tbuckley/cabot-search huggingface dataset:
Histone deacetylase 6–mediated selective autophagy regulates COPD-associated cilia dysfunction
Authors: Hilaire C. Lam, Suzanne M. Cloonan, Abhiram R. Bhashyam, Jeffery A. Haspel, Anju Singh, J. Fah Sathirapongsasuti, Morgan Cervo, Hongwei Yao, Anna L. Chung, Kenji Mizumura, Chang Hyeok An, Bin Shan, Jonathan M. Franks, Kathleen J. Haley, Caroline A. Owen, Yohannes Tesfaigzi, George R. Washko, John Quackenbush, Edwin K. Silverman, Irfan Rahman, Hong Pyo Kim, Ashfaq Mahmood, Shyam S. Biswal, Stefan W. Ryter, Augustine M.K. Choi
Journal: Journal of Clinical Investigation (2020)

During the preparation of this manuscript, two panels of Figure 9B were inadvertently duplicated, resulting in an incorrect image
Abstract 15843: Increased Early Waitlist Mortality Among Infants With Pulmonary Atresia/Intact Ventricular Septum Listed for Cardiac Transplantation: A Multi-Institutional Study
Authors: Anna Joong, Elizabeth Pruitt, Warren A Zuckerman, James W Blackston, Rebecca K Ameduri, Juan C Alejos, Gerard J Boyle, Amy C Rothkopf, James K Kirklin, Robert J Garjarski
Journal: Circulation (2017)

Introduction: Management of infants having Pulmonary Atresia/Intact Ventricular Septum (PAIVS) with coronary anomalies is variable; some undergo single ventricle (SV) palliation (mortality 19-50%),...
Abstract 16794: Induction of miR-302a by Rapamycin Protects Human Pluripotent Stem Cells Derived Cardiomyocytes Against Simulated Ischemia/Reoxygenation Injury Under Hyperglycemic Condition
Authors: Arun Samidurai, Sean K Roh, Rakesh C Kukreja, Anindita Das
Journal: Circulation (2017)

Background: Diabetes is a major risk factor for myocardial infarction (MI). We have previously reported that mTOR inhibition with rapamycin (Rapa) protects diabetic rabbit heart against myocardial ...
Monocyte Regulation in Homeostasis and Malignancy
Authors: Amy Robinson, Claudia Z. Han, Christopher K. Glass, Jeffrey W. Pollard
Journal: Trends in Immunology (2021)

Monocytes are progenitors to macrophages and a subclass of dendritic cells (monocyte-derived dendritic cells, MoDCs), but they also act as circulating sensors that respond to environmental changes and disease. Technological advances have defined the production of classical monocytes in the bone marrow through the identification of lineage-determining transcription factors (LDTFs) and have proposed alternative routes of differentiation. Monocytes released into the circulation can be recruited to tissues by specific chemoattractants where they respond to sequential niche-specific signals that determine their differentiation into terminal effector cells. New aspects of monocyte biology in the circulation are being revealed, exemplified by the influence of cancer on the systemic alteration of monocyte subset abundance and transcriptional profiles. These changes can act to enhance the metastatic spread of primary cancers and may offer therapeutic opportunities.
Social determinants of mortality from COVID-19: A simulation study using NHANES
Authors: Benjamin Seligman, Maddalena Ferranna, David E. Bloom
Journal: PLoS Medicine (2021)

Background The COVID-19 epidemic in the United States is widespread, with more than 200,000 deaths reported as of September 23, 2020. While ecological studies show higher burdens of COVID-19 mortality in areas with higher rates of poverty, little is known about social determinants of COVID-19 mortality at the individual level. Methods and findings We estimated the proportions of COVID-19 deaths by age, sex, race/ethnicity, and comorbid conditions using their reported univariate proportions among COVID-19 deaths and correlations among these variables in the general population from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). We used these proportions to randomly sample individuals from NHANES. We analyzed the distributions of COVID-19 deaths by race/ethnicity, income, education level, and veteran status. We analyzed the association of these characteristics with mortality by logistic regression. Summary demographics of deaths include mean age 71.6 years, 45.9% female, and 45.1% non-Hispanic white. We found that disproportionate deaths occurred among individuals with nonwhite race/ethnicity (54.8% of deaths, 95% CI 49.0%–59.6%, p &lt; 0.001), individuals with income below the median (67.5%, 95% CI 63.4%–71.5%, p &lt; 0.001), individuals with less than a high school level of education (25.6%, 95% CI 23.4% –27.9%, p &lt; 0.001), and veterans (19.5%, 95% CI 15.8%–23.4%, p &lt; 0.001). Except for veteran status, these characteristics are significantly associated with COVID-19 mortality in multiple logistic regression. Limitations include the lack of institutionalized people in the sample (e.g., nursing home residents and incarcerated persons), the need to use comorbidity data collected from outside the US, and the assumption of the same correlations among variables for the noninstitutionalized population and COVID-19 decedents. Conclusions Substantial inequalities in COVID-19 mortality are likely, with disproportionate burdens falling on those who are of racial/ethnic minorities, are poor, have less education, and are veterans. Healthcare systems must ensure adequate access to these groups. Public health measures should specifically reach these groups, and data on social determinants should be systematically collected from people with COVID-19.
Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and Their Delivery Strategies
Authors: Calvin Chang, Jerry Yan, Zhicheng Yao, Chi Zhang, Xiaowei Li, Hai‐Quan Mao
Journal: Advanced Healthcare Materials (2021)

Abstract Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes modulation of inflammation response, macrophage polarization toward proregenerative lineage, promotion of angiogenesis, and reduction in fibrosis. This review focuses on profiling the effects of paracrine signals of MSCs, commonly referred to as the secretome, and highlighting the various engineering approaches to tune the MSC secretome. Recent advances in biomaterials‐based therapeutic strategies for delivery of MSCs and MSC‐derived secretome in the form of extracellular vesicles are discussed, along with their advantages and challenges.
Rapid Implementation of Model-Based Dosing Recommendations During the Coronavirus Disease 2019 Pandemic
Authors: Saskia N. de Wildt, Laurens F. M. Verscheijden, Tjitske M. van der Zanden
Journal: JAMA Pediatrics (2021)

Anil R. Maharaj, PhD; Huali Wu, PhD; Christoph P. Hornik, MD, PhD, MPH; Stephen J. Balevic, MD; Chi D. Hornik, PharmD; P. Brian Smith, MD; Daniel Gonzalez, PharmD, PhD; Kanecia O. Zimmerman, MD; Daniel K. Benjamin Jr, MD, PhD, MPH; Michael Cohen-Wolkowiez, MD, PhD; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee
Trailblazing perspectives on targeting breast cancer stem cells
Authors: Juntao Li, Dan Qi, Tze-Chen Hsieh, Jason H. Huang, Joseph M. Wu, Erxi Wu
Journal: Pharmacology & Therapeutics (2021)

Breast cancer (BCa) is one of the most prevalent malignant tumors affecting women's health worldwide. The recurrence and metastasis of BCa have made it a long-standing challenge to achieve remission-persistent or disease-undetectable clinical outcomes. Cancer stem cells (CSCs) possess the ability to self-renew and generate heterogeneous tumor bulk. The existence of CSCs has been found to be vital in the initiation, metastasis, therapy resistance, and recurrence of tumors across cancer types. Because CSCs grow slowly in their dormant state, they are insensitive to conventional chemotherapies; however, when CSCs emerge from their dormant state and become clinically evident, they usually acquire genetic traits that make them resistant to existing therapies. Moreover, CSCs also show evidence of acquired drug resistance in synchrony with tumor relapses. The concept of CSCs provides a new treatment strategy for BCa. In this review, we highlight the recent advances in research on breast CSCs and their association with epithelial-mesenchymal transition (EMT), circulating tumor cells (CTCs), plasticity of tumor cells, tumor microenvironment (TME), T-cell modulatory protein PD-L1, and non-coding RNAs. On the basis that CSCs are associated with multiple dysregulated biological processes, we envisage that increased understanding of disease sub-classification, selected combination of conventional treatment, molecular aberration directed therapy, immunotherapy, and CSC targeting/sensitizing strategy might improve the treatment outcome of patients with advanced BCa. We also discuss novel perspectives on new drugs and therapeutics purposing the potent and selective expunging of CSCs.
External validation of INCREMENT-CPE score in a retrospective cohort of carbapenemase-producing Klebsiella pneumoniae bloodstream infections in critically ill patients
Authors: Matthaios Papadimitriou-Olivgeris, Christina Bartzavali, Alexandra Georgakopoulou, Fevronia Kolonitsiou, Virginia Mplani, Iris Spiliopoulou, Myrto Christofidou, Fotini Fligou, Markos Marangos
Journal: Clinical Microbiology and Infection (2021)
Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2
Authors: Dongliang Wang, Chaoshuai Zhao, Fei Xu, Aimi Zhang, Mingming Jin, Kunchi Zhang, Liu Liu, Qian Hua, Jian Zhao, Jianjun Liu, Hao Yang, Gang Huang
Journal: Theranostics (2021)

Hypoxia is commonly observed in solid tumors and contributes to the resistance of DNA damage drugs. However, the mechanisms behind this resistance are still unclear. In this study, we aimed to explore the effects of hypoxia-induced exosomes on non-small cell lung cancer (NSCLC). Methods: NSCLC cells were subjected to either normoxic or hypoxic conditions to assess cell survival and changes in the expression levels of key proteins. Comparative proteomics were performed to identify exosomal PKM2 in normoxic or hypoxic cisplatin-resistant NSCLC cells-derived exosomes. Functions of hypoxia induced-exosomal PKM2 in promoting cisplatin resistance to NSCLC cells were evaluated both in vitro and in vivo experiments and the molecular mechanisms of hypoxia induced-exosomal PKM2 were demonstrated using flow cytometry, immunoblotting, oxidative stress detection and histological examination. A series of in vitro experiments were performed to evaluate the function of hypoxia-induced exosomes on cancer-associated fibroblasts (CAFs). Results: Hypoxia exacerbated the cisplatin resistance in lung cancer cells due to the increased expression of PKM2 that was observed in the exosomes secreted by hypoxic cisplatin-resistance cells. We identified that hypoxia-induced exosomal PKM2 transmitted cisplatin-resistance to sensitive NSCLC cells in vitro and in vivo. Mechanistically, hypoxia-induced exosomal PKM2 promoted glycolysis in NSCLC cells to produce reductive metabolites, which may neutralize reactive oxygen species (ROS) induced by cisplatin. Additionally, hypoxia-induced exosomal PKM2 inhibited apoptosis in a PKM2-BCL2-dependent manner. Moreover, hypoxia-induced exosomal PKM2 reprogrammed CAFs to create an acidic microenvironment promoting NSCLC cells proliferation and cisplatin resistance. Conclusions: Our findings revealed that hypoxia-induced exosomes transmit cisplatin resistance to sensitive NSCLC cells by delivering PKM2. Exosomal PKM2 may serve as a promising biomarker and therapeutic target for cisplatin resistance in NSCLC.
MO01.14 Real-World Effectiveness and Safety of Afatinib Following Immunotherapy (IO) in the Treatment of Metastatic, Squamous Cell/Mixed Histology Carcinoma of the Lung: A Multi-Site Retrospective Chart Review Trial in the US
Authors: E.S. Kim, J. Subramanian, J. Kish, A. Cseh, W. Tang, E. Terlizzi
Journal: Journal of Thoracic Oncology (2021)
Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice
Authors: Mallory Little, Moumita Dutta, Hao Li, Adam Matson, Xiaojian Shi, Gabby Mascarinas, Bruk Molla, Kris Weigel, Haiwei Gu, Sridhar Mani, Julia Yue Cui
Journal: Acta Pharmaceutica Sinica B (2021)

Pharmacological activation of the xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is well-known to increase drug metabolism and reduce inflammation. Little is known regarding their physiological functions on the gut microbiome. In this study, we discovered bivalent hormetic functions of PXR/CAR modulating the richness of the gut microbiome using genetically engineered mice. The absence of
Human basophils release the anti-inflammatory cytokine IL-10 following stimulation with α-melanocyte–stimulating hormone
Authors: Svea Kleiner, Urda Rüdrich, Manuela Gehring, Karin Loser, Britta Eiz-Vesper, Gaetan A. Noubissi Nzeteu, Nikolaos Patsinakidis, N. Helge Meyer, Bernhard F. Gibbs, Ulrike Raap
Journal: Journal of Allergy and Clinical Immunology (2021)
Dermoscopy Proficiency Expectations for US Dermatology Resident Physicians
Authors: Lauren J. Fried, Andrea Tan, Elizabeth G. Berry, Ralph P. Braun, Clara Curiel-Lewandrowski, Julia Curtis, Laura K. Ferris, Rebecca I. Hartman, Natalia Jaimes, John C. Kawaoka, Caroline C. Kim, Aimilios Lallas, Sancy A. Leachman, Alan Levin, Patricia Lucey, Michael A. Marchetti, Ashfaq A. Marghoob, Debbie Miller, Kelly C. Nelson, Edward Prodanovic, Elizabeth V. Seiverling, Susan M. Swetter, Stephanie A. Savory, Richard P. Usatine, Maria L. Wei, David Polsky, Jennifer A. Stein, Tracey N. Liebman
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know. <h3>Objectives</h3> To identify consensus-based learning constructs representing an appropriate foundational proficiency in dermoscopic image interpretation for dermatology resident physicians, including dermoscopic diagnoses, associated features, and representative teaching images. Defining these foundational proficiency learning constructs will facilitate further skill development in dermoscopic image interpretation to help residents achieve clinical proficiency. <h3>Design, Setting, and Participants</h3> A 2-phase modified Delphi surveying technique was used to identify resident learning constructs in 3 sequential sets of surveys—diagnoses, features, and images. Expert panelists were recruited through an email distributed to the 32 members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group. Twenty-six (81%) opted to participate. Surveys were distributed using RedCAP software. <h3>Main Outcomes and Measures</h3> Consensus on diagnoses, associated dermoscopic features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for US dermatology resident physicians. <h3>Results</h3> Twenty-six pigmented lesion and dermoscopy specialists completed 8 rounds of surveys, with 100% (26/26) response rate in all rounds. A final list of 32 diagnoses and 116 associated dermoscopic features was generated. Three hundred seventy-eight representative teaching images reached consensus with panelists. <h3>Conclusions and Relevance</h3> Consensus achieved in this modified Delphi process identified common dermoscopic diagnoses, associated features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for dermatology residency training. This list of validated objectives provides a consensus-based foundation of key learning points in dermoscopy to help resident physicians achieve clinical proficiency in dermoscopic image interpretation.
Neoadjuvant Immunotherapy for High-Risk, Resectable Malignancies: Scientific Rationale and Clinical Challenges
Authors: Mithunah Krishnamoorthy, John G Lenehan, Saman Maleki Vareki
Journal: JNCI Journal of the National Cancer Institute (2020)

Neoadjuvant immunotherapy involves administering immune checkpoint inhibitors before surgical resection in high-risk resectable disease. This strategy was shown to have a high pathological response rate and prolonged relapse-free survival in randomized trials in melanoma, glioblastoma, and colon cancer with small numbers of patients. In resectable cancers, immune checkpoint inhibitors such as anti-programmed cell death-1 (PD1) and anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) can enhance antitumor immunity by activating antigen-specific T cells found in the primary tumor. These tumor-reactive T cells continue to exert antitumor effects on remaining neoplastic cells after the resection of the primary tumor, potentially preventing relapses from occurring. Based on the scientific rationale and early clinical observations with surrogate survival endpoints, neoadjuvant immunotherapy may provide an effective alternative to other therapeutic strategies such as adjuvant treatment. However, this can be determined only by conducting randomized controlled trials comparing neoadjuvant immunotherapy with the current standard of care for each tumor site. This review discusses the cellular mechanisms that occur during successful neoadjuvant immunotherapy and highlights the clinical data from the available human studies that support the preclinical mechanistic data. Here we also discuss strategies required for successful neoadjuvant immunotherapy, including combination treatment strategies and resistance mechanisms to neoadjuvant treatment.
SAT0201 ASSOCIATION OF CARDIAC TROPONIN T MEASURED WITH A HIGHLY SENSITIVE ASSAY WITH CARDIOVASCULAR EVENTS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (TROPOPLUS STUDY)
Authors: J. Chezel, N. Costedoat-Chalumeau, D. Rouzaud, V. Le Guern, C. Gobeaux, N. Morel, M. Pha, Z. Amoura, T. Papo, K. Sacre
Journal: Annals of the Rheumatic Diseases (2020)

Background: Mortality is still 2 to 5 times superior in SLE patients as compared to general population and is mainly due to cardiovascular event (CVE). Although cardiovascular traditional risk factors contribute to early-onset atherosclerosis in SLE, the phenomenon is not fully explained by a higher frequency of smoking habits, hypertension, or dyslipidemia and the Framingham risk equation usually underestimates the 10-year cardiovascular risk in this population. Thus, identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. Objectives: Our study aimed to determine whether serum cardiac troponin T measured with a highly sensitive assay (HS-cTnT) was associated with CVE in systemic lupus erythematosus (SLE) patients. Methods: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicenter PLUS trial were retrospectively screened. Patients with no past history of CVE and a follow-up period of &gt; 20 months were analyzed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed. Results: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analyzed for the primary outcome with a median follow up of 110 (IQR: 99-120) months. Among them 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (IQR: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidemia, duration of SLE disease and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT &gt; 4.27 ng/L at inclusion increased by 2.7 (HR 2.7 [1.3-5.6], p=0.0083) the risk of CVE in SLE. Conclusion: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients Disclosure of Interests: Julie Chezel: None declared, Nathalie Costedoat-Chalumeau Grant/research support from: UCB to my institution, Diane Rouzaud: None declared, Véronique LE GUERN Grant/research support from: UCB for GR2 study (to our institution), Camille Gobeaux: None declared, Nathalie Morel: None declared, Micheline Pha: None declared, Zahir Amoura: None declared, Thomas Papo: None declared, karim sacre: None declared
Chemotherapy Related Neuropsychological Changes in Patients with Hodgkin's Lymphoma and Acute Lymphoblastic Leukemia
Authors: Sergei Khrushchev, Dmitry Vybornykh, Lada Olexenko, Alexandra Nesterova, Alexander Tkhostov, Larisa A. Kuzmina, Elena N. Parovichnikova, Valeriy G. Savchenko
Journal: Blood (2017)
Patient-Reported Symptom Burden as a Predictor of Emergency Department Use and Unplanned Hospitalization in Head and Neck Cancer: A Longitudinal Population-Based Study
Authors: Christopher W. Noel, Rinku Sutradhar, Haoyu Zhao, Victoria Delibasic, David Forner, Jonathan C. Irish, Jonathan Kim, Zain Husain, Alyson Mahar, Irene Karam, Danny J. Enepekides, Kelvin K. W. Chan, Simron Singh, Julie Hallet, Natalie G. Coburn, Antoine Eskander
Journal: Journal of Clinical Oncology (2021)

PURPOSE: To determine the association between patient-reported symptom burden and subsequent emergency department use and unplanned hospitalization (ED/Hosp) in a head and neck cancer (HNC) patient population. METHODS: This was a population-based study of patients diagnosed with HNC who had completed at least one outpatient Edmonton Symptom Assessment System (ESAS) assessment between January 2007 and March 2018 in Ontario, Canada. Logistic regression models were used to determine the relationship between outpatient ESAS scores and subsequent 14-day ED/Hosp use. A generalized estimating equation approach with an exchangeable correlation structure was incorporated to account for patient-level clustering RESULTS: There were 11,761 patients identified, completing a total of 73,282 ESAS assessments and experiencing 5,203 ED/Hosp events. Six of the nine ESAS symptom scores were positively associated with ED/Hosp use, with pain, appetite, shortness of breath, and tiredness demonstrating the strongest associations. A global ESAS score was calculated by selecting the highest individual symptom score (h-ESAS). Among patients reporting a maximum h-ESAS score of 10, 15.1% had an ED/Hosp event within 14 days compared with 1.5% for those with the lowest possible score of zero. In adjusted analysis, the odds of ED/Hosp use increased with h-ESAS (1.23 per one-unit increase [95% CI, 1.22 to 1.25]). When treated as a categorical variable, patients with the maximum h-ESAS score of 10 had 9.23 (95% CI, 7.22 to 11.33) higher odds of ED/Hosp use, relative to the minimum score of zero. CONCLUSION: ESAS scores are strongly associated with subsequent ED/Hosp events in patients with HNC. Clinician education around how ESAS data might inform patient care may enhance symptom detection and management.
Replacement of L-amino acid peptides with D-amino acid peptides mitigates anti-PEG antibody generation against polymer-peptide conjugates in mice
Authors: Meilyn Sylvestre, Shixian Lv, Lucy F. Yang, Nicholas Luera, David J. Peeler, Bing-Mae Chen, Steve R. Roffler, Suzie H. Pun
Journal: Journal of Controlled Release (2021)