bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and Predictive Value of BGN in Colon Cancer Outcomes and Response to Immunotherapy
Authors: He Zi-Xuan , Zhao Sheng-Bing , Fang Xue , E Ji-Fu , Fu Hong-Yu , Song Yi-Hang , Wu Jia-Yi , Pan Peng , Gu Lun , Xia Tian , Liu Yi-Long , Li Zhao-Shen , Wang Shu-Ling , Bai Yu
Published: January 2022

Background

Colon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation.

Methods

The differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms.

Results

BGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients.

Conclusion

BGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.
Characterization of Synonymous BRCA1:c.132C>T as a Pathogenic Variant
Authors: Li Jun , Wang Ping , Zhang Cuiyun , Han Sile , Xiao Han , Liu Zhiyuan , Wang Xiaoyan , Liu Weiling , Wei Bing , Ma Jie , Li Hongle , Guo Yongjun
Published: January 2022

Breast cancer gene 1 (BRCA1) and BRCA2 are tumor suppressors involved in DNA damage response and repair. Carriers of germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2 have significantly increased lifetime risks of breast cancer, ovarian cancer, and other cancer types; this phenomenon is known as hereditary breast and ovarian cancer (HBOC) syndrome. Accurate interpretation of BRCA1 and BRCA2 variants is important not only for disease management in patients, but also for determining preventative measures for their families. BRCA1:c.132C>T (p.Cys44=) is a synonymous variant recorded in the ClinVar database with “conflicting interpretations of its pathogenicity”. Here, we report our clinical tests in which we identified this variant in two unrelated patients, both of whom developed breast cancer at an early age with ovarian presentation a few years later and had a family history of relevant cancers. Minigene assay showed that this change caused a four-nucleotide loss at the end of exon 3, resulting in a truncated p.Cys44Tyrfs*5 protein. Reverse transcription-polymerase chain reaction identified two fragments (123 and 119 bp) using RNA isolated from patient blood samples, in consistency with the results of the minigene assay. Collectively, we classified BRCA1:c.132C>T (p.Cys44=) as a pathogenic variant, as evidenced by functional studies, RNA analysis, and the patients’ family histories. By analyzing variants recorded in the BRCA Exchange database, we found synonymous changes at the ends of exons could potentially influence splicing; meanwhile, current in silico tools could not predict splicing changes efficiently if the variants were in the middle of an exon, or in the deep intron region. Future studies should attempt to identify variants that influence gene expression and post-transcription modifications to improve our understanding of BRCA1 and BRCA2, as well as their related cancers.
Procedural Pain Assessment in Infants Without Analgosedation: Comparison of Newborn Infant Parasympathetic Evaluation and Skin Conductance Activity - A Pilot Study
Authors: Walas Wojciech , Halaba Zenon P. , Szczapa Tomasz , Latka-Grot Julita , Maroszyńska Iwona , Malinowska Ewelina , Rutkowska Magdalena , Kubiaczyk Agata , Wrońska Monika , Skrzypek Michał , De Jonckheere Julien , Jean-Noel Mickael , Piotrowski Andrzej
Published: January 2022

Objective: New technologies to measure pain responses, such as heart rate variability and skin conductance hold promise in the development of tools that can be reliable and quantifiable of detecting pain. The main objective of this study was to assess the capability of two monitors i.e., Newborn Infant Parasympathetic Evaluation (NIPE) and Skin Conductance Algesimeter for detecting procedural pain in non-anesthetized infants.

Materials and Methods: Thirty-three non-anesthetized infants were enrolled to the study. To detect pain caused by heel stick, NIPE, and Skin Conductance monitors and behavioral pain scales were used. Three minutes before and just after heel stick, pain was evaluated by behavioral scales, and simultaneously over the whole period by NIPE and SCA.

Results: A statistically significant decrease of NIPE Index and an increase of SCA values were found after the HS procedure. There were no statistically significant differences between the decrease in NIPEi values and the increase in PPS values between subgroups based on pain assessment by behavioral-scale scores.

Conclusion: Both NIPE and SCA can be useful for detection of procedural pain and may constitue an additional valuable tool for better handling of pain among patients treated in NICUs. More studies on larger groups of patients are needed.
PAX2 Mutation-Related Renal Hypodysplasia: Review of the Literature and Three Case Reports
Authors: Chang Yu-Ming , Chen Chih-Chia , Lee Ni-Chung , Sung Junne-Ming , Chou Yen-Yin , Chiou Yuan-Yow
Published: January 2022

Paired box 2 (PAX2)-related disorder is an autosomal dominant genetic disorder associated with kidney and eye abnormalities and can result in end stage renal disease (ESRD). Despite reported low prevalence of PAX2 mutations, the prevalence of PAX2 related disorders may have been underestimated in past studies. With improved genetic sequencing techniques, more genetic abnormalities are being detected than ever before. Here, we report three patients from two families with PAX2 mutations identified within 1 year. Two patients were adults with chronic kidney disease and were followed for decades without correct diagnoses, including one with ESRD who had even undergone kidney transplant. The third patient was a neonate in whom PAX2-related disorder manifested as oligohydramnios, coloboma, and renal failure that progressed to ESRD within 1 year after birth. The phenotypes of PAX2 gene mutation were shown to be highly variable, even within the same family. Early detection promoted genetic counseling and guided clinical management. The appropriate time point for genetic study is an important issue. Clinicians must be more alert for PAX2 mutation when facing patients with congenital kidney and urinary tract anomalies, chronic kidney disease of unknown etiology, involvement of multiple systems, and/or a family history of renal disease.
Magnetic Resonance Imaging-Proton Density Fat Fraction vs. Transient Elastography-Controlled Attenuation Parameter in Diagnosing Non-alcoholic Fatty Liver Disease in Children and Adolescents: A Meta-Analysis of Diagnostic Accuracy
Authors: Jia Shuangzhen , Zhao Yuzhen , Liu Jiaqi , Guo Xu , Chen Moxian , Zhou Shaoming , Zhou Jianli
Published: January 2022

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents, and its prevalence increases with obesity. Magnetic resonance imaging (MRI) and transient elastography (TE) have been widely used to non-invasively evaluate NAFLD in adults. This study aimed to determine the efficacy and accuracy of MRI-proton density fat fraction (MRI-PDFF) and TE-controlled attenuation parameter (TE-CAP) in distinguishing hepatic steatosis in children and adolescents.

Materials and Methods: In this meta-analysis, the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases were searched for articles that reported studies on the accuracy of MRI-PDFF or TE-CAP in grading the steatosis in children and adolescents with NAFLD. This study compared the sensitivity, specificity, and hierarchical summary receiver operating characteristic curves (HSROCs) of MRI-PDFF and TE-CAP in distinguishing between steatosis grades S0 and S1–3.

Results: A total of eight articles involving 874 children and adolescents with NAFLD were included in this study. The proportions of steatosis grades were 5 and 95% for S0 and S1–3, respectively. MRI-PDFF accurately diagnosed S1–3 steatosis, with a summary sensitivity of 0.95 (95% CI, 0.92–0.97), specificity of 0.92 (95% CI, 0.77–0.98), and HSROC of 0.96 (95% CI, 0.94–0.98). Likewise, TE-CAP accurately diagnosed S1–3 steatosis, with a summary sensitivity of 0.86 (95% CI, 0.70–0.94), specificity of 0.88 (95% CI, 0.71–0.96), and HSROC of 0.94 (95% CI, 0.91–0.95). Following a “positive” measurement (over the threshold value) for S1–3, the corresponding post-test probabilities of MRI-PDFF and TE-CAP for the presence of steatosis reached 92 and 88%, respectively, at the pretest probability of 50%. When the values were below the mentioned threshold values (“negative” results), the post-test probabilities of MRI-PDFF and TE-CAP became 5 and 13%, respectively.

Conclusion: Both MRI-PDFF and TE-CAP are highly accurate non-invasive methods to grade the hepatic steatosis in children and adolescents with NAFLD. Furthermore, MRI-PDFF is significantly more accurate in assessing steatosis grade than TE-CAP.

Systematic Review Registration: PROSPERO, identifier: CRD42021220422.
Eszopiclone and Zolpidem Produce Opposite Effects on Hippocampal Ripple Density
Authors: Becker Logan A. , Penagos Hector , Flores Francisco J. , Manoach Dara S. , Wilson Matthew A. , Varela Carmen
Published: January 2022

Clinical populations have memory deficits linked to sleep oscillations that can potentially be treated with sleep medications. Eszopiclone and zolpidem (two non-benzodiazepine hypnotics) both enhance sleep spindles. Zolpidem improved sleep-dependent memory consolidation in humans, but eszopiclone did not. These divergent results may reflect that the two drugs have different effects on hippocampal ripple oscillations, which correspond to the reactivation of neuronal ensembles that represent previous waking activity and contribute to memory consolidation. We used extracellular recordings in the CA1 region of rats and systemic dosing of eszopiclone and zolpidem to test the hypothesis that these two drugs differentially affect hippocampal ripples and spike activity. We report evidence that eszopiclone makes ripples sparser, while zolpidem increases ripple density. In addition, eszopiclone led to a drastic decrease in spike firing, both in putative pyramidal cells and interneurons, while zolpidem did not substantially alter spiking. These results provide an explanation of the different effects of eszopiclone and zolpidem on memory in human studies and suggest that sleep medications can be used to regulate hippocampal ripple oscillations, which are causally linked to sleep-dependent memory consolidation.
Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews
Authors: Song Yun-Kyoung , Song Junu , Kim Kyungim , Kwon Jin-Won
Published: January 2022

The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.
Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus
Authors: Yang Yang , Luan Ying , Feng Qi , Chen Xing , Qin Bo , Ren Kai-Di , Luan Yi
Published: January 2022

Diabetes mellitus is a global public health challenge with high morbidity. Type 2 diabetes mellitus (T2DM) accounts for 90% of the global prevalence of diabetes. T2DM is featured by a combination of defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. However, the pathogenesis of this disease is complicated by genetic and environmental factors, which needs further study. Numerous studies have demonstrated an epigenetic influence on the course of this disease via altering the expression of downstream diabetes-related proteins. Further studies in the field of epigenetics can help to elucidate the mechanisms and identify appropriate treatments. Histone methylation is defined as a common histone mark by adding a methyl group (-CH3) onto a lysine or arginine residue, which can alter the expression of downstream proteins and affect cellular processes. Thus, in tthis study will discuss types and functions of histone methylation and its role in T2DM wilsed. We will review the involvement of histone methyltransferases and histone demethylases in the progression of T2DM and analyze epigenetic-based therapies. We will also discuss the potential application of histone methylation modification as targets for the treatment of T2DM.
Template Matching and Matrix Profile for Signal Quality Assessment of Carotid and Femoral Laser Doppler Vibrometer Signals
Authors: Seoni Silvia , Beeckman Simeon , Li Yanlu , Aasmul Soren , Morbiducci Umberto , Baets Roel , Boutouyrie Pierre , Molinari Filippo , Madhu Nilesh , Segers Patrick
Published: January 2022

Background: Laser-Doppler Vibrometry (LDV) is a laser-based technique that allows measuring the motion of moving targets with high spatial and temporal resolution. To demonstrate its use for the measurement of carotid-femoral pulse wave velocity, a prototype system was employed in a clinical feasibility study. Data were acquired for analysis without prior quality control. Real-time application, however, will require a real-time assessment of signal quality. In this study, we (1) use template matching and matrix profile for assessing the quality of these previously acquired signals; (2) analyze the nature and achievable quality of acquired signals at the carotid and femoral measuring site; (3) explore models for automated classification of signal quality.

Methods: Laser-Doppler Vibrometry data were acquired in 100 subjects (50M/50F) and consisted of 4–5 sequences of 20-s recordings of skin displacement, differentiated two times to yield acceleration. Each recording consisted of data from 12 laser beams, yielding 410 carotid-femoral and 407 carotid-carotid recordings. Data quality was visually assessed on a 1–5 scale, and a subset of best quality data was used to construct an acceleration template for both measuring sites. The time-varying cross-correlation of the acceleration signals with the template was computed. A quality metric constructed on several features of this template matching was derived. Next, the matrix-profile technique was applied to identify recurring features in the measured time series and derived a similar quality metric. The statistical distribution of the metrics, and their correlates with basic clinical data were assessed. Finally, logistic-regression-based classifiers were developed and their ability to automatically classify LDV-signal quality was assessed.

Results: Automated quality metrics correlated well with visual scores. Signal quality was negatively correlated with BMI for femoral recordings but not for carotid recordings. Logistic regression models based on both methods yielded an accuracy of minimally 80% for our carotid and femoral recording data, reaching 87% for the femoral data.

Conclusion: Both template matching and matrix profile were found suitable methods for automated grading of LDV signal quality and were able to generate a quality metric that was on par with the signal quality assessment of the expert. The classifiers, developed with both quality metrics, showed their potential for future real-time implementation.
Emerging Roles for Aberrant Astrocytic Calcium Signals in Parkinson’s Disease
Authors: Bancroft Eric A. , Srinivasan Rahul
Published: January 2022

Astrocytes display a plethora of spontaneous Ca2+ signals that modulate vital functions of the central nervous system (CNS). This suggests that astrocytic Ca2+ signals also contribute to pathological processes in the CNS. In this context, the molecular mechanisms by which aberrant astrocytic Ca2+ signals trigger dopaminergic neuron loss during Parkinson’s disease (PD) are only beginning to emerge. Here, we provide an evidence-based perspective on potential mechanisms by which aberrant astrocytic Ca2+ signals can trigger dysfunction in three distinct compartments of the brain, viz., neurons, microglia, and the blood brain barrier, thereby leading to PD. We envision that the coming decades will unravel novel mechanisms by which aberrant astrocytic Ca2+ signals contribute to PD and other neurodegenerative processes in the CNS.
Constipation Caused by Anti-calcitonin Gene-Related Peptide Migraine Therapeutics Explained by Antagonism of Calcitonin Gene-Related Peptide’s Motor-Stimulating and Prosecretory Function in the Intestine
Authors: Holzer Peter , Holzer-Petsche Ulrike
Published: January 2022

The development of small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) and of monoclonal antibodies targeting the CGRP system has been a major advance in the management of migraine. In the randomized controlled trials before regulatory approval, the safety of these anti-CGRP migraine therapeutics was considered favorable and to stay within the expected profile. Post-approval real-world surveys reveal, however, constipation to be a major adverse event which may affect more than 50% of patients treated with erenumab (an antibody targeting the CGRP receptor), fremanezumab or galcanezumab (antibodies targeting CGRP). In this review article we address the question whether constipation caused by inhibition of CGRP signaling can be mechanistically deduced from the known pharmacological actions and pathophysiological implications of CGRP in the digestive tract. CGRP in the gut is expressed by two distinct neuronal populations: extrinsic primary afferent nerve fibers and distinct neurons of the intrinsic enteric nervous system. In particular, CGRP is a major messenger of enteric sensory neurons which in response to mucosal stimulation activate both ascending excitatory and descending inhibitory neuronal pathways that enable propulsive (peristaltic) motor activity to take place. In addition, CGRP is able to stimulate ion and water secretion into the intestinal lumen. The motor-stimulating and prosecretory actions of CGRP combine in accelerating intestinal transit, an activity profile that has been confirmed by the ability of CGRP to induce diarrhea in mice, dogs and humans. We therefore conclude that the constipation elicited by antibodies targeting CGRP or its receptor results from interference with the physiological function of CGRP in the small and large intestine in which it contributes to the maintenance of peristaltic motor activity, ion and water secretion and intestinal transit.
The Phloem Intercalated With Xylem-Correlated 3 Receptor-Like Kinase Constitutively Interacts With Brassinosteroid Insensitive 1-Associated Receptor Kinase 1 and Is Involved in Vascular Development in Arabidopsis
Authors: Xu Ke , Jourquin Joris , Njo Maria Fransiska , Nguyen Long , Beeckman Tom , Fernandez Ana Ibis
Published: January 2022

Leucine-rich repeat receptor-like kinases (LRR-RLKs) play fundamental roles in cell-to-cell and plant-environment communication. LRR-RLKs can function as receptors perceiving endogenous or external ligands, or as coreceptors, which stabilize the complex, and enhance transduction of the intracellular signal. The LRR-RLK BAK1 is a coreceptor for different developmental and immunity pathways. In this article, we identified PXY-CORRELATED 3 (PXC3) as a BAK1-interacting LRR-RLK, which was previously reported to be transcribed in vascular tissues co-expressed with PHLOEM INTERCALATED WITH XYLEM (PXY), the receptor of the TDIF/CLE41 peptide. Characterization of pxc3 loss-of-function mutants revealed reduced hypocotyl stele width and vascular cells compared to wild type, indicating that PXC3 plays a role in the vascular development in Arabidopsis. Furthermore, our data suggest that PXC3 might function as a positive regulator of the CLE41/TDIF–TDR/PXY signaling pathway.
Improve Soybean Variety Selection Accuracy Using UAV-Based High-Throughput Phenotyping Technology
Authors: Zhou Jing , Beche Eduardo , Vieira Caio Canella , Yungbluth Dennis , Zhou Jianfeng , Scaboo Andrew , Chen Pengyin
Published: January 2022

The efficiency of crop breeding programs is evaluated by the genetic gain of a primary trait of interest, e.g., yield, achieved in 1 year through artificial selection of advanced breeding materials. Conventional breeding programs select superior genotypes using the primary trait (yield) based on combine harvesters, which is labor-intensive and often unfeasible for single-row progeny trials (PTs) due to their large population, complex genetic behavior, and high genotype-environment interaction. The goal of this study was to investigate the performance of selecting superior soybean breeding lines using image-based secondary traits by comparing them with the selection of breeders. A total of 11,473 progeny rows (PT) were planted in 2018, of which 1,773 genotypes were selected for the preliminary yield trial (PYT) in 2019, and 238 genotypes advanced for the advanced yield trial (AYT) in 2020. Six agronomic traits were manually measured in both PYT and AYT trials. A UAV-based multispectral imaging system was used to collect aerial images at 30 m above ground every 2 weeks over the growing seasons. A group of image features was extracted to develop the secondary crop traits for selection. Results show that the soybean seed yield of the selected genotypes by breeders was significantly higher than that of the non-selected ones in both yield trials, indicating the superiority of the breeder's selection for advancing soybean yield. A least absolute shrinkage and selection operator model was used to select soybean lines with image features and identified 71 and 76% of the selection of breeders for the PT and PYT. The model-based selections had a significantly higher average yield than the selection of a breeder. The soybean yield selected by the model in PT and PYT was 4 and 5% higher than those selected by breeders, which indicates that the UAV-based high-throughput phenotyping system is promising in selecting high-yield soybean genotypes.
Highly Efficient Generation of Canker-Resistant Sweet Orange Enabled by an Improved CRISPR/Cas9 System
Authors: Huang Xiaoen , Wang Yuanchun , Wang Nian
Published: January 2022

Sweet orange (Citrus sinensis) is the most economically important species for the citrus industry. However, it is susceptible to many diseases including citrus bacterial canker caused by Xanthomonas citri subsp. citri (Xcc) that triggers devastating effects on citrus production. Conventional breeding has not met the challenge to improve disease resistance of sweet orange due to the long juvenility and other limitations. CRISPR-mediated genome editing has shown promising potentials for genetic improvements of plants. Generation of biallelic/homozygous mutants remains difficult for sweet orange due to low transformation rate, existence of heterozygous alleles for target genes, and low biallelic editing efficacy using the CRISPR technology. Here, we report improvements in the CRISPR/Cas9 system for citrus gene editing. Based on the improvements we made previously [dicot codon optimized Cas9, tRNA for multiplexing, a modified sgRNA scaffold with high efficiency, citrus U6 (CsU6) to drive sgRNA expression], we further improved our CRISPR/Cas9 system by choosing superior promoters [Cestrum yellow leaf curling virus (CmYLCV) or Citrus sinensis ubiquitin (CsUbi) promoter] to drive Cas9 and optimizing culture temperature. This system was able to generate a biallelic mutation rate of up to 89% for Carrizo citrange and 79% for Hamlin sweet orange. Consequently, this system was used to generate canker-resistant Hamlin sweet orange by mutating the effector binding element (EBE) of canker susceptibility gene CsLOB1, which is required for causing canker symptoms by Xcc. Six biallelic Hamlin sweet orange mutant lines in the EBE were generated. The biallelic mutants are resistant to Xcc. Biallelic mutation of the EBE region abolishes the induction of CsLOB1 by Xcc. This study represents a significant improvement in sweet orange gene editing efficacy and generating disease-resistant varieties via CRISPR-mediated genome editing. This improvement in citrus genome editing makes genetic studies and manipulations of sweet orange more feasible.
Identification of Candidate Forage Yield Genes in Sorghum (Sorghum bicolor L.) Using Integrated Genome-Wide Association Studies and RNA-Seq
Authors: Wang Lihua , Liu Yanlong , Gao Li , Yang Xiaocui , Zhang Xu , Xie Shaoping , Chen Meng , Wang Yi-Hong , Li Jieqin , Shen Yixin
Published: January 2022

Genetic dissection of forage yield traits is critical to the development of sorghum as a forage crop. In the present study, association mapping was performed with 85,585 SNP markers on four forage yield traits, namely plant height (PH), tiller number (TN), stem diameter (SD), and fresh weight per plant (FW) among 245 sorghum accessions evaluated in four environments. A total of 338 SNPs or quantitative trait nucleotides (QTNs) were associated with the four traits, and 21 of these QTNs were detected in at least two environments, including four QTNs for PH, ten for TN, six for SD, and one for FW. To identify candidate genes, dynamic transcriptome expression profiling was performed at four stages of sorghum development. One hundred and six differentially expressed genes (DEGs) that were enriched in hormone signal transduction pathways were found in all stages. Weighted gene correlation network analysis for PH and SD indicated that eight modules were significantly correlated with PH and that three modules were significantly correlated with SD. The blue module had the highest positive correlation with PH and SD, and the turquoise module had the highest negative correlation with PH and SD. Eight candidate genes were identified through the integration of genome-wide association studies (GWAS) and RNA sequencing. Sobic.004G143900, an indole-3-glycerol phosphate synthase gene that is involved in indoleacetic acid biosynthesis, was down-regulated as sorghum plants grew in height and was identified in the blue module, and Sobic.003G375100, an SD candidate gene, encoded a DNA repair RAD52-like protein 1 that plays a critical role in DNA repair-linked cell cycle progression. These findings demonstrate that the integrative analysis of omics data is a promising approach to identify candidate genes for complex traits.
Phosphoproteomics Reveals Regulation of Secondary Metabolites in Mahonia bealei Exposed to Ultraviolet-B Radiation
Authors: Liu Amin , Liu Shengzhi , Li Yaohan , Tao Minglei , Han Haote , Zhong Zhuoheng , Zhu Wei , Tian Jingkui
Published: January 2022

Mahonia bealei (M. bealei) is a traditional Chinese medicine containing a high alkaloid content used to treat various diseases. Generally, only dried root and stem are used as medicines, considering that the alkaloid content in M. bealei leaves is lower than in the stems and roots. Some previous research found that alkaloid and flavonoid contents in the M. bealei leaves may increase when exposed to ultraviolet B (UV-B) radiation. However, the underlying mechanism of action is still unclear. In this study, we used titanium dioxide material enrichment and mass-based label-free quantitative proteomics techniques to explore the effect and mechanism of M. bealei leaves when exposed to UV-B treatment. Our data suggest that UV-B radiation increases the ATP content, photosynthetic pigment content, and some enzymatic/nonenzymatic indicators in the leaves of M. bealei. Moreover, phosphoproteomics suggests phosphoproteins related to mitogen-activated protein kinase (MAPK) signal transduction and the plant hormone brassinosteroid signaling pathway as well as phosphoproteins related to photosynthesis, glycolysis, the tricarboxylic acid cycle, and the amino acid synthesis/metabolism pathway are all affected by UV-B radiation. These results suggest that the UV-B radiation activates the oxidative stress response, MAPK signal transduction pathway, and photosynthetic energy metabolism pathway, which may lead to the accumulation of secondary metabolites in M. bealei leaves.
Calcium/Calmodulin-Mediated Defense Signaling: What Is Looming on the Horizon for AtSR1/CAMTA3-Mediated Signaling in Plant Immunity
Authors: Yuan Peiguo , Tanaka Kiwamu , Poovaiah B. W.
Published: January 2022

Calcium (Ca2+) signaling in plant cells is an essential and early event during plant-microbe interactions. The recognition of microbe-derived molecules activates Ca2+ channels or Ca2+ pumps that trigger a transient increase in Ca2+ in the cytoplasm. The Ca2+ binding proteins (such as CBL, CPK, CaM, and CML), known as Ca2+ sensors, relay the Ca2+ signal into down-stream signaling events, e.g., activating transcription factors in the nucleus. For example, CaM and CML decode the Ca2+ signals to the CaM/CML-binding protein, especially CaM-binding transcription factors (AtSRs/CAMTAs), to induce the expressions of immune-related genes. In this review, we discuss the recent breakthroughs in down-stream Ca2+ signaling as a dynamic process, subjected to continuous variation and gradual change. AtSR1/CAMTA3 is a CaM-mediated transcription factor that represses plant immunity in non-stressful environments. Stress-triggered Ca2+ spikes impact the Ca2+-CaM-AtSR1 complex to control plant immune response. We also discuss other regulatory mechanisms in which Ca2+ signaling activates CPKs and MAPKs cascades followed by regulating the function of AtSR1 by changing its stability, phosphorylation status, and subcellular localization during plant defense.
Sodium Nitroprusside Functions in Browning Control and Quality Maintaining of Postharvest Rambutan Fruit
Authors: Zhang Ruining , Yuan Zhouyu , Jiang Yuwei , Jiang Fan , Chen Ping
Published: January 2022

Surface browning after harvest is the primary constraint affecting the storage life and market circulation of rambutans. In this study, rambutan fruits were soaked in sodium nitroprusside at different concentrations and stored at 25°C for 8 days to explore the effects on postharvest quality and browning. The weight loss, browning index and superoxide anion radical, hydrogen peroxide and malondialdehyde contents of the treated fruits were reduced compared to those of the control fruits (soaked in distilled water). And fruits treated with sodium nitroprusside had a higher total phenolic content and lower polyphenol oxidase and peroxidase activity. In addition, compared with the control, the treated fruits exhibited higher phenylalanine ammonia lyase, ascorbate peroxidase and superoxide dismutase activities; titratable acidity; and soluble solid, vitamin C and protein contents, indicating high fruit quality. Overall, sodium nitroprusside treatment at 200 μmol L−1 demonstrated the most positive preservation effects. Therefore, sodium nitroprusside treatment, particularly at 200 μmol L−1, can be used as an eco-friendly, safe and convenient method for postharvest quality management and high-efficiency preservation of rambutan fruits.
Eye Size Affects Cuteness in Different Facial Expressions and Ages
Authors: Yao Lichang , Dai Qi , Wu Qiong , Liu Yang , Yu Yiyang , Guo Ting , Zhou Mengni , Yang Jiajia , Takahashi Satoshi , Ejima Yoshimichi , Wu Jinglong
Published: January 2022

Researchers have suggested that infants exhibiting baby schema are considered cute. These similar studies have mainly focused on changes in overall baby schema facial features. However, whether a change in only eye size affects the perception of cuteness across different facial expressions and ages has not been explicitly evaluated until now. In the present study, a paired comparison method and 7-point scale were used to investigate the effects of eye size on perceived cuteness across facial expressions (positive, neutral, and negative) and ages (adults and infants). The results show that stimuli with large eyes were perceived to be cuter than both unmanipulated eyes and small eyes across all facial expressions and age groups. This suggests not only that the effect of baby schema on cuteness is based on changes in a set of features but also that eye size as an individual feature can affect the perception of cuteness.
University Credits as a Measure of Teachers’ Pre-service and In-Service Training: A Longitudinal Approach Using Swedish Data
Authors: Johansson Stefan , Hansson Åse , Alatalo Tarja
Published: January 2022

In this study, we accessed information about the university credits of all teachers born after 1971 in Sweden as a means of ascertaining the development of their subject knowledge. We examined the university credits they earned during pre-service and in-service training. Data comes from registers Gothenburg Educational Longitudinal Database (GOLD) and the teacher register. We linked GOLD to the teacher register in order to describe the knowledge development of teachers in compulsory school 1998–2014. Special focus was on Swedish language and mathematics. Multiple regression and multilevel growth modeling were used as our main methods. Results show an increase in pre-service credits during the time period and more credits in Swedish language than in mathematics. To analyze teachers’ in-service training, we followed the development of their university credits over time. Teachers with higher prerequisites in terms of grade point average tended to gain more credits in-service. The study included discussions on ideas and the implications for future research.
Through the Looking Glass: A Scoping Review of Cinema and Video Therapy
Authors: Sacilotto Elena , Salvato Gerardo , Villa Federica , Salvi Fulvia , Bottini Gabriella
Published: January 2022

Background: Cinematherapy and video treatments are artistic therapeutic techniques by which the individuals are exposed to their psycho-physical difficulties through the stories of the characters on the screen who are coping with the same issues that the patients are. Although these techniques are increasingly common within modern art therapies, there are neither comprehensive classifications of the different approaches nor agreement on their effectiveness. We performed a scoping review, describing different methodological approaches and outcome measures in cinematherapy and video treatments.

Methodology: We searched articles in PubMed, PsycINFO and Google Scholar. We included: (i) articles in which subjects were treated for their difficulties with videos or films, (ii) articles written in English. Review articles and papers describing a research protocol without data collection were not included.

Results: We analyzed 38 studies. Thirty-six reported a positive effect of the treatment. Seven studies used classical cinematherapy, adopting a qualitative approach to measure the therapy outcome. Thirty-one studies used different video treatments, 8 of which were defined as randomized controlled trials with specific objective therapy outcomes. Studies were mainly focused on behavioral and psychological difficulties in Autism Spectrum Disorders and Schizophrenia.

Conclusion: Studies using video treatments more often rely upon structured experimental designs; on the contrary, those who used classical cinematherapy produced descriptive results. A more standardized methodological approach in terms of experimental design, procedure, and objective outcome measure is needed to provide evidence on the effectiveness of these techniques, promoting its application in the clinical field.
Effects of Top Management Team Characteristics on Patent Strategic Change and Firm Performance
Authors: Zhou Yongtao , Zhou Yi , Zhang Li , Zhao Xu , Chen Weijing
Published: January 2022

Patent strategy is increasingly recognized as a vital contributor in promoting core competitiveness of an enterprise. A top management team (TMT) has been indicated as one of the key factors driving changes in patent strategy. Based on upper echelons theory, this study examines how TMT characteristics, including, team diversity, emotional intelligence, and safety climate, influence enterprise patent strategic change and, hence, the business outcome. The data from 930 top managers in 228 enterprises showed that the changes in patent strategies are significantly influenced by the characteristics of top managers. These aforementioned internal TMT factors have diverse effects on the speed and scope of the enterprise patent strategic change, which in turn affects firm performance in a positive and negative way, respectively.
The Effectiveness of Mating Induction on Men’s Financial Risk-Taking: Relationship Experience Matters
Authors: Liu Tingting , Wang Zhuanzhuan , Zhu Anrun , Zhang Xi , Xing Cai
Published: January 2022

Substantial evidence from experimental studies has shown that mating motivation increases men’s financial risk-taking behaviors. The present study proposed a new moderator, men’s past relationship experience, for this well-accepted link between mating motivation and financial risk-taking tendency. Heterosexual young men were randomly assigned to the mating condition and control condition, and they completed a set of financial risk-taking tasks and reported their past relationship experience. A significant main effect of mating motivation and a significant interaction effect between experimental conditions (mating group and control group) and relationship experience emerged, suggesting that mating motivation increased financial risk-taking tendency only among men who have never been committed in a romantic relationship, rather than those who have had such experience. This moderating effect was replicated in two experiments. The present study contributed to the understanding of individual differences in the relationship between mating motivation and male financial risk-taking. The present findings also have important implications for financial industry and gambling companies to better target clients and advertise their high-risk products.
The Relationship Between Business Environment and Single Champion Enterprise Entrepreneurship
Authors: Wu Chanti , Lin Jinjin
Published: January 2022

What kind of business environment can produce high single champion enterprise entrepreneurship is a new issue for discussion in research on entrepreneurship. Based on institutional configuration theory and the fcQCA method, the present paper analyses the relationship between the business environment and single champion enterprise entrepreneurship from the perspective of configuration. This paper studies the role of the business environment in 80 case cities all over the country in promoting high single champion enterprise entrepreneurship and discusses three business environment configurations concerning high single champion enterprise entrepreneurship and two configurations concerning non-high single champion enterprise entrepreneurship. Three typical business environment element configurations can promote high single champion enterprise entrepreneurship, namely, the market innovation type dominated by multiple resources, the financial service–driven type assisted by resources, and the market-driven type led by financial services, which reflects the significance of financial services and the market environment.
A Role of Production on E-Commerce and Foreign Policy Influencing One Belt One Road: Mediating Effects of International Relations and International Trade
Authors: Wang Hanxiao , Liu Bei
Published: January 2022

One Road One Belt has made a drastic change not only to the lives of people but also to their minds and future prospective. This initiative has connected not only countries but has consolidated trading patterns. It has not only impacted physical trade but has also boosted the e-commerce of China. Therefore, this study has tried to find the major patterns of trading across the globe and digital commerce considering the factors of production. China, being the cheapest country for manufacturing, has excelled in the e-commerce as well. The targeted population for this study was contractors, marketers, logistic service providers, and engineers. The sample size in this study was 329. Data collection was done through a survey developed on the Likert scale. The software used for the data analysis was Smart-PLS for structural equation modeling. Findings of the study show that factors of production and international trade have an impact on e-commerce. Moreover, the foreign policy and international relations have also been found to have a significant role in e-commerce (digital entrepreneurship).
How Work–Family Conflict and Work–Family Facilitation Affect Employee Innovation: A Moderated Mediation Model of Emotions and Work Flexibility
Authors: Wang Zhicheng , Qiu Xingyu , Jin Yixing , Zhang Xinyan
Published: January 2022

This paper aims to verify the effects of work–family conflict and work–family facilitation on employee innovation in the digital era. Based on resource conservation theory, this study regards the work–family relationship as a conditional resource. Employees who are in a state of lack of resources caused by work–family conflict will maintain existing resources by avoiding the consumption of further resources to perform innovation activities; employees who are in a state of sufficient resources are more willing to invest existing resources to obtain more resources. In this study, 405 employees from enterprises in the Chinese provinces of Jiangsu, Anhui, Sichuan, and Guangdong, and in the municipality of Tianjin were selected as the research object. These enterprises are knowledge-based companies, and their employees frequently transfer knowledge at work. We collected questionnaires from the frontline employees of these companies. The results show that negative and positive emotions mediate the effect of work–family conflict and work–family facilitation on employee innovation. Moreover, work flexibility has a significant moderating effect on the mediating role of emotions between work–family facilitation and employee innovation behavior. In the digital era, when facing different work–family situations, employees need to pay attention to and dredge their negative emotions to avoid reducing their innovative behaviors due to self-abandonment; in parallel, they need to guide their positive emotions toward innovation, so as to promote their innovative consciousness and behavior. This paper expands the research perspective of employee innovation behavior.
Ehlers-Danlos Syndrome in the Field of Psychiatry: A Review
Authors: Ishiguro Hiroki , Yagasaki Hideaki , Horiuchi Yasue
Published: January 2022

Ehlers-Danlos syndrome (EDS) comprises a series of rare hereditary connective tissue diseases characterized by joint hypermobility, joint dislocation, and hyperextensibility of the skin, as well as cardiovascular involvement. EDS is often associated with chronic widespread physical pain, which can lead to psychological pain. Poor awareness and limited diagnosis of EDS and related symptoms result in decreased self-esteem and confusion regarding physical sensation. Furthermore, EDS imposes substantial psychological burden on patients due to exercise restriction, scars, keloids, and subcutaneous fat accumulation on the extremities, which leads to parental overprotection and bullying experiences from other children at school age. Recent large-scale studies have suggested that patients with EDS have a higher risk of mood disorders than the general population. Other cohort studies indicated high prevalence of anorexia nervosa, addiction, obsessive compulsive disorder, and anxiety disorder were found in patients with EDS. Case reports instead indicated that some psychiatric disorders were secondary symptoms due to physical problems from EDS. Therefore, psychiatrists must be more knowledgeable and proactive about EDS in their practice. We review the previous case reports and literature for patients with EDS, along with our own case of complicated psychiatric problems, which are strongly related to early stressful situations through childhood and adolescence. This is to aid general psychiatrists in the discussion of appropriate medical management in such infrequent, yet challenging conditions.