tbuckley/cabot-search huggingface dataset:
TGR5 deficiency activates antitumor immunity in non-small cell lung cancer via restraining M2 macrophage polarization
Authors: Lifang Zhao, Hongyan Zhang, Xueqing Liu, Shan Xue, Dongfang Chen, Jing Zou, Handong Jiang
Journal: Acta Pharmaceutica Sinica B (2021)

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.
Allergen shedding in human milk: Could it be key for immune system education and allergy prevention?
Authors: Patricia Macchiaverni, Akila Rekima, Lieke van den Elsen, Harald Renz, Valerie Verhasselt
Journal: Journal of Allergy and Clinical Immunology (2021)

In addition to being a source of nutrients for the developing newborn, human milk contains thousands of bioactive compounds, which influence infant health in the short-term as exemplified by its major benefits on infectious disease prevention. Many of the human milk compounds also have the required characteristics to instruct immune development and guide long-term health. Prebiotics, probiotics, and varied antimicrobial molecules all have the potential to shape the composition and function of the establishing gut microbiota, which is known to be a major determinant of immune function. Another and less explored way human milk can instruct long-term immunity is through antigen shedding. Here, we will review the evidence that antigens from maternal environment and more specifically from allergen sources are found in human milk. We will discuss data from rodent models and birth cohorts showing that allergen shedding in breast milk may influence long-term allergy risk. We will uncover the variables that may underlie heterogeneity in oral tolerance induction and allergy prevention in children breast-fed by allergen-exposed mothers. We will focus on the parameters that control antigen transfer to breast milk, on the unique biological characteristics of allergens in breast milk, and on the milk bioactive compounds that were found to influence immune response in offspring. We propose this understanding is fundamental to guide maternal interventions leading to lifelong allergen tolerance.
P30-3 Clinical experience of tumour lysis syndrome in patients with extensive disease small cell lung cancer
Authors: Megumi Kawamoto, Yoshiyuki Sano, Yoshitaka Zenke, Kenji Kawasumi, Hiroki Izumi, Kaname Nosaki, Takaya Ikeda, Hibiki Udagawa, Shingo Matsumoto, Kiyotaka Yoh, Koichi Goto, Toshikatsu Kawasaki
Journal: Annals of Oncology (2021)
Abstract 302: Chronic Neuropathic Pain Increases Susceptibility to Myocardial Ischemia/Reperfusion Injury by Sirt1 Carbonylative Inactivation
Authors: Chen Li, Jingrun Yang, Lu Yu, Chunhu Gu, Heng Ma
Journal: Circulation Research (2017)

Pain is not a symptom that exists alone, but whether chronic pain enhances susceptibility to myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanisms remain unknown. Reactive aldehydes contribute to pain pathologies and cardiac injury, suggesting that aldehyde dehydrogenase (ALDH2), which detoxifies aldehydes, may regulate chronic pain related MI/R injury. In this study, chronic neuropathic pain was induced by chronic compression of the dorsal root ganglion (CCD). CCD for 2 weeks, ALDH2 KO or wild-type (WT) littermates were subjected to in vivo MI/R. CCD-WT mice exhibited heightened nociception and correlated with circulating aldehyde (4-HNE) accumulation and cardiac protein carbonylation. CCD induced 4-HNE overload provoked cardiac SIRT1 carbonylative inactivation and impairment the cardioprotection of LKB1-mediated AMPK activation, which resulting in enhanced MI/R injury and higher mortality compare with pain free WT mice. Chronic neuropathic pain enhanced susceptibility to MI/R injury was further exacerbated by ALDH2 deficiency in which associated with more impaired SIRT1-LKB1-AMPK signaling. However, treatment of CCD-WT mice with ALDH2-selective activator (Alda-1) or cardiac specific ALDH2 upregulation by AAV9-cTNT-mediated gene delivery significantly reduced chronic neuropathic pain-induced SIRT1 carbonylative inactivation and decreased MI/R injury (minor infarct size, less apoptosis, and elevated cardiac function). These results strongly suggest that elevated reactive aldehyde concentration, like that observed in the presence of chronic pain, may render cardiomyocytes more susceptible to MI/R injury by SIRT1 carbonylative inactivation and impairment the cardioprotection of LKB1-mediated AMPK activation. ALDH2 activation blocked reactive aldehyde overproduction induced carbonyl stress and attenuated myocardial ischemic vulnerability in chronic pain individual. Keywords: chronic pain; myocardial ischemia/reperfusion; ALDH2; 4-HNE; carbonylation
Progress Toward Hepatitis B Control — World Health Organization European Region, 2016–2019
Authors: Nino Khetsuriani, Liudmila Mosina, Pierre Van Damme, Antons Mozalevskis, Siddhartha Datta, Rania A. Tohme
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In 2019, an estimated 14 million persons in the World Health Organization (WHO) European Region* (EUR) were chronically infected with hepatitis B virus (HBV), and approximately 43,000 of these persons died from complications of chronic HBV infection (1). In 2016, the WHO Regional Office for Europe set hepatitis B control program targets for 2020, including 1) ≥90% coverage with 3 doses of hepatitis B vaccine (HepB3), 2) ≥90% coverage with interventions to prevent mother-to-child transmission (MTCT) of HBV,
Acute Febrile Neutrophilic Dermatosis
Authors: Ali M. Ayyash, Rahul Sampath
Journal: New England Journal of Medicine (2021)

A 46-year-old woman presented with an erythematous lesion on her thumb. Despite treatment with an antibiotic agent, the lesion increased in size, and painful raised lesions developed on her arms and other areas. A biopsy was performed, and a diagnosis of acute febrile neutrophilic dermatosis was made.
Mental health care in Eastern Europe and Central Asia: An analysis of needs and a call for greater investment
Authors: Kimberly Hook, Sergiy Bogdanov
Journal: The Lancet Regional Health - Europe (2021)

Over the past decade, there has been increased attention to global mental health, which emphasizes improving access to quality mental health care in order to reduce the worldwide treatment gap. However, Eastern European and Central Asian countries and their specific mental health needs have largely been under-emphasized, evidenced by a dearth in literature and funding. Here, we provide an overview of the mental health needs in Ukraine and its challenges with quality care provision as a key example in highlighting these gaps, then broaden our discussion to include parallels with other countries in the Eastern European and Central Asian region. We describe the unique strengths relative to mental health care provision that are present in Eastern Europe and Central Asia and suggest the importance of post-graduate training, regional collaboration, and capacity building specific to research management as strategies to address the current challenges. We stress that greater investment from funders, government, and the global mental health community are needed to improve the current mental health situation in Ukraine, specifically, and Eastern Europe and Central Asia, broadly. We argue that greater attention to Eastern Europe and Central Asia is needed to fully advance the agenda of the global mental health field.
Association between atopic dermatitis and hypertension: a systematic review and meta‐analysis*
Authors: M. Yousaf, M. Ayasse, A. Ahmed, E.C. Gwillim, S.R. Janmohamed, A. Yousaf, K.R. Patel, J.P. Thyssen, J.I. Silverberg
Journal: British Journal of Dermatology (2021)

Previous studies have found conflicting results about the association of atopic dermatitis (AD) with hypertension.To determine whether AD and AD severity are associated with hypertension.A systematic review was performed of published studies in Ovid MEDLINE, Embase, Scopus, Web of Science, and GREAT (Global Resource for EczemA Trials) databases. At least two reviewers conducted title/abstract, full-text review and data extraction. Quality of evidence was assessed using the Newcastle-Ottawa Scale.Fifty-one studies met the inclusion criteria and 19 had sufficient data for meta-analysis. AD was associated with higher odds of hypertension compared with healthy controls [increased in nine of 16 studies; pooled prevalence 16·4% vs. 13·8%; random-effects regression, pooled unadjusted odds ratio (OR) 1·16, 95% confidence interval (CI) 1·04-1·30], but lower odds of hypertension compared with psoriasis [decreased in five of eight studies; 15·4% vs. 24·8% (OR 0·53, 95% CI 0·37-0·76)]. In particular, moderate-to-severe AD was associated with hypertension compared with healthy controls [increased in four of six studies; 24·9% vs. 14·7% (OR 2·33, 95% CI 1·10-4·94)]. Hypertension was commonly reported as an adverse event secondary to AD treatments, particularly systemic ciclosporin A. Limitations include lack of longitudinal studies or individual-level data, and potential confounding.AD, particularly moderate-to-severe disease, was associated with increased hypertension compared with healthy controls, but with lower odds than for psoriasis.
PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity
Authors: Joseph M. Gozgit, Melissa M. Vasbinder, Ryan P. Abo, Kaiko Kunii, Kristy G. Kuplast-Barr, Bin Gui, Alvin Z. Lu, Jennifer R. Molina, Elena Minissale, Kerren K. Swinger, Tim J. Wigle, Danielle J. Blackwell, Christina R. Majer, Yue Ren, Mario Niepel, Zacharenia A. Varsamis, Sunaina P. Nayak, Ellen Bamberg, Jan-Rung Mo, W. David Church, Ahmed S.A. Mady, Jeff Song, Luke Utley, Patricia E. Rao, Timothy J. Mitchison, Kevin W. Kuntz, Victoria M. Richon, Heike Keilhack
Journal: Cancer Cell (2021)
Reply: Spermatogonia stem cell technology: a new avenue for all age Klinefelter patients
Authors: Nicholas A Deebel, Guillermo Galdon, Nima Pourhabibi Zarandi, Kimberly Stogner-Underwood, Stuart Howards, James Lovato, Stanley Kogan, Anthony Atala, Yanhe Lue, Hooman Sadri-Ardekani
Journal: Human Reproduction Update (2021)

Sir, As the authors for the manuscript, 'Age-related presence of spermatogonia in patients with Klinefelter syndrome: a systematic review and meta-analysis', we would like to address the comments, from Winge and Almstrup's letter (Winge and Almstrup, 2021). As correctly summarized by Winge and Almstrup, the primary endpoint of spermatogonial presence by binary age group was recalculated and found to be consistent with our original findings: that spermatogonia were found in 100%, 83%, 43% and 49% of the biopsies from patients with Klinefelter syndrome (KS) in the fetal/infantile, prepubertal, peripubertal/adolescent and adult groups, respectively. A secondary endpoint and a particular area of interest is the percentage of patients that were found to be spermatozoa negative and spermatogonia positive on biopsy. As mentioned in page 63 in the original manuscript, 'Secondary analysis was conducted to examine patients with both spermatozoa and spermatogonia data present'. Therefore, studies or patients within studies...
Serious Infections in Children Born to Mothers With Inflammatory Bowel Disease With In Utero Exposure to Thiopurines and Anti-Tumor Necrosis Factor
Authors: Antoine Meyer, Marion Taine, Jérôme Drouin, Alain Weill, Franck Carbonnel, Rosemary Dray-Spira
Journal: Clinical Gastroenterology and Hepatology (2021)
Omission of Radiotherapy in Older Adults With Early-Stage Breast Cancer—Reply
Authors: Mudit Chowdhary, Arpit M. Chhabra, Sachin R. Jhawar
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Netupitant/Palonosetron: A Review in Chemotherapy-Induced Nausea and Vomiting
Authors: Matt Shirley
Journal: Drugs (2021)

Netupitant/palonosetron (NEPA; Akynzeo®), available in oral and intravenous (IV) formulations, is a fixed-dose combination of the neurokinin 1 (NK1) receptor antagonist netupitant (or the prodrug, fosnetupitant, in the IV formulation) and the second-generation serotonin 3 (5-HT3) receptor antagonist palonosetron. Administered as a single dose, (fos)netupitant/palonosetron (in combination with dexamethasone) is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in adults. In clinical trials, (fos)netupitant/palonosetron plus dexamethasone was associated with high complete response rates (no emesis and no rescue medication) in the acute, delayed and overall phases in patients receiving highly or moderately emetogenic chemotherapy, with efficacy maintained over multiple cycles. Further, oral netupitant/palonosetron was found to be superior to palonosetron and non-inferior to aprepitant plus granisetron in preventing CINV in individual trials. Both the oral and IV formulations of the drug combination are well tolerated. The fixed-dose combination is concordant with guideline recommendations and provides a simple and convenient option for prophylaxis against acute and delayed CINV in patients receiving highly or moderately emetogenic chemotherapy.Chemotherapy-induced nausea and vomiting (CINV) is a common problem during cancer treatment. Netupitant/palonosetron (NEPA; Akynzeo®) is a fixed-dose combination of two drugs (netupitant, a neurokinin 1 receptor antagonist; and palonosetron, a serotonin 3 receptor antagonist) which target two different signalling pathways involved in the induction of vomiting. Approved for use in the prevention of acute and delayed CINV in adults, netupitant/palonosetron is given orally or via intravenous infusion as a single dose prior to chemotherapy. In clinical trials, high proportions of patients who received netupitant/palonosetron (used in combination with the corticosteroid dexamethasone) prior to chemotherapy reported no vomiting, no requirement for rescue medication, and no significant nausea in the 5 days post chemotherapy. Both the oral and intravenous formulations of the drug combination are well tolerated. In conclusion, netupitant/palonosetron is a simple, convenient and effective drug combination for the prevention of acute and delayed CINV in patients receiving chemotherapy that has a moderate to high potential to cause nausea and vomiting.
Strategies to Overcome the Market Dominance of Hospitals
Authors: Benjamin S. Kornitzer
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Natriuretic peptide receptor B maintains heart rate and sinoatrial node function via cyclic GMP-mediated signalling
Authors: Tristan W Dorey, Martin Mackasey, Hailey J Jansen, Megan D McRae, Loryn J Bohne, Yingjie Liu, Darrell D Belke, Logan Atkinson, Robert A Rose
Journal: Cardiovascular Research (2021)

Abstract Aims Heart rate (HR) is a critical indicator of cardiac performance that is determined by sinoatrial node (SAN) function and regulation. Natriuretic peptides, including C-type NP (CNP), have been shown to modulate ion channel function in the SAN when applied exogenously. CNP is the only NP that acts as a ligand for natriuretic peptide receptor-B (NPR-B). Despite these properties, the ability of CNP and NPR-B to regulate HR and intrinsic SAN automaticity in vivo, and the mechanisms by which it does so, are incompletely understood. Thus, the objective of this study was to determine the role of NPR-B signalling in regulating HR and SAN function. Methods and results We have used NPR-B deficient mice (NPR-B+/−) to study HR regulation and SAN function using telemetry in conscious mice, intracardiac electrophysiology in anaesthetized mice, high-resolution optical mapping in isolated SAN preparations, patch-clamping in isolated SAN myocytes, and molecular biology in isolated SAN tissue. These studies demonstrate that NPR-B+/− mice exhibit slow HR, increased corrected SAN recovery time, and slowed SAN conduction. Spontaneous AP firing frequency in isolated SAN myocytes was impaired in NPR-B+/− mice due to reductions in the hyperpolarization activated current (If) and L-type Ca2+ current (ICa,L). If and ICa,L were reduced due to lower cGMP levels and increased hydrolysis of cAMP by phosphodiesterase 3 (PDE3) in the SAN. Inhibiting PDE3 or restoring cGMP signalling via application of 8-Br-cGMP abolished the reductions in cAMP, AP firing, If, and ICa,L, and normalized SAN conduction, in the SAN in NPR-B+/− mice. NPR-B+/− mice did not exhibit changes in SAN fibrosis and showed no evidence of cardiac hypertrophy or changes in ventricular function. Conclusions NPR-B plays an essential physiological role in maintaining normal HR and SAN function by modulating ion channel function in SAN myocytes via a cGMP/PDE3/cAMP signalling mechanism.
Abstract 10799: Mean Platelet Volume and Long-Term Cardiovascular Outcomes in Patients With Stable Coronary Artery Disease
Authors: Hideki Wada, Tomotaka Dohi, Katsumi Miyauchi, Mitsuhiro Takeuchi, Norihito Takahashi, Manabu Ogita, Takatoshi Kasai, Shinya Okazaki, Satoru Suwa, Hiroyuki Daida
Journal: Circulation (2018)

Introduction: Although an elevated mean platelet volume (MPV) has been associated with poor clinical outcomes after acute coronary syndrome (ACS), the association between MPV and long-term cardiova...
Overexpression of CD200 is a stem cell-specific mechanism of immune evasion in AML
Authors: Shelley Herbrich, Natalia Baran, Tianyu Cai, Connie Weng, Marisa J L Aitken, Sean M Post, Jared Henderson, Chunhua Shi, Ondrej Havranek, Guillame Richard-Carpentier, Guy Sauvageau, Keith Baggerly, Gheath Al-Atrash, R Eric Davis, Naval Daver, Dongxing Zha, Marina Konopleva
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Acute myeloid leukemia (AML) stem cells (LSCs) are capable of surviving current standard chemotherapy and are the likely source of deadly, relapsed disease. While stem cell transplant serves as proof-of-principle that AML LSCs can be eliminated by the immune system, the translation of existing immunotherapies to AML has been met with limited success. Consequently, understanding and exploiting the unique immune-evasive mechanisms of AML LSCs is critical. Methods Analysis of stem cell datasets and primary patient samples revealed CD200 as a putative stem cell–specific immune checkpoint overexpressed in AML LSCs. Isogenic cell line models of CD200 expression were employed to characterize the interaction of CD200 + AML with various immune cell subsets both in vitro and in peripheral blood mononuclear cell (PBMC)–humanized mouse models. CyTOF and RNA-sequencing were performed on humanized mice to identify novel mechanisms of CD200-mediated immunosuppression. To clinically translate these findings, we developed a fully humanized CD200 antibody (IgG1) that removed the immunosuppressive signal by blocking interaction with the CD200 receptor while also inducing a potent Fc-mediated response. Therapeutic efficacy of the CD200 antibody was evaluated using both humanized mice and patient-derived xenograft models. Results Our results demonstrate that CD200 is selectively overexpressed in AML LSCs and is broadly immunosuppressive by impairing cytokine secretion in both innate and adaptive immune cell subsets. In a PBMC-humanized mouse model, CD200 + leukemia progressed rapidly, escaping elimination by T cells, compared with CD200 − AML. T cells from mice with CD200 + AML were characterized by an abundance of metabolically quiescent CD8 + central and effector memory cells. Mechanistically, CD200 expression on AML cells significantly impaired OXPHOS metabolic activity in T cells from healthy donors. Importantly, CD200 antibody therapy could eliminate disease in the presence of graft-versus-leukemia in immune competent mice and could significantly improve the efficacy of low-intensity azacitidine/venetoclax chemotherapy in immunodeficient hosts. Conclusions Overexpression of CD200 is a stem cell–specific marker that contributes to immunosuppression in AML by impairing effector cell metabolism and function. CD200 antibody therapy is capable of simultaneously reducing CD200-mediated suppression while also engaging macrophage activity. This study lays the groundwork for CD200-targeted therapeutic strategies to eliminate LSCs and prevent AML relapse.