bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time studies of plasma membrane damage trigger cell apoptosis from sulfhydryl nanoparticles to support safety assessment of nanoscale materials
Authors: Wang Ting , Qu Guanwen , Cai Chenglong , Wang Yichuan , You Boru , Shuai Zhewei , Zhang Yixin , Feng Zhangqi , Shang Jing
Published: July 2021

Background: Sulfhydryl groups are present on the surface of nanoparticles in unburned vehicle exhaust and most air pollutants produced by combustion, which raises the risk for exposure of human. Sulfhydride nanoparticles not only penetrate the skin range from the stratum corneum to pass below the dermis, they also entering the systemis circulation from cell endocytosis pass way. The potential risk of skin and body healthy associated from sulfhydride nanoparticles were attach much attentions. It is important to illuminate the underlying toxicity of sulfhydride nanoparticles to humanbody, but the mechanisms underlying the toxicity of nanoparticles on cells remain unclear, especially the relationship from the damage of cells plasma membrane and the cell cycle.Methods: We performed time-response studies and cells-membrane interaction studies in C6 cells to observe the effects of 50nm and 200nm sulfhydryl nanoparticles on the activities, cell metabolism and cell cycle. The cells were exposed to 0, 10 or 20 Nano particles for 12, 36, 24, 48 or 72h to finish the particle- response studies. On the time of treatment, cells were collected to assess the expression of tight junction-associated proteins, P21, FBW7 and cyclin E. To further investigate the mechanisms underlying nanoparticle-induced dysregulation of tight junction-associated protein, we studied the change of lipid bilayers. Sum frequency generation optic spectrum was carried out to study the membrane change. Results: The results show that the smaller particles penetrate the plasma membrane and without bilayer disruption, whereas the larger one will pilled off one leaflet of the membrane, they are mostly trapped in endosomes. The larger ones result in slow but unrepairable cell necrosis and caused cell cycle regulation disorders via disturbing the expression of p21, cyclin E, and FBW-7. Conclusion: The results suggest that the destruction of membrane structure by the particles will cause irreversible biological damage, and particles entering cells through protein assisted process will increase the expression of cell cycle related proteins and cells self-repair can be observed from the in vitro experiments. From the interactions between mitochondria lipid model and nanoparticles, we deduced that, the efficiencies of nano-scaled drugs could be enhanced by altering the interaction models of nano systems and mitochondria. In the future, mitochondria membrane proteins would also be carefully explored to confirm their roles in the active mitochondrial uptake of nanoparticles and provide new channels for safe and effective mitochondria targeting drug delivery. Real-time studies of plasma membrane damage from sulfhydryl nanoparticles, and analysis the triggering of cell apoptosis, will support safety assessment of nanoscale materials.
The Prevalence of Small Intestinal Bacterial Overgrowth in Diabetes Mellitus: A Systematic Review and Meta-analysis
Authors: Li Xiao-Qing , Feng Xin , Jiang Zheng
Published: July 2021

Objective: The reported prevalence of small intestinal bacterial overgrowth (SIBO) among patients with diabetes mellitus (DM) is highly variable. We conducted this systematic review and meta-analysis to estimate the prevalence of SIBO in DM.Methods: A comprehensive literature search of the PubMed, Cochrane Library and Embase databases from inception to December 2020 was conducted for studies correlating SIBO with DM. Studies were screened, and relevant data were extracted and analysed. The pooled prevalence of SIBO among DM patients and the odds ratio (OR) of SIBO among DM patients compared with controls were calculated. Publication bias was assessed using Egger’s test and funnel plots.Results: Fourteen studies including 1417 diabetes patients and 649 controls met the inclusion criteria. The pooled prevalence of SIBO in DM was 29% (95% CI 20–39%). The OR of SIBO in diabetes patients was 2.91 (95% CI 0.82–10.32, p=0.1) compared with controls. Subgroup analyses showed that the prevalence of SIBO in DM was higher in studies using jejunal aspirate culture (JAC) for diagnosis (39%, 95% CI 12–66%) than in those that used the lactulose breath test (LBT) (31%, 95% CI 18–43%) or glucose breath test (GBT) (29%, 95% CI 14–43%). The prevalence of SIBO in DM was higher in studies conducted in Western countries (35%, 95% CI 21–49%) than in those conducted in Eastern countries (24%, 95% CI 14–34%), and the prevalence of SIBO in type 1 DM (25%, 95% CI 14%–36%) was not significantly different from that in type 2 DM (30%, 95% CI 13%–47%).Conclusion: Twenty-nine percent of diabetes patients tested positive for SIBO and had a significantly higher risk than the controls. The prevalence of SIBO in DM varied according to the diagnostic test performed and geographic area. DM could be a predisposing factor for the development of SIBO, especially among patients diagnosed by JAC or those in Western populations.
Ferroptosis-related Gene AKR1C1 Predicts the Prognosis of Non-small Cell Lung Cancer
Authors: Huang Fangfang , Zheng Yushi , Li Xiaoling , Luo Hui , Luo Lianxiang
Published: July 2021

BackgroundFerroptosis is a newly discovered mode of cell death distinct from apoptosis and necrosis, and its activation contributes to anticancer therapy in a variety of cancers. However, the prognostic value of ferroptosis-related genes in non-small cell lung cancer (NSCLC) remains to be further investigated.MethodsNSCLC transcriptome mRNA-seq data set and corresponding clinical data set were downloaded from the Cancer Genome Atlas (TCGA). Then, bioinformatics approaches were subsequently employed to identify potential prognostic markers. Finally, the effects of candidate markers on NSCLC cell proliferation, migration, and ferroptosis were assessed by CCK8, colony formation, wound-healing assay, and functional assays related to ferroptosis.ResultsA total of 37 common differentially expressed genes were screened based TCGA database. Six overall survival associated genes (ENPP2, ULK1, CP, LURAP1L, HIC1, AKR1C1) were selected to build survival model, of which hub gene AKR1C1 was with high expression and low ferroptosis level in NSCLC tumor. Further research showed that AKR1C1 was related with many pathways involved in the process of ferroptosis and associated with diverse cancer-infiltrating immune cells. Moreover, the results of in vitro experiments indicated that the expression of AKR1C1 was upregulated in NSCLC cell lines, and silencing AKR1C1 can inhibit the proliferation and migration of NSCLC cells and promote the occurrence of ferroptosis.ConclusionOur study revealed the potential role of ferroptosis-related gene AKR1C1 in NSCLC, which can be used for prognostic prediction in NSCLC.
Situational Analysis of Mental Health System in The West Region of Cameroon Using The World Health Organization’s Assessment Instrument for Mental Health Systems (WHO-AIMS)
Authors: michael Toguem guy , KUMAR Manassi , NDETEI David , NJENGOUE Francois Erero , OWITI Frederick
Published: July 2021

Background The burden of mental illnesses is increasing in Cameroon and there is no available published work on the mechanisms put in place to address this issue. The government recognizes this burden and tries to feel the gap. In line to this, this study aimed at describing the mental health services available in West Cameroon to provide an evidence based support to this process. Method We used the world health organization assessment instrument for mental health systems (WHO-AIMS) version 2.2 to collect, analyze, and report, data on mental health services offered in 2020 in the west region of Cameroon. We extracted our data from the registers of the different mental health facilities of the region and we interviewed staffs in these facilities and at the ministry of public health. Results The region is divided into 20 health districts, of which 06 offered mental health services. As a whole, Cameroon had a mental health policy, mental health plan, but no mental health legislation and emergency plan. There was no specific budget for mental health in the country. In the west region of Cameroon, there was no psychiatrist. Mental health services were offered by nurses, psychologists, general practitioner and neurologists; representing 1.87 human resources in mental health facilities per 100,000 population, of which 1.4 were nurses. 1 in 1.4 of these nurses worked in the main city. There was no formal link of mental health services with other sectors and no publication in the previous 5 years about mental health in the region referenced on PubMed. Conclusion In 2020, access too mental health services in the west region of Cameroon was unequitable, and was not supported by scientific evidence.
Salmonella Meningitis in Chinese Children: A Series of Three Cases Over A 13-Year Period
Authors: Zhao Jing-Li , Hua Chun-Zhen , Zhou Ming-Ming , Wang Hong-Jiao , Xie Yong-Ping , Wang Gao-Liang
Published: July 2021

Background: Salmonella is a common pathogen for gastroenteritis, but it rarely causes intracranial infection in China. To improve the understanding of pediatric Salmonella meningitis, we report three cases of Salmonella meningitis in Chinese children.Case presentation: The patients were aged from 1 day to 14 months. Fever was the first symptom in two patients, while loose stool with a little mucus occurred in one patient during the course of disease. Peripheral white blood cell count, neutrophils count, and C-reactive protein were 20.08 - 25.2 *109/L, 15.4 - 19.7 *109/L, and 1.6 - >160 mg/L, respectively. CSF analysis showed that white blood cell count, glucose, and protein were 70 - 1473 *106/L, 0.18 - 3.19 mmol/L, and 598.1 - 6639.0 mg/L, respectively. Three isolates of Salmonella were detected in cerebrospinal fluid cultures, including Salmonella newport, Salmonella paratyphi, and Salmonella typhimurium (one case per each). All strains were sensitive to ceftriaxone, ceftazidime, cefoperazone / sulbactam, meropenem, and imipenem, while one strain was resistant to ampicillin. The blood cultures were all negative. All patients were treated with carbapenems after failed therapies of cefotaxime or ceftriaxone, for a total duration of 3 - 5 weeks. One patient died, and subdural effusion occurred in one of the two survivors. Conclusions: Salmonella meningitis was rare, but the clinical conditions were serious. Carbapenems might be the first choice for treating Salmonella meningitis.
The Caucasus Territory Hot-Cold Spots Determination and Description Using 2D Surface Waves Tomography
Authors: Abrehdari Seyed Hossein , Karapetyan Jon K. , Rahimi Habib , Gyodakyan Eduard
Published: July 2021

Many questions have been raised about the thermal-mechanical development of faults movement, passive margins based on the effects of plate-boundary interactions, lithospheric processes, and mantle activity, in addition to continental thinning and generally the heat beneath our feet. This study attempts to identify and describe the hot-cold spots deep inside the Earth by using the 2D tomography velocity images obtained from surface wave seismic interferometry and regional tectonic activities in different geological units of the Caucasus region continent-continent ongoing collisional-compressed edge of the Eurasian-Arabic plates. Furthermore, this study could be helpful in identifying and proper understanding of the location of hotspots as renewable energy resources (geothermal) in areas near tectonic plate boundaries, rocks, arcs, and sediment interactions. To conduct this, after the preliminary correction of the raw data, a generalized 2D linear inversion procedure has been applied to construct the surface wave tomography to generate group velocity maps in a period range of 5-70 seconds and grid spacing of 0.2º×0.5º. The digital records of 800 earthquakes (M≥4) have been collected over the Caucasus region and these signals, recorded during the period of 1999-2018, come from 45 three-component broadband and short-period digital stations.
Body Mass Index and Healthcare Costs: Using Genetic Variants from the HUNT Study as Instrumental Variables
Authors: Edwards Christina Hansen , Vie Gunnhild Åberge , Edwards Christina Hansen
Published: July 2021

Background: Past studies have found associations between obesity and healthcare costs, however, these studies have suffered from bias due to omitted variables, reverse causality, and omitted variables. Methods: We used genetic variants related to body mass index (BMI) as instruments for BMI; thereby exploiting the natural randomization of genetic variants that occurs at conception. We used data on measured height and weight, genetic information, and sociodemographic factors from the Nord-Trøndelag Health Studies (HUNT), and individual-level registry data on healthcare costs, educational level, registration status, and biological relatives. We studied associations between BMI and general practitioner (GP)-, specialist-, and total healthcare costs in the Norwegian setting using instrumental variable (IV) regressions, and compared our findings with effect estimates from ordinary least squares (OLS) regressions. The sensitivity of our findings to underlying IV-assumptions was explored using two-sample Mendelian randomization methods, non-linear analyses, sex-, healthcare provider-, and age-specific analyses, within-family analyses, and outlier removal. We also conducted power calculations to assess the likelihood of detecting an effect given our sample 60 786 individuals.Results: We found that increased BMI resulted in significantly higher GP costs; however, the IV-based effect estimate was smaller than the OLS-based estimate. We found no evidence of an association between BMI and specialist or total healthcare costs. Conclusions: The effect of obesity on GP- and specialist costs may have been overestimated in previous studies.
Bakuchiol Dimers From Psoraleae Fructus That Inhibit Nitric Oxide Production in RAW264.7 Macrophages Cells
Authors: Xu Qingxia , Lv Qian , Liu Lu , Zhang Yingtao , Yang Xiuwei
Published: July 2021

Background: Dried fruit of Psoralea corylifolia L. (Psoraleae Fructus) is one of the most popular traditional Chinese medicine with treatment for nephritis, spermatorrhea, pollakiuria, asthma, and various inflammatory diseases. Bakuchiol is main meroterpenoid with bioactive diversity from Psoraleae Fructus.Methods: Various column chromatography methods were used for isolation experiment. Structures and configurations of these compounds were determined by spectroscopic methods and single-crystal X-ray diﬀraction. Their inhibition on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were evaluated by the Griess reaction.Results: Twelve unpresented bakuchiol dimmers, bisbakuchiols M–U (1–9) and bisbakuchiol ethers A–C (10–12), along with five known compounds (13–17), were isolated from the fruits of Psoralea corylifolia L. Compounds 1–3 and 10–14 exhibited inhibitory activities against LPS-induced NO production in RAW264.7 macrophages, and the inhibition of compound 1 (IC50 = 11.47 ± 1.57 μM) was equal to that of L-NIL (IC50 = 10.29 ± 1.10 μM) as a positive control.Conclusions: Seventeen bakuchiol dimers (1–17), including 12 undescribed dimers and 5 known compounds, were isolated. Bisbakuchiol M (1), whose other bakuchiol unit was cyclized to form a 6/6/5 tricyclic system, was a new skeleton compound. Some compounds exhibited NO inhibition activities and the inhibition of compound 1 was equal to that of L-NIL, a positive control. These findings suggested that Psoraleae Fructus provided natural anti-inflammatory constituents and bisbakuchiol M had the potential to be novel NO inhibitor.
Severe Adaptive Immune Suppression May be Why Patients with Severe COVID-19 Cannot be Discharged From the ICU Even After Negative Viral Tests
Authors: Zhou Yue , Liao Xuelian , Song Xiangrong , He Min , Xiao Fei , Jin Xiaodong , Xie Xiaoqi , Zhang Zhongwei , Wang Bo , Zhou Chenliang , Kang Yan , Zhang Wei
Published: July 2021

Background: During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. In general, continuous negative viral tests are thought to indicate that the virus has been cleared from the body and that the patients can be considered "recovered". However, because these patients were still critically ill, they obviously had not truly recovered from the disease. We sought to investigate why these patients were still critically ill even though they exhibited negative viral tests by analyzing the gene expression profiles of their peripheral immune cells using transcriptome sequencing.Methods: Fourteen severe COVID-19 patients with at least 3 negative virus tests but were still in critical ill and could not be discharged from the ICU were enrolled. Blood samples from 14 patients and 5 healthy donors were collected. Total RNA was extracted from nucleated cells for RNA-Sequencing. FeatureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. Results: All enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. This adaptive immune suppression is unlikely due to classic immune checkpoint molecules such as PD-1 or long-term use of glucocorticoids but may be caused by an unknown mechanism that has not yet been discovered.Conclusions: Our findings strongly suggest that an initial recovery of these severe COVID-19 patients, as indicated by negative viral tests, may not indicate actual recovery. They still suffer from secondary infections for a long period of time because of severe adaptive immunosuppression and need to receive a variety of antibiotics, antifungal drugs, or combination therapies. Appropriate methods should be used to detect their adaptive immune function, and appropriate immunotherapy that can activate the adaptive immune response should be developed. Trial registration: Not applicable (this study does not involve intervention on human participants).
Interactome Based Identification and Validation of Prefoldin 5α for Prognosing CNS Leukemia in B-All Patients
Authors: Xavier Tessy , Vijayachandran Lakshmi Sumitra , Mony Ullas , Augustine Anitha , Sidharthan Neeraj , Keechilat Pavithran , Sundaram K.R , Menon Krishnakumar N
Published: July 2021

BackgroundThe gold standard for central nervous system (CNS) B cell acute lymphoblastic leukemia (B-ALL) diagnosis is cerebrospinal fluid (CSF) cytology with poor sensitivity. Thus, prophylactic intrathecal chemotherapy is implemented, which has severe neurological consequences necessitating discovery of CNS leukemia prognostic markers. MethodsTwo-dimensional (2D) far-western interactome analysis was performed to identify CNS+ve/-ve B-ALL CSF reactivity to lymphoblastic proteins profiled on a 2D-western blot. Those specific CNS+ve reacting spots were identified using mass spectrometry. The identified proteins were further validated by both 1D western and ELISA. An ROC curve was generated to identify the cut-off value for prognostication of CNS leukemia in B-ALL patients. ResultsUsing interactome analysis with B-ALL CNS+ve/-ve CSF, we identified prefoldin 5α (PFDN5α), cytokine induced protein 29 (CIP29), enoyl CoA hydratase (ECH1) and peroxiredoxin 6 (PRDX6). Among these proteins, PFDN5α showed statistically significant consistent low reactivity to CNS+ve CSF compared to CNS-ve. Further validation of PFDN5α-CSF reactivity using 1D western and ELISA platform confirmed our interactome analysis. Receiver Operating Characteristic (ROC) curve analysis generated from B-ALL CNS +ve (n = 25) and –ve (n = 40) CSF samples identified PFDN5α-CSF reactivity cut-off value as 0.456. In contrast, CIP29, ECH1 and PRDX6 proteins did not show any differences in CSF reactivity as seen in interactome analysis. ConclusionsUsing far-western interactome approach, we identified the prognostic significance of PFDN5α in predicting CNS leukemia. Further validation by 1D western and ELISA confirmed the significance of differential CSF reactivity of CNS+ve/-ve B-ALL CSF to PFDN5α towards prognostication of CNS leukemia. ROC curve analysis identified the cut-off value for CNS leukemia prediction as 0.456. Values above or below 0.456 could discriminate B-ALL patients either not requiring or requiring intrathecal chemotherapy respectively. Considering the prophylactic chemotherapy associated neurological consequences, PFDN5α-CSF reactivity based prognosis of CNS leukemia is important in avoiding prophylactic intrathecal chemotherapy for the effective clinical management of patients.
The Complete Chloroplast Genome of Chinese Hickory (Carya Cathayensis) and Genetic Comparison to Its Closely Related Species
Authors: Zhu Xiangtao , Shen Jianshuang , Li Xueqin , Chen Xia , Huang Xiaoling , Jin Songheng
Published: July 2021

Background: Carya cathayensis, an important economic nut tree, is narrowly endemic to Eastern China in the wild. Although the nuclear genome of this plant has been reported recently, its chloroplast (cp) genome is yet to be decrypted. Results: Here, the complete cp genome of C. cathayensis was sequenced with NGS Illumina HiSeq2500, analyzed, and compared to its closely related species. The cp genome is 160,825 bp in length with an overall GC content of 36.13%. It displays a quadripartite structure with a large single copy (LSC) region of 90,127 bp and a small single copy (SSC) region of 18,760 bp, separated by a pair of inverted repeats (IRs) of 25,969 bp. The genome contains 131 genes, including 86 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The codon usage frequency and repeat sequences (including 252 simple sequence repeats (SSRs) and 55 long-repeats were identified. Conclusions: Phylogenetic analysis revealed that Juglandaceae is monophyletic, and that C. cathayensis is sister to C. kweichowensis and C. sinensis. Comparison of the C. cathayensis cp genome with those of the closely related species in Juglandaceae revealed that the noncoding regions are highly mutated, suggesting a great potential in phylogenetic researches. The newly characterized cp genome of C. cathayensis provides valuable information for further studies of this economically important species.
Pseudoexfoliation Syndrome Association with Aging and Ocular Changes in Cornea, Lens, Retina
Authors: Rumelaitienė Ugnė , Žaliūnienė Dalia , Špečkauskas Martynas , Tamošiūnas Abdonas , Radišauskas Ričardas , Peto Tunde , Larsen Morten Bøgelund , Bernotienė Gailutė
Published: July 2021

Purpose: To examine the 10-year incidence of the pseudoexfoliation syndrome (PEX), possible risk factors of PEX, and its association with aging and ocular changes in cornea, lens, retina within a population-based follow-up study.Methods: The baseline examination was conducted in 2006 on a random sample of 1,033 adult participants from Kaunas city (Lithuania) population. Out of them 631 participants returned to the follow-up study in 2016. Ophthalmological examination included keratometry, central corneal pachymetry, after diagnostic mydriasis lens opacification was evaluated by LOCS III International classification, PEX was diagnosed by the presence of typical grayish-white exfoliation material on the anterior capsule surface of the lens.Results: During the 10 years follow-up, the prevalence of the PEX increased from 9.8% to 34.2%. Nuclear cataract was diagnosed the most both in the PEX-group and those without, however, there was no statistically significantly increased risk of developing cataract in those with PEX when compared to those without PEX (OR 1.2; p=0.61). Central corneal thickness (CCT) was thinner in PEX group (529±34μm) and in the eldest group (525±36μm) (p<0.001). Compared to baseline, corneal curvature (CC) became steeper both in the PEX and the no-PEX groups during the follow-up (p=0.013), but the difference didn’t reach significance between groups. The biggest part of corneal astigmatism was with-the-rule in no-PEX and PEX groups (37 vs 148; p>0.05). The age, sex and PEX had no influence to age related macular degeneration distribution.Conclusion: The prevalence of the PEX increased significantly with age. CCT was thinner in PEX group and in elder people. CC was flatter in PEX group.
Risk Factors and Incidence for HAI in Elderly Patients Undergoing Neurosurgery in a Single Center
Authors: Liu Yunyun , Zhou Tian , Ji Yuanyuan , Zhang Hongqi , Wang Jun
Published: July 2021

Background: Health care-associated-infection (HAI) is an important issue in neurosurgery department. With the aging population, we are receiving an increasing number of elderly patients who have a higher risks of HAI. AIM: We want to better understand risk factors of HAI and prevent HAI in elderly patients who accept neurosurgeries.Methods: This was a case-control study. We took review of the medical records of patients aged 60 and older who underwent neurosurgical operations from 1 January to 31 December 2016 in a single centre. Patients with infection and intubation before admission were excluded. Risk factors and outcomes were analysed, including age, sex, activities of daily living (ADL) score, smoking history, emergency admission status, ICU stay, ventilator use, ventilation time, diabetes, coronary heart disease, immune system disease, consciousness at admission, albumin decrease, blood sugar, unplanned second operation, indwelling venous catheter, external ventricular drainage (EVD), discharge ADL, length of stay (LOS), and medical costs.Results: A total of 1757 geriatric patients over 60 years underwent neurosurgical procedure were enrolled. Their age ranged from 60 to 93 years, with an average of 67.56 ± 6.16 years, including 1083 males(61.6%)and 674 females(38.4%).Among 1757 patients in 14703 hospital days, 95 cases of infection were diagnosed with HAIs in 78 patients, The HAI rate was 4.4% (78/1757) and HAI case rate was 5.4%(95/1757),incidence of HAI in neurosurgical geriatric patients was 6.5‰. Of these 95 infections, the most common types were pneumonia (65.3%), followed by primary bloodstream infection (13.7%), central nervous system infection (8.4%), urinary tract infection (6.3%), and wound infection (6.3%). Multivariable logistic regression showed that the independent risk factors for HAI in elderly patients were ICU stay, mechanical ventilation, plasma albumin below 35g/L, unplanned reoperation, and venous catheterization.Conclusions: To prevent HAI, we should improve the ICU standards, decrease ventilation time, improve the nutrition supply, and dynamically evaluate the necessity of deep venous catheters and remove them as early as possible. Such measures could not only help reduce HAI and shorten hospital stays for elderly patients, but also decrease medical insurance cost for the government.
On geometry parameterization for simulation-driven design closure of antenna structures
Authors: Koziel Slawomir , Pietrenko-Dabrowska Anna
Published: July 2021

Full-wave electromagnetic (EM) simulation tools have become ubiquitous in antenna design, especially final tuning of geometry parameters. From the reliability standpoint, the recommended realization of EM-driven design is through rigorous numerical optimization. It is a challenging endeavor with the major issues related to the high computational cost of the process, but also the necessity of handling several objectives and constraints over often highly-dimensional parameter spaces. From the numerical perspective, making decisions about the formulation of the optimization problem, the approach to handling the design constraints, but also parameterization of the antenna geometry, are all non-trivial. At the same time, these issues are interleaved, and may play an important role in the performance and reliability of the simulation-based design closure process. This paper demonstrates that the approach to arranging the structure parameterization (e.g., the use of absolute or relative parameters) may have a major effect of the optimization outcome. Our investigations are carried out using three broadband monopole antennas optimized under different scenarios and using different parameterizations. In particular, the results indicate that relative parameterization is preferred for optimization of input characteristics, whereas absolute parameterization is more suitable for size reduction.
Regeneration of Collagen Fibrils at the Papillary Dermis by Reconstructing Basement Membrane at the Dermal-Epidermal Junction
Authors: Iriyama Shunsuke , Ogura Yuki , Nishikawa Saori , Hosoi Junichi , Amano Satoshi
Published: July 2021

The epidermal basement membrane deteriorates with aging. We previously reported that basement membrane reconstruction not only serves to maintain epidermal stem/progenitor cells in the epidermis, but also increases collagen fibers in the papillary dermis. Here, we investigated the mechanism of the latter action. Collagen fibrils in the papillary dermis were increased in organotypic human skin culture treated with matrix metalloproteinase and heparinase inhibitors. The expression levels of COL5A1 and COL1A1 genes (encoding collagen type V α 1 chain and collagen type I α 1 chain, respectively) were increased in fibroblasts cultured with conditioned medium from a skin equivalent model cultured with the inhibitors and in keratinocytes cultured on laminin-511 fragment-coated plates. We then examined cytokine expression, and found that the inhibitors increased the expression of PDGF-BB (platelet-derived growth factor consisting of two B subunits) in epidermis. Expression of COL5A1 and COL1A1 genes was increased in cultured fibroblasts stimulated with PDGF-BB. Further, the bifunctional inhibitor hydroxyethyl imidazolidinone (HEI) increased skin elasticity and the thickness of the papillary dermis in the skin equivalent. Taken together, our data suggests that reconstructing the basement membrane promotes secretion of PDGF-BB by epidermal keratinocytes, leading to increased collagen expression at the papillary dermis.
Validity of a Portable Spirometer in the Communities of China
Authors: Xiao Shan , Wu Fan , Wang Zihui , Chen Jianmin , Yang Huajing , Zheng Youlan , Deng Zhishan , Peng Jieqi , Wen Xiang , Huang Peiyu , Dai Cuiqiong , Lu Lifei , Zhao Ningning , Ran Pixin , Zhou Yumin
Published: July 2021

Background: The lack of simple and affordable spirometry has led to the missed and delayed diagnoses of chronic respiratory diseases in communities. The PUS201P is a portable spirometry developed to solve this problem.Objective: We aimed to verify the consistency of the PUS201P spirometer with conventional Jaeger spirometer.Methods: In this cross-sectional study, we randomly recruited 202 subjects aged ＞40 years. Testing with the portable spirometry and conventional spirometry were performed on all participants. We compared forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC measured by the PUS201P device with the conventional spirometer. Pearson correlation coefficient and Interclass Correlation Coefficient (ICC) were assessed to confirm the consistency of the measures from two instruments. Bland–Altman graph was created to assess the agreement of the measures from two devices.Results: 202 participants were included in this study. The ICC on forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC measured by the portable spirometer and the conventional spirometer were 0.95[95% confidence interval (CI): 0.94-0.96], 0.92(95%CI: 0.90-0.94), 0.93(95%CI: 0.91-0.95), respectively. The Bland-Altman plots showed that the mean difference between the measures from two spirometers are always located in the 95% limits of agreement (LoA). Conclusions: Our results support that the measures from the portable spirometer and the conventional spirometer have a good agreement and reproducibility. And the portable spirometer is a reliable tool to screen and diagnose chronic airway diseases in the primary care settings.
Computational mass spectrometry accelerates C=C position-resolved untargeted lipidomics using oxygen attachment dissociation
Authors: Uchino Haruki , Tsugawa Hiroshi , Takahashi Hidenori , Arita Makoto
Published: July 2021

Mass spectrometry-based untargeted lipidomics has revealed the lipidome atlas of living organisms at the molecular species level. Despite the double bond (C=C) position being a crucial factor for enzyme preference, cellular membrane milieu, and biological activity, the C=C defined structures have not yet been characterized. Here, we present a novel approach for C=C position-resolved untargeted lipidomics using a combination of oxygen attachment dissociation and computational mass spectrometry to increase the rate of annotation. We validated the accuracy of our platform as per the authentic standards of 21 lipid subclasses and the biogenic standards of 51 molecules containing polyunsaturated fatty acids (PUFAs) from the cultured cells fed with various fatty acid-enriched media. By analyzing human and mice-derived biological samples, we characterized 675 unique lipid structures with the C=C position-resolved level encompassing 22 lipid subclasses defined by LIPID MAPS. Our platform also illuminated the unique profiles of tissue-specific lipids containing n-3 and/or n-6 very long-chain PUFAs (carbon M 28 and double bonds a 4) in the eye, testis, and brain of the mouse.
Variation in Use of Damage Control Laparotomy for Trauma By Trauma Centers in the United States, Canada, and Australasia
Authors: Roberts Derek J. , Faris Peter D. , Ball Chad G. , Kirkpatrick Andrew W. , Moore Ernest E. , Feliciano David V. , Rhee Peter , D’Amours Scott , Stelfox Henry T.
Published: July 2021

Background: It is unknown how frequently damage control (DC) laparotomy is used across trauma centers in different countries. We conducted a cross-sectional survey of trauma centers in the United States, Canada, and Australasia to study variations in use of the procedure and predictors of more frequent use of DC laparotomy.Methods: A self-administered, electronic, cross-sectional survey of trauma centers in the United States, Canada, and Australasia was conducted. The survey collected information about trauma center and program characteristics. It also asked how often the trauma program director estimated DC laparotomy was performed on injured patients at that center on average over the last year. Multivariable logistic regression was used to identify predictors of a higher reported frequency of use of DC laparotomy.Results: Of the 366 potentially eligible trauma centers sent the survey, 199 (51.8%) trauma program directors or leaders responded [United States=156 (78.4%), Canada=26 (13.1%), and Australasia=17 (8.5%)]. The reported frequency of use of DC laparotomy was highly variable across trauma centers. DC laparotomy was used more frequently in level-1 than level-2 or -3 trauma centers. Further, high-volume level-1 centers used DC laparotomy significantly more often than lower volume level-1 centers (p=0.02). Nearly half (48.4%) of high-volume volume level-1 trauma centers reported using the procedure at least once weekly. Significant adjusted predictors of more frequent use of DC laparotomy included country of origin [odds ratio (OR) for the United States vs. Canada=7.49; 95% confidence interval (CI)=1.39-40.27], level-1 verification status (OR=6.02; 95% CI=2.01-18.06), and the assessment of a higher number of severely injured (Injury Severity Scale score >15) patients (OR per-100 patients=1.62; 95% CI=1.20-2.18) and patients with penetrating injuries (OR per-5% increase=1.27; 95% CI=1.01-1.58) in the last year.Conclusions: The reported frequency of use of DC laparotomy was highly variable across trauma centers. Those centers that most need to evaluate the benefit-to-risk ratio of using DC laparotomy in different scenarios may include high-volume, level-1 trauma centers, particularly those that often manage penetrating injuries.
Identification of de novo mutations in the Chinese ASD cohort via whole-exome sequencing unveils brain regions implicated in autism
Authors: Yuan Bo , Wang Mengdi , Wu Xinran , Cheng Peipei , Zhang Ran , Zhang Ran , Yu Shunying , Zhang Jie , Du Yasong , Wang Xiaoqun , Qiu Zilong
Published: July 2021

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts is still under-represented in the genome-wide genetic studies. Here we performed whole-exome sequencing on 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combining with single-cell sequencing data from the developing human brain, we found that expression of genes with de novo mutations were specifically enriched in pre-, post-central gyrus (PRC, PC) and banks of superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and health controls, we found that the gray volume of the right BST in ASD patients significantly decreased comparing to health controls, suggesting the potential structural deficits associated with ASD. Finally, we found that there was decrease in the seed-based functional connectivity (FC) between BST/PC/PRC and sensory areas, insula, as well as frontal lobes in ASD patients. This work indicated that the combinatorial analysis with genome-wide screening, single-cell sequencing and brain imaging data would reveal brain regions contributing to etiology of ASD.
Synergistic regenerative therapy of thin endometrium by human placenta-derived mesenchymal stem cells encapsulated within hyaluronic acid hydrogels
Authors: Lin Yifeng , Dong Shunni , Ye Xiaohang , Liu Juan , Li Jiaqun , Zhang Yanye , Tu Mixue , Wang Siwen , Ying Yanyun , Chen Ruixue , Wang Feixia , Ni Feida , Chen Jianpeng , Du Binyang , Dan Zhang
Published: July 2021

Background: Endometrial injury is one of the major causes of thin endometrium and subfertility. Stem cell-based therapies have made strides towards further efficacious treatment of injured endometrium. However, reported therapeutic stem cells that can be used for thin endometrium are difficult to acquire for large-scale clinical application. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs for their robuster expansion ability, lower immunogenicity as well as extensive sources. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and ﻿possible underlying mechanisms.﻿Methods: The murine endometrial injury model was established by ethanol (95%) perfusion, with further intrauterine instillation of treating materials. The retention time of HP-MSCs ﻿was detected by in vivo imaging and ex vivo frozen section. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry (Ki67). The stromal and glandular cells were isolated from the human endometrium to determine proliferation, migration, signaling pathway changes via EdU assay, transwell migration assay, and western blot respectively. Results: Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri compared with normal HP-MSCs. ﻿In vitro data showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness, decrease fibrous area, promote the proliferation of endometrial cells, and improve the embryo implantation rate. In vitro assays indicated that HP-MSCs-HA could not only promote the proliferation and migration of human endometrial stromal via the JNK/Erk1/2-Stat3-VEGF pathway but also promote the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. Conclusion: Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings.
A Comprehensive Analysis of Renal Cell Carcinoma as First and Second Primary Cancers
Authors: Chen Jinchao , Lou Jianmin , He Yedie , Zhu Zhenjie , Zhu Shaoxing
Published: July 2021

Background Renal cell carcinoma may be a first primary cancer (first primary RCC, 1st RCC), or it can occur as a second primary RCC (2nd RCC) in patients with a previous history of malignancy. However, the studies of comparison between 2nd RCC and 1st RCC are rare.Methods Patients with localized RCC were retrospectively collected. They were classified as 2nd RCC or 1st RCC according to a previously diagnosed cancer, including 113 cases of 2nd RCC and 749 cases of 1st RCC. ResultsThe most common types of extrarenal malignancies in patients with 2nd RCC include lung, colorectal, breast, gynecological, and gastric cancers. The age and smoking rate of 2nd RCC patients were significantly higher than those of 1st RCC patients. Fewer 2nd RCC patients had clinical symptoms and a large renal mass. One hundred and eight (95.6%) patients with 2nd RCC received surgical interventions. All patients with 1st RCC underwent renal surgery. More patients with 2nd RCC underwent partial nephrectomy. Pathologically, there was no significant difference in postoperative pathological types between the 2nd and 1st RCCs. However, the 2nd RCCs commonly occurred in the early stages. The median overall survival (OS) of 2nd RCC patients was 117 months, which was shorter than that of 1st RCC patients. ConclusionsPatients with 2nd RCC are not uncommon. More attention should be paid to screening for 2nd RCC in cancer survivors. There are some differences between patients with 2nd and 1st RCCs that should be viewed separately.
Microbial Distribution and Antibiotic Susceptibility of Bloodstream Infections in Different Intensive Care
Authors: Duan Nan , Li Haixia , Sun Liying , Huang Chenwei
Published: July 2021

Background: Bloodstream infection (BSI) is an increasing public health concern worldwide, representing a serious infection with significant morbidity and mortality, especially in children and elderly. The predominant microbial distribution and antibiotic susceptibility were investigated among BSIs in the pediatric intensive care unit (PICU), surgical intensive care unit (SICU), cardiac intensive care unit (CICU), respiratory intensive care unit (RICU) and geriatric intensive care unit (GICU) in order to achieve more efficient and appropriate therapies for patients in various ICUs.Methods: In this retrospective cross-sectional study, 516 positive cultures out of 6597 （positive rate 7.82%）blood specimens among BSIs in the five ICUs from 2017 to 2020 were analyzed for pathogen incidence and drug-susceptibility.Results: The incidence of BSIs was the highest in the RICU (9.48%) followed by the PICU (8.36%). The total prevalence of Gram-positive (G+) bacterial strains (especially Staphylococcus spp. and Enterococcus spp.) in the PICU (44.55%), SICU (57.58%), CICU (55.00%) and GICU (49.06%) was higher than Gram-negative (G-) bacteria. The major bacterial strain was Acinetobacter baumannii (G-) in the PICU (21.82%), Klebsiella pneumoniae (G-) in the SICU (12.88%), CICU (30.00%) and RICU (30.39%), and Escherichia coli (G-) in GICU (20.75%). Staphylococcus hominis of BSIs remained highly susceptible (>70%) to gentamicin, linezolid, daptomycin, teicoplanin, vancomycin, tigecycline and rifampicin in all the ICUs. Its antibiotic sensitivity to levofloxacin was moderate in the PICU and CICU, but mild (<30%) in the SICU, RICU and GICU. K. pneumoniae was highly susceptible to doxycycline, minocycline, tigecycline in all the ICUs except RICU, and its antibiotic sensitivity to imipenem, meropenem, amikacin, ciprofloxacin and levofloxacin in the GICU was high/moderate in PICU, CICU and GICU, but mild in the SICU and RICU.Conclusions: The current study demonstrated the distribution of prevalent microorganisms and their antimicrobial susceptibility exhibited a high divergence among BSIs in PICU, SICU, CICU, RICU and GICU from a tertiary hospital in Beijing. Therefore, different antibiotic therapies for various wards and distinct age groups (especially between pediatric and elderly patients) should be considered to control the emergence and spread of highly antibiotic-resistant infections.
Effects of Transcranial Ultrasound Stimulation Pulsed at 40 Hz on Aβ Plaques and Brain Rhythms in 5XFAD Mice
Authors: Park Mincheol , Hoang Gia Minh , Nguyen Thien , Lee Eunkyung , Jung Hyun Jin , Choe Youngshik , Kim Jae Gwan , Kim Tae
Published: July 2021

BackgroundAlzheimer’s disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological treatments. The impairment in the gamma oscillations, which play an important role in perception and cognitive function, has been shown in mouse AD models and human patients. Recently the therapeutic effect of gamma entrainment treatment on the AD mouse model was reported. Given that ultrasound is an emerging modality of neuromodulation, we investigated the effect of ultrasound stimulation pulsed at gamma frequency (40Hz) on an AD mouse model. MethodsWe implanted electroencephalogram (EEG) electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-months-old 5XFAD and wild-type control mice (n=12 and 6, respectively). Six 5XFAD mice were treated with daily two-hour ultrasound stimulation at 40Hz for two weeks, and the other six mice received sham treatment. Soluble and insoluble Aβ levels in the brain were measured by enzyme-linked immunosorbent assay. Spontaneous EEG gamma power was computed by wavelet analysis, and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling. ResultsWe found that total Aβ 42 and 40 levels, especially insoluble, in the treatment group decreased compared to that of the sham treatment group. The reduction in the number of Aβ plaques in PIL also has been shown. In addition, spontaneous gamma power was increased, and brain connectivity was improved. ConclusionsThese results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβ load and improving brain connectivity
The Anomalous Weather Parameters that Lead to the Extreme Rainfall of Kerala in August 2018
Authors: Sreedha Suneela , Mathew Basil , Sivanpillai Sureshkumar
Published: July 2021

Extremely heavy rainfall has been occurred over Kerala, southwest coast of India, during mid-August 2018. The meteorological conditions during this period are analysed, and it is found that a combination of many rain favouring conditions prevailed at that time. The positive phase of Madden Julian Oscillation coupled with a monsoon depression in the Bay of Bengal and a weak trough in the south-eastern Arabian Sea strengthened the Monsoon Low Level Jet bringing moisture-laden winds over Kerala. The rising limb of Walker and Hadley circulations was also found over Kerala, which gave favourable updraft for cloud formation. In addition, the core of the Tropical Easterly Jet was found over the Kerala and Karnataka region. The cyclonic circulation in the mid-troposphere observed around the monsoon depression extended up to the west coast of India. Simultaneous occurrences of all these could have contributed to the extreme rainfall events and severe floods over Kerala.