bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of TaqMan-based real-time RT-PCR assay based on N gene for the quantitative detection of feline morbillivirus
Authors: Makhtar Siti Tasnim , Tan Sheau Wei , Nasruddin Nur Amalina , Abdul Aziz Nor Azlina , Omar Abdul Rahman , Mustaffa-Kamal Farina
Published: March 2021

Background

Morbilliviruses are categorized under the family of Paramyxoviridae and have been associated with severe diseases, such as Peste des petits ruminants, canine distemper and measles with evidence of high morbidity and/or could cause major economic loss in production of livestock animals, such as goats and sheep. Feline morbillivirus (FeMV) is one of the members of Morbilliviruses that has been speculated to cause chronic kidney disease in cats even though a definite relationship is still unclear. To date, FeMV has been detected in several continents, such as Asia (Japan, China, Thailand, Malaysia), Europe (Italy, German, Turkey), Africa (South Africa), and South and North America (Brazil, Unites States). This study aims to develop a TaqMan real-time RT-PCR (qRT-PCR) assay targeting the N gene of FeMV in clinical samples to detect early phase of FeMV infection.

Results

A specific assay was developed, since no amplification was observed in viral strains from the same family of Paramyxoviridae, such as canine distemper virus (CDV), Newcastle disease virus (NDV), and measles virus (MeV), and other feline viruses, such as feline coronavirus (FCoV) and feline leukemia virus (FeLV). The lower detection limit of the assay was 1.74 × 104 copies/μL with Cq value of 34.32 ± 0.5 based on the cRNA copy number. The coefficient of variations (CV) values calculated for both intra- and inter-assay were low, ranging from 0.34–0.53% and 1.38–2.03%, respectively. In addition, the clinical sample evaluation using this assay showed a higher detection rate, with 25 (35.2%) clinical samples being FeMV-positive compared to 11 (15.5%) using conventional RT-PCR, proving a more sensitive assay compared to the conventional RT-PCR.

Conclusions

The TaqMan-based real-time RT-PCR assay targeting the N gene described in this study is more sensitive, specific, rapid, and reproducible compared to the conventional RT-PCR assay targeting the N gene, which could be used to detect early infection in cats.
CMTM6 promotes migration, invasion, and EMT by interacting with and stabilizing vimentin in hepatocellular carcinoma cells
Authors: Huang Xiaoting , Xiang Leyang , Wang Baiyao , Hu Jijie , Liu Chunshan , Ren Anbang , Du Kunpeng , Ye Gengtai , Liang Yingying , Tang Yunqiang , Yang Dinghua , Yuan Yawei
Published: March 2021

Background

CKLF like MARVEL transmembrane domain containing 6 (CMTM6) has been associated with the development in many kinds of cancers. However, the roles of CMTM6 in hepatocellular carcinoma (HCC) are largely unknown. Thus, the present study aimed to investigate the function of CMTM6 in HCC.

Methods

We analysed CMTM6 levels and functions using human HCC cell lines, paired HCC and adjacent non-tumorous tissues, and a tissue microarray. CMTM6 expression was silenced using short hairpin RNAs and its was overexpressed from a lentivirus vector. CMTM6 mRNA and protein levels were determined using quantitative real-time reverse transcription PCR and western blotting, respectively. Proliferation, colony formation, migration, and invasion were assessed using a Cell counting kit-8, colony formation, wound-healing, and Matrigel invasion assays, respectively. Immunohistochemistry was used to score the expression of CMTM6 in tissue samples. The localization and binding partners of CMTM6 were investigated using immunofluorescence and coimmunoprecipitation experiments, respectively. A mouse xenograft model was used for in vivo studies.

Results

Compared with that in adjacent, non-cancerous tissue, Here, CMTM6 levels were increased in HCC tissue samples. Silencing ofCMTM6suppressed the proliferation, migration, and invasion of HCC cells. Conversely,CMTM6overexpression enhanced HCC cell invasion, migration, and proliferation. Mechanistically, CMTM6 physically interacts with and stabilizes vimentin, thus inducing epithelial–mesenchymal transition (EMT), which promotes proliferation, migration and invasion. Importantly, in HCC tissues, CMTM6 expression correlated positively with vimentin levels. Poor prognosis of HCC was associated significantly with higher CMTM6 expression.

Conclusions

CMTM6 has an important function in HCC proliferation, migration, and invasion, via its interaction with and stabilization of vimentin. CMTM6 might represent a potential biomarker and therapeutic target to treat HCC.
Magnetic resonance imaging findings in children with Parry-Romberg syndrome and en coup de sabre
Authors: Knights Harry , Minas Elizabeth , Khan Faraan , Shaw Lindsay , Al Obaidi Muthana , Mankad Kshitij , Eleftheriou Despina
Published: March 2021

Background

The aim of this study was to: (i) describe the abnormalities seen on brain imaging in a group of children with en coup de sabre (EDCS) with/without Parry-Romberg syndrome (PRS); and (ii) identify clinical predictors of brain imaging abnormalities.

Methods

This was a single centre (Great Ormond Street Hospital, London) retrospective case series of patients with ECDS/PRS seen from 2000 to 2018. We identified patients with cutaneous manifestations consistent with the clinical descriptions of ECDS/PRS. Presenting clinical, laboratory, and radiological brain findings are described. Results are expressed as medians and ranges or frequencies and percentages. Fisher’s exact test was used to identify clinical associations with magnetic resonance imaging (MRI) abnormalities.

Results

Fourteen patients were studied: 6 males and 8 females; median age 14 years (range 3–20). We observed neuroimaging abnormalities in 2/6 ECDS and 5/8 ECDS/PRS patients. White matter signal abnormality, dystrophic calcification, leptomeningeal enhancement, and sulcal crowding were the typical findings on brain imaging. A total of 50% of patients had no MRI abnormality despite some of these patients having neurological symptoms. The presence of seizures was significantly associated with ipsilateral enhanced white matter signalling on MRI (p < 0.05).

Conclusions

In summary, we observed several distinct radiographic patterns associated with ECDS/PRS. Seizure disorder was strongly associated with the presence of ipsilateral enhanced white matter signalling. Improved neuroimaging techniques that combine morphological with functional imaging may improve the detection rate of brain involvement in children with ECDS/PRS in the future.
Diagnosis and management of adenosine deaminase 2 deficiency children: the experience from China
Authors: Wang Wei , Zhang Tiannan , Zheng Wenjie , Zhong Linqing , Wang Lin , Li Ji , Liu Qian , Dong Yanqing , Song Hongmei
Published: March 2021

Background

Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease caused by mutations in the ADA2 gene. Few Chinese cases have been reported. We describe and compare the clinical features, genotypes, and treatments of Chinese DADA2 patients and non-Chinese patients.

Methods

Primary immunodeficiency disease panel or whole-exome sequencing was performed for suspected cases, and assays for adenosine deaminase 2 (ADA2) enzyme activity were also carried out for the patients and their parents. Case reports of Chinese and non-Chinese patients with DADA2 were searched in PubMed and Chinese national databases.

Results

Seven unrelated children from China with DADA2 were included in our study. Five were identified at Peking Union Medical College Hospital, and two had been reported previously (1 on PubMed and 1 in Chinese literature). Fourteen mutations in ADA2 were identified, 7 of which have not previously been reported in non-Chinese patients. Four children who underwent enzymatic analysis had lower ADA2 activity compared with their parents. Phenotypic manifestations included fever, skin symptoms, vasculitis, and neurologic involvement. Treatments varying from steroids, immunosuppressants, and tocilizumab, anti-TNF therapy and hematopoietic stem cell transplantation (HSCT) were effective depending on phenotype and severity.

Conclusion

This study includes the largest number of Chinese DADA2 patients to date. We recommend the combination of enzymatic analysis with gene screening to confirm the diagnosis. Different genotypes were observed among Chinese DADA2 patients; most phenotypes were similar to those of non-Chinese DADA2 patients, except for growth retardation. Disease remission might not be achieved with anti-IL-6 therapy.
Activated STAT3 signaling pathway by ligature-induced periodontitis could contribute to neuroinflammation and cognitive impairment in rats
Authors: Hu Yi , Zhang Xu , Zhang Jing , Xia Xinyi , Li Huxiao , Qiu Che , Liao Yue , Chen Huiwen , He Zhiyan , Song Zhongchen , Zhou Wei
Published: March 2021

Background

Increasing evidence suggests a causal link between periodontitis and cognitive disorders. Systemic inflammation initiated by periodontitis may mediate the development of cognitive impairment. Our study aims to investigate the effect of ligature-induced periodontitis on cognitive function and the role of signal transducers and activators of transcription 3 (STAT3) in this process.

Materials and methods

Ligature-induced periodontitis was established, and the rats were treated intraperitoneally with/without the pSTAT3 inhibitor cryptotanshinone (CTS). Alveolar bone resorption and periodontal inflammation were detected by micro-computed tomography analysis and histopathological evaluation. Locomotor activity and cognitive function were evaluated by the open field test and the Morris water maze test, respectively. The activation of microglia and astrocytes in the hippocampus and cortex was assessed by immunohistochemistry (IHC). The expression of interleukins (IL-1β, IL-6, IL-8, IL-21) in both the periphery and cortex was evaluated by RT-PCR and ELISA. The expression of TLR/NF-κB and ROS cascades was evaluated by RT-PCR. The expression of pSTAT3 and the activation of the STAT3 signaling pathway (JAK2, STAT3, and pSTAT3) in the periodontal tissue and cortex were assessed by IHC and Western blot. The expression of amyloid precursor protein (APP) and its key secretases was evaluated by RT-PCR. The level of amyloid β-protein (Aβ) and the ratio of Aβ1-40/1-42 were measured via ELISA in the plasma and cortex while IHC was used to detect the level of Aβ1-42 in the brain.

Results

In periodontal ligature rats, significant alveolar bone resorption and local inflammatory cell infiltration were present. Apparent increases in inflammatory cytokines (IL-1β, IL-6, IL-8, and IL-21) were detected in peripherial blood and brain. Additionally, spatial learning and memory ability was impaired, while locomotor activity was not affected. Activated microglia and astrocytes were found in the cortex and hippocampus, presenting as enlarged cell bodies and irregular protrusions. Levels of TLR/NF-kB, PPAR and ROS were altered. The STAT3 signaling pathway was activated in both the periodontal tissue and cortex, and the processing of APP by β- and γ-secretases was promoted. The changes mentioned above could be relieved by the pSTAT3 inhibitor CTS.

Conclusions

Ligature-induced periodontitis in rats resulted in systemic inflammation and further abnormal APP processing, leading to cognitive impairments. In this progress, the activation of the STAT3 signaling pathway may play an important role by increasing inflammatory load and promoting neuroinflammation.
Mechanistic insights into the role of the chemokine CCL2/CCR2 axis in dorsal root ganglia to peripheral inflammation and pain hypersensitivity
Authors: Dansereau Marc-André , Midavaine Élora , Bégin-Lavallée Valérie , Belkouch Mounir , Beaudet Nicolas , Longpré Jean-Michel , Mélik-Parsadaniantz Stéphane , Sarret Philippe
Published: March 2021

Background

Pain is reported as the leading cause of disability in the common forms of inflammatory arthritis conditions. Acting as a key player in nociceptive processing, neuroinflammation, and neuron-glia communication, the chemokine CCL2/CCR2 axis holds great promise for controlling chronic painful arthritis. Here, we investigated how the CCL2/CCR2 system in the dorsal root ganglion (DRG) contributes to the peripheral inflammatory pain sensitization.

Methods

Repeated intrathecal (i.t.) administration of the CCR2 antagonist, INCB3344 was tested for its ability to reverse the nociceptive-related behaviors in the tonic formalin and complete Freund’s adjuvant (CFA) inflammatory models. We further determined by qPCR the expression of CCL2/CCR2, SP and CGRP in DRG neurons from CFA-treated rats. Using DRG explants, acutely dissociated primary sensory neurons and calcium mobilization assay, we also assessed the release of CCL2 and sensitization of nociceptors. Finally, we examined by immunohistochemistry following nerve ligation the axonal transport of CCL2, SP, and CGRP from the sciatic nerve of CFA-treated rats.

Results

We first found that CFA-induced paw edema provoked an increase in CCL2/CCR2 and SP expression in ipsilateral DRGs, which was decreased after INCB3344 treatment. This upregulation in pronociceptive neuromodulators was accompanied by an enhanced nociceptive neuron excitability on days 3 and 10 post-CFA, as revealed by the CCR2-dependent increase in intracellular calcium mobilization following CCL2 stimulation. In DRG explants, we further demonstrated that the release of CCL2 was increased following peripheral inflammation. Finally, the excitation of nociceptors following peripheral inflammation stimulated the anterograde transport of SP at their peripheral nerve terminals. Importantly, blockade of CCR2 reduced sensory neuron excitability by limiting the calcium mobilization and subsequently decreased peripheral transport of SP towards the periphery. Finally, pharmacological inhibition of CCR2 reversed the pronociceptive action of CCL2 in rats receiving formalin injection and significantly reduced the neurogenic inflammation as well as the stimuli-evoked and movement-evoked nociceptive behaviors in CFA-treated rats.

Conclusions

Our results provide significant mechanistic insights into the role of CCL2/CCR2 within the DRG in the development of peripheral inflammation, nociceptor sensitization, and pain hypersensitivity. We further unveil the therapeutic potential of targeting CCR2 for the treatment of painful inflammatory disorders.
High throughput sequencing from Angolan citrus accessions discloses the presence of emerging CTV strains
Authors: Pais da Cunha Aderito Tomàs , Chiumenti Michela , Ladeira Laurindo Chambula , Abou Kubaa Raied , Loconsole Giuliana , Pantaleo Vitantonio , Minafra Angelantonio
Published: March 2021

Background

Citrus industry is worldwide dramatically affected by outbreaks of Citrus tristeza virus (CTV). Controls should be applied to nurseries, which could act as diversity hotspots for CTV. Early detection and characterization of dangerous or emerging strains of this virus greatly help to prevent outbreaks of disease. This is particularly relevant in those growing regions where no dedicated certification programs are currently in use.

Methods

Double-stranded RNA extracted from Citrus spp. samples, collected in two locations in Angola, were pooled and submitted to a random-primed RNA-seq. This technique was performed to acquire a higher amount of data in the survey, before the amplification and sequencing of genes from single plants. To confirm the CTV infection in individual plants, as suggested by RNA-seq information from the pooled samples, the analysis was integrated with multiple molecular marker amplification (MMM) for the main known CTV strains (T30, T36, VT and T3).

Results

From the analysis of HTS data, several assembled contigs were identified as CTV and classified according to their similarity to the established strains. By the MMM amplification, only five individual accessions out of the eleven pooled samples, resulted to be infected by CTV. Amplified coat protein genes from the five positive sources were cloned and sequenced and submitted to phylogenetic analysis, while a near-complete CTV genome was also reconstructed by the fusion of three overlapping contigs.

Conclusion

Phylogenetic analysis of the ORF1b and CP genes, retrieved by de novo assembly and RT-PCR, respectively, revealed the presence of a wide array of CTV strains in the surveyed citrus-growing spots in Angola. Importantly, molecular variants among those identified from HTS showed high similarity with known severe strains as well as to recently described and emerging strains in other citrus-growing regions, such as S1 (California) or New Clade (Uruguay).
Hyperpigmented spots at fundus examination: a new ocular sign in Neurofibromatosis Type I
Authors: Moramarco Antonietta , Mallone Fabiana , Sacchetti Marta , Lucchino Luca , Miraglia Emanuele , Roberti Vincenzo , Lambiase Alessandro , Giustini Sandra
Published: March 2021

Background

Neurofibromatosis Type I (NF1), also termed von Recklinghausen disease, is a rare genetic disorder that is transmitted by autosomal dominant inheritance, with complete penetrance and variable expressivity. It is caused by mutation in the NF1 gene on chromosome 17 encoding for neurofibromin, a protein with oncosuppressive activity, and it is 50% sporadic or inherited. The disease is characterized by a broad spectrum of clinical manifestations, mainly involving the nervous system, the eye and skin, and a predisposition to develop multiple benign and malignant neoplasms. Ocular diagnostic hallmarks of NF1 include optic gliomas, iris Lisch nodules, orbital and eyelid neurofibromas, eyelid café-au-lait spots. Choroidal nodules and microvascular abnormalities have recently been identified as additional NF1-related ocular manifestations. The present study was designed to describe the features and clinical significance of a new sign related to the visual apparatus in NF-1, represented by hyperpigmented spots (HSs) of the fundus oculi.

Results

HSs were detected in 60 (24.1%) out of 249 patients with NF1, with a positive predictive value of 100% and a negative predictive value of 44.2%. None of the healthy subjects (150 subjects) showed the presence of HSs. HSs were visible under indirect ophthalmoscopy, ultra-wide field (UWF) pseudocolor imaging and red-only laser image, near-infrared reflectance (NIR)-OCT, but they were not appreciable on UWF green reflectance. The location and features of pigmentary lesions matched with the already studied NF1-related choroidal nodules. No significant difference was found between the group of patients (n = 60) with ocular HSs and the group of patients (n = 189) without ocular pigmented spots in terms of age, gender or severity grading of the disease. A statistically significant association was demonstrated between the presence of HSs and neurofibromas (p = 0.047), and between the presence of HSs and NF1-related retinal microvascular abnormalities (p = 0.017).

Conclusions

We described a new ocular sign represented by HSs of the fundus in NF1. The presence of HSs was not a negative prognostic factor of the disease. Following multimodal imaging, we demonstrated that HSs and choroidal nodules were consistent with the same type of lesion, and simple indirect ophthalmoscopy allowed for screening of HSs in NF1.
Hydroxyurea and blood transfusion therapy for Sickle cell disease in South Asia: inconsistent treatment of a neglected disease
Authors: Darshana Thamal , Rees David , Premawardhena Anuja
Published: March 2021

Background

Hydroxyurea and blood transfusion therapies remain the main therapeutic strategies for Sickle cell disease. Preliminary data suggest substantial variation and inconsistencies in practice of these two therapeutic modalities in South Asia. In this systematic review we searched Medline, Cochrane library and Scopus for articles on usage of hydroxyurea and blood transfusion therapies for sickle cell disease in South Asia published in English between October 2005 and October 2020.

Results

We selected 41 papers: 33 from India, 3 from Sri Lanka, 2 each from Pakistan and Bangladesh and one from Nepal. Only 14 prospective trials focused on hydroxyurea therapy from which majority (n = 10; 71.4%) adopted fixed low dose (10 mg/kg/day) regimen. With hydroxyurea therapy, 12 and 9 studies reported significant reductions in vaso-occlusive crises and transfusion requirement respectively. Severe anaemia (haemoglobin level < 6–7 g/dl) was the commonest indicator (n = 8) for transfusion therapy followed by vaso-occlusive crisis.

Conclusions

Published data on the hydroxyurea and transfusion therapies in South Asia are limited and heterogeneous. A clear gap of knowledge exists about the nature of the sickle cell disease in the Indian subcontinent particularly from countries outside India necessitating further evidence-based assessments and interventions.
Correction to: Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1
Authors: Zhang Yuhui , Huang Weibin , Yuan Yujie , Li Jin , Wu Jing , Yu Jie , He Yulong , Wei Zhewei , Zhang Changhua
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Role of the active cycle of breathing technique combined with phonophoresis for the treatment of patients with chronic obstructive pulmonary disease (COPD): study protocol for a preliminary randomized controlled trial
Authors: Shen M. D. , Guo L. R. , Li Y. W. , Gao R. T. , Sui X. , Du Z. , Xu L. Q. , Shi H. Y. , Ni Y. Y. , Zhang X. , Pang Y. , Zhang W. , Yu T. Z. , Li F.
Published: March 2021

Background

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by coughing, the production of excess sputum, and dyspnea. Patients with excessively thick sputum may have frequent attacks or develop more serious disease. The guidelines recommend airway clearance for patients with excessive sputum who are hospitalized with COPD. The active cycle of breathing technique is the most common non-pharmacological airway clearance technique used by physiotherapists. However, the effectiveness of the technique is not always guaranteed. Active cycle of breathing techniques require the initial dilution of the sputum, usually by inhalation drugs, which may have limited effects. Recent studies have found that phonophoresis decreases inflammation, suggesting the potential of the combined usage of active cycle of breathing techniques and phonophoresis. Therefore, the aim of this study is to explore the effectiveness and safety of combining active cycle of breathing technique and phonophoresis in treating COPD patients.

Methods and analysis

We propose a single-blind randomized controlled trial using 75 hospitalized patients diagnosed with COPD with excessive sputum production. The patients will be divided into three groups. The intervention group will receive active cycle of breathing techniques combined with phonophoresis. The two comparison groups will be treated with active cycle of breathing techniques and phonophoresis, respectively. The program will be implemented daily for 1 week. The primary outcomes will be changes in sputum viscosity and production, lung function, and pulse oximetry. Secondary outcomes include the assessment of COPD and anxiety, measured by the COPD Assessment Test scale and the Anxiety Inventory for Respiratory Disease, respectively; self-satisfaction; the degree of cooperation; and the length of hospital stay. All outcome measures, with the exception of sputum production and additional secondary outcomes, will be assessed at the commencement of the study and after 1 week’s intervention. Analysis of variance will be used to investigate differences between the groups, and a p-value of less than 0.05 (two-tailed) will be considered statistically significant.

Discussion

This study introduces a combination of active cycle of breathing techniques and phonophoresis to explore the impact of these interventions on patients hospitalized with COPD. If this combined intervention is shown to be effective, it may prove to be a better treatment for patients with COPD.

Trial registration

The trial was registered prospectively on the Chinese Clinical Trial Registry on 24 December 2019.ClinicalTrials.gov ChiCTR1900028506. Registered on December 2019.
An adaptive kernel width convex combination method for maximum correntropy criterion
Authors: Fontes Aluisio I. R. , Linhares Leandro L. S. , F. Guimarães João P. , Silveira Luiz F. Q. , Martins Allan M.
Published: March 2021

Recently, the maximum correntropy criterion (MCC) has been successfully applied in numerous applications regarding nonGaussian data processing. MCC employs a free parameter called kernel width, which affects the convergence rate, robustness, and steady-state performance of the adaptive filtering. However, determining the optimal value for such parameter is not always a trivial task. Within this context, this paper proposes a novel method called adaptive convex combination maximum correntropy criterion (ACCMCC), which combines an adaptive kernel algorithm with convex combination techniques. ACCMCC takes advantage from a convex combination of two adaptive MCC-based filters, whose kernel widths are adjusted iteratively as a function of the minimum error value obtained in a predefined estimation window. Results obtained in impulsive noise environment have shown that the proposed approach achieves equivalent convergence rates but with increased accuracy and robustness when compared with other similar algorithms reported in literature.
Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development
Authors: Ellegood J. , Petkova S. P. , Kinman A. , Qiu L. R. , Adhikari A. , Wade A. A. , Fernandes D. , Lindenmaier Z. , Creighton A. , Nutter L. M. J. , Nord A. S. , Silverman J. L. , Lerch J. P.
Published: March 2021

Background

One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs.

Methods

A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays.

Results

We validated decreased Arid1b mRNA and protein in Arid1b+/− mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b+/− cerebellum. During neonatal development, Arid1b+/− mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/− mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b+/− mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male–female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b+/− mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans.

Limitations

The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b.

Conclusions

This study represents a full validation and investigation of a novel model of Arid1b+/− haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.
Geology and geotechnical investigations of part of the Anambra Basin, Southeastern Nigeria: implication for gully erosion hazards
Authors: Ocheli Azuka , Ogbe Ovie Benjamin , Aigbadon Godwin Okumagbe
Published: March 2021

Background

Geologic and geotechnical conditions of soils where Nanka and Ajali Formations outcropped in Anambra Basin, Southeastern Nigeria were investigated and accessed. This was done using detailed mapping and mechanical soil laboratory tests to unravel the genesis and continued expansion of gully erosion in the study areas.

Results

Field study revealed that gully erosions are more pronounced in the study area with poor vegetation cover and a high degree of slope steepness. Grain size analysis revealed that the soils of the Nanka Formation have an average sand content value of 90.90% (sandy) and silt content value of 3.0% (low fine portions). The plasticity index of the fine portions indicates that the soils are weak plastic, with a mean value of 5.29%. The soils have an average cohesion value of 0.30 kg/cm2 indicating a very weak cohesion. The soils are highly permeable; with an average value of 2.67 × 10–3 cm/s. The compaction test further revealed that the soils are loosely compacted. The soils for the Ajali Formation have an average sand content value of 95.10% (sandy) and silt content value of 1.43% (low fine portions). The plasticity index of the fine portions indicates that the soils are weak plastic, with a mean value of 2.70%. The soils have an average cohesion value of 0.30 kg/cm2 indicating a very weak cohesion. The soils are highly permeable; with an average value of 2.70 × 10–3 cm/s. The compaction test revealed that the soils are loosely compacted.

Conclusion

After field surveys and laboratory analyses, it was found that the gully erosions have been developing respectively on steep slopes and non-vegetated areas, and their genesis facilitated by the cohesionless and very permeable nature of the sandy formations. Following those key findings, it was proposed many practices (agronomic and engineering mainly) that can help mitigate the formations as well as the expansion of this very damaging hazard type. The potential implications of these gully erosion include damaging of buildings, residential houses, bridges, and roads, loss of farmland and vegetation, isolation of villages and towns, increased migration of inhabitants as well as degradation of agricultural fertile land.
Exploring big data traits and data quality dimensions for big data analytics application using partial least squares structural equation modelling
Authors: Wook Muslihah , Hasbullah Nor Asiakin , Zainudin Norulzahrah Mohd , Jabar Zam Zarina Abdul , Ramli Suzaimah , Razali Noor Afiza Mat , Yusop Nurhafizah Moziyana Mohd
Published: March 2021

The popularity of big data analytics (BDA) has boosted the interest of organisations into exploiting their large scale data. This technology can become a strategic stimulation for organisations to achieve competitive advantage and sustainable growth. Previous BDA research, however, has focused more on introducing more traits, known as Vs for big data traits, while ignoring the quality of data when examining the application of BDA. Therefore, this study aims to explore the effect of big data traits and data quality dimensions on BDA application. This study has formulated 10 hypotheses that comprised of the relationships of big data traits, accuracy, believability, completeness, timeliness, ease of operation, and BDA application constructs. This study conducted a survey using a questionnaire as a data collection instrument. Then, the partial least squares structural equation modelling technique was used to analyse the hypothesised relationships between the constructs. The findings revealed that big data traits can significantly affect all constructs for data quality dimensions and that the ease of operation construct has a significant effect on BDA application. This study contributes to the literature by bringing new insights to the field of BDA and may serve as a guideline for future researchers and practitioners when studying BDA application.
3D printing in neurosurgery education: a review
Authors: Thiong’o Grace M. , Bernstein Mark , Drake James M.
Published: March 2021

Objectives

The objectives of this manuscript were to review the literature concerning 3D printing of brain and cranial vault pathology and use these data to define the gaps in global utilization of 3D printing technology for neurosurgical education.

Methods

Using specified criteria, literature searching was conducted to identify publications describing engineered neurosurgical simulators. Included in the study were manuscripts highlighting designs validated for neurosurgical skill transfer. Purely anatomical designs, lacking aspects of surgical simulation, were excluded. Eligible manuscripts were analyzed. Data on the types of simulators, representing the various modelled neurosurgical pathologies, were recorded. Authors’ countries of affiliation were also recorded.

Results

A total of thirty-six articles, representing ten countries in five continents were identified. Geographically, Africa as a continent was not represented in any of the publications. The simulation-modelling encompassed a variety of neurosurgical subspecialties including: vascular, skull base, ventriculoscopy / ventriculostomy, craniosynostosis, skull lesions / skull defects, intrinsic brain tumor and other. Finally, the vascular and skull base categories together accounted for over half (52.8 %) of the 3D printed simulated neurosurgical pathology.

Conclusions

Despite the growing body of literature supporting 3D printing in neurosurgical education, its full potential has not been maximized. Unexplored areas of 3D printing for neurosurgical simulation include models simulating the resection of intrinsic brain tumors or of epilepsy surgery lesions, as these require complex models to accurately simulate fine dissection techniques. 3D printed surgical phantoms offer an avenue for the advancement of global-surgery education initiatives.
Communication infrastructure for situational awareness enhancement in WAMS with optimal PMU placement
Authors: Appasani Bhargav , Jha Amitkumar Vidyakant , Mishra Sunil Kumar , Ghazali Abu Nasar
Published: March 2021

Real time monitoring and control of a modern power system has achieved significant development since the incorporation of the phasor measurement unit (PMU). Due to the time-synchronized capabilities, PMU has increased the situational awareness (SA) in a wide area measurement system (WAMS). Operator SA depends on the data pertaining to the real-time health of the grid. This is measured by PMUs and is accessible for data analytics at the data monitoring station referred to as the phasor data concentrator (PDC). Availability of the communication system and communication delay are two of the decisive factors governing the operator SA. This paper presents a pragmatic metric to assess the operator SA and ensure optimal locations for the placement of PMUs, PDC, and the underlying communication infrastructure to increase the efficacy of operator SA. The uses of digital elevation model (DEM) data of the surface topography to determine the optimal locations for the placement of the PMU, and the microwave technology for communicating synchrophasor data is another important contribution carried out in this paper. The practical power grid system of Bihar in India is considered as a case study, and extensive simulation results and analysis are presented for validating the proposed methodology.
Analysis of human aldehyde dehydrogenases (ALDH) gene expression pattern in breast cancer tissue samples: rutin-copper complex inhibit the breast cancer cell proliferation
Authors: Pattar Shridhar V. , Mirjankar Manisha R. , Kulkarni Suyamindra , Gai Pramod B. , Pujar Namadev K. , Premakshi H. G. , Mulla Sikandar I. , Babu R. L. , Kamanavalli Chandrappa M.
Published: March 2021

Background

Higher aldehyde dehydrogenases (ALDH) activity is one of the important signatures of breast cancer appearance and has been associated with poor prognosis.ALDH1A3has been over-expressed in breast cancer patients. This study aims to analyze gene expression patterns of 18ALDHisozymes in breast cancer tissue samples. It is carried out using a chip-based microarray, next-generation DNA sequencing ofALDH2gene following in silico study to identify the natural products which act as inhibitors for over-expressedALDHisoforms. The synthesis of rutin-copper complex and cell viability assay is carried out on MDA-MB-468 cell line.

Results

ALDH1A3andALDH18A1have shown the highest positive mean fold of variation; whereas,ALDH2andALDH1A2have shown the highest negative mean fold variation. In silico studies revealed that rutin has the highest binding affinity with bothALDH1A3andALDH18A1and supported with IC50value of rutin against MDA-MB-468 cells (144.50 μg/ml). Chemically synthesized rutin-copper complex significantly lowered the IC50value to 119.40 μg/ml. The next-generation sequencing study provides the novel single nucleotide polymorphism (SNP) from T to G in theALDH2gene.

Conclusion

The present study signifies that, along withALDH1A3,ALDH18A1also acts as a marker for breast cancer. Apart from that, inhibitors ofALDH1A3andALDH18A1were attained. Perhaps the single nucleotide polymorphism (SNP) obtained during the mutation analysis may be the probable cause of the highest downregulation ofALDH2in breast cancer.
Voltage and frequency control of standalone wind-driven self-excited reluctance generator using switching capacitors
Authors: Sedky Joseph S. , Yassin Haitham M. , Hanafy H. H. , Ismail Farouk
Published: March 2021

This paper presents a methodology for voltage and frequency (V–f) control of a standalone wind-driven self-excited reluctance generator (WDSERG). The methodology is based on proposing two different compensation configurations using two switching capacitors (short-shunt and long-shunt compensation) for (V–f) control. The dynamic and steady-state performances of the two configurations are discussed under different operating conditions: wind speeds, load currents and power factors. This analysis is done by developing a complete dynamic model of WDSERG including the excitation capacitors and load. Therefore, complete equivalent circuits are proposed. The values of capacitors are controlled by adjusting the duty cycle of H-bridge circuits with PI controllers. To validate the proposed configurations and their dynamic models and equivalent circuits, simulation results for a 1.5-kW standalone WDSERG and experimental results for 0.2 kW reluctance generator driven by a DC motor, emulating the wind turbine, are carried out. The results show a significant enhancement in voltage and frequency regulation with the selected optimal capacitances for each configuration; however, short-shunt compensation is the preferred configuration as it controls the output voltage and frequency with minimum values of capacitances and minimum required duty variation.
Clinical Germline Testing Results of Men With Prostate Cancer: Patient-Level Factors and Implications of NCCN Guideline Expansion
Authors: Greenberg Samantha E. , Hunt Trevor C. , Ambrose Jacob P. , Lowrance William T. , Dechet Christopher B. , O'Neil Brock B. , Tward Jonathan D.
Published: March 2021

PURPOSE

Germline likely pathogenic or pathogenic variants (PVs) have been identified in up to 17% of men with prostate cancer (PC) and may drive disease severity or be targetable by novel therapies. National Comprehensive Cancer Network (NCCN) guidelines encouraging germline testing in metastatic PC were recently expanded to include all men with high-risk, very high-risk, or regional PC. Our aim was to assess the impact of expanded NCCN guidelines on the detection rate of germline PVs and to determine patient-level factors associated with a PV germline testing result.

PATIENTS AND METHODS

Men with PC underwent multigene germline genetic testing for PVs from June 2016 to December 2018, and trends were compared. The association of patient-level factors with a PV germline testing result, where ≥ 1 PV was identified, was assessed using analysis of variance and univariate logistic regression. Sensitivity analyses were limited to clinically actionable variants and those associated with disease severity or progression ( BRCA1/2 and ATM).

RESULTS

Of 408 men undergoing germline testing, 42 (10.3%) men had PVs and 366 (89.7%) men did not have PVs identified. The proportion of men identified with a germline PV remained stable following testing criteria expansion (9.4% v 10.6%, P = .73). No patient-level factors were significantly associated with increased odds of a PV germline testing result, including age at diagnosis, race, pretreatment prostate-specific antigen, Gleason grade group, NCCN risk group, and family history of cancer (breast and/or ovarian, prostate, or any cancer).

CONCLUSION

This study demonstrated a stable PV detection rate in men with PC using expanded criteria aligned to the updated NCCN testing guidelines. However, we did not find strong evidence to suggest that patient-level factors are associated with PV germline testing results. These findings support the recent expansion of NCCN germline testing guidelines in PC.
Association Between Neutrophil-Lymphocyte Ratio and Gestational Diabetes—A Systematic Review and Meta-Analysis
Authors: Pace Nikolai Paul , Vassallo Josanne
Published: March 2021

A growing body of evidence shows that the neutrophil-lymphocyte ratio (NLR) is a surrogate index of systemic inflammation in several chronic diseases. Conflicting associations between NLR and gestational diabetes mellitus (GDM) have been reported in individual studies. This meta-analysis sought to investigate the association between NLR and GDM. The PubMed, EMBASE, and Google Scholar databases were searched to identify relevant articles. The pooled standardized mean difference with 95% CI was calculated using a random-effects model. Subgroup and meta-regression analysis were carried out to control for the effects of GDM diagnostic criteria, ethnicity, body mass index (BMI), and age. Eleven eligible articles were included, containing 1271 participants with GDM and 1504 controls. Pooled outcomes indicated a higher NLR in GDM pregnancies than in normoglycemic controls (SMD = 0.584; 95% CI, 0.339–0.830; P < .001), although extensive heterogeneity between studies was noted. Subgroup analysis revealed that the higher pooled estimate in GDM was not affected by diagnostic criteria, ethnicity, or BMI, although matching for BMI reduced heterogeneity between studies. This meta-analysis supports the higher NLR in GDM described by some individual studies.
Hemodynamic and Intestinal Microcirculatory Changes in a Phenylephrine Corrected Porcine Model of Hemorrhage
Authors: Davies Simon J. , Mythen Monty
Published: March 2021

BACKGROUND:

Intraoperative hypotension is a common event, and a recent study suggests that maintenance of blood pressure may reduce complications. The splanchnic circulation provides a reservoir of blood that can be mobilized during hemorrhage; hence, intestinal microcirculation is sensitive to volume changes. The aim of this study was to assess the impact of hemorrhage on intestinal microcirculation and hemodynamics, and the effects of phenylephrine on these parameters.

METHODS:

Eight anesthetized, mechanically ventilated Yorkshire/Landrace crossbreed pigs were studied. Graded hemorrhage was performed with the removal of 20% of blood volume in 5% increments. Hemodynamic and intestinal microcirculatory measurements were performed at each stage with side-stream dark field microscopy, following which mean arterial pressure (MAP) was corrected with phenylephrine to baseline values and measurements repeated. A repeated measurement 1-way analysis of variance (ANOVA) was used to compared changes from baseline measurements.

RESULTS:

The mean baseline microcirculation score was 42 (standard deviation [SD] = 5). A 5% hemorrhage decreased the microcirculation score by a mean difference of 19 (95% confidence interval [CI], 12-27; P < .0001), and an additional 5% hemorrhage further reduced the microcirculation score by a mean difference of 12 (95% CI, 4-19; P = .0001). Subsequent hemorrhage or administration of phenylephrine did not significantly change the microcirculation scores except when phenylephrine was administered at the 15% hemorrhage stage, which increased the microcirculation score by a mean difference of 7 (95% CI, 1-13; P = .003). All hemodynamic variables were returned to baseline values following hemorrhage by the phenylephrine infusion.

CONCLUSIONS:

Intestinal microcirculatory flow is reduced early in hemorrhage and is uncorrected by phenylephrine infusion. Hemodynamic changes associated with hemorrhage are corrected by phenylephrine and do not reflect microcirculatory flow status.
The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions
Authors: Benzon Honorio T. , Maus Timothy P. , Kang Hye-Ryun , Provenzano David A. , Bhatia Anuj , Diehn Felix , Nelson Ariana , McCormick Zachary L. , Liu Benjamin P. , de Andres Ares Javier , Anitescu Magdalena , Blackham Kristine , Bhaskar Arun , Brill Silviu , Collins Jeremy , Gulve Ashish , Hurley Robert W. , Jeon Young Hoon , Moon Jee Youn , Rauck Richard L. , Rodes Meghan , Lee Ryan K. , Shah Vinil , Shanthanna Harsha , van Zundert Jan , Huntoon Marc , Rathmell James P. , Borges Mario Sanchez , Cohen Steven P. , Greenberger Paul A.
Published: March 2021

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.