bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Evaluation of Long-Term Radiation Safety in the Vicinity of Qinshan Nuclear Power Plant, China
Authors: Cao Yiyao , Lin Junping , Zhai Kangle , Jiang Wei , Zou Hua , Ren Hong , Wang Peng , Gao Xiangjing , Zhang Meibian , Yu Shunfei , Zhao Yaoxian , Xuan Zhiqiang , Zhang Dongxia , Liu Yulian , Lou Xiaoming
Published: November 2021

To evaluate the impact of the Qinshan Nuclear Power Plant (Qinshan NPP) in normal operation on the surrounding environment and population, the radioactivity levels of drinking water and the ambient environment, as well as the residents’ cancer incidence, were continuously monitored for a period of 9 years (2012-2020). All of the gross α and β radioactivity concentrations in drinking water were less than the WHO recommended values (0.5 Bq/L for gross α and 1 Bq/L for gross β). The results of ambient environment accumulated dose monitored by thermoluminescent dosimeters (TLDs) indicated that the ambient environment radioactive level around Qinshan NPP is consistently at natural background radiation levels. The age-dependent annual effective doses due to the ingestion of tap water or exposure to the outdoor ambient environment are lower than the reference dose of 0.1 mSv/y. The corresponding excess risks are at relatively low levels. Thus, the consumption of drinking water and outdoor activities are not expected to give rise to any detectable adverse effects on the health of the public around the Qinshan NPP. For all cancers combined, the age-standardized incidence rate by the Chinese 2000 standard population of the inhabitants living around Qinshan NPP is consistent with that of Zhejiang Province as a whole. No excess incidence of leukaemia was observed around the Qinshan NPP. The incidence of thyroid cancer is high and increasing, but it is also in line with the increasing trends in Zhejiang Province and all of China. Based on current radiation risk estimates, radiation exposure is not a plausible explanation for any excess cancers observed in the vicinity of the Qinshan NPP.
Determinants of Place Birth: A Multinomial Logistic Regression and Spatial Analysis of the 2019 Ethiopian Mini Demographic and Health Survey Data
Authors: Gudayu Temesgen
Published: November 2021

Background: The presence of skilled attendants at birth and institutional delivery with quality serves significantly improves maternal and neonatal health. However, in countries where a practice of home birth is common, maternal and neonatal mortality remained high. Thus, this study aimed to determine the spatial distribution of home birth and to identify determinants of place of birth in Ethiopia. Methods: Ethiopian mini-DHS-2019 data was used in this analysis. A survey multinomial logistic regression model was used to analyze determinants of place of birth. An adjusted relative risk ratio and its 95% confidence interval with a p-value of < 0.05 and marginal effect and its 95% confidence interval with a p-value of < 0.05 were used to declare statistical significance. The Global Moran’s I analysis was done by using ArcMap 10.8 to evaluate the clustering of home birth. The magnitude of home birth was predicted by ordinary kriging interpolation. Then, scanning was done by SaTScan V.9.6 software to detect scanning windows with low or high rates of home birth. Result: Prevalence of home birth in Ethiopia was 52.19% (95% CI: 46.49 – 57.83). Whereas, only 2.99% (95% CI: 1.68 – 5.25) of mothers gave birth in the health posts. Bigger family size, family wealth, multiparity, none and fewer antenatal visits, and low cluster level coverage of 4+ antenatal visits were predictors of home birth. Homebirth was clustered across enumeration areas and it was over 40% in most parts of the country with >75% in the Somali region. SaTScan analysis detected most likely clusters in the Somali region, eastern and southern zones of Oromia region, central zones of Amhara region, and eastern zones of the South Nations Nationalities and People’s region. Conclusion: Home birth is a common practice in Ethiopia. Among public health facilities, health posts are the least utilized institutions for labor and delivery care. Nationally implementing the 2016 WHO’s recommendations on antenatal care for a positive pregnancy experience and providing quality antenatal and delivery care in public facilities through qualified providers with midwifery skills and systems of back-up in place could be supportive.
Novel Homozygous Nonsense Mutation Associated with Bardet-Biedl Syndrome in Fetus with Congenital Renal Malformation
Authors: Cai Meiying , Fu Xianguo , Xu Liangpu , Lin Na , Huang Hailong , Lin Min
Published: November 2021

Background: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive genetic disorder with clinical and genetic heterogeneity. BBS is more commonly reported in adults and children than in fetuses. Method: Here, a retrospective study of 210 fetuses with congenital renal malformation was performed. These fetuses were performed invasive prenatal diagnosis. Chromosome karyotype analysis, whole exome sequencing (WES), and a single nucleotide polymorphism array (SNP-array) were used.Results: We found the intrauterine phenotype of a fetus with enlarged kidneys, enhanced echo, and oligohydramnios, and the molecular characterizations of the fetus with BBS. The results of chromosome karyotype analysis and SNP-array on the fetus were normal. WES, however, revealed homozygous mutation of c.1177C>T (p.Arg393*) on exon 12 of the BBS1 gene, and heterozygous variation of c.2704G>A (p.Asp902Asn) on exon 22 of the CC2D2A gene. According to ACMG guidelines, c.1177C> T was identified as a pathogenic mutation and c.2704G>A was identified as an uncertain significance. Sanger sequencing showed that there was heterozygous mutation of c.1177C>T and heterozygous variation of c.2704G>A in the parents of the fetus. Conclusion: WES identified a novel homozygous nonsense mutation c.1177C>T in the BBS1 gene of a Chinese fetus with congenital renal malformation. The finding provides more insight into BBS1 mutations in Asian populations in general, and provides a basis for genetic counseling.
Recombinant neutralizing secretory IgA antibodies for preventing mucosal carriage and transmission of SARS-CoV-2
Authors: Göritzer Kathrin , Groppelli Elisabetta , Grünwald-Gruber Clemens , Figl Rudolf , Ni Fengfeng , Hu Huimin , Li Yuncheng , Liu Yalan , Hu Qinxue , Puligedda Rama Devudu , Strasser Richard , Dessain Scott , Ma Julian
Published: November 2021

Passive delivery of antibodies to mucosal sites might be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. However, monoclonal IgG antibody therapies, currently used for treatment of severe infections, are unlikely to prove useful in mucosal sites where SARS-CoV-2 resides and replicates in early infection. Here, we investigated the feasibility of producing neutralising monoclonal IgA antibodies against SARS-COV-2. We identified two class-switched mAbs that express well as monomeric and secretory IgA variants with retained antigen binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralisation activities than IgG mAbs and were able to reduce SARS-CoV-2 infection in an in vivo murine model. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.
Theoretical and Experimental Study of New Dihydroorotate Dehydrogenase and Tryparedoxin Peroxidase Inhibitors: One More Step in the Study of Leishmaniasis Infection
Authors: Espinosa-Saez Roger , Robledo Sara M. , Pineda Tatiana , Murillo Javier , Patiño Gilmar Santafé , Zúñiga César , Yañez Osvaldo , Cantero-López Plinio , Guzmán Camilo
Published: November 2021

In this study, the viability of new dihydroorotate dehydrogenase and tryparedoxin peroxidase inhibitors is reported. In vitro antileishmanial activity was evaluated using a Leishmania (V) panamensis strain, and the cytotoxicity of the compounds was assessed using U-937 cells. The in vivo therapeutic response was evaluated in golden hamsters (Mesocricetus auratus) experimentally infected with L. (V) panamensis and treated with a 1% topical formulation of compounds 4a–f. On the other hand, in silico studies considering the synthesized compounds were also carried out. All of the compounds showed promising in vitro activity, with mean EC50 effective concentration values ​​ranging from 3.8 µM to 19.3 µM. Likewise, treatment with compounds 4a–f produced improvement in most of the hamsters and cured some; in particular, those treated with compounds 4b, 4c, 4d, and 4f reacted the best. Molecular dynamics (MD) simulations, computational docking, and MM/GBSA studies indicate the promising bioavailability and absorption characteristics of the studied compounds, which are expected to be orally active. In addition, the studied 2-arylquinolines are absorbable at the blood–brain barrier, but not in the gastrointestinal tract. Finally, ADMET properties suggest that these molecules can be safely used as leishmaniasis inhibitors.
Inflammatory Cloacogenic Polyps In Children: Diagnostic Yield of Rectal Retroflexion During Colonoscopy
Authors: Kim You Ie , Joo Jung Yeon , Yang Hye Ran
Published: November 2021

Background and Aims: Inflammatory cloacogenic polyps (ICPs) are inflammatory lesions occurring around the anal transitional zone. These are rare in the pediatric population, and most reported cases are found in adults. Therefore, this study aimed to evaluate the usefulness of rectal retroflexion (RR) during colonoscopy in detecting ICPs in children.Methods: A total of 1,837 colonoscopies were performed in 1,278 children between September 2003 and August 2020 at the Seoul National University Bundang Hospital. The laboratory test results and colonoscopic and histopathological findings were retrospectively reviewed. ICP was detected using the RR and was diagnosed based on the histologic findings of the polyp. Results: A total of 69 patients were diagnosed with juvenile polyps (n = 62) or ICP (n = 7), with the latter being detected through RR. All children with ICP were diagnosed from 2013 onwards when RR during colonoscopy came to be routinely performed in our medical center. The patients with ICP were older at diagnosis and more associated with a family history of colorectal polyps than JP. Stool occult blood and the polyps’ endoscopic characteristics, such as number, location, volume, and shape, significantly varied between the two groups. Additionally, there was a statistically significant difference in the polypectomy method. During the long-term follow-up, there was no recurrence of ICP. Conclusions: Due to their location at the anorectal junction, ICPs may be overlooked during colonoscopy, leading to misdiagnosis. Therefore, a retroflexion view during colonoscopy may help detect ICPs in pediatric patients, especially those presenting with hematochezia.
Validation of a Spanish-Language Scale for Evaluating Perceived Quality of Care of Medical Abortions Before 9 Weeks Gestation
Authors: Cabedo-Ferreiro Rosa , Vicente-Hernández Maria-Mercedes , Manresa-Domínguez Josep-Maria , Gómez-Masvidal Miriam , Montero-Pons Laura , Reyes-Lacalle Azahara , Falguera-Puig Gemma
Published: November 2021

Background: Spanish Organic Law 2/2010 legalizes abortion within 14 weeks of gestation. Medical abortion with mifepristone and misoprostol is around 97% effective and is offered at primary care centers during the first 9 weeks of gestation. It consists administration of 200 mg of mifepristone by healthcare professional and of the self-administration 800 mg of misoprostol by the patient at home, along with prescribed analgesics. However, the quality of this process as perceived by patients has never been assessed. This study aims to validate a scale designed to assess the perceived quality of this process.Methods: Validation study of a Spanish adaptation of the SERVPERF scale. In total, 289 patients completed a self‑administered questionnaire consisting of 26 items previously evaluated by a group of experts. A re-test was performed on 53 of these patients 15 days later to assess interobserver consistency.Results: The non-response rate did not exceed 2.1%. The floor effect was 26% and the ceiling effect did not surpass 83%. The linearly weighted Kappa coefficient was good to excellent, in general. An exploratory factor analysis was performed with varimax rotation, obtaining a total of 7 dimensions that explain 65.9% of the variability. The internal consistency (Cronbach's alpha) for all items was 0.862.Conclusion: This psychometric instrument is valid and reliable for assessing the quality of care of medical abortion.Medical abortion is efficient, effective and eliminates the need for hospital care, anesthesia and surgical risk. However, user satisfaction has yet to be determined. This study offers a validated scale to assess perceived quality of care, their quality experience and person-centered care for abortion as a fundamental part of overall service quality as a fundamental part of overall service quality.
Integrated 3D Ionic Electrets Electronic Skin (e-Skin) For Harvesting of TENG Energy Through Push-Pull 3D Ionic Electrets and Ion-ion Hopping Mechanism
Authors: Cheedarala Ravi Kumar , Song Jung Il
Published: November 2021

The development of highly durable, stretchable, and steady triboelectric nanogenerators (TENGs) is highly desirable to satisfy the tight requirement of energy demand. Here, we presented a novel integrated polymeric membrane that is designed by PEDOT:PSSa-naphthalene sulfonated polyimide (PPNSP)-EMI. BF4 Electronic skin (e-skin) for potential TENG applications. The proposed TENG e-skin is fabricated by an interconnected architecture with push-pull 3D ionic electrets that can threshold the transfer of charges through an ion-hopping mechanism for the generation of a higher output voltage (Voc) and currents (Jsc) against an electronegative PTFE film. PPNSP was synthesized from the condensation of naphthalene-tetracarboxylic dianhydride, 2, 2’-benzidine sulfonic acid, and 4,4’diaminodiphenyl ether through an addition copolymerization protocol, and PEDOT:PSSa was subsequently deposited using the dip-coating method. Porous networked PPNSP e-skin with continuous ion transport nano-channels is synthesized by introducing simple and strong molecular push-pull 3D interactions via intrinsic ions. In addition, EMI. BF4 ionic liquid (IL) is doped inside the PPNSP skin to interexchange ions to enhance the potential window for higher output Voc and Iscs. In this article, we investigated the push-pull dynamic interactions between PPNSP-EMI.BF4 e-skin and PTFE and tolerable output performance. The novel PPNSP- EMI.BF4 e-skin TENG produced upto 49.1 V and 1.03 µA at 1 Hz, 74 V and 1.45 µA at 2 Hz, 122.3 V and 2.21 µA at 3 Hz and 171 V and 3.6 µA at 4 Hz, and 195 V and 4.43 µA at 5 Hz, respectively. The proposed novel TENG device was shown to be highly flexible, highly durable, commercially viable, and a prospective candidate to produce higher electrical charge outputs at various applied frequencies.
IVF/ICSI outcomes of euthyroid infertile women with TAI: does treating with aspirin plus prednisone matter?
Authors: Zhou Ping , Yao Qiuping , Yang Lihua , Yu Ya , Xie Jilai , Zhao Qiaohang , Feng Chun , Zhou Liming , Jin Min
Published: November 2021

Background

Thyroid autoimmunity (TAI) has been associated with adverse pregnancy outcomes. To settle with fertility problem, prescribing aspirin combined with prednisone (P+A) to women positive for antithyroid antibodies (ATA) is frequent in clinical practice, but the real effect remains controversial.
Methods

A multicenter, retrospective study was conducted in three reproductive centers from 2017 to 2020. We recruited 494 euthyroid infertile women positive for anti-thyroperoxidase and/or thyroglobulin antibodies (TPOAb and TgAb, respectively) with thyroid stimulating hormone (TSH) levels ranging 0.35-4.0mIU/L who were undergoing their first in vitro fertilization and embryo transfer (IVF-ET) cycle. Ultimately, 346 women were included of which 150 women were treated with prednisone (10mg/d) and aspirin (100mg/d), while the remaining 196 women were untreated (control group). Treatment started on the day of embryo transfer and continued until clinical pregnancy was determined.
Results

Clinical pregnancy rate (CPR) was 57.5% vs. 63.5% in the control and treated groups (P=0.414) for first fresh embryo transfer cycles and 57.8% vs. 61.8% for frozen-thawed embryo transfer cycles (P=0.606). Additionally, the live birth rate (LBR) at the fresh embryo transfer was 49.6% vs. 47.3% in the control and treated groups (P=0.762). Logistic regression revealed that P+A did not improve CPR or miscarriage rates (MR). Furthermore, we observed that low free triiodothyronine (FT3) was associated with high MR.
Conclusions

Utilizing an adjuvant treatment of P+A after the embryo transfer may be unnecessary in euthyroid women with TAI undergoing their first IVF-ET, regardless of embryo type (fresh or frozen).
Targeting Monoacylglycerol Lipase in Triple Negative Breast Cancer Reduced Tumor-Associated Inflammation, Tumor Growth and Tumor Colonization in the Brain
Authors: Benchama Othman , Tyukhtenko Sergiy , Malamas Michael S. , Williams Mark K. , Makriyannis Alexandros , Avraham Hava K
Published: November 2021

While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using the selective MAGL inhibitor AM9928 (hMAGL IC50 = 9nM, with prolonged pharmacodynamic effects of 46 hours residence time). AM9928 blocked TNBC cell adhesion and transmigration across human brain microvascular endothelial cells (HBMECs) in 3D co-cultures. In addition, AM9928 inhibited the secretion of IL-6, IL-8, and VEGF-A from TNBC cells. TNBC-derived exosomes activated HBMECs resulting in secretion of elevated levels of IL-8 and VEGF, which were inhibited by AM9928. Knockdown of MAGL by siRNA or treatment with AM9928 increased the expression of the adherent junction E-cadherin, known to be regulated by MAGL. Using in vivo studies of syngeneic GFP-4T1-BrM5 mammary tumor cells, AM9928 inhibited tumor growth in the mammary fat pads and attenuated blood brain barrier (BBB) permeability changes, resulting in reduced TNBC colonization in brain. Together, these results support the potential clinical application of MAGL inhibitors as novel treatments for TNBC.
Obtainment of Lignocellulose Degradation Microbial Community: The Effect of Acid-Base Combination After Restrictive Enrichment
Authors: Hua Binbin , Wang Xiaofen , Cui Zongjun
Published: November 2021

Acid-base combination is used in some cases expecially after restricted enrichment, and has created many lignocellulose-degrading communities. While how it worked is not well understood. In this study, compost was used as inoculum source. Induced community structure changes were analyzed with high throughput sequencing to elucidate the formation processes and determine the mechanisms of acid-base combination. We found that after restricted enrichment, retaining primarily bacteria not only included that could decompose and utilize lignocellulose, such as Clostridium and Pseudomonas, but also synergistic microbiota such as Pseudoxanomonas and Alkalobacillaceae. When the proportion of these two types of bacteria was not balanced, the degradation ability of the microbial community was low or pH changes of it did not compound regular changes , which maybe lead to the failure of restricted enrichment. Microbial communities were re-constituted by acid-base combination, whereby the degrading and synergistic strains were adjusted to a more appropriate proportion. Acid-base combination fixed the instability of microbial communities caused by randomness of restrictive screening enrichment. In this study, the mechanism of acid-base combination was analyzed, which enriched the theoretical system of restricted culture, and provided an effective and controllable technical method for obtaining high-quality lignocellulose-degrading microbial community resources.
Sorption Behavior of Lead (Pb) onto Agricultural Soils of Khyber Pakhtunkhwa, ‎Pakistan: Potentials for Leaching
Authors: Ahmad Iqbal , Khan Bushra , Gul Nida , Khan Muhammad , Iqbal Javaid , Muhammad Nisar
Published: November 2021

Lead (Pb) contamination in soil and subsequent transport in groundwater poses severe threats to the food safety and human health. In current study, the effects of soil organic matter on sorption behavior of Pb onto six agricultural soils were investigated by batch sorption experiments and microscopic characterization. Results indicated that Pb sorption onto agricultural soils was dominated by the soil organic matter content and soil texture. The decrease of organic matter content reduced the sorption capacity of Pb onto agricultural soils. Based on soil texture, the Pb sorption was highest in clay soil and lowest in silt type of soil. The overall Pb sorption was in the order of clay > clay loam > silty clay loam ≈ loam > silt loam > silt. The sorption isotherms of measured aqueous and soil phase Pb concentrations were fit well with the linear sorption model. The organic carbon normalized partition coefficients (Log KOC) ranged from 2.90 to 2.99. Linear partition coefficient (Kd) values were positively correlated with the soil properties, such as clay (R2 =0.90), OC (R2 =0.94) and pH (R2 = 0.45); however, weak correlation was found between Kd and soil sand contents (R2 = 0.12). The leachability model showed potential risk of Pb leaching from silt soil with lowest organic matter content. The findings are of significant importance for understanding potential threats of Pb to the soil ecosystem, groundwater, plants, and humans.
The Effect of Noise Sensitivity on Psychophysiological Response Through Virtual Reality Environment Experience: A Randomized Control Trial
Authors: Jo Hyun In , Lee Kounseok , Jeon Jin Yong
Published: November 2021

Noise sensitivity is a crucial factor affecting subjective psychophysiological responses to the acoustic environment of various indoor and outdoor spaces. This study examines how noise sensitivity or hyperacusis affects emotional recovery and recovery of the autonomic nervous system (ANS) response in experiencing various environments (urban and natural) of virtual reality (VR) that represents the actual environment. A total of 60 general participants with mild depression, stress, and anxiety were examined using a survey to investigate individual characteristics, including noise sensitivity, and used K-means clustering to classify the sensitivity groups. Emotional responses were measured using the Korean edition of Profile of Mood States and physiological responses were measured by assessing heart rate variability. Overall, the emotional recovery effect was greater in the natural environment than the urban environment, and the homeostatic mechanism of the ANS was better maintained, thereby increasing stress resistance. We discovered that noise sensitivity does not have much effect on psychophysiological recovery in the natural environment, but has a significant effect on emotional response in the urban environment. This can be used as basic data in seeking customized emotional recovery for individuals using VR technology in the future.
SMS: A Novel Approach for Bacterial Strain Genome Reconstruction in Multiple Samples
Authors: Wang Saidi , Ventolero Minerva Fatimae , Hu Haiyan , Li Xiaoman
Published: November 2021

BackgroundThe analysis of the bacterial strains is important for the understanding of drug resistance. Despite the existence of dozens of computational tools for bacterial strain studies, most of them are developed for the limited number of known bacterial strains. Almost all remaining tools are designed to analyze individual samples or local regions instead of the entire bacterial genomes. With multiple shotgun metagenomic samples routinely generated in a project, it is necessary to create methods to reconstruct novel bacterial strain genomes in multiple samples.ResultsWe developed a novel computational approach called SMS to de novo reconstruct bacterial Strain genomes from Multiple shotgun sequencing Samples. Tested on 702 simulated and 195 experimental datasets, SMS reliably identified the strain number, strain abundance, and strain polymorphisms. Compared with two existing approaches, SMS showed superior performance in terms of more accurate estimation of the strain number, abundance and variations.ConclusionsSMS is a useful tool for novel bacterial strain reconstruction in multiple shotgun metagenomic samples.
An Exploration of Person-Centred Approach in End-of-Life Care Policies in England and Japan
Authors: Fang Chao , Tanaka Miho
Published: November 2021

Background: Increasing evidence has suggested that a person-centred approach is beneficial not only for improving care outcomes but also for mitigating the pressure on public health systems. However, policy implementation gaps have prevented the translation of this complex framework into useful practical, ethical and moral stances for end-of-life care. This article aims to explore the meaning and implications of person-centredness in end-of-life care policy discourses.Methods: By perceiving policy documents as a medium embodied with socio-political and cultural norms, we analysed how person-centred approach in end-of-life care is constructed within specific socio-cultural contexts and the implications of these contexts on resultant care. Focusing on England and Japan, we conducted a critical policy analysis to examine and compare key policy and legal documents collected between 2007 and 2019 in these two post-industrial and socio-culturally distinctive countries. Results: Our analysis found that the person-centred approach is mobilised in policy discourses primarily through three interconnected dimensions: individual, relational and existential. While acknowledging that both countries have developed varied policy and legal mechanisms to emphasise holistic and integrated care with respect to these three dimensions, we also identified significant gaps in the policies both within and between England and Japan. They include ambiguity in defining patients’ best interests, fragmented support for social and family care and the neglect of existential needs. Conclusions: This cross-cultural analysis has revealed the complex nature of discourses around person-centred approach in English and Japanese end-of-life care policies, which often concentrate on the multifaceted aspects of experiences as one approaches the end of life. Despite this, we argue that a more holistic construction of person-centred approach is needed in end-of-life care policies not only in England and Japan but also more broadly, to encapsulate the richness of end-of-life experiences.
Evaluation of the Effects of Chitosan on Methotrexate-Induced Oral Mucositis in Rats
Authors: Bilginaylar Kani , Aykac Asli , Sayiner Serkan , Özkayalar Hanife , Şehirli Ahmet Özer
Published: November 2021

I. Background: Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. II. Methods and Results: Wistar albino rats were randomly divided into three groups, 8 in each group as follow: Control (saline via oral gavage for 5 days), MTX (60 mg/kg single dose MTX intraperitoneally on 1st day and for following 4 days saline via oral gavage), and MTX+Chitosan(1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg Chitosan via oral gavage for 4 days). After 24 hours of the last dose, animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, and tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared to the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + Chitosan group, all parameters approached the values of control group. III. Conclusion: Chitosan has been found to have a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.
WITHDRAWN: A Histopathology Model of Astrocytoma
Authors: Arabestanino Alireza , Ai Arman , Jalali Hastin
Published: November 2021

Neoplastic transformation occurs in all glial cell types of the human nervous system, producing a wide variety of clinic-pathological entities and morphological variants. As the molecular events responsible for astrocytoma formation and progression are being clarified, it is becoming possible to correlate these alterations with the specific histopathological and biological features of astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. Diagnosis, treatment, and prognostication in brain stem astrocytoma’s have been hindered by the occurrence in the same site of two distinct pathological entities-fibrillary and pilocytic astrocytoma. The small size of the specimens from this region adds an additional confounding factor in tumor classification. Nevertheless, histological assignment to either of these two prognostically different categories is often possible, especially if the importance of this distinction is recognized. In the face of a nonspecific histological diagnosis, e.g. "low-grade astrocytoma', certain radiographic and clinical features may, in combination with the pathological findings, be useful in tumor subclassification.
In Silico-guided Metabolic Engineering of Bacillus Subtilis for Efficient Biosynthesis of Purine Nucleosides by Blocking the Key Backflow Nodes
Authors: Deng Aihua , Qiu Qidi , Sun Qinyun , Chen Zhenxiang , Wang Junyue , Zhang Yu , Liu Shuwen , Wen Tingyi
Published: November 2021

Background: Purine nucleosides play essential roles in cellular physiological processes and have a wide range of applications in the fields of antitumor/antiviral drugs and food. However, microbial overproductions of purine nucleosides by de novo metabolic engineering have been a great challenge due to their strict and complex regulatory machinery involved in the biosynthetic pathways. Results: In this study, we designed an in silico-guided strategy for overproducing purine nucleosides based on the genome-scale metabolic network model in Bacillus subtilis. The metabolic flux was analyzed to predict two key backflow nodes Drm (Purine nucleotides toward PPP) and YwjH (PPP-EMP) for resolving the competitive relationship between biomass and purine nucleotides synthesis. In terms of the purine synthesis pathway, the first backflow node Drm was inactivated to block the degradation of purine nucleotides and greatly increased the inosine production to 13.98–14.47 g/L without affecting cell growth. Furthermore, releasing feedback inhibition of purine operon by promoter replacement further enhanced the accumulation of purine nucleotides. In terms of the central carbon metabolic pathways, deleting the second backflow node YwjH and overexpressing Zwf were combined to increase the inosine production to 22.01±1.18 g/L by enhancing the metabolic flow of PPP. Through switching on the flux node of the glucose-6- phosphate to PPP or EMP, the final inosine engineered strain produced up to 25.81±1.23 g/L of inosine by a pgi-based metabolic switch in shake-flask cultivation, suggesting the highest yield in de novo engineered inosine bacteria. Under the guidance of the in silico-designed strategy, a general chassis bacterium was generated for the first time to efficiently synthesize inosine, adenosine, guanosine, IMP, and GMP, providing the sufficient precursor for the synthesis of various purine intermediates. Conclusions: Overall, in silico-guided metabolic engineering successfully optimized the purine synthesis pathway by exploring the efficient targets, representing a superior strategy for efficient biosynthesis of the biotechnological products.
A Meta-analysis Study of Association Between FecB Polymorphism and Litter Size in Sheep
Authors: Barazandeh Arsalan , Mokhtari Morteza , Roudbari Zahra , Mirmahmoudi Rouhollah
Published: November 2021

Litter size is perhaps the main commercial trait since it has an observable effect on benefit in the sheep industry. Fecundity genes, play a vital role in expression of litter size. One of the most popular of these genes is the Booroola gene (FecB). In many past researches there was a dependency between the BMPR1B gene polymorphism and litter size of sheep. In the current study, a meta-analysis directed by coalescing outcoming of 9902 cases of 26 published research wherein various breeds of sheep to assess the influence of the FecB gene on litter size utilizing additive, recessive, dominant, and co-dominant genetic models. The random effects model was used for data analysis according to the Cochran Q test and I2 quantity. Under additive (SMD = 0.528), dominant (SMD = 0.468) and recessive (SMD = 0.250) models, the significant effect (P<0.01) of FecB genotypes has been identified. Furthermore, under the co-dominant (SMD = -0.050, P = 0.3332) model, the association between FecB genotypes and litter size trait had not been detected. A growth in litter size by about 0.47 lambs (Dominant model) was associated with the first copy of the FecB gene and 0.25 lambs (Recessive model) with the second copy of this gene. Consequences of the current study support the idea that BMPR1B fundamentally influenced litter size and subsequently it may be utilized for Marker-assisted selection programmers for improved genetic merit of reproductive futures and furthermore insert this gene by crossbreeding in low prolific breeds may improve reproductive characteristics.
Identification of 10 Gene Signatures as Prognostic Biomarkers for Peritoneal Metastatic Gastric Cancer
Authors: Li Junliang , Zhang Lingfang , Guo Tiankang
Published: November 2021

Background. Peritoneal metastatic gastric cancer (PMGC) is very common, and usually, the prognosis is poor. There is currently an absence of accurate methods for the early diagnosis and prediction of peritoneal metastasis (PM). This highlights the need to develop strategies to identify the risk of PMGC. Methods. We performed a comprehensive discovery of biomarkers to predict PM by analyzing profiling datasets from GSE62254. The prognostic PM-related genes were obtained using the univariate Cox regression analysis, followed by a least absolute shrinkage and selection operator regression (LASSO) to establish a risk score model. The gene set enrichment analysis (GSEA) was used to determine the pathway enrichment in both the high- and low-risk groups. The 1-, 3-, and 5-year overall survival (OS) rates and area under the receiver operating characteristic curve (ROC) were used to compare the predictive accuracy-based risk stratification. In addition, an unsupervised clustering algorithm was applied to divide patients into subgroups according to the PM-related genes. Results. We identified 10 genes (MMP12, TAC1, TSPYL5, PPP1R14A, TMSB15B, NPY1R, PCDH9, EPM2AIP1, TIG7, and DYNC1I1) for PMGC diagnosis. The OS rates between the high- and low-risk groups at 1-, 3-, and 5-years were significantly different in the training and validation sets. The AUCs at 1-, 3-, and 5-years in the training set were 0.71, 0.74, and 0.73, respectively. In the validation set, the AUCs at 1-, 3-, and 5-years were 0.68, 0.66, and 0.69, respectively. The 10 gene signatures were correlated with immune cell infiltration in both the high- and low-risk groups. In addition, based on the GSEA, several significant pathways were enriched in the high-risk PMGC group, such as the Wnt and transforming growth factor beta (TGF-β) signaling pathway and leukocyte transendothelial migration pathway. Furthermore, unsupervised cluster analysis showed that the model could distinguish the level of risk among patients with PMGC. Conclusions. Overall, 10 gene signatures were identified for PMGC risk prediction. These may be valuable in making clinical decisions to improve treatment outcomes in patients with PMGC.
Incidence and Predictors of Acute Kidney Injury Among Women With Severe Pre-eclampsia at Mbarara Regional Referral Hospital
Authors: Hassan Mariam , Mayanja Roland , Ssalongo Wasswa G.M , Robert Natumanya , Mark Lugobe Henry , Samson Okello , Muhindo Rose
Published: November 2021

BackgroundThe presence of acute kidney injury (AKI) in pre-eclampsia complicates treatment including; increasing length of hospital stay and a need to access services like dialysis which are largely expensive in resource-limited settings. We aimed to determine incidence and predictors of acute kidney injury among women with severe pre-eclampsia at Mbarara Regional Referral Hospital in southwestern Uganda. MethodsWe carried out a hospital-based prospective cohort study from 16 November 2018 to 18 April 2019, among pregnant women with severe preeclampsia followed up in the hospital. We enrolled 70 mothers with severe pre-eclampsia and eclampsia; we excluded patients with a history of chronic renal disease, chronic hypertension, and gestational hypertension.Data on socio-demographics, laboratory parameters, health system, obstetric and medical factors were collected. Baseline serum creatinine, complete blood count, and CD4 T-cell count were all done at admission (0-hour). Second serum creatinine was done at 48-hours to determine the presence of AKI. AKI was defined as a rise in serum creatinine of 0.3mg/dl or more from the baseline. The proportion of women diagnosed with acute kidney injury among the total number of women with severe pre-eclampsia was reported as incidence proportion. Univariate and multivariate logistic regression was used to establish the association of acute kidney injury and severe pre-eclampsia.ResultsIncidence of acute kidney injury was high (41.4%) among women with severe pre-eclampsia. Antenatal care attendance was protective 0.36 (0.16, 0.80), p<0.013 at bivariate analysis but had no statistical significance at multivariate analysis. Eclampsia was an independent risk factor for acute kidney injury. (aRR 2.74 (1.06, 7.08), P<0. 037.ConclusionThe incidence of acute kidney injury in patients with preeclampsia is high. Eclampsia is an independent risk factor of acute kidney injury.
Multimodal Analysis Reveals New Genetic Effectors in Parkinson'S Disease-Related Gene LRRK2 Gly2019Ser Mutation
Authors: Yao Longping , Zhang Shizhong
Published: November 2021

BackgroundMutations in the LRRK2 gene, which encodes leucine-rich repeat kinase 2 (LRRK2), generate one of the most prevalent monogenic forms of Parkinson's disease (PD). Patients with autosomal dominant PD and apparent sporadic PD, who are clinically indistinguishable from those with idiopathic PD, are found to have LRRK2 mutations, particularly the most prevalent variant Gly2019Ser. Nonetheless, potential effectors of Gly2019Ser remain unknown.MethodsWe used the GEO database to undertake and evaluate a multitiered bioinformatic investigation to look into the gene expression implicated in the development of Parkinson's disease. Individual differences in gene expression were then confirmed in whole blood samples collected in the clinic. These genetic factors were also subjected to an interaction analysis and prediction. ResultsIn total, 607 genes in the LRRK2 Gly2019Ser mutation group expressed differently from those in the wild group. The following 10 top hub genes were discovered in protein-protein interaction (PPI) networks: CD44, CTGF, THBS1, VEGFA, SPP1, EGF, VCAM1, MMP3, CXCR4, and LOX. The gene expression of CD44, CTGF, THBS1, SPP1, EGF, and LOX was considerably higher in the LRRK2 Gly2019Ser mutant group than in the LRRK2 wild group. Meanwhile, CXCR4 gene expression in the LRRK2 Gly2019Ser mutant group was significantly lower than in the LRRK2 wild group. We then confirmed the expression of the hub genes in LRRK2 Gly2019Ser mutated iPSC-induced DA cells. As a result, the levels of CD44, CTGF, THBS1, VEGFA, SPP1 were positively correlated to the mutation of LRRK2, displayed promising effectors for discriminating the pathogenesis of PD. ConclusionsWe identified CD44, CTGF, THBS1, VEGFA, and SPP1 as the potential genetic effectors responding to the mutation of LRRK2. They could be a promising mechanism for discriminating the PD and potential factors contributing to the disease's development.
Adipose Stem Cell-Derived Exosomes Exert a Synergic Anti-Inflammatory Effect with Glucocorticoids and Override Their Detrimental Effects on Rotator Cuff Tendons
Authors: Zhang Xuancheng , Li Ang , Han Kang , Zhang He , Huangfu Xiaoqiao , Huang Jinghuan , Jiang Jia , Zhao Jinzhong
Published: November 2021

Background: Glucocorticoids (GCs) injections are commonly used to relieve pain and improve function in patients with multiple shoulder disability, they cause detrimental effects on the rotator cuff tendons. Adipose stem cell-derived exosomes (ASC-Exos) reportedly recover impaired tendon matrix metabolism by maintaining tissue homeostasis. It is unclear whether additional ASC-Exos treatment overrides the detrimental effects of GCs without interfering with their anti-inflammatory effects.Methods: The in vitro studies included inflammatory analysis and cytoprotective analysis. In the inflammatory analysis, rat raw cells were treated with saline, GCs, or GCs + ASC-Exos and evaluated regarding cellular proliferation, migration, and secretion of inflammatory-related cytokines. In the cytoprotective analysis, rat tenocytes were treated with saline, GCs, or GCs + ASC-Exos and evaluated regarding cellular proliferation, migration, senescence, apoptosis, and transcription of tenocytic genes. In the in vivo studies, a subacromial injection of saline, GCs, or GCs + ASC-Exos was performed in a chronic injured-intact rotator cuff rat model. Histological and biomechanical analysis were performed 1 week to evaluate the protective effect of ASC-Exos against GCs-induced detriments on injured-intact in rotator cuffs.Results: In the in vitro inflammatory analysis, GCs treatment significantly decreased the proliferation, migration, and secretion of pro-inflammatory cytokines in raw cells, and increased the secretion of anti-inflammatory cytokines; additional ASC-Exos treatment further significantly decreased the secretion of pro-inflammatory cytokines and increased the secretion of anti-inflammatory cytokines, while restoring GCs-suppressed cellular proliferation and migration. In the in vitro cytoprotective analysis, GCs treatment significantly decreased the proliferation, migration, and transcription of tenocytic matrix molecules of tenocytes, and significantly increased their senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes; additional ASC-Exos treatment significantly improved the GCs-suppressed cellular proliferation, migration, and transcription of tenocytic matrix molecules, transcription of tenocytic degradative enzyme inhibitors, and significantly decreased the GCs-induced cell senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes. In the in vivo studies, an additional ASC-Exos injection restored the impaired histological and biomechanical properties owing to GCs administration.Conclusion: ASC-Exos may exert a stronger anti-inflammatory effect in combination with GCs, and override their detrimental effects on the rotator cuff.
Socioeconomic Disadvantage and Homicide: A Spatial Ecological Case-Control Study of US ZIP Codes
Authors: Gobaud Ariana N , Mehranbod Christina A. , Dong Beidi , Dodington James , Morrison Christopher N.
Published: November 2021

Background: Homicide is a major cause of death and a determinant of health disparities in the United States. This burden overwhelmingly affects people from racial and ethnic minority populations as homicide occurs more often in neighborhoods with high proportions of racial and ethnic minority residents. Research has identified that social and physical environmental conditions contribute to variation in homicide rates between neighborhoods; however, it is not clear why some neighborhoods with high concentrations of racial and ethnic minority residents have high homicide rates while neighborhoods with similar demographic compositions do not. The aim of this study was to assess whether relative socioeconomic disadvantage, (i.e., income inequality), or absolute socioeconomic disadvantage (i.e., income) measured at the ZIP code- and state-levels, is associated with high homicide rates in US neighborhoods, independent of racial and ethnic composition.Methods: This ecological case-control study compared median household income and income inequality in 250 ZIP codes with the highest homicide rate in 2017 (cases) to 250 ZIP codes that did not experience any homicide deaths in 2017 (controls). Cases were matched to controls 1:1 based on demographic composition. Variables were measured at both the ZIP code- and state-levels.Results: Lower median household income at the ZIP code-level contributed most substantially to the homicide rate. Income inequality at the state-level, however, was additionally significant when controlling for both ZIP code- and state-level factors.Conclusions: Area-based interventions that improve absolute measures of neighborhood socioeconomic disadvantage may reduce gaps in homicide rates.
Wheat Grain Width: A Clue for Re-Exploring Visual Indicators of Grain Weight
Authors: Haghshenas Abbas , Emam Yahya , Jafarizadeh Saeid
Published: November 2021

Background

Mean grain weight (MGW) is among the most frequently measured parameters in wheat breeding and physiology. Although in the recent decades, various wheat grain analyses (e.g. counting, and determining the size, color, or shape features) have been facilitated thanks to the automated image processing systems, MGW estimations has been limited to using few number of image-derived indices; i.e. mainly the linear or power models developed based on the projected area (Area). Following a preliminary observation which indicated the potential of grain width in improving the predictions, the present study was conducted to explore potentially more efficient indices for increasing the precision of image-based MGW estimations. For this purpose, an image archive of the grains was processed, which was harvested from a two-year field experiment carried out with 3 replicates under two irrigation conditions and included 15 cultivar mixture treatments (so the archive was consisted of 180 images taken from an overall number of more than 72000 grains).
Results

It was observed that among the more than 30 evaluated indices of grain size and shape, indicators of grain width (i.e. Minor & MinFeret) along with 8 other empirical indices had a higher correlation with MGW, compared with Area. The most precise MGW predictions were obtained using the Area×Circularity, Perimeter×Circularity, and Area/Perimeter indices. In general, two main common factors were detected in the structure of the major indices, i.e. either grain width or the Area/Perimeter ratio. Moreover, comparative efficiency of the superior indices almost remained stable across the 4 environmental conditions. Eventually, using the selected indices, ten simple linear models were developed and validated for MGW prediction, which indicated a relatively higher precision than the current Area-based models. The considerable effect of enhancing image resolution on the precision of the models has been also evidenced.
Conclusions

It is expected that the findings of the present study, along with the simple predictive linear models developed and validated using the new image-derived indices, could improve the precision of the image-based MGW estimations, and consequently facilitate wheat breeding and physiological assessments.