bluuebunny/crossref_metadata_2025 huggingface dataset:
El arborigrama. Estrategia didáctica de comprensión lectora de textos narrativos
Authors: Loayza-Maturrano Edward F.
Published: May 2021

El bajo nivel de comprensión de lectura evidenciado por los estudiantes de la educación básica exige plantear propuestas que vinculen de forma eficaz dos variables socioeducativas: la didáctica y la lectura. La investigación planteó como objetivo principal determinar si existe influencia entre la estrategia del arborigrama y la mejora de la comprensión lectora en una población pre-adolescente del grupo etario de 11 a 13 años del primer grado del nivel Secundaria en el distrito de La Molina. Se diseñó un estudio cuasiexperimental que consideró una pre-prueba y post-prueba respecto de la aplicación del módulo del arborigrama. Los resultados indican la existencia de influencia causal moderada alta entre las variables estrategia del arborigrama y la comprensión de lectura en los estudiantes. La conclusión principal del estudio establece que el arborigrama como estrategia didáctica influye de forma significativa en la mejora de la comprensión de lectura de textos narrativos en estudiantes de la educación básica.
Calibration of a Heterogeneous Brain Model Using a Subject-Specific Inverse Finite Element Approach
Authors: Giudice J. Sebastian , Alshareef Ahmed , Wu Taotao , Knutsen Andrew K. , Hiscox Lucy V. , Johnson Curtis L. , Panzer Matthew B.
Published: May 2021

Central to the investigation of the biomechanics of traumatic brain injury (TBI) and the assessment of injury risk from head impact are finite element (FE) models of the human brain. However, many existing FE human brain models have been developed with simplified representations of the parenchyma, which may limit their applicability as an injury prediction tool. Recent advances in neuroimaging techniques and brain biomechanics provide new and necessary experimental data that can improve the biofidelity of FE brain models. In this study, the CAB-20MSym template model was developed, calibrated, and extensively verified. To implement material heterogeneity, a magnetic resonance elastography (MRE) template image was leveraged to define the relative stiffness gradient of the brain model. A multi-stage inverse FE (iFE) approach was used to calibrate the material parameters that defined the underlying non-linear deviatoric response by minimizing the error between model-predicted brain displacements and experimental displacement data. This process involved calibrating the infinitesimal shear modulus of the material using low-severity, low-deformation impact cases and the material non-linearity using high-severity, high-deformation cases from a dataset of in situ brain displacements obtained from cadaveric specimens. To minimize the geometric discrepancy between the FE models used in the iFE calibration and the cadaveric specimens from which the experimental data were obtained, subject-specific models of these cadaveric brain specimens were developed and used in the calibration process. Finally, the calibrated material parameters were extensively verified using independent brain displacement data from 33 rotational head impacts, spanning multiple loading directions (sagittal, coronal, axial), magnitudes (20–40 rad/s), durations (30–60 ms), and severity. Overall, the heterogeneous CAB-20MSym template model demonstrated good biofidelity with a mean overall CORA score of 0.63 ± 0.06 when compared to in situ brain displacement data. Strains predicted by the calibrated model under non-injurious rotational impacts in human volunteers (N = 6) also demonstrated similar biofidelity compared to in vivo measurements obtained from tagged magnetic resonance imaging studies. In addition to serving as an anatomically accurate model for further investigations of TBI biomechanics, the MRE-based framework for implementing material heterogeneity could serve as a foundation for incorporating subject-specific material properties in future models.
Role of ex vivo Expanded Mesenchymal Stromal Cells in Determining Hematopoietic Stem Cell Transplantation Outcome
Authors: Crippa Stefania , Santi Ludovica , Berti Margherita , De Ponti Giada , Bernardo Maria Ester
Published: May 2021

Overall, the human organism requires the production of ∼1 trillion new blood cells per day. Such goal is achieved via hematopoiesis occurring within the bone marrow (BM) under the tight regulation of hematopoietic stem and progenitor cell (HSPC) homeostasis made by the BM microenvironment. The BM niche is defined by the close interactions of HSPCs and non-hematopoietic cells of different origin, which control the maintenance of HSPCs and orchestrate hematopoiesis in response to the body’s requirements. The activity of the BM niche is regulated by specific signaling pathways in physiological conditions and in case of stress, including the one induced by the HSPC transplantation (HSCT) procedures. HSCT is the curative option for several hematological and non-hematological diseases, despite being associated with early and late complications, mainly due to a low level of HSPC engraftment, impaired hematopoietic recovery, immune-mediated graft rejection, and graft-versus-host disease (GvHD) in case of allogenic transplant. Mesenchymal stromal cells (MSCs) are key elements of the BM niche, regulating HSPC homeostasis by direct contact and secreting several paracrine factors. In this review, we will explore the several mechanisms through which MSCs impact on the supportive activity of the BM niche and regulate HSPC homeostasis. We will further discuss how the growing understanding of such mechanisms have impacted, under a clinical point of view, on the transplantation field. In more recent years, these results have instructed the design of clinical trials to ameliorate the outcome of HSCT, especially in the allogenic setting, and when low doses of HSPCs were available for transplantation.
The Role of Irisin in Exercise-Mediated Bone Health
Authors: Liu Lifei , Guo Jianmin , Chen Xi , Tong Xiaoyang , Xu Jiake , Zou Jun
Published: May 2021

Exercise training promotes physical and bone health, and is the first choice of non-drug strategies that help to improve the prognosis and complications of many chronic diseases. Irisin is a newly discovered peptide hormone that modulates energy metabolism and skeletal muscle mass. Here, we discuss the role of irisin in bone metabolism via exercise-induced mechanical forces regulation. In addition, the role of irisin in pathological bone loss and other chronic diseases is also reviewed. Notably, irisin appears to be a key determinant of bone mineral status and thus may serve as a novel biomarker for bone metabolism. Interestingly, the secretion of irisin appears to be mediated by different forms of exercise and pathological conditions such as diabetes, obesity, and inflammation. Understanding the mechanism by which irisin is regulated and how it regulates skeletal metabolism via osteoclast and osteoblast activities will be an important step toward applying new knowledge of irisin to the treatment and prevention of bone diseases such as osteolysis and other chronic disorders.
Ru0·Run+/Al2O3 as a Versatile Catalyst in the Isomerization of Allyl Alcohol
Authors: Enciso Julián , Ramírez Alfonso , Ostos Carlos , Echavarría Adriana , Córdoba Misael , Lederhos Cecilia , Miranda Cristian
Published: May 2021

This study focuses on examining the isomerization of allyl alcohol using ruthenium (Ru) supported on alumina as a heterogeneous catalyst. The synthesized Ru/Al solids were characterized by various characterization techniques. The content of Ru was estimated by the energy dispersive x-ray technique. The x-ray diffraction (XRD) confirmed the presence of phases in the support and active species in the catalysts. The surface area of the support after Ru impregnation and the pore volume were determined by nitrogen physisorption. The analysis of programmed temperature (TPR and TPO) shows different redox sites which is confirmed by XPS. The catalytic results suggest a dependence on the amount of available metallic Ru, as well as the importance of the continuous regeneration of the metal using H2to achieve a good conversion of the allyl alcohol. For comparison purposes, the commercial Ru on alumina 5% (CAS 908142) was used. The results show up to 68% alcohol conversion and 27% yield of the isomerization product using Ru(1,5.4h)/Al catalyst in comparison with 86% conversion and 39% yield of the isomerization product using CAS 908142. In contrast, our catalysts always presented higher TOF values (149–160) in comparison with CAS 908142 (101).
Genetic Diversity and Prevalence of Giardia duodenalis in Qatar
Authors: Chourabi Marwa , Boughattas Sonia , Abdallah Atiyeh M. , Ismail Ahmed , Behnke Jerzy M. , Al-Mekhlafi Hesham M. , Abu-Madi Marawan
Published: May 2021

Background

Giardia duodenalis is a common human intestinal parasite worldwide, and the causative agent of diarrhea, with the severity of disease ranging from asymptomatic to intense and debilitating infection. G. duodenalis is known to consist of eight genetically distinct assemblages, named from A to H. No data available on the genotypes and genetic diversity of G. duodenalis circulating in Qatar.

Methods

We genotyped 54 human Giardia isolates, collected from asymptomatic immigrants in Qatar, using a multilocus genotyping (MLGs) tool. We also investigated relationships between the subjects’ genotypes and their demographic data.

Results

Genomic DNA from 54 isolates were tested by PCR and sequence analysis at three loci: glutamate dehydrogenase (gdh), β-giardin (bg) and triose phosphate (tpi)). Assemblage A was identified in nine (16.67%), assemblage B in thirty (55.55%), and a mixture of assemblages A+B in fifteen (27.78%) isolates. All assemblage A isolates, genotyped in different loci, were assigned to sub-assemblage AII, and six of them had MLGs AII-1 while one new MLG was identified in two isolates. Sequences of assemblage B isolates have high level of genetic diversity and high presence of heterogeneous peaks, especially within the gdh gene. No significant associations between genotypes and the immigrants’ demographic data were found due to the extensive number of new variants.

Conclusions

MLGs was used herein to genotype 54 immigrant Giardia isolates. The high level of genetic variability found in our isolates hampered MLGs determination, more investigations are now required to consolidate our findings, and to enable a comprehensive understanding of the diversity within G. duodenalis assemblage B isolates.
The Sabatier Principle in Electrocatalysis: Basics, Limitations, and Extensions
Authors: Ooka Hideshi , Huang Jun , Exner Kai S.
Published: May 2021

The Sabatier principle, which states that the binding energy between the catalyst and the reactant should be neither too strong nor too weak, has been widely used as the key criterion in designing and screening electrocatalytic materials necessary to promote the sustainability of our society. The widespread success of density functional theory (DFT) has made binding energy calculations a routine practice, turning the Sabatier principle from an empirical principle into a quantitative predictive tool. Given its importance in electrocatalysis, we have attempted to introduce the reader to the fundamental concepts of the Sabatier principle with a highlight on the limitations and challenges in its current thermodynamic context. The Sabatier principle is situated at the heart of catalyst development, and moving beyond its current thermodynamic framework is expected to promote the identification of next-generation electrocatalysts.
Recovering Supply Chain Disruptions in Post-COVID-19 Pandemic Through Transport Intelligence and Logistics Systems: India's Experiences and Policy Options
Authors: Sudan Tapas , Taggar Rashi
Published: May 2021

Before the COVID-19 pandemic, Indian firms have focused on interconnected and lean supply chains to ameliorate the gaps through increased efficiency of supply chains. However, the pandemic has exposed most Indian firms to severe supply chain disruptions (SCDs) due to undiscovered supply chain vulnerabilities. Against this background, we reviewed the existing relevant literature on SCDs and transportation disruption in general context and pandemic specific context and identified that there exists very little research on this issue especially in the context of Indian firms, and offered policy options by developing a new model of robust transport and advanced logistics system (ALS) for speedier supply chains recovery (SCR). We have utilized and analyzed the rich available literature on SCDs, transport intelligence (TI), and ALS using gray literature. The study revealed that many Indian firms have experienced major disruptions in transportation and logistics services, including impact on transportation and logistics data, time delays, and cargo cancellations due to cramped freight capacity, restricted circulation, closure of ports, and slow customs clearances. This has also impacted adversely the production and transport consignments including logistics services and led to delays and rerouting to final consumers. With the gradual removal of restrictions, firms are making concerted efforts to recover from SCDs; however, with weak applications of robust TI and ALS, the SCR is relatively very slow. This called for a review of current transport and ALS used by priority firms. Therefore, we offered a new model for addressing the SCDs using robust intelligence transportation systems and ALS.
Exosome-Contained APOH Associated With Antiphospholipid Syndrome
Authors: Tan Yuan , Bian Yiding , Song Yunfeng , Zhang Qinhua , Wan Xiaoping
Published: May 2021

Background

Antiphospholipid syndrome (APS) is a systemic autoimmune disease that can lead to thrombosis and/or pregnancy complications. Exosomes, membrane-encapsulated vesicles that are released into the extracellular environment by many types of cells, can carry signals to recipient cells to affect angiogenesis, apoptosis, and inflammation. There is increasing evidence suggesting that exosomes play critical roles in pregnancy. However, the contribution of exosomes to APS is still unknown.

Methods

Peripheral plasma was collected from healthy early pregnancy patients (NC-exos) and early pregnancy patients with APS (APS-exos) for exosome extraction and characterization. The effect of exosomes from different sources on pregnancy outcomes was determined by establishing a mouse pregnancy model. Following the coincubation of exosomes and human umbilical vein endothelial cells (HUVECs), functional tests examined the features of APS-exos. The APS-exos and NC-exos were analyzed by quantitative proteomics of whole protein tandem mass tag (TMT) markers to explore the different compositions and identify key proteins. After incubation with HUVECs, functional tests investigated the characteristics of key exosomal proteins. Western blot analysis was used to identify the key pathways.

Results

In the mouse model, APS-exos caused an APS-like birth outcome. In vitro experiments showed that APS-exos inhibited the migration and tube formation of HUVECs. Quantitative proteomics analysis identified 27 upregulated proteins and 9 downregulated proteins in APS-exos versus NC-exos. We hypothesized that apolipoprotein H (APOH) may be a core protein, and the analysis of clinical samples was consistent with finding from the proteomic TMT analysis. APOH-exos led to APS-like birth outcomes. APOH-exos directly enter HUVECs and may play a role through the phospho-extracellular signal-regulated kinase pathway.

Conclusions

Our study suggests that both APS-exos and APOH-exos impair vascular development and lead to pregnancy complications. APOH-exos may be key actors in the pathogenesis of APS. This study provides new insights into the pathogenesis of APS and potential new targets for therapeutic intervention.
Allogeneic Hemopoietic Stem Cell Transplantation for Myelofibrosis: 2021
Authors: Bacigalupo Andrea , Innocenti Idanna , Rossi Elena , Sora Federica , Galli Eugenio , Autore Francesco , Metafuni Elisabetta , Chiusolo Patrizia , Giammarco Sabrina , Laurenti Luca , Benintende Giulia , Sica Simona , De Stefano Valerio
Published: May 2021

The aim of this review is to update the current status of allogeneic hemopoietic stem cell transplants (HSCT) for patients with myelofibrosis (MF). We have first summarized the issue of an indication for allogeneic HSCT, discussing several prognostic scoring systems, developed to predict the outcome of MF, and therefore to identify patients who will benefit of an allogeneic HSCT. Patients with low risk MF are usually not selected for a transplant, whereas patients with intermediate or high risk MF are eligible. A separate issue, is how to predict the outcome of HSCT: we will outline a clinical molecular myelofibrosis transplant scoring system (MTSS), which predicts overall survival, ranging from 90% for low risk patients, to 20% for very high risk patients. We will also discuss transfusion burden and spleen size, as predictors of transplant outcome. The choice of a transplant platform including the conditioning regimen, the stem cell source and GvHD prophylaxis, are crucial for a successful program in MF, and will be outlined. Complications such as poor graft function, graft failure, GvHD and relapse of the disease, will also be reviewed. Finally we discuss monitoring the disease after HSCT with donor chimerism, driver mutations and hematologic data. We have made an effort to make this review as comprehensive and up to date as possible, and we hope it will provide some useful data for the clinicians.
ATP Facilitates Staphylococcal Enterotoxin O Induced Neutrophil IL-1β Secretion via NLRP3 Inflammasome Dependent Pathways
Authors: Hou Fengqing , Peng Lianci , Jiang Jiali , Chen Tingting , Xu Dongyi , Huang Qingyuan , Ye Chao , Peng Yuanyi , Hu Dong-Liang , Fang Rendong
Published: May 2021

Staphylococcus aureus (S. aureus) is an important zoonotic food-borne pathogen causing severe invasive infections, such as sepsis, pneumonia, food poisoning, toxic shock syndrome and autoimmune diseases. Staphylococcal enterotoxin O (SEO) is a new type of enterotoxins of S. aureus with superantigenic and emetic activity. However, it is still unclear about SEO-induced host inflammatory response. Therefore, the mechanism of SEO-induced interleukin-1β (IL-1β) secretion in mouse neutrophils was investigated in this study. Our results showed that recombinant SEO had superantigenic activity with high level of gamma interferon (IFN-γ) production in mouse spleen cells and induced inflammatory cytokines expression including IL-1α, IL-1β, IL-6 and TNF-α in neutrophils under the action of ATP. In addition, SEO-induced IL-1β secretion was dependent on activation of Toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways. However, SEO-induced IL-1β secretion was abolished in the neutrophils of NLRP3-/- mice compared with those of wild type mice, indicating that activation of NLRP3 inflammasome mediated IL-1β secretion during neutrophils stimulation with SEO under the action of ATP. Moreover, this process of SEO+ATP-induced IL-1β secretion was dependent on potassium (K+) efflux. Taken together, our study suggests that activation of TLR4/JNK/NLRP3 inflammasome signaling pathway mediate maturation and secretion of IL-1β and provides a new insight on S. aureus virulence factor-induced host immune response.
Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size?
Authors: Lamptey Helena , Bonney Evelyn Y. , Adu Bright , Kyei George B.
Published: May 2021

Fc gamma receptors (FcγR) are cell surface glycoproteins which trigger specific effector-cell responses when cross-linked with the Fc portions of immunoglobulin (IgG) antibodies. During HIV-1 infection, the course of disease progression, ART response, and viral reservoir size vary in different individuals. Several factors may account for these differences; however, Fc gamma receptor gene polymorphisms, which influence receptor binding to IgG antibodies, are likely to play a key role. FcγRIIa (CD32) was recently reported as a potential marker for latent HIV reservoir, however, this assertion is still inconclusive. Whether FcγR polymorphisms influence the size of the viral reservoir, remains an important question in HIV cure studies. In addition, potential cure or viral suppression methods such as broadly neutralizing antibody (bNAbs) may depend on FcγRs to control the virus. Here, we discuss the current evidence on the potential role played by FcγR polymorphisms in HIV-1 infection, treatment and vaccine trial outcomes. Importantly, we highlight contrasting findings that may be due to multiple factors and the relatively limited data from African populations. We recommend further studies especially in sub-Saharan Africa to confirm the role of FcγRIIa in the establishment of latent reservoir and to determine their influence in therapies involving bNAbs.
Mycobacterium tuberculosis Rv2145c Promotes Intracellular Survival by STAT3 and IL-10 Receptor Signaling
Authors: Park Hye-Soo , Back Yong Woo , Jang In-Taek , Lee Kang-In , Son Yeo-Jin , Choi Han-Gyu , Dang Thi Binh , Kim Hwa-Jung
Published: May 2021

Although Mycobacterium tuberculosis (Mtb) is an intracellular pathogen in phagocytic cells, the factors and mechanisms by which they invade and persist in host cells are still not well understood. Characterization of the bacterial proteins modulating macrophage function is essential for understanding tuberculosis pathogenesis and bacterial virulence. Here we investigated the pathogenic role of the Rv2145c protein in stimulating IL-10 production. We first found that recombinant Rv2145c stimulated bone marrow-derived macrophages (BMDMs) to secrete IL-10, IL-6 and TNF-α but not IL-12p70 and to increase the expression of surface molecules through the MAPK, NF-κB, and TLR4 pathways and enhanced STAT3 activation and the expression of IL-10 receptor in Mtb-infected BMDMs. Rv2145c significantly enhanced intracellular Mtb growth in BMDMs compared with that in untreated cells, which was abrogated by STAT3 inhibition and IL-10 receptor (IL-10R) blockade. Expression of Rv2145c in Mycobacterium smegmatis (M. smegmatis) led to STAT3-dependent IL-10 production and enhancement of intracellular growth in BMDMs. Furthermore, the clearance of Rv2145c-expressing M. smegmatis in the lungs and spleens of mice was delayed, and these effects were abrogated by administration of anti-IL-10R antibodies. Finally, all mice infected with Rv2145c-expressing M. smegmatis died, but those infected with the vector control strain did not. Our data suggest that Rv2145c plays a role in creating a favorable environment for bacterial survival by modulating host signals.
The Zinc Nutritional Immunity of Epinephelus coioides Contributes to the Importance of znuC During Pseudomonas plecoglossicida Infection
Authors: Huang Lixing , Zuo Yanfei , Qin Yingxue , Zhao Lingmin , Lin Mao , Yan Qingpi
Published: May 2021

Previously, the dual RNA-seq was carried out in a Pseudomonas plecoglossicida- Epinephelus coioides infection model to investigate the dynamics of pathogen-host interplay in vivo. ZnuC, a member of ZnuCBA Zn importer, was found transcriptionally up-regulated during infection. Thus, this study aimed to assess its role during the trade-off for Zn between host and P. plecoglossicida. ICP-MS analysis and fluorescent staining showed that Zn was withheld from serum and accumulated in the spleen, with increased Zn uptake in the Golgi apparatus of macrophages after infection. Additionally, growth assay, macrophage infection and animal infection after gene knockout / silencing revealed that znuC was necessary for growth in Zn-limiting conditions, colonization, intracellular viability, immune escape and virulence of P. plecoglossicida. Further analysis with dual RNA-seq revealed associations of host’s Zn nutritional immunity genes with bacterial Zn assimilation genes. IL6 and ZIP4 played key roles in this network, and markedly affected znuB expression, intracellular viability and immune escape, as revealed by gene silencing. Moreover, EMSA and GFP reporter gene analysis showed that Fur sensed changes in Fe concentration to regulate znuCBA in P. plecoglossicida. Jointly, these findings suggest a trade-off for Zn between host and P. plecoglossicida, while ZnuC is important for P. plecoglossicida Zn acquisition.
Patients With Epilepsy Who Underwent Epilepsy Surgery During the COVID-19 Pandemic Showed Less Depressive Tendencies
Authors: Niimi Keiko , Fujimoto Ayataka , Sato Keishiro , Enoki Hideo , Okanishi Tohru
Published: May 2021

Introduction: Our hypothesis in this study was that differences might exist between patients with epilepsy (PWE) who underwent epilepsy surgery before and within the period of the coronavirus disease 2019 (COVID-19) pandemic. The purpose of this study was to compare results of the Zung Self-Rating Depression Scale (SDS) between PWE who underwent epilepsy surgery before and during the pandemic period.

Methods: Participants were PWE who underwent open cranial epilepsy surgery between February 2019 and February 2021 in our hospital. Patients who underwent surgery in the first half of this period, between February 2019 and January 2020, were defined as the pre-pandemic period group (pre-Group) and those treated in the second half, between February 2020 and February 2021, were categorized as the pandemic period group (within-Group). All patients completed the SDS before surgery, and scores were compared between groups.

Results: SDS score was significantly higher in the pre-Group than in the within-Group (p = 0.037). Other factors, including age (p = 0.51), sex (p = 0.558), epilepsy duration from onset to SDS score evaluation (p = 0.190), seizure frequency (p = 0.794), number of anti-seizure medications (p = 0.787), and intelligence quotient (p = 0.871) did not differ significantly between groups.

Conclusion: SDS score was higher in the pre-pandemic group than in the within-pandemic group, which may indicate that PWE with less-positive outlooks may be less likely to seek medical attention during stressful periods.
Self-Related Stimuli Decoding With Auditory and Visual Modalities Using Stereo-Electroencephalography
Authors: Ye Huanpeng , Fan Zhen , Chai Guohong , Li Guangye , Wei Zixuan , Hu Jie , Sheng Xinjun , Chen Liang , Zhu Xiangyang
Published: May 2021

Name recognition plays important role in self-related cognitive processes and also contributes to a variety of clinical applications, such as autism spectrum disorder diagnosis and consciousness disorder analysis. However, most previous name-related studies usually adopted noninvasive EEG or fMRI recordings, which were limited by low spatial resolution and temporal resolution, respectively, and thus millisecond-level response latencies in precise brain regions could not be measured using these noninvasive recordings. By invasive stereo-electroencephalography (SEEG) recordings that have high resolution in both the spatial and temporal domain, the current study distinguished the neural response to one's own name or a stranger's name, and explored common active brain regions in both auditory and visual modalities. The neural activities were classified using spatiotemporal features of high-gamma, beta, and alpha band. Results showed that different names could be decoded using multi-region SEEG signals, and the best classification performance was achieved at high gamma (60–145 Hz) band. In this case, auditory and visual modality-based name classification accuracies were 84.5 ± 8.3 and 79.9 ± 4.6%, respectively. Additionally, some single regions such as the supramarginal gyrus, middle temporal gyrus, and insula could also achieve remarkable accuracies for both modalities, supporting their roles in the processing of self-related information. The average latency of the difference between the two responses in these precise regions was 354 ± 63 and 285 ± 59 ms in the auditory and visual modality, respectively. This study suggested that name recognition was attributed to a distributed brain network, and the subsets with decoding capabilities might be potential implanted regions for awareness detection and cognition evaluation.
Peripherally Acting Opioids in Orofacial Pain
Authors: Liu Qing , He Hongwen , Mai Lijia , Yang Shengyan , Fan Wenguo , Huang Fang
Published: May 2021

The activation of opioid receptors by exogenous or endogenous opioids can produce significant analgesic effects in peripheral tissues. Numerous researchers have demonstrated the expression of peripheral opioid receptors (PORs) and endogenous opioid peptides (EOPs) in the orofacial region. Growing evidence has shown the involvement of PORs and immune cell-derived EOPs in the modulation of orofacial pain. In this review, we discuss the role of PORs and EOPs in orofacial pain and the possible cellular mechanisms involved. Furthermore, the potential development of therapeutic strategies for orofacial pain is also summarized.
Dietary Tomato Consumption and the Risk of Prostate Cancer: A Meta-Analysis
Authors: Luo Jie , Ke Dandan , He Qingwei
Published: May 2021

Objective:Several epidemiological studies have linked tomato products consumption with prostate cancer risk; however, the findings yielded inconsistent results. The aim of the present meta-analysis is to summary the evidence on this association based on eligible cohort studies.

Materials and Methods:A comprehensive literature search of articles was performed in March 2021 using PubMed, ISI Web of Science, and Scopus databases. A random-effects model was used to calculate the combined relative risks (RRs) and their corresponding 95% confidence intervals (CIs). Heterogeneity across studies was assessed using Cochran's Q statistic and theI2score.

Results:A total of 10 prospective studies were finally included in our meta-analysis. There was no evidence of a significant association between tomato products consumption and prostate cancer risk (RR 0.91, 95% CI 0.79–1.03,P= 0.138). Subgroup meta-analyses were performed by tomato types, geographical region, publication year, study quality and number of cases. No significant associations were observed in any subgroups (allP> 0.05). No significant publication bias was observed using Begg's test (P= 0.602) or Egger's test (P= 0.957).

Conclusion:The results of this meta-analysis indicated that tomato consumption was not related with the risk of prostate cancer. Further prospective large-scale cohort studies are still warranted to verify our findings.
MiR-454-3p Promotes Oxaliplatin Resistance by Targeting PTEN in Colorectal Cancer
Authors: Qian Xiao-Lan , Zhou Fang , Xu Song , Jiang Jian , Chen Zhi-Peng , Wang Shao-Kai , Zuo Yun , Ni Chen
Published: May 2021

Colorectal cancer is one of the most common malignancies worldwide. Oxaliplatin is the first-line chemotherapeutic agent for the treatment of advanced colorectal cancer. However, acquired resistance to oxaliplatin limits its therapeutic efficacy, and the underlying mechanism remains largely unclear. In this study, we compared the expression of a panel of microRNAs (miRNAs) between oxaliplatin-sensitive and -resistant HCT-116 colorectal cancer cells. We found that miR-454-3p was significantly up-regulated in oxaliplatin-resistant cells and was the most differently expressed miRNA. Interestingly, we observed that inhibition of miR-454-3p resensitized resistant cells to oxaliplatin and enhanced oxaliplatin-induced cellular apoptosis. Moreover, we determined that miR-454-3p promoted oxaliplatin resistance through targeting PTEN and activating the AKT signaling pathway. In vivo study revealed that overexpression of miR-454-3p decreased the sensitivity of HCT-116 xenograft tumors to oxaliplatin treatment in a mouse model. Clinically, overexpression of miR-454-3p was associated with decreased responsiveness to oxaliplatin-based chemotherapy, as well as a short progression-free survival. Taken together, our study indicated that the expression of miR-454-3p could be used to predict oxaliplatin sensitivity, and targeting miR-454-3p could overcome oxaliplatin resistance in colorectal cancer.
Recommendations for Assessment of Social, Emotional, and Behavioral Health for the National Children's Study
Authors: Nowinski Cindy J. , DeWalt Darren A. , Carter Alice S. , Chacko Anil , Gross Heather E. , Perrin Eliana M. , Krug Chelsea Weaver , Holl Jane L. , Gershon Richard C.
Published: May 2021

The Social Emotional Behavioral (SEB) Team of the National Children's Study (NCS) was tasked with making recommendations for assessment of important aspects of social-emotional health and function in children. This paper describes the constructs recommended for assessment along with the rationale for their assessment. These constructs, representing aspects of Social Relationships, Social Capital, Temperament, Negative Affect, Externalizing Behavior, Social Competence, Self-efficacy, Self-image, Psychological well-being, Ethnic/racial Socialization, Perceived Discrimination, Sexual Orientation, Religiosity, and Perceived Stress and Resilience were identified as being critical to the understanding of children's health and development from birth to age 21.
MiR-19a-3p Suppresses M1 Macrophage Polarization by Inhibiting STAT1/IRF1 Pathway
Authors: Zhu Xiaoxiao , Guo Qiang , Zou Jing , Wang Bin , Zhang Zhen , Wei Ran , Zhao Lin , Zhang Yunhong , Chu Chu , Fu Xiaoxiao , Li Xia
Published: May 2021

Macrophages, an important type of immune cells, are generally polarized to classically activated macrophage (M1) or alternatively activated macrophage (M2) to respond to environmental stimuli. Signal transducer and activator of transcription 1 (STAT1), a very important transcription factor, can promote M1 macrophage polarization. However, the mechanisms of regulating STAT1 in macrophage polarization remain unclear. In the present study, STAT1 was markedly elevated, however, miR-19a-3p was down-regulated in interferon (IFN)-γ and lipopolysaccharide (LPS) treated RAW264.7 cells, and dual-luciferase reporter assay identified that miR-19a-3p directly targeted STAT1 by binding to its 3′UTR. Up-regulated miR-19a-3p inhibited M1 polarization by targeting STAT1/interferon regulatory factor 1 (IRF1) and vice versa in vitro. Consistently, overexpression of miR-19a-3p in LPS treated mice by systemically administering agomiR-19a-3p effectively reduced the inflammation in mouse lung tissues, and inhibited M1 macrophage polarization via suppressing STAT1/IRF1 pathway. In summary, our study confirmed that miR-19a-3p, as a direct regulator of STAT1, inhibited M1 macrophages polarization. The miR-19a-3p/STAT1/IRF1 pathway can potentially be used to design novel immunotherapy for modulating macrophage polarization.
Evaluation of Factors Impacting the Efficacy of Single or Combination Therapies of Valproic Acid, Carbamazepine, and Oxcarbazepine: A Longitudinal Observation Study
Authors: Peng Qilin , Ma Mubai , Gu Xurui , Hu Yani , Zhou Boting
Published: May 2021

Objective: This study aimed to determine the efficacy and clinical factors related to the pharmacodynamics of single or combination therapies of valproic acid (VPA), carbamazepine (CBZ), and oxcarbazepine (OXC), three commonly used anti-epileptic drugs (AEDs) in China.

Methods: The study evaluated the records of 2027 outpatients in a Changsha hospital, located in China, from December 23, 2015 to October 28, 2019. The baseline seizure frequency was assessed during the first visit. AED efficacy was determined based on the reduction in seizures from baseline at the subsequent visits. Multivariable ordinal regression analysis was used to determine the association between the clinical factors (demographic characteristics, clinical features, and medication situation) and AED efficacy. For validation, the clinical efficacies of AEDs were compared as both single agents and in combinations. Differences in adverse effect (AEs) categories were analyzed by Chi-square between AED groups.

Results: Records of patients receiving VPA, CBZ, and OXC were evaluated. Serum concentrations of VPA and CBZ is significantly correlated with efficacy (OR 1.030 [1.024–1.037], p < 0 0.0001; OR 1.250 [1.146–1.63], p < 0.0001, respectively) and OXC efficacy correlated to the serum concentration of the metabolite 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD) serum concentrations (OR 1.060 [1.031–1.089], p < 0.0001). Significant differences existed between females and males in VPA efficacy (OR 1.318 [1.033–1.682], p = 0.027). After validation, VPA, in combination with OXC (OR 1.93 [1.38–2.70], p<0.001), or with VGB (Vigabatrin) (OR 2.36 [1.38–2.70], p = 0.002), showed significantly better efficacy than as a single agent. OXC efficacy was also affected by the duration of epilepsy (OR 0.965 [0.946–0.984], p < 0.001). Additionally, the efficacies of OXC and VPA were also affected by the seizure type. Seizure reduction improved significantly with an increasing number of pharmacists’ educations in the first three visits period. There were no differences in AEs incidence among these 3 AEDs except for Psychiatric (0.02) and nervous system disorders (0.0001).

Conclusion: Serum concentrations of VPA and CBZ may positively affect their efficacies, while OXC efficacies are correlated to MHD serum concentrations. The efficacy of VPA was higher in females compared to males. VPA-OXC and VPA-VGB combinations had higher efficacies compared to monotherapy. Besides, OXC efficacy is probably reducing by the duration of epilepsy. Additionally, VPA efficacy for focal or generalized seizures is superior to mixed-type seizures. OXC was more effective for focal seizures compared to mixed-type ones. Education provided by pharmacists improved the seizures to some extent, and there were no significant differences between most categories of adverse effects for the investigated AEDs.
Pharmacokinetics and Pharmacodynamics of Nemonoxacin in a Neutropenic Murine Lung Infection Model Against Streptococcus Pneumoniae
Authors: Li Xin , Chen Yuancheng , Xu Xiaoyong , Li Yi , Fan Yaxin , Liu Xiaofen , Bian Xingchen , Wu Hailan , Zhao Xu , Feng Meiqing , Guo Beining , Zhang Jing
Published: May 2021

Nemonoxacin, a novel nonfluorinated quinolone for the treatment of community-acquired pneumonia. We reported the pharmacokinetic/pharmacodynamic (PK/PD) targets and PK/PD breakpoints of nemonoxacin against Streptococcus pneumoniae using a neutropenic murine lung infection model. Single-dose PK analysis after subcutaneous administration of nemonoxacin at doses from 2.5 to 80 mg/kg showed maximum plasma concentration (Cmax) 0.56–7.32 mg/L, area under the concentration-time curve from 0 to 24 h (AUC0-24) 0.67–26.10 mg·h/L, and elimination half-life (T1/2) 0.8–1.4 h. The epithelial lining fluid (ELF) penetration ratio of total drug was 1.40. Dose fractionation (1.25–80 mg/kg/day, every 24, 12, 8, and 6 h) and dose escalation studies (1.25–160 mg/kg, every 24 h) were conducted. The sigmoid Emax Hill equation was used to describe the dose-response data. The free-drug plasma fAUC0-24/MIC ratio was considered the PK/PD index most closely associated with efficacy (R2 0.9268). Median fAUC0-24/MIC associated with static, 1-log10 and 2-log10 CFU reduction from baseline were 8.6, 23.2 and 44.4, respectively. Monte Carlo simulation showed 500 mg qd and 750 mg qd oral doses of nemonoxacin were able to achieve 90% probability of target attainment (PTA) against bacteria with MIC of 0.5 mg/L and 1 mg/L. We recommended susceptibility (S) ≤ 0.5 mg/L, intermediate (I) = 1 mg/L and resistant (R) ≥ 2 mg/L as the PK/PD breakpoints for nemonoxacin against S. pneumoniae.
Irreversible Thermodynamics and Bioeconomy: Toward a Human-Oriented Sustainability
Authors: Lucia Umberto , Grisolia Giulia
Published: May 2021

The present age is characterized by a very complex economic relationship among finance, technology, social needs, etc., which can be summarized in the word “sustainability.” The sustainable consumption and production policies represent the keys to realize sustainable development. But, the analysis of the carbon footprint data points out that the present economies are still carbon-consumption production. The reduction of greenhouse gasses emissions is based on a shift from fossil to renewable and bio-based industrial raw materials, with a related reorganization of the chains of the energy and manufacturing sectors. But, this requirement implies technological choices based on a sustainable measurement of their impacts on the ecological and economical contexts. So, social and economic requirements must also be taken into account by the decision-makers. Bioeconomy can represent a possible approach to deal with the requirements of the present time. But, new needs emerge in relation to sustainability. So, sustainable policies require new indicators, in order to consider the link among economics, technologies, and social well-being. In this paper, an irreversible thermodynamic approach is developed, in order to introduce a thermoeconomic indicator, based on thermodynamic optimization methods, but also on socioeconomic and ecological evaluations. The entropy production rate is introduced in relation to the CO2emission flows from human activities, and it is related to the income index, in order to consider the economic and social equity. This approach is of interest of the researchers in the field of econophysics, thermoeconomy, economics, and bioeconomy.
Cardioprotective Effect of Whole Body Periodic Acceleration in Dystrophic Phenotype mdx Rodent
Authors: Uryash Arkady , Mijares Alfredo , Esteve Eric , Adams Jose A. , Lopez Jose R.
Published: May 2021

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and the development of a dilated cardiomyopathy (DCM), which is the leading cause of death in DMD patients. Despite knowing the cause of DMD, there are currently no therapies which can prevent or reverse its inevitable progression. We have used whole body periodic acceleration (WBPA) as a novel tool to enhance intracellular constitutive nitric oxide (NO) production. WBPA adds small pulses to the circulation to increase pulsatile shear stress, thereby upregulating endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) and subsequently elevating the production of NO. Myocardial cells from dystrophin-deficient 15-month old mdx mice have contractile deficiency, which is associated with elevated concentrations of diastolic Ca2+ ([Ca2+]d), Na+ ([Na+]d), and reactive oxygen species (ROS), increased cell injury, and decreased cell viability. Treating 12-month old mdx mice with WBPA for 3 months reduced cardiomyocyte [Ca2+]d and [Na+]d overload, decreased ROS production, and upregulated expression of the protein utrophin resulting in increased cell viability, reduced cardiomyocyte damage, and improved contractile function compared to untreated mdx mice.
Comparative Transcriptome Profiling of Cold Exposure and β3-AR Agonist CL316,243-Induced Browning of White Fat
Authors: Li Yu , Ping Xiaodan , Zhang Yankang , Li Guoqiang , Zhang Ting , Chen Geng , Ma Xinran , Wang Dongmei , Xu Lingyan
Published: May 2021

Beige adipocytes are newly identified thermogenic-poised adipocytes that could be activated by cold or β3-adrenergic receptor (β3-AR) signaling and offer therapeutic potential for treating obesity and metabolic diseases. Here we applied RNA-sequencing analysis in the beige fat of mice under cold exposure or β3-AR agonist CL316,243 (CL) treatment to provide a comparative and comprehensive analysis for the similarity and heterogeneity of these two stimulants. Importantly, via KEGG analysis, we found that cold and CL commonly induced oxidative phosphorylation. Meanwhile, cold increased glycerolipid and amino acids metabolism while CL treatment triggered a broader spectrum of metabolic responses including carbohydrate metabolism. Besides, cold or CL treatment featured greater heterogeneity in downregulated gene programs. Of note, the top changed genes in each category were confirmed by qPCR analysis. Overall, our analysis provided a better understanding of the heterogeneity of differential models for beige adipocytes activation and a possible clue for optimizing β3-AR agonists in the future.
Genomic Characterization of the Fruity Aroma Gene, FaFAD1, Reveals a Gene Dosage Effect on γ-Decalactone Production in Strawberry (Fragaria × ananassa)
Authors: Oh Youngjae , Barbey Christopher R. , Chandra Saket , Bai Jinhe , Fan Zhen , Plotto Anne , Pillet Jeremy , Folta Kevin M. , Whitaker Vance M. , Lee Seonghee
Published: May 2021

Strawberries produce numerous volatile compounds that contribute to the unique flavors of fruits. Among the many volatiles, γ-decalactone (γ-D) has the greatest contribution to the characteristic fruity aroma in strawberry fruit. The presence or absence of γ-D is controlled by a single locus,FaFAD1. However, this locus has not yet been systematically characterized in the octoploid strawberry genome. It has also been reported that the volatile content greatly varies among the strawberry varieties possessingFaFAD1, suggesting that another genetic factor could be responsible for the different levels of γ-D in fruit. In this study, we explored the genomic structure ofFaFAD1and determined the allele dosage ofFaFAD1that regulates variations of γ-D production in cultivated octoploid strawberry. The genome-wide association studies confirmed the major locusFaFAD1that regulates the γ-D production in cultivated strawberry. With the hybrid capture-based next-generation sequencing analysis, a major presence–absence variation ofFaFAD1was discovered among γ-D producers and non-producers. To explore the genomic structure ofFaFAD1in the octoploid strawberry, three bacterial artificial chromosome (BAC) libraries were developed. A deletion of 8,262 bp was consistently found in theFaFAD1region of γ-D non-producing varieties. With the newly developed InDel-based codominant marker genotyping, along with γ-D metabolite profiling data, we revealed the impact of gene dosage effect for the production of γ-D in the octoploid strawberry varieties. Altogether, this study provides systematic information of the prominent role ofFaFAD1presence and absence polymorphism in producing γ-D and proposes that both alleles ofFaFAD1are required to produce the highest content of fruity aroma in strawberry fruit.
Unraveling the Relationship Between Seed Yield and Yield-Related Traits in a Diversity Panel of Brassica juncea Using Multi-Traits Mixed Model
Authors: Saroj Ranjit , Soumya S. L. , Singh Satbeer , Sankar S. Mukesh , Chaudhary Rajat , Yashpal  , Saini Navinder , Vasudev Sujata , Yadava Devendra K.
Published: May 2021

The response to selection in any crop improvement program depends on the degree of variance and heritability. The objective of the current study was to explain variance and heritability components in Indian mustard Brassica juncea (L). Czern & Coss to recognize promising genotypes for effective breeding. Two hundred and eighty-nine diverse accessions of Indian mustard belonging to four continents were analyzed for yield and yield-related traits (20 traits) over two seasons (2017–2018 and 2018–2019) using an alpha lattice design. The genetic variance was found to be significant (P ≤ 0.01) for the individual and under pooled analysis for all of the evaluated traits, demonstrating the presence of significant genetic variability in the diversity panel, which bids greater opportunities for utilizing these traits in future breeding programs. High heritability combined with high genetic advance as percent of mean and genotypic coefficient of variation was observed for flowering traits, plant height traits, seed size, and seed yield/plant; hence, a better genetic gain is expected upon the selection of these traits over subsequent generations. Both correlation and stepwise regression analysis indicated that the main shoot length, biological yield, total seed yield, plant height up to the first primary branch, seed size, total siliqua count, days to flowering initiation, plant height at maturity, siliquae on the main shoot, main shoot length, and siliqua length were the most significant contributory traits for seed yield/plant. Also, promising genotypes were identified among the diversity panel, which can be utilized as a donor to improve Indian mustard further. These results indicated a greater scope for improving seed yield per plant directly through a selection of genotypes having the parsimonious combination of these nine traits.