bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing cyclists’ routing preferences by analyzing extensive user setting data from a bike-routing engine
Authors: Hardinghaus Michael , Nieland Simon 
Published: July 2021

Abstract
Introduction
Many municipalities aim to support the uptake of cycling as an environmentally friendly and healthy mode of transport. It is therefore crucial to meet the demand of cyclists when adapting road infrastructure. Previous studies researching cyclists’ route choice behavior deliver valuable insights but are constrained by laboratory conditions, limitations in the number of observations, or the observation period or relay on specific use cases.

Methods
The present study analyzes a dataset of over 450,000 observations of cyclists’ routing settings for the navigation of individual trips in Berlin, Germany. It therefore analyzes query data recorded in the bike-routing engine BBBike and clusters the many different user settings with regard to preferred route characteristics.

Results and Conclusion
Results condense the large number of routing settings into characteristic preference clusters. Compared with earlier findings, the big data approach highlights the significance of short routes, side streets and the importance of high-quality surfaces for routing choices, while cycling on dedicated facilities seems a little less important.
Consequentially, providing separated cycle facilities along main roads – often the main focal point of cycle plans – should be put into the context of an integrated strategy which fulfills distinct preferences to achieve greater success. It is therefore particularly important to provide a cycle network in calm residential streets as well as catering for short, direct cycle routes.
Comparative transcriptome analysis reveals sesquiterpenoid biosynthesis among 1-, 2- and 3-year old Atractylodes chinensis
Authors: Zhao Jianhua , Sun Chengzhen , Shi Fengyu , Ma Shanshan , Zheng Jinshuang , Du Xin , Zhang Liping 
Published: July 2021

Abstract
Background
Atractylodes chinensis (DC.) Koidz is a well-known medicinal plant containing the major bioactive compound, atractylodin, a sesquiterpenoid. High-performance liquid chromatography (HPLC) analysis demonstrated that atractylodin was most abundant in 3-year old A. chinensis rhizome, compared with those from 1- and 2-year old rhizomes, however, the molecular mechanisms underlying accumulation of atractylodin in rhizomes are poorly understood.

Results
In this study, we characterized the transcriptomes from rhizomes of 1-, 2- and 3-year old (Y1, Y2 and Y3, respectively) A. chinensis, to identify differentially expressed genes (DEGs). We identified 240, 169 and 131 unigenes encoding the enzyme genes in the mevalonate (MVA), methylerythritol phosphate (MEP), sesquiterpenoid and triterpenoid biosynthetic pathways, respectively. To confirm the reliability of the RNA sequencing analysis, eleven key gene encoding factors involved in the sesquiterpenoid and triterpenoid biosynthetic pathway, as well as in pigment, amino acid, hormone and transcription factor functions, were selected for quantitative real time PCR (qRT-PCR) analysis. The results demonstrated similar expression patterns to those determined by RNA sequencing, with a Pearson’s correlation coefficient of 0.9 between qRT-PCR and RNA-seq data. Differential gene expression analysis of rhizomes from different ages revealed 52 genes related to sesquiterpenoid and triterpenoid biosynthesis. Among these, seven DEGs were identified in Y1 vs Y2, Y1 vs Y3 and Y2 vs Y3, of which five encoded four key enzymes, squalene/phytoene synthase (SS), squalene-hopene cyclase (SHC), squalene epoxidase (SE) and dammarenediol II synthase (DS). These four enzymes directly related to squalene biosynthesis and subsequent catalytic action. To validate the result of these seven DEGs, qRT-PCR was performed and indicated most of them displayed lower relative expression in 3-year old rhizome, similar to transcriptomic analysis.

Conclusion
The enzymes SS, SHC, SE and DS down-regulated expression in 3-year old rhizome. This data corresponded to the higher content of sesquiterpenoid in 3-year old rhizome, and confirmed by qRT-PCR. The results of comparative transcriptome analysis and identified key enzyme genes laid a solid foundation for investigation of production sesquiterpenoid in A. chinensis.
Association of dietary calcium intake, total and ionized serum calcium levels with preeclampsia in Ethiopia
Authors: Gebreyohannes Rahel D. , Abdella Ahmed , Ayele Wondimu , Eke Ahizechukwu C. 
Published: July 2021

Abstract
Background
Preeclampsia is a well-known cause of maternal mortality and morbidity in Ethiopia. The exact pathophysiology has not been fully understood. Calcium and magnesium deficiencies have been given emphasis to play roles in the pathophysiology. Although evidence is abundant, they are equivocal. The study aimed to see the association of dietary calcium intake, serum total calcium level and ionized calcium level with preeclampsia. It also evaluated the association between dietary calcium intake and serum calcium levels.

Materials and methods
An unmatched case–control study was conducted in Gandhi Memorial, Tikur Anbessa, and Zewditu Memorial Hospitals, all in Addis Ababa, between October to December, 2019. Cases were 42 women with preeclampsia and controls were 42 normotensive women. The medical and obstetric history was gathered using a structured questionnaire and the dietary calcium intake information using a 24-h dietary recall. The serum levels of total serum calcium and ionized (free) calcium were measured using an inductively coupled mass spectrophotometer. Bivariate and multivariate logistic regression and Pearson correlation test were utilized during data analysis.

Results
In comparison with controls, women with preeclampsia had lower mean (± 1SD) levels of ionized calcium level (1.1 mmol/l ± 0.11), total serum calcium level (1.99 mmol/l ± 0.35) and lower median (IQR) dietary calcium intake (704 mg/24 h,458–1183). The odds of having preeclampsia was almost eight times greater in those participants with low serum ionized calcium level (OR 7.5, 95% CI 2.388–23.608) and three times higher in those with low total serum calcium level (OR 3.0, 95% CI 1.024–9.370). Low dietary calcium intake also showed statistically significant association with preeclampsia (OR 3.4, 95% CI 1.092 -10.723). Serum ionized calcium level and total serum calcium level showed positive correlation of moderate strength (p = 0.004, r = 0.307), but no correlation was found between dietary calcium intake with both forms of serum calcium levels.

Conclusion
This study showed significant association between low dietary calcium intake and low serum calcium levels with preeclampsia, hence this can be used as a supportive local evidence for the current context-specific recommendation of calcium supplementation in societies with low-dietary calcium consumption in an attempt to prevent preeclampsia, therefore implementation study should be considered in Ethiopia to look for the feasibility of routine supplementation.
Validity and reliability of the simplified Chinese patient-reported outcomes version of the common terminology criteria for adverse events
Authors: Yang Shan-Shan , Chen Lei , Liu Ying , Lu Hai-Jun , Huang Bo-Jie , Lin Ai-Hua , Sun Ying , Ma Jun , Xie Fang-Yun , Mao Yan-Ping 
Published: July 2021

Abstract
Background
The psychometric properties of the simplified Chinese version of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) have not been assessed. Therefore, we aimed to assess its validity, reliability, and responsiveness.

Patients and methods
A Chinese version of the PRO-CTCAE and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) were distributed to 1580 patients from four cancer hospitals in China. Validity assessments included construct validity, measured by Pearson’s correlations and confirmatory factor analysis (CFA), and known-groups validity, measured by t-tests. The assessment of reliability included internal consistency, measured by Cronbach’s ɑ, and test-retest reliability, measured by the intraclass correlation (ICC). Responsiveness was assessed by standardized response means (SRMs).

Results
Data from 1555 patients who completed the instruments were analyzed. The correlations were high between PRO-CTCAE items and parallel QLQ-C30 symptom scales (r > 0.60, p < 0.001), except for fatigue (severity: r = 0.49). Moreover, CFA showed the PRO-CTCAE structure was a good fit with the data (Root Mean Square Error of Approximation = 0.046). Known-groups validity was also confirmed. Cronbach’s ɑ of all item clusters were greater than 0.9 and the median test-retest reliability coefficients of the 38 items were 0.85 (range = 0.71–0.91). In addition, the SRMs of PRO-CTCAE items were greater than 0.8, indicating strong responsiveness.

Conclusion
The simplified Chinese version of the PRO-CTCAE showed good reliability, validity, and responsiveness.
Topiramate induced bilateral hypopyon uveitis and choroidal detachment: a report of two cases and review of literature
Authors: Tyagi Mudit , Behera Shashwat , Senthil Sirisha , Pappuru Rajeev R. , Ambiya Vikas , Dikshit Siddharth 
Published: July 2021

AbstractBackgroundTopiramate (TPM) is a drug commonly used by neurophysicians and psychiatrists for a plethora of indications. Topiramate has been reported to induce acute angle closure glaucoma as an adverse effect. However, there is limited literature on Topiramate causing hypopyon uveitis and intense ocular inflammation. It is imperative for ophthalmologists as well as physicians to be aware of the potential sight threatening ocular adverse effects of Topiramate. We report 2 rare consecutive cases of severe hypopyon uveitis and choroidal detachments after using Topiramate.Case presentationTwo patients presented with sudden onset of angle closure, bilateral hypopyon uveitis and choroidal detachments. On reassessing a detailed treatment history, it was found that both patient were taking oral Topiramate which had been started 2 weeks before the onset of ocular symptoms. The bilateral hypopyon and angle closure were considered to be induced by Topiramate and the drug was discontinued. The patients were started on oral and topical steroids which led to resolution of hypopyon uveitis and choroidal detachments. The visual acuity improved and the intraocular pressure also got normalised in both the cases.ConclusionsTopiramate can lead to a bilateral hypopyon uveitis and severe ocular inflammation. An urgent cessation of topiramate along with topical and systemic steroids is required to prevent serious complications.
Prognosis and treatment of 46 Chinese pediatric cystic fibrosis patients
Authors: Chen Qionghua , Shen Yuelin , Xu Hui , Tang Xiaolei , Yang Haiming , Zhao Shunying 
Published: July 2021

Abstract
Background
Since public awareness of cystic fibrosis (CF) has increased, more children have been diagnosed with CF in China. This study aimed to investigate medical and other challenges faced by pediatric CF patients in China.

Method
Treatments and treatment outcomes were retrospectively analyzed for 46 pediatric CF patients diagnosed from August 2009 to June 2019. Pre- and post-treatment results were compared using independent samples t-test.

Results
Of 46 pediatric CF study patients, four died and five were lost to follow-up. Thirty-seven patients were monitored for 0.03 to 9.21 years; patients exhibited fewer attacks of respiratory tract infections after diagnosis (4.49 ± 2.13 episodes/year before diagnosis vs 1.97 ± 1.87 times/year after 1-year treatment, p < 0.05), significantly reduced sputum production and experienced 1.62 ± 1.71 exacerbations/year. Patient mean body mass index was 16.87 ± 3.53 and pancreatic malfunction persisted in 15 patients. For 17 children, no significant differences in lung function were found at follow-up as compared to lung function at diagnosis (FEV1: 82.45% ± 16.56% vs 75.26% ± 22.34%, FVC: 87.18% ± 13.64% vs 86.99% ± 19.95%, FEF75%: 46.51% ± 28.78% vs 36.63% ± 24.30%, P = 0.27, 0.97, 0.20, respectively). Pseudomonas aeruginosa (17/27) and bronchiectasis (22/22) were found during follow-up evaluation. Twenty-four patients (64.8%) maintained good adherence to therapies. Overall, azithromycin and tobramycin treatments were administered for 0.5–62 months and 0.5–48 months, respectively, and triggered no obvious adverse reactions.

Conclusion
No obvious declines in clinical presentation or lung function were found in Chinese pediatric CF patients after receiving standard therapeutic and active treatments, although malnutrition and low compliance were persistent challenges.
Using health impact assessment (HIA) to understand the wider health and well-being implications of policy decisions: the COVID-19 ‘staying at home and social distancing policy’ in Wales
Authors: Green Liz , Ashton Kathryn , Azam Sumina , Dyakova Mariana , Clemens Timo , Bellis Mark A. 
Published: July 2021

Abstract
Background
Health Impact Assessment (HIA) is promoted as a decision-informing tool by public health and governmental agencies. HIA is beneficial when carried out as part of policy development but is also valuable as a methodology when a policy is being implemented to identify and understand the wider health and well-being impacts of policy decisions, particularly when a decision needs to be taken rapidly to protect the population. This paper focusses on a HIA of the ‘Staying at Home and Social Distancing Policy’ or ‘lockdown’ in response to the COVID-19 pandemic in Wales conducted by the Welsh national public health institute. It describes the process and findings, captures the learning and discusses how the process has been used to better understand the wider health and well-being impacts of policy decisions beyond direct health harm. It also examines the role of public health institutes in promoting and using HIA.

Methods
A HIA was conducted following a standard HIA five step process. A literature review was undertaken alongside 15 qualitative semi-structured interviews with key stakeholders, and relevant health and demographic data were collated. The results were triangulated and analysed to form a holistic assessment of the policy decision and its impacts.

Results
A wide range of major health and well-being impacts of the lockdown in Wales were identified across the determinants of health, which included positive and negative social, economic, environmental and mental well-being impacts beyond the impact on direct health. Populations affected included children and young people, those on low incomes and women as well as those whose health has been directly impacted by COVID-19 such as older people. The work highlighted the benefit that HIA can bring in emphasizing impacts which can inform policy and shared learning with others.

Conclusion
HIA is a largely underused tool to understand the impact of policy and political decisions, particularly when a decision has been taken at speed. This case study highlights how HIA provide evidence and information for advocacy and further work by public health institutes, health agencies and policy makers.
Analysis of conventional and alternative CRISPR/Cas9 genome editing to enhance a single-base pair knock-in mutation
Authors: Edmondson Carina , Zhou Qi , Liu Xuan 
Published: July 2021

Abstract
Background
The use of CRISPR/Cas9 technologies in generating single-base pair knock-in mutations has recently exploded in the number of methods available. However, with the growing expansion of new technologies, it can be difficult to determine the best method for genome editing.

Results
In this study, we evaluated a number of CRISPR/Cas9 approaches for deriving cell lines with knock-in base pair edits to create a phosphorylation mutation and provide a breakdown of editing efficiencies and suggestions for improvement. Overall, our studies suggest that using pre-formed ribonucleoprotein (RNP) complexes is a reliable editing method to generate homozygous single-base pair mutations. We also show that antibiotic selection coupled homologous recombination is an efficient tool for generating highly specific heterozygous mutations.

Conclusion
The methods and/or combination of methods outlined in this study can be used to help other researchers with similar goals in single-base pair genome editing.
Medical student wellness in the United States during the COVID-19 pandemic: a nationwide survey
Authors: Nikolis Louis , Wakim Andrea , Adams William , DO Prempreet Bajaj 
Published: July 2021

Abstract
Background
As United States (US) medical students suffer higher rates of depression and anxiety than the general population, the wellness of medical students is particularly salient. One definition describes wellness as having eight dimensions: Intellectual, emotional, physical, social, occupational, financial, environmental, and spiritual. As the coronavirus (COVID-19) pandemic poses unique challenges for medical students, we aimed to compare medical student wellness before and during the COVID-19 pandemic.

Methods
An informal survey was created to assess eight wellness dimensions and was distributed via Survey Monkey to US allopathic and osteopathic medical students via email and social media. The survey was administered from March 29, 2020 to June 23, 2020. Univariable and multivariable linear mixed-effects models were used to estimate the change in students’ overall wellness using an 11-point scale ranging from 0 (least well) to 10 (most well). Generalized estimating equations were used to estimate the change in students’ responses to the eight dimensions before and during the COVID-19 pandemic.

Results
On multivariable analysis, students reported a decline in their overall wellness during COVID-19 (Mdiff = -1.08; p < .001). Asian respondents reported little change in overall wellness (M = -0.65) when compared to White respondents (M = -1.16) and Black respondents (M = -1.57). Students felt less supported and comfortable with their social (OR = 0.47) and daily (OR = 0.45) environments and expressed decreased satisfaction with their exercise (OR = 0.85), sense of purpose (OR = 0.33), and financial status (OR = 0.75). Students also expressed lower confidence (OR = 0.15) and satisfaction (OR = 0.11) with their medical education and increased anxiety (OR = 3.37) and depression (OR = 2.05).

Conclusions
Medical students reported declines in overall wellness and individual wellness dimensions. These findings can be used to implement changes to improve medical student wellness.
Reallocations in acne healthcare: exploring the possible roles and added value of non-physicians by a mixed-methods study design
Authors: de Vries Femke , Welbie Marlies , Tjin Esther , Driessen Rieke , van de Kerkhof Peter 
Published: July 2021

Abstract
Background
A highly promoted opportunity for optimizing healthcare services is to expand the role of non-physician care providers by care reallocation. Reallocating care from physicians to non-physicians can play an important role in solving systemic healthcare problems such as care delays, hospital overcrowding, long waiting lists, high work pressure and expanding healthcare costs. Dermatological healthcare services, such as the acne care provision, are well suited for exploring the opportunities for care reallocation as many different types of care professionals are involved in the care process. In the Netherlands, acne care is mainly delivered by general practitioners and dermatologists. The Dutch healthcare system also recognizes non-physician care providers, among which dermal therapists and beauticians are the most common professions. However, the role and added value of non-physicians is still unclear. The present study aimed to explore the possibilities for reallocating care to non-physicians and identify drivers for and barriers to reallocation.

Methods
A mixed-method design was used collecting quantitative and qualitative data from representatives of the main 4 Dutch professions providing acne care: dermatologists, GP’s, Dermal therapists and beauticians.

Results
A total of 560 questionnaires were completed and 24 semi-structured interviews were conducted. A broad spectrum of non-physician tasks and responsibilities were delineated. Interviewed physicians considered acne as a low-complexity skin condition which made them willing to explore the possibilities for reallocating. A majority of all interviewees saw a key role for non-physicians in counselling and supporting patients during treatment, which they considered an important role for increasing patients’ adherence to proposed treatment regimes, contributing to successful clinical outcome. Also, the amount of time non-physicians spend on patients was experienced as driver for reallocation. Legislation and regulations, uncertainties about the extent of scientific evidence and proper protocols use within the non-physician clinical practice were experienced as barriers influencing the possibilities for reallocation.

Conclusions
Delineated roles and drivers demonstrate there is room and potential for reallocation between physicians and non-physicians within acne healthcare, when barriers are adequately addressed.
Perturbation of semaphorin and VEGF signaling in ACDMPV lungs due to FOXF1 deficiency
Authors: Karolak Justyna A. , Gambin Tomasz , Szafranski Przemyslaw , Maywald Rebecca L. , Popek Edwina , Heaney Jason D. , Stankiewicz Paweł 
Published: July 2021

Abstract
Background
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal congenital lung disorder in neonates characterized by severe progressive respiratory failure and refractory pulmonary hypertension, resulting from underdevelopment of the peripheral pulmonary tree. Causative heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving FOXF1 or its distant lung-specific enhancer on chromosome 16q24.1 have been identified in 80–90% of ACDMPV patients. FOXF1 maps closely to and regulates the oppositely oriented FENDRR, with which it also shares regulatory elements.

Methods
To better understand the transcriptional networks downstream of FOXF1 that are relevant for lung organogenesis, using RNA-seq, we have examined lung transcriptomes in 12 histopathologically verified ACDMPV patients with or without pathogenic variants in the FOXF1 locus and analyzed gene expression profile in FENDRR-depleted fetal lung fibroblasts, IMR-90.

Results
RNA-seq analyses in ACDMPV neonates revealed changes in the expression of several genes, including semaphorins (SEMAs), neuropilin 1 (NRP1), and plexins (PLXNs), essential for both epithelial branching and vascular patterning. In addition, we have found deregulation of the vascular endothelial growth factor (VEGF) signaling that also controls pulmonary vasculogenesis and a lung-specific endothelial gene TMEM100 known to be essential in vascular morphogenesis. Interestingly, we have observed a substantial difference in gene expression profiles between the ACDMPV samples with different types of FOXF1 defect. Moreover, partial overlap between transcriptome profiles of ACDMPV lungs with FOXF1 SNVs and FENDRR-depleted IMR-90 cells suggests contribution of FENDRR to ACDMPV etiology.

Conclusions
Our transcriptomic data imply potential crosstalk between several lung developmental pathways, including interactions between FOXF1-SHH and SEMA-NRP or VEGF/VEGFR2 signaling, and provide further insight into complexity of lung organogenesis in humans.