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Article: Quantification of transgene expression in GSH AAVS1 with a novel CRISPR/Cas9-based approach reveals high transcriptional variation.

Inderbitzin, Anne / Loosli, Tom / Kouyos, Roger D / Metzner, Karin J

Molecular therapy. Methods & clinical development

2022 Volume 26, Page(s) 107–118

Abstract: Genomic safe harbors (GSH) are defined as sites in the host genome that allow stable expression of inserted transgenes while having no adverse effects on the host cell, making them ideal for use in basic research and therapeutic applications. Silencing ... ...

Abstract	Genomic safe harbors (GSH) are defined as sites in the host genome that allow stable expression of inserted transgenes while having no adverse effects on the host cell, making them ideal for use in basic research and therapeutic applications. Silencing and fluctuations in transgene expression would be highly undesirable effects. We have previously shown that transgene expression in Jurkat T cells is not silenced for up to 160 days after CRISPR-Cas9-mediated insertion of reporter genes into the adeno-associated virus site 1 (AAVS1), a commonly used GSH. Here, we studied fluctuations in transgene expression upon targeted insertion into the GSH AAVS1. We have developed an efficient method to generate and validate highly complex barcoded plasmid libraries to study transgene expression on the single-cell level. Its applicability is demonstrated by inserting the barcoded transgene Cerulean into the AAVS1 locus in Jurkat T cells via the CRISPR-Cas9 technology followed by next-generation sequencing of the transcribed barcodes. We observed large transcriptional variations over two logs for transgene expression in the GSH AAVS1. This barcoded transgene insertion model is a powerful tool to investigate fluctuations in transgene expression at any GSH site.
Language	English
Publishing date	2022-06-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2022.06.003
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Article: The effect of combining antibiotics on resistance: A systematic review and meta-analysis.

Siedentop, Berit / Kachalov, Viacheslav N / Witzany, Christopher / Egger, Matthias / Kouyos, Roger D / Bonhoeffer, Sebastian

medRxiv : the preprint server for health sciences

2023

Abstract: When and under which conditions antibiotic combination therapy decelerates rather than accelerates resistance evolution is not well understood. We examined the effect of combining antibiotics on within-patient resistance development across various ... ...

Abstract	When and under which conditions antibiotic combination therapy decelerates rather than accelerates resistance evolution is not well understood. We examined the effect of combining antibiotics on within-patient resistance development across various bacterial pathogens and antibiotics. We searched CENTRAL, EMBASE and PubMed for (quasi)-randomised controlled trials (RCTs) published from database inception to November 24
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.10.23292374
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Article ; Online: Mortality and morbidity related to hepatitis C virus infection in hospitalized adults-A propensity score matched analysis.

Hovaguimian, Frédérique / Beeler, Patrick E / Müllhaupt, Beat / Günthard, Huldrych F / Maeschli, Bettina / Bruggmann, Philip / Fehr, Jan S / Kouyos, Roger D

Journal of viral hepatitis

2023 Volume 30, Issue 9, Page(s) 765–774

Abstract: The World Health Organization (WHO) aims to reduce HCV mortality, but estimates are difficult to obtain. We aimed to identify electronic health records of individuals with HCV infection, and assess mortality and morbidity. We applied electronic ... ...

Abstract	The World Health Organization (WHO) aims to reduce HCV mortality, but estimates are difficult to obtain. We aimed to identify electronic health records of individuals with HCV infection, and assess mortality and morbidity. We applied electronic phenotyping strategies on routinely collected data from patients hospitalized at a tertiary referral hospital in Switzerland between 2009 and 2017. Individuals with HCV infection were identified using International Classification of Disease (ICD)-10 codes, prescribed medications and laboratory results (antibody, PCR, antigen or genotype test). Controls were selected using propensity score methods (matching by age, sex, intravenous drug use, alcohol abuse and HIV co-infection). Main outcomes were in-hospital mortality and attributable mortality (in HCV cases and study population). The non-matched dataset included records from 165,972 individuals (287,255 hospital stays). Electronic phenotyping identified 2285 stays with evidence of HCV infection (1677 individuals). Propensity score matching yielded 6855 stays (2285 with HCV, 4570 controls). In-hospital mortality was higher in HCV cases (RR 2.10, 95%CI 1.64 to 2.70). Among those infected, 52.5% of the deaths were attributable to HCV (95%CI 38.9 to 63.1). When cases were matched, the fraction of deaths attributable to HCV was 26.9% (HCV prevalence: 33%), whilst in the non-matched dataset, it was 0.92% (HCV prevalence: 0.8%). In this study, HCV infection was strongly associated with increased mortality. Our methodology may be used to monitor the efforts towards meeting the WHO elimination targets and underline the importance of electronic cohorts as a basis for national longitudinal surveillance.
MeSH term(s)	Humans ; Adult ; Hepacivirus ; Propensity Score ; Hepatitis C ; HIV Infections/complications ; Morbidity ; Prevalence
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/jvh.13861
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Zs.A 4119: Show issues

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Article: Cohort Profile: The Zurich Primary HIV Infection Study.

Freind, Matt C / Tallón de Lara, Carmen / Kouyos, Roger D / Wimmersberger, David / Kuster, Hebert / Aceto, Leonardo / Kovari, Helen / Flepp, Markus / Schibli, Adrian / Hampel, Benjamin / Grube, Christina / Braun, Dominique L / Günthard, Huldrych F

Microorganisms

2024 Volume 12, Issue 2

Abstract: The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV infection. The ZPHI enrolls individuals with documented primary ...

Abstract	The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV infection. The ZPHI enrolls individuals with documented primary HIV-1 infection. At the baseline and thereafter, the socio-demographic, clinical, and laboratory data are systematically collected, and regular blood sampling is performed for biobanking. By the end of December 2022, 486 people were enrolled, of which 353 were still undergoing active follow-up. Of the 486 participants, 86% had an acute infection, and 14% a recent HIV-1 infection. Men who have sex with men accounted for 74% of the study population. The median time from the estimated date of infection to diagnosis was 32 days. The median time from diagnosis to the initiation of antiretroviral therapy was 11 days, and this has consistently decreased over the last two decades. During the seroconversion phase, 447 (92%) patients reported having symptoms, of which only 73% of the patients were classified as having typical acute retroviral syndrome. The ZPHI study is a well-characterized cohort belonging to the most extensively studied primary HIV infection cohort. Its findings contribute to advancing our understanding of the early stages of HIV infection and pathogenesis, and it is paving the way to further improve HIV translational research and HIV medicine.
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms12020302
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Article ; Online: Characterization and Determinants of Long-Term Immune Recovery Under Suppressive Antiretroviral Therapy.

Turk, Teja / Labarile, Marco / Braun, Dominique L / Rauch, Andri / Stöckle, Marcel / Cavassini, Matthias / Hoffmann, Matthias / Calmy, Alexandra / Bernasconi, Enos / Notter, Julia / Pasin, Chloé / Günthard, Huldrych F / Kouyos, Roger D

Journal of acquired immune deficiency syndromes (1999)

2024 Volume 96, Issue 1, Page(s) 68–76

Abstract: Objective: We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia.: Methods: Using data from ... ...

Abstract	Objective: We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia. Methods: Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in people living with HIV on ART for at least 8 years by fitting nonlinear mixed-effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed. Results: Overall, our population showed good immune recovery (median plateau [interquartile range]-CD4: 718 [555-900] cells/μL, CD8: 709 [547-893] cells/μL, CD4/CD8: 1.01 [0.76-1.37]). The following factors were predictive of recovery: age, sex, nadir/zenith value, pre-ART HIV-1 viral load, hepatitis C, ethnicity, acquisition risk, and timing of ART initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4 and CD8 cell recovery dynamics: Compared with carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3%-18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using predictors derived from the recovery dynamics improved most model fits. Conclusion: We described and validated a method to characterize individual immune recovery trajectories of people living with HIV on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia.
MeSH term(s)	Humans ; HIV Infections ; Cohort Studies ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; Anti-Retroviral Agents/therapeutic use ; Pneumonia, Bacterial/drug therapy ; Pneumonia, Bacterial/etiology ; Viral Load ; Antiretroviral Therapy, Highly Active/methods ; Anti-HIV Agents/therapeutic use
Chemical Substances	Anti-Retroviral Agents ; Anti-HIV Agents
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000003388
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Zs.A 2442: Show issues

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Article ; Online: Early off-label treatment during pandemics? A dilemma.

Roth, Jan A / Ballouz, Tala / Kouyos, Roger D / Battegay, Manuel

Swiss medical weekly

2020 Volume 150, Page(s) w20281

MeSH term(s)	COVID-19 ; Humans ; Off-Label Use ; Pandemics
Keywords	covid19
Language	English
Publishing date	2020-05-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2036179-8
ISSN	1424-3997 ; 1424-7860
ISSN (online)	1424-3997
ISSN	1424-7860
DOI	10.4414/smw.2020.20281
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Ua VI Zs.152: Show issues

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Article ; Online: Author Correction: Efficient microbial colony growth dynamics quantification with ColTapp, an automated image analysis application.

Bär, Julian / Boumasmoud, Mathilde / Kouyos, Roger D / Zinkernagel, Annelies S / Vulin, Clément

Scientific reports

2021 Volume 11, Issue 1, Page(s) 6050

Language	English
Publishing date	2021-03-09
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-85033-8
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Article ; Online: Modifiable and nonmodifiable risk factors for non-ventilator-associated hospital-acquired pneumonia identified in a retrospective cohort study.

Kachalov, Viacheslav N / Kuster, Stefan P / Balakrishna, Suraj / Schreiber, Peter W / Jakob, Werner / Sax, Hugo / Kouyos, Roger D / Wolfensberger, Aline

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2022 Volume 28, Issue 11, Page(s) 1451–1457

Abstract: Objectives: Hospital-acquired pneumonia in nonventilated patients (nvHAP) belongs to the most common healthcare-associated infections. This study aimed to investigate risk factors for nvHAP in patients outside the intensive care unit, focusing on ... ...

Abstract	Objectives: Hospital-acquired pneumonia in nonventilated patients (nvHAP) belongs to the most common healthcare-associated infections. This study aimed to investigate risk factors for nvHAP in patients outside the intensive care unit, focusing on modifiable risk factors. Methods: All inpatients admitted to an academic teaching hospital in Switzerland between 2017 and 2018 were included. nvHAP was defined according to European Centre for Disease Prevention and Control criteria. Patient days during and after ICU stay were excluded. Candidate risk factors-both constant and time varying-were included in uni- and multivariable Cox proportional hazards models. The decay ratio and the characteristic time of influence of hazard ratios (HRs) was estimated by adopting a linear decay in the Cox model. Results: A total of 66 001 hospitalizations with 314 (0.48%) nvHAP and 471 401 patient days were included. Median age was 57 years (interquartile range: 38 to 71 years) and 32 253 (48.9%) patients were male. Among nonmodifiable risk factors, age (adjusted HR (aHR) 2.66 for age ≥60 years, 95% CI 1.59 to 4.45) and male sex (aHR 1.71, 95% CI 1.34 to 2.18) were independently associated with nvHAP. Time-varying exposures showing strongest independent association with nvHAP were tube feeding (aHR 3.24, 95% CI 2.17 to 4.83), impaired consciousness (aHR 2.32, 95% CI 1.63 to 3.31), and severely impaired activity and mobility (aHR 2.06, 95% CI 1.50 to 2.84). The association with nvHAP decayed within 7.1 to 13.2 days after these exposures ended. Discussion: The risk for nvHAP varies with time, depending on the patient's medical condition and medical interventions. Several risk factors for nvHAP represent potential targets for specific prevention measures.
MeSH term(s)	Humans ; Male ; Middle Aged ; Female ; Retrospective Studies ; Healthcare-Associated Pneumonia/epidemiology ; Healthcare-Associated Pneumonia/prevention & control ; Cross Infection/microbiology ; Intensive Care Units ; Risk Factors ; Hospitals, Teaching
Language	English
Publishing date	2022-05-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2022.05.011
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Zs.A 4541: 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)
Zs.MO 284: Show issues

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Article ; Online: Identifying Contact Risks for SARS-CoV-2 Transmission to Healthcare Workers during Outbreak on COVID-19 Ward.

Zeeb, Marius / Weissberg, Dana / Rampini, Silvana K / Müller, Rouven / Scheier, Thomas / Zingg, Walter / Kouyos, Roger D / Wolfensberger, Aline

Emerging infectious diseases

2022 Volume 28, Issue 10, Page(s) 2134–2137

Abstract: We assessed the risk for different exposures to SARS-CoV-2 during a COVID-19 outbreak among healthcare workers on a hospital ward in late 2020. We found working with isolated COVID-19 patients did not increase the risk of COVID-19 among workers, but ... ...

Abstract	We assessed the risk for different exposures to SARS-CoV-2 during a COVID-19 outbreak among healthcare workers on a hospital ward in late 2020. We found working with isolated COVID-19 patients did not increase the risk of COVID-19 among workers, but working shifts with presymptomatic healthcare coworkers did.
MeSH term(s)	COVID-19/epidemiology ; Disease Outbreaks ; Health Personnel ; Hospitals ; Humans ; SARS-CoV-2
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Letter
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2810.220266
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Zs.A 4778: Show issues

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Article ; Online: Editorial Commentary: The Irreversibility of HIV Drug Resistance.

Kouyos, Roger D / Günthard, Huldrych F

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2015 Volume 61, Issue 5, Page(s) 837–839

MeSH term(s)	Drug Resistance, Viral/genetics ; Female ; HIV Infections/epidemiology ; HIV Infections/virology ; HIV-1/classification ; HIV-1/genetics ; Humans ; Male
Language	English
Publishing date	2015-09-01
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/civ400
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Zs.MO 480: Show issues

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