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Article ; Online: Cardiothoracic Radiologist Workload, Work Capacity, and Burnout Post-COVID: Results of a Survey From the Society of Thoracic Radiology.

Meyer, Cristopher A / Klein, Jeffrey S / Liubauskas, Rokas / Bhalla, Sanjeev / Eisenberg, Ronald L

2023 Volume 38, Issue 5, Page(s) 261–269

Abstract: In this report and analysis of the results of a late 2021 post-COVID pandemic survey of members of the Society of Thoracic Radiology, we compared cardiothoracic radiologist workloads and burnout rates with those obtained from a prepandemic survey of ... ...

Abstract	In this report and analysis of the results of a late 2021 post-COVID pandemic survey of members of the Society of Thoracic Radiology, we compared cardiothoracic radiologist workloads and burnout rates with those obtained from a prepandemic survey of society members. The more recent survey also asked respondents to provide a subjective assessment of their individual workload capacity should they be required to read cases at a section average daily case work volume, and this assessment was correlated with burnout rates. To measure nonrelative value unit workload, we requested data on non-case-related work responsibilities including teaching and multidisciplinary conferences that were not assessed in the first survey. In addition, we asked respondents to provide information on the availability of support services, personnel, and hardware and software tools that could improve work efficiency and reduce radiologist stress levels thereby mitigating burnout. We found that postpandemic case workload and cardiothoracic radiologists' burnout rates were similarly high compared with prepandemic levels with an overall burnout rate of 88% including a 100% burnout rate among women which had significantly increased. The range of radiologists' workload capacity is broad, although 80% of respondents reported that reading at an average sectional case volume was at or above their capacity, and the perceived capacity correlated with burnout measures. The presence of fellows and computer-aided diagnosis/artificial intelligence tools were each associated with significant decreases in burnout, providing 2 potential strategies that could be employed to address high cardiothoracic radiologist burnout rates.
MeSH term(s)	Humans ; Female ; Workload ; Artificial Intelligence ; COVID-19 ; Radiologists ; Surveys and Questionnaires ; Burnout, Professional ; Radiology/education
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	632900-7
ISSN	1536-0237 ; 0883-5993
ISSN (online)	1536-0237
ISSN	0883-5993
DOI	10.1097/RTI.0000000000000710
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Article ; Online: Prevalence of Age-related Maculopathy: The Beaver Dam Eye Study.

Klein, Ronald / Klein, Barbara E K / Linton, Kathryn L P

Ophthalmology

2020 Volume 127, Issue 4S, Page(s) S122–S132

Abstract: Purpose: The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study.: Methods: The ... ...

Abstract	Purpose: The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study. Methods: The presence and severity of various characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. Results: One or more drusen were present in the macular area of at least 1 eye in 95.5% of the population. People 75 years of age or older had significantly higher frequencies (P < 0.01) of the following characteristics than people 43 to 54 years of age: larger sized drusen (>125 /μm, 24.0% versus 1.9%), soft indistinct drusen (23.0% versus 2.1%), retinal pigment abnormalities (26.6% versus 7.3%), exudative macular degeneration (5.2% versus 0.1%), and geographic atrophy (2.0% versus 0%). Conclusion: These data indicate signs of age-related maculopathy are common in people 75 years of age or older and may pose a substantial public health problem.
MeSH term(s)	Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Disease Progression ; Female ; Geographic Atrophy/diagnosis ; Geographic Atrophy/epidemiology ; Humans ; Incidence ; Macula Lutea/pathology ; Macular Degeneration/diagnosis ; Macular Degeneration/epidemiology ; Male ; Middle Aged ; Photography ; Prevalence ; Retinal Drusen/diagnosis ; Retinal Drusen/epidemiology ; Retinal Pigment Epithelium/pathology ; Risk Factors ; Wisconsin/epidemiology
Language	English
Publishing date	2020-03-23
Publishing country	United States
Document type	Classical Article ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	392083-5
ISSN	1549-4713 ; 0161-6420
ISSN (online)	1549-4713
ISSN	0161-6420
DOI	10.1016/j.ophtha.2020.01.033
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Article ; Online: A pharmacokinetic drug-drug interaction study between rosuvastatin and emvododstat, a potent anti-SARS-CoV-2 (COVID-19) DHODH (dihydroorotate dehydrogenase) inhibitor.

Morton, Terri L / Laskin, Oscar L / Kaushik, Diksha / Lee, Lucy / Ma, Jiyuan / Kristensen, Allan / O'Keefe, Kylie / Golden, Lee / Klein, Matthew / Kong, Ronald

Pharmacology research & perspectives

2023 Volume 11, Issue 2, Page(s) e01076

Abstract: A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) management. Emvododstat (PTC299) was found ... ...

Abstract	A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) management. Emvododstat (PTC299) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by the inhibition of dihydroorotate dehydrogenase (DHODH) to reduce SARS-CoV-2 replication. DHODH is the rate-limiting enzyme of the de novo pyrimidine nucleotide biosynthesis pathway. This drug interaction study was performed to determine whether emvododstat was an inhibitor of breast cancer resistance protein (BCRP) transporters in humans. Potential drug-drug interactions (DDIs) between emvododstat and a BCRP transporter substrate (rosuvastatin) were investigated by measuring plasma rosuvastatin concentrations before and after emvododstat administration. There was no apparent difference in rosuvastatin plasma exposure. The geometric means of maximum plasma rosuvastatin concentrations (C
MeSH term(s)	Humans ; Rosuvastatin Calcium/pharmacology ; Rosuvastatin Calcium/therapeutic use ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Dihydroorotate Dehydrogenase ; SARS-CoV-2 ; Pyrimidines ; COVID-19 ; Neoplasm Proteins/metabolism ; Membrane Transport Proteins/metabolism ; Drug Interactions
Chemical Substances	Rosuvastatin Calcium (83MVU38M7Q) ; emvododstat (053QD2I96A) ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Dihydroorotate Dehydrogenase ; Pyrimidines ; Neoplasm Proteins ; Membrane Transport Proteins
Language	English
Publishing date	2023-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2740389-0
ISSN	2052-1707 ; 2052-1707
ISSN (online)	2052-1707
ISSN	2052-1707
DOI	10.1002/prp2.1076
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Article ; Online: Facing Uncertainty: Interpretation of Ambiguous Emotional Faces in Childhood Social Anxiety Disorder.

Mobach, Lynn / Rinck, Mike / Becker, Eni S / Carl, Talia / Klein, Anke M / Rapee, Ronald M / Hudson, Jennifer L

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53

2022 Volume 51, Issue 6, Page(s) 955–969

Abstract: Objective: The current study examined whether children with a social anxiety disorder (SAD) demonstrate divergent facial emotion processing and a disorder-specific negative interpretation bias in the processing of facial emotional expressions. This ... ...

Abstract	Objective: The current study examined whether children with a social anxiety disorder (SAD) demonstrate divergent facial emotion processing and a disorder-specific negative interpretation bias in the processing of facial emotional expressions. This study aimed to overcome previous study limitations by including both a nonsocially anxious control group and a healthy control group to examine whether childhood SAD is characterized by a general emotion labeling deficit, and/or by a negative interpretation bias, indicated by systematic misclassifications, or a lower threshold for recognizing threatening emotions. Method: Participants were 132 children aged 7-12 years ( Results: Children with SAD did not differ from other groups in their accuracy of identifying emotions. They did not show systematic misclassifications or a heightened sensitivity to negative, threatening faces either. Rather, children with nonsocial anxiety disorders showed a generally heightened sensitivity to emotional faces. Conclusions: The current study does not provide evidence for a general deficit in labeling of emotional faces in childhood SAD. Childhood SAD was not characterized by an interpretation bias in processing emotional faces. Children with nonsocial anxiety disorders may benefit from assistance in accurately interpreting the degree of emotionality in interpersonal situations.
MeSH term(s)	Child ; Female ; Humans ; Male ; Phobia, Social ; Uncertainty ; Emotions ; Facial Expression ; Anxiety Disorders ; Anxiety
Language	English
Publishing date	2022-05-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2073310-0
ISSN	1537-4424 ; 1537-4416
ISSN (online)	1537-4424
ISSN	1537-4416
DOI	10.1080/15374416.2022.2070850
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Article ; Online: A clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor.

Morton, Terri L / Laskin, Oscar L / Kaushik, Diksha / Lee, Lucy / Ma, Jiyuan / Bar, Cristian M / Kristensen, Allan / O'Keefe, Kylie / Golden, Lee / Klein, Matthew / Kong, Ronald

European journal of clinical pharmacology

2023 Volume 79, Issue 8, Page(s) 1073–1080

Abstract: Purpose: A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2, coronavirus disease 2019, COVID-19) ... ...

Abstract	Purpose: A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2, coronavirus disease 2019, COVID-19) management. Emvododstat (PTC299; 4-chlorophenyl 6-chloro-1-[4-methoxyphenyl]-1,3, 4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by inhibition of dihydroorotate dehydrogenase to reduce the severity of SARS-CoV-2 infections This drug interaction study was performed to determine if emvododstat was an inhibitor of CYP2D6. Methods: Potential drug-drug interactions between emvododstat and a CYP2D6 probe substrate (dextromethorphan) were investigated by measuring plasma dextromethorphan and metabolite (dextrorphan) concentrations before and after emvododstat administration. On day 1, 18 healthy subjects received an oral dose of 30 mg dextromethorphan followed by a 4-day washout period. On day 5, subjects received an oral dose of 250 mg emvododstat with food. Two hours later, 30 mg dextromethorphan was administered. Results: When given with emvododstat, plasma dextromethorphan concentrations increased substantially, while metabolite levels (dextrorphan) remained essentially the same. Maximum plasma dextromethorphan concentration (C Conclusion: Emvododstat appears to be a strong CYP2D6 inhibitor. No drug-related treatment emergent adverse effects (TEAEs) were considered to be severe or serious. Trial registration: EudraCT 2021-004626-29, 11 May 2021.
MeSH term(s)	Humans ; Cytochrome P-450 CYP2D6/metabolism ; Dextromethorphan/pharmacokinetics ; Dihydroorotate Dehydrogenase ; SARS-CoV-2 ; Dextrorphan ; COVID-19 ; Drug Interactions
Chemical Substances	Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Dextromethorphan (7355X3ROTS) ; emvododstat (053QD2I96A) ; Dihydroorotate Dehydrogenase ; Dextrorphan (04B7QNO9WS)
Language	English
Publishing date	2023-06-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	121960-1
ISSN	1432-1041 ; 0031-6970
ISSN (online)	1432-1041
ISSN	0031-6970
DOI	10.1007/s00228-023-03513-4
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Article ; Online: Acetylenotrophic and Diazotrophic

Akob, Denise M / Sutton, John M / Bushman, Timothy J / Baesman, Shaun M / Klein, Edina / Shrestha, Yesha / Andrews, Robert / Fierst, Janna L / Kolton, Max / Gushgari-Doyle, Sara / Oremland, Ronald S / Freeman, John L

Applied and environmental microbiology

2022 Volume 88, Issue 22, Page(s) e0121922

Abstract: Acetylene ( ... ...

Abstract	Acetylene (C
MeSH term(s)	Bradyrhizobium ; Trichloroethylene/metabolism ; Nitrogen Fixation/genetics ; Soil/chemistry ; Acetylene/metabolism ; Phylogeny ; Symbiosis ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/microbiology ; DNA, Bacterial/genetics ; Sequence Analysis, DNA
Chemical Substances	Trichloroethylene (290YE8AR51) ; Soil ; Acetylene (OC7TV75O83) ; RNA, Ribosomal, 16S ; DNA, Bacterial
Language	English
Publishing date	2022-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/aem.01219-22
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Article ; Online: Gene vector 'magic bullet': targeted expression in the central nervous system after peripheral delivery using the synapsin promoter.

Jackson, Kasey L / Dayton, Robert D / Klein, Ronald L

Expert opinion on therapeutic targets

2016 Volume 20, Issue 10, Page(s) 1153–1154

Language	English
Publishing date	2016-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2016.1212016
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Article ; Online: More expansive gene transfer to the rat CNS: AAV PHP.EB vector dose-response and comparison to AAV PHP.B.

Dayton, Robert D / Grames, Mychal S / Klein, Ronald L

Gene therapy

2018 Volume 25, Issue 5, Page(s) 392–400

Abstract: Engineered recombinant adeno-associated virus (AAV) vectors have advanced the transduction of neurons in the CNS on an expansive, wide-scale basis since the papers first using AAV9 for this purpose. Wide-scale CNS expression is relevant to gene therapy ... ...

Abstract	Engineered recombinant adeno-associated virus (AAV) vectors have advanced the transduction of neurons in the CNS on an expansive, wide-scale basis since the papers first using AAV9 for this purpose. Wide-scale CNS expression is relevant to gene therapy as well as indispensable for basic studies such as disease modeling. For example, the wide-scale gene transfer approach could expedite hypothesis testing in vivo relative to the generation of germ-line transgenic mice for all of the genes of interest. Wide-scale gene transfer is more efficient in neonates than in adults, so improving gene transfer efficiency in adults is an important goal. Here we characterized the relatively novel AAV PHP.EB vector for expansive gene transfer in the CNS of adult rats at three doses. The dose-response data were consistent; expression levels can be controlled in a reproducible manner in the rat from moderate to robust levels. Within the CNS, the AAV PHP.EB-derived expression was neuron-selective to neuron-specific, while outside the CNS, organs such as the liver and heart were transduced by the parenteral gene delivery. Though we demonstrated graded expression levels, only the high dose, 1.2 × 10
MeSH term(s)	Animals ; Brain/metabolism ; Cell Line ; Central Nervous System/immunology ; Central Nervous System/physiology ; Dependovirus/genetics ; Dose-Response Relationship, Drug ; Female ; Gene Transfer Techniques ; Genetic Therapy/methods ; Genetic Vectors ; Mice ; Mice, Transgenic ; Motor Neurons/metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Transduction, Genetic/methods
Language	English
Publishing date	2018-07-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1191036-7
ISSN	1476-5462 ; 0969-7128
ISSN (online)	1476-5462
ISSN	0969-7128
DOI	10.1038/s41434-018-0028-5
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Article: 600-ns pulsed electric fields affect inactivation and antibiotic susceptibilities of Escherichia coli and Lactobacillus acidophilus.

Martens, Stacey L / Klein, Savannah / Barnes, Ronald A / TrejoSanchez, Patricia / Roth, Caleb C / Ibey, Bennett L

AMB Express

2020 Volume 10, Issue 1, Page(s) 55

Abstract: Cell suspensions of Escherichia coli and Lactobacillus acidophilus were exposed to 600-ns pulsed electric fields (nsPEFs) at varying amplitudes (Low-13.5, Mid-18.5 or High-23.5 kV ... ...

Abstract	Cell suspensions of Escherichia coli and Lactobacillus acidophilus were exposed to 600-ns pulsed electric fields (nsPEFs) at varying amplitudes (Low-13.5, Mid-18.5 or High-23.5 kV cm
Keywords	covid19
Language	English
Publishing date	2020-03-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2621432-5
ISSN	2191-0855
ISSN	2191-0855
DOI	10.1186/s13568-020-00991-y
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Article: Corrigendum: Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B.

Jackson, Kasey L / Dayton, Robert D / Deverman, Benjamin E / Klein, Ronald L

Frontiers in molecular neuroscience

2016 Volume 9, Page(s) 154

Abstract: This corrects the article on p. 116 in vol. 9, PMID: 27867348.]. ...

Abstract	[This corrects the article on p. 116 in vol. 9, PMID: 27867348.].
Language	English
Publishing date	2016-12-22
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2452967-9
ISSN	1662-5099
ISSN	1662-5099
DOI	10.3389/fnmol.2016.00154
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