tbuckley/cabot-search huggingface dataset:
Blood eosinophil cationic protein and eosinophil-derived neurotoxin are associated with different asthma expression and evolution in adults
Authors: Vanessa Granger, Farid Zerimech, Jinan Arab, Valerie Siroux, Patricia de Nadai, Anne Tsicopoulos, Régis Matran, Zeina Akiki, Rachel Nadif
Journal: Thorax (2021)

Background Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are proteins released by activated eosinophils whose role in adult asthma remains unclear. Objective To study associations between ECP, EDN and various asthma characteristics in adults from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). Methods Plasma ECP and EDN levels were measured by ELISA. Cross-sectional analyses were performed in 941 adults (43±16 years old, 39% with asthma) at EGEA2 (2003–2007). Longitudinal analyses investigated the associations between EDN level at EGEA2 and changes in asthma characteristics between EGEA2 and EGEA3 (2011–2013, n=817). We used generalised estimated equations adjusted for age, sex, smoking status and body mass index to take into account familial dependence. Results At EGEA2, both high ECP and EDN levels were associated with current asthma (adjusted OR (aOR) (95% CI): 1.69 (1.35–2.12) and 2.12 (1.76–2.57)). Among asthmatics, high EDN level was associated with asthma attacks (aOR: 1.50 (1.13–1.99)), wheezing and breathlessness (aOR: 1.38 (1.05–1.80)), use of asthma treatments (aOR: 1.91 (1.37–2.68)) and bronchial hyper-responsiveness (aOR: 2.03 (1.38–2.97)), even after further adjustment on ECP. High ECP level was associated with high neutrophil count and tended to be associated with chronic bronchitis. High EDN level at EGEA2 was associated with persistent asthma (aOR: 1.62 (1.04–2.52)), nocturnal symptoms (aOR from 2.19 to 3.57), worsening wheezing and breathlessness (aOR: 1.97 (1.36–2.85)) and nocturnal shortness of breath (aOR: 1.44 (1.04–1.98)) between EGEA2 and EGEA3. Conclusions EDN and ECP were associated with different asthma expression in adults. EDN could be a potential biomarker to monitor asthma evolution in adults.
LBA12 Predictive value of gene-expression profiles (GEPs) and their dynamics during therapy in the NeoTRIPaPDL1 trial
Authors: G. Bianchini, M. Dugo, C-S. Huang, D. Egle, B. Bermejo, R.S. Seitz, T.J.J. Nielsen, C. Zamagni, M. Thill, A. Anton, S. Russo, E.M. Ciruelos, B.L. Schweitzer, R. Greil, V. Semiglazov, B. Gyorffy, P. Valagussa, G. Viale, M. Callari, L. Gianni
Journal: Annals of Oncology (2021)
Exosomes: Emerging implementation of nanotechnology for detecting and managing novel corona virus- SARS-CoV-2
Authors: Akhilesh Dubey, Cynthia Lizzie Lobo, Ravi Gs, Amitha Shetty, Srinivas Hebbar, Sally A El-Zahaby
Journal: Asian Journal of Pharmaceutical Sciences (2021)

The spread of SARS-CoV-2 as an emerging novel coronavirus disease (COVID-19) had progressed as a worldwide pandemic since the end of 2019. COVID-19 affects firstly lungs tissues which are known for their very slow regeneration. Afterwards, enormous cytokine stimulation occurs in the infected cells immediately after a lung infection which necessitates good management to save patients. Exosomes are extracellular vesicles of nanometric size released by reticulocytes on maturation and are known to mediate intercellular communications. The exosomal cargo serves as biomarkers in diagnosing various diseases; moreover, exosomes could be employed as nanocarriers in drug delivery systems. Exosomes look promising to combat the current pandemic since they contribute to the immune response against several viral pathogens. Many studies have proved the potential of using exosomes either as viral elements or host systems that acquire immune-stimulatory effects and could be used as a vaccine or drug delivery tool. It is essential to stop viral replication, prevent and reverse the massive storm of cytokine that worsens the infected patients' situations for the management of COVID-19. The main benefits of exosomes could be; no cells will be introduced, no chance of mutation, lack of immunogenicity and the damaged genetic material that could negatively affect the recipient is avoided. Additionally, it was found that exosomes are static with no ability for in vivo reproduction. The current review article discusses the possibilities of using exosomes for detecting novel coronavirus and summarizes state of the art concerning the clinical trials initiated for examining the use of COVID-19 specific T cells derived exosomes and mesenchymal stem cells derived exosomes in managing COVID-19.
Antifragility of healthcare systems in Croatia and Bosnia and Herzegovina: Learning from man-made and natural crises
Authors: Ružica Tokalić, Marin Viđak, Mersiha Mahmić Kaknjo, Ana Marušić
Journal: The Lancet Regional Health - Europe (2021)

Acute crises, such as a war or a pandemic, are the ultimate tests for health care systems' resilience (temporary response to stress with change and adaptation) and antifragility (permanent benefit from change in response to stress). In this Health Policy paper, we analyse and discuss how the healthcare systems of two European countries – Bosnia and Herzegovina and Croatia – adapted to war as a man-made disaster, and how they adapted to COVID-19 pandemic twenty-five years later. These countries experienced full scale wars in recent history, which significantly changed their political and healthcare systems. This experience prepared the countries for the response to the pandemic, which coincided with two earthquakes in Croatia. We argue that healthcare systems in Croatia and Bosnia and Herzegovina are not only resilient but antifragile, and that they benefited from stressors they were exposed to. The antifragility of the two systems were primarily based on human effort – the strength, adaptability and resilience of health care professionals. We will look at lessons from the wars that were applied to the pandemic and discuss newly recognized opportunities and improvements.
Advances and highlights in T and B cell responses to drug antigens
Authors: Ruben Fernandez‐Santamaria, Adriana Ariza, Tahia D. Fernandez, José A Cespedes, Marina Labella, Cristobalina Mayorga, María J Torres
Journal: Allergy (2021)

Abstract The immunological mechanisms involved in drug hypersensitivity reactions (DHRs) are complex, and despite important advances, multiple aspects remain poorly understood. These not fully known aspects are mainly related to the factors that drive towards either a tolerant or a hypersensitivity response and specifically regarding the role of B and T cells. In this review, we focus on recent findings on this knowledge area within the last 2 years. We highlight new evidences of covalent and non‐covalent interactions of drug antigen with proteins, as well as the very first characterization of naturally processed flucloxacillin‐haptenated human leukocyte antigen (HLA) ligands. Moreover, we have analysed new insights into the identification of risk factors associated with the development of DHRs, such as the role of oxidative metabolism of drugs in the activation of the immune system and the discovery of new associations between DHRs and HLA variants. Finally, evidence of IgG‐mediated anaphylaxis in humans and the involvement of specific subpopulations of effector cells associated with different clinical entities are also topics explored in this review. All these recent findings are relevant for the underlying pathology mechanisms and advance the field towards a more precise diagnosis, management and treatment approach for DHRs.
Hepatic miR-378 modulates serum cholesterol levels by regulating hepatic bile acid synthesis
Authors: Chao Sun, Wei Liu, Zhiqiang Lu, Yan Li, Shengnan Liu, Zhili Tang, Ying Yan, Zhiyang Li, Hua Feng, Duo Zhang, Yun Liu, Zhong-Ze Fang, Changtao Jiang, Qiurong Ding, Jingjing Jiang, Hao Ying
Journal: Theranostics (2021)

Rationale: An improved understanding of thyroid hormone (TH) action on cholesterol metabolism will facilitate the identification of novel therapeutic targets for hypercholesterolemia. TH-regulated microRNAs (miRNAs) have been implicated in TH-controlled biological processes; however, whether and how TH-regulated miRNAs mediate the cholesterol-lowering effect of TH remains unclear. Our aim was to identify TH-regulated microRNAs that have cholesterol-lowering effects and explore the underlying mechanism. Method: Microarray and RNA-seq were performed to identify TH-regulated microRNAs and the genes regulated by mmu-miR-378-3p (miR-378) in the liver of mice, respectively. Recombinant adenoviruses encoding miR-378, Mafg, and shRNA for Mafg, antagomiR-378, liver-specific miR-378 transgenic mice, and miR-378 knockout mice were employed to investigate the roles of hepatic miR-378 and MAFG in cholesterol and bile acid homeostasis. The levels of bile salt species were determined by using UFLC-Triple-time of flight/MS. Results: Here, we show that hepatic miR-378 is positively regulated by TH. Transient overexpression of miR-378 in the liver of mice reduces serum cholesterol levels, accompanied with an increase in the expression of key enzymes in primary bile acid synthetic pathways and corresponding increases in biliary and fecal bile acid levels. Consistently, liver-specific miR-378 transgenic mice with moderate overexpression of hepatic miR-378 display decreased serum cholesterol levels and resistance to diet-induced hypercholesterolemia, while mice lacking miR-378 exhibit defects in bile acid and cholesterol homeostasis. Mechanistically, hepatic miR-378 regulates the expression of key enzymes in both classic and alternative bile acid synthetic pathways through MAFG, a transcriptional repressor, thereby modulating bile acid and cholesterol metabolism. Conclusions: TH-responsive hepatic miR-378 is capable of modulating serum cholesterol levels by regulating both the classic and alternative BA synthetic pathways. Our study not only identifies a previously undescribed role of hepatic miR-378 but also provides new cholesterol-lowering approaches.
Texture Analysis and Its Applications in Biomedical Imaging: A Survey
Authors: Maryam Khaksar Ghalati, Ana Nunes, Hugo Ferreira, Pedro Serranho, Rui Bernardes
Journal: IEEE Reviews in Biomedical Engineering (2021)

Texture analysis describes a variety of image analysis techniques that quantify the variation in intensity and pattern. This paper provides an overview of several texture analysis approaches addressing the rationale supporting them, their advantages, drawbacks, and applications. This survey's emphasis is in collecting and categorising over five decades of active research on texture analysis. Brief descriptions of different approaches are presented along with application examples. From a broad range of texture analysis applications, this survey's final focus is on biomedical image analysis. An up-to-date list of biological tissues and organs in which disorders produce texture changes that may be used to spot disease onset and progression is provided. Finally, the role of texture analysis methods as biomarkers of disease is summarised.
Editing outside the body: Ex vivo gene-modification for β-hemoglobinopathy cellular therapy
Authors: Tolulope O. Rosanwo, Daniel E. Bauer
Journal: Molecular Therapy (2021)

Genome editing produces genetic modifications in somatic cells, offering novel curative possibilities for sickle cell disease and β-thalassemia. These opportunities leverage clinical knowledge of hematopoietic stem cell transplant and gene transfer. Advantages to this mode of ex vivo therapy include locus-specific alteration of patient hematopoietic stem cell genomes, lack of allogeneic immune response, and avoidance of insertional mutagenesis. Despite exciting progress, many aspects of this approach remain to be optimized for ideal clinical implementation, including the efficiency and specificity of gene modification, delivery to hematopoietic stem cells, and robust and nontoxic engraftment of gene-modified cells. This review highlights genome editing as compared to other genetic therapies, the differences between editing strategies, and the clinical prospects and challenges of implementing genome editing as a novel treatment. As the world's most common monogenic disorders, the β-hemoglobinopathies are at the forefront of bringing genome editing to the clinic and hold promise for molecular medicine to address human disease at its root.
Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition
Authors: Lisa Osbelt, Marie Wende, Éva Almási, Elisabeth Derksen, Uthayakumar Muthukumarasamy, Till R Lesker, Eric J C Galvez, Marina C Pils, Enrico Schalk, Patrick Chhatwal, Jacqueline Färber, Meina Neumann-Schaal, Thomas Fischer, Dirk Schlüter, Till Strowig
Journal: Cell Host & Microbe (2021)
Disrupted PI3K subunit p110α signaling protects against pulmonary hypertension and reverses established disease in rodents
Authors: Eva M. Berghausen, Wiebke Janssen, Marius Vantler, Leoni L. Gnatzy-Feik, Max Krause, Arnica Behringer, Christine Joseph, Mario Zierden, Henrik ten Freyhaus, Anna Klinke, Stephan Baldus, Miguel A. Alcazar, Rajkumar Savai, Soni Savai Pullamsetti, Dickson W.L. Wong, Peter Boor, Jean J. Zhao, Ralph T. Schermuly, Stephan Rosenkranz
Journal: Journal of Clinical Investigation (2021)

Enhanced signaling via RTKs in pulmonary hypertension (PH) impedes current treatment options because it perpetuates proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Here, we demonstrated hyperphosphorylation of multiple RTKs in diseased human vessels and increased activation of their common downstream effector phosphatidylinositol 3'-kinase (PI3K), which thus emerged as an attractive therapeutic target. Systematic characterization of class IA catalytic PI3K isoforms identified p110α as the key regulator of pathogenic signaling pathways and PASMC responses (proliferation, migration, survival) downstream of multiple RTKs. Smooth muscle cell-specific genetic ablation or pharmacological inhibition of p110α prevented onset and progression of pulmonary hypertension (PH) as well as right heart hypertrophy in vivo and even reversed established vascular remodeling and PH in various animal models. These effects were attributable to both inhibition of vascular proliferation and induction of apoptosis. Since this pathway is abundantly activated in human disease, p110α represents a central target in PH.
414P Does adjuvant chemotherapy compared to surveillance improve recurrence free and overall survival in stage 3 rectal cancer patients?
Authors: S.M. Adeleke, S. George, J.R. Galante, M. Karova, L. Dahal, A. Choy, F. Elwes, N.F. Brown, J. Summers, A.A. Edwards, M. Durve, C. Mikropoulos, K. Lees, J. Hall, R. Shah, M. Hill, R. Raman, A. Clarke
Journal: Annals of Oncology (2021)
Successful treatment using a side-viewing duodenoscope for esophagojejunal varices on the jejunal side of the anastomosis site after total gastrectomy
Authors: Hirotsugu Maruyama, Akira Higashimori, Natsumi Maeda, Masaki Ominami, Shusei Fukunaga, Yasuaki Nagami, Yasuhiro Fujiwara
Journal: Endoscopy (2021)

Esophagojejunal varices arising after total gastrectomy and esophagojejunostomy are a rare complication of portal hypertension [1] [2] [3]. Endoscopic treatments can become challenging due to fibrosis and bleeding on the jejunal side after anastomosis. Few reports have documented the successful treatment of esophagojejunal varices after gastrectomy. We report a case of esophagojejunal variceal hemorrhage treated using a side-viewing duodenoscope.
456P Prognostic and predictive value of tumor-infiltrating lymphocytes in combination with systemic inflammatory markers in colon cancer
Authors: S.C. Efil, G. Güner, D.C. Guven, B. Çelikten, E. Çelebiyev, H. Taban, A. Akyol, S. Kilickap, Ş. Yalcin, Ö. Dizdar
Journal: Annals of Oncology (2021)
Looking Over the Drape—Anesthesiologists’ Volume and Surgical Outcomes—Reply
Authors: Julie Hallet, Angela Jerath, Rinku Sutradhar
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
LBA3 Pembrolizumab versus placebo after complete resection of high-risk stage II melanoma: Efficacy and safety results from the KEYNOTE-716 double-blind phase III trial
Authors: J.J. Luke, P. Rutkowski, P. Queirolo, M. Del Vecchio, J. Mackiewicz, V. Chiarion Sileni, L. de la Cruz Merino, M.A. Khattak, D. Schadendorf, G.V. Long, P.A. Ascierto, M. Mandala, F. De Galitiis, V. Sondak, R.A. Scolyer, J.M. Kirkwood, K. Chen, N. Ibrahim, S. Ahsan, A.M.M. Eggermont
Journal: Annals of Oncology (2021)
1176P Neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in patients with potentially resectable NSCLC: An open-label, single-arm, phase II trial
Authors: X. Zhu, L. Sun, N. Song, F. Sun, J. Yang, L. Duan, D. Zhao, W. He, J. Luo, H. Zhang, C. Wu, Y. Zhu, P. Zhang, G. Jiang
Journal: Annals of Oncology (2021)
265P Study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in combination with fulvestrant in patients with advanced hormone receptor positive HER2 negative breast cancer (HR+BC)
Authors: S.J. Howell, M.G. Krebs, S. Lord, L. Kenny, A. Bahl, G. Clack, E. Ainscow, H-T. Arkenau, J.L. Mansi, C. Palmieri, P. Richards, R. Jeselsohn, Z. Mitri, W.J. Gradishar, S. Sardesai, J. O'Shaughnessy, M. Lehnert, S. Ali, S. McIntosh, R.C. Coombes
Journal: Annals of Oncology (2021)
845P Incidence of second primary malignancies (SPM) in relapsed/refractory (r/r) B-cell non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM) patients in England
Authors: M. Miret, S. Lee, F.E. Vegni, P. Hindocha, L. Cirneanu, C. Lymperopoulou, E. Markov, S. Hitov
Journal: Annals of Oncology (2021)
Sodium–Glucose Cotransporter-2 Inhibitors Versus Glucagon-like Peptide-1 Receptor Agonists and the Risk for Cardiovascular Outcomes in Routine Care Patients With Diabetes Across Categories of Cardiovascular Disease
Authors: Elisabetta Patorno, Phyo T. Htoo, Robert J. Glynn, Sebastian Schneeweiss, Deborah J. Wexler, Ajinkya Pawar, Lily G. Bessette, Kristyn Chin, Brendan M. Everett, Seoyoung C. Kim
Journal: Annals of Internal Medicine (2021)

Background: Both sodium–glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in placebo-controlled trials of patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD). Objective: To evaluate whether SGLT2 inhibitors and GLP-1 RAs are associated with differential cardiovascular benefit among T2D patients with and without CVD. Design: Population-based cohort study. Setting: Medicare and 2 U.S. commercial claims data sets (April 2013 to December 2017). Participants: 1:1 propensity score–matched adult T2D patients with and without CVD (52 901 and 133 139 matched pairs) initiating SGLT2 inhibitor versus GLP-1 RA therapy. Measurements: Primary outcomes were myocardial infarction (MI) or stroke hospitalization and hospitalization for heart failure (HHF). Pooled hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, with 95% CIs, controlling for 138 preexposure covariates. Results: The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with a slightly lower risk for MI or stroke in patients with CVD (HR, 0.90 [95% CI, 0.82 to 0.98]; RD, −2.47 [CI, −4.45 to −0.50]) but similar risk in those without CVD (HR, 1.07 [CI, 0.97 to 1.18]; RD, 0.38 [CI, −0.30 to 1.07]). The initiation of SGLT2 inhibitor versus GLP-1 RA therapy was associated with reductions in HHF risk regardless of baseline CVD in patients with CVD (HR, 0.71 [CI, 0.64 to 0.79]; RD, −4.97 [CI, −6.55 to −3.39]) and in those without CVD (HR, 0.69 [CI, 0.56 to 0.85]; RD, −0.58 [CI, −0.91 to −0.25]). Limitation: Treatment selection was not randomized. Conclusion: Use of SGLT2 inhibitors versus GLP-1 RAs was associated with consistent reductions in HHF risk among T2D patients with and without CVD, although the absolute benefit was greater in patients with CVD. There were no large differences in risk for MI or stroke among T2D patients with and without CVD. Primary Funding Source: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School.
1591P Immune response after vaccination against SARS-COV-2 in lung cancer (LC) patients (p). Prospective study in the Medical Oncology Department at the Catalan Institute of Oncology-Badalona, Spain: COVID-lung vaccine
Authors: E. Felip, A. Hernandez, L. Notario, M. Cucurull, B. Quirant, M. Saigí, R. Gómez-Castellà, E. Estevez-Macas, S. Coll Fonollosa, P. Torres Bertral, E. Carcereny Costa, M. Domenech, A. Estival, A. López Paradís, A. Pous Badía, M. Romeo Marín, M.T. Moran Bueno
Journal: Annals of Oncology (2021)
993P Glycolytic tumor burden on pretreatment 18F-FDG PET/CT correlates with response and survival in metastatic NSCLC undergoing immune checkpoint inhibitors
Authors: S.B. Silva, C.W.D.S. Wanderley, J.F.G. Marin, M.P. de Macedo, E.C.T. do Nascimento;, F.F. Antonacio;, F.D.Q. Cunha;, G. de Castro
Journal: Annals of Oncology (2021)
Precision Medicine Approaches for Infantile-Onset Developmental and Epileptic Encephalopathies
Authors: Kenneth A. Myers, Ingrid E. Scheffer
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Epilepsy is an etiologically heterogeneous condition; however, genetic factors are thought to play a role in most patients. For those with infantile-onset developmental and epileptic encephalopathy (DEE), a genetic diagnosis is now obtained in more than 50% of patients. There is considerable motivation to utilize these molecular diagnostic data to help guide treatment, as children with DEEs often have drug-resistant seizures as well as developmental impairment related to cerebral epileptiform activity. Precision medicine approaches have the potential to dramatically improve the quality of life for these children and their families. At present, treatment can be targeted for patients with diagnoses in many genetic causes of infantile-onset DEE, including genes encoding sodium or potassium channel subunits, tuberous sclerosis, and congenital metabolic diseases. Precision medicine may refer to more intelligent choices of conventional antiseizure medications, repurposed agents previously used for other indications, novel compounds, enzyme replacement, or gene therapy approaches.