bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection
Authors: Bhavsar Disha , Singh Gagandeep , Sano Kaori , Gleason Charles , Srivastava Komal ,   PARIS Study Group, Carreno Juan Manuel , Simon Viviana , Krammer Florian , Oostenink Annika , Salimbangon Ashley-Beathrese , Monahan Brian , Cognigni Christian , Andre Dalles , Bielak Dominika , Cai Gianna Y. , Kleiner Giulio , Kang Hyun Min , Mauldin Jacob , Mischka Jacob , Nardulli Jessica , Sullivan Leeba , Bermúdez-González Maria C. , Fried Miriam , Kesteren Morgan Van , Lyttle Neko , Morris Sara , Yellin Temima , Chen Yuexing 
Published: December 2023

ABSTRACT
Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG, and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.

IMPORTANCE
Antibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG, and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.
Genome sequence of a measles virus strain with a novel loss of stop codon mutation in the phosphoprotein gene
Authors: Zubach Vanessa , Schulz Helene , Kim Kihun , Hole Darian , Severini Alberto , Hiebert Joanne 
Published: December 2023

ABSTRACT
Measles virus genotype B3 coding-complete genome sequence from a 2019 case showed a novel mutation in the phosphoprotein (P) gene that abrogates the established stop codon. A downstream stop codon has been identified, resulting in a putative P that would be 19 amino acids longer than wild type.
The role of autophagy in tick-endosymbiont interactions: insights from
Ixodes scapularis
and
Rickettsia buchneri
Authors: Wang Xin-Ru , Cull Benjamin , Oliver Jonathan D. , Kurtti Timothy J. , Munderloh Ulrike G. 
Published: December 2023

ABSTRACT

Approximately 80 identified tick species are recognized as vectors and impact global public health by transmitting a wide range of pathogens; however, little is known about the interactions of ticks with the microbiome that they harbor, let alone their bacterial symbionts. In this study, we used the black-legged tick,
Ixodes scapularis
Say (Acari: Ixodidae), a vector of seven human pathogens in the United States, and utilized
Rickettsia buchneri sensu stricto
ISO7
T
(Rickettsiales: Rickettsiaceae), a spotted fever group (SFG) rickettsia that is an endosymbiont of
I. scapularis,
to investigate the role of autophagy in symbiont and tick interactions. We found that the expression profile of most autophagy family member proteins (ATGs) is down-regulated after
R. buchneri
infection in tick cell cultures. The autophagic process was observed by assessment of autophagosome formation and maturation
in vitro
(tick cell culture) and
in vivo
(tick ovary) in the presence of
R. buchneri
, whereas apoptosis was not induced. We further showed that
R. buchneri
infection triggered the accumulation of plasma membranes within cells. Suppressing autophagy via
Atg8
siRNA interference inhibited intracellular rickettsial replication. This research indicates that autophagy regulation is important for the maintenance of
R. buchneri
in its
I. scapularis
tick host and provides more clues to solve the tick-symbiont interaction puzzle.

IMPORTANCE
Ticks are second only to mosquitoes in their importance as vectors of disease agents; however, tick-borne diseases (TBDs) account for the majority of all vector-borne disease cases in the United States (approximately 76.5%), according to Centers for Disease Control and Prevention reports. Newly discovered tick species and their associated disease-causing pathogens, and anthropogenic and demographic factors also contribute to the emergence and re-emergence of TBDs. Thus, incorporating different tick control approaches based on a thorough knowledge of tick biology has great potential to prevent and eliminate TBDs in the future. Here we demonstrate that replication of a transovarially transmitted rickettsial endosymbiont depends on the tick’s autophagy machinery but not on apoptosis. Our findings improve our understanding of the role of symbionts in tick biology and the potential to discover tick control approaches to prevent or manage TBDs.
Sikh and Muslim perspectives on kidney transplantation: phase 1 of the DiGiT project – a qualitative descriptive study
Authors: Brand Sarah , Daga Sunil , Mistry Kirit , Morsy Mohamed , Bagul Atul , Hamer Rizwan , Malik Shafi 
Published: December 2023

ObjectivesKidney transplantation offers patients better quality of life and survival compared with dialysis. The risk of end stage renal disease is higher among ethnic minorities and they experience longer wait times on transplant lists. This inequality stems from a high need for kidney transplantation combined with a low rate of deceased donation among ethnic minority groups. This study aimed to explore the perspectives around living donor kidney transplantation of members of the Sikh and Muslim communities with an aim to develop a digital intervention to overcome any barriers.DesignA qualitative descriptive study using in person focus groups.SettingUniversity Teaching Hospital and Transplant Centre.ParticipantsConvenience sampling of participants from the transplant population. Three focus groups were held with 20 participants, all were of South Asian ethnicity belonging to the Sikh and Muslim communities.MethodsInterviews were digitally audio-recorded and transcribed verbatim; transcripts were analysed thematically.ResultsFour themes were identified: (a) religious issues; (b) lack of knowledge within the community; (c) time; (d) cultural identification with transplantation.ConclusionsNot only is the information given and when it is delivered important, but also the person giving the information is crucial to enhance consideration of live donor kidney transplantation. Information should be in a first language where possible and overtly align to religious considerations. A more integrated approach to transplantation counselling should be adopted which includes healthcare professionals and credible members of the target cultural group.Trial registration numberNCT04327167.
Placebo effects in mental health disorders: protocol for an umbrella review
Authors: Huneke Nathan TM , Amin Jay , Baldwin David S , Chamberlain Samuel R , Correll Christoph U , Garner Matthew , Hill Catherine M , Hou Ruihua , Howes Oliver D , Sinclair Julia MA , Solmi Marco , Cortese Samuele 
Published: December 2023

IntroductionGiven the high prevalence of mental health disorders and their significant socioeconomic burden, there is a need to develop improved treatments, and to evaluate them through placebo-controlled trials. However, the magnitude of the placebo response in randomised controlled trials to test medications may be substantial, affecting their interpretation. Therefore, improved understanding of the patient, trial and mental disorder factors that influence placebo responses would inform clinical trial design to better detect active treatment effects. There is a growing literature exploring the placebo response within specific mental health disorders, but no overarching synthesis of this research has been produced to date. We present a protocol for an umbrella review of systematic reviews and/or meta-analyses in which we aim to understand the effect size and potential predictors of placebo response within, and across, mental health disorders.Methods and analysisWe will systematically search databases (Medline, PsycINFO, EMBASE+EMBASE Classic, Web of Knowledge) for systematic reviews and/or meta-analyses that report placebo effect size in clinical trials in patients with mental health disorders (initial search date 23 October 2022). Screening of abstracts and full texts will be done in pairs. We will extract data to qualitatively examine how placebo effect size varies across mental health disorders. We also plan to qualitatively summarise predictors of increased placebo response identified either quantitatively (eg, through meta-regression) or qualitatively. Risk of bias will be assessed using the AMSTAR-2 tool. We aim to not only summarise the current literature but also to identify gaps in knowledge and generate further hypotheses.Ethics and disseminationWe do not believe there are any specific ethical considerations relevant to this study. We will publish the results in a peer-reviewed journal.
Sleep quality and associated factors among patients with chronic kidney disease in Nigeria: a cross-sectional study
Authors: Adejumo Oluseyi Ademola , Edeki Imuetinyan Rashida , Mamven Manmak , Oguntola Olawale Stephen , Okoye Ogochukwu Chinedum , Akinbodewa Akinwumi Ayodeji , Okaka Enajite Ibiene , Ahmed Sulaiman Dazumi , Egbi Oghenekaro Gódwin , Falade Joshua , Dada Samuel Ayokunle , Ogiator Monday Ogiagah , Okoh Barbara 
Published: December 2023

ObjectivePoor sleep quality adversely affects the overall well-being and outcomes of patients with chronic kidney disease (CKD). However, it has not been well studied in Africans with CKD. We determined the prevalence of poor sleep quality and associated factors among patients with CKD.DesignThis was a cross-sectional study that involved patients with CKD .SettingsThe study was carried out in the outpatient clinic of nine hospitals in Nigeria.MethodsSleep quality, depressive and anxiety symptoms and quality of life (QoL) were assessed among 307 patients with CKD using Pittsburgh Sleep Quality Index Questionnaire, Hospital Anxiety Depression Scale Questionnaire and 12-item Short Form Health Survey Quality of Life Questionnaire, respectively. The prevalence of poor sleep quality and associated factors were determined. A p<0.05 was considered as statistically significant.ResultsThe mean age of the study participants was 51.40±15.17 years. The male:female ratio was 1.5:1 One hundred and twenty-one (39.4%) of the patients were on maintenance haemodialysis (MHD). The prevalence of poor sleep quality, anxiety symptoms and depressive symptoms among the patients was 50.2%, 37.8% and 17.6%, respectively. The prevalence of poor sleep quality in the CKD stages 3, 4, 5 and 5D was 38.1%, 42.6%, 52.2% and 58.7%, respectively. The prevalence of poor sleep quality was significantly higher in MHD patients compared with predialysis CKD (59.5% vs 43.6%; p=0.008). Factors associated with poor sleep quality were CKD stage (p=0.035), anaemia (p=0.003), pruritus (p=0.045), anxiety symptoms (p≤0.001), depressive symptoms (p≤0.001) and reduced QoL (p≤0.001). On multivariate analysis, factors associated with poor sleep were anxiety (AOR 2.19; 95% CI 1.27 to 3.79; p=0.005), anaemia (AOR 5.49; 95% CI 1.43 to 21.00;p=0.013) and reduced physical component of QoL (AOR 4.11; 95% CI 1.61 to 10.47; p=0.003).ConclusionPoor sleep quality is common among patients with CKD especially in the advanced stage. The significant factors associated with poor sleep quality were QoL, anaemia and anxiety symptoms. These factors should be adequately managed to improve the overall outcomes of patients with CKD.
Socioeconomic inequality and contributors in accepting attitudes toward people living with HIV among adults in Ethiopia from 2005 to 2016: a population-based cross-sectional study
Authors: Endalamaw Aklilu , Gilks Charles F , Ambaw Fentie , Assefa Yibeltal 
Published: December 2023

IntroductionThe public’s accepting attitude toward people living with HIV is crucial in reducing HIV-related stigma and discrimination, increasing people’s access to HIV service. This study examines the inequalities in accepting attitudes toward people living with HIV in Ethiopia from 2005 to 2016.MethodsThis cross-sectional study was based on the 2005, 2011 and 2016 Ethiopian Demographic Health Surveys. A total of 17 075, 28 478 and 25 542 adults were included in the 2005, 2011 and 2016 surveys, respectively. Socioeconomic inequality was investigated using the concentration curve and Erreygers’ concentration index (ECI), which is scaled from −1 (pro-poor) to +1 (pro-rich). The ECI was decomposed to identify the contributors to socioeconomic inequality using generalised linear regression with the logit link function.ResultsAccepting attitude toward people living with HIV was 17.9% (95% CI: 16.6%, 19.3%) in 2005, which increased to 33.5% (95% CI: 31.8%, 35.3%) in 2011 and 39.6% (95% CI: 37.6%, 41.9%) in 2016. ECI was 0.342 (p<0.001), 0.436 (p<0.001) and 0.388 (p<0.001), respectively, for 2005, 2011 and 2016. The trend line illustrates socioeconomic inequality seems diverging over time, with an increasing ECI of 0.005 every year (r=0.53; p=0.642; slope=0.005).ConclusionsThe current study found that there was pro-rich inequality from 2005 to 2016. People with higher socioeconomic status had a better attitude toward people living with HIV. Comprehensive knowledge about HIV/AIDS, education status, residence, and access to electronic and paper-based media, as well as HIV testing, contribute to a better accepting attitude toward people living with HIV. It is of utmost importance for the country to enhance accepting attitude toward people living with HIV to reduce stigma and discrimination. This requires whole-system response according to the primary healthcare approach toward ending the epidemic of HIV/AIDS in the country.
Inhibition of bradykinin in SARS-CoV-2 infection: a randomised, double-blind trial of icatibant compared with placebo (ICASARS)
Authors: Bailey Melanie , Linden Dermot , Earley Olivia , Guo Parke Hong , McAuley Daniel Francis , Peto Tunde , Taggart Cliff , Kidney Joe 
Published: December 2023

SARS-CoV-2 binds to ACE2 receptors and enters cells. The symptoms are cough, breathlessness, loss of taste/smell and X-ray evidence of infiltrates on chest imaging initially caused by oedema, and subsequently by a lymphocytic pneumonitis. Coagulopathy, thrombosis and hypotension occur. Worse disease occurs with age, obesity, ischaemic heart disease, hypertension and diabetes.These features may be due to abnormal activation of the contact system. This triggers coagulation and the kallikrein-kinin system, leading to accumulation of bradykinin and its derivatives, which act on receptors B1R and B2R. Receptor activation causes cough, hypotension, oedema and release of the cytokine interleukin-6 (IL-6) which recruits lymphocytes. These effects are core features seen in early SARS CoV-2 infection.Methods and analysisIn this study, hypoxic patients with COVID-19 with symptom onset ≤7 days will be randomised to either a bradykinin inhibitor (icatibant) or placebo. Patients and investigators will be blinded. The primary outcome will be blood oxygenation, measured by arterial blood sampling. The secondary outcome will be cardiovascular status. Retinal imaging will be performed to assess vessel size. Blood samples will be taken for measurement of inflammatory analyses including IL-6. As a separate substudy, we will also take comparator blood inflammatory samples from a COVID-19-negative cohort.Ethics and disseminationThe study has received the following approvals: West Midlands–Edgbaston Research Ethics Committee. Medicines and Healthcare products Regulatory Agency has issued a clinical trial authorisation. Belfast Health and Social Care Trust is the study sponsor. Results will be made available to participants upon request and findings will be presented and published.Trial registration numberNCT05407597
Validating a framework to guide the implementation of high-quality virtual primary care: an international eDelphi study protocol
Authors: Carvalho Joana Miguel , Li Edmond , Hayhoe Benedict , Beaney Thomas , Majeed Azeem , Greenfield Geva , Neves Ana Luísa 
Published: December 2023

BackgroundThere is an urgent need to support primary care organisations in implementing safe and high-quality virtual consultations. We have previously performed qualitative research to capture the views of 1600 primary care physicians across 20 countries on the main benefits and challenges of using virtual consultations. Subsequently, a prototype of a framework to guide the implementation of high-quality virtual primary care was developed.AimTo explore general practitioners’ perspectives on the appropriateness and relevance of each component of the framework’s prototype, to further refine it and optimise its practical use in primary care facilities.Methods and analysisParticipants will be primary care physicians with active experience providing virtual care, recruited through convenience and snowball sampling. This study will use a systematic and iterative online Delphi research approach (eDelphi), with a minimum of three rounds. A pre-round will be used to circulate items for initial feedback and adjustment. In subsequent rounds, participants will be asked to rate the relevance of the framework’s components. Consensus will be defined as >70% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing with a component. Data will be collected using structured online questionnaires. The primary outcome of the study will be a list of the essential components to be incorporated in the final version of the framework.Ethics and disseminationThe study has received ethical approval conceded by the Imperial College London Science, Engineering and Technology Research Ethics Committee (SETREC) (reference no .6559176/2023). Anonymous results will be made available to the public, academic organisations and policymakers.
Preconceptual administration of doxycycline in women with recurrent miscarriage and chronic endometritis: protocol for the Chronic Endometritis and Recurrent Miscarriage (CERM) trial, a multicentre, double-blind, placebo-controlled, adaptive randomised trial with an embedded translational substudy
Authors: Odendaal Joshua , Black Naomi , Bouliotis Georgios , Guck Jonathan , Underwood Martin , Fisher Joanne , Quenby Siobhan 
Published: December 2023

IntroductionRecurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The aetiology of CE remains uncertain. An association between CE and recurrent miscarriage has been shown. This study will aim to determine if preconceptual administration of doxycycline, in women with recurrent miscarriages, and CE, reduces first trimester miscarriages, increasing live births.Methods and analysisChronic Endometritis and Recurrent Miscarriage is a multicentre, double-blind adaptive trial with an embedded translational substudy. Women with a history of two or more consecutive first trimester losses with evidence of CE on endometrial biopsy (defined as ≥5 CD138 positive cells per 10 mm2) will be randomised to oral doxycycline or placebo for 14 days. A subset will be recruited to a mechanistic substudy in which microbial swabs and preintervention/postintervention endometrial samples will be collected. Up to 3062 women recruited from 29 National Health Service (NHS) hospital sites across the UK are expected to be screened with up to 1500 women randomised in a 1:1 ratio. Women with a negative endometrial biopsy (defined as <5 CD138 positive cells per 10 mm2) will also be followed up to test validity of the tool. The primary outcome is live births plus pregnancies ≥24 + 0 weeks gestation at the end of the trial, in the first or subsequent pregnancy. Secondary clinical outcomes will also be assessed. Exploratory outcomes will assess the effect of doxycycline treatment on the endometrial microbiota, the differentiation capacity of the endometrium and the senescent profile of the endometrium with CE.Ethics and disseminationEthical approval has been obtained from the NHS Research Ethics Committee Northwest-Haydock (19/NW/0462). Written informed consent will be gained from all participants. The results will be published in an open-access peer-reviewed journal and reported in the National Institute for Health and Care Research journals library.Trial registration numberISRCTN23947730.
Enhanced CD1d phosphatidylserine presentation using a single-domain antibody promotes immunomodulatory CD1d-TIM-3 interactions
Authors: Lameris Roeland , Shahine Adam , Veth Myrthe , Westerman Bart , Godfrey Dale I , Lutje Hulsik David , Brouwer Patricia , Rossjohn Jamie , de Gruijl Tanja D , van der Vliet Hans J 
Published: December 2023

BackgroundCD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T-cell subsets and can be expressed by various malignancies. Antibody-mediated targeting of CD1d on multiple myeloma cells was reported to induce apoptosis and could therefore constitute a novel therapeutic approach.MethodsTo determine how a CD1d-specific single-domain antibody (VHH) enhances binding of the early apoptosis marker annexin V to CD1d+tumor cells we use in vitro cell-based assays and CRISPR-Cas9-mediated gene editing, and to determine the structure of the VHH1D17-CD1d(endogenous lipid) complex we use X-ray crystallography.ResultsAnti-CD1d VHH1D17 strongly enhances annexin V binding to CD1d+tumor cells but this does not reflect induction of apoptosis. Instead, we show that VHH1D17 enhances presentation of phosphatidylserine (PS) in CD1d and that this is saposin dependent. The crystal structure of the VHH1D17-CD1d(endogenous lipid) complex demonstrates that VHH1D17 binds the A′-pocket of CD1d, leaving the lipid headgroup solvent exposed, and has an electro-negatively charged patch which could be involved in the enhanced PS presentation by CD1d. Presentation of PS in CD1d does not trigger phagocytosis but leads to greatly enhanced binding of T-cell immunoglobulin and mucin domain containing molecules (TIM)-1 to TIM-3, TIM-4 and induces TIM-3 signaling.ConclusionOur findings reveal the existence of an immune modulatory CD1d(PS)-TIM axis with potentially unexpected implications for immune regulation in both physiological and pathological conditions.