tbuckley/cabot-search huggingface dataset:
Buddhadasa Dharmawansa Weerasinghe
Authors: Rachel Weerasinghe
Journal: BMJ (2021)

Buddhadasa Dharmawansa Weerasinghe (“Das”) died unexpectedly but peacefully at the age of 89. He was born on 13 March 1931 in Kochchikade, Sri Lanka, and was educated at St Thomas’ College, Mount Lavinia. He gained his medical degree at Colombo Medical School in October 1955. For a short time, he practised medicine in the USA before moving …
The role of endoscopic papillary large balloon dilatation without sphincterotomy
Authors: Simon Phillpotts, George Webster
Journal: Endoscopy (2021)

See also: Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trialEndoscopy 2020; 52(09): 736-744DOI: 10.1055/a-1145-3377 See also: Reply to Phillpotts and WebsterEndoscopy 2021; 53(05): 560-560DOI: 10.1055/a-1308-2228
THU0154 PERCEPTIONS ABOUT INTERVENTIONS TO ENHANCE INFLUENZA VACCINE UPTAKE DIFFER BETWEEN VACCINATED AND UNVACCINATED RA/JIA PATIENTS
Authors: V. Valerio, M. Bazan, M. Wang, B. Mazer, E. M. Hazel, C. Pineau, S. Bernatsky, I. Colmegna
Journal: Annals of the Rheumatic Diseases (2020)

Background: To optimize the control of vaccine preventable diseases, high immunization coverage rates must be achieved. Influenza vaccination rates among patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are suboptimal. Understanding patient preferences for interventions that may increase vaccine uptake is the first step to inform the development of specific strategies to enhance vaccine coverage in RA/JIA. Objectives: To compare the perceptions of vaccinated and unvaccinated RA/JIA patients on a multi-modal intervention to enhance seasonal influenza vaccine coverage. Methods: During the 2018-2019 influenza season, a multi-modal intervention was implemented at a large Canadian academic center. This consisted of (i) a letter sent from the Division of Rheumatology to patients addressing common misconceptions about flu vaccines and encouraging patients to plan for immunization; (ii) a nurse providing inactivated influenza vaccine at the rheumatology clinics for the first 7 weeks after the vaccine was released, and (iii) clinics posters specifically designed for rheumatic patients and rheumatologists to prompt a discussion on influenza prevention. Patients that were vaccinated on site completed a survey evaluating the relevance of the individual components of the intervention. After the intervention, during a scheduled rheumatology visit, RA/JIA patients were asked to complete a similar survey. We compared the responses from RA/JIA patients that were vaccinated at our institution, to those of patients that reported not having received the influenza vaccine in 2018-2019. Results: During the intervention, 116 immunized RA/JIA patients completed the first survey. Forty RA/JIA patients not vaccinated during the 2018-2019 season completed the post-intervention survey. Both vaccinated and unvaccinated groups were mostly female (74.1% versus 87.2%), but vaccinated patients were older (50.8±19.4 versus: 40.5±14.9; 95% CI 3.7%,17%), and had shorter disease duration (10.1±9.3 versus 15.0±9.8; 95% CI -8.9%,-1.1%) than those not vaccinated. Unvaccinated patients were less likely than vaccinated patients to approve of the clinic’s provision of influenza vaccine (98.2% versus 75%; 95% CI 12.8%, 43.5%). When asked about elements of the intervention, unvaccinated patients were less likely than vaccinated patients to consider posters (65.2% versus 38.9%; 95% CI 7.9%, 42.9%), letters (69.4% versus 35.3%; 95% CI 16.2%, 51.2%), or phone calls (58.0% versus 41.7%; 95% CI 2.1%, 33.5%) as good reminders. Conclusion: Unvaccinated RA/JIA patients’ opinions about interventions to increase vaccine uptake differ from vaccinated patients. Alternative, novel strategies to target vaccine hesitant RA/JIA patients are needed to optimize vaccine coverage. Disclosure of Interests: None declared
Incidence of and risk factors for neighboring synchronous skin cancers during Mohs micrographic surgery: A prospective cohort study
Authors: Leora Aizman, Al A. Damavandy, Christopher K. Snider, Tess M. Lukowiak, Allison M. Perz, Jeremy R. Etzkorn, Jacob Beer, Thuzar M. Shin, Joseph F. Sobanko, Cerrene N. Giordano, H. William Higgins, John Fischer, Robert M. Brody, Howard Rogers, Christopher J. Miller
Journal: Journal of the American Academy of Dermatology (2021)
Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal Treg cells
Authors: Zhipeng Xu, Xiaoyun Zhang, Hao Chang, Yue Kong, Yangyue Ni, Ran Liu, Xiaolin Zhang, Yang Hu, Zhi Yang, Min Hou, Rui Mao, Wen-Tao Liu, Yasong Du, Shunying Yu, Zhen Wang, Minjun Ji, Zikai Zhou
Journal: Nature Neuroscience (2021)
Correction: <i>PIK3CA</i> C2 Domain Deletions Hyperactivate Phosphoinositide 3-kinase (PI3K), Generate Oncogene Dependence, and Are Exquisitely Sensitive to PI3Kα Inhibitors
Authors: Sarah Croessmann, Jonathan H. Sheehan, Kyung-min Lee, Gregory Sliwoski, Jie He, Rebecca Nagy, David Riddle, Ingrid A. Mayer, Justin M. Balko, Richard Lanman, Vincent A. Miller, Lewis C. Cantley, Jens Meiler, Carlos L. Arteaga
Journal: Clinical Cancer Research (2019)
Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial
Authors: Tracy J Ruckwardt, Kaitlyn M Morabito, Emily Phung, Michelle C Crank, Pamela J Costner, LaSonji A Holman, Lauren A Chang, Somia P Hickman, Nina M Berkowitz, Ingelise J Gordon, Galina V Yamshchikov, Martin R Gaudinski, Bob Lin, Robert Bailer, Man Chen, Ana M Ortega-Villa, Thuy Nguyen, Azad Kumar, Richard M Schwartz, Lisa A Kueltzo, Judith A Stein, Kevin Carlton, Jason G Gall, Martha C Nason, John R Mascola, Grace Chen, Barney S Graham, Anita Arthur, Jennifer Cunningham, Aba Eshun, Brenda Larkin, Floreliz Mendoza, Laura Novik, Jamie Saunders, Xiaolin Wang, William Whalen, Cristina Carter, Cynthia Starr Hendel, Sarah Plummer, Abidemi Ola, Alicia Widge, Maria C Burgos Florez, Lam Le, Iris Pittman, Ro Shauna S Rothwell, Olga Trofymenko, Olga Vasilenko, Preeti Apte, Renunda Hicks, Cora Trelles Cartagena, Pernell Williams, LaShawn Requilman, Colin Tran, Shufeng Bai, Elizabeth Carey, Amy L Chamberlain, Ya-chen Chang, Mingzhong Chen, Peifeng Chen, Jon Cooper, Colleen Fridley, Mridul Ghosh, Deepika Gollapudi, Janel Holland-Linn, Joe Horwitz, Althaf Hussain, Vera Ivleva, Florence Kaltovich, Kristin Leach, Christopher Lee, Amy Liu, Xun Liu, Slobodanka Manceva, Amritha Menon, Attila Nagy, Sarah O'Connell, Rahul Ragunathan, Jennifer Walters, Zhong Zhao
Journal: The Lancet Respiratory Medicine (2021)
Screening and management of atrial fibrillation in primary care
Authors: Shiva P Ponamgi, Konstantinos C Siontis, David R Rushlow, Jonathan Graff-Radford, Victor Montori, Peter A Noseworthy
Journal: BMJ (2021)

Atrial fibrillation is a common chronic disease seen in primary care offices, emergency departments, inpatient hospital services, and many subspecialty practices. Atrial fibrillation care is complicated and multifaceted, and, at various points, clinicians may see it as a consequence and cause of multi-morbidity, as a silent driver of stroke risk, as a bellwether of an acute medical illness, or as a primary rhythm disturbance that requires targeted treatment. Primary care physicians in particular must navigate these priorities, perspectives, and resources to meet the needs of individual patients. This includes judicious use of diagnostic testing, thoughtful use of novel therapeutic agents and procedures, and providing access to subspecialty expertise. This review explores the epidemiology, screening, and risk assessment of atrial fibrillation, as well as management of its symptoms (rate and various rhythm control options) and stroke risk (anticoagulation and other treatments), and offers a model for the integration of the components of atrial fibrillation care.
Association of Atopic Dermatitis Severity With Learning Disability in Children
Authors: Joy Wan, Nandita Mitra, Stephen R. Hooper, Ole J. Hoffstad, David J. Margolis
Journal: JAMA Dermatology (2021)

Recent population-based data indicate that atopic dermatitis (AD) is associated with learning disability (LD) in children, but the association between AD severity and LD is unknown.
Intestinal microbiota drives cholestasis-induced specific hepatic gene expression patterns
Authors: Oriol Juanola, Mohsin Hassan, Pavitra Kumar, Bahtiyar Yilmaz, Irene Keller, Cédric Simillion, Cornelius Engelmann, Frank Tacke, Jean-François Dufour, Andrea De Gottardi, Sheida Moghadamrad
Journal: Gut Microbes (2021)

Intestinal microbiota regulates multiple host metabolic and immunological processes. Consequently, any difference in its qualitative and quantitative composition is susceptible to exert significant effects, in particular along the gut-liver axis. Indeed, recent findings suggest that such changes modulate the severity and the evolution of a wide spectrum of hepatobiliary disorders. However, the mechanisms linking intestinal microbiota and the pathogenesis of liver disease remain largely unknown. In this work, we investigated how a distinct composition of the intestinal microbiota, in comparison with germ-free conditions, may lead to different outcomes in an experimental model of acute cholestasis. Acute cholestasis was induced in germ-free (GF) and altered Schaedler's flora (ASF) colonized mice by common bile duct ligation (BDL). Studies were performed 5 days after BDL and hepatic histology, gene expression, inflammation, lipids metabolism, and mitochondrial functioning were evaluated in normal and cholestatic mice. Differences in plasma concentration of bile acids (BA) were evaluated by UHPLC-HRMS. The absence of intestinal microbiota was associated with significant aggravation of hepatic bile infarcts after BDL. At baseline, we found the absence of gut microbiota induced altered expression of genes involved in the metabolism of fatty and amino acids. In contrast, acute cholestasis induced altered expression of genes associated with extracellular matrix, cell cycle, autophagy, activation of MAPK, inflammation, metabolism of lipids, and mitochondrial functioning pathways. Ductular reactions, cell proliferation, deposition of collagen 1 and autophagy were increased in the presence of microbiota after BDL whereas GF mice were more susceptible to hepatic inflammation as evidenced by increased gene expression levels of osteopontin, interleukin (IL)-1β and activation of the ERK/MAPK pathway as compared to ASF colonized mice. Additonally, we found that the presence of microbiota provided partial protection to the mitochondrial functioning and impairment in the fatty acid metabolism after BDL. The concentration of the majority of BA markedly increased after BDL in both groups without remarkable differences according to the hygiene status of the mice. In conclusion, acute cholestasis induced more severe liver injury in GF mice compared to mice with limited intestinal bacterial colonization. This protective effect was associated with different hepatic gene expression profiles mostly related to tissue repair, metabolic and immune functions. Our findings suggest that microbial-induced differences may impact the course of cholestasis and modulate liver injury, offering a background for novel therapies based on the modulation of the intestinal microbiota.
Abstract IA-010: Deciphering DNA end resection at DSBs
Authors: Dipanjan Chowdhury
Journal: Clinical Cancer Research (2021)

Abstract Double stranded DNA break (DSB)s are repaired by two major mechanistically distinct pathways, homologous recombination (HR) and non-homologous end joining (NHEJ). A decisive factor in the choice between DSB repair pathways is in the competition between DNA end protection (necessary for NHEJ) and DNA end resection (necessary for HR). As the ‘master regulator’ of DSB repair pathway choice, 53BP1, a chromatin-associated reader of epigenetic marks at DSBs, helps channel DSBs into the NHEJ pathway by restricting BRCA1-dependent end resection. 53BP1 nucleates the assembly of a higher order ensemble that includes the Shieldin complex, CST complex, and DNA polymerase (Pol) a-primase complex. Loss of BRCA1 provides a therapeutic opportunity as these tumors are exquisitely sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP), and are also susceptible to platinum-based drugs. Loss of 53BP1 or any of the 53BP1-interacting proteins restores end resection and causes PARPi resistance in BRCA1-mutant tumors. We recently identified Dynein light chain like protein 1 (DYNLL1) as as anti-resection factor. Loss of DYNLL1 allowed DNA end resection and restored HR, thereby inducing resistance to platinum drugs and PARPi in BRCA1-mutant tumors. At the molecular level, DYNLL1 limited the nucleolytic resection of DNA ends by interacting with the resection machinery. Importantly, purified DYNLL1 interacted with MRE11 and inhibited its exonuclease activity in vitro. Now we observe that 53BP1 loss prevents DYNLL1 recruitment to DSBs and more broadly to chromatin. We hypothesize that 53BP1 inhibits MRE11-mediated DNA end resection by recruiting DYNLL1 and that DYNLL1 functions in parallel of Shieldin-CST to regulate DNA end resection and DSB repair pathway choice. We are investigating the crosstalk between the Shieldin-CST and DYNLL1-MRE11 arms of the 53BP1-dependent anti-DNA end resection machinery. Citation Format: Dipanjan Chowdhury. Deciphering DNA end resection at DSBs [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-010.
Reply to: Response to “Inconsistent platelet-rich plasma product from Food and Drug Administration cleared devices: A retrospective review of clinic data”
Authors: Ronda S. Farah, Noora Hussain, Javed A. Shaik, Neil Sadick, Graham Gregorich, Jessica Asiala, Rebecca Freese, Maria Hordinsky
Journal: Journal of the American Academy of Dermatology (2021)
Repurposing of Anticancer Drugs Expands Possibilities for Antiviral and Anti-Inflammatory Discovery in COVID-19
Authors: Mihaela Aldea, Jean-Marie Michot, Francois-Xavier Danlos, Antoni Ribas, Jean-Charles Soria
Journal: Cancer Discovery (2021)

Abstract In 2020, the COVID-19 pandemic led to an unprecedented destabilization of the world's health and economic systems. The rapid spread and life-threatening consequences of COVID-19 have imposed testing of repurposed drugs, by investigating interventions already used in other indications, including anticancer drugs. The contours of anticancer drug repurposing have been shaped by similarities between the pathogenesis of COVID-19 and malignancies, including abnormal inflammatory and immunologic responses. In this review, we discuss the salient positive and negative points of repurposing anticancer drugs to advance treatments for COVID-19. Significance: Targeting anti-inflammatory pathways with JAK/STAT inhibitors or anticytokine therapies aiming to curb COVID-19–related cytokine storm, using antiangiogenic drugs to reduce vascular abnormalities or immune-checkpoint inhibitors to improve antiviral defenses, could be of value in COVID-19. However, conflicting data on drug efficacy point to the need for better patient selection and biomarker studies.
Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes
Authors: Thomas A. Zelniker, Itamar Raz, Ofri Mosenzon, Jamie P. Dwyer, Hiddo H. J. L. Heerspink, Avivit Cahn, Erica L. Goodrich, Kyungah Im, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P. H. Wilding, Ingrid Gause-Nilsson, Anna Maria Langkilde, Marc S. Sabatine, Stephen D. Wiviott
Journal: JAMA Cardiology (2021)

Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown.
Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis
Authors: Cindy G Boer, Ingrid Szilagyi, N Long Nguyen, Tuhina Neogi, Ingrid Meulenbelt, M Arfan Ikram, André G Uitterlinden, Sita Bierma-Zeinstra, Bruno H Stricker, Joyce B van Meurs
Journal: Annals of the Rheumatic Diseases (2021)

Objectives Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP. Methods We investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association. Results Acenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94–3.20), both for knee (OR=2.34, 95% CI=1.67–3.22) and hip OA (OR=2.74, 95% CI=1.82–4.11). Among acenocoumarol users, carriers of the high VKORC1(BB ) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69–6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78–1.33). Conclusions These findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.
Health Benefits of Electrifying Chicago's Municipal Vehicle Fleet
Authors: Anastasia Montgomery, Jordan L Schnell, Amy Rogin, Daniel E Horton
Journal: The Lancet Planetary Health (2021)

BackgroundApproximately 100 000 American citizens die prematurely each year from air pollution exposure. To lower ambient pollution and co-emitted greenhouse gases, some cities have enacted vehicle electrification policies. In this study, we aimed to simulate changes in atmospheric composition due to the electrification of Chicago's municipal vehicle fleet and quantify the corresponding health and climate benefits of this policy.MethodsWe simulated air quality at the neighbourhood scale (1·3 × 1·3 km) over the Chicago metropolitan area using the coupled Weather Research Forecast and Community Multiscale Air Quality Modelling System chemistry-climate model. We modified the 2014–16 National Emissions Inventory to create input emissions for baseline and electric vehicle adoption scenarios in Summer (August 2018) and Winter (January 2019) months. In the electric vehicle adoption scenario, we removed combustion products of the municipal vehicle fleet (school buses, transit buses, and refuse trucks) from the emissions data. To quantify the health effects of electric vehicle adoption, we calculated the difference in health response between the baseline and electrification scenarios by use of a suite of health response functions.FindingsWe found that fleet electrification reduced CO2 emissions (–1·4%) and NO2 concentrations (–1·0%) while modestly increasing O3 concentrations (+0·3%). Monthly average NO2 reductions were found in high-density areas and along interstate highways, whereas O3 increases were more prominent in the Chicagoland suburbs. Particulate matter changes were modest and spatially heterogenous. The pollutant changes resulted in both positive and negative health outcomes that were largely off setting.InterpretationThe inverse relationship between O3 and NO2 is known as the "weekend effect", in which the removal of NO2 results in an increase in O3 due to titration in volatile organic compound-limited environments. This relationship is particularly evident over the highways, where excess NO2 reduces O3 concentrations. The decision to electrify vehicles should consider air quality changes in addition to CO2 due to complicating chemical interactions within urban environments.FundingUbben Program for Carbon and Climate Science at Northwestern University, US National Science Foundation.
Amino acids and RagD potentiate mTORC1 activation in CD8<sup>+</sup> T cells to confer antitumor immunity
Authors: Yiwen Zhang, Hongrong Hu, Weiwei Liu, Shu-Mei Yan, Yuzhuang Li, Likai Tan, Yingshi Chen, Jun Liu, Zhilin Peng, Yaochang Yuan, Wenjing Huang, Fei Yu, Xin He, Bo Li, Hui Zhang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background In the tumor microenvironment, tumor cells are able to suppress antitumor immunity by competing for essential nutrients, including amino acids. However, whether amino acid depletion modulates the activity of CD8 + tumor-infiltrating lymphocytes (TILs) is unclear. Method In this study, we evaluated the roles of amino acids and the Rag complex in regulating mammalian target of rapamycin complex 1 (mTORC1) signaling in CD8 + TILs. Results We discovered that the Rag complex, particularly RagD, was crucial for CD8 + T-cell antitumor immunity. RagD expression was positively correlated with the antitumor response of CD8 + TILs in both murine syngeneic tumor xenografts and clinical human colon cancer samples. On RagD deficiency, CD8 + T cells were rendered more dysfunctional, as demonstrated by attenuation of mTORC1 signaling and reductions in proliferation and cytokine secretion. Amino acids maintained RagD-mediated mTORC1 translocation to the lysosome, thereby achieving maximal mTORC1 activity in CD8 + T cells. Moreover, the limited T-cell access to leucine (LEU), overshadowed by tumor cell amino acid consumption, led to impaired RagD-dependent mTORC1 activity. Finally, combined with antiprogrammed cell death protein 1 antibody, LEU supplementation improved T-cell immunity in MC38 tumor-bearing mice in vivo. Conclusion Our results revealed that robust signaling of amino acids by RagD and downstream mTORC1 signaling were crucial for T-cell receptor-initiated antitumor immunity. The characterization the role of RagD and LEU in nutrient mTORC1 signaling in TILs might suggest potential therapeutic strategies based on the manipulation of RagD and its upstream pathway.