tbuckley/cabot-search huggingface dataset:
Performance of the Insulin-Only iLet Bionic Pancreas and the Bihormonal iLet Using Dasiglucagon in Adults With Type 1 Diabetes in a Home-Use Setting
Authors: Luz E. Castellanos, Courtney A. Balliro, Jordan S. Sherwood, Rabab Jafri, Mallory A. Hillard, Evelyn Greaux, Rajendranath Selagamsetty, Hui Zheng, Firas H. El-Khatib, Edward R. Damiano, Steven J. Russell
Journal: Diabetes Care (2021)

Reductions in blood glucose levels in people with diabetes are often achieved at the expense of increased hypoglycemia. A novel approach is to automatically deliver microdose glucagon when automation of insulin delivery alone is not sufficient to prevent hypoglycemia. The approach requires a bihormonal device and a stable form of glucagon or glucagon analog. The iLet bionic pancreas (Beta Bionics, Inc.) is a purpose-built, fully integrated device that receives a signal from a continuous glucose monitor (CGM) and contains autonomous, lifelong learning, mathematical dosing algorithms, which are initialized only with the patient’s body weight (1). We evaluated the function and safety of the iLet in both its insulin-only configuration and its bihormonal configuration delivering dasiglucagon, a chemically stable glucagon analog (Zealand Pharma), in a home-use study in adults with type 1 diabetes (T1D).

This open-label, random-order, crossover, home-use trial (clinical trial reg. no. NCT03840278, ClinicalTrials.gov) was the first human study to test the bihormonal iLet configuration and the first multiday use of dasiglucagon in people with T1D (2). Ten participants used the insulin-only iLet for 7 days with insulin lispro (Eli Lilly) or aspart (Novo Nordisk), the bihormonal iLet for 7 days with dasiglucagon (4 mg/mL) and insulin lispro or aspart, or both, using the same glucose target (110 mg/dL), in random order. There were no restrictions on diet or exercise. The primary outcomes were prespecified iLet operational thresholds. The key secondary outcome was the median time with CGM glucose <54 mg/dL on days 2–7 (after one day of adaptation).

All participants completed the study. …
In adults, NSAID use vs. nonuse in the past 4 mo was not linked to increased risk for COVID-19–related mortality
Authors: Catherine E. Varner
Journal: Annals of Internal Medicine (2021)

Source CitationWong AY, MacKenna B, Morton CE, et al. Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts. Ann Rheum Dis. 2021. [Epub ahead of print.] https://pubmed.ncbi.nlm.nih.gov/33478953/AbstractClinical Impact RatingsGIM/FP/GP: Emergency Med: Hospitalists:
SINGLE VS. DUAL ANTIPLATELET THERAPY IN PATIENTS WITH ACUTE CORONARY SYNDROME - A META-ANALYSIS
Authors: Waqas Ullah, Mohammed Faisal Uddin, Harigopal Sandhyavenu, Yasar Sattar, Mohamed Zghouzi, Abdul-Rahman M. Suleiman, Ahmed Pasha, Salman Zahid, M. Chadi Alraies, Pierre Sabouret, David Fischman
Journal: Journal of the American College of Cardiology (2021)
Single-cell sequencing of the small and AT-skewed genome of malaria parasites
Authors: Shiwei Liu, Adam C. Huckaby, Audrey C. Brown, Christopher C. Moore, Ian Burbulis, Michael J. McConnell, Jennifer L. Güler
Journal: Genome Medicine (2021)

Abstract Single-cell genomics is a rapidly advancing field; however, most techniques are designed for mammalian cells. We present a single-cell sequencing pipeline for an intracellular parasite, Plasmodium falciparum , with a small genome of extreme base content. Through optimization of a quasi-linear amplification method, we target the parasite genome over contaminants and generate coverage levels allowing detection of minor genetic variants. This work, as well as efforts that build on these findings, will enable detection of parasite heterogeneity contributing to P. falciparum adaptation. Furthermore, this study provides a framework for optimizing single-cell amplification and variant analysis in challenging genomes.
Fred Riach Ironside Middleton
Authors: Stephanie Marlow
Journal: BMJ (2021)

Fred Riach Ironside Middleton was born in Dartmouth Square (south Dublin City, Ireland) on 22 September 1942. He enjoyed a happy childhood, growing up with his parents, older brother, Ian, and younger brother and sister, Bruce and Janet.

He attended school at Christ Church Leeson Park National School and then St Andrew’s College Dublin. He developed a love for music at a young age being active in St Bartholomew’s choir, Dublin, as well as becoming a talented pianist. Music became increasingly important to him, took him through the stresses of academia in his early years, and remained a source of solace for him throughout his life. As well as his music, sport was a huge passion for Fred. He was a successful athlete …
COMPARISON OF ISR VS DE NOVO LESION TREATMENT DURING OCT GUIDED PCI: INSIGHTS FROM THE LIGHTLAB INITIATIVE
Authors: Brian Bergmark, Mordechai Golomb, Jana Buccola, Jason Wollmuth, John Lopez, Hiram Bezerra, Judah Rauch, Bassem Chehab, Richard Rapoza, Nick West, Kevin Croce
Journal: Journal of the American College of Cardiology (2021)
Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration
Authors: Frank G. Holz, Piotr Oleksy, Federico Ricci, Peter K. Kaiser, Joachim Kiefer, Steffen Schmitz-Valckenberg
Journal: Ophthalmology (2021)

This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD).This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study.A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239).Patients received FYB201 or reference ranibizumab 0.5 mg by intravitreal (IVT) injection in the study eye every 4 weeks.The primary end point was change from baseline in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks before the third monthly IVT injection. Biosimilarity of FYB201 to its originator was assessed via a 2-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters.The BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters with a 90% confidence interval (CI) of -1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups.FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.
DIAGNOSIS DISCOVERED POST VENTRICULAR ASSIST DEVICE IMPLANT: ATTR AMYLOIDOSIS
Authors: Amit Nanda, Kerry Shanklin, Melissa Manzuk, William Cotts, Antone Tatooles, Deborah Tabachnik, Patroklos Pappas, Prutha Lavani, Karolina Marinescu, Tisha Suboc
Journal: Journal of the American College of Cardiology (2021)
Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios — United States, April–September 2021
Authors: Rebecca K. Borchering, Cécile Viboud, Emily Howerton, Claire P. Smith, Shaun Truelove, Michael C. Runge, Nicholas G. Reich, Lucie Contamin, John Levander, Jessica Salerno, Wilbert van Panhuis, Matt Kinsey, Kate Tallaksen, R. Freddy Obrecht, Laura Asher, Cash Costello, Michael Kelbaugh, Shelby Wilson, Lauren Shin, Molly E. Gallagher, Luke C. Mullany, Kaitlin Rainwater-Lovett, Joseph C. Lemaitre, Juan Dent, Kyra H. Grantz, Joshua Kaminsky, Stephen A. Lauer, Elizabeth C. Lee, Hannah R. Meredith, Javier Perez-Saez, Lindsay T. Keegan, Dean Karlen, Matteo Chinazzi, Jessica T. Davis, Kunpeng Mu, Xinyue Xiong, Ana Pastore y Piontti, Alessandro Vespignani, Ajitesh Srivastava, Przemyslaw Porebski, Srinivasan Venkatramanan, Aniruddha Adiga, Bryan Lewis, Brian Klahn, Joseph Outten, James Schlitt, Patrick Corbett, Pyrros Alexander Telionis, Lijing Wang, Akhil Sai Peddireddy, Benjamin Hurt, Jiangzhuo Chen, Anil Vullikanti, Madhav Marathe, Jessica M. Healy, Rachel B. Slayton, Matthew Biggerstaff, Michael A. Johansson, Katriona Shea, Justin Lessler
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.
Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis
Authors: Willeke de Haan, Wouter Dheedene, Katerina Apelt, Sofiane Décombas-Deschamps, Stefan Vinckier, Stefaan Verhulst, Andrea Conidi, Thomas Deffieux, Michael W Staring, Petra Vandervoort, Ellen Caluwé, Marleen Lox, Inge Mannaerts, Tsuyoshi Takagi, Joris Jaekers, Geert Berx, Jody Haigh, Baki Topal, An Zwijsen, Yujiro Higashi, Leo A van Grunsven, Wilfred F J van IJcken, Eskeatnaf Mulugeta, Mickael Tanter, Franck P G Lebrin, Danny Huylebroeck, Aernout Luttun
Journal: Cardiovascular Research (2021)

Abstract Aims Hepatic capillaries are lined with specialized liver sinusoidal endothelial cells (LSECs) which support macromolecule passage to hepatocytes and prevent fibrosis by keeping hepatic stellate cells (HSCs) quiescent. LSEC specialization is co-determined by transcription factors. The zinc-finger E-box-binding homeobox (Zeb)2 transcription factor is enriched in LSECs. Here, we aimed to elucidate the endothelium-specific role of Zeb2 during maintenance of the liver and in liver fibrosis. Methods and results To study the role of Zeb2 in liver endothelium we generated EC-specific Zeb2 knock-out (ECKO) mice. Sequencing of liver EC RNA revealed that deficiency of Zeb2 results in prominent expression changes in angiogenesis-related genes. Accordingly, the vascular area was expanded and the presence of pillars inside ECKO liver vessels indicated that this was likely due to increased intussusceptive angiogenesis. LSEC marker expression was not profoundly affected and fenestrations were preserved upon Zeb2 deficiency. However, an increase in continuous EC markers suggested that Zeb2-deficient LSECs are more prone to dedifferentiation, a process called ‘capillarization’. Changes in the endothelial expression of ligands that may be involved in HSC quiescence together with significant changes in the expression profile of HSCs showed that Zeb2 regulates LSEC–HSC communication and HSC activation. Accordingly, upon exposure to the hepatotoxin carbon tetrachloride (CCl4), livers of ECKO mice showed increased capillarization, HSC activation, and fibrosis compared to livers from wild-type littermates. The vascular maintenance and anti-fibrotic role of endothelial Zeb2 was confirmed in mice with EC-specific overexpression of Zeb2, as the latter resulted in reduced vascularity and attenuated CCl4-induced liver fibrosis. Conclusion Endothelial Zeb2 preserves liver angioarchitecture and protects against liver fibrosis. Zeb2 and Zeb2-dependent genes in liver ECs may be exploited to design novel therapeutic strategies to attenuate hepatic fibrosis.
PROGNOSTIC UTILITY OF LEFT ATRIAL STRAIN IN CARDIAC RESYNCHRONIZATION THERAPY PATIENTS WITH LEFT BUNDLE BRANCH BLOCK PATIENT WITH A WIDE QRS COMPLEX
Authors: Peter Huntjens, Masataka Sugahara, Yuko Soyama, Joost Lumens, Samir Saba, John Gorcsan
Journal: Journal of the American College of Cardiology (2021)
ESTIMATED CARDIOVASCULAR BENEFITS OF INCLISIRAN IN PATIENTS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
Authors: Kausik Kumar Ray, Lorena Garcia Conde, Laura H. Gunn, Frederick Raal, R. Scott Wright, Nathalie H. Gosselin, Guillaume Bonnefois, Patrick F. Smith, Lawrence A. Leiter, Wolfgang Koenig, Gregory S. Schwartz, David G. Kallend, Ulf Landmesser
Journal: Journal of the American College of Cardiology (2021)
SUCCESSFUL USE OF ECMO FOR FULMINANT LYMPHOCYTIC MYOCARDITIS IN EARLY PREGNANCY
Authors: Renee Newby, Justin Parizo, Hemal Parekh, Garrett Nintzel, Megan Stephenson, Jessica Tsui, John M. Swanson, Gerald Berry, Seema Pursnani, Richard-Tien Ha
Journal: Journal of the American College of Cardiology (2021)
Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential
Authors: Mihnea R Mangalea, David Paez-Espino, Kristopher Kieft, Anushila Chatterjee, Meagan E Chriswell, Jennifer A Seifert, Marie L Feser, M Kristen Demoruelle, Alexandra Sakatos, Karthik Anantharaman, Kevin D Deane, Kristine A Kuhn, V Michael Holers, Breck A Duerkop
Journal: Cell Host & Microbe (2021)
Cancer and COVID-19 vaccines: a complex global picture
Authors: Aasim Yusuf, Diana Sarfati, Christopher M Booth, C S Pramesh, Dorothy Lombe, Ajay Aggarwal, Nirmala Bhoo-Pathy, Audrey Tsunoda, Verna Vanderpuye, Tezer Kutluk, Alice Sullivan, Deborah Mukherji, Miriam Mutebi, Mieke van Hemelrijck, Richard Sullivan
Journal: The Lancet Oncology (2021)
Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review
Authors: Sze Wan Hung, Ruizhe Zhang, Zhouyurong Tan, Jacqueline Pui Wah Chung, Tao Zhang, Chi Chiu Wang
Journal: Medicinal Research Reviews (2021)

Abstract Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF‐κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor‐β, Wnt/β‐catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N‐acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti‐inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.
TENDYNE™ VALVE EXPANDED CLINICAL STUDY EXPERIENCE: 90-DAY OUTCOMES AND PREDICTORS OF EARLY MORTALITY
Authors: Vinay Badhwar, Paul Sorajja, Alison Duncan, Brian Bethea, Gry Dahle, Vasilis Babaliaros, Mayra Guerrero, Vinod Thourani, Nicolas Dumonteil, Thomas Modine, Lenard Conradi, Andrea Garatti, Paolo Denti, Philipp Blanke, Chuang Michael, Jonathan Leipsic, David Muller
Journal: Journal of the American College of Cardiology (2021)
Financial incentives and deposit contracts to promote HIV retesting in Uganda: A randomized trial
Authors: Gabriel Chamie, Dalsone Kwarisiima, Alex Ndyabakira, Kara Marson, Carol S. Camlin, Diane V. Havlir, Moses R. Kamya, Harsha Thirumurthy
Journal: PLoS Medicine (2021)

Background Frequent retesting for HIV among persons at increased risk of HIV infection is critical to early HIV diagnosis of persons and delivery of combination HIV prevention services. There are few evidence-based interventions for promoting frequent retesting for HIV. We sought to determine the effectiveness of financial incentives and deposit contracts in promoting quarterly HIV retesting among adults at increased risk of HIV. Methods and findings In peri-urban Ugandan communities from October to December 2018, we randomized HIV–negative adults with self-reported risk to 1 of 3 strategies to promote HIV retesting: (1) no incentive; (2) cash incentives (US$7) for retesting at 3 and 6 months (total US$14); or (3) deposit contracts: participants could voluntarily deposit US$6 at baseline and at 3 months that would be returned with interest (total US$7) upon retesting at 3 and 6 months (total US$14) or lost if participants failed to retest. The primary outcome was retesting for HIV at both 3 and 6 months. Of 1,482 persons screened for study eligibility following community-based recruitment, 524 participants were randomized to either no incentive ( N = 180), incentives ( N = 172), or deposit contracts ( N = 172): median age was 25 years (IQR: 22 to 30), 44% were women, and median weekly income was US$13.60 (IQR: US$8.16 to US$21.76). Among participants randomized to deposit contracts, 24/172 (14%) made a baseline deposit, and 2/172 (1%) made a 3-month deposit. In intent-to-treat analyses, HIV retesting at both 3 and 6 months was significantly higher in the incentive arm (89/172 [52%]) than either the control arm (33/180 [18%], odds ratio (OR) 4.8, 95% CI: 3.0 to 7.7, p &lt; 0.001) or the deposit contract arm (28/172 [16%], OR 5.5, 95% CI: 3.3 to 9.1, p &lt; 0.001). Among those in the deposit contract arm who made a baseline deposit, 20/24 (83%) retested at 3 months; 11/24 (46%) retested at both 3 and 6 months. Among 282 participants who retested for HIV during the trial, three (1%; 95%CI: 0.2 to 3%) seroconverted: one in the incentive group and two in the control group. Study limitations include measurement of retesting at the clinic where baseline enrollment occurred, only offering clinic-based (rather than community-based) HIV retesting and lack of measurement of retesting after completion of the trial to evaluate sustained retesting behavior. Conclusions Offering financial incentives to high-risk adults in Uganda resulted in significantly higher HIV retesting. Deposit contracts had low uptake and overall did not increase retesting. As part of efforts to increase early diagnosis of HIV among high-risk populations, strategic use of incentives to promote retesting should receive greater consideration by HIV programs. Trial registration clinicaltrials.gov: NCT02890459 .
Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with <scp>non‐Hodgkin</scp> lymphoma treated with B‐cell depleting immunotherapy
Authors: Rémy Duléry, Sylvain Lamure, Marc Delord, Roberta Di Blasi, Adrien Chauchet, Thomas Hueso, Cédric Rossi, Bernard Drenou, Bénédicte Deau Fischer, Carole Soussain, Pierre Feugier, Nicolas Noël, Sylvain Choquet, Serge Bologna, Bertrand Joly, Laure Philippe, Milena Kohn, Sandra Malak, Guillemette Fouquet, Etienne Daguindau, Yassine Taoufik, Karine Lacombe, Guillaume Cartron, Catherine Thiéblemont, Caroline Besson
Journal: American Journal of Hematology (2021)

Abstract Prolonged Covid‐19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in‐hospital stay (LOS) due to Covid‐19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid‐19 to 16 French hospitals in March and April, 2020 were included. Length of in‐hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety‐four patients (85%) had B‐cell non‐Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid‐19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti‐CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow‐up of 191 days (3–260), the 6‐month overall survival was 69%. In multivariable analyses, recent administration of anti‐CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p &lt; 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti‐CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid‐19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
Usefulness of Thrombopoietin Receptor Agonists for Thrombocytopenia after Allogeneic Stem Cell Transplantation. An Eight-Year Single Center Experience
Authors: Daniel Rivera, Jose Maria Bastida, Lucia Lopez Corral, Fermin Sanchez-Guijo, Lourdes Vázquez, Monica Cabrero, Estefania Pérez-López, Miriam López-Parra, Ana A. Martín, Javier Carrillo, Alejandro Avendaño, Alvaro Veiga, Monica Baile, Nerea Arratibel, Dolores Caballero, Consuelo Del Cañizo, Jose Ramon González-Porras
Journal: Blood (2017)