bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of benchmarking to quality improvement in healthcare. A systematic literature review
Authors: Willmington Claire , Belardi Paolo , Murante Anna Maria , Vainieri Milena 
Published: February 2022

Abstract
Background
Benchmarking has been recognised as a valuable method to help identify strengths and weaknesses at all levels of the healthcare system. Despite a growing interest in the practice and study of benchmarking, its contribution to quality of care have not been well elucidated. As such, we conducted a systematic literature review with the aim of synthesizing the evidence regarding the relationship between benchmarking and quality improvement. We also sought to provide evidence on the associated strategies that can be used to further stimulate quality improvement.

Methods
We searched three databases (PubMed, Web of Science and Scopus) for articles studying the impact of benchmarking on quality of care (processes and outcomes). Following assessment of the articles for inclusion, we conducted data analysis, quality assessment and critical synthesis according to the PRISMA guidelines for systematic literature review.

Results
A total of 17 articles were identified. All studies reported a positive association between the use of benchmarking and quality improvement in terms of processes (N = 10), outcomes (N = 13) or both (N = 7). In the majority of studies (N = 12), at least one intervention, complementary to benchmarking, was undertaken to stimulate quality improvement. The interventions ranged from meetings between participants to quality improvement plans and financial incentives. A combination of multiple interventions was present in over half of the studies (N = 10).

Conclusions
The results generated from this review suggest that the practice of benchmarking in healthcare is a growing field, and more research is needed to better understand its effects on quality improvement. Furthermore, our findings indicate that benchmarking may stimulate quality improvement, and that interventions, complementary to benchmarking, seem to reinforce this improvement. Although this study points towards the benefit of combining performance measurement with interventions in terms of quality, future research should further analyse the impact of these interventions individually.
Angiogenic content of microparticles in patients with diabetes and coronary artery disease predicts networks of endothelial dysfunction
Authors: Marei Isra , Chidiac Omar , Thomas Binitha , Pasquier Jennifer , Dargham Soha , Robay Amal , Vakayil Muneera , Jameesh Mohammad , Triggle Christopher , Rafii Arash , Jayyousi Amin , Al Suwaidi Jassim , Abi Khalil Charbel 
Published: February 2022

Abstract
Background
Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD).

Methods
A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS). MPs were isolated from the peripheral circulation, and EMPs were characterized using flow cytometry of CD42 and CD31. CD62E was used to determine EMPs’ apoptotic/activation state. MPs content was extracted and profiled using an angiogenesis array.

Results
Levels of CD42- CD31 + EMPs were significantly increased in T2D with ACS (257.5 ± 35.58) when compared to healthy subjects (105.7 ± 12.96, p < 0.01). There was no significant difference when comparing T2D with and without chronic CAD. The ratio of CD42-CD62 +/CD42-CD31 + EMPs was reduced in all T2D patients, with further reduction in ACS when compared to chronic CAD, reflecting a release by apoptotic endothelial cells. The angiogenic content of the full population of MPs was analyzed. It revealed a significant differential expression of 5 factors in patients with ACS and diabetes, including TGF-β1, PD-ECGF, platelet factor 4, serpin E1, and thrombospondin 1. Ingenuity Pathway Analysis revealed that those five differentially expressed molecules, mainly TGF-β1, inhibit key pathways involved in normal endothelial function. Further comparison of the three diabetes groups to healthy controls and diabetes without cardiovascular disease to diabetes with CAD identified networks that inhibit normal endothelial cell function. Interestingly, DDP-IV was the only differentially expressed protein between chronic CAD and ACS in patients with diabetes.

Conclusion
Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that indicate vascular dysfunction.
RNA-seq of nine canine prostate cancer cell lines reveals diverse therapeutic target signatures
Authors: Packeiser Eva-Maria , Taher Leila , Kong Weibo , Ernst Mathias , Beck Julia , Hewicker-Trautwein Marion , Brenig Bertram , Schütz Ekkehard , Murua Escobar Hugo , Nolte Ingo 
Published: February 2022

AbstractBackgroundCanine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) are typically characterized by metastasis and chemoresistance. Cell lines are important model systems for developing new therapeutic strategies. However, as they adapt to culturing conditions and undergo clonal selection, they can diverge from the tissue from which they were originally derived. Therefore, a comprehensive characterization of cell lines and their original tissues is paramount.MethodsThis study compared the transcriptomes of nine canine cell lines derived from PAC, PAC metastasis and TCC to their respective original primary tumor or metastasis tissues. Special interests were laid on cell culture-related differences, epithelial to mesenchymal transition (EMT), the prostate and bladder cancer pathways, therapeutic targets in the PI3K-AKT signaling pathway and genes correlated with chemoresistance towards doxorubicin and carboplatin.ResultsIndependent analyses for PAC, PAC metastasis and TCC revealed 1743, 3941 and 463 genes, respectively, differentially expressed in the cell lines relative to their original tissues (DEGs). While genes associated with tumor microenvironment were mostly downregulated in the cell lines, patient-specific EMT features were conserved. Furthermore, examination of the prostate and bladder cancer pathways revealed extensive concordance between cell lines and tissues. Interestingly, all cell lines preserved downstream PI3K-AKT signaling, but each featured a unique therapeutic target signature. Additionally, resistance towards doxorubicin was associated with G2/M cell cycle transition and cell membrane biosynthesis, while carboplatin resistance correlated with histone, m- and tRNA processing.ConclusionComparative whole-transcriptome profiling of cell lines and their original tissues identifies models with conserved therapeutic target expression. Moreover, it is useful for selecting suitable negative controls, i.e., cell lines lacking therapeutic target expression, increasing the transfer efficiency from in vitro to primary neoplasias for new therapeutic protocols. In summary, the dataset presented here constitutes a rich resource for canine prostate and bladder cancer research.
DDX10 promotes the proliferation and metastasis of colorectal cancer cells via splicing RPL35
Authors: Zhou Xin , Liu Zhihong , He Tengfei , Zhang Cuifeng , Jiang Manman , Jin Yuxiao , Wu Ziyu , Gu Changji , Zhang Wei , Yang Xiaodong 
Published: February 2022

Abstract
Background
Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated.

Methods
In our study, we analysed the expression data of CRC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed cytological experiments and animal experiments to explore the role of DDX10 in CRC cells. Furthermore, we performed Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein–protein interaction (PPI) network analyses. Finally, we predicted the interacting protein of DDX10 by LC–MS/MS and verified it by coimmunoprecipitation (Co-IP) and qPCR.

Results
In the present study, we identified that DDX10 mRNA was extremely highly expressed in CRC tissues compared with normal colon tissues in the TCGA and GEO databases. The protein expression of DDX10 was measured by immunochemistry (IHC) in 17 CRC patients. The biological roles of DDX10 were explored via cell and molecular biology experiments in vitro and in vivo and cell cycle assays. We found that DDX10 knockdown markedly reduced CRC cell proliferation, migration and invasion. Then, we constructed a PPI network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA) showed that DDX10 was closely related to RNA splicing and E2F targets. Using LC–MS/MS and Co-IP assays, we discovered that RPL35 is the interacting protein of DDX10. In addition, we hypothesize that RPL35 is related to the E2F pathway and the immune response in CRC.

Conclusions
In conclusion, provides a better understanding of the molecular mechanisms of DDX10 in CRC and provides a potential biomarker for the diagnosis and treatment of CRC.
CD4+ICOS+Foxp3+: a sub-population of regulatory T cells contribute to malaria pathogenesis
Authors: Chauhan Rubika , Awasthi Vikky , Thakur Reva Sharan , Pande Veena , Chattopadhyay Debprasad , Das Jyoti 
Published: February 2022

AbstractBackgroundRegulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4+CD25+Foxp3+in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4+ICOS+Foxp3+T cells in resistance/susceptibility during malaria parasite is explored in this study.Methods5 × 105red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay.ResultsThin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4+ICOS+T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4+ICOS+FoxP3+Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite.ConclusionTaken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved.Graphical Abstract
Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy
Authors: Chen Hu , Zhang Pengfei , Shi Yesi , Liu Chao , Zhou Qianqian , Zeng Yun , Cheng Hongwei , Dai Qixuan , Gao Xing , Wang Xiaoyong , Liu Gang 
Published: February 2022

Abstract
Background
Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery.

Results
The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen–antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions.

Conclusions
aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy.

Graphic Abstract
Prevalence of autoantibodies in patients with juvenile idiopathic arthritis: results from the German inception cohort ICON-JIA
Authors: Schulz Caroline , Fuehner Sabrina , Schlüter Bernhard , Fobker Manfred , Sengler Claudia , Klotsche Jens , Niewerth Martina , Minden Kirsten , Foell Dirk 
Published: February 2022

Abstract
Background
An association of different autoimmune diseases is suspected. In juvenile idiopathic arthritis (JIA), only few and partially conflicting data on the co-existence of other autoimmune disorders are available. The prevalence of autoantibodies in patients with JIA in Germany is not known.

Methods
Samples from 499 patients (median age at time of blood collection 11 years, median disease duration 4.4 years) in the prospective, multicenter inception cohort of children newly diagnosed with JIA (ICON-JIA) were analysed for the presence of anti-thyroid antibodies, celiac disease-specific antibodies (anti-tTG IgA, anti-tTG IgG), and connective tissue disease-associated antibodies (CTD-screen).

Results
A total of 76 (15.2%) patients had either clinically diagnosed autoimmune comorbidity or elevated autoantibodies. Of 21 patients with clinical autoimmune comorbidity, only 8 were also serologically positive at the time of testing, while 55 patients had autoantibodies without clinical diagnosis. Thus, 63 patients (12.6%) had at least one elevated autoantibody. Antibodies against thyroglobulin were found in 3% and against thyreoperoxidase in 4% of the samples. TSH receptor antibodies could not be detected in any of the 499 patients. Tissue transglutaminase antibodies were elevated in 0.4% of the patients. A positive screen for CTD-specific antinuclear antibodies was found in 7%, but only rarely specific antibodies (anti-dsDNA 1.4%, anti-SS-A and -SS-B 0.2% each, anti-CENP-B 0.4%) were confirmed.

Conclusions
In our study, a specific correlation between JIA and other autoimmune phenomena could not be confirmed. The lack of well-matched control groups makes interpretation challenging. Further data need to corroborate the suspected increased risk of developing other autoimmune phenomena in JIA patients.
Elevated proportion of TLR2- and TLR4-expressing Th17-like cells and activated memory B cells was associated with clinical activity of cerebral cavernous malformations
Authors: Castro Camilla , Oyamada Hugo A. A. , Cafasso Marcos Octávio S. D. , Lopes Lana M. , Monteiro Clarice , Sacramento Priscila M. , Alves-Leon Soniza Vieira , da Fontoura Galvão Gustavo , Hygino Joana , de Souza Jorge Paes Barreto Marcondes , Bento Cleonice A. M. 
Published: February 2022

Abstract
Background
Recent evidences have suggested the involvement of toll-like receptor (TLR)-4 in the pathogenesis of cerebral cavernous malformations (CCM). Elevated frequency of TLR+T-cells has been associated with neurological inflammatory disorders. As T-cells and B-cells are found in CCM lesions, the objective of the present study was to evaluate the cytokine profile of T-cells expressing TLR2 and TLR4, as well as B-cell subsets, in asymptomatic (CCMAsympt) and symptomatic (CCMSympt) patients.

Methods
For our study, the cytokine profile from TLR2+ and TLR4+ T-cell and B-cell subsets in CCMAsympt and CCMSympt patients was investigated using flow cytometry and ELISA. T-cells were stimulated in vitro with anti-CD3/anti-CD28 beads or TLR2 (Pam3C) and TLR4 (LPS) ligands.

Results
CCMSymptc patients presented a higher frequency of TLR4+(CD4+ and CD8+) T-cells and greater density of TLR4 expression on these cells. With regard to the cytokine profile, the percentage of TLR2+ and TLR4+ Th17 cells was higher in CCMSympt patients. In addition, an elevated proportion of TLR4+ Tc-1 cells, as well as Tc-17 and Th17.1 cells expressing TLR2 and TLR4, was observed in the symptomatic patients. By contrast, the percentage of TLR4+ IL-10+CD4+ T cells was higher in the CCMAsympt group. Both Pam3C and LPS were more able to elevate the frequency of IL-6+CD4+T cells and Th17.1 cells in CCMSympt cell cultures. Furthermore, in comparison with asymptomatic patients, purified T-cells from the CCMSympt group released higher levels of Th17-related cytokines in response to Pam3C and, mainly, LPS, as well as after activation via TCR/CD28. Concerning the B-cell subsets, a higher frequency of memory and memory activated B-cells was observed in CCMSympt patients.

Conclusions
Our findings reveal an increase in circulating Th17/Tc-17 cell subsets expressing functional TLR2 and, mainly, TLR4 molecules, associated with an increase in memory B-cell subsets in CCM patients with clinical activity of the disease.
Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat
Authors: Ujvári Balázs , Pytel Bence , Márton Zsombor , Bognár Máté , Kovács László Ákos , Farkas József , Gaszner Tamás , Berta Gergely , Kecskés Angéla , Kormos Viktória , Farkas Boglárka , Füredi Nóra , Gaszner Balázs 
Published: February 2022

Abstract
Background
The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson’s disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger–Westphal nucleus in human Parkinson’s disease is a known phenomenon, its possible significance in mood status has never been elucidated. In this work we aimed at investigating whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger–Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.

Methods
Systemic chronic rotenone administration as well as targeted leptin–saporin-induced lesions of EWcp/UCN1 neurons were conducted. Rotarod, open field and sucrose preference tests were performed to assess motor performance and mood status. Multiple immunofluorescence combined with RNAscope were used to reveal the functional–morphological changes. Two-sample Student’s t test, Spearman’s rank correlation analysis and Mann–Whitney U tests were used for statistics.

Results
In the rotenone model, besides motor deficit, an anxious and depression-like phenotype was detected. Well-comparable neuron loss, cytoplasmic alpha-synuclein accumulation as well as astro- and microglial activation were observed both in the substantia nigra pars compacta and EWcp. Occasionally, UCN1-immunoreactive neuronal debris was observed in phagocytotic microglia. UCN1 peptide content of viable EWcp cells correlated with dopaminergic substantia nigra cell count. Importantly, other mood status-related dopaminergic (ventral tegmental area), serotonergic (dorsal and median raphe) and noradrenergic (locus ceruleus and A5 area) brainstem centers did not show remarkable morphological changes. Targeted partial selective EWcp/UCN1 neuron ablation induced similar mood status without motor symptoms.

Conclusions
Our findings collectively suggest that neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson’s disease in the rat.
A CBCT based analysis of the correlation between volumetric morphology of the frontal sinuses and the facial growth pattern in caucasian subjects. A cross-sectional study
Authors: Abate Andrea , Gaffuri Francesca , Lanteri Valentina , Fama Andrea , Ugolini Alessandro , Mannina Laura , Maspero Cinzia 
Published: February 2022

Abstract
Background
The aim of this study was to evaluate the relationship between frontal sinus shape and facial growth pattern.

Methods
The three-dimensional examination was carried out by means of 80 CBCT scans selected from a sample of 1247 records of patients treated, for different reason, at the Department of Biomedical Surgical and Dental Sciences at University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico Milan. The sample (age ranges between 12 and 40 years) was divided according to gender and age in four groups (12-17, 18-20, 21-30, 31-40). Left and right frontal sinus volume (VOL), surface (SUP) and linear maximum width (XMAX), depth (ZMAX) and height (YMAX) were calculated using Mimics Research 17.0 (Materialise N.V., Leuven, Belgium). Cephalometric analysis has been performed for all subjects to categorize the patients depending on their facial growth pattern. Univariate and multivariate regression analysis were performed to investigate any association of frontal sinuses measurements (height, width, depth, volume and surface) and cephalometric variables. P value < 0.05 was considered statistically significant.

Results
A total of 160 frontal sinuses were measures in 80 patients: 40 men and 40 women, average age of 23.5 ±14.6. Globally the frontal sinuses had the following average dimensions: volumes of 9055.8 ± 6505 mm3 and surfaces of 3820.3 ± 2125 mm2. The statistical analysis showed that frontal sinus volume was statistically significant (p=0.003) greater for male (11,425 mm3) than female (6597.5 mm3). Similarly, the surface showed to be greater in men than in women (p=0.005). No correlation between age and frontal sinuses characteristics has been found. A statistically significant (p<0.05) increase of frontal sinus depth, surface and volume was correlated with SNB angle. In addition, frontal sinus volume increased in subjects with greater anterior skeletal dimension values and with a superior length of the cranial base. Furthermore, a decrease of ANB has been found related to an increase in frontal sinus volume (p=0.04).

Conclusions
The present study showed a correlation between frontal sinuses dimensions and craniofacial aspects, despite the inter-individual variability of their morphology. The results suggested that young adults in whom the frontal sinuses have reached their maximum size, while vertical growth continues, a larger frontal sinus may be associated with future vertical growth.