tbuckley/cabot-search huggingface dataset:
Evolution of Renal-Disease Factor APOL1 Results in <i>Cis</i> and <i>Trans</i> Orientations at the Endoplasmic Reticulum That Both Show Cytotoxic Effects
Authors: Daria Müller, Jürgen Schmitz, Katharina Fischer, Daniel Granado, Ann-Christin Groh, Vanessa Krausel, Simona Mareike Lüttgenau, Till Maximilian Amelung, Hermann Pavenstädt, Thomas Weide
Journal: Molecular Biology and Evolution (2021)

Abstract The recent and exclusively in humans and a few other higher primates expressed APOL1 (apolipoprotein L1) gene is linked to African human trypanosomiasis (also known as African sleeping sickness) as well as to different forms of kidney diseases. Whereas APOL1’s role as a trypanolytic factor is well established, pathobiological mechanisms explaining its cytotoxicity in renal cells remain unclear. In this study, we compared the APOL family members using a combination of evolutionary studies and cell biological experiments to detect unique features causal for APOL1 nephrotoxic effects. We investigated available primate and mouse genome and transcriptome data to apply comparative phylogenetic and maximum likelihood selection analyses. We suggest that the APOL gene family evolved early in vertebrates and initial splitting occurred in ancestral mammals. Diversification and differentiation of functional domains continued in primates, including developing the two members APOL1 and APOL2. Their close relationship could be diagnosed by sequence similarity and a shared ancestral insertion of an AluY transposable element. Live-cell imaging analyses showed that both expressed proteins show a strong preference to localize at the endoplasmic reticulum (ER). However, glycosylation and secretion assays revealed that—unlike APOL2—APOL1 membrane insertion or association occurs in different orientations at the ER, with the disease-associated mutants facing either the luminal (cis) or cytoplasmic (trans) side of the ER. The various pools of APOL1 at the ER offer a novel perspective in explaining the broad spectrum of its observed toxic effects.
Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic — United States, 2020–2021
Authors: Sonja J. Olsen, Amber K. Winn, Alicia P. Budd, Mila M. Prill, John Steel, Claire M. Midgley, Krista Kniss, Erin Burns, Thomas Rowe, Angela Foust, Gabriela Jasso, Angiezel Merced-Morales, C. Todd Davis, Yunho Jang, Joyce Jones, Peter Daly, Larisa Gubareva, John Barnes, Rebecca Kondor, Wendy Sessions, Catherine Smith, David E. Wentworth, Shikha Garg, Fiona P. Havers, Alicia M. Fry, Aron J. Hall, Lynnette Brammer, Benjamin J. Silk
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.
Effect of ibrutinib treatment on hemolytic anemia and acrocyanosis in cold agglutinin disease/cold agglutinin syndrome
Authors: Marit Jalink, Sigbjørn Berentsen, Jorge J. Castillo, Steven P. Treon, Marjan Cruijsen, Bruno Fattizzo, Ramona Cassin, Despina Fotiou, Efstathios Kastritis, Masja De Haas, Liesbeth E. M. Oosten, Henrik Frederiksen, Andrea Patriarca, Shirley D'Sa, Josephine M.I. Vos
Journal: Blood (2021)
Ethics Frameworks and Beyond—Advancing Our Understanding of the Contingency Phase to Improve Health Care Quality During Public Health Emergencies
Authors: D. Alfandre, V. Sharpe, C. Geppert, M. Foglia, K. Berkowitz, B. Chanko, T. Schonfeld
Journal: The American Journal of Bioethics (2021)

This article refers to:Between Usual and Crisis Phases of a Public Health Emergency: The Mediating Role of Contingency MeasuresAddressing a Missing Link in Emergency Preparedness: New Insights on the Ethics of Care in Contingency Conditions from the Minnesota COVID Ethics CollaborativeEthically Navigating the Murky Waters of “Contingency Standards of Care”The Divided Principle of Justice: Ethical Decision-Making at Surge CapacitySupporting Real-Time Ethical Deliberation in Contingency Capacity During the COVID-19 PandemicContingency Measures During the COVID-19 Pandemic in China: An Analysis Based on a New Ethical FrameworkLimitations to Contingency Measures: Reflections from COVID-19 Surges in the UKInsights from Blood Products Management for Pre-Crisis Ethical Resource AllocationThe Need for an Ethics of Care in the Contingency Response to Public Health EmergenciesA Real-World Ethical Analysis of Contingency Measures Enacted for Crisis Standards of Care during the COVID-19 Pandemic
Telmisartan use and risk of dementia in type 2 diabetes patients with hypertension: A population-based cohort study
Authors: Chi-Hung Liu, Pi-Shan Sung, Yan-Rong Li, Wen-Kuan Huang, Tay-Wey Lee, Chin-Chang Huang, Tsong-Hai Lee, Tien-Hsing Chen, Yi-Chia Wei
Journal: PLoS Medicine (2021)

Background Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has additional benefits compared to other ARBs remains unclear. Methods and findings Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p &lt; 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data. Conclusions The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population.
Fractures and Osteoporosis in Patients With Diabetes With Charcot Foot
Authors: Oliver Christian Rabe, Matilde Winther-Jensen, Kristine Højgaard Allin, Ole Lander Svendsen
Journal: Diabetes Care (2021)

Charcot foot is a serious complication of diabetes, with degeneration of the bones and joints in the foot and ankle. It is unknown whether patients with diabetes with a Charcot foot have an increased risk of osteoporosis and fractures. The aim of this study was to investigate whether patients with diabetes with a Charcot foot have an increased risk of fracture and/or osteoporosis compared with patients with diabetes without Charcot foot.A Danish register-based, nationwide population-based matched cohort study was conducted. During 1995-2018, we identified 1,602 patients with diabetes with Charcot foot and matched them on sex and date of diagnosis of diabetes with 16,296 patients with diabetes without Charcot foot. We used logistic regression to estimate odds ratios (ORs) with 95% CIs for fracture and osteoporosis. Information about exposure, outcome, and comorbidities was retrieved from the Danish National Patient Register.Diabetes patients with Charcot foot had higher risk of fractures compared with those without Charcot foot (i.e., ORs for any fracture, lower-leg fracture, foot fracture, and osteoporotic fracture were 1.8 [95% CI 1.6-2.0], 2.4 [2.0-2.8], 2.9 [2.6-3.3], and 1.3 [1.1-1.4], respectively). Furthermore, patients with diabetes with Charcot foot had higher risk of osteoporosis compared with the patients without Charcot foot, with an OR of 1.3 (95% CI 1.1-1.5).Patients with diabetes with a Charcot foot have an increased risk of fractures and osteoporosis compared with patients with diabetes without a Charcot foot.
P3-8 Lipocalin-2 expression might be a novel biomarker for patients with scirrhous-type gastric cancer
Authors: Sadaaki Nishimura, Masakazu Yashiro, Gen Tsujio, Yurie Yamamoto, Atsushi Sugimoto, Shuhei Kushiyama, Kenji Kuroda, Shingo Togano, Masaichi Ohira
Journal: Annals of Oncology (2021)
Sustained reduction in no-show rate with the integration of teledermatology in a Federally Qualified Health Center
Authors: Abigail Cline, Jia C. Gao, Juliana Berk-Krauss, Laura Kaplan, Amanda Bienenfeld, Ankuri Desai, Amy Huang, Brady Bleicher, Rishi Chopra, Shweta Shukla, JoNise Caleb, Bridget Rodriguez, Nikeisha James, Shoshana Marmon
Journal: Journal of the American Academy of Dermatology (2021)
SOURCE-PANC: A Prediction Model for Patients With Metastatic Pancreatic Ductal Adenocarcinoma Based on Nationwide Population-Based Data
Authors: Héctor G. van den Boorn, Willemieke P.M. Dijksterhuis, Lydia G.M. van der Geest, Judith de Vos-Geelen, Marc G. Besselink, Johanna W. Wilmink, Martijn G.H. van Oijen, Hanneke W.M. van Laarhoven
Journal: Journal of the National Comprehensive Cancer Network (2021)

A prediction model for overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (PDAC) including patient and treatment characteristics is currently not available, but it could be valuable for supporting clinicians in patient communication about expectations and prognosis. We aimed to develop a prediction model for OS in metastatic PDAC, called SOURCE-PANC, based on nationwide population-based data.Data on patients diagnosed with synchronous metastatic PDAC in 2015 through 2018 were retrieved from the Netherlands Cancer Registry. A multivariate Cox regression model was created to predict OS for various treatment strategies. Available patient, tumor, and treatment characteristics were used to compose the model. Treatment strategies were categorized as systemic treatment (subdivided into FOLFIRINOX, gemcitabine/nab-paclitaxel, and gemcitabine monotherapy), biliary drainage, and best supportive care only. Validation was performed according to a temporal internal-external cross-validation scheme. The predictive quality was assessed with the C-index and calibration.Data for 4,739 patients were included in the model. Sixteen predictors were included: age, sex, performance status, laboratory values (albumin, bilirubin, CA19-9, lactate dehydrogenase), clinical tumor and nodal stage, tumor sublocation, presence of distant lymph node metastases, liver or peritoneal metastases, number of metastatic sites, and treatment strategy. The model demonstrated a C-index of 0.72 in the internal-external cross-validation and showed good calibration, with the intercept and slope 95% confidence intervals including the ideal values of 0 and 1, respectively.A population-based prediction model for OS was developed for patients with metastatic PDAC and showed good performance. The predictors that were included in the model comprised both baseline patient and tumor characteristics and type of treatment. SOURCE-PANC will be incorporated in an electronic decision support tool to support shared decision-making in clinical practice.
Immune cells surveil aberrantly sialylated <i>O</i>-glycans on megakaryocytes to regulate platelet count
Authors: Melissa M. Lee-Sundlov, Robert T. Burns, Taylor O. Kim, Renata Grozovsky, Silvia Giannini, Leonardo Rivadeneyra, Yongwei Zheng, Simon H. Glabere, Walter H. A. Kahr, Reza Abdi, Jenny M. Despotovic, Demin Wang, Karin M. Hoffmeister
Journal: Blood (2021)
Post-acute Sequelae of SARS-CoV-2 Infection and Subjective Memory Problems
Authors: Esther S. Oh, Tracy D. Vannorsdall, Ann M. Parker
Journal: JAMA Network Open (2021)

Arne Søraas, PhD; Ragnhild Bø, PhD; Karl Trygve Kalleberg, PhD; Nathalie C. Støer, PhD; Merete Ellingjord-Dale, PhD; Nils Inge Landrø, PhD
Current status and future prospects of nanomedicine for arsenic trioxide delivery to solid tumors
Authors: Marthe Sönksen, Kornelius Kerl, Hana Bunzen
Journal: Medicinal Research Reviews (2021)

Abstract Despite having a rich history as a poison, arsenic and its compounds have also gained a great reputation as promising anticancer drugs. As a pioneer, arsenic trioxide has been approved for the treatment of acute promyelocytic leukemia. Many in vitro studies suggested that arsenic trioxide could also be used in the treatment of solid tumors. However, the transition from bench to bedside turned out to be challenging, especially in terms of the drug bioavailability and concentration reaching tumor tissues. To address these issues, nanomedicine tools have been proposed. As nanocarriers of arsenic trioxide, various materials have been examined including liposomes, polymer, and inorganic nanoparticles, and many other materials. This review gives an overview of the existing strategies of delivery of arsenic trioxide in cancer treatment with a focus on the drug encapsulation approaches and medicinal impact in the treatment of solid tumors. It focuses on the progress in the last years and gives an outlook and suggestions for further improvements including theragnostic approaches and targeted delivery.
2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia
Authors: Salim S. Virani, Pamela B. Morris, Anandita Agarwala, Christie M. Ballantyne, Kim K. Birtcher, Penny M. Kris-Etherton, Amanda B. Ladden-Stirling, Michael Miller, Carl E. Orringer, Neil J. Stone
Journal: Journal of the American College of Cardiology (2021)
Gut Microbiome Modulation by Antibiotics in Adult Asthma: A Human Proof-of-Concept Intervention Trial
Authors: Tjitske S.R. Van Engelen, Jack Yang, Bastiaan W. Haak, Peter I. Bonta, Tom Van Der Poll, W. Joost Wiersinga, Tjitske S.R. van Engelen, Jack Yang, Bastiaan W. Haak, Floor Hugenholtz, Peter I. Bonta, Christof J. Majoor, Cornelis van ‘t Veer, E. Marleen Kemper, Elisabeth H. Bel, Tom van der Poll, W. Joost Wiersinga
Journal: Clinical Gastroenterology and Hepatology (2021)

Although the pathophysiology of asthma is complex, perturbation of the gut microbiota has been associated with an increased risk of asthma development in childhood.
Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of <scp>Self Antigen</scp>–Specific Clones
Authors: Salome Glauzy, Brennan Olson, Christopher K. May, Daniele Parisi, Christopher Massad, James E. Hansen, Changwan Ryu, Erica L. Herzog, Eric Meffre
Journal: Arthritis & Rheumatology (2021)

Early selection steps preventing autoreactive naive B cell production are often impaired in patients with autoimmune diseases, but central and peripheral B cell tolerance checkpoints have not been assessed in patients with systemic sclerosis (SSc). This study was undertaken to characterize early B cell tolerance checkpoints in patients with SSc.Using an in vitro polymerase chain reaction-based approach that allows the expression of recombinant antibodies cloned from single B cells, we tested the reactivity of antibodies expressed by 212 CD19+CD21low CD10+IgMhigh CD27- new emigrant/transitional B cells and 190 CD19+CD21+CD10-IgM+CD27- mature naive B cells from 10 patients with SSc.Compared to serum from healthy donors, serum from patients with SSc displayed elevated proportions of polyreactive and antinuclear-reactive new emigrant/transitional B cells that recognize topoisomerase I, suggesting that defective central B cell tolerance contributes to the production of serum autoantibodies characteristic of the disease. Frequencies of autoreactive mature naive B cells were also significantly increased in SSc patients compared to healthy donors, thus indicating that a peripheral B cell tolerance checkpoint may be impaired in SSc.Defective counterselection of developing autoreactive naive B cells in SSc leads to the production of self antigen-specific B cells that may secrete autoantibodies and allow the formation of immune complexes, which promote fibrosis in SSc.
Evaluating the inclusiveness of common allergens in expanded series patch tests for children in the pediatric allergic contact dermatitis registry
Authors: Reid W. Collis, Idy Tam, Alan Snyder, John Plante, Eric Grisham, Alejandra Onate, Jennifer K. Chen, Walter J. Liszewski, Ari M. Goldminz, Colleen Cotton, Raegan Hunt, Kari L. Martin, David Sheinbein, JiaDe Yu
Journal: Journal of the American Academy of Dermatology (2021)
ST上昇型心筋梗塞におけるDoor-to-Door Timeを減じるための効果的なアプローチとしてのQCストーリー
Authors: Miyata Kenji, Yamamoto Unpei, Kikuchi Kan, Origuchi Hideki, Hayashidani Shunji, Sakamoto Ichiro, Dokura Junichiro, Kamiharaguchi Aya, Yamamoto Hideo, Mohri Masahiro
Journal: Circulation (2010)
Accreditation rules ensure that CME serves the needs of patients and the public
Authors: Graham T McMahon
Journal: BMJ (2021)

Fugh-Berman is correct in recognising the threat to our profession when prescribers are influenced by the marketing efforts of drug and device manufacturers.1 These companies invest in marketing because it works. But the author’s conflation of accredited continuing medical education (CME) and industry marketing is misinformed, and she makes several misleading and inaccurate statements. The Accreditation Council for Continuing Medical Education (ACCME) and the …
Anti–platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein
Authors: Andreas Greinacher, Kathleen Selleng, Julia Mayerle, Raghavendra Palankar, Jan Wesche, Sven Reiche, Andrea Aebischer, Theodore E. Warkentin, Maximilian Muenchhoff, Johannes C. Hellmuth, Oliver T. Keppler, Daniel Duerschmied, Achim Lother, Siegbert Rieg, Meinrad Paul Gawaz, Karin Anne Lydia Mueller, Christian S. Scheer, Matthias Napp, Klaus Hahnenkamp, Guglielmo Lucchese, Antje Vogelgesang, Agnes Flöel, Piero Lovreglio, Angela Stufano, Rolf Marschalek, Thomas Thiele
Journal: Blood (2021)
Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis
Authors: Satoshi Nakamizo, Charles-Antoine Dutertre, Ahad Khalilnezhad, Xiao Meng Zhang, Shawn Lim, Josephine Lum, Geraldine Koh, Charlene Foong, Pearly Jean Ai Yong, Kahbing Jasmine Tan, Reiko Sato, Kaori Tomari, Laurent Yvan-Charvet, Helen He, Emma Guttman-Yassky, Benoit Malleret, Rintaro Shibuya, Masashi Iwata, Baptiste Janela, Tsuyoshi Goto, Tan Siyun Lucinda, Mark B.Y. Tang, Colin Theng, Valerie Julia, Feriel Hacini-Rachinel, Kenji Kabashima, Florent Ginhoux
Journal: The Journal of Experimental Medicine (2021)

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)–mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.
MO25-4 Safety and efficacy of the combination of platinum, pemetrexed, and pembrolizumab in chemo-naive patients with NSCLC
Authors: Yuko Oya, Daichi Fujimoto, Satoru Miura, Kenichi Yoshimura, Kazushige Wakuda, Toshihide Yokoyama, Takashi Yokoi, Tetsuhiko Asao, Motohiro Tamiya, Atsushi Nakamura, Hiroshige Yoshioka, Koji Haratani, Akito Hata, Satoshi Hara, Takeshi Masuda, Takayuki Takahama, Kazuhisa Nakashima, Keisuke Tomii, Nobuyuki Yamamoto
Journal: Annals of Oncology (2021)
Small molecule inhibition of deubiquitinating enzyme JOSD1 as a novel targeted therapy for leukemias with mutant JAK2
Authors: Jing Yang, Ellen L. Weisberg, Xiaoxi Liu, Robert S. Magin, Wai Cheung Chan, Bin Hu, Nathan J. Schauer, Shengzhe Zhang, Ilaria Lamberto, Laura Doherty, Chengcheng Meng, Martin Sattler, Lucia Cabal-Hierro, Eric Winer, Richard Stone, Jarrod A. Marto, James D. Griffin, Sara J. Buhrlage
Journal: Leukemia (2021)
Abstract 14014: Atrial Tachyarrhythmias in Adult Patients With Tetralogy of Fallot and Congenital Pulmonary Stenosis: Long Term Catheter Ablation Results and Rates of Recurrence
Authors: Christopher S Grubb, Marlon S Rosenbaum, Hasan Garan, Angelo B Biviano
Journal: Circulation (2019)

Introduction: Catheter ablation is a well described treatment strategy for atrial tachyarrhythmias (AT) in adult congenital heart disease patients, such as those with Tetralogy of Fallot (TOF) or c...
Serious adverse events associated with yellow fever 17DD vaccine
Authors: Pedro F C Vasconcelos, Expedito J Luna, Ricardo Galler, Luiz J Silva, Terezinha L Coimbra, Vera L R S Barros, Thomas P Monath, Suely G Rodrigues, Cristina Laval, Zouraide G Costa, Maria F. G Vilela, Cecília L S Santos, Cristina M. O Papaiordanou, Venancio A F Alves, Liliana D Andrade, Helena K Sato, Elisabeth S T Rosa, Gustavo B Froguas, Ethel Lacava, Leda M R Almeida, Ana C R Cruz, Iray M Rocco, Raimunda T. M Santos, Otávio F P Oliva
Journal: The Lancet (2001)