tbuckley/cabot-search huggingface dataset:
Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies
Authors: Jérémy Dufloo, Ludivine Grzelak, Isabelle Staropoli, Yoann Madec, Laura Tondeur, François Anna, Stéphane Pelleau, Aurélie Wiedemann, Cyril Planchais, Julian Buchrieser, Rémy Robinot, Marie-Noelle Ungeheuer, Hugo Mouquet, Pierre Charneau, Michael White, Yves Lévy, Bruno Hoen, Arnaud Fontanet, Olivier Schwartz, Timothée Bruel
Journal: Cell Reports Medicine (2021)

Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and 21 hospitalized patients with COVID-19. We measure anti-spike immunoglobulin G (IgG), IgA, and IgM levels with the S-Flow assay and map IgG-targeted epitopes with a Luminex assay. We also evaluate neutralization, complement deposition, and antibody-dependent cellular cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC, and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than they are in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.
COVID-19 in pediatric cancer: Where are the brain tumors?
Authors: Rebecca Ronsley, Eric Bouffet
Journal: Neuro-Oncology (2021)

COVID-19 in pediatric cancer:Where are the brain tumors?Recently, Carai et al published a report highlighting the risk of delayed diagnosis of pediatric central nervous system (CNS) tumors during the novel coronavirus disease 2/SARS-CoV-2 2019 (COVID-19) virus pandemic. 1In this article and others, 2 the authors highlight the fragility of pediatric patients with CNS tumors and the importance of early diagnosis and optimal care delivery, which may have been impacted during the pandemic.CNS tumors are the largest group of solid tumors within pediatric oncology patients, accounting for 20%-25% of all childhood cancers.Treatment is variable in its intensity and potential for immunosuppression primarily depends on the tumor type.The risk of COVID-19 to this tumor group is not clear from current publications and here we reviewed the literature to identify pediatric CNS tumors patients reported to have COVID-19 and their outcomes.Through review of PubMed, Google Scholar, and the International Society for Pediatric Oncology (SIOP) and St. Jude Children's Research Hospital COVID-19 website, we identified 18 published studies describing COVID-19 cases in pediatric oncology patients worldwide (Table 1).Within these studies, there are 551 reported cases of COVID-19 in pediatric oncology patients of which 31 (5.6%) are patients with CNS tumors.Within all cases, reported rate of severe illness or hospitalization requirement ranged from 5% to 84%.Within these hospitalized cases, 40%-86% were already hospitalized for planned oncologic therapy.Within the 551 total cases, there were 26 deaths, of which 6 were attributed to COVID-19, and the remaining 20 the authors attributed to cancer or oncologic therapy-related mortality.No deaths were reported within the patients with brain tumors in these publications.Based on these publications, children with cancer do not seem to have a higher rate of mortality from COVID-19 than immunocompetent children.This finding is difficult to fully understand in this population with such significant comorbidities, which may independently result in death.The mortality rate from COVID-19 for these combined reports was 1.1%.Recently, Vijenthira et al summarized 34 reports that included predominantly adult oncology patients with concurrent COVID-19 infections.A small proportion of these patients were children in which the rate of mortality attributed to COVID-19 was 4.0%. 3NS tumors are significantly underrepresented within published cases of COVID-19 in children with cancer.The reasons for this are unclear.This may reflect that most therapies for CNS tumor patients are not significantly myelosuppressive with hospital admissions due to complications occurring less often than in other pediatric oncology patients. 4To support this
Isolation, chemistry, and biology of pyrrolo[1,4]benzodiazepine natural products
Authors: Guna Sakaine, Anastasija Ture, Julia Pedroni, Gints Smits
Journal: Medicinal Research Reviews (2021)

Abstract The isolation of the antitumor antibiotic anthramycin in the 1960s prompted extensive research into pyrrolo[1,4]benzodiazepines (PBD) as potential therapeutics for the treatment of cancers. Since then, nearly 60 PBD natural products have been isolated and evaluated with regard to their biological activity. Synthetic studies and total syntheses have enabled access to PBD analogues, culminating in the development of highly potent anticancer agents. This review provides a summary of the occurrence and biological activity of PBD natural products and covers the strategies employed for their total syntheses.
Direct assessment of individual skin barrier components by electrical impedance spectroscopy
Authors: Roman Mannweiler, Sophia Bergmann, Sabine Vidal‐y‐Sy, Johanna M. Brandner, Dorothee Günzel
Journal: Allergy (2021)

Expression of the tight junction proteins Cldn1 and 4 is altered in skin diseases such as atopic dermatitis, and Cldn1 deficiency affects skin barrier formation. Impedance spectroscopy (IS) has been proven to allow detection of alterations in the skin barrier but is currently unable to separate effects on viable epidermis (VE) and stratum corneum (SC).Effects of siRNA-mediated Cldn1 and 4 knockdown in reconstructed human epidermis (RHE) on VE and SC barrier function were investigated with Ussing chamber-based IS. Barrier components were sequentially altered, employing iron oxide nanoparticles and EGTA, to identify their contribution to the impedance spectrum. Resistance changes due to apically applied hyperosmolar electrolyte were used to identify barrier defects non-invasively.IS of RHE yielded two relaxation frequencies, representing the barrier properties of the SC (~1000 Hz) and VE (~100 Hz). As proof of concept, it was shown that the Cldn1 knockdown-induced resistance drop arises from the impairment of both SC and VE, indicated by a shift of both relaxation frequencies. Hyperosmolar electrolyte penetration allowed non-invasive detection of Cldn1 knockdown via time-dependent frequency shifts. The absence of Cldn4 knockdown-induced changes revealed the weaknesses of transepithelial electrical resistance analysis.In conclusion, the present technique allows to separately measure the barrier properties of SC and VE and further evaluate the Cldn1 and 4 knockdown impact on the skin barrier. As the measurement with agarose-embedded electrolyte allowed non-invasive identification of the Cldn1 knockdown, this opens the way to detailed in vivo skin barrier assessment.
Abstract 13407: Trends in Discharge Prescription of Digoxin After Norwood Operation: An Analysis of Data From the Pediatric Health Information Systems Database (PHIS)
Authors: Michael L Obyrne, Lihai Song, JING HUANG, David J Goldberg, Monique A Gardner, Chitra Ravishankar, Jonathan J Rome, Andrew C Glatz
Journal: Circulation (2020)

Background: Quality improvement efforts have focused on reducing interstage mortality for infants with hypoplastic left heart syndrome (HLHS). In 2016 two publications reported that digoxin use was associated with reduced interstage mortality. The degree to which these findings have affected real world practice has not been evaluated. Methods: A multicenter retrospective cohort study of rates of digoxin prescription at discharge was performed of neonates with HLHS surviving to discharge without transplant from 1/2006-12/2018 at PHIS hospitals. A difference in difference analysis was performed using mixed effects models to adjust for measurable covariates (known arrhythmia, prematurity, renal insufficiency, etc.) with the hypothesis that the likelihood of digoxin prescription increased after 1/2016. Inter-hospital practice variation was measured, calculating the median odds ratio (MOR). Likelihood of furosemide and aspirin prescriptions were studied as falsification tests. Results: Over the study period 6091 subjects from 35 hospitals were included. Likelihood of receiving digoxin, furosemide, and aspirin are depicted (Figure). After adjusting for measurable covariates, discharge after 1/2016 was associated with increased odds of receiving digoxin (OR: 3.9, p&lt;0.001). No association was seen between date of discharge and furosemide (p=0.26) or aspirin (p=0.12). Prior to 1/2016, the likelihood of receiving digoxin was decreasing (OR: 0.9 per year, p&lt;0.001), while after 1/2016 the likelihood has increased (OR: 2.4 per year, p&lt;0.001). Significant inter-hospital variation in the likelihood of receiving digoxin was seen (MOR=3.5, p&lt;0.001 with no significant difference before and after 2016). Conclusion: The use of digoxin increased after publication of data about potential benefit in the interstage period. However, despite concerted quality improvement efforts, there is persistent large magnitude inter-hospital variation in practice.
Abstract 16694: Left Ventricular Global Longitudinal Strain Predicts Ventricular Arrhythmias in Patients With Implanted Cardiac Devices
Authors: Zain Ul Abideen Asad, Brian Kliewer, Tiffany F Mao, Isma N Javed, Abdul Ghani Iqbal, Ali Jafry, Khawaja Akhtar, Khaled Elkholey, Phuong E Ngo, Stavros Stavrakis
Journal: Circulation (2020)

Introduction: Abnormal left ventricular ejection fraction (LVEF) is the traditional parameter used to assess the risk of sudden cardiac death (SCD), but most SCD events occur in patients with LVEF &gt;40%. Hypothesis: We hypothesized that global longitudinal strain (GLS) can predict SCD in patients with heart failure and implantable cardiac devices. Methods: This was a retrospective cohort study. Device interrogation and chart review was done for demographic, clinical and echocardiographic characteristics and assessment of outcomes; ventricular tachycardia (VT) or ventricular fibrillation (VF), all-cause mortality, cardiac hospitalizations, non-sustained VT and new atrial fibrillation (AF). Cox-regression analysis was performed for the association between GLS, other clinical and echocardiographic parameters and outcomes. Results: A total of 180 patients were included with males 176 (98%), HFrEF (LVEF&lt;40%) 58 (33%), HFmEF (LVEF 40-50%) 37 (21%), HFpEF 83 (46%), ischemic cardiomyopathy 78 (43%) and non-ischemic cardiomyopathy 39 (22%). Over a median follow up of 31 months, 29 (16%) developed sustained VT/VF, 33 (18%) died, 55 (31%) had cardiac hospitalization, 74 (41%) had non-sustained VT and 25 (14%) developed new AF. Abnormal GLS (≥-17%) predicted VT/VF (HR=4.0, 95% CI 1.2 - 13.3, p=0.02) and mortality (HR=4.2, 95% CI 1.5 - 11.9, p=0.008) in the entire population. Notably, in the HFpEF group, abnormal GLS was the only predictor of mortality (HR=3.5, 95% CI 1.1 - 10.8, p=0.02; Figure 1). Conclusions: Abnormal GLS is a predictor of ventricular arrhythmias and mortality in patients with heart failure. In patients with HFpEF, GLS may be used for risk stratification upon further validation in larger studies.
Towards Taming the Bugs to Improve the Drugs for Breast Cancer
Authors: Dipali Sharma
Journal: Cancer Research (2021)

Abstract The identification of microbial networks that are predictive of disease progression and response to therapy will not only increase our understanding of the connection between microbiota and breast cancer, but also pave the way for the development of novel microbiota-based therapeutic interventions. The study by Di Modica and colleagues points to the existence of specific microbiota in patients with HER2+ breast cancer that can influence their response to trastuzumab. This information can potentially be used to develop novel therapeutic regimens combining fecal microbiota transplant with standard cancer therapy. See related article by Di Modica et al., p. 2195
Abstract P335: Salt Sensitivity and Incidence of Hypertension: The GenSalt Study
Authors: Jiang He, Dongfeng Gu, Jing Chen, Jichun Chen, Qi Zhao, Jianfeng Huang, Jianxin Li, Jie Cao, Treva Rice, Katherine Mills, Chung-Shiuan Chen, Lee Hamm
Journal: Circulation (2013)

It is well known that blood pressure (BP) responses to dietary sodium and potassium intakes vary among individuals (salt- and potassium-sensitivity). However, it is unknown whether salt- and/or potassium-sensitivity predict the risk of hypertension. We conducted a dietary sodium and potassium intervention study among 1,906 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12. The dietary intervention included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high sodium-feeding with an oral potassium supplementation (60 mmol/day). Three BP measurements were obtained on each of the last 3 days of each intervention period at the baseline and each of the 3 days of follow-up examinations. Systolic BP responses (mean ± SD) to dietary intervention were -5.5±7.0 for low-sodium, 4.9±6.0 for high-sodium, and -3.5±5.5 for potassium-supplementation. Over an average of 7.4 years of follow-up, we identified 455 incidence hypertension cases (systolic BP≥140 mmHg and/or diastolic BP ≥90 mmHg and/or use of antihypertensive medication). The age-adjusted cumulative incidences of hypertension by the quartiles of systolic BP responses to dietary intervention were showed in the following table. These associations remained after adjustment for multiple covariates. These data indicate that BP responses to dietary sodium and potassium intervention are related to the subsequent risk of hypertension. Furthermore, our study suggests that individuals who are more sensitive to dietary sodium and potassium intake are at an increased risk for hypertension and should be target for dietary intervention.
Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93
Authors: Jinling Huang, Hae-youn Lee, Xiaohong Zhao, Jinyi Han, Yang Su, Qinli Sun, Jing Shao, Jiwan Ge, Yuxi Zhao, Xue Bai, Yi He, Xinquan Wang, Xiaohu Wang, Chen Dong
Journal: Immunity (2021)
Eczema herpeticum in atopic dermatitis
Authors: Stephan Traidl, Lennart Roesner, Jana Zeitvogel, Thomas Werfel
Journal: Allergy (2021)

Abstract Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases leading to pruritic skin lesions. A subset of AD patients exhibits a disseminated severe HSV infection called eczema herpeticum (EH) that can cause life‐threatening complications. This review gives an overview of the clinical picture, and characteristics of the patients as well as the diagnosis and therapy of EH. A special focus lies on the pathophysiological hallmarks identified so far that predispose for EH. This aspect covers genetic aberrations, immunological changes, and environmental influences displaying a complex multifactorial situation, which is not completely understood. Type 2 skewing of virus‐specific T cells in ADEH + patients has been implicated in immune profile abnormalities, along with impaired functions of dendritic cells and natural killer cells. Furthermore, aberrations in interferon pathway‐related genes such as IFNG and IFNGR1 have been identified to increase the risk of EH. IL‐4, IL‐25, and thymic stromal lymphopoietin (TSLP) are overexpressed in EH, whereas antimicrobial peptides like human β‐defensins and LL‐37 are reduced. Concerning the epidermal barrier, single nucleotide polymorphisms (SNPs) in skin barrier proteins such as filaggrin were identified in ADEH + patients. A dysbalance of the skin microbiome also contributes to EH due to an increase of Staphylococcus aureus , which provides a supporting role to the viral infection via secreted toxins such as α‐toxin. The risk of EH is reduced in AD patients treated with dupilumab. Further research is needed to identify and specifically target risk factors for EH in AD patients.
Endoscopic ultrasound-guided rendezvous recanalization of a completely obstructed esophagogastric anastomosis
Authors: Yu-Yan Zhang, Lian-Song Ye, Yi Mou, Chun-Cheng Wu, Qing-Hua Tan, Ke Liao, Bing Hu
Journal: Endoscopy (2021)

A 63-year-old woman who had undergone resection of adenocarcinoma at the gastroesophageal junction was admitted with complete obstruction of the esophagogastric anastomosis ([Fig. 1]). For the past 2 years, gastrostomy tube feeding had been her only source of enteral nutrition. Endoscopic ultrasound (EUS)-guided rendezvous recanalization of the obstruction was attempted to allow her to resume oral intake ([Video 1]).
Abstract MP98: Circulating Phospholipid n-3 Polyunsaturated Fatty Acids and Incident Atherothrombotic and Cardioembolic Ischemic Stroke in 3 Large US Cohorts
Authors: Hamidreza Saber, Mohammad Y Yakoob, Peilin Shi, Will Longstreth, Eric B Rimm, Rozenn N Lemaitre, David Siscovick, Kathryn Rexrode, Walter C Willett, Dariush Mozaffarian
Journal: Circulation (2016)

Introduction: The associations of individual seafood n-3 polyunsaturated fatty acids with incident ischemic stroke, and its subtypes (atherothrombotic and cardioembolic stroke), are not well-established. Individual n-3 fatty acids, which are best assessed by circulating biomarkers, may also have differential effects on atherothrombotic vs. cardioembolic stroke. Objective: To prospectively investigate the relationship of circulating eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke. Methods: We measured circulating phospholipid fatty acids (erythrocyte or plasma) at baseline in the Cardiovascular Health Study (CHS), Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). Ischemic stroke was prospectively adjudicated and classified into atherothrombotic (large and small vessel infarctions) or cardioembolic (cardiac mural thrombi, valvular heart disease, atrial fibrillation, other sources) stroke by imaging studies and medical records. Risk was assessed using conditional logistic regression (for prospective nested case-control studies: NHS, HPFS) or Cox proportional hazards model (full cohort: CHS). Findings were pooled by fixed-effects meta-analysis. Results: A total of 953 incident ischemic strokes were identified that included 408 atherothrombotic and 256 cardioembolic strokes, during mean follow-up of 11.4 (CHS) and 8.3 (NHS,HPFS) years (the remaining 289 ischemic strokes could not be sub-classified). After adjustment for age, race, sex, smoking, physical activity, alcohol intake, family history of MI and diabetes, menopausal status, BMI, aspirin use and intakes of fruits, vegetables, and meats, lower risk of total ischemic stroke was seen with DPA (highest vs. lowest-quartiles, pooled HR=0.74, 95%CI=0.58-0.92) and DHA (0.80, 0.64-1.00), but not EPA (0.94, 0.77-1.19). Among stroke subtypes, DHA was associated with substantially lower risk of atherothrombotic (0.53, 0.34-0.83), but not cardioembolic stroke; and DPA with substantially lower risk of cardioembolic (0.58, 0.37-0.92), but not atherothrombotic stroke. Findings in each individual cohort were similar to the pooled results. Conclusions: In 3 US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke, and DPA, with cardioembolic stroke. EPA was not associated with ischemic stroke. These novel findings highlight the importance of separately evaluating ischemic stroke subtypes as well as specific individual fatty acids, and suggest differential pathways of benefit for DHA, DPA, and EPA.
Abstract 9967: Cardiac Warburg Effect is Controlled by Single Serine on TSC2 and Protects Against Ischemia-Reperfusion Injury
Authors: Christian U Oeing, Seungho Jun, Brittany Dunkerly-Eyring, Sumita Mishra, Usman Tahir, Guangshuo Zhu, Gizem Keceli, Robert Gerszten, Mark Ranek, Nazareno Paolocci, David Kass
Journal: Circulation (2019)

Introduction: Tumor cells survive hypoxic, nutrient challenged environments by shifting metabolism to aerobic glycolysis while reducing oxidative phosphorylation; known as the Warburg effect. A maj...
Alternatives to Perpetual Chemotherapy for Metastatic Pancreatic Cancer
Authors: Kim A. Reiss, Robert H. Vonderheide
Journal: Clinical Cancer Research (2021)

Abstract With the advent of multiagent chemotherapy for metastatic pancreatic cancer, subgroups of patients whose disease responds durably to treatment are emerging. Although this is wonderful progress in the face of a deadly illness, cumulative toxicities of perpetual chemotherapy over months or even years of treatment degrade quality of life and organ function, in addition to fueling eventual therapeutic resistance. The POLO trial demonstrated a benefit of maintenance olaparib compared with placebo in patients with germline pathogenic variants in BRCA1 or BRCA2. The success of this trial, albeit in a limited subset of patients, suggests that there may be opportunity to study this alternative treatment strategy as a paradigm for a broader group of patients with advanced pancreatic cancer. This article discusses the phenotypic and genotypic signatures of patients with pancreatic cancer that may provide the basis upon which to design rational maintenance clinical trials.
Abstract 14721: Suspected Arrhythmogenic Bileaflet Mitral Valve Prolapse Syndrome in the Absence of Sudden Cardiac Death: A Single Center Experience
Authors: John Giudicessi, Peter A Noseworthy, Michael J Ackerman
Journal: Circulation (2019)

Introduction: Arrhythmogenic bileaflet mitral valve prolapse syndrome (ABiMVPS) is a sudden death-predisposing disorder characterized clinically by bileaflet mitral valve prolapse (MVP), inferolate...
Endoscopic ultrasound-guided recanalization of a complete esophageal stricture
Authors: Ramzi Mulki, Mohamed M. Abdelfatah
Journal: Endoscopy (2021)

Complete esophageal strictures are rare and pose technical challenges in management. We present a case of a 34-year-old man with a long-standing history of uncontrolled gastroesophageal reflux disease (GERD) who was referred for management of a complete esophageal stricture. Prior to his presentation, a gastrostomy tube was placed surgically owing to severe malnutrition.
Pulmonary Arterial Hypertension: Diagnosis, Treatment, and Novel Advances
Authors: Bradley A. Maron, Steven H. Abman, C. Greg Elliott, Robert P. Frantz, Rachel K. Hopper, Evelyn M. Horn, Mark R. Nicolls, Oksana A. Shlobin, Sanjiv J. Shah, Gabor Kovacs, Horst Olschewski, Erika B. Rosenzweig
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

The diagnosis and management of pulmonary arterial hypertension (PAH) includes several advances, such as a broader recognition of extrapulmonary vascular organ system involvement, validated point-of-care clinical assessment tools, and focus on the early initiation of multiple pharmacotherapeutics in appropriate patients. Indeed, a principal goal in PAH today is an early diagnosis for prompt initiation of treatment to achieve a minimal symptom burden; optimize the patient's biochemical, hemodynamic, and functional profile; and limit adverse events. To accomplish this end, clinicians must be familiar with novel risk factors and the revised hemodynamic definition for PAH. Fresh insights into the role of developmental biology (i.e., perinatal health) may also be useful for predicting incident PAH in early adulthood. Emergent or underused approaches to PAH management include a novel TGF-β ligand trap pharmacotherapy, remote pulmonary arterial pressure monitoring, next-generation imaging using inert gas-based magnetic resonance and other technologies, right atrial pacing, and pulmonary arterial denervation. These and other PAH state of the art advances are summarized here for the wider pulmonary medicine community.