bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro
enhancement of Zika virus infection by preexisting West Nile virus antibodies in human plasma-derived immunoglobulins revealed after P2 binding site-specific enrichment
Authors: He Yong , Zhong Lilin , Yan Hailing , Virata Maria Luisa , Deng Lu , Mishra Ashish K. , Struble Evi , Scott Dorothy , Zhang Pei 
Published: April 2024

ABSTRACT

Human immunoglobulin preparations contain a diverse range of polyclonal antibodies that reflect past immune responses against pathogens encountered by the blood donor population. In this study, we examined a panel of intravenous immunoglobulins (IGIVs) manufactured over the past two decades (1998–2020) for their capacity to neutralize or enhance Zika virus (ZIKV) infection
in vitro
. These IGIVs were selected specifically based on their production dates in relation to the occurrences of two flavivirus outbreaks in the U.S.: the West Nile virus (WNV) outbreak in 1999 and the ZIKV outbreak in 2015. As demonstrated by enzyme-linked immunosorbent assay (ELISA) experiments, IGIVs made before the ZIKV outbreak already harbored antibodies that bind to various peptides across the envelope protein of ZIKV because of the WNV outbreak. Using phage display, the most dominant binding site was mapped precisely to the P2 peptide between residues 211 and 230 within domain II, where BF1176-56, an anti-ZIKV monoclonal antibody, also binds. When tested in permissive Vero E6 cells for ZIKV neutralization, the IGIVs, even after undergoing rigorous enrichment for P2 binding specificity, failed, as did BF1176-56. Meanwhile, BF1176-56 enhanced ZIKV infection in both FcγRII-expressing K562 cells and human peripheral blood mononuclear cells. However, for enhancement by the IGIVs to be detected in these cells, a substantial increase in their P2 binding specificity was required, thus linking the P2 site with ZIKV enhancement
in vitro
. Our findings warrant further study of the significance of elevated levels of anti-WNV antibodies in IGIVs, considering that various mechanisms operating
in vivo
may modulate ZIKV infection outcomes.

IMPORTANCE

We investigated the capacity of intravenous immunoglobulins manufactured previously over two decades (1998–2020) to neutralize or enhance Zika virus infection
in vitro
. West Nile virus antibodies in IGIVs could not neutralize Zika virus initially; however, once the IGIVs were concentrated further, they enhanced its infection. These findings lay the groundwork for exploring how preexisting WNV antibodies in IGIVs could impact Zika infection, both
in vitro
and
in vivo
. Our observations are historically significant, since we tested a panel of IGIV lots that were carefully selected based on their production dates which covered two major flavivirus outbreaks in the U.S.: the WNV outbreak in 1999 and the ZIKV outbreak in 2015. These findings will facilitate our understanding of the interplay among closely related viral pathogens, particularly from a historical perspective regarding large blood donor populations. They should remain relevant for future outbreaks of emerging flaviviruses that may potentially affect vulnerable populations.
Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies
Authors: Bian Zilong , Wang Lijuan , Fan Rong , Sun Jing , Yu Lili , Xu Meihong , Timmers Paul R H J , Shen Xia , Wilson James F , Theodoratou Evropi , Wu Xifeng , Li Xue 
Published: April 2024

ObjectiveTo investigate the associations across genetic and lifestyle factors with lifespan.DesignA longitudinal cohort study.SettingUK Biobank.Participants353 742 adults of European ancestry, who were recruited from 2006 to 2010 and were followed up until 2021.ExposuresA polygenic risk score for lifespan with long (<lowest quintile), intermediate (quintiles 2 to 4), and short (>highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, moderate alcohol consumption, regular physical activity, healthy body shape, adequate sleep duration, and a healthy diet, categorised into favourable, intermediate, and unfavourable lifestyles.Main outcome measuresLifespan defined as the date of death or the censor date minus the date of birth.ResultsOf the included 353 742 participants of European ancestry with a median follow-up of 12.86 years, 24 239 death cases were identified. Participants were grouped into three genetically determined lifespan categories including long (20.1%), intermediate (60.1%), and short (19.8%), and into three lifestyle score categories including favourable (23.1%), intermediate (55.6%), and unfavourable (21.3%). The hazard ratio (HR) of death for individuals with a genetic predisposition to a short lifespan was 1.21 (95% CI 1.16 to 1.26) compared to those with a genetic predisposition to a long lifespan. The HR of death for individuals in the unfavourable lifestyle category was 1.78 (95% CI 1.71 to 1.85), compared with those in the favourable lifestyle category. Participants with a genetic predisposition to a short lifespan and an unfavourable lifestyle had 2.04 times (95% CI 1.87 to 2.22) higher rates of death compared with those with a genetic predisposition to a long lifespan and a favourable lifestyle. No multiplicative interaction was detected between the polygenic risk score of lifespan and the weighted healthy lifestyle score (p=0.10). The optimal combination of healthy lifestyles, including never smoking, regular physical activity, adequate sleep duration, and a healthy diet, was derived to decrease risk of premature death (death before 75 years).ConclusionGenetic and lifestyle factors were independently associated with lifespan. Adherence to healthy lifestyles could largely attenuate the genetic risk of a shorter lifespan or premature death. The optimal combination of healthy lifestyles could convey better benefits for a longer lifespan, regardless of genetic background.
Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis
Authors: Chandran Elias B A , Iannantuono Giovanni Maria , Atiq Saad O , Akbulut Dilara , Sinaii Ninet , Simon Nicholas I , Banday Abdul Rouf , Boudjadi Salah , Gurram Sandeep , Nassar Amin H , Rosenberg Jonathan E , Butera Gisela , Teo Min Yuen , Sonpavde Guru , Coleman Jonathan A , Apolo Andrea B 
Published: April 2024

BackgroundMismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) occur in a subset of cancers and have been shown to confer sensitivity to immune checkpoint inhibition (ICI); however, there is a lack of prospective data in urothelial carcinoma (UC).Methods and analysisWe performed a systematic review to estimate the prevalence of dMMR and MSI-H in UC, including survival and clinical outcomes. We searched for studies published up to 26 October 2022 in major scientific databases. We screened 1745 studies and included 110. Meta-analyses were performed if the extracted data were suitable.ResultsThe pooled weighted prevalences of dMMR in bladder cancer (BC) and upper tract UC (UTUC) were 2.30% (95% CI 1.12% to 4.65%) and 8.95% (95% CI 6.81% to 11.67%), respectively. The pooled weighted prevalences of MSI-H in BC and UTUC were 2.11% (95% CI 0.82% to 5.31%) and 8.36% (95% CI 5.50% to 12.53%), respectively. Comparing localised versus metastatic disease, the pooled weighted prevalences for MSI-H in BC were 5.26% (95% CI 0.86% to 26.12%) and 0.86% (95% CI 0.59% to 1.25%), respectively; and in UTUC, they were 18.04% (95% CI 13.36% to 23.91%) and 4.96% (95% CI 2.72% to 8.86%), respectively. Cumulatively, the response rate in dMMR/MSI-H metastatic UC treated with an ICI was 22/34 (64.7%) compared with 1/9 (11.1%) with chemotherapy.ConclusionBoth dMMR and MSI-H occur more frequently in UTUC than in BC. In UC, MSI-H occurs more frequently in localised disease than in metastatic disease. These biomarkers may predict sensitivity to ICI in metastatic UC and resistance to cisplatin-based chemotherapy.
Effect of visual impairment on subjective cognitive decline in older adults: a cross-sectional study in China
Authors: Luo Liyan , Jiang Ning , Zheng Xiaolei , Wang Ping , Bi Jianzhong , Xu Feng , Xie Zhaohong , Yang Liping 
Published: April 2024

ObjectivePeople with visual impairment have more functional limitations associated with subjective cognitive decline (SCD), and those with SCD are extremely susceptible to transitioning to irreversible cognitive impairment. This study aimed to explore if visual impairment is a significant predictor of SCD compared with other socioeconomic and health factors associated with SCD.DesignCross-sectional study.Setting and participantsThe investigation aimed to assess the factors influencing SCD among 428 participants aged 60 and above in Zhaoyuan, China.Primary outcome measuresThe primary outcome variable was SCD, measured by the Chinese version of SCD questionnaire. Multiple logistic regression and propensity score matching (PSM) were used to analyse the influence of visual impairment on the subjective cognition of the elderly.32.2% of the elderly were experiencing SCD. Older adults with SCD showed a higher prevalence of visual impairment (72.5%) than the elderly without SCD (58.6%) (P=0.006). Multivariate logistic regression analysis showed that bad self-reported health status, lack of physical exercise and visual impairment were the risk factors for SCD in older adults, while more than 9 years of education was a protective factor. In addition, PSM model showed that after eliminating the dominant biases caused by the individual observable heterogeneity of older adults with and without visual impairment, the risk of SCD in the elderly with visual impairment was increased by 13.6%–14.5% and the difference was statistically significant (P<0.05).ConclusionsIt was found that older adults experiencing visual impairments are at an elevated risk of developing SCD compared with their counterparts without such impairments. Additionally, visual impairment remains a significant risk factor for SCD in the elderly, even adjusting for potential biases arising from individual observable heterogeneity.
Adjuvant Wilms’ tumour 1-specific dendritic cell immunotherapy
complementing conventional therapy for paediatric patients with high-grade
glioma and diffuse intrinsic pontine glioma: protocol of a monocentric phase
I/II clinical trial in Belgium
Authors: Van Genechten Toon , De Laere Maxime , Van den Bossche Jolien , Stein Barbara , De Rycke kim , Deschepper Caroline , Hazes Katja , Peeters Renke , Couttenye Marie-Madeleine , Van De Walle Katrien , Roelant Ella , Maes Sabine , Vanden Bossche Stephanie , Dekeyzer Sven , Huizing Manon , Caluwaert Kim , Nijs Griet , Cools Nathalie , Verlooy Joris , Norga Koen , Verhulst Stijn , Anguille Sebastien , Berneman Zwi , Lion Eva 
Published: April 2024

Introduction
Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade
glioma (pHGG) are aggressive glial tumours, for which conventional
treatment modalities fall short. Dendritic cell (DC)-based immunotherapy
is being investigated as a promising and safe adjuvant therapy. The
Wilms’ tumour protein (WT1) is a potent target for this type of
antigen-specific immunotherapy and is overexpressed in DIPG and pHGG.
Based on this, we designed a non-randomised phase I/II trial, assessing
the feasibility and safety ofWT1mRNA-loaded
DC (WT1/DC) immunotherapy in combination with conventional treatment in
pHGG and DIPG.

Methods and analysis
10 paediatric patients with newly diagnosed or pretreated HGG or
DIPG were treated according to the trial protocol. The trial protocol
consists of leukapheresis of mononuclear cells, the manufacturing of
autologous WT1/DC vaccines and the combination of WT1/DC-vaccine
immunotherapy with conventional antiglioma treatment. In newly diagnosed
patients, this comprises chemoradiation (oral temozolomide
90 mg/m2daily+radiotherapy 54 Gy in 1.8 Gy
fractions) followed by three induction WT1/DC vaccines
(8–10×106cells/vaccine) given on a weekly basis
and a chemoimmunotherapy booster phase consisting of six 28-day cycles
of oral temozolomide (150–200 mg/m2on days 1–5) and
a WT1/DC vaccine on day 21. In pretreated patients, the induction and
booster phase are combined with best possible antiglioma treatment at
hand. Primary objectives are to assess the feasibility of the production
of mRNA-electroporated WT1/DC vaccines in this patient population and to
assess the safety and feasibility of combining conventional antiglioma
treatment with the proposed immunotherapy. Secondary objectives are to
investigate in vivo immunogenicity of WT1/DC vaccination and to assess
disease-specific and general quality of life.

Ethics and dissemination
The ethics committee of the Antwerp University Hospital and the
University of Antwerp granted ethics approval. Results of the clinical
trial will be shared through publication in a peer-reviewed journal and
presentations at conferences.

Trial registration number

NCT04911621
Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI)
Authors: Saraiva Ivan E , Hamahata Natsumi , Huang David T , Kane-Gill Sandra L , Rivosecchi Ryan M , Shiva Sruti , Nolin Thomas D , Chen Xinlei , Minturn John , Chang Chung-Chou H , Li Xiaotong , Kellum John , Gómez Hernando 
Published: April 2024

IntroductionAcute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI.Methods and analysisBlind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate.Ethics and disseminationThis study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis.Trial registration numberNCT05900284.
Life skills and reproductive health empowerment intervention for newly married women and their families to reduce unintended pregnancy in India: protocol for the TARANG cluster randomised controlled trial
Authors: Diamond-Smith Nadia , Gopalakrishnan Lakshmi , Leslie Hannah , Katz Elizabeth , Harper Cynthia , Weiser Sheri , Patil Sumeet R 
Published: April 2024

IntroductionIn South Asia, younger women have high rates of unmet need for family planning and low empowerment. Life skills interventions can equip young women with agency, but the effectiveness of these interventions in reproductive and sexual autonomy and contraception has not been examined.Methods and analysisA two-arm, parallel, cluster randomised controlled trial will evaluate the impact of TARANG (Transforming Actions for Reaching and Nurturing Gender Equity and Empowerment), a life skills and reproductive health empowerment group-based intervention for newly married women, compared with usual services in the community in rural and tribal Rajasthan, India. TARANG will also provide light-touch sessions to husbands and mothers-in-law of newly married women. We will test the impact of TARANG in 80 village clusters among 800 eligible households comprising newly married women aged 18–25 years who are at risk of pregnancy but do not want a pregnancy within 1 year at the time of enrolment, their husbands and mothers-in-law who consent to participate. Women in the intervention villages will receive 14 sessions over a 6-month period, while husbands and mothers-in-law will receive 1 and 4 sessions (respectively) each. Three rounds of surveys will be collected over 18 months. Control villages will receive the intervention after the endline surveys. Primary outcomes include rate of unintended pregnancy and modern contraceptive use. We plan to start recruitment of participants and data collection in April 2024. We will estimate unadjusted and adjusted intention-to-treat effects using survival analysis and mixed models.Ethics and disseminationStudy protocols have been reviewed and approved by the human subjects review boards at the University of California, San Francisco, and the Centre for Media Studies, India (IRB00006230) and ACE Independent Ethics Committee, Bangalore (NET0062022). Results will be disseminated in international peer-reviewed journals and conferences, to stakeholders including local government and non-governmental organisations, and directly to the communities and individuals that participated in the intervention.Trial registration numberNCT06024616.
Digital micro-banking as a health and protection intervention for street-connected children and youth? Analysis from a Togolese pilot
Authors: Howard Neil 
Published: April 2024

BackgroundThe SaVa pilot offered street-connected children and youth (C&Y) access to digital micro-banking services to help them save money and thus avoid the violence associated with theft at night. It further used the micro-banking service as a gateway to attract C&Y towards other health and protection services. It took place over 12 months in Lomé, Togo and involved one social worker (SW) plus volunteers running ‘the bank’ in a non-governmental organisation-funded drop-in centre.MethodsC&Y peer researchers were trained to interview and use collective drawing with peers, which they did on a bi-monthly basis. The SW recorded information about case management, training and additional services offered. He administered a survey to C&Y at the point of entry into the project and after 1 year, asking questions about recent experiences of violence or theft. At the end of 12 months, the author conducted interviews with C&Y using the bank, C&Y researchers who used the bank, project staff and steering committee partners and child protection stakeholders. One focus group was conducted with C&Y participants, alongside limited participant observation of where C&Y sleep and work.ResultsFindings suggest that the intervention was successful in encouraging children to open accounts and save money, and in contributing to a reduction in theft and associated violence. The incidence of theft reduced 90%; 95% of C&Y account holders were happy with the service; 200 accounts were opened. The project supported the delivery of additional services, including counselling, school reinsertion and removal from the streets.ConclusionsAnalysis suggests that it is possible to offer street-connected C&Y formal financial services but that this offer has potential as a health and protection intervention, especially in combination with the provision of a safe space, dedicated SW support and add-on services.
ScRNA-seq reveals novel immune-suppressive T cells and investigates CMV-TCR-T cells cytotoxicity against GBM
Authors: Long Xinmiao , Zhang Zuping , Li Yuzhe , Deng Kun , Gao Wei , Huang Meng , Wang Xiangyu , Lin Xiang , She Xiaoling , Zhao Yiming , Zhang Minfu , Huang Cheng , Wang Shiyi , Du Yinfei , Du Peng , Chen Shuai , Liu Qing , Wu Minghua 
Published: April 2024

BackgroundGlioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date.MethodsWe evaluated the CMV infection status of patients with GBM’s tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro.ResultsWe identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+tumor-associated macrophages and FXYD6+T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+T cells rather than regulatory T cells (Tregs), whereas, FXYD6+T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model.ConclusionsThese findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.
Prednisone use, disease activity and the occurrence of hyperglycaemia and diabetes in patients with early rheumatoid arthritis: a 10-year subanalysis of the BeSt study
Authors: van der Pol Joy Ardjuna , Allaart Cornelia F , Lems Willem , van der Kooij Sjoerd M , Huizinga Tom W J , Bergstra Sytske Anne 
Published: April 2024

ObjectivesTo assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA).MethodsWe included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years. The associations between DAS and prednisone use with glucose levels and the occurrence of hyperglycaemia over time were assessed with linear and logistic mixed effects regression models. Development of diabetes was analysed with Cox regression. Sensitivity analyses were performed in patients who had a first episode of hyperglycaemia.Results31 of 504 patients (6.2%) with a mean age of 54 years developed diabetes during follow-up; 11 of these (35%) had received prior treatment with prednisone. Prednisone use was not associated with development of hyperglycaemia or diabetes after correction for multiple testing in main or sensitivity analyses. In the main analyses, DAS was significantly associated with development of diabetes (HR 1.802 per 1 point DAS increase, 95% CI 1.284 to 2.529) but not with glucose levels nor hyperglycaemia. In patients with previous hyperglycaemia, DAS was associated with glucose levels, recurrence of hyperglycaemia and diabetes.ConclusionsIn non-diabetic early RA patients, the use of prednisone was not associated with developing hyperglycaemia or diabetes. However, high DAS increased the risk of diabetes. Potential risks associated with prednisone use may have been mitigated by its effect on DAS.