bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commissioned reports in Swedish healthcare governance – descriptive mapping and a content analysis
Authors: Höglund Anna T. , Falkenström Erica , Svallfors Stefan 
Published: December 2022

Abstract
Background
In order to support decisions regarding governance, organization and control models of the healthcare system, the Swedish government, as well as regional-level agencies, regularly commissions expert reports that are supposed to form the basis for decisions on new steering forms in healthcare.

Aim
The aim of this study was a) to perform a descriptive mapping of commissioned reports on Swedish healthcare governance and b) to pursue an in-depth content analysis of a strategic sample of such reports.

Method
Initially, 106 reports from both national and regional levels were gathered and analysed. A matrix was constructed, consisting of questions on who had commissioned the report, who had produced it, what problems the report set out to solve and what solutions were suggested. Further, questions were posed on whether the report was research-based and whether ethical assumptions and arguments were presented. Thereafter, a strategic sample of 36 reports was selected for an in-depth analysis, using inductive content analysis.

Results
The descriptive mapping showed that the aim of the analysed reports differed in form and content, and that they varied from giving an overview and investigating effects and consequences of new control models to more concrete goals, such as suggesting improvement measures. Academic experts involved in creating the reports often represented economics or business studies. The content analysis revealed examples of standardization in care, characterized by requirements to follow national guidelines, but also examples of requests for increased respect for professionals’ competence and experience. Further, the analysis showed how the definition of equity in care had changed, from a focus on equity in access to care in the reports produced in the 1990s to an emphasis of arguments for geographical sameness and equity in quality of care in the later reports.

Discussion
Two dominant trends were identified in the material, namely increased standardization and arguments for trust in the system. The great number of reports implies that the system risks requesting more information than it can handle and result in documents where the same message is recurrently repeated or create conflicts of interest and value tensions between different suggestions.

Conclusion
Commissioned reports can have substantial consequences for new reforms of management practices in healthcare. It is therefore important to investigate them critically. The results of our investigation may contribute to a more comprehensive and adequate model for acquiring and using expert reports regarding healthcare governance, both in Sweden and in similar healthcare systems.
Knock down of TIMP-2 by siRNA and CRISPR/Cas9 mediates diverse cellular reprogramming of metastasis and chemosensitivity in ovarian cancer
Authors: Escalona Ruth M. , Chu Simon , Kadife Elif , Kelly Jason K. , Kannourakis George , Findlay Jock K. , Ahmed Nuzhat 
Published: December 2022

AbstractBackgroundThe endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2), through its homeostatic action on certain metalloproteinases, plays a vital role in remodelling extracellular matrix (ECM) to facilitate cancer progression. This study investigated the role of TIMP-2 in an ovarian cancer cell line in which the expression of TIMP-2 was reduced by either siRNA or CRISPR/Cas9.MethodsOVCAR5 cells were transiently and stably transfected with either single or pooled TIMP-2 siRNAs (T2-KD cells) or by CRISPR/Cas9 under the influence of two distinct guide RNAs (gRNA1 and gRNA2 cell lines). The expression of different genes was analysed at the mRNA level by quantitative real time PCR (qRT-PCR) and at the protein level by immunofluorescence (IF) and western blot. Proliferation of cells was investigated by 5-Ethynyl-2′-deoxyuridine (EdU) assay or staining with Ki67. Cell migration/invasion was determined by xCELLigence. Cell growth in vitro was determined by 3D spheroid cultures and in vivo by a mouse xenograft model.ResultsApproximately 70–90% knock down of TIMP-2 expression were confirmed in T2-KD, gRNA1 and gRNA2 OVCAR5 ovarian cancer cells at the protein level. T2-KD, gRNA1 and gRNA2 cells exhibited a significant downregulation of MMP-2 expression, but concurrently a significant upregulation in the expression of membrane bound MMP-14 compared to control and parental cells. Enhanced proliferation and invasion were exhibited in all TIMP-2 knocked down cells but differences in sensitivity to paclitaxel (PTX) treatment were observed, with T2-KD cells and gRNA2 cell line being sensitive, while the gRNA1 cell line was resistant to PTX treatment. In addition, significant differences in the growth of gRNA1 and gRNA2 cell lines were observed in in vitro 3D cultures as well as in an in vivo mouse xenograft model.ConclusionsOur results suggest that the inhibition of TIMP-2 by siRNA and CRISPR/Cas-9 modulate the expression of MMP-2 and MMP-14 and reprogram ovarian cancer cells to facilitate proliferation and invasion. Distinct disparities in in vitro chemosensitivity and growth in 3D culture, and differences in tumour burden and invasion to proximal organs in a mouse model imply that selective suppression of TIMP-2 expression by siRNA or CRISPR/Cas-9 alters important aspects of metastasis and chemosensitivity in ovarian cancer.
Survey of malaria vectors on the Cambodia, Thailand and China-Laos Borders
Authors: Zhang Canglin , Yang Rui , Wu Linbo , Luo Chunhai , Yang Yaming , Deng Yan , Wu Jing , Liu Yan , Zhou Hongning 
Published: December 2022

Abstract
Background
Anopheles maculatus, Anopheles minimus and Anopheles dirus are the major vectors of malaria transmission in the Greater Mekong Subregion (GMS). The malaria burden in this region has decreased significantly in recent years as all GMS countries progress towards malaria elimination. It is necessary to investigate the Anopheles diversity and abundance status and assess the Plasmodium infection rates to understand the malaria transmission potential of these vector species in GMS countries to guide the development of up-to-date vector control strategies and interventions.

Methods
A survey of mosquitoes was conducted in Stung Treng, Sainyabuli and Phongsaly Provinces on the Cambodia-Laos, Thailand-Laos and China-Laos borders, respectively. Mosquito collection was done by overnight trapping at sentinel sites in each province. After morphological identification, the 18S rRNA-based nested-PCR was performed to detect malaria parasites in the captured Anopheles mosquitoes.

Results
A total of 18 965 mosquitoes comprising of 35 species of 2 subgenera (Subgenus Anopheles and Subgenus Cellia) and 4 tribes (Tribes Culicini, Aedini, Armigerini and Mansoniini) were captured. Tribe Culicini accounted for 85.66% of captures, followed by Subgenus Anopheles (8.15%). Anopheles sinensis dominated the Subgenus Anopheles by 99.81%. Plasmodium-infection was found in 25 out of the 1 683 individual or pooled samples of Anopheles. Among the 25 positive samples, 19, 5 and 1 were collected from Loum, Pangkhom and Siem Pang village, respectively. Eight Anopheles species were found infected with Plasmodium, i.e., An. sinensis, Anopheles kochi, Anopheles vagus, An. minimus, Anopheles annularis, Anopheles philippinensis, Anopheles tessellatus and An. dirus. The infection rates of Plasmodium falciparum, Plasmodium vivax and mixture of Plasmodium parasite species were 0.12% (2/1 683), 1.31% (22/1 683) and 0.06% (1/1 683), respectively.

Conclusions
Overall, this survey re-confirmed that multiple Anopheles species carry malaria parasites in the international border areas of the GMS countries. Anopheles sinensis dominated the Anopheles collections and as carriers of malaria parasites, therefore may play a significant role in malaria transmission. More extensive investigations of malaria vectors are required to reveal the detailed vector biology, ecology, behaviour, and genetics in GMS regions in order to assist with the planning and implementation of improved malaria control strategies.

Graphical Abstract
Roles of extracellular vesicles in periodontal homeostasis and their therapeutic potential
Authors: Deng Dao-Kun , Zhang Jiu-Jiu , Gan Dian , Zou Jie-Kang , Wu Rui-Xin , Tian Yi , Yin Yuan , Li Xuan , Chen Fa-Ming , He Xiao-Tao 
Published: December 2022

AbstractPeriodontal tissue is a highly dynamic and frequently stimulated area where homeostasis is easily destroyed, leading to proinflammatory periodontal diseases. Bacteria–bacteria and cell–bacteria interactions play pivotal roles in periodontal homeostasis and disease progression. Several reviews have comprehensively summarized the roles of bacteria and stem cells in periodontal homeostasis. However, they did not describe the roles of extracellular vesicles (EVs) from bacteria and cells. As communication mediators evolutionarily conserved from bacteria to eukaryotic cells, EVs secreted by bacteria or cells can mediate interactions between bacteria and their hosts, thereby offering great promise for the maintenance of periodontal homeostasis. This review offers an overview of EV biogenesis, the effects of EVs on periodontal homeostasis, and recent advances in EV-based periodontal regenerative strategies. Specifically, we document the pathogenic roles of bacteria-derived EVs (BEVs) in periodontal dyshomeostasis, focusing on plaque biofilm formation, immune evasion, inflammatory pathway activation and tissue destruction. Moreover, we summarize recent advancements in cell-derived EVs (CEVs) in periodontal homeostasis, emphasizing the multifunctional biological effects of CEVs on periodontal tissue regeneration. Finally, we discuss future challenges and practical perspectives for the clinical translation of EV-based therapies for periodontitis.
Graphical Abstract
A review of radiomics and genomics applications in cancers: the way towards precision medicine
Authors: Li Simin , Zhou Baosen 
Published: December 2022

AbstractThe application of radiogenomics in oncology has great prospects in precision medicine. Radiogenomics combines large volumes of radiomic features from medical digital images, genetic data from high-throughput sequencing, and clinical-epidemiological data into mathematical modelling. The amalgamation of radiomics and genomics provides an approach to better study the molecular mechanism of tumour pathogenesis, as well as new evidence-supporting strategies to identify the characteristics of cancer patients, make clinical decisions by predicting prognosis, and improve the development of individualized treatment guidance. In this review, we summarized recent research on radiogenomics applications in solid cancers and presented the challenges impeding the adoption of radiomics in clinical practice. More standard guidelines are required to normalize radiomics into reproducible and convincible analyses and develop it as a mature field.
GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway
Authors: Xu Anran , Fan Yuanyuan , Liu Song , Sheng Lianbing , Sun Yanyan , Yang Huijun 
Published: December 2022

AbstractPolycystic ovary syndrome (PCOS) is a gynaecological endocrine disease. The objective of the present study was to investigate the role of GTPase immunity-associated protein (GIMAP) 7 in PCOS. A PCOS rat model was established using dehydroepiandrosterone injection. The data showed that GIMAP7 was mainly located in granulosa cells and was abundantly expressed in the ovarian granulosa cells of PCOS rats. GIMAP7 silencing decreased blood glucose levels, HOMA-IR scores, and number of cystic follicles. In addition, GIMAP7 silencing corrected erratic oestrous cycles, inhibited apoptosis and reduced c-caspase-3 protein expression in the ovarian tissues of PCOS rats. GIMAP7 silencing reduced malondialdehyde (MDA) but increased glutathione (GSH) and superoxide dismutase (SOD) levels in the serum and ovarian tissues of PCOS rats. The effects of GIMAP7 were further investigated in human ovarian granulosa KGN cells. GIMAP7 silencing increased the viability, promoted proliferation, and increased the percentage of S-phase KGN cells. The apoptosis rate was significantly decreased by GIMAP7 silencing. GIMAP7 also inhibited oxidative stress in KGN cells, resulting in decreased levels of reactive oxygen species (ROS) and MDA and increased levels of GSH and SOD. Notably, GIMAP7 inhibited the sonic hedgehog (SHH) signalling pathway, and GIMAP7 silencing increased the expression of the SHH signalling pathway downstream genes SHH, SMO, and Gli1. Inhibition of the SHH signalling pathway using cyclopamine reduced the effect of GIMAP7 silencing on KGN cells. This study proved that GIMAP7 promotes oxidative stress and apoptosis in ovarian granulosa cells in PCOS by inhibiting the SHH signalling pathway.
SPOP inhibits BRAF-dependent tumorigenesis through promoting non-degradative ubiquitination of BRAF
Authors: Feng Kai , Shi Qing , Jiao Dongyue , Chen Yingji , Yang Wanqi , Su Ke , Wang Yalan , Huang Yan , Zhang Pingzhao , Li Yao , Wang Chenji 
Published: December 2022

Abstract
Background
The gene encoding the E3 ubiquitin ligase substrate-binding adapter Speckle-type BTB/POZ protein (SPOP) is frequently mutated in prostate cancer (PCa) and endometrial cancer (EC); however, the molecular mechanisms underlying the contribution of SPOP mutations to tumorigenesis remain poorly understood.

Methods
BRAF harbors a potential SPOP-binding consensus motif (SBC) motif. Co-immunoprecipitation assays demonstrated that BRAF interacts with SPOP. A series of functional analyses in cell lines were performed to investigate the biological significance of MAPK/ERK activation caused by SPOP mutations.

Results
Cytoplasmic SPOP binds to and induces non-degradative ubiquitination of BRAF, thereby reducing the interaction between BRAF and other core components of the MAPK/ERK pathway. SPOP ablation increased MAPK/ERK activation. EC- or PCa-associated SPOP mutants showed a reduced capacity to bind and ubiquitinate BRAF. Moreover, cancer-associated BRAF mutations disrupted the BRAF-SPOP interaction and allowed BRAF to evade SPOP-mediated ubiquitination, thereby upregulating MAPK/ERK signaling and enhancing the neoplastic phenotypes of cancer cells.

Conclusions
Our findings provide new insights into the molecular link between SPOP mutation-driven tumorigenesis and aberrant BRAF-dependent activation of the MAPK/ERK pathway.
Impact of selective reporting of antibiotic susceptibility testing results on meropenem prescriptions for the treatment of Pseudomonas aeruginosa infections after 2020 EUCAST criteria update: an observational study in a university hospital
Authors: Munting Aline , Damas José , Viala Benjamin , Prod’hom Guy , Guery Benoit , Senn Laurence 
Published: December 2022

Abstract
Background
We previously reported an increase in meropenem prescriptions for Pseudomonas aeruginosa infections in our hospital after the implementation of the 10th version of the EUCAST breakpoints table for P. aeruginosa in January 2020. As a consequence, antibiotic susceptibility testing results were adapted by masking meropenem for P. aeruginosa isolates susceptible to either ceftazidime, cefepime or piperacillin-tazobactam. We aimed to assess the changes in meropenem prescriptions after the implementation of the selective reporting.

Methods
In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed for P. aeruginosa infections after the susceptibility testing results have been made available over three periods: “before EUCAST update”, “after EUCAST update without selective reporting” and “after EUCAST update with selective reporting”, at Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological and clinical data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after the release of susceptibility testing results. Secondary outcomes were the use of increased dosage of non-meropenem anti-pseudomonal drugs, and IDs’ consultations rates after the release of susceptibility testing results.

Results
Among the 457 patients included, 65 (14.2%) received meropenem: 5/148 (3.4%) before EUCAST update, 51/202 (25.3%) after EUCAST update without selective reporting, and 9/107 (8.4%) after EUCAST update with selective reporting. Supervision and counselling from IDs as well as the use of increased dosages of non-carbapenem antibiotics increased in both periods after EUCAST update, compared to the first period, respectively: 40.5% (60/148) versus 61.4% (124/202) versus 51.4% (55/107) (P < 0.001), and 57.9% (84/148) versus 91.1% (183/202) versus 90.7% (97/107) (P < 0.001).

Conclusions
Selective reporting of antibiotic susceptibility testing results might decrease unnecessary meropenem prescriptions for the treatment of P. aeruginosa infections and could be part of multimodal antibiotic stewardship interventions.
Mapping the early life gut microbiome in neonates with critical congenital heart disease: multiomics insights and implications for host metabolic and immunological health
Authors: Huang Yuan , Lu Wenlong , Zeng Min , Hu Xiaoyue , Su Zhanhao , Liu Yiwei , Liu Zeye , Yuan Jianhui , Li Li , Zhang Xiaoling , Huang Long , Hu Wanjin , Wang Xu , Li Shoujun , Zhang Hao 
Published: December 2022

Abstract
Background
The early life gut microbiome is crucial in maintaining host metabolic and immune homeostasis. Though neonates with critical congenital heart disease (CCHD) are at substantial risks of malnutrition and immune imbalance, the microbial links to CCHD pathophysiology remain poorly understood. In this study, we aimed to investigate the gut microbiome in neonates with CCHD in association with metabolomic traits. Moreover, we explored the clinical implications of the host-microbe interactions in CCHD.

Methods
Deep metagenomic sequencing and metabolomic profiling of paired fecal samples from 45 neonates with CCHD and 50 healthy controls were performed. The characteristics of gut microbiome were investigated in three dimensions (microbial abundance, functionality, and genetic variation). An in-depth analysis of gut virome was conducted to elucidate the ecological interaction between gut viral and bacterial communities. Correlations between multilevel microbial features and fecal metabolites were determined using integrated association analysis. Finally, we conducted a subgroup analysis to examine whether the interactions between gut microbiota and metabolites could mediate inflammatory responses and poor surgical prognosis.

Results
Gut microbiota dysbiosis was observed in neonates with CCHD, characterized by the depletion of Bifidobacterium and overgrowth of Enterococcus, which was highly correlated with metabolomic perturbations. Genetic variations of Bifidobacterium and Enterococcus orchestrate the metabolomic perturbations in CCHD. A temperate core virome represented by Siphoviridae was identified to be implicated in shaping the gut bacterial composition by modifying microbial adaptation. The overgrowth of Enterococcus was correlated with systemic inflammation and poor surgical prognosis in subgroup analysis. Mediation analysis indicated that the overgrowth of Enterococcus could mediate gut barrier impairment and inflammatory responses in CCHD.

Conclusions
We demonstrate for the first time that an aberrant gut microbiome associated with metabolomic perturbations is implicated in immune imbalance and adverse clinical outcomes in neonates with CCHD. Our data support the importance of reconstituting optimal gut microbiome in maintaining host metabolic and immunological homeostasis in CCHD.
Prevalence of wasting and associated factors among children aged 2–5 years, southern Ethiopia: a community-based cross-sectional study
Authors: Ewune Helen Ali , Abebe Reta Kassa , Sisay Daniel , Tesfa Getanew Aschalew 
Published: December 2022

Abstract
Background
Wasting (acute malnutrition) is the most serious form of malnutrition for children in the near term. Malnutrition has a variety of causes, all of which are interconnected and hierarchically related. The purpose of this study was to assess the prevalence of wasting and its associated determinants among children under the age of five in the Wonago district, Gedeo zone, southern Ethiopia.

Methods
Community based cross-sectional study was conducted from October 1 to 30, 2021 using a systematic random sampling technique. Data were entered using Epidata manager and STATA v.20 software was used for analysis. Descriptive statistics were reported to describe the study population. To identify associated factors of wasting, bivariate and multivariate logistic regression analysis were fitted. Variables having p-value < 0.05 were declared statistically significant predictors of wasting.

Results
A total of 390 respondents participated with a response rate of 92.6%. The prevalence of wasting among children aged 2–5 years in Wonago district was 36.4% (95% CI: 31.76–41.32). Moderate household food insecurity (AOR = 0.35, 95%CI: 0.14–0.83), history of recurrent illness (AOR = 0.15, 95%CI: 0.26–0.84), and duration of breastfeeding greater than 2 years (AOR = 0.15, 95%CI: 0.26–0.84) were significantly associated with wasting.

Conclusion
Almost one-third of the children were wasted. Household food insecurity, breastfeeding, and recurrent illness were significantly associated with wasting among children aged 24–59 months. It is recommended that interventions be designed with food security, disease prevention, and breastfeeding awareness in mind and put the spotlight on food and nutrition policy to insure children’s nutritional status.
Periosteum-inspired in situ CaP generated nanocomposite hydrogels with strong bone adhesion and superior stretchability for accelerated distraction osteogenesis
Authors: Lou Tengfei , Chen Kai , Luo Qiyu , Liu Changsheng , Yuan Yuan , Fan Cunyi 
Published: December 2022

Abstract

Background
Distraction osteogenesis (DO) is an efficacious but lengthy procedure to reconstruct segmental bone defects under the principle of tension-stress, during which the periosteum-mediated mechanical stimulation plays a pivotal role. Inspired by the dynamic process of DO and the mechanical stimulation of periosteum, a new design of bionic periosteum was developed to simulate the mechanical transduction of natural periosteum for the application in DO procedure.

Methods
In this study, an injectable organic-inorganic hybrid hydrogel was developed based on a novel combination of the PEGylated poly (glycerol sebacate) (PEGS) polymer network and in situ formed CaP nanoparticles (ICPNs). Rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cultured and tested in vitro to evaluate biocompatibility, cell adhesion, proliferation, and pro-osteogenic and pro-angiogenic activity. In vivo experiments were conducted in the rat tibial model of distraction osteogenesis.

Results
The developed nanocomposite hydrogels exhibited excellent injectability, robust bone adhesion, superior stretchability, and enhanced osteogenic activity. The results of in vitro and in vivo studies showed that PEGS/ICPN hydrogels could promote new bone formation and mineralization during the dynamic distraction process through the synergistic effects of angiogenesis and osteogenesis.

Conclusions
This periosteum-inspired nanocomposite hydrogel represents a mechanobiology approach for effectively restoring large bone defects through the dynamic DO process.