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 , Aziz Nor Azlina Abdul , Omar Abdul Rahman , Mustaffa-Kamal Farina
Published: December 2020

Background: Feline morbillivirus (FeMV) is a member of genus Morbillivirus which has been associated with the chronic kidney disease in cats even though a definite relationship is still unclear. Morbilliviruses are associated with severe diseases such as Peste des petits ruminants, canine distemper and measles. FeMV has been detected in many countries including Malaysia. 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 Paramyxoviridae family, 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 x 104 copies/L 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. Besides that, the clinical sample evaluation using this assay showed a higher detection rate, with 26 (37%) 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 here is more sensitive, specific, rapid and reproducible compared to the conventional RT-PCR assay targeting the N gene and it could be used to detect early infection in cats.
Caloric Restriction, Physical Exercise, and CB1 Receptor Blockade as an Efficient Combined Strategy for Bodyweight Control and Cardiometabolic Status Improvement.
Authors: Trinidad Luisa Lopez , Martínez Rosario , Kapravelou Garyfallia , Galisteo Milagros , Aranda Pilar , Porres Jesus , Lopez-Jurado Maria
Published: December 2020

Obesity is critically associated with the development of insulin resistance and related cardiovascular and kidney diseases. Several strategies for weight loss have been developed but most of them exhibit a post-intervention rebound effect. Here, we aimed to design combined weight-loss strategies of caloric restriction, physical exercise, and administration of a food-intake inhibitor that also accomplish the objectives of post-intervention lost-weight maintenance and improvement of cardiovascular and renal functionality. Diet-induced obesity (DIO) was generated in Sprague Dawley rats for 12 weeks to test the effects of single or combined strategies (i.e. caloric restriction, mixed training protocol, and/or administration of appetite suppressant) on caloric intake, body weight, cardiovascular and renal functionality resulting from a weight-loss intervention period of 3 weeks followed by 6 weeks of weight maintenance. Consumption of a high-fat diet (HFD) caused a significant increase in body weight (5th week of the experimental period) and led to the development of insulin resistance, cardiovascular, and renal alterations. The different interventions tested, resulted in a significant body weight loss and improved glucose metabolism, aerobic capacity, electrocardiographic parameters, vascular expression of adhesion molecules and inflammatory mediators, and renal functionality, reaching values similar to the control normocaloric group or even improving them. Successful maintenance of lost weight was achieved along a 6-week post-intervention period in addition to adequate health status. In conclusion, the weight-loss and maintenance intervention strategies tested were efficient at reversing the obesity-related alterations in body weight, glucose metabolism, aerobic capacity, cardiovascular and renal functionality. The beneficial action was very consistent for caloric restriction and physical exercise, whereas administration of a food-intake inhibitor complemented the effects of the prior interventions in some parameters like body weight or aerobic capacity, and showed specific actions in renal metabolism.
In Silico Method for Selecting Residue Pairs for Single-Molecule Microscopy and Spectroscopy
Authors: Sikkema Henkrik , Poolman Bert
Published: December 2020

Obtaining (dynamic) structure related information on proteins is key for understanding their function. Methods as single-molecule Förster Resonance Energy Transfer (smFRET) and Electron Paramagnetic Resonance (EPR) that measure distances between labeled residues to obtain dynamic information rely on selection of suitable residue pairs for chemical modification. Selection of pairs of amino acids, that show sufficient distance changes upon activity of the protein, can be a tedious process. Here we present an in silico approach that makes use of two or more structures (or structure models) to filter suitable residue pairs for FRET or EPR from all possible pairs within the protein. We apply the method for the study of the conformational dynamics of the substrate-binding domain of the osmoregulatory ATP-Binding Cassette transporter OpuA. This method speeds up the process of designing mutants, and because of its systematic nature, the chances of missing promising candidates are reduced.
Integrative Genomics of the Mammalian Alveolar Macrophage Response to Intracellular Mycobacteria
Authors: Hall Thomas J. , Mullen Michael P. , McHugo Gillian P. , Killick Kate E. , Ring Siobhán C. , Berry Donagh P. , Correia Carolina N. , Browne John A. , Gordon Stephen V. , MacHugh David E.
Published: December 2020

BackgroundBovine TB (BTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production, particularly in many developing countries. The key innate immune that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection.ResultsThe host gene expression data consisted of bovine RNA-seq data from alveolar macrophages infected with M. bovis at 24 and 48 hours post-infection. These RNA-seq data were analysed using three distinct analysis pipelines and novel response pathways and modules were further refined using cross-comparison and integration of the results. First, a differential expression analysis was carried out to determine the most significantly differentially expressed (DE) genes between conditions at each time point. Second, two networks were constructed at each time point using gene correlation patterns to determine changes in expression across conditions. Functional sub-modules within each correlation network were selected by statistical criteria for modularity. Third, a base gene interaction network of the mammalian host response to mycobacterial infection was generated using the GeneCards database and InnateDB. Differential gene expression data were superimposed on this base network to extract functional modules of interconnected DE genes.ConclusionsBovine GWAS data was obtained from a published BTB susceptibility/resistance study. The results from the three parallel analyses were integrated with this data to determine which of the three approaches identified genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets.
A Splice-site Variant (C.3289-1G>T) in OTOF Underlies Profound Hearing Loss in a Pakistani Kindred
Authors: ahmed ashfaque , Wang Meng , Khan Rizwan , Shah Abid Ali , Guo Hui , Malik Sajid , Xia Kun , Hu Zhengmao
Published: December 2020

Background: Hearing loss/deafness is a common otological disorder found in the Pakistani population due to the high prevalence of consanguineous unions, but the full range of genetic causes is still unknown.Methods: A large consanguineous Pakistani kindred with hearing loss was studied. Whole-exome sequencing and Sanger sequencing were performed to search for the candidate gene underlying the disease phenotype. A minigene assay and reverse transcription polymerase chain reaction were used to assess the effect of splicing variants.Results: The splicing variants of OTOF (NM_194248, c.3289-1G>T) cosegregated with the disease phenotype in this Pakistani family. The substitution of a single base pair causes the deletion of 10 bp (splicing variant 1) or 13 bp (splicing variant 2) from exon 27, which results in truncated proteins of 1141 and 1140 amino acids, respectively.Conclusion: Our findings reveal an OTOF splice-site variant as pathogenic for profound hearing loss in this family.
The Convergence of Racial and Income Disparities in Health Insurance Coverage in the United States
Authors: Lee De-Chih , Liang Hailun , Shi Leiyu
Published: December 2020

ObjectiveThis study applies the vulnerability framework and examines the combined effect of race and income on health insurance coverage in the US. Results of the study could assist policymakers in targeting limited resources on subpopulations likely most in need of assistance for insurance coverage.Data sourcesThe household component of the US Medical Expenditure Panel Survey (MEPS-HC) in 2017 was used for the study.Study designLogistic regression models were used to estimate the associations between insurance coverage status and vulnerability measure, comparing insured with uninsured or partially insured, partially insured only, and uninsured only, respectively.Data collection/extraction methodsWe constructed a vulnerability measure that reflects the convergence of predisposing (race/ethnicity), enabling (income), and need (self-perceived health status) attributes of risk. Principal findingsWhile income was a significant predictor of health insurance coverage (a difference of 6.1%-7.2% between high- and low-income Americans), race/ethnicity was independently associated with lack of insurance. The combined effect of income and race on insurance coverage was devastating as low-income minorities with bad health had 66% less odds of being insured instead of uninsured or partially insured than high-income Whites with good health.ConclusionsPolicymakers should target insurance coverage for the most vulnerable subpopulation, i.e., those who have low income and are racial/ethnic minorities.
Iron Oxide Nanoparticle - Multiwall Carbon Nanotube Composite Materials for Batch or Chromatographic Biomolecule Separation
Authors: Schwaminger Sebastian Patrick , Brammen Markus , Zunhammer Florian , Däumler Nicklas , Fraga-García Paula , Berensmeier Sonja
Published: December 2020

Carbon-based materials are the spearhead of research in multiple fields of nanotechnology. Moreover, their role as stationary phase in chromatography is gaining relevance. We investigate a hybrid material consisting of multiwall carbon nanotubes (CNTs) and superparamagnetic iron oxide nanoparticles (SPIONs) towards its use as a mixed-mode chromatography material. The idea is to immobilize the ion exchange material iron oxide on CNTs as a stable matrix for chromatography processes without a 2 significant pressure drop. Iron oxide nanoparticles are synthesized and used to decorate the CNTs via a co-precipitation route. They bind to the walls of oxidized CNTs, thereby enabling to magnetically separate the hybrid material. This hybrid material is investigated with transmission electron microscopy, magnetometry, X-ray diffraction, X-ray photoelectron and Raman spectroscopy. Moreover, we determine its specific surface area and its wetting behavior. We also demonstrate its applicability as chromatography material for amino acid retention, describing the adsorption and desorption of different amino acids in a complex porous system surrounded by aqueous media. Thus, this material can be used as chromatographic matrix and as a magnetic batch adsorbent material due to the iron oxide nanoparticles. Our work contributes to current research on composite materials. Such materials are necessary for developing novel industrial applications or improving the performance of established processes.
High Sensitive Chiral Molecule Detector Based on The Amplified Lateral Shift in Kretschmann Configuration Involving Chiral TDBCs
Authors: Wang Song , Ye Qihui , Chen Xudong , Hu Yanzhu , Song Gang
Published: December 2020

We investigate a high sensitive chiral molecule detector based on Goos-Hanchen shift (S) in Kretschmann configuration involving chiral TDBCs. Fresnel equations and the stationary phase method are employed to calculate S. Due to the interaction between surface plasmon polaritons and chiral TDBCs, S with chiral TDBCs are amplified at near the resonant wavelengths of chiral TDBCs. Our calculation results show that although the difference between the resonant wavelengths of left and right TDBCs is 4.5nm, the difference of S with chiral TDBCs (ΔS) can reach to 400 times as the incident wavelength in certain conditions, which can be easily observed in experiments. There is an optimal thickness of the metal film to realize the largest difference of S between Kretschmann configurations with left TDBCs and right TDBCs. We also find that the positions of the largest S for the structures with left TDBCs and right TDBCs do not overlap. Furthermore, we discuss the oscillator strength f, which is mainly determined by TDBC concentration. We find that our proposed detector is quite sensitive with f. By changing f from 0.008 to 0.014 with the step of 0.002, the change of ΔS is no less than 5 times of the incident wavelength (2.9μm). Our proposed structure is very sensitive and has potential applications in experiments.
Transcriptome and Genome Evolution During HER2-amplified Breast Neoplasia
Authors: Lu Peipei , Foley Joseph , Zhu Chunfang , McNamara Katherine , Sirinukunwattana Korsuk , Vennam Sujay , Varma Sushama , Fehri Hamid , Srivast Arunima , Zhu Shirley , Rittscher Jens , Mallick Parag , Curtis Christina , West Robert
Published: December 2020

The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia’s fitness is less understood. Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue. By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage.
Efficacy of Pediatric Integrative Manual Therapy In Cervical Movement Limitation In Infants With Positional Plagiocephaly: A Randomized Controlled Trial
Authors: Pastor-Pons Iñaki , García Cesar Hidalgo , Lucha-López María Orosia , Barrau-Lalmolda Marta , Rodes-Pastor Iñaki , Rodríguez-Fernández Ángel Luis , Tricás-Moreno José Miguel
Published: December 2020

Background: Positional plagiocephaly (PP) is a cranial deformation frequent amongst children and consisting in a flattened and asymmetrical head shape. PP is associated with excessive time in supine and with congenital muscular torticollis (CMT). Few studies have evaluated the efficiency of a manual therapy approach in PP. The purpose of this parallel randomized controlled trial is to compare the effectiveness of adding a manual therapy approach to a caregiver education program focusing on active rotation range of motion (AROM) and neuromotor development in a PP pediatric sample. Methods: 34 children with PP and less than 28 week old were randomly distributed into two groups. AROM and neuromotor development with Alberta Infant Motor Scale (AIMS) were measured. The evaluation was performed by an examiner, blinded to the randomization of the subjects. A pediatric integrative manual therapy (PIMT) group received 10-sessions involving manual therapy and a caregiver education program. The control group received the caregiver education program exclusively. To compare intervention effectiveness across the groups, improvement indexes of AROM and AIMS were calculated using the difference of the final measurement values minus the baseline measurement values. If the distribution was normal, the improvement indexes were compared using the Student t-test for independent samples; if not, the Mann-Whitney U test was used. The effect size of the interventions was calculated using Cohen's d. Results: All randomized subject were analysed. After the intervention, the PIMT group showed a significantly higher increase in rotation (29.68 ± 18.41º) than the control group (6.13 ± 17.69º) (p< 0.05). Both groups improved the neuromotor development but no statistical significant differences were found. No harm was reported during the study.Conclusion: The PIMT intervention program was more effective in increasing AROM than using only a caregiver education program.
Autism Spectrum Disorder and Anorexia Nervosa. Is There a Link? An Italian Experience
Authors: Pruccoli Jacopo , Solari Altea , Terenzi Letizia , Malaspina Elisabetta , Angotti Marida , Pignataro Veronica , Gualandi Paola , Sacrato Leonardo , Cordelli Duccio Maria , Franzoni Emilio , Parmeggiani Antonia
Published: December 2020

Background: Potential overlaps exist between psychopathological features of Anorexia Nervosa (AN) and Autism Spectrum Disorder (ASD). The impact of malnutrition on autistic traits in patients with AN should be considered. This study aims to investigate possible associations between Eating Disorders (ED) psychopathology, ASD traits and BMI in a group of young patients with AN, using the EDI-3 (Eating Disorder Inventory-3) test and gold-standard measures for ASD.Methods: Prospective study involving 23 inpatients admitted to an Italian Centre for paediatric ED. ASD traits and ED psychopathology were assessed administering ADOS-2 (Autism Diagnostic Observation Schedule-2), AQ (Autism Quotient) and EDI-3 tests. Both present and past autistic traits were investigated using different versions of AQ. Possible effect of BMI, Obsessive Compulsive Disorder (OCD) comorbidity and psychopharmacological treatments on results were evaluated with multiple linear regressions.Results: An ASD diagnosis was possible in 22% of patients. EDI-3 Interpersonal Problems (IPC), Affective Problems (APC), and Global Psychological Maladjustment (GPMC) subscales showed correlations with different ASD measures on ADOS-2 and AQ. Scores for ASD and their correlations with EDI-3 subscales were independent of BMI, age, OCD and psychopharmacological treatments.Conclusions: ASD traits presented high prevalence in a group of young inpatients with AN. These traits were significantly correlated to 3 specific EDI-3 subscales and independent of BMI. This is the first study to investigate the relationship between ASD traits as measured with gold-standard measures, EDI-3 scores, and BMI.
Knowledge of Neonatal Danger Signs and Associated Factors Among Mothers Who Gave Birth in the Past Six Months in Chole District, Arsi Zone, South East Ethiopia: Cross sectional Study
Authors: Getachew Tamirat , Assebe Tesfaye , Dheresa Merga , Eyeberu Addis , Gereziher Teklehaimanot
Published: December 2020

Background: Early detection of neonatal illness by mothers is an important step towards improving newborn survival. Even though mother’s knowledge of neonatal danger signs plays a critical role in reducing neonatal morbidity and mortality, studies on the area are limited and most of them are institution-based study which do not include rural mothers and mothers with home delivery. Therefore, the study aimed to assess knowledge of neonatal danger signs and associated factors among mother’s who gave birth in the past 6 months.Methods: Community-based cross-sectional study was conducted on 520 postnatal mothers by using multistage sampling method from March 1-15, 2019. The data were entered into Epi data version 3.1 and then exported into SPSS version 20 for analysis. Bivariate and multivariate analysis were used by using binary logistic regression to identify factors associated with mother’s knowledge of neonatal danger signs. Statistical significance was declared at p-value less than 0.05. Results: Mother’s level of knowledge on neonatal danger signs was found to be 50.2% (95%CI: 46.3%, 54.3%). Mother’s and husband’s secondary and above educational level [AOR= 2.15 95%CI: (1.11, 4.17)], and [AOR: 2.05, 95%CI: (1.07, 3.94) respectively, being in Urban [AOR=5.83, 95%CI: (2.77, 12.24)], had four or more antenatal visits [AOR: 2.10, 95%CI: (1.13, 3.90)], counseled during antenatal care [AOR= 4.33 95%CI: (1.88, 9.98)] and knowledge about essential newborn care [AOR=3.91 95%CI: (2.05, 7.48)] were significantly associated with mother’s knowledge of neonatal danger signs. Conclusion: The study revealed that mother’s level of knowledge towards neonatal danger signs was low. Mother’s educational status, husband’s educational status, place of residence, number of antenatal visits, counseled during antenatal visit and knowledge about essential newborn care were significantly associated.
Antiparasitic Effects of Plant Species from the Diet of Great Bustards
Authors: Bolívar Paula , Bautista Luis M. , Gómez María Teresa , Martínez Rafael A. , Andrés María Fe , Alonso Juan Carlos , Bravo Carolina , González-Coloma Azucena
Published: December 2020

Background: Diets combine food types according to some trade-offs, as for example maximising nutrients and minimising toxins. But some diets include elements because of their activity against the host parasites and other pathogens. This so-called medicinal role of food is under-reported in the literature, either because toxic elements in diets of livestock and wildlife are infrequent, or because their activity against parasites and pathogens has not been fully documented. We contribute to fill this knowledge gap by testing the activity of extracts and essential oils from Papaver rhoeas and Echium plantagineum against a selection of laboratory pathogens. These plants are strongly selected by great bustards Otis tarda during the mating season. Results: During this season we found a significantly higher frequency of P. rhoeas in male than in female faeces. The activity of different extracts of these plants against some laboratory models including a flagellated protozoan (Trichomonas gallinae), a nematode (Meloidogyne javanica) and a fungus (Aspergillus niger) was evaluated. We found activity against nematodes and trichomonads in non-polar and polar extracts of the aerial parts of P. rhoeas, especially the extracts of flowers and capsules, and E. plantagineum, especially the extracts of leaves and flowers.Conclusions: Both plants showed anti-parasitic activity, a result compatible with the hypothesis that great bustards eat plants for non-nutritional purposes, likely to assist them in coping with parasites and other pathogens, and P. rhoeas could be especially helpful for males during the mating season, when their immune system is weakened by the investment in secondary sexual characters and sexual display. The self-medication properties of plants and animals included in diets should be considered in studies of foraging behaviour, habitat selection, and even conservation biology of wildlife.
WITHDRAWN: Process Parameter Optimization in Fused Deposition Modeling (FDM) Using Response Surface Methodology (RSM)
Authors: Mustafa Muhammad Salman , Zafar Muhammad Qasim , Muneer Muhammad Arslan , Arif Muhammad , Siddiqui Farrukh Arsalan , Javed Hafiz Muhammad Asif
Published: December 2020

Fused Deposition Modeling (FDM) is a widely adopted additive manufacturing process to produce complex 3D structures and it is typically used in the fabrication of biodegradable materials e.g. PLA/PHA for biomedical applications. However, FDM as a fabrication process for such material needs to be optimized to enhance mechanical properties. In this study, dogbone and notched samples are printed with the FDM process to determine optimum values of printing parameters for superior mechanical properties. The effect of layer thickness, infill density, and print bed temperature on mechanical properties is investigated by applying response surface methodology (RSM). Optimum printing parameters are identified for tensile and impact strength and an empirical relation has been formulated with response surface methodology (RSM). Furthermore, the analysis of variance (ANOVA) was performed on the experimental results to determine the influence of the process parameters and their interactions. ANOVA results demonstrate that 44.7% infill density, 0.44 mm layer thickness, and 20C° printing temperatures are the optimum values of printing parameters owing to improved tensile and impact strength respectively. The experimental results were found in strong agreement with the predicted theoretical results.
Uterus Size May Affect Reproductive Outcome in Women with Adenomyosis After Gnrh- Agonist Pretreatment Undergoing Frozen Embryo Transfer Cycles: A Retrospective Cohort Study
Authors: Xiong Wei , Tang Ruiyi , Wu Peng , Sun Zhengyi , zhen jingran , Yu Qi
Published: December 2020

Background: GnRH-agonist is used to treat adenomyosis, but its efficacy in adenomyosis patients with uterine enlargement undergoing frozen embryo transfer (FET) is unclear. Methods：The retrospective cohort study comprised 112 adenomyosis patients with uterine enlargement undergoing the first FET circle. A long-term GnRH-a pretreatment was administered to 112 patients with uterine enlargement. These patients were divided into two groups according to the therapeutic effect: patients with a normal-size uterus after GnRH-a treatment (GN group) and patients with an enlarged uterus after GnRH-a treatment (GL group). Results：Not all patients can shrink their uterus to a satisfactory level. After receiving GnRH-a pretreatment, the uterus returned to normal size in 77% of patients (GN group), and 23% of patients had a persistently enlarged uterus (GL group). The pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were significantly higher in the GN group than in the GL group. Controlling for the confounding factors, normal uterus size (odds ratio [OR] 4.50; P=0.03) and low body mass index (OR 3.13; P=0.03) affected the odds of achieving live birth. The cut-off value selected on the ROC curve of uterus volume after GnRH-a treatment for detecting live birth was 144.7Conclusions：GnRH-a pretreatment was associated with the regression of adenomyosis lesions and improved clinical pregnancy outcomes in the adenomyosis patients with uterine enlargement whose lesion are GnRH-a susceptible on FET cycles. However, about a quarter of patients may not be less responsive to GnRH-a and have poorer pregnancy outcomes, especially in overweight women.
SPAK-p38 MAPK Signal Pathway Modulates Claudin-18 and Barrier Function of Alveolar Epithelium after Hyperoxic Exposure
Authors: Shen Chih-Hao , Lin Jr-Yu , Lu Cheng-Yo , Yang Sung-Sen , Peng Chung-Kan , Huang Kun-Lun
Published: December 2020

Background: Hyperoxia downregulates the tight junction (TJ) proteins of the alveolar epithelium and leads to barrier dysfunction. Previous study has showed that STE20/SPS1-related proline/alanine-rich kinase (SPAK) interferes with the intestinal barrier function in mice. The aim of the present study is to explore the association between SPAK and barrier function in the alveolar epithelium after hyperoxic exposure. Methods: Hyperoxic acute lung injury (HALI) was induced by exposing mice to >99% oxygen for 64 hours. The mice were randomly allotted into four groups comprising two control groups and two hyperoxic groups with and without SPAK knockout. Mouse alveolar MLE-12 cells were cultured in control and hyperoxic conditions with or without SPAK knockdown. Transepithelial electric resistance and transwell monolayer permeability were measured for each group. In-cell western assay was used to screen the possible mechanism of p-SPAK being induced by hyperoxia.Results: Compared with the control group, SPAK knockout mice had a lower protein level in the bronchoalveolar lavage ﬂuid in HALI, which was correlated with a lower extent of TJ disruption according to transmission electron microscopy. Hyperoxia down-regulated claudin-18 in the alveolar epithelium, which was alleviated in SPAK knockout mice. In MLE-12 cells, hyperoxia up-regulated phosphorylated-SPAK by reactive oxygen species (ROS), which was inhibited by indomethacin. Compared with the control group, SPAK knockdown MLE-12 cells had higher transepithelial electrical resistance and lower transwell monolayer permeability after hyperoxic exposure. The expression of claudin-18 was suppressed by hyperoxia, and down-regulation of SPAK restored the expression of claudin-18. The process of SPAK suppressing the expression of claudin-18 and impairing the barrier function was mediated by p38 mitogen-activated protein kinase (MAPK).Conclusions: Hyperoxia up-regulates the SPAK-p38 MAPK signal pathway by ROS, which disrupts the TJ of the alveolar epithelium by suppressing the expression of claudin-18. Down-regulation of SPAK attenuates this process and protects the alveolar epithelium against the barrier dysfunction induced by hyperoxia.
GSK3β Rephosphorylation Rescues ALPL Deficiency Induced-impairment of Odontoblastic Differentiation of DPSCs
Authors: Zhang Liqiang , Zhao Jiangdong , Dong Jiayi , Liu Yuting , Xuan Kun , Liu Wenjia
Published: December 2020

Background: Premature exfoliation of deciduous teeth is a common manifestation in childhood patients with Hypophosphatasia (HPP), which is an autosomal inherited disease caused by ALPL mutations. Dysplasia of cementum, dentin and alveolar bone have been proposed to be the main reasons for the exfoliation of teeth, while the extraordinarily complex intracellular mechanisms remain elusive. Dental pulp stem cells (DPSCs) have been demonstrated to successfully regenerate functional pulp-dentin like tissue. Dental pulp cells derived from HPP patients impaired mineralization, however insight into the deeper mechanism is still unclear. Methods: The effects of ALPL on odontoblastic differentiation of DPSCs from HPP patient were assessed by Alizarin Red staining, immunofluorescent staining, Western blot and RT-PCR, and micro-CT assays. Results: Here, we found DPSCs from HPP patient exhibited low ALP activity and impaired odontoblastic differentiation. Meanwhile, we found that loss of function of ALPL reduced phosphorylation of GSK3β in DPSCs. While GSK3β rephosphorylation improved odontoblastic differentiation of HPP DPSCs with LiCl treatment. Finally, we demonstrated systemic LiCl injection ameliorated tooth associated defects in ALPL+/- mice by enhanced phosphorylation of GSK3β in teeth. Conclusions: Our study indicates that ALPL regulates odontoblastic differentiation of DPSCs, and provides useful information for understanding how ALPL deficiency leaded to tooth dysplasia and, ultimately, may inform efforts at improvement tooth defects in HPP patients.
The Effect of Magnesium Ions on Chromosome Structure: Insights from G-Banding
Authors: Dwiranti Astari , Kartapradja Hannie , Mualifah Mualifah
Published: December 2020

Magnesium ion (Mg2+) plays a fundamental role in the chromosome condensation which is important for genetic material segregation. Studies about the effects of Mg2+ on the overall chromosome structure have been reported. Nevertheless, its effects on the distribution of heterochromatin and euchromatin region have yet to be investigated. This study was aimed to evaluate the effects of Mg2+ on the banding pattern of the chromosome structure. Chromosome analysis was performed using the GTL-banding technique on synchronized HeLa cells. The effect of Mg2+ was evaluated by subjecting the chromosomes to three different solutions, namely XBE5 (5 mM Mg2+) as a control, XBE (0 mM Mg2+), and 1 mM EDTA as cations chelator. The results showed a condensed chromosome structure with a clear banding pattern when it was treated with a buffer containing 5 mM Mg2+. In contrast, chromosomes treated with a buffer containing no Mg2+ and those treated with an ions chelator showed an expanded and fibrous structure with the lower intensity of the banding pattern. Elongation of the chromosome caused by decondensation resulted in the band splitting. The results of this study further emphasized the role of Mg2+ on chromosome structure and gave insights into Mg2+ effects on the banding distribution.
Classification of Marine Mammals Using Trained Multilayer Perceptron Neural Network With Whale Algorithm Developed With Fuzzy System
Authors: Saffari Abbas , Khishe Mohammad
Published: December 2020

The existence of various sounds from different natural and unnatural sources in the deep sea has caused the classification and identification of marine mammals intending to identify different endangered species to become one of the topics of interest for researchers and activists field. In this paper, first, an experimental data set was created using a designed scenario. The Whale Optimization Algorithm (WOA) is then used to train the multilayer perceptron neural network (MLP-NN). However, due to the large size of the data, the algorithm has not determined a clear boundary between the exploration and extraction phases. Next, to support this shortcoming, the fuzzy inference is used as a new approach to developing and upgrading WOA called FWOA. Fuzzy inference By setting FWOA control parameters can well define the boundary between the two phases of exploration and extraction. To measure the performance of the designed categorizer, in addition to using it to categorize benchmark datasets, five benchmarking algorithms CVOA, WOA, ChOA, BWO, PGO, were also used for MLP-NN training. The measured criteria are concurrency speed, ability to avoid local optimization, and classification rate. The simulation results showed that FWOA has the highest classification accuracy in classifying both sets of marine mammal datasets and provides better results than the other five benchmark algorithms.
Jian-Gan-Xiao-Zhi Decoction Ameliorates Nonalcoholic Fatty Liver Disease Through Modulating Gut Microbiota, Decreasing Gut Permeability, and Alleviating Liver Inflammation
Authors: Liao Jiabao , Xie Xuehua , Gao Jinmei , Zhang Zhaiyi , Qv Fei , Cui Huantian , Cao Yongjun , Han Xue , Zhao Jie , Wen Weibo , Wang Hongwu
Published: December 2020

BackgroundJian-Gan-Xiao-Zhi decoction (JGXZ), composed of Salvia miltiorrhiza Bunge, Panax notoginseng, Curcuma zedoaria, and other 9 types of herbs, has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms behind JGXZ’s impact on NAFLD remain unknown. MethodsIn this study, a NAFLD rat model induced by a high-fat diet (HFD) received oral treatment of JGXZ (8 or 16 g crude herb/kg) for 8 weeks. The therapeutic effects of JGXZ on NAFLD model rats were investigated through blood lipid levels and pathological liver changes. 16s rRNA analysis was used to study the changes in gut microbiota after JGXZ treatment. The expressions of occludin and tight junction protein 1 (ZO-1) in colon were investigated using immunostaining to study the effects of JGXZ on gut permeability. The anti-inflammatory effects of JGXZ were also studied through measuring the levels of IL-1β, IL-6 and TNF-α in serum and liver.ResultsJGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and Oil Red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells into the liver. 16s rRNA analysis exhibited that JGXZ impacted the diversity of gut microbiota, decreasing the Firmicutes to Bacteroidetes ratio and increasing the relative abundance of probiotics, such as Alloprevotella, Lactobacillus, and Turicibacter. Gut permeability evaluation found that the expressions of ZO-1 and occludin in the colon were increased after JGXZ treatment, and inflammation analysis showed decreased levels of IL-1β, IL-6, and TNF-α in the serum and liver after treatment. ConclusionsOur study illustrates that JGXZ ameliorates NAFLD through modulating gut microbiota, decreasing gut permeability, and alleviating liver inflammation.
Identification of an autophagy-related prognostic signature in head neck squamous cell carcinoma
Authors: Jiang Yue , Li Yuanyuan , Ge Han , Wu Yaping , Zhang Yuchao , Guo Songsong , Zhang Ping , Cheng Jie , Wang Yanling
Published: December 2020

Background

Autophagy-related genes (ARGs) have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop an ARGs-based prognostic signature for head neck squamous cell carcinoma (HNSCC).
Methods

Prognostic ARG candidates were identified by univariate and multivariate Cox regression analysis in training set (TCGA-HNSC) and incorporated into a 3-ARGs (EGFR, FADD, PARK2) prognostic signature, which further verified in two independent validation cohorts (GSE41613 and GSE42743). Kaplan-Meier plots, Cox regression analyses and receiver operating characteristics curves (ROC) were employed to evaluate the prognostic prediction of 3-ARGs signature. Differential expression of these 3 ARG between cancer and normal counterparts as well as their associations with autophagy markers were assessed using Human Protein Profiles dataset.
Results

Patients with high-risk score had significantly inferior overall survival. Multivariate survival analyses revealed that 3-ARGs signature could be an independent prognostic factor. ROC analyses revealed the high predictive accuracy and sensitivity of 3-ARGs signature. Increased expression of EGFR, FADD, PARK2 were found in HNSCC samples and their expression significantly correlated with levels of ATG5, Beclin1 and LC3.
Conclusions

Our results reveal that 3-ARGs signature is a powerful prognostic biomarker for HNSCC, which could be integrated into current prognostic regime to realize individualized outcome prediction.
Co-Creation and Prototyping of An Intervention Focusing On Health Literacy In Management of Malaria At Community-Level In Ghana
Authors: Boateng Millicent Addai , Agyei-Baffour Peter , Angel Sanne , Asare Ofeibea , Prempeh Benjamin , Enemark Ulrika
Published: December 2020

Introduction: Collaborating with end-users to develop interventions tailored to fit unique circumstances is proposed as a way to improve relevance and effectiveness of an intervention. This study used a local needs driven approach to develop a health literacy intervention for caregivers in Ghana concerning management of malaria in children under five years. Method: A three-phase framework including: 1) needs assessment based on data from questionnaires, focus groups, individual interviews and observations, 2) Co-creation of a borad game and brochures for health education at Child Welfare Clinics to address needs in health literacy concerning malaria and 3)Development of a prototype of the game, brochures as well as determining user feasibility. Findings: The needs assessment resulted in a useful intervention to bridge the gaps in health literacy among caregivers. Co-creation of the materials and prototyping yielded a varying sense of ownership among stakeholders. End-users’ engagement and participation in developing the intervention resulted in a high interest and adherence to interventions. However, high attrition rates of health workers and caregivers’ inconsistent use of the Child Welfare Clinics challenged sustainability of this intervention.Conclusion: The interactive nature of this approach to health delivery interventions resulted in a better caregiver-health provider relationship and a sense of recognition of a more participatory approach to health delivery. A stronger buy-in at the top-level of health management and scaling it out into communities would improve sustainability and reach a larger audience.
Women Empowerment and Frequency of Meal Intake Among Children in Ghana
Authors: Dadzie Louis Kobina , Amo-Adjei Joshua , Esia-Donkoh Kobina
Published: December 2020

BackgroundQuality nutrition is an important basis of health and well-being, especially for children as their bodies need to grow, develop and reach their physical and mental potential. Women’s empowerment is not only important for women’s human rights, but also improves nutrition outcomes of both mothers and their children. This study sought to investigate the association between women’s empowerment and minimum meal frequency in Ghana.MethodsThe study used data from the 2014 Ghana Demographic and Health Survey (GDHS). A sample of 1,640 mother-child (6-23 months) dyad was used and univariate and multiple linear regression techniques were applied.ResultsDecisions on large household purchases (β=0.351, p<0.01) and family visits (β=0.743, p<0.01), ownership over house (β=-0.245, p<0.10), age of child (β=1.387, p<0.01), mother’s educational attainment (β=0.496, p<0.10) and residence (β=-0.298, p<0.10) were significantly associated with minimum meal frequency in Ghana.ConclusionMinimum meal frequency was largely influenced by economic and socio-familial empowerment of women as decisions on large household purchases and family visits showed association with minimum meal frequency. Interventional programs should target households and mothers with lower socio-demographics characteristics such as lower educational level.
Identification of Biomarkers and Pathogenesis in Severe Asthma by Co-expression Network Analysis
Authors: Zhang Zeyi , Chen Ou , Wang Jingjing
Published: December 2020

BackgroundSevere asthma is a heterogeneous inflammatory disease. The rise of precise immunotherapy for severe asthmatics underlines more understanding of molecular mechanisms and biomarkers. In this study, we aim to identify underlying mechanisms and hub genes that define asthma severity.MethodsDifferentially expressed genes were screened out based on bronchial epithelial brushings from mild and severe asthmatics. Then, the weighted gene co-expression network analysis was adopted to identify gene networks and the most significant module associated with asthma severity. Meanwhile, hub genes screening and functional enrichment analysis was performed. Receiver operating characteristic was conducted to validate the hub genes.ResultsWeighted gene co-expression network analysis identified 6 modules associated with asthma severity. Three modules were positively correlated (P < 0.001) with asthma severity, containing genes upregulated in severe asthmatics. Functional enrichment analysis found genes in the highlighted module mainly enriched in neutrophil degranulation and activation, leukocyte migration and chemotaxis. Hub genes identified in the module were CXCR1, CXCR2, CCR1, CCR7, TLR2, FPR1, FCGR3B, FCGR2A, ITGAM, and PLEK. Combining these hub genes possessed a moderate ability for discriminating between severe asthmatics and mild-moderate asthmatics with an area under the curve of 0.75.ConclusionOur results identified biomarkers and potential pathogenesis of severe asthma, which provides sight into treatment targets and prognostic markers.
Synthesis of n.c.a. [188, 189, 191pt] Cisplatin From a Cyclotron-produced n.c.a. 188, 189, 191PtCl42- Complex
Authors: Obata Honoka , Minegishi Katsuyuki , Nagatsu Kotaro , Ogawa Mikako , Zhang Ming
Published: December 2020

We developed a novel method for production of no-carrier-added (n.c.a.) [188, 189, 191Pt]PtⅡCl42- from an Ir target material, and then synthesized n.c.a. [*Pt]cis-[PtⅡCl2(NH3)2] ([*Pt]cisplatin) from [*Pt]PtⅡCl42-. [*Pt]PtⅡCl42- was prepared as a synthetic precursor of n.c.a. *Pt complex by a combination of resin extraction and anion-exchange chromatography after the selective reduction of IrⅣCl62- with ascorbic acid. The ligand-substitution reaction of Cl with NH3 was promoted by treating n.c.a. [*Pt]PtⅡCl42- with excess NH3 and heating the reaction mixture, and n.c.a [*Pt]cisplatin was successfully produced without employing precipitation routes. After this treatment, [*Pt]cisplatin was isolated through preparative HPLC with a radiochemical purity of 99+% at the end of synthesis (EOS).
Early Rescue Intracytoplasmic Sperm Injection in Partial Fertilization Failure Is Necessary and Safe: A Retrospective Analysis of 1223 Patients
Authors: Zeng Jun , Yao Zhongyuan , Zhang Yeqing , Tian Fen , Liao Tingting , Wu Lingqian , Li Yanping
Published: December 2020

BACKGROUND: Total or near total fertilization failure remains inevitable in conventional in vitro fertilization (IVF). The experts searched for the release of the second polar body 6 h after initial insemination, and rescued those oocytes with unclear second polar body by ICSI (early R-ICSI). Studies found that early R-ICSI can effectively decrease complete IVF fertilization failure and excessive ICSI treatment.METHODS: We performed a retrospective study in 16,769 patients (short-term IVF, n=12,094; ICSI, n=3,452; early R-ICSI, n=1,223) who received IVF/ICSI treatment in our hospital from January 2009 to October 2018. Fertilization and clinical outcomes were compared among those three groups.RESULTS: When considering the R-ICSI embryos in the early R-ICSI group independently, the rates of fertilization and day-3 cleaved embryos in 2PN oocytes were comparable, the rates of fertilization (2PN) and high-quality embryos were lower, whereas the multi-PN fertilization rate (3.27%) was significantly higher than the ICSI group (1.26%). The difference of clinical pregnancy rate between the part of transferred R-ICSI embryos (40.81%) and the ICSI group (44.73) remained nonsignificant. Furthermore, the rate of congenital birth defects in the early R-ICSI group (0.99%) was not significantly different from those in the short-term IVF (0.76%) and ICSI groups (1.07%).CONCLUSIONS: Despite the multi-PN fertilization rate, our study highlights early R-ICSI as a safe and effective alternative in assisted reproduction to reduce ICSI utilization. Additional large amount and long-term follow-up studies are needed to further validate the use of early R-ICSI.