tbuckley/cabot-search huggingface dataset:
Minimally Invasive Surfactant Therapy vs Sham Treatment and Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome
Authors: Abdul Razak
Journal: JAMA (2022)

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Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses
Authors: Ramachandran Thiruvengadam, Amit Awasthi, Guruprasad Medigeshi, Sankar Bhattacharya, Shailendra Mani, Sridhar Sivasubbu, Tripti Shrivastava, Sweety Samal, Deepika Rathna Murugesan, Bapu Koundinya Desiraju, Pallavi Kshetrapal, Rajesh Pandey, Vinod Scaria, Praveen Kumar Malik, Juhi Taneja, Akshay Binayke, Tarini Vohra, Aymaan Zaheer, Deepak Rathore, Naseem Ahmad Khan, Heena Shaman, Shubbir Ahmed, Rajesh Kumar, Suprit Deshpande, Chandru Subramani, Nitya Wadhwa, Nimesh Gupta, Anil K Pandey, Jayanta Bhattacharya, Anurag Agrawal, Sudhanshu Vrati, Shinjini Bhatnagar, Pramod Kumar Garg
Journal: The Lancet Infectious Diseases (2021)

SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination.
Authors’ Reply
Authors: James B. Wetmore, Kirsten L. Johansen, Eric D. Weinhandl
Journal: Journal of the American Society of Nephrology (2022)

We thank Jacobs et al . for their interest in our recent report,[1][1] which concerned treatment changes in patients with incident ESKD during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in the United States. In their letter, Jacobs et al. report an 8% decrease in the number
Abstract P109: Association Of The 2017 ACC/AHA Blood Pressure Guideline With Blood Pressure Change In Community-dwelling Older Adults Between 2016-2019: A Difference-in-differences Analysis In The ARIC Study
Authors: Michael C Wang, Lucia Petito, Lindsay Pool, Kathryn Foti, Stephen P Juraschek, John William McEvoy, Vijay Nambi, Mercedes R Carnethon, Erin D Michos, Sadiya Khan
Journal: Circulation (2022)

Introduction: In 2017, the ACC/AHA revised the blood pressure (BP) guideline to lower the BP threshold for diagnosing and treating hypertension in older adults. Pharmacologic treatment is recommended for systolic BP (SBP) ≥130 mmHg in all older adults aged ≥65 years. Data on BP changes before and after publication of the guideline are needed to inform quality of care initiatives. Methods: We included participants from the Atherosclerosis Risk in Communities Study who attended a pre-guideline (2016-2017) and post-guideline (2018-2019) visit with a pre-guideline SBP between 120-159 mm Hg. We categorized participants based on their pre-guideline SBP according to the 2017 guideline: not reclassified to treatment (SBP 120-129), reclassified to stage 1 hypertension (SBP 130-139), or reclassified to stage 2 hypertension (SBP 140-159). To estimate the association of the 2017 guideline with SBP change, we performed a quasi-experimental analysis using difference-in-differences (DiD) regression. We compared changes in SBP between participants affected (SBP 130-139, 140-159) and those not affected (SBP 120-129) by the new SBP target, adjusted for traditional risk factors. Results: Of 2195 participants aged 71-94 years, mean (SD) SBP was 137.2 (10.8) mm Hg, and 77% were on antihypertensive therapy at the pre-guideline visit. Among participants with SBP ≥130 pre-guideline, 31% were at goal SBP &lt;130 post-guideline. In adjusted DiD analyses, participants with SBP ≥130 pre-guideline had significantly lower mean SBP at the post-guideline visit (Stage 1 hypertension: -5.0 [95% CI: -6.7, -3.3]; Stage 2 hypertension: -9.7 [-11.3, -8.0]) compared with participants with SBP 120-129 pre-guideline ( Table ). Results were similar when stratified by sex and race. Conclusions: In a sample of community-based older adults, the post-guideline period was associated with significantly lower SBP in those reclassified to Stage 1 or Stage 2 hypertension. However, significant gaps exist in BP control and only a minority met the updated treatment goal.
Abstract P083: Predicting Dementia In Heart Failure And Atrial Fibrillation
Authors: Sheila M Manemann, Alanna M Chamberlain, Suzette Bielinski, Ruoxiang Jiang, Susan Weston, Veronique L Roger
Journal: Circulation (2022)

Introduction: The Framingham Heart Study Dementia Risk Score (FDRS) was developed in a general population of elderly individuals. It is unknown how the FDRS variables predict dementia in heart failure (HF) and atrial fibrillation (AF) populations. Thus, we aimed to evaluate the predictive ability of the FDRS variables in population-based cohorts of individuals with HF and AF and to determine whether the addition of other comorbidities and risk factors improves risk prediction for dementia. Methods: Residents aged ≥50 from 7 southeast MN counties with a first diagnosis of HF (ICD-9 428/ICD-10 I50) or AF (ICD-9 427.3/ICD-10 I48 with AF on electrocardiogram/Holter monitor) between 1/1/2013 and 12/31/2017 were identified. Patients with dementia (defined by ICD codes) prior to or within 6 months after their index event and patients who died within 6 months after index were excluded. For both cohorts, models were constructed to predict dementia ≥ 6 months post index including the variables in the FDRS (age, marital status, BMI, stroke/TIA, diabetes and cancer). Additional comorbidities and risk factors were added to the models. For all models c-statistics were calculated. Results: Among 3,291 patients with HF (mean age 76 years, 53% male), 626 cases of dementia occurred and among 4,107 patients with AF (mean age 74 years, 57% male), 736 cases of dementia occurred. Among patients with HF, the FDRS variables predicted dementia with a c-statistic of 0.68 (Table). Adding additonal comorbidities and risk factors impoved the c-statistic slightly to 0.69 (p=0.01). Among patients with AF, the FDRS variables also performed well (c-stastic: 0.73; Table) and adding other comorbidities and risk factors improved the performance (c-statistic: 0.75; p&lt;0.01). Conclusions: The variables from the FDRS predict dementia well in both HF and AF populations. The addition of comorbidities and other CVD risk factors only modestly improved prediction, thus indicating that the FDRS variables are appropriate to predict dementia in patients with HF and AF.
Pericoronary Adipose Tissue Attenuation, Low-Attenuation Plaque Burden, and 5-Year Risk of Myocardial Infarction
Authors: Evangelos Tzolos, Michelle C Williams, Priscilla McElhinney, Andrew Lin, Kajetan Grodecki, Guadalupe Flores Tomasino, Sebastien Cadet, Jacek Kwiecinski, Mhairi Doris, Philip D Adamson, Alastair J Moss, Shirjel Alam, Amanda Hunter, Anoop S V Shah, Nicholas L Mills, Tania Pawade, Chengjia Wang, Jonathan R Weir-McCall, Giles Roditi, Edwin J R van Beek, Leslee J Shaw, Edward D Nicol, Daniel S Berman, Piotr J Slomka, Marc R Dweck, David E Newby, Damini Dey
Journal: JACC. Cardiovascular imaging (2022)
geneBasis: an iterative approach for unsupervised selection of targeted gene panels from scRNA-seq
Authors: Alsu Missarova, Jaison Jain, Andrew Butler, Shila Ghazanfar, Tim Stuart, Maigan Brusko, Clive Wasserfall, Harry Nick, Todd Brusko, Mark Atkinson, Rahul Satija, John C. Marioni
Journal: Genome biology (2021)

scRNA-seq datasets are increasingly used to identify gene panels that can be probed using alternative technologies, such as spatial transcriptomics, where choosing the best subset of genes is vital. Existing methods are limited by a reliance on pre-existing cell type labels or by difficulties in identifying markers of rare cells. We introduce an iterative approach, geneBasis, for selecting an optimal gene panel, where each newly added gene captures the maximum distance between the true manifold and the manifold constructed using the currently selected gene panel. Our approach outperforms existing strategies and can resolve cell types and subtle cell state differences.
Assay design for unambiguous identification and quantification of circulating pathogen-derived peptide biomarkers
Authors: Qingbo Shu, Shan Liu, Tonino Alonzi, Sylvia M. LaCourse, Dhiraj Kumar Singh, Duran Bao, Dalton Wamalwa, Li Jiang, Christopher J. Lyon, Grace John-Stewart, Deepak Kaushal, Delia Goletti, Tony Hu
Journal: Theranostics (2022)

Rationale: Circulating pathogen-derived proteins can serve as useful biomarkers for infections but may be detected with poor sensitivity and specificity by standard immunoassays due to masking effects and cross-reactivity. Mass spectrometry (MS)-read immunoassays for biomarker-derived peptides can resolve these issues, but lack standard workflows to select species-specific peptides with strong MS signal that are suitable for antibody generation. Methods:Using a Mycobacterium tuberculosis (Mtb) protein as an example, candidate peptides were selected by length, species-specificity, MS intensity, and antigenicity score. MS data from spiked healthy serum was employed to define MS feature thresholds, including a novel measure of internal MS data correlation, to produce a peak detection algorithm. Results: This algorithm performed better in rejecting false positive signal than each of its criteria, including those currently employed for this purpose. Analysis of an Mtb peptide biomarker (CFP-10pep) by this approach identified tuberculosis cases not detected by microbiologic assays, including extrapulmonary tuberculosis and tuberculosis cases in children infected with HIV-1. Circulating CFP-10pep levels measured in a non-human primate model of tuberculosis distinguished disease from asymptomatic infection and tended to correspond with Mtb granuloma size, suggesting that it could also serve as a surrogate marker for Mtb burden and possibly treatment response. Conclusions: These biomarker selection and analysis approach appears to have strong potential utility for infectious disease diagnosis, including cryptic infections, and possibly to monitor changes in Mtb burden that may reflect disease progression or a response to treatment, which are critical needs for more effective disease control.
Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer
Authors: Mihir Rajurkar, Aparna R. Parikh, Alexander Solovyov, Eunae You, Anupriya S. Kulkarni, Chong Chu, Katherine H. Xu, Christopher Jaicks, Martin S. Taylor, Connie Wu, Katherine A. Alexander, Charly R. Good, Annamaria Szabolcs, Stefanie Gerstberger, Antuan V. Tran, Nova Xu, Richard Y. Ebright, Emily E. Van Seventer, Kevin D. Vo, Eric C. Tai, Chenyue Lu, Jasmin Joseph-Chazan, Michael J. Raabe, Linda T. Nieman, Niyati Desai, Kshitij S. Arora, Matteo Ligorio, Vishal Thapar, Limor Cohen, Padric M. Garden, Yasmeen Senussi, Hui Zheng, Jill N. Allen, Lawrence S. Blaszkowsky, Jeffrey W. Clark, Lipika Goyal, Jennifer Y. Wo, David P. Ryan, Ryan B. Corcoran, Vikram Deshpande, Miguel N. Rivera, Martin J. Aryee, Theodore S. Hong, Shelley L. Berger, David R. Walt, Kathleen H. Burns, Peter J. Park, Benjamin D. Greenbaum, David T. Ting
Journal: Cancer Discovery (2022)

Abstract Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements. Significance: Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy. This article is highlighted in the In This Issue feature, p. 1397
Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Hanny Al-Samkari, Jaroslaw Kolb-Sielecki, Sufiia Z Safina, Xiaoqiang Xue, Brian D Jamieson
Journal: The Lancet Haematology (2022)
Unusual Illustration of Richter Transformation in Chronic Lymphocytic Leukemia on FDG PET/CT
Authors: Yiyan Liu
Journal: Clinical Nuclear Medicine (2022)

A man with history of chronic lymphocytic leukemia (CLL) in remission had multiple rapidly growing lumps in recent 2 months. FDG PET/CT demonstrated disseminated FDG-avid nodal and extranodal lesions including those in unusual locations such as the nasopharynx, salivary glands, lungs, gastric wall, peritoneum, bones, and muscles. Subsequent biopsy of the right axillary mass showed absolute lymphocytosis with focus of large B-cell lymphoma. Flow cytometric immunophenotyping demonstrated κ-restricted CLL and B-cell lymphoma, consistent with Richter transformation of CLL. FDG PET/CT images of this case illustrated the most severe and most disseminated nodal and extranodal involvements of Richter transformation in CLL.
Asthma Phenotypes and COVID-19 Risk: A Population-based Observational Study
Authors: Chloe I. Bloom, Paul Cullinan, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Studies have suggested some patients with asthma are at risk of severe coronavirus disease (COVID-19), but they have had limited data on asthma phenotype and have not considered if risks are specific to COVID-19. Objectives: To determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalization rates with influenza and pneumonia. Methods: Electronic medical records were used to identify patients with asthma and match them to the general population. Patient-level data were linked to Public Health England severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type 2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression. Measurements and Main Results: A total of 434,348 patients with asthma and 748,327 matched patients were included. All patients with asthma had a significantly increased risk of a General Practice diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01-1.61), intermittent ICS plus add-on asthma medication use (HR, 2.00; 95% CI, 1.43-2.79), regular ICS plus add-on use (HR, 1.63; 95% CI, 1.37-1.94), or with frequent exacerbations (HR, 1.82; 95% CI, 1.34-2.47) was significantly associated with hospitalization. These phenotypes were significantly associated with influenza and pneumonia hospitalizations. Only patients with regular ICS plus add-on asthma therapy (HR, 1.70; 95% CI, 1.27-2.26) or frequent exacerbations (HR, 1.66; 95% CI, 1.03-2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes. Conclusions: More severe asthma was associated with more severe COVID-19 outcomes, but type 2 inflammation was not. The risk of COVID-19 hospitalization appeared to be similar to the risk with influenza or pneumonia.
Abstract P056: Quality Assessment Of Consumer-facing Sodium Reduction Websites
Authors: Tasfia Hussain, Taha Ahmedna, Matti Marklund, Lawrence J Appel, Megan Henry
Journal: Circulation (2022)

Objective: To evaluate the quality of information and guidance on dietary sodium reduction available on consumer-facing websites. Methods: Google Trends was used to identify the five most used search terms related to sodium reduction. For each term, the top 20 websites were collected. Of 93 unique websites, 69 met inclusion criteria. Each website was evaluated using 14 questions in three categories ("information", "guidance", “accuracy”). For each question, the website was scored using a 3-step scale (“none”, “somewhat”, “adequate”). Results: Overall, only three of 14 questions were addressed adequately by a majority of websites (Figure). Many provided information on adverse health effects of a high sodium diet (74%, n=51) or mentioned intake recommendations (64%, n=44). Information on dietary sources of sodium and potassium or the difference between salt and sodium was largely missing. Most websites (80%, n=55) provided information on lifestyle strategies to reduce blood pressure, but a majority did not provide guidance for purchasing or preparing food with less sodium. Misinformation was uncommon. Conclusion: Consumers seeking information and guidance online will find most websites offer accurate but limited information, and insufficient guidance on how to lower sodium intake. Practical tools and relevant skills should be included for effective sodium reduction. Figure. Quality of guidance and information of identified websites (n=69) to help consumers lower sodium intake. Google trends was used to identify five frequently used search terms regarding sodium reduction. The 14 questions applied to each website were designed to evaluate the presence and quality of information and guidance for dietary sodium reduction. For each question, the information, guidance, or accuracy of the website was scored as “none”, “somewhat”, or “adequate”. Two researchers (TH and TA) independently assessed each question for each website, and disagreements were resolved by consensus or by consulting a third investigator (MEH).
Abstract 070: Area Deprivation Index Is Associated With Oral Anticoagulation Provision In Incident Atrial Fibrillation
Authors: Toluwa D Omole, William Garrard, Suresh R Mulukutla, Floyd W Thoma, Jianhui Zhu, Jared W Magnani
Journal: Circulation (2022)

Introduction: Oral anticoagulation (OAC) is a standard of care for stroke prevention in individuals with atrial fibrillation (AF). Social determinants of health have had limited investigation in AF and particularly in relation to OAC. We examined the effect of area deprivation index (ADI) on OAC prescription and agent selection (warfarin or direct-acting OAC). Hypotheses: (1) Individuals with AF living in neighborhoods with higher ADI (i.e., higher deprivation), are less likely to receive OAC for stroke prevention than those living in neighborhoods with lower ADI. (2) Among those prescribed OAC, those living in neighborhoods with higher ADI are more likely to receive warfarin as opposed to direct OAC. Methods: We conducted a retrospective analysis of patients with incident, non-valvular AF from 2015-2020 receiving care at a large, regional health center. We extracted demographics, medications, and problem lists and used administrative coding to identify comorbid conditions and relevant covariates, and the Zip+4 to ascertain ADI. We examined the relation between ADI and OAC prescription and selection at 90 days following the AF diagnosis in multivariable-adjusted models. Results: Following exclusions, the dataset included 20,210 individuals (age 74.5±10.9 years; 51% (10,270 of 20,210) women; 94% (19,053 of 20,210) white race. Individuals in the highest quartile of ADI were 13% less likely to receive OAC than those in the lowest quartile (adjusted Odds Ratio [OR] 0.87; 95% Confidence Interval [CI], 0.77-0.98) at 90 days following AF diagnosis. In those receiving OAC, individuals in the highest quartile of ADI were 21% less likely to receive a more modern direct-acting OAC as opposed to warfarin compared to those in the lowest quartile (aOR 0.79; 95% CI, 0.63-0.99) at 90 days following AF diagnosis. Conclusions: We demonstrate the association of ADI with (1) access to OAC for stroke prevention in AF and (2) likelihood of treatment with a more contemporary direct-acting OAC (rather than warfarin). Our results suggest health inequities in the provision of anticoagulation for stroke prevention in AF in a large, regional health care system.
Combustible and Electronic Cigarette Exposures Increase ACE2 Activity and SARS-CoV-2 Spike Binding
Authors: Arunava Ghosh, Vishruth Girish, Monet Lou Yuan, Raymond D. Coakley, Joe A. Wrennall, Neil E. Alexis, Erin L. Sausville, Anand Vasudevan, Alexander R. Chait, Jason M. Sheltzer, Robert Tarran
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

The outbreak of coronavirus disease (COVID-19) has extensively impacted global health.The spike protein on the surface of the causative pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a metallocarboxypeptidase, which is expressed in both mACE2 (membrane-anchored ACE2) and sACE2 (soluble ACE2) forms in the lung.Although mACE2 is responsible for viral