bluuebunny/crossref_metadata_2025 huggingface dataset:
EDUCAÇÃO DE SURDOS: IDEIAS INICIAIS DE UM ESTUDO BIBLIOGRÁFICO EM PERIÓDICOS NACIONAIS
Authors: Feio Lima Reinaldo , Cardoso Cavalcante Rabelo Lucélia , Machado Ferreira Arnaldo
Published: May 2021

O presente artigo assume uma abordagem qualitativa e tem como objetivo construir oestado do conhecimento da produção sobre Educação de Surdos. Trata-se de investigação de caráterbibliográfico, a partir de pesquisas com os descritores “surdez”, “surdo”, “deficiência auditiva” e“educação de surdos” no ensino de Matemática, a respeito de trabalhos publicados na RevistaParanaense em Educação Matemática (RPEM) e Educação Matemática em Revista (EMR), sobreEducação de Surdos. Nesse sentido, desenvolvemos uma pesquisa do tipo “Estado do Conhecimento”,nas edições especiais disponibilizadas online sobre Educação Matemática Inclusiva e verificamos aexistência de oito trabalhos. Por meio desta investigação bibliográfica, buscamos indícios de repostaspara as questões de pesquisa: o que os artigos científicos do campo Educação Matemática Inclusiva(EMI), publicados em periódicos nacionais, têm discutido sobre a proposição da Educação de Surdos?Quais são os contextos das pesquisas presentes nessa parcela da produção científica na Educação deSurdos? Quais os pressupostos teórico-metodológicos da investigação sobre Educação de Surdos?Quais as origens e autorias dos trabalhos assumidos nas pesquisas? Neste artigo, constatamos que hápoucas investigações realizadas na Educação de Surdos, considerando o mapeamento feito em duasrevistas brasileiras que publicaram edições temáticas indicando a relevância desse tema, e destacamosque mais pesquisadores deveriam desenvolver trabalhos nesse campo emergencial de estudo.
PERCEPÇÕES DE PROFESSORES DE UM CURSO DE GRADUAÇÃO EM MATEMÁTICA SOBRE A UTILIZAÇÃO DE OBJETOS DE APRENDIZAGEM EM SUAS PRÁTICAS PEDAGÓGICAS.
Authors: Ricardo Antunes Ribeiro André , De Souza Motta Marcelo , Aurélio Kalinke Marco
Published: May 2021

Este artigo apresenta resultados de uma pesquisa qualitativa, com professores envolvidosem um curso de Licenciatura em Matemática, na modalidade a distância, de uma instituição de ensinosuperior privada, localizada em Curitiba, Paraná, Brasil. O objetivo desta pesquisa foi obter respostassobre as motivações dos professores perante a utilização de objetos de aprendizagem em suasrespectivas práticas pedagógicas. Para tanto, desenvolvemos um embasamento teórico que justificasseo uso das tecnologias digitais em práticas pedagógicas. A partir disso, definimos critérios para análise,utilizando a metodologia de Bardin (2016), realizando as etapas, de modo que fosse possível ainterpretação dos dados coletados. Durante a análise, constatamos que a maioria dos participantesadmitiu a importância da utilização dos objetos de aprendizagem nas práticas pedagógicas. Entretanto,foi possível verificar a existência de percepções sobre a persistência de algumas demandas, como nocaso da ausência de novas propostas metodológicas de aplicação das tecnologias digitais na literaturaatual, assim como a inacessibilidade de determinadas tecnologias digitais para a execução de projetoscom essa temática nas escolas
An Immune-Related Long Non-Coding RNA Signature to Predict the Prognosis of Ewing’s Sarcoma Based on a Machine Learning Iterative Lasso Regression
Authors: Ren En-hui , Deng Ya-jun , Yuan Wen-hua , Zhang Guang-zhi , Wu Zuo-long , Li Chun-ying , Xie Qi-qi
Published: May 2021

The aim of this study was to construct a new immune-associated long non-coding RNA (lncRNA) signature to predict the prognosis of Ewing sarcoma (ES) and explore its molecular mechanisms. We downloaded transcriptome and clinical prognosis data from the Gene Expression Omnibus (GSE17679, which included 88 ES samples and 18 matched normal skeletal muscle samples), and used it as a training set to identify immune-related lncRNAs with different expression levels in ES. Univariable Cox regression was used to screen immune-related lncRNAs related to ES prognosis, and an immune-related lncRNA signature was constructed based on machine learning iterative lasso regression. An external verification set was used to confirm the predictive ability of the signature. Clinical feature subgroup analysis was used to explore whether the signature was an independent prognostic factor. In addition, CIBERSORT was used to explore immune cell infiltration in the high- and low-risk groups, and to analyze the correlations between the lncRNA signature and immune cell levels. Gene set enrichment and variation analyses were used to explore the possible regulatory mechanisms of the immune-related lncRNAs in ES. We also analyzed the expression of 17 common immunotherapy targets in the high- and low-risk groups to identify any that may be regulated by immune-related lncRNAs. We screened 35 immune-related lncRNAs by univariate Cox regression. Based on this, an immune-related 11-lncRNA signature was generated by machine learning iterative lasso regression. Analysis of the external validation set confirmed its high predictive ability. DPP10 antisense RNA 3 was negatively correlated with resting dendritic cell, neutrophil, and γδ T cell infiltration, and long intergenic non-protein coding RNA 1398 was positively correlated with resting dendritic cells and M2 macrophages. These lncRNAs may affect ES prognosis by regulating GSE17721_CTRL_VS_PAM3CSK4_12H_BMDC_UP, GSE2770_IL4_ACT_VS_ACT_CD4_TCELL_48H_UP, GSE29615_CTRL_VS_DAY3_ LAIV_IFLU_VACCINE_PBMC_UP, complement signaling, interleukin 2-signal transducer and activator of transcription 5 signaling, and protein secretion. The immune-related 11-lncRNA signature may also have regulatory effects on the immunotherapy targets CD40 molecule, CD70 molecule, and CD276 molecule. In conclusion, we constructed a new immune-related 11-lncRNA signature that can stratify the prognoses of patients with ES.
Experiment in a Box (XB): An Interactive Technology Framework for Sustainable Health Practices
Authors: schraefel m. c. , Muresan George Catalin , Hekler Eric
Published: May 2021

This paper presents the Experiment in a Box (XB) framework to support interactive technology design for building health skills. The XB provides a suite of experiments—time-limited, loosely structured evaluations of health heuristics for a user-as-experimenter to select from and then test in order to determine that heuristic’s efficacy, and to explore how it might be incorporated into the person’s life and when necessary, to support their health and wellbeing. The approach leverages self-determination theory to support user autonomy and competence to build actionable, personal health knowledge skills and practice (KSP). In the three studies of XB presented, we show that with even the short engagement of an XB experiment, participants develop health practices from the interventions that are still in use long after the intervention is finished. To situate the XB approach relative to other work around health practices in HCI in particular, we contribute two design continua for this design space: insourcing to outsourcing and habits to heuristics. From this analysis, we demonstrate that XB is situated in a largely under-explored area for interactive health interventions: the insourcing and heuristic oriented area of the design space. Overall, the work offers a new scaffolding, the XB Framework, to instantiate time-limited interactive technology interventions to support building KSP that can thrive in that person, significantly both post-interventions, and independent of that technology.
Pre-clinical Evidence: Berberine as a Promising Cardioprotective Candidate for Myocardial Ischemia/Reperfusion Injury, a Systematic Review, and Meta-Analysis
Authors: Chen Cong , Lin Qian , Zhu Xue-Ying , Xia Junyan , Mao Tianshi , Chi Tiange , Wan Jie , Lu Jin-Jin , Li Yan , Cui Jie , Liu Jing , Cui Xiao-Yun , Zhang Jingqian , Zhou Kun , Li Dong
Published: May 2021

Objective: Myocardial ischemia/reperfusion (I/R) injury is one of the causes of most cardiomyocyte injuries and deaths. Berberine (BBR) has been suggested a potential to exert protective effects against myocardial I/R injury. This systematic review aims to determine the intrinsic mechanisms of BBR's protective effects in myocardial I/R injury.

Methods: Seven databases were searched for studies performed from inception to July 2020. Methodological quality was assessed by SYRCLE's-RoB tool.

Results: Ten studies including a total of 270 animals were included in this study. The methodology quality scores of the included studies ranged from 5 to 7 points. The meta-analysis we conducted demonstrated that BBR significantly reduced myocardial infarct size and the incidence of ventricular arrhythmia, compared to control groups (P < 0.00001). Cardiac function of animals in the BBR treatment group was also markedly increased (P < 0.00001). The index of myocardial apoptosis and the levels of biomarkers of myocardial infarction (LDH and CK) were also decreased in the BBR treatment groups compared to the control groups (P < 0.00001).

Conclusions: The pre-clinical evidence, according to our study, showed that BBR is a promising therapeutic agent for myocardial I/R injury. However, this conclusion should be further investigated in clinical studies.
Cryoballoon Ablation of Atrial Fibrillation Without Demonstration of Pulmonary Vein Occlusion—The Simplify Cryo Study
Authors: Kühne Michael , Knecht Sven , Spies Florian , Aeschbacher Stefanie , Haaf Philip , Zellweger Michael , Schaer Beat , Osswald Stefan , Sticherling Christian
Published: May 2021

Background: The demonstration of pulmonary vein (PV) occlusion is routinely performed and considered a prerequisite for successful cryoballoon (CB) ablation of atrial fibrillation (AF). The purpose of this study was to assess the feasibility and impact on procedural parameters and outcome of a standardized procedural protocol without demonstrating PV occlusion.

Methods and Results: Consecutive patients undergoing CB pulmonary vein isolation (PVI) were studied. After cMRI assessment, patients treated by PVI using a novel no-contrast (NC) protocol without routine contrast injections to demonstrate PV occlusion (NC group) were compared to patients undergoing PVI with contrast injections to demonstrate PV occlusion (standard group). One hundred patients with paroxysmal or persistent AF (age 61 ± 10 years, ejection fraction 59 ± 11%, left atrial volume index 37.2 ± 2.0 mL/m2) were studied. The NC protocol was feasible in 72 of 75 patients (96%). Total procedure time and fluoroscopy time were 64.0 ± 14.1 min and 11.0 ± 4.6 min in the NC group and 92.0 ± 25.3 min and 18.0 ± 6.0 min in the standard group, respectively (all p < 0.001). Dose area product was 368 ± 362 cGy*cm2 in the NC group compared to 1928 ± 1541 cGy*cm2 in the standard group (p < 0.001). Forty-five of 75 patients (60%) in the NC group and 16 of 25 patients (64%) in the standard group remained in stable sinus rhythm after a single PVI and a 1-year follow-up (p = 0.815).

Conclusions: Performing CB ablation without using contrast injections to demonstrate PV occlusion was feasible, resulted in reduced radiation exposure, and increased the efficiency of the procedure.
Search Engine Gender Bias
Authors: Wijnhoven Fons , van Haren Jeanna
Published: May 2021

This article discusses possible search engine page rank biases as a consequence of search engine profile information. After describing search engine biases, their causes, and their ethical implications, we present data about the Google search engine (GSE) and DuckDuckGo (DDG) for which only the first uses profile data for the production of page ranks. We analyze 408 search engine screen prints of 102 volunteers (53 male and 49 female) on queries for job search and political participation. For job searches via GSE, we find a bias toward stereotypically “female” jobs for women but also for men, although the bias is significantly stronger for women. For political participation, the bias of GSE is toward more powerful positions. Contrary to our hypothesis, this bias is even stronger for women than for men. Our analysis of DDG does not give statistically significant page rank differences for male and female users. We, therefore, conclude that GSE’s personal profiling is not reinforcing a gender stereotype. Although no gender differences in page ranks was found for DDG, DDG usage in general gave a bias toward “male-dominant” vacancies for both men and women. We, therefore, believe that search engine page ranks are not biased by profile ranking algorithms, but that page rank biases may be caused by many other factors in the search engine’s value chain. We propose ten search engine bias factors with virtue ethical implications for further research.
Variable Thrust Rates of the Eastern Qilianshan Mountain Front, Northeastern Margin of the Tibet Plateau and Its Implication to the Topography of the Yongchangnan Shan
Authors: Jinghao Lei , Youli Li , Zhikun Ren , Xiu Hu , Jianguo Xiong , Fei Liu , Jinrui Liu
Published: May 2021

It is commonly assumed a thrust has a constant slip and uplifting rate along strike, however, this simplified model cannot always be consistent with field observations. The along strike slip patterns with variable offsets and rates contain plenty of information about the characteristics of the faulting behavior and its relationship with adjacent faults. The east Qilian Shan, located at the northeastern margin of the Tibetan Plateau, provides us an excellent opportunity to study the faulting behavior in a thrust-bounded range area. Besides the previously reported slip rates of the N-W trending tectonics across the region, we augmented the data by surveying the Fengle fault (FF), one of the north bounding thrusts of the Yongchangnan Shan. Another north bounding fault is the Kangningqiao Fault (KNF), east of the FF. Based on the vertical offsets and rates along the fault, we constructed the slip pattern along strike. The results show the vertical slip rate of the FF ranges from 0.7 ± 0.1 mm/a to 2.8 ± 1.3 mm/a across three surveyed sites. The slip rate decreases from the east to the west. The FF and KNF might be inferred as two segments of a single segmented thrust controlling the uplift of the Yongchangnan Shan. By comparing the uplift onsets in the study region, we discuss the northeastward propagated deformation along the northeastern margin of the Tibet plateau.
Plastic as a Vector of Dispersion for Marine Species With Invasive Potential. A Review
Authors: García-Gómez José Carlos , Garrigós Marta , Garrigós Javier
Published: May 2021

Plastic debris constitutes up to 87% of marine litter and represents one of the most frequently studied vectors for marine alien species with invasive potential in the last 15 years. This review addresses an integrated analysis of the different factors involved in the impact of plastic as a vector for the dispersal of marine species. The sources of entry of plastic materials into the ocean are identified as well as how they move between different habitats affecting each trophic level and producing hot spots of plastic accumulation in the ocean. The characterization of plastic as a dispersal vector for marine species has provided information about the inherent properties of plastics which have led to its impact on the ocean: persistence, buoyancy, and variety in terms of chemical composition, all of which facilitate colonization by macro and microscopic species along with its dispersion throughout different oceans and ecosystems. The study of the differences in the biocolonization of plastic debris according to its chemical composition provided fundamental information regarding the invasion process mediated by plastic, and highlighted gaps of knowledge about this process. A wide range of species attached to plastic materials has been documented and the most recurrent phyla found on plastic have been identified from potentially invasive macrofauna to toxic microorganisms, which are capable of causing great damage in places far away from their origin. Plastic seems to be more efficient than the natural oceanic rafts carrying taxa such as Arthropoda, Annelida, and Mollusca. Although the differential colonization of different plastic polymers is not clear, the chemical composition might determine the community of microorganisms, where we can find both pathogens and virulent and antibiotic resistance genes. The properties of plastic allow it to be widely dispersed in practically all ocean compartments, making this material an effective means of transport for many species that could become invasive.
Cancer Biomarkers Discovery of Methylation Modification With Direct High-Throughput Nanopore Sequencing
Authors: Zhang Junjie , Xie Shuilian , Xu Jingxiang , Liu Hui , Wan Shaogui
Published: May 2021

Cancer is a complex disease, driven by a combination of genetic and epigenetic alterations. DNA and RNA methylation modifications are the most common epigenetic events that play critical roles in cancer development and progression. Bisulfite converted sequencing is a widely used technique to detect base modifications in DNA methylation, but its main drawbacks lie in DNA degradation, lack of specificity, or short reads with low sequence diversity. The nanopore sequencing technology can directly detect base modifications in native DNA as well as RNA without harsh chemical treatment, compared to bisulfite sequencing. Furthermore, CRISPR/Cas9-targeted enrichment nanopore sequencing techniques are straightforward and cost-effective when targeting genomic regions are of interest. In this review, we mainly focus on DNA and RNA methylation modification detection in cancer with the current nanopore sequencing approaches. We also present the respective strengths, weaknesses of nanopore sequencing techniques, and their future translational applications in identification of epigenetic biomarkers for cancer detection and prognosis.
Pre-breeding Diets in the Seahorse Hippocampus reidi: How Do They Affect Fatty Acid Profiles, Energetic Status and Histological Features in Newborn?
Authors: Planas Miquel , Olivotto Ike , González María Jesús , Laurà Rosaria , Angeletti Carlo , Amici Adolfo , Zarantoniello Matteo
Published: May 2021

Seahorses (Hippocampus spp.) are exceptional marine species considering their reproductive patterns and other features. Due to the iconic characteristics of these fishes, aquarium trade, and research efforts have increased in the last years. Consequently, novel rearing techniques have been developed; however, there is a need for improvements on a series of issues, namely reproduction success enhancement. The tropical species Hippocampus reidi is the most traded seahorse but many aspects of breeding and its impact on the quality of neonates are still poorly understood. In the present study, we assessed the effects of two pre-breeding diets on newborn quality and viability considering biochemical characteristics, energetic status, and ultrastructural aspects of muscular tissue. During the whole pre-breeding season (5 months), the breeders were fed on one of the following diets: M0 (adult non-enriched Artemia) and M5 (adult non-enriched Artemia + mysidaceans). From the onset of the reproduction period, all breeders were fed for 6 months on diet M5. Breeding success and energetic status (ATP, total adenylic nucleotides, AEC, and NAD) of newborns resulted considerably enhanced in treatment M5. However, initial differences in neonates quality did not affect further newborn performance (survival and growth until day 7 after male’s pouch release) while gaining access to high-quality preys (copepods). Besides, morphological alterations in muscle tissue were not observed. The reproduction in the species followed a capital–income continuum pattern characterized by an initial mixed capital-income period (until 70–100 days since the onset of the breeding season) followed by an income breeding period with progressive exhaustion of body reserves, especially in M0-newborns. Interestingly, the effects of pre-breeding diets were also noticed in the second half of the breeding period. Our results seemed to indicate that the requirements in essential fatty acids in H. reidi are lower than in other seahorse species (e.g., Hippocampus guttulatus). Globally, the results achieved revealed that high-quality pre-breeding diets enhanced reproduction success and would likely result advantageous to improve newborn endurance in conditions of moderate starvation or sub-optimal feeding.
What Are the Impacts of a Coastal Zone Protection Policy on Farmers’ Livelihood Capital? Empirical Analysis From the Perspective of Farmer Participation
Authors: Cheng Peng , Wang Han , Nie Xin , Zhu Siyang , Chen Zhoupeng , Wu Xingyi , Zhang Anlu , Wang Jing
Published: May 2021

To restore and protect the ecosystem service function of coastal zones, some farmers have changed their certain original production methods and lifestyles and some have even relinquished a portion of the economic benefits that could be obtained directly. What impacts do the coastal zone ecological protection policies bring to the livelihoods of coastal farmers? The strict coastline protection of Beibu Gulf, Hepu County, Beihai City, Guangxi Zhuang Autonomous Region, China, is taken as an example. Combined with the sustainable livelihood framework (SLF), this paper set up an evaluation index system for the livelihood capital of farmers in the Beibu Gulf coastal zone, obtaining 568 valid questionnaires through a field survey, and use the propensity score matching and difference-in-difference (PSM-DID) method to study the impacts of a coastal ecological protection policy on the livelihood capital of coastal farmers from the perspective of farmer participation. The results show that (1) the coastal ecological protection policy had a significant impact on the natural capital and social capital of coastal farmers that actively participated in coastal ecological protection, which increased by 0.181 and 0.052, respectively. (2) However, it did not have a significant impact on the total livelihood capital, human capital, physical capital or financial capital. Therefore, this paper presents policy suggestions for constructing coastal ecological compensation mechanisms and for promoting active participation by coastal farmers in coastal ecological protection efforts.
Role of P2X7 Receptors in Immune Responses During Neurodegeneration
Authors: Oliveira-Giacomelli Ágatha , Petiz Lyvia Lintzmaier , Andrejew Roberta , Turrini Natalia , Silva Jean Bezerra , Sack Ulrich , Ulrich Henning
Published: May 2021

P2X7 receptors are ion-gated channels activated by ATP. Under pathological conditions, the extensive release of ATP induces sustained P2X7 receptor activation, culminating in induction of proinflammatory pathways with inflammasome assembly and cytokine release. These inflammatory conditions, whether occurring peripherally or in the central nervous system (CNS), increase blood-brain-barrier (BBB) permeability. Besides its well-known involvement in neurodegeneration and neuroinflammation, the P2X7 receptor may induce BBB disruption and chemotaxis of peripheral immune cells to the CNS, resulting in brain parenchyma infiltration. For instance, despite common effects on cytokine release, P2X7 receptor signaling is also associated with metalloproteinase secretion and activation, as well as migration and differentiation of T lymphocytes, monocytes and dendritic cells. Here we highlight that peripheral immune cells mediate the pathogenesis of Multiple Sclerosis and Parkinson’s and Alzheimer’s disease, mainly through T lymphocyte, neutrophil and monocyte infiltration. We propose that P2X7 receptor activation contributes to neurodegenerative disease progression beyond its known effects on the CNS. This review discusses how P2X7 receptor activation mediates responses of peripheral immune cells within the inflamed CNS, as occurring in the aforementioned diseases.
Leber Hereditary Optic Neuropathy: Review of Treatment and Management
Authors: Hage Rabih , Vignal-Clermont Catherine
Published: May 2021

Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease that specifically targets the retinal ganglion cells by reducing their ability to produce enough energy to sustain. The mutations of the mitochondrial DNA that cause LHON are silent until an unknown trigger causes bilateral central visual scotoma. After the onset of loss of vision, most patients experience progressive worsening within the following months. Few of them regain some vision after a period of ~1 year. Management of LHON patients has been focused on understanding the triggers of the disease and its pathophysiology to prevent the onset of visual loss in a carrier. Medical treatment is recommended once visual loss has started in at least one eye. Research evaluated drugs that are thought to be able to restore the mitochondrial electron transport chain of the retinal ganglion cells. Significant advances were made in evaluating free radical cell scavengers and gene therapy as potential treatments for LHON. Although encouraging the results of clinical trial have been mixed in stopping the worsening of visual loss. In patients with chronic disease of over 1 year, efficient treatment that restores vision is yet to be discovered. In this review, we summarize the management strategies for patients with LHON before, during, and after the loss of vision, explain the rationale and effectiveness of previous and current treatments, and report findings about emerging treatments.
A2B Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis
Authors: Coppi Elisabetta , Cencetti Francesca , Cherchi Federica , Venturini Martina , Donati Chiara , Bruni Paola , Pedata Felicita , Pugliese Anna Maria
Published: May 2021

Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain. Impairments in the process of myelination, or demyelinating insults, might cause chronic diseases such as multiple sclerosis (MS). Under physiological conditions, remyelination is an ongoing process throughout adult life consisting in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes (OLs). During pathological events, this process fails due to unfavorable environment. Adenosine and sphingosine kinase/sphingosine 1-phosphate signaling axes (SphK/S1P) play important roles in remyelination processes. Remarkably, fingolimod (FTY720), a sphingosine analog recently approved for MS treatment, plays important roles in OPC maturation. We recently demonstrated that the selective stimulation of A2B adenosine receptors (A2BRs) inhibit OPC differentiation in vitro and reduce voltage-dependent outward K+ currents (IK) necessary to OPC maturation, whereas specific SphK1 or SphK2 inhibition exerts the opposite effect. During OPC differentiation A2BR expression increases, this effect being prevented by SphK1/2 blockade. Furthermore, selective silencing of A2BR in OPC cultures prompts maturation and, intriguingly, enhances the expression of S1P lyase, the enzyme responsible for irreversible S1P catabolism. Finally, the existence of an interplay between SphK1/S1P pathway and A2BRs in OPCs was confirmed since acute stimulation of A2BRs activates SphK1 by increasing its phosphorylation. Here the role of A2BR and SphK/S1P signaling during oligodendrogenesis is reviewed in detail, with the purpose to shed new light on the interaction between A2BRs and S1P signaling, as eventual innovative targets for the treatment of demyelinating disorders.
Statistical Evaluation of Different Mathematical Models for Diffusion Weighted Imaging of Prostate Cancer Xenografts in Mice
Authors: Merisaari Harri , Laakso Hanne , Liljenbäck Heidi , Virtanen Helena , Aronen Hannu J. , Minn Heikki , Poutanen Matti , Roivainen Anne , Liimatainen Timo , Jambor Ivan
Published: May 2021

Purpose

To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer.

Methods

Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm2, respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential).

Results

Significant changes were observed in DWI data during the tumor growth, indicated by ADCm, ADCs, and ADCk. Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1−4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model.

Conclusion

Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.
The Incorporation of Immunotherapy and Targeted Therapy Into Chemoradiation for Cervical Cancer: A Focused Review
Authors: Odiase Otasowie , Noah-Vermillion Lindsay , Simone Brittany A. , Aridgides Paul D.
Published: May 2021

In 2011 the Food and Drug Administration (FDA) approved anti-vascular endothelial growth factor (VEGF) therapy, bevacizumab, for intractable melanoma. Within the year, immunotherapy modulators inhibiting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) were approved in addition to programmed death-ligand 1 (PD-L1) antibodies in 2012. Since then, research showing the effectiveness of targeted therapies in a wide range of solid tumors has prompted studies incorporating their inclusion as part of upfront management as well as refractory or relapsed disease. For treatment of cervical cancer, which arises from known virus-driven oncogenic pathways, the incorporation of targeted therapy is a particularly attractive prospect. The current standard of care for locally advanced cervical cancer includes concurrent platinum-based chemotherapy with radiation therapy (CRT) including external beam radiation therapy (EBRT) and brachytherapy. Building upon encouraging results from trials testing bevacizumab or immunotherapy in recurrent cervical cancer, these agents have begun to be incorporated into upfront CRT strategies for prospective study. This article will review background data establishing efficacy of angiogenesis inhibitors and immunotherapy in the treatment of cervical cancer as well as results of prospective studies combining targeted therapies with standard CRT with the aim of improving outcomes. In addition, the role of immunotherapy and radiation on the tumor microenvironment (TME) will be discussed.
Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma
Authors: Li Tian-Hao , Qin Cheng , Zhao Bang-Bo , Cao Hong-Tao , Yang Xiao-Ying , Wang Yuan-Yang , Li Ze-Ru , Zhou Xing-Tong , Wang Wei-Bin
Published: May 2021

Methyltransferase-like 18 (METTL18), a METTL family member, is abundant in hepatocellular carcinoma (HCC). Studies have indicated the METTL family could regulate the progress of diverse malignancies while the role of METTL18 in HCC remains unclear. Data of HCC patients were acquired from the cancer genome atlas (TCGA) and gene expression omnibus (GEO). The expression level of METTL18 in HCC patients was compared with normal liver tissues by Wilcoxon test. Then, the logistic analysis was used to estimate the correlation between METTL18 and clinicopathological factors. Besides, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to explore relevant functions and quantify the degree of immune infiltration for METTL18. Univariate and Multivariate Cox analyses and Kaplan–Meier analysis were used to estimate the association between METTL18 and prognosis. Besides, by cox multivariate analysis, a nomogram was conducted to forecast the influence of METTL18 on survival rates. METTL18-high was associated with Histologic grade, T stage, Pathologic stage, BMI, Adjacent hepatic tissue inflammation, AFP, Vascular invasion, and TP53 status (P < 0.05). HCC patients with METTL18-high had a poor Overall-Survival [OS; hazard ratio (HR): 1.87, P < 0.001), Disease-Specific Survival (DSS, HR: 1.76, P = 0.015), and Progression-Free Interval (PFI, HR: 1.51, P = 0.006). Multivariate analysis demonstrated that METTL18 was an independent factor for OS (HR: 2.093, P < 0.001), DSS (HR: 2.404, P = 0.015), and PFI (HR: 1.133, P = 0.006). Based on multivariate analysis, the calibration plots and C-indexes of nomograms showed an efficacious predictive effect for HCC patients. GSEA demonstrated that METTL18-high could activate G2M checkpoint, E2F targets, KRAS signaling pathway, and Mitotic Spindle. There was a positive association between the METTL18 and abundance of innate immunocytes (T helper 2 cells) and a negative relation to the abundance of adaptive immunocytes (Dendritic cells, Cytotoxic cells etc.). Finally, we uncovered knockdown of METTL18 significantly suppressed the proliferation, invasion, and migration of HCC cells in vitro. This research indicates that METTL18 could be a novel biomarker to evaluate HCC patients’ prognosis and an important regulator of immune responses in HCC.
Maternal and Neonatal Factors Affecting Bone Mineral Content of Indonesian Term Newborns
Authors: Wibowo Tunjung , Nurani Neti , Hastuti Janatin , Anggraini Alifah , Susilowati Rina , Hakimi Mohammad , Julia Madarina , Van Weissenbruch Mirjam
Published: May 2021

Background: Interactions between the genome and intrauterine environment can affect bone mineralization in newborns and even in adult life. Several studies show that intrauterine fetal bone mineralization or early postnatal bone condition influences the risk of osteoporosis in later life.

Objectives: To determine whole body bone mineral content (WB BMC) and factors that influence neonatal WB BMC in Indonesian term newborns.

Subjects/Methods: A cross-sectional study was conducted in Dr. Sardjito General Hospital, Yogyakarta, Indonesia. A total of 45 term, appropriate for gestational age (AGA) newborns were included in this study. BMC was assessed by dual-energy x-ray absorptiometry (DXA) in the first week of life. Weight (g), length (cm) and head circumference (cm) were measured at birth. Data on maternal characteristics were obtained from the maternal health records or reported by the mothers.

Results: WB BMC measured in the present study (mean ± SD: 33.2 ± 9.3 g) was lower than WB BMC of similar populations in developed countries. Multiple linear regression showed that birth weight, birth length, and gestational age had a positive association with WB BMC (p = 0.048, 0.017, and <0.001, respectively), while maternal cigarette exposure had a negative association with WB BMC (p = 0.012). Male infants had significantly higher of WB BMC than female (p = 0.025). These determinants contribute to 55% variability of WB BMC.

Conclusions: WB BMC in Indonesian term newborns is lower than populations in developed countries. Birth weight, length, gestational age, sex, and maternal cigarette exposure during pregnancy are significantly associated with WB BMC observed in Indonesian newborns.
Traditional Chinese Medicine Reduces the Incidence of Chemotherapy-Induced Stroke: A Five-Year Nationwide Population-Based Cohort Study From Taiwan
Authors: Huang Chien-Chen , Yang Yu-Cih , MacDonald Iona , Lai Ching-Yuan , Tu Cheng-Hao , Chen Yi-Hung
Published: May 2021

Background: Chemotherapy is suspected to be a risk factor for stroke in patients with cancer, athough the results from large-scale studies are controversial. Few strategies are available for reducing the stroke-related risks.

Methods: We analyzed stroke incidence rates in Taiwan’s Longitudinal Health Insurance database 2000 (LHID2000) for patients aged ≥20 years with newly-diagnosed cancer between Jan 1, 2000 and Dec 31, 2006, who did or did not receive chemotherapy. Moreover, we compared stroke incidence rates among chemotherapy users who did or did not use traditional Chinese medicine. All study participants were followed-up for 5 years or until they had a stroke.

Results: In adjusted Kaplan-Meier analysis, the incidence of stroke was higher within the first year of cancer diagnosis among chemotherapy recipients compared with those who did not receive chemotherapy (31.1 vs. 9.75; adjusted subdistribution hazard ratio [sHR] 2.21; 95% confidence interval [CI], 1.52–3.20; p < 0.001). This between-group difference persisted at 4 years of follow-up (13.6 vs. 5.42; adjusted sHR 1.94; 95% CI, 1.53–2.46; p < 0.001). Similarly, the 5-year incidence rate of stroke was significantly lower among chemotherapy recipients using TCM vs. non-TCM users (0.19 vs. 0.46; adjusted sHR 0.45; 95% CI, 0.26–0.79; p < 0.001), as was the mortality rate (adjusted sHR 0.55; 95% CI, 0.44–0.68; p < 0.001).

Conclusion: These Taiwanese data suggest that chemotherapy is a risk factor for stroke and that the use of TCM can significantly mitigate this risk. TCM also appears to reduce the mortality risk associated with chemotherapy.
Mitochondrial Targeting of Herbal Medicine in Chronic Kidney Disease
Authors: Li Qing , Xing Changying , Yuan Yanggang
Published: May 2021

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of nephrons and an eventual decline in glomerular filtration rate. CKD increases mortality and has a significant impact on the quality of life and the economy, which is becoming a major public health issue worldwide. Since current conventional-medicine treatment options for CKD are not satisfactory, many patients seek complementary and alternative medicine treatments including Traditional Chinese Medicine. Herbal medicine is often used to relieve symptoms of renal diseases in the clinic. The kidney is abundant in the number of mitochondria, which provide enough energy for renal function and metabolism. In recent years, a vital role for mitochondrial dysfunction has been suggested in CKD. Mitochondria have become a new target for the treatment of diseases. A growing number of studies have demonstrated herbal medicine could restore mitochondrial function and alleviate renal injury both in vivo and in vitro. In this review, we sum up the therapeutic effect of herbal medicine in CKD via targeting mitochondrial function. This implies future strategies in preventing CKD.
Total Flavonoids of Rhizoma Drynariae Promotes Differentiation of Osteoblasts and Growth of Bone Graft in Induced Membrane Partly by Activating Wnt/β-Catenin Signaling Pathway
Authors: Li Shuyuan , Zhou Hongliang , Hu Cheng , Yang Jiabao , Ye Jinfei , Zhou Yuexi , Li Zige , Chen Leilei , Zhou Qishi
Published: May 2021

Total flavonoids of Rhizoma drynariae (TFRD), a Chinese medicine, is widely used in the treatment of fracture, bone defect, osteoporosis and other orthopedic diseases, and has achieved good effects. Purpose of this trial was to explore efficacy of TFRD on bone graft’s mineralization and osteoblasts’ differentiation in Masquelet induced membrane technique in rats. Forty male Sprague-Dawley rats were randomly divided into high dose group (H-TFRD), middle dose group (M-TFRD), low dose group (L-TFRD) and control group (control). The critical size bone defect model of rats was established with 10 rats in each group. Polymethyl methacrylate (PMMA) spacer was implanted into the defect of right femur in rats. After the formation of the induced membrane, autogenous bone was implanted into the induced membrane. After 12 weeks of bone graft, bone tissues in the area of bone graft were examined by X-ray, Micro-CT, hematoxylin-eosin (HE) and Masson trichrome staining to evaluate the growth of the bone graft. The β-catenin, c-myc, COL1A1, BMP-2 and OPN in bone graft were quantitatively analyzed by Western blot and Immunohistostaining. Osteoblasts were cultured in the medium containing TFRD. Cell Counting Kit-8 (CCK-8) method, Alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, Western blot, RT-PCR and other methods were used to detect the effects of TFRD on the proliferation of osteoblasts and the regulation of Wnt/β-catenin signaling pathway. In vivo experiments showed that the growth and mineralization of bone graft in TFRD group was better. Moreover, the expression of Wnt/β-catenin and osteogenesis-related proteins in bone tissue of TFRD group was more than that in other groups. In vitro experiments indicated that osteoblasts proliferated faster, activity of ALP was higher, number of mineralized nodules and proteins related to osteogenesis were more in TFRD group. But blocking Wnt/β-catenin signaling pathway could limit these effects. Therefore, TFRD could promote mineralization of bone graft and differentiation of osteoblasts in a dose-dependent manner during growing period of the bone graft of induced membrane technique, which is partly related to the activation of Wnt/β-catenin signaling pathway.
The Aerobic and Anaerobic Contribution During Repeated 30-s Sprints in Elite Cyclists
Authors: Almquist Nicki Winfield , Sandbakk Øyvind , Rønnestad Bent R. , Noordhof Dionne
Published: May 2021

Although the ability to sprint repeatedly is crucial in road cycling races, the changes in aerobic and anaerobic power when sprinting during prolonged cycling has not been investigated in competitive elite cyclists. Here, we used the gross efficiency (GE)-method to investigate: (1) the absolute and relative aerobic and anaerobic contributions during 3 × 30-s sprints included each hour during a 3-h low-intensity training (LIT)-session by 12 cyclists, and (2) how the energetic contribution during 4 × 30-s sprints is affected by a 14-d high-volume training camp with (SPR,n= 9) or without (CON,n= 9) inclusion of sprints in LIT-sessions. The aerobic power was calculated based on GE determined before, after sprints, or the average of the two, while the anaerobic power was calculated by subtracting the aerobic power from the total power output. When repeating 30-s sprints, the mean power output decreased with each sprint (p< 0.001, ES:0.6–1.1), with the majority being attributed to a decrease in mean anaerobic power (first vs. second sprint: −36 ± 15 W,p< 0.001, ES:0.7, first vs. third sprint: −58 ± 16 W,p< 0.001, ES:1.0). Aerobic power only decreased during the third sprint (first vs. third sprint: −17 ± 5 W,p< 0.001, ES:0.7, second vs. third sprint: 16 ± 5 W,p< 0.001, ES:0.8). Mean power output was largely maintained between sets (first set: 786 ± 30 W vs. second set: 783 ± 30 W,p= 0.917, ES:0.1, vs. third set: 771 ± 30 W,p= 0.070, ES:0.3). After a 14-d high-volume training camp, mean power output during the 4 × 30-s sprints increased on average 25 ± 14 W in SPR (p< 0.001, ES:0.2), which was 29 ± 20 W more than CON (p= 0.008, ES: 0.3). In SPR, mean anaerobic power and mean aerobic power increased by 15 ± 13 W (p= 0.026, ES:0.2) and by 9 ± 6 W (p= 0.004, ES:0.2), respectively, while both were unaltered in CON. In conclusion, moderate decreases in power within sets of repeated 30-s sprints are primarily due to a decrease in anaerobic power and to a lesser extent in aerobic power. However, the repeated sprint-ability (multiple sets) and corresponding energetic contribution are maintained during prolonged cycling in elite cyclists. Including a small number of sprints in LIT-sessions during a 14-d training camp improves sprint-ability mainly through improved anaerobic power.
Identification of Novel Marker–Trait Associations for Lint Yield Contributing Traits in Upland Cotton (Gossypium hirsutum L.) Using SSRs
Authors: Kumar Pawan , Nimbal Somveer , Sangwan Rajvir Singh , Budhlakoti Neeraj , Singh Varsha , Mishra Dwijesh Chandra , Sagar  , Choudhary Raju Ram
Published: May 2021

Improving the yield of lint is the main objective for most of the cotton crop improvement programs throughout the world as it meets the demand of fiber for textile industries. In the current study, 96 genotypes ofGossypium hirsutumwere used to find novel simple sequence repeat marker-based associations for lint yield contributing traits by linkage disequilibrium. Extensive phenotyping of 96 genotypes for various agronomic traits was done for two consecutive years (2018 and 2019) in early, normal, and late sown environments. Out of 168 SSR markers screened over the 96 genotypes, a total of 97 polymorphic markers containing 293 alleles were used for analysis. Three different models, i.e., mixed linear model (MLM), compressed mixed linear model (CMLM), and multiple locus mixed linear model (MLMM), were used to detect the significant marker–trait associations for six different environments separately. A total of 38 significant marker–trait associations that were common to at least two environments were considered as promising associations and detailed annotation of the significant markers has been carried out. Twenty-two marker–trait associations were found to be novel in the current study. These results will be very useful for crop improvement programs using marker-assisted cotton breeding.
Psychometric Properties of the RESTQ-Sport-36 in a Collegiate Student-Athlete Population
Authors: Gnacinski Stacy L. , Meyer Barbara B. , Wahl Carly A.
Published: May 2021

The purpose of the current study was to examine the reliability and validity of the RESTQ-Sport-36 for use in the collegiate student-athlete population. A total of 494 collegiate student-athletes competing in National Collegiate Athletic Association Division I, II, or III sanctioned sport completed the RESTQ-Sport-36 and Brief Profile of Mood States (POMS). Structural equation modeling (SEM) procedures were used to compare first order to hierarchical model structures. Results of a confirmatory factor analysis (χ2[528] = 1129.941, p < 0.001; SRMR = 0.050; CFI = 0.929) and exploratory structural equation modeling analysis (χ2[264] = 575.424, p < 0.001; SRMR = 0.013; CFI = 0.963) indicated that the first order 12-factor structure demonstrated the best fit of all models tested. Support was not observed for the fit of any hierarchical model. Moderate to strong correlations were observed between stress and recovery subscales and mood states, thus supporting the construct validity of the abbreviated RESTQ measurement model. The current findings provide support for the measure’s use in this population and give pause as it relates to the scoring and interpretation of hierarchical factors such as Total Stress and Total Recovery. Overall, the current results indicate that the RESTQ-Sport-36 may be a useful tool for collegiate student-athlete training load and competition monitoring.