the standard chemotherapy for advanced pancreatic cancer (APC), produces low response rates and short time to progression. Preclinical studies suggest that zoledronic acid inhibits pancreatic cell lines by interfering with the p21ras/raf-1/MEK1/ERKL signaling pathway. We conducted this trial to evaluate the efficacy and toxicity of gemcitabine and zoledronic acid in subjects with APC. Methods: Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma (Stage IV) not amenable to resection with curative intent. Gemcitabine 1000 mg/m 2 IV was given on Days 1, 8, 15, and 22 in Cycle 1 and Days 1, 8, and 15 in subsequent cycles. Zoledronic acid 4 mg IV was given on Day 1 every 4 weeks. Toxicity was assessed at each visit. Results: Between December 2004 and July 2005, 35 subjects were enrolled. Baseline characteristics: 20 males (57%), median age 66.7 years (range, 40–83.5), and KPS of 70/80/90/100 = 8%/29%/34%/29%, respectively. Four patients had locally advanced disease (3 stage IIB and 1 stage III), 86% of subjects had Stage IV disease at diagnosis; 91% of subjects had adenocarcinoma. Prior therapy included surgery (n=15, 43%), chemotherapy (n=3, 9%), and radiotherapy (n=2, 6%). To date, there has been 1 PR and 9 SD; the clinical benefit rate (PR+SD≥6 months) was 14%. Grade 3 and 4 treatment-related toxicities included: neutropenia (22%); thrombocytopenia and fatigue, (12.5% each); and anemia, nausea/vomiting, dehydration, and diarrhea (6% each). Seven treatment-related SAEs have been reported; 28 subjects are off study. Patients discontinued treatment due to: progressive disease (PD) (n=15), toxicity (n=4, 1 each DVT, infection, back pain, and generalized weakness), withdrew consent (n=3), MD decision (n=2), patient request (n=2), and death (n=2), To date, 21 subjects have died; deaths were attributed to PD (n=16), CVA (n=1), and unknown (n=4). Conclusions: Pancreatic cancer, typically advanced at diagnosis, remains a major treatment challenge. Zoledronic acid in combination with gemcitabine was well-tolerated in this study. Future genomic testing is proposed for responders. Updated toxicity, response, and survival data will be presented. Supported by Novartis Pharmaceuticals Corp., East Hanover, NJ. No significant financial relationships to disclose.
Efficacy and tolerability in an open-label phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC).
Authors: Johanna C. Bendell, Chloe Evelyn Atreya, Thierry André, Josep Tabernero, Michael S. Gordon, Rene Bernards, Eric Van Cutsem, Sabine Tejpar, Roger Sidhu, William Y. Go, Alicia Allred, Monica Motwani, Benjamin B. Suttle, Yuehui Wu, Axel Hoos, Keith W. Orford, Ryan Bruce Corcoran, Jan HM Schellens
Journal: Journal of Clinical Oncology (2014)

3515 Background: BRAF V600 mutations occur in 5–10% of CRC and confer poor prognosis. Unlike in BRAF mutant (BRAFm) melanoma, BRAF and MEK inhibitors show limited activity in BRAFm CRC. Preclinical data suggest that EGFR can mediate resistance in BRAFm CRC, which can be overcome by combined inhibition of BRAF and EGFR. Therefore, combined inhibition of the BRAF pathway (with D or D + T and with anti-EGFR agent P) to prevent EGFR-mediated resistance is a rational and promising approach to treat BRAFm CRC. Methods: Eligible pts with BRAFm CRC enrolled in Parts 1 and 2 of the ongoing 3-part study, dose escalation (DE; Part 1), cohort expansion (CE; Part 2) and a planned randomized comparison (Part 3), received either the doublet (D + P) or triplet (D + P + T) combination. Results: 19 pts received D + P ± T in DE or CE. Doublet: 6 pts received the full doublet dose (D 150 mg twice daily [BID] + P 6 mg/kg every 2 weeks [Q2W]) in Cohort 1 DE and 3 pts received the doublet in Part 2 CE. Triplet: 3 pts received the lowest combination dose of the triplet (D 150 mg BID + P 4.8 mg/kg Q2W + T 1.5 mg once daily [QD]) in Cohort 2. DE Cohorts 3A (D 150 mg BID + P 4.8 mg/kg Q2W + T 2 mg QD), n = 4 and 3B (D 150 mg BID + P 6 mg/kg Q2W + T 1.5 mg QD), n = 3 were opened simultaneously. No dose-limiting toxicities have been seen in any cohorts. Most common drug-related adverse event (AE) was dermatitis acneiform for doublet (5/9 pts, all Grade [Gr] 1) and triplet (5/10 pts, 3 Gr 1 and 2 Gr 2) pts. In the doublet group, no possibly drug-related Gr > 3 events were reported. In the triplet group, Gr > 3 events at least possibly drug-related, included vomiting (n = 1), rash (n = 1) and skin fissures (n = 1). In preliminary efficacy data, partial responses have been seen in 4/6 evaluable pts on the triplet dose (3/4 ongoing, 1 > 7 months) with 2 pts with stable disease (SD; 1 ongoing and 1 discontinued due to AE). Of the 8 evaluable pts on the doublet dose, 7/8 achieved SD (lasting 6–26 weeks; 2 pts ongoing) as the best overall response. Updated results will be presented. Conclusions: P can be safely combined with D or D/T. Encouraging evidence of clinical activity has been seen. Clinical trial information: NCT01750918.
Acute rheumatic fever and rheumatic heart disease
Authors: Jonathan R. Carapetis, Andrea Beaton, Madeleine W. Cunningham, Luiza Guilherme, Ganesan Karthikeyan, Bongani M. Mayosi, Craig Sable, Andrew Steer, Nigel Wilson, Rosemary Wyber, Liesl Zühlke
Journal: Nature Reviews Disease Primers (2016)
Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial
Authors: Erin A. Bohula, Robert P. Giugliano, Christian T. Ruff, Julia F. Kuder, Sabina A. Murphy, Elliott M. Antman, Eugene Braunwald
Journal: Circulation (2016)

Background: Edoxaban, an oral factor Xa inhibitor with 50% renal clearance, was noninferior to well-managed warfarin for stroke or systemic embolism (S/SE) prevention and reduced bleeding in patients with atrial fibrillation. We evaluated the efficacy and safety of edoxaban versus warfarin across the range of baseline creatinine clearance (CrCl) in the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) with a focus on the higher-dose edoxaban regimen (HDER) and the upper range of CrCl. Methods: A total of 14 071 patients with atrial fibrillation at moderate to high risk for stroke were randomized to warfarin or HDER (60 mg daily or a 50% dose reduction to 30 mg daily for CrCl 30–50 mL/min, body weight of ≤60 kg, or use of a potent phosphorylated glycoprotein inhibitor). CrCl &lt;30 mL/min was exclusionary. End points of S/SE, International Society on Thrombosis and Haemostasis major bleeding, and the net clinical outcome of S/SE/major bleeding or death were evaluated by intention-to-treat analysis using the prespecified CrCl cut point of 50 mL/min and additional exploratory cut points with the Cockcroft-Gault formula. A sensitivity analysis was performed with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula for estimating renal function. Results: The relative risk of S/SE with HDER versus warfarin in patients with CrCl &gt;50 mL/min (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.72–1.04) was similar to that in patients with CrCl ≤50 mL/min (HR, 0.87; 95% CI, 0.65–1.18; P for interaction=0.94). Several exploratory analyses suggested lower relative efficacy for the prevention of S/SE with HDER compared with warfarin at higher levels of CrCl (CrCl ≤50 mL/min: HR, 0.87; 95% CI, 0.65–1.18; CrCl &gt;50–95 mL/min: HR, 0.78; 95% CI, 0.64–0.96; CrCl &gt;95 mL/min: HR, 1.36; 95% CI, 0.88–2.10; P for interaction=0.08). Bleeding rates were lower at all levels of CrCl with HDER ( P for interaction=0.11). Because of the preserved effect on bleeding, the net clinical outcome was more favorable with HDER across the range of CrCl ( P for interaction=0.73). Similar findings were observed in the sensitivity analysis using the CKD-EPI formula. Conclusions: Although there was an apparent decrease in relative efficacy to prevent arterial thromboembolism in the upper range of CrCl, the safety and net clinical benefit of HDER compared with warfarin are consistent across the range of renal function. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.
Salvage pathways in heart rejuvenation
Authors: Emilio Hirsch
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Cardiac salvage by tweaking with beta-3-adrenergic receptors' by J.-L. Balligand, pp. 128–133. 

This editorial refers to ‘Succinate metabolism: a new therapeutic target for myocardial reperfusion injury' V.R. Pell et al ., pp. 134–141. 

This editorial refers to ‘Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation' by A. Cannata et al ., pp. 142–153. 

This editorial refers to ‘Old dogs, new tricks: novel cardiac targets and stress regulation by protein kinase G' by P.P. Rainer and D.A. Kass, pp. 154–162. 

Aging of the population is a concern in the near future for a significant fraction of countries worldwide. While in several members of the European Union having people over 60 largely outnumbering newborns is a reality, this is now predicted to occur also in Asia, and in the near future, elderly people will represent more than a fourth of the global population. Such predictions prompt to address the linked healthcare challenge in time and efforts in defining new treatments for the diseases of the elderly are currently under intense investigation. It is along this line that the Myocardial Function and Cellular Biology Working Groups of the European Society of Cardiology gathered in the biannual Varenna meeting in the spring of 2015. This conference entitled ‘Salvage Pathways in Heart Rejuvenation’ intended to provide the latest findings in cardiovascular …