tbuckley/cabot-search huggingface dataset:
Development and validation of combined symptom‐medication scores for allergic rhinitis*
Authors: Bernardo Sousa‐Pinto, Luís Filipe Azevedo, Marek Jutel, Ioana Agache, G. Walter Canonica, Wienczyslawa Czarlewski, Nikolaos G. Papadopoulos, Karl‐Christian Bergmann, Philippe Devillier, Daniel Laune, Ludger Klimek, Aram Anto, Josep M. Anto, Patrik Eklund, Rute Almeida, Anna Bedbrook, Sinthia Bosnic‐Anticevich, Helen A. Brough, Luisa Brussino, Victoria Cardona, Thomas Casale, Lorenzo Cecchi, Denis Charpin, Tomás Chivato, Elisio M. Costa, Alvaro A. Cruz, Stephanie Dramburg, Stephen R. Durham, Giulia De Feo, Roy Gerth van Wijk, Wystke J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Maddalena Illario, Juan Carlos Ivancevich, Violeta Kvedariene, Piotr Kuna, Désirée E. Larenas‐Linnemann, Michael Makris, Eve Mathieu‐Dupas, Erik Melén, Mario Morais‐Almeida, Ralph Mösges, Joaquim Mullol, Kari C. Nadeau, Nhân Pham‐Thi, Robyn O’Hehir, Frederico S. Regateiro, Sietze Reitsma, Boleslaw Samolinski, Aziz Sheikh, Cristiana Stellato, Ana Todo‐Bom, Peter Valentin Tomazic, Sanna Toppila‐Salmi, Antonio Valero, Arunas Valiulis, Maria Teresa Ventura, Dana Wallace, Susan Waserman, Arzu Yorgancioglu, Govert De Vries, Michiel van Eerd, Petra Zieglmayer, Torsten Zuberbier, Oliver Pfaar, João Almeida Fonseca, Jean Bousquet
Journal: Allergy (2021)

Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs.We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]).We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820).The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.
Abstract 11972: Ivabradine Attenuates Hypoxia/Reoxygenation-Induced Excessive Autophagy in H9c2 Cardiomyocyte by Modulation of the PI3K/Akt/mTOR Pathway
Authors: min yang, Hui Li, Wu Jiatian, Hua Tianfeng
Journal: Circulation (2021)

Introduction: Despite recent advances in resuscitation techniques, the mortality associated with survival from cardiac arrest (CA) still remains low. Cardiovascular ischemia/reperfusion injury (IRI) is one of the primary pathophysiology involved. Hypothesis: We assessed the hypothesis that ivabradine could attenuate hypoxia/reoxygenation injury of H9c2 cardiomyocytes by inhibiting excessive autophagy through PI3K/Akt/mTOR Pathway. Methods: Cultured H9c2 were randomly divided into 3 groups: CON (normoxia), H/R (hypoxia reoxygenation) and IVA. The IVA was divided into 4 subgroups, in which H9c2 were treated with or without ivabradine(20μM or 100μM) or PI3-kinase inhibitor LY294002(10μM) for 12 hours and then subjected to 12 hours of hypoxia and 24 hours of reoxygenation. Hypoxia was achieved by a hypoxia chamber filled with 5%CO 2 and 95% N 2 at 37°C. Cell viability were measured with CCK-8 assay kits. Cell autophagy was assessed by transmission electron microscopy (TEM). The expressions of autophagy marker protein (LC3, Beclin-1), PI3K, Akt and mTOR were determined by Western-blot assay. Results: A decrease of cell viability and an increase formulation of autophagosomes /autophagy lysozymes occurred after H/R. Significant improvement was noted in cells treated with ivabradine compared to H/R(Figure 1). Ivabradine promoted pmTOR/mTOR expression and lower expressions of LC3II/LC3I and Beclin 1. LY294002 antagonized the effects of ivabradine on antophagy (Figure 2). Conclusions: Ivabradine could protect H9c2 against H/R injury via inhibiting excessive autophagy through PI3K/Akt/mTOR pathway.
A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
Authors: Karin Welén, Ebba Rosendal, Magnus Gisslén, Annasara Lenman, Eva Freyhult, Osvaldo Fonseca-Rodríguez, Daniel Bremell, Johan Stranne, Åse Östholm Balkhed, Katarina Niward, Johanna Repo, David Robinsson, Anna J. Henningsson, Johan Styrke, Martin Angelin, Elisabeth Lindquist, Annika Allard, Miriam Becker, Stina Rudolfsson, Robert Buckland, Camilla Thellenberg Carlsson, Anders Bjartell, Anna C. Nilsson, Clas Ahlm, Anne-Marie Fors Connolly, Anna K. Överby, Andreas Josefsson
Journal: European Urology (2021)

Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
Intensive Serum Urate Lowering With Oral Urate‐Lowering Therapy for Erosive Gout: A Randomized Double‐Blind Controlled Trial
Authors: Nicola Dalbeth, Anthony J. Doyle, Karen Billington, Greg D. Gamble, Paul Tan, Kieran Latto, Thrishila Parshu Ram, Ravi Narang, Rachel Murdoch, David Bursill, Borislav Mihov, Lisa K. Stamp, Anne Horne
Journal: Arthritis & Rheumatology (2021)

Objective To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout. Methods We undertook a 2‐year, double‐blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate–lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of &lt;0.20 mmoles/liter or a standard target of &lt;0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate–lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points. Results Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period ( P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P &lt; 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P &lt; 0.001) and received more combination therapy ( P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between‐group difference ( P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health‐related quality of life, and activity limitation) improved in both groups over 2 years, with no between‐group differences. Adverse event and serious adverse event rates were similar between the groups. Conclusion Compared to a serum urate target of &lt;0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate‐lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout.
Response to: ‘Anakinra for palmoplantar pustulosis: results from a randomized, double‐blind, multicentre, two‐staged, adaptive placebo‐controlled trial (APRICOT)’: reply from the authors
Authors: S. Cro, C.H Smith
Journal: British Journal of Dermatology (2021)

We believe that there is significant interest in the role of IL-1 in the pathomechanism of palmoplantar pustulosis. However, the APRICOT study failed to demonstrate a therapeutic effect of the IL-1 receptor antagonist. So, we recommend that the authors perform an additional subgroup analysis based on the presence or absence of plaque psoriasis.
Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy
Authors: Sarah A M Cuddy, Michael Jerosch-Herold, Rodney H Falk, Marie Foley Kijewski, Vasvi Singh, Frederick L Ruberg, Vaishali Sanchorawala, Heather Landau, Matthew S Maurer, Andrew J Yee, Giada Bianchi, Marcelo F Di Carli, Ronglih Liao, Raymond Y Kwong, Sharmila Dorbala
Journal: JACC. Cardiovascular imaging (2021)
Mechanisms of Sinoatrial Node Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Thassio Mesquita, Rui Zhang, Jae Hyung Cho, Rui Zhang, Yen-Nien Lin, Lizbeth Sanchez, Joshua I. Goldhaber, Joseph K. Yu, Jialiu A. Liang, Weixin Liu, Natalia A. Trayanova, Eugenio Cingolani
Journal: Circulation (2021)

The ability to increase heart rate during exercise and other stressors is a key homeostatic feature of the sinoatrial node (SAN). When the physiological heart rate response is blunted, chronotropic incompetence limits exercise capacity, a common problem in patients with heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, the mechanisms of chronotropic incompetence remain unknown.
Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party
Authors: Jesse M. Tettero, Sylvie Freeman, Veit Buecklein, Adriano Venditti, Luca Maurillo, Wolfgang Kern, Roland B. Walter, Brent L. Wood, Christophe Roumier, Jan Philippé, Barbara Denys, Jeffrey L. Jorgensen, Marie C. Bene, Francis Lacombe, Adriana Plesa, Monica L. Guzman, Agnieszka Wierzbowska, Anna Czyz, Lok Lam Ngai, Adrian Schwarzer, Costa Bachas, Jacqueline Cloos, Marion Subklewe, Michaela Fuering-Buske, Francesco Buccisano
Journal: HemaSphere (2021)

Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization.
BNT162b2 Vaccine Booster and Mortality Due to Covid-19
Authors: Ronen Arbel, Ariel Hammerman, Ruslan Sergienko, Michael Friger, Alon Peretz, Doron Netzer, Shlomit Yaron
Journal: New England Journal of Medicine (2021)

The emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 and the reduced effectiveness over time of the BNT162b2 vaccine (Pfizer-BioNTech) led to a resurgence of coronavirus disease 2019 (Covid-19) cases in populations that had been vaccinated early. On July 30, 2021, the Israeli Ministry of Health approved the use of a third dose of BNT162b2 (booster) to cope with this resurgence. Evidence regarding the effectiveness of the booster in lowering mortality due to Covid-19 is still needed.We obtained data for all members of Clalit Health Services who were 50 years of age or older at the start of the study and had received two doses of BNT162b2 at least 5 months earlier. The mortality due to Covid-19 among participants who received the booster during the study period (booster group) was compared with that among participants who did not receive the booster (nonbooster group). A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of booster status with death due to Covid-19, with adjustment for sociodemographic factors and coexisting conditions.A total of 843,208 participants met the eligibility criteria, of whom 758,118 (90%) received the booster during the 54-day study period. Death due to Covid-19 occurred in 65 participants in the booster group (0.16 per 100,000 persons per day) and in 137 participants in the nonbooster group (2.98 per 100,000 persons per day). The adjusted hazard ratio for death due to Covid-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% confidence interval, 0.07 to 0.14; P<0.001).Participants who received a booster at least 5 months after a second dose of BNT162b2 had 90% lower mortality due to Covid-19 than participants who did not receive a booster.
NDRG1 in Aggressive Breast Cancer Progression and Brain Metastasis
Authors: Emilly S Villodre, Xiaoding Hu, Bedrich L Eckhardt, Richard Larson, Lei Huo, Ester C Yoon, Yun Gong, Juhee Song, Shuying Liu, Naoto T Ueno, Savitri Krishnamurthy, Stefan Pusch, Debu Tripathy, Wendy A Woodward, Bisrat G Debeb
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background N-Myc downstream regulated gene 1 (NDRG1) suppresses metastasis in many human malignancies, including breast cancer, yet has been associated with worse survival in patients with inflammatory breast cancer. The role of NDRG1 in the pathobiology of aggressive breast cancers remains elusive. Methods To study the role of NDRG1 in tumor growth and brain metastasis in vivo, we transplanted cells into cleared mammary fat pads or injected them in tail veins of SCID/Beige mice (n = 7-10 per group). NDRG1 protein expression in patient breast tumors (n = 216) was assessed by immunohistochemical staining. Kaplan-Meier method with 2-sided log-rank test was used to analyze the associations between NDRG1 and time-to-event outcomes. A multivariable Cox regression model was used to determine independent prognostic factors. All statistical tests were 2-sided. Results We generated new sublines that exhibited a distinct propensity to metastasize to the brain. NDRG1-high–expressing cells produced more prevalent brain metastases (100% vs 44.4% for NDRG1-low sublines, P = .01, Fisher’s exact test), greater tumor burden, and reduced survival in mice. In aggressive breast cancer cell lines, silencing NDRG1 led to reduced migration, invasion, and tumor-initiating cell subpopulations. In xenograft models, depleting NDRG1 inhibited primary tumor growth and brain metastasis. In patient breast tumors, NDRG1 was associated with aggressiveness: NDRG1-high expression was also associated with shorter overall survival (hazard ratio [HR] = 2.27, 95% confidence interval [95% CI] = 1.20 to 4.29, P = .009) and breast cancer–specific survival (HR = 2.19, 95% CI = 1.07 to 4.48, P = .03). Multivariable analysis showed NDRG1 to be an independent predictor of overall survival (HR = 2.17, 95% CI = 1.10 to 4.30, P = .03) and breast cancer–specific survival rates (HR = 2.27, 95% CI = 1.05 to 4.92, P = .04). Conclusions We demonstrated that NDRG1 drives tumor progression and brain metastasis in aggressive breast cancers and that NDRG1-high expression correlates with worse clinical outcomes, suggesting that NDRG1 may serve as a therapeutic target and prognostic biomarker in aggressive breast cancers.
Abstract 12990: The Association of Modifiable Mechanical Ventilation Settings, Blood Gas Changes and Survival After Extracorporeal Cardiopulmonary Resuscitation
Authors: Joseph Tonna, Craig Selzman, Jason Bartos, Zhining Ou, Yeonjung Jo, Lance B Becker, Scott T Youngquist, Ravi R Thiagarajan, Michael Johnson, Peter Rycus, Heather Keenan
Journal: Circulation (2021)

Introduction: Gas exchange during ECMO can occur independent of the lungs through ECMO, enabling a wider range of ventilator settings and blood gas values. Yet it is not known if potentially modifiable mechanical ventilation parameters or blood gas values are associated with survival for patients who receive ECPR. Hypothesis: To determine associations between ventilation parameters, blood gas values, and survival. Methods: Cohort analysis among 7,488 ECPR patients ≥18yrs of age from the Extracorporeal Life Support Organization (ELSO) Registry from 2008 - 2019. We examined the association between mechanical ventilation parameters on-ECMO with case-mix adjusted hospital survival. We used generalized estimating equation logistic regression, accounting for center level variation. Results: Case-mix adjusted patient-level mechanical ventilation parameters and blood gas values on-ECMO varied across individual hospitals, including arterial pressure of oxygen (PaO2) and carbon dioxide (PaCO2), and changes in these values from pre-ECMO to on-ECMO. Increasing absolute on-ECMO PaO2 (OR 0.88 [95% CI 0.86, 0.9]; p&lt;0.001), and relative increases in PaO2 from pre- to on-ECMO (OR 0.91 [0.89,0.93]; p&lt;0.001) were both associated with decreased survival. Relative increases in pre- to on-ECMO PaCO2 (OR 1.31 [1.14, 1.1.54]; p&lt;0.001) were associated with improved survival. Decreasing peak inspiratory pressure (OR 0.77, per 5 centimeters of water (cmH2O) [0.72, 0.81]; p&lt;0.001) and fraction of inspired oxygen (OR 0.94, per 5% [0.92, 0.96]; p&lt;0.001) were both associated with improved survival. Conclusions: Mechanical ventilation parameters of ECPR patients varies across hospitals. Potentially modifiable parameters and blood gas values are associated with survival and should be the focus of future research.
Convalescent Plasma for Outpatients with Covid-19
Authors: Frederick K Korley, Valerie Durkalski-Mauldin, Clifton W Callaway
Journal: New England Journal of Medicine (2021)

Dr. Scully replies: Patients in the three cohorts presented with this new clinical syndrome of VITT after receiving their first dose of the ChAdOx1 nCoV-19 vaccine, and they met the diagnostic criteria for VITT, including the presence of anti-PF4 antibodies.Important considerations included the role of SARS-CoV-2 infection and the presence of antibodies, both to SARS-CoV-2 and to the vaccine.In our cohort, we conducted extensive SARS-CoV-2 antibody testing with a flow cytometer (CytoFLEX, Beckman Coulter).SARS-CoV-2 spike, receptor-binding domain, and nucleocapsid IgG serum angiotensin-converting-enzyme 2-receptor binding inhibition and spike antibodies to seasonal coronaviruses HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E were measured by a multiplexed electrochemiluminescent assay (Meso Scale Discovery), as previously described. 1These confirmed antibody levels were compatible with the receipt of one dose of vaccine only and were not suggestive of antibodies to SARS-CoV-2.Persons may have asymptomatic SARS-CoV-2 infection, and the antibodies may not be detectable by current assays.A plausible hypothesis is SARS-CoV-2 antibodies could be stimulated in relation to an acute event, such as VITT.SARS-CoV-2 was not detected in any patient on polymerase-chain-reaction (PCR) testing.Santin asks why T-cell-receptor sequencing tests were not also used.The assay was approved by the FDA only under emergency use authorization, and we rely on evaluated PCR-based tests.As documented by the FDA, 2 it is unknown how
滥用酒精的患者对银屑病全身治疗的反应较差
Journal: British Journal of Dermatology (2021)

这项研究位于英国, 旨在了解哪些因素会影响银屑病患者的治疗结果。之前的研究表明, 不良银屑病和饮酒之间存在关联, 这项研究的目的是确定饮酒与治疗反应之间是否有任何关联。研究人群是前往英格兰地区诊所就诊的患者。所有患者均患有中度至重度银屑病, 以常规方式使用外用或口服疗法进行治疗 (常规疗法) , 但有些患者曾接受新型生物治疗。所有患者均填写了一份问卷, 其中包括患者自我估计的酒精滥用情况以及银屑病严重程度, 在治疗期间的不同时间点进行记录。相关信息被记录在国家数据库中。酗酒和肥胖均与常规疗法治疗反应较差存在相关性。此外, 未能依从治疗方案也与不良结果存在相关性。这项研究中至少 40% 的患者报告有心理困扰。
Solving the Equation of Structural Inequities in the Oncology Workforce
Authors: Frederick Lansigan, Charles R. Thomas
Journal: JAMA Oncology (2021)

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