bluuebunny/crossref_metadata_2025 huggingface dataset:
Friend or Frenotomy: A Single Institution’s Experience With Ankyloglossia
Authors: Kelly Aine , Corbett Mel , Cleere Eoin , Patil Aishan , Davey Matthew G , McGlynn Bridgene , Choo Marcus
Published: August 2021

Introduction/AimAnkyloglossia, or ‘tongue-tie’, is a common congenital anomaly in which a short lingual frenulum or genioglossus muscle restricts tongue movement. Ankyloglossia can be graded from 1 (most severe) to 4 (least severe). The effects of ankyloglossia can include breastfeeding and articulation issues; however, many infants will have no symptoms or developmental problems. The surgical intervention for ankyloglossia is frenotomy. This can be performed in the outpatient setting in small infants. Ankyloglossia referrals in neonates and small infants necessitate an urgent referral to the ear nose and throat (ENT) clinic in order to facilitate breast feeding and weight gain. We sought to analyse the ankyloglossia service in a district general hospital setting from referral to outpatient clinic. MethodsWe retrospectively analysed a consecutive cohort of babies referred to the Ear Nose and Throat service for consideration of frenotomy over an 18 month period, We analysed data from referral including demographics and clinical information, we recorded information from the clinical consultation and procedure details if frenotomy was performed.ResultsBetween 1 January 2019 and 31 January 2021 referrals were made for consideration of frenotomy, all appointments were seen within 2 weeks. 55.3% of referrals were sent from public health nurses, 25.5% from primary care, 10.6% from lactation consultants and 8.5% from paediatric consultants. Of 47 referrals, a frenotomy was performed in 30 babies. All frenotomies were performed without complications.ConclusionInformation on ankyloglossia is varied and available information is conflicting, without any clear standardised guideline or treatment algorithm. Referral indications can be unclear and result in unnecessary clinic appointments in an already heavily burdened service. Frenotomy can be performed safely by a trained clinician in an outpatient setting with minimal equipment.
Pedigree Derived Mutation Rate Across the Entire Mitochondrial Genome of the Norfolk Island Population
Authors: Connell Jasmine , Benton Miles , Lea Rodney , Sutherland Heidi , Chaseling Janet , Haupt Larisa , Wright Kirsty , Griffiths Lyn
Published: August 2021

Estimates of mutation rates for various regions of the mitochondrial genome (mtGenome) vary widely, depending on whether they are inferred using a phylogenetic approach or obtained directly from pedigrees. Traditionally, only the control region, or small portions of the coding region have been targeted for analysis due to the cost and effort required to produce whole mtGenome Sanger profiles. Here, we report one of the first pedigree derived mutation rates for the entire human mtGenome. The entire mtGenome from 225 individuals originating from Norfolk Island was analysed to estimate the population mutation rate and compared against published mutation rates. These individuals were from 45 maternal lineages spanning 345 generational events. Mutation rates for various portions of the mtGenome were calculated. Nine mutations (including two transitions and seven cases of heteroplasmy) were observed, resulting in a rate of 0.063 mutations/site/million years (95% confidence interval: 0.033 – 0.118). These mutation rates are approximately 17 times higher than estimates derived from phylogenetic analysis with heteroplasmy detected in 13 samples (n=225, 5.8% individuals). Providing one of the first pedigree derived estimates for the entire mtGenome, this study provides a better understanding of mtGenome evolution and has relevance to many research fields, including medicine, anthropology and forensics.
Ground-Truth based Performance Assessment of Landslide Susceptibility Mapping: A Case Study after Elazig Earthquake (24 Jan 2020, Mw 6.8), Turkey
Authors: Karakas Gizem , Kocaman Sultan , Gokceoglu Candan
Published: August 2021

Quality assessment for landslide susceptibility maps (LSMs) is essential to increase their usability. Ground-truth based quality assessment is crucial for performance evaluation of LSM production methods. Landslides triggered by earthquakes can be employed for this purpose as they occur frequently throughout the active seismic regions of the world. After an earthquake occurred in Elazig, Turkey on 24 Jan 2020 (Mw 6.8), several landslides were activated in the mountainous parts. Here, the performances of two state-of-the-art machine learning methods, i.e., random forest (RF) and multi-layer perceptron (MLP), were investigated using the activated landslides. The landslide inventory was derived by using pre- and post-event aerial photogrammetric datasets; whereas only the pre-event datasets were utilized for LSM production. The inventory includes activity classes of inactive (L1) and active mass movements (L2), areas having new active zones occurred after 2018 inside the existing landslide (L3), and new activity after 2018 (L4). The L1 and L2 type landslides were used in model training, while L3 and L4 type landslides triggered by the earthquake were used for validation. The area under curve (AUC) values and volumetric change maps obtained from the pre- and post-event datasets were also used for the performance assessment. Furthermore, only a part of the study area was used for model training while the LSMs were produced for the whole area. The results demonstrated that RF exhibited higher classification accuracy (AUC = 0.93) than MLP (AUC = 0.87); and accurate LSMs could be produced by using a sub-part of the basin for training.
Water-stable Perovskite-loaded Nanogels Containing Antioxidant Property for Highly Sensitive and Selective Detection of Roxithromycin in Animal-derived Food Products
Authors: Han Jinsol , Sharipov Mirkomil , Lee Youngil , Huy Bui The , LEE YONG-ILL , Hwang Soojin
Published: August 2021

Luminescent inorganic lead halide perovskite nanoparticles lack stability in aqueous solutions, which limits their application to optical sensors. Here, hybrid CsPbBr3-loaded MIP nanogels were developed with enhanced stability in aqueous media. Multifunctional MIP nanogels with antioxidant function and hydrophobic cavities were synthesized from HEMA derivatives in the presence of roxithromycin as a template. The CsPbBr3 nanoparticles were loaded into pre-synthesized MIP nanogels via in-situ synthesis with a size distribution of 200 nm. The developed CsPbBr3-nanogel exhibit excellent stability to air/moisture and enhanced stability toward an aqueous solvent. The developed CsPbBr3-loaded MIP nanogels showed a selective and sensitive detection of ROX with a limit of detection calculated to be 1.7 × 10− 5 µg/mL (20.6 pM). The developed CsPbBr3-loaded MIP antioxidant-nanogels were evaluated on practical application for quantitative determination of ROX antibiotic in animal-derived food products with excellent analytical performance. The detection of ROX in animal-derived food products showed good recovery results making them an ideal candidate for sensing ROX.
Emulating interacting waveguide quantum electrodynamics with wire metamaterials
Authors: Koreshin Eugene , Sakhno Denis , Poddubny Alexander , Belov Pavel
Published: August 2021

Arrays of atoms coupled to photons, propagating in a waveguide, are now actively studied due to their prospects for generation and detection of quantum light. Quantum simulators based on waveguides with long-range couplings were also predicted to manifest unusual many-body quantum states. However, quantum tomography for large arrays with N > 20 atoms remains elusive since it requires independent access to every atom. Here, we present a novel concept for analogue quantum simulations by mapping the setup of waveguide quantum electrodynamics to the classical problem of an electromagnetic wave, propagating in a wire metamaterial. By experimentally measuring the near electromagnetic field we emulate the localization arising from polariton-polariton interactions in the quantum problem. Our results demonstrate the potential of wire metamaterials to visualize quantum light-matter coupling in a table-top experiment and may be applied to emulate other exotic quantum effects, such as quantum chaos, and self-induced topological states.
Trait Rumination and Social Anxiety Separately Predict Stress Induced Rumination and Hemodynamic Responses
Authors: Laicher Hendrik , Int-Veen Isabell , Torka Florian , Kroczek Agnes , Bihlmaier Isabel , Storchak Helena , Velten-Schurian Kerstin , Dresler Thomas , Täglich Ramona , Fallgatter Andreas J. , Ehlis Ann-Christine , Rosenbaum David
Published: August 2021

We aimed to investigate the stress-reactive rumination response to social stress and its association with social anxiety and trait rumination. From previous investigations we know that people with a certain vulnerability to rumination show increased stress-reactive rumination. However, up to date the possible influence of social anxiety to this relationship is still unclear. Therefore, we reanalyzed the data of two of our previous studies assessing healthy low and high trait ruminators and depressed patients performing the Trier Social Stress Test (TSST). We measured cortical oxygenation using functional Near-Infrared Spectroscopy (fNIRS) as well as different behavioral outcome measures (subjective stress levels, negative affect, state rumination). On a behavioral level, we found an influence of both, social anxiety and trait rumination, on state rumination, even when correcting for the other factor, respectively, implying two potentially independent factors of influence. On a neural level, we observed reduced activation in socially anxious subjects in the right inferior frontal gyrus (IFG), as well as time-dependent changes in the left IFG and in the right dorsolateral prefrontal cortex. Results indicate a specific role of social anxiety, at least on a behavioral level, and therefore implicate a crucial factor to be considered in the treatment of depression.
Malignancy and Immune Disorders in Patients With Hereditary Angioedema
Authors: Stepaniuk Peter , Kanani Amin
Published: August 2021

Background
With the advent of new therapies, patients with hereditary angioedema (HAE) are living longer lives. Although complement dysregulation has been linked to various disease states, it is currently not known if HAE patients are at an increased risk of developing malignancy or autoimmune conditions.
Case Presentation
: We reviewed the charts of 49 HAE patients and identified 6 patients who had a co-existing malignancy diagnosis (two with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer and one with cervical dysplasia) and 6 patients who had a diagnosis of a co-existing immune disorder (two with rheumatoid arthritis, two with ulcerative colitis, one with chronic urticaria with hypothyroidism and one with Sjogren’s syndrome). Nearly all malignancy cases occurred in older HAE patients (> 50 years) and malignancy was diagnosed before HAE in 3 of the patients.
Conclusions
Our case series has identified multiple hereditary angioedema (HAE) patients with co-existing malignancy and immune disorders. Based on these findings, we would advocate that physicians managing HAE patients should maintain a high index of suspicion for these conditions.
Convergent evolution of a nutritional symbiosis in ants
Authors: Jackson Raphaella , Monnin David , Patapiou Patapios Alexandros , Golding Gemma , Helanterä Heikki , Oettler Jan , Heinze Jürgen , Wurm Yannick , Economou Chloe , Chapuisat Michel , Henry Lee
Published: August 2021

Ants are among the most successful organisms on earth. It has been suggested that forming symbioses with nutrient-supplementing microbes may have contributed to their success, by allowing ants to invade otherwise inaccessible niches. However, it is unclear whether ants have repeatedly evolved symbioses to overcome the same nutrient limitations. Here, we address this question by comparing the independently evolved symbioses in Camponotus, Cardiocondyla, Formica and Plagiolepis ants. Our analysis reveals the only metabolic function consistently retained in all of the symbiont genomes is the capacity to synthesise tyrosine, which is essential for insect cuticles. We also reveal that in certain multi-queen lineages, only a fraction of queens carry the symbiont, suggesting ants differ in their colony-level reliance on symbiont-derived nutrients. Our results suggest symbioses can arise to solve common problems, but hosts may differ in their dependence on symbionts, highlighting the evolutionary forces influencing the persistence of long-term endosymbiotic mutualisms.
Genome Survey Sequencing of Common Vetch (Vicia Sativa L.) and Genetic Diversity Analysis of Chinese Germplasm with Genomic SSR Markers
Authors: ma lin , Wang Xiao , Yan Min , Liu Fang , Wang Xuemin
Published: August 2021

Common vetch (Vicia sativa L.) is an annual legume with excellent suitability in cold and dry regions. Despite its great applied potential, the genomic information regarding common vetch currently remains unavailable. In the present study, the whole genome survey of common vetch was performed using the next-generation sequencing (NGS). A total of 79.84 Gbp high quality sequence data were obtained and assembled into 3,754,145 scaffolds with an N50 length of 3,556 bp. According to the K-mer analyses, the genome size, heterozygosity rate and GC content of common vetch genome were estimated to be 1,568 Mbp, 0.4345% and 35%, respectively. In addition, a total of 76,810 putative simple sequence repeats (SSRs) were identified. Among them, dinucleotide was the most abundant SSR type (44.94%), followed by Tri- (35.82%), Tetra- (13.22%), Penta- (4.47%) and Hexanucleotide (1.54%). Furthermore, a total of 58,175 SSR primer pairs were designed and ten of them were validated in Chinese common vetch. Further analysis showed that Chinese common vetch harbored high genetic diversity and could be clustered into two main subgroups. This is the first report about the genome features of common vetch, and the information will help to design whole genome sequencing strategies. The newly identified SSRs in this study provide basic molecular markers for germplasm characterization, genetic diversity and QTL mapping studies for common vetch.
Differences in Stem Cell Marker and Osteopontin Expression in Primary and Recurrent Glioblastoma
Authors: Polat Bülent , Wohlleben Gisela , Kosmala Rebekka , Lisowski Dominik , Mantel Frederick , Lewitzki Victor , Löhr Mario , Blum Robert , Herud Petra , Flentje Michael , Monoranu Camelia-Maria
Published: August 2021

Background: Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells. Methods: Paired samples from glioma patients were analyzed by immunohistochemistry for expression of the following stem cell markers: CD133, Musashi, Nanog, Nestin, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (Sox2). In addition, the expression of osteopontin (OPN) was investigated. The relative number of positively stained cells was determined. By means of Kaplan-Meier analysis, a possible association with overall survival by marker expression was investigated. Results: Sixty tissue samples from 30 patients (17 male, 13 female) were available for analysis. For Nestin, Musashi and OPN a significant increase was seen. There was also an increase (not significant) for CD133 and Oct4. Patients with mutated Isocitrate Dehydrogenase-1/2 (IDH-1/2) status had a reduced expression for CD133 and Nestin in their recurrent tumors. Significant correlations were seen for CD133 and Nanog between OPN in the primary and recurrent tumor and between CD133 and Nestin in recurrent tumors. By confocal imaging we could demonstrate a co-expression of CD133 and Nestin within recurrent glioma cells. Patients with high CD133 expression had a worse prognosis (22.6 vs 41.1 months, p = 0.013). A similar trend was seen for elevated Nestin levels (24.9 vs 41.1 months, p = 0.08). Conclusions: Most of the evaluated markers showed an increased expression in their recurrent tumor. CD133 and Nestin were associated with survival and are candidate markers for further clinical investigation.
Asymmetric Relationships Between Information and Communication Technology (ICT), Globalization, and Human Development in India: Evidence From Non-Linear ARDL Analysis
Authors: Behera Jayanti , Sahoo Dukhabandhu
Published: August 2021

The objective of the paper is to examine the asymmetric relationships between ICT, globalization, and human development in India by analyzing the annual data from 1991 to 2019 through the non-linear autoregressive distributed lag (NARDL) model. The result shows that positive and negative changes in globalization lead to a decline in human development in the long run, consistent with the literature. Further, a positive change in mobile density increases human development in the long run. A decline in internet density has a positive impact on human development in the long run, and it needs further investigation. In the short run, a positive shock in globalization with one lag has a positive impact on human development. Moreover, a previous year positive and negative shocks in internet density have a positive effect on human development while the previous two years positive and negative shocks in internet density have a negative effect on human development in the short run. It is also found that the global financial crisis 2008 has a negative impact on human development. Thus, it is suggested that India has to promote both globalization and ICT judiciously and consciously in order to improve the human development. JEL Classification: O47, F00, I32, C51
BODIPY Nanoparticles Functionalized With Lactose for Cancer-Targeted and Fluorescence Imaging-guided Photodynamic Therapy
Authors: Mai Duy Khuong , Kim Chanwoo , Lee Joomin , Vales Temmy Pegarro , Baldon Isabel Wen , Sung Cho , Yang Jaesung , Kim Ho-Joong
Published: August 2021

A series of four lactose-modified BODIPY photosensitizers (PSs) with different substituents (-I, -H, -OCH3, and -NO2) in the para-phenyl moiety attached to the meso-position of the BODIPY core were synthesized; the photophysical properties and photodynamic anticancer activities of these sensitizers were investigated, focusing on the electronic properties of the different substituent groups. Iodine substitution (BODIPY I) enhanced the intersystem crossing (ISC) to produce singlet oxygen (1O2) due to the heavy atom effect, and maintained a high fluorescence quantum yield (ΦF) of 45.3%. Substitution with the electron-donating group (-OCH3) (BODIPY OMe) resulted in a high 1O2 generation capability and a ΦF of 49.2% while substitution with the electron-withdrawing group (-NO2) led to the PeT process. Thus, instead of assisting ISC as typically expected, this BODIPY PS induced non-radiative charge recombination, prohibiting both fluorescence emission and 1O2 generation. The BODIPY PSs formed water-soluble nanoparticles (NPs) functionalized with lactose as liver cancer-targeting ligands. BODIPY I and OMe NPs showed good fluorescence imaging and PDT activity against various tumor cells (HeLa and Huh-7 cells). Collectively, the BODIPY NPs demonstrated high 1O2 generation capability and ΦF may create a new opportunity to develop useful imaging-guided PDT agents for tumor cells.
A Personalized FEM Model for Reproducible Measurement of Anti-inflammatory Drugs in Transdermal Administration to Knee
Authors: Arpaia Pasquale , Crauso Federica , Frosolone Mirco , Mariconda Massimo , Minucci Simone , Moccaldi Nicola
Published: August 2021

A personalized model of the human knee for enhancing the inter-individual reproducibility of a measurement method for monitoring Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) after transdermal delivery is proposed. The model is based on the solution of Maxwell Equations in the electric-quasi-stationary limit via Finite Element Analysis. The dimensions of the custom geometry are estimated on the basis of knee circumference at the patella, body mass index, and sex of each individual. An optimization algorithm allows to find out the electrical parameters of each subject by experimental impedance spectroscopy data. Muscular tissues were characterized anisotropically, by extracting Cole-Cole equation parameters from experimental data acquired with twofold excitation, both transversal and parallel to tissue fibers. A sensitivity and optimization analysis aiming at reducing computational burden in model customization achieved a worst-case reconstruction error lower than 5%. The personalized knee model and the optimization algorithm were validated in vivo by an experimental campaign on thirty volunteers, 67% healthy and 33% affected by knee osteoarthritis (Kellgren-Lawrence grade [1,4]), with an average error of 3%.
Multivariate Data Analysis Identifies Natural Clusters of Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND)
Authors: de Vries Petrus J , Leclezio Loren , Gardner-Lubbe Sugnet , Krueger Darcy , Sahin Mustafa , Sparagana Steven , De Waele Liesbeth , Jansen Anna
Published: August 2021

BackgroundTuberous Sclerosis Complex (TSC), a multi-system genetic disorder, is associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND). Individuals have apparently unique TAND profiles, challenging diagnosis, psycho-education, and intervention planning. We proposed that identification of natural TAND clusters could lead to personalized identification and treatment of TAND. Two small-scale studies showed cluster and factor analysis could identify clinically meaningful natural TAND clusters. Here we set out to identify definitive natural TAND clusters in a large, international dataset.MethodCross-sectional, anonymized TAND Checklist data of 453 individuals with TSC were collected from six international sites. Data-driven methods were used to identify natural TAND clusters. Mean squared contingency coefficients were calculated to produce a correlation matrix, and various cluster analyses and exploratory factor analysis were examined. Statistical robustness of clusters was evaluated with 1000-fold bootstrapping, and internal consistency calculated with Cronbach’s alpha.ResultsWard’s method rendered seven natural TAND clusters with good robustness on bootstrapping. Cluster analysis showed significant convergence with an exploratory factor analysis solution, and, with the exception of one cluster, internal consistency of the emerging clusters was good to excellent. Clusters showed good clinical face validity.ConclusionsOur findings identified a data-driven set of natural TAND clusters from within highly variable TAND Checklist data. The seven natural TAND clusters could be used to train families and professionals and to develop tailored approaches to identification and treatment of TAND. Natural TAND clusters may also have differential aetiological underpinnings and responses to molecular and other treatments.
Estimating SARS-COV-2 Exposure Indoors in Delhi Given Outdoor Pollution Metrics Using Machine Learning
Authors: Biswas Bitan , Kaushik Ravi
Published: August 2021

The Global Burden of Disease journal by the Lancet(Ritchie and Roser, 2013) and states that one million deaths have occurred from 1990 to 2017 due to air pollution. In 2018, the WHO estimated a death toll of 3.8 million due to indoor pollution(WHO,2018). In these times of the pandemic, it is quintessential for countries like India, with a huge population and high levels of pollution, to take severe measures for controlling pollution. The 2020 US Policy Report in the Lancet(2020) affirmed that there is a positive correlation between the PM2.5 or PM10 particles concentration and COVID-19 infection as the virus uses the particulate matter as a piggyback. The case study here, is based on the Indian urban locality and aims to analyze and estimate the correlations between PM2.5 particles, the AQI, weather conditions and COVID-19 particles using Machine Learning models. The optimum model is also to be used for predicting the outdoor AQI and Covid-19 infection rates in the suburban localities of northwestern Delhi and the data so obtained, would aid to calculating ,and extrapolating the mortality probability due to Covid-19 infection, indoors, in the metropolitan cities of India, like Delhi.
A Study on the Heat Effect and Kinetics During Magnesiothermic Reduction of Porous SiO2
Authors: Zhang Boxia , wang Fei , Chen Jianshe , Li Binchuan , Liu Kuiren , Han Qing
Published: August 2021

Magnesiothermic reduction reaction (MRR) is an effective method to synthesis Si nanoparticles. In this paper, the heat effect and MRR kinetics were investigated by real-time temperature monitoring and analyzing the DSC curve of the MRR. It was found that the MRR onset temperature is about 465 °C, and the system temperature rose sharply at 535 °C. After the disappearance of the magnesium phase, the system temperature remained consistent with the set value. The exothermic peak lags and the spike decreases when adding NaCl into the system. The MRR was chemical reaction control, corresponding with the apparent activation energy was 193.456 kJ·mol-1 (without NaCl) and 191.434 kJ·mol-1 (with NaCl) in the temperature interval 465 °C −700 °C, respectively. NaCl affects the reaction mechanism by lowering the temperature of the system. Our work successfully prepared the spherical Si nanoparticles, which average grain size increased from 25 nm to 40 nm with the extended reaction duration. The conversion rate of porous SiO2 precursor was as high as 92%.
Modulatory Effects of Circadian Rhythms in the Lung Adenocarcinoma Tumor Microenvironment
Authors: Huang Qianzhun , Su Xiaoyang , Fang Ning , Huang Jian
Published: August 2021

Background: Dysregulated circadian dynamic balance is strongly associated with cancer development. However, biological functions of circadian rhythms in lung adenocarcinoma (LUAD) have not been elucidated. This study aimed at valuating the modulatory effects of circadian rhythms in the LUAD tumor microenvironment.Methods: Multiple open-source bioinformatics research platforms are used to comprehensively elucidate the expression level, prognosis, potential biological function, drug sensitivity, and immune microenvironment of circadian clock genes in LUAD.Results: Most circadian clock genes in LUAD are dysregulated and are strongly correlated with patient prognosis, and missense mutations at splicing sites of these genes. Besides, these genes are closely associated with some well-known cancer-related marker pathways, which are mainly involved in the inhibition of the Apoptosis, Cell cycle, and DNA Damage Response Pathway. Furthermore, functional enrichment analysis revealedthat circadian clock genes regulate transcription factor activities and circadian rhythms in LUAD tissues. As for drug sensitivity, high expression of CLOCK, CRY1, and NR1D2 as well as suppressedPER2 and CRY2 expression levels are associated with drug resistance. The expression levels of circadian clock genes in LUAD correlate with immune infiltration and are involved in the regulation of immunosuppression.Conclusions: Our multi-omics analysis provides a more comprehensive understanding of the molecular mechanisms of the circadian clock genes in LUAD and provides new insights for a more precise screening of prognostic biomarkers and immunotherapy.
Taurine Alleviates Chronic Social Defeat Stress-Induced Depression by Protecting Cortical Neurons from Dendritic Spine Loss
Authors: Zhu Yuanyuan , Wang Rui , Fan Ze , Luo Danlei , Cai Guohong , Li Xinyang , Han Jiao , Zhuo Lixia , Zhang Li , Zhang Haifeng , Li Yan , Wu Shengxi
Published: August 2021

Abnormal amino acid metabolism in neural cells is involved in the occurrence and development of major depressive disorder. Taurine is an important amino acid required for brain development. Here, microdialysis combined with metabonomics analysis showed that the level of taurine in the extracellular fluid of the cerebral medial prefrontal cortex (mPFC) was significantly reduced in mice with chronic social defeat stress (CSDS)-induced depression. Therefore, taurine supplementation may be an intervention for depression. We found that taurine supplementation could effectively rescue the decreased preference for sucrose consumption and the increased immobility time during a tail suspension assay and improve social avoidance behaviors in CSDS mice. Moreover, taurine treatment protected the CSDS mice from impairments of dendrite complexity, spine density, and spine ratios. The expression of N-methyl D-aspartate receptor subunit 2A (NR2A), an important synaptic receptor, was largely restored in the mPFC after taurine supplementation. These results demonstrated that taurine exhibited an antidepressive effect by protecting cortical neurons from dendritic spine loss and synaptic protein deficits.
The adenoviral E1B-55k protein present in HEK293 cells mediates abnormal accumulation of key WNT signaling proteins in large cytoplasmic aggregates
Authors: Olsen Petter Angell , Krauss Stefan
Published: August 2021

HEK293 cells are one of the most widely used cell lines in research and HEK293 cells are frequently used as an in vitro model for studying the WNT signaling pathway. The HEK293 cell line was originally established by transfection of human embryonic kidney cells with sheared adenovirus 5 DNA and it is known that that HEK293 cells stably express the adenoviral E1A and E1B-55k proteins. Here we show that HEK293 cells display an unexpected distribution of key components of the WNT/β-catenin signaling pathway where AXIN1, APC, DVL2 and tankyrase are all co-localized in large spherical cytoplasmic aggregates. The cytoplasmic aggregates are enclosed by a narrow layer of the adenoviral E1B-55k protein. Reduction of E1B-55k protein levels leads to disappearance of the cytoplasmic aggregates thus corroborating an essential role of the E1B-55k protein in mediating the formation of the aggregates. Furthermore, HEK293 cells with reduced E1B-55k protein levels display reduced levels of transcriptional activation of WNT/β-catenin signaling upon stimulation by the Wnt3A agonist. The demonstrated influence of the E1B-55k protein on the cellular localization of WNT/β-catenin signaling components and on transcriptional regulation of WNT/β-catenin signaling asks for caution in the interpretation of data derived from the HEK293 cell line.
Clitorin, a Flavonoid Compound of Papaya, Ameliorates Non-Alcoholic Fatty Liver Disease in Western Diet- induced Mice and Oleic Acid-induced HepG2 Cells
Authors: Cominguez Divina C. , Park Yea-Jin , Kang Yun-Mi , Nugroho Agung , Kim Suhyun , An Hyo-Jin
Published: August 2021

Nonalcoholic fatty liver disease (NAFLD) is usually correlated with metabolic diseases, such as obesity, insulin resistance, and hyperglycemia. Herein, we investigated the inhibitory effects and underlying governing mechanism of clitorin in a western diet (WD)-induced mouse model, and in oleic acid-induced HepG2 cells. Male C57BL/6 mice were fed a normal diet, WD, WD + 10 or 20 mg/kg orlistat, and WD + 10 or 20 mg/kg clitorin. HepG2 cells were treated with 1 mM oleic acid to induce lipid accumulation with or without clitorin. Clitorin administration reduced body weight gain and hepatic steatosis symptoms in WD-induced mice. Additionally, clitorin administration decreased the expression of sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα) in WD-induced mice. Moreover, clitorin administration significantly decreased the mRNA levels of liver X receptor (LXR) and acetyl-CoA carboxylase (ACC); additionally, it enhanced the mRNA levels of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltranserase-1 (CTP-1), as well as adenosine monophosphate-activated protein kinase (AMPK) mRNA levels, in the liver of WD-induced mice. Furthermore, clitorin treatment significantly impeded lipid accumulation in oleic acid-induced HepG2 cells. Our findings demonstrated that clitorin is a potentially efficacious candidate for NAFLD treatment.
Role of NRF2 cascade in determining the differential response of cervical cancer cells to anticancer drugs- an in vitro study
Authors: Ramesh Pushkal Sinduvadi , Raja Sharanya , Udayakumar Shwethambari Harave , Chandrashekar Shruthi , Nataraj Suma M , Devegowda Devananda
Published: August 2021

The prognosis of cervical cancer patients with metastasis remains unfavorable due to the fact that most of the cervical carcinomas are either resistant to anticancer drugs or show signs of relapse after initial treatment. Therefore, it is important to control the chemoresistance as it is the key to develop effective treatment options. NRF2 (nuclear factor erythroid-2-related factor 2), a transcription factor whose aberrant expression is known to induce chemoresistance in various cancers was assessed in the study. It was evaluated whether the differences in the expression profiles of antioxidant genes regulated by NRF2 led to the variations in the sensitivities of the cervical cancer cells to cisplatin and oxaliplatin treatment. The variations in the ROS profile as well as the addition of exogenous drugs to manipulate the intracellular ROS and its effect on NRF2 pathway genes was also investigated. HeLa and SiHa cells which had significantly lower NRF2 gene levels, NQO1 enzyme activity and basal GSH levels than C33A cells were more sensitive to treatment. Levels of ROS induced were higher in HeLa than C33A cells. Overall, the differences in the cellular levels of antioxidant regulatory genes led to the differential response of cervical cancer cells to anti-cancer drugs.
First reported case of acute megakaryoblastic leukemia successfully treated with decitabine and venetoclax combined with imatinib
Authors: Xie Wanzhuo
Published: August 2021

Acute megakaryocytic leukemia (AMKL) is a rare type of acute myeloid leukemia (AML), which is characterized by its effect on megakaryocytes in bone marrow. Despite standard doses of anthracycline plus cytarabine based regimen, AMKL is notorious for its poor prognosis. With the continuous development of targeted drugs, the choice of chemotherapy regimens for AML patients has been gradually enriched. However, as far as we known, there is little data with this regimen in AMKL with decitabine and Bcl-2 inhibitor combined with imatinib. Herein, we reported the first case of adult AMKL with BCR-ABL positive successfully treated with decitabine and venetoclax combined with imatinib.
Determination of representative elementary volume (REV) for jointed rock masses exhibiting scale-dependent behavior: A numerical investigation
Authors: Sari Mehmet
Published: August 2021

Representative elementary volume (REV) is defined as the usual size of a rock mass structure beyond which its mechanical properties are homogenous and isotropic, and its behavior can be modeled using the equivalent continuum approach. Determination of REV is a complex problem in rock engineering due to its definition ambiguity and application area. This study is one of the first attempts to define a REV for jointed rock masses using the equivalent continuum approach. It is aimed to numerically search a ratio between the characteristic size of an engineering structure and pre-existing joint spacing, which are the two most important contributing elements in assessing REV. For this purpose, four hypothetical engineering cases were investigated using the RS2 (Phase2 v. 9.0) finite element (FE) analysis program. An underground circular opening with a constant diameter, an open-pit mine with varying bench heights, a single bench with a constant height, and an underground powerhouse cavern with a known dimension were executed for possible changes in the safety factor and total displacement measurements under several joint spacing values. Different cut-off REVs were calculated for FE models depending on the type of excavation and measurement method. An average REV size of 19.0, ranging between a minimum of 2 for tunnels and a maximum of 48 for slopes, was found in numerical analysis. The calculated sizes of REV were significantly larger than the range of values (5 to 10) commonly reported in the relevant geotechnical literature.
Manipulação segura de hortaliças: experiência extensionista em tempos de pandemia de COVID-19
Authors: GENTIL Daniel Felipe Oliveira
Published: August 2021

O presente relato descreve as atividades realizadas pelos integrantes da ação curricular de extensão da Universidade Federal do Amazonas, intitulada "Manipulação segura de hortaliças", em uma comunidade de agricultores familiares de Manaus, Amazonas, no decorrer do segundo semestre de 2020. Desse modo, são apresentados os objetivos, as estratégias e os instrumentos metodológicos para o desenvolvimento da ação extensionista. As novas experiências, com o uso de tecnologias de informação e comunicação e mídias digitais, possibilitaram alcançar os objetivos propostos, mesmo com as dificuldades no acesso e no uso dessas tecnologias.
A POLÍTICA DAS INTERVENÇÕES HUMANITÁRIAS
Authors: Mello Valença Marcelo , Bizzo Affonso Luiza
Published: August 2021

A partir de uma visão solidarista, este artigo explora a evolução das operações de paz ao longo do tempo de acordo com as mudanças percebidas na forma dos conflitos armados contemporâneos e seus impactos no debate sobre intervenção humanitária. Para tanto, utilizamos como objeto de análise as intervenções conduzidas sob a égide da ONU de forma a prevenir crises humanitárias. Acusamos que a politização do processo decisório no tocante às suas autorizações e definição de mandato leva ao agravamento de tais crises. Apontamos que o conceito de emergência complexa pode apontar condições de verificação para a necessidade e intervenção, complementando o princípio da Responsabilidade de Proteger e superando zonas cinzentas no tocante ao decidir quando intervir.
Hydraulic characterization of porous pipes
Authors: Silva Yasmin Fernandes , Lima Luiz Antonio , Thebaldi Michael Silveira , Barros Nogueira Virgílio Henrique , Diotto Adriano Valentim , Andrade Julia Fonseca Colombo
Published: August 2021

Increased anthropic activity in the environment leads to degradation and increased waste generation that includes tires, which can be used for the manufacture of porous pipes by extrusion for irrigation or aeration. There are no defined methodologies for the hydraulic characterization of porous pipes; in addition, their performance is questionable because the permeability of the wall in contact with water seems to decrease with time. Thus, this study aimed to perform the hydraulic characterization of porous pipes. Experiments were performed to assess the variation in permeability over time, the head loss, the friction factor, and the roughness. Statistical tests were performed to investigate possible significant differences between treatments. The results showed that the permeability varies over time and tends to decrease with each application of water. After a certain period, the permeability tends to become constant, and a stable flux can be determined, being the lowest average permeability and flux values found 0.591 × 10−15 m² 0.109 m³·m−2·s−1. There is variability in the permeability between pipe samples from the same batch as well as variability within the same sample, as indicated by the fact that some samples are similar to each other while others differ when performing a pairwise multiple comparison.
Water quality trend analysis in a citywide water distribution system
Authors: Chowdhury Keya , Akter Aysha
Published: August 2021

Rapid urbanization poses challenges to meet the increased water supply demands. Apart from the quantity, the distributed water quality often fails to meet the permissible level. This study aimed to conduct a citywide spatio-temporal variation of water quality parameters. Water sampling points were selected by applying the Analytical Hierarchical Process (AHP) technique using ArcGIS considering pipe leakage, source water quality, pipe age, and pipe materials. The Chattogram city comprises 397 km of pipes; pipe material distribution shows 71.28% PVC, 20.94% asbestos, 5.16% mild steel, 2.17% ductile, and 0.45% cast iron. The citywide pipe network was established in 1963; 20.87% of pipes aged over 30 years, 15.07% 20–30 years, 26.38% 10–20 years, and 37.68% pipelines are relatively new, i.e., within 0–10 years. Eight water quality parameters, i.e., pH, temperature, turbidity, biochemical oxygen demand after five days (BOD5), total coliform, fecal coliform, chloride, and residual chlorine, were collected from the secondary source cross-checked by field survey. Computation of the Water Quality Index (WQI) was interpolated using Inverse Distance Weighted (IDW) method to generate a WQI map. Thus, this study could be a basis to improve the treatment system and proper distribution network maintenance.
Adverse Drug Reaction Profile of Anticancer Agents in a Tertiary Care Hospital: An Observational Study
Authors: Shaikh Sana Parveen , Nerurkar Rajan
Published: August 2021

Background:

Anti-cancer agents are known to be toxic, leading to a number of adverse
drug reactions (ADRs). ADRs not only increase the financial burden on the patient/healthcare system
but also decrease the quality of life. Understanding the burden of ADR will help strengthen the
knowledge on patient safety and implement intervention strategies to reduce it.

Objectives:

The objectives of the study are as follows:
1. To study the pattern of adverse drug reactions of anticancer agents of patients admitted in the oncology
ward.
2. To assess the causality, severity, and preventability of the adverse drug reactions observed.

Methods:

This was a cross-sectional, observational study carried out in 200 adult patients in the
daycare center for chemotherapy. Details of ADRs noted in the previous and current cycles were
noted. Causality assessment was done using Naranjo and WHO scales. For severity and preventability
assessment, Hartwig Siegel and Modified Schumock Thorton scale were used, respectively.

Conclusion:

Alopecia was the most common ADR reported. Most of the ADRs could be causally
related to drugs. These ADRs were mild to moderate in severity and were not preventable. There is
a need to identify the underlying factors that predispose patients to these ADRs and target them in
future research.

Results:

Out of the total 732 ADRs encountered, alopecia was the most common ADR. The average
number of ADRs observed per patient was 3.66 + 1.59 (mean + SD). The maximum number of
ADRs were seen in Paclitaxel-carboplatin 3 weekly regimen. Nausea and alopecia were the most
common ADRs reported with most regimens.
On causality assessment, 95 (12.97%) were definitely related according to Naranjo’s Causality
scale, while 15.71% were certainly related according to the WHO scale. Of all the ADRs recorded,
47.81% were of moderate intensity, while 52.18% were of mild intensity. The majority of ADRs,
i.e., 87.59%, were not preventable.
Identification of Drug-Disease Associations by Using Multiple Drug and
Disease Networks
Authors: Yang Ying , Chen Lei
Published: August 2021

Background:

Drug repositioning is a new research area in drug development. It aims to discover
novel therapeutic uses of existing drugs. It could accelerate the process of designing novel drugs
for some diseases and considerably decrease the cost. The traditional method to determine novel therapeutic
uses of an existing drug is quite laborious. It is alternative to design computational methods to
overcome such defect.

Objective:

This study aims to propose a novel model for the identification of drug–disease associations.

Method:

Twelve drug networks and three disease networks were built, which were fed into a powerful
network-embedding algorithm called Mashup to produce informative drug and disease features. These
features were combined to represent each drug–disease association. Classic classification algorithm,
random forest, was used to build the model.

Results:

Tenfold cross-validation results indicated that the MCC, AUROC, and AUPR were 0.7156,
0.9280, and 0.9191, respectively.

Conclusion:

The proposed model showed good performance. Some tests indicated that a small dimension
of drug features and a large dimension of disease features were beneficial for constructing the
model. Moreover, the model was quite robust even if some drug or disease properties were not available.
Prospects of Treating Prostate Cancer through Apalutamide: A Mini-Review
Authors: Singh Ranapartap , Alsayadi Yunes M.M.A. , Singh Vikram Jeet , Chawla Pooja A. , Rawal Ravindra Kumar
Published: August 2021

Background:

Prostate cancer is considered the second most diagnosed cancer, and one of the most common
causes of death from cancer in men. Apalutamide is an effective, safe, and well-tolerated agent used for the treatment
of men with non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) and metastatic Hormone-Naive Prostate
Cancer (mHNPC). Androgen receptor signaling is a leading factor that drives these prostate tumors. USFDA has approved
apalutamide on 14 February 2018 as an agent that targets androgen receptor signaling through inhibition causing
significant improvement in metastasis-free survival in patients with prostate cancer.

Objective:

In this review, various aspects related to apalutamide have been summarized which involve the mechanism
of action, chemistry, synthesis, pharmacokinetics, pharmacodynamics, adverse reactions, and safety parameters.

Methods:

The literature was thoroughly searched in the relevant databases to identify studies published in this field
during recent years. Special attention has been given to apalutamide clinical trials phases and its promising future as
one of the first-line agents for the treatment of patients with advanced prostate cancer.

Results:

Ongoing trials are progressing for apalutamide monotherapy and also for its combinations in other disease
settings. The expected results of such trials will shape the future scenario of prostate cancer therapy.

Conclusion:

This review article has highlighted different aspects of Apalutamide like its mechanism of action, adverse
effects, pharmacokinetics, pharmacodynamics, clinical trials among others. The contents of this article should make an
excellent read for prospective researchers in this field.
Speech Acts in Trials of Underage Sexual Criminal Case
Authors: Ahmad Amirah , Ardi Norizah , Rashidin Rozaimah
Published: August 2021

Language usage in a court trial of a criminal case is usually associated with utterances that lead to justification of the imposed punishment for the offender. Utterances of justification are usually categorized as a performative speech act. Each utterance can be categorized into five types of speech, namely representatives, directives, commissive, expressive, and declaratives. This descriptive study uses the text analysis technique, by analysing the utterance delivered in the court trial. The findings showed that mostly the Deputy Public Prosecutor and the advocates are using the directive speech act whereas the OKT and the witnesses are using representative speech acts.
Keywords: speech acts; court trial; under age criminal case
eISSN: 2398-4287 © 2021. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer-review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.
DOI: https://doi.org/10.21834/ebpj.v6iSI5.2922