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Article ; Online: Structural insights into viral genome replication by the severe fever with thrombocytopenia syndrome virus L protein.

Williams, Harry M / Thorkelsson, Sigurdur R / Vogel, Dominik / Milewski, Morlin / Busch, Carola / Cusack, Stephen / Grünewald, Kay / Quemin, Emmanuelle R J / Rosenthal, Maria

Nucleic acids research

2023 Volume 51, Issue 3, Page(s) 1424–1442

Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for ... ...

Abstract	Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 Å. We identify how the L protein binds the 5' viral RNA in a hook-like conformation and show how the distal 5' and 3' RNA ends form a duplex positioning the 3' RNA terminus in the RdRp active site ready for initiation. We also observe the L protein stalled in the early and late stages of elongation with the RdRp core accommodating a 10-bp product-template duplex. This duplex ultimately splits with the template binding to a designated 3' secondary binding site. The structural data and observations are complemented by in vitro biochemical and cell-based mini-replicon assays. Altogether, our data provide novel key insights into the mechanism of viral genome replication by the SFTSV L protein and will aid drug development against segmented negative-strand RNA viruses.
MeSH term(s)	Humans ; Severe Fever with Thrombocytopenia Syndrome/genetics ; Cryoelectron Microscopy ; RNA, Viral/genetics ; RNA-Dependent RNA Polymerase/metabolism ; Phlebovirus/genetics ; Virus Replication ; Genome, Viral
Chemical Substances	RNA, Viral ; RNA-Dependent RNA Polymerase (EC 2.7.7.48)
Language	English
Publishing date	2023-01-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac1249
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Zs.A 1067: Show issues

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Article ; Online: The clinical presentation and detection of tuberculosis during pregnancy and in the postpartum period in low- and middle-income countries: A systematic review and meta-analysis.

Simpson, Grace / Philip, Moira / Vogel, Joshua P / Scoullar, Michelle J L / Graham, Stephen M / Wilson, Alyce N

PLOS global public health

2023 Volume 3, Issue 8, Page(s) e0002222

Abstract: For women infected with Mycobacterium tuberculosis, pregnancy is associated with an increased risk of developing or worsening TB disease. TB in pregnancy increases the risk of adverse maternal and neonatal outcomes, however the detection of TB in ... ...

Abstract	For women infected with Mycobacterium tuberculosis, pregnancy is associated with an increased risk of developing or worsening TB disease. TB in pregnancy increases the risk of adverse maternal and neonatal outcomes, however the detection of TB in pregnancy is challenging. We aimed to identify and summarise the findings of studies regarding the clinical presentation and diagnosis of TB during pregnancy and the postpartum period (within 6 months of birth) in low-and middle-income countries (LMICs). A systematic review was conducted searching Ovid MEDLINE, Embase, CINAHL and Global Index Medicus databases. We included any primary research study of women diagnosed with TB during pregnancy or the postpartum period in LMICs that described the clinical presentation or method of diagnosis. Meta-analysis was used to determine pooled prevalence of TB clinical features and health outcomes, as well as detection method yield. Eighty-seven studies of 2,965 women from 27 countries were included. 70.4% of women were from South Africa or India and 44.7% were known to be HIV positive. For 1,833 women where TB type was reported, pulmonary TB was most common (79.6%). Most studies did not report the prevalence of presenting clinical features. Where reported, the most common were sputum production (73%) and cough (68%). Having a recent TB contact was found in 45% of women. Only six studies screened for TB using diagnostic testing for asymptomatic antenatal women and included mainly HIV-positive women ‒ 58% of women with bacteriologically confirmed TB did not report symptoms and only two were in HIV-negative women. Chest X-ray had the highest screening yield; 60% abnormal results of 3036 women tested. Screening pregnant women for TB-related symptoms and risk factors is important but detection yields are limited. Chest radiography and bacteriological detection methods can improve this, but procedures for optimal utilisation remain uncertain in this at-risk population. Trial registration: Prospero registration number: CRD42020202493.
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ISSN	2767-3375
ISSN (online)	2767-3375
DOI	10.1371/journal.pgph.0002222
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Article ; Online: Mucosal Infection with Unmasked Candida albicans Cells Impacts Disease Progression in a Host Niche-Specific Manner.

Wagner, Andrew S / Vogel, Amanda K / Lumsdaine, Stephen W / Phillips, Elise K / Willems, Hubertine M E / Peters, Brian M / Reynolds, Todd B

Infection and immunity

2022 Volume 90, Issue 12, Page(s) e0034222

Abstract: Shielding the immunogenic cell wall epitope β(1, 3)-glucan under an outer layer of mannosylated glycoproteins is an essential virulence factor deployed by Candida albicans during systemic infection. Accordingly, mutants with increased β(1, 3)-glucan ... ...

Abstract	Shielding the immunogenic cell wall epitope β(1, 3)-glucan under an outer layer of mannosylated glycoproteins is an essential virulence factor deployed by Candida albicans during systemic infection. Accordingly, mutants with increased β(1, 3)-glucan exposure (unmasking) display increased immunostimulatory capabilities
MeSH term(s)	Animals ; Female ; Male ; Mice ; Candida albicans ; Candidiasis/microbiology ; Candidiasis, Oral ; Candidiasis, Vulvovaginal/microbiology ; Disease Progression ; Glucans
Chemical Substances	Glucans
Language	English
Publishing date	2022-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/iai.00342-22
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Zs.A 684: Show issues

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Article ; Online: TAK1 is essential for endothelial barrier maintenance and repair after lung vascular injury.

Wang, Dong-Mei / Soni, Dheeraj / Regmi, Sushil C / Vogel, Stephen M / Tiruppathi, Chinnaswamy

Molecular biology of the cell

2022 Volume 33, Issue 7, Page(s) ar65

Abstract: TGF-β-activated kinase 1 (TAK1) plays crucial roles in innate and adaptive immune responses and is required for embryonic vascular development. However, TAK1's role in regulating vascular barrier integrity is not well defined. Here we show that ... ...

Abstract	TGF-β-activated kinase 1 (TAK1) plays crucial roles in innate and adaptive immune responses and is required for embryonic vascular development. However, TAK1's role in regulating vascular barrier integrity is not well defined. Here we show that endothelial TAK1 kinase function is required to maintain and repair the injured lung endothelial barrier. We observed that inhibition of TAK1 with 5Z-7-oxozeaenol markedly reduced expression of β-catenin (β-cat) and VE-cadherin at endothelial adherens junctions and augmented protease-activated receptor-1 (PAR-1)- or toll-like receptor-4 (TLR-4)-induced increases in lung vascular permeability. In inducible endothelial cell (EC)-restricted TAK1 knockout (
MeSH term(s)	Animals ; Glycogen Synthase Kinase 3 beta ; Lung ; MAP Kinase Kinase Kinases ; Mice ; Proto-Oncogene Proteins c-akt ; Toll-Like Receptor 4 ; Vascular System Injuries
Chemical Substances	Toll-Like Receptor 4 ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP kinase kinase kinase 7 (EC 2.7.11.25)
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E21-11-0563
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Zs.A 2853: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Kinetically Controlled Linker Binding in Rare Earth-2,5-Dihydroxyterepthalic Acid Metal-Organic Frameworks and Its Predicted Effects on Acid Gas Adsorption.

Henkelis, Susan E / Vogel, Dayton J / Metz, Peter C / Valdez, Nichole R / Rodriguez, Mark A / Rademacher, David X / Purdy, Stephen / Percival, Stephen J / Rimsza, Jessica M / Page, Katharine / Nenoff, Tina M

ACS applied materials & interfaces

2021 Volume 13, Issue 47, Page(s) 56337–56347

Abstract: In the pursuit of highly stable and selective metal-organic frameworks (MOFs) for the adsorption of caustic acid gas species, an entire series of rare earth MOFs have been explored. Each of the MOFs in this series (RE-DOBDC; RE = La, Ce, Pr, Nd, Sm, Eu, ... ...

Abstract	In the pursuit of highly stable and selective metal-organic frameworks (MOFs) for the adsorption of caustic acid gas species, an entire series of rare earth MOFs have been explored. Each of the MOFs in this series (RE-DOBDC; RE = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu; DOBDC = 2,5-dihydroxyterepthalic acid) was synthesized in the tetragonal space group
Language	English
Publishing date	2021-11-18
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.1c17670
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Article ; Online: CD47 expression is critical for CAR T-cell survival in vivo.

Beckett, Alex N / Chockley, Peter / Pruett-Miller, Shondra M / Nguyen, Phuong / Vogel, Peter / Sheppard, Heather / Krenciute, Giedre / Gottschalk, Stephen / DeRenzo, Christopher

Journal for immunotherapy of cancer

2023 Volume 11, Issue 3

Abstract: Background: CD47 is an attractive immunotherapeutic target because it is highly expressed on multiple solid tumors. However, CD47 is also expressed on T cells. Limited studies have evaluated CD47-chimeric antigen receptor (CAR) T cells, and the role of ... ...

Abstract	Background: CD47 is an attractive immunotherapeutic target because it is highly expressed on multiple solid tumors. However, CD47 is also expressed on T cells. Limited studies have evaluated CD47-chimeric antigen receptor (CAR) T cells, and the role of CD47 in CAR T-cell function remains largely unknown. Methods: Here, we describe the development of CD47-CAR T cells derived from a high affinity signal regulatory protein α variant CV1, which binds CD47. CV1-CAR T cells were generated from human peripheral blood mononuclear cells and evaluated in vitro and in vivo. The role of CD47 in CAR T-cell function was examined by knocking out CD47 in T cells followed by downstream functional analyses. Results: While CV1-CAR T cells are specific and exhibit potent activity in vitro they lacked antitumor activity in xenograft models. Mechanistic studies revealed CV1-CAR T cells downregulate CD47 to overcome fratricide, but CD47 loss resulted in their failure to expand and persist in vivo. This effect was not limited to CV1-CAR T cells, since CD47 knockout CAR T cells targeting another solid tumor antigen exhibited the same in vivo fate. Further, CD47 knockout T cells were sensitive to macrophage-mediated phagocytosis. Conclusions: These findings highlight that CD47 expression is critical for CAR T-cell survival in vivo and is a 'sine qua non' for successful adoptive T-cell therapy.
MeSH term(s)	Humans ; T-Lymphocytes ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive/methods ; CD47 Antigen/genetics ; CD47 Antigen/metabolism ; Leukocytes, Mononuclear/metabolism ; Cell Survival ; Cell Line, Tumor
Chemical Substances	Receptors, Chimeric Antigen ; CD47 Antigen ; CD47 protein, human
Language	English
Publishing date	2023-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-005857
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Article ; Online: ADHD medicine consumption in Europe after COVID-19: catch-up or trend change?

Gimbach, Sophie / Vogel, Daniel / Fried, Roland / Faraone, Stephen V / Banaschewski, Tobias / Buitelaar, Jan / Döpfner, Manfred / Ammer, Richard

BMC psychiatry

2024 Volume 24, Issue 1, Page(s) 112

Abstract: Background: Although the COVID-19 pandemic and its implications have been associated with mental health services utilization and medication consumption, there is no longitudinal study on the long-term impact on ADHD medication use trends.: Methods: ... ...

Abstract	Background: Although the COVID-19 pandemic and its implications have been associated with mental health services utilization and medication consumption, there is no longitudinal study on the long-term impact on ADHD medication use trends. Methods: This study examines the European ADHD medication consumption in 2020 to 2022 compared to the predicted consumption assuming the persistence of pre-pandemic trends. Predictions are calculated using Seasonal Autoregressive Integrated Moving Average (SARIMA) models. Results: While European ADHD medication sales recorded a drop in 2020, they returned to the predicted level in 2021, even slightly exceeding it. In 2022, we found a clear exceedance of the predicted level by 16.4% on average at country level. Furthermore, the increase in consumption growth in the post-pandemic period (2021-2022) compared to the pre-pandemic period (2014-2019) was significant in 26 of the 28 European countries under consideration. Conclusion: There is strong evidence of a trend change in the ADHD medicine consumption growth throughout Europe after the COVID-19 pandemic.
MeSH term(s)	Humans ; Attention Deficit Disorder with Hyperactivity/drug therapy ; Attention Deficit Disorder with Hyperactivity/epidemiology ; Pandemics ; COVID-19 ; Europe/epidemiology ; Mental Health Services
Language	English
Publishing date	2024-02-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2050438-X
ISSN	1471-244X ; 1471-244X
ISSN (online)	1471-244X
ISSN	1471-244X
DOI	10.1186/s12888-024-05505-9
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Article ; Online: Neurophysiology of sustained attention in early infancy: Investigating longitudinal relations with recognition memory outcomes.

Brandes-Aitken, Annie / Metser, Maya / Braren, Stephen H / Vogel, Sarah C / Brito, Natalie H

Infant behavior & development

2023 Volume 70, Page(s) 101807

Abstract: The ability to sustain attention is a critical cognitive domain that emerges in infancy and is predictive of a multitude of cognitive processes. Here, we used a heart rate (HR) defined measure of sustained attention to assess corresponding changes in ... ...

Abstract	The ability to sustain attention is a critical cognitive domain that emerges in infancy and is predictive of a multitude of cognitive processes. Here, we used a heart rate (HR) defined measure of sustained attention to assess corresponding changes in frontal electroencephalography (EEG) power at 3 months of age. Second, we examined how the neural underpinnings of HR-defined sustained attention were associated with sustained attention engagement. Third, we evaluated if neural or behavioral sustained attention measures at 3-months predicted subsequent recognition memory scores at 9 months of age. Seventy-five infants were included at 3 months of age and provided usable attention and EEG data and 25 infants returned to the lab at 9 months and provided usable recognition memory data. The current study focuses on oscillatory power in the theta (4-6 Hz) frequency band during phases of HR-defined sustained attention and inattention phases. Results revealed that theta power was significantly higher during phases of sustained attention. Second, higher theta power during sustained attention was positively associated with proportion of time in sustained attention. Third, longitudinal analyses indicated a significant positive association between theta power during sustained attention on 9-month visual paired comparison scores such that higher theta power predicted higher visual paired comparison scores at 9-months. These results highlight the interrelation of the attention and arousal systems which have longitudinal implications for subsequent recognition memory processes.
MeSH term(s)	Humans ; Infant ; Electroencephalography/methods ; Memory/physiology ; Cognition/physiology ; Recognition, Psychology ; Arousal
Language	English
Publishing date	2023-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	224510-3
ISSN	1934-8800 ; 1879-0453 ; 0163-6383
ISSN (online)	1934-8800 ; 1879-0453
ISSN	0163-6383
DOI	10.1016/j.infbeh.2022.101807
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Zs.B 2273: Show issues

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Article ; Online: Understanding the Value of International Research Networks: An Evaluation of the International Cancer Screening Network of the US National Cancer Institute.

Vogel, Amanda L / Puricelli Perin, Douglas M / Lu, Ya-Ling / Taplin, Stephen H

Journal of global oncology

2019 Volume 5, Page(s) 1–12

Abstract: Purpose: International research networks have the potential to accelerate scientific progress via knowledge sharing and collaboration. In 2018, the US National Cancer Institute evaluated the International Cancer Screening Network (ICSN), in operation ... ...

Abstract	Purpose: International research networks have the potential to accelerate scientific progress via knowledge sharing and collaboration. In 2018, the US National Cancer Institute evaluated the International Cancer Screening Network (ICSN), in operation since 1988. Methods: ICSN hosts a biennial scientific meeting and scientific working groups. A survey was fielded to 665 ICSN participants, and a bibliometric analysis was conducted for ICSN publications. Results: A total of 243 individuals completed the survey (36.5%). They reported that participating in the ICSN helped advance their knowledge of cancer screening research (75.7%), policy development (56%), and implementation (47.7%). Approximately three-quarters agreed that ICSN facilitated knowledge sharing and networking among researchers and implementers (79.9%) and those working on different continents (74.0%) and cancer sites (73.7%). More than half reported that participating helped them form new collaborations in screening implementation (58.0%) or research (57.6%). Most agreed that ICSN helped to advance screening research and evaluation (75.4%), effective screening practices (71.2%), and screening policies (60.9%). Many reported that participating informed advances in their own research (68.7%) and screening implementation (50.2%) and policies (49.4%) in their settings. Approximately two-thirds agreed that ICSN helped advance career development among current experts (66.6%) and train the next generation (62.2%). Half (51.4%) reported that participating advanced their own careers. The 20 ICSN publications included 75 coauthors. They were cited in 589 publications with more than 2,000 coauthors. Conclusion: Findings provide evidence of the influence of ICSN on international knowledge dissemination, collaboration, and advances in cancer screening research, implementation, and policies and highlight the potential value of longstanding international research networks.
MeSH term(s)	Early Detection of Cancer ; Humans ; National Cancer Institute (U.S.) ; United States
Language	English
Publishing date	2019-10-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2378-9506
ISSN (online)	2378-9506
DOI	10.1200/JGO.19.00197
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Article ; Online: Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients.

Li, Michael / Wong, Danny / Sack, Jordan S / Vogel, Alexander S / Hodi, F Stephen / Fong, Lawrence / Lai, Jennifer C / Zucker, Stephen D / Grover, Shilpa

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2024

Abstract: Background & aims: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings.: Methods: We conducted a multicenter, retrospective cohort study ...

Abstract	Background & aims: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings. Methods: We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis. The primary outcome was time to alanine aminotransferase (ALT) normalization (≤40); secondary outcomes included time to ALT ≤100 U/L and time to death. To account for confounding by indication, inverse probability of treatment weighting was applied to perform Cox regression. A sensitivity analysis was performed excluding patients with grade 4 hepatitis. Results: One hundred and sixty-six patients (56.5%) were hospitalized for a median of 6 (interquartile range, 3-11) days. On inverse probability of treatment weighting Cox regression, hospitalization was not associated with time to ALT normalization (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.86-1.43; P = .436) or time to ALT ≤100 U/L (HR, 1.11; 95% CI, 0.86-1.43; P = .420). In the sensitivity analysis limited to patients with grade 3 hepatitis, hospitalization was also not associated with time to ALT normalization (HR, 1.11; 95% CI, 0.83-1.50; P = .474) or time to ALT ≤100 U/L (HR, 1.19; 95% CI, 0.90-1.58; P = .225). In a subgroup analysis of 152 patients with melanoma, hospitalization was not associated with reduced risk of all-cause death (HR, 0.93; 95% CI, 0.53-1.64; P = .798). Notably, despite their Common Terminology Criteria for Adverse Events classification of high-grade hepatitis, 94% of patients had "mild" liver injury based on International Drug-Induced Liver Injury Criteria. Conclusions: Hospitalization of patients with high-grade ICI hepatitis was not associated with faster hepatitis resolution and did not affect mortality. Routine hospitalization may not be necessary in all patients with high-grade ICI hepatitis and Common Terminology Criteria for Adverse Events criteria may overestimate severity of liver injury.
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2024.02.006
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