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  • Oxford University Press (OUP)  (5)
  • Medicine  (5)
  • 1
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 224, No. 10 ( 2021-11-22), p. 1796-1805
    Abstract: Diversity in the HLA genes might be associated with disease outcomes—the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods We utilized DNA from & gt; 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the 2 HLA alleles at that locus. Results Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend = 1.18 × 10–7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend = .031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio = 1.40; 95% confidence interval, 1.06–1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control. Conclusions Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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  • 2
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 223, No. 3 ( 2021-02-13), p. 441-444
    Abstract: Nasopharyngeal carcinoma (NPC) is caused by Epstein-Barr virus (EBV) and is more likely to occur in susceptible families. Whether genetic susceptibility operates through altered EBV control is incompletely understood. We used a NPC risk prediction model based on 14 EBV markers to compare risk score distribution in unaffected members from multiplex families with that in population-based controls. Despite the absence of NPC at the time of antibody measurement, we observed an upward shift in risk score among multiplex family members compared to the general population, consistent with the possibility that genetic factors affect NPC risk through alterations in EBV control.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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  • 3
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 11 ( 2021-12-06), p. e4154-e4165
    Abstract: Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren’t well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. Methods We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. Results Compared with children, older patients ( & gt;50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P & lt; .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P & lt; .025). Conclusions Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2002229-3
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  • 4
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 3 ( 2023-02-08), p. e336-e341
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the Delta and Omicron variants, have been reported to show significant resistance to approved neutralizing monoclonal antibodies (mAbs) and vaccines. We previously identified a mAb named 35B5 that harbors broad neutralization to SARS-CoV-2 VOCs. Herein, we explored the protection efficacy of a 35B5-based nasal spray against SARS-CoV-2 VOCs in a small-scale clinical trial. Methods We enrolled 30 healthy volunteers who were nasally administered the modified 35B5 formulation. At 12, 24, 48, and 72 hours after nasal spray, the neutralization efficacy of nasal mucosal samples was assayed with pseudoviruses coated with SARS-CoV-2 spike protein of the wild-type strain or the Alpha, Beta, Delta, or Omicron variants. Results The nasal mucosal samples collected within 24 hours after nasal spray effectively neutralized SARS-CoV-2 VOCs (including Delta and Omicron). Meanwhile, the protection efficacy was 60% effective and 20% effective at 48 and 72 hours after nasal spray, respectively. Conclusions A single nasal spray of 35B5 formation conveys 24-hour effective protection against SARS-CoV-2 VOCs, including the Alpha, Beta, Delta, or Omicron variants. Thus, 35B5 nasal spray might be potential in strengthening SARS-CoV-2 prevention, especially in high-risk populations. Clinical Trials Registration 2022-005-02-KY.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002229-3
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2019
    In:  International Journal of Epidemiology Vol. 48, No. 4 ( 2019-08-01), p. 1091-1100
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 48, No. 4 ( 2019-08-01), p. 1091-1100
    Abstract: Available data on the effects of heatwaves on hospitalizations for diabetes and the post-discharge status of diabetics are scarce. This study aimed to assess the effects of heatwaves on hospitalizations and post-discharge deaths for diabetes, and to identify the individual- and community-level characteristics [i.e. age, gender, Socio-economic Indexes for Areas (SEIFA), and normalized difference vegetation index (NDVI)] that modified heatwave effects. Methods Health data were extracted from a cohort study which included patients in Brisbane, Australia, who were hospitalized due to diabetes from 1st January 2005 to 31st December 2013, and died within 2 months after they were discharged. Data on community-level modifiers, including SEIFA and NDVI (i.e. urban vegetation), were obtained from Australian Bureau of Statistics and Australian Bureau of Meteorology, respectively. Case-crossover design was used to quantify the effects of heatwaves on hospitalizations and post-discharge deaths due to diabetes. Four heatwave definitions incorporating both intensity (i.e. 90th, 95th, 97th and 99th percentiles of mean temperature distribution) and duration (2 days), as well as excess heat factor (EHF), were used. A case-only design was adopted to identify the modifiers of heatwave effects. Results There were 10 542 hospitalizations for diabetes, and 513 patients died due to diabetes within 2 months after discharge. During low-intensity heatwave days (i.e. 90th percentile & 2 days), we did not observe a significant increase in hospitalizations for diabetes [9% at lag 0; 95% confidence interval (CI): –3%, 23%; P = 0.146], but we observed a significant increase in post-discharge deaths (46% at lag 2; 95% CI: 3%, 107%; P = 0.036). During middle-intensity heatwave days (i.e. 95th percentile & 2 days), hospitalizations for diabetes increased by 19% at lag 0 (95% CI: 2%, 39%; P = 0.026), and post-discharge deaths increased by 64% at lag 0 (95% CI: 6%, 154%; P = 0.027). During high-intensity heatwave days (i.e. 97th percentile & 2 days), hospitalizations for diabetes increased by 37% at lag 1 (95% CI: 11%, 69%; P = 0.004) and post-discharge deaths increased by 137% at lag 1 (95% CI: 39%, 303%; P = 0.002). When heatwave intensity increased to 99th percentile, we did not observe a significant increase in hospitalizations (–1% at lag 0; 95% CI: –38%, 59%; P = 0.870) or post-discharge deaths (79% at lag 0; 95% CI: –39%, 431%; P = 0.301). When we used EHF to define heatwaves, we observed significant increases of hospitalizations (7%; 95% CI: 1%, 15%; P = 0.039) and post-discharge deaths (68%, 95% CI: 10%, 158%; P = 0.017) during heatwave days, compared with non-heatwave days. Children and male diabetics were particularly vulnerable to heatwave effects, but we did not find any significant modification effect of SEIFA or NDVI on the associations of heatwaves with hospitalizations and post-discharge deaths due to diabetes. Conclusion Heatwaves may lead to hospitalizations of diabetics and their premature deaths. Heat-related diabetes burden in children may increase as climate warms and with increasing obesity rates in adolescents.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1494592-7
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