tbuckley/cabot-search huggingface dataset:
SAT0232 PERCEPTION OF THE DISEASE IN PATIENTS WITH EARLY SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: M. Garabajiu, L. Mazur-Nicorici, T. Rotaru, V. Salaru, S. B. Victoria, S. Vetrila, N. Loghin-Oprea, M. Mazur
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus is an autoimmune disease with a major impact on patient’s quality of life. Objectives: To evaluate patient’s attitude toward early disease and factors that influence it. Methods: Performed case-control study included SLE patients that fulfilled SLICC, 2012 classification criteria. The research included two groups of patients: early SLE – 1 st group (disease duration ≤24 months) and non-early SLE – 2 nd group control (disease duration &gt;24 months). The pattern of the disease activity was assessed by patient global assessment (PGA), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Activity Measure (SLAM), for SLE activity, SLICC/ACR Damage Index (DI) for disease irreversible changes and SF-8 for the Quality of Life (QoL). Results: A total of 101 SLE patients with 34 in the 1 st group (early SLE) and 67 in the 2 nd group (non-early SLE) was analyzed. The disease activity showed high disease activity in both groups by SLEDAI (7,02±4,16 and 6,26±4,43 points, p&gt;0,05) and SLAM (7,47±4,40 and 7,31±4,10 points, p&gt;0,05) such as (46,97±19,39 vs 47,98±22,41 points). The QoL was appreciated as low, by both components (mental and physical), in groups. The damage index was higher in the 2nd group (0,23±0,43 and 1,07±1,29, p&lt;0,001), which can be explained by the development of irreversible changes with the increase of disease duration. The PGA in early SLE was influenced by subjective symptoms contained in SLAM index (r=0,48, p&lt;0,05), such as fatigue and depression, and the level of the quality of life (r=0,65, p&lt;0,001). Meantime, PGA in patients with longer disease duration (&gt;2 years), was influenced by the presence of organ damage by SLICC/ACR DI (0,23, p&lt;0,05) and objective findings of the disease activity contained in SLEDAI (r=0,33, p&lt;0,005) and SLAM (0,44, p&lt;0,001). Conclusion: The disease recognition in patients with early SLE was determined by subjective and psycho-emotional signs, while in patients with longer disease duration it was influenced by organ damage and complications. References: no references Disclosure of Interests: None declared
A Novel Mechanism to Induce BRCAness in Cancer Cells
Authors: Changmeng Cai
Journal: Cancer Research (2020)

Cancer cells with germline deleterious mutations of BRCA1 or BRCA2 are deficient in homologous recombination repair and therefore sensitive to PARP inhibitor treatment. However, wild-type BRCA1/2-expressing cells with defects in other DNA damage repair pathway components may also exhibit "BRCAness," which in combination with PARP inhibition can similarly induce synthetic lethality. In this issue of Cancer Research, Luo and colleagues report a novel mechanism by which BRCA1 protein degradation in response to DNA double-strand breaks is regulated by prolyl isomerase Pin1. Inactivation of Pin1 can establish BRCAness in cancer cells and thus sensitize cells to PARP inhibitor treatment.See related articles by Luo et al., p. 3033.
Gene expression and <i>in situ</i> protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue
Authors: Jennifer A. Aguiar, Benjamin J-M. Tremblay, Michael J. Mansfield, Owen Woody, Briallen Lobb, Arinjay Banerjee, Abiram Chandiramohan, Nicholas Tiessen, Quynh Cao, Anna Dvorkin-Gheva, Spencer Revill, Matthew S. Miller, Christopher Carlsten, Louise Organ, Chitra Joseph, Alison John, Paul Hanson, Richard C. Austin, Bruce M. McManus, Gisli Jenkins, Karen Mossman, Kjetil Ask, Andrew C. Doxey, Jeremy A. Hirota
Journal: European Respiratory Journal (2020)

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression and
PTH-038 Cyanoacrylate injection therapy of small bowel varices by double-balloon enteroscopy (dbe): a tertiary centre experience
Authors: A Murino, N Koukias, E Vlachou, K Planche, D Patch, EJ Despott
Journal: Gut (2017)

Introduction  Small bowel varices (SBV) occur as a consequence of portal hypertension and may result in life-threatening mid-gut bleeding. First line management usually involves radiological intervention (RI) (e.g. TIPSS, stenting of occluded mesenteric veins +/- embolisation of culprit varices). In cases where RI is impossible, management options become very limited. This case series evaluated the usefulness of DBE facilitated cyanoacrylate injection of SBV.  Method  Retrospective review of DBE facilitated cyanoacrylate injection of SBV at our institution (December 2015 to August 2016). Demographic, clinical, endoscopic and radiological findings, interventions and follow-up data were analysed.  Results  Seven DBEs were performed in 5 patients (3 women, median age: 73 years). Four patients had previous surgery (hemi-hepatectomy (n=2); SB resection (n=2)); one patient had a history of intra-abdominal sepsis in childhood causing portal vein thrombosis. No radiological or surgical options were deemed feasible in any case. SBV were diagnosed at capsule endoscopy and triple phase CT mesenteric angiography. At DBE, a total of 10 nests of SBV were identified and injected with cyanoacrylate glue. There were no haemorrhagic or embolic complications but 1 patient developed an infection of a congenital urachal cyst, which was treated successfully with antibiotics. All patients underwent DBEs via the anterograde route and 1 patient required bi-directional DBE for treatment of both proximal and distal SBV and another patient required a 2nd anterograde DBE for treatment of further patent proximal SBV. At 30 day follow-up post-therapy, only 1 patient had experienced a mild recurrence of mid-gut bleeding.  Conclusion  Cyanoacrylate injection therapy of SBV at DBE appears to be a safe and effective management strategy for this condition when other first-line options are not feasible.  Disclosure of Interest  A. Murino: None Declared, N Koukias: None Declared, E Vlachou Conflict with: Fujifilm and Aquilant Medical, K Planche: None Declared, D Patch: None Declared, E Despott Conflict with: Fujifilm and Aquilant Medical
Interrogating the immune-modulating roles of radiation therapy for a rational combination with immune-checkpoint inhibitors in treating pancreatic cancer
Authors: Kenji Fujiwara, May Tun Saung, Hao Jing, Brian Herbst, MacKenzie Zarecki, Stephen Muth, Annie Wu, Elaine Bigelow, Linda Chen, Keyu Li, Neolle Jurcak, Alex B Blair, Ding Ding, Michael Wichroski, Jordan Blum, Nathan Cheadle, Jennifer Koenitzer, Lei Zheng
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Radiation therapy (RT) has the potential to enhance the efficacy of immunotherapy, such as checkpoint inhibitors, which has dramatically altered the landscape of treatments for many cancers, but not yet for pancreatic ductal adenocarcinoma (PDAC). Our prior studies demonstrated that PD ligand-1 and indoleamine 2,3-dioxygenase 1 (IDO1) were induced on tumor epithelia of PDACs following neoadjuvant therapy including RT, suggesting RT may prime PDAC for PD-1 blockade antibody (αPD-1) or IDO1 inhibitor (IDO1i) treatments. In this study, we investigated the antitumor efficacy of the combination therapies with radiation and PD-1 blockade or IDO1 inhibition or both. Methods We developed and used a mouse syngeneic orthotopic model of PDAC suitable for hypofractionated RT experiments. Results The combination therapy of αPD-1 and RT improved survival. The dual combination of RT/IDO1i and triple combination of RT/αPD-1/IDO1i did not improve survival compared with RT/αPD-1, although all of these combinations offer similar local tumor control. RT/αPD-1 appeared to result in the best systemic interferon-γ response compared with other treatment groups and the highest local expression of immune-activation genes, including Cd28 and Icos . Conclusion Our RT model allows examining the immune-modulatory effects of RT alone and in combination with immune-checkpoint inhibitors in the pancreas/local microenvironment. This study highlights the importance of choosing the appropriate immune-modulatory agents to be combined with RT to tip the balance toward antitumor adaptive immune responses.
Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series
Authors: Benjamin T Bradley, Heather Maioli, Robert Johnston, Irfan Chaudhry, Susan L Fink, Haodong Xu, Behzad Najafian, Gail Deutsch, J Matthew Lacy, Timothy Williams, Nicole Yarid, Desiree A Marshall
Journal: The Lancet (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. The median age of our cohort was 73·5 years (range 42-84; IQR 67·5-77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. None.
The role of lysosome in regulated necrosis
Authors: Aqu Alu, Xuejiao Han, Xuelei Ma, Min Wu, Yuquan Wei, Xiawei Wei
Journal: Acta Pharmaceutica Sinica B (2020)

Lysosome is a ubiquitous acidic organelle fundamental for the turnover of unwanted cellular molecules, particles, and organelles. Currently, the pivotal role of lysosome in regulating cell death is drawing great attention. Over the past decades, we largely focused on how lysosome influences apoptosis and autophagic cell death. However, extensive studies showed that lysosome is also prerequisite for the execution of regulated necrosis (RN). Different types of RN have been uncovered, among which, necroptosis, ferroptosis, and pyroptosis are under the most intensive investigation. It becomes a hot topic nowadays to target RN as a therapeutic intervention, since it is important in many patho/physiological settings and contributing to numerous diseases. It is promising to target lysosome to control the occurrence of RN thus altering the outcomes of diseases. Therefore, we aim to give an introduction about the common factors influencing lysosomal stability and then summarize the current knowledge on the role of lysosome in the execution of RN, especially in that of necroptosis, ferroptosis, and pyroptosis.
Abstract 15190: Predictors for Seizures in Neonates Following Surgery With Cardiopulmonary Bypass
Authors: Maryam Y Naim, Shavonne L Massey, Andrew T Costarino, Stephanie Fuller, J. William Gaynor, Stephen E Kimmel, Daniel J Licht, Christopher E Mascio, Susan C Nicolson, Mary Putt, Nicholas S Abend
Journal: Circulation (2019)

Introduction: Electrographic seizures (ES) are an important predictor of neurodevelopmental outcome in neonates undergoing cardiopulmonary bypass (CPB). Following implementation of postoperative co...
One Year Outcomes of Coronary Angiography After Cardiac Arrest
Authors: Jorrit Lemkes, Gladys Janssens, Nina van der Hoeven, Lucia Jewbali, Eric Dubois, Martijn Meuwissen, Tom Rijpstra, Hans Bosker, Michiel Blans, Gabe Bleeker, Remon Baak, Georgios Vlachojannis, Bob Eikemans, Pim van der Harst, Iwan van der Horst, Michiel Voskuil, Joris van der Heijden, Albertus Beishuizen, Martin Stoel, Cyril Camaro, Hans van der Hoeven, Jose Henriques, Alexander Vlaar, Maarten Vink, Ton Heestermans, Thijs Delnoij, Gillian Jessurun, Pranobe Oemrawsingh, Marcel Gosselink, Koos Plomp, Michael Magro, Paul Elbers, Peter van de Ven, Heleen Oudemans-van Straaten, Niels van Royen
Journal: Circulation (2019)
Association of <i>BRAF</i> V600E/K Mutation Status and Prior BRAF/MEK Inhibition With Pembrolizumab Outcomes in Advanced Melanoma
Authors: Igor Puzanov, Antoni Ribas, Caroline Robert, Jacob Schachter, Marta Nyakas, Adil Daud, Ana Arance, Matteo S. Carlino, Steven J. O’Day, Georgina V. Long, Kim A. Margolin, Reinhard Dummer, Dirk Schadendorf, Jose Lutzky, Paolo A. Ascierto, Ahmad Tarhini, Jianxin Lin, Robin Mogg, Blanca Homet Moreno, Nageatte Ibrahim, Omid Hamid
Journal: JAMA Oncology (2020)

<h3>Importance</h3> The optimal sequencing of immune checkpoint inhibitors and targeted therapy for<i>BRAF</i>V600E/K-mutant melanoma is not well established. <h3>Objective</h3> To assess the association of<i>BRAF</i>wild-type (WT) or<i>BRAF</i>V600E/K-mutant status and BRAF inhibitor (BRAFi) with or without MEK inhibitor (MEKi) therapy with response to pembrolizumab. <h3>Design, Setting, and Participants</h3> This study is a post hoc subgroup analysis of pooled data from 3 multinational, multisite studies: KEYNOTE-001 (data cutoff September 1, 2017), KEYNOTE-002 (data cutoff May 30, 2018), and KEYNOTE-006 (data cutoff December 4, 2017). Patients included in this analysis were adults with advanced melanoma and known<i>BRAF</i>V600E/K tumor status who had received pembrolizumab. <h3>Interventions</h3> Patients received pembrolizumab in dosages of 2 mg/kg every 3 weeks, 10 mg/kg every 2 weeks, or 10 mg/kg every 3 weeks. <h3>Main Outcomes and Measures</h3> End points were objective response rate (ORR) and progression-free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival (OS). Objective response rates, 4-year PFS, and OS rates were compared in the following patient subgroups:<i>BRAF</i>WT vs<i>BRAF</i>V600E/K-mutant melanoma and<i>BRAF</i>V600E/K-mutant melanoma with vs without previous treatment with BRAFi with or without MEKi therapy. <h3>Results</h3> The overall study population (N = 1558) included 944 men (60.6%) and 614 women (39.4%). The mean (SD) age was 60.0 years (14.0). The ORR was 38.3% (596/1558), 4-year PFS rate was 22.0%, and 4-year OS rate was 36.9%. For patients with<i>BRAF</i>WT (n = 1124) and<i>BRAF</i>V600E/K-mutant melanoma (n = 434), ORR was 39.8% (n = 447) and 34.3% (n = 149), 4-year PFS rate was 22.9% and 19.8%, and 4-year OS rate was 37.5% and 35.1%, respectively. Patients with<i>BRAF</i>V600E/K-mutant melanoma who had (n = 271) vs had not (n = 163) previously received BRAFi with or without MEKi therapy had baseline characteristics with worse prognosis; ORR was 28.4% (n = 77) and 44.2% (n = 72), 4-year PFS rate was 15.2% and 27.8%, and 4-year OS rate was 26.9% and 49.3%, respectively. <h3>Conclusions and Relevance</h3> Results of this subgroup analysis support the use of pembrolizumab for treatment of advanced melanoma regardless of<i>BRAF</i>V600E/K mutation status or receipt of prior BRAFi with or without MEKi therapy.
Physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries
Authors: Nazrul Islam, Stephen J Sharp, Gerardo Chowell, Sharmin Shabnam, Ichiro Kawachi, Ben Lacey, Joseph M Massaro, Ralph B D’Agostino, Martin White
Journal: BMJ (2020)

Abstract Objective To evaluate the association between physical distancing interventions and incidence of coronavirus disease 2019 (covid-19) globally. Design Natural experiment using interrupted time series analysis, with results synthesised using meta-analysis. Setting 149 countries or regions, with data on daily reported cases of covid-19 from the European Centre for Disease Prevention and Control and data on the physical distancing policies from the Oxford covid-19 Government Response Tracker. Participants Individual countries or regions that implemented one of the five physical distancing interventions (closures of schools, workplaces, and public transport, restrictions on mass gatherings and public events, and restrictions on movement (lockdowns)) between 1 January and 30 May 2020. Main outcome measure Incidence rate ratios (IRRs) of covid-19 before and after implementation of physical distancing interventions, estimated using data to 30 May 2020 or 30 days post-intervention, whichever occurred first. IRRs were synthesised across countries using random effects meta-analysis. Results On average, implementation of any physical distancing intervention was associated with an overall reduction in covid-19 incidence of 13% (IRR 0.87, 95% confidence interval 0.85 to 0.89; n=149 countries). Closure of public transport was not associated with any additional reduction in covid-19 incidence when the other four physical distancing interventions were in place (pooled IRR with and without public transport closure was 0.85, 0.82 to 0.88; n=72, and 0.87, 0.84 to 0.91; n=32, respectively). Data from 11 countries also suggested similar overall effectiveness (pooled IRR 0.85, 0.81 to 0.89) when school closures, workplace closures, and restrictions on mass gatherings were in place. In terms of sequence of interventions, earlier implementation of lockdown was associated with a larger reduction in covid-19 incidence (pooled IRR 0.86, 0.84 to 0.89; n=105) compared with a delayed implementation of lockdown after other physical distancing interventions were in place (pooled IRR 0.90, 0.87 to 0.94; n=41). Conclusions Physical distancing interventions were associated with reductions in the incidence of covid-19 globally. No evidence was found of an additional effect of public transport closure when the other four physical distancing measures were in place. Earlier implementation of lockdown was associated with a larger reduction in the incidence of covid-19. These findings might support policy decisions as countries prepare to impose or lift physical distancing measures in current or future epidemic waves.
Spirituality in Medical Training—An Agnostic’s Prayer
Authors: Henry Bair
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
DNA methylation mediates development of HbA1c-associated complications in type 1 diabetes
Authors: Zhuo Chen, Feng Miao, Barbara H. Braffett, John M. Lachin, Lingxiao Zhang, Xiwei Wu, Delnaz Roshandel, Melanie Carless, Xuejun Arthur Li, Joshua D. Tompkins, John S. Kaddis, Arthur D. Riggs, Andrew D. Paterson, Barbara H. Braffet, John M. Lachin, Zhuo Chen, Feng Miao, Lingxiao Zhang, Rama Natarajan, Andrew D. Paterson, Rama Natarajan
Journal: Nature Metabolism (2020)
Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 From the Mother to the Infant
Authors: Francis B. Mimouni, Patrick Gallagher, Joseph Mendlovic
Journal: JAMA Pediatrics (2020)

To the Editor We read the Research Letter by Zeng et al on "Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China."1 We are grateful to this group of Chinese investigators for sharing their experience because we all are facing similar issues.
The gut microbiome stability is altered by probiotic ingestion and improved by the continuous supplementation of galactooligosaccharide
Authors: Chenchen Ma, Sanjeev Wasti, Shi Huang, Zeng Zhang, Rajeev Mishra, Shuaiming Jiang, Zhengkai You, Yixuan Wu, Haibo Chang, Yuanyuan Wang, Dongxue Huo, Congfa Li, Zhihong Sun, Zheng Sun, Jiachao Zhang
Journal: Gut Microbes (2020)

The stable gut microbiome plays a key role in sustaining host health, while the instability of gut microbiome also has been found to be a risk factor of various metabolic diseases. At the ecological and evolutionary scales, the inevitable competition between the ingested probiotic and indigenous gut microbiome can lead to an increase in the instability. It remains largely unclear if and how exogenous prebiotic can improve the overall gut microbiome stability in probiotic consumption. In this study, we used Lactobacillus plantarum HNU082 (Lp082) as a model probiotic to examine the impact of the continuous or pulsed supplementation of galactooligosaccharide (GOS) on the gut microbiome stability in mice using shotgun metagenomic sequencing. Only continuous GOS supplement promoted the growth of probiotic and decreased its single-nucleotide polymorphisms (SNPs) mutation under competitive conditions. Besides, persistent GOS supplementation increased the overall stability, reshaped the probiotic competitive interactions with Bacteroides species in the indigenous microbiome, which was also evident by over-abundance of carbohydrate-active enzymes (CAZymes) accordingly. Also, we identified a total of 793 SNPs arisen in probiotic administration in the indigenous microbiome. Over 90% of them derived from Bacteroides species, which involved genes encoding transposase, CAZymes, and membrane proteins. However, neither GOS supplementation here de-escalated the overall adaptive mutations within the indigenous microbes during probiotic intake. Collectively, our study demonstrated the beneficial effect of continuous prebiotic supplementation on the ecological and genetic stability of gut microbiomes.