bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-creating physical activity interventions: a mixed methods evaluation approach
Authors: Popp Johanna , Grüne Eva , Carl Johannes , Semrau Jana , Pfeifer Klaus 
Published: March 2021

Abstract
Background
Co-creation strategies, such as cooperative planning, are promising as a means to ensure that physical activity interventions address real-world problems and are tailored to the target group. This has already been validated in diverse settings. However, questions targeting the transferability of cooperative planning to new settings and the key factors influencing its success or failure remain unclear. At the same time, co-creation processes are complex, and evaluation can be challenging. Following calls for detailed reporting, this paper describes the programme activities, the underlying logic, and methodological design of a study that aims to evaluate the transfer of cooperative planning to new settings and to explore the associated key determinants.

Methods
Cooperative planning was utilized as a strategy to target physical activity promotion in three real-world German settings in the nursing care and automotive mechatronics sectors. This involved researchers working alongside stakeholders from practice and policy to conjointly develop new interventions to promote physical activity in physically demanding jobs. A pragmatic approach is used to evaluate both the transferability and key determinants of this strategy. We developed a logic model for this co-creation process that describes the underlying assumptions and guides the evaluation. The evaluation outcomes of this study include planning meetings, newly developed interventions, and the determinants that are likely to affect cooperative planning. Quantitative and qualitative data will be collected using questionnaires, documents, and interviews. The quantitative data will be analysed descriptively, while the qualitative data will mainly be analysed using qualitative content analysis, split by settings. Subsequently, data triangulation will be used to integrate the quantitative and qualitative findings, which will then be compared across all three settings.

Discussion
The study findings will contribute to a better understanding of co-creation strategies, their transferability, and key determinants. The practical implications can include a checklist for assessing key determinants and a guideline for transferring cooperative planning into new settings to benefit more people. Ultimately, this study will help to advance co-creation strategies and may be relevant for researchers, practitioners, and policy-makers targeting physical activity promotion in various contexts.
Trial registration: Open Science Framework: https://osf.io/r6xnt/ (retrospectively registered).
Differential effects of intense exercise and pollution on the airways in a murine model
Authors: Decaesteker Tatjana , Vanhoffelen Eliane , Trekels Kristel , Jonckheere Anne-Charlotte , Cremer Jonathan , Vanstapel Arno , Dilissen Ellen , Bullens Dominique , Dupont Lieven J. , Vanoirbeek Jeroen A. 
Published: March 2021

Abstract
Background
Exercise-induced bronchoconstriction (EIB) is a transient airway narrowing, occurring during or shortly after intensive exercise. It is highly prevalent in non-asthmatic outdoor endurance athletes suggesting an important contribution of air pollution in the development of EIB. Therefore, more research is necessary to investigate the combination of exercise and pollutants on the airways.

Methods
Balbc/ByJ mice were intranasally challenged 5 days a week for 3 weeks with saline or 0.2 mg/ml diesel exhaust particles (DEP), prior to a daily incremental running session or non-exercise session. Once a week, the early ventilatory response was measured and lung function was determined at day 24. Airway inflammation and cytokine levels were evaluated in bronchoalveolar lavage fluid. Furthermore, innate lymphoid cells, dendritic cells and tight junction mRNA expression were determined in lung tissue.

Results
Submaximal exercise resulted in acute alterations of the breathing pattern and significantly improved FEV0.1 at day 24. DEP exposure induced neutrophilic airway inflammation, accompanied with increased percentages of CD11b+ DC in lung tissue and pro-inflammatory cytokines, such as IL-13, MCP-1, GM-CSF and KC. Occludin and claudin-1(Cldn-1) expression were respectively increased and decreased by DEP exposure. Whereas, exercise increased Cldn-3 and Cldn-18 expression. Combining exercise and DEP exposure resulted in significantly increased SP-D levels in the airways.

Conclusion
DEP exposure induced typical airway neutrophilia, DC recruitment and pro-inflammatory cytokine production. Whereas, intensive exercise induced changes of the breathing pattern. The combination of both triggers resulted in a dysregulation of tight junction expression, suggesting that intensive exercise in polluted environments can induce important changes in the airway physiology and integrity.
Kaposiform Hemangioendothelioma: clinicopathological characteristics of 8 cases of a rare vascular tumor and review of literature
Authors: Chundriger Qurratulain , Tariq Muhammad Usman , Abdul-Ghafar Jamshid , Ahmed Arsalan , Din Nasir Ud 
Published: March 2021

Abstract
Background
Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumor of intermediate malignant potential which shows locally aggressive growth but only rarely metastasizes. It is mostly considered to be a tumor of pediatric population but its occurrence in the adults is not uncommon as once considered. Histologically, KHE can mimic other soft tissue neoplasms of different behaviors (e.g. Kaposi Sarcoma, hemangioma) and establishing the correct diagnosis is important for appropriate treatment. Herein, we describe the clinicopathological features of 8 cases of KHE which will be helpful in making their diagnosis.

Methods
We reviewed pathology reports, microscopy glass slides and obtained follow up information about 8 cases of KHE which were diagnosed at our institution from January 2008 till June 2020. Immunohistochemical stain for HHV8 was also performed.

Results
Age ranged from 7 months to 25 years. Seven patients were less than 20 years of age and one patient was 25 years old. Equal gender distribution was observed. Extremities were the most common sites of involvement, followed by head and neck, pancreas and ischiorectal region. 2 cases were resection specimen and all others were incisional biopsies. The largest tumor size was 5.5 cm in one of the resections. The incisional/fragmented tissues were all less than 5 cm in aggregate. Most cases showed predominance of nodular growth and a minor component of spindle cell population along with lymphangiomatosis like vascular channels, with evidence of microthrombi in 2 cases. Few multinucleated giant cells were observed in 2 cases. None of the cases exhibited significant nuclear atypia or mitotic activity. One of the cases arising in dermis showed underlying bone involvement. HHV8 was negative in 7/7 cases.

Conclusions
KHE can also involve adult population and it should always be considered in the differential diagnoses of a vascular lesion. Presence of multinucleated giant cells is a rare finding. Knowledge about histological features and potential mimics is helpful in avoiding misdiagnosis.
Advantages of patient-specific cutting guides with disposable instrumentation in total knee arthroplasty: a case control study
Authors: Moerenhout Kevin , Allami Behrang , Gkagkalis Georgios , Guyen Olivier , Jolles Brigitte M. 
Published: March 2021

Abstract
Background
Total knee arthroplasty (TKA) is most frequently planned using conventional two-dimensional weight-bearing lower limb radiographs and is performed with conventional femoral and tibial cutting guides. Questions have been raised about the accuracy of conventional TKA instrumentation and planning for an anatomically standard or complex joint. Use of computed tomography (CT)-based three-dimensional (3D) templating and patient-specific cutting guides printed in 3D has shown improved postoperative lower limb alignment parameters. This case-control study compared costs and operative times of using CT-based, patient-specific, single-use instruments versus conventional metal instruments for TKA.

Methods
In this case-control, retrospective chart review, all TKAs were performed by one senior surgeon, using the F.I.R.S.T. posterior-stabilised knee prosthesis (Symbios, CH), with a similar protocol and identical operating room setup. Group A included 51 TKAs performed with patient-specific cutting guides and conventional metal instruments. Group B included 49 TKAs performed with patient-specific cutting guides and patient-specific, single-use instrumentation. Operation duration, number of instrumentation trays and sterilisation costs were evaluated.

Results
The groups were similar for age, body mass index, hip-knee-ankle angle and operation duration. The mean number of instrumentation trays was 8.0 ± 0.8 for group A (controls) and 5.1 ± 0.9 for group B (p<0.001). The mean sterilisation costs were 380 ± 47 Swiss Francs (CHF) for group A and 243 ± 55 CHF for group B (p<0.001), for a mean cost reduction of 130.50 CHF per intervention in group B. The time interval between two consecutive surgeries was 24 min for group A and 18 min for group B. There were no adverse events or complications, instrument-related or otherwise.

Conclusion
Compared to conventional instrumentation, use of patient-specific, single-use instruments for TKA reduced the number of instrumentation trays by more than one-third and saved 36% in sterilisation costs. If fabrication costs of single-use instruments are included by the company, the total cost is significantly diminished. There was no operative time advantage for single-use instrumentation.
Machine learning analysis of gene expression profile reveals a novel diagnostic signature for osteoporosis
Authors: Chen Xinlei , Liu Guangping , Wang Shuxiang , Zhang Haiyang , Xue Peng 
Published: March 2021

Abstract
Background
Osteoporosis (OP) is increasingly prevalent with the aging of the world population. It is urgent to identify efficient diagnostic signatures for the clinical application.

Method
We downloaded the mRNA profile of 90 peripheral blood samples with or without OP from GEO database (Number: GSE152073). Weighted gene co-expression network analysis (WGCNA) was used to reveal the correlation among genes in all samples. GO term and KEGG pathway enrichment analysis was performed via the clusterProfiler R package. STRING database was applied to screen the interaction pairs among proteins. Protein–protein interaction (PPI) network was visualized based on Cytoscape, and the key genes were screened using the cytoHubba plug-in. The diagnostic model based on these key genes was constructed, and 5-fold cross validation method was applied to evaluate its reliability.

Results
A gene module consisted of 176 genes predicted to be associated with the occurrence of OP was identified. A total of 16 significantly enriched GO terms and 1 significantly enriched KEGG pathway were obtained based on the 176 genes. The top 50 key genes in the PPI network were identified. Then 22 genes were screened based on stepwise regression analysis from the 50 key genes. Of which, 9 genes were further screened out by multivariate regression analysis with the significant threshold of P value < 0.01. The diagnostic model was established based on the optimal 9 key genes, which efficiently separated the normal samples and OP samples.

Conclusion
A diagnostic model established based on nine key genes could reliably separate OP patients from healthy subjects, which provided novel lightings on the diagnostic research of OP.
PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways
Authors: Uzozie Anuli C. , Ergin Enes K. , Rolf Nina , Tsui Janice , Lorentzian Amanda , Weng Samuel S. H. , Nierves Lorenz , Smith Theodore G. , Lim C. James , Maxwell Christopher A. , Reid Gregor S. D. , Lange Philipp F. 
Published: March 2021

Abstract
Background
Murine xenografts of pediatric leukemia accurately recapitulate genomic aberrations. How this translates to the functional capacity of cells remains unclear. Here, we studied global protein abundance, phosphorylation, and protein maturation by proteolytic processing in 11 pediatric B- and T- cell ALL patients and 19 corresponding xenografts.

Methods
Xenograft models were generated for each pediatric patient leukemia. Mass spectrometry-based methods were used to investigate global protein abundance, protein phosphorylation, and limited proteolysis in paired patient and xenografted pediatric acute B- and T- cell lymphocytic leukemia, as well as in pediatric leukemia cell lines. Targeted next-generation sequencing was utilized to examine genetic abnormalities in patients and in corresponding xenografts. Bioinformatic and statistical analysis were performed to identify functional mechanisms associated with proteins and protein post-translational modifications.

Results
Overall, we found xenograft proteomes to be most equivalent with their patient of origin. Protein level differences that stratified disease subtypes at diagnostic and relapse stages were largely recapitulated in xenografts. As expected, PDXs lacked multiple human leukocyte antigens and complement proteins. We found increased expression of cell cycle proteins indicating a high proliferative capacity of xenografted cells. Structural genomic changes and mutations were reflected at the protein level in patients. In contrast, the post-translational modification landscape was shaped by leukemia type and host and only to a limited degree by the patient of origin. Of 201 known pediatric oncogenic drivers and drug-targetable proteins, the KMT2 protein family showed consistently high variability between patient and corresponding xenografts. Comprehensive N terminomics revealed deregulated proteolytic processing in leukemic cells, in particular from caspase-driven cleavages found in patient cells.

Conclusion
Genomic and host factors shape protein and post-translational modification landscapes differently. This study highlights select areas of diverging biology while confirming murine patient-derived xenografts as a generally accurate model system.
Reliability of a dried urine test for comprehensive assessment of urine hormones and metabolites
Authors: Newman Mark , Curran Desmond A. 
Published: March 2021

Abstract
Background
Mass spectrometry allows for analysis of multiple hormone and organic acid metabolites from small urine volumes; however, to assess the full extent of daily hormone production, 24-h urine collections are usually required. The aims of this study were, first, to confirm that mass spectrometric analysis of an array of hormones and organic acids would yield similar results in both liquid and dried urine, and, second, to determine if collection of four dried spot urine samples could be substituted for a 24-h collection when measuring reproductive hormones.

Methods
Two study populations were included in this prospective observational study. Twenty individuals collected both a spot liquid urine and dried urine on filter paper to analyze eight organic acids. A second group of 26 individuals collected both a 24-h urine and four dried spot urines during waking hours throughout the same day for evaluation of 17 reproductive hormones and metabolites; data from 18 of these individuals were available to compare liquid versus dried urine results. Dried urine was extracted, hydrolyzed, and derivatized before analysis by mass spectrometry; all analytes from dried urine were normalized to urine creatinine.

Results
Reproductive hormone results from dried and liquid urine were in excellent agreement with intraclass correlation coefficients (ICCs) greater than 0.90; comparison of dried to liquid urine for organic acids showed good to excellent agreement (ICC range: 0.75 to 0.99). Comparison between the 4-spot urine collection and 24-h urine collection methods showed excellent agreement (ICC > 0.9) for 14 of the 17 urine metabolites and good agreement for the others (ICC 0.78 to 0.85) with no systematic differences between the two methods of collection.

Conclusions
The burden of urine collection can be reduced using collection of four spot dried urines on filter paper without compromising comparability with hormone results from a 24-h urine collection. A large number of urine analytes can be assessed from the dried urine with similar results to those from liquid urine. Given the ease of sample handling, this 4-spot dried urine assay would be useful for both clinical assessment of patients and for large epidemiologic studies.
Exploring alterations in hematological and biochemical parameters, enzyme activities and serum cortisol in Besnoitia besnoiti naturally infected dairy cattle
Authors: Villa Luca , Gazzonis Alessia Libera , Zanzani Sergio Aurelio , Mazzola Silvia , Giordano Alessia , Manfredi Maria Teresa 
Published: March 2021

Abstract
Background
Besnoitia besnoiti is an Apicomplexan protozoa causative of bovine besnoitiosis, a chronic and debilitating disease of cattle, with a variety of pathological findings that could alter some laboratory parameters. A study was conducted in a bovine besnoitiosis endemically infected dairy herd located in Italy characterized by high intra-herd seroprevalence and cattle with clinical signs of the disease. In the study, alterations in laboratory parameters, i.e. hematological and biochemical parameters, enzyme activities and serum cortisol levels, in Besnoitia besnoiti naturally infected cows were investigated in depth.

Methods
Laboratory parameters in 107 cows, of which 61 were seronegative and 46 were seropositive to B. besnoiti, including 27 with clinical signs of bovine besnoitiosis, were compared. Generalized linear models were used to evaluate the effect of Besnoitia infection on the considered laboratory parameters.

Results
Hematological analyses revealed that B. besnoiti infection determined a significant alteration to the leukocyte differential, with a higher percentage of granulocytes and a lower percentage of lymphocytes in seropositive and clinically affected animals (Mann–Whitney U-test, P = 0.022); erythrocyte and platelet counts did not show any difference between the considered groups of cows. Biochemistry tests evidenced that the parasite infection influenced serum protein values in seropositive cows and glutamate dehydrogenase values in clinically affected animals. No or only slight differences were revealed for all of the other biochemical and enzyme activity parameters in B. besnoiti-infected animals. In addition, despite the lack of statistical significance, seropositive and clinically affected cows evidenced higher concentrations of serum cortisol values compared to seronegative animals.

Conclusions
Although physiological, pathological and farm-related factors could have influenced the results in investigated animals, further studies involving more animals from different farms would be advisable to infer the role of B. besnoiti on these alterations, since laboratory parameters could help veterinarians in the diagnosis of bovine besnoitiosis in cattle.
Prevalence of scabies and impetigo in school-age children in Timor-Leste
Authors: Matthews Alexander , Le Brandon , Amaral Salvador , Arkell Paul , Monteiro Merita , Clarke Naomi , Barros Terlinda , de Jesus Mendonça Joaquim , Gusmão Sonia Maria Exposto , dos Reis Seixas Leonia Maria , da Piedade João Henrique Araújo , Engelman Daniel , Steer Andrew C. , Fancourt Nicholas S. S. , Yan Jennifer , Kaldor John , Francis Joshua R. , Nery Susana Vaz 
Published: March 2021

Abstract
Background
Scabies and impetigo are endemic in many tropical, low- and middle-income countries. Mass drug administration (MDA) with ivermectin has emerged as a control strategy for these conditions. In 2019, Timor-Leste Ministry of Health planned to implement MDA including ivermectin for the control of lymphatic filariasis, so we undertook a baseline assessment of scabies and impetigo to better understand local epidemiology and contribute to future surveys assessing the impact of MDA.

Methods
A cross-sectional school survey was conducted in April–May 2019 at six primary schools in a semi-urban (Dili) and two rural (Ermera and Manufahi) settings. Children under 19 years of age present at school on survey days were eligible to participate, of whom we enrolled 1183. Trained health workers interviewed and examined 1043 participants to clinically diagnose scabies using the 2020 International Alliance for the Control of Scabies (IACS) diagnostic criteria, as well as impetigo. Prevalence was adjusted for age and sex. Mixed-effects logistic regression models were used to analyse odds of scabies and impetigo infection. All models accounted for clustering at the school level through the use of random effect terms. Population attributable risk of scabies as a cause of impetigo was also estimated.

Results
The overall weighted prevalence of scabies was 30.6%. Children in rural Manufahi were more likely to have scabies than those in semi-urban Dili (53.6% vs 28.2%, adjusted odds ratio [AOR] 3.5). Most cases of scabies were mild (3 to 10 lesions), and lesions were usually distributed on more than one body region. Scabies prevalence was lower among 10 to 14 year olds compared to 5 to 9 year olds. Overall weighted prevalence of impetigo was 11.3%. Relative to Dili, children in rural Ermera and Manufahi were twice as likely to have impetigo. Impetigo was twice as common in children with scabies than in those without, corresponding to an attributable risk of scabies as a cause of impetigo of 22.7%.

Conclusions
Scabies and impetigo prevalence in Timor-Leste is among the highest reported globally, particularly in rural areas. Scabies infestation was strongly associated with impetigo. Comprehensive control strategies are urgently needed in Timor-Leste.

Graphical Abstract
SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription
Authors: Almuqrin Abdulaziz , Davidson Andrew D. , Williamson Maia Kavanagh , Lewis Philip A. , Heesom Kate J. , Morris Susan , Gilbert Sarah C. , Matthews David A. 
Published: March 2021

Abstract
Background
ChAdOx1 nCoV-19 is a recombinant adenovirus vaccine against SARS-CoV-2 that has passed phase III clinical trials and is now in use across the globe. Although replication-defective in normal cells, 28 kbp of adenovirus genes is delivered to the cell nucleus alongside the SARS-CoV-2 S glycoprotein gene.

Methods
We used direct RNA sequencing to analyse transcript expression from the ChAdOx1 nCoV-19 genome in human MRC-5 and A549 cell lines that are non-permissive for vector replication alongside the replication permissive cell line, HEK293. In addition, we used quantitative proteomics to study over time the proteome and phosphoproteome of A549 and MRC5 cells infected with the ChAdOx1 nCoV-19 vaccine.

Results
The expected SARS-CoV-2 S coding transcript dominated in all cell lines. We also detected rare S transcripts with aberrant splice patterns or polyadenylation site usage. Adenovirus vector transcripts were almost absent in MRC-5 cells, but in A549 cells, there was a broader repertoire of adenoviral gene expression at very low levels. Proteomically, in addition to S glycoprotein, we detected multiple adenovirus proteins in A549 cells compared to just one in MRC5 cells.

Conclusions
Overall, the ChAdOx1 nCoV-19 vaccine’s transcriptomic and proteomic repertoire in cell culture is as expected. The combined transcriptomic and proteomics approaches provide a detailed insight into the behaviour of this important class of vaccine using state-of-the-art techniques and illustrate the potential of this technique to inform future viral vaccine vector design.