bluuebunny/crossref_metadata_2025 huggingface dataset:
Síntese e aplicação do material mesoporoso do tipo Nb-MCM com líquido iônico utilizando sílica derivada das cinzas da casca de arroz em elastômeros
Authors: Todero Adriele Sabrina , Pereira Fabiana de Oliveira , Macieski Ricardo Jorge , Finkler Diana Exenberger , Petkowicz Diego , Lago Rogério Marcos Dal , Mignoni Marcelo Luís
Published: April 2022

A visibilidade de reaproveitamento de materiais, subprodutos e coprodutos vem ganhando cada vez mais espaço em pesquisas acadêmicas, utilização industrial e inovação, com isso, o propósito do presente estudo são as possibilidades de utilização da solução de silicato de sódio proveniente da cinza da casca de arroz (CCA). Além disso, adicionou-se Líquido Iônico (LI) e diferentes relações de silício e nióbio para buscar melhorias nas propriedades físico-químicas dos elastômeros. Por meio de Difração de Raios X (DRX) comprovou-se a obtenção do material mesoporoso do tipo MCM-48 pura e quando empregada variadas relações molares de Si/Nb, Nb-MCM-48. Ao aplicar em elastômeros, concluiu-se por meio de torque máximo e mínimo; tempo ótimo e scorch, que o acréscimo de LI e também da Nb-MCM causaram efeitos nos seus desempenhos, como aceleramento do tempo de scorch e melhorias nas propriedades mecânicas.
Formação continuada de professores para a educação das relações étnico-raciais: análise sobre uma prática estadual
Authors: Gatinho Andrio Alves
Published: April 2022

O estudo objetiva analisar práticas de formação continuada que visam preparar os professores para o trabalho com os conteúdos do ensino de história e cultura afro-brasileira e africana (EHCAA). Metodologicamente trata da análise de formações realizadas, planos de aulas e um conjunto de grupos focais realizados em quatro escolas públicas do Acre que contaram com a participação de professores e gestores. Os resultados indicam que a busca de soluções técnicas marca a fase de um novo gerenciamento da prática pedagógica e, neste caso, o EHCAA é reduzido às habilidades propostas pela lógica da Secretaria de Educação, o que mostra um tipo de encenação da política comprometida com a lógica externa à escola. Os discursos dos agentes, ao invés de afirmar a autonomia docente apontam um caminho dirigido pela rotina imposta pela administração, com planejamentos altamente dirigidos, o que os deixa dependentes de imperativos determinados externamente. Os agentes escolares desenvolvem um tipo de cultura profissional que deve obediência a regras geradas de forma exógena, o que faz seu profissionalismo ser medido por uma forma de desempenho em que a prática da sala de aula é cada vez mais remodelada para responder às novas demandas externas, o que compromete a função da escola e a possível reeducação das relações étnico-raciais.
The modulatory effect of acupuncture on amygdala functional connectivity: narrative review of the clinical research
Authors: Almeida Marcos dos Santos de
Published: April 2022

The amygdala is a brain area crucial for emotional, behavioural and visceral sensitivity/motor signals processing. To exert these functions, the amygdala is reciprocally connected with cortical and subcortical regions. Some studies have showed that acupuncture modulates the activity of the amygdala and its circuits. However, there is no literature review synthesizing and evidencing the actual research status about this subject. Thus, the aim of this paper is to present and discuss the newest evidence about the effect of acupuncture on the amygdala resting-state functional connectivity (rsFC) in the context of clinical research. The narrative review of clinical research was focused on published clinical trials (controlled and randomized) designed to analyze the effect of acupuncture on the modulation of the amygdala rsFC in clinical conditions. The search was conducted on Pubmed, ScienceDirect and Scielo databases up to March, 2022. The studies found were about patients with major depressive disorder, functional dyspepsia and premenstrual syndrome, which demonstrated that acupuncture significantly decreases its symptoms. In addition, this therapeutic effect were correlated with the modulation of the amygdala rsFC with a range of brain regions. According to the data reviewed, it can be concluded that the brain action’s mechanisms of acupuncture is related, at least in part for the clinical conditions analyzed, to its modulatory effect on the amygdala network. However, the studies about this theme are rare, and more studies should be done to clarify the amygdala involvement in the effect of the acupuncture.
Tax Salience, Escrow, and Support for Property Tax
Authors: Young Sarah , Thornburg Matthew
Published: April 2022

Scholars find that tax presentation is a key factor influencing the salience of a tax to those who pay it. We test Cabral and Hoxby’s 2012 hypothesis that homeowners who escrow their property tax payments will express more support for property tax increases than non-escrow taxpayers. Using original data collected from a mailed survey of South Carolina voters our multi-variate regression analysis shows that homeowners who escrow property taxes express more support for increasing school tax than do non-escrow payers. We also find significant knowledge limits among respondents in understanding the actual school tax costs on taxpayers in South Carolina. Most S.C. homeowners are exempt from paying property taxes for school operations, but we find that this is not widely understood. Note: This project was funded by an ASPIRE I research grant from the Office of the Vice President of Research for the University of SC system.
Characterization of Polymer Degrading Lipases, LIP1 and LIP2 From Pseudomonas chlororaphis PA23
Authors: Mohanan Nisha , Wong Chun Hin , Budisa Nediljko , Levin David B.
Published: April 2022

The outstanding metabolic and bioprotective properties of the bacterial genusPseudomonasmake these species a potentially interesting source for the search of hydrolytic activities that could be useful for the degradation of plastics. We identified two genes encoding the intracellular lipases LIP1 and LIP2 of the biocontrol bacteriumPseudomonas chlororaphisPA23 and subsequently performed cloning and expression inEscherichia coli. Thelip1gene has an open reading frame of 828 bp and encodes a protein of 29.7 kDa whereas thelip2consists of 834 bp and has a protein of 30.2 kDa. Although secondary structure analyses of LIP1 and LIP2 indicate a dominant α/β-hydrolase-fold, the two proteins differ widely in their amino acid sequences (15.39% identity), substrate specificities, and hydrolysis rates. Homology modeling indicates the catalytic serine in both enzymes located in a GXSXG sequence motif (lipase box). However, LIP1 has a catalytic triad of Ser152-His253-Glu221 with a GGX-type oxyanion pocket, whereas LIP2 has Ser138-His249-Asp221 in its active site and a GX-type of oxyanion hole residues. However, LIP1 has a catalytic triad of Ser152-His253-Glu221 with an oxyanion pocket of GGX-type, whereas LIP2 has Ser138-His249-Asp221 in its active site and a GX-type of oxyanion hole residues. Our three-dimensional models of LIP1 and LIP2 complexed with a 3-hydroxyoctanoate dimer revealed the core α/β hydrolase-type domain with an exposed substrate binding pocket in LIP1 and an active-site capped with a closing lid domain in LIP2. The recombinant LIP1 was optimally active at 45°C and pH 9.0, and the activity improved in the presence of Ca2+. LIP2 exhibited maximum activity at 40°C and pH 8.0, and was unaffected by Ca2+. Despite different properties, the enzymes exhibited broadsubstrate specificity and were able to hydrolyze short chain length and medium chain length polyhydroxyalkanoates (PHAs), polylactic acid (PLA), and para-nitrophenyl (pNP) alkanoates. Gel Permeation Chromatography (GPC) analysis showed a decrease in the molecular weight of the polymers after incubation with LIP1 and LIP2. The enzymes also manifested some polymer-degrading activity on petroleum-based polymers such as poly(ε-caprolactone) (PCL) and polyethylene succinate (PES), suggesting that these enzymes could be useful for biodegradation of synthetic polyester plastics. The study will be the first report of the complete characterization of intracellular lipases from bacterial and/orPseudomonasspecies. The lipases, LIP1 and LIP2 are different from other bacterial lipases/esterases in having broad substrate specificity for polyesters.
Using Machine Learning Models to Forecast Severity Level of Traffic Crashes by R Studio and ArcGIS
Authors: Al-Mistarehi Bara’ W. , Alomari Ahmad H. , Imam Rana , Mashaqba Mohammad
Published: April 2022

This study describes crash causes, conditions, and distribution of accident hot spots along with an analysis of the risk factors that significantly affect severity levels of crashes and their effects on pedestrian safety using machine learning (ML) techniques. Supervised ML algorithm–random forest and decision tree–based algorithm-AdaBoost algorithms are applied and compared to predict the severity level and future crashes based on road crash elements. Association rule, an unsupervised learning algorithm, is utilized to understand the association between driver characteristics, geometric elements of the highway, the environment, time, weather, and speed. Slight, medium, and severe injuries and fatalities in crashes are also considered to understand the behavior of road drivers, who are most likely to cause crashes. Fatalities and injuries are studied with spatial statistics analysis. The variables most affecting the severity of the crash are determined and discussed in detail. The results are checked for accuracy, sensitivity, specificity, recall, precision, and F1 score performance. The impact of drivers, vehicles, and road characteristics is investigated in traffic crashes. The random forest model was found to be the most suitable algorithm to predict crash severity levels.
EpCAM as a Novel Biomarker for Survivals in Prostate Cancer Patients
Authors: Liao Yang , Wu Mingxin , Jia Yingjie , Mou Ruiyu , Li Xiaojiang
Published: April 2022

Background: Due to the insufficient understanding of the biological mechanisms, the improvement of therapeutic effects of prostate cancer (PCa) is limited. There is an urgent need to find the molecular mechanisms and underlying PCa to improve its early diagnosis, treatment, and prognosis.

Methods: The mRNA expression profiles, survival and methylation data of PRAD were downloaded from The Cancer Genome Atlas (TCGA) database. The identification of differentially expressed genes (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed by R software. Subsequently, we identified the key gene and validated its prognostic role from the Human Protein Atlas (HPA) database, UALCAN and the LinkedOmics database. We performd correlation analysis and constructed the ceRNA network based on the data obtained from miRbase and starBase. Finally, we performed methylation analysis and evaluated the immune cell infiltration by Tumor Immune Estimation Resource (TIMER).

Results: A total of 567 DEGs were identified in PCa. ARHGEF38, SLPI, EpCAM, C1QTNF1, and HBB were regarded as target genes related to favorable overall survival (OS). Among them, EpCAM was considered as the most significant gene through the HPA database and receiver operating characteristic (ROC) analysis. A prognostic ceRNA network was constructed with EBLN3P, miR-204-5p, and EpCAM. EpCAM was found to be related to DNA methylation and tumor-infiltrating immune cells.

Conclusion: Our findings provide novel insights into the tumorigenesis mechanism of PCa and contribute to the development of EpCAM as a potential prognostic biomarker in PCa.
Mixed Land Uses and Community Decline: Opportunities and Challenges for Mitigating Residential Vacancy in Peri-Urban Villages of China
Authors: Ma Wenqiu , Jiang Guanghui , Zhou Tao , Zhang Ruijuan
Published: April 2022

Residential vacancy is a visible symptom of community decline in peri-urban villages of China. Mixed-use development has emerged as a possible approach for land use planning to help mitigate community decline and residential vacancy. By applying an integrated framework, this study explores whether mixed land use (MLU) can help counter residential vacancy based on the classification of four types of peri-urban villages. Results show that the degree of MLU and residential vacancy rate both present increasing tendencies. Also, impacts of MLU on residential vacancy differ across villages: the disorderly and excessive mixed uses in some villages exacerbated residential vacancy, even threatening the neighborhood safety and livability; whereas for some villages with compatible mixed uses, the land use pattern could assist in reducing the residential vacancy, as well as promoting the compact and high-density development. Undeniably, planning for the increased mixed-use environment like urban communities is unsuitable for rural communities. Sustainable planning to counter residential vacancy should combine the compatible mixed-use development together with the rational functional zoning, which is also considered a constructive tool in mitigating community decline, and bringing human settlements development, vitality, and diversity. This research contributes to reconcile residential vacancy in the depopulating and declining communities.
The Potential Role of m6A RNA Methylation in the Aging Process and Aging-Associated Diseases
Authors: Sun Jin , Cheng Bokai , Su Yongkang , Li Man , Ma Shouyuan , Zhang Yan , Zhang Anhang , Cai Shuang , Bao Qiligeer , Wang Shuxia , Zhu Ping
Published: April 2022

N6-methyladenosine (m6A) is the most common and conserved internal eukaryotic mRNA modification. m6A modification is a dynamic and reversible post-transcriptional regulatory modification, initiated by methylase and removed by RNA demethylase. m6A-binding proteins recognise the m6A modification to regulate gene expression. Recent studies have shown that altered m6A levels and abnormal regulator expression are crucial in the ageing process and the occurrence of age-related diseases. In this review, we summarise some key findings in the field of m6A modification in the ageing process and age-related diseases, including cell senescence, autophagy, inflammation, oxidative stress, DNA damage, tumours, neurodegenerative diseases, diabetes, and cardiovascular diseases (CVDs). We focused on the biological function and potential molecular mechanisms of m6A RNA methylation in ageing and age-related disease progression. We believe that m6A modification may provide a new target for anti-ageing therapies.
Cochlear Marginal Cell Pyroptosis Is Induced by Cisplatin via NLRP3 Inflammasome Activation
Authors: Yu Wenting , Zong Shimin , Zhou Peng , Wei Jiahui , Wang Enhao , Ming Ruijie , Xiao Hongjun
Published: April 2022

Better understanding the mechanism of cisplatin-induced ototoxicity is of great significance for clinical prevention and treatment of cisplatin-related hearing loss. However, the mechanism of cisplatin-induced inflammatory response in cochlear stria vascularis and the mechanism of marginal cell (MC) damage have not been fully clarified. In this study, a stable model of cisplatin-induced MC damage was established in vitro, and the results of PCR and Western blotting showed increased expressions of NLRP3, Caspase-1, IL-1β, and GSDMD in MCs. Incomplete cell membranes including many small pores appearing on the membrane were also observed under transmission electron microscopy and scanning electron microscopy. In addition, downregulation of NLRP3 by small interfering RNA can alleviate cisplatin-induced MC pyroptosis, and reducing the expression level of TXNIP possesses the inhibition effect on NLRP3 inflammasome activation and its mediated pyroptosis. Taken together, our results suggest that NLRP3 inflammasome activation may mediate cisplatin-induced MC pyroptosis in cochlear stria vascularis, and TXNIP is a possible upstream regulator, which may be a promising therapeutic target for alleviating cisplatin-induced hearing loss.
Can ERAP1 and ERAP2 Form Functional Heterodimers? A Structural Dynamics Investigation
Authors: Papakyriakou Athanasios , Mpakali Anastasia , Stratikos Efstratios
Published: April 2022

Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) play important roles in the generation of antigenic peptides presented by Major Histocompatibility Class I (MHCI) molecules and indirectly regulate adaptive immune responses. Although the discrete function of these enzymes has been extensively characterized, recent reports have suggested that they can also form heterodimers with functional consequences. However, lack of structural characterization of a putative ERAP1/ERAP2 dimer has limited our understanding of its biological role and significance. To address this, we employed computational molecular dynamics calculations to explore the topology of interactions between these two, based on experimentally determined homo-dimerization interfaces observed in crystal structures of ERAP2 or homologous enzymes. Our analysis of 8 possible dimerization models, suggested that the most likely ERAP1/ERAP2 heterodimerization topology involves the exon 10 loop, a non-conserved loop previously implicated in interactions between ERAP1 and the disulfide-bond shuffling chaperone ERp44. This dimerization topology allows access to the active site of both enzymes and is consistent with a previously reported construct in which ERAP1 and ERAP2 were linked by Fos/Jun zipper tags. The proposed model constitutes a tentative structural template to help understand the physiological role and significance of ERAP1/ERAP2 molecular interactions.
Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita
Authors: Tukaj Stefan , Mantej Jagoda , Sitko Krzysztof , Zillikens Detlef , Ludwig Ralf J. , Bieber Katja , Kasperkiewicz Michael
Published: April 2022

Stress-induced heat shock protein 70 (Hsp70) is a key intra- and extracellular molecular chaperone implicated in autoimmune processes. Highly immunogenic extracellular Hsp70 can activate innate and acquired (adaptive) immune responses driving the generation of anti-Hsp70 autoantibodies that are frequently observed in inflammatory/autoimmune disorders. We recently described the direct pathological role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-mediated autoimmune blistering skin disease. Here, we determined the role of anti-Hsp70 autoantibodies in EBA. We observed that circulating anti-Hsp70 IgG autoantibodies were significantly elevated in EBA patients compared to healthy individuals and positively correlated with serum levels of pro-inflammatory interferon gamma (IFN-γ). The pathophysiological relevance of anti-Hsp70 IgG autoantibodies was demonstrated in an antibody transfer-induced EBA mouse model in which elevated serum levels of anti-Hsp70 IgG were found. In addition, anti-Hsp70 IgG-treated animals had a more intense clinical and histological disease activity, as well as upregulated nuclear factor kappa B (NF-κB) activation in skin biopsies compared to isotype-treated animals. Our results suggest that autoantibodies to Hsp70 may contribute to EBA development via enhanced neutrophil infiltration to the skin and activation of the NF-κB signaling pathway in an IFN-γ-associated manner.
Strategy to Identify Areas of Use of Amazon River dolphins
Authors: Mosquera-Guerra Federico , Trujillo Fernando , Pérez-Torres Jairo , Mantilla-Meluk Hugo , Franco-León Nicole , Paschoalini Mariana , Valderrama María J. , Usma Oviedo José S. , Campbell Elizabeth , Alfaro-Shigueto Joanna , Mena José L. , Mangel Jeffrey C. , Gilleman Cédric , Zumba Moisés , Briceño Yurasi , Valencia Kelly Y. , Torres-Forero Paula A. , Sánchez Leonardo , Ferrer Arnaldo , Barreto Sebastian , van Damme Paul A. , Armenteras-Pascual Dolors
Published: April 2022

Unsustainable fisheries practices carried out in large parts of the Amazon, Tocantins, and Orinoco basins have contributed to the decline in the populations of the Amazon River dolphins (Iniaspp.), considered Endangered by the International Union for Conservation of Nature (IUCN). Amazon River dolphin byproducts are often obtained through unregulated fisheries and from stranded and incidentally caught individuals that are traded for the flesh and blubber used forCalophysus macropterusfisheries, traditional and other medicinal purposes, and more recently for human consumption. To identify localities of use of Amazon River dolphins, we conducted a systematic review of the related literature published since 1980, complemented with structured surveys of researchers that allowed the identification of 57 localities for uses ofInia(33 in the Amazon, two in the Tocantins, and 22 in the Orinoco basins), and two more on the Brazilian Atlantic coast, with recent reports of targeted consumption in the upper Orinoco River. Subsequently, the localities of use or bushmeat markets where Amazon River dolphin byproducts are trafficked were identified. This information was integrated with a kernel density analysis of the distribution of theIniaspp. populations establishing core areas. Our spatial analysis indicated that the use ofIniaspp. is geographically widespread in the evaluated basins. It is urgent that decision-makers direct policies towards mitigating the socioeconomic and cultural circumstances associated with illegal practices affecting Amazon River dolphin populations in South America.
Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development
Authors: Tan Jian , Taitz Jemma , Sun Shir Ming , Langford Lachlan , Ni Duan , Macia Laurence
Published: April 2022

Modern industrial practices have transformed the human diet over the last century, increasing the consumption of processed foods. Dietary imbalance of macro- and micro-nutrients and excessive caloric intake represent significant risk factors for various inflammatory disorders. Increased ingestion of food additives, residual contaminants from agricultural practices, food processing, and packaging can also contribute deleteriously to disease development. One common hallmark of inflammatory disorders, such as autoimmunity and allergies, is the defect in anti-inflammatory regulatory T cell (Treg) development and/or function. Treg represent a highly heterogeneous population of immunosuppressive immune cells contributing to peripheral tolerance. Tregs either develop in the thymus from autoreactive thymocytes, or in the periphery, from naïve CD4+ T cells, in response to environmental antigens and cues. Accumulating evidence demonstrates that various dietary factors can directly regulate Treg development. These dietary factors can also indirectly modulate Treg differentiation by altering the gut microbiota composition and thus the production of bacterial metabolites. This review provides an overview of Treg ontogeny, both thymic and peripherally differentiated, and highlights how diet and gut microbiota can regulate Treg development and function.
Evaluation of the Combination of Artificial Intelligence and Radiologist Assessments to Interpret Malignant Architectural Distortion on Mammography
Authors: Wan Yun , Tong Yunfei , Liu Yuanyuan , Huang Yan , Yao Guoyan , Chen Daniel Q. , Liu Bo
Published: April 2022

Purpose

To compare the mammographic malignant architectural distortion (AD) detection performance of radiologists who read mammographic examinations unaided versus those who read these examinations with the support of artificial intelligence (AI) systems.

Material and Methods

This retrospective case-control study was based on a double-reading of clinical mammograms between January 2011 and December 2016 at a large tertiary academic medical center. The study included 177 malignant and 90 benign architectural distortion (AD) patients. The model was built based on the ResNeXt-50 network. Algorithms used deep learning convolutional neural networks, feature classifiers, image analysis algorithms to depict AD and output a score that translated to malignant. The accuracy for malignant AD detection was evaluated using area under the curve (AUC).

Results

The overall AUC was 0.733 (95% CI, 0.673-0.792) for Reader First-1, 0.652 (95% CI, 0.586-0.717) for Reader First-2, and 0.655 (95% CI, 0.590-0.719) for Reader First-3. and the overall AUCs for Reader Second-1, 2, 3 were 0.875 (95% CI, 0.830-0.919), 0.882 (95% CI, 0.839-0.926), 0.884 (95% CI, 0.841-0.927),respectively. The AUCs for all the reader-second radiologists were significantly higher than those for all the reader-first radiologists (Reader First-1 vs. Reader Second-1, P= 0.004). The overall AUC was 0.792 (95% CI, 0.660-0.925) for AI algorithms. The combination assessment of AI algorithms and Reader First-1 achieved an AUC of 0.880 (95% CI, 0.793-0.968), increased than the Reader First-1 alone and AI algorithms alone. AI algorithms alone achieved a specificity of 61.1% and a sensitivity of 80.6%. The specificity for Reader First-1 was 55.5%, and the sensitivity was 86.1%. The results of the combined assessment of AI and Reader First-1 showed a specificity of 72.7% and sensitivity of 91.7%. The performance showed significant improvements compared with AI alone (p<0.001) as well as the reader first-1 alone (p=0.006).

Conclusion

While the single AI algorithm did not outperform radiologists, an ensemble of AI algorithms combined with junior radiologist assessments were found to improve the overall accuracy. This study underscores the potential of using machine learning methods to enhance mammography interpretation, especially in remote areas and primary hospitals.
Benzodiazepine Sedation and Postoperative Neurological Deficits after Awake Craniotomy for Brain Tumor – An Exploratory Retrospective Cohort Study
Authors: Plitman Eric , Chowdhury Tumul , Paquin-Lanthier Gabriel , Takami Hirokazu , Subramaniam Sudhakar , Leong Kok Weng , Daniels Abigail , Bernstein Mark , Venkatraghavan Lashmi
Published: April 2022

An awake craniotomy is a common neurosurgical procedure for excising brain tumor(s) located near or in eloquent areas. The use of benzodiazepine (BZD) for sedation in some patients with neuropathological conditions (e.g., stroke, brain tumors) has been previously linked with re-appearance of neurological deficits including limb incoordination, ataxia, and motor weakness, resulting in complications for the patient along with procedural challenges. Whether or not these findings can be extrapolated to patients undergoing brain tumor resection is largely unknown. The current work primarily sought to compare neurological outcome(s) in the immediate postoperative period between BZD-free and BZD-based sedation techniques in patients undergoing awake craniotomy. Using a database composed of awake craniotomies conducted within a single center and by a single surgeon, patients were retrospectively classified based on midazolam administration into BZD-free sedation (n=125) and BZD-based sedation (n=416) groups. Patients from each group were matched based on age, sex, tumor location, tumor grade, preoperative neurological deficits, non-operative BZD use, and Karnofsky Performance Scale scores, resulting in 108 patients within each group. Postoperative neurological deficits were recorded. Logistic regression analyses were conducted comparing postoperative neurological deficits between the matched groups. Postoperative neurological deficits were more prevalent within the BZD-based sedation group compared to the BZD-free sedation group (adjusted odds ratio (aOR)=1.903, 95% CI=1.018-3.560, p=0.044). In addition, subgroup analysis of the matched cohort showed a relationship between preoperative neurological symptoms and postoperative neurological deficits in the BZD-based sedation group (aOR=3.756, 95% CI=1.390-10.147, p=0.009). Our findings support the notion that the increased incidence of postoperative neurological deficits with BZD sedation may in part be related to the unmasking of preoperative neurological deficits. Further studies are required to confirm this phenomenon.
Peabody Developmental Motor Scales-2: The Use of Rasch Analysis to Examine the Model Unidimensionality, Motor Function, and Item Difficulty
Authors: Valentini Nadia Cristina , Zanella Larissa Wagner
Published: April 2022

The Peabody Developmental Motor Scales-Second Edition (PDMS-2) is a valid and reliable instrument used in several countries, including Brazil, to assess gross and fine motor skills and identify motor deficits and eligibility for intervention for children with and without disabilities. However, the analysis of PDMS-2 items regarding the unidimensionality of the model, order of item difficulty, and whether the items portray the children's developmental trajectories still lacks investigation. Therefore, this study aims to: (1) analyze the unidimensionality of PDMS-2, (2) verify the model's capacity to explain the variance in the motor function responses, and (3) identify the level of difficulty of the items for Brazilian children. Children (n = 637; 51% girls) newborn to 71 months (M age = 21.7, SD = 18.6) were assessed using the PDMS-2. The Rasch analysis was conducted; the indexes of infit and outfit, and the point-biserial correlations coefficient were analyzed. The model unidimensionality was investigated using percentages of variance in the Rasch model (40% of variance). Results indicated that (1) for reflexes subscale, 62.5% of the items had correlations with the factor above 0.60, and two items had unadjusted infit and outfit; (2) for stationary subscale, 83.3% of the correlations of the items with the factor were above 0.50, and one item had unadjusted infit and outfit; (3) for locomotion subscale, 80.0% of the correlation of the items with the factor were above 0.50; all items had adequate infit and outfit; (4) for object manipulation subscale, 79.9% of the correlation of the items with the factor were above 0.50, and one item had unadjusted infit and outfit; (5) for grasping subscale, 92.3% of the correlation of the items with the factor were above 0.50, and one item had unadjusted infit and outfit; and (6) for the visual-motor integration subscale, 73.6% of the correlation of the items with the factor were above 0.50, and six items had unadjusted infit and outfit. The items with unadjusted fit were removed for further analysis. No changes in reliability and separation of items and people scores were observed without the unadjusted items; therefore, all items were maintained. A unidimensional model was found, and the reliability and discriminant capability of the items were adequate, and all items should be used to assess children. The PDMS-2 is appropriate for assessing Brazilian children.
Autoimmune Encephalitis and Other Neurological Syndromes With Rare Neuronal Surface Antibodies in Children: A Systematic Literature Review
Authors: Ancona Claudio , Masenello Valentina , Tinnirello Matteo , Toscano Luca Mattia , Leo Andrea , La Piana Chiara , Toldo Irene , Nosadini Margherita , Sartori Stefano
Published: April 2022

Neuronal surface antibody syndromes (NSAS) are an expanding group of autoimmune neurological diseases, whose most frequent clinical manifestation is autoimmune encephalitis (AE). Anti-NMDAR, anti-LGI1, and anti-CASPR2 autoimmunity represent the most described forms, while other NSAS are rarer and less well-characterized, especially in children. We carried out a systematic literature review of children with rare NSAS (with antibodies targeting D2R, GABAAR, GlyR, GABABR, AMPAR, amphiphysin, mGluR5, mGluR1, DPPX, IgLON5, and neurexin-3alpha) and available individual data, to contribute to improve their clinical characterization and identification of age-specific features. Ninety-four children were included in the review (47/94 female, age range 0.2–18 years). The most frequent NSAS were anti-D2R (28/94, 30%), anti-GABAAR (23/94, 24%), and anti-GlyR (22/94, 23%) autoimmunity. The most frequent clinical syndromes were AE, including limbic and basal ganglia encephalitis (57/94, 61%; GABAAR, D2R, GABABR, AMPAR, amphiphysin, and mGluR5), and isolated epileptic syndromes (15/94, 16%; GlyR, GABAAR). With the limitations imposed by the low number of cases, the main distinctive features of our pediatric literature cohort compared to the respective NSAS in adults included: absent/lower tumor association (exception made for anti-mGluR5 autoimmunity, and most evident in anti-amphiphysin autoimmunity); loss of female preponderance (AMPAR); relatively frequent association with preceding viral encephalitis (GABAAR, D2R). Moreover, while SPS and PERM are the most frequent syndromes in adult anti-GlyR and anti-amphiphysin autoimmunity, in children isolated epileptic syndromes and limbic encephalitis appear predominant, respectively. To our knowledge, this is the first systematic review on rare pediatric NSAS. An improved characterization may aid their recognition in children.
Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis
Authors: Liu Dan , Zhao Ran , Wu Yajing , Wang Yunhong , Yang Rongping , Ke Xiumei
Published: April 2022

Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1β, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.
Drug Therapies for COPD: A Bibliometric Review From 1980 to 2021
Authors: Zhen Gao , Yingying Liu , Jingcheng Dong
Published: April 2022

Objective: To analyze all chronic obstructive pulmonary disease (COPD) drugs-related articles that were indexed in the Web of Science Core Collection (WOSCC) database until August 28, 2021 using bibliometric analysis, in order to provide a reliable reference for the treatment of COPD.

Methods: A comprehensive search was conducted to analyze all COPD drugs-related articles using WOSCC database from inception to August 28, 2021. Abstracts and potentially eligible articles, which were retrieved during literature search, were screened by two reviewers. Besides, the CiteSpace (5.8.R1) software was utilized to analyze the overall structure of the network, the network clusters, the links between clusters, the key nodes or pivot points, and the pathways.

Results: A total of 2552 COPD-drugs related articles were retrieved. From the perspective of categorization of published articles based on country, the United States is the country with the largest number of published articles and completed clinical trials, highlighting the important role of this country in the treatment of COPD. However, in terms of the proportion of ongoing clinical trials, China has the highest proportion, suggesting that China will play a more pivotal role in the medication of COPD in the future. From the perspective of cooperation among countries, the cooperation among European countries was closer than that among Asian countries. In the recent three decades, the top 20 institutions, with a particular concentration on the treatment of COPD, were from North America and Europe. The co-citation analysis showed that, among 2,552 articles, 53154 citations were recorded, and the co-citation network indicated that 24 clusters could be achieved.

Conclusion: The administration of bronchodilators and pulmonary drug delivery systems, as well as consideration of elderly COPD patients remained the hotspots, while triple therapy and comorbidity of COPD, as well as the prevention and treatment of elderly COPD patients had been frontiers in recent years.
Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics
Authors: Tempark Therdpong , John Shobana , Rerknimitr Pawinee , Satapornpong Patompong , Sukasem Chonlaphat
Published: April 2022

SCARs are rare and life-threatening hypersensitivity reactions. In general, the increased duration of hospital stays and the associated cost burden are common issues, and in the worst-case scenario, they can result in mortality. SCARs are delayed T cell-mediated hypersensitivity reactions. Recovery can take from 2 weeks to many months after dechallenging the culprit drugs. Genetic polymorphism of the HLA genes may change the selection and presentation of antigens, allowing toxic drug metabolites to initiate immunological reactions. However, each SCARs has a different onset latency period, clinical features, or morphological pattern. This explains that, other than HLA mutations, other immuno-pathogenesis may be involved in drug-induced severe cutaneous reactions. This review will discuss the clinical morphology of various SCARs, various immune pathogenesis models, diagnostic criteria, treatments, the association of various drug-induced reactions and susceptible alleles in different populations, and the successful implementation of pharmacogenomics in Thailand for the prevention of SCARs.
Orphan Nuclear Receptor NR4A2 Is Constitutively Expressed in Cartilage and Upregulated in Inflamed Synovium From hTNF-Alpha Transgenic Mice
Authors: Lilley Cullen M. , Alarcon Andrea , Ngo My-Huyen , Araujo Jackeline S. , Marrero Luis , Mix Kimberlee S.
Published: April 2022

Orphan nuclear receptor 4A2 (NR4A2/Nurr1) is a constitutively active transcription factor with potential roles in the onset and progression of inflammatory arthropathies. NR4A2 is overexpressed in synovium and cartilage from individuals with rheumatoid arthritis (RA), psoriatic arthritis, and osteoarthritis. This study documents the expression and tissue localization of NR4A2 and upstream regulator nuclear factor kappa B (NF-κB) in the human tumor necrosis factor-alpha (hTNF-α) transgenic mouse model of RA. Since TNF-α is a potent inducer of NR4A2in vitro, we hypothesized that NR4A2 would also be upregulated and active during disease progression in this model. Expression levels of NR4A2, related receptors NR4A1 (Nur77) and 3 (NOR1), and NF-κB1transcripts were quantified by RT-qPCR in hTNF-α and wild-type joints at three stages of disease. The protein distribution of NR4A2 and NF-κB subunit RelA (p65) was analyzed by quantitative immunohistochemistry. Global gene expression of 88 RA-related genes was also screened and compared between groups. Consistent with previous reports on the hTNF-α model, transgenic mice exhibited significant weight loss and severely swollen paws by 19 weeks of age compared to age-matched wild-type controls. NR4A1-3 and NF-κB1were constitutively expressed at disease onset and in healthy joints. NF-κB1transcript levels increased 2-fold in hTNF-α paws with established disease (12 weeks), followed by a 2-fold increase in NR4A2 at the late disease stage (19 weeks). NR4A2 and RelA proteins were overexpressed in inflamed synovium prior to symptoms of arthritis, suggesting that gene expression changes documented in whole paws were largely driven by elevated expression in diseased synovium. Broader screening of RA-related genes by RT-qPCR identified several differentially expressed genes in hTNF-α joints including those encoding inflammatory cytokines and chemokines, matrix-degrading enzymes and inhibitors, cell surface receptors, intracellular signaling proteins and transcription factors. Consensus binding sites for NR4A receptors and NF-κB1were enriched in the promoters of differentially expressed genes suggesting central roles for these transcription factors in this model. This study is the first comprehensive analysis of NR4A2 in an animal model of RA and validates the hTNF-α model for testing of small molecules and genetic strategies targeting this transcription factor.
SIRT6 Activator UBCS039 Inhibits Thioacetamide-Induced Hepatic Injury In Vitro and In Vivo
Authors: Jiao Fangzhou , Zhang Zongwei , Hu Hongtu , Zhang Yongxi , Xiong Yong
Published: April 2022

SIRT6 has been reported to have multiple functions in inflammation and metabolism. In the present study, we explored the regulatory effects and mechanisms of SIRT6 in thioacetamide (TAA)-induced mice acute liver failure (ALF) models. The SIRT6 activator UBCS039 was used in this animal and cell experiments. We observed that UBCS039 ameliorated liver damage, including inflammatory responses and oxidative stress. Further study of mechanisms showed that the upregulation of SIRT6 inhibited the inflammation reaction by suppressing the nuclear factor-κB (NF-κB) pathway in the TAA-induced ALF mice model and lipopolysaccharide-stimulated macrophages. In addition, the upregulation of SIRT6 alleviated oxidative stress damage in hepatocytes by regulating the Nrf2/HO-1 pathway. These findings demonstrate that pharmacologic activator of SIRT6 could be a promising target for ALF.
FGF9 Alleviates the Fatty Liver Phenotype by Regulating Hepatic Lipid Metabolism
Authors: Zhao Fanrong , Zhang Lei , Zhang Menglin , Huang Jincan , Zhang Jun , Chang Yongsheng
Published: April 2022

Although the fatty liver has been linked to numerous impairments of energy homeostasis, the molecular mechanism responsible for fatty liver development remains largely unknown. In the present study, we show that fibroblast growth factors 9 (FGF9) expression is increased in the liver of diet-induced obese (DIO), db/db, and ob/ob mice relative to their respective controls. The long-term knockdown of hepatic FGF9 expression mediated by adeno-associated virus expressing FGF9-specific short hairpin RNA (AAV-shFGF9) aggravated the fatty liver phenotype of DIO mice. Consistently, downregulation of FGF9 expression mediated by adenovirus expressing FGF9-specific shRNA (Ad-shFGF9) in the primary hepatocyte promoted the cellular lipid accumulation, suggesting that FGF9 exerts its effects in an autocrine manner. In contrast, adenoviruses expressing FGF9 (Ad-FGF9) mediated FGF9 overexpression in the liver of DIO mice alleviated hepatic steatosis and improved the insulin sensitivity and glucose intolerance. Moreover, the liver-specific FGF9 transgenic mice phenocopied the Ad-FGF9-infected mice. Mechanistically, FGF9 inhibited the expression of genes involved in lipogenesis and increased the expression of genes involved in fatty acid oxidation, thereby reducing cellular lipid accumulation. Thus, targeting FGF9 might be exploited to treat nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome.
The Expression of Cytokine Profiles and Related Receptors in Idiopathic Inflammatory Myopathies
Authors: Zhou Junyu , Zhao Lijuan , Xiao Yizhi , Xie Shasha , Long Ying , Wei Yu , Meng Qiming , Li Xiaojing , Luo Hui , Zhu Honglin
Published: April 2022

Background: Cytokines play a vital role in the pathogenesis of idiopathic inflammatory myopathies (IIMs). Here, we investigated the expression of serum cytokine profiles in untreated IIMs and their correlations with clinical indicators, and further studied the expression of related cytokines receptors in IIMs.

Methods: The Human 48-Plex Luminex assay for cytokines was performed in the serum of IIMs, including 93 untreated and 18 follow-up (39 samples) patients, and 32 healthy controls (HC). Mann-Whitney U test with bonferroni adjusted was used to identify the differentially expressed cytokines among groups. Celltalker software was used to identify the receptors of differentially expressed cytokines. The expression of receptors was further validated by published GEO datasets (muscle, blood and skin), RT-qPCR, western blot and flow cytometry.

Results: The serum levels of Eotaxin, IL7, IL18, IP10, MCP1, MCSF, MIG and SCGFβ were elevated in the 93 untreated patients. Except for IL7, all other cytokines were decreased after treatment and their levels were positively correlated with clinical indices such as LDH, ESR, CRP, ALT, IgA, AST and IgG while negatively correlated with albumin and MMT8. According to the serum myositis-specific antibodies (MSAs), patients were classified into three groups: anti-ARS (Jo-1, OJ, EJ, PL7, PL12), anti-MDA5 positive, and anti-TIF1γ positive. Compared with HC, the levels of IP10 and MIG were increased in three groups. Moreover, IL18 and MSCF were increased in anti-ARS patients, and CTACK, Eotaxin, IL1Rα, IL7, IL18, MCP1, MCP3, MCSF and SCGFβ were elevated in anti-MDA5 patients. Twenty receptors of the 8 differentially expressed cytokines were matched by celltalker software, among them, IL18R1 and CCR1 were up-regulated in blood, muscle and skin of IIMs from the analysis of GEO published datasets. RT-qPCR and western blot further validated IL18R1 was upregulated in the muscle tissues of dermatomyositis. The number of IL18R1+CD4+ cells was increased while IL18R1+CD8+ cells was decreased in peripheral blood of anti-MDA5 patients.

Conclusion: This study showed that cytokine profiles were significantly changed in IIMs, and different MSA groups had unique cytokine expression patterns. The levels of some cytokine were correlated with clinical indices. The IL18 receptor IL18R1 might play important roles in IIMs.