tbuckley/cabot-search huggingface dataset:
Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic Stents
Authors: Sabato Sorrentino, Gennaro Giustino, Roxana Mehran, Anapoorna S. Kini, Samin K. Sharma, Michela Faggioni, Serdar Farhan, Birgit Vogel, Ciro Indolfi, George D. Dangas
Journal: Journal of the American College of Cardiology (2017)
CMR-Verified Regression of Cardiac AL Amyloid After Chemotherapy
Authors: Ana Martinez-Naharro, Amna Abdel-Gadir, Thomas A. Treibel, Giulia Zumbo, Daniel S. Knight, Stefania Rosmini, Thirusha Lane, Shameem Mahmood, Sajitha Sachchithanantham, Carol J. Whelan, Helen J. Lachmann, Ashutosh D. Wechalekar, Peter Kellman, Julian D. Gillmore, James C. Moon, Philip N. Hawkins, Marianna Fontana
Journal: JACC. Cardiovascular imaging (2017)
Progress and prospects for the control of HIV and tuberculosis in South Africa: a dynamical modelling study
Authors: Brian G Williams, Somya Gupta, Matthew Wollmers, Reuben Granich
Journal: The Lancet Public Health (2017)

BackgroundIn September, 2016, South Africa adopted a policy of providing antiretroviral treatment to everyone infected with HIV irrespective of their CD4 cell count. Studies of universal treatment and expanded prevention of HIV differ widely in their projections of effects and the associated costs, so we did this analysis to attempt to find a consensus.MethodsWe used data on HIV from the Joint UN Programme on HIV and AIDS (UNAIDS) from 1988 to 2013 and from data from WHO on tuberculosis from 1980 to to 2013 to fit a dynamical model to time trends in HIV prevalence, antiretroviral therapy (ART) coverage, and tuberculosis notification rates in South Africa. We then used the model to estimate current trends and project future patterns in HIV prevalence and incidence, AIDS-related mortality, and tuberculosis notification rates, and we used data from the South African National AIDS Council to assess current and future costs under different combinations of treatment and prevention approaches. We considered two treatment strategies: the Constant Effort strategy, in which people infected with HIV continue to start treatment at the rate in 2016, and the Expanded Treatment and Prevention (ETP) strategy, in which testing rates are increased, treatment is started immediately after HIV is detected, and prevention programmes are expanded.FindingsOur estimates show that HIV incidence among adults aged 15 years or older fell from 2·3% per year in 1996 to 0·65% per year in 2016, AIDS-related mortality decreased from 1·4% per year in 2006 to 0·37% per year in 2016, and both continue to fall at a relative rate of 17% per year. Our model shows that maintenance of Constant Effort will have a substantial effect on HIV but will not end AIDS, whereas ETP could end AIDS by 2030, with incidence of HIV and AIDs-related mortality rates both at less than one event per 1000 adults per year. Under ETP the annual cost of health care and prevention will increase from US$2·3 billion in 2016 to $2·9 billion in 2018, then decrease to $1·7 billion in 2030 and $0·9 billion in 2050. Over the next 35 years, the expansion of treatment will avert an additional 3·8 million new infections, save 1·1 million lives, and save $3·2 billion compared with continuing Constant Effort up to 2050. Expansion of prevention, including provision of pre-exposure prophylaxis, condom distribution, and male circumcision, could avert a further 150 000 new infections, save 5000 lives, and cost an additional $5·7 billion compared with Constant Effort.InterpretationOur results suggest that South Africa is on track to reduce HIV incidence and AIDS-related mortality substantially by 2030, saving both lives and money. Success will depend on high rates of HIV testing, ART delivery and adherence, good patient monitoring and support, and data to monitor progress.FundingNone.
Abstract P045: Two Forms of Autophagy in the Heart: Constitutive Autophagy via an LC3-Dependent Pathway and Starvation-Induced Autophagy via a Rab9-Dependent Pathway
Authors: Yoshiya Monden, Yasuhiro Maejima, Masaaki Komatsu, Mondira Kundu, Junichi Sadoshima
Journal: Circulation Research (2011)

Autophagy is an intracellular bulk degradation process in which cytosolic proteins/organelles are sequestered into double-membrane vesicles termed autophagosomes to be fused with lysosomes for degradation. Recent evidence suggests that an alternative form of autophagy, which utilizes distinct sources of membrane for autophagosome formation, may exist. Whether alternative autophagy exists in the heart is unknown. Cardiac-specific Atg7 -KO ( Atg7 -CKO) and systemic Ulk1 -KO mice were subjected to starvation for 48 hours. LC3-II expression and p62 degradation were increased in wild-type (WT) mice after starvation (ST), indicating increased autophagy. In Atg7 -CKO mice, LC3-II expression was reduced and p62 was markedly increased at baseline and in response to ST, indicating inhibition of LC3-dependent autophagy. In contrast, in Ulk1 -KO mice, neither LC3-II nor p62 was affected at baseline or in response to ST. However, autolysosome formation evaluated by Lamp2/Rab9 staining, indicators of unconventional autophagy, was abolished. Furthermore, the level of polyubiquitinated protein was increased after ST. Echocardiographic analyses showed that fractional shortening (FS) was maintained after ST in WT mice (38%). However, in Atg7 -CKO mice, FS deteriorated at baseline (22%) but was not further affected by ST (20%). In contrast, in Ulk1 -KO mice, FS was relatively preserved at baseline (32%) but remarkably decreased during ST (19%). After glucose deprivation (GD) GFP-LC3 was co-localized with calnexin (ER marker) in Ad-sh-Control- and Ad-sh-Ulk1-transduced, but not in Ad-sh-Atg7-transduced, cultured cardiomyocytes (CMs) in vitro. In contrast, Lamp2 was co-localized with TGN46 (Golgi marker) in Ad-sh-Control and Ad-sh-Atg7-transduced, but not in Ad-sh-Ulk1-transduced, CMs after GD. These results suggest that the autophagosomes are derived from ER in LC3-dependent autophagy and Golgi in Rab9-dependent autophagy in CMs. Atg7 is required for maintaining cardiac function at baseline in an LC3-dependent manner, whereas Ulk1 is required for preserving cardiac function during ST, possibly through stimulation of Rab9-dependent autophagy. These results support the presence of alternative autophagy in the heart.
Abstract 338: Cardiac Overexpression of Creatine Kinase Improves Cardiomycytes Function in Heart Failure and During Increased Redox Stress
Authors: Carlo G Tocchetti, Michelle Leppo, Djahida Bedja, Yibin Wang, Robert G Weiss, Nazareno Paolocci
Journal: Circulation Research (2015)

Aims: Several studies suggest that abnormal energy metabolism contributes to heart failure or that the failing heart is energy starved. Here we aim at testing whether an increase in intracellular CK improves myocellular contractility in experimental myocardial dysfunction and protects from increased oxidative conditions. Methods-Results: We tested the response to the β-agonist isoproterenol (2.5 nM, ISO) in field-stimulated (.5 Hz, RT) adult cardiomyocytes isolated from wild-type (WT) mice and mice overexpressing cardiac myofibrillar or mitochondrial CK (CK-M or CK-mito) from sham and failing (8 wk transverse aortic constriction (TAC)) hearts, to dissect whether overexpressing CK alters myocyte function at baseline and during increased energetic demand. There were no differences in sarcomere fractional shortening (FS) or Ca2+ transients at baseline and with ISO among sham WT, CK-M or CK-mito myocytes. However, ISO effects were significantly reduced in WT TAC myocytes, consistent with prior reports. Conversely, in CK-M or CK-mito TAC myocytes, ISO-induced inotropy was fully preserved. Interestingly, incubation with the AMPK-stimulator AICAR (1mM for at least 90’) did not have any effect on WT TAC, but increased FS in TAC CK-M (+82%) and CK-mito (+42%) myocytes significantly, supporting the important metabolic role played by enhancing CK in failing hearts. To test whether overexpressing CK-M or CK-mito confer protection against acute oxidative stress, sham myocytes were exposed to H2O2 (50μM, 10’) and the interval (seconds) between the beginning of H2O2 superfusion and the appearance of irreversible arrhythmias was measured. WT and CK-M myocytes had a similar response (416±91s vs 411±68s), whereas in CK-mito this interval was significantly prolonged (600±64s). Similarly, upon acute infusion of the anticancer TKI sunitinib (2μM), whose cardiotoxic properties have been linked also to an increase in ROS, irreversible arrhythmias appeared after 657±43s in CK-mito (p&lt;.5 vs 561±66 for WT and 467±88 for CK-M). Conclusions: Overexpressing CK-M and CK-mito under failing-TAC conditions improves myocyte function likely through better preserved Ca2+ handling, whereas only the up-regulation of CK-mito is more effective in buffering ROS effects.
Mechanisms of acquired afatinib resistance in HER2-positive breast cancer cells.
Authors: Alexandra Canonici, Neil Conlon, Clare Morgan, Mattia Cremona, Alex J Eustace, Bryan Hennessy, John Crown, Norma O'Donovan
Journal: Journal of Clinical Oncology (2015)

620 Background: Afatinib is a potent irreversible ErbB family tyrosine kinase inhibitor. We have previously shown that afatinib has anti-proliferative activity in a panel of 8 HER2 positive breast cancer cell lines (IC50values 5-80 nM). The aim of this study was to investigate potential mechanisms by which HER2 positive breast cancer cells may develop acquired resistance to afatinib. Methods: SKBR3 cells were continuously exposed to 150 nM afatinib for 6 months. Proliferation assays were performed to determine the IC50values for the parental (SKBR3-P) and the afatinib conditioned cells (SKBR3-A), and to assess sensitivity to lapatinib and neratinib. The molecular profiles of the resistant cells were examined by Reverse Phase Protein Array (RPPA). Results: The SKBR3-A cells were more resistant to afatinib than the SKBR3-P cells (IC50 > 500 nM vs IC50 = 10.9 ± 3.4 nM). Furthermore, the resistant cells were cross-resistant to lapatinib (IC50 = 1.0 µM ± 44.0 nM vs IC50 = 25.9 ± 3.0 nM)and neratinib (IC50 = 287.2 ± 14.0 nM vs IC50 < 10 nM). Of the 73 analytes tested by RPPA, 14 were significantly different in the SKBR3-A cells compared to SKBR3-P (p < 0.05). The level of phosphorylation of 5 proteins, including HER3 (Y1289), Akt (S473 and T308) and ERK1/2 (T202/Y204) was decreased in the afatinib resistant cells. The level of 9 proteins, including Akt2, EGFR, p38 MAPK, Bcl2 and phospho-Src (Y416) was increased. Conclusions: RPPA analysis of afatinib resistant cells suggests that alternative signaling pathways or alterations in apoptosis may play a role in acquired afatinib resistance. Further investigation of the proteins identified may facilitate the development of novel therapeutic strategies to overcome resistance.
Glycoprotein Ibα Forms Catch Bonds with von Willebrand Factor A1 Domain but Not with Mutant A1 Domains Exhibiting Properties of Type 2B von Willebrand Disease.
Authors: Tao Wu, Tadayuki Yago, Jun Yang, Jonathan Miner, Leslie Coburn, Jose A. Lopez, Miguel A. Cruz, Larry V. McIntire, Rodger P. McEver, Cheng Zhu
Journal: Blood (2007)
TCTAP A-059 Bioresorbable Vascular Scaffold Implantation for the Treatment of Coronary in Stent Restenosis: Long-term Clinical Outcomes of a Multicenter Italian Experience
Authors: Elisabetta Moscarella, Alfonso Ielasi, Maria Carmen De Angelis, Bernardo Cortese, Sebastian Coscarelli, Akihito Tanaka, Azeem Latib, Maurizio Tespili, Attilio Varricchio
Journal: Journal of the American College of Cardiology (2017)
Outcome of metastatic sarcomatoid renal cell carcinoma (sRCC): Results from the International mRCC Database Consortium.
Authors: Namita Chittoria, Hui Zhu, Toni K. Choueiri, Nils Kroeger, Jae-Lyun Lee, Sandy Srinivas, Jennifer Knox, Georg A. Bjarnason, Mary J. MacKenzie, Lori Wood, Ulka N. Vaishamayan, Neeraj Agarwal, Sumanta Kumar Pal, Min-Han Tan, Sun Young Rha, Takeshi Yuasa, Frede Donskov, Scott A. North, Brian I. Rini, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2013)

4565 Background: Sarcomatoid differentiation in metastatic RCC (sRCC) is associated with poor prognosis. Robust data regarding outcome in the targeted therapy era is lacking. Methods: Clinical features, prognostic factors, and treatment outcomes in mRCC patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed and compared. Results: 2,286 patients were identified (non-sRCC(n=2,056); sRCC(n=230)). sRCC patients had significantly worse Heng prognostic group distribution compared to non-sRCC (11% vs 19% favorable risk, 49% vs 57% intermediate risk, and 40% vs 24% poor risk; p&lt;0.0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) in the sRCC patients was 18.8 months compared to 42.9 months in non-sRCC group; p&lt;0.0001. There was no significant difference in the incidence of CNS metastases (6-8%) or underlying clear cell histology (87-88%). Greater than 93% of patients received VEGF inhibitors as first line therapy; 21% achieved an objective response in the sRCC group as compared to 26% in the non-sRCC group with significantly more sRCC patients (43% vs. 21%) having primary refractory disease (p&lt;0.0001, for both). sRCC patients had significantly less use of second-line (p=0.018) and third-line (p=0.0004) systemic therapy. The median PFS / OS was 4.5 months / 10.4 months in sRCC patients and 7.8 months / 22.5 months in non-sRCC patients (p&lt;0.0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for the individual Heng risk factors in multivariable analysis (HR 1.5, p&lt;0.0001 for both). Conclusions: Patients with sRCC have worse baseline prognostic criteria, a shorter time to relapse and worse clinical outcome to targeted therapy compared to patients with non-sRCC. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.
A Three Amino Acid Deletion in Glycoprotein IIIa Is Responsible for Type I Glanzmann's Thrombasthenia: Importance of Residues Ile325Pro326Gly327 for β3 Integrin Subunit Association
Authors: Marie-Christine Morel-Kopp, Cécile Kaplan, Valérie Proulle, Vincent Jallu, Chantal Melchior, Olivier Peyruchaud, Marie-Hélène Aurousseau, Nelly Kieffer
Journal: Blood (1997)
Population-Based Survival Outcomes in Adult Patients with Burkitt Lymphoma (BL) Treated with Cyclophosphamide, Vincristine, Doxorubicin, High-Dose Methotrexate (CODOX-M)/Ifosfamide, Etoposide and High-Dose Cytarabine (IVAC) Plus or Minus Rituximab (R) in British Columbia (BC), Canada
Authors: Katie Y. Zhu, Kevin W. Song, Joseph M Connors, Tracy Tucker, Graham W. Slack, Yasser Abou Mourad, Michael J Barnett, Donna L. Forrest, Donna E. Hogge, Stephen H. Nantel, Sujaatha Narayanan, Thomas J. Nevill, Maryse M Power, David Sanford, Cynthia L. Toze, Heather J. Sutherland, Laurie H. Sehn, Raewyn Broady, Alina S. Gerrie
Journal: Blood (2016)
TCTAP A-131 Distal Vessel Diameter Is Predictor of Stent Restenosis in the TASC C, D Lesions of Femoropopliteal Artery
Authors: Hiroaki Nakamura, Makoto Kadotani, Atsusuke Yatomi, Yasuhiro Kaetsu
Journal: Journal of the American College of Cardiology (2017)
Encouraging young and old to interact
Authors: Anne Gulland
Journal: BMJ (2017)

Devon Michelle Photography

Care homes and childcare providers in the UK are taking only baby steps towards collaboration, says Stephen Burke, director of United for All Ages, an organisation that campaigns for stronger communities by bringing people of different ages together.

The organisation hosted a meeting between care homes and childcare providers earlier this month to encourage initiatives such as this one pictured at the Providence Mount St Vincent care facility in Seattle. Here, a …
Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis.
Authors: Marie Yan, Alexander Kumachev, Lillian L. Siu, Kelly Lien, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2014)

6024 Background: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal carcinoma (LANPC). Many alternative regimens have been reported in the literature; however, it is unknown how effective these regimens are compared to each other due to the lack of direct comparisons. Our aim was to perform a network meta-analysis (NMA) to determine the relative survival benefits of these treatments in LANPC. Methods: We performed a systematic review following the Cochrane methodology, using MEDLINE, EMBASE, and CENTRAL to identify all randomized controlled trials (RCTs) that compared different chemoradiotherapy regimens in LANPC. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes of interest. Hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with random effects were conducted using WinBUGS to compare all regimens simultaneously and improve precision. Results: Twenty-four RCTs (5,492 patients) were included in this review. All together, these trials compared seven different regimens: radiotherapy (RT), concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A, RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly better than RT. The combined HRs for CRT-A vs. CRT were 0.96 (95% credible regions: 0.69–1.31) for OS and 0.86 (0.55–1.39) for PFS. For N-CRT vs. CRT, the HRs were 1.01 (0.65–1.46) for OS and 0.65 (0.34–1.18) for PFS. When CRT-A was compared against N-CRT, the resulting HRs were 0.96 (0.64–1.46) for OS and 1.33 (0.67–2.87) for PFS. CRT, CRT-A and N-CRT all had similar probabilities of being the best regimen (23%, 34% and 28% respectively) among all seven regimens based on OS. Conclusions: To our knowledge, this is the first NMA to study chemoradiotherapy regimens in LANPC. Contrary to common clinical practice, adjuvant chemotherapy does not appear to improve survival following CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further studies are warranted to examine whether omitting additional chemotherapy phases can decrease side effects without adversely affecting survival.
<i>Notes from the Field</i>: Complications of Mumps During a University Outbreak Among Students Who Had Received 2 Doses of Measles-Mumps-Rubella Vaccine — Iowa, July 2015–May 2016
Authors: Matthew Donahue, Allison Schneider, Ugochi Ukegbu, Minesh Shah, Jacob Riley, Andrew Weigel, Lisa James, Kathleen Wittich, Patricia Quinlisk, Cristina Cardemil
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
Evaluation of the reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index and the Cutaneous Assessment Tool-Binary Method in juvenile dermatomyositis among paediatric dermatologists, rheumatologists and neurologists
Authors: J. Tiao, R. Feng, E.M. Berger, J.F. Brandsema, C.C. Coughlin, N. Khan, E.A. Kichula, M.A. Lerman, S. Lvovich, P.J. McMahon, L.G. Rider, A.I. Rubin, L.V. Scalzi, D.M. Smith, A.J. Taxter, J.R. Treat, R.P. Williams, S.W. Yum, J. Okawa, V.P. Werth
Journal: British Journal of Dermatology (2017)

The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and Cutaneous Assessment Tool-Binary Method (CAT-BM) have been shown to be reliable and valid outcome measures to assess cutaneous disease in adult dermatomyositis (DM) and juvenile DM (JDM), respectively.This study compared the CDASI and CAT-BM for use by paediatric dermatologists, paediatric rheumatologists and paediatric neurologists in patients with JDM.Five paediatric dermatologists, five paediatric rheumatologists and five paediatric neurologists each evaluated 14 patients with JDM using the CDASI, CAT-BM, and skin Physician Global Assessment (PGA) scales. Inter-rater reliability, intra-rater reliability, construct validity and completion time were compared.Inter-rater reliability for CDASI activity and damage scores was good to moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists. The inter-rater reliability for CAT-BM activity scores was moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists and poor across all specialties for damage scores. Intra-rater reliability for the CDASI and CAT-BM activity and damage scores was moderate to excellent for paediatric dermatologists, rheumatologists and neurologists. Strong associations were found between skin PGA activity and damage scores and CDASI or CAT-BM activity and damage scores, respectively (P < 0·002). The CDASI had a mean completion time of 5·4 min compared with that for the CAT-BM of 3·1 min.Our data confirm the reliability of the CDASI activity and damage scores and the CAT-BM activity scores when used by paediatric dermatologists and rheumatologists in assessing JDM. Significant variation existed in the paediatric neurologists' scores.
Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults
Authors: Gail Nicola Hayward, Alastair D. Hay, Michael V. Moore, Sena Jawad, Nicola Williams, Merryn Voysey, Johanna Cook, Julie Allen, Matthew Thompson, Paul Little, Rafael Perera, Jane Wolstenholme, Kim Harman, Carl Heneghan
Journal: JAMA (2017)

<h3>Importance</h3> Acute sore throat poses a significant burden on primary care and is a source of inappropriate antibiotic prescribing. Corticosteroids could be an alternative symptomatic treatment. <h3>Objective</h3> To assess the clinical effectiveness of oral corticosteroids for acute sore throat in the absence of antibiotics. <h3>Design, Setting, and Participants</h3> Double-blind, placebo-controlled randomized trial (April 2013-February 2015; 28-day follow-up completed April 2015) conducted in 42 family practices in South and West England, enrolled 576 adults recruited on the day of presentation to primary care with acute sore throat not requiring immediate antibiotic therapy. <h3>Interventions</h3> Single oral dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283). <h3>Main Outcomes and Measures</h3> Primary: proportion of participants experiencing complete resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours, duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to 100, worst imaginable), health care attendance, days missed from work or education, consumption of delayed antibiotics or other medications, adverse events. <h3>Results</h3> Among 565 eligible participants who were randomized (median age, 34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65 participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 4.7% (95% CI, −1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78;<i>P</i> = .14). At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. At 48 hours, 102 participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 8.7% (95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68;<i>P</i> = .03). This difference also was observed in participants not offered delayed antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%) and a relative risk of 1.37 (95% CI, 1.01 to 1.87;<i>P</i> = .046). There were no significant differences in any other secondary outcomes. <h3>Conclusions and Relevance</h3> Among adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours. <h3>Trial Registration</h3> isrctn.org Identifier:ISRCTN17435450