bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rationally designed antimicrobial peptide from structural and functional insights of
Clostridioides difficile
translation initiation factor 1
Authors: Alanis Elvira , Aguilar Faith , Banaei Niaz , Dean Frank B. , Villarreal Alexa , Alanis Miguel , Lozano Karen , Bullard James M. , Zhang Yonghong 
Published: February 2024

ABSTRACT

A significant increase of hospital-acquired bacterial infections during the COVID-19 pandemic has become an urgent medical problem.
Clostridioides difficile
is an urgent antibiotic-resistant bacterial pathogen and a leading causative agent of nosocomial infections. The increasing recurrence of
C. difficile
infection and antibiotic resistance in
C. difficile
has led to an unmet need for the discovery of new compounds distinctly different from present antimicrobials, while antimicrobial peptides as promising alternatives to conventional antibiotics have attracted growing interest recently. Protein synthesis is an essential metabolic process in all bacteria and a validated antibiotic target. Initiation factor 1 from
C. difficile
(Cd-IF1) is the smallest of the three initiation factors that acts to establish the 30S initiation complex to initiate translation during protein biosynthesis. Here, we report the solution nuclear magnetic resonance (NMR) structure of Cd-IF1 which adopts a typical β-barrel fold and consists of a five-stranded β-sheet and one short α-helix arranged in the sequential order β1-β2-β3-α1-β4-β5. The interaction of Cd-IF1 with the 30S ribosomal subunit was studied by NMR titration for the construction of a structural model of Cd-IF1 binding with the 30S subunit. The short α-helix in IF1 was found to be critical for IF1 ribosomal binding. A peptide derived from this α-helix was tested and displayed a high ability to inhibit the growth of
C. difficile
and other bacterial strains. These results provide a clue for the rational design of new antimicrobials.

IMPORTANCE

Bacterial infections continue to represent a major worldwide health hazard due to the emergence of drug-resistant strains.
Clostridioides difficile
is a common nosocomial pathogen and the causative agent in many infections resulting in an increase in morbidity and mortality. Bacterial protein synthesis is an essential metabolic process and an important target for antibiotic development; however, the precise structural mechanism underlying the process in
C. difficile
remains unknown. This study reports the solution structure of
C. difficile
translation initiation factor 1 (IF1) and its interaction with the 30S ribosomal subunit. A short α-helix in IF1 structure was identified as critically important for ribosomal binding and function in regulating the translation initiation, which allowed a rational design of a new peptide. The peptide demonstrated a high ability to inhibit bacterial growth with broad-spectrum antibacterial activity. This study provides a new clue for the rational design of new antimicrobials against bacterial infections.
Structural Transformations and Formation of Microstructures and Nanostructures in Thin Films of Chalcogenide Vitreous Semiconductors
Authors: Zabotnov S. V. , Kashkarov P. K. , Kolobov A. V. , Kozyukhin S. A. 
Published: February 2024

Abstract
Chalcogenide vitreous semiconductors (ChVSs) are of both fundamental and applied interest as materials in which reversible structural transformations within the amorphous phase and phase transitions to the crystalline state can be effectively implemented and various microstructures and nanostructures can be obtained as a result of external effects. One of the most promising methods for such ChVS modifications is the pulsed-laser-irradiation technique, which is a noncontact technology of local impact and makes it possible to change the structural, optical, and electrical properties of samples in a wide range. This includes methods based on the precision formation of a surface microrelief and nanorelief, and high contrast in the conductivity and refractive index between the crystalline and amorphous phases. This work reviews key publications on the structural modification of thin films from the most widely studied binary and ternary ChVS compounds (As2S3, As2Se3, Ge2Sb2Te5, etc.) to show the use of irradiated samples as metasurfaces for photonic applications and promising phase-change data storage.
Physiologically Based Pharmacokinetic Modelling of Accumulation Kinetics of Silver Nanoparticles in a Mammalian Organism
Authors: Antsiferova A. A. , Loginova M. A. , Kashkarov P. K. 
Published: February 2024

Abstract
A mathematical model of the biokinetics of silver nanoparticles in the mammalian organism using the example of C57Bl/6 laboratory mice with application of the concept of physiologically based pharmacokinetic (PBPK) modeling and the previously obtained by a highly precise technique of instrumental neutron activation analysis (INAA) experimental data is proposed. A numerical solution of this model was recieved. The applicability of the various assumptions was considered and justified. The obtained solution was analyzed, and the biokinetic transition-rate constants, the times of reaching the plateau and the mass content of the stable equilibrium were calculated. The numerical parameters were compared with the previously obtained parameters on the biokinetics of silver nanoparticles of the same brand. It is concluded that the proposed approach is well applicable for modeling the biokinetics of silver nanoparticles in a living organism.
Can an integrated intervention package including peer support increase the proportion of health facility births? A cluster randomised controlled trial in Northern Uganda
Authors: Nankabirwa Victoria , Mukunya David , Ndeezi Grace , Odongkara Beatrice , Arach Agnes A , Achora Vicentina , Mugenyi Levi , Sebit Mohammad Boy , Wandabwa Julius N , Waako Paul , Tylleskär Thorkild , Tumwine James K 
Published: February 2024

ObjectiveTo assess the effect of an integrated intervention package compared with routine government health services on the frequency of health facility births.SettingThree subcounties of Lira district in Northern Uganda.DesignA cluster randomised controlled trial where a total of 30 clusters were randomised in a ratio of 1:1 to intervention or standard of care.ParticipantsPregnant women at ≥28 weeks of gestation.InterventionsParticipants in the intervention arm received an integrated intervention package of peer support, mobile phone messaging and birthing kits during pregnancy while those in the control arm received routine government health services (‘standard of care’).Primary and secondary outcome measuresThe primary outcome was the proportion of women giving birth at a health facility in the intervention arm compared with the control arm. Secondary outcomes were perinatal and neonatal deaths.ResultsIn 2018–2019, 995 pregnant women were included in 15 intervention clusters and 882 in 15 control clusters. The primary outcome was ascertained for all except one participant who died before childbirth. In the intervention arm, 754/994 participants (76%) gave birth at a health facility compared with 500/882 (57%) in the control arm. Participants in the intervention arm were 35% more likely to give birth at a health facility compared with participants in the control arm, (risk ratio 1.35 (95% CI 1.20 to 1.51)) and (risk difference 0.20 (95% CI 0.13 to 0.27)). Adjusting for baseline differences generated similar results. There was no difference in secondary outcomes (perinatal or neonatal mortality or number of postnatal visits) between arms.ConclusionThe intervention was successful in increasing the proportion of facility-based births but did not reduce perinatal or neonatal mortality.Trial registration numberNCT02605369
Treatment pathways, economic burden and clinical outcomes in new users of inhaled corticosteroid/long-acting B2-agonist dual therapy with chronic obstructive pulmonary disease in a primary care setting in England: a retrospective cohort study
Authors: Czira Alexandrosz , Banks Victoria , Requena Gema , Wood Robert , Tritton Theo , Wild Rosie , Compton Chris , Ismaila Afisi 
Published: February 2024

ObjectiveManagement of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) improves lung function and health status and reduces COPD exacerbation risk versus monotherapy. This study described treatment use, healthcare resource utilisation (HCRU), healthcare costs and outcomes following initiation of single-device ICS/LABA as initial maintenance therapy (IMT).DesignRetrospective cohort study.SettingPrimary care, England.Data sourcesLinked data from the Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets.ParticipantsPatients with COPD and ≥1 single-device ICS/LABA prescription between July 2015 and December 2018 were included.Primary and secondary outcome measuresTreatment pathways, COPD-related HCRU and healthcare costs, COPD exacerbations, time to triple therapy, medication adherence (proportion of days covered ≥80%) and indexed treatment time to discontinuation. Data for patients without prior maintenance therapy history (IMT users) and non-triple users were assessed over a 12-month follow-up period.ResultsOf 13 451 new ICS/LABA users, 5162 were IMT users (budesonide/formoterol, n=1056; beclomethasone dipropionate/formoterol, n=2427; other ICS/LABA, n=1679), for whom at 3 and 12 months post-index, 45.6% and 39.4% were still receiving any ICS/LABA. At >6 to ≤12 months, the proportion of IMT users with ≥1 outpatient visit (10.1%) and proportion with ≥1 inpatient stay (12.6%) had increased from those at 3 months (9.0% and 7.4%, respectively). Inpatient stays contributed most to total COPD-related healthcare costs. For non-triple IMT users, at 3 and 12 months post-index, 4.5% and 13.7% had ≥1 moderate-to-severe COPD exacerbation. Time to triple therapy initiation and time to discontinuation of index medication ranged from 45.9 to 50.2 months and 2.3 to 2.8 months between treatments. Adherence was low across all time points (21.5–27.6%). Results were similar across indexed therapies.ConclusionsIn the year following treatment initiation, ICS/LABA adherence was poor and many patients discontinued or switched therapies, suggesting that more consideration and optimisation of treatment is required in England for patients initiating single-device ICS/LABA therapy.
Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD
Authors: Jørgensen Torben , Dantoft Thomas Meinertz , Petersen Marie Weinreich , Gormsen Lise , Winter-Jensen Matilde , Fink Per , Linneberg Allan , Benros Michael Eriksen , Eplov Lene Falgaard , Bjerregaard Anne Ahrendt , Schovsbo Signe Ulfbeck , Brinth Louise Schouborg 
Published: February 2024

ObjectivesIt has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case–control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association.DesignA cross-sectional general population-based study.SettingThe Danish Study of Functional Somatic Disorders conducted 2013–2015 in 10 municipalities in the western part of Greater Copenhagen, Denmark.ParticipantsA total of 6891 men and women aged 18–72 years were included in the analyses after exclusion of 602 persons with missing HRV data. Various delimitations of FSD (chronic fatigue, chronic widespread pain, irritable bowel and bodily distress syndrome) were identified by validated questionnaires and diagnostic interviews. HRV parameters in time and frequency domains were calculated from successive beat-to-beat heart rate (HR) data using the ‘E-motion’ HR monitor device during 7 min of supine rest. Chronic stress was assessed by Cohen’s self-perceived stress scale.Outcome measuresLogistic regression analyses were used to calculate possible associations between the various delimitations of FSD and HRV adjusting for chronic stress.ResultsPersons with FSD had a slightly higher mean HR and lower HRV as measured by time domain parameters, whereas associations with frequency domain parameters were not consistent. Adjusting for chronic stress attenuated associations slightly.ConclusionThe study supports a sympathetic predominance in persons with FSD, which could not be entirely explained by chronic stress. However, it is not possible to conclude whether the association is a causal factor to or a consequence of FSD.
Efficacy of biological agents combined with oral immunotherapy (OIT) for food allergy: a protocol for a systematic review and meta-analysis
Authors: Honda Aiko , Okada Yoshiyuki , Matsushita Tomomi , Hasegawa Takeshi , Ota Erika , Noma Hisashi , Imai Takanori , Kwong Joey 
Published: February 2024

IntroductionFood allergy affects a large population throughout the world. Recently, oral immunotherapy (OIT) has been reported as an effective treatment for severe food allergy. Although OIT was successful in numerous trials in desensitisation, adverse events including anaphylaxis during OIT frequently occur. Additionally, some patients fail to be desensitised after OIT and the response to treatment is often not sustained. As a further adjunctive therapy to facilitate OIT, the role of biological agents has been identified. For example, efficacy and safety of omalizumab as an adjuvant therapy of OIT has become apparent through some RCTs and observational studies. Interest towards this topic is growing worldwide, and ongoing trials will provide additional data on the biologics in food allergy.We aim to systematically analyse the efficacy and safety of OIT combined with biological agents for food allergy.Methods and analysisThis paper provides a protocol for a systematic review of the relevant published analytical studies using an aggregate approach following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Two authors will perform a comprehensive search for studies on MEDLINE/PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Subsequently, two independent authors will perform abstract screening, full-text screening and data extraction. A meta-analysis will be conducted as appropriate.Ethics and disseminationThe protocol of this systematic review will be provided in a peer-reviewed journal. As the researchers will not identify the individual patients included in the studies, they do not need to acquire ethics approval.PROSPERO registration numberCRD42022373015.
Study protocol for a prediction model for mild cognitive impairment in older adults with diabetes mellitus and construction of a nurse-led screening system: a prospective observational study
Authors: Miao Weiwei , Lu Yanling , Xv Honglian , Zheng Chen , Yang Wenwen , Qian Xiangyun , Chen Jianqun , Geng Guiling 
Published: February 2024

IntroductionWith an increasing number of older adults in China, the number of people with cognitive impairment is also increasing. To decrease the risk of dementia, it is necessary to timely detect mild cognitive impairment (MCI), which is the preliminary stage of dementia. The prevalence of MCI is relatively high among older adults with diabetes mellitus (DM); however, no effective screening strategy has been designed for this population. This study will construct a nurse-led screening system to detect MCI in community-dwelling older adults with DM in a timely manner.Methods and analysisA total of 642 participants with DM will be recruited (n=449 for development, n=193 for validation). The participants will be divided into MCI and none-MCI groups. The candidate predictors will include demographic variables, lifestyle factors, history of diseases, physical examinations, laboratory tests and neuropsychological tests. Univariate analysis, least absolute shrinkage and selection operator regression screening, and multivariate logistic regression analysis will be conducted to identify the outcome indicators. Based on the multivariate logistic regression equation, we will develop a traditional model as a comparison criterion for the machine learning models. The Hosmer-Lemeshow goodness-of-fit test and calibration curve will be used to evaluate the calibration. Sensitivity, specificity, area under the curves and clinical decision curve analysis will be performed for all models. We will report the sensitivity, specificity, area under the curve and decision curve analysis of the validation dataset. A prediction model with better performance will be adopted to form the nurse-led screening system.Ethics and disseminationThis prospective study has received institutional approval of the Medical Ethics Committee of Qidong Hospital of TCM (QDSZYY-LL-20220621). Study results will be disseminated through conference presentations, Chinese Clinical Trial Registry and publication.Trial registration numberChiCTR2200062855.
Seroprevalence of Japanese encephalitis virus-specific antibodies in Australia following novel epidemic spread: protocol for a national cross-sectional study
Authors: Winkler Noni Ella , Koirala Archana , Kaur Guddu , Prasad Shayal , Hirani Rena , Baker Jannah , Hoad Veronica , Gosbell Iain B , Irving David O , Hueston Linda , O'Sullivan Matthew VN , Kok Jen , Dwyer Dominic E , Macartney Kristine 
Published: February 2024

IntroductionJapanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors.MethodSamples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses.AnalysisTwo analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model.EthicsNational Mutual Acceptance ethical approval was obtained from the Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC). Local approvals were planned to be sought in each jurisdiction, as per local ethics processes. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC.DisseminationFindings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.
Developing interfaith interventions to address hesitancy towards COVID-19 vaccination: protocol for a focus group-based, exploratory qualitative study
Authors: Ali Farzana , Garfield Sara , Murdan Sudaxshina 
Published: February 2024

IntroductionThe COVID-19 pandemic demonstrated how vaccine hesitancy impacts are translated nationally and internationally. A predictor of vaccine hesitancy is religious beliefs (eg, the body being sacred and should be healed by God). Additionally, the perceived content of vaccines can conflict with religious dietary restrictions. Despite the main faith organisations in the UK endorsing COVID-19 vaccination, vaccine hesitancy remains a challenge. Most faith-based research and interventions have been investigated in individual faiths, in isolation from others. Therefore, the aim of our research is to inform the development of interfaith interventions to address COVID-19 vaccine hesitancy, following the identification of potential facilitators and barriers and codesign of interfaith intervention(s).Methods and analysisWe will facilitate six face-to-face focus groups in London, each comprising eight participants. There will also be the option of joining an online focus group. A semistructured topic guide will include questions on experiences around interfaith, vaccine hesitancy, facilitators and barriers, and potential interfaith interventions to increase vaccine acceptance. Focus group participants will be invited to join a subsequent interfaith codesign workshop where the researchers will share the tentative findings and facilitate discussion to develop one or more interventions. Purposive sampling will be used to recruit 48 participants from different faith groups, ethnicities and backgrounds to capture diversity in the sample. Reflexive thematic analysis will guide a systematic process of constant comparison, coding data into categories and refining into overarching themes.Ethics and disseminationThe University College London (UCL) Research Ethics Committee granted ethics approval (Project ID 4359.006) on 3 May 2022. Minor amendments to the study were approved on 15 May 2023 to accommodate participants’ requests for online or face-to-face focus groups at a UCL venue. Informed consent is required from all participants. The findings will be disseminated in journals and to the public and key stakeholders.