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Cardiovascular Outcomes in Aortopathy: GenTAC Registry of Genetically Triggered Aortic Aneurysms and Related Conditions.

J Am Coll Cardiol 2022 May;79(21):2069-2081

Division of Cardiology, Weill Cornell Medicine, New York, New York, USA.

Background: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.

Objectives: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.

Methods: The GenTAC study had a retrospective/prospective design. Read More

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Efficacy of bivalent vaccines of porcine circovirus type 2 and in specific pathogen-free pigs challenged with porcine circovirus type 2d.

J Vet Sci 2022 May;23(3):e49

Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

Background: Porcine circovirus type 2 (PCV2) and (MHP) are economically significant pathogens in the pig industry. The use of combined vaccines against PCV2 and MHP is one of the most effective ways of protecting pigs from both diseases, and it has become a part of general management.

Objectives: This study evaluated the efficacy of two new bivalent vaccines of PCV2 and MHP (Myco-X and Myco-XD) in SPF pigs. Read More

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Tumor-associated Tregs obstruct antitumor immunity by promoting T cell dysfunction and restricting clonal diversity in tumor-infiltrating CD8+ T cells.

J Immunother Cancer 2022 May;10(5)

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

Background: Accumulation of regulatory T cells (Treg) has been described to often correlate with poor prognosis in many solid tumors. How Treg presence impinges on limited functionality and clonal composition of tumor-associated CD8 +T cells has important implications for their therapeutic targeting in the tumor microenvironment. In the present study, we investigated how accumulation of Tregs contributes to T cell dysfunction and clonal constriction of tumor-infiltrating CD8 +T cells. Read More

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Spatial transcriptomics of macrophage infiltration in non-small cell lung cancer reveals determinants of sensitivity and resistance to anti-PD1/PD-L1 antibodies.

J Immunother Cancer 2022 May;10(5)

Department of Medecine, Institut Bergonié, Bordeaux, France

Background: Tumor-associated macrophages (TAMs) having immunosuppressive properties are one of the most abundant immune cells in the tumor microenvironment (TME). Preclinical studies have highlighted the potential role of TAMs in resistance to immune checkpoint blockers (ICBs). Here, we investigated the predictive value of TAM infiltration in patients with non-small cell lung cancer (NSCLC) treated with ICBs and characterized their transcriptomic profiles. Read More

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An emerging phenotype of pulmonary arterial hypertension patients carrying variants.

Eur Respir J 2022 May 26. Epub 2022 May 26.

Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.

Introduction: The phenotype of pulmonary arterial hypertension (PAH) patients carrying pathogenic variants remains mostly unknown.

Methods: We report the genetic analysis findings, characteristics and outcomes of patients with heritable PAH carrying variants from the French Pulmonary Hypertension Network.

Results: Twenty patients and eight unaffected relatives were identified. Read More

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Excess ventilation and exertional dyspnoea in heart failure and pulmonary hypertension.

Eur Respir J 2022 May 26. Epub 2022 May 26.

Professor Emeritus, John Rankin Laboratory of Pulmonary Medicine, Dept of Population Health Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Increased ventilation relative to metabolic secondary to alveolar hyperventilation and/or increased physiological dead space (excess ventilation) is a key cause of exertional dyspnoea. Excess ventilation has assumed a prominent role in the functional assessment of patients with heart failure (HF) with reduced (r) or preserved (p) ejection fraction, pulmonary arterial hypertension (PAH), and chronic thromboembolic PH (CTEPH). We herein provide the key pieces of information to the caring physician to a) gain unique insights into the seeds of patients' shortness of breath, and b) develop a rationale for therapeutically lessening excess ventilation to mitigate this distressing symptom. Read More

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Peptide location fingerprinting identifies species- and tissue-conserved structural remodelling of proteins as a consequence of ageing and disease.

Matrix Biol 2022 May 23. Epub 2022 May 23.

Divisions of Cell Matrix Biology & Regenerative Medicine and Cardiovascular Sciences, School of Biological Science, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. Electronic address:

Extracellular matrix (ECM) in the intervertebral disc (IVD), lung and artery are thought to undergo the age-dependant accumulation of damage by chronic exposure to mechanisms such as reactive oxygen species, proteases and glycation. It is unknown whether this damage accumulation is species-dependant (via differing lifespans and hence cumulative exposures) or whether it can influence the progression of age-related diseases such as atherosclerosis. Peptide location fingerprinting (PLF) is a new proteomic analysis method, capable of the non-targeted identification of structure-associated changes within proteins. Read More

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Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer.

Clin Immunol 2022 May 23:109045. Epub 2022 May 23.

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, PR China. Electronic address:

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Read More

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Characterization of phospholipid-modified lung surfactant in vitro and in a neonatal ARDS model reveals anti-inflammatory potential and surfactant lipidome signatures.

Eur J Pharm Sci 2022 May 23:106216. Epub 2022 May 23.

Division of Immunobiophysics, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany; Kiel Nano, Surface and Interface Science KiNSIS, Kiel University, Germany. Electronic address:

A strong inflammatory immune response drives the lung pathology in neonatal acute respiratory distress syndrome (nARDS). Anti-inflammatory therapy is therefore a promising strategy for improved treatment of nARDS. We demonstrate a new function of the anionic phospholipids POPG, DOPG, and PIP2 as inhibitors of IL-1β release by LPS and ATP-induced inflammasome activation in human monocyte-derived and lung macrophages. Read More

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Halofuginone micelle nanoparticles eradicate Nrf2-activated lung adenocarcinoma without systemic toxicity.

Free Radic Biol Med 2022 May 23. Epub 2022 May 23.

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan. Electronic address:

The Keap1-Nrf2 system is the master regulator of the cellular response against oxidative and xenobiotic stresses. Constitutive activation of Nrf2 is frequently observed in various types of cancers. Nrf2 hyperactivation induces metabolic reprogramming in cancer cells, which supports the increased energy demand required for rapid proliferation and confers high-level resistance against anticancer radio/chemotherapy. Read More

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Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Biochimie 2022 May 23. Epub 2022 May 23.

Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Golestan University of Medical Sciences, Babol, Iran. Electronic address:

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Read More

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Joint effect of indoor size-fractioned particulate matters and black carbon on cardiopulmonary function and relevant metabolic mechanism: A panel study among school children.

Environ Pollut 2022 May 23:119533. Epub 2022 May 23.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, 100191, China. Electronic address:

Indoor particulate matter (PM) and black carbon (BC) are associated with adverse cardiopulmonary effect. However, the cumulative and interactive effects of the mixture of size-fractioned PMs and BC on cardiopulmonary function are not well understood, and its underlying biological mechanisms remain unclear. This repeated-measure study was conducted to assess the joint cardiopulmonary effect and metabolic mechanisms of multiple-size particles and BC among 46 children. Read More

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Exposure to greenspace and cancer incidence, prevalence, and mortality: A systematic review and meta-analyses.

Sci Total Environ 2022 May 23:156180. Epub 2022 May 23.

Univ Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, F-35000 Rennes, France. Electronic address:

We conducted a systematic review and meta-analysis of the available literature on the association between greenspace exposure and all-sites and site-specific cancer incidence, prevalence, and mortality in adults. We searched PubMed, Scopus, and Web of Science for original articles published, without language restriction until September 2021. We assessed the risk of bias in each study and the overall quality of evidence for exposure-outcome pairs that were reported in two or more studies. Read More

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Acute effects of ambient temperature on lung function of a panel of school children living in Dhaka, Bangladesh.

Sci Total Environ 2022 May 23:156139. Epub 2022 May 23.

National Institute of Environmental Sciences, 16-2 Onogawa, Tsukuba 305-8506, Japan.

Introduction: Short-term exposure to ambient temperature plays a significant role in human health. However, studies examining ambient temperature and lung function are scarce in locations with a tropical environment. To address this research gap, the current study investigated the effects of short-term ambient temperature on lung function in children and seasonal variation in this association in Dhaka, Bangladesh. Read More

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Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial.

Radiother Oncol 2022 May 23. Epub 2022 May 23.

CRUK & UCL Cancer Trials Centre, London, United Kingdom.

Background: Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival.

Patients And Method: SCORAD is a randomised trial of 686 patients comparing a single dose of 8Gy radiotherapy with 20Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). Read More

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Uncertainty-guided man-machine integrated patient-specific quality assurance.

Radiother Oncol 2022 May 23. Epub 2022 May 23.

School of Automation, Central South University, Changsha, Peoples' Republic of China. Electronic address:

Purpose: Providing the confidence level (Uncertainty) of prediction results and guiding patient-specific quality assurance (pQA) can enhance the safety of AI (Artificial intelligence)-based automatic pQA models. However, even state-of-the-art automatic pQA models can only predict the gamma passing rate (GPR) and cannot quantify the prediction uncertainty, limiting the safe clinical translation of these models. This study aims to develop an uncertainty-guided man-machine integrated pQA (UgMi-pQA) method to address this issue. Read More

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Machine learning to refine prognostic and predictive nodal burden thresholds for post-operative radiotherapy in completely resected stage III-N2 non-small cell lung cancer.

Radiother Oncol 2022 May 23. Epub 2022 May 23.

Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, United States. Electronic address:

Background: The role of post-operative radiotherapy (PORT) for completely resected N2 non-small-cell lung cancer (NSCLC) is controversial in light of recent randomized data. We sought to utilize machine learning to identify a subset of patients who may still benefit from PORT based on extent of nodal involvement.

Materials/methods: Patients with completely resected N2 NSCLC were identified in the National Cancer Database. Read More

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PROPHYLACTIC EFFECT OF NITRIC OXIDE DONORS ON RAT MODELS OF EGFR INHIBITORS-INDUCED CUTANEOUS TOXICITIES.

J Invest Dermatol 2022 May 23. Epub 2022 May 23.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China. Electronic address:

Epidermal growth factor receptor inhibitors (EGFRIs) have been established as first-line standard-of-care therapies for non-small cell lung cancer (NSCLC) but are frequently accompanied by adverse dermatological effects, in particular, acneiform rash. There is no effective clinical intervention, partially because of its poorly understood etiology. Here, we show that inhibition of EGFR initiated keratinocyte HaCaT cell cycle arrest and apoptosis, which fueled a robust secondary inflammatory response. Read More

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NLRP3 inflammasome contributes to endothelial dysfunction in angiotensin II-induced hypertension in mice.

Microvasc Res 2022 May 23:104384. Epub 2022 May 23.

Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Institute of Life Sciences, Chongqing Medical University, Chongqing, PR China; Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address:

Aims: Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension.

Materials And Methods: We analyzed blood pressure and vascular function of wild-type (WT) and Nlrp3 knockout (Nlrp3) mice, treated with Ang II. Read More

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The contribution of the neuroendocrine system to adaption after repeated daily ozone exposure in rats.

Toxicol Appl Pharmacol 2022 May 23:116085. Epub 2022 May 23.

Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States of America. Electronic address:

Ozone-induced lung injury/inflammation dissipates despite continued exposure for 3 or more days; however, the mechanisms of adaptation/habituation remain unclear. Since ozone effects are mediated through adrenal-derived stress hormones, which also regulate longevity of centrally-mediated stress response, we hypothesized that ozone-adaptation is linked to diminution of neuroendocrine stress-axes activation and glucocorticoid levels. Male Wistar-Kyoto-rats (12-week-old) were injected with vehicle or a therapeutically-relevant dexamethasone dose (0. Read More

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Inflammation resolution in environmental pulmonary health and morbidity.

Toxicol Appl Pharmacol 2022 May 23:116070. Epub 2022 May 23.

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address:

Inflammation and resolution are dynamic processes comprised of inflammatory activation and neutrophil influx, followed by mediator catabolism and efferocytosis. These critical pathways ensure a return to homeostasis and promote repair. Over the past decade research has shown that diverse mediators play a role in the active process of resolution. Read More

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A Novel LncRNA PTH-AS Upregulates Interferon-Related DNA damage resistance Signature genes and Promotes Metastasis in Human Breast Cancer Xenografts.

J Biol Chem 2022 May 23:102065. Epub 2022 May 23.

Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.

Long non-coding RNAs (lncRNAs) are important tissue-specific regulators of gene expression, and their dysregulation can induce aberrant gene expression leading to various pathological conditions, including cancer. Although many lncRNAs have been discovered by computational analysis, most of these are as yet unannotated. Herein, we describe the nature and function of a novel lncRNA detected downstream of the human parathyroid hormone (PTH) gene in both extremely rare ectopic PTH-producing retroperitoneal malignant fibrous histiocytoma and parathyroid tumors with PTH overproduction. Read More

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A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent anti-tumor activity against non-small cell lung cancers.

J Biol Chem 2022 May 23:102063. Epub 2022 May 23.

Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address:

Tumor angiogenesis is closely associated with the metastasis and progression of non-small cell lung cancer (NSCLC), a highly vascularized solid tumor. However, novel therapeutics are lacking for the treatment of this cancer. Here, we developed a series of 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazol analogs (6a-6x) as colchicine binding site-tubulin inhibitors, aiming to find a novel promising drug candidate for NSCLC treatment. Read More

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Ginsenoside CK induces apoptosis in triple-negative breast cancer cells by targeting glutamine metabolism.

Biochem Pharmacol 2022 May 23:115101. Epub 2022 May 23.

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China. Electronic address:

Breast cancer (BC) has replaced lung cancer as the most common cancer worldwide. Ginsenoside CK (CK) can effectively inhibit triple-negative breast cancer (TNBC), the occurrence and development of which are associated with glutamine addiction. However, the connection between CK and glutamine metabolism in TNBC proliferation and the mechanism of cell death induction remains unclear. Read More

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Pulmonary Heterotopic Ossification Simulating a Pulmonary Hamartoma: Imaging and Pathologic Findings and Differential Diagnosis.

Korean J Radiol 2022 Jun;23(6):688-690

Department of Radiology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (SKKU-SOM), Changwon, Korea.

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Potential Overdiagnosis with CT Lung Cancer Screening in Taiwanese Female: Status in South Korea.

Korean J Radiol 2022 Jun;23(6):571-573

National Cancer Control Institute, National Cancer Center, Goyang, Korea.

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Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

Lancet Oncol 2022 May 18. Epub 2022 May 18.

Population Health Sciences, University of Bristol, Bristol, UK.

Background: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level.

Methods: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Read More

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A drug-responsive multicellular human spheroid model to recapitulate drug-induced pulmonary fibrosis.

Biomed Mater 2022 May 26. Epub 2022 May 26.

Department of Bioengineering / EgeSAM-Ege University Translational Pulmonary Research Center, Ege University, Bornova, Izmir, 35040, TURKEY.

Associated with a high mortality rate, pulmonary fibrosis (PF) is the end stage of several interstitial lung diseases. Although many factors are linked to PF progression, initiation of the fibrotic process remains to be studied. Current research focused on generating new strategies to gain a better understanding of the underlying disease mechanism as the animal models remain insufficient to reflect human physiology. Read More

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Is there a need for individualized adjustment of electrode belt position during EIT-guided titration of positive end-expiratory pressure?

Physiol Meas 2022 May 26. Epub 2022 May 26.

Institute of Technical Medicine, Furtwangen University, Jakob-Kienzle-Strasse 17, Villingen-Schwenningen, D-78054, GERMANY.

Objective: The aim of the present study was to evaluate the variation of tidal volume-to-impedance ratio (VT/ZT) during positive end-expiratory pressure (PEEP) titration with electrical impedance tomography (EIT) measurement.

Approach: Forty-two patients with acute respiratory distress syndrome were retrospectively analyzed. An incremental and subsequently a decremental PEEP trial were performed with steps of 2 cmH2O and duration of 2 minutes per step during volume-controlled ventilation with decelerating flow. Read More

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