bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell aggregation mediated by
ACE2
deletion in
Candida auris
modulates fungal colonization and host immune responses in the skin
Authors: Balakumar Abishek , Cox Abigail , Thangamani Shankar 
Published: October 2024

ABSTRACT

Candida auris
is an emerging multi-drug-resistant fungal pathogen that colonizes the skin and causes invasive infections in hospitalized patients. Multi-cellular aggregative phenotype is widely reported in the
C. auris
isolates, but its role in skin colonization and host immune response is not yet known. In this study, we generated aggregative phenotype by deleting the
ACE2
gene in
C. auris
and determined the fungal colonization and host immune response using an intradermal mouse model of
C. auris
skin infection. Our results indicate that mice infected with
ace2
Δ strain had significantly lower fungal load after 3 and 14 days post-infections compared to the non-aggregative wild-type and the
ACE2
reintegrated strain. The colonization of
ace2
Δ is associated with increased recruitment of CD11b
+
Ly6G
+
neutrophils and decreased accumulation of CD11b
+
Ly6 C
hi
inflammatory monocytes and CD11b
+
MHCII
+
CD64
+
macrophages. Furthermore, Th17 cells and type 3 innate lymphoid cells (ILCs) were significantly increased in the skin tissue of
ace2
Δ infected mice. Our findings suggest that aggregative phenotype mediated by
ACE2
deletion in
C. auris
induces potent neutrophil and IL-17-mediated immune response and reduces fungal colonization in the skin.

IMPORTANCE

C. auris
is a rapidly emerging fungal pathogen that can colonize hospitalized patients, especially in skin tissue, and cause invasive infections.
C. auris
isolates exhibit morphological heterogeneity, and the multicellular aggregative phenotype of
C. auris
is reported frequently in clinical settings. Understanding the role of fungal morphotypes in colonization, persistence, and immune response in the skin microenvironment will have potential applications in clinical diagnosis and novel preventive and therapeutic measures. Here, we utilized the murine model of intradermal infection and determined that the aggregative phenotype of
C. auris
as the result of
ACE2
gene deletion elicits potential innate and adaptive immune responses in mice. These observations will help explain the differences in the skin colonization and immune responses of the aggregative morphotype of
C. auris
and open the door to developing novel antifungal therapeutics.
Intranasal administration of
Clostridium butyricum
and its derived extracellular vesicles alleviate LPS-induced acute lung injury
Authors: Liu Li , Zheng Cihua , Xu Zhenyang , Wang Zhuoya , Zhong Yuchun , He Zhidong , Zhang Wenming , Zhang Yuanbing 
Published: October 2024

ABSTRACT

Acute lung injury (ALI) is associated with high morbidity and mortality rates. However, its clinical treatment is limited. Currently, the treatment of lung diseases by regulating the lung microbiota has become a research hotspot. In this study, we investigated the protective effects of the intranasal administration of
Clostridium butyricum
and its derived extracellular vesicles (EVs) against lipopolysaccharide (LPS)-induced ALI. The results demonstrated that compared with the LPS group, the pre-treatment group with
C. butyricum
and its EVs reduced the expression of pro-inflammatory cytokines and alleviated the symptoms in ALI mice by inhibiting the TLR4/MyD88 signaling pathway. Moreover,
C. butyricum
and its derived EVs inhibited the expression of apoptosis-related proteins and increased the expression of lung barrier proteins. Additionally, the intervention of
C. butyricum
changed the composition of the pulmonary microbiota. At the species level, LPS significantly increased the relative abundance of
Acinetobacter johnsonii
, while
C. butyricum
reversed this effect. In conclusion, these data demonstrate that intranasal administration of
C. butyricum
and its EVs can prevent LPS-induced ALI by reducing inflammation, inhibiting apoptosis, and improving lung barrier function. Additionally,
C. butyricum
regulated the pulmonary microbiota of mice to alleviate LPS-induced ALI.

IMPORTANCE

The disorder of pulmonary microbiota plays an important role in the progression of acute lung injury (ALI). However, very few studies have been conducted to treat ALI by modulating pulmonary microbiota. In this study, the diversity and composition of pulmonary microbiota were altered in lipopolysaccharide (LPS)-induced ALI mice, but the ecological balance of the pulmonary microbiota was restored by intranasal administration of
Clostridium butyricum
. Moreover, the study reported the mechanism of
C. butyricum
and its derived extracellular vesicles for the treatment of LPS-induced ALI. These results reveal the importance of pulmonary microbiota in ALI disease. It provides a new approach for the treatment of ALI with new-generation probiotics.
Distinguishing fault offset from climatically modulated channel deflections: Insights from the Pearblossom slip-rate site, Mojave section of the San Andreas fault, California, USA
Authors: Anderson-Merritt Emery O. , Cowgill Eric , Keen-Zebert Amanda , Young Elaine K. , Dailey Mary 
Published: October 2024

Abstract
Fault slip histories are essential for understanding seismic hazard and regional fault system development but fundamentally depend on identifying, dating, and reconstructing displaced markers. Here, we use a case study of the Pearblossom site along the Mojave section of the San Andreas fault in California (USA) to show how pulses of sediment aggradation during wet periods can complicate such reconstructions by producing “imposter offsets”—landforms that develop with an initial deflection that is easily misread as tectonic displacement caused by fault slip. Specifically, we document two channels on the downstream side of the fault: a subtle one that we interpret to have been beheaded and displaced 24–49 m from a source channel on the upstream side of the fault, and a second and more prominent one that we interpret as an imposter offset of 36–88 m. Using optically stimulated luminescence dating, we determine that the source channel incised between 1.44 ± 0.43 ka and 1.27 ± 0.18 ka with a subsequent phase of alluvial fan aggradation at ~0.6 ka, when the channel with the imposter offset formed. Because the pulse of fan deposition coincides temporally with a wet period in Southern California precipitation records, we attribute formation of the imposter offset and the alluvial fan into which it incised to climatically modulated deposition at the site. Comparing precipitation records with charcoal ages compiled from multiple Mojave Desert region locations suggests that other slip-rate sites may be similarly affected. Although climatic effects can complicate slip-rate studies, we show that the morphology and upstream position of the deflected channel can indicate whether a site likely records useful information about fault slip.
Cascade testing effectively identifies undiagnosed sickle cell disease in The Gambia: a quality improvement project
Authors: Deans-Louis Etienne , Allen Angela , Allen Stephen John 
Published: October 2024

ObjectiveSickle cell disease (SCD) has a high mortality during childhood in many low and middle-income countries (LMICs). Early diagnosis improves outcomes but newborn screening is not well established in LMICs. Cascade testing may be feasible and effective in identifying undiagnosed SCD and carriers of haemoglobin (Hb) S.DesignQuality improvement project using existing clinic and laboratory resources.SettingThe Haematology Clinic at the Edward Francis Small Teaching Hospital, Banjul, The Gambia.ParticipantsFamilies of index cases with SCD.MethodsHb phenotype was determined in full or half-siblings of a SCD index case over a 6-week period using the HemoTypeSC test and confirmed by Hb electrophoresis.Main outcome measureIdentifying undiagnosed SCD.ResultsOf 102 families invited, 31 (30%) attended during the study period and 53 siblings were tested. Except for one indeterminate test, HemoType SC agreed with Hb electrophoresis. Ten (19%; 95% CI 10 to 32) siblings were diagnosed with HbSS, 25 (47%; 34 to 60) as carriers (HbAS) and 18 (34%; 23 to 48) were unaffected (HbAA). Some symptoms and signs of SCD occurred significantly more frequently in HbSS than in HbAA and HbAS, but none was sufficiently common to help in identifying children for testing.ConclusionsCascade testing was effective in identifying undiagnosed HbSS as well as children carrying the sickle cell gene. In routine care settings in LMICs, cascade testing facilitated by point-of-care tests may be feasible and affordable in increasing the detection of SCD and improving outcomes through earlier diagnosis.
Impact of a national tsetse control programme to eliminate Gambian sleeping sickness in Uganda: a spatiotemporal modelling study
Authors: Longbottom Joshua , Esterhuizen Johan , Hope Andrew , Lehane Michael J , Mangwiro TN Clement , Mugenyi Albert , Dunkley Sophie , Selby Richard , Tirados Inaki , Torr Steve J , Stanton Michelle C 
Published: October 2024

IntroductionTsetse flies (Glossina) transmitTrypanosoma brucei gambiense, which causes gambiense human African trypanosomiasis (gHAT). As part of national efforts to eliminate gHAT as a public health problem, Uganda implemented a large-scale programme of deploying Tiny Targets, which comprise panels of insecticide-treated material which attract and kill tsetse. At its peak, the programme was the largest tsetse control operation in Africa. Here, we quantify the impact of Tiny Targets and environmental changes on the spatial and temporal patterns of tsetse abundance across North-Western Uganda.MethodsWe leverage a 100-month longitudinal dataset detailingGlossina fuscipes fuscipescatches from monitoring traps between October 2010 and December 2019 within seven districts in North-Western Uganda. We fitted a boosted regression tree (BRT) model assessing environmental suitability, which was used alongside Tiny Target data to fit a spatiotemporal geostatistical model predicting tsetse abundance across our study area (~16 000 km2). We used the spatiotemporal model to quantify the impact of Tiny Targets and environmental changes on the distribution of tsetse, alongside metrics of uncertainty.ResultsEnvironmental suitability across the study area remained relatively constant over time, with suitability being driven largely by elevation and distance to rivers. By performing a counterfactual analysis using the fitted spatiotemporal geostatistical model, we show that deployment of Tiny Targets across an area of 4000 km2reduced the overall abundance of tsetse to low levels (median daily catch=1.1 tsetse/trap, IQR=0.85–1.28). No spatial–temporal locations had high (>10 tsetse/trap/day) numbers of tsetse compared with 18% of locations for the counterfactual.ConclusionsIn Uganda, Tiny Targets reduced the abundance ofG. f. fuscipesand maintained tsetse populations at low levels. Our model represents the first spatiotemporal geostatistical model investigating the effects of a national tsetse control programme. The outputs provide important data for informing next steps for vector control and surveillance.
Cost and cost-effectiveness of digital technologies for support of tuberculosis treatment adherence: a systematic review
Authors: Kafie Cedric , Mohamed Mona Salaheldin , Zary Miranda , Chilala Chimweta Ian , Bahukudumbi Shruti , Gore Genevieve , Foster Nicola , Fielding Katherine L , Subbaraman Ramnath , Schwartzman Kevin 
Published: October 2024

BackgroundDigital adherence technologies (DATs) may provide a patient-centred approach to supporting tuberculosis (TB) medication adherence and improving treatment outcomes. We synthesised evidence addressing costs and cost-effectiveness of DATs to support TB treatment.MethodsA systematic review (PROSPERO-CRD42022313531) identified relevant literature from January 2000 to April 2023 in MEDLINE, Embase, CENTRAL, CINAHL, Web of Science along with preprints from medRxiv, Europe PMC and ClinicalTrials.gov. Studies with observational, experimental or quasi-experimental designs (minimum 20 participants) and modelling studies reporting quantitative data on the cost or cost-effectiveness of DATs for TB infection or disease treatment were included. Study characteristics, cost and cost-effectiveness outcomes were extracted.ResultsOf 3619 titles identified by our systematic search, 29 studies met inclusion criteria, of which 9 addressed cost-effectiveness. DATs included short message service (SMS) reminders, phone-based technologies, digital pillboxes, ingestible sensors and video-observed therapy (VOT). VOT was the most extensively studied (16 studies) and was generally cost saving when compared with healthcare provider directly observed therapy (DOT), particularly when costs to patients were included—though findings were largely from high-income countries. Cost-effectiveness findings were highly variable, ranging from no clinical effect in one study (SMS), to greater effectiveness with concurrent cost savings (VOT) in others. Only eight studies adequately reported at least 80% of the elements required by Consolidated Health Economic Evaluation Reporting Standards, a standard reporting checklist for health economic evaluations.ConclusionDATs may be cost saving or cost-effective compared with healthcare provider DOT, particularly in high-income settings. However, more data of higher quality are needed, notably in lower-income and middle-income countries which have the greatest TB burden.
Characteristics of non-randomised studies of drug treatments: cross sectional study
Authors: Yaacoub Sally , Porcher Raphael , Pellat Anna , Bonnet Hillary , Tran Viet-Thi , Ravaud Philippe , Boutron Isabelle 
Published: October 2024

ObjectiveTo examine the characteristics of comparative non-randomised studies that assess the effectiveness or safety, or both, of drug treatments.DesignCross sectional study.Data sourcesMedline (Ovid), for reports published from 1 June 2022 to 31 August 2022.Eligibility criteria for selecting studiesReports of comparative non-randomised studies that assessed the effectiveness or safety, or both, of drug treatments were included. A randomly ordered sample was screened until 200 eligible reports were found.Data on general characteristics, reporting characteristics, and time point alignment were extracted, and possible related biases,witha piloted form inspired by reporting guidelines and the target trial emulation framework.ResultsOf 462 reports of non-randomised studies identified, 262 studies were excluded (32% had no comparator and 25% did not account for confounding factors). To assess time point alignment and possible related biases, three study time points were considered: eligibility, treatment assignment, and start of follow-up. Of the 200 included reports, 70% had one possible bias, related to: inclusion of prevalent users in 24%, post-treatment eligibility criteria in 32%, immortal time periods in 42%, and classification of treatment in 23%. Reporting was incomplete, and only 2% reported all six of the key elements considered: eligibility criteria (87%), description of treatment (46%), deviations in treatment (27%), causal contrast (11%), primary outcomes (90%), and confounding factors (88%). Most studies used routinely collected data (67%), but only 7% reported using validation studies of the codes or algorithms applied to select the population. Only 7% of reports mentioned registration on a trial registry and 3% had an available protocol.ConclusionsThe findings of the study suggest that although access to real world evidence could be valuable, the robustness and transparency of non-randomised studies need to be improved.
Effectiveness and acceptability of different lifestyle interventions for women with polycystic ovary syndrome: protocol for a systematic review and network meta-analysis
Authors: Shangguan Fuliang , Liu Hui , Guo Yu , Yu Juping , Liang Yinni , Yu Huixi , Su Yinhua , Li Zhongyu 
Published: October 2024

IntroductionWomen with polycystic ovary syndrome (PCOS) experience various metabolic, endocrine, reproductive and psychosocial manifestations. Lifestyle modification is crucial for the management of PCOS to reduce long-term complications. Nonetheless, the efficacy and acceptability of lifestyle interventions differs, and there are no uniform methods of clinical application. Hence, a systematic review and network meta-analysis (NMA) are needed to explore the efficacy and acceptability of lifestyle interventions to inform clinical practice.Methods and analysisTen databases (Cochrane Gynaecology and Fertility Specialised Register, Cochrane Register of Studies Online, PubMed, EMBASE (Excerpta Medica Database), PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Chinese National Knowledge Infrastructure, WanFang, VIP, and Sinomed) and four clinical trial registry platforms will be searched to identify literature published in English or Chinese reporting results of randomised clinical trials conducted to evaluate the effects of lifestyle interventions for women with PCOS. The reference lists of the included studies will be manually searched. Primary outcomes will include biochemical and clinical hyperandrogenism, recruitment and retention rates. Secondary outcomes will encompass menstrual regularity, ovulation, anthropometry and quality of life. Literature selection and extraction of data will be performed independently by at least two researchers. An NMA random-effects model will be implemented for amalgamating evidence. All treatments will be ranked based on the value of p. OpenBUGS will be used for Bayesian modelling, with output verifications generated in Stata and R. The quality of evidence supporting network estimates of major outcomes will also be appraised using the Grading of Recommendations Assessment, Development, and Evaluation framework.Ethics and disseminationEthical approval is not required for this review as no data will be collected from human participants. Results will be presented in a peer-reviewed publication.PROSPERO registration numberCRD42024499819
Effect of diet on the management of hypertension and type 2 diabetes mellitus in adults from low-income and middle-income countries: protocol for a systematic review of randomised controlled trials
Authors: Tarazona-Meza Carla , Garcia Larsen Vanessa , Matsuzaki Mika , Checkley William 
Published: October 2024

IntroductionHypertension and type 2 diabetes mellitus (T2DM) are two highly prevalent non-communicable diseases worldwide, both leading to disability and premature mortality in low-and-middle-income countries (LMICs). Nutritional interventions towards a healthier dietary pattern or food and nutrients intake have an important role on the management of this disease. This systematic review aims to evaluate the effect of nutritional interventions on the management of blood pressure and glycaemia in adults with hypertension and T2DM from LMICs.Methods and analysisWe will conduct a systematic review of randomised controlled trials (RCTs) on the effect of nutritional interventions on blood pressure and glycaemia in adult patients with hypertension and T2DM. Literature search will be conducted in MEDLINE, EMBASE, Scopus, Cochrane and Web of Science databases from anytime until April 2024. Nutritional interventions would have been applied in addition to regular or standard treatment, which is prescribed and/or provided by the healthcare system. Studies in English and Spanish will be selected and reviewed by two independent reviewers. Risk of bias will be assessed using the Cochrane tool for RCTs. Heterogeneity and publication bias will be estimated using the I2and Egger’s test, respectively.Ethics and disseminationEthics approval was not required for this systematic review, considering there was no direct data collection or participation of patients. The investigators will write a manuscript of the final detailed report with the study development and main findings to be published in a peer- reviewed journal. The main findings may be shared with academia partners and groups working on similar topics in LMICs, in addition to policymakers and authorities in these countries.PROSPERO registration numberCRD42023483847.
Resource allocation efficiency in 68 county-level traditional Chinese medicine hospitals in China: a data envelopment analysis
Authors: Xiao Xiaoyue , Shen Keyi , Zheng Xinyue , Wu Dan , Pei Tong , Lin Xin-hao , Meng Xuehui 
Published: October 2024

ObjectiveAnalysing and evaluating how efficiently health resources are allocated to county-level Traditional Chinese Medicine (TCM) hospitals in Zhejiang Province, this study aims to provide empirical evidence for improving operational efficiency and optimising resource allocation in these hospitals.Design and settingThe study employed a three-stage Data Envelopment Analysis (DEA) model to assess efficiency, using data from 68 county-level TCM hospitals. Four input and five output variables related to TCM services were selected for the analysis.ResultsThe first-stage DEA results indicated that in 2022, the technical efficiency (TE) of TCM hospitals in Zhejiang Province was 0.788, the pure technical efficiency (PTE) was 0.876 and the scale efficiency (SE) was 0.903. The classification of hospitals into four groups based on the bed size showed statistically significant differences in returns to scale (p<0.001). The Stochastic Frontier Analysis regression results were significant at the 1% level across four regressions, showing that environmental variables such as per capita GDP, population density and the number of hospitals impacted efficiency. In the third stage DEA, after adjusting the input variables, the TE, PTE and SE improved to 0.809, 0.833 and 0.917, respectively. The adjusted mean TE rankings by region were West (0.860) > East (0.844) > South (0.805) > North (0.796) > Central (0.731).ConclusionThere is an imbalance between the inputs and outputs of county-level TCM hospitals. Each region must consider factors such as the local economy, population and medical service levels, along with the specific development characteristics of hospitals, to reasonably determine the scale of county-level TCM hospital construction. Emphasis should be placed on improving hospital management and technical capabilities, coordinating regional development, promoting the rational allocation and efficient use of TCM resources and enhancing the efficiency of resource allocation in county-level TCM hospitals.
Interactive hygiene training using free open source software
Authors: Eisenmann Michael , Rauschenberger Vera , Maschmann Jens , König Sarah , Krone Manuel 
Published: October 2024

ObjectivesRegular hygiene trainings are an important way to refresh and improve knowledge about hygiene measures and the prevention of healthcare-associated infections. We aimed to develop an e-learning course to allow healthcare workers (HCWs) to learn these contents through a self-paced online format.MethodsWe developed an interactive hygiene training for HCWs of a tertiary care hospital using different content types of the HTML-5 package (H5P) plugin embedded into a Moodle-based learning management system. We evaluated the course using a short online questionnaire.ResultsWe present various suitable topics for online hygiene trainings as well as their implementation in an e-learning course. Examples include content on hand hygiene indications and techniques, information on multidrug-resistant organisms and other current topics in infection control. HCWs reported high overall satisfaction, perceived increase in knowledge, practical relevance as well as good usability and comprehensibility.DiscussionCurrently available commercial and non-commercial hygiene trainings present a number of specific advantages but also drawbacks. The presented approach combines the advantages of both approaches. The majority of the presented content can be readily adapted to suit various hospitals and care facilities or serve as inspiration for creating similar courses while remaining cost-effective.ConclusionH5P course presentations are a low-threshold, cost-effective way to implement digital hygiene trainings in a wide variety of clinical settings.