bluuebunny/crossref_metadata_2025_split huggingface dataset:
A data-driven analysis of the potential of public transport for German commuters using accessibility indicators
Authors: Mocanu Tudor , Joshi Jigeeshu , Winkler Christian 
Published: September 2021

Abstract
Background
A significant mode shift will be required in order to meet the ambitious greenhouse gas emissions reduction targets in Germany and elsewhere. Such a mode shift can only be achieved by a combination of drastic push and pull measures. Getting commuters to switch modes might be particularly difficult and have a negative impact on their access to employment and welfare.

Methodology
We investigate the potential for a mode shift from car to public transport for German commuters using a data-driven approach based mainly on open data sources that avoids complex transport model runs. Different datasets on the home and workplace location of all employees in Germany are consolidated to create an origin-destination commuter matrix at traffic analysis zone level. The commuter matrix is merged with travel time data for car and public transport to calculate a spatially disaggregated and mode-specific measure of accessibility. The comparison of accessibility by car and public transport is used to derive the potential for a mode shift and identify potential challenges and barriers.

Results
Public transport accessibility to workplaces is poorer across the country compared to access by car. On average, public transport travel times are almost three times higher than the corresponding car travel times. The differences in accessibility are largely independent of the region type. Results are validated by an independent dataset from a household travel survey. Based on these results, the potential for a mode shift appears to be very low.
Assessing self-reported risky behavior among two-wheeled vehicle users: an exploratory analysis comparing e-bikers to other riders
Authors: Ragot-Court Isabelle , Rodon Carole , Van Elslande Pierre , Zhuo Jian 
Published: September 2021

AbstractThe current deployment of e-bikes in large cities all over the world raises new road safety problems. The shared features of e-bikes and other types of two-wheelers, notably in terms of size and maneuverability, can lead to common road safety issues and similar accident mechanisms. This paper outlines the value of a comparative approach that includes all kinds of two-wheelers, motorized or not: bicycles, e-bikes of both the bicycle type and the scooter type, LPG and gasoline scooters, and motorcycles. For this purpose, a new self-reported risky behavior inventory was developed and its validity tested among 400 two-wheeler users in Shanghai. China, where the spread of e-bikes and other two-wheelers took place several years ago, is a useful country to study to shed light on issues that are emerging in Europe. Results indicate highly satisfactory psychometric properties of the inventory with a single-factor 12-item structure (52.81% of variance explained, α = .93) and very satisfactory fit indexes. In terms of construct validity, the eta (η) correlation ratio indicates its significant relation with self-reported previous accidents and with several criterion related experience variables. Furthermore, a high correlation was noted between the inventory scores and the maximum speed of the participants’ vehicles. Ultimately, the inventory will enable future research to characterize and explain risky riding behaviors by riders of e-bikes compared to riders of other two-wheelers in China and, with some slight adaptations, these results can be applied to the European context.
A targeted solution for estimating the cell-type composition of bulk samples
Authors: van den Oord Edwin J. C. G. , Xie Lin Y. , Tran Charles J. , Zhao Min , Aberg Karolina A. 
Published: September 2021

Abstract
Background
To avoid false-positive findings and detect cell-type specific associations in methylation and transcription investigations with bulk samples, it is critical to know the proportions of the major cell-types.

Results
We present a novel approach that allows for precise estimation of cell-type proportions using only a few highly informative methylation markers. The most reliable estimates were obtained with 17 amplicons (34 CpGs) using the MuSiC estimator, for which the average correlations between the estimated and the true cell-type proportions were 0.889. Furthermore, the estimates were not significantly different from the true values (P = 0.95) indicating that the estimator is unbiased and the standard deviation of the estimates further indicate high precision. Moreover, the overall variability of the estimates as measured by the Root Mean Squared Error (RMSE), which is a function of both bias and precision, was low (mean RMSE = 0.038). Taken together, these results indicate that the approach produced reliable estimates that are both unbiased and highly precise.

Conclusion
This cost-effective approach for estimating cell-type proportions in bulk samples allows for enhanced targeted analysis, which in turn will minimize the risk of reporting false-positive findings and allowing for detection of cell-type specific associations. The approach is applicable across platforms and can be extended to assess cell-type proportions for various tissues.
Hematological profiles of visceral leishmaniasis patients before and after treatment of anti-leishmanial drugs at University of Gondar Hospital; Leishmania Research and Treatment Center Northwest, Ethiopia
Authors: Shiferaw Elias , Murad Fadil , Tigabie Mitikie , Abebaw Mareye , Alemu Tadele , Abate Sefanit , Mohammed Rezika , Yeshanew Arega , Tajebe Fitsumbrhan 
Published: September 2021

Abstract
Background
Visceral leshimaniasis is a parasitic disease characterized by systemic infection of phagocytic cells and an intense inflammatory response. The progression of the disease or treatment may have an effect on hematological parameters of these patients'. Thus, the current study sought to compare the hematological profiles of visceral leishmaniasis patients before and after treatment with anti-leishmaniasis drugs.

Method
An institutional-based retrospective cohort study was conducted among visceral leishmaniasis patients admitted to the University of Gondar comprehensive specialized referral hospital leishmaniasis research and treatment centre between September 2013 and August 2018. Hematological profiles were extracted from the laboratory registration book before and after treatment. Data were entered to Epi-info and exported to SPSS for analysis. Descriptive statistics were summarized using frequency and percentage to present with the table. The mean, standard deviation, median, and interquartile range were used to present the data. Furthermore, using the paired t-test and the Wilcoxon Signed rank test, the mean difference for normally and non-normally distributed data was compared. Spearman and Pearson correlation analysis were used to describe the relationship between hematological parameters and various variables. A P value of 0.05 was considered statistically significant.

Result
With the exception of the absolute neutrophil count, all post-treatment hematological parameters show a significant increase when compared to pre-treatment levels. Prior to treatment, the prevalence of anemia, leukopenia, and thrombocytopenia was 85.5, 83.4, and 75.8%, respectively, whereas it was 58.3, 38.2, and 19.2% following treatment. Furthermore, parasite load was found to have a statistically significant negative correlation with hematological profiles, specifically with white blood cell and red blood cell parameters.

Conclusion
According to our findings, patients with visceral leishmaniasis had improved hematological profiles after treatment. The effect of treatment on parasite proliferation and concentration within visceral organs, in which the parasite load could directly affect the patient's hematological profiles, may be associated with the change in hematological profiles.
The utility of basic blood counts, WBC histogram and C-reactive protein in detecting malaria
Authors: Nishimura Jun , Dharap Parag , Raimbault Sebastien 
Published: September 2021

Abstract
Background
Hematology analyzers display abnormal parameters during malaria infection providing insightful information for suspecting and assessing malaria infection. The goal of this study is to demonstrate the potential of a three-part differential hematology analyzer to assess malaria, provide information about the parasitemia, and discuss the importance of combining C-reactive protein (CRP) with hematology parameters to obtain further information about the malaria infection.

Methods
The present study shows the results of a case–control study during the monsoon season of years 2018 and 2019 in Mumbai, India. The study considers 1008 non-malaria febrile cases, 209 P. vivax and 31 P. falciparum positive malaria samples, five cases of mixed P. vivax and P. falciparum infection, and three co-infection cases of P. vivax and dengue. Raw data from the three-part analyzer LC-667G CRP (HORIBA) and the corresponding microscopic findings (golden standard for diagnosis of malaria) were obtained for each sample.

Results
The medians of platelet counts (PLT) were 102.5, 109.0, and 223.0 × 103/µL, while CRP medians were 67.4, 81.4 and 10.4 mg/L in P. vivax, P. falciparum and control groups respectively (p < 0.001 in Mann–Whitney U tests between malaria and control groups). Compared with negative samples, platelets counting less than 161.5 × 103/µL were observed on malaria patients (OR 19.12, 95% CI 11.89–30.75). Especially in P. vivax cases, an abnormal peak was frequently observed in the white blood cells (WBC) histogram around the 37fL channel. The events counted around that channel showed a linear correlation with the counting of red blood cells infected predominantly with larger parasitic forms. Parameters like CRP (rs = 0.325, p < 0.001), WBC (rs = 0.285, p < 0.001) and PLT (rs = − 0.303, p < 0.001) were correlated with the parasitemia of P. vivax samples. Between the malaria and dengue groups, the highest area under the receiver operating characteristic curve was observed on CRP (0.867, CRP ≥ 26.85 mg/L).

Conclusions
A three-part differential hematology analyzer has the potential to not only trigger malaria diagnosis confirmation but also assess the severity of the infection when CRP is considered.
Artificial intelligence for pre-operative lymph node staging in colorectal cancer: a systematic review and meta-analysis
Authors: Bedrikovetski Sergei , Dudi-Venkata Nagendra N. , Kroon Hidde M. , Seow Warren , Vather Ryash , Carneiro Gustavo , Moore James W. , Sammour Tarik 
Published: September 2021

Abstract
Background
Artificial intelligence (AI) is increasingly being used in medical imaging analysis. We aimed to evaluate the diagnostic accuracy of AI models used for detection of lymph node metastasis on pre-operative staging imaging for colorectal cancer.

Methods
A systematic review was conducted according to PRISMA guidelines using a literature search of PubMed (MEDLINE), EMBASE, IEEE Xplore and the Cochrane Library for studies published from January 2010 to October 2020. Studies reporting on the accuracy of radiomics models and/or deep learning for the detection of lymph node metastasis in colorectal cancer by CT/MRI were included. Conference abstracts and studies reporting accuracy of image segmentation rather than nodal classification were excluded. The quality of the studies was assessed using a modified questionnaire of the QUADAS-2 criteria. Characteristics and diagnostic measures from each study were extracted. Pooling of area under the receiver operating characteristic curve (AUROC) was calculated in a meta-analysis.

Results
Seventeen eligible studies were identified for inclusion in the systematic review, of which 12 used radiomics models and five used deep learning models. High risk of bias was found in two studies and there was significant heterogeneity among radiomics papers (73.0%). In rectal cancer, there was a per-patient AUROC of 0.808 (0.739–0.876) and 0.917 (0.882–0.952) for radiomics and deep learning models, respectively. Both models performed better than the radiologists who had an AUROC of 0.688 (0.603 to 0.772). Similarly in colorectal cancer, radiomics models with a per-patient AUROC of 0.727 (0.633–0.821) outperformed the radiologist who had an AUROC of 0.676 (0.627–0.725).

Conclusion
AI models have the potential to predict lymph node metastasis more accurately in rectal and colorectal cancer, however, radiomics studies are heterogeneous and deep learning studies are scarce.

Trial registration
PROSPERO CRD42020218004.
Synergistic efficacy of inhibiting MYCN and mTOR signaling against neuroblastoma
Authors: Kling Matthew J. , Griggs Connor N. , McIntyre Erin M. , Alexander Gracey , Ray Sutapa , Challagundla Kishore B. , Joshi Shantaram S. , Coulter Don W. , Chaturvedi Nagendra K. 
Published: September 2021

Abstract
Background
Neuroblastoma (NB) patients with MYCN amplification or overexpression respond poorly to current therapies and exhibit extremely poor clinical outcomes. PI3K-mTOR signaling-driven deregulation of protein synthesis is very common in NB and various other cancers that promote MYCN stabilization. In addition, both the MYCN and mTOR signaling axes can directly regulate a common translation pathway that leads to increased protein synthesis and cell proliferation. However, a strategy of concurrently targeting MYCN and mTOR signaling in NB remains unexplored. This study aimed to investigate the therapeutic potential of targeting dysregulated protein synthesis pathways by inhibiting the MYCN and mTOR pathways together in NB.

Methods
Using small molecule/pharmacologic approaches, we evaluated the effects of combined inhibition of MYCN transcription and mTOR signaling on NB cell growth/survival and associated molecular mechanism(s) in NB cell lines. We used two well-established BET (bromodomain extra-terminal) protein inhibitors (JQ1, OTX-015), and a clinically relevant mTOR inhibitor, temsirolimus, to target MYCN transcription and mTOR signaling, respectively. The single agent and combined efficacies of these inhibitors on NB cell growth, apoptosis, cell cycle and neurospheres were assessed using MTT, Annexin-V, propidium-iodide staining and sphere assays, respectively. Effects of inhibitors on global protein synthesis were quantified using a fluorescence-based (FamAzide)-based protein synthesis assay. Further, we investigated the specificities of these inhibitors in targeting the associated pathways/molecules using western blot analyses.

Results
Co-treatment of JQ1 or OTX-015 with temsirolimus synergistically suppressed NB cell growth/survival by inducing G1 cell cycle arrest and apoptosis with greatest efficacy in MYCN-amplified NB cells. Mechanistically, the co-treatment of JQ1 or OTX-015 with temsirolimus significantly downregulated the expression levels of phosphorylated 4EBP1/p70-S6K/eIF4E (mTOR components) and BRD4 (BET protein)/MYCN proteins. Further, this combination significantly inhibited global protein synthesis, compared to single agents. Our findings also demonstrated that both JQ1 and temsirolimus chemosensitized NB cells when tested in combination with cisplatin chemotherapy.

Conclusions
Together, our findings demonstrate synergistic efficacy of JQ1 or OTX-015 and temsirolimus against MYCN-driven NB, by dual-inhibition of MYCN (targeting transcription) and mTOR (targeting translation). Additional preclinical evaluation is warranted to determine the clinical utility of targeted therapy for high-risk NB patients.
Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer
Authors: Lin Yingying , Zhou Xusheng , Peng Wei , Wu Jing , Wu Xiufeng , Chen Yan , Cui Zhaolei 
Published: September 2021

Abstract
Background
Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC).

Methods
We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results
No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively.

Conclusions
BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.
Factors Associated with Health Check-up and Cancer Screening Participation among Family Caregivers of Patients with Dementia: A Cross-Sectional Study
Authors: Kim Bomgyeol , Lee Yejin , Noh Jin-Won , Kim Tae Hyun 
Published: September 2021

Abstract
Background
Providing care for patients with dementia can negatively influence the physical health and health behaviours of family caregivers. A better understanding of the factors associated with health check-up and cancer screening participation is vital for developing effective interventions. Thus, this study aimed to identify factors associated with health check-up and cancer screening participation among family caregivers of patients with dementia.

Methods
This was a cross-sectional study that analysed the data of 2,414 family caregivers of patients with dementia collected by the Korea Community Health Survey in 2017. A binomial logistic regression analysis was performed to identify demographic, socioeconomic, and health status factors associated with health check-up and cancer screening participation among family caregivers of patients with dementia.

Results
Health check-up and cancer screening rates among family caregivers of patients with dementia were 68.7% and 61.4%, respectively, which were significantly lower than the rates for individuals who were not caregivers of patients with dementia. Those with lower education levels had lower odds ratios (OR) for both health check-up (OR: 0.60) and cancer screening (OR: 0.59) participation. In addition, symptoms of depression were associated with lower participation (health check-up OR: 0.67; cancer screening OR: 0.65).

Conclusions
More targeted disease prevention and management strategies must be developed for family caregivers of patients with dementia, particularly those with depressive symptoms and lower education levels.
Prevention of sick leave at the workplace: design of a cluster-randomized controlled trial of a problem-solving intervention among employees with common mental disorders
Authors: Björk Brämberg E. , Arapovic-Johansson B. , Bültmann U. , Svedberg P. , Bergström G. 
Published: September 2021

Abstract
Background
Common mental disorders are highly prevalent in the working population, affecting about 1 in 5 persons in the Organisation for Economic Co-operation and Development countries. About 30% of those affected have a first period of sick leave. Despite several attempts to reduce the risk of sick leave among employees with common mental disorders, there is a lack of knowledge about effective, preventive interventions which aim to reduce such risks. This protocol describes the design of a study to evaluate the effectiveness of a problem-solving intervention delivered by first-line managers to employees with common mental disorders on the prevention of sick leave during the 12-month follow-up.

Methods/design
The study applies a two-armed cluster-randomized trial design of a problem-solving intervention conducted in private-sector companies. First-line managers are randomized into intervention- or control groups by computer-generated random numbers, allocation ratio 1:1. Employees are eligible if at risk for future sick leave due to common mental disorders. These are identified by self-reported psychological health measured by the General Health Questionnaire 12-item, cut-off ≥3, or a positive answer to risk of sick leave.
The intervention is based on problem-solving principles. It involves the training of the first-line managers who then deliver the intervention to employees identified at risk of sick leave. First-line managers in the control group receives a lecture. Primary outcome is number of registered days of sick leave due to common mental disorders during the 12-month follow-up. Secondary outcomes are general health, psychological symptoms, work performance, work ability and psychosocial work environment. A process evaluation will examine the intervention’s reach, fidelity, dose delivered, dose received, satisfaction and context. Research assistants managing the screening procedure, outcome assessors and employees are blinded to randomization and allocation.

Discussion
The study includes analyses of the intervention’s effectiveness and an alongside process evaluation. Methodological strengths and limitations, for example the risk of selection bias, attrition and risk of contamination are discussed.

Trial registration
Clinicaltrials.gov NCT04975750 Date of registration: 08/16/2021.