tbuckley/cabot-search huggingface dataset:
Abstract 17805: Gut Microbiota Promote Arterial Hypertension and Vascular Dysfunction by Facilitating Remote Interleukin-17 Signaling
Authors: Susanne Karbach, Nives Hörmann, Sven Jäckel, Tanja Schönfelder, Rebecca Schüler, Stefanie Finger, Maike Knorr, Sabine Kossmann, Moritz Brandt, Thomas Münzel, Fredric Bäckhed, Christoph Reinhardt, Philip Wenzel
Journal: Circulation (2015)

Background: The presence of gut microbiota is essential for proper function of the immune cells. Its impact on the blood pressure regulation and systemic vascular function - processes that are described to be immune cell regulated - is unknown. Methods and Results: Unchallenged germfree mice (GF) showed no differences in endothelial function or vascular oxidative stress compared to conventionally reared mice (CONV-R), but they provided a dampened systemic T-bet / Interferon gamma (IFNγ) skewing in lymphoid cells. Re-colonization of GF with regular gut microbiota (conventionally-derived, CONV-D) normalized this phenotype. Angiotensin II (1mg/kg/d for 7d)-infused GF mice showed reduced oxidative stress levels in the vasculature, attenuated vascular expression of monocyte chemoattractant protein-1 and iNOS, blocked systemic up-regulation of T-bet / IFNγ and retinoic-acidreceptor-related orphan receptor-γt (ROR-γt) / interleukin-17 (IL-17) signaling in lymphoid cells and protection from endothelial dysfunction compared to CONV-R mice. Flow cytometric analysis showed a reduced infiltration of Ly6G+ neutrophils into the vessel wall and consequently we found an attenuation of arterial hypertension in Angiotensin II infused GF mice compared to Angiotensin II infused CONV-R mice. Protection from Angiotensin II induced vascular injury and the IFNγ / Ly6C+ monocyte axis as well as the IL-17/Ly6G+ axis was reversed in CONV-D mice. Conclusion: Gut microbiota seem to facilitate Angiotensin II induced hypertension by supporting a T-bet / IFNγ and ROR-γt / IL-17 driven vascular inflammation with infiltration of Ly6G+ neutrophils.
Handling of allergen immunotherapy in the COVID‐19 pandemic: An ARIA‐EAACI statement
Authors: Ludger Klimek, Marek Jutel, Cezmi Akdis, Jean Bousquet, Mübeccel Akdis, Claus Bachert, Ioana Agache, Ignacio Ansotegui, Anna Bedbrook, Sinthia Bosnic‐Anticevich, G. Walter Canonica, Tomas Chivato, Alvaro A. Cruz, Wiencyslawa Czarlewski, Stefano Del Giacco, Hui Du, Joao A. Fonseca, Yadong Gao, Tari Haahtela, Karin Hoffmann‐Sommergruber, Juan‐Carlos Ivancevich, Nikolai Khaltaev, Edward F. Knol, Piotr Kuna, Desiree Larenas‐Linnemann, Erik Melén, Joaquim Mullol, Robert Naclerio, Ken Ohta, Yoshitaka Okamoto, Liam O’Mahony, Gabrielle L Onorato, Nikos G. Papadopoulos, Ruby Pawankar, Oliver Pfaar, Boleslaw Samolinski, Jurgen Schwarze, Sanna Toppila‐Salmi, Mohamed H. Shamji, Maria Teresa Ventura, Arunas Valiulis, Arzu Yorgancioglu, Paolo Matricardi, Torsten Zuberbier
Journal: Allergy (2020)
Co‐Delivery of Paclitaxel and Interleukin‐12 Regulating Tumor Microenvironment for Cancer Immunochemotherapy
Authors: Qian Hu, Lihuan Shang, Mengmeng Wang, Kun Tu, Mei Hu, Yulin Yu, Mingwang Xu, Li Kong, Yuanyuan Guo, Zhiping Zhang
Journal: Advanced Healthcare Materials (2020)

In the treatment of malignant tumors, the combination of chemotherapy that can directly kill tumor cells and immunotherapy that can activate the body's immune system and regulate tumor microenvironments is becoming one of the most promising cancer treatments. However, to co-deliver agents with different physicochemical properties for immunochemotherapy is still facing a challenge. Here, nanoparticles are developed for the co-delivery of the hydrophobic chemotherapeutic drug paclitaxel (PTX) and biomacromolecule interleukin-12 (IL-12) through the acid-sensitive material mPEG-Dlinkm -PDLLA and low-temperature expansion effect of Pluronic F127. The nanoparticles encrich in the tumor site, significantly inhibit the growth and metastasis of breast cancer cells 4T1, and prolong the overall survival of tumor-bearing mice. The underlying immune mechanism is further explored. The combination of PTX and IL-12 activates T lymphocytes and NK cells to release IFN-γ, selectively inhibits regulatory T cells and induces M1-type differentiation of tumor-related macrophages, thereby improving tumor immunosuppressive microenvironments. This study may provide an effective strategy for cancer immunochemotherapy through co-delivery of chemotherapeutic drug and immune cytokine by the facile thermo-sponge nanoparticles.
Durable Antibacterial Cotton Fabrics Based on Natural Borneol‐Derived Anti‐MRSA Agents
Authors: Liu Yang, Chengdong Zhan, Xiangyue Huang, Liangzhi Hong, Liming Fang, Wen Wang, Jianyu Su
Journal: Advanced Healthcare Materials (2020)

Abstract Borneol, a natural extract with unique bicyclic monoterpene structure, has attracted increasing attention due to its broad‐spectrum antibacterial properties via membrane disruption mechanism. However, the negligible water solubility of borneol limits its antibacterial efficiency. Herein, borneol‐based water‐soluble antibacterial agents are designed and synthesized to combat multi‐drug resistant bacteria. The integration of borneol with hydrophilic poly( N , N ‐dimethylethyl methacrylate) (PDMAEMA) polymer chains boosts the antibacterial capability of borneol against Gram‐negative, Gram‐positive, and even multi‐drug resistant bacteria. Methicillin‐resistant Staphylococcus aureus (MRSA) are completely killed upon treatment with 50 µg mL −1 of borneol‐based polymers and Escherichia coli are annihilated at 39 µg mL −1 . It is further demonstrated that the borneol‐based antibacterial agents can be grafted onto cotton fabrics as a nonleaching antibacterial agent, which have higher sustained antibacterial activity than cotton fabrics coated with the commercial quaternary ammonium finishing agents (AEM 5700). The functionalized fabrics with excellent bactericidal activity, especially against MRSA, may have great potential applications in managing hospital‐acquired infections.
Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a need for a more accurate control group?
Authors: Philippe Mertz, Laurent Arnaud
Journal: Annals of the Rheumatic Diseases (2020)

Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a need for a more accurate control group?We read with great interest the recent paper by Zhu et al 1 which studied the risk of developing systemic lupus erythematosus (SLE) in a population of patients with idiopathic thrombocytopenic purpura (ITP).In their paper, Zhu et al performed a population-based retrospective cohort study in which they analysed the risk of SLE in a cohort of patients newly diagnosed with ITP between 2000 and 2013.Controls were selected at a 1:2 ratio through propensity score matching using the greedy algorithm.Zhu et al found an incidence rate of 62.0 per 100 000 person-months (95% CI 44.3 to 86.8) in the ITP group and of 2.10 per 100 000 personmonths (95% CI 1.44 to 3.06) in the non-ITP group, with an average follow-up time of 80 months.The adjusted HR of incidental SLE in the ITP group was 25.1 (95% CI 13.7 to 46.0).Given that ITP is an immune-mediated disease, a control group consisting in patients with other autoimmune diseases (autoimmune haemolytic anaemia, Evans syndrome, thyroiditis…) might have been more accurate in order to compare the risk of developing SLE with other autoimmune diseases instead of using a standard control group, which could have artificially overestimated the risk of SLE.
Regulatory myeloid cells paralyze T cells through cell–cell transfer of the metabolite methylglyoxal
Authors: Tobias Baumann, Andreas Dunkel, Christian Schmid, Sabine Schmitt, Michael Hiltensperger, Kerstin Lohr, Vibor Laketa, Sainitin Donakonda, Uwe Ahting, Bettina Lorenz-Depiereux, Jan E. Heil, Johann Schredelseker, Luca Simeoni, Caroline Fecher, Nina Körber, Tanja Bauer, Norbert Hüser, Daniel Hartmann, Melanie Laschinger, Kilian Eyerich, Stefanie Eyerich, Martina Anton, Matthew Streeter, Tina Wang, Burkhart Schraven, David Spiegel, Farhah Assaad, Thomas Misgeld, Hans Zischka, Peter J. Murray, Annkristin Heine, Mathias Heikenwälder, Thomas Korn, Corinna Dawid, Thomas Hofmann, Percy A. Knolle, Bastian Höchst
Journal: Nature Immunology (2020)
Standardisation of diet and exercise in clinical trials of NAFLD-NASH: Recommendations from the Liver Forum
Authors: Oliver Glass, Claudia Filozof, Mazen Noureddin, Mark Berner-Hansen, Elmer Schabel, Stephanie O. Omokaro, Jörn M. Schattenberg, Katherine Barradas, Veronica Miller, Sven Francque, Manal F. Abdelmalek
Journal: Journal of Hepatology (2020)
Reliability and usefulness of a rapid IgM‐IgG antibody test for the diagnosis of SARS-CoV-2 infection: A preliminary report.
Authors: Lucia Spicuzza, Arturo Montineri, Rosa Manuele, Claudia Crimi, Maria P Pistorio, Raffaele Campisi, Carlo Vancheri, Nunzio Crimi
Journal: Journal of Infection (2020)
Conditional survival in ovarian cancer: A SEER database analysis
Authors: M. Choi, C. D. Fuller, C. R. Thomas, S. J. Wang
Journal: Journal of Clinical Oncology (2008)

6620 Background: Survival statistics for patients with ovarian cancer are typically reported in terms of survival from time of diagnosis. For patients who have survived a period of time since diagnosis, however, conditional survival (CS) is a more clinically relevant measure, as it accounts for the changes in risk over time. The purpose of this study was to estimate CS for ovarian cancer patients through analysis of large-scale cancer registry data. Methods: Ovarian cancer cases were extracted from the Surveillance, Epidemiology, and End Results (SEER 17) database from the National Cancer Institute for patients diagnosed between 1988–2001. Five-year relative CS calculations were performed with stratification by age, race, stage, histology, and grade for patients who had already survived up to 5 years from diagnosis. Results: The 5-year overall relative CS improved over time for up to 5 years after diagnosis for ovarian cancer patients. The largest gains in CS over time were seen for patients with advanced stage disease, poor grade, and serous and undifferentiated epithelioid histologies. For patients with stage IV disease, 5-year CS more than tripled over the first 5 years of surveillance (17%-56%). Among histological types, patients with undifferentiated epithelioid histology saw 5-year CS rise from 29% at diagnosis to 84% after 5 years. Conclusions: Prognosis improves over time for almost all groups of ovarian cancer patients. For ovarian cancer survivors, CS provides a more relevant measure of prognosis than conventional survival estimates that are made at the time of diagnosis. Conditional Survival of All Patients By AJCC Stage Years after Diagnosis 0 1 2 3 4 5 Stage I 90% 91% 93% 93% 94% 95% Stage II 65% 71% 76% 79% 82% 85% Stage III 34% 38% 44% 51% 57% 65% Stage IV 17% 24% 30% 38% 47% 56% No significant financial relationships to disclose.
Characteristics and outcomes of patients with therapy-related acute myeloid leukemia with normal karyotype
Authors: Bachar Samra, Guillaume Richard-Carpentier, Tapan M. Kadia, Farhad Ravandi, Naval Daver, Courtney D. DiNardo, Ghayas C. Issa, Prithviraj Bose, Marina Y. Konopleva, Musa Yilmaz, Maro Ohanian, Gautam Borthakur, Guillermo Garcia-Manero, Sherry Pierce, Jorge E. Cortes, Hagop Kantarjian, Nicholas J. Short
Journal: Blood Cancer Journal (2020)

Abstract Normal karyotype in therapy-related acute myeloid leukemia (t-AML) is rare and the relative contribution of prior exposure to chemotherapy or radiotherapy to outcomes in these patients remains uncertain. We performed a retrospective study of 742 patients with newly diagnosed AML and normal karyotype (t-AML, n = 61, and non-t-AML, n = 681). Patients with t-AML were older but had a similar mutational profile compared to those with non-t-AML. Overall survival (OS) and relapse-free survival (RFS) were significantly worse for patients with t-AML ( P &lt; 0.01 and P = 0.02, respectively). Patients with t-AML had a higher cumulative incidence of death in remission (51% versus 16%, P &lt; 0.01), but not higher cumulative incidence of relapse (42% versus 56%, respectively, P = 0.21). Both intensive induction and allogeneic hematopoietic stem cell transplantation in first remission were associated with improved OS and RFS in non-t-AML but not in t-AML. Overall, although disease biology appears similar between t-AML and non-t-AML with normal karyotype as indicated by similar risks of relapse, death in remission is the main driver of inferior outcome in t-AML. Careful therapeutic decisions are required to mitigate potential treatment-related toxicity in this rare subgroup of patients with t-AML and normal karyotype.
A major genetic determinant of autoimmune diseases is associated with the presence of autoantibodies in hypersensitivity pneumonitis
Authors: Ivette Buendía-Roldán, Luis Santiago-Ruiz, Gloria Pérez-Rubio, Mayra Mejía, Jorge Rojas-Serrano, Enrique Ambrocio-Ortiz, Geovanni Benítez-Valdez, Moisés Selman, Ramcés Falfán-Valencia
Journal: European Respiratory Journal (2020)

Background Hypersensitivity pneumonitis is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with hypersensitivity pneumonitis develops autoantibodies with or without clinical manifestations of autoimmune disease. However, the mechanisms involved in this process and the effect of the autoantibodies on clinical course in hypersensitivity pneumonitis is unknown. We evaluated the association between human leukocyte antigen (HLA) class II alleles and hypersensitivity pneumonitis patients with and without autoantibodies. Methods 170 hypersensitivity pneumonitis patients were included. We analysed the presence of antinuclear antibodies, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-CCP at the time of diagnosis. In addition, in a subset of patients we evaluated anti-Scl-70, anti-neutrophil cytoplasmic antibody, and anti-DNA. HLA typing was performed using PCR sequence-specific primers in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing Epi-Info v7 and SPSS v20. Results 60 hypersensitivity pneumonitis patients showed sera autoantibodies (HPAbs + ), and 110 hypersensitivity pneumonitis patients did not (HPAbs − ). The frequency of the allele HLA-DRB1*03:01 was remarkably increased in the HPAbs + group (10.8% versus 0.45%; OR 30.14, 95% CI 3.83–237.1; p=1.65×10 -4 after Bonferroni's correction). Likewise, we found that the haplotype DRB1*03:01-DQB1*02:01 , which is part of the 8.1 ancestral haplotype, a major genetic determinant of autoimmune diseases, confers significant risk to develop autoantibodies (OR 19.23, 95% CI 2.37–155.9; p=0.0088 after Bonferroni's correction). In addition, the HLA-DRB1*03:01 allele was associated with higher mortality in patients with hypersensitivity pneumonitis (adjusted OR 5.9, 95% CI 1.05–33.05; p=0.043). Conclusions A subset of hypersensitivity pneumonitis patients presents circulating autoantibodies and higher mortality that are associated with some alleles of 8.1 ancestral haplotype.
Abstract 13912: Protein Phosphatase 2C-alpha Knockdown Reduces Angiotensin II-Mediated Skeletal Muscle Wasting via Restoration of Mitochondrial Recycling and Function
Authors: Alexander M Tabony, Tadashi Yoshida, Patrice Delafontaine
Journal: Circulation (2014)

Circulating Angiotensin II (AngII) is elevated in congestive heart failure (CHF), and leads to skeletal muscle wasting, which is strongly associated with poor patient outcomes. We previously found that AngII upregulates protein phosphatase 2C-alpha (PP2Cα) and dephosphorylates AMP-Activated Protein Kinase (AMPK), a critical regulator of cellular metabolism, in skeletal muscle. To determine the role of PP2Cα in AngII-induced wasting, gastrocnemius (Gas) muscles of FVB mice were injected with scrambled or PP2Cα siRNA and mice were infused with saline or AngII for 4 days. Knockdown of PP2Cα reduced AngII wasting by 50% (p<0.001), blocked AngII upregulation of PP2Cα by 62% (p<0.01), increased p-T172-AMPK by 60% versus scrambled siRNA (p<0.01), and inhibited AngII-mediated reductions in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α, p<0.05), in complex IV activity (p<0.01), and in ATP (p<0.05) by 35-51%. AngII impaired autophagic flux as determined by a 165% increase in p62/SQSTM1 (p62) e...
Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use by County and Rural-Urban Classification — United States, 2017
Authors: Claudine M. Samanic, Kamil E. Barbour, Yong Liu, Yan Wang, Jing Fang, Hua Lu, Linda Schieb, Kurt J. Greenlund
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2017, approximately one in three U.S. adults reported having been told by a health care professional that they had high blood pressure (hypertension) (1). Although hypertension prevalence is well documented at national and state levels, less is known about rural-urban variation and county-level prevalence. To examine prevalence of self-reported hypertension and antihypertensive medication use by rural-urban classification and county, CDC analyzed data reported by 442,641 adults aged ≥18 years who participated in the 2017 Behavioral Risk Factor Surveillance System (BRFSS). In rural (noncore) areas, 40.0% (unadjusted prevalence) of adults reported having hypertension, whereas in the most urban (large central metro) areas, 29.4% reported having hypertension. Age-standardized hypertension prevalence was significantly higher in the most rural areas, compared with the most urban areas within nearly all categories of age, sex, and other demographic characteristics. Model-based hypertension prevalence across counties ranged from 18.0% to 55.0% and was highest in Southeastern* and Appalachian
Harmonized Outcome Measures for Use in Depression Patient Registries and Clinical Practice
Authors: Richard E. Gliklich, Michelle B. Leavy, Lisa Cosgrove, Gregory E. Simon, Bradley N. Gaynes, Lars E. Peterson, Bryan Olin, Collette Cole, J. Raymond DePaulo, Philip Wang, Chris M. Crowe, Cristina Cusin, Mary Nix, Elise Berliner, Madhukar H. Trivedi
Journal: Annals of Internal Medicine (2020)

Major depressive disorder is a common mental health condition that affects an estimated 16.2 million adults and 3.1 million adolescents in the United States. Yet, a lack of uniformity remains in measurements and monitoring for depression both in clinical practice and in research settings. This project aimed to develop a minimum set of standardized outcome measures relevant to both patients and clinicians that can be collected in depression registries and clinical practice. Twenty-nine depression registries and related data collection efforts were identified and invited to submit outcome measures. Additional measures were identified through literature searches and reviews of quality measures. A multistakeholder panel representing clinicians; payers; government agencies; industry; and medical specialty, health care quality, and patient advocacy organizations categorized the 27 identified measures using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework. The panel identified 10 broadly relevant measures and harmonized definitions for these measures through in-person and virtual meetings. The harmonized measures represent a minimum set of outcomes that are relevant to clinicians and patients and appropriate for use in depression research and clinical practice. Routine and consistent collection of these measures in registries and other systems would support creation of a national research infrastructure to efficiently address new questions, improve patient management and outcomes, and facilitate care coordination.
TMEM9‐v‐ATPase Activates Wnt/β‐Catenin Signaling Via APC Lysosomal Degradation for Liver Regeneration and Tumorigenesis
Authors: Youn‐Sang Jung, Sabrina A. Stratton, Sung Ho Lee, Moon‐Jong Kim, Sohee Jun, Jie Zhang, Biyun Zheng, Christopher L. Cervantes, Jong‐Ho Cha, Michelle C. Barton, Jae‐Il Park
Journal: Hepatology (2020)

Background and Aims How Wnt signaling is orchestrated in liver regeneration and tumorigenesis remains elusive. Recently, we identified transmembrane protein 9 (TMEM9) as a Wnt signaling amplifier. Approach and Results TMEM9 facilitates v‐ATPase assembly for vesicular acidification and lysosomal protein degradation. TMEM9 is highly expressed in regenerating liver and hepatocellular carcinoma (HCC) cells. TMEM9 expression is enriched in the hepatocytes around the central vein and acutely induced by injury. In mice, Tmem9 knockout impairs hepatic regeneration with aberrantly increased adenomatosis polyposis coli (Apc) and reduced Wnt signaling. Mechanistically, TMEM9 down‐regulates APC through lysosomal protein degradation through v‐ATPase. In HCC, TMEM9 is overexpressed and necessary to maintain β‐catenin hyperactivation. TMEM9–up‐regulated APC binds to and inhibits nuclear translocation of β‐catenin, independent of HCC‐associated β‐catenin mutations. Pharmacological blockade of TMEM9‐v‐ATPase or lysosomal degradation suppresses Wnt/β‐catenin through APC stabilization and β‐catenin cytosolic retention. Conclusions Our results reveal that TMEM9 hyperactivates Wnt signaling for liver regeneration and tumorigenesis through lysosomal degradation of APC.
ERRα Expression in Bone Metastases Leads to an Exacerbated Antitumor Immune Response
Authors: Mathilde Bouchet, Alexandra Lainé, Cyril Boyault, Mathilde Proponnet-Guerault, Emmanuelle Meugnier, Lamia Bouazza, Casina W.S. Kan, Sandra Geraci, Soumaya El-Moghrabi, Hector Hernandez-Vargas, Claire Benetollo, Yuji Yoshiko, Martine Duterque-Coquillaud, Philippe Clézardin, Julien C. Marie, Edith Bonnelye
Journal: Cancer Research (2020)

Abstract Bone is the most common metastatic site for breast cancer. Although the estrogen-related receptor alpha (ERRα) has been implicated in breast cancer cell dissemination to the bone from the primary tumor, its role after tumor cell anchorage in the bone microenvironment remains elusive. Here, we reveal that ERRα inhibits the progression of bone metastases of breast cancer cells by increasing the immune activity of the bone microenvironment. Overexpression of ERRα in breast cancer bone metastases induced expression of chemokines CCL17 and CCL20 and repressed production of TGFβ3. Subsequently, CD8+ T lymphocytes recruited to bone metastases escaped TGFβ signaling control and were endowed with exacerbated cytotoxic features, resulting in significant reduction in metastases. The clinical relevance of our findings in mice was confirmed in over 240 patients with breast cancer. Thus, this study reveals that ERRα regulates immune properties in the bone microenvironment that contributes to decreasing metastatic growth. Significance: This study places ERRα at the interplay between the immune response and bone metastases of breast cancer, highlighting a potential target for intervention in advanced disease.
A Syndrome of Immunoglobulin A Deficiency, Diabetes Mellitus, Malabsorption, and a Common HLA Haplotype
Authors: David H. Van Thiel, William I. Smith, Bruce S. Rabin, Stanley E. Fisher, Roger Lester
Journal: Annals of Internal Medicine (2020)

Abstract Three persons in a kindred of 43 had variable expression of a syndrome consisting of immunoglobulin A deficiency, diabetes mellitus, malabsorption, and a common HLA haplotype. Findings fro...