bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review
Authors: Ziogas Dimitrios C. , Mandellos Dimitrios , Theocharopoulos Charalampos , Lialios Panagiotis-Petros , Bouros Spyros , Ascierto Paolo A. , Gogas Helen
Published: October 2021

More than 40 tyrosine kinase inhibitors (TKIs) have received hematological or oncological indications over the past 20 years, following the approval of imatinib, and many others are currently being tested in clinical and preclinical level. Beyond their common toxicities, no certain agent from this large class of molecularly targeted therapies was strongly associated with “off-target” impairment of neuromuscular transmission, and although myasthenia gravis (MG) is a well-characterized autoimmune disorder, only few sporadic events proven by serologically detected causative autoantibodies and/or by positive electrophysiological tests are reported in the literature. Herein, we present the first case of anti-MUSK (+) MG in a woman with metastatic BRAF-mutant melanoma after long-term treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Triggered by this report, a systematic literature review was conducted, summarizing all other cancer cases that developed MG, after exposure to any type of targeted agent and regardless of the underlying malignancy. All available data on the clinical diagnosis, the potential of administered TKIs to induce a seropositive myasthenic syndrome, the immune and non-immune-mediated pathogenesis of postsynaptic damage, and the challenging management of this neuromuscular toxicity were collected and discussed. In the presented case, MG was confirmed by both autoantibodies and nerve-conduction tests, while its reactivation after TKIs rechallenge supports a more than coincidental association. The following review identified 12 cancer cases with TKI-related MG in six case reports and one case series. In most of them, the myasthenia diagnosis was challenging, since the clinical symptomatology of fatigable weakness was not corroborating with consistent laboratory and electrophysiological findings. In fact, anti-AchR titers were positive in five and anti-MuSK only in the abovementioned individual. The symptomatology corresponded to TKI discontinuation and standard treatment with pyridostigmine and prednisolone; intravenous immunoglobulin was added only in three, and two required mechanical ventilation. In an era where TKIs will be prescribed more frequently for various malignancies, even in combinations with immune-checkpoint inhibitors, this report synthesizes their risk for neuromuscular complications and increases the clinicians’ awareness in order to extend the on-treatment and overall survival of TKI-treated cancer patients.
SNHG8 Promotes the Progression of Epstein–Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28
Authors: Zou Changyan , Liao Jinrong , Hu Dan , Su Ying , Lin Huamei , Lin Keyu , Luo Xingguan , Zheng Xiongwei , Zhang Lurong , Huang Tao , Lin Xiandong
Published: October 2021

SNHG8, a family member of small nucleolar RNA host genes (SNHG), has been reported to act as an oncogene in gastric carcinoma (GC). However, its biological function in Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) remains unclear. This study investigated the role of SNHG8 in EBVaGC. Sixty-one cases of EBVaGC, 20 cases of non-EBV-infected gastric cancer (EBVnGC), and relative cell lines were studied for the expression of SNHG8 and BHRF1 (BCL2 homolog reading frame 1) encoded by EBV with Western blot and qRT-PCR assays. The relationship between the expression levels of SNHG8 and the clinical outcome in 61 EBVaGC cases was analyzed. Effects of overexpression or knockdown of BHRF1, SNHG8, or TRIM28 on cell proliferation, migration, invasion, and cell cycle and the related molecules were determined by several assays, including cell proliferation, colony assay, wound healing assay, transwell invasion assay, cell circle with flow cytometry, qRT-PCR, and Western blot for expression levels. The interactions among SNHG8, miR-512-5p, and TRIM28 were determined with Luciferase reporter assay, RNA immunoprecipitation (RIP), pull-down assays, and Western blot assay. The in vivo activity of SNHG8 was assessed with SNHG8 knockdown tumor xenografts in zebrafish. Results demonstrated that the following. (1) BHRF1 and SNHG8 were overexpressed in EBV-encoded RNA 1-positive EBVaGC tissues and cell lines. BHRF1 upregulated the expressions of SNHG8 and TRIM28 in AGS. (2) SNHG8 overexpression had a significant correlation with tumor size and vascular tumor thrombus. Patients with high SNHG8 expression had poorer overall survival (OS) compared to those with low SNHG8 expression. (3) SNHG8 overexpression promoted EBVaGC cell proliferation, migration, and invasion in vitro and in vivo, cell cycle arrested at the G2/M phase via the activation of BCL-2, CCND1, PCNA, PARP1, CDH1, CDH2 VIM, and Snail. (4) Results of dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assays indicated that SNHG8 sponged miR-512-5p, which targeted on TRIM28 and promoted cancer malignant behaviors of EBVaGC cells. Our data suggest that BHRF1 triggered the expression of SNHG8, which sponged miR-512-5p and upregulated TRIM28 and a set of effectors (such as BCL-2, CCND1, CDH1, CDH2 Snail, and VIM) to promote EBVaGC tumorigenesis and invasion. SNHG8 could be an independent prognostic factor for EBVaGC and sever as target for EBVaGC therapy.
Decision-Making at End-of-Life for Children With Cancer: A Systematic Review and Meta-Bioethical Analysis
Authors: Juárez-Villegas Luis Enrique , Altamirano-Bustamante Myriam M. , Zapata-Tarrés Marta M.
Published: October 2021

Background

Evidence shows that medical education includes a variety of basic and clinical skills. Ethical and human values are not typically considered in medical school curricula, and this is evident in medical practice in certain scenarios such as decision-making at pediatric cancer patients' end of life.

Methods

This study explores a bioethical approach to address complex decision-making at the end of life in children and adolescents with cancer. We are a cross-functional group of scientists from several academic disciplines who conducted a systematic review of the literature using our newly developed meta-bioethical analysis and synthesis of findings. The search was carried out in five databases, resulting in 10 research papers. Following quality screening, seven articles were ultimately selected for further analysis.

Results

Our focus is on the state of the art to better understand the bioethical deliberation at the end of life in pediatric oncology. Here, we report a systematic review that includes (i) classification of the screened articles by the type of decision-making they use, ii) the system values that are at the core of the decision-making at the end of life, and iii) bioethical and ethical discernment queries. We conclude with a discussion regarding the best practices of ethical discernment and decision-making at the end of life.

This study highlights the need to develop more research to better understand the influence and origin of these multidimensional factors determining critical decisions that define the quality of life of patients in a highly sensitive moment.

Conclusion

We conclude that personal aspects of the physician define their actions more than knowledge or organized structure. It is thus necessary that pediatric oncologists receive ethics and humanistic education.
Identification of N6-Methyladenosine-Related LncRNAs for Predicting Overall Survival and Clustering of a Potentially Novel Molecular Subtype of Breast Cancer
Authors: Zhong Xiaoxiao , Li Jun , Wu Xin , Wu Xianrui , Hu Lin , Ding Boni , Qian Liyuan
Published: October 2021

We aimed to identify a signature comprising N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and molecular subtypes associated with breast cancer (BRCA). We obtained data of BRCA samples from The Cancer Genome Atlas database. The m6A-related lncRNA prognostic signature (m6A-LPS) included 10 lncRNAs previously identified as prognostic m6A-related lncRNAs and was constructed using integrated bioinformatics analysis and validated. Accordingly, a risk score based on the m6A-LPS signature was established and shown to confirm differences in survival between high-risk and low-risk groups. Three distinct genotypes were identified, whose characteristics included features of the tumor immune microenvironment in each subtype. Our results indicated that patients in Cluster 2 might have a worse prognostic outcome than those in other clusters. The three genotypes and risk subgroups were enriched in different biological processes and pathways, respectively. We then constructed a competing endogenous RNA network based on the prognostic m6A-related lncRNAs. Finally, we validated the expression levels of target lncRNAs in 72 clinical samples. In summary, the m6A-LPS and the potentially novel genotype may provide a theoretical basis for further study of the molecular mechanism of BRCA and may provide novel insights into precision medicine.
Enhancer RNA SLIT2 Inhibits Bone Metastasis of Breast Cancer Through Regulating P38 MAPK/c-Fos Signaling Pathway
Authors: Li Peng , Lin Zhiping , Liu Qianzheng , Chen Siyuan , Gao Xiang , Guo Weixiong , Gong Fan , Wei Jinsong , Lin Hao
Published: October 2021

Background

Breast cancer (BRCA) is the most common cancer in women, while the bones are one of the most common sites of metastasis. Although new diagnostic methods or radiation or chemotherapies and targeted therapies have made huge advances, the occurrence of bone metastasis is also linked with poorer survival. Enhancer RNAs (eRNAs) have been demonstrated to participate in the progression of tumorigenesis and metastasis. However, the role of eRNAs in BRCA bone metastasis remains largely unclear.

Method

Gene expression profiling of 1,211 primary BRCA and 17 bone metastases samples were retrieved from The Cancer Genome Atlas (TCGA) database, and the significant prognostic eRNAs were identified by Cox regression and least absolute shrinkage and selection operator (LASSO) regression. The acceptable accuracy and discrimination of the nomogram were indicated by the receiver operating characteristic (ROC) and the calibration curves. Then target genes of eRNA, immune cell percentage by CIBERSORT analysis, immune genes by single-sample gene set enrichment analysis (ssGSEA), hallmark of cancer signaling pathway by gene set variation analysis (GSVA), and reverse phase protein array (RPPA) protein chip were used to build a co-expression regulation network and identified the key eRNAs in bone metastasis of BRCA. Finally, Cell Counting Kit-8 (CCK8) assay, cell cycle assay, and transwell assay were used to study changes in cell proliferation, migration, and invasiveness. Immunoprecipitation assay and Western blotting were used to test the interaction and the regulation signaling pathways.

Results

The 27 hub eRNAs were selected, and a survival-related linear risk assessment model with a relatively high accuracy (area under curve (AUC): 0.726) was constructed. In addition, seven immune-related eRNAs (SLIT2, CLEC3B, LBPL1, FRY, RASGEF1B, DST, and ITIH5) as prognostic signatures for bone metastasis of BRCA were further confirmed by LASSO and multivariate Cox regression and CIBERSORT analysis. Finally, in vitro assay demonstrated that overexpression of SLIT2 reduced proliferation and metastasis in BRCA cells. Using high-throughput co-expression regulation network, we identified that SLIT2 may regulating P38 MAPK/c-Fos signaling pathway to promote the effects of metastasis.

Conclusion

Based on the co-expression network for bone metastasis of BRCA, we screened key eRNAs to explore a prognostic model in predicting the bone metastasis by bioinformatics analysis. Besides, we identified the potential regulatory signaling pathway of SLIT2 in BRCA bone metastasis, which provides a promising therapeutic strategy for metastasis of BRCA.
N6-Methyladenosine-Sculpted Regulatory Landscape of Noncoding RNA
Authors: Zhang Zhongyuan , Wei Wei , Wang Hao , Dong Jiangning
Published: October 2021

The exploration of dynamic N6-methyladenosine (m6A) RNA modification in mammalian cells has attracted great interest in recent years. M6A modification plays pivotal roles in multiple biological and pathological processes, including cellular reprogramming, fertility, senescence, and tumorigenesis. In comparison with growing research unraveling the effects of m6A modifications on eukaryotic messenger RNAs, reports of the association between noncoding RNAs and m6A modification are relatively limited. Noncoding RNAs that undergo m6A modification are capable of regulating gene expression and also play an important role in epigenetic regulation. Moreover, the homeostasis of m6A modification can be affected by noncoding RNAs across a broad spectrum of biological activities. Importantly, fine-tuning and interaction between these processes are responsible for cell development, as well as the initiation and progression of the disease. Hence, in this review, we provide an account of recent developments, revealing biological interactions between noncoding RNAs and m6A modification, and discuss the potential clinical applications of interfering with m6A modification.
CircITCH: A Circular RNA With Eminent Roles in the Carcinogenesis
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Taheri Mohammad , Jamali Elena
Published: October 2021

Circular RNAs (circRNAs) are a group of long non-coding RNAs with enclosed structure generated by back-splicing events. Numerous members of these transcripts have been shown to affect carcinogenesis. Circular RNA itchy E3 ubiquitin protein ligase (circITCH) is a circRNA created from back splicing events in ITCH gene, a protein coding gene on 20q11.22 region. ITCH has a role as a catalyzer for ubiquitination through both proteolytic and non-proteolytic routes. CircITCH is involved in the pathetiology of cancers through regulation of the linear isoform as well as serving as sponge for several microRNAs, namely miR-17, miR-224, miR-214, miR-93-5p, miR-22, miR-7, miR-106a, miR-10a, miR-145, miR-421, miR-224-5p, miR-197 and miR-199a-5p. CircITCH is also involved in the modulation of Wnt/β-catenin and PTEN/PI3K/AKT pathways. Except from a single study in osteosarcoma, circITCH has been found to exert tumor suppressor role in diverse cancers. In the present manuscript, we provided a comprehensive review of investigations that reported function of circITCH in the carcinogenesis.
Diagnostic Errors in Initial Misdiagnosis of Foreign Body Aspiration in Children: A Retrospective Observational Study in a Tertiary Care Hospital in China
Authors: Zhu Yingchao , Fan Qijun , Cheng Lijun , Chen Bobei
Published: October 2021

Background: Foreign body aspiration (FBA) in children is a common emergency that can easily be missed, leading to delays in treatment. Few large cohort studies have focused on errors in diagnostic assessment. The main purpose of this study was to analyze factors contributing to the initial misdiagnosis of FBA in children.

Methods: We retrospectively reviewed the charts of 226 children diagnosed with FBA at the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2018 to November 2020. Cases were divided into two groups according to whether or not patients were initially misdiagnosed. The clinical characteristics of the two groups were then compared. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was applied to cases with initial misdiagnosis.

Results: Of the 226 included children with a final diagnosis of FBA, 153 (67.7%) were boys. Ninety percent of patients were under 3 years old. More than half (61.9%) of the children were referred from primary institutions, and 38.1% visited tertiary hospitals directly. A total of 80 (35.4%) patients were initially misdiagnosed. More than half of misdiagnosed children received an alternative diagnosis of bronchiolitis (51.3%), the most common alternative diagnosis. Test failures (i.e., errors in test ordering, test performance, and clinician processing) were primarily responsible for the majority of initial diagnostic errors (76.3%), followed by failure or delay in eliciting critical case history information (20.0%). Characteristics significantly associated with initial misdiagnosis were: presentation over 24 h (OR 9.2, 95% CI 4.8–17.5), being referred from primary institutions (OR 8.8, 4.1–19.0), no witnessed aspiration crisis (OR 7.8, 3.0–20.3), (4) atypical signs or symptoms (OR 3.2, 1.8–5.7), foreign body not visible on CT (OR 36.2, 2.1–636.8), foreign body located in secondary bronchi (OR 4.8, 1.3–17.2), organic foreign body (OR 6.2, 1.4–27.2), and history of recurrent respiratory infections (OR 2.7, 1.4–5.3). Children with misdiagnosis tended to have a longer time from symptom onset to the definitive diagnosis of FBA (P < 0.001).

Conclusions: More than one-third of children with FBA were missed at first presentation. Errors in diagnostic testing and history taking were the main reasons leading to initial misdiagnosis.
Neuroprem 2: An Italian Study of Neurodevelopmental Outcomes of Very Low Birth Weight Infants
Authors: Lugli Licia , Bedetti Luca , Guidotti Isotta , Pugliese Marisa , Picciolini Odoardo , Roversi Maria Federica , DellaCasa Muttini Elisa , Lucaccioni Laura , Bertoncelli Natascia , Ancora Gina , Gargano Giancarlo , Mosca Fabio , Sandri Fabrizio , Corvaglia Luigi Tommaso , Solinas Agostina , Perrone Serafina , Stella Marcello ,   The Neuroprem Working Group, Iughetti Lorenzo , Berardi Alberto , Ferrari Fabrizio
Published: October 2021

Background: Despite the increased survival of preterm newborns worldwide, the risk of neurodevelopmental disabilities remains high. Analyzing the outcomes of the preterm population can identify risk factors and enable specific early interventions.

Aims: Neuroprem is a prospective cohort study of very low birth weight (VLBW) infants that aims to evaluate the neurodevelopmental outcomes and risk factors for severe functional disability at 2 years of corrected age.

Methods: Nine Italian neonatal intensive care units participated in the network. The Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and a neuro-functional evaluation (according to the International Classification of Disability and Health and Neuro-Functional Assessment, or NFA ICF-CY) were administered to VLBW infants at 24 months of corrected age. The primary outcome measure was severe functional disability, defined as cerebral palsy, bilateral blindness, deafness, an NFA ICF-CY of >2, a BSDI III cognitive composite score of <2 SD, or a GMDS-R global quotient score of <2 SD. Perinatal risk factors for severe functional disability were assessed through multivariate logistic regression analysis.

Results: Among 502 VLBW survivors who completed the 24-month follow-up, 48 (9.6%) presented severe functional disability, of whom 27 had cerebral palsy (5.4%). Rates of severe functional disability and cerebral palsy were higher in neonates with a lower gestational age (p < 0.001). Overall, 147 infants (29.3%) were referred to neuromotor intervention. In the multivariate regression model, gestational age at birth OR 0.79; 95% CI 0.67–0.90; p = 0.001) and periventricular-intraventricular hemorrhage (OR 2.51; 95% CI 1.19–5.26; p = 0.015) were significantly associated with severe functional disability.

Conclusion: Neuroprem 2 provides updated information on the neurodevelopmental outcomes of VLBW infants in a large Italian cohort. The overall rate of neurodevelopmental disabilities was quite lower than reported in the previous literature. These data indicate the need for structured follow-up programs from a national neonatal network perspective.
Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer
Authors: Liu Guoliang , Wang Min , He Hongyu , Li Jiannan
Published: October 2021

Colorectal cancer is the third most common malignant disease worldwide, and chemotherapy has been the standard treatment for colorectal cancer. However, the therapeutic effects of chemotherapy are unsatisfactory for advanced and recurrent colorectal cancers. Thus, increasing the treatment efficacy of chemotherapy in colorectal cancer is a must. In this study, doxorubicin (DOX)-loaded tumor-targeting peptide-decorated mPEG-P(Phe-co-Cys) nanoparticles were developed to treat orthotopic colon cancer in mice. The peptide VATANST (STP) can specifically bind with vimentin highly expressed on the surface of colon cancer cells, thus achieving the tumor-targeting effects. The nanoparticles are core-shell structured, which can protect the loaded DOX while passing through the blood flow and increase the circulation time. The disulfide bonds within the nanoparticles are sensitive to the glutathione-rich microenvironment of tumor tissues. Rupture of disulfide bonds of the nanoparticles leads to the continuous release of DOX, thus resulting in the apoptosis of the tumor cells. The in vivo experiments in mice with orthotopic colon cancer demonstrated that the synthesized DOX-loaded tumor-targeting peptide-decorated polypeptide nanoparticles showed properties of drug delivery systems and exhibited good antitumor properties. The synthesized nanoparticles show appropriate properties as one of the drug delivery systems and exhibit good antitumor properties after encapsulating DOX.
Cardiac Autonomic Modulation Response Before, During, and After Submaximal Exercise in Older Adults With Intellectual Disability
Authors: Font-Farré Manel , Farche Ana Claudia Silva , de Medeiros Takahashi Anielle C. , Guerra-Balic Myriam , Figueroa Arturo , Oviedo Guillermo R.
Published: October 2021

The analysis of the heart rate variability (HRV) consists of changes in the time intervals between consecutive R waves. It provides information on the autonomic nervous system regulation and it is a predictor of adverse cardiovascular events. Several studies analyzed this parameter in youth and adults with Intellectual Disability (ID). Nevertheless, there is a lack of information regarding the HRV before, during, and after exercise in older adults with ID. Therefore, we aimed to describe and compare the cardiac autonomic modulation before, during, and after the six-minute walk test (6MWT) in older adults with and without ID. Twenty-four volunteers with ID and 24 without ID (non-ID) participated in this study. HRV was assessed by R-R intervals at rest, during and after the 6MWT. At rest and recovery periods, the participants remained sited. The symbolic analysis was used to evaluate non-linear HRV components. The recovery HR kinetics was assessed by the mean response time, which is equivalent to time constant (τ)+time delay (TD). Between groups differences in HRV variables were not significant. During the recovery period, HR kinetics time variables showed significant better results in non-ID participants (TD: 6±5s vs. 15±11s; τ: 19±10s vs. 35±17s; and MRT: 25±9s vs. 50±11s, all p<0.050). In conclusion, our results suggest that the HRV in older adults with and without ID is similar during rest, exercise, and recovery. Recovery HR kinetics after the 6MWT was slower in older adults with ID. The reason for these results may be a reduced post-exercise vagal rebound in older adults with ID.
Paradoxical Potentiation of Acid-Sensing Ion Channel 3 (ASIC3) by Amiloride via Multiple Mechanisms and Sites Within the Channel
Authors: Matasic Daniel S. , Holland Nicholas , Gautam Mamta , Gibbons David D. , Kusama Nobuyoshi , Harding Anne M. S. , Shah Viral S. , Snyder Peter M. , Benson Christopher J.
Published: October 2021

Acid-Sensing Ion Channels (ASICs) are proton-gated sodium-selective cation channels that have emerged as metabolic and pain sensors in peripheral sensory neurons and contribute to neurotransmission in the CNS. These channels and their related degenerin/epithelial sodium channel (DEG/ENaC) family are often characterized by their sensitivity to amiloride inhibition. However, amiloride can also cause paradoxical potentiation of ASIC currents under certain conditions. Here we characterized and investigated the determinants of paradoxical potentiation by amiloride on ASIC3 channels. While inhibiting currents induced by acidic pH, amiloride potentiated sustained currents at neutral pH activation. These effects were accompanied by alterations in gating properties including (1) an alkaline shift of pH-dependent activation, (2) inhibition of pH-dependent steady-state desensitization (SSD), (3) prolongation of desensitization kinetics, and (4) speeding of recovery from desensitization. Interestingly, extracellular Ca2+ was required for paradoxical potentiation and it diminishes the amiloride-induced inhibition of SSD. Site-directed mutagenesis within the extracellular non-proton ligand-sensing domain (E79A, E423A) demonstrated that these residues were critical in mediating the amiloride-induced inhibition of SSD. However, disruption of the purported amiloride binding site (G445C) within the channel pore blunted both the inhibition and potentiation of amiloride. Together, our results suggest that the myriad of modulatory and blocking effects of amiloride are the result of a complex competitive interaction between amiloride, Ca2+, and protons at probably more than one site in the channel.
Proper Immune Response Depends on Early Exposure to Gut Microbiota in Broiler Chicks
Authors: Rodrigues Denise R. , Wilson Kim M. , Bielke Lisa R.
Published: October 2021

The successional changes in the early intestinal microbiota occur concomitantly with the development, expansion, and education of the mucosal immune system. Although great attention of researchers has been focused on understanding the linkage between microbiota and immune functions, many essential details of the symbiotic relationship between the intestinal pioneer microbiota and the avian immune system remain to be discovered. This study was conducted to understand the impact of different early life intestinal colonizers on innate and adaptive immune processes in chicks and further identify immune-associated proteins expressed in the intestinal tissue. To accomplish it, we performed an in ovo application of two apathogenic Enterobacteriaceae isolates and lactic acid bacteria (L) to determine their influences on the intestinal proteome profile of broilers at the day of hatch (DOH) and at 10 days old. The results indicated that there were predicted biological functions of L-treated chicks associated with the activation and balanced function of the innate and adaptive immune systems. At the same time, the Enterobacteriaceae-exposed birds presented dysregulated immunological mechanisms or downregulated processes related to immune development. Those findings suggested that a proper immune function was dependent on specific gut microbiota exposure, in which the prenatal probiotic application may have favored the fitting programming of immune functions in chicks.
Investigations on Regulation of MicroRNAs in Rice Reveal [Ca2+]cyt Signal Transduction Regulated MicroRNAs
Authors: Kansal Shivani , Panwar Vaishali , Mutum Roseeta Devi , Raghuvanshi Saurabh
Published: October 2021

MicroRNAs (miRNAs) are critical components of the multidimensional regulatory networks in eukaryotic systems. Given their diverse spectrum of function, it is apparent that the transcription, processing, and activity of the miRNAs themselves, is very dynamically regulated. One of the most important and universally implicated signaling molecules is [Ca2+]cyt. It is known to regulate a plethora of developmental and metabolic processes in both plants and animals; however, its impact on the regulation of miRNA expression is relatively less explored. The current study employed a combination of internal and external calcium channel inhibitors to establishing that [Ca2+]cyt signatures actively regulate miRNA expression in rice. Involvement of [Ca2+]cyt in the regulation of miRNA expression was further confirmed by treatment with calcimycin, the calcium ionophore. Modulation of the cytosolic calcium levels was also found to regulate the drought-responsive expression as well as ABA-mediated response of miRNA genes in rice seedlings. The study further establishes the role of calmodulins and Calmodulin-binding Transcription Activators (CAMTAs) as important components of the signal transduction schema that regulates miRNA expression. Yeast one-hybrid assay established that OsCAMTA4 & 6 are involved in the transcriptional regulation of miR156a and miR167h. Thus, the study was able to establish that [Ca2+]cyt is actively involved in regulating the expression of miRNA genes both under control and stress conditions.
Phylogenomics of Salvia L. subgenus Calosphace (Lamiaceae)
Authors: Lara-Cabrera Sabina Irene , Perez-Garcia Maria de la Luz , Maya-Lastra Carlos Alonso , Montero-Castro Juan Carlos , Godden Grant T. , Cibrian-Jaramillo Angelica , Fisher Amanda E. , Porter J. Mark
Published: October 2021

The evolutionary relationships ofSalviahave been difficult to estimate. In this study, we used the Next Generation Sequencing method Hyb-Seq to evaluate relationships among 90 Lamiaceae samples, including representatives ofMentheae, Ocimeae, SalviasubgeneraAudibertia, Leonia, Salvia, and 69 species of subgenusCalosphace, representing 32 of Epling's sections. A bait set was designed in MarkerMiner using available transcriptome data to enrich 119 variable nuclear loci. Nuclear and chloroplast loci were assembled withhybphylomaker(HPM), followed by coalescent approach analyses for nuclear data (ASTRAL, BEAST) and a concatenated Maximum Likelihood analysis of chloroplast loci. The HPM assembly had an average of 1,314,368 mapped reads for the sample and 527 putative exons. Phylogenetic inferences resolved strongly supported relationships for the deep-level nodes, agreeing with previous hypotheses which assumed that subgenusAudibertiais sister to subgenusCalosphace. Within subgenusCalosphace, we recovered eight monophyletic sectionssensuEpling,Cardinalis, Hastatae, Incarnatae, andUricaein all the analyses (nDNA and cpDNA),Biflorae, Lavanduloideae, andSigmoideaein nuclear analyses (ASTRAL, BEAST) andCurtifloraein ASTRAL trees. Network analysis supports deep node relationships, some of the main clades, and recovers reticulation within the coreCalosphace. The chloroplast phylogeny resolved deep nodes and four monophyleticCalosphacesections. Placement ofS. axillarisis distinct in nuclear evidence and chloroplast, as sister to the rest of theS. subg.Calosphacein chloroplast and a clade with “Hastataeclade” sister to the rest of the subgenus in nuclear evidence. We also tested the monophyly ofS. hispanica, S. polystachia, S. purpurea, andS.tiliifolia, including two samples of each, and found thatS. hispanicaandS. purpureaare monophyletic. Our baits can be used in future studies of Lamiaceae phylogeny to estimate relationships between genera and among species. In this study, we presented a Hyb-Seq phylogeny for complex, recently divergedSalvia, which could be implemented in other Lamiaceae.
Lab-to-Field Transition of RNA Spray Applications – How Far Are We?
Authors: Rank Aline Pereira , Koch Aline
Published: October 2021

The drastic loss of biodiversity has alarmed the public and raised sociopolitical demand for chemical pesticide-free plant production, which is now treated by governments worldwide as a top priority. Given this global challenge, RNAi-based technologies are rapidly evolving as a promising substitute to conventional chemical pesticides. Primarily, genetically modified (GM) crops expressing double-stranded (ds)RNA-mediating gene silencing of foreign transcripts have been developed. However, since the cultivation of GM RNAi crops is viewed negatively in numerous countries, GM-free exogenous RNA spray applications attract tremendous scientific and political interest. The sudden rise in demand for pesticide alternatives has boosted research on sprayable RNA biopesticides, generating significant technological developments and advancing the potential for field applications in the near future. Here we review the latest advances that could pave the way for a quick lab-to-field transition for RNA sprays, which, as safe, selective, broadly applicable, and cost-effective biopesticides, represent an innovation in sustainable crop production. Given these latest advances, we further discuss technological limitations, knowledge gaps in the research, safety concerns and regulatory requirements that need to be considered and addressed before RNA sprays can become a reliable and realistic agricultural approach.
A Rational Model of Incremental Argument Interpretation: The Comprehension of Swedish Transitive Clauses
Authors: Hörberg Thomas , Jaeger T. Florian
Published: October 2021

A central component of sentence understanding is verb-argument interpretation, determining how the referents in the sentence are related to the events or states expressed by the verb. Previous work has found that comprehenders change their argument interpretations incrementally as the sentence unfolds, based on morphosyntactic (e.g., case, agreement), lexico-semantic (e.g., animacy, verb-argument fit), and discourse cues (e.g., givenness). However, it is still unknown whether these cues have a privileged role in language processing, or whether their effects on argument interpretation originate in implicit expectations based on the joint distribution of these cues with argument assignments experienced in previous language input. We compare the former,linguisticaccount against the latter,expectation-basedaccount, using data from production and comprehension of transitive clauses in Swedish. Based on a large corpus of Swedish, we develop a rational (Bayesian) model of incremental argument interpretation. This model predicts the processing difficulty experienced at different points in the sentence as a function of the Bayesian surprise associated with changes in expectations over possible argument interpretations. We then test the model against reading times from a self-paced reading experiment on Swedish. We find Bayesian surprise to be a significant predictor of reading times, complementing effects of word surprisal. Bayesian surprise also captures the qualitative effects of morpho-syntactic and lexico-semantic cues. Additional model comparisons find that it—with a single degree of freedom—captures much, if not all, of the effects associated with these cues. This suggests that the effects of form- and meaning-based cues to argument interpretation are mediated through expectation-based processing.
The Native Speaker in Italian-Dialects Bilingualism: Insights From the Acquisition of Vicentino by Preschool Children
Authors: Sanfelici Emanuela , Roch Maja
Published: October 2021

This paper investigates the bilingualism originating from the native competence of a standard language (Italian) and a vernacular non-standardized local dialect (henceforth, bilectalism). We report results on the comprehension and production of narrative stories by 44 3- to 5-year-old typically developing children exposed to both Italian and Vicentino from birth. Our findings show that all children produced and comprehended Italian. As for the dialect, children can comprehend Vicentino, despite not producing any dialectal element. The study further revealed an implicational scale in dialectal competence: if a child exhibits some productions with dialectal syntax, s/he also produces dialects at the phonological, morphological, and lexical levels. These findings are in line with the dialectological studies on adult speakers: dialectal competence should be arranged along a fine-grained continuum and the dialectal speaker should be considered as a multi-factorial notion. Our study extends this observation to children’s dialectal acquisition.
Research on the Direction of Innovation and Entrepreneurship Education Reform Within the Digital Media Art Design Major in the Digital Economy
Authors: Yu Wenhui , Jiang Tan
Published: October 2021

This research analysed the integration of innovation and entrepreneurship education for students, majoring in digital media art design. Using a grounded theory approach, we investigated the experiences of two research groups: five leaders of digital media art design courses in colleges and universities, and five successful entrepreneurs who had majored in digital media art design and had achieved significantly in the industry after graduation. From the two dimensions of ‘innovation’ and ‘entrepreneurship’, as well as the two perspectives of ‘implementer’ and ‘party’, semi-structured interviews were conducted on the core competencies that innovation and entrepreneurship talents should have the methods and experience of innovation and entrepreneurship education, the difficulties and problems in the implementation of innovation and entrepreneurship education, the need for talent among enterprises and the factors affecting entrepreneurship success. By analysing and clustering the data, we were able to comprehensively identify the main problems and aspects that require more attention in terms of cultivating innovative and entrepreneurial talents in the digital media art design major. Based on the grounded theory research method, this paper established a theoretical model, outlining the innovation of the digital media art design major and the entrepreneurship education reform path. The key internal elements of the model include mechanisms for professional talent training, curriculum integration, teacher team construction and resource support. The school-enterprise cooperation mechanism is recognised as the key external element for innovation and entrepreneurship education reform. The results provide direction for future education and teaching reform, as well as professional input for the digital media art design major. The findings encourage those involved in the digital media art design major to cultivate more high-level, pioneering professionals, so as to adapt to the transformation and upgrading of economic and social development in the context of a growing digital economy.
Exploring Chinese EFL Learners' Achievement Emotions and Their Antecedents in an Online English Learning Environment
Authors: Yang Yingli , Gao Zihan , Han Yawen
Published: October 2021

Drawing on the control-value theory, this study adopted a qualitative approach to explore the various achievement emotions Chinese EFL learners experienced in an online English learning environment and their antecedents during the COVID-19 pandemic period. Data were collected from six Chinese EFL students through semi-structured interviews and reflective journals supplemented with their class notes. Thematic analysis was performed using the qualitative data management software NVivo 12 plus. Results showed that the students experienced diverse emotions such as enjoyment, relaxation, anxiety, guilt, boredom and helplessness. Apart from the environmental antecedents of teacher and peer factors and individual antecedents of control-value appraisals, four novel antecedents were identified which had influence on emotions experienced in the online learning context, including environmental antecedents of internet connection and workload outside classroom, as well as the individual antecedents of students' self-regulation of learning behavior and learning environment.
A Review of Functions of Speculative Thinking
Authors: Huang Lun , Xie Yibo , Chen Xiaolin
Published: October 2021

Speculative thinking refers to thinking about past or future possibilities; it includes counterfactual thinking, prefactual thinking, and other types. In this narrative review, we discuss the traditional function of speculative thinking in improving future performance (i.e., the preparatory function). We also explore several non-preparatory functions of speculative thinking that have not been widely covered, namely the functions of conveying information and of supporting lying. In addition, we address temporal asymmetry; one perspective focuses on psychological distance in speculative thinking about the past and future, while another focuses on temporal asymmetry and reality/hypothetical differences in the preparatory function of speculative thinking. Overall, this review suggests that a broader functional theory is needed to address non-preparatory functions and the traditional preparatory function. Such a theory should cover all speculative thinking about the past and future rather than simply counterfactual thinking.
A Pilot Study of a Parent Emotion Socialization Intervention: Impact on Parent Behavior, Child Self-Regulation, and Adjustment
Authors: Bølstad Evalill , Havighurst Sophie S. , Tamnes Christian K. , Nygaard Egil , Bjørk Rune Flaaten , Stavrinou Maria , Espeseth Thomas
Published: October 2021

Adequate emotion regulation in children is crucial for healthy development and is influenced by parent emotion socialization. The current pilot study aimed to test, for the first time in a Scandinavian population, whether an emotion-focused intervention, Tuning in to Kids (TIK), had positive effects on parent emotion-related socialization behaviors (ERSBs), and children's self-regulation, anxiety, and externalizing behavior problems. We conducted a controlled trial of the 6-week evidence-based TIK parenting program with 20 parents of preschool children aged 5–6 years and 19 wait-list controls. Assessments at baseline and 6 months after the intervention included parent-report questionnaires on parent ERSBs and child adjustment, as well as aspects of children's self-regulation assessed with two behavioral tasks, the Emotional Go/No-Go task (EGNG) and the AX-Continuous Performance Task (AX-CPT). Results showed a significant increase in reported parent emotion coaching behavior and an uncorrected significant decrease in parents' report of child externalizing problems in intervention participants compared to controls. The behavioral data showed an uncorrected significant improvement in child emotion discrimination in the control condition compared to the intervention condition, while measures of children's executive control improved from baseline to follow-up for both conditions but were not significantly different between conditions. These findings suggest that this emotion-focused parenting intervention contributed to improvement in parents' emotion coaching and their appraisal of child externalizing problems, while children's self-regulation showed mainly normative developmental improvements. Further research with a larger sample will be the next step to determine if these pilot findings are seen in an adequately powered study.
The Influence of Spiritual Leadership on Harmonious Passion: A Case Study of the Hotel Industry in China
Authors: Wang Yingda , Jin Yixing , Cheng Lin , Li Ying
Published: October 2021

The hotel manager has the responsibility to stimulate the passion of the staff. The vision, hope/faith, and altruistic love advocated by spiritual leaders can meet the independent psychological needs of employees, thus enhancing their harmonious passion. This study is based on self-determination theory, intrinsic motivation theory and psychological capital theory, and explores the relationship between spiritual leadership and employees’ harmonious passion. This study uses 260 employees of star hotels in Beijing, Shanghai, Hangzhou, Hefei, Huangshan, and other cities in China. Results show that spiritual leadership positively impacts employees’ harmonious passion, and calling plays an mediation role between spiritual leadership and employees’ harmonious passion. The results are helpful to clarify the formation mechanism of employees’ harmonious passion from the perspective of self-determination theory, intrinsic motivation theory and psychological capital theory and show that spiritual leadership can drive employees’ harmonious passion, especially when hotel vision and employee calling are consistent. Furthermore, the altruistic love of spiritual leaders for their followers also plays a key role in employee calling and promoting harmonious passion. Therefore, this study also emphasizes the importance of calling in improving the harmonious passion of employees. The theoretical and management implications that help to enhance the harmonious passion of employees are discussed in detail.
Dysfunctional Timing in Traumatic Brain Injury Patients: Co-occurrence of Cognitive, Motor, and Perceptual Deficits
Authors: Verga Laura , Schwartze Michael , Stapert Sven , Winkens Ieke , Kotz Sonja A.
Published: October 2021

Timing is an essential part of human cognition and of everyday life activities, such as walking or holding a conversation. Previous studies showed that traumatic brain injury (TBI) often affects cognitive functions such as processing speed and time-sensitive abilities, causing long-term sequelae as well as daily impairments. However, the existing evidence on timing capacities in TBI is mostly limited to perception and the processing of isolated intervals. It is therefore open whether the observed deficits extend to motor timing and to continuous dynamic tasks that more closely match daily life activities. The current study set out to answer these questions by assessing audio motor timing abilities and their relationship with cognitive functioning in a group of TBI patients (n= 15) and healthy matched controls. We employed a comprehensive set of tasks aiming at testing timing abilities across perception and production and from single intervals to continuous auditory sequences. In line with previous research, we report functional impairments in TBI patients concerning cognitive processing speed and perceptual timing. Critically, these deficits extended to motor timing: The ability to adjust to tempo changes in an auditory pacing sequence was impaired in TBI patients, and this motor timing deficit covaried with measures of processing speed. These findings confirm previous evidence on perceptual and cognitive timing deficits resulting from TBI and provide first evidence for comparable deficits in motor behavior. This suggests basic co-occurring perceptual and motor timing impairments that may factor into a wide range of daily activities. Our results thus place TBI into the wider range of pathologies with well-documented timing deficits (such as Parkinson’s disease) and encourage the search for novel timing-based therapeutic interventions (e.g., employing dynamic and/or musical stimuli) with high transfer potential to everyday life activities.
COVID-19 to Green Entrepreneurial Intention: Role of Green Entrepreneurial Self-Efficacy, Optimism, Ecological Values, Social Responsibility, and Green Entrepreneurial Motivation
Authors: Wang Wenke , Cao Qilin , Zhuo Chaoyang , Mou Yunhan , Pu Zihao , Zhou Yunhuan
Published: October 2021

This research was aimed to investigate the impact of the COVID-19 pandemic on the green entrepreneurial intention of college students through green entrepreneurial self-efficacy, optimism, ecological values, and social responsibility, as well as the mediating role of green entrepreneurial motivation. This study used structural equation model to test the hypothesis on samples of 410 Chinese colleges’ students. COVID-19 has a strong beneficial effect on green entrepreneurial self-efficacy, optimism, ecological values, and social responsibility, according to the research findings. Optimism and social responsibility also were found to have a significant positive impact on green entrepreneurial self-efficacy. Moreover, green entrepreneurial motivations moderated the relationship between optimism, ecological values, social responsibility, and green entrepreneurial intention in a positive and significant way. Finally, the findings indicate that a significant positive correlation exists between green entrepreneurial self-efficacy and optimism, as well as a significant positive correlation between ecological values and social responsibility.