bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Acute Kidney Injury Using a Dual Enzyme Embedded Metal-organic Framework-mediated Cascade That Catalyzes in Vivo ROS Scavenging
Authors: Hou Xinyue , Shi Jianxiang , Zhang Jie , Wang Zhigang , Zhang Sen , Li Ruifeng , Jiang Wei , Guo Jiancheng , Shang Wenjun
Published: May 2021

Background: Significant advances have been made in recent years to utilize natural enzymes with antioxidant properties for the treatment of acute kidney injury (AKI). However, these enzymes have limited clinical utility due to their limited cellular uptake, poor pharmacokinetic properties, and suboptimal stability. We prepared a novel biomimetic mineralization approach to overcome these limitations.Results: Catalase (CAT) and superoxide dismutase (SOD) were encapsulated in a zeolitic imidazolate framework-8 (ZIF-8), then this SOD@CAT@ZIF-8 complex was anchored with MPEG2000-COOH to yield an MPEG2000-SOD@CAT@ZIF-8 (PSCZ) composite. This composite was then utilized as a stable tool with antioxidant properties for the integrated cascade-based treatment of AKI, remarkably improved intracellular enzyme delivery. The PSCZ composite showed a significantly relieve ability of H2O2 induced ROS and prevented apoptosis in HEK293 cells. In vivo, this composite showed a protective effect in the cisplatin-induced AKI mouse model. In addition, PSCZ treatment mitigated renal dysfunction and histological injury, like tubulointerstitial infiltration. RNA sequencing results further confirmed the protective effect of PSCZ and the potential molecular mechanism was revealed. PSCZ treatment reduced renal inflammation and inflammatory gene expression and ameliorated increased apoptosis and inflammatory infiltration of renal tubules. Moreover, PSCZ administration regulated renal injury via the p53 signaling pathway. These renoprotective effects of PSCZ treatment were more potent in CP-AKI mice than those of SOD or CAT alone. This dual-enzyme-embedded metal-organic framework was able to scavenge reactive oxygen species synergistically and effectively. Conclusion: PSCZ can remarkably improve intracellular enzyme delivery, and it can be used as a stable tool with antioxidant properties for the integrated cascade-based treatment of AKI. The ZIF-8-based “armor plating” represents an effective means of shielding enzymes with improved therapeutic utility to guide the precision medicine-based treatment of AKI.
Cropland Changes Enhance Carbon Sequestration in Northwest China From 1995 to 2015
Authors: Kong Junqia , He Zhibin , Yang Rong , Chen Longfei , Du Jun
Published: May 2021

Background: The Northwest China has experienced dramatic changes in agricultural land area in recent years; the effects of these changes on carbon storage are unknown and cannot guide further land development policies related to carbon emissions. In this study, we evaluated the effects of cropland changes (reclamation and transfer) during 1995-2015 on carbon storage in Northwest China by using land use data, carbon density data, and statistical yearbooks with the Intergovernmental Panel on Climate Change (IPCC) method. Results: The results indicated that the area of cropland increased by 1.48×106 ha from 1995 to 2005, resulting in a total carbon sequestration of 12.46 Tg, in which conversion of cropland to forest (11.16 Tg) and other land to cropland (8.92 Tg) were the main sources of the increase in carbon storage. Specifically, regional carbon sequestration due to cropland changes exhibited an increasing trend during 1995-2002 (dominated by cropland transfer), a gradually decreasing trend during 2002-2009 (dominated by cropland reclamation), and stabilization since then (during 2009-2015). Conclusions: These results suggest that the development of high carbon density lands or the conversion of low carbon density lands are critical to increasing future carbon sequestration due to cropland change. We used a novel approach of combining land use data, carbon density data, and statistical yearbooks to assess the impact of cropland change on carbon storage; this method is promising in applications which guide agricultural land-use management.
Enhancement of Light Absorption in Plasmonic Based Photodetector with Double Nanograting Structure
Authors: Kashyap Savita , Kaur Harsimranjit
Published: May 2021

This era of high speed photonic system demand photodetectors to have large bandwidth, gain and improved light enhancement competence. Amongst the different light absorption enhancement methods being researched by the investigators, plasmonic has acquired increased attention in the last decades. Although single layer plasmonic supported metal semiconductor metal photodetector (MSM-PD) has been explored for higher light absorption efficiency, but exploration for double-layer structure is lacking in the literature. This paper presents the performance of plasmonic based photodetectors (PDs) with double layer of nanogratings optimized at wavelength of 1.4 µm for night vision applications. Proposed design of plasmonic supported photodetector with double nanograting reports Quenching factor (QF) of 92.14% and provides enhancement in light with the optimized height of subwavelength aperture (SWA) at 60 nm. This can be credited to fact that both top and bottom layer of grating contributes to light trapping.
Evaluation of Insertion/deletion (I/D) Polymorphisms of ACE Gene in Congenital Anomalies of The Kidney and Urinary Tract From a Brazilian Pediatric Population
Authors: Pousa Pedro Antunes , Mendonça Tamires Sara Campos , Fonseca Larissa Marques , Oliveira Eduardo Araújo , Belisário André Rolim , Silva Ana Cristina Simões e
Published: May 2021

Background: Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) are defined as a heterogeneous group of anomalies that resulted from defects in kidney and urinary tract embryogenesis. CAKUT have a complex etiology. Genetic, epigenetic and environmental factors have been investigated in this context. Angiotensin II is a potent vasoconstrictor and exerts an important role in kidney embryogenesis. The angiotensin-converting enzyme (ACE) converts Angiotensin I into Angiotensin II and ACE gene has insertion/deletion (I/D) polymorphisms that have been evaluated in several nephropathies. This study aimed to evaluate whether the I/D polymorphisms of ACE gene are associated with any CAKUT phenotype or CAKUT in general. Methods and Results: Our study was performed with 225 pediatric patients diagnosed with CAKUT and 210 age-and-sex matched healthy controls. ACE I/D alleles were analysed by real-time polymerase chain reaction (RT-PCR). The distribution of ACE I/D polymorphisms were compared between CAKUT patients and healthy controls, as well between ureteropelvic junction obstruction (UPJO), vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK) phenotypes and control group. No statistical association of ACE I/D genotypes and allelic frequency between patients and controls was found among general CAKUT and UPJO, VUR and MCDK phenotypes. Conclusion: Although CAKUT is a complex disease and the ACE gene may exert a role in kidney embryogenesis, CAKUT was not associated with any ACE I/D polymorphisms in this Brazilian pediatric population.
A Novel Chronic Dural Port Platform for Continuous Collection of Large Volumes of Cerebrospinal Fluid and Intrathecal Drug Delivery in Free-Moving Mice.
Authors: Nakajima Tsuneo , Takeda Shuko , Ito Yuki , Oyama Akane , Takami Yoichi , Takeya Yasushi , Yamamoto Koichi , Sugimoto Ken , Shimizu Hideo , Shimamura Munehisa , Rakugi Hiromi , Morishita Ryuichi
Published: May 2021

BackgroundCerebrospinal fluid (CSF) provides a direct representation of the pathophysiological changes occurring in the central nervous system (CNS); therefore, it has been used for pathogenesis research and biomarker development for CNS disorders. The CSF obtained from valid mouse models relevant to CNS disorders can be an important resource for successful biomarker and drug development. However, the limited volume of CSF that can be collected from the tiny intrathecal space and the technical difficulties involved in CSF sampling have been bottlenecks that have hindered the detailed analysis of CSF in mouse models. ResultsWe have developed a novel chronic dural port (CDP) method without cannulation for mouse CSF collection. This method allows easy and repeated access to the intrathecal space in a free-moving, unanesthetized mouse, thereby enabling continuous long-term CSF collection with minimal tissue damage and providing a large volume of high-quality CSF from a single mouse. When combined with chemical biosensors, the CDP method allows real-time monitoring of the dynamic changes in neurochemicals in the CSF at a one-second temporal resolution in free-moving mice. The CDP can also serve as a direct access point for intrathecal injection of CSF tracers and drugs. The spatio-temporal distribution of CSF tracers delivered via CDP revealed a dynamic metabolism of CSF at distinct brain areas. Direct intrathecal delivery of centrally acting drugs via CDP enabled real-time behavioral assessment in free-moving mice. ConclusionsThe CDP method allows collection of a large volume of high-quality CSF and direct intrathecal drug administration with real-time behavioral assessment in free-moving mice. Combined with animal models relevant to CNS disorders, this method provides a unique and valuable platform for biomarker and therapeutic drug research.
Cardiopulmonary Exercise Testing and Pulmonary Function Testing for Predicting Aggravation of CTEPH
Authors: Hanqing Zhu , Xingxing Sun , Yuan Cao , Wenlan Yang , Liu Jinming , Jian Guo
Published: May 2021

BackgroundCardiopulmonary exercise testing (CPET) and pulmonary function testing (PFT) are noninvasive methods to evaluate the respiratory and circulatory systems. This research aimed to evaluate and monitor chronic thromboembolic pulmonary hypertension (CTEPH) noninvasively and effectively. At the same time assess the predictive value of CPET and PFT parameters for the aggravation of CTEPH. MethodsWe used data from 86 CTEPH patients (55 for test set, and 31 for validation set) at the Shanghai Pulmonary Hospital Affiliated to Tongji University. The clinical, PFT and CPET parameters of mild, moderate and severe CPET patients classified according to PAP (mm Hg) were compared. Logistic regression analysis was performed to appraise the predictive value of each potential predictor for severe CTEPH. The performance of PFT and CPET parameters for predicting severe CTEPH was determined by receiver operating characteristic (ROC) curves and calibration curves.ResultsData showed that Load @ Peak (W), FEV1/FVC (%), and VE @ AT (L/min) were independent risk factors for severe CTEPH classified according to PAP (mm Hg). Additionally, the efficacy of the use of Load @ Peak (W), FEV1/FVC (%) and VE @ AT (L/min) in identifying severe CTEPH was found to be moderate with area under the curve (AUC) of ROC curves of 0.736, 0.696 and 0.769, respectively. Furthermore, combination with Load @ Peak (W), FEV1/FVC (%) and VE @ AT (L/min) had a moderate utility value in identifying severe CTEPH with an AUC of 0.897.ConclusionOur data suggests that PFT and CPET parameters can noninvasively and effectively evaluate, monitor and predict the aggravation of CTEPH.
Biological Activity of Wastewater Assessed Using in Vitro Cell-Based Assays
Authors: Petosa Adamo R. , Nowierski Monica , Yargeau Viviane
Published: May 2021

Bioanalytical tools, namely in vitro bioassays, can be employed in tandem with chemical analyses to assess the efficacy of wastewater treatment and the potential for adverse effects from the discharges of wastewater into receiving waters. In the present study, samples of untreated wastewater (i.e. influent) and treated wastewater (i.e. effluent) were collected from two wastewater treatment plants and a wastewater treatment lagoon serving municipalities in southern Ontario, Canada. In addition, grab samples of surface water were collected downstream of the lagoon discharge. After solid phase extraction (SPE) using ion-exchange columns for basic/neutral and acidic compounds, respectively, the extracts were analyzed for a suite of 16 indicator compounds. The two SPE extracts were combined for analysis of biological responses in four in vitro cell-based bioassays. The concentrations of several indicator compounds, including the estrogens, 17β-estradiol and 17α-ethinylestradiol, were below the limits of detection. However, androstenedione and estrone were detected in several influent samples. The concentrations of these steroid hormones and some of the other indicator compounds declined during treatment but acesulfame K, carbamazepine, trimethoprim and DEET persisted in the effluent. The MTS- CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS) indicated that cell viability was not affected by exposure to the extracts. The Qiagen Nuclear Receptors 10-Pathway Reporter Array indicated that several cellular pathways were upregulated, with the greatest upregulation observed with the estrogen receptor (i.e. induction ratios 12 to 47) and the liver X receptor (i.e. induction ratios 10 to 45). The ERα CALUX assay indicated that estrogenic activity was lower in effluents compared to influents, with the greatest estrogenic activity observed for grab samples of influent from the lagoon (i.e. 56-215 ng L-1 17β-estradiol equivalents). Finally, the results of the Nrf2 Luciferase Luminescence Assay indicated a lower oxidative stress in the effluent samples. Overall, the present study demonstrates that chemical analyses are limited in their ability to predict or explain reductions in the toxicity of treated wastewater. There are thus advantages to using a combination of chemical analyses and in vitro bioassays to monitor the treatment efficiency of wastewater treatment plants and to predict the potential impacts of wastewater discharges into receiving waters.
Efficacy of Platelet-Rich Plasma and Plasma for Symptomatic Treatment of Knee Osteoarthritis: A Double-Blinded Placebo-Controlled Randomized Clinical Trial.
Authors: Dório Murillo , Pereira Rosa Maria Rodrigues , Luz Alexandre Galeno Branco , Deveza Leticia Alle , Oliveira Ricardo Manoel , Fuller Ricardo
Published: May 2021

Background: Platelet-rich plasma (PRP) has a still conflicting efficacy for knee osteoarthritis (KOA) and might be a minimally invasive and safe treatment alternative. The potential benefit of only plasma (non-enriched) has never been investigated. Our aim was to evaluate the efficacy of intra-articular platelet-rich plasma (PRP) and plasma to improve pain and function in participants with KOA over 24 weeks. Methods: Randomized, double-blind, placebo-controlled trial with 3 groups (n = 62): PRP (n = 20), plasma (n = 21) and saline (n = 21). Two ultrasound-guided knee injections were performed with a 2-week interval. The primary outcome was visual analog scale 0-10 cm (VAS) for overall pain at week 24, with intermediate assessments at weeks 6 and 12. Main secondary outcomes were: KOOS, OMERACT-OARSI criteria and TUGT. Results: At baseline, 92% of participants were female, with a mean age of 65 years, mean BMI of 28.0 Kg/m2and mean VAS pain of 6.2 cm. Change in pain from baseline at week 24 were -2.9 (SD 2.5), -2.4 (SD 2.5) and -3.5 cm (SD 3.3) for PRP, plasma and saline, respectively (p intergroup = 0.499). There were no differences between the three groups at weeks 6 and 12. Similarly, there were no differences between groups regarding secondary outcomes. The PRP group showed higher frequency of adverse events (65% versus 24% and 33% for plasma and saline, respectively, p = 0.02), mostly mild transitory increase in pain.Conclusions: PRP and plasma were not superior to placebo for pain and function improvement in KOA over 24 weeks. The PRP group had a higher frequency of mild transitory increase in pain.Trial registration: ClinicalTrials.gov, NCT03138317, 03/05/2017.
Neurokinin 3 Receptor Effects on Cognitive Behaviour in a Rat Model of Alzheimer's Disease
Authors: Koca Raviye Ozen , Gormus Zulfikare Isik Solak , Solak Hatice , Koc Aynur , Kılınç İbrahim , İyisoy Sinan , Kutlu Selim
Published: May 2021

Alzheimer's disease (AD) is accepted as a form of progressive and irreversible dementia. It is known that cholinergic systems are commonly affected in AD. Neurokinin 3 receptor (NK3R) is involved in learning and memory related processes. Activation of NK3R is known to facilitate the release of many neurotransmitters such as acetylcholine (Ach), dopamine (DA), noradrenaline (NA). Based on this information, hypothesis of the study that NK3R agonism can have positive effects on behavioral and learning parameters through cholinergic and catecholaminergic mechanisms. The aim of this study was to investigate the effects of NK3R agonist senktide on cognitive and neurobehavioral mechanisms in model of AD.50 adult male Wistar albino rats were obtained; Control, AD, Control+NK3R agonist, AD+NK3R agonist, AD+NK3R agonist+antagonist groups. AD model was established by administering Aβ1-42 intracerebroventricularly. Following NK3R agonist+antagonist injections, open field (OF) and Morris water maze (MWM) were applied for behavioral and learning parameters. Hippocampus and cortex tissues were extracted. Analysis of cholinergic mechanisms from these tissues were performed by ELISA method.Group-time effect was significant in OF (p<0.05). Distance moved parameter was significant between groups in MWM (p<0.05). There was a significant difference between groups in AChE and ChAT levels (p<0.05). DA concentrations of brainstem samples were significant (p<0.05). There was no significant difference in NA concentration (p>0.05). NK3R agonists were found to be effective in improving cognitive functions in rats with AD pathology. It has been observed that positive effects on learning and memory performances can be mediated by cholinergic mechanisms.
Evaluation of Parental Knowledge, Attitudes and Practices Regarding Antibiotic Use in Acute Upper Respiratory Tract Infections in Children in a Tertiary Care Hospital in Turkey
Authors: Albayrak Aslınur , Karakaş Nazmi Mutlu , Karahalil Bensu
Published: May 2021

BackgroundUpper respiratory tract infections (URTIs) are common in children. Most URTIs have been shown to be of viral origin. Inappropriate use of antibiotics is one of the main causes of antibiotic resistance. The problem of unnecessary antibiotic use among children is a concern for antibiotic resistance in low- and middle-income developing countries.MethodsOur study is a cross-sectional survey study. It was carried out between 14 December 2020 and 1 April 2021 for parents over 18 years of age with a child under 18 years’ old who applied to the general pediatrics outpatient clinics of Gazi University Faculty of Medicine Hospital Department of Pediatrics.Results554 parents responded to the questionnaire. A total of 15.7% of parents stated to use antibiotics in any child with fever. 37% of parents believed that antibiotics could cure infections caused by viruses. 6.3% of parents declared that they put pressure on pediatricians to prescribe antibiotics. 85.6% of the parents stated that they never gave their children non-prescription antibiotics when they had a high fever. 80.9% of them declared that they never used past antibiotics in the presence of a new infection. Female gender, high level of education, high income level and low number of antibiotics used in the last 1 year were found to be statistically significant with the better knowledge level of the parents (p <0.05).ConclusionAccording to the results of our study of parents' lack of knowledge about antibiotics in Turkey, though generally it shows proper attitude and behavior. It shows that some of the restrictions imposed by the National Action Plan are partially working. However, it is still necessary to continue to inform parents, pediatricians and pharmacists about the use of antibiotics, and to be more sensitive about the prescribing of antibiotics, and if necessary, sanctions should be imposed by the state in order to prevent unnecessary antibiotic prescriptions.
A Whole-slide Imaging Based Workflow Reduces the Reading Time of Pathologists
Authors: Baidoshvili Alexi , Kacheishvili Mariam , Laak Jeroen van der , Diest Paul van
Published: May 2021

Aims: Even though entirely digitized microscopic tissue sections (whole slide images) are increasingly being used in histopathology diagnostics, little data is still available on the effect of this technique on pathologists’ reading time. This study aimed to compare the time required to perform microscopic assessment by pathologists between a conventional workflow (using an optical microscope and glass slides) and digitized whole slide images (WSI).Methods: The study was performed in the Laboratory for Pathology Eastern Netherlands (LabPON, Hengelo, The Netherlands), which has been using WSI in primary diagnostics for several years. Cases were either read in a conventional workflow, while the pathologist recorded the time required for diagnostics and reporting or were read using a fully digitized workflow. The digitized workflow was fully integrated with the laboratory information system, and reading times were extracted from the log files of the image management system. Results: Analysis of over 3800 cases showed a time gain in favour of the digital workflow for most case categories, with the highest gain (68% time gain) for prostate biopsies (prostate care program). On average, a gain of 12.3% was found for the digital workflow, taking the case distribution into account. Conclusions: It was concluded that transitioning from conventional microscopy to use of WSI significantly reduces the pathologists’ reading times. A fully integrated pathologist working environment is required to fully benefit from the benefits of a digital workflow.
Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites
Authors: Yan Yuqing , Gao Ye , Fang Qingli , Zhang Nianping , Kumar Gajendra , Yan Hailong , Song Lijuan , Li Jiehui , Zhang Yuna , Sun Jingxian , Wang Jiawei , Zhao Linhu , Skaggs Keith , Zhang Han-Ting , Ma Cun-Gen
Published: May 2021

Background: Fasudil, a Rho kinase inhibitor, exerts therapeutic effects in the mouse model of Alzheimer’s disease (AD), a chronic neurodegenerative disease with progressive loss of memory. However, the mechanisms remain unclear. In addition, the gut microbiota and its metabolites have been implicated in AD. Methods: Here, we examined the effect of fasudil on learning and memory using the Morris water-maze (MWM) test in APPswe/PSEN1dE9 transgenic (APP/PS1) mice (8 months old) treated (i.p.) with fasudil (25 mg/kg/day; ADF) or saline (ADNS) and in age- and gender-matched wild-type (WT) mice. Fecal metagenomics and metabolites were analyzed to identify novel biomarkers of AD and to elucidate the mechanisms whereby fasudil produced beneficial effects in AD mice. Results: Morris water maze test showed significant improvement of spatial memory in APP/PS1 mice treated with fasudil as compared to ADNS. The metagenomic analysis revealed the abundance of the dominant phyla in all the three groups, including Bacteroidetes (23.7% - 44%) and Firmicutes (6.4% - 26.6%), and the increased relative abundance ratio of Firmicutes/Bacteroidetes in ADNS (59.1%) compared to WT (31.7%). In contrast, the Firmicutes/Bacteroidetes ratio was decreased to the WT level in ADF (32.8%). Lefse analysis results of metagenomics showed s_Prevotella_sp_CAG873 as an ADF potential biomarker, while s_Helicobacter_typhlonius and s_Helicobacter_sp_MIT_03-1616 as ADNS potential biomarkers. Metabolite analysis revealed the increment of various metabolites, including glutamate, hypoxanthine, thymine, hexanoyl-CoA, and leukotriene, were relative to ADNS or ADF microbiota potential biomarkers and mainly involved in the metabolism of nucleotide, lipids, sugars, and the inflammatory pathway. Conclusions: Memory deficit in APP/PS1 mice was correlated with the gut microbiome and metabolite status. Fasudil reversed the abnormal gut microbiota and subsequently regulated the related metabolisms to normal in the AD mice. It is believed that fasudil can be a novel strategy for the treatment of AD via remodeling of the gut microbiota and metabolites. The novel results also provide valuable references for the use of gut microbiota and metabolites as diagnostic biomarkers and/or therapeutic targets in clinical studies of AD.
Do We Really Need to Repair the Pronator Quadratus in Volar Plating of Distal Radius Fracture？A Protocol for Systematic Review and Meta Analysis
Authors: Li Qiujiang , Long Xingxia , Wang Yinbin , Wang Zhaofu , Guo Donggeng , Lv Jinhan , Ma Feng , Cai Lijun
Published: May 2021

IntroductionDistal radius fracture is a common type of fracture in clinical practice.Over recent years, Volar locking plate internal fixation remains the most commonly used surgical treatment method in the treatment of distal radius fractures. To better expose the distal radius and fracture segment, the surgeons have to cut the pronator quadratus(PQ) muscle.However, whether the PQ muscle need to be repaired remains controversial. This study aims to provide a plan to evaluate the clinical efficacy whether to repair the PQ muscle in volar plate fixation of distal radius fractures.Methods and analysisWe will search PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI),and Wanfang databases from the beginning to February 2021 to compare clinical outcomes whether to repair the PQ muscle. Quality assessment will be evaluated using the risk of bias tool recommended by the Cochrane Handbook 5.2.0. Subsequently, Revman software version 5.3 will be used for data analysis when a meta-analysis is allowed including subgroup and sensitivity analysis.PROSPERO registration number CRD42020206959
Proteomic Characterization of Primary and Metastatic Prostate Cancer Reveals Reduced Proteinase Activity in Aggressive Tumors
Authors: Li Qing Kay , Chen Jing , Hu Yingwei , Hoti Naseruddin , Thomas Stefani N , Chen Li , Roy Sujayita , Meeker Alan , Shah Punit , Chen Lijun , Bova G. Steven , Zhang Bai , Zhang Hui
Published: May 2021

BackgroundProstate cancer (PCa) is a heterogeneous group of tumors with variable clinical courses. Clinically, it is critical to separate and treat aggressive PCa (AG) from non-aggressive PCa (NAG). Although recent genomic studies have identified a spectrum of molecular abnormalities associated with PCa, it is still challenge to separate AG from NAG. To better understand the functional consequence of PCa progression and the unique features of AG from NAG, we studied proteomic signatures of primary AG, NAG and metastatic PCa.Methodes39 PCa and 10 benign prostate controls in discovery cohort and 57 PCa in independent-collected validation cohort were analyzed using data-independent acquisition (DIA) SWATH–MS platform. Proteins with the highest variances (top 500 proteins) were annotated for the pathway enrichment analysis. Functional analysis of differentially expressed proteins in NAG and AG was performed. Data was further validated using validation cohort, as well as by comparison with TCGA mRNA expression and immnunochemistry on PCa tissue microarray (TMA).Results4,415 proteins were identified in the tumor and benign control tissues, including 158 up-regulated and 116 down-regulated proteins in AG tumors. A functional analysis of tumor-associated proteins revealed the reduced expression of several proteinases, including dipeptidyl peptidase 4 (DPP4), carboxypeptidase E (CPE) and prostate specific antigen (KLK3) in AG and metastatic PCa. A targeted analysis using SWATH data further identified that the reduced expression of DPP4 was associated with the accumulation of DPP4 substrates in AG tumors, including the reduced ratio of DPP4 cleaved peptide to intact substrate peptide. Findings were further validated using independent-collected cohort, by comparison with TCGA mRNA data, and the immunochemical stains of our tumor microarray (TMA).ConclusionsOur study is the first large-scale proteomics analysis of PCa tissue using DIA SWATH-MS platform. It not only provides an interrogative proteomic signature of PCa subtypes, but also indicates critical roles of certain proteinases, especially DPP4, in PCa progression. The spectrum map and protein profile generated in the study can be used to investigate potential biological mechanisms involved in the PCa progression as well as for the development of a clinical assay to distinguish aggressive from indolent PCa.
Knowledge, Attitude, and Awareness of Health Insurance in Travel during the Covid-19 Pandemics
Authors: Yang Chia-Jung , Lu Chia-Wen , Chiang Chien-Hsieh , Chang Hao-Hsiang , Yao Chien-An , Huang Kuo-Chin
Published: May 2021

Background

Travel has become one of the most popular leisure activities in the world, especially international traveling. The risk of accident and travel related illness including infectious and non-communicable diseases should not be neglected. To provide more comprehensive pre-travel consultation to the international travelers, we aimed to investigate the knowledge, attitude, and awareness of travel health insurance for travelers.
Methods

Anonymous structured questionnaires were distributed to 1,000 visitors of the Taiwan International Travel Fair in May 2019.
Results

The top three kinds of travel health insurance were accidental death and disablement insurance (92%), accidental medical reimbursement (90.4%) and 24 hours of emergency assistance (89%). In addition to education level, travel-associated illness, and special activities during travel, a significant association was observed between the willingness to buy various travel insurance and willingness of pre-travel consultation.
Conclusions

Although most travelers would buy travel health insurance, disproportional respondents understood the content of travel insurance. Most travelers considered travel clinics to be the most reliable information resources of travel insurance. Therefore, travel specialists are encouraged to offer more information about travel insurance during pre-travel consultation, especially during the COVID-19 pandemic.
Insights Into the Diversity of Terrestrial Soil Bacterial Communities Associated With Four Contrasting Köppen Climatic Zones.
Authors: Nair Girish R , Raja Suresh S.S.
Published: May 2021

Background: The multidirectional relationship between soil, its microbiota, and climate is crucial in modulating the bacterial community diversity and its survival in the terrestrial ecosystem. Therefore, it is imperative to understand the dynamics of soil bacterial communities thriving in geographical areas of varied climatic exposure. Results: The diversity of terrestrial soil bacterial communities thriving in four contrasting Köppen climatic zones of India was investigated for the first time using high-throughput sequencing. The results revealed that the bacterial species diversity, evenness and richness were highest in HSCZ (humid subtropical climatic zone). Firmicutes was the most abundant phylum in TWCZ (tropical wet climatic zone), ACZ (arid climatic zone), and HSCZ (humid subtropical climatic zone) while Proteobacteria in MCZ (Mountain climatic zone). The predominance of class Alphaproteobacteria, Actinobacteria with genera Bradyrhizobium, Chthoniobacter, and Mycobacterium, was observed in MCZ in contrast to class Bacilli with genera Bacillus and Paenibacillus in the rest of the zones. Correlation analysis showed that H’ (Shannon diversity) index, S (species richness), OTU abundance were positively correlated with moisture, TOC, K, MAP (mean annual precipitation) and negatively correlated with pH, Ca, N, B. Fe, P, Mg and MAT (mean annual temperature). Conclusion: This work mapped the occurrence and distribution of terrestrial soil bacterial communities in contrasting climatic zones that enabled us to assess the effect of climate in mentioned Köppen climatic zones on a taxonomic scale.
Emergence of SARS-CoV-2 Spike Escape Mutation Q493R After Bamlanivimab/Etesevimab Treatment for COVID-19
Authors: Focosi Daniele , Novazzi Federica , Genoni Angelo , Dentali Francesco , gasperina Daniela Dalla , Baj Andreina , Maggi Fabrizio
Published: May 2021

We report here the first in vivo selection of a Spike mutation (Q493R) conferring simultaneoius full resistance to both bamlanivimab and etesivimab.
Delay to initiate treatment is associated with unsuccessful treatment outcome among new pulmonary tuberculosis patients in Tigray, Northern Ethiopia: a follow up study
Authors: Tedla kiros , Medhin Girmay , Berhe Gebretsadik , Mulugeta Afework , Berhe Nega
Published: May 2021

Background : Previous studies in Ethiopia indicated that tuberculosis (TB) patient’s elapse long time before treatment initiation. However, there is very limited evidence on the association of delay to initiate treatment with treatment outcome.
Objective : To investigate the association of time to treatment initiation delay with treatment outcomes of new adult TB patients in Tigray region of Ethiopia.
Methods : We conducted a follow up study from October 2018 to April 2020 by recruiting 875 newly diagnosed Pulmonary Tuberculosis (PTB) patients from 21 randomly selected health facilities. Study participants were selected using simple random sampling technique during treatment initiation from October 1/2018 to October 30/2019. Delay to initiate treatment and treatment outcome were collected using standardized questionnaire and laboratory investigation. Adherence of TB patients to their treatment was collected using a 10 points linear visual analogue scale (VAS) at the end of treatment. The association of delay to initiate treatment with treatment outcome was modeled using log binomial regression model. Statistical significance was reported whenever p-value was less than 0.05. Data was analyzed using SPSS software version 21.
Result : The median total delay to treatment initiation was 62 days with inter-quartile range of 16-221 days. A unite increase in a day to initiate treatment results in increment of risk of unsuccessful treatment outcome by 2.3. Other factors associated with unsuccessful treatment outcomes were being less adherent to the treatment, HIV co infection, being smear positive at initiation of treatment and after 2 months of treatment initiation.
Conclusion : delay in a day to initiate treatment is associated with increased risk of unsuccessful treatment outcome. Any effort targeted towards reducing the negative effects of PTB should target on strategies that reduces the length of delay to initiate treatment and strengthen community engagement to improve treatment adherence of patients that have started treatment.
Investigation of the Role of Crown Crack in Cohesive Soil Slope and Its Effect on Slope Stability Based on Extended Finite Element Method
Authors: Bao Yiding , Li Yuchao , Zhang Yansong , Yan Jianhua , Zhou Xin
Published: May 2021

Tensile cracks in soil slopes, especially developing at the crown, have been increasingly recognized as the signal of slope metastability. In this paper, the role of crown cracks in natural soil slopes was investigated and their effect on stability was studied. A numerical slope model based on the extended finite element method (XFEM) simulating the tensile behavior of soil was used. Before the simulation, a numerical soil tensile test was applied to validate the use of XFEM on tensile behavior of soil. Slope failure was simulated by using strength reduction technique, which can determine the potential slip surface of slope. The simulation results show that the crown crack forms in natural soil slopes when the plastic zone starts penetrating, and therefore it is reasonable to consider the crown crack as the signal of slope metastability. A sensitivity analysis shows that cracks are at the position of the tension zone or very long can obviously affect the slope stability. The stress variation analysis from the initial deformation to slip surface penetration shows that the slope is at a state of compressive stress initially. When plastic zone starts to penetrate, the upper part of slope generates tension zone, but the extent of tension zone is limited until slope failure. This shows why tensile cracks are difficult to form and be stretched in the deep part of the slope. The application of XFEM on slope stability analysis can be used to assess the tensile strength of soil and predict slope failure disaster.
IGF- I induced growth and metatasis suppressed by calycosin via STAT3/ BATF2/ NF-κB /FOXM1 in colorectal cancer cells
Authors: Wang Qun , Lu Weijun , Lu Li , Pi Guoliang , De Wu Dong , Wei Shaozhong
Published: May 2021

To determine whether up-regulation of BATF2 by calycosin suppresses IGF- I induced growth and metastasis in human CRC,Cells were cultured and treated with calycosin and IGF-I. Protein and mRNA levels were determined by western-blot and real-time PCR respectively. Cell migration and invasion were assessed by transwell experiments. Apoptosis was measured by Flow cytometry. Cell proliferation was evaluated by the MTT assay.Co-immunoprecipitation and luciferase assays were used to analyze the interaction between BATF2 and MAT2Aand FOXM1.Cytoimmunofluorescence staining was applied for β-catenin and FOXM1 cellular localization.As results,Calycosin induced the up-regulation of BATF2 antagonized by IGF- I via STAT3, STAT1and NF-κB pathways resulting in cell apoptosis promotion via increasing BAX/Bcl-2 ratio subsequent contribute to caspase-3 and caspase-9 release. IGF- I induced cell migration,invasion and EMT suppressed by calycosin via BATF2 to block FOXM1 mediated β-catenin nuclear accumulation in three CRC cells. IGF- I induced cell proliferation was inhibited by calycosin down-regulating MAT2A and FOXM1. IGF-I and calycosin impacted MAT2A on transcriptional level. BATF2 interated with MAT2A and FOXM1 directly.We believed up-regulation of BATF2 may be a practicable treatment strategy for suppression IGF-1 induced growth and metatasis in CRC.
Full-length Genome of the Ogataea polymorpha strain HU-11 reveals large duplicated segments in subtelomeric regions
Authors: Chang jia , Bei Jinlong , Wang Hemu , Yang Jun , Li Xin , Yau Tung On , Bu Wenjun , Ruan Jishou , Duan Guangyou , Gao Shan
Published: May 2021

Background: Currently, methylotrophic yeasts (e.g., Pichia pastoris, Hansenula polymorpha, and Candida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genus Ogataea, most research is focused on three basic O. polymorpha strains—CBS4732, NCYC495, and DL-1. However, these three strains are of independent origin and unclear relationship. As a high-yield engineered O. polymorpha strain, HU-11 can be regarded as identical to CBS4732, because the only difference between them is a 5-bp insertion. Results: In the present study, we have assembled the full-length genome of O. polymorpha HU-11 using high-depth PacBio and Illumina data. Long terminal repeat (LTR) retrotransposons, rDNA, 5' and 3' telomeric, subtelomeric, low complexity and other repeat regions were curated to improve the genome quality. We took advantage of the full-length HU-11 genome sequence for the genome annotation and comparison. Particularly, we determined the exact location of the rDNA genes and LTR retrotransposons in seven chromosomes and detected large duplicated segments in the subtelomeric regions. Three novel findings are: (1) O. polymorpha NCYC495 is so phylogenetically close to CBS4732/HU-11 that the syntenic regions covers nearly 100% of their genomes with a nucleotide identity of 99.5%, while NCYC495 is significantly distinct from DL-1; (2) large segment duplication in subtelomeric regions is the main reason for genome expansion in yeasts; and (3) the duplicated segments in subtelomeric regions may be integrated at telomeric tandem repeats (TRs) through a molecular mechanism, which can be used to develop a simple and highly efficient genome editing system to integrate or cleave large segments into yeast genomes. Conclusions: Our findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications of O. polymorpha HU-11 and CBS4732. The full-length genome of the O. polymorpha strain HU-11 should be included into the NCBI RefSeq database for future studies of O. polymorpha CBS4732, NCYC495, and their derivative strains.
The effects of estimated remnant-like particle cholesterol on incident cardiovascular disease: Insights from a general Chinese population
Authors: Chen Yanli , Li Guangxiao , Guo Xiaofan , Ouyang Nanxiang , Li Zhao , Ye Ning , Yu Shasha , Yang Hongmei , Sun Yingxian
Published: May 2021

Background

Growing evidence suggests that remnant cholesterol (RC) may contribute to residual atherosclerotic cardiovascular disease (ASCVD) risk. But the cut-off point to treat RC for reducing ASCVD is still not known. This study was aimed to investigate the relationships between RC and combined cardiovascular diseases (CVDs) in a general China cohort, with 11,956 subjects aged ≥ 35 years.
Methods

Baseline RC was estimated with the Friedewald formula for 8782 subjects. The outcome was the incidence of combined CVD, including fatal and nonfatal stroke and coronary heart disease (CHD). Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Restricted cubic spline model was used to evaluate dose-response relationship between continuous RC and the natural log of HRs.
Results

After a mean follow-up of 4.66 years, 431 CVD events occurred. In the cox proportional models, participants with high level of categorial RC had significantly higher risk for combined CVD (HR: 1.37; 95% CI: 1.07–1.74) and CHD (HR: 1.63; 95% CI: 1.06–2.53), compared to those with medium level of RC. In the stratification analyses, high level of RC significantly increased combined CVD risk for subgroups females, age < 65years, non-current smokers, non-current drinkers, normal weight, renal dysfunction, and no hyperuricemia. Same trends were found for CHD among subgroups males, age < 65 years, overweight, renal dysfunction, and normal uric acid; stroke for subgroup females. In the restricted cubic spline models, significantly linear association between RC and combined CVD and non-linear association between RC and CHD were shown. The risk of outcomes was relatively flat until 0.84mmol/l of RC and increased rapidly afterwards, with HR of 1.308 (1.102 to 1.553) for combined CVD and 1.411 (1.061 to 1.876) for CHD. Stratified analyses showed significant nonlinearity association between RC and CVD outcomes in subgroup aged < 65 years or subgroup diabetes.
Conclusions

In this large-scale and long-term follow-up cohort study, participants with higher RC levels had significantly worse prognosis, especially for subgroup aged 35–65 years or subgroup diabetes mellitus.
Mechanical Power Normalized to Predicted Body Weight is Associated with Mortality in Critically Ill Patients: A Cohort Study
Authors: Zhu Yanhong , Peng Wenyong , Zhen Shuai , Jiang Xiaofeng
Published: May 2021

Background: Mechanical power (MP), defined as the amount of energy produced by mechanical ventilation and released into the respiratory system, has long been considered a critical factor in the pathogenesis of ventilator-induced lung injury. However, our knowledge suggests that the effects of MP may be proportional to their involvement in total lung function size. Therefore, MP normalized to predicted body weight (norMP) should be greater than absolute MP value. The objective of this research is to determine the connection between norMP and mortality in critically ill patients who have been on invasive ventilation for at least 48 hours.Methods: This is a study of data stored in the databases of the MIMIC–III, which contains data of critically ill patients for over 50,000. The study involved critically ill patients who had been on invasive ventilation for at least 48 hours. norMP was the relevant exposure. The major endpoint was ICU mortality, the secondary endpoints were 30-day, 90-day mortality; ICU length of stay, the number of ventilator-free days at day 28.Result: The study involved a total of 1301 critically ill patients. This study revealed that norMP was correlated with ICU mortality [OR per quartile increase 1.20 (95% CI 1.07–1.35), p = 0.009]. Similarly, norMP was correlated with ventilator-free days at day 28, ICU length of stay. In the subgroup analysis, high norMP was associated with ICU mortality whether low or high Vt (OR 1.22, 95% CI 1.01–1.47, p = 0.040; OR 1.28, 95% CI 1.06–1.54, p = 0.011, respectively). But high norMP was associated with ICU mortality only in low PIP (OR 1.18, 95% CI 1.01–1.37, p = 0.034)Conclusion: Our findings indicate that higher norMP is independently linked with elevated ICU mortality and various other clinical findings in critically ill patients with a minimum of 48 hours of invasive ventilation.
Motor control and olfaction – Influence of pleasant and disgusting odors on the Adaptive Force
Authors: Schaefer Laura V , Dech Silas , Aehle Markus , Bittmann Frank N
Published: May 2021

The Adaptive Force (AF) characterizes the capability of the neuromuscular system to adapt to external forces. The aim was to measure the effects of different olfactory inputs on the AF of the hip and elbow flexors, respectively. The AF of 10 subjects was examined manually by experienced testers while smelling at sniffing sticks with neutral, pleasant or disgusting odors. The reaction force and the position of the tested limb were recorded by a handheld device. The results show, inter alia, a significantly lower maximal isometric AF and a significantly higher AF at the onset of oscillations with disgusting odor compared to pleasant or neutral odors (p < 0.001). The AF seems to reflect the functionality of the neuromuscular control, which can be impaired by disgusting olfactory inputs. An undisturbed functioning neuromuscular system appears to be characterized by a proper length-tension control and by an earlier onset of mutual oscillations during an external force increase under isometric conditions.
Liver Resection Combined with Radiotherapy versus Liver Resection Alone in the Treatment of Hepatocellular Carcinoma: A Population-based Study
Authors: Chen Lei , Guo Xiaopeng , Ren Yanqiao , Sun Tao , Zheng Chuansheng
Published: May 2021

BackgroundRadiotherapy has been used in the treatment of hepatocellular carcinoma (HCC) more widely. However, little research focus on comparing the efficacy of patients with liver resection combined with radiotherapy with that received liver resection alone. The study was conducted to evaluate whether the efficacy of liver resection combined with radiotherapy in the treatment of patients with HCC is better than liver resection alone.MethodsThe study utilized the data from SEER database. Patients diagnosed with HCC between 2004 and 2015 who received liver resection or the combination of liver resection and radiotherapy were included in the analysis. The propensity score matching model (PSM) was used to reduce selection bias.ResultsBefore PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) of patients treated with liver resection alone were longer than in patients treated with the combination of liver resection and radiotherapy (P<0.001). However, there was no statistically significant difference in mOS and mCSS between the groups after PSM (P>0.05). The subgroup analysis after PSM documented that patients with AJCC stage I and II who were treated with liver resection and radiotherapy had no longer mOS and mCSS than patients subjected to the combination of liver resection alone (P=0.151 and P=0.185). Similar results were obtained in the subgroup group of patients with a single tumor smaller than 5 cm.ConclusionThe combination of liver resection and radiotherapy does not prolong the survival of HCC patients more than liver resection alone.