bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Structural Gendered Racism in Effective Healthcare Utilization among Black American Women with Herpes Simplex Virus
Authors: Cazeau-Bandoo Stephanie I. V. , Ho Ivy K.
Published: November 2021

The sexual health of Black women has been compromised by racial and discriminatory healthcare practices from slavery through current medical and institutional barriers to care. This paper proposes a conceptual framework that identifies the link between stigma, gendered racism, and historical underpinnings that contribute to ineffective healthcare utilization of Black women diagnosed with the chronic sexually transmitted infection (STI), genital herpes. This paper also draws attention to different social factors that act as barriers to effective healthcare utilization and influence the health outcomes of Black women beyond individual factors. Using a socio-ecological framework, this paper reviews multi-level (i.e., individual, interpersonal, community, and institutional/policy) influences of the experience of genital herpes among Black women. Recommendations are provided to improve the ability of health systems and medical providers to deliver appropriate services to diverse populations, thereby improving healthcare utilization and reducing disparities for Black women.
Rice Brittle Culm19 Encoding Cellulose Synthase Subunit CESA4 Causes Dominant Brittle Phenotype But has No Distinct Influence on Growth and Grain Yield
Authors: Ma Xiaozhi , Li Chunmei , Huang Rui , Zhang Kuan , Wang Qian , Fu Chongyun , Liu Wuge , Sun Changhui , Wang Pingrong , Wang Feng , Deng Xiaojian
Published: November 2021

Background

Mechanical strength is a crucial agronomic trait in rice (Oryza sativa), and brittle mutants are thought suitable materials to investigate the mechanism of cell wall formation. So far, almost all brittle mutants are recessive, and most of them are defected in multiple morphologies and/or grain yield, limiting their application in hybrid breeding and in rice straw recycling.

Results

We identified a semi-dominant brittle mutant Brittle culm19 (Bc19) isolated from the japonica variety Nipponbare through chemical mutagenesis. The mutant showed the same apparent morphologies and grain yield to the wild type plant except for its weak mechanical strength. Its development of secondary cell wall in sclerenchyma cells was affected, along with reduced contents of cellulose, hemicellulose, lignin and sugars in culms and leaves. Positional cloning suggested that the Bc19 gene was allelic to OsCESA4, encoding one of the cellulose synthase A (CESA) catalytic subunits. In this mutant, a C-to-T substitution occurred in the coding sequence of BC19, causing the P507S missense mutation in its encoded product, which was located in the second cytoplasmic region of the OsCESA4 protein. Furthermore, introducing mutant gene Bc19 into the wild-type plant resulted in brittle plants, confirming that the P507S point mutation in OsCESA4 protein was responsible for the semi-dominant brittle phenotype of Bc19 mutant. Reverse correlation was revealed between cellulose contents and expression levels of mutant gene Bc19 among the homozygous mutant, the hybrid F1 plant, and the Bc19 overexpression transgenic plants, implying that gene Bc19 might affect cellulose synthesis in a dosage-dependent manner.

Conclusions

Bc19, a semi-dominant brittle mutant allele of gene OsCESA4, was identified using map-based cloning approach. The mutated protein of Bc19 possessing the P507S missense mutation behaved in a dosage-dependent semi-dominant manner. Unique brittle effect on phenotype and semi-dominant genetic quality of gene Bc19 indicated its potential application in grain-straw dual-purpose hybrid rice breeding.
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

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

Background

To 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.

Results

Comparing 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.

Conclusions

The 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

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

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

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

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

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

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

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

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

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.
PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
Authors: Lee So-Young , An Hyun-Ju , Kim Jin Man , Sung Min-Ji , Kim Do Kyung , Kim Hyung Kyung , Oh Jongbeom , Jeong Hye Yun , Lee Yu Ho , Yang Taeyoung , Kim Jun Han , Lim Ha Jeong , Lee Soonchul
Published: November 2021

Background

PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited.

Methods

We adopted an ovariectomy model in female wildtype and Pink1−/− mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson’s trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients.

Results

A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1−/− mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease.

Conclusions

In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.
The effect of noise on the predictive limit of QSAR models
Authors: Kolmar Scott S. , Grulke Christopher M.
Published: November 2021

A key challenge in the field of Quantitative Structure Activity Relationships (QSAR) is how to effectively treat experimental error in the training and evaluation of computational models. It is often assumed in the field of QSAR that models cannot produce predictions which are more accurate than their training data. Additionally, it is implicitly assumed, by necessity, that data points in test sets or validation sets do not contain error, and that each data point is a population mean. This work proposes the hypothesis that QSAR models can make predictions which are more accurate than their training data and that the error-free test set assumption leads to a significant misevaluation of model performance. This work used 8 datasets with six different common QSAR endpoints, because different endpoints should have different amounts of experimental error associated with varying complexity of the measurements. Up to 15 levels of simulated Gaussian distributed random error was added to the datasets, and models were built on the error laden datasets using five different algorithms. The models were trained on the error laden data, evaluated on error-laden test sets, and evaluated on error-free test sets. The results show that for each level of added error, the RMSE for evaluation on the error free test sets was always better. The results support the hypothesis that, at least under the conditions of Gaussian distributed random error, QSAR models can make predictions which are more accurate than their training data, and that the evaluation of models on error laden test and validation sets may give a flawed measure of model performance. These results have implications for how QSAR models are evaluated, especially for disciplines where experimental error is very large, such as in computational toxicology.

Graphical Abstract
FAIR data representation in times of eScience: a comparison of instance-based and class-based semantic representations of empirical data using phenotype descriptions as example
Authors: Vogt Lars
Published: November 2021

Background

The size, velocity, and heterogeneity of Big Data outclasses conventional data management tools and requires data and metadata to be fully machine-actionable (i.e., eScience-compliant) and thus findable, accessible, interoperable, and reusable (FAIR). This can be achieved by using ontologies and through representing them as semantic graphs. Here, we discuss two different semantic graph approaches of representing empirical data and metadata in a knowledge graph, with phenotype descriptions as an example. Almost all phenotype descriptions are still being published as unstructured natural language texts, with far-reaching consequences for their FAIRness, substantially impeding their overall usability within the life sciences. However, with an increasing amount of anatomy ontologies becoming available and semantic applications emerging, a solution to this problem becomes available. Researchers are starting to document and communicate phenotype descriptions through the Web in the form of highly formalized and structured semantic graphs that use ontology terms and Uniform Resource Identifiers (URIs) to circumvent the problems connected with unstructured texts.

Results

Using phenotype descriptions as an example, we compare and evaluate two basic representations of empirical data and their accompanying metadata in the form of semantic graphs: the class-based TBox semantic graph approach called Semantic Phenotype and the instance-based ABox semantic graph approach called Phenotype Knowledge Graph. Their main difference is that only the ABox approach allows for identifying every individual part and property mentioned in the description in a knowledge graph. This technical difference results in substantial practical consequences that significantly affect the overall usability of empirical data. The consequences affect findability, accessibility, and explorability of empirical data as well as their comparability, expandability, universal usability and reusability, and overall machine-actionability. Moreover, TBox semantic graphs often require querying under entailment regimes, which is computationally more complex.

Conclusions

We conclude that, from a conceptual point of view, the advantages of the instance-based ABox semantic graph approach outweigh its shortcomings and outweigh the advantages of the class-based TBox semantic graph approach. Therefore, we recommend the instance-based ABox approach as a FAIR approach for documenting and communicating empirical data and metadata in a knowledge graph.
Prefrontal fNIRS-based clinical data analysis of brain functions in individuals abusing different types of drugs
Authors: Gu Xuelin , Yang Banghua , Gao Shouwei , Yan Lin Feng , Xu Ding , Wang Wen
Published: November 2021

Background

The activation degree of the orbitofrontal cortex (OFC) functional area in drug abusers is directly related to the craving for drugs and the tolerance to punishment. Currently, among the clinical research on drug rehabilitation, there has been little analysis of the OFC activation in individuals abusing different types of drugs, including heroin, methamphetamine, and mixed drugs. Therefore, it becomes urgently necessary to clinically investigate the abuse of different drugs, so as to explore the effects of different types of drugs on the human brain.

Methods

Based on prefrontal high-density functional near-infrared spectroscopy (fNIRS), this research designs an experiment that includes resting and drug addiction induction. Hemoglobin concentrations of 30 drug users (10 on methamphetamine, 10 on heroin, and 10 on mixed drugs) were collected using fNIRS and analyzed by combining algorithm and statistics.

Results

Linear discriminant analysis (LDA), Support vector machine (SVM) and Machine-learning algorithm was implemented to classify different drug abusers. Oxygenated hemoglobin (HbO2) activations in the OFC of different drug abusers were statistically analyzed, and the differences were confirmed. Innovative findings: in both the Right-OFC and Left-OFC areas, methamphetamine abusers had the highest degree of OFC activation, followed by those abusing mixed drugs, and heroin abusers had the lowest. The same result was obtained when OFC activation was investigated without distinguishing the left and right hemispheres.

Conclusions

The findings confirmed the significant differences among different drug abusers and the patterns of OFC activations, providing a theoretical basis for personalized clinical treatment of drug rehabilitation in the future.
Prevalence and risk factors of depression in Chinese patients with type 2 diabetes mellitus: a protocol of systematic review and meta-analysis
Authors: Liu Xiaobo , Dong Chao , Jiang Hong , Zhong Dongling , Li Yuxi , Zhang Huiling , Zhang Jun , Fan Jin , Li Juan , Guan Li , Jin Rongjiang
Published: November 2021

Background

The prevalence of type 2 diabetes mellitus (T2DM) is growing in China. Depression is a significant complication of T2DM, leading to poor management of T2DM. Thus, early detection and treatment of depression in patients with T2DM are essential and effective. Therefore, we plan to conduct a systematic review and meta-analysis to evaluate the prevalence of depression in Chinese patients with T2DM and explore potential risk factors of depression in T2DM.

Methods

We will search literatures recorded in MEDLINE, EMBASE, the Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and WanFang Database from their inception onwards. We will manually search gray literatures, reference lists of identified studies, relevant websites, and consult experts in this field. We will include population-based, cross-sectional surveys that investigated the prevalence of depression in Chinese patients with T2DM or/and the possible risk factors of depression in T2DM. Two reviewers will screen studies, extract data, and evaluate risk of bias independently. Agency for Healthcare Research and Quality methodology checklist will be used to assess the risk of bias. If feasible, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence, and use odds ratio for categorical data to explore potential risk factors. Prevalence estimates will be stratified according to age, gender, and other factors. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. We will conduct meta-regression to investigate the potential sources of heterogeneity, sensitivity analyses to assess robustness of the synthesized results, and funnel plots and Egger’s test to assess publication bias.

Discussion

This systematic review and meta-analysis will provide comprehensive evidence of the prevalence and potential risk factors of depression in Chinese patients with T2DM. We expect to provide evidence for healthcare practitioners and policy makers to pay attention to the mental health of patients with T2DM. Our data will highlight the need and importance of early detection and intervention for depression in patients with T2DM.

Systematic review registration

PROSPERO CRD42020182979.
Cross-national comparisons of health indicators require standardized definitions and common data sources
Authors: Tolonen Hanna , Reinikainen Jaakko , Koponen Päivikki , Elonheimo Hanna , Palmieri Luigi , Tijhuis Mariken J. ,   for the Joint Action on Health Information (InfAct)
Published: November 2021

Background

Health indicators are used to monitor the health status and determinants of health of the population and population sub-groups, identify existing or emerging health problems which would require prevention and health promotion activities, help to target health care resources in the most adequate way as well as for evaluation of the success of public health actions both at the national and international level. The quality and validity of the health indicator depends both on available data and used indicator definition. In this study we will evaluate existing knowledge about comparability of different data sources for definition of health indicators, compare how selected health indicators presented in different international databases possibly differ, and finally, present the results from a case study from Finland on comparability of health indicators derived from different data sources at national level.

Methods

For comparisons, four health indicators were selected that were commonly available in international databases and available for the Finnish case study. These were prevalence of obesity, hypertension, diabetes, and asthma in the adult populations. Our evaluation has three parts: 1) a scoping review of the latest literature, 2) comparison of the prevalences presented in different international databases, and 3) a case study using data from Finland.

Results

Literature shows that comparability of estimated outcomes for health indicators using different data sources such as self-reported questionnaire data from surveys, measured data from surveys or data from administrative health registers, varies between indicators. Also, the case study from Finland showed that diseases which require regular health care visits such as diabetes, comparability is high while for health outcomes which can remain asymptomatic for a long time such as hypertension, comparability is lower. In different international health related databases, country specific results differ due to variations in the used data sources but also due to differences in indicator definitions.

Conclusions

Reliable comparison of the health indicators over time and between regions within a country or across the countries requires common indicator definitions, similar data sources and standardized data collection methods.
Assessing the migratory histories, trophic positions, and conditions of lake sturgeon in the St. Croix and Mississippi Rivers using fin ray microchemistry, stable isotopes, and fatty acid profiles
Authors: Ziegeweid Jeffrey R. , Bartsch Michelle R. , Bartsch Lynn A. , Zigler Steven J. , Kennedy Robert J. , Love Seth A.
Published: November 2021

Background

Reproducing populations of invasive carps (Hypophthalmichthys spp.) could alter aquatic food webs and negatively affect native fishes in the Mississippi National River and Recreation Area (MISS) and the St. Croix National Scenic Riverway (SACN). However, proposed invasive carp barriers may also threaten populations of native migratory fishes by preventing movements of fish between rivers that are necessary for life history requirements. In this study, nonlethal chemical techniques were used to provide baseline data related to the condition, trophic position, and migratory histories of lake sturgeon (Acipenser fulvescens) captured in the Mississippi and St. Croix Rivers.

Results

Fish length and weight measurements and age estimates determined from pectoral fin rays demonstrated that lake sturgeon from the Mississippi River had greater lengths-at-age compared to sturgeon from the St. Croix River. However, length–weight relations were similar for sturgeon from the Mississippi and St. Croix Rivers. Lake sturgeon captured from different locations had distinguishable fatty acid signatures, and stable isotope analyses demonstrated that lake sturgeon from the Mississippi River generally feed at a higher trophic level than those in the St. Croix River. Strontium-to-calcium ratios (Sr:Ca) from fin ray cross sections indicated that sturgeon captured from the Mississippi River had higher Sr:Ca values than sturgeon captured from the St. Croix River, and natal origins and capture locations were not significantly different among sturgeon captured within individual rivers. Most sturgeon were captured in water with a similar Sr:Ca signature as their natal waters, indicating that there is some separation between populations of lake sturgeon in the St. Croix and Mississippi Rivers. However, Sr:Ca data indicated substantial variation in movement patterns among individual lake sturgeon, indicating that populations interact through migrations of individual fish between rivers.

Conclusions

Study results provide baseline condition and food web structure index data for assessing changes in lake sturgeon populations should invasive carps become established in these areas of the Mississippi and St. Croix Rivers. Controlled-exposure and telemetry studies would help verify and enhance the relations between Sr:Ca signatures in water and lake sturgeon pectoral fin rays to further assess mixing of sturgeons between rivers.
Serological responses to a soluble recombinant circumsporozoite protein-VK210 of Plasmodium vivax (rPvCSP-VK210) among Iranian malaria patients
Authors: Nateghpour Mehdi , Etemadi Soudabeh , Motevalli Haghi Afsaneh , Eslami Hamid , Mohebali Mehdi , Farivar Leila
Published: November 2021

Background

Circumsporozoite protein (CSP) has a central immune domain that includes short regions of repeating amino acid sequences. This immunodynamic region is an epitope of B cells that can elicit an immune response in human and laboratory animals. The aim of the present study was to express the recombinant PvCSP-VK210 antigen and evaluate it for assaying antibodies obtained during humanP. vivaxinfection by Western blotting and indirect ELISA (enzyme-linked immunosorbent assay).

Method

Genomic DNA ofP. vivaxwas isolated from a blood sample of an Iranian person with vivax malaria, and by PCR, the fragment of the PvCSP-VK210 gene was amplified. The gene fragment was cut after gel purification by BamHI and HindIII enzymes and then cloned into pET28a expression vector. Finally, the recombinant pET28a was transformed into theE.coliBL21 (DE3) as the expression host. In order to produce His-tagged protein, the expression host was cultured in LB medium. The protein was purified by Ni–NTA columns and immobilized metal affinity chromatography, and after confirmation by Western blotting technique, was used as the antigen in the indirect ELISA test.

Results

The recombinant protein was expressed and purified as a 32-kDa protein. The sensitivity and specificity of the indirect ELISA test with the recombinant PvCSP-VK210 antigen were 61.42% and 97.14%, respectively, based on OD  =  0.313. Between the results of the microscopic test and the indirect ELISA test with the recombinant PvCSP-VK210 antigen there was a Kappa coefficient of 0.586. The positive and negative predictive value and validity of the ELISA test with the recombinant PvCSP-VK210 antigen were 95.55%, 71.57%, 79.28%, respectively.

Conclusion

The sensitivity of the indirect ELISA method with the recombinant PvCSP-VK210 antigen was 61.42%, which is the first report from Iran.