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PhosIDN: an integrated deep neural network for improving protein phosphorylation site prediction by combining sequence and protein-protein interaction information.

Bioinformatics 2021 Jul 28. Epub 2021 Jul 28.

School of Information Science and Technology, University of Science and Technology of China, Hefei AH230027, China.

Motivation: Phosphorylation is one of the most studied post-translational modifications, which plays a pivotal role in various cellular processes. Recently, deep learning methods have achieved great success in prediction of phosphorylation sites, but most of them are based on convolutional neural network that may not capture enough information about long-range dependencies between residues in a protein sequence. In addition, existing deep learning methods only make use of sequence information for predicting phosphorylation sites, and it is highly desirable to develop a deep learning architecture that can combine heterogeneous sequence and protein-protein interaction (PPI) information for more accurate phosphorylation site prediction. Read More

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Magnetic anisotropy and critical behavior of the quaternary van der Waals ferromagnetic material CrGeSiTe.

J Phys Condens Matter 2021 Jul 28. Epub 2021 Jul 28.

Beijing National Laboratory for Condensed Matter Physics, Chinese Academy of Sciences Institute of Physics, Institute of Physics Chinese Academy of Sciences, Beijing 100190, Beijing, 100190, CHINA.

Recently, two-dimensional ferromagnetism in the family of Chromium compounds CrXTe(X=Si, Ge) has attracted a broad research interest. Despite the structural similarity in CrTeoctahedra, the size effect of inserted Ge or Si dimer contributes to significant differences in magnetism. Here, we report a new family of quaternary van der Waals ferromagnetic material CrGeSiTe(δ<0. Read More

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Equivalent time active cavitation imaging.

Phys Med Biol 2021 Jul 28. Epub 2021 Jul 28.

1 Engineering Physics Department, Polytechnique Montreal, Montreal, Quebec, CANADA.

Rationale: Despite the development of a large number of neurologically active drugs, brain diseases are difficult to treat due to the inability of many drugs to penetrate the blood-brain barrier. High-intensity focused ultrasound blood-brain barrier opening in a site-specific manner could significantly expand the spectrum of available drug treatments. However, without monitoring, brain damage and off target effects can occur during these treatments. Read More

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Metabolically controlled histone H4K5 acylation/acetylation ratio drives BRD4 genomic distribution.

Cell Rep 2021 Jul;36(4):109460

CNRS UMR 5309/INSERM U1209/Université Grenoble-Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France; Pôle Franco-Chinois de Recherche en Sciences du Vivant et Génomique, 200025 Shanghai, China. Electronic address:

In addition to acetylation, histones are modified by a series of competing longer-chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions hinder our understanding of histone acylations' specific roles. Read More

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Emodin alleviates hypertrophic scar formation by suppressing macrophage polarization and inhibiting the Notch and TGF-β pathways in macrophages.

Braz J Med Biol Res 2021 23;54(8):e11184. Epub 2021 Jul 23.

Department of Plastic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. Read More

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Single Adrenal Metastasis From Prostate Cancer Detected by 68Ga-PSMA PET/CT and Confirmed by Biopsy: A Case Report.

Clin Nucl Med 2021 Jul 26. Epub 2021 Jul 26.

From the Departments of Nuclear Medicine Clinical Oncology Pathologic Anatomy, A.C.Camargo Cancer Center, São Paulo, Brazil.

Abstract: This image demonstrates an unusual presentation of an adrenal metastasis from prostate cancer detected by 68Ga-prostate-specific membrane antigen PET/CT and confirmed by biopsy. A 68-year-old man with prostate cancer persisted with elevated levels of prostate-specific antigen after radical prostatectomy. Imaging identified a single abnormal uptake in the left adrenal gland. Read More

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Loss of the mitochondrial phosphate carrier SLC25A3 induces remodeling of the cardiac mitochondrial protein acylome.

Am J Physiol Cell Physiol 2021 Jul 28. Epub 2021 Jul 28.

Division of Pediatric Cardiology, Department of Pediatrics, grid.189967.8Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, GA, United States.

Mitochondria are recognized as signaling organelles because, under stress, mitochondria can trigger various signaling pathways to coordinate the cell's response. The specific pathway(s) engaged by mitochondria in response to mitochondrial energy defects in vivo and in high-energy tissues like the heart are not fully understood. Here, we investigated cardiac pathways activated in response to mitochondrial energy dysfunction by studying mice with cardiomyocyte-specific loss of the mitochondrial phosphate carrier (SLC25A3), an established model that develops cardiomyopathy as a result of defective mitochondrial ATP synthesis. Read More

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First Report of Lotus Seedpod Withering Caused by Fusarium proliferatum on Nelumbo nucifera Plants in China.

Plant Dis 2021 Jul 28. Epub 2021 Jul 28.

Jiangxi Agricultural University, 91595, College of Agronomy, Zhimin Road, Nanchang, China, 330045;

Nelumbo nucifera (Nymphaeaceae family) is a well-known plant in China and with the increasing value of this crop, the planting area of lotus is expanding. In May 2019, an unknown withering lotus seedpod was obtained in Guangchang County of Jiangxi Province (26.79°N, 116. Read More

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Mucinomics as the Next Frontier of Mass Spectrometry.

ACS Chem Biol 2021 Jul 28. Epub 2021 Jul 28.

Department of Chemistry, Yale University, 275 Prospect Street, New Haven, Connecticut 06511, United States.

Mucin-domain glycoproteins comprise a class of proteins whose densely O-glycosylated mucin domains adopt a secondary structure with unique biophysical and biochemical properties. The canonical family of mucins is well-known to be involved in various diseases, especially cancer. Despite this, very little is known about the site-specific molecular structures and biological activities of mucins, in part because they are extremely challenging to study by mass spectrometry (MS). Read More

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Macrophage depletion increases target specificity of bone-targeted nanoparticles.

J Biomed Mater Res A 2021 Jul 28:e37279. Epub 2021 Jul 28.

Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA.

Despite efforts to achieve tissue selectivity, the majority of systemically administered drug delivery systems (DDSs) are cleared by the mononuclear phagocyte system (MPS) before reaching target tissues regardless of disease or injury pathology. Previously, we showed that while tartrate-resistant acid phosphatase (TRAP) binding peptide (TBP)-targeted polymeric nanoparticles (TBP-NP) delivering a bone regenerative Wnt agonist improved NP fracture accumulation and expedited healing compared with controls, there was also significant MPS accumulation. Here we show that TBP-NPs are taken up by liver, spleen, lung, and bone marrow macrophages (Mϕ), with 76 ± 4%, 49 ± 11%, 27 ± 9%, and 92 ± 5% of tissue-specific Mϕ positive for NP, respectively. Read More

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Synthesis of Oligonucleotides Containing trans Mitomycin C DNA Adducts at N6 of Adenine and N2 of Guanine.

Chemistry 2021 Jul 28. Epub 2021 Jul 28.

The City College of New York, Chemistry, UNITED STATES.

Mitomycin C, (MC), an antitumor drug, is a DNA alkylating agent currently used in the clinics. Inert in its native form, MC is reduced to reactive mitosenes which undergo nucleophilic attack by guanine or adenine bases in DNA to form monoadducts as well as interstrand crosslinks (ICLs). Although ICLs are considered the most cytotoxic lesions, the role of each individual adduct in the drug's cytotoxicity is still not fully understood. Read More

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Low efficiency of leucocyte plugging-based drug delivery to cancer in mice.

Drug Deliv Transl Res 2021 Jul 28. Epub 2021 Jul 28.

Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 365, 69120, Heidelberg, Germany.

Cells of the immune system were proposed for use as Trojan horse for tumour-specific drug delivery. The efficacy of such cell-based drug delivery depends on the site-specific cell homing. This present study was aimed to investigate the potential of leucocytes for intratumoural site-specific enrichment using a locoregional application route in experimental liver tumours. Read More

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Nanopore Stochastic Sensing Based on Non-covalent Interactions.

Anal Chem 2021 Jul 28. Epub 2021 Jul 28.

Department of Chemistry, Illinois Institute of Technology, 3101 S. Dearborn Street, Chicago, Illinois 60616, United States.

A variety of species could be detected by using nanopores engineered with various recognition sites based upon non-covalent interactions, including electrostatic, aromatic, and hydrophobic interactions. The existence of these engineered non-covalent bonding sites was supported by the single-channel recording technique. The advantage of the non-covalent interaction-based sensing strategy was that the recognition site of the engineered nanopore was not specific for a particular molecule but instead selective for a class of species (e. Read More

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Allosteric Inhibition of a Vesicular Glutamate Transporter by an Isoform-Specific Antibody.

Biochemistry 2021 Jul 28. Epub 2021 Jul 28.

Departments of Neurology and Physiology, UCSF School of Medicine, 600 16th Street, San Francisco, California 94143, United States.

The role of glutamate in excitatory neurotransmission depends on its transport into synaptic vesicles by the vesicular glutamate transporters (VGLUTs). The three VGLUT isoforms exhibit a complementary distribution in the nervous system, and the knockout of each produces severe, pleiotropic neurological effects. However, the available pharmacology lacks sensitivity and specificity, limiting the analysis of both transport mechanism and physiological role. Read More

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RNA editing affects cis-regulatory elements and predicts adverse cancer survival.

Cancer Med 2021 Jul 28. Epub 2021 Jul 28.

Guizhou Provincial People's Hospital, Guiyang, China.

Background: RNA editing exerts critical impacts on numerous biological processes and thus are implicated in crucial human phenotypes, including tumorigenesis and prognosis. While previous studies have analyzed aggregate RNA editing activity at the sample level and associated it with overall cancer survival, there is not yet a large-scale disease-specific survival study to examine genome-wide RNA editing sites' prognostic value taking into account the host gene expression and clinical variables.

Methods: In this study, we solved comprehensive Cox proportional models of disease-specific survival on individual RNA-editing sites plus host gene expression and critical demographic covariates. Read More

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Venous access devices for the delivery of long-term chemotherapy: the CAVA three-arm RCT.

Health Technol Assess 2021 Jul;25(47):1-126

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

Background: Venous access devices are used for patients receiving long-term chemotherapy. These include centrally inserted tunnelled catheters or Hickman-type devices (Hickman), peripherally inserted central catheters (PICCs) and centrally inserted totally implantable venous access devices (PORTs).

Objectives: To evaluate the clinical effectiveness, safety, cost-effectiveness and acceptability of these devices for the central delivery of chemotherapy. Read More

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PARP-Targeted Auger Therapy in p53 Mutant Colon Cancer Xenograft Mouse Models.

Mol Pharm 2021 Jul 28. Epub 2021 Jul 28.

Department of Biological Sciences Hunter College, City University of New York, New York, New York 10065, United States.

Despite Auger electrons being highly appealing due to their short-range and high linear energy transfer to surrounding tissues, the progress in the field has been limited due to the challenge in delivering a therapeutic dose within the close proximity of cancer cell's DNA. Here, we demonstrate that the PARP inhibitor I-MAPi is a viable agent for the systemic administration and treatment of p53 mutant cancers. Significantly, minimal off-site toxicity was observed in mice administered with up to 74 MBq of I-PARPi. Read More

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Protonation-Deprotonation Switch Controls the Amyloid-like Misfolding of Nucleic-Acid-Binding Domains of TDP-43.

J Phys Chem B 2021 Jul 28. Epub 2021 Jul 28.

Physical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.

Nutrient starvation stress acidifies the cytosol and leads to the formation of large protein assemblies and misfolded aggregates. However, how starvation stress is sensed at the molecular level and leads to protein misfolding is poorly understood. TDP-43 is a vital protein, which, under stress-like conditions, associates with stress granule proteins via its functional nucleic-acid-binding domains (TDP-43) and misfolds to form aberrant aggregates. Read More

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Identification of covalent modifications regulating immune signaling complex composition and phenotype.

Mol Syst Biol 2021 Jul;17(7):e10125

Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany.

Cells signal through rearrangements of protein communities governed by covalent modifications and reversible interactions of distinct sets of proteins. A method that identifies those post-transcriptional modifications regulating signaling complex composition and functional phenotypes in one experimental setup would facilitate an efficient identification of novel molecular signaling checkpoints. Here, we devised modifications, interactions and phenotypes by affinity purification mass spectrometry (MIP-APMS), comprising the streamlined cloning and transduction of tagged proteins into functionalized reporter cells as well as affinity chromatography, followed by MS-based quantification. Read More

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Integrated respiratory chemoreflex-mediated regulation of cerebral blood flow in hypoxia: Implications for oxygen delivery and acute mountain sickness.

Exp Physiol 2021 Jul 27. Epub 2021 Jul 27.

Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK.

New Findings: What is the central question of this study? To what extent does hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery and corresponding implications for acute mountain sickness susceptibility? What is the main finding and its importance? Evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilation may prove an alternative hemodynamic risk factor that predisposes to acute mountain sickness.

Abstract: The aim of the present study was to determine to what extent hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF), oxygen delivery (CDO ) and corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Read More

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Histidine protonation states are key in the LigI catalytic reaction mechanism.

Proteins 2021 Jul 27. Epub 2021 Jul 27.

Department of Clinical Sciences, Lund University, Box 50332, SE-202 13, Malmö, Sweden.

Lignin is one of the world's most abundant organic polymers, and 2-pyrone-4,6-dicarboxylate lactonase (LigI) catalyzes the hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) in the degradation of lignin. The pH has profound effects on enzyme catalysis and therefore we studied this in the context of LigI. We found that changes of the pH mostly affects surface residues, while the residues at the active site are more subject to changes of the surrounding microenvironment. Read More

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Effects of Host Species Identity and Diet on the Biodiversity of the Microbiota in Puerto Rican Bats.

Curr Microbiol 2021 Jul 27. Epub 2021 Jul 27.

Institute of the Environment, Center for Environmental Sciences & Engineering, and Department of Ecology & Evolutionary Biology, University of Connecticut, 3107 Horsebarn Hill Road, Storrs, CT, 06269-4210, USA.

Microbiota perform vital functions for their mammalian hosts, making them potential drivers of host evolution. Understanding effects of environmental factors and host characteristics on the composition and biodiversity of the microbiota may provide novel insights into the origin and maintenance of these symbiotic relationships. Our goals were to (1) characterize biodiversity of oral and rectal microbiota in bats from Puerto Rico; and (2) determine the effects of geographic location and host characteristics on that biodiversity. Read More

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Development of a Porcine Model to Assess the Effect of In-Situ Knee Joint Loading On Site-Specific Cartilage Gene Expression.

J Biomech Eng 2021 Jul 28. Epub 2021 Jul 28.

Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.

Cyclic mechanical loading of cartilage induces stresses and fluid flow which are thought to modulate chondrocyte metabolism. The uneven surface, plus the heterogeneity of cartilage within a joint, makes stress and fluid pressure distribution in the tissue non-uniform, and gene expression may vary at different sites as a function of load magnitude, frequency and time. In previous studies, cartilage explants were used for loading tests to investigate biological responses of the cartilage to mechanical loading. Read More

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Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.

Lancet Reg Health Eur 2021 Jul 23:100178. Epub 2021 Jul 23.

Medizinische Klinik und Poliklinik III, Universitätsklinikum, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Background: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.

Methods: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273.

Results: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). Read More

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Profiling of ribose methylations in ribosomal RNA from diffuse large B-cell lymphoma patients for evaluation of ribosomes as drug targets.

NAR Cancer 2020 Dec 22;2(4):zcaa035. Epub 2020 Dec 22.

Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, 3B Blegdamsvej, 18.2.20, DK-2200 Copenhagen N, Denmark.

Cancer cells are addicted to ribosome biogenesis and high levels of translation. Thus, differential inhibition of cancer cells can be achieved by targeting aspects of ribosome biogenesis or ribosome function. Using RiboMeth-seq for profiling of the ∼112 2'-O-Me sites in human ribosomal RNA, we demonstrated pronounced hypomethylation at several sites in patient-derived diffuse large B-cell lymphoma (DLBCL) cell lines with a more severe perturbation in ABC-DLBCL compared to GBC-DLBCL. Read More

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December 2020

Parkinsonism and chronic manganese exposure: Pilot study with clinical, environmental and experimental evidence.

Clin Park Relat Disord 2020 6;3:100057. Epub 2020 May 6.

Laboratory of Bio-Organic and Macromolecular Chemistry, Department of Biology, Faculty of Sciences and Techniques, Marrakech, Morocco.

Parkinsonism related to chronic Manganese exposure is notably due to focal lesions of the basal ganglia. Our study focused on epidemiological, clinical, toxicological and experimental aspects of Manganese-induced Parkinsonism in south of Morocco. It is a prospective study concerning the workers and the residents bordering on the 2 mines in the south of Morocco. Read More

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Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study.

Br J Cancer 2021 Jul 27. Epub 2021 Jul 27.

BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Background: Cortisol's immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation. Read More

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Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results.

Leukemia 2021 Jul 28. Epub 2021 Jul 28.

Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.

In acute myeloid leukemia (AML) internal tandem duplications of the FLT3 gene (FLT3-ITD) are associated with poor prognosis. Retrospectively, we investigated the prognostic and predictive impact of FLT3-ITD insertion site (IS) in 452 patients randomized within the RATIFY trial, which evaluated midostaurin additionally to intensive chemotherapy. Next-generation sequencing identified 908 ITDs, with 643 IS in the juxtamembrane domain (JMD) and 265 IS in the tyrosine kinase domain-1 (TKD1). Read More

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Lowering DNA binding affinity of SssI DNA methyltransferase does not enhance the specificity of targeted DNA methylation in E. coli.

Sci Rep 2021 Jul 27;11(1):15226. Epub 2021 Jul 27.

Biological Research Centre, Institute of Biochemistry, Laboratory of DNA-Protein Interactions, Eötvös Loránd Research Network (ELKH), Temesvári krt. 62, Szeged, 6726, Hungary.

Targeted DNA methylation is a technique that aims to methylate cytosines in selected genomic loci. In the most widely used approach a CG-specific DNA methyltransferase (MTase) is fused to a sequence specific DNA binding protein, which binds in the vicinity of the targeted CG site(s). Although the technique has high potential for studying the role of DNA methylation in higher eukaryotes, its usefulness is hampered by insufficient methylation specificity. Read More

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Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional.

Nat Commun 2021 07 27;12(1):4566. Epub 2021 Jul 27.

Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

The airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Read More

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