bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-examining the origin and functions of the urea cycle
Authors: Song Xiliang , Teng Linhong , Zhao Ximei
Published: April 2022

Urea cycle (UC) was first discovered in vertebrates and functioned to remove excess ammonia. To better understand the origination and evolutionary history of UC, we performed a comprehensive investigation on UC genes distribution among various lineages. We found that complete UC genes are widely distributed from prokaryotes to eukaryotes. These genes underwent purifying selection during evolution. The first enzyme carbamoyl phosphate synthase (CPS) fused and duplicated in the common ancestor of metazoans and SAR, formed pyrimidine specific and arginine/urea specific CPS. Prokaryotes and green plants retain one generalized CPS composed of separated small and large subunits. A rather unusual finding was that ARG in plants has closer relationship with agmatinase (AGM) than non-plant ARG. in silico expression analysis shows that UC genes in Arabidopsis are up-regulated in seedlings and stress conditions. ARG in Arabidopsis exhibited coordinately expression with arginine decarboxylase, the first enzyme to produce putrescine. Taken together, UC has increased in importance in vertebrates and SAR supergroup through duplication of the first enzyme. ARG in plants more resemble the paralogous AGM of prokaryotes. In plant species lacking ornithine decarboxylase, ARG were predicted to work as AGM, which participate in polyamine biosynthesis with urea as a byproduct.
Antibiotic resistance, biofilm formation and virulence genes of Streptococcus agalactiae serotypes of Indian origin
Authors: Verma Shalini , Kumari Monika , Pathak Anurag , Yadav Vikas , Johri Atul Kumar , Yadav Puja
Published: April 2022

Introduction:Streptococci are diverse group of gram-positive bacteria which causes serious life-threatening infections in developed as well as developing nations. Group B Streptococcus (GBS) or Streptococci agalactiae is one of the serologically distinct species of genus streptococcus which colonizes genitourinary and lower gastrointestinal tracts of female populations. GBS is a causative agent of various infections in new-born, non-pregnant adults and pregnant women. Understanding antibiotic resistance profiling will provide insight into the development of antibiotic prophylaxis against GBS infection. The aim of this study was to determine biofilm forming ability, presence of virulence genes and antibiotic susceptibility pattern of GBS clinical isolates.Methods: Previously, identified 30 GBS isolates were used to check antibiotic susceptibility and resistance by Kirby-Bauer disk-diffusion method. All GBS isolates were subjected to biofilm detection using the Congo Red Agar (CRA) and Crystal Violet Assay (CVA). GBS isolates were subjected to PCR for the detection of various virulence genes involved in adhesion and invasion. Results:Resistance towards penicillin was observed to be 26.6% (n=8 strains) as compared to other tested antibiotics which indicates the emergence of penicillin resistance among GBS isolates. Susceptibility for ofloxacin as 93.33% (n=28) was found to be highest, followed by azithromycin as it exhibited a 90% (n=27) susceptibility rate. Majority of the GBS isolates were found to be strong biofilm producers 70% (n=21) and 30% (n=9) were found to be moderate biofilm producers. Conclusions:We demonstrated, GBS isolates exhibited resistance towards penicillin and a negative correlation between biofilm formation and penicillin was found. Further, we found, both strong and moderate biofilm producing isolates have most of the virulence genes at genetic level, however, strong biofilm formation phenotype was not significantly associated with the expression of any virulence gene.
Mesenchymal stem cells alleviate epithelial-to-mesenchymal transition by modulating the IRE1α branch of the endoplasmic reticulum stress response
Authors: Luo Ruixi , Wei Yaqiong , Chen Peng , Zhang Jing , Wang La , Wang Wenjia , Wang Ping , Tian Weiyi
Published: April 2022

Background: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease, and it carries a poor prognosis due to the lack of efficient diagnosis and treatments. Epithelial-mesenchymal transition (EMT) plays a key role in the pathogenesis of IPF. Endoplasmic reticulum (ER) stress contributes to fibrosis via EMT-mediated pathways. Mesenchymal stem cells (MSCs) are a promising treatment for pulmonary fibrosis and ameliorate lung fibrosis via paracrine effects in animal models. However, the specific mechanisms are not known. We previously reported that MSCs attenuated endothelial injury by modulating ER stress and endothelial-to-mesenchymal transition (EndMT). The present investigated whether modulation of ER stress and EMT-related pathways played essential roles in MSC-mediated alleviation of IPF.Methods and results: We constructed a transforming growth factor-β1 (TGF-β1)-induced fibrosis model in A549 cells. TGF-β1 induced EMT in A549 cells, and MSC coculture ameliorated EMT, which was characterized by increased E-cadherin and decreased vimentin levels. ER stress participated in TGF-β1-induced EMT in A549 cells, and MSCs inhibited the expression of XBP-1s XBP-1u and BiP, which were upregulated by TGF-β1. Inhibition of ER stress contributed to MSC-mediated amelioration of EMT in A549 cells, in which modulation of the IRE1α-XBP1 branch of the ER stress pathway may play an important role. MSC transplantation alleviated bleomycin-induced pulmonary fibrosis in mice. MSC treatment decreased the expression of ER stress- and EMT-related genes and proteins, and inhibition of the IRE1α/XBP1 pathway was the most obvious effect.Conclusions: The present study demonstrated that MSCs alleviated EMT by modulating ER stress and blockade of the IRE1α-XBP1 pathway may play a critical role. The current study provides a novel vision for the application of MSCs for IPF treatment and elucidates the mechanism of the preventive effects of MSCs against pulmonary fibrosis.
Papillary Tumor of The Pineal Region Rare Pediatric CNS Tumor :Case Series Treated in King Fahad Medical City (KFMC)
Authors: Abedalthagafi Malak , Mobark Nahla Ali , Alharbi Musa , Alotabi Fahad , Alshoumer Azhar , AlSaad Abdulaziz N , AlNaqib Zaid G. , Shakweer Wafa Al , Alsolme Ebtehal , Jabarat Wael A. Al , Balbaid Ali Abdullah O.
Published: April 2022

The clinical behaviors, prognosis, and appropriate treatments of Papillary tumors of the pineal region (PTPR) are not fully defined due to the rarity of these tumors. At diagnosis, PTPR may present with clinical symptoms including headache with obstructive hydrocephalus, diplopia, vomiting, and lethargy as well as neurological signs including Argyll Robertson pupils and Parinaud’s syndrome due to compression of the dorsal midbrain, specifically the periaqueductal region with horizontal nystagmus. Radiological assessment of pineal region lesions is challenging, with a wide range of potential differential diagnoses. PTPR typically presents as a heterogeneous, well-circumscribed mass in the pineal region, which might contain cystic areas, calcifications, hemorrhages or protein accumulations. Here, we report three female pediatric patients with PTPR treated in King Fahad Medical City (KFMC) in Saudi Arabia. Histological and immunohistochemical diagnosis was confirmed by analysis of genome-wide DNA methylation profiles. This case series expands on the available reports on the clinical presentations of PTPR and provides important information on the responses to different treatment modalities.
Cholinergic signals promote esophageal squamous cell carcinoma metastasis by activating EGFR/AKT signaling pathway
Authors: Wang Tao , Ge Bei-Bei , Liu Chang , Xu Li-Juan , Wei Bin , Gao Yong
Published: April 2022

Purpose Increasing evidence has shown that the nervous system plays a vital role in the regulation of tumorigenesis. However, the regulatory mechanism of the parasympathetic nervous system in the progression of esophageal squamous cell carcinoma (ESCC) has not been elucidated. Methods Vesicular acetylcholine transporter (VAChT) protein expression was detected by immunohistochemistry (IHC) and parasympathetic nerve density was analyzed in human ESCC tissues. The co-culture model of ESCC cells and dorsal root ganglia (DRG) was established in vitro. The effects of cholinergic stimulation on cell growth, migration and invasion were investigated through CCK-8, Transwell and wound healing assays using acetylcholine (ACh). PCR and western blotting were utilized respectively for the purpose of detecting Epithelial-to-mesenchymal transition (EMT) related transcripts proteins. M3 muscarinic receptor (CHRM3) was knocked down using small interfering RNA (siRNA). RNA sequencing explored the possible altered gene transcriptome and signal pathways, which were further verified by Western blotting and CO-IP analysis. Results The intensity of parasympathetic nerve in ESCC was significantly higher than that in adjacent tissues, and was positively correlated with higher clinical staging and poorer prognosis. Co-incubation with DRG enhanced the migration and invasion ability of ESCC cells in vitro. Moreover, exogenous choline stimulation enhanced the migration, invasion ability together with EMT of ESCC cells, while CHRM3 knockdown were opposite. Mechanistically, cholinergic activation enhanced the phosphorylation levels of EGFR and AKT through CHRM3, which bound directly to EGFR.Conclusion We revealed a critical role of cholinergic signals ACh/CHRM3 in mediating the effects of parasympathetic nerve activity on ESCC through the EGFR/AKT signaling pathway, which might provide a novel therapeutic target for ESCC.
Samaki Salama for healthy child growth and sustainable fisheries in coastal Kenya: study protocol
Authors: Blackmore Ivy , Wamakota Andrew , Kamau-Mbuthia Elizabeth , Humphries Austin , Lesorogol Carolyn , Cohn Rachel , Sarange Catherine , Mbogholi Francis , Obata Clay , Cheupe Christopher , Cheupe Joaquim , Sherburne Lisa , Chapnick Melissa , Cartmill Mary Kate , Iannotti Lora
Published: April 2022

Background
One in five young children globally suffer the consequences of stunted growth and development and millions experience deficiencies in zinc, iron, iodine, vitamins A and B12, nutrients found bioavailable in fish foods. Small-scale fisheries have the potential to generate income and augment fish consumption while being environmentally sustainable if appropriately managed. However, those engaged in small-scale fisheries are often marginalized, poor, and malnourished. The Samaki Salama project seeks to better understand and address these challenges through a three-arm, longitudinal matched cluster study which evaluates the impact of an integrated nutrition social marketing and modified fishing trap intervention.
Methods
There will be 400 small-scale fisher households enrolled from Kilifi county, Kenya and residing in communities matched on location (rural), livelihoods, and child nutritional status. The sample will include mothers and other caregivers, children 6–60 months, and fishers in the family. Applying a cluster design, the matched communities will be divided into three groups: (1) control; (2) multi-tiered nutrition social marketing intervention to fishers, mothers, and health workers; and (3) multi-tiered nutrition social marketing intervention plus modified fishing traps and training. Primary outcomes include child growth, fish food intakes, and fisheries yield of mature fish. Secondary outcomes are diet diversity, child diarrheal morbidity, and fisheries revenue. A process evaluation will be used to monitor and ensure fidelity of intervention delivery.
Discussion
This study builds on a growing body of literature illustrating the effectiveness of nutrition focused social marketing campaigns to promote active engagement of participants, high compliance to the intervention, and sustained behavior change. The second intervention element of modified fishing traps that allow immature fish to escape enables participants to act on the messaging they receive and promotes sustainable fishing through increased harvest efficiency and reduced catch of immature fish. Samaki Salama’s integrated approach provides an example of how to leverage multiple disciplines to address key challenges to human and environmental health and illustrates a pathway for scaling study innovations to other small-scale fisheries systems.
Towards measuring effective coverage: critical bottlenecks in quality- and user-adjusted coverage for major depressive disorder in São Paulo metropolitan area, Brazil.
Authors: Franca Mariane Henriques , Bharat Chrianna , Novello Ercole , Hwang Irving , Medina-Mora Maria Elena , Benjet Corina , Andrade Laura Helena , Vigo Daniel V. , Viana Maria Carmen
Published: April 2022

Background: Major Depressive Disorder (MDD) contributes to a significant proportion of disease burden, disability, economic losses, and impact on need of treatment and health care in Brazil, but systematic information about its treatment coverage is scarce. This paper aims to estimate the gap in treatment coverage for MDD and identify key bottlenecks in obtaining adequate treatment among adult residents in the São Paulo Metropolitan area, Brazil. Methods: A representative face-to-face household survey was conducted among 2,942 respondents aged 18+ years to assess 12-month MDD, characteristics of 12-month treatment received, and bottlenecks to deliver care through the World Mental Health Composite International Diagnostic Interview. Results: Among those with MDD (n=491), 164 (33.3% [SE, 1.9]) were seen in health services, with an overall 66.7% treatment gap, and only 25.2% [SE, 4.2] received effective treatment coverage, which represents 8.5% of those in need, with a 91.5% gap in adequate care (66.4% due to lack of utilization and 25.1% due to inadequate quality and adherence). Critical service bottlenecks identified were: use of psychotropic medication (12.2 percentage points drop), use of antidepressants (6.5), adequate medication control (6.8), receiving psychotherapy (19.8). Conclusions: This is the first study demonstrating the huge treatment gaps for MDD in Brazil, considering not only overall coverage, but also identifying specific quality- and user-adjusted bottlenecks in delivering pharmacological and psychotherapeutic care. These results call for urgent combined actions focused in reducing effective treatment gaps within services utilization, as well as in reducing gaps in availability and accessibility of services, and acceptability of care for those in need.
High dynamic range dual-modal white light imaging system improves the accuracy of tumor bed sampling after neoadjuvant therapy for breast cancer
Authors: Liu Yueping , Yao Jianhua , Bu Hong , Zhang Meng , Liao Jun , Jia Zhanli , Qin Chenchen , Zhang Lingling , Wang Han , Liu Yao , Jiang Cheng , Han Mengxue , Li Jinze , Wang Kun , Wang Xinran
Published: April 2022

Background
Accurate evaluation of residual cancer burden (RCB) remains challenging due to the lack of appropriate techniques for tumor bed sampling. Therefore, this study evaluated the application of white light imaging system in assisting pathologists differentiating the components and location of tumor bed in specimens.
Methods
The high dynamic range dual-mode white light imaging system (HDWIS) was developed to capture anti-glare reflection and high dynamic range (HDR) transmission images and was tested in sixty specimens of modified radical mastectomy after neoadjuvant therapy. We observed the differential transmittance among tumor tissue, fibrosis tissue and adipose tissue. The sensitivity and specificity of HDWIS were compared with x-ray or visual examination to determine whether HDWIS was superior in identifying tumor beds.
Results
We found tumor tissues had lower transmittance (0.12 ± 0.03) than fibers (0.15 ± 0.04) and fats (0.27 ± 0.07) (P < 0.01). HDWIS was more sensitive in identifying fiber and tumor tissues than cabinet X-ray and visual observation (P < 0.01). In addition, HDWIS could identify more fibrosis areas than the currently used Whole Slide Imaging (WSI) did in 12 samples (12/60).
Conclusions
We have determined that HDWIS can provide more in-depth tumor bed information than X-ray and visual examination do, which will help prevent the diagnostic error in tumor bed sampling.
The Impact of the Preoperative Red Blood Cell Distribution Width Value on Weight Loss Estimation After Sleeve Gastrectomy
Authors: Erozkan Kamil , Firat Ozgur , Demir Batuhan , Vatansever Safa , Sezer Taylan Ozgur , Ersin Sinan
Published: April 2022

PurposeMorbid obesity is a common health problem. One of the most effective methods for losing weight is surgery. There are many studies to predict weight loss after surgery and these studies generally preferred inflammatory parameters, especially C-reactive protein. We aimed to evaluate whether RDW has a predictive impact on weight loss after obesity surgery.MethodsThis was a single-institution retrospective study. The lowest weight and BMI were determined and %EBMIL and %EWL were calculated. Multiple linear regression analysis was used to determine the variables affecting the %EBMIL and %EWL values. In univariate analysis between dependent and independent variables and descriptive and clinical characteristics, variables with a p-value of <0.25 were considered as confounding factors. Surgery of patients with %EMBIL ³ 50% and %EWL ³ 25% was consideredResultsHundred and ten patients were included in the study. The %EBMIL values of patients with RDW>14.5% were 10.51 units lower than patients with RDW≤14.5%. The %EWL values are 5.17 units lower. In the evaluation of successful surgeries, the probability of failure for those with RDW>14.5% is 10.93 times higher for %EBMIL and 21.55 times for %EWL.ConclusionPreoperative RDW value can be used as a predictor of weight loss and surgical success after sleeve gastrectomy. It can provide an idea about whether the patient will lose enough weight and the success of the surgery. This study will shed light on larger studies that will examine the effect of inflammatory parameters on weight loss after bariatric surgery.
Human primary Omicron BA.1 and BA.2 infections result in sub-lineage-specific neutralization
Authors: Stiasny Karin , Medits Iris , Springer David , Graninger Marianne , Camp Jeremy , Höltl Eva , Aberle Stephan , Traugott Marianna , Hoepler Wolfgang , Deutsch Josef , Lammel Oliver , Borsodi Christian ,   Elisabeth Puchhammer-Stö, Zoufaly Alexander , Weseslindtner Lukas , Aberle Judith
Published: April 2022

The recently emerged Omicron variant is the most antigenically distinct SARS-CoV-2 variant of concern to date. As the heavily mutated spike protein enables escape from neutralizing antibodies, we studied the neutralizing activities of sera after Omicron BA.1 and BA.2 infections of naïve and vaccinated individuals. We show that primary BA.1 infections yielded reduced neutralizing antibody titers against wildtype (WT), Delta, and BA.2, while serum samples from individuals after BA.2 infection showed no cross-neutralization against the other variants. Fully vaccinated individuals were still able to neutralize both Omicron sub-lineages up to three months after vaccination, and Omicron-breakthrough infections showed equal cross-neutralizing activities against WT, Delta, BA.1, and BA.2. Our data demonstrate that Omicron variants are able to enhance cross-neutralizing antibodies in pre-immune individuals. Primary infections with one of the Omicron sub-lineages, however, induced variant-specific neutralizing antibodies. In particular, BA.2 infections generated a sub-lineage-specific response, emphasizing its antigenic distance.
Desert dunes transformed by end-of-century changes in wind climate
Authors: Baas Andreas , Delobel Lucie
Published: April 2022

Sand dunes in arid regions are significant mobile landforms which require adaptation and mitigation strategies for protecting human infrastructure and economic assets from encroachment, and which play a significant role in desertification and atmospheric dust emissions. Here we show how the shape, migration speed and direction of active desert dunes around the world are projected to change by the end of this century, in response to shifts in sand-moving wind regime associated with climate change under the SSP5-8.5 scenario. We find significant transformations in dune dynamics for many sand seas and dune fields across the Sahara, The Horn of Africa, the Southern Arabian Peninsula, South-Asia, China, and Australia – as well as increased potential of sand sea expansion and re-activation of dormant dune fields – which we can link to alterations in the Hadley circulation, extra-tropical cyclone activity, and monsoon systems resulting from global warming.
MIR99AHG promotes invadopodia formation in colorectal cancer metastasis by tuning PTBP1-mediated splicing modulation of SMARCA1
Authors: Li Danxiu , Wang Xin , Miao Hui , Liu Hao , Pang Maogui , Guo Hao , Ge Minghui , Ye Xiaoni , Glass Sarah E. , Emmrich Stephan , Wang Jing , Liu Qi , Kim Taewan , Klusmann Jan-Henning , Li Cunxi , Ji Gang , Nie Yongzhan , Wu Kaichun , Fan Daiming , Song Xu , Wang Xing , Li Ling , Lu Yuanyuan , Zhao Xiaodi
Published: April 2022

Background
Metastasis leads to recurrence and death in colorectal cancer (CRC) patients; however, mechanisms underlying CRC metastasis, especially in its initial stages, remain largely unknown. In this study, we aim to identify long noncoding RNAs (lncRNAs) functionally involved in CRC metastasis initiation and their regulation that could lead to targeted therapeutics.
Methods
We performed whole transcriptome sequencing using CRC cell lines with divergent spontaneous metastatic properties. The biological roles and mechanisms of lncRNA MIR99AHG were characterized with a series of in vitro and in vivo models and molecular analyses.
Results
MIR99AHG was upregulated in CRC patients and associated with tumor stage and prognosis. MIR99AHG potently drove migration, invasion and metastasis in CRC cells, and these effects were dependent on its role in promoting invadopodia formation. MIR99AHG interacted with RNA splicing factor PTBP1, which cooperatively modulated alternative splicing of chromatin remodeling gene SMARCA1. Mechanistically, MIR99AHG acted as an address label for PTBP1 to direct its binding to the 5’ splice site of SMARCA1 intron 12, thereby facilitating inclusion of the alternative exon 13 to generate a long isoform (SMARCA1-L). The canonical SMARCA1 inhibited cell migration and invasion and suppressed a core set of genes involved in invadopodia, but the SMARCA1-L was functionally inert in metastasis suppression. Clinically, SMARCA1-L levels were positively correlated with MIR99AHG and PTBP1 in patients with metastatic CRC.
Conclusions
This study identified that invadopodia was regulated by a splicing switch of SMARCA1 due to the interaction between MIR99AHG and PTBP1, highlighting a novel regulatory mode mediated by lncRNA in alternative splicing of chromatin remodeler during CRC metastasis.
Development of molecular subtype and prognostic model related to metabolism-related genes in high-grade serous ovarian cancer: A study based on ten cohorts
Authors: Li Tianren , Sun Dan , Xue Hui
Published: April 2022

Background
High-grade serous ovarian cancer (HGSOC) is a subtype of ovarian cancer with poor survival. At present, there are no good prognostic markers to guide treatment. Tumor metabolism plays a vital role in HGSOC; however, current knowledge on this topic is incomplete.
Method
We downloaded ten ovarian cancer cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases and identified 1525 platinum-treated HGSOC samples. Metabolic-related genes were identified in the Molecular Signatures Database, and consensus clustering was used to identify HGSOC metabolic subtypes. We used the least absolute shrinkage and the selection operator to construct a metabolic-related prognostic model. Finally, we analyzed the potential biological characteristics of high- and low-risk groups by calculating the degree of immune cell infiltration and enrichment analysis.
Results
We identified two metabolic subtypes (clusters 1 and 2) in the cohort of TCGA-OV. Cluster 2 was poor, primarily enriched in carbohydrate processes, and cluster 1 was enriched primarily in respiratory processes. We constructed a 16-metabolic gene-related model that successfully predicted the overall survival rate in TCGA-OV, GPL96-OV, GPL570-OV, and GPL6480-OV cohorts. The model was suitable for predicting progression-free survival. Patients at high risk were prone to infiltration with activated mast cells, while patients at low risk were prone to infiltration of T cell follicular helper cells. Pathway enrichment analysis showed significant DNA replication enrichment in the low-risk group.
Conclusion
We performed a comprehensive analysis of metabolic genes that will aid the study of the metabolic mechanisms of ovarian cancer. Identifying metabolic gene-related subtypes and generating a prognostic model will help predict the risk of HGSOC and identify appropriate treatments to prolong survival and improve quality of life in HGSOC patients.
Quantifying Neurological Examination in 21st Century:Yilmaz-Ilbay Plantar Flexion Test, A Reliable Test for Evaluating Plantar Flexion in L5-S1 Disc Herniation
Authors: Yilmaz Murat , Ilbay Gul , Yilmaz Huriye Erbak , Ertem Onder , Erbayraktar Serhat , Ilbay Konuralp
Published: April 2022

ObjectivesTo evaluate a new examination technique that can quantitatively measure plantar flexion in L5-S1 disc herniation.Materials and methodsIn this study only subjects with L5-S1 disc herniations were included total number of patients was 32 and 18 had left sided herniations while 14 had right sided herniations. The patient to be tested stands next to a table on which they can lean with their hands. The leg closer to the table is fully flexed at the knee and the other foot is brought to maximum plantar flexion on the toes. At this point a stopwatch is started to measure the time that passes until the muscles fatigue and the heel falls. During the application of the test, the differences between the right and left plantar flexion times were noted. At the same time, three different physicians graded muscle strength with the classical "The Medical Research Council of the United Kingdom" method. All findings were recorded.ResultsYilmaz-Ilbay plantar flexion test gave the correct classification for all cases. In our series, the average age was 49.4 years (range: 23 to 78). In all patients, the time until fatigue in right and left plantar flexion was measured with the method we described, and video recording of each test was taken with the permission of the patients. Data gathered from the patients were analyzed.ConclusionsWe suggest our novel method ‘’Yilmaz-Ilbay plantar flexion test’’ as a useful, practical and effective test to detect quantitative evaluation of plantar flexion in L5-S1 herniation.
Gold nanoparticles’ concentration dependent reactivity to alendronate, memantine, and tobramycin
Authors: Mabrouk Mokhtar M. , Ebeid El Zeiny M. , Hamid Mohamed A. Abdel , Eissa Dina M.
Published: April 2022

Turkevich Gold nanoparticles are the original nanoparticles that have been modified over time. Combining nanoparticles with targeting medications such as alendronate, memantine, and tobramycin will provide additional benefits in targeting specific areas in the bone, brain, and microorganisms, respectively. The reactivity and stability of nanoparticles in the presence of various drug concentrations (micro-, nano-, and milli-levels) have been studied. The absorbance spectra of nanoparticles at λmax 520 nm were always stable with alendronate, whereas with memantine and tobramycin, the spectra were unchanged (no color change) in the nano- level over twenty minutes and red shifts (color change) occurred in the micro-level. High Resolution Transmission Electron Microscopy (HRTEM) and • Dynamic light scattering (DLS) revealed that the core diameter was relatively stable in all cases, whereas the hydrodynamic diameter and zeta potential varied with drug concentration. Increasing concentration increased hydrodynamic diameter slightly with memantine (from 64.99 to 98.41 nm), dramatically with tobramycin (from 135.3 to 332.16 nm), and almost negligibly with alendronate (from 52.08 to 58.94 nm). Zeta potential, conversely, is reduced as concentration increases. Memantine had the greatest reduction in negativity, followed by tobramycin, but alendronate had a slight increase in negativity. This research would be useful for the application of gold nanoparticles in targeted drug delivery, where the stability and reactivity of gold nanoparticles are critical.
Evaluation of the relationship between different variants of Alpha 1 antitrypsin and the severity of COVID-19 disease
Authors: Hakhamaneshi Mohammad Saeed , Khalilzadeh¹ Parisa , Abdi Mohammad , Nouri Bijan , Nasseri Karim , Nasseri Sherko
Published: April 2022

Background and Aim: In late 2019, incidence of respiratory diseases increased due to the outbreak of Corona virus. A1AT is a serine protease which its deficiency causes lung disease. In this study, it was hypothesized that different variants of SERPINA1 gene affect the severity of COVID-19 disease.Materials and methods: 42 Swab samples containing purified DNA along with RNA virus, patients with COVID-19 from the age of 25-60 years were classified into three study groups contain of 14 patients each; outpatients, inpatients and the patients that admitted in intensive care units. The PCR method were used to amplification, of SERPINA1 gene, then the PCR product were sequenced by Sanger sequencing and the results were analyzed. Results: The result of this study depicted that in the 3 outpatient, inpatient, and ICU study groups, the non-synonymous SNP, polymorphism in locus 5895 C> G (exon 2) with a frequency of 33.3% in which the amino acid alanine was changed to glycine was observed in the ICU group ,while in outpatient, inpatient groups two non-synonymous polymorphisms in locus 5646 and 5892 (exon 2) were reported , due to the high frequency of polymorphisms at position 5895 in the ICU group compared to other study groups may be related to the severity of symptoms of COVID-19 disease with this polymorphism Also, among the synonymous polymorphisms of SNP, in locus 11295 (exon 5) with a frequency of 21.4% in the outpatient group, probably showed the highest resistance against COVID-19.
Radiographic assessment of different autogenous bone grafts in the alveolar cleft: a retrospective longitudinal study
Authors: Strujak Guilherme , Marlière Daniel Amaral Alves , Medeiros Yuri de Lima , Carlini João Luiz , de Lima Antônio Adilson Soares
Published: April 2022

Purpose: To assess feasibility and maintenance of bone after alveolar cleft reconstructions using graft from iliac crest and mandibular synthesis.Methods: 51 alveolar clefts grafted with iliac crest and 51 ones grafted with mandibular symphysis bones were selected from patients aged between 7 and 12 years. At three (T1) and 12 months (T2) after surgeries, periapical radiographs were performed to measure the height of the grafted bone based on the Bergland scale. Chi-square and Mann-Whitney-Wilcoxon tests compared differences between T1 and T2 according to each bone graft. Results: From the clefts grafted with mandibular symphysis bone, 47 were classified as type I (92.5%) and 04 as type II (7.84%) at T1. At T2, 36 were classified as type II (25.49%) and 02 as type III (3.92%). In the analysis of the clefts grafted with iliac crest at T1, 48 were classified as type I (94.11 %) and three as type II (5.88%). At T2, 37 classifieds as type I (72.54%), 12 as type II (23.52%) and two as type III (3.92%). There was no statistically significant difference between treatments.Conclusions: It was concluded that iliac crest and mandibular symphysis are adequate areas from which bone grafts can be obtained for reconstruction of alveolar cleft.
Quercetin activates autophagy suppresses apoptosis, inflammation and cartilage matrix degradation in LPS-induced chondrocytes through targeting AMPK/mTOR/ULK1 signaling pathway
Authors: Wang Lei , Xu Bin , Li Shenghua
Published: April 2022

Background: Osteoarthritis (OA) is a chronic joint disease characterised by degeneration of articular cartilage, massive apoptosis of chondrocytes and changes in subchondral bone. Quercetin (QUE), a naturally occurring flavonoid, has shown potent anti-inflammatory effects; however, its effects and underlying mechanisms on OA have seldom been systematically illuminated. In this study, we explored the protective effects of QUE on repairing OA-induced chondrocytes injuries and its possible mechanisms.Methods: Human articular chondrocytes were isolated and cultured, and then induced by lipopolysaccharide (LPS). Chondrocytes were assigned into Control group (normal complete culture medium), LPS induction group (Model group), QUE+LPS induction group (QUE group), 3-MA+LPS induction group (3-MA group), 3-MA+QUE+LPS induction group (3-MA+QUE group), compound C (Com C) +LPS induction group (Com C group) and Com C+QUE+LPS induction group (Com C +QUE group). The optimal intervention concentration of LPS and QUE were selected by the Cell Cycle Kit‑8 assay (CCK‑8), osteoarthritis and inflammatory factors relevant to osteoarthritis, interleukin‑1β (LI-1β) and tumor necrosis factor‑α(TNF-α), were tested by enzyme‑linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect mRNA expressions of autophagy-related genes (LC3 Ⅱ and P62). Western blotting and Immunofluorescence staining were utilized to detect expressions of cartilage matrix degradation, apoptosis and autophagy-related proteins and of relevant proteins in the AMPK/mTOR/ULK1 signaling pathway. Cell cycle and apoptosis were detected by flow cytometry. Transmission electron microscope (TEM) images were used to detect autophagosomes, and Lyso-Tracker Red was applied to measure lysosomal activity.Results: In current study, we demonstrated that QUE can activate autophagy in LPS-induced chondrocytes. And, QUE can suppress apoptosis, inflammation and cartilage matrix degradation in LPS-induced chondrocytes by autophagy-based. Furthermore, these results demonstrated that QUE activates autophagy can suppress apoptosis, inflammation and cartilage matrix degradation in LPS-induced chondrocytes through targeting AMPK/mTOR/ULK1 signaling pathway.Conclusions: QUE activates autophagy alleviated LPS-induced chondrocytes injuries through targeting AMPK/mTOR/ULK1 signaling pathway.
Severity and prognostic factors of SARS-CoV-2-induced pneumonia: the value of clinical and laboratory biomarkers and the A-DROP score
Authors: Szabó Miklós , Kardos Zsófia , Oláh Csaba , Tamáska Péter , Hodosi Katalin , Csánky Eszter , Szekanecz Zoltán
Published: April 2022

Introduction. Numerous clinical and laboratory scores that include C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), interleukin 6 (IL-6), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine levels and oxygenation (PaO2 and SaO2) have been used for the prognosis of COVID-19. In addition, composite scores have been developed for the assessment of general state and risk in community-acquired pneumonia (CAP) that may be applied for COVID-19 as well. In this study, we assessed severity and potential prognostic risk factors for unfavourable outcome among hospitalized COVID-19 patients. We also applied the A-DROP general scoring system used in CAP to COVID-19. Patients and methods. Altogether 233 patients admitted to our center with COVID-19 were included in the study. Clinical status, several laboratory biomarkers described above, indicators of oxygenation were determined at hospital admission. We also applied the A-DROP composite scoring system that includes Age (≥ 70 years in males and ≥ 75 years in females), Dehydration (BUN ≥ 7.5 mmol/l), Respiratory failure (SaO2 ≤ 90% or PaO2 ≤ 60 mmHg), Orientation disturbance (confusion) and low blood Pressure (systolic BP ≤ 90 mmHg) to COVID-19. Results. At the time of admission, most patients had elevated CRP, LDH, ferritin, D-dimer and IL-6 levels indicating multisystemic inflammatory syndrome (MIS). Altogether 49 patients (21.2%) required admission to ICU, 46 (19.7%) needed ventilation and 40 patients (17.2%) died. In the binary analysis, admission to ICU, the need for ventilation and death were all significantly associated with the duration of hospitalization, history of hypertension or obesity, confusion/dizziness, as well as higher absolute leukocyte and neutrophil and lower lymphocyte counts, elevated CRP, PCT, LDH, ferritin, IL-6, BUN and creatinine levels, low PaO2 and SaO2 and higher A-DROP score at the time of admission (p<0.05). Conclusions. Numerous laboratory biomarkers in addition to obesity, dizziness at the time of admission and the history of hypertension may predict the need for ICU admission and ventilation, as well as mortality in COVID-19. Moreover, A-DROP may be a suitable scoring system for the assessment of general health and disease outcome in COVID-19.
Association between born by caesarian section and anxiety, self-harm: a gene-environment interaction study using UK Biobank data
Authors: jia yumeng , Cheng Shiqiang , Liu Li , Cheng Bolun , Liang Chujun , Ye Jing , Chu Xiaomeng , Yao Yao , Wen Yan , Kafle Om Prakash , Zhang Feng
Published: April 2022

Background
Limited efforts have been paid to explore the underlying genetic mechanisms of born by caesarian section (CS) affecting the risks of adult anxiety and self-harm.
Methods
Using UK Biobank cohort, logistic regression model was first applied to evaluate the associations of adult anxiety and self-harm with born by CS. Using born by CS as exposure variables, genome-wide by environment interaction study (GWEIS) was then applied by PLINK2.0 to identify associated genes interacting with born by CS for anxiety and self-harm.
Results
In the observational study, significant associations were observed between born by CS and anxiety (odds ratio (OR) = 1.25; 95% confidence interval (CI), 1.13–1.37; P = 1.19 × 10− 4), and self-harm (OR = 1.18; 95% CI, 1.07–1.29; P = 3.62 × 10− 3). GWEIS revealed multiple significant gene interacted with born by CS at P-value < 5.0 × 10− 8 for anxiety, such as DKK2 (rs13137764, P = 1.24 × 10− 9) and ATXN1 (rs62389045, P = 4.38 × 10− 8). For self-harm, significant gene-environment interactions of born by CS on self-harm were detected, such as ALDH1A2 (rs77828167, P = 1.62 × 10− 8) and DAB1 (rs116124269, P = 3.20 × 10− 8).
Conclusion
Our results suggested that born by CS was associated with the risk of adult anxiety and self-harm. We also discovered some genes interacted with born by CS might influence the risk of anxiety and self-harm, which may provide novel clues for the pathogenesis of those mental disorders.
Access and utilization of healthcare services among Rural-urban migrants in Ghana and Nigeria: scoping review protocol
Authors: Otchere Godfred , Jung Petra
Published: April 2022

Background: Internal migration patterns in both Ghana and Nigeria have tended to be more rural-urban since the second half of the 20th century. While this form of migration brings advantages to many, it also has negative impact on health outcomes. People, who migrate from the rural areas to the urban areas in their quest for better opportunities, face unpleasant and difficult conditions when accessing health care. Health system interventions designed to promote access to healthcare services particularly for the vulnerable populations are often highly fragmented and under-resourced. Consequently, rural-urban migrants compromise their health by living unhealthy lifestyles and seeking unprofessional alternative assistance for their ill health, leading to poor health outcomes.The main objective of this review is to describe and synthesize findings from the existing literature to examine rural-urban migrants’ access and utilization of healthcare services in Ghana and Nigeria.Methods: The search strategy for this scoping review will involve the PubMed, Psych INFO, Medline (via OVID), CINAHL, and EconLit electronic databases. A grey literature search will be conducted on websites such as the goggle scholar and the World Health Organization websites to find other relevant articles. The period for the search is from 2012 to 2022. All references will be exported to Endnote library. Two reviewers will independently apply the eligibility criteria to screen full text of selected titles and abstract. Thematic summary and analytical description will be used to analyze the data extracted from the included studies.Discussion: This review is envisaged to provide in-depth understanding of barriers rural-urban migrants face in accessing healthcare, their coping strategies when faced with these barriers, and possible health system interventions to address access problems they face.
Finite-State Parameter Space Maps for Pruning Partitions in Modularity-Based Community Detection
Authors: Gibson Ryan , Mucha Peter
Published: April 2022

Partitioning networks into communities of densely connected nodes is an important tool used widely across different applications, with numerous methods and software packages available for community detection. Modularity-based methods require parameters to be selected (or assume defaults) to control the resolution and, in multilayer networks, interlayer coupling. Meanwhile, most useful algorithms are heuristics yielding different near-optimal results upon repeated runs (even at the same parameters). To address these difficulties, we combine recent developments into a simpler framework for pruning a set of partitions to a subset that are self-consistent by an equivalence with stochastic block model (SBM) inference. The pruning typically highlights only a small number of “stable” partitions in our examples. We also derive resolution parameter upper bounds for fitting a constrained SBM of K blocks and demonstrate that these bounds hold in practice, further guiding parameter space regions to consider. With publicly available code (http://github.com/ragibson/ModularityPruning), our pruning procedure provides a new baseline for using modularity-based community detection in practice.
Examining Mental Health Disorders in Overweight and Obese Pediatric Patients
Authors: Carroll Rachel , Bice April A. , Roberto Anka , Prentice Christopher R.
Published: April 2022

Introduction: We investigated the frequency and variation in three mental health diagnoses among obese or overweight children and adolescents.Methods: Logistic regression was used to examine the association between each of the outcome variables – anxiety, depressive, and adjustment disorders – with the following covariates: overweight/obesity status, sex, age, and race.Results: Findings show anxiety, depressive, and adjustment disorder diagnoses were significantly higher for overweight or obese youth in our sample. Additionally, diagnosis rates for one or more of these disorders increase as children grow into adolescence. Further, we found significantly higher rates of depression and significantly lower rates of anxiety among youth who live in places with higher rates of poverty. Discussion: Findings indicate a target age for providers to focus on mental health screening among overweight/obese patients: (a) early adolescence (11-14 years old) for depression and adjustment disorder, and (b) early childhood (2-4 years old) for anxiety disorder.
Risk-adjusted design basis earthquake's adequacy for use in seismic design codes
Authors: Ghayamghamian Mohammad Reza , Zaman Mohammad
Published: April 2022

In most buildings’ seismic design codes, the design basis peak ground acceleration (PGADBE) is provided by employing a uniform-hazard approach. However, a new trend in updating seismic codes is to adopt a risk-informed method to estimate the PGADBE so-called risk-adjusted design basis peak ground acceleration (PGARDBE). An attempt is made here to examine the adequacy of the PGARDBE to fulfill the assumptions made in seismic codes for converting the maximum considered earthquake’s (MCE) intensity to PGADBE. To this end, the performance of regular intermediate steel moment frames (IMF) is assessed in terms of collapse margin (CMR) and residual drift ratios in the event of MCE and design basis earthquake (DBE), respectively. The PGARDBEs are computed for Karaj County, Iran. A set of 96 index archetypes of regular IMF is designed considering four design parameters, which include the number of stories (2, 3, 6, 9, 12, and 15), span lengths (4 and 8 meters), occupancies (residential and commercial), and seismic demands (0.15, 0.25, 0.35 and 0.45g). Although PGARDBE fulfills the acceptance criteria, results show that it does not necessarily meet the implicit assumption made in codes that the code-conforming buildings designed for the PGADBE have an acceptable CMR if the MCE occurs. This emphasizes that the PGARDBE should not be used without examining the CMR fulfillment. The results recommend that a lower limit needs to be set on PGARDBEs, which is found to be 0.35g for regions with high seismicity. This lower limit is set to achieve at least a CMR of 1.5 in the event of MCE. Outcomes also reveal that the code-conforming buildings designed with the proposed PGARDBE can fulfill both repairability and life-safety performances at the seismic demands of DBE and MCE, respectively. These buildings also have a high chance to be even considered repairable at the seismic demand of MCE. Furthermore, regardless of the employed method for estimating PGADBE, various relationships between design parameters with different performance indicators such as CMR, residual drift ratio, ductility demand, imposed drift ratio, and building’s normalized weight are presented. These relationships can be used to evaluate the buildings’ safety factor against collapse and repairability, justification of using IMF in regions with high seismicity, level of structural and nonstructural damage as well as the economic consequence of changes in PGADBE. Furthermore, they could be incorporated in developing a multi-criteria decision-making tool to decide on the optimum PGADBE leading to an affordable alternative and acceptable life-safety risk.
FACTORS OF CREATING THE INVESTMENT IMAGE OF PRIMORSKY KRAY WITHIN RUSSIA’S “TURN TO THE EAST” POLICY
Authors:   Far Eastern Federal University, Vladivostok, Davyborets Е. , Golovacheva L. ,   Far Eastern Federal University, Vladivostok, Madyanova A. ,   Far Eastern Federal University, Vladivostok
Published: April 2022

With Russia “turning to the East”，the issue of cooperation between Russian Far Eastern territories and the countries of the Asia-Pacific Region has gained special importance. For successful cooperation, it is necessary to form an effective image that will attract partners, tourists, and investors, whose funding is a necessary condition for successful development of the economy and the region as a whole. The object of the research is the image of the region. The subject of the research is the factors of forming investment image of Primorsky Kray. The objective of the research is to scientifically substantiate the factors of forming investment image of Primorsky Kray within the policy of Russia's turn to the East. Research methods. Principles of objectivity, development, universal ties have been used in the work. The study is based on traditional scientific methods - logical, theo-retical, empirical. Analysis, synthesis, induction, and deduction have been actively used. The authors examine the investment image of Primorsky Kray at the present stage: the problems the territory faces, its strengths, the direction it should be developed in the future. Nine objective factors of the investment potential of the region essential for the investment image have been identified and analyzed. The investment policy of the authorities in Primorsky Kray and the activities of development institutions have been investigated: regulatory and legal framework, ongoing activities, services provided to potential investors, etc. The image policy of the authorities of Primorsky Kray have also been analyzed