bluuebunny/crossref_metadata_2025_split huggingface dataset:
Video observation of encounters between the automated shuttles and other traffic participants along an approach to right-hand priority T-intersection
Authors: Pokorny Petr , Skender Belma , Bjørnskau Torkel , Hagenzieker Marjan P. 
Published: November 2021

Abstract
Introduction
Increasing numbers of deployment projects of automated shuttles have been taking place worldwide. Safety is one of the main concerns for their successful implementation. Therefore, it is vital to gain the knowledge about interactions between these shuttles and other traffic participants.

Method
Given the lack of behavioural observational studies under regular traffic conditions, the presented study applies external video recordings to explore encounters between the shuttles approaching a T-intersection and other traffic participants. The encounters of interest included a vulnerable road user in the bicycle lane, a pedestrian on the zebra crossing and a road user overtaking the shuttle. The shuttles were identified from the video by RUBA software. We analysed the encounters using T-Analyst software together with the manual observation of traffic participants' behaviour.

Results
From 220 h of video, 318 unique manoeuvres of the shuttle were observed and 83 encounters with other traffic participants were identified and explored. Several types of risks and behavioural patterns were identified, such as road users misusing the defensive style of the shuttles or cyclists in the bicycle lane not being sure about the shuttle’s intention. Frequent hard stops of the shuttles might be dangerous for the passengers inside and can increase the risk of rear end accidents.

Conclusions
The findings provide a valuable insight into the interactions between automated shuttles and other traffic participants under regular traffic conditions on one location in Oslo, Norway. The study showed that introducing automated shuttles into regular traffic can lead to the emergence of new types of interactions between the shuttles and other traffic participants.
Genetic basis of orange spot formation in the guppy (Poecilia reticulata)
Authors: Kawamoto Mayuko , Ishii Yuu , Kawata Masakado 
Published: November 2021

AbstractBackgroundTo understand the evolutionary significance of female mate choice for colorful male ornamentation, the underlying regulatory mechanisms of such ornamentation must be understood for examining how the ornaments are associated with “male qualities” that increase the fitness or sexual attractiveness of offspring. In the guppy (Poecilia reticulata), an established model system for research on sexual selection, females prefer males possessing larger and more highly saturated orange spots as potential mates. Although previous studies have identified some chromosome regions and genes associated with orange spot formation, the regulation and involvement of these genetic elements in orange spot formation have not been elucidated. In this study, the expression patterns of genes specific to orange spots and certain color developmental stages were investigated using RNA-seq to reveal the genetic basis of orange spot formation.ResultsComparing the gene expression levels of male guppy skin with orange spots (orange skin) with those without any color spots (dull skin) from the same individuals identified 1102 differentially expressed genes (DEGs), including 630 upregulated genes and 472 downregulated genes in the orange skin. Additionally, the gene expression levels of the whole trunk skin were compared among the three developmental stages and 2247 genes were identified as DEGs according to color development. These analyses indicated that secondary differentiation of xanthophores may affect orange spot formation.ConclusionsThe results suggested that orange spots might be formed by secondary differentiation, rather than de novo generation, of xanthophores, which is induced by Csf1 and thyroid hormone signaling pathways. Furthermore, we suggested candidate genes associated with the areas and saturation levels of orange spots, which are both believed to be important for female mate choice and independently regulated. This study provides insights into the genetic and cellular regulatory mechanisms underlying orange spot formation, which would help to elucidate how these processes are evolutionarily maintained as ornamental traits relevant to sexual selection.
Genome-wide investigation of the AP2/ERF gene family in ginger: evolution and expression profiling during development and abiotic stresses
Authors: Xing Haitao , Jiang Yusong , Zou Yong , Long Xiaoling , Wu Xiaoli , Ren Yun , Li Yuan , Li Hong-Lei 
Published: November 2021

Abstract
Background
AP2/ERF transcription factors (TFs) constitute one of the largest TF families in plants, which play crucial roles in plant metabolism, growth, and development as well as biotic and abiotic stresses responses. Although the AP2/ERF family has been thoroughly identified in many plant species and several AP2/ERF TFs have been functionally characterized, little is known about this family in ginger (Zingiber officinale Roscoe), an important affinal drug and diet vegetable. Recent completion of the ginger genome sequencing provides an opportunity to investigate the expression profiles of AP2/ERF genes in ginger on a genome-wide basis.

Results
A total of 163 AP2/ERF genes were obtained in the Z.officinale genome and renamed according to the chromosomal distribution of the ZoAP2/ERF genes. Phylogenetic analysis divided them into three subfamilies, of which 35 belonged to the AP2 subfamily, 120 to ERF, three to RAV, and five to Sololist, respectively, which is in accordance with the number of conserved domains and gene structure analysis. A total of 10 motifs were detected in ZoAP2/ERF genes, and some of the unique motifs were found to be important for the function of ZoAP2/ERF genes. The chromosomal localization, gene structure, and conserved protein motif analyses, as well as the characterization of gene duplication events provided deep insight into the evolutionary features of these ZoAP2/ERF genes. The expression profiles derived from the RNA-seq data and quantitative reserve transcription (qRT-PCR) analysis of ZoAP2/ERFs during development and responses to abiotic stresses were investigated in ginger.

Conclusion
A comprehensive analysis of the AP2/ERF gene expression patterns in various tissues by RNA-seq and qRT-PCR showed that they played an important role in the growth and development of ginger, and genes that might regulate rhizome and flower development were preliminary identified. In additionally, the ZoAP2/ERF family genes that responded to abiotic stresses were also identified. This study is the first time to identify the ZoAP2/ERF family, which contributes to research on evolutionary characteristics and better understanding the molecular basis for development and abiotic stress response, as well as further functional characterization of ZoAP2/ERF genes with an aim of ginger crop improvement.
Changes in the dollar value of per capita alcohol, essential, and non-essential retail sales in Canada during COVID-19
Authors: Myran Daniel T. , Smith Brendan T. , Cantor Nathan , Li Lennon , Saha Sudipta , Paradis Catherine , Jesseman Rebecca , Tanuseputro Peter , Hobin Erin 
Published: November 2021

Abstract
Background
Multiple survey reports suggest that alcohol use has increased in Canada during the COVID-19 pandemic. However, less is known about how per capita alcohol sales, which predict population-level alcohol use, have changed and whether changes in alcohol sales differ from changes in sales of other products due to pandemic factors.

Methods
We obtained monthly retail sales data by industry from Statistics Canada, for the six largest provinces in Canada (containing 93% of the national population), between January 2010 and November 2020, representing time before and 9 months after the start of the pandemic in Canada. We used an interrupted time series analysis to estimate pandemic impacts on the dollar value of monthly per capita (per individuals 15+ years) alcohol, essential and non-essential retail sales. We adjusted our analyses for pre-pandemic sales trends, inflation, seasonality and changing population demographics over time.

Results
During the first 9 months of the pandemic, the values of per capita alcohol, essential and non-essential sales were, respectively, 13.2% higher, 3.6% higher and 13.1% lower than the average values during the same period in the prior 3 years. Interrupted time series models showed significant level change for the value of monthly per capita alcohol sales (+$4.86, 95% CIs: 2.88, 6.83), essential sales (−$59.80, 95% CIs: − 78.47, − 41.03) and non-essential sales (−$308.70, 95% CIs: − $326.60, − 290.79) during the pandemic. Alcohol sales were consistently elevated during the pandemic, and the pre- and post-pandemic slopes were comparable. In contrast, essential and non-essential retail sales declined in the early months of the pandemic before returning to regular spending levels.

Conclusion
During the first 9 months of the pandemic, per capita alcohol sales were moderately elevated in Canada. In contrast, non-essential sales were lower than prior years, driven by large decreases during the initial months of the pandemic. These findings suggest that the pandemic was associated with increased population-level alcohol consumption, which may lead to increased alcohol-related harms. Ongoing research is needed to examine how factors, including pandemic-related stressors and specific alcohol sales-related policies, may have influenced changes in alcohol use and harms.
Perceptions of workplace heat exposure and adaption behaviors among Chinese construction workers in the context of climate change
Authors: Han Shu-Rong , Wei Mingru , Wu Zhifeng , Duan Shanshan , Chen Xiangzhe , Yang Jiayuan , Borg Matthew A. , Lin Jinfeng , Wu Chuancheng , Xiang Jianjun 
Published: November 2021

Abstract
Background
Workplace heat exposure can cause a series of heat-related illnesses and injuries. Protecting workers especially those undertake work outdoors from the risk of heat strain is a great challenge for many workplaces in China under the context of climate change. The aim of this study is to investigate the perceptions and adaptation behaviors of heat exposure among construction workers and to provide evidence for the development of targeted heat adaptation strategies nationally and internationally.

Methods
In 2020, we conducted a cross-sectional online questionnaire survey via WeChat Survey Star in China, using a purposive snowball sampling approach. A total of 326 construction workers submitted completed questionnaires. The perceptions of workplace heat exposure were measured using seven indicators: concerns over high temperature, perception of high temperature injury, attitudes towards both heat-related training and regulations, adjustment of working habits during heat, heat prevention measures in the workplace, and reduction of work efficiency. Bivariate and multivariate regression analyses were used to identify the factors significantly associated with workers’ heat perceptions and behavioral responses.

Results
33.3% of the respondents were moderately or very concerned about heat exposure in the workplace. Less than half of the workers (43.8%) were worried about heat-related injuries. Workers who have either experienced work-related injuries (OR = 1.30, 95% CI 1.03–1.62) or witnessed injuries to others during high temperatures (OR = 1.12, 95% CI 1.02–1.27) were more concerned about heat exposure compared to other workers. Most respondents (63.5%) stated that their work efficiency declined during extremely hot weather. The factors significantly associated with a reduction of work efficiency included undertaking physically demanding jobs (OR = 1.28, 95% CI 1.07–1.54) and witnessing other workers’ injuries during high temperatures (OR = 1.26, 95% CI 1.11–1.43). More than half of the workers were willing to adjust their work habits to adapt to the impact of high temperatures (81.6%). The internet was the most common method to obtain heat prevention information (44.7%), and the most frequently used heat prevention measure was the provision of cool drinking water (64.8%).

Conclusions
Chinese construction workers lack heat risk awareness and are not well prepared for the likely increasing heat exposure in the workplace due to global warming. Therefore, there is a need to improve their awareness of heat-related injuries, strengthen high temperature related education and training, and update the current heat prevention policies to ensure compliance and implementation.
Physicians’ approach to end of life care: comparison of two tertiary care university hospitals in Lebanon
Authors: Dabar George , Akl Imad Bou , Sader Mirella 
Published: November 2021

Abstract
Background
The care of terminally ill patients is fraught with ethical and medical dilemmas carried by healthcare professionals. The present study aims to explore the approaches of Lebanese attending physicians towards palliative care, end of life (EOL) care, and patient management in two tertiary care university hospitals with distinct medical culture.

Methods
Four hundred attending physicians from the American University of Beirut Medical Center (AUBMC) and Hotel Dieu de France (HDF) were recruited. Participants were Medical Doctors in direct contact with adult patients that could be subject to EOL situations providing relevant demographic, educational, religious as well as personal, medical or patient-centric data.

Results
The majority of physicians in both establishments were previously exposed to life-limiting decisions but remains uncomfortable with the decision to stop or limit resuscitation. However, physicians with an American training (AUBMC) were significantly more likely to exhibit readiness to initiate and discuss DNR with patients (p<0.0001). While the paternalistic medicinal approach was prevalent in both groups, physicians with a European training (HDF) more often excluded patient involvement based on family preference (p<0.0001) or to spare them from a traumatic situation (p=0.003). The majority of respondents reported that previous directives from the patient were fundamental to life-limiting decisions. However, the influence of patient and medical factors (e.g. culture, religion, life expectancy, age, socioeconomic status) was evidenced in the HDF group.

Conclusion
Early physician-initiated EOL discussions remain challenged in Lebanon. Paternalistic attitudes limit shared decision making and are most evident in European-trained physicians. Establishing a sound and effective framework providing legal, ethical and religious guidance is thus needed in Lebanon.
Sulforaphane enhances the antitumor response of chimeric antigen receptor T cells by regulating PD-1/PD-L1 pathway
Authors: Shen Chunyi , Zhang Zhen , Tian Yonggui , Li Feng , Zhou Lingxiao , Jiang Wenyi , Yang Li , Zhang Bin , Wang Liping , Zhang Yi 
Published: November 2021

Abstract
Background
Chimeric antigen receptor T (CAR-T) cell therapy has limited effects in the treatment of solid tumors. Sulforaphane (SFN) is known to play an important role in inhibiting tumor growth, but its effect on CAR-T cells remains unclear. The goal of the current study was to determine whether combined CAR-T cells and SFN could provide antitumor efficacy against solid tumors.

Methods
The effect of combined SFN and CAR-T cells was determined in vitro using a co-culture system and in vivo using a xenograft mouse model. We further validated the effects of combination therapy in patients with cancer.

Results
In vitro, the combination of SFN and CAR-T cells resulted in enhanced cytotoxicity and increased lysis of tumor cells. We found that SFN suppressed programmed cell death 1 (PD-1) expression in CAR-T cells and potentiated antitumor functions in vitro and in vivo. As a ligand of PD-1, programmed cell death ligand 1 (PD-L1) expression was also decreased in tumor cells after SFN treatment. In addition, β-TrCP was increased by SFN, resulting in higher activation of ubiquitination-mediated proteolysis of PD-L1, which induced PD-L1 degradation. The combination of SFN and CAR-T cell therapy acted synergistically to promote better immune responses in vivo compared with monotherapy. In clinical treatments, PD-1 expression was lower, and proinflammatory cytokine levels were higher in patients with various cancers who received CAR-T cells and took SFN orally than that in the control group.

Conclusion
SFN improves the cytotoxicity of CAR-T cells by modulating the PD-1/PD-L1 pathway, which may provide a promising strategy for the combination of SFN with CAR-T cells for cancer immunotherapy.
“Chiropractic is manual therapy, not talk therapy”: a qualitative analysis exploring perceived barriers to remote consultations by chiropractors
Authors: Derbyshire Shane , Field Jonathan , Vennik Jane , Sanders Marc , Newell Dave 
Published: November 2021

Abstract
Background
Remote consultations (RCs) enable clinicians to continue to support patients when face-to-face appointments are not possible. Restrictions to face-to-face care during the COVID-19 pandemic has accelerated a pre-existing trend for their adoption. This is true for many health professionals including some chiropractors. Whilst most chiropractors in the UK have used RCs in some form during the pandemic, others have not. This study seeks to understand the views of chiropractors not using RCs and to explore perceived potential barriers.

Methods
A national online survey was completed by 534 registered practicing UK chiropractors on the use of RCs. Respondents had the opportunity of providing open-ended responses concerning lack of engagement in RCs during the COVID-19 pandemic. Textual responses obtained from 137 respondents were coded and analysed using thematic analysis.

Results
The use of RCs provided an opportunity for chiropractors to deliver ongoing care during the COVID-19 pandemic. However, many chiropractors expressed concern that RCs misaligned with their strong professional identity of providing ‘hands-on’ care. Some chiropractors also perceived that patients expected physical interventions during chiropractic care and thus considered a lack of demand when direct contact is not possible. In the absence of a physical examination, some chiropractors had concerns about potential misdiagnosis, and perceived lack of diagnostic information with which to guide treatment. Clinic closures and change in working environment led to practical difficulties of providing remote care for a few chiropractors.

Conclusions
The COVID-19 pandemic may have accelerated changes in the way healthcare is provided with RCs becoming more commonplace in primary healthcare provision. This paper highlights perceived barriers which may lead to reduced utilisation of RCs by chiropractors, some of which appear fundamental to their perceived identity, whilst others are likely amenable to change with training and experience.
Identification of factors related to immunotherapy efficacy and prognosis in patients with advanced head and neck squamous cell carcinoma
Authors: Xu Xuanli , Li Rongrong , Zhang Lin , Zhu Guopei , Ren Dandan , Wu Lijia , Gong Xiaoli 
Published: November 2021

Abstract
Background
Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Therefore, the aim of this study was to identify predictive biomarkers of immunotherapy response for HNSCC in order to improve treatment outcomes.

Methods
Survival analyses and comparative efficacy evaluation were performed to investigate prognostic and therapeutic impact factors in patients with advanced HNSCC following immunotherapy, and to examine the effects of factors including gene mutations, tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and immune cell infiltration on the survival and efficacy.

Results
Anti-PD-1 treatment led to a prolonged overall survival (OS) in HNSCC patients with gene mutations compared with those without the mutations, while no significant difference in the OS was found between the two groups of patients. And no marked association between the MATH value and OS was detected in HNSCC patients, whereas patients with either high TMB scores in tissues and blood or high immune cell infiltration displayed a significantly longer OS. Further analysis with efficacy as the primary endpoint revealed no significant differences in the tissue TMB, blood TMB, and MATH value between the patients who responded to immunotherapy and those who did not. Moreover, no significant differences in the expression percentages of positive immune cells in tumor, stroma, and total regions were identified between the above two groups of patients.

Conclusion
HNSCC is characterized by high mutation rate, high mutation burden, and high level of immune cell infiltration, and a subset of HNSCC patients respond to immunotherapy. Here, we showed that high mutation burden and immune cell infiltration may improve the prognosis of HNSCC patients with immunotherapy, while there was no remarkable effect on the efficacy.
Development and validation of an equation to predict the incidence of coronary heart disease in patients with type 2 diabetes in Japan
Authors: Yamashita Yasunari , Inoue Gaku , Nozaki Yoichi , Kitajima Rina , Matsubara Kiyoshi , Horii Takeshi , Mohri Junichi , Atsuda Koichiro , Matsubara Hajime 
Published: November 2021

Abstract
Objective
In the diabetes treatment policy after the Kumamoto Declaration 2013, it is difficult to accurately predict the incidence of complications in patients using the JJ risk engine. This study was conducted to develop a prediction equation suitable for the current diabetes treatment policy using patient data from Kitasato University Kitasato Institute Hospital (Hospital A) and to externally validate the developed equation using patient data from Kitasato University Hospital (Hospital B). Outlier tests were performed on the patient data from Hospital A to exclude the outliers. Prediction equation was developed using the patient data excluding the outliers and was subjected to external validation.

Results
By excluding outlier data, we could develop a new prediction equation for the incidence of coronary heart disease (CHD) as a complication of type 2 diabetes, incorporating the use of antidiabetic drugs with a high risk of hypoglycemia. This is the first prediction equation in Japan that incorporates the use of antidiabetic drugs. We believe that it will be useful in preventive medicine for treatment for people at high risk of CHD as a complication of diabetes or other diseases. In the future, we would like to confirm the accuracy of this equation at other facilities.
A new primer pair for barcoding of bees (Hymenoptera: Anthophila) without amplifying the orthologous coxA gene of Wolbachia bacteria
Authors: Bleidorn Christoph , Henze Katharina 
Published: November 2021

Abstract
Objectives
DNA barcoding became an effective method for the identification and monitoring of bees. However, standard primer pairs used for barcoding often result in (co-) amplification of bacterial endosymbionts of the genus Wolbachia, which are widespread among bee species. Here we designed a new primer pair and compared it with the performance of the standard Folmer-primers for a small sample set of bees representing the main taxonomic groups of bees.

Results
The newly designed primer pair (BeeCox1F1/BeeCox1R2) outperformed the standard barcoding primer (LCO1490/HCO2198). By generating barcodes for a small test set of bees we found that the new primer pair produced high-quality sequences in all cases for unambiguous species identification using BOLD. Conversely, the standard barcoding primers often co-amplified the homologous Wolbachia gene and resulted in mixed chromatogram signals. These sequences showed high similarity with the bacterial endosymbiont instead of the host.