bluuebunny/crossref_metadata_2025 huggingface dataset:
Prioritizing Molecular Biomarkers in Asthma and Respiratory Allergy Using Systems Biology
Authors: Cremades-Jimeno Lucía , de Pedro María Ángeles , López-Ramos María , Sastre Joaquín , Mínguez Pablo , Fernández Ignacio Mahillo , Baos Selene , Cárdaba Blanca
Published: April 2021

Highly prevalent respiratory diseases such as asthma and allergy remain a pressing health challenge. Currently, there is an unmet need for precise diagnostic tools capable of predicting the great heterogeneity of these illnesses. In a previous study of 94 asthma/respiratory allergy biomarker candidates, we defined a group of potential biomarkers to distinguish clinical phenotypes (i.e. nonallergic asthma, allergic asthma, respiratory allergy without asthma) and disease severity. Here, we analyze our experimental results using complex algorithmic approaches that establish holistic disease models (systems biology), combining these insights with information available in specialized databases developed worldwide. With this approach, we aim to prioritize the most relevant biomarkers according to their specificity and mechanistic implication with molecular motifs of the diseases. The Therapeutic Performance Mapping System (Anaxomics’ TPMS technology) was used to generate one mathematical model per disease: allergic asthma (AA), non-allergic asthma (NA), and respiratory allergy (RA), defining specific molecular motifs for each. The relationship of our molecular biomarker candidates and each disease was analyzed by artificial neural networks (ANNs) scores. These analyses prioritized molecular biomarkers specific to the diseases and to particular molecular motifs. As a first step, molecular characterization of the pathophysiological processes of AA defined 16 molecular motifs: 2 specific for AA, 2 shared with RA, and 12 shared with NA. Mechanistic analysis showed 17 proteins that were strongly related to AA. Eleven proteins were associated with RA and 16 proteins with NA. Specificity analysis showed that 12 proteins were specific to AA, 7 were specific to RA, and 2 to NA. Finally, a triggering analysis revealed a relevant role for AKT1, STAT1, and MAPK13 in all three conditions and for TLR4 in asthmatic diseases (AA and NA). In conclusion, this study has enabled us to prioritize biomarkers depending on the functionality associated with each disease and with specific molecular motifs, which could improve the definition and usefulness of new molecular biomarkers.
Two Small Extracellular Vesicle sRNAs Derived From Mycobacterium tuberculosis Serve as Diagnostic Biomarkers for Active Pulmonary Tuberculosis
Authors: Lu Geng , Jiang XinRui , Wu Anni , Zhou Jiawei , Liu Hengjun , He Fei , Zhang Qiuling , Zen Ke , Gu Shuangshuang , Wang Jun
Published: April 2021

The rapid diagnosis of tuberculosis (TB) is of great significance for the control and treatment of TB. However, TB remains a major healthy, social, and economic burden worldwide because of the lack of ideal diagnostic biomarkers. Mycobacterium tuberculosis (M. tuberculosis)-encoded small RNA (sRNA) is a class of regulation small RNA. Several studies have identified M. tuberculosis encoded-sRNAs in the serum/plasm of M. tuberculosis-infected patients. Small extracellular vesicles are small membrane vesicles secreted by many cell types during physiological and pathological conditions. Recent evidence has indicated that most of the nucleic acids in the serum/plasma are packaged in the small extracellular vesicles and could serve as ideal diagnostic biomarkers. In this study, we attempted a novel approach for TB diagnosis: targeting small extracellular vesicles M. tuberculosis encoded sRNA (sRNA) by qRT-PCR. The results showed that M. tuberculosis-encoded ASdes and MTB-miR5 only existed in tuberculosis patients and have the potential to serve as a sensitive and accurate methodology for TB diagnosis.
Yeast Fermentate-Mediated Reduction of Salmonella Reading and Typhimurium in an in vitro Turkey Cecal Culture Model
Authors: Feye Kristina M. , Dittoe Dana K. , Rubinelli Peter M. , Olson Elena G. , Ricke Steven C.
Published: April 2021

Salmonella Reading is an ongoing public health issue in the turkey industry, leading to significant morbidity in humans in the United States. Pre-harvest intervention strategies that contribute to the reduction of foodborne pathogens in food animals, such as the yeast fermentation metabolites of Original XPCTM (XPC), may become the key to multi-hurdle farm to fork strategies. Therefore, we developed an anaerobic in vitro turkey cecal model to assess the effects of XPC on the ceca of commercial finisher tom turkeys fed diets void of XPC and antibiotics. Using the in vitro turkey cecal culture method, ceca were tested with and without XPC for their anti-Salmonella Reading and the previously defined anti-Typhimurium (ST97) effects. Ultimately, the anti-Salmonella effects were independent of serovar (P > 0.05). At 0 h post inoculation (hpi), Salmonella levels were equivalent between treatments at 7.3 Log10 CFU/mL, and at 24 hpi, counts in XPC were reduced by 5 Log10 CFU/mL, which was 2.1 Log10 lower than the control (P < 0.05). No differences in serovar prevalence existed (P > 0.05), with a 92% reduction in Salmonella positive XPC-treated ceca cultures by 48 hpi (P < 0.05). To evaluate changes to the microbiota independent of the immune response, the 16S rDNA was sequenced using the Illumina MiSeq platform. Data indicated a profound effect of time and treatment for the reduction of Salmonella irrespective of serovar. XPC sustained diversity metrics compared to the control, demonstrating a reduction in diversity over time (Q < 0.05).
GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance
Authors: Otaru Nize , Ye Kun , Mujezinovic Denisa , Berchtold Laura , Constancias Florentin , Cornejo Fabián A. , Krzystek Adam , de Wouters Tomas , Braegger Christian , Lacroix Christophe , Pugin Benoit
Published: April 2021

The high neuroactive potential of metabolites produced by gut microbes has gained traction over the last few years, with metagenomic-based studies suggesting an important role of microbiota-derived γ-aminobutyric acid (GABA) in modulating mental health. Emerging evidence has revealed the presence of the glutamate decarboxylase (GAD)-encoding gene, a key enzyme to produce GABA, in the prominent human intestinal genus Bacteroides. Here, we investigated GABA production by Bacteroides in culture and metabolic assays combined with comparative genomics and phylogenetics. A total of 961 Bacteroides genomes were analyzed in silico and 17 metabolically and genetically diverse human intestinal isolates representing 11 species were screened in vitro. Using the model organism Bacteroides thetaiotaomicron DSM 2079, we determined GABA production kinetics, its impact on milieu pH, and we assessed its role in mitigating acid-induced cellular damage. We showed that the GAD-system consists of at least four highly conserved genes encoding a GAD, a glutaminase, a glutamate/GABA antiporter, and a potassium channel. We demonstrated a high prevalence of the GAD-system among Bacteroides with 90% of all Bacteroides genomes (96% in human gut isolates only) harboring all genes of the GAD-system and 16 intestinal Bacteroides strains producing GABA in vitro (ranging from 0.09 to 60.84 mM). We identified glutamate and glutamine as precursors of GABA production, showed that the production is regulated by pH, and that the GAD-system acts as a protective mechanism against acid stress in Bacteroides, mitigating cell death and preserving metabolic activity. Our data also indicate that the GAD-system might represent the only amino acid-dependent acid tolerance system in Bacteroides. Altogether, our results suggest an important contribution of Bacteroides in the regulation of the GABAergic system in the human gut.
Rostral Intralaminar Thalamus Engagement in Cognition and Behavior
Authors: Cover Kara K. , Mathur Brian N.
Published: April 2021

The thalamic rostral intralaminar nuclei (rILN) are a contiguous band of neurons that include the central medial, paracentral, and central lateral nuclei. The rILN differ from both thalamic relay nuclei, such as the lateral geniculate nucleus, and caudal intralaminar nuclei, such as the parafascicular nucleus, in afferent and efferent connectivity as well as physiological and synaptic properties. rILN activity is associated with a range of neural functions and behaviors, including arousal, pain, executive function, and action control. Here, we review this evidence supporting a role for the rILN in integrating arousal, executive and motor feedback information. In light of rILN projections out to the striatum, amygdala, and sensory as well as executive cortices, we propose that such a function enables the rILN to modulate cognitive and motor resources to meet task-dependent behavioral engagement demands.
SIRT1 Deacetylates TET2 and Promotes Its Ubiquitination Degradation to Achieve Neuroprotection Against Parkinson's Disease
Authors: Li Xuan , Liu Te , Wu Ting-Ting , Feng Ya , Peng Si-Jia , Yin Huiyong , Wu Yun-Cheng
Published: April 2021

The epigenetic modifications, such as DNA methylation and histone acetylation, play a critical role in the pathogenesis of Parkinson's disease (PD). However, the relationship between DNA methylation and histone acetylation in PD is not fully understood. Previous studies have shown that patients with PD exhibit an epigenetic and transcriptional upregulation of Ten-Eleven Translocation 2 (TET2), a member of the DNA hydroxylases family. Silence information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, also plays a critical role in PD development and might be a potential target for PD therapy. Our previous data indicated that demethylation in the Cyclin-dependent kinase inhibitor 2A (CDKN2A) promoter by the TET2 directly activated its expression, then promoted the cell cycle arrest and cell death induced by 1-methyl-4-phenyl-pyridinium ion (MPP+). In this study, we found that the enzyme activity of SIRT1 is negatively correlated with the protein level of TET2. In addition, the deacetylation of TET2 induced by SIRT1 promotes TET2 degradation via the ubiquitin–proteasome pathway. Furthermore, the activation of endogenous SIRT1 by resveratrol (RV) leads to CDKN2A DNA hypermethylation due to the decreased TET2 protein levels, which relieves the inhibitory effect on CDK4 and upregulation of pRb, allowing cell proliferation and growth. Similar effects are observed for the inhibition of endogenous TET2 enzyme activity with TET2 inhibitor. Together, we discover a new mechanism by which the SIRT1-TET2-CDKN2A pathway is involved in the pathogenesis of PD, which may provide a potential target for PD treatment.
Advances in Proteomics Allow Insights Into Neuronal Proteomes
Authors: Fingleton Erin , Li Yan , Roche Katherine W.
Published: April 2021

Protein–protein interaction networks and signaling complexes are essential for normal brain function and are often dysregulated in neurological disorders. Nevertheless, unraveling neuron- and synapse-specific proteins interaction networks has remained a technical challenge. New techniques, however, have allowed for high-resolution and high-throughput analyses, enabling quantification and characterization of various neuronal protein populations. Over the last decade, mass spectrometry (MS) has surfaced as the primary method for analyzing multiple protein samples in tandem, allowing for the precise quantification of proteomic data. Moreover, the development of sophisticated protein-labeling techniques has given MS a high temporal and spatial resolution, facilitating the analysis of various neuronal substructures, cell types, and subcellular compartments. Recent studies have leveraged these novel techniques to reveal the proteomic underpinnings of well-characterized neuronal processes, such as axon guidance, long-term potentiation, and homeostatic plasticity. Translational MS studies have facilitated a better understanding of complex neurological disorders, such as Alzheimer’s disease (AD), Schizophrenia (SCZ), and Autism Spectrum Disorder (ASD). Proteomic investigation of these diseases has not only given researchers new insight into disease mechanisms but has also been used to validate disease models and identify new targets for research.
Visual Outcomes in Experimental Rodent Models of Blast-Mediated Traumatic Brain Injury
Authors: Evans Lucy P. , Roghair Ariel M. , Gilkes Noah J. , Bassuk Alexander G.
Published: April 2021

Blast-mediated traumatic brain injuries (bTBI) cause long-lasting physical, cognitive, and psychological disorders, including persistent visual impairment. No known therapies are currently utilized in humans to lessen the lingering and often serious symptoms. With TBI mortality decreasing due to advancements in medical and protective technologies, there is growing interest in understanding the pathology of visual dysfunction after bTBI. However, this is complicated by numerous variables, e.g., injury location, severity, and head and body shielding. This review summarizes the visual outcomes observed by various, current experimental rodent models of bTBI, and identifies data showing that bTBI activates inflammatory and apoptotic signaling leading to visual dysfunction. Pharmacologic treatments blocking inflammation and cell death pathways reported to alleviate visual deficits in post-bTBI animal models are discussed. Notably, techniques for assessing bTBI outcomes across exposure paradigms differed widely, so we urge future studies to compare multiple models of blast injury, to allow data to be directly compared.
Naturalistic Spike Trains Drive State-Dependent Homeostatic Plasticity in Superficial Layers of Visual Cortex
Authors: Chokshi Varun , Grier Bryce D. , Dykman Andrew , Lantz Crystal L. , Niebur Ernst , Quinlan Elizabeth M. , Lee Hey-Kyoung
Published: April 2021

The history of neural activity determines the synaptic plasticity mechanisms employed in the brain. Previous studies report a rapid reduction in the strength of excitatory synapses onto layer 2/3 (L2/3) pyramidal neurons of the primary visual cortex (V1) following two days of dark exposure and subsequent re-exposure to light. The abrupt increase in visually driven activity is predicted to drive homeostatic plasticity, however, the parameters of neural activity that trigger these changes are unknown. To determine this, we first recorded spike trains in vivo from V1 layer 4 (L4) of dark exposed (DE) mice of both sexes that were re-exposed to light through homogeneous or patterned visual stimulation. We found that delivering the spike patterns recorded in vivo to L4 of V1 slices was sufficient to reduce the amplitude of miniature excitatory postsynaptic currents (mEPSCs) of V1 L2/3 neurons in DE mice, but not in slices obtained from normal reared (NR) controls. Unexpectedly, the same stimulation pattern produced an up-regulation of mEPSC amplitudes in V1 L2/3 neurons from mice that received 2 h of light re-exposure (LE). A Poisson spike train exhibiting the same average frequency as the patterns recorded in vivo was equally effective at depressing mEPSC amplitudes in L2/3 neurons in V1 slices prepared from DE mice. Collectively, our results suggest that the history of visual experience modifies the responses of V1 neurons to stimulation and that rapid homeostatic depression of excitatory synapses can be driven by non-patterned input activity.
Mucosal Invasion, but Not Incomplete Excision, Has Negative Impact on Long-Term Survival in Patients With Extramammary Paget’s Disease
Authors: Hashimoto Hiroki , Kaku-Ito Yumiko , Furue Masutaka , Ito Takamichi
Published: April 2021

Background

Extramammary Paget’s disease (EMPD) sometimes spreads from the skin to mucosal areas, and curative surgical excision of these areas is challenging. The aim of this study is to analyze the impact of mucosal involvement and surgical treatment on the survival of patients with EMPD.

Methods

We conducted a retrospective review of 217 patients with EMPD. We also assessed the associations between tumor involvement in boundary areas (anal canal, external urethral meatus, vaginal introitus), prognostic factors, and survival in 198 patients treated with curative surgery.

Results

Of 217 patients, 75 (34.6%) had mucosal boundary area involvement. Lesions in these areas were associated with frequent lymphovascular invasion (p = 0.042), lymph node metastasis (p = 0.0002), incomplete excision (p < 0.0001), and locoregional recurrence (p < 0.0001). Boundary area involvement was an independent prognostic factor associated with disease-specific survival, per multivariate analysis (HR: 11.87, p = 0.027). Incomplete excision was not significantly correlated with disease-specific survival (HR: 1.05, p = 0.96).

Conclusion

Boundary area tumor involvement was a major risk factor for incomplete excision, local recurrence, and poor survival outcomes. However, incomplete removal of primary tumors was not significantly associated with poor prognosis. A less invasive surgical approach for preserving anogenital and urinary functions may be acceptable as the first-line treatment for resectable EMPD.
LINC00518 Promotes Cell Proliferation by Regulating the Cell Cycle of Lung Adenocarcinoma Through miR-185-3p Targeting MECP2
Authors: Han Xu , Wu Jixiang , Zhang Yajun , Song Jianxiang , Shi Zhan , Chang Huiwen
Published: April 2021

Previous studies have shown that long intergenic non-protein coding RNA 00518 (LINC00518) are essential for the cell growth and metastasis of human cancer. However, the role of LINC00518 in lung adenocarcinoma (LUAD) is still unknown. This research put emphasis on the function of LINC00518 on the cell growth of LUAD. The lncRNA, miRNA and mRNA expression were measured by using qRT-PCR. Protein levels were measured by using Western blotting. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Bioinformatic analysis and luciferase reporter assays were chosen to confirm the mechanism of LINC00518 in LUAD. We found that LINC00518 was highly expressed in LUAD specimens and the high-expression was negatively correlated with the overall survival rates. This finding was also proved in the LUAD cell lines. Through a series of in vitro and in vivo experiments, we proved that LICN00518 promoted the cell growth of LUAD by regulating the cell cycle. Moreover, LICN00518 upregulated the expression of MECP2 by mutagenesis of miR-185-3p. The results suggested that LICN00518 could be used as a survival indicator and potential therapeutic target for LUAD patients.
Transition of Treatment for Ground Glass Opacity–Dominant Non-Small Cell Lung Cancer
Authors: Handa Yoshinori , Tsutani Yasuhiro , Okada Morihito
Published: April 2021

Lobectomy has been the standard surgical treatment for non-small cell lung cancer (NSCLC). Over the decades, with the dramatic development of radiographic tools, such as high-resolution computed tomography (HRCT), and the widespread practice of low-dose helical CT for screening, the number of cases diagnosed with small-cell lung cancers with ground glass opacity (GGO) at early stages has been increasing. Accordingly, mainly after 2000, many retrospective studies and prospective trials have shown that patients with lung adenocarcinoma with GGO have a good prognosis and may be candidates for sublobar resection. Previous studies indicated that HRCT findings including the maximum diameter of the tumor, GGO ratio, and a consolidation/tumor ratio (CTR) are simple and useful tools to predict tumor invasiveness and prognosis in patients with NSCLC with GGO. Thus, sublobar resection may be considered a “standard therapy” for peripheral GGO-dominant small-cell lung adenocarcinomas. Ultimately, some of such tumors might not require surgical resection. A multicenter, prospective study has just begun in Japan to evaluate the validity of follow-up for small-sized GGO-dominant small-cell lung cancer. Lung cancers that do not require surgery should be identified. This study reviewed retrospective and prospective studies on GGO tumors and discussed the treatment strategies for such tumors.
The LncRNA CASC11 Promotes Colorectal Cancer Cell Proliferation and Migration by Adsorbing miR-646 and miR-381-3p to Upregulate Their Target RAB11FIP2
Authors: Zhang Wei , Li Xiaomin , Zhang Wenjuan , Lu Yanxia , Lin Weihao , Yang Lawei , Zhang Zheying , Li Xuenong
Published: April 2021

Background

We previously reported that the long non-coding RNA (lncRNA) CASC11 promotes colorectal cancer (CRC) progression as an oncogene by binding to HNRNPK. However, it remains unknown whether CASC11 can act as a competitive endogenous RNA (ceRNA) in CRC. In this study, we focused on the role of CASC11 as a ceRNA in CRC by regulating miR-646 and miR-381-3p targeting of RAB11FIP2.

Methods

We identified the target microRNAs (miRNAs) of CASC11 and the target genes of miR-646 and miR-381-3p using bioinformatic methods. A dual-luciferase reporter assay was performed to validate the target relationship. Quantitative real-time PCR (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC) were used to measure the RNA and protein expression levels. Rescue experiments in vitro and in vivo were performed to investigate the influence of the CASC11/miR-646 and miR-381-3p/RAB11FIP2 axis on CRC progression.

Results

We found that CASC11 binds to miR-646 and miR-381-3p in the cytoplasm of CRC cells. Moreover, miR-646 and miR-381-3p inhibitors reversed the suppressive effect of CASC11 silencing on CRC growth and metastasis in vitro and in vivo. We further confirmed that RAB11FIP2 is a mutual target of miR-646 and miR-381-3p. The expression levels of CASC11 and RAB11FIP2 in CRC were positively correlated and reciprocally regulated. Further study showed that CASC11 played an important role in regulating PI3K/AKT pathway by miR-646 and miR-381-3p/RAB11FIP2 axis.

Conclusion

Our study showed that CASC11 promotes the progression of CRC as a ceRNA by sponging miR-646 and miR-381-3p. Thus, CASC11 is a potential biomarker and a therapeutic target of CRC.
Case Report: ANXA2 Associated Life-Threatening Coagulopathy With Hyperfibrinolysis in a Patient With Non-APL Acute Myeloid Leukemia
Authors: Ruhnke Leo , Stölzel Friedrich , Wagenführ Lisa , Altmann Heidi , Platzbecker Uwe , Herold Sylvia , Rump Andreas , Schröck Evelin , Bornhäuser Martin , Schetelig Johannes , von Bonin Malte
Published: April 2021

Patients with acute promyelocytic leukemia (APL) often present with potentially life-threatening hemorrhagic diathesis. The underlying pathomechanisms of APL-associated coagulopathy are complex. However, two pathways considered to be APL-specific had been identified: 1) annexin A2 (ANXA2)-associated hyperfibrinolysis and 2) podoplanin (PDPN)-mediated platelet activation and aggregation. In contrast, since disseminated intravascular coagulation (DIC) is far less frequent in patients with non-APL acute myeloid leukemia (AML), the pathophysiology of AML-associated hemorrhagic disorders is not well understood. Furthermore, the potential threat of coagulopathy in non-APL AML patients may be underestimated. Herein, we report a patient with non-APL AML presenting with severe coagulopathy with hyperfibrinolysis. Since his clinical course resembled a prototypical APL-associated hemorrhagic disorder, we hypothesized pathophysiological similarities. Performing multiparametric flow cytometry (MFC) and immunofluorescence imaging (IF) studies, we found the patient’s bone-marrow mononuclear cells (BM-MNC) to express ANXA2 - a biomarker previously thought to be APL-specific. In addition, whole-exome sequencing (WES) on sorted BM-MNC (leukemia-associated immunophenotype (LAIP)1: ANXAlo, LAIP2: ANXAhi) demonstrated high intra-tumor heterogeneity. Since ANXA2 regulation is not well understood, further research to determine the coagulopathy-initiating events in AML and APL is indicated. Moreover, ANXA2 and PDPN MFC assessment as a tool to determine the risk of life-threatening DIC in AML and APL patients should be evaluated.
The Clinical and Pathological Features of Children With Microscopic Polyangiitis
Authors: Li Qian , Yu Li-Chun , Li Feng-Xia , Wang Jing , Chen Yuan , Sun Shu-Zhen
Published: April 2021

Objective: The aim of this study was to explore the clinical features, pathological characteristics, and the prognosis of children with microscopic polyangiitis (MPA).

Methods: Ten children with MPA that were hospitalized in our hospital were included in this study. The children's pre-diagnosis status, clinical manifestations, renal pathology, treatment, and prognosis data were analyzed retrospectively.

Results: All 10 cases included female patients with a median age of 8.9 years old at the time of diagnosis. MPO-ANCA antibody was positive in all cases, combined with a positive anti-GBM antibody in two cases. Nine cases had primary AAV and one had antithyroid drug (ATD)-associated MPA (secondary to methimazole). Renal involvement was found in all 10 patients, lung impairment was present in eight cases, and anemia was present in nine patients. Renal biopsies were performed in all 10 patients. Segmental focal or global glomerular necrosis was observed in 70% of the patients (7/10). The treatment mainly included steroid use combined with Cyclophosphamide and Mycophenolate. The follow-up s of the patients revealed normal renal function in eight patients and progression to end-stage renal disease (ESRD) in two patients.

Conclusions: Female predisposition and positive MPO-ANCA antibody were prominent in children with MPA. The patients' kidneys and lungs were the most frequently involved organs. Corticosteroid combined with immunosuppressive therapy was recommended for the treatment of MPA. Early diagnosis, prompt aggressive treatment, and regular follow-ups are also very important factors associated with a good prognosis.
Bexarotene Impairs Cognition and Produces Hypothyroidism in a Mouse Model of Down Syndrome and Alzheimer’s Disease
Authors: Vidal Verónica , Puente Alba , García-Cerro Susana , García Unzueta María Teresa , Rueda Noemí , Riancho Javier , Martínez-Cué Carmen
Published: April 2021

All individuals with Down syndrome (DS) eventually develop Alzheimer’s disease (AD) neuropathology, including neurodegeneration, increases inβ-amyloid (Aβ) expression, and aggregation and neurofibrillary tangles, between the third and fourth decade of their lives. There is currently no effective treatment to prevent AD neuropathology and the associated cognitive degeneration in DS patients. Due to evidence that the accumulation of Aβ aggregates in the brain produces the neurodegenerative cascade characteristic of AD, many strategies which promote the clearance of Aβ peptides have been assessed as potential therapeutics for this disease. Bexarotene, a member of a subclass of retinoids that selectively activates retinoid receptors, modulates several pathways essential for cognitive performance and Aβ clearance. Consequently, bexarotene might be a good candidate to treat AD-associated neuropathology. However, the effects of bexarotene treatment in AD remain controversial. In the present study, we aimed to elucidate whether chronic bexarotene treatment administered to the most commonly used murine model of DS, the Ts65Dn (TS) mouse could reduce Aβ expression in their brains and improve their cognitive abilities. Chronic administration of bexarotene to aged TS mice and their CO littermates for 9 weeks diminished the reference, working, and spatial learning and memory of TS mice, and the spatial memory of CO mice in the Morris water maze. This treatment also produced marked hypoactivity in the plus maze, open field, and hole board tests in TS mice, and in the open field and hole board tests in CO mice. Administration of bexarotene reduced the expression of Aβ1-40, but not of Aβ1-42, in the hippocampi of TS mice. Finally, bexarotene increased Thyroid-stimulating hormone levels in TS mice and reduced Thyroid-stimulating hormone levels in CO mice, while animals of both karyotypes displayed reduced thyroxine levels after bexarotene administration. The bexarotene-induced hypothyroidism could be responsible for the hypoactivity of TS and CO mice and their diminished performance in the Morris water maze. Together, these results do not provide support for the use of bexarotene as a potential treatment of AD neuropathology in the DS population.
Population Pharmacokinetics of Lithium in Young Pediatric Patients With Intellectual Disability
Authors: Yuan Junying , Zhang Bohao , Xu Yiran , Zhang Xiaoli , Song Juan , Zhou Wenhao , Hu Kai , Zhu Dengna , Zhang Lirong , Shao Fengmin , Zhang Shusheng , Ding Junjie , Zhu Changlian
Published: April 2021

Background: Lithium is a well-established treatment for bipolar disorders and has been shown to be neuroprotective, and thus low doses might be useful for the treatment of childhood brain injury and neurological sequelae. However, pharmacokinetic (PK) data in children are limited. This study was to investigate the PKs after oral administration of low-dose lithium carbonate in young children with intellectual disability.

Methods: Fifty-two children with intellectual disability aged 4–10 years old were enrolled. A series of blood samples were collected after a single-dose administration of lithium carbonate. The serum lithium concentration was measured using a validated ion chromatography assay, and the PK concentration data were modeled using a nonlinear mixed effect model in the NONMEM program.

Results: The lithium concentration over time was adequately described by a two-compartment disposition, with a transient absorption and first-order elimination process. The inclusion of body weight as an allometric factor significantly improved the model fit, but age and gender were not associated with the PKs of lithium. The clearance, central volume, inter-compartmental clearance, and peripheral volume estimates from the final population PK model were 0.98 L/h, 13.1 L, 0.84 L/h, and 8.2 L for children with a body weight of 20 kg. The model evaluation suggested that there is no obvious discrepancy between the observations and predictions in the proposed model. A visual predictive check demonstrated the good predictive performance of the final model.

Conclusions: The lithium PK properties in young children were similar to those in older children and adults. The proposed model can be used for further PK/PD analysis to optimize the dosage regimen of lithium in children.
Targeting Liver Sinusoidal Endothelial Cells: An Attractive Therapeutic Strategy to Control Inflammation in Nonalcoholic Fatty Liver Disease
Authors: Wang Xue-Kai , Peng Zong-Gen
Published: April 2021

Nonalcoholic fatty liver disease (NAFLD), especially its advanced stage nonalcoholic steatohepatitis (NASH), has become a threatened public health problem worldwide. However, no specific drug has been approved for clinical use to treat patients with NASH, though there are many promising candidates against NAFLD in the drug development pipeline. Recently, accumulated evidence showed that liver sinusoidal endothelial cells (LSECs) play an essential role in the occurrence and development of liver inflammation in patients with NAFLD. LSECs, as highly specialized endothelial cells with unique structure and anatomical location, contribute to the maintenance of liver homeostasis and could be a promising therapeutic target to control liver inflammation of NAFLD. In this review, we outline the pathophysiological roles of LSECs related to inflammation of NAFLD, highlight the pro-inflammatory and anti-inflammatory effects of LSECs, and discuss the potential drug development strategies against NAFLD based on targeting to LSECs.
High-Resolution Optical Imaging and Sensing Using Quantum Emitters in Hexagonal Boron-Nitride
Authors: Bradac Carlo
Published: April 2021

Super-resolution microscopy has allowed optical imaging to reach resolutions well beyond the limit imposed by the diffraction of light. The advancement of super-resolution techniques is often an application-driven endeavor. However, progress in material science plays a central role too, as it allows for the synthesis and engineering of nanomaterials with the unique chemical and physical properties required to realize super-resolution imaging strategies. This aspect is the focus of this review. We show that quantum emitters in two-dimensional hexagonal boron nitride are proving to be excellent candidate systems for the realization of advanced high-resolution imaging techniques, and spin-based quantum sensing applications.
Organelle Visualization With Multicolored Fluorescent Markers in Bamboo
Authors: Zhang Mengdi , Hu Shuai , Yi Fang , Gao Yanli , Zhu Dongmei , Wang Yizhu , Cai Yi , Hou Dan , Lin Xinchun , Shen Jinbo
Published: April 2021

Bamboo is an important model plant to study the molecular mechanisms of rapid shoot growth and flowering once in a lifetime. However, bamboo research about protein functional characterization is largely lagged behind, mainly due to the lack of gene transformation platforms. In this study, a protoplast transient gene expression system in moso bamboo has been first established. Using this reliable and efficient system, we have generated a set of multicolored fluorescent markers based on the targeting sequences from endogenous proteins, which have been validated by their comparative localization withArabidopsisorganelle markers, in a combination with pharmaceutical treatments. Moreover, we further demonstrated the power of this multicolor marker set for rapid, combinatorial analysis of the subcellular localization of uncharacterized proteins, which may play potential functions in moso bamboo flowering and fast growth of shoots. Finally, this protoplast transient gene expression system has been elucidated for functional analysis in protein–protein interaction by fluorescence resonance energy transfer (FRET) and co-immunoprecipitation analysis. Taken together, in combination with the set of moso bamboo organelle markers, the protoplast transient gene expression system could be used for subcellular localization and functional study of unknown proteins in bamboo and will definitely promote rapid progress in diverse areas of research in bamboo plants.
Personality and Mind-Wandering Self-Perception: The Role of Meta-Awareness
Authors: Ibaceta Miguel , Madrid Hector P.
Published: April 2021

Mind-wandering is a psychological process involving the emergence of spontaneous thoughts in daily life. Research has shown that mind-wandering influences diverse psychological outcomes; however, less is known about possible individual differences that may drive mind-wandering. In this study, we argue that personality traits, expressed in neuroticism and openness to experience, may lead to the individual’s self-perception of their mind-wandering activity, due to meta-awareness processes. In a three-wave survey study with 273 college students, we gathered data which supported a positive association of both neuroticism and openness to experience with mind-wandering self-perception, mediated by the individual’s meta-awareness. Thus, this study contributes to the literature on spontaneous thinking by showing that mind-wandering processes may be a function of individual differences expressed in personality traits.
Depression and Anxiety in Patients With Cancer: A Cross-Sectional Study
Authors: Naser Abdallah Y. , Hameed Anas Nawfal , Mustafa Nour , Alwafi Hassan , Dahmash Eman Zmaily , Alyami Hamad S. , Khalil Haya
Published: April 2021

Objectives

Depression and anxiety persist in cancer patients, creating an additional burden during treatment and making it more challenging in terms of management and control. Studies on the prevalence of depression and anxiety among cancer patients in the Middle East are limited and include many limitations such as their small sample sizes and restriction to a specific type of cancer in specific clinical settings. This study aimed to describe the prevalence and risk factors of depression and anxiety among cancer patients in the inpatient and outpatient settings.

Materials and Methods

A total of 1,011 patients (399 inpatients and 612 outpatients) formed the study sample. Patients’ psychological status was assessed using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder 7-item (GAD-7) scale. The prevalence rate of depressive and anxious symptomatology was estimated by dividing the number of patients who exceeded the borderline score: 10 or more for each subscale of the HADS scale, 15 or more for the GAD-7 scale, and 15 or more in the PHQ-9 by the total number of the patients. Risk factors were identified using logistic regression.

Results

The prevalence of depressive and anxious symptomatology among all patients was 23.4% and 19.1–19.9%, respectively. Depressive symptomatology was more prevalent across patients who were hospitalized (37.1%) compared with patients in the outpatient setting (14.5%) (p < 0.001). Similarly, anxious symptomatology was more prevalent in the inpatient setting (p < 0.001). In the inpatient setting, depressive symptomatology was more prevalent among patients with bladder cancer, while severe anxious symptomatology was more prevalent across patients with lung cancer. In the outpatient setting, depressive and anxious symptomatology was more prevalent among breast and prostate cancer patients, respectively. Despite that, around 42.7% and 24.8% of the patients, respectively, reported that they feel anxious and depressed, and only 15.5% of them were using medications to manage their conditions.

Conclusion

Our study findings demonstrated a higher prevalence of depressive and anxious symptomatology in the inpatient setting and advanced disease stages. In addition, the underutilization of antidepressant therapy was observed. There is a need to consider mental disorders as part of the treatment protocol for cancer patients. Enhanced clinical monitoring and treatment of depression and anxiety of cancer patients are required.
The Curvilinear Relationships Between Top Decision Maker Goal Orientations and Firm Ambidexterity: Moderating Effect of Role Experience
Authors: Pryor Christopher , Santos Susana C. , Xie Jiangpei
Published: April 2021

Ambidextrous firms are those that can simultaneously manage exploitative and explorative innovation, which is why ambidexterity is key for firms that desire to pursue strategic entrepreneurship. Researchers have explored many of the reasons why some firms are more ambidextrous than others. However, little attention has been devoted to understanding how attributes of top decision makers can influence their firms' ambidexterity. By drawing on upper echelons theory and goal orientations research, we explain how firms' ambidexterity can be affected by top decision makers' motivations in achievement situations (i.e., goal orientations). Testing our hypotheses on a sample of 274 top decision makers of firms in the United States, we find that top decision makers' learning goal orientation – their desire to take risks and maximize learning–has an inverted U-shaped relationship with ambidexterity while top decision makers' performance prove goal orientation – their desire to demonstrate competence with existing skills – has a U-shaped relationship with ambidexterity. These effects are weaker for top decision makers who have greater role experience.
Music Student’s Approach to the Forced Use of Remote Performance Assessments
Authors: Ritchie Laura , Sharpe Benjamin T.
Published: April 2021

Music students at the University of Chichester Conservatoire completed questionnaires about their experience of the forced use of remote teaching and learning due to Lockdown, as imposed in the United Kingdom from March to June 2020, and how this impacted their self-beliefs, decision making processes, and methods of preparation for their performance assessments. Students had the choice to either have musical performance assessed in line with originally published deadlines (still in Lockdown) via self-recorded video or defer the assessment until the following academic year. Student’s choice to defer or submit the assessment during Lockdown was influenced by a range of forced factors, such as adaptions required by online teaching, limitations of rehearsal in their home environment, and the challenges in facilitating and recording their own assessments. Students completed online questionnaires about their self-efficacy, resilience, wellbeing, and provided free text responses explaining the reasoning for their decision to record their performance or to defer the assessment were coded to reveal patterns impacting their decision and preparation processes. Those choosing to submit their assessments demonstrated more strategies in their preparation and reported higher perceived self-efficacy scores. The specific conditions for this assessment, as a result of Lockdown, revealed correlations between resilience and both self-efficacy and wellbeing. The impact on teaching and the student experience is discussed and suggestions to support students in future settings of blended delivery are presented. Theoretical and practical implications are discussed.
How to Develop Entrepreneurial Talent More Effectively? A Comparison of Different Entrepreneurship Educational Methods
Authors: Yang Qixing , Chen Jiachun , Yang Lijun , Liu Zhenhuan
Published: April 2021

Recently, scholars have begun to shift focus toward the effectiveness of different teaching methods for entrepreneurship education. However, the establishment of a unified and clear standard for the division of entrepreneurship educational methods remains unfulfilled, affecting the accuracy of research conclusions. In the present study, for the first time, the aim was to divide the entrepreneurship educational method into the classroom teaching method (CTM) and the extracurricular activity method (EAM) from the perspective of competency level training. On the basis of the modified planning behavior theory, the influence of entrepreneurship education on entrepreneurial intention (EI) was explored. In the present study, 514 college students of 14 universities in China were surveyed. The results reveal that the CTM and EAM had a direct positive bearing on EI, with indirect impact exerted by attitude toward entrepreneurship (ATE) and perceived behavioral control (PBC). Although the direct effects of the two teaching methods were similar, EAM could effectively improve ATE and PBC, thereby resulting in a positive effect on EI to a greater extent. Further observations were made that the participation of research University students in CTM was significantly lower than that of applied University students, leading to lower EI. Additionally, higher EI could be attributed to the more active participation in EAM of male students than female students, while no significant difference was indicated between different majors in EI. The results are of significant reference value for promoting the reform of entrepreneurship education and improving the quality of entrepreneurship education in colleges and universities.
The Indexical Voice: Communication of Personal States and Traits in Humans and Other Primates
Authors: Locke John L.
Published: April 2021

Many studies of primate vocalization have been undertaken to improve our understanding of the evolution of language. Perhaps, for this reason, investigators have focused on calls that were thought to carry symbolic information about the environment. Here I suggest that even if these calls were in fact symbolic, there were independent reasons to question this approach in the first place. I begin by asking what kind of communication system would satisfy a species’ biological needs. For example, where animals benefit from living in large groups, I ask how members would need to communicate to keep their groups from fragmenting. In this context, I discuss the role of social grooming and “close calls,” including lip-smacking and grunting. Parallels exist in human societies, where information is exchanged about all kinds of things, often less about the nominal topic than the communicants themselves. This sort of indexical (or personal) information is vital to group living, which presupposes the ability to tolerate, relate to, and interact constructively with other individuals. Making indexical communication the focus of comparative research encourages consideration of somatic and behavioral cues that facilitate relationships and social benefits, including cooperation and collaboration. There is ample room here for a different and potentially more fruitful approach to communication in humans and other primates, one that focuses on personal appraisals, based on cues originating with individuals, rather than signals excited by environmental events.
Enhancing Literacy and Communicative Skills of Students With Disabilities in Special Schools Through Dialogic Literary Gatherings
Authors: Fernández-Villardón Aitana , Valls-Carol Rosa , Melgar Alcantud Patricia , Tellado Itxaso
Published: April 2021

Enhancing the quality of learning opportunities for students with disabilities and the learning level attained is a pending challenge. This challenge is especially relevant in the context of special schools, where the learning possibilities derived from interactions with others is limited. However, providing these students with a sufficient level of instrumental learning, such as literacy, and communicative and reasoning abilities is crucial for their subsequent educational and social opportunities. In this case study we analyse a special school that has implemented Dialogic Literary Gatherings with their students as a means to increase learning interactions within the group around the reading and debate of classical books. Semi-structured interviews were conducted with the school principal and with a teacher of the transition to adult life course, and two focus groups were conducted with teachers–one with primary education teachers and one with secondary education teachers–and two focus groups with students–one with primary education students and one secondary education and transition to adult life students–. On the one hand, results show the characteristics of the Dialogic Literary Gatherings that allowed these students to participate and learn. On the other hand, several improvements have been observed. First, regarding instrumental learning, students increased their motivation for reading, and improved their communicative and reasoning abilities and in their reading proficiency. Second, regarding students' behavior, conflict has reduced, solidarity attitudes have increased, and they have acquired dialogic and argumentative habits. Finally, at the emotional level, they gained self-esteem and confidence and feel more empowered to make their voice heard.
Psychometric Properties of the Persian Version of the Teasing Questionnaire 23
Authors: Ebrahimi Ali , Elhami Athar Mojtaba , Hakim Shooshtari Mitra , Karsazi Hossain , Storch Eric A
Published: April 2021

The current study was a cross-sectional research and aimed to investigate the factor structure, internal consistency, and validities of the Persian version of the Teasing Questionnaire-Revised (TQ-R). Forward and backward translations of the TQ-R were performed; face and content validities were determined based on comments by a sample of psychology students and specialists. Using the cluster sampling method, 290 participants were recruited, and 201 valid data (Mage = 23.53, SD = 3.53, 64.2% men) were analyzed. The factor structure was assessed by confirmatory and exploratory factor analysis (EFA). The result of the confirmatory factor analysis(es) did not confirm the proposed three, four, and five-factor models. EFA revealed four factors with 23 items, explaining 52.03% of the total variance. The internal consistency of the Persian version of Teasing Questionnaire 23 was in the excellent range (α = 0.92), and its expected associations with external correlates (e.g., depression and anxiety) supported the measure’s convergent validity. The findings indicated that the Persian version of the TQ-R has sound psychometric properties and can be used as a valid and reliable tool in research and clinical outcomes.