tbuckley/cabot-search huggingface dataset:
Tick Bite Linked to Red Meat Allergy
Authors: Bridget M. Kuehn
Journal: JAMA (2018)

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Effectiveness of systemic family therapy versus treatment as usual for young people after self-harm: a pragmatic, phase 3, multicentre, randomised controlled trial
Authors: David J Cottrell, Alexandra Wright-Hughes, Michelle Collinson, Paula Boston, Ivan Eisler, Sarah Fortune, Elizabeth H Graham, Jonathon Green, Allan O House, Michael Kerfoot, David W Owens, Eirini-Christina Saloniki, Mima Simic, Fiona Lambert, Justine Rothwell, Sandy Tubeuf, Amanda J Farrin
Journal: The Lancet Psychiatry (2018)

BackgroundSelf-harm in adolescents is common and repetition occurs in a high proportion of these cases. Scarce evidence exists for effectiveness of interventions to reduce self-harm.MethodsThis pragmatic, multicentre, randomised, controlled trial of family therapy versus treatment as usual was done at 40 UK Child and Adolescent Mental Health Services (CAMHS) centres. We recruited young people aged 11–17 years who had self-harmed at least twice and presented to CAMHS after self-harm. Participants were randomly assigned (1:1) to receive manualised family therapy delivered by trained and supervised family therapists or treatment as usual by local CAMHS. Participants and therapists were aware of treatment allocation; researchers were masked. The primary outcome was hospital attendance for repetition of self-harm in the 18 months after group assignment. Primary and safety analyses were done in the intention-to-treat population. The trial is registered at the ISRCTN registry, number ISRCTN59793150.FindingsBetween Nov 23, 2009, and Dec 31, 2013, 3554 young people were screened and 832 eligible young people consented to participation and were randomly assigned to receive family therapy (n=415) or treatment as usual (n=417). Primary outcome data were available for 795 (96%) participants. Numbers of hospital attendances for repeat self-harm events were not significantly different between the groups (118 [28%] in the family therapy group vs 103 [25%] in the treatment as usual group; hazard ratio 1·14 [95% CI 0·87–1·49] p=0·33). Similar numbers of adverse events occurred in both groups (787 in the family therapy group vs 847 in the treatment as usual group).InterpretationFor adolescents referred to CAMHS after self-harm, having self-harmed at least once before, our family therapy intervention conferred no benefits over treatment as usual in reducing subsequent hospital attendance for self-harm. Clinicians are therefore still unable to recommend a clear, evidence-based intervention to reduce repeated self-harm in adolescents.FundingNational Institute for Health Research Health Technology Assessment programme.
Synthesis and evaluation of in vitro and in vivo antitumoral activity of 1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-1,4-dien-3-one and derivatives
Authors: Claudete Valduga, Daniela Rando, Joao Carvalho, Durvanei Maria, Fernanda Flores, Danilo Inada, Reginaldo Santos, Jose Suarez
Journal: Cancer Research (2008)

4152   Introduction and Objective: Compounds chemically known as 1,5-diaryl-penta-1,4-dien-3-ones have been widely explored as promising pharmacological agents due to their similarity with curcumin, a natural product found as a major pigment in the Indian spice turmeric (Curcuma longa, Zingiberaceae), known for its antitumor, antioxidant, antiarthritic, anti-amyloid and anti-inflammatory properties. The current study was designed to synthesize 1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-1,4-dien-3-one (HB1) and derivatives at high yield and to evaluate their cytotoxicity against tumoral cell lines, the  in vivo  toxicity and antitumoral activity in B16F10 melanoma-bearing mice for the compound with more expressive cytotoxic action.  Materials and Methods: Five pentadienones were synthesized following Claisen-Condensation reaction, starting from vanillin derivatives and acetone in acid medium under ultrasonic irradiation conditions (40 kHz). MTT method was used to evaluate the cytotoxicity of these compounds, diluted in Miglyol 810, at the concentrations ranging from 0.2 to 250 μ g/mL against tumoral human cell lines as lung carcinoma NCI460, melanoma UACC62, breast MCF-7, breast expressing multidrug resistance phenotype NCI-ADR, colon HT-29, renal 786-O, ovary OVCAR-3, prostate PC-3 and leukemia K-562. Lethal dose determined in groups of ten female C57BL/6J mice. To evaluate the antitumoral activity, HB1 diluted in Miglyol 810, was administered at 1.15 μ g/kg/day dose during fifteen days, beginning at the fourth day after the B16F10 melanoma inoculation in mice. Miglyol 810 and saline were used as control.  Results: Five pentadienones were obtained by Claisen-Condensation reaction with 92% yield and 99% purity, assayed by HPLC. Between the synthesized compounds, HB1 exhibited the most potent cytotoxic action against the nine human cell lines assayed. Despite the cytostatic and cytotoxic actions shown by the other compounds, HB1 was chosen for  in vivo  experiments because of its high IC 50  level (equal or less than 0.75 μ g/mL). Regarding the animal toxicity performed in female C57BL/6J mice, it was noticed a very low toxicity rate for HB1 (LD 50  = 8.54g/kg) for HB1 diluted in dimethylsulphoxide, when it was diluted in Miglyol 810, lethal dose was not found. Antitumoral activity evaluated in B16F10 melanoma-bearing mice with HB1 shown that this active principle does not allow the tumor growing. The control groups (Miglyol 810 or saline) showed an exponential growth of the tumor. The tumor growth inhibition for HB1 was higher than 98% compared to the control groups.  Conclusion: The synthetic method used here was feasible to obtain pentadienones at high-yield. The selected compound HB1 gave us very strong evidences about its powerful antitumoral therapeutic properties.
Paradigm Shift for Treatment of Atrial Fibrillation in Heart Failure
Authors: Mark S. Link
Journal: New England Journal of Medicine (2018)

Congestive heart failure and atrial fibrillation often coexist. Up to 50% of patients who present with new-onset congestive heart failure have atrial fibrillation; conversely, among those patients with new-onset atrial fibrillation, close to one third have congestive heart failure.1 It is difficult to sort out which is cause and which is effect, yet it would seem logical that being in atrial fibrillation is not ideal for patients with congestive heart failure and that maintenance of normal sinus rhythm would probably improve functional status and possibly reduce mortality in this population. In the absence of congestive heart failure, the data to . . .
Double incision and snare resection in symptomatic Zenker’s diverticulum: a modification of the stag-beetle knife technique
Authors: Sauid Ishaq, Giorgio Battaglia, Alessandro Antonello
Journal: Endoscopy (2018)

See also: Double incision and snare resection in symptomatic Zenker’s diverticulum: a modification of the stag beetle knife techniqueEndoscopy eFirstDOI: 10.1055/s-0043-119286 See also: Differences in endoscopic techniques for symptomatic Zenker’s diverticulumEndoscopy 2018; 50(02): 183-184DOI: 10.1055/s-0043-123936
Abstract 20052: Mortality Reduction With Angiotensin Receptor Blockers in Hypertension Patients With Left Ventricular Hypertrophy
Authors: Olufunso W Odunukan, David M Filsoof, David O Hodge, Alison B Schultz, Mark A Nyman, Vuyisile T Nkomo
Journal: Circulation (2015)

Background: Left ventricular hypertrophy (LVH) is considered a marker of stage B heart failure according to the ACC/AHA classification. Current guidelines recommend beta-blocker (BB) therapy for treatment but randomized control trials suggest that Angiotensin Receptor Blocker (ARB) therapy may be superior. Purpose: To compare survival among cohorts of LVH patients classified according to use of BB, ARB or neither (NONE) class of medications. Methods: A retrospective analysis of hypertension patients seen in the outpatient clinics was done. LVH was defined using the most stringent electrocardiogram (ECG) criteria whereas patients with minimal and moderate voltage criteria were excluded. Using hypertension medications from the year 2009 outpatient visits notes, 869 LVH patients were classified into BB (604), ARB (115) and NONE (150) cohort groups. Cox proportional hazard models were built. Results: Survival at 5 years was 85.2% with 17 deaths and 98 censored patients, (unadjusted hazard ratio HR 0.53, p=0.03) in the ARB cohort and 75.5 % with 148 deaths, 456 censored patients (HR 0.91, p=0.61) in the BB group compared to 74.0% in the NONE cohort with 39 deaths and 111 censored patients. After adjusting for age, sex, atrial fibrillation/flutter, heart failure, chronic kidney disease (CKD), coronary artery disease (CAD), acute myocardial infarction, stroke, obesity, diabetes, sleep apnea and pulmonary hypertension, HR was 0.40, p=0.006 for ARB and HR=0.80, p=0.278 for BB compared to the NONE group. At baseline, there was no significant difference in age, sex, and the prevalence in heart failure, stroke, obesity, sleep apnea, and pulmonary hypertension in all three groups although the BB group had significantly highest prevalence of atrial fibrillation/flutter, CAD, CKD and the lowest prevalence of diabetes. Conclusion: There was a significant mortality reduction benefit to hypertension patients with ECG diagnosed LVH treated with ARB which was not seen in similar patients on BB when compared to those treated with none of both medication classes. This effect persisted even after adjusting for cardiovascular comorbidities.
Abstract 14955: An Early Appointment to Outpatient Cardiac Rehabilitation at Hospital Discharge Improves Attendance at Orientation: A Randomized, Single-Blind, Controlled Trial
Authors: Quinn R Pack, Mayo Clinic, Mouhamad Mansour, Joaquim S Barboza, Brooks A Hibner, Meredith G Mahan, Jonathan K Ehrman, Melissa A Vanzant, John R Schairer, Steven J Keteyian
Journal: Circulation (2012)

Quinn R Pack, 2012 Finalist and Presenting Author
Oligonucleotide microarray analysis of CD34+cells in patients with low risk myelodysplasia and age-matched healthy subjects.
Authors: A Sternberg, M Ahmed, S Johnson, S Killick, D Bowen, C Chapman, B Vadher, R Girish, G Vassilou, T Freeman, T Seidl, L Bruno, P Vyas
Journal: Blood (2003)
Association between acute respiratory disease events and the <i>MUC5B</i> promoter polymorphism in smokers
Authors: Samuel Y Ash, Rola Harmouche, Rachel K Putman, James C Ross, Fernando J Martinez, Augustine M Choi, Russell P Bowler, Elizabeth A Regan, Jeffrey L Curtis, MeiLan K Han, Richard C Boucher, Wanda K O’Neal, Hiroto Hatabu, David A Lynch, Ivan O Rosas, Gary M Hunninghake, Raul San Jose Estepar, George R Washko
Journal: Thorax (2018)

A single-nucleotide polymorphism (rs35705950) in the mucin 5B ( MUC5B ) gene promoter is associated with pulmonary fibrosis and interstitial features on chest CT but may also have beneficial effects. In non-Hispanic whites in the COPDGene cohort with interstitial features (n=454), the MUC5B promoter polymorphism was associated with a 61% lower odds of a prospectively reported acute respiratory disease event (P=0.001), a longer time-to-first event (HR=0.57; P=0.006) and 40% fewer events (P=0.016). The MUC5B promoter polymorphism may have a beneficial effect on the risk of acute respiratory disease events in smokers with interstitial CT features.
The Benefits and Risks of Quantified Relationship Technologies: Response to Open Peer Commentaries on “The Quantified Relationship”
Authors: John Danaher, Sven Nyholm, Brian D. Earp
Journal: The American Journal of Bioethics (2018)

Our critics argue that quantified relationships (QR) will threaten privacy, undermine autonomy, reinforce problematic business models, and promote epistemic injustice. We do not deny these risks. B...
Body mass index status and peripheral airway obstruction in school-age children: a population-based cohort study
Authors: Sandra Ekström, Jenny Hallberg, Inger Kull, Jennifer L P Protudjer, Per Thunqvist, Matteo Bottai, Per Magnus Gustafsson, Anna Bergström, Erik Melén
Journal: Thorax (2018)

Background Few large prospective studies have investigated the impact of body mass index (BMI) on lung function during childhood. Methods Using data collected between 2002 and 2013, we analysed associations between BMI status and lung function (assessed by spirometry) from 8 to 16 years, as well as cross-sectional associations with small airway function (impulse oscillometry) at 16 years in the BAMSE cohort (n=2889). At 16 years, cross-sectional associations with local and systemic inflammation were investigated by analysing FE NO , blood eosinophils and neutrophils. Results Overweight and obesity at 8 years were associated with higher FVC, but lower FEV 1 /FVC ratio at 8 and 16 years. In boys, but not girls, obesity at 8 years was associated with a further reduction in FEV 1 /FVC between 8 and 16 years. In cross-sectional analyses, overweight and obesity were associated with higher frequency dependence of resistance (R 5–20 ) and larger area under the reactance curve (AX 0.5 ) at 16 years. Increased blood neutrophil counts were seen in overweight and obese girls, but not in boys. No association was found between BMI status and FE NO . Persistent, but not transient, overweight/obesity between 8 and 16 years was associated with higher R 5–20 and AX 0.5 and lower FEV 1 /FVC (−2.8% (95% CI −4.1 to −1.2) in girls and −2.7% (95% CI −4.4 to −1.1) in boys) at 16 years, compared with persistent normal weight. Conclusion In childhood and adolescence, overweight and obesity, particularly persistent overweight, were associated with evidence of airway obstruction, including the small airways.
Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day 1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor Antagonist and Palonosetron in High-Emetogenic Chemotherapy
Authors: Yuka Ito, Takashi Tsuda, Hiroko Minatogawa, Sayaka Kano, Kentaro Sakamaki, Masahiko Ando, Koichiro Tsugawa, Yasuyuki Kojima, Naoki Furuya, Kunihiro Matsuzaki, Mamoru Fukuda, Sadatoshi Sugae, Ichiro Ohta, Hitoshi Arioka, Yutaka Tokuda, Kazutaka Narui, Ayako Tsuboya, Takashi Suda, Satoshi Morita, Narikazu Boku, Takeharu Yamanaka, Takako Eguchi Nakajima
Journal: Journal of Clinical Oncology (2018)

Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK 1 -RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m 2 or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK 1 -RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at −15.0% (Arm D1 − Arm D3). Results A total of 396 patients—196 and 200 patients in Arms D3 and D1, respectively—were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, −12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, −8.1% to 10.6%; P &lt; .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, −14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK 1 -RA and Palo in HEC.
Abstract 23082: Gemcabene Add-On Therapy to High- and Moderate-Intensity Statin Stratums in Hypercholesterolemic Subjects (ROYAL-1, a Phase 2b Study)
Authors: Juan Frias, John Kastelein, Rebecca Bakker-Arkema, Liz Masson, Lee Golden, Charles Bisgaier, Evan Stein
Journal: Circulation (2017)

Introduction: Recent large cardiovascular event outcome trials with ezetimibe and a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to statins demonstrated benefit from additional LDL-C reduction. Despite availability of approved injectable PCSK9 inhibitors, there still remains a need for novel, efficacious, safe, well-tolerated, and cost-effective oral LDL-C lowering therapies. Gemcabene (GEM) has been shown to significantly lower LDL-C, non-HDL-C, ApoB, and hsCRP further in hypercholesterolemic subjects when added to background statin therapy. GEM neither interacts pharmacokinetically nor has shown increased adverse effects with statins. Hypothesis: GEM added to high- or moderate-intensity statin +/-ezetimibe therapy will provide additional LDL-C reduction for subjects not at goal. Methods: High-risk subjects including those with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease on appropriate diet and stable statin therapy for at least 12 weeks and LDL-C ≥ 100 mg/dL (2.59 mmol/L) and triglycerides &lt; 500 mg/dL (5.65 mmol/L) were randomized into a 12-week, placebo-controlled, parallel-group, double-blind study to assess the efficacy of GEM 600 mg QD on LDL-C and other lipoproteins and hsCRP. Safety and tolerability were evaluated. The subjects were stratified by high- or moderate-intensity statin therapy, with or without ezetimibe, with a target of 52 subjects (26 GEM; 26 placebo) in each stratum. The study (NCT02634151) enrolled 105 subjects (53% women, 77% Caucasian, mean age 61 years). Mean baseline LDL-C for all subjects was approximately 134 mg/dL (3.48 mmol/L) with most subjects in the high-intensity statin stratum on atorvastatin and most subjects in the moderate-intensity stratum on either simvastatin or atorvastatin. Results: Data for the full cohort was previously reported. Data by statin-intensity stratum (high and moderate) including LDL-C, non-HDL-C, ApoB, Lp(a) and hsCRP as well as safety and tolerability will now be reported. Conclusion: The trial and data analysis by statin-intensity stratification, including efficacy and safety, will be completed in October 2017 in time for presentation at the American Heart Association Scientific Sessions.
Microglia are required for protection against lethal coronavirus encephalitis in mice
Authors: D. Lori Wheeler, Alan Sariol, David K. Meyerholz, Stanley Perlman
Journal: Journal of Clinical Investigation (2018)

Recent findings have highlighted the role of microglia in orchestrating normal development and refining neural network connectivity in the healthy CNS. Microglia are not only vital cells in maintaining CNS homeostasis, but also respond to injury, infection, and disease by undergoing proliferation and changes in transcription and morphology. A better understanding of the specific role of microglia in responding to viral infection is complicated by the presence of nonmicroglial myeloid cells with potentially overlapping function in the healthy brain and by the rapid infiltration of hematopoietic myeloid cells into the brain in diseased states. Here, we used an inhibitor of colony-stimulating factor 1 receptor (CSF1R) that depletes microglia to examine the specific roles of microglia in response to infection with the mouse hepatitis virus (MHV), a neurotropic coronavirus. Our results show that microglia were required during the early days after infection to limit MHV replication and subsequent morbidity and lethality. Additionally, microglia depletion resulted in ineffective T cell responses. These results reveal nonredundant, critical roles for microglia in the early innate and virus-specific T cell responses and for subsequent host protection from viral encephalitis.
RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis
Authors: Jose R. Cortes, Alberto Ambesi-Impiombato, Lucile Couronné, S. Aidan Quinn, Christine S. Kim, Ana C. da Silva Almeida, Zachary West, Laura Belver, Marta Sanchez Martin, Laurianne Scourzic, Govind Bhagat, Olivier A. Bernard, Adolfo A. Ferrando, Teresa Palomero
Journal: Cancer Cell (2018)
Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'
Authors: Sattva S. Neelapu, Sudhakar Tummala, Partow Kebriaei, William Wierda, Frederick L. Locke, Yi Lin, Nitin Jain, Naval Daver, Alison M. Gulbis, Sherry Adkins, Katayoun Rezvani, Patrick Hwu, Elizabeth J. Shpall
Journal: Nature Reviews Clinical Oncology (2018)
Red distribution width (RDW) and ferritin as prognostic factors in acute pancreatitis
Authors: Sandra Milić, Ivana Mikolašević, Goran Poropat, Mladen Radić, Neven Franjić, Davor Štimac
Journal: Gut (2010)

Introduction: RDW is a standard parameter of complete blood count. The usefulness of determining the value of RDW examined in many pathological inflammatory and non-inflammatory conditions such as inflammatory bowel diseases, myocardial infarction, heart failure, renal failure, but not in acute pancreatitis (AP). Ferritin is an acute phase reactant and thus may be increased in patients with inflammation, like AP, and also in liver disease, chronic infection, autoimmune disorders, and some types of cancer. Ferritin is not typically used to detect or monitor these conditions. Objectives: To determine correlation of RDW and ferritin with the clinically used predictors of severity of acute pancreatitis such as complex scoring systems (Ranson and APACHE II). Patients and Methods: One hundred and forty-one patients (52%male and 48% female) in a 2-year period (2007-2008) were enrolled in this study. RDW and ferritin values were obtained on an automated hematology analyzer (Olympus AU 640, Tokio, Japan). Statistical methods used Pearson’s correlation test. Results: RDW showed moderate correlation to Ranson (r = 0.201, p = 0.017) and moderate correlation to APACHE II (r = 0.256, p = 0.002) as a marker for predicting severity of AP. There was neither significant correlation between ferritin and Ranson (r = 0.007, p = 0.932), as well as Appache II scores (r = 0.070, p = 0.414). Conclusion: To our knowledge, our study demonstrates for the first time that RDW is inexpensive, easily obtained, and powerful prognostic marker for AP, but warrants furtherconfirming studies in larger series of patients.