tbuckley/cabot-search huggingface dataset:
Elevated C-Reactive Protein in Patients With Depression, Independent of Genetic, Health, and Psychosocial Factors: Results From the UK Biobank
Authors: Maria C. Pitharouli, Saskia P. Hagenaars, Kylie P. Glanville, Jonathan R.I. Coleman, Matthew Hotopf, Cathryn M. Lewis, Carmine M. Pariante
Journal: American Journal of Psychiatry (2021)

Objective: The authors investigated the pathways (genetic, environmental, lifestyle, medical) leading to inflammation in major depressive disorder using C-reactive protein (CRP), genetic, and phenotypic data from the UK Biobank. Methods: This was a case-control study of 26,894 participants with a lifetime diagnosis of major depressive disorder from the Composite International Diagnostic Interview and 59,001 control subjects who reported no mental disorder and had not reported taking any antidepressant medication. Linear regression models of log CRP level were fitted to regress out the effects of age, sex, body mass index (BMI), and smoking and to test whether the polygenic risk score (PRS) for major depression was associated with log CRP level and whether the association between log CRP level and major depression remained after adjusting for early-life trauma, socioeconomic status, and self-reported health status. Results: CRP levels were significantly higher in patients with depression relative to control subjects (2.4 mg/L compared with 2.1 mg/L, respectively), and more case than control subjects had CRP levels >3 mg/L (21.2% compared with 16.8%, respectively), indicating low-grade inflammation. The PRS for depression was positively and significantly associated with log CRP levels, but this association was no longer significant after adjustment for BMI and smoking. The association between depression and increased log CRP level was substantially reduced, but still remained significant, after adjustment for the aforementioned clinical and sociodemographic factors. Conclusions: The data indicate that the “genetic” contribution to increased inflammation in depression is due to regulation of eating and smoking habits rather than an “autoimmune” genetic predisposition. Moreover, the association between depression and increased inflammation even after full adjustment indicates either the presence of yet unknown or unmeasured psychosocial and clinical confounding factors or that a core biological association between depression and increased inflammation exists independently from confounders.
Emergency Department Visits for Bicycle-Related Traumatic Brain Injuries Among Children and Adults — United States, 2009–2018
Authors: Kelly Sarmiento, Tadesse Haileyesus, Dana Waltzman, Jill Daugherty
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Bicycling leads to the highest number of sport and recreation-related emergency department (ED) visits for traumatic brain injuries (TBIs) in the United States (1).Because bicycling continues to grow in popularity,* primarily among U.S. adults, examining the strategies that mitigate the risk for TBI is important.CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP) to determine the incidence of EDs for bicycle-related TBIs during 2009-2018.An estimated 596,972 ED visits for bicycle-related TBIs occurred in the United States during the study period.Rates of ED visits were highest among adult males (aged ≥18 years) and among children and adolescents aged 10-14 years during 2009-2018.Overall, the rate of ED visits for bicycle-related TBIs decreased by approximately one half (48.7%) among children and by 5.5% among adults.As the number of persons riding bicycles increases, expansion of comprehensive bicycling safety interventions for bicyclists and drivers by states and local communities, such as interventions to increase driver compliance with traffic laws and helmet use among riders, improvements in bicycling infrastructure, and customized interventions for males and other groups at high risk might help reduce bicycle-related injuries.NEISS-AIP, operated by the U.S. Consumer Product Safety Commission, contains annual data on patients treated in hospital EDs drawn from a nationally representative, stratified probability sample of hospitals, † and weighted by the inverse probability of selection to provide national estimates.This analysis included data on bicycling-related TBIs that occurred among adults aged ≥18 years and children and adolescents (children) aged ≤17 years during 2009-2018.A case was classified as a TBI if the primary body part injured was the head * https://www.npd.com/wps/portal/npd/us/news/press-releases/2020/cycling-industry-sales-growth-accelerates
Abstract 17071: Cell Communication Inference in Macrophages
Authors: Nika Taghdiri, Kevin R King, David Calcagno, Zhenxing Fu, Kenneth Huang, R weissleder
Journal: Circulation (2020)

Introduction: Tissue macrophages play diverse roles in the cardiovascular system during health and disease. They have diverse functions within tissues, but our understanding of their dynamics is limited because most macrophage characterization assays are destructive and have low temporal resolution. We asked whether these cells are dynamic and interconnected. Methods: Here, we describe experimental and analytical methods for measuring cell dynamics and inferring communication between cells in vitro and in vivo. We created a mouse (Csf1r-Cre x GCaMP5) expressing the Cre-inducible genetically encoded calcium indicator GCaMP5 under the regulation of the innate immune promoter, Csf1r, to non-destructively quantify high-frequency cell dynamics and differentiated them in culture using m-CSF. We developed custom image analysis routines and parameterization strategies for classifying calcium responses. Results: Our studies revealed that calcium reporter BMDMs display minimal fluctuations at baseline but exhibit a dynamic response to immunogenic DNA sensing. DNA-induced isolated cell injury and death, which precipitated cell communication that spread with a velocity of [9μm/s], consistent with an extracellular diffusion mechanism. We developed quantitative image analysis methods that corrected for random calcium fluctuations and identified statistically significant areas of correlated calcium changes suggestive of communication. An analytical pipeline enabled quantification of calcium spike dynamics and correlations of dynamic calcium profiles of single cell sharing a local microenvironment. This resulted in an “improbable synchrony” metric that allowed localization of communication in time and space. We adapted the pipeline for in vivo studies and tested them in a dorsal window chamber model using intravital microscopy. At 2Hz sampling frequency, we identified 27 potential communication events as they responded to complex microenvironmental cues in vivo. Conclusion: The experimental and analytical methods for inferring cell communication provide a new quantitative toolkit for investigating known as-yet undiscovered cell communication pathways.
Targeting monoamine oxidase A for T cell–based cancer immunotherapy
Authors: Xi Wang, Bo Li, Yu Jeong Kim, Yu-Chen Wang, Zhe Li, Jiaji Yu, Samuel Zeng, Xiaoya Ma, In Young Choi, Stefano Di Biase, Drake J. Smith, Yang Zhou, Yan-Ruide Li, Feiyang Ma, Jie Huang, Nicole Clarke, Angela To, Laura Gong, Alexander T. Pham, Heesung Moon, Matteo Pellegrini, Lili Yang
Journal: Science Immunology (2021)

Monoamine oxidase A (MAO-A) restrains antitumor T cell immunity, suggesting potential use of MAO-A inhibitors in cancer immunotherapy.
Safety and Clinical Activity of Combined Romidepsin and Azacitidine Therapy in High Risk Acute Myeloid Leukemia: Preliminary Results of the Romaza Trial
Authors: Charles Craddock, Eleni Tholouli, Samuel Munoz Vicente, Emmanouela Gbandi, Aimee E Houlton, Mark W Drummond, Jiri Pavlu, Paresh Vyas
Journal: Blood (2017)
Covid-19: “Exhausted” GPs need more support for future crises, says leader
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The government must provide “real and meaningful support” to help general practice recover from the covid-19 pandemic and ensure it is better prepared for future crises, the UK’s GP leader has urged.

In a speech to GPs from across the four UK nations at the virtual annual conference of local medical committees on 11 May, Richard Vautrey, the chair of the BMA’s UK General Practitioners Committee, said that the past 14 months had tested “every GP team and individual like never before.”

He said, “It has been a hard and difficult time that has left many physically exhausted …
Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Kristian Reich, Henrique D Teixeira, Marjolein de Bruin-Weller, Thomas Bieber, Weily Soong, Kenji Kabashima, Thomas Werfel, Jiewei Zeng, Xiaohong Huang, Xiaofei Hu, Barbara A Hendrickson, Barry Ladizinski, Alvina D Chu, Jonathan I Silverberg
Journal: The Lancet (2021)
Women harmed by faulty breast implants should be compensated, says French court
Authors: Clare Dyer
Journal: BMJ (2021)

A Paris appeals court has ruled that around 2700 women, including 540 from the UK, are entitled to compensation from the German company which certified as safe faulty implants made by a French manufacturer.

The court ruled that TUV Rhineland was negligent when it certified the safety of implants made by Poly Implant Prothese (PIP).

PIP implants, which were marketed for 10 years, were made with cheap industrial grade silicone used in mattresses and not cleared for human use, rather than medical grade silicone. The European safety certificates given by TUV allowed PIP to market the product around the world.

The implants are thought to have been given …
Antibody responses to single‐dose SARS‐CoV‐2 vaccination in patients receiving immunomodulators for immune‐mediated inflammatory disease
Authors: A. Al‐Janabi, Z. Littlewood, C.E.M. Griffiths, H.J.A. Hunter, H. Chinoy, C. Moriarty, Z.Z.N. Yiu, R.B. Warren
Journal: British Journal of Dermatology (2021)

There are few data on whether immunomodulator therapy attenuates humoral response to vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some vaccines require two doses for maximum protection, with international variation in dosing schedules. A 3 month interval between doses is being used in the U.K. We evaluated antibody titres to SARS-CoV-2 following initial-dose BNT162b2 (Pfizer/BioNTech) or AZD1222 (AstraZeneca) vaccines in adults with psoriasis and other immune-mediated inflammatory diseases (IMIDs) receiving biologic and/or oral non-biologic immunomodulators.
Preparing for the next pandemic
Authors: Clare Wenham, Matthew Kavanagh, Irene Torres, Gavin Yamey
Journal: BMJ (2021)

Make it the last pandemic," urges the report of the Independent Panel for Pandemic Preparedness and Response, convened by the World Health Organization to assess the handling of covid-19. 1 The report highlights how several governments and international organisations did too little to mitigate covid-19.It proposes a plan to end this pandemic-what it calls "the 21st century's Chernobyl moment"-and prevent another one.The panel makes six recommendations.Governments must urgently provide oxygen, diagnostics, and vaccines equitably worldwide to halt the spread of SARS-CoV-2.All nations must strengthen their capacity to prevent, detect, and respond to pandemics.A high level global council on health threats should be established for political attention and allocation of pandemic funds.Countries should adopt a new, legally binding pandemic treaty.A global platform should be built for equitable development and distribution of drugs, vaccines, and medical supplies.And WHO should get more power and money.
Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial
Authors: Evan Y Yu, Daniel P Petrylak, Peter H O'Donnell, Jae-Lyun Lee, Michiel S van der Heijden, Yohann Loriot, Mark N Stein, Andrea Necchi, Takahiro Kojima, Michael R Harrison, Se Hoon Park, David I Quinn, Elisabeth I Heath, Jonathan E Rosenberg, Joyce Steinberg, Shang-Ying Liang, Janet Trowbridge, Mary Campbell, Bradley McGregor, Arjun V Balar
Journal: The Lancet Oncology (2021)
33P Epigenetic biomarkers ID1, HOXB2 and ATOH8 could predict response to chemotherapy and prognosis in early breast cancer
Authors: V. Quiroga Garcia, S. Moran, C. Queralt, S. Cabrero, A. Bernat, A. Ferrando Diez, L. Perez, B. Cirauqui Cirauqui, E. Felip, I. Teruel-Garcia, M. Romeo Marin, A. Pous, E. Castellà, A. Martinez-Cardús, M. Margeli
Journal: Annals of Oncology (2021)
Abstract 15135: Liver Fibrosis Scores Predict Cardiovascular Outcomes in Patients With Previous Myocardial Infarction
Authors: Yexuan Cao, Meng Zhang, Huiwen Zhang, Jinglu Jin, Hui-Hui Liu, Yan Zhang, Yuan-Lin Guo, Na-Qiong Wu, Cheng-Gang Zhu, Rui-Xia Xu, Qian Dong, Jian-jun Li
Journal: Circulation (2020)

Introduction: Liver fibrosis score (LFS) has been used for predicting the cardiovascular outcomes (CVOs) in diverse populations. However, the association of LFS with CVOs in patients with previous myocardial infarction (MI) remains undetermined. Hypothesis: The aim of the present study was to examine the prognostic value of LFS in patients with prior MI in a prospective cohort. Methods: A total of 3718 patients with previous MI were consecutively enrolled from March 2009 to January 2019. Five LFSs were used including the fibrosis-4 (FIB-4) score, non-alcohol fatty liver disease fibrosis score (NFS), Forns score, HUI score and BARD score in the current study. The CVOs covered major adverse cardiac event (MACE), hard endpoint, cardiovascular mortality and all-cause mortality. Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Results: During a mean follow-up of 47.4±24.8 months, 431 (11.6%) MACE occurred. Kaplan-Meier analysis demonstrated that higher LFSs resulted in a significantly higher probability of CVOs. Compared to the lowest score group, multivariable-adjusted HRs (95% CI) for the highest group of FIB-4, NFS, Forns score, HUI score and BARD score were 1.76 (1.33-2.34), 2.39 (1.71-3.34), 2.46 (1.62-3.74), 1.60 (1.18-2.17) and 1.28 (1.03-1.58), respectively. These LFSs were also independent predictors of hard endpoint, cardiovascular mortality and all-cause mortality. Similar results were observed across subgroups analysis. The addition of LFSs to a prediction model significantly increased the C-statistic for CVOs. Conclusions: The present study firstly demonstrated that LF scores might affect the prognosis in patients with previous MI, suggesting that LF scores may be helpful to further risk stratification and supporting LF scores screening in patients with previous MI.
Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk
Authors: Keenan A. Walker, Jingsha Chen, Jingning Zhang, Myriam Fornage, Yunju Yang, Linda Zhou, Morgan E. Grams, Adrienne Tin, Natalie Daya, Ron C. Hoogeveen, Aozhou Wu, Kevin J. Sullivan, Peter Ganz, Scott L. Zeger, Elias F. Gudmundsson, Valur Emilsson, Lenore J. Launer, Lori L. Jennings, Vilmundur Gudnason, Nilanjan Chatterjee, Rebecca F. Gottesman, Thomas H. Mosley, Eric Boerwinkle, Christie M. Ballantyne, Josef Coresh
Journal: Nature Aging (2021)
Abstract MP48: Racial And Urban-rural Disparities In The Frequency Of Ischemic Stroke As First Manifestation Of Atrial Fibrillation
Authors: Jingchuan Guo, Nico Gabriel, Jared W Magnani, Utibe Essien, Walid Gellad, Maria M Brooks, Ludovic Trinquart, Emelia J Benjamin, Inmaculada Hernandez
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) may be asymptomatic and remain undiagnosed until the development of complications, which precludes primary prevention efforts. We aimed to quantify racial and rural-urban disparities in the frequency of incident AF presenting with ischemic stroke in a nationally representative sample of Medicare beneficiaries. Hypothesis: Black patients have higher frequency of stroke as the first presentation with AF than White patients. Methods: We used a 5% random sample of Medicare claims data to identify patients newly diagnosed with AF in 2016. The primary outcome was stroke as first AF manifestation, and was defined by inpatient diagnosis of ischemic stroke within 7 days prior to the first AF diagnosis. We computed age- and sex-adjusted proportion of AF diagnosis manifesting as stroke and used multivariable logistic regression to quantify the association of race and urban/rural residence with the outcome, adjusting for demographic and clinical characteristics. Results: Among 39,437 patients newly diagnosed with AF, 2,821 (7.2%) had ischemic stroke as the first AF manifestation. In urban areas, age- and sex-adjusted proportions of AF diagnosis manifesting as stroke were 7.2(95%CI: 6.8,7.4)% for White and 9.5(8.4,10.8)% for Black, compared to 5.9(5.4,6.4)% and 8.1(5.8,11.1)% in rural areas ( Figure ). After adjusting for age, sex, CHA 2 DS 2 -VASc score, Alzheimer's disease, Medicaid enrollment, and receipt of low-income subsidy, Black race (adjusted OR [95%CI]: 1.21 [1.05, 1.40], vs. White) and urban residence (1.16 [1.06, 1.28], vs. rural) were associated with increased risk of stroke as first AF manifestation. Conclusion: We observed uneven distributions in the frequency of stroke as first manifestation of AF between White and Black patients and between rural and urban residents. Further research is needed to evaluate the effectiveness of AF screening efforts in reducing inequities in health outcomes associated with AF.
Abstract 16191: Association of Left Ventricular Mass Progression With Heart Failure Events: Implications for Understanding the Hispanic Paradox
Authors: Nestor Vasquez, Cecilia Castro-Diehl, Un Jung Lee, Gregory Burke, Alain G Bertoni, Lynne E Wagenknecht, Joao Ac Lima, David A Bluemke, Carlos J Rodriguez
Journal: Circulation (2020)

Introduction: Hispanics have been described as paradoxically having a higher prevalence of cardiovascular (CV) risk factors (RFs) but lower CV mortality compared to non-Hispanic Whites (NHW). The association of left ventricular mass (LVM) change with heart failure (HF) has not been well studied and variability across race-ethnic groups is unknown. Methods: MESA participants with LVM measurements by cardiac MRI at baseline and exam 5 (10-year interval) were included and followed for HF events after exam 5. LVM was calculated as the percentage of the predicted value based on height, weight and sex in a healthy population. LVM absolute (exam 5 - baseline) and relative change were compared across race-ethnic groups (Hispanics, non-Hispanic blacks [NHB], NHW, Chinese). HF RFs included hypertension, diabetes and obesity. The association between LVM change with incident HF events was evaluated using age-gender adjusted Cox proportional hazard models. Results: Among 2,981 participants (mean age 60 years, 53% female, 20% Hispanics, 42% NHW, 25% NHB, 13% Chinese) LVM at both exams was higher in NHB followed by Hispanics, whereas NHW and Chinese had the lowest LVM (Table) . Over 10-years, NHB had the highest LVM relative change (+4.4%) and Hispanics had the lowest (+1.7%). HF RFs were more prevalent in NHB and Hispanics compared to the other groups (p&lt;0.01). After a mean follow-up time from exam 5 of 6.4 years, an 18% increase in HF risk was seen per 5-unit increase in LVM in the total population. In race-ethnicity stratified analyses, this association was seen only in NHB (22% increase in HF risk per 5-unit LVM increase, p=0.01), and Hispanics (34% increase in HF risk per 5-unit LVM increase, p&lt;0.01). Conclusions: Hispanics and NHBs had a high burden of HF risk factors and higher baseline LVM relative to other groups. Hispanics paradoxically exhibited the lowest whereas NHB had the highest degree of LVM change over time, and yet both groups had similarly increased HF risk associated with LVM change.
GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness
Authors: Julie Agopian, Quentin Da Costa, Quang Vo Nguyen, Giulia Scorrano, Paraskevi Kousteridou, Min Yuan, Rabie Chelbi, Armelle Goubard, Remy Castellano, Julien Maurizio, Cristina Teodosio, Paulo De Sepulveda, John M. Asara, Alberto Orfao, Olivier Hermine, Patrice Dubreuil, Fabienne Brenet
Journal: Blood (2021)
Druggable epigenetic suppression of interferon-induced chemokine expression linked to <i>MYCN</i> amplification in neuroblastoma
Authors: Johanna A Seier, Julia Reinhardt, Kritika Saraf, Susanna S Ng, Julian P Layer, Dillon Corvino, Kristina Althoff, Frank A Giordano, Alexander Schramm, Matthias Fischer, Michael Hölzel
Journal: Journal for ImmunoTherapy of Cancer (2021)

Amplification of the
<i>TERT</i> promoter mutations and other prognostic factors in patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor
Authors: Ivan de Kouchkovsky, Li Zhang, Errol J Philip, Francis Wright, Daniel M Kim, Divya Natesan, Daniel Kwon, Hansen Ho, Son Ho, Emily Chan, Sima P Porten, Anthony C Wong, Arpita Desai, Franklin W Huang, Jonathan Chou, David Y Oh, Raj S Pruthi, Lawrence Fong, Eric J Small, Terence W Friedlander, Vadim S Koshkin
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI. Methods We undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors. Results We identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03). Conclusions The presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.