tbuckley/cabot-search huggingface dataset:
Comparative Effects of Enalapril and Verapamil on Myocardial Blood Flow in Systemic Hypertension
Authors: OberdanParodi, DaniloNeglia, CarloPalombo, GianmarioSambuceti, AssueroGiorgetti, ClaudioMarabotti, MichelaGallopin, IgnazioSimonetti, AntonioL’Abbate
Journal: Circulation (1997)

Background The comparative effects of calcium channel blockers and ACE inhibitors on myocardial blood flow (MBF) in hypertensive patients after long-term treatment are still unknown. Methods and Results Twenty hypertensive subjects with normal coronary arteries were randomly assigned to verapamil 240 to 480 mg/d or enalapril 10 to 40 mg/d. MBF was quantified at rest, during pacing tachycardia, and after dipyridamole by positron emission tomography and 13N-ammonia before and 6 months after treatment after 1 week of pharmacological washout. In both groups, blood pressure and heart rate during flow measurements were not different before and after therapy. Before treatment, mean MBF at rest, during pacing tachycardia, and after dipyridamole infusion was similar in the two groups; however, pacing and dipyridamole flows were significantly lower than those obtained in a control group of normotensive subjects. After treatment, in the enalapril-treated patients, MBF did not change in the three study conditions. In...
Improving public health control of schistosomiasis with a modified WHO strategy: a model-based comparison study
Authors: Emily Y Li, David Gurarie, Nathan C Lo, Xuewei Zhu, Charles H King
Journal: The Lancet Global Health (2019)

Schistosomiasis is endemic in many low-income and middle-income countries. To reduce infection-associated morbidity, WHO has published guidelines for control of schistosomiasis based on targeted mass drug administration (MDA) and, in 2017, on supplemental snail control. We compared the current WHO guideline-based strategies from 2012 to an alternative, adaptive decision making framework for control in heterogeneous environments, to estimate their predicted relative effectiveness and time to achievement of defined public health goals.In this model-based comparison study, we adapted an established transmission model for Schistosoma infection that couples local human and snail populations and includes aspects of snail ecology and parasite biology. We calibrated the model using data from high-risk, moderate-risk, and lower-risk rural villages in Kenya, and then simulated control via MDA. We compared 2012 WHO guidelines with a modified adaptive strategy that tested a lower-prevalence threshold for MDA and shorter intervals between implementation, evaluation, and modification. We also explored the addition of snail control to this modified strategy. The primary outcomes were the proportion of simulations that achieved the WHO targets in children aged 5-14 years of less than 5% (2020 morbidity control goal) and less than 1% (2025 elimination as a public health problem goal) heavy infection and the mean duration of treatment required to achieve these goals.In high-risk communities (80% baseline prevalence), current WHO strategies for MDA were not predicted to achieve morbidity control (<5% prevalence of heavy infections) in 80% of simulations over a 10-year period, whereas the modified adaptive strategy was predicted to achieve this goal in over 50% of simulations within 5 years. In low-risk and moderate-risk communities, current WHO guidelines from 2012 were predicted to achieve morbidity control in most simulations (96% in low-risk and 41% for moderate-risk), although the proposed adaptive strategy reached this goal in a shorter period (mean reduction of 5 years). The model predicted that the addition of snail control to the proposed adaptive strategy would achieve morbidity control in all high-risk communities, and 54% of communities could reach the goal for elimination as a public health problem (<1% heavy infection) within 7 years.The modified adaptive decision making framework is predicted to be more effective than the current WHO guidelines in reaching 2025 public health goals, especially for high-prevalence regions. Modifications in current guidelines could reduce the time and resources needed for countries who are currently working on achieving public health goals against schistosomiasis.University of Georgia Research Foundation, The Bill & Melinda Gates Foundation, and the Medical Scientist Training Program at Stanford University School of Medicine.
Abstract 17135: Distribution of Anti-oxidative Activity During Remodeling of High Density Lipoprotein: Studies With CSL112
Authors: Alexandre M Cukier, Svetlana A Diditchenko, Alexei V Navdaev, Martin O Spycher, M J Chapman, Samuel D Wright, Anatol Kontush
Journal: Circulation (2015)

We have previously shown that reconstituted HDL has the ability to inactivate phospholipid hydroperoxides (PLOOH) in oxidized LDL by virtue of redox-active Met residues present in apolipoprotein A-I (apoA-I), with the level of activity being proportional to the amount of apoA-I protein added. CSL112 is human apoA-I, reconstituted with phosphatidylcholine to form HDL particles suitable for infusion. Infusing CSL112 into human subjects or adding it to human plasma ex vivo, causes remodeling of endogenous HDL. Similar remodeling occurs upon incubation of CSL112 with purified HDL3 and results in accumulation of three HDL species: enlarged HDL (HDL2), a smaller, dense species (HDL3c-like), and lipid-poor apoA-I (pre-β1 HDL). Here we examine the distribution of anti-oxidant activity upon remodeling of native plasma HDL induced by CSL112. We incubated CSL112 with human plasma HDL3, isolated the three populations of remodeled HDL particles by density gradient ultracentrifugation and compared (on a total protein basis) their ability to inactivate PLOOH derived from oxidized LDL as well as their apoA-I content of unoxidized and oxidized Met residues. Both parent CSL112 and HDL3 displayed anti-oxidative activity, inactivating 22±4 and 47±9% of PLOOH, respectively (n=4). Upon remodeling, this activity was mainly found in enlarged HDL2 and smaller HDL3c-like species (PLOOH inactivation, 46±3 and 47±9%, respectively) and was low (23±17%) in lipid-poor apoA-I. In parallel, apoA-I Met residues were oxidized in HDL; oxidation was several fold lower in the lipid-poor apoA-I (12±3%) compared to larger species (62±1% and 69±2% in HDL2 and HDL3c-like particles), consistent with a limited accessibility of apoA-I Met to PLOOH molecules in the lipid-poor particles. These studies further confirm the unequal distribution of HDL function among HDL subclasses and emphasize the important role of HDL remodeling in the production and maintenance of HDL functionality. The antioxidant properties of CSL112 add to its potential as a promising therapy for reducing the high risk of early recurrent atherothrombotic events following acute MI (AMI). A Phase IIb trial (AEGIS-I; NCT02108262) of CSL112 in AMI patients is ongoing.
Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention
Authors: Tracy O'Connor, Xiaolan Zhou, Jan Kosla, Arlind Adili, Maria Garcia Beccaria, Elena Kotsiliti, Dominik Pfister, Anna-Lena Johlke, Ankit Sinha, Roman Sankowski, Markus Schick, Richard Lewis, Nikolaos Dokalis, Bastian Seubert, Bastian Höchst, Donato Inverso, Danijela Heide, Wenlong Zhang, Petra Weihrich, Katrin Manske, Dirk Wohlleber, Martina Anton, Alexander Hoellein, Gitta Seleznik, Juliane Bremer, Sabine Bleul, Hellmut G. Augustin, Florian Scherer, Uwe Koedel, Achim Weber, Ulrike Protzer, Reinhold Förster, Thomas Wirth, Adriano Aguzzi, Felix Meissner, Marco Prinz, Bernd Baumann, Uta E. Höpken, Percy A. Knolle, Louisa von Baumgarten, Ulrich Keller, Mathias Heikenwalder
Journal: Cancer Cell (2019)
Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers
Authors: Elizabeth C. Page, Elizabeth K. Bancroft, Mark N. Brook, Melissa Assel, Mona Hassan Al Battat, Sarah Thomas, Natalie Taylor, Anthony Chamberlain, Jennifer Pope, Holly Ni Raghallaigh, D. Gareth Evans, Jeanette Rothwell, Lovise Maehle, Eli Marie Grindedal, Paul James, Lyon Mascarenhas, Joanne McKinley, Lucy Side, Tessy Thomas, Christi van Asperen, Hans Vasen, Lambertus A. Kiemeney, Janneke Ringelberg, Thomas Dyrsø Jensen, Palle J.S. Osther, Brian T. Helfand, Elena Genova, Rogier A. Oldenburg, Cezary Cybulski, Dominika Wokolorczyk, Kai-Ren Ong, Camilla Huber, Jimmy Lam, Louise Taylor, Monica Salinas, Lidia Feliubadaló, Jan C. Oosterwijk, Wendy van Zelst-Stams, Jackie Cook, Derek J. Rosario, Susan Domchek, Jacquelyn Powers, Saundra Buys, Karen O'Toole, Margreet G.E.M. Ausems, Rita K. Schmutzler, Kerstin Rhiem, Louise Izatt, Vishakha Tripathi, Manuel R. Teixeira, Marta Cardoso, William D. Foulkes, Armen Aprikian, Heleen van Randeraad, Rosemarie Davidson, Mark Longmuir, Mariëlle W.G. Ruijs, Apollonia T.J.M. Helderman van den Enden, Muriel Adank, Rachel Williams, Lesley Andrews, Declan G. Murphy, Dorothy Halliday, Lisa Walker, Annelie Liljegren, Stefan Carlsson, Ashraf Azzabi, Irene Jobson, Catherine Morton, Kylie Shackleton, Katie Snape, Helen Hanson, Marion Harris, Marc Tischkowitz, Amy Taylor, Judy Kirk, Rachel Susman, Rakefet Chen-Shtoyerman, Allan Spigelman, Nicholas Pachter, Munaza Ahmed, Teresa Ramon y Cajal, Janez Zgajnar, Carole Brewer, Neus Gadea, Angela F. Brady, Theo van Os, David Gallagher, Oskar Johannsson, Alan Donaldson, Julian Barwell, Nicola Nicolai, Eitan Friedman, Elias Obeid, Lynn Greenhalgh, Vedang Murthy, Lucia Copakova, Sibel Saya, John McGrath, Peter Cooke, Karina Rønlund, Kate Richardson, Alex Henderson, Soo H. Teo, Banu Arun, Karin Kast, Alexander Dias, Neil K. Aaronson, Audrey Ardern-Jones, Chris H. Bangma, Elena Castro, David Dearnaley, Diana M. Eccles, Karen Tricker, Jorunn Eyfjord, Alison Falconer, Christopher Foster, Henrik Gronberg, Freddie C. Hamdy, Vigdis Stefansdottir, Vincent Khoo, Geoffrey J. Lindeman, Jan Lubinski, Karol Axcrona, Christos Mikropoulos, Anita Mitra, Clare Moynihan, Gadi Rennert, Mohnish Suri, Penny Wilson, Tim Dudderidge, Judith Offman, Zsofia Kote-Jarai, Andrew Vickers, Hans Lilja, Rosalind A. Eeles
Journal: European Urology (2019)

Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.
Electronic Health Records—A System Only as Beneficial as Its Data
Authors: Nathalie Jetté, Churl-Su Kwon
Journal: JAMA Network Open (2019)

Carl T. Berdahl, MD, MS; Gregory J. Moran, MD; Owen McBride, MD; Alexandra M. Santini, BS; Ilya A. Verzhbinsky, BS; David L. Schriger, MD, MPH
Blood Culture Results Before and After Antimicrobial Administration in Patients With Severe Manifestations of Sepsis
Authors: Matthew P. Cheng, Robert Stenstrom, Katryn Paquette, Sarah N. Stabler, Murtaza Akhter, Adam C. Davidson, Marko Gavric, Alexander Lawandi, Rehman Jinah, Zahid Saeed, Koray Demir, Kelly Huang, Amirali Mahpour, Chris Shamatutu, Chelsea Caya, Jean-Marc Troquet, Greg Clark, Cedric P. Yansouni, David Sweet
Journal: Annals of Internal Medicine (2019)

Background: Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. Objective: To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Design: Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905) Setting: 7 emergency departments in North America. Participants: Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Intervention: Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Measurements: Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Results: Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients. Limitation: Only a proportion of screened patients were recruited. Conclusion: Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. Primary Funding Source: Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Santé–Québec, and the Maricopa Medical Foundation.
High-throughput genome-wide phenotypic screening via immunomagnetic cell sorting
Authors: Barbara Mair, Peter M. Aldridge, Randy S. Atwal, David Philpott, Meng Zhang, Sanna N. Masud, Mahmoud Labib, Amy H. Y. Tong, Edward H. Sargent, Stéphane Angers, Jason Moffat, Shana O. Kelley
Journal: Nature Biomedical Engineering (2019)
Association of Timing of Adverse Childhood Experiences and Caregiver Support With Regionally Specific Brain Development in Adolescents
Authors: Joan L. Luby, Rebecca Tillman, Deanna M. Barch
Journal: JAMA Network Open (2019)

Few data are available to inform the associations and timing of the associations between adversity, caregiver support, and brain outcomes. Consideration of timing has important public health implications to inform more precise prevention strategies.To evaluate the timing and regional specificity of the association between adverse childhood experiences (ACEs) and caregiver support to structural development of limbic and striatal brain regions in middle childhood and adolescence.This 15-year developmental, neuroimaging cohort study included 211 children and their caregivers screened from day care centers and preschools in the St Louis, Missouri, metropolitan area during the preschool period, with an additional 4 waves of neuroimaging at school age through adolescence from November 14, 2007, to August 29, 2017. The cohort was oversampled for preschoolers with elevated symptoms of depression using a brief screener. Data analysis was performed from March 19, 2019, to July 26, 2019.Volumes in adolescence and developmental trajectories of volumes of the amygdala, hippocampus, caudate, subgenual cingulate, and insula during 4 waves of scanning; ACEs and observed caregiver support at preschool and school age; and volumes of amygdala, hippocampus, insula, and subgenual cingulate during 4 waves of scanning.A total of 211 children (107 [50.7%] male) completed at least 1 scan. At preschool (mean [SD] age, 5.5 [0.8] years), ACE data were available for 164 children (84 [51.2%] male) and maternal support data for 155 children; at school age (mean [SD], 8.3 [1.2] years), ACE data were available for 172 children and maternal support data for 146 children. Unique patterns of the association between ACEs and support were found, with an association between the interaction of preschool ACEs and school-age support and the development of the hippocampus (t = -2.27; P = .02) and amygdala (t = -2.12; P = .04). A buffering hypothesis was not confirmed because high caregiver support was more strongly associated with the development of these regions only in the context of low ACEs. In contrast, preschool ACEs (t = -2.30; P = .02) and support (t = 2.59; P = .01) had independent associations with the development of the caudate.The findings suggest that there are unique regional associations of support and adversity with key brain structures important for emotional regulation. Results may inform the timing and potential targets of preventive action for the range of poor developmental outcomes.
Impact of endoscopic submucosal dissection of an anal squamous intraepithelial lesion with indistinct border
Authors: Kengo Kasuga, Yutaka Saito, Shih Y. S. Wu, Hiroyuki Takamaru, Taku Sakamoto, Shigeki Sekine, Toshio Uraoka
Journal: Endoscopy (2019)

A 35-year-old woman, with negative results from a human immunodeficiency virus (HIV) antibody test, underwent colonoscopy that revealed whitish nodules and elevated papillary lesions of various sizes situated in the anal transitional zone ([Fig. 1]). Biopsy of the whitish nodules revealed high grade squamous intraepithelial lesions. The protruding lesions were distributed almost circumferentially. It was difficult to identify the lateral margins of the high grade squamous intraepithelial lesions with magnified narrow band imaging (NBI) ([Fig. 1 c], [Fig. 2 a, b]) and indigo carmine dye spraying ([Fig. 1 b]).
Labour pledges free personal care for over 65s most in need
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The Labour Party has pledged to introduce free personal care in England for the people aged over 65 who need it the most.

The policy, which will cost an estimated £6bn (€6.8bn; $7.5bn), was announced at the party’s annual conference by the shadow chancellor, John McDonnell, on 23 September.

Currently, people with savings that exceed a threshold of £14 250 have to contribute to the cost of their care.

If enacted, Labour’s policy would double the number of people in England receiving state funded social care. It would also move England into line with Scotland, where free personal care is already available for people with …
Greater efficacy of SPF 100+ sunscreen compared with SPF 50+ in sunburn prevention during 5 consecutive days of sunlight exposure: A randomized, double-blind clinical trial
Authors: Indermeet Kohli, Cynthia L. Nicholson, Joshua D. Williams, Alexis B. Lyons, InSeok Seo, Prithwiraj Maitra, Xiaoyan Tian, Evren Atillasoy, Henry W. Lim, Iltefat H. Hamzavi
Journal: Journal of the American Academy of Dermatology (2019)
Immunomodulatory Mechanism of Acyclic Nucleoside Phosphates in Treatment of Hepatitis B Virus Infection
Authors: Kazumoto Murata, Senko Tsukuda, Futoshi Suizu, Akihiro Kimura, Masaya Sugiyama, Koichi Watashi, Masayuki Noguchi, Masashi Mizokami
Journal: Hepatology (2019)

Background and Aims Current treatment with nucleos(t)ide analogs (NUCs) safely controls the replication of hepatitis B virus (HBV) and improves prognosis in patients with HBV. However, the inability to completely clear HBV is problematic, and novel therapies are desired. It has been believed that all NUCs have similar functions to inhibit HBV reverse transcriptase. However, our recent findings that only acyclic nucleoside phosphonates (ANPs; adefovir dipivoxil and tenofovir disoproxil fumarate) had an additional effect of inducing interferon (IFN)‐λ3 in the gastrointestinal tract suggests that ANPs are not only distinct from nucleoside analogs (lamivudine and entecavir) in their structures but also in their functions. Because enteric lipopolysaccharide (LPS) can cross the intestine and affect peripheral blood mononuclear cells (PBMCs), we hypothesized that orally administered ANPs could have further additional effects to modulate LPS‐mediated cytokine profile in PBMCs. Approach and Results This study showed that pretreatment of PBMCs, from either healthy volunteers or patients with HBV, with ANPs inhibited LPS‐mediated interleukin (IL)‐10 production, which reciprocally induced IL‐12p70 and tumor necrosis factor‐α production in a dose‐dependent manner. Furthermore, the combination of IFN‐α and ANPs synergistically enhanced LPS‐mediated IL‐12p70 production in PBMCs. Mechanistic analyses revealed that cellular metabolites of ANPs directly bound the Akt protein, inhibiting its translocation to the plasma membrane, thereby impairing Akt phosphorylation. Therefore, pretreatment of PBMCs with ANPs impairs LPS‐mediated IL‐10 production. Conclusions Among NUCs, only ANPs have an additional pharmacological effect modulating LPS‐mediated cytokine production, which is expected to produce favorable immune responses toward HBV elimination. This additional immunomodulation by ANPs in PBMCs, as well as IFN‐λ3 induction in the gastrointestinal tract, provides insights into HBV treatment.
Modifiable pathways for colorectal cancer: a mendelian randomisation analysis
Authors: Alex J Cornish, Philip J Law, Maria Timofeeva, Kimmo Palin, Susan M Farrington, Claire Palles, Mark A Jenkins, Graham Casey, Hermann Brenner, Jenny Chang-Claude, Michael Hoffmeister, Iva Kirac, Tim Maughan, Stefanie Brezina, Andrea Gsur, Jeremy P Cheadle, Lauri A Aaltonen, Ian Tomlinson, Malcolm G Dunlop, Richard S Houlston
Journal: The Lancet. Gastroenterology & hepatology (2019)

Epidemiological studies have linked lifestyle, cardiometabolic, reproductive, developmental, and inflammatory factors to the risk of colorectal cancer. However, which specific factors affect risk and the strength of these effects are unknown. We aimed to examine the relationship between potentially modifiable risk factors and colorectal cancer.
Optimal Gestational Weight Gain—Reply
Authors: Ellis Voerman, Vincent W. V. Jaddoe, Romy Gaillard
Journal: JAMA (2019)

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Ph Positive ALL: Real World Experience from a Tertiary Care Center in North India
Authors: Sanjeevan Sharma, Uday Yanamandra, Mir Moslem, Rajan Kapoor, Suman Pramanik, Rajiv Kumar, Harshit Khurana, Tarun Verma, Singh Jasjit, Satyaranjan Das, Ajay Sharma, Velu Nair
Journal: Blood (2018)
Relationship between Hospital Volume and Inpatient Mortality Among Patients Diagnosed with Thrombotic Thrombocytopenic Purpura (TTP) in the United States
Authors: Smith Giri, Ranjan Pathak, Robert Franklin, Nikolai A. Podoltsev, Scott Huntington, Kathan Dilipbhai Mehta, Amer M. Zeidan
Journal: Blood (2017)
TCT-278 Application and Outcomes of the Hybrid Approach to Chronic Total Occlusion Percutaneous Coronary Intervention: an Update from a Contemporary Multicenter US Registry
Authors: Aris Karatasakis, Barbara Anna Danek, Dimitri Karmpaliotis, Khaldoon Alaswad, Farouc Amin Jaffer, Robert Yeh, David Kandzari, Nicholas Lembo, Mitul Patel, John Bahadorani, William Lombardi, R. Michael Wyman, J. Aaron Grantham, Anthony Doing, Catalin Toma, James Choi, Barry Uretsky, Santiago Garcia, Jeffrey Moses, Ajay Kirtane, Ziad Ali, Manish Parikh, Judit Karacsonyi, Bavana Rangan, Craig Thompson, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2016)