bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN-λ drives distinct lung immune landscape changes and antiviral responses in human metapneumovirus infection
Authors: Sojati Jorna , Parks Olivia B. , Zhang Yu , Walters Sara , Lan Jie , Eddens Taylor , Lou Dequan , Fan Li , Chen Kong , Oury Tim D. , Williams John V. 
Published: March 2024

ABSTRACT

Human metapneumovirus (HMPV) is a primary cause of acute respiratory infection, yet there are no approved vaccines or antiviral therapies for HMPV. Early host responses to HMPV are poorly characterized, and further understanding could identify important antiviral pathways. Type III interferon (IFN-λ) displays potent antiviral activity against respiratory viruses and is being investigated for therapeutic use. However, its role in HMPV infection remains largely unknown. Here, we show that IFN-λ is highly upregulated during HMPV infection
in vitro
in human and mouse airway epithelial cells and
in vivo
in mice. We found through several immunological and molecular assays that type II alveolar cells are the primary producers of IFN-λ. Using mouse models, we show that IFN-λ limits lung HMPV replication and restricts virus spread from upper to lower airways but does not contribute to clinical disease. Moreover, we show that IFN-λ signaling is predominantly mediated by CD45
-
non-immune cells. Mice lacking IFN-λ signaling showed diminished loss of ciliated epithelial cells and decreased recruitment of lung macrophages in early HMPV infection along with higher inflammatory cytokine and interferon-stimulated gene expression, suggesting that IFN-λ may maintain immunomodulatory responses. Administration of IFN-λ for prophylaxis or post-infection treatment in mice reduced viral load without inflammation-driven weight loss or clinical disease. These data offer clinical promise for IFN-λ in HMPV treatment.

IMPORTANCE
Human metapneumovirus (HMPV) is a common respiratory pathogen and often contributes to severe disease, particularly in children, immunocompromised people, and the elderly. There are currently no licensed HMPV antiviral treatments or vaccines. Here, we report novel roles of host factor IFN-λ in HMPV disease that highlight therapeutic potential. We show that IFN-λ promotes lung antiviral responses by restricting lung HMPV replication and spread from upper to lower airways but does so without inducing lung immunopathology. Our data uncover recruitment of lung macrophages, regulation of ciliated epithelial cells, and modulation of inflammatory cytokines and interferon-stimulated genes as likely contributors. Moreover, we found these roles to be distinct and non-redundant, as they are not observed with knockout of, or treatment with, type I IFN. These data elucidate unique antiviral functions of IFN-λ and suggest IFN-λ augmentation as a promising therapeutic for treating HMPV disease and promoting effective vaccine responses.
Evaluation of vector susceptibility in
Aedes aegypti
and
Culex pipiens pallens
to Tibet orbivirus
Authors: Ren Nanjie , Jin Qianqian , Wang Fei , Huang Doudou , Yang Cihan , Zaman Wahid , Salazar Ferdinand Villanueva , Liu Qiyong , Yuan Zhiming , Xia Han 
Published: March 2024

ABSTRACT

Mosquito-borne viruses cause various infectious diseases in humans and animals. Tibet orbivirus (TIBOV), a newly identified arbovirus, efficiently replicates in different types of vertebrate and mosquito cells, with its neutralizing antibodies detected in cattle and goats. However, despite being isolated from
Culicoides
midges
, Anopheles,
and
Culex
mosquitoes, there has been a notable absence of systematic studies on its vector competence. Thus, in this study,
Aedes aegypti
and
Culex pipiens pallens
were reared in the laboratory to measure vector susceptibility through blood-feeding infection. Furthermore, RNA sequencing was used to examine the overall alterations in the
Ae. aegypti
transcriptome following TIBOV infection. The results revealed that
Ae. aegypti
exhibited a high susceptibility to TIBOV compared to
Cx. p. pallens
. Effective replication of the virus in
Ae. aegypti
midguts occurred when the blood-feeding titer of TIBOV exceeded 10
5
plaque-forming units mL
−1
. Nevertheless, only a few TIBOV RNA-positive samples were detected in the saliva of
Ae. aegypti
and
Cx. p. pallens
, suggesting that these mosquito species may not be the primary vectors for TIBOV. Moreover, at 2 dpi of TIBOV, numerous antimicrobial peptides downstream of the Toll and Imd signaling pathways were significantly downregulated in
Ae. aegypti
, indicating that TIBOV suppressed mosquitos’ defense to survive in the vector at an early stage. Subsequently, the stress-activated protein kinase JNK, a crucial component of the MAPK signaling pathway, exhibited significant upregulation. Certain genes were also enriched in the MAPK signaling pathway in TIBOV-infected
Ae. aegypti
at 7 dpi.

IMPORTANCE

Tibet orbivirus (TIBOV) is an understudied arbovirus of the genus
Orbivirus
. Our study is the first-ever attempt to assess the vector susceptibility of this virus in two important mosquito vectors,
Aedes aegypti
and
Culex pipiens pallens
. Additionally, we present transcriptome data detailing the interaction between TIBOV and the immune system of
Ae. aegypti
, which expands the knowledge about orbivirus infection and its interaction with mosquitoes.
Bacillus subtilis
remains translationally active after CRISPRi-mediated replication initiation arrest
Authors: Muñoz-Gutierrez Vanessa , Cornejo Fabián A. , Schmidt Katja , Frese Christian K. , Halte Manuel , Erhardt Marc , Elsholz Alexander K. W. , Turgay Kürşad , Charpentier Emmanuelle 
Published: March 2024

ABSTRACT

Initiation of bacterial DNA replication takes place at the origin of replication (
oriC
), a region characterized by the presence of multiple DnaA boxes that serve as the binding sites for the master initiator protein DnaA. This process is tightly controlled by modulation of the availability or activity of DnaA and
oriC
during development or stress conditions. Here, we aimed to uncover the physiological and molecular consequences of stopping replication in the model bacterium
Bacillus subtilis
. We successfully arrested replication in
B. subtilis
by employing a clustered regularly interspaced short palindromic repeats interference (CRISPRi) approach to specifically target the key DnaA boxes 6 and 7, preventing DnaA binding to
oriC
. In this way, other functions of DnaA, such as a transcriptional regulator, were not significantly affected. When replication initiation was halted by this specific artificial and early blockage, we observed that non-replicating cells continued translation and cell growth, and the initial replication arrest did not induce global stress conditions such as the SOS response.

IMPORTANCE

Although bacteria constantly replicate under laboratory conditions, natural environments expose them to various stresses such as lack of nutrients, high salinity, and pH changes, which can trigger non-replicating states. These states can enable bacteria to (i) become tolerant to antibiotics (persisters), (ii) remain inactive in specific niches for an extended period (dormancy), and (iii) adjust to hostile environments. Non-replicating states have also been studied because of the possibility of repurposing energy for the production of additional metabolites or proteins. Using clustered regularly interspaced short palindromic repeats interference (CRISPRi) targeting bacterial replication initiation sequences, we were able to successfully control replication initiation in
Bacillus subtilis
. This precise approach makes it possible to study non-replicating phenotypes, contributing to a better understanding of bacterial adaptive strategies.
Delirium and incident dementia in hospital patients in New South Wales, Australia: retrospective cohort study
Authors: Gordon Emily H , Ward David D , Xiong Hao , Berkovsky Shlomo , Hubbard Ruth E 
Published: March 2024

Abstract

Objectives
To determine the strength and nature of the association between delirium and incident dementia in a population of older adult patients without dementia at baseline.

Design
Retrospective cohort study using large scale hospital administrative data.

Setting
Public and private hospitals in New South Wales, Australia between July 2001 and March 2020.

Participants
Data were extracted for 650 590 hospital patients aged ≥65 years. Diagnoses of dementia and delirium were identified from ICD-10 (international classification of diseases, 10th revision) codes. Patients with dementia at baseline were excluded. Delirium-no delirium pairs were identified by matching personal and clinical characteristics, and were followed for more than five years.

Main outcome measures
Cox proportional hazards models and Fine-Gray hazard models were used to estimate the associations of delirium with death and incident dementia, respectively. Delirium-outcome dose-response associations were quantified, all analyses were performed in men and women separately, and sensitivity analyses were conducted.

Results
The study included 55 211 matched pairs (48% men, mean age 83.4 years, standard deviation 6.5 years). Collectively, 58% (n=63 929) of patients died and 17% (n=19 117) had a newly reported dementia diagnosis during 5.25 years of follow-up. Patients with delirium had 39% higher risk of death (hazard ratio 1.39, 95% confidence interval 1.37 to 1.41) and three times higher risk of incident dementia (subdistribution hazard ratio 3.00, 95% confidence interval 2.91 to 3.10) than patients without delirium. The association with dementia was stronger in men (P=0.004). Each additional episode of delirium was associated with a 20% increased risk of dementia (subdistribution hazard ratio 1.20, 95% confidence interval 1.18 to 1.23).

Conclusions
The study findings suggest delirium was a strong risk factor for death and incident dementia among older adult patients. The data support a causal interpretation of the association between delirium and dementia. The clinical implications of delirium as a potentially modifiable risk factor for dementia are substantial.
Effectiveness, reach, uptake and feasibility of digital health interventions for adults with venous thromboembolism: protocol of a systematic review and meta-analysis
Authors: Fu Yan , Pu Hongji , Wang Yanjie , Lu Xinwu , Qiu Peng , Hu Min , Cheng Yong 
Published: March 2024

IntroductionPrevention of recurrence after an episode of venous thromboembolism (VTE), and also the post-thrombotic syndrome (PTS), is still a recognised challenge. In this meta-analysis, we will summarise existing evidence to compare intelligent system follow-up and routine follow-up for patients with VTE.Methods and analysisRelevant randomised controlled trials (RCTs) and cohort studies will be included from the following databases: MEDLINE/PubMed, Web of Science and the Cochrane Library. The last search time will be 31 March 2024. Two reviewers will independently identify RCTs and cohort studies according to eligibility and exclusion criteria. The risk of bias of included cohort studies will be assessed with the Newcastle-Ottawa Scale, Methodological Index of Non-Randomised Studies, and the risk of bias of RCTs will be assessed with and Cochrane Collaboration’s tool. The primary outcomes include overall survival rate and PTS incidence rate. The Grades of Recommendations, Assessment, Development and Evaluation tool will be used to assess the level of evidence for outcome from RCTs. RevMan V.5.4 software will be used to pool outcomes.Ethics and disseminationEthical approval was obtained from Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine Science Research Ethics Committee (SH9H-2023-T466-1). The findings will be disseminated to the public through conference presentations and publication in peer-reviewed scientific journals.PROSPERO registration numberCRD42023410644.
Correlates of post-traumatic stress disorder among adult residents of conflict-affected communities in Cross River State, Nigeria: a cross-sectional study
Authors: Awa Theresa Mark , Ugbe Ugbe Maurice-Joel , Onwusaka Obiageli Chiezey , Abua Eucheria Ekugeni , Esu Ekpereonne Babatunde 
Published: March 2024

BackgroundConflict-affected communities in Nigeria experience a range of problems. These experiences have been associated with different types of mental disorders, most notably, post-traumatic stress disorder (PTSD).AimThis study sought to assess PTSD and its associated factors among adults in conflict-affected communities in Odukpani Local Government Area (LGA), Cross River State, Nigeria.MethodsA cross-sectional study was conducted using non-probability and probability sampling techniques. The sample size for this study was 486 conflict-affected adults. The symptoms of PTSD were assessed using the Harvard Trauma Questionnaire and a semistructured questionnaire was employed to collect data on sociodemographic and trauma-related characteristics. Data were analysed using descriptive statistics, χ2and multivariable logistic regression.ResultsThe prevalence of PTSD in conflict-affected communities in Odukpani LGA, Cross River State, Nigeria was 73.9%. The multivariate analysis revealed that higher educational attainment (AOR 5.66; p<0.001; 95% CI 2.37 to 13.54), family size >4 (AOR 1.72; p=0.03; 95% CI 1.06 to 2.77), discrimination because of present status (AOR 1.96; p=0.03; 95% CI 1.26 to 3.06) and family history of mental illnesses (AOR 2.08; p=0.002; 95% CI 1.31 to 3.31) showed statistically significant relationships with PTSD in the study population.ConclusionA multisectoral approach for creating and routinely arranging mental health interventions and aid programmes aimed at improving social outcomes such as employment, living conditions and social networks for conflict-affected communities is recommended.
The association of degree of polypharmacy before and after among hospitalised internal medicine patients and clinical outcomes: a retrospective, population-based cohort study
Authors: Jonsdottir Freyja , Blondal Anna B , Gudmundsson Adalsteinn , Bates Ian , Stevenson Jennifer Mary , Sigurdsson Martin I 
Published: March 2024

ObjectivesTo determine the prevalence and incidence of polypharmacy/hyperpolypharmacy and which medications are most prescribed to patients with varying burden of polypharmacy.DesignRetrospective, population-based cohort study.SettingIceland.ParticipantsIncluding patients (≥18 years) admitted to internal medicine services at Landspitali – The National University Hospital of Iceland, between 1 January 2010 with a follow-up of clinical outcomes through 17 March 2022.Main outcomes measuresParticipants were categorised into medication use categories of non-polypharmacy (<5), polypharmacy (5–10) and hyperpolypharmacy (>10) based on the number of medications filled in the year predischarge and postdischarge. The primary outcome was prevalence and incidence of new polypharmacy. Secondary outcomes were mortality, length of hospital stay and re-admission.ResultsAmong 85 942 admissions (51% male), the median (IQR) age was 73 (60–83) years. The prevalence of preadmission non-polypharmacy was 15.1% (95% CI 14.9 to 15.3), polypharmacy was 22.9% (95% CI 22.6 to 23.2) and hyperpolypharmacy was 62.5% (95% CI 62.2 to 62.9). The incidence of new postdischarge polypharmacy was 33.4% (95% CI 32.9 to 33.9), and for hyperpolypharmacy was 28.9% (95% CI 28.3 to 29.5) for patients with preadmission polypharmacy. Patients with a higher level of medication use were more likely to use multidose drug dispensing and have a diagnosis of adverse drug reaction. Other comorbidities, including responsible subspeciality and estimates of comorbidity and frailty burden, were identical between groups of varying polypharmacy. There was no difference in length of stay, re-admission rate and mortality.ConclusionsPreadmission polypharmacy/hyperpolypharmacy and postdischarge new polypharmacy/hyperpolypharmacy is common amongst patients admitted to internal medicine. A higher level of medication use category was not found to be associated with demographic, comorbidity and clinical outcomes. Medications that are frequently inappropriately prescribed were among the most prescribed medications in the group. An increased focus on optimising medication usage is needed after hospital admission.Trial registration numberNCT05756400.
Community-based interventions targeting multiple forms of malnutrition among adolescents in low-income and middle-income countries: protocol for a scoping review
Authors: Kurniawan Adi Lukas , Ranisavljev Marijana , Partap Uttara , Shinde Sachin , Ferrero Elisabetta , Ostojic Sergej , Mkwanazi Ntombizodumo , Alangea Deda Ogum , Neumann Christine , Liu Shuyan , Bärnighausen Till , Fawzi Wafaie W. 
Published: March 2024

BackgroundAdolescent malnutrition is a significant public health challenge in low-income and middle-income countries (LMICs), with long-term consequences for health and development. Community-based interventions have the potential to address multiple forms of malnutrition and improve the health outcomes of adolescents. However, there is a limited understanding of the content, implementation and effectiveness of these interventions. This scoping review aims to synthesise evidence on community-based interventions targeting multiple forms of malnutrition among adolescents in LMICs and describe their effects on nutrition and health.Methods and analysisA comprehensive search strategy will be implemented in multiple databases including MEDLINE (through PubMed), Embase, CENTRAL (through Cochrane Library) and grey literature, covering the period from 1 January 2000 to 14 July 2023. We will follow the Participants, Concept and Context model to design the search strategy. The inclusion criteria encompass randomised controlled trials and quasi-experimental studies focusing on adolescents aged 10–19 years. Various types of interventions, such as micronutrient supplementation, nutrition education, feeding interventions, physical activity and community environment interventions, will be considered. Two reviewers will perform data extraction independently, and, where relevant, risk of bias assessment will be conducted using standard Cochrane risk-of-bias tools. We will follow the PRISMA Extension for Scoping Reviews checklist while reporting results.Ethics and disseminationThe scope of this scoping review is restricted to publicly accessible databases that do not require prior ethical approval for access. The findings of this review will be shared through publications in peer-reviewed journals, and presentations at international and regional conferences and stakeholder meetings in LMICs.Scoping review registrationThe final protocol was registered prospectively with the Open Science Framework on 19 July 2023 (https://osf.io/t2d78).
Associations between use of diabetes technology and diabetes distress: a Danish cross-sectional survey of adults with type 1 diabetes
Authors: Lorenzen Johanne Triantafyllou , Madsen Kristoffer Panduro , Cleal Bryan , Joensen Lene Eide , Nørgaard Kirsten , Pedersen-Bjergaard Ulrik , Schmidt Signe , Rytter Karen , Willaing Ingrid 
Published: March 2024

IntroductionThe study aimed to investigate independent and combined associations between insulin delivery method (insulin pump therapy (IPT) vs multiple daily injections (MDI)), glucose monitoring method (intermittently scanned continuous glucose monitoring (isCGM) and real-time continuous glucose monitoring (rtCGM) vs blood glucose metre (BGM)) and diabetes distress (DD) in adults with type 1 diabetes (T1D).Research design and methodsWe combined data from two Danish questionnaire-based surveys, the Steno Tech Survey (n=1591) and the Type 1 Diabetes Distress Scale (T1-DDS) validation survey (n=4205), in which individuals aged ≥18 years with T1D were invited to participate. The 28-item T1-DDS was used to measure DD and DD scores were categorised as little or no distress (score <2.0), moderate distress (2.0–2.9) and high distress (score ≥3.0). Associations between insulin delivery, glucose monitoring methods and DD were assessed using linear regression.ResultsAmong 2068 adults with T1D who responded to one of the surveys, the use of IPT was associated with a lower total T1-DDS score (−0.09, 95% CI 0.16 to −0.03) compared with MDI and adjusted for glucose monitoring method. The use of CGM was associated with a higher total T1-DDS score (0.11, 95% CI 0.05 to 0.18) compared with BGM and adjusted for the insulin delivery method. IPT was still associated with a lower T1-DDS score, regardless of being combined with BGM (−0.17, 95% CI −0.28 to −0.06) or CGM (−0.13, 95% CI −0.21 to −0.05), compared with MDI with CGM. No association was found between the type of CGM (isCGM vs rtCGM) and DD among either IPT or MDI users when restricting analysis to individuals using CGM.ConclusionsAmong Danish adults with T1D, the use of IPT was associated with lower levels of DD, while CGM use was associated with higher levels of DD. DD should be addressed when introducing people with T1D to diabetes technology, CGM in particular.Trial registration numberNCT04311164(Results).
Efficacy and safety of traditional Chinese manual therapy (Tuina) in patients with non-specific chronic low back pain: a study protocol for a randomised controlled trial
Authors: Cao Ben , Fang Sitong , Wu Zhiwei , Zhou Xin , Kong Lingjun , Zhu Qingguang , Zhu Bowen , Tang Cheng , Fang Min 
Published: March 2024

IntroductionNon-pharmacological interventions play a crucial role in the management of non-specific chronic low back pain (NSCLBP). One prime example is Tuina, a traditional Chinese manual therapy that incorporates pressing, kneading and rubbing techniques to alleviate physical discomfort and enhance overall well-being. It serves as a widely used technique in China and other East Asian countries. However, the effectiveness and safety of Tuina for managing NSCLBP have not been substantiated through rigorous clinical research. We sought to carry out a randomised controlled trial with an open-label design, blinded assessors and parallel arms to assess the effectiveness and safety of Tuina as a treatment for NSCLBP. The trial aims to provide high-quality evidence regarding the efficacy and safety of Tuina in improving outcomes for patients with NSCLBP.Methods and analysisA total of 150 patients aged 18–60 years with NSCLBP will be recruited. Participants will be randomly assigned to one of the two groups. Both groups will receive standard health education. In addition, the treatment group will receive Tuina therapy, while the control group will participate in core stability exercises. Each group will undergo a total of 18 interventions over 6 weeks, with the interventions administered three times per week. The primary outcome measure is the patient’s pain intensity, assessed using the Numerical Rating Scale, at week 6 following randomisation. Secondary outcomes encompass disability (measured by the Roland-Morris Disability Questionnaire), quality of life (assessed using the EuroQoL-5 dimensions questionnaire), adverse emotions (evaluated with the Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia and Depression Anxiety Stress Scale), biomechanical outcomes, socioeconomic indicators (medication use, healthcare utilisation and absenteeism), patient satisfaction, treatment adherence and other relevant factors.The statistical analysis will follow the intention-to-treat principle. Two-way repeated measures analysis of variance will be used to compare the clinical data across different time points within both groups.Ethics and disseminationThe study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1366-133-01). All study participants will be required to give written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results.Trial registration numberChiCTR2300076257.