-
EBioMedicine Jun 2024Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC,...
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking.
METHODS
We screened fourteen patient-derived PDAC cultures which reflect the intra- and intertumoural heterogeneity of PDAC for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H-1PV. Live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays and titration of viral progeny were conducted. Transcriptome profiling was employed to identify potential predictive biomarkers for response to OV treatment.
FINDINGS
Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the classical molecular subtype, the quasi-mesenchymal or basal-like subtype of PDAC was found to be more sensitive to H-1PV, jin-3, and T-VEC. Generally, expression of viral entry receptors did not correlate with sensitivity to OV treatment, with one exception: Expression of Galectin-1 (LGALS1), a factor involved in H-1PV entry, positively correlated with H-1PV induced cell killing. Rather, cellular pathways controlling immunological, metabolic and proliferative signaling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas low cyclic GMP-AMP synthase (cGAS) expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures and cells overexpressing cGAS were found to be less sensitive to MV oncolysis.
INTERPRETATION
Considering the heterogeneity of PDAC and the complexity of biological therapies such as OVs, no single biomarker can explain the spectrum of response patterns. For selection of a particular OV, PDAC molecular subtype, ISG expression as well as activation of distinct signaling and metabolic pathways should be considered. Combination therapies can overcome resistance in specific constellations. Overall, oncolytic virotherapy is a viable treatment option for PDAC, which warrants further development. This study highlights the need for personalised treatment in OVT. By providing all primary data, this study provides a rich source and guidance for ongoing developments.
FUNDING
German National Science Foundation (Deutsche Forschungsgemeinschaft, DFG), German Cancer Aid (Deutsche Krebshilfe), German National Academic Scholarship Foundation (Studienstiftung des deutschen Volkes), Survival with Pancreatic Cancer Foundation.
PubMed: 38941955
DOI: 10.1016/j.ebiom.2024.105219 -
Veterinary Microbiology Jun 2024Rabies, caused by lyssavirus rabies (Rabies lyssavirus, RABV), is a fatal disease among humans and almost all warm-blooded animals. In this study, we found that RABV...
Rabies, caused by lyssavirus rabies (Rabies lyssavirus, RABV), is a fatal disease among humans and almost all warm-blooded animals. In this study, we found that RABV infection induces the up-regulation of receptor transporter protein 4 (RTP4) in mouse brains and different cells of nervous tissue. Over-expression of RTP4 reduces the viral titer of RABV in different neuronal cells. Furthermore, a recombinant RABV expressing RTP4, named rRABV-RTP4, was constructed and displayed a lower viral titer in different neuronal cells due to the expression of RTP4. Moreover, the survival rates of mice infected with rRABV-RTP4 were significantly higher than those of mice infected with parent virus rRABV or control virus rRABV-RTP4(-). In terms of mechanism, RTP4 could bind viral genomic RNA (vRNA) of RABV, and suppress the whole viral genome amplification. In addition, we found that the zinc finger domain (ZFD) of RTP4 exerts the antiviral function by truncation analysis, and an important amino acids site (C95) in the RTP4 3CxxC motif which is essential for its antiviral function was identified by mutation analysis. This study contributes to our understanding of how RTP4 or other RTP proteins play a role in defense against the invasion of RABV or other viruses.
PubMed: 38941768
DOI: 10.1016/j.vetmic.2024.110159 -
Annual Review of Immunology Jun 2024The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities... (Review)
Review
The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.
Topics: Humans; Immunity, Innate; COVID-19; SARS-CoV-2; Cytokine Release Syndrome; Cytokines; Animals; Coronavirus Infections; Immune Evasion
PubMed: 38941608
DOI: 10.1146/annurev-immunol-083122-043545 -
Annual Review of Immunology Jun 2024Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic... (Review)
Review
Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and the ensuing production of type I interferon and other soluble mediators, which orchestrate innate and adaptive responses. We review several aspects of pDC biology that have recently come to the fore. We discuss emerging questions regarding the lineage affiliation and origin of pDCs and argue that these cells constitute an integral part of the dendritic cell lineage. We emphasize the specific function of pDCs as innate sentinels of virus infection, particularly their recognition of and distinct response to virus-infected cells. This essential evolutionary role of pDCs has been particularly important for the control of coronaviruses, as demonstrated by the recent COVID-19 pandemic. Finally, we highlight the key contribution of pDCs to systemic lupus erythematosus, in which therapeutic targeting of pDCs is currently underway.
Topics: Dendritic Cells; Humans; COVID-19; Animals; Immunity, Innate; SARS-CoV-2; Lupus Erythematosus, Systemic; Toll-Like Receptors; Cell Differentiation; Cell Lineage
PubMed: 38941603
DOI: 10.1146/annurev-immunol-090122-041105 -
Medicine Jun 2024There has been significant interest in the changes in menstrual cycles following coronavirus disease 2019 (COVID-19) infection or vaccination. This study aimed to...
There has been significant interest in the changes in menstrual cycles following coronavirus disease 2019 (COVID-19) infection or vaccination. This study aimed to investigate the evidence for such changes and their potential risk factors. We used a descriptive study design and gathered data by sharing an online survey questionnaire on social media platforms. The questionnaire included questions regarding sociodemographic factors, menstrual cycle changes, and COVID-19 anxiety. The study population comprised women aged 18 to 49 years from Izmir. All data analyses were performed using Statistical Package for the Social Sciences 21.0. The risk factors influencing menstrual irregularities were determined after the COVID binary logistic regression analysis, including univariate and multivariate models. Among the 465 participants, those with an associate's degree had a significantly higher risk of menstrual irregularities than those with a high school diploma (P = .012). Anxiety scores emerged as a significant risk factor for menstrual cycle irregularities (P = .026). However, neither COVID-19 infection nor vaccination resulted in significant changes in the menstrual cycle characteristics (P > .05). Other sociodemographic variables, such as age, body mass index, and smoking, were not significantly associated with menstrual cycle changes(P > .05). The study findings suggest that educational level and anxiety may play a role in menstrual irregularities, whereas COVID-19 infection or vaccination itself may not directly affect menstrual cycle.
Topics: Humans; Female; COVID-19; Adult; Risk Factors; Anxiety; Middle Aged; Young Adult; Adolescent; COVID-19 Vaccines; Menstruation Disturbances; SARS-CoV-2; Surveys and Questionnaires; Vaccination; Educational Status
PubMed: 38941384
DOI: 10.1097/MD.0000000000038771 -
PloS One 2024Spinal cord injury (SCI) is a consequence of significant disability and health issues globally, and long COVID represents the symptoms of neuro-musculoskeletal,...
BACKGROUND
Spinal cord injury (SCI) is a consequence of significant disability and health issues globally, and long COVID represents the symptoms of neuro-musculoskeletal, cardiovascular and respiratory complications.
PURPOSE
This study aimed to identify the symptom responses and disease burden of long COVID in individuals with spinal cord injury.
METHODS
This case-control study was conducted on patients with SCI residing at a specialised rehabilitation centre in Bangladesh. Forty patients with SCI with and without long COVID symptoms (LCS) were enrolled in this study at a 1:1 ratio according to WHO criteria.
RESULT
Twelve LCS were observed in patients with SCI, including fatigue, musculoskeletal pain, memory loss, headache, respiratory problems, anxiety, depression, insomnia, problem in ADL problem in work, palpitation, and weakness. The predictors of developing long COVID include increasing age (p<0.002), increasing BMI (p<0.03), and longer duration of spinal cord injury (p<0.004). A significant difference (p<0.01) in overall years of healthy life lost due to disability (YLD) for non-long COVID cases was 2.04±0.596 compared to long COVID (LC) cases 1.22±2.09 was observed.
CONCLUSION
Bangladeshi patients of SCI presented 12 long COVID symptoms and have a significant disease burden compared to non long COVID cases.
Topics: Humans; Spinal Cord Injuries; Male; Female; COVID-19; Case-Control Studies; Adult; Middle Aged; Bangladesh; Disabled Persons; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 38941308
DOI: 10.1371/journal.pone.0304824 -
PloS One 2024Data on COVID-19 vaccine effectiveness to support regional vaccine policy and practice are limited in Africa. Thus, this review aimed to evaluate the efficacy and...
BACKGROUND
Data on COVID-19 vaccine effectiveness to support regional vaccine policy and practice are limited in Africa. Thus, this review aimed to evaluate the efficacy and effectiveness of COVID-19 vaccines administered in Africa.
METHODS
We systematically searched peer-reviewed randomized controlled trials (RCTs), prospective and retrospective cohort studies, and case-control studies that reported on VE in Africa. We carried out a risk of bias assessment, and the findings of this review were synthesized and presented in a narrative form, including tables and figures. The synthesis was focused on COVID-19 VE against various levels of the disease condition and outcomes (infection, hospitalization or critical, and death), time points, and variants of concern.
RESULTS
A total of 13 studies, with a total sample size of 913,285 participants, were included in this review. The majority (8/13) of studies were from South Africa and 38.5% (5/13) were randomized clinical trials. The studies reported that a full dose of Pfizer-BioNTech vaccine had a VE of 100% against COVID-19 infection by Beta (B.1.351) and Delta variants and 96.7% against hospitalization by Delta variant. The Johnson and Johnson vaccine had VE ranging from 38.1%-62.0% against hospitalization and 51.9%- 86% against critical disease by Beta (B 1.351) variant. The Oxford-AstraZeneca vaccine had a VE of 89.4% against hospitalization by the Omicron variant but was not effective against the B.1.351 variant (10.4%). The Sinopharm vaccine had a VE of 67% against infection and 46% against hospitalization by Delta variant.
CONCLUSIONS
COVID-19 vaccines administered in Africa were effective in preventing infections, hospitalization, and death. These review findings underscore the need for concerted efforts of all stakeholders to enhance the access and availability of COVID-19 vaccines and reinforce public awareness to reach the high-risk, unvaccinated group of the African population.
Topics: Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Africa; Vaccine Efficacy; Hospitalization; Randomized Controlled Trials as Topic
PubMed: 38941303
DOI: 10.1371/journal.pone.0306309 -
PloS One 2024During the Omicron pandemic, clinical first-line nurses played a crucial role in healthcare. Their innovative behavior enhanced the quality of nursing and served as a...
Innovative behavior and organizational innovation climate among the Chinese clinical first-line nurses during the Omicron pandemic: The mediating roles of self-transcendence.
BACKGROUND
During the Omicron pandemic, clinical first-line nurses played a crucial role in healthcare. Their innovative behavior enhanced the quality of nursing and served as a vital factor in driving the sustainable development of the nursing discipline and healthcare industry. Many previous studies have confirmed the significance of nurses' innovative behavior worldwide. However, the correlations among innovative behaviors, organizational innovation climate, self-transcendence, and their mediating roles in Chinese clinical first-line nurses need further research.
METHODS
A cross-sectional study was conducted, and the quality reporting conformed to the STROBE Checklist. From March 2022 to February 2023, a convenience sample of 1,058 Chinese clinical first-line nurses was recruited from seven tertiary grade-A hospitals of Tianjin city in Northern China. The Demographic Characteristics Questionnaire, Nurse Innovative Behavior Scale (NIBS), Nurse Organizational Innovation Climate Scale, and the Self-Transcendence Scale were used. The data was analyzed using descriptive statistics, correlation, and process plug-in mediation effect analyses.
RESULTS
The total scores of innovative behavior, organizational innovation climate, and self-transcendence were 33.19 ± 6.71, 68.88 ± 12.76, and 41.25 ± 7.83, respectively. Innovative behavior was positively correlated with the organizational innovation climate (r = 0.583, p < 0.01) and self-transcendence (r = 0.635, p < 0.01). Self-transcendence partially mediated mediating role between innovative behavior and organizational innovation climate, accounting for 41.7%.
CONCLUSION
The innovative behavior, organizational innovation climate, and self-transcendence among the first-line nurses during the Omicron pandemic were relatively moderate, which needs improving. Organizational innovation climate can directly affect the innovative behavior among Chinese clinical first-line nurses and indirectly through the mediating role of self-transcendence. It is recommended that nursing managers adjust their management strategies and techniques based on the unique characteristics of nurses during the pandemic. This includes fostering a positive and inclusive environment for organizational innovation, nurturing nurses' motivation and awareness for innovation, enhancing their ability to gather information effectively, overcoming negative emotions resulting from the pandemic, and promoting personal growth. These efforts will ultimately enhance nursing quality and satisfaction during the Omicron pandemic.
Topics: Humans; COVID-19; China; Cross-Sectional Studies; Adult; Female; Male; Organizational Innovation; Surveys and Questionnaires; Pandemics; Nurses; SARS-CoV-2; Organizational Culture; Middle Aged; East Asian People
PubMed: 38941294
DOI: 10.1371/journal.pone.0306109 -
PloS One 2024Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and...
Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and risk factors remain limited in sub-Saharan Africa. In Ghana, HCV-related deaths are estimated to have increased since 2015. Risk factors associated with HCV infection in Ghana are not well described. The aim of this study was to determine the prevalence of, and risk factors associated with hepatitis C virus infection in the Upper East Region located in the northern part of Ghana. A community-based cross-sectional study was conducted in 9 communities in the Upper East region of Ghana. A total of 1,769 participants aged ≥12 years were screened for HCV antibody (anti-HCV) using rapid diagnostic testing (RDT). Seventy-four participants undertook HCV RNA testing after a positive anti-HCV result. Multivariate logistic regression was used to determine risk factors associated with HCV seropositivity. The anti-HCV prevalence was 8.4%, with 149 out of 1,769 testing anti-HCV positive. Mean age (±SD) of seropositive persons was 45.4 (±16.3) years. The highest anti-HCV seroprevalence was amongst persons aged 60 years and above. Forty-four out of 74 (59.5%) seropositive cases had viremic infection and the estimated viremic prevalence in the screened population was 5.0%. Predictors of HCV seropositivity were age (OR 1.03 95% CI 1.01-1.04), history of female genital mutilation or circumcision (OR 1.63 95% CI 1.04-2.55), sexual activity (OR 2.57 95% CI 1.38-4.79), positive maternal HCV status (OR 10.38 95% CI 4.13-26.05) and positive HIV status (OR 4.03 95% CI 1.35-12.05). In conclusion, the Upper East Region demonstrates a high Hepatitis C antibody prevalence. Almost 60% of individuals have viremic infection, however the cost of RNA testing is a barrier to virological diagnosis. There is a need to educate the population about HCV-associated risk factors to reduce HCV transmission and burden of disease.
Topics: Humans; Ghana; Female; Male; Middle Aged; Cross-Sectional Studies; Risk Factors; Adult; Hepatitis C; Prevalence; Hepacivirus; Young Adult; Seroepidemiologic Studies; Adolescent; Hepatitis C Antibodies; Aged; Child
PubMed: 38941280
DOI: 10.1371/journal.pone.0306292 -
Journal of Primary Health Care Jun 2024Introduction From a coronavirus disease (COVID-19) pandemic perspective, Aotearoa New Zealand (NZ) rural residents formed an at-risk population, and disparities between...
He Aroka Urutā. Rural health provider perspectives of the COVID-19 vaccination rollout in rural Aotearoa New Zealand with a focus on Māori and Pasifika communities: a qualitative study.
Introduction From a coronavirus disease (COVID-19) pandemic perspective, Aotearoa New Zealand (NZ) rural residents formed an at-risk population, and disparities between rural and urban COVID-19 vaccination coverage have been found. Aim To gain insight into factors contributing to the urban-rural COVID-19 vaccination disparity by exploring NZ rural health providers' experiences of the vaccine rollout and pandemic response in rural Māori and Pasifika communities. Methods Rural health providers at four sites participated in individual or focus group semi-structured interviews exploring their views of the COVID-19 vaccine rollout. Thematic analysis was undertaken using a framework-guided rapid analysis method. Results Twenty interviews with 42 participants were conducted. Five themes were identified: Pre COVID-19 rural situation, fragile yet resilient; Centrally imposed structures, policies and solutions - urban-centric and Pakehā focused; Multiple logistical challenges - poor/no consideration of rural context in planning stages resulting in wasted resource and time; Taking ownership - rural providers found geographically tailored, culturally anchored and locally driven solutions; Future directions - sustained investment in rural health services, including funding long-term integrated (rather than 'by activity') health services, would ensure success in future vaccine rollouts and other health initiatives for rural communities. Discussion In providing rural health provider perspectives from rural areas serving Māori and Pasifika communities during the NZ COVID-19 vaccine rollout, the importance of the rural context is highlighted. Findings provide a platform on which to build further research regarding models of rural health care to ensure services are designed for rural NZ contexts and capable of meeting the needs of diverse rural communities.
Topics: Humans; New Zealand; COVID-19 Vaccines; COVID-19; Qualitative Research; Native Hawaiian or Other Pacific Islander; Rural Health Services; Rural Population; SARS-CoV-2; Female; Health Personnel; Interviews as Topic; Male; Focus Groups; Healthcare Disparities; Attitude of Health Personnel; Pandemics; Adult; Maori People
PubMed: 38941251
DOI: 10.1071/HC23171