bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Internal Validation of a Disability Algorithm for Multiple Sclerosis in Administrative Data
Authors: Marrie Ruth Ann , Tan Qier , Ekuma Okechukwu , Marriott James J.
Published: November 2021

Objective: We developed and internally validated an algorithm for disability status in multiple sclerosis (MS) using administrative data.

Methods: We linked administrative data from Manitoba, Canada to a clinical dataset with Expanded Disability Status Scale (EDSS) scores for people with MS. Clinical EDSS scores constituted the reference standard. We created candidate indicators using the administrative data. These included indicators based on use of particular health care services (home care, long-term care, rehabilitation admission), use of specific diagnostic codes (such as spasticity, quadriplegia), and codes based on use of Employment and Income Insurance. We developed algorithms to predict severe disability (EDSS ≥6.0), and to predict disability as a continuous measure. We manually developed algorithms, and also employed regression approaches. After we selected our preferred algorithms for disability, we tested their association with health care use due to any cause and infection after potential confounders.

Results: We linked clinical and administrative data for 1,767 persons with MS, most of whom were women living in urban areas. All individual indicators tested had specificities >90% for severe disability, and all but a diagnosis of visual disturbance had positive predictive values (PPV) >70%. The combination of home care or long-term care use or rehabilitation admission had a sensitivity of 61.9%, specificity of 90.76%, PPV of 70.06% and negative predictive of 87.21%. Based on regression modeling, the best-performing algorithm for predicting the EDSS as a continuous variable included age, home care use, long-term care admission, admission for rehabilitation, visual disturbance, other paralytic syndromes and spasticity. The mean difference between observed and predicted values of the EDSS was −0.0644 (95%CI −0.1632, 0.0304). Greater disability, whether measured using the clinical EDSS or either of the administrative data algorithms was similarly associated with increased hospitalization rates due to any cause and infection.

Conclusion: We developed and internally validated an algorithm for disability in MS using administrative data that may support population-based studies that wish to account for disability status but do not have access to clinical data sources with this information. We also found that more severe disability is associated with increased health care use, including due to infection.
A Systematic Review and Meta-Analysis of the Prevalence of Congenital Myopathy
Authors: Huang Kun , Bi Fang-Fang , Yang Huan
Published: November 2021

Background: Congenital myopathy constitutes a heterogeneous group of orphan diseases that are mainly classified on the basis of muscle biopsy findings. This study aims to estimate the prevalence of congenital myopathy through a systematic review and meta-analysis of the literature.

Methods: The PubMed, MEDLINE, Web of Science, and Cochrane Library databases were searched for original research articles published in English prior to July 30, 2021. The quality of the included studies was assessed by a checklist adapted from STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using the random effects model. Heterogeneity was assessed using the Cochrane Q statistic as well as the I2 statistic.

Results: A total of 11 studies were included in the systematic review and meta-analysis. Of the 11 studies included, 10 (90.9%) were considered medium-quality, one (9.1%) was considered low-quality, and no study was assessed as having a high overall quality. The pooled prevalence of congenital myopathy in the all-age population was 1.62 (95% CI, 1.13–2.11) per 100,000, while the prevalence in the child population was 2.76 (95% CI, 1.34–4.18) per 100,000. In the pediatric population, the prevalence among males was 2.92 (95% CI, −1.70 to 7.55) per 100,000, while the prevalence among females was 2.47 (95% CI, −1.67 to 6.61) per 100,000. The prevalence estimates of the all-age population per 100,000 were 0.20 (95% CI 0.10–0.35) for nemaline myopathy, 0.37 (95% CI 0.21–0.53) for core myopathy, 0.08 (95% CI −0.01 to 0.18) for centronuclear myopathy, 0.23 (95% CI 0.04–0.42) for congenital fiber-type disproportion myopathy, and 0.34 (95% CI, 0.24–0.44) for unspecified congenital myopathies. In addition, the prevalence estimates of the pediatric population per 100,000 were 0.22 (95% CI 0.03–0.40) for nemaline myopathy, 0.46 (95% CI 0.03–0.90) for core myopathy, 0.44 (95% CI 0.03–0.84) for centronuclear myopathy, 0.25 (95% CI −0.05 to 0.54) for congenital fiber-type disproportion myopathy, and 2.63 (95% CI 1.64–3.62) for unspecified congenital myopathies.

Conclusions: Accurate estimates of the prevalence of congenital myopathy are fundamental to supporting public health decision-making. The high heterogeneity and the lack of high-quality studies highlight the need to conduct higher-quality studies on orphan diseases.
Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease
Authors: Soman Smijin K. , Dagda Ruben K.
Published: November 2021

Mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson’s disease (PD). Consistent with this concept, loss of function mutations in the serine/threonine kinase- PINK1 (PTEN-induced putative kinase-1) causes autosomal recessive early onset PD. While the functional role of f-PINK1 (full-length PINK1) in clearing dysfunctional mitochondria via mitophagy is extensively documented, our understanding of specific physiological roles that the non-mitochondrial pool of PINK1 imparts in neurons is more limited. PINK1 is proteolytically processed in the intermembrane space and matrix of the mitochondria into functional cleaved products (c-PINK1) that are exported to the cytosol. While it is clear that posttranslational processing of PINK1 depends on the mitochondria’s oxidative state and structural integrity, the functional roles of c-PINK1 in modulating neuronal functions are poorly understood. Here, we review the diverse roles played by c-PINK1 in modulating various neuronal functions. Specifically, we describe the non-canonical functional roles of PINK1, including but not limited to: governing mitochondrial movement, neuronal development, neuronal survival, and neurogenesis. We have published that c-PINK1 stimulates neuronal plasticity and differentiation via the PINK1-PKA-BDNF signaling cascade. In addition, we provide insight into how mitochondrial membrane potential-dependent processing of PINK1 confers conditional retrograde signaling functions to PINK1. Further studies delineating the role of c-PINK1 in neurons would increase our understanding regarding the role played by PINK1 in PD pathogenesis.
Proteomic Profiling of Astrocytic O-GlcNAc Transferase-Related Proteins in the Medial Prefrontal Cortex
Authors: Fan Jun , Zhong Qiu-Ling , Mo Ran , Lu Cheng-Lin , Ren Jing , Mo Jia-Wen , Guo Fang , Wen You-Lu , Cao Xiong
Published: November 2021

The medial prefrontal cortex (mPFC), a key part of the brain networks that are closely related to the regulation of behavior, acts as a key regulator in emotion, social cognition, and decision making. Astrocytes are the majority cell type of glial cells, which play a significant role in a number of processes and establish a suitable environment for the functioning of neurons, including the brain energy metabolism. Astrocyte’s dysfunction in the mPFC has been implicated in various neuropsychiatric disorders. Glucose is a major energy source in the brain. In glucose metabolism, part of glucose is used to convert UDP-GlcNAc as a donor molecule for O-GlcNAcylation, which is controlled by a group of enzymes, O-GlcNAc transferase enzyme (OGT), and O-GlcNAcase (OGA). However, the role of O-GlcNAcylation in astrocytes is almost completely unknown. Our research showed that astrocytic OGT could influence the expression of proteins in the mPFC. Most of these altered proteins participate in metabolic processes, transferase activity, and biosynthetic processes. GFAP, an astrocyte maker, was increased after OGT deletion. These results provide a framework for further study on the role of astrocytic OGT/O-GlcNAcylation in the mPFC.
Multidimensional Mutational Profiling of the Indian HNSCC Sub-Population Provides IRAK1, a Novel Driver Gene and Potential Druggable Target
Authors: Desai Sagar Sanjiv , K Raksha Rao , Jain Anika , Bawa Pushpinder Singh , Dutta Priyatam , Atre Gaurav , Subhash Anand , Rao Vishal U. S. , J Suvratha , Srinivasan Subhashini , Choudhary Bibha
Published: November 2021

Head and neck squamous cell carcinomas (HNSCC) include heterogeneous group of tumors, classified according to their anatomical site. It is the sixth most prevalent cancer globally. Among South Asian countries, India accounts for 40% of HNC malignancies with significant morbidity and mortality. In the present study, we have performed exome sequencing and analysis of 51 Head and Neck squamous cell carcinoma samples. Besides known mutations in the oncogenes and tumour suppressors, we have identified novel gene signatures differentiating buccal, alveolar, and tongue cancers. Around 50% of the patients showed mutation in tumour suppressor genes TP53 and TP63. Apart from the known mutations, we report novel mutations in the genes AKT1, SPECC1, and LRP1B, which are linked with tumour progression and patient survival. A highly curated process was developed to identify survival signatures. 36 survival-related genes were identified based on the correlation of functional impact of variants identified using exome-seq with gene expression from transcriptome data (GEPIA database) and survival. An independent LASSO regression analysis was also performed. Survival signatures common to both the methods led to identification of 4 dead and 3 alive gene signatures, the accuracy of which was confirmed by performing a ROC analysis (AUC=0.79 and 0.91, respectively). Also, machine learning-based driver gene prediction tool resulted in the identification of IRAK1 as the driver (p-value = 9.7 e-08) and also as an actionable mutation. Modelling of the IRAK1 mutation showed a decrease in its binding to known IRAK1 inhibitors.
Glia Maturation Factor Beta as a Novel Biomarker and Therapeutic Target for Hepatocellular Carcinoma
Authors: Sun Wan , Hu Changchang , Wang Tianyu , Wang Juan , Zhang Jieping , Gao Furong , Ou Qingjian , Tian Haibin , Jin Caixia , Xu Jingying , Zhang Jingfa , Xu Guo-Tong , Lu Lixia
Published: November 2021

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. The novel sensitive biomarkers and therapeutic targets are urgently needed for the early diagnosis of HCC and improvement of clinical outcomes. Glia maturation factor-β (GMFB) is a growth and differentiation factor for both glia and neurons and has been found to be tightly involved in inflammation and neurodegeneration conditions. In our study, the expression level of GMFB was significantly up-regulated in patients with HCC and positively co-expression with tumor node metastases (TNM) stage and histopathological grade of HCC. The high expression level of GMFB was remarkably associated with poor overall survival, which mainly occurred in males rather than females. Multivariate analysis revealed GMFB to be an independent prognostic factor for overall survival in patients with HCC. Results of Gene Ontology (GO) and KEGG pathways analysis showed that down-regulation of pathways related to protein translation and mitochondria function were enriched. Protein-protein interaction analysis revealed the central role of mitochondria protein in HCC. The downregulation of genes involved in glycolysis and gluconeogenesis was observed among the co-expression genes of GMFB. Knockdown of GMFB in Hep3B significantly inhibited proliferation, migration, and invasion of Hep3B cells, and also downregulated the expression levels of some of metal matrix proteinase (MMP), increased mtDNA copy number and loss of mitochondrial transmembrane potential. GMFB influences the malignancy rate of HCC possibly through regulation of the expression of MMPs, mtDNA function and glycolysis. We proposed that GMFB was a promising HCC diagnostic and prognostic biomarker and therapeutic target in HCC.
High RPS27A Expression Predicts Poor Prognosis in Patients With HPV Type 16 Cervical Cancer
Authors: Wang Qiming , Cai Yan , Fu Xuewen , Chen Liang
Published: November 2021

In recent years, the incidence and the mortality rate of cervical cancer have been gradually increasing, becoming one of the major causes of cancer-related death in women. In particular, patients with advanced and recurrent cervical cancers present a very poor prognosis. In addition, the vast majority of cervical cancer cases are caused by human papillomavirus (HPV) infection, of which HPV16 infection is the main cause and squamous cell carcinoma is the main presenting type. In this study, we performed screening of differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) database and GSE6791, constructed a protein–protein interaction (PPI) network to screen 34 hub genes, filtered to the remaining 10 genes using the CytoHubba plug-in, and used survival analysis to determine that RPS27A was most associated with the prognosis of cervical cancer patients and has prognostic and predictive value for cervical cancer. The most significant biological functions and pathways of RPS27A enrichment were subsequently investigated with gene set enrichment analysis (GSEA), and integration of TCGA and GTEx database analyses revealed that RPS27A was significantly expressed in most cancer types. In this study, our analysis revealed that RPS27A can be used as a prognostic biomarker for HPV16 cervical cancer and has biological significance for the growth of cervical cancer cells.
Long Non−Coding RNA H19 Regulates Glioma Cell Growth and Metastasis via miR-200a-Mediated CDK6 and ZEB1 Expression
Authors: Chen Xuezhu , Li Yuhong , Zuo Chenghai , Zhang Kaiyuan , Lei Xuejiao , Wang Ju , Yang Yang , Zhang Jianmin , Ma Kang , Wang Shi , Mu Ning , Yang Chuanyan , Xian Jishu , Feng Hua , Tang Rongrui , Chen Tunan
Published: November 2021

Long non-coding RNAs (lncRNAs) serve essential roles on various biological functions. Previous studies have indicated that lncRNAs are involved in the occurrence, growth and infiltration of brain tumors. LncRNA H19 is key regulator in the pathogenesis of gliomas, but the underlying mechanisms of H19-regulated tumor progression remain unknown. Therefore, we investigated the effects and mechanism of action of lncRNA H19 on the homeostasis of glioma cells. As a novel oncogenic factor, up-regulation of H19 was able to promote the proliferation of glioma cells by targeting miR-200a. Furthermore, elevated miR-200a levels could reverse H19-induced cell growth and metastasis. Overexpression of miR-200a could significantly suppress the proliferation, migration and invasion of glioma cells. These biological behavior changes in glioma cells were dependent on the binding to potential target genes including CDK6 and ZEB1. CDK6 could promote cell proliferation and its expression was remarkably increased in glioma. In addition, up-regulation of miR-200a lead to reduction of CDK6 expression and inhibit the proliferation of glioma cells. ZEB1 could be a putative target gene of miR-200a in glioma cells. Thus, miR-200a might suppress cell invasion and migration through down-regulating ZEB1. Moreover, overexpression of miR-200a resulted in down-regulation of ZEB1 and further inhibited malignant phenotype of glioma cells. In summary, our findings suggested that the expression of H19 was elevated in glioma, which could promote the growth, invasion and migration of tumor cells via H19/miR-200a/CDK6/ZEB1 axis. This novel signaling pathway may be a promising candidate for the diagnosis and targeted treatment of glioma.
Clinical and Laboratory Characteristics of Kikuchi-Fujimoto Disease According to Age
Authors: Kim Hye-Young , Jo Ha Young , Kim Seong Heon
Published: November 2021

Background: Little information exists regarding the differences in the clinical and laboratory characteristics of Kikuchi-Fujimoto disease (KFD) according to age.

Objective: To evaluate the clinical and laboratory characteristics of KFD according to age.

Methods: The relevance of sex, age, clinical features, laboratory findings, courses, and follow-up results were retrospectively evaluated in patients diagnosed with KFD at Pusan National University Hospital between 2010 and 2020.

Results: Eighty patients (46 children and 34 adults) with a mean age of 21.5 ± 11.8 years (range, 3–49 years) were included in the study. Those aged 10–19 years accounted for the largest number of patients (42.5%). Among children, the male sex ratio was higher, especially for patients aged ≤ 9 years. In adults, the female sex ratio was higher, especially for patients aged 20–29 years. Fever, tenderness in the lymph node, and skin rashes were more common in children, while myalgia and weight loss were more common in adults. In children, the recurrence rate was significantly higher among boys than among girls (15.8 vs. 0.0%, P = 0.001); lower platelet count and higher CRP levels were observed among boys than among girls. EBV and ANA positivity rates were higher in boys than in girls. In adults, the recurrence rate was significantly higher in women than in men (18.2 vs. 0.0%, P = 0.005). ANA positivity rates were higher in women than in men.

Conclusion: The clinical features, laboratory findings, and recurrence of KFD may differ depending on age and sex. Clinicians should be aware of this.
TNF-α in Uveitis: From Bench to Clinic
Authors: Jiang Qi , Li Zhaohuai , Tao Tianyu , Duan Runping , Wang Xianggui , Su Wenru
Published: November 2021

Uveitis is an inflammation of the iris, ciliary body, vitreous, retina, or choroid, which has been shown to be the first manifestation of numerous systemic diseases. Studies about the immunopathogenesis and treatment of uveitis are helpful to comprehend systemic autoimmune diseases, and delay the progression of systemic autoimmune diseases, respectively. Tumor necrosis factor-alpha (TNF-α), a pleiotropic cytokine, plays a pivotal role in intraocular inflammation based on experimental and clinical data. Evidence of the feasibility of using anti-TNF-α agents for uveitis management has increased. Although there are numerous studies on TNF-α in various autoimmune diseases, the pathological mechanism and research progress of TNF-α in uveitis have not been reviewed. Therefore, the objective of this review is to provide a background on the role of TNF-α in the immunopathogenesis of uveitis, as well as from bench to clinical research progress, to better guide TNF-α-based therapeutics for uveitis.
Effects of Shexiang Baoxin Pill for Coronary Microvascular Function: A Systematic Review and Meta-Analysis
Authors: Wang Mengxi , Shan Yiwen , Sun Weixin , Han Jie , Tong Huaqin , Fan Manlu , Chen Jiandong , Yu Peng , Shen Le , Chen Xiaohu
Published: November 2021

Background: The coronary microvascular dysfunction has attracted more and more attention in recent years, but there is still a lack of effective treatment. Shexiang Baoxin Pill is one of the commonly used drugs for the treatment of coronary artery disease in China. More recently, some studies found that it has the effect of improving coronary microvascular function.

Objective: To evaluate the effects of Shexiang Baoxin Pill for coronary microvascular function.

Methods: Databases including MEDLINE, Web of Science, CNKI, Wanfang, The Cochrane Library, EMbase, VIP and CBM were searched from inception to June 2021 to screen out relevant clinical studies. The 2019 version 2 of the Cochrane risk of bias tool (RoB2) were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis.

Results: Eleven studies meeting the criteria were included, with a total of 1,075 patients. The results of meta-analysis showed that compared with conventional treatment alone, combination of Shexiang Baoxin Pill and conventional treatment can further increase the coronary flow reserve (CFR) [mean difference (MD) = 0.43, 95%CI (0.28, 0.58), p < 0.000 01], decrease the index of microvascular resistance (IMR) [MD = −4.23, 95%CI (−5.49, −2.97), p < 0.000 01], increase serum nitric oxide (NO) [MD = 11.96, 95%CI (2.74, 21.18), p = 0.001] and decrease serum hypersensitive C-reactive protein (hs-CRP) [MD = −2.49, 95%CI (−3.08, −1.90), p < 0.000 01], but did not increase the time of duration on the exercise testing (TET) [MD = 3.64, 95%CI (−1.17, 8.45), p = 0.14]. In terms of safety, a total of 10 patients developed adverse reactions in the intervention group and 17 patients developed adverse reactions in the control group.

Conclusion: Current evidence suggests that Shexiang Baoxin Pill may be effective in the improvement of coronary microvascular function when used in combination with conventional treatment. However, due to the low quality of the included studies, lack of placebo control and high heterogeneity among different studies, we should take a cautious attitude towards this conclusion. Moreover, the safety of Shexiang Baoxin Pill remains uncertain, more high-quality clinical studies are needed to verify the efficacy and safety of this drug in the future.

Systematic Review Registration: [website], identifier [registration number: CRD42021265113].
Advances in miR-132-Based Biomarker and Therapeutic Potential in the Cardiovascular System
Authors: Xu Kaizu , Chen Chungui , Wu Ying , Wu Meifang , Lin Liming
Published: November 2021

Atherosclerotic cardiovascular disease and subsequent heart failure threaten global health and impose a huge economic burden on society. MicroRNA-132 (miR-132), a regulatory RNA ubiquitously expressed in the cardiovascular system, is up-or down-regulated in the plasma under various cardiac conditions and may serve as a potential diagnostic or prognostic biomarker. More importantly, miR-132 in the myocardium has been demonstrated to be a master regulator in many pathological processes of ischemic or nonischemic heart failure in the past decade, such as myocardial hypertrophy, fibrosis, apoptosis, angiogenesis, calcium handling, neuroendocrine activation, and oxidative stress, through downregulating target mRNA expression. Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease.
Restoring the Extracellular Matrix: A Neuroprotective Role for Collagen Mimetic Peptides in Experimental Glaucoma
Authors: McGrady Nolan R. , Pasini Silvia , Baratta Robert O. , Del Buono Brian J. , Schlumpf Eric , Calkins David J.
Published: November 2021

Optic neuropathies are a major cause of visual disabilities worldwide, causing irreversible vision loss through the degeneration of retinal ganglion cell (RGC) axons, which comprise the optic nerve. Chief among these is glaucoma, in which sensitivity to intraocular pressure (IOP) leads to RGC axon dysfunction followed by outright degeneration of the optic projection. Current treatments focus entirely on lowering IOP through topical hypotensive drugs, surgery to facilitate aqueous fluid outflow, or both. Despite this investment in time and resources, many patients continue to lose vision, underscoring the need for new therapeutics that target neurodegeneration directly. One element of progression in glaucoma involves matrix metalloproteinase (MMP) remodeling of the collagen-rich extracellular milieu of RGC axons as they exit the retina through the optic nerve head. Thus, we investigated the ability of collagen mimetic peptides (CMPs) representing various single strand fractions of triple helix human type I collagen to protect RGC axons in an inducible model of glaucoma. First, using dorsal root ganglia maintained in vitro on human type I collagen, we found that multiple CMPs significantly promote neurite outgrowth (+35%) compared to vehicle following MMP-induced fragmentation of the α1(I) and α2(I) chains. We then applied CMP to adult mouse eyes in vivo following microbead occlusion to elevate IOP and determined its influence on anterograde axon transport to the superior colliculus, the primary RGC projection target in rodents. In glaucoma models, sensitivity to IOP causes early degradation in axon function, including anterograde transport from retina to central brain targets. We found that CMP treatment rescued anterograde transport following a 3-week +50% elevation in IOP. These results suggest that CMPs generally may represent a novel therapeutic to supplement existing treatments or as a neuroprotective option for patients who do not respond to IOP-lowering regimens.
Combating Dual Challenges in Maize Under High Planting Density: Stem Lodging and Kernel Abortion
Authors: Shah Adnan Noor , Tanveer Mohsin , Abbas Asad , Yildirim Mehmet , Shah Anis Ali , Ahmad Muhammad Irfan , Wang Zhiwei , Sun Weiwei , Song Youhong
Published: November 2021

High plant density is considered a proficient approach to increase maize production in countries with limited agricultural land; however, this creates a high risk of stem lodging and kernel abortion by reducing the ratio of biomass to the development of the stem and ear. Stem lodging and kernel abortion are major constraints in maize yield production for high plant density cropping; therefore, it is very important to overcome stem lodging and kernel abortion in maize. In this review, we discuss various morphophysiological and genetic characteristics of maize that may reduce the risk of stem lodging and kernel abortion, with a focus on carbohydrate metabolism and partitioning in maize. These characteristics illustrate a strong relationship between stem lodging resistance and kernel abortion. Previous studies have focused on targeting lignin and cellulose accumulation to improve lodging resistance. Nonetheless, a critical analysis of the literature showed that considering sugar metabolism and examining its effects on lodging resistance and kernel abortion in maize may provide considerable results to improve maize productivity. A constructive summary of management approaches that could be used to efficiently control the effects of stem lodging and kernel abortion is also included. The preferred management choice is based on the genotype of maize; nevertheless, various genetic and physiological approaches can control stem lodging and kernel abortion. However, plant growth regulators and nutrient application can also help reduce the risk for stem lodging and kernel abortion in maize.
Combined Transcriptome and Proteome Analysis to Elucidate Salt Tolerance Strategies of the Halophyte Panicum antidotale Retz
Authors: Hussain Tabassum , Asrar Hina , Zhang Wensheng , Gul Bilquees , Liu Xiaojing
Published: November 2021

Panicum antidotale, a C4 monocot, has the potential to reclaim saline and drylands and to be utilized as fodder and forage. Its adaptability to survive saline stress has been proven with eco-physiological and biochemical studies. However, little is known about its molecular mechanisms of salt tolerance. In this study, an integrated transcriptome and proteome analysis approach, based on RNA sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS), was used to identify the said mechanisms. Plants were treated with control (0 mM), low (100 mM), and high (300 mM) sodium chloride (NaCl) treatments to distinguish beneficial and toxic pathways influencing plant biomass. The results indicated differential expression of 3,179 (1,126 upregulated/2,053 downregulated) and 2,172 (898 upregulated/1,274 downregulated) genes (DEGs), and 514 (269 upregulated/245 downregulated) and 836 (494 upregulated/392 downregulated) proteins (DEPs) at 100 and 300 mM NaCl, respectively. Among these, most upregulated genes and proteins were involved in salt resistance strategies such as proline biosynthesis, the antioxidant defense system, ion homeostasis, and sugar accumulation at low salinity levels. On the other hand, the expression of several genes and proteins involved in the respiratory process were downregulated, indicating the inability of plants to meet their energy demands at high salinity levels. Moreover, the impairments in photosynthesis were also evident with the reduced expression of genes regulating the structure of photosystems and increased expression of abscisic acid (ABA) mediated pathways which limits stomatal gas exchange. Similarly, the disturbance in fatty acid metabolism and activation of essential ion transport blockers damaged the integrity of the cell membrane, which was also evident with enhanced malondialdehyde (MDA). Overall, the analysis of pathways revealed that the plant optimal performance at low salinity was related to enhanced metabolism, antioxidative defense, cell growth, and signaling pathways, whereas high salinity inhibited biomass accumulation by altered expression of numerous genes involved in carbon metabolism, signaling, transcription, and translation. The data provided the first global analysis of the mechanisms imparting salt stress tolerance of any halophyte at transcriptome and proteome levels.
Factors Influencing Pre-service Teachers' Intention to Use Digital Learning Materials: A Study Conducted During the COVID-19 Pandemic in Germany
Authors: Paetsch Jennifer , Drechsel Barbara
Published: November 2021

The COVID-19 pandemic necessitated an abrupt change in university teacher education, in that most face-to-face courses were replaced by online education, which had a profound impact on students. Pandemic distance learning required students to possess a high degree of self-regulation concerning their learning environment and to find new ways of communicating with their peers and instructors. At the same time, the novel situation offered opportunities to experience new educational applications. To learn more about the possible benefits of distance learning, this study examines how the first online semester during the pandemic contributed to pre-service teachers' intentions to use digital learning materials in the future. Pre-service teachers enrolled in a German university (n = 348) answered an online questionnaire at the end of the summer term of 2020. Findings from structural equation modeling showed that the perceived quality of teacher training during the online semester and self-reported improvements in digital skills predicted significantly students' intentions to use digital learning materials for future teaching. Moreover, results revealed that attentional regulation predicted perceived quality of teacher training and self-reported improvements in digital skills during distance learning. Thus, attentional regulation had a significant indirect effect on pre-service teachers' behavioral intentions. The indirect effects of other resource management strategies (effort and time management) and intrinsic motivation were not significant. Our results show that the quality of online instruction was an important factor in student teachers' learning processes during the pandemic. Based on our results, we discuss implications for the promotion of pre-service teachers' intentions to use digital learning materials for teaching in schools.
The Need for a Paradigm Shift in Approaching Ageing-Related Design Research and Practice
Authors: Comincioli Elena , Chirico Alice , Gaggioli Andrea , Masoodian Masood
Published: November 2021

Despite a rapidly ageing world population, ageism – particularly in its implicit form – is widespread in society. In this article, we propose that a paradigm shift is needed in how we approach ageing-related design research and practice in areas such as assistive technologies. We also put forward the idea of using the Healthy Ageing (HA) framework of the WHO as the basis for new lines actions that can be taken by design researchers and practitioners to address implicit ageism in society through their work.
The Roles of Salience and Value in Inattention Among Children With Attention-Deficit/Hyperactivity Disorder: A Pilot Investigation
Authors: Musser Erica D. , Morris Stephanie S. J. , Feeney Kathleen , Pintos Lobo Rosario , Ester Edward F.
Published: November 2021

Although inattention is a key symptom subdomain of attention-deficit/hyperactivity disorder (ADHD), the mechanisms underlying this subdomain and related symptoms remain unclear. There is a need for more granular approaches that allow for greater specificity in linking disruptions in specific domains of cognitive performance (e.g., executive function and reward processing) with behavioral manifestations of ADHD. Such approaches may inform the development of more targeted therapeutic interventions. Here, we describe the results of a pilot study of elementary-aged children (ages 6–12years) with ADHD (n=50) and typically developing children (n=48) utilizing a cognitive science task designed to target two dissociable mechanisms of attentional selection: a goal-driven mechanism (i.e., reward/value-driven) and a salience-driven mechanism. Participants were asked to optimally extract and combine information about stimulus salience and value to maximize rewards. While results of this pilot study are ambiguous due to the small sample size and limited number of task trials, data suggest that neither participants with ADHD nor typically developing participants performed optimally to maximize rewards, though typically developing participants were somewhat more successful at the task (i.e., more likely to report high-value targets) regardless of task condition. Further, the manuscript examines several follow-up questions regarding group differences in task response times and group differences in task performance as related to sustained attention across the duration of the task. Finally, the manuscript examines follow-up questions related to heterogeneity in the ADHD group (i.e., age, DSM 5 presentation, and comorbid diagnosis) in predicting task performance.
Serum Lipid Concentrations Are Associated With Negative Mental Health Outcomes in Healthy Women Aged 35–49 Years
Authors: Yu Jingjie , Zhang Zhihui , Li Chunjun , Zhang Jiarui , Ding Zengbo , Zhu Weili , Wang Qiang
Published: November 2021

Background: Although the relevant underlying biological mechanisms are still lacking, mental disorders have been closely associated with several metabolic abnormalities including high rates of obesity and metabolic syndrome especially in vulnerable populations. Therefore, the current study aims to examine how metabolic parameters increase the risk for developing mood disorders in individuals stratified by gender and age.

Methods: In a routine physical examination, 319 healthy participants were recruited and assigned to six different groups according to age (young adults: 25–34 Y, middle age: 35–49 Y, and older age: 50–65 Y) in both males and females. A linear regression and bivariate correlation analysis were used to analyze the relationship between mood health outcomes measured by the Kessler 10 Psychological Distress Scale (K10) and the metabolic function.

Results: The results demonstrated that there was a significant association between K10 scores and metabolic parameters, including Body Mass Index (BMI), total-, LDL-cholesterol, and triglyceride. Furthermore, poor mental health (higher K10 scores) was observed in individuals with increased BMI, total-, LDL-cholesterol, and triglyceride levels particularly in middle-aged women relative to other groups.

Limitations: This is a cross-sectional study with a small sample size and lacks longitudinal follow-up evidence and preventive interventions and therefore could not provide the causal inference of metabolic pathophysiology on the increased sensitivity to mental disorders.

Conclusions: The potential association suggests that targeting of the metabolic parameters might give us a better understanding of the underlying mechanisms of psychiatric diseases and provide preventive strategies and potential treatment for those with metabolic disturbances especially in middle-aged females.
The Cost of Plastics in Compost
Authors: Yesaya Mabvuto , Mpanang'ombe Wrixon , Tilley Elizabeth
Published: November 2021

In urban Blantyre, there is ample green-waste and widespread interest in compost, but the feedstock is often contaminated with plastics. If composting is going to become more widely implemented, it must be profitable and ideally, competitive with chemical nutrients, however the time and cost associated with plastics removal is currently a bottleneck to profitability. In this study we investigated the financial sustainability of compost production using a Time-Driven Activity-Based Costing method over 16-weeks to identify the types and duration of each activity required. Combining these data with capital and operating costs, we then modeled the profitability of the facility to identify cost-bottlenecks and to determine scenarios that would lead to improved profitability. The results show that it took 1 h 50 min of labor to produce 165-L (0.065 m3) bag of compost. A total of 12.3% of the active labor time was spent sorting out plastics from the organic waste before composting, during composting and from the finished product before packaging. Until similar work is published on the topic, these values cannot be evaluated as being either optimal or wasteful, but rather, serve as a baseline against which future interventions—e.g., source separation, especially at markets can be evaluated. Though based in Malawi, the documented and modeled costs can be converted and scaled by other entrepreneurs/agencies who are interested in estimating the financial feasibility of composting in their own context.
Prevalence and Demographic Risk Factors of Mycobacterium tuberculosis Infections in Captive Asian Elephants (Elephas maximus) Based on Serological Assays
Authors: Angkwanish Taweepoke , Vernooij Hans J. C. M. , Sirimalaisuwan Anucha , Charernpan Pattara , Nielen Mirjam , Rutten Victor P. M. G.
Published: November 2021

To address putative TB statuses of elephants and to identify and quantify potential demographic risk factors for TB, three ELISAs specific for different mycobacterial antigens (ESAT6, CFP10, MPB83) and the TB Stat-Pak assay were used as surrogate serological markers for TB infection in elephants. In view of the low number of animals of which the infected status could be confirmed (4 out of 708) Latent Class Analyses of TB serology test outcomes was used to predict the putative TB status of each of 708 elephants as positive (17.3%), inconclusive (48.7%), or negative (34%) when assessed on a population basis. Correlation between test performance of the individual assays was high between the ELISAs, but low with that of the TB Stat-Pak assay. Risk factors, assessed based on cut off values for each of the ELISAs determined by ROC analysis, included sex, BCS, age, working time, feed type, management system, camp size and region. Old age elephants were more likely to show a positive TB serology test outcome, than younger ones. Elephants working 7 h per day and the ones in good condition BCS (7–11) were less likely to be positive in TB serology testing. In addition, fewer animals in the large camp size (31–50 elephants) were found to be positive in ELISA tests, compared to elephants in the other camp sizes. In this study, the North region had the lowest percentages of elephants with positive TB test outcome, the West region and to a lesser extend the other regions showed clearly higher percentages of positive animals. Even though assays used in the present study have not been validated yet, results obtained showed promise as diagnostic or screening tests. For the diagnosis of animals suspected to be infected, the ELISA tests, once further optimized for the individual antigens, can be used in parallel. For screening of complete camps for presence or absence of infection, a single optimized ELISA test can be utilized.
Design and Experiment of the Buckwheat Hill-Drop Planter Hole Forming Device
Authors: Chen Yu , Cheng Yuming , Chen Jun , Zheng Zhiqi , Hu Chenwei , Cao Jiayu
Published: November 2021

The hole forming device is an important element of the buckwheat hill-drop planter, and its design level directly affects the seeding quality of the hill-drop planter. A hole forming device with a duckbill structure is widely used in hill-drop planters for wheat, cotton, peanuts, etc. According to the requirements of buckwheat seeding operations, this study designs the components of the duckbill hole forming device. It is determined that the duckbill upper jaw length is 65 mm, the duckbills number is 10, the pressure plate on the spring side length is 90 mm, the duckbill opening size is 8.79 mm, and the duckbill effective opening time is 0.1 s. Through co-simulation analysis of discrete element software EDEM (DEM-Solutions, Edinburgh, United Kingdom) and multi-body dynamics software RecurDyn (FunctionBay, Inc., Seongnam-si, South Korea), it is measured that when the pressure plate on the spring side is directly below the rotation axis of the dibber wheel, the spring compression is 33.3 mm, the pressure on the pressure plate is 95–102.6 N, and the contact time of a single duckbill with the soil is 0.2 s at a speed of 40 r/min. Based on the results of the design and simulation analysis, the large end diameter, small end diameter, original length and wire diameter of the duckbill spring are 36 mm, 26 mm, 60 mm, and 1.8 mm, respectively. An experimental bench for the seeding wheel of a buckwheat hill-drop planter was built, and three wire diameter duckbill springs of 1.6 mm, 1.8 mm and 2.0 mm were tested to verify the simulation and calculation results. The experimental results show that the optimal wire diameter of the duckbill spring is 1.8 mm. Finally, a single factor experiment of the dibber wheel rotation speed was carried out. The experimental results show that when the rotation speed of the dibber wheel is 40–65 r/min, the seeding qualification rate, seeding void hole rate and seeding damage rate of the buckwheat hill-drop planter are ≥85.3%, 0, and <0.3%, respectively. This study provides a basis and reference for the hole forming device design of a buckwheat hill-drop planter.
Contribution of Awns to Seed Yield and Seed Shattering in Siberian Wildrye Grown under Irrigated and Rainfed Environments
Authors: Ntakirutimana Fabrice , Wan Yiyang , Liu Wenhui , Xie Wengang
Published: November 2021

The seed yield of grass species is greatly dependent on inflorescence morphological traits, starting with spikelets per inflorescence and seeds per spikelet, to kernel size, and then to awns. Previous studies have attempted to estimate the contribution of these traits on the harvested yield of major cereal crops, but little information can be accessed on the influence of awns on seed yield of forage grass species. Siberian wildrye (Elymus sibiricus L.) is a widely important perennial forage grass used to increase forage production in arid and semi-arid grasslands. The grass has long inflorescences with long awns developed at the tip end of the lemmas in the florets. In order to evaluate the effect of awns on Siberian wildrye seed production, awn excision analyses from 10 accessions were performed at flowering stage under irrigated and rainfed regimes. Overall, awn excision reduced thousand-seed weight and seed size under both irrigated and rainfed regimes, which decreased final seed yield per plant. De-awned plants produced significantly more seeds per inflorescence, but spikelets per inflorescence was not influenced by awn excision in either condition. Moreover, histological analyses showed a high degradation of the abscission layer in the awned plants than de-awned ones, and awn excision evidently improved average seed breaking tensile strength (BTS), and thus decreased the degree of seed shattering. In conclusion, the observed significant impact of awn excision on different yield-related traits mirrored the impact of awns on the performance of Siberian wildrye under diverse growing conditions. These results provide useful information for plant breeders, seed producers, and researchers to efficiently improve seed production in Siberian wildrye.
In Vitro Studies on the Influence of Meloxicam on Cytotoxic Activity Induced by Risedronate Sodium in Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines
Authors: Poradowski Dominik , Janus Izabela , Chrószcz Aleksander , Obmińska-Mrukowicz Bożena
Published: November 2021

The study describes the cytotoxic effect against human and canine osteosarcoma (U-2 OS and D-17) cell lines induced by risedronate sodium and meloxicam per se and in combination. Both cell lines were prepared according to standard procedures for cell cultures studies. The cell viability was estimated in both cell lines treated with chosen concentrations of risedronate sodium and meloxicam. The apoptosis assessment was carried out using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. EC50 values, computed for risedronate sodium and meloxicam cytotoxicity, showed comparable effects against the canine OS cell line in similar concentration of both drugs. In case of human OS, the stronger cytotoxic effect of risedronate sodium was proved. The EC50 values for meloxicam in both cell lines were, statistically, significantly different (* p < 0.05). Moreover, the cytotoxic effect of a combined administration of meloxicam and risedronate sodium in doses 100 µg/mL, compared with the negative control showed statistically significant differences. The human OS cell line was more resistant to both compounds than the canine OS cell line. The apoptotic effect in canine and human osteosarcoma triggered by risedronate sodium and meloxicam was statistically significant (p < 0.05). The cytotoxic effect induced with 100 µg/mL of risedronate sodium proved statistically significant differences between both tested cell lines compared to negative control. The results obtained with 10 and 100 µg/mL of meloxicam were not statistically significant. The study showed the synergic mechanism of action of risedronate sodium and meloxicam, but the concentrations used in vitro will not be possible to achieve in in vivo. Therefore, our results serve as basis only to design future studies on the tissue level.