-
The New England Journal of Medicine Jun 2024The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an...
BACKGROUND
The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern.
METHODS
We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient.
RESULTS
A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with and mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques.
CONCLUSIONS
Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).
Topics: Female; Humans; Middle Aged; Biological Products; Clonal Hematopoiesis; Herpesvirus 4, Human; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Neoplasms, Second Primary; Receptors, Chimeric Antigen; Antineoplastic Agents, Immunological; Virus Integration
PubMed: 38865660
DOI: 10.1056/NEJMoa2401361 -
PLOS Global Public Health 2024Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis...
Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women's perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development. We conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women's experiences of Zika virus (ZIKV) test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews. Participants in Brazil and Colombia reported that the healthcare system's lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy. Communication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families' preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication.
PubMed: 38865420
DOI: 10.1371/journal.pgph.0002808 -
The South African Journal of Psychiatry... 2023There are a wide range of neuropsychiatric conditions associated with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). These mental...
BACKGROUND
There are a wide range of neuropsychiatric conditions associated with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). These mental disorders may be unrecognised yet their presence can significantly affect outcome.
AIM
This study aimed to determine psychiatric comorbidity associated with HIV and AIDS.
SETTING
The HIV clinic of a tertiary hospital in North-Eastern Nigeria.
METHODS
A cross-sectional descriptive study consecutively recruiting 328 adult persons living with HIV. The Mini International Neuropsychiatric Interview and a sociodemographic questionnaire were administered to the participants.
RESULTS
Two-thirds of the respondents were females. The mean age (±s.d.) was 42 years (±11.24). Majority of the participants had World Health Organization stage 1 HIV disease. The prevalence of psychiatry comorbidity among our respondents was 82.9%. Social phobia was the leading disorder (69.8%). Others were mixed depression anxiety disorder (49.4%) and post-traumatic stress disorder (36.6%). Current psychosis was 27.7%, while major depressive disorder was 12.2%. Psychiatric comorbidity was significantly associated with male gender, religion, ethnicity, marital status and being unemployed with < 0.01. Human immunodeficiency virus stage was related to panic disorder with < 0.01, while viral load was significantly associated with depressive disorder with = 0.001.
CONCLUSION
Majority of our HIV patients attending the clinic have undetected psychiatric morbidity. Clinicians need to be aware of the features of major psychiatric disorders and refer appropriately for improved overall outcome.
CONTRIBUTION
This study contributes to the body of work on unrecognised psychiatric comorbidity in people living with HIV and AIDS, especially in North-Eastern Nigeria, identifying issues which are relevant to clinical practice and buttressing the need for integration of mental healthcare services into HIV treatment and prevention services.
PubMed: 38860146
DOI: 10.4102/sajpsychiatry.v29i0.2022 -
International Journal of General... 2024Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study...
PURPOSE
Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.
PATIENTS AND METHODS
We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.
RESULTS
After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.
CONCLUSION
HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.
PubMed: 38859910
DOI: 10.2147/IJGM.S462844 -
Animal Models and Experimental Medicine Jun 2024This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.
BACKGROUND
This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.
METHODS
Humanized fragments, consisting of the endothelial cell-specific K18 promoter, human ST6GAL1-encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.
RESULTS
Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range.
CONCLUSION
A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.
PubMed: 38859745
DOI: 10.1002/ame2.12449 -
PLOS Global Public Health 2024The COVID-19 pandemic had an unprecedented impact on global mental health and well-being, including across the Asia-Pacific. Efforts to mitigate virus spread led to...
The COVID-19 pandemic had an unprecedented impact on global mental health and well-being, including across the Asia-Pacific. Efforts to mitigate virus spread led to far-reaching disruption in the delivery of health and social services. In response, there was a rapid shift to the use of digital mental health (DMH) approaches. Though these technologies helped to improve access to care for many, there was also substantial risk of access barriers leading to increased inequities in access to mental health care, particularly among at-risk and equity-deserving populations. The objective of this study was to conduct a needs assessment and identify priorities related to equitable DMH access among at-risk and equity-deserving populations in the Asia Pacific region during the first year of the COVID-19 pandemic. The study consisted of a modified Delphi consensus methodology including two rounds of online surveys and online consultations with stakeholders from across the region. Study participants included policy makers, clinicians and service providers, and people with lived experience of mental health conditions. Results demonstrate that vulnerabilities to negative mental health impacts and access barriers were compounded during the pandemic. Access barriers included a lack of linguistically and culturally appropriate DMH options, low mental health literacy and poor access to technological infrastructure and devices, low levels of awareness and trust of DMH options, and lack of policies and guidelines to support effective and equitable delivery of DMH. Recommendations to improve equitable access include ensuring that diverse people with lived experience are engaged in research, co-design and policy development, the development and implementation of evidence-based and equity-informed guidelines and frameworks, clear communication about DMH evidence and availability, and the integration of DMH into broader health systems. Study results can inform the development and implementation of equitable DMH as its use becomes more widespread across health systems.
PubMed: 38857265
DOI: 10.1371/journal.pgph.0002661 -
Trends in Molecular Medicine Jun 2024Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs.... (Review)
Review
Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation.
PubMed: 38853085
DOI: 10.1016/j.molmed.2024.05.009 -
Virologica Sinica Jun 2024The landscape of hepatitis B virus (HBV) integration in the plasma cell-free DNA (cfDNA) of HBV-infected patients with different stages of liver diseases [chronic...
The landscape of hepatitis B virus (HBV) integration in the plasma cell-free DNA (cfDNA) of HBV-infected patients with different stages of liver diseases [chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC)] remains unclear. In this study, we developed an improved strategy for detecting HBV DNA integration in plasma cfDNA, based on DNA probe capture and next-generation sequencing. Using this optimized strategy, we successfully detected HBV integration events in chimeric artificial DNA samples and HBV-infected HepG2-NTCP cells at day one post infection, with high sensitivity and accuracy. The characteristics of HBV integration events in the HBV-infected HepG2-NTCP cells and plasma cfDNA from HBV-infected individuals (CHB, LC, and HCC) were further investigated. A total of 112 and 333 integration breakpoints were detected in the HepG2-NTCP cells and 22 out of 25 (88%) clinical HBV-infected samples, respectively. In vivo analysis showed that the normalized number of support unique sequences (nnsus) in HCC was significantly higher than in CHB or LC patients (P values < 0.05). All integration breakpoints are randomly distributed on human chromosomes and are enriched in the HBV genome around nt 1800. The majority of integration breakpoints (61.86%) are located in the gene-coding region. Both non-homologous end-joining (NHEJ) and microhomology-mediated end-joining (MMEJ) interactions occurred during HBV integration across the three different stages of liver diseases. Our study provides evidence that HBV DNA integration can be detected in the plasma cfDNA of HBV-infected patients, including those with CHB, LC, or HCC, using this optimized strategy.
PubMed: 38852920
DOI: 10.1016/j.virs.2024.06.003 -
Parasitology Research Jun 2024This study aims to assess the effect of the COVID-19 pandemic on the consumption of self-care products for pediculosis capitis management, in Portugal. A segmented...
This study aims to assess the effect of the COVID-19 pandemic on the consumption of self-care products for pediculosis capitis management, in Portugal. A segmented regression analysis of interrupted time series (March 2020) was performed from January 2017 to August 2023 to analyze the short- and long-term impact of the COVID-19 pandemic on the consumption of pediculicides and related products. Monthly rates of absolute consumption were estimated by community pharmacies' dispensing records. Portuguese municipalities were organized into quintiles according to their purchasing power index and percentage of youth, to study the association of these social and demographic variables on the sale of these products. COVID-19 pandemic significantly reduced the sales of products indicated for pediculosis. Since the start of the pandemic, an absolute decrease of 21.0 thousand packages was observed in the monthly average consumption (p < 0.0001) compared to the pre-pandemic period. After this reduction, the average monthly trend increased in the pandemic period in comparison with the previous period, although not significant (267.0 packages per month, p = 0.1102). Regions with higher disposable income and more young people were associated with higher sales of these products. The outbreak of the COVID-19 pandemic has had a notable impact on the sales of self-care products for pediculosis capitis in Portugal, in the short term. The lockdowns and other isolation measures implemented to control the spread of the virus may have led to a decrease in the number of head lice cases, consequently resulting in a reduction in sales of products.
Topics: Portugal; Humans; COVID-19; Interrupted Time Series Analysis; Self Care; Lice Infestations; SARS-CoV-2; Animals; Scalp Dermatoses; Insecticides; Adolescent; Pandemics
PubMed: 38850458
DOI: 10.1007/s00436-024-08258-2 -
Scientific Reports Jun 2024The ongoing COVID-19 pandemic continues to pose significant challenges worldwide, despite widespread vaccination. Researchers are actively exploring antiviral treatments...
The ongoing COVID-19 pandemic continues to pose significant challenges worldwide, despite widespread vaccination. Researchers are actively exploring antiviral treatments to assess their efficacy against emerging virus variants. The aim of the study is to employ M-polynomial, neighborhood M-polynomial approach and QSPR/QSAR analysis to evaluate specific antiviral drugs including Lopinavir, Ritonavir, Arbidol, Thalidomide, Chloroquine, Hydroxychloroquine, Theaflavin and Remdesivir. Utilizing degree-based and neighborhood degree sum-based topological indices on molecular multigraphs reveals insights into the physicochemical properties of these drugs, such as polar surface area, polarizability, surface tension, boiling point, enthalpy of vaporization, flash point, molar refraction and molar volume are crucial in predicting their efficacy against viruses. These properties influence the solubility, permeability, and bio availability of the drugs, which in turn affect their ability to interact with viral targets and inhibit viral replication. In QSPR analysis, molecular multigraphs yield notable correlation coefficients exceeding those from simple graphs: molar refraction (MR) (0.9860), polarizability (P) (0.9861), surface tension (ST) (0.6086), molar volume (MV) (0.9353) using degree-based indices, and flash point (FP) (0.9781), surface tension (ST) (0.7841) using neighborhood degree sum-based indices. QSAR models, constructed through multiple linear regressions (MLR) with a backward elimination approach at a significance level of 0.05, exhibit promising predictive capabilities highlighting the significance of the biological activity (Half maximal inhibitory concentration). Notably, the alignment of predicted and observed values for Remdesivir's with obs ,pred ( represents the negative logarithm of ) underscores the accuracy of multigraph-based QSAR analysis. The primary objective is to showcase the valuable contribution of multigraphs to QSPR and QSAR analyses, offering crucial insights into molecular structures and antiviral properties. The integration of physicochemical applications enhances our understanding of factors influencing antiviral drug efficacy, essential for combating emerging viral strains effectively.
Topics: Quantitative Structure-Activity Relationship; Antiviral Agents; Humans; COVID-19 Drug Treatment; SARS-CoV-2; COVID-19; Linear Models
PubMed: 38849399
DOI: 10.1038/s41598-024-63007-w