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Article ; Online: Parent-Child Communication regarding Sport-Related Concussion: An Application of the Theory of Planned Behavior.

Fontana, Joseph / Cranmer, Gregory A / Ash, Erin / Mazer, Joseph P / Denham, Bryan E

2021 Volume 37, Issue 8, Page(s) 923–934

Abstract: Extant research has discussed the importance of social climates surrounding sport-related concussion (SRC) reporting, especially the need to address parents/guardians' role in concussion management. This study explores parents/guardians' intentions ... ...

Abstract	Extant research has discussed the importance of social climates surrounding sport-related concussion (SRC) reporting, especially the need to address parents/guardians' role in concussion management. This study explores parents/guardians' intentions toward SRC-related conversations with their children and their seeking of conversational resources via the Theory of Planned Behavior (TPB). Data collected from 292 parents/guardians of 1
MeSH term(s)	Brain Concussion ; Communication ; Humans ; Intention ; Parent-Child Relations ; Parents ; Sports
Language	English
Publishing date	2021-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1038723-7
ISSN	1532-7027 ; 1041-0236
ISSN (online)	1532-7027
ISSN	1041-0236
DOI	10.1080/10410236.2021.1876326
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Zs.A 2769: Show issues

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Article: Reversal of Clinically Significant Portal Hypertension After Immunosuppressive Treatment in a Patient With Sarcoidosis.

Yardeni, David / Hercun, Julian / Rodriguez, Gracia Viana / Fontana, Joseph R / Kleiner, David E / Koh, Christopher / Heller, Theo

ACG case reports journal

2022 Volume 9, Issue 10, Page(s) e00874

Abstract: Sarcoidosis is a multisystemic disease which features non-necrotizing granulomas in lungs and other organs. Hepatic involvement in sarcoidosis varies between a mild asymptomatic disease and a progressive inflammatory granulomatous disease with or without ...

Abstract	Sarcoidosis is a multisystemic disease which features non-necrotizing granulomas in lungs and other organs. Hepatic involvement in sarcoidosis varies between a mild asymptomatic disease and a progressive inflammatory granulomatous disease with or without cirrhosis. In this case presentation, we present a case of hepatic sarcoidosis complicated by clinically significant portal hypertension including splenomegaly and gastroesophageal varices successfully treated with immunosuppression to achieve portal hypertension reversal.
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Case Reports
ZDB-ID	2814825-3
ISSN	2326-3253
ISSN	2326-3253
DOI	10.14309/crj.0000000000000874
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Article ; Online: PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.

Edwards, Courtney M / Kane, Jeremy F / Smith, Jailyn A / Grant, Déja M / Johnson, Jasmine A / Diaz, Maria A Hernandez / Vecchi, Lawrence A / Bracey, Kai M / Omokehinde, Tolu N / Fontana, Joseph R / Karno, Breelyn A / Scott, Halee T / Vogel, Carolina J / Lowery, Jonathan W / Martin, T John / Johnson, Rachelle W

Breast cancer research : BCR

2024 Volume 26, Issue 1, Page(s) 34

Abstract: The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by ... ...

Abstract	The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.
MeSH term(s)	Humans ; Female ; Parathyroid Hormone-Related Protein/genetics ; Parathyroid Hormone-Related Protein/metabolism ; Breast Neoplasms/pathology ; Receptors, OSM-LIF ; Nuclear Localization Signals ; Cell Proliferation/genetics ; Leukemia Inhibitory Factor Receptor alpha Subunit
Chemical Substances	Parathyroid Hormone-Related Protein ; Receptors, OSM-LIF ; Nuclear Localization Signals ; LIFR protein, human ; Leukemia Inhibitory Factor Receptor alpha Subunit
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-024-01791-z
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Zs.A 5494: Show issues

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Article ; Online: Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation.

Fontana, Joseph R / Crews, Stephen T

Developmental biology

2012 Volume 372, Issue 1, Page(s) 131–142

Abstract: One of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are ... ...

Abstract	One of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are established during development. In this paper, we use fluorescence activated cell sorting and RNA-seq to determine the transcriptome of the Drosophila CNS midline cells, which consist of a small number of well-characterized neurons and glia. These data revealed that midline cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and 31 small-molecule neurotransmitter receptor genes. In situ hybridization and high-resolution confocal analyses were carried-out to determine the midline cell identity for these neuropeptides and the neuropeptide receptors. The results revealed a surprising level of diversity. Neuropeptide genes are expressed in a variety of midline cell types, including motoneurons, GABAergic interneurons, and midline glia. These data revealed previously unknown functional differences among the highly-related iVUM neurons. There also exist segmental differences in expression for the same neuronal sub-type. Similar experiments on midline-expressed neuropeptide receptor genes reveal considerable diversity in synaptic inputs. Multiple receptor types were expressed in midline interneurons and motoneurons, and, in one case, link feeding behavior to gut peristalsis and locomotion. There were also segmental differences, variations between the 3 iVUMs, and three hormone receptor genes were broadly expressed in most midline cells. The Drosophila Castor transcription factor is present at high levels in iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor gene. Genetic and misexpression experiments indicated that castor specifically controls expression of the short neuropeptide F precursor gene, but does not affect iVUM cell fate or expression of Gad1. This indicates a novel function for castor in regulating neuropeptide gene expression.
MeSH term(s)	Animals ; Cell Differentiation ; Central Nervous System/cytology ; Central Nervous System/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Drosophila/embryology ; Drosophila/genetics ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Interneurons/metabolism ; Neurons/cytology ; Neurons/metabolism ; Neuropeptides/metabolism
Chemical Substances	DNA-Binding Proteins ; Drosophila Proteins ; Neuropeptides ; cas protein, Drosophila
Language	English
Publishing date	2012-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2012.09.010
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Zs.B 508: Show issues

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Article ; Online: Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer.

Vaishampayan, Ulka N / Thakur, Archana / Chen, Wei / Deol, Abhinav / Patel, Meera / Dobson, Kimberlee / Dickow, Brenda / Schalk, Dana / Schienschang, Amy / Whitaker, Sarah / Polend, Amanda / Fontana, Joseph A / Heath, Elisabeth I / Lum, Lawrence G

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 29, Issue 1, Page(s) 122–133

Abstract: Purpose: A phase II study was conducted to evaluate the safety and efficacy of the combination of HER2 bispecific antibody (HER2Bi)-armed activated T cells (HER2 BAT) and programmed death 1 inhibitor, pembrolizumab.: Patients and methods: Patients ... ...

Abstract	Purpose: A phase II study was conducted to evaluate the safety and efficacy of the combination of HER2 bispecific antibody (HER2Bi)-armed activated T cells (HER2 BAT) and programmed death 1 inhibitor, pembrolizumab. Patients and methods: Patients with metastatic castration-resistant prostate cancer (mCRPC) with 0 to 1 performance status and normal liver, kidney, and marrow function, pre- or post-docetaxel chemotherapy were eligible. Primary endpoint was 6-month progression-free survival (PFS). Peripheral blood mononuclear cells were obtained by a single apheresis, shipped to University of Virginia, activated with OKT3 and expanded for 14 days in IL2, harvested, and armed with HER2Bi and cryopreserved. HER2 BATs were infused twice weekly for 4 weeks and pembrolizumab was administered every 21 days for a maximum duration of 6 months starting 1 to 3 weeks prior to HER2 BATs infusion. Results: Fourteen patients were enrolled with a median age of 69 (range 57-82 years) and median PSA of 143.4 (range 8.2-4210 ng/dL). Two patients had peritoneal metastases, 1 had lymph node (LN) only metastases and 11 had bone metastases of which 7 had bone and LN metastases. All were pretreated with androgen receptor axis targeted agents and 7 (50%) had prior docetaxel chemotherapy. The toxicities were grade1-2 infusion reactions with fever, chills, headaches, nausea and/or myalgias. Primary endpoint of 6 month PFS was achieved in 5 of 14 patients (38.5%; 95% confidence interval, 19.5%-76.5%). Median PFS was 5 months and median survival was 31.6 months. Conclusions: The safety and promising efficacy makes this combination worthy of future investigation in mCRPC.
MeSH term(s)	Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Docetaxel/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Leukocytes, Mononuclear ; T-Lymphocytes ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Chemical Substances	pembrolizumab (DPT0O3T46P) ; Docetaxel (15H5577CQD)
Language	English
Publishing date	2022-10-25
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-1601
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Zs.A 4223: Show issues

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Article ; Online: Down regulation of miR-202 modulates Mxd1 and Sin3A repressor complexes to induce apoptosis of pancreatic cancer cells.

Farhana, Lulu / Dawson, Marcia I / Fontana, Joseph A

Cancer biology & therapy

2015 Volume 16, Issue 1, Page(s) 115–124

Abstract: Aberrant regulation of microRNA expression in pancreatic cancers has been shown to play an important role in its inherent poor prognosis and malignant potential. MicroRNAs have also been shown to inhibit translation of genes by targeting the 3'- ... ...

Abstract	Aberrant regulation of microRNA expression in pancreatic cancers has been shown to play an important role in its inherent poor prognosis and malignant potential. MicroRNAs have also been shown to inhibit translation of genes by targeting the 3'-untranslated region (3-UTR) of mRNAs resulting in the inhibition of translation and often destruction of the mRNA. In the present study we investigated the role of the microRNA miR-202 in the apoptotic pathways of pancreatic cancer cells. The adamantyl-related molecule, 3-Cl-AHPC down-regulated expression of miR-202 and miR-578 resulting in the increased expression of mRNA and protein expression of their target genes, Max dimerization protein 1 (Mxd1/Mad1) and the Sin3A associated protein 18 (SAP18). Overexpression of pre-miR-202 led to diminished levels of Mxd1 and blocked the 3-Cl-AHPC-mediated increase in Mxd1 mRNA expression. The addition of the microRNA inhibitor 2'-O-methylated miR-202 enhanced the 3-Cl-AHPC-mediated increase of Mxd1 mRNA levels as well as 3-CI-AHPC-mediated apoptosis. We found increased Mxd1 bound to the Sin3A repressor protein complex through its increased binding with HDAC-2 and subsequently enhanced transcriptional repression in cells as evidenced by increased HDAC activity. Mxd1 also repressed human telomerase reverse transcriptase (hTERT) mRNA expression through its increased binding to the hTERT promoter site and resulted in decreased telomerase activity in cells. Our results demonstrate that down regulation of miR-202 increased the expression of its target Mxd1, followed by Mxd1 recruitment to the Sin3A repressor complex and through its dimerization with Max, and increased repression of Myc-Max target proteins.
MeSH term(s)	3' Untranslated Regions ; Adamantane/analogs & derivatives ; Adamantane/pharmacology ; Apoptosis/drug effects ; Apoptosis/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Cell Line, Tumor ; Cinnamates/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MicroRNAs/genetics ; Pancreatic Neoplasms/genetics ; Protein Binding ; RNA Interference ; Repressor Proteins/genetics ; Telomerase/genetics ; Telomerase/metabolism
Chemical Substances	3' Untranslated Regions ; 4-(3-(1-adamantyl)-4-hydroxyphenyl)-3-chlorocinnamic acid ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Cinnamates ; MIRN202 microRNA, human ; MXD1 protein, human ; MicroRNAs ; Repressor Proteins ; SIN3A transcription factor ; TERT protein, human (EC 2.7.7.49) ; Telomerase (EC 2.7.7.49) ; Adamantane (PJY633525U)
Language	English
Publishing date	2015-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2146305-0
ISSN	1555-8576 ; 1538-4047
ISSN (online)	1555-8576
ISSN	1538-4047
DOI	10.4161/15384047.2014.987070
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Zs.A 5887: Show issues

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Article ; Online: Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics.

Iannuzzi, Michael C / Fontana, Joseph R

JAMA

2011 Volume 305, Issue 4, Page(s) 391–399

Abstract: Sarcoidosis is a multisystem granulomatous disorder that most often affects the lungs and may cause significant morbidity. Sarcoidosis can manifest as neurological disease, uveitis, blindness, end-stage pulmonary fibrosis, pulmonary hypertension, ... ...

Abstract	Sarcoidosis is a multisystem granulomatous disorder that most often affects the lungs and may cause significant morbidity. Sarcoidosis can manifest as neurological disease, uveitis, blindness, end-stage pulmonary fibrosis, pulmonary hypertension, dysrhythmias, cardiomyopathy, hypercalcemia, and renal failure. Sarcoidosis persists as chronic disease in approximately one-third of those affected. Clinical pitfalls and misconceptions about the course of disease place this population at risk for delayed or inadequate care. While noncaseating granulomas are the histopathological hallmark of sarcoidosis, they also are nonspecific. No pathognomonic diagnostic test exists for sarcoidosis, so the diagnosis remains one of exclusion. While the etiology of sarcoidosis is still unknown, recent insights into its immunopathogenesis have moved investigators closer to finding more effective treatments. Corticosteroids remain the standard of care when treatment is indicated, despite their adverse effect profile. Clinical investigations of novel drugs and biological agents targeting mechanisms involving CD4 type 1 helper T cells may provide more effective, better tolerated therapies.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Delayed Diagnosis ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Molecular Targeted Therapy ; Sarcoidosis/diagnosis ; Sarcoidosis/drug therapy ; Sarcoidosis/genetics ; Sarcoidosis/immunology ; Sarcoidosis/pathology
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2011-01-26
Publishing country	United States
Document type	Case Reports ; Clinical Conference ; Journal Article
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2011.10
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Ua VI Zs.88: Show issues

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Article: Retinoid signaling in breast carcinoma cells.

Fontana, Joseph A

Cancer investigation

2003 Volume 21, Issue 2, Page(s) 327–329

MeSH term(s)	Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Breast Neoplasms/physiopathology ; Female ; Humans ; Retinoids/analysis ; Retinoids/therapeutic use ; Signal Transduction
Chemical Substances	Antineoplastic Agents ; Retinoids
Language	English
Publishing date	2003-04-28
Publishing country	England
Document type	Comment ; Editorial
ZDB-ID	604942-4
ISSN	0735-7907
ISSN	0735-7907
DOI	10.1081/cnv-120016429
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Zs.A 1862: Show issues

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Article ; Online: The peptidomimetic, 1-adamantyl-substituted, and flex-het classes of retinoid-derived molecules: structure-activity relationships and retinoid receptor-independent anticancer activities.

Dawson, Marcia I / Fontana, Joseph A

Mini reviews in medicinal chemistry

2010 Volume 10, Issue 6, Page(s) 455–491

Abstract: Increasing evidence demonstrates that three classes of molecules originally derived from all-trans-retinoic acid and its synthetic analogues, which function by interacting with the retinoid nuclear receptors, exert their anticancer activities through ... ...

Abstract	Increasing evidence demonstrates that three classes of molecules originally derived from all-trans-retinoic acid and its synthetic analogues, which function by interacting with the retinoid nuclear receptors, exert their anticancer activities through alternative signaling pathways. Thus, the methylene-linked analogues (4-HBR, 4-HPRCG, and 4-HBRCG) of N-(4-hydroxyphenyl) retinamide (4-HPR) and its O-glucuronide metabolite (4-HPROG), the cinnamic acid analogues (3-Cl-AHPC and AHPC/ST1926) of 6-[3'-(1-adamantyl)-4'-hydroxyphenyl)]-2-naphthalenecarboxylic acid, and N-(2,3-dihydro-2,2,4,4-tetramethyl-6-benzothiopyranyl),N'-(4-nitrophenyl)thiourea (SHetA2) induce cancer cell-cycle arrest and apoptosis mediated most likely through mitochondrial and/or endoplasmic reticulum stress responses. Structure-activity relationships and potential for clinical translation as anticancer therapeutics are presented.
MeSH term(s)	Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cinnamates/chemical synthesis ; Cinnamates/chemistry ; Cinnamates/pharmacology ; Fenretinide/analogs & derivatives ; Fenretinide/chemical synthesis ; Fenretinide/chemistry ; Fenretinide/pharmacology ; Glucuronates/chemical synthesis ; Glucuronates/chemistry ; Glucuronates/pharmacology ; Receptors, Retinoic Acid/chemistry ; Receptors, Retinoic Acid/metabolism ; Retinoids/chemical synthesis ; Retinoids/chemistry ; Retinoids/pharmacology ; Structure-Activity Relationship
Chemical Substances	Antineoplastic Agents ; Cinnamates ; Glucuronates ; N-((4-hydroxyphenyl)retinamide)-O-glucuronide ; Receptors, Retinoic Acid ; Retinoids ; cinnamic acid (140-10-3) ; Fenretinide (187EJ7QEXL)
Language	English
Publishing date	2010-03-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2104081-3
ISSN	1875-5607 ; 1389-5575
ISSN (online)	1875-5607
ISSN	1389-5575
DOI	10.2174/138955710791384045
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Zs.A 5891: Show issues

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Article: Prognostic significance of pulmonary function tests in dyskeratosis congenita, a telomere biology disorder.

Giri, Neelam / Ravichandran, Sandhiya / Wang, Youjin / Gadalla, Shahinaz M / Alter, Blanche P / Fontana, Joseph / Savage, Sharon A

ERJ open research

2019 Volume 5, Issue 4

Abstract: Pulmonary fibrosis and pulmonary arteriovenous malformations are known manifestations of dyskeratosis congenita (DC), a telomere biology disorder (TBD) and inherited bone marrow failure syndrome caused by germline mutations in telomere maintenance genes ... ...

Abstract	Pulmonary fibrosis and pulmonary arteriovenous malformations are known manifestations of dyskeratosis congenita (DC), a telomere biology disorder (TBD) and inherited bone marrow failure syndrome caused by germline mutations in telomere maintenance genes resulting in very short telomeres. Baseline pulmonary function tests (PFTs) and long-term clinical outcomes have not been thoroughly studied in DC/TBDs. In this retrospective study, 43 patients with DC and 67 unaffected relatives underwent baseline PFTs and were followed for a median of 8 years (range 1-14). Logistic regression and competing risk models were used to compare PFT results in relation to clinical and genetic characteristics, and patient outcomes. Restrictive abnormalities on spirometry and moderate-to-severe reduction in diffusing capacity of the lung for carbon monoxide were significantly more frequent in patients with DC than relatives (42%
Language	English
Publishing date	2019-11-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00209-2019
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