tbuckley/cabot-search huggingface dataset:
<i>QuickStats:</i> Age-Adjusted Percentage* of Adults Aged ≥18 Years Who Currently Have Asthma,† by Sex and Race/Ethnicity§ ─ National Health Interview Survey, United States, 2017–2018¶
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Department of Health and Human Services/Centers for Disease Control and Prevention * Age-adjusted percentages are based on the 2000 U.S. Census standard population, using age groups 18-44, 45-64, 65-74, and ≥75 years, with 95% confidence intervals indicated by error bars.† Adults who were ever told by a doctor or other health professional that they had asthma were asked "Do you still have asthma?"§ Categories shown for non-Hispanic respondents are only for those who selected one racial group; respondents had the option to select more than one racial group.Hispanic respondents might be of any race or combination of races.Only selected groups are shown in the individual race/ethnicity bars, but total bar shows results for all adults aged ≥18 years.¶ Estimates are based on household interviews of a sample of the civilian, noninstitutionalized U.S. population and are derived from the National Health Interview Survey Sample Adult component.
NSAID Use and Clinical Outcomes in COVID-19
Authors: M. Pan, T. Azam, H. Shadid, H. Berlin, C. Meloche, R. Feroze, J. Leya, P. O'Hayer, E. Anderson, R. Kaakati, A. Bitar, K. Padalia, D. Perry, P. Blakely, P. Y. Zhao, L. L. Zhao, S. Hayek
Journal: Circulation (2020)
Comparison of the Efficacy and Safety Outcomes of Edoxaban in 8040 Women Versus 13 065 Men With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial
Authors: Thomas A. Zelniker, Maddalena Ardissino, Felicita Andreotti, Michelle L. O’Donoghue, Ophelia Yin, Jeong-Gun Park, Sabina A. Murphy, Christian T. Ruff, Hans J. Lanz, Elliott M. Antman, Eugene Braunwald, Robert P. Giugliano, Piera Angelica Merlini
Journal: Circulation (2021)

Background: Female sex is an independent risk factor for stroke and systemic embolic events in patients with atrial fibrillation. This study aimed to examine the efficacy and safety profile of edoxaban in women versus men. Methods: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) randomly assigned 21 105 patients (8040 women) with atrial fibrillation and CHADS 2 score ≥2 either to a higher-dose edoxaban regimen, a lower-dose edoxaban regimen, or warfarin. The primary end points of the trial were the composite of stroke or systemic embolic events (efficacy), and International Society on Thrombosis and Haemostasis–defined major bleeding (safety). Results: In comparison with men, women were older, had lower body weight, were more likely to have hypertension and renal dysfunction, but less likely to smoke, drink alcohol, or have diabetes or coronary artery disease. Pretreatment endogenous factor Xa activity was significantly higher in women than in men (92.5% versus 86.1%, P &lt;0.001). Treatment with edoxaban in women resulted in greater peak edoxaban concentration and inhibition of endogenous factor Xa in comparison with men, resulting in similar endogenous factor Xa activity between the sexes 2 to 4 hours after dose. Treatment with higher-dose edoxaban regimen (versus warfarin) resulted in similar reduction in the risk of stroke/systemic embolic events (women: hazard ratio [HR], 0.87 [0.69–1.11], men: HR, 0.87 [0.71–1.06]; P -interaction=0.97) and major bleeding (women: HR, 0.74 [0.59–0.92], men: HR, 0.84 [0.72–0.99]; P -interaction=0.34) in women and men. However, women assigned to higher-dose edoxaban regimen experienced greater reductions in hemorrhagic stroke (HR, 0.30 [95% CI, 0.15–0.59] versus HR, 0.70 [95% CI, 0.46–1.06]), intracranial bleeding (HR, 0.20 [95% CI, 0.10–0.39] versus HR, 0.63 [95% CI, 0.44–0.89]), and life-threatening or fatal bleeding (HR, 0.25 [95% CI, 0.15–0.42] versus HR, 0.72 [95% CI, 0.54–0.96]) than men (each P -interaction&lt;0.05). Conclusions: Despite many differences in baseline characteristics between women and men and higher baseline endogenous factor Xa levels in women, the intensity of anticoagulation achieved with edoxaban between the sexes was similar. Treatment with higher-dose edoxaban regimen resulted in an even greater reduction in hemorrhagic stroke and several serious bleeding outcomes in women than in men, whereas the efficacy profile was similar between sexes.
Simultaneous Imaging of Lung Perfusion and Glucose Metabolism in COVID-19 Pneumonia
Authors: Celso Dario Ramos, Alins P. Fernandes, Stephan P. M. Souza, Mariana Fujiwara, Natalia Tobar, Sergio S. J. Dertkigil, Maria Emília S. Takahashi, Eduardo S. L. Gonçales, Plinio Trabasso, Denise E. Zantut-Wittmann
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
Abstract 19953: Interactions of MyD88 and TRIF-Pathways of Innate Immune Responses Regulate Angiotensin II Hypertension
Authors: Madhu V Singh, Michael Z Cicha, Mark W Chapleau, François M Abboud
Journal: Circulation (2015)

We have reported that angiotensin II (Ang II) induces toll-like receptors (TLRs) in the innate immune system. Here we tested which of the two major adaptor proteins of TLRs, the myeloid differentiation protein 88 (MyD88) or the TIR-domain containing adaptor inducing interferon β (TRIF) mediates the Ang II-induced responses. Infusion of Ang II (3000 ng/kg/min) subcutaneously for 3 weeks in WT mice (C57BL/6J) increased systolic blood pressure to a peak value of 147 ± 4 mm Hg and resulted in a 40% increase in heart weight to body weight ratio (HW/BW). Surprisingly, in MyD88-/- mice the pressor response was enhanced significantly to 163 ± 6 mm Hg (P&lt;0.05) and the HW/BW was increased by 60%. Cardiac and renal RNA expression of TNF-α, NOX4 and Type IA -Ang II receptor were also significantly more elevated in MyD88-/- than in WT. In contrast, in a mouse strain with nonfunctional TRIF gene, Trifmut (C57BL/6J-Ticam1Lps2/J), all the Ang II responses were either uniformly decreased or abrogated. We tested whether the enhanced response in MyD88-/- mice represented a phenomenon of ‘Signaling Flux Redistribution” whereby blockade of one signaling pathway (i.e., MyD88) results in a flux of signaling substrates through the alternative pathway (TRIF). We found that expression of the RNA for chemokine CXCL10 which is dependent on TRIF pathway, was significantly enhanced in MyD88-/- hearts. We also found that expression of transcripts for TLR3, TLR4 and the TRIF adaptor protein were all enhanced in MyD88-/- and must have contributed to the exaggerated Ang II response. Conversely, Trifmut had enhanced MyD88 expression. These results suggest that: (1) Ang II induced hypertension, hypertrophy and inflammatory gene expression are primarily mediated by the TRIF pathway and (2) the MyD88 pathway is simultaneously activated by Ang II and exerts a negative regulatory influence on the pressor and inflammatory responses. We conclude that dual activation of two innate immune pathways defines the net response in WT mice with a significant translational potential. Accordingly, impairment of MyD88 may contribute to pathogenesis of hypertension. Conversely, targeting the TRIF pathway may be therapeutic by blocking the inflammatory response and enhancing the negative regulatory effects of MyD88.
Structural studies of CXCR4, an antimetastatic target
Authors: John O. Trent, Zi-Xuan Wang, James L. Murray, Wenhai Shao, Hirokazu Tamamura, Nobutaka Fujii, Stephen C. Peiper
Journal: Cancer Research (2004)

1028  CXCR4 is a G protein coupled receptor (GPCR) that has multiple critical functions in normal and pathologic physiology that include regulation of the metastatic behavior of mammary carcinoma, and utilization as a coreceptor for infection by T-tropic strains of HIV-1. Molecular dynamics simulations of CXCR4 were performed in a solvated lipid bilayer to reproduce the microenvironment of this integral membrane protein. The structural basis for the interaction of T140 and AMD3100 with CXCR4 confirms that the mechanisms used by these agents are different. This complementary utilization of molecular, physical, and computation analysis provides a powerful approach to elucidate GPCR conformation and other membrane proteins.
Involving Patients in Their Own Health Care Choices—Altruism Begets Altruism
Authors: Ala Moshiri, Ata S. Moshiri
Journal: JAMA Network Open (2021)

Danyal Malik, BS; Xuan Cao, MD; Jaron Castillo Sanchez, BS; Tianshun Gao, PhD; Jiang Qian, PhD; Silvia Montaner, PhD, MPH; Akrit Sodhi, MD, PhD
Treatment of Patients With Anorexia Nervosa in the US—A Crisis in Care
Authors: Walter H. Kaye, Cynthia M. Bulik
Journal: JAMA Psychiatry (2021)

Anorexia Nervosa in the US-A Crisis in CareThe United States is facing a crisis in the treatment of anorexia nervosa (AN)-a debilitating, expensive, and frequently fatal illness.Annually, eating disorders cost the US more than $65 billion. 1 Despite scientific advances, treatments do not yet exist that target the core biology of AN.Moreover, the absence of standards of care has left a vacuum to be filled by programs offering untested interventions.Many academic medical center programs have dwindled or closed, functionally steering insured patients and families to private programs and limiting treatment access for the uninsured and underinsured.Herein, we describe the crisis and propose solutions.Anorexia nervosa frequently requires prolonged hospitalization for weight restoration and medical and psychiatric stabilization. 2 Relapse rates approach 50%, and the standardized mortality ratio is approximately 6, 3 rendering it one of the most lethal of psychiatric disorders.Although empirically supported treatments in youth, such as family-based treatment, have moderate success, recovery is often prolonged, and the evidence base for treatment in adults is weak. 4Approximately 20% of patients with AN develop a severe and protracted illness.No US Food and Drug Administrationapproved medications exist. 2 How the Crisis of Care Has Grown Few TreatmentsAs mentioned previously, evidence-based treatments for AN that are based on biology do not yet exist.Recent innovations in genetic and biobehavioral research elucidate neurobiological contributions to AN disease risk and chronicity but have yet to be translated into clinical interventions.In part, this lack of evidence-based treatment reflects gross underfunding of AN research relative to its disability-adjusted life-years.
Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis
Authors: Brandon Ginley, Kuang-Yu Jen, Seung Seok Han, Luís Rodrigues, Sanjay Jain, Agnes B. Fogo, Jonathan Zuckerman, Vighnesh Walavalkar, Jeffrey C. Miecznikowski, Yumeng Wen, Felicia Yen, Donghwan Yun, Kyung Chul Moon, Avi Rosenberg, Chirag Parikh, Pinaki Sarder
Journal: Journal of the American Society of Nephrology (2021)

Glomerulosclerosis, interstitial fibrosis, and tubular atrophy (IFTA) are histologic indicators of irrecoverable kidney injury. In standard clinical practice, the renal pathologist visually assesses, under the microscope, the percentage of sclerotic glomeruli and the percentage of renal cortical involvement by IFTA. Estimation of IFTA is a subjective process due to a varied spectrum and definition of morphological manifestations. Modern artificial intelligence and computer vision algorithms have the ability to reduce inter-observer variability through rigorous quantitation. In this work, we apply convolutional neural networks for the segmentation of glomerulosclerosis and IFTA in periodic acid-Schiff stained renal biopsies. The convolutional network approach achieves high performance in intra-institutional holdout data, and achieves moderate performance in inter-intuitional holdout data, which the network had never seen in training. The convolutional approach demonstrated interesting properties, such as learning to predict regions better than the provided ground truth as well as developing its own conceptualization of segmental sclerosis. Subsequent estimations of IFTA and glomerulosclerosis percentages showed high correlation with ground truth.
Abstract PS1-57: Mastectomy versus breast conserving surgery for the management of locally advanced breast cancer
Authors: Roochi Arora, Ghazaleh Kazemi, Graydon Lucas
Journal: Cancer Research (2021)

Abstract Background: Breast conserving surgery (BCS) has become increasingly employed as a surgical option for patients with locally advanced breast cancer (LABC). However, guidelines on selecting appropriate LABC patients for BCS remain vague. Methods: Our Local Integrated Health Network (LHIN) conducted a multidisciplinary conference, known as the LHIN4 day, during which consensus criteria on which LABC patients may be safely offered BCS were established. These criteria included: clinical T3 or smaller, clinical and/or radiographic response to neoadjuvant therapy, patient seen by radiation oncology and deemed a candidate for post-operative radiation, and surgeon confident that negative margins could be achieved. A retrospective chart review was then performed of patients treated with neoadjuvant systemic therapy for LABC in the one year before, and three years after the LHIN4 day, which was between June 2015 and June 2019. Objectives: The primary objective of this study was to determine the rates of local and distant breast cancer recurrence in LABC patients treated with BCS using our consensus guidelines. The secondary objectives were: (1) to determine if there was an increase in BCS being performed following the LHIN4 educational day as compared to before this day, (2) to determine the rates of mastectomy followed by reconstruction among the patients treated within the past 3 years, and (3) to determine the rates of pathologic complete response (PCR). Results: A total of 391 patients were included in this study. Among the 26 patients who underwent BCS, the rate of local recurrence was 0% (0/26), and the rate of distant recurrence was 12% (3/26). Rates of BCS were 1.9% (2/108) before the LHIN4 day, and 8.5% (24/283) after the LHIN4 day. Rates of mastectomy followed by reconstruction were 12% (21/181) in the last 3 years. PCR was achieved in 15% (58/391) of all patients, of which 57% (33/58) were Her2 positive and 24% (14/58) were triple negative. Conclusion: We propose specific criteria for appropriately selecting LABC patients for BCS. Our results indicate that these criteria can be feasibly applied with low rates of local and distant breast cancer recurrence. A minority of patients with LABC who do not undergo BCS, either due to ineligibility or personal preference, are opting for mastectomy with reconstruction. Citation Format: Roochi Arora, Ghazaleh Kazemi, Graydon Lucas. Mastectomy versus breast conserving surgery for the management of locally advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-57.
Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease
Authors: Peter Hermann, Brian Appleby, Jean-Philippe Brandel, Byron Caughey, Steven Collins, Michael D Geschwind, Alison Green, Stephane Haïk, Gabor G Kovacs, Anna Ladogana, Franc Llorens, Simon Mead, Noriyuki Nishida, Suvankar Pal, Piero Parchi, Maurizio Pocchiari, Katsuya Satoh, Gianluigi Zanusso, Inga Zerr
Journal: The Lancet Neurology (2021)
Feasibility of Embedding a Scalable, Virtually Enabled Biorepository in the Electronic Health Record for Precision Medicine
Authors: Kimberley M. DeMerle, Jason N. Kennedy, Octavia M. Peck Palmer, Emily Brant, Chung-Chou H. Chang, Robert P. Dickson, David T. Huang, Derek C. Angus, Christopher W. Seymour
Journal: JAMA Network Open (2021)

<h3>Importance</h3> A cornerstone of precision medicine is the identification and use of biomarkers that help subtype patients for targeted treatment. Such an approach requires the development and subsequent interrogation of large-scale biobanks linked to well-annotated clinical data. Traditional means of creating these data-linked biobanks are costly and lengthy, especially in acute conditions that require time-sensitive clinical data and biospecimens. <h3>Objectives</h3> To develop a virtually enabled biorepository and electronic health record (EHR)–embedded, scalable cohort for precision medicine (VESPRE) and compare the feasibility, enrollment, and costs of VESPRE with those of a traditional study design in acute care. <h3>Design, Setting, and Participants</h3> In a prospective cohort study, the EHR-embedded screening alert was generated for 3428 patients, and 2199 patients (64%) were eligible and screened. Of these, 1027 patients (30%) were enrolled. VESPRE was developed for regulatory compliance, feasibility, internal validity, and cost in a prospective cohort of 1027 patients (aged ≥18 years) with sepsis-3 within 6 hours of presentation to the emergency department. The VESPRE infrastructure included (1) automated EHR screening, (2) remnant blood collection for creation of a virtually enabled biorepository, and (3) automated clinical data abstraction. The study was conducted at an academic institution in southwestern Pennsylvania from October 17, 2017, to June 6, 2019. <h3>Main Outcomes and Measures</h3> Regulatory compliance, enrollment, internal validity of automated screening, biorepository acquisition, and costs. <h3>Results</h3> Of the 1027 patients enrolled in the study, 549 were included in the proof-of-concept analysis (305 [56%] men); median (SD) age was 59 (17) years. VESPRE collected 12 963 remnant blood and urine samples and demonstrated adequate feasibility for clinical, biomarker, and microbiome analyses. Over the 20-month test, the total cost beyond the existing operations infrastructure was $39 417.50 ($14 880.00 project management, $22 717.50 laboratory supplies/staff, and $1820.00 data management)—approximately $39 per enrolled patient vs $239 per patient for a traditional cohort study. <h3>Conclusions and Relevance</h3> Results of this study suggest that, in a large US health system that collects data using a common EHR platform and centralized laboratory system, VESPRE, a large-scale, inexpensive EHR-embedded infrastructure for precision medicine can be used. Tested in the sepsis setting, VESPRE appeared to capture a high proportion of eligible patients at low incremental cost.
Effect of Early Palliative Care on Quality of Life of Advanced Head and Neck Cancer Patients: A Phase III Trial
Authors: Vijay Maruti Patil, Pankaj Singhai, Vanita Noronha, Atanu Bhattacharjee, Jayita Deodhar, Naveen Salins, Amit Joshi, Nandini Sharrel Menon, Anuja Abhyankar, Ashwini Khake, Sachin Babanrao Dhumal, Rupali Tambe, Mary Ann Muckaden, Kumar Prabhash
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Early palliative care (EPC) is an important aspect of cancer management but, to our knowledge, has never been evaluated in patients with head and neck cancer. Hence, we performed this study to determine whether the addition of EPC to standard therapy leads to an improvement in the quality of life (QOL), decrease in symptom burden, and improvement in overall survival. Methods Adult patients with squamous cell carcinoma of the head and neck region planned for palliative systemic therapy were allocated 1:1 to either standard systemic therapy without or with comprehensive EPC service referral. Patients were administered the revised Edmonton Symptom Assessment Scale and the Functional Assessment of Cancer Therapy for head and neck cancer (FACT-H&amp;N) questionnaire at baseline and every 1 month thereafter for 3 months. The primary endpoint was a change in the QOL measured at 3 months after random assignment. All statistical tests were 2-sided. Results Ninety patients were randomly assigned to each arm. There was no statistical difference in the change in the FACT-H&amp;N total score (P = .94), FACT-H&amp;N Trial Outcome Index (P = .95), FACT-general total (P = .84), and Edmonton Symptom Assessment Scale scores at 3 months between the 2 arms. The median overall survival was similar between the 2 arms (hazard ratio for death = 1.01, 95% confidence interval = 0.74 to 1.35). There were 5 in-hospital deaths in both arms (5.6% for both, P = .99). Conclusions In this phase III study, the integration of EPC in head and neck cancer patients did not lead to an improvement in the QOL or survival.
Individualized elective irradiation of the clinically node‐negative neck in definitive radiotherapy for head and neck squamous cell carcinoma
Authors: Jia Kou, Li Lin, Cheng‐Yang Jiao, Meng‐Qiu Tian, Guan‐Qun Zhou, Xue Jiang, Jun Ma, Zhen‐Yu Qi, Yao Lu, Ying Sun
Journal: Cancer Communications (2021)

Abstract Background Oral cavity (OC), oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (LA) squamous cell carcinoma (SCC) have a high incidence of regional lymph node metastasis (LNM). Elective irradiation for clinically node‐negative neck is routinely administered to treat lymph nodes harboring occult metastasis. However, the optimal elective irradiation schemes are still inconclusive. In this study, we aimed to establish individualized elective irradiation schemes for the ipsilateral and contralateral node‐negative neck of these four types of cancer. Methods From July 2005 to December 2018, 793 patients with OC‐SCC, 464 with OP‐SCC, 413 with HP‐SCC, and 645 with LA‐SCC were recruited retrospectively. Based on the actual incidence of LNM and the tumor characteristics, risk factors for contralateral LNM, as well as node level coverage schemes for elective irradiation, were determined using logistic regression analysis. Additionally, we developed a publicly available online tool to facilitate the widespread clinical use of these schemes. Results For the ipsilateral node‐negative neck, elective irradiation at levels I‐III for OC‐SCC and levels II‐IVa for OP‐, HP‐ and LA‐SCC are generally recommended. In addition, level VIIa should be included in patients with OP‐SCC. Multivariate analyses revealed that posterior hypopharyngeal wall and post‐cricoid region involvement were independently associated with level VIIa metastasis in HP‐SCC (all P &lt; 0.05). For the contralateral node‐negative neck, multivariate analyses revealed that ipsilateral N2b2‐N3, tumors with body midline involvement, and degree of tumor invasion were the independent factors for contralateral LNM (all P &lt; 0.05). In patients who require contralateral neck irradiation, levels I‐II are recommended for OC‐SCC, and additional level III is recommended for patients with ipsilateral N3 disease. Levels II‐III are recommended for OP‐, HP‐, and LA‐SCC, and additional level IVa is recommended for patients with advanced T or ipsilateral N classifications. Furthermore, additional level VIIa is recommended only for OP‐SCC with T4 and ipsilateral N3 disease. Conclusion Based on our findings, we suggest that individualized and computer‐aided elective irradiation schemes could reduce irradiation volumes in OC‐, OP‐ and HP‐SCC patients, as compared to current guidelines, and could thus positively impact the patients' quality of life after radiotherapy.