bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial, chemical and isotopic monitoring integrated approach to assess potential leachate contamination of groundwater in a landfill district in Apulia region (Italy).
Authors: Beneduce Luciano , Piergiacomo Federica , Limoni Pier Paolo , Zuffianò Livia Emanuela , Polemio Maurizio
Published: March 2022

Landfill sites are a major concern for soil and groundwater pollution in the disposal area. The impact of accidental spill of leachate through the soil and consequential contamination of the groundwater can seriously threaten human health and the environment. Given the impact of other anthropic activities (i.e., agriculture, cattle farming etc.) coexisting in the same site, the perturbation of groundwater environment may be due my multiple factors. Therefore, it is a challenging issue to correctly establish the pollution source of an aquifer where landfill is not isolated from other anthropic land uses. The present study aimed to realize an integrated environmental monitoring that included microbiological and chemical methods to evaluate potential groundwater pollution in a landfill district in the south of Italy. Conventional (microbial plate count, physical-chemical analyses) and advanced methods (PCR-ARISA, isotope analysis) were included in the study, to characterize both the groundwater aquifer in nine sites surrounding the landfill district and the leachate of the active landfills. By the integration of the acquired data, it was possible to reconstruct the scenario by which agriculture and other human activities, together with seawater intrusion in the karst aquifer, were the main drivers of altered groundwater features in the monitored site. It was possible to exclude any contribution of the landfill leachate to the groundwater environment perturbations.
Long-term analysis of ventricular function in patients with symptomatic coronary disease undergone on-pump or off-pump coronary artery bypass graft
Authors: Silva Rafael Rocha Mol , Hueb Whady , Lima Eduardo Gomes , Rezende Paulo Cury , Soares Paulo Rogério , Ramires José Antonio Franchini , Filho Roberto Kalil
Published: March 2022

Background: Systemic non-physiological effects of cardiopulmonary bypass have been observed in the periprocedural period. Long-term assessment, including ventricular function (VF), is unclear. The objective of this study was to compare the evolution of left ventricular ejection fraction (LVEF) in a long-term follow-up among patients with coronary artery disease (CAD) who underwent off-pump (OPCAB) or on-pump coronary artery bypass graft (ONCAB).Methods: This study is a pre-specified analysis of the MASS III trial, a single-center and prospective study that enrolled patients with stable CAD initially preserved VF and randomized to OPCAB or ONCAB. They accomplished a new measure of LVEF by transthoracic echocardiogram in the follow-up, and the primary endpoint was the difference between final and baseline LVEF.Results: Of 308 patients randomized, 225 had a new evaluation of LVEF in a mean of 5.9 years of follow-up: 113 in ONCAB and 112 in the OPCAB group. Baseline characteristics were similar between groups, except for higher subjects with the 3-vessel disease in ONCAB. There was no difference in LVEF at the beginning (P=0.08) but, there was a discrete decrease in both LVEF for ONCAB and OPCAB groups (P <0.001 in both groups) in 5.9 years. Despite this, the decline was not significantly different between groups (delta of -6% for ONCAB and -5% for OPCAB; P=0.78). In a multivariate analysis, myocardial infarction was a predictor of LVEF <40%.Conclusions: Despite non-physiologic effects, there was no difference in the long-term follow-up of LVEF between the ONCAB and OPCAB groups in this studied sample.
A Th2-score in the tumor microenvironment as a predictive biomarker of response to BCG in patients with non-muscle invasive bladder carcinoma. A retrospective study.
Authors: Villoldo Gustavo Martín , Pombo María Teresa , Aris Mariana , Chemi Joaquín , Mandó Pablo , Nagaraju Supriya , Camean Juan , Burioni Adrián , Egea Deborah , Amat Mora , Mellado José León , Mordoh José , Villaronga Alberto , Barrio María Marcela
Published: March 2022

Intravesical BCG is the gold standard therapy for intermediate/high-risk NMIBC. However, the response rate is ~60%, and 50% of non-responders will progress to muscle invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1), and ultimately cytotoxic tumor elimination. We searched for a predictive biomarker of BCG response by analyzing TILs polarization in the TME in pre-treatment biopsies. Materials and Methods: Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillations of BCG (n=32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with the BCG response. In most nonresponders, Th1/Th2 markers were compared in pre-and post-BCG biopsies.ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and higher number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p=0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity, but with lower specificity. Relapse-free survival was significantly associated with the Th2-score (p=0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the BCG response.Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.
Rare event of NTRK3 rearrangement and amplification in esophageal squamous cell carcinoma
Authors: Xu Huijuan , Jiang Dongxian , Zhang Fuhan , Yu Zixiang , Huang Jie , Sujie Akesu , Xu Jianfang , Hou Yingyong
Published: March 2022

Background: TRK tyrosine kinase inhibitors (larotrectinib or entrectinib) can cause an unknown histological response in NTRK fusion-positive cancer patients,and it has been approved by the US Food and Drug Administration.The neurotrophic tyrosine kinase receptor (NTRK) 3 gene rearrangements is a target of tyrosine kinase inhibitors.We attempted to assess the correlation of NTRK3 gene rearrangement and gene copy number changes with ESCC prognosis.Methods: The tissue microarray of 478 cases was detected by fluorescence in situ hybridization (FISH) assay.Kaplan-Meier survival and Cox regression analysis were performed to evaluate the prognostic significance of NTRK3 rearrangement and amplification in esophageal squamous cell carcinoma.Results: This study show that both NTRK3 gene rearrangement and copy number variation are rare events in ESCC. Gene rearrangement and copy number changes have little influence on the prognosis.Except when gene copy number was greater than or equal to 4, patients with stage I+II showed a trend of poor prognosis (P=0.120; OS, P=0.095). Conclusion: NTRK3 gene rearrangement and gene copy number variation are rare in esophageal cancer, and gene rearrangement does not affect prognosis, while the number of gene copies was 4 as the threshold, there was a tendency of poor prognosis.
Seasonal Response of Crab Disturbance to nitrogen at the Sediment-Water Interface in coastal tidal wetlands
Authors: Hua Guofen , Liu Shangqing , Li Jinli , Liu Xiangdong , Kong Jun
Published: March 2022

This study is to explore the seasonal response of crab disturbances to nitrogen at the sediment-water interface in coastal tidal flat wetlands, adopting field experiment and indoor control test device. Results showed that crab disturbance showed significant seasonality, and there were significant seasonal differences in cave density and depth. The crab disturbance made the nitrogen flux at the sediment water interface in the crab box much larger than that in the control box. And in summer the NH4+-N showed a positive flux released from the sediment to the overlying water, but the NO2--N and NO3--N showed a positive flux released from the sediment to the overlying water only in early stage. In winter the NH4+-N showed a positive flux released from the sediment to the overlying water, but the NO2--N and NO3--N both showed positive and negative fluxes. These results indicated that the presence of crab burrows could make the aerobic layer move down approximately 8~15 cm in summer and directly promote sediment surface nitrification.
Bile duct stone size may influence the efficacy of endoscopic sphincterotomy with or without large-balloon dilation - A meta-analysis
Authors: Chuang Tang-Wei , Leung Joseph , Chen Jyh-Jou , Lee Pei-Lun , Tung Hung-Da , Fang Min-Lin , Ou-Yang Mei-Chen , Chen Jyu-Lin
Published: March 2022

Background
Endoscopic sphincterotomy (EPT) and/or large balloon dilation (EPBD) are used to remove common bile duct (CBD) stones. This meta-analysis compared the efficacy of EPT + EPBD versus EPT alone in removal stones based on stone size.
Methods
Twenty-one studies (10 randomized control trials (RCTs) and 11 non-RCTs) were identified and reviewed from searches of Embase, PubMed, and Web of Science. CBD stone’s size was measured with reference to the diameter of the duodenoscope (13mm) and the size of the large dilatation balloon (17mm) from cholangiogram. The stone clearance rate was compared according to the mean stone size and further divided into group A (small) < 13mm, B (medium) 13–17 mm, and C (large) > 17 mm. The study protocol was registered with Prospero (number CRD42020171689).
Results
In RCTs, EPT + EPBD had a significantly better stone clearance rate (OR = 1.95, 95% CI: 1.15 ~ 3.30) and required less mechanical lithotripsy (ML) (OR = 0.39, 95% CI: 0.23 ~ 0.65) than EPT for removing CBD stones. These results were also supported by analysis of non-RCTs. In subgroup analysis, EPT + EPBD had a significantly better initial stone clearance rate than EPT in groups B and C, but not A. EPT + EPBD also required significantly less ML than EPT in groups B and C. In meta-regression analysis, group B has a better correlation of log OR with the size of CBD stone in initial stone clearance and less ML usage rates but not for group C with larger stones.
Conclusions
EPT + EPBD had a significantly better initial stone clearance rate and required less ML than EPT for medium CBD stones but the efficacy was limited for the large CBD stones.
Trial registration:
The protocol for this review was registered in PROSPERO (registration number CRD42020171689).
Prevalence and correlation of C-shaped root canals of mandibular premolars and molars in Eastern Chinese individuals
Authors: Chen Cheng , Yang Lianfeng , Zhu Tingting , Wu Huili , Zhao Xiao , Wu Daming
Published: March 2022

Background
To investigate the prevalence, correlation, and differences of C-shaped root canals (CSRCs) morphology in permanent mandibular premolars and molars in Eastern Chinese individuals using cone-beam computed tomography (CBCT).
Methods
A total of 8000 mandibular premolars and molars CBCT images from 1000 patients (692 females and 308 males) were collected. The prevalence, correlation, bilateral/unilateral presence, morphology of CSRCs, level of canal bifurcation, sex differences, and location of radicular grooves (RGs) were evaluated. The correlation between the prevalence of CSRCs and RGs in different tooth positions and age groups was analyzed.
Results
The prevalence of CSRCs in mandibular first premolars (MFPs), mandibular second premolars (MSPs), mandibular first molars (MFMs) and mandibular second molars (MSMs) were 10.25%, 0.25%, 0.55% and 47.05%, respectively. There was no correlation between the presence of CSRCs in mandibular premolars and molars. The prevalence of CSRCs in MFPs of males was higher than that in females, while CSRCs in MSMs of females were higher than that in males (P < 0.05). The bilateral symmetry presence of CSRCs in MSMs was significant but not in MFPs. RGs were predominantly found on the mesiolingual surface of premolars and the lingual surface of molars. There was no significant difference in the prevalence of CSRCs in different types of RGs in premolars. The incidence of CSRCs was significantly lower in the non-bifurcation group.
Conclusions
There was a high prevalence of CSRCs in MFPs and MSMs in the Eastern Chinese population, but there was no correlation. The symmetry of CSRCs was significant in MSMs but not in MFPs. The prevalence of CSRCs in MFPs of males was higher than that in females, while the prevalence of CSRCs in MSMs of females was higher than that in males. In the process of RCT of teeth with CSRCs, CBCT should be taken if necessary, and the treatment should be carried out with the aid of a microscope. Clinicians should pay special attention to CSRCs.
Acceptance of Clinical Decision Support System to Prevent Venous Thromboembolism Among Nurses: an Extension of the UTAUT Model
Authors: Zha Huixian , Liu Kouying , Tang Ting , Yin Yue-Heng , Dou Bei , Jiang Ling , Yan Hongyun , Wang Rong , Xie Weping
Published: March 2022

Background Venous thromboembolism (VTE) has been a major public health problem and caused a heavy disease burden. VTE Clinical decision support system (CDSS) was proved to have a positive influence on the prevention and management of VTE. As the direct users, nurses' acceptance of VTE CDSS is of great importance to support the successful implementation of the system. However, there are few relevant studies to investigate nurses' acceptance and the associated factors are still unclear. Objective To investigate the determinant factors of nurses' acceptance of VTE CDSS with the modified Unified Theory of Acceptance and Use of Technology (UTAUT).Methods We designed a questionnaire based on the modified UTAUT and then a cross-sectional survey was conducted among nurses in a tertiary hospital in Nanjing, China. Statistically, a Structural Equation Modeling (SEM)-Partial Least Squares (PLS) path modeling approach was applied to examine the research model.Results A total of 1100 valid questionnaires were recycled. The modified model explained 74.7%, 83.0% and 86% of the variance in user satisfaction, behavioral intention and user behavior, respectively. The results showed that performance expectancy (r=0.254, p=0.000), social influence (r=0.136, p=0.047), facilitating conditions (r=0.245, p=0.000), self-efficacy (r=0.121, p=0.048) and user satisfaction (r=0.193, p=0.001) all had significant effects on nurses' intention. Although effort expectancy (r=0.010, p=0.785) did not have a direct effect on nurses' intention, it could indirectly influence nurses' intention with user satisfaction as the mediator (r=0.296, p=0.000). User behavior was significantly predicted by facilitating conditions (r=0.298, p=0.000) and user intention (r=0.654, p=0.001). Conclusion The research enhances our understanding of the determinants of nurses' acceptance of VTE CDSS. Among these factors, performance expectancy was considered as the top priority. It highlights the importance of optimizing system performance to fit the users' needs. Generally, the findings in our research provide clinical technology designers and administrators with valuable information to better meet users' requirements and promote the implementation of VTE CDSS.
Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases
Authors: Nutma Erik , Fancy Nurun , Marzin Manuel , Tsartsalis Stergios , Muirhead Robert C.J , Falk Irene , de Bruin Joy , Hollaus David , Pieterman Robin , Anink Jasper , Story David , Chandran Siddharthan , Tang Jiabin , Trolese Maria , Saito Takashi , Saido Takaomi , Weinert Maria , Moore Craig , Bendotti Caterina , Aronica Eleonora , Radulescu Carola , Jacobson Steve , Barnes Samuel , Hampton David , Valk Paul van der , Matthews Paul , Amor Sandra , Owen David
Published: March 2022

Microglial activation plays central roles in neuro-inflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. For the first time, we show that TSPO gene and protein expression increases in activated microglia in mouse brain disease models postmortem, but does not change in a non-human primate (Callithrix jacchus) disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter that may be responsible for this, which is consistent with the hypothesis that the increase in TSPO in activated myeloid cells is unique to a subset of species within the Muroidea superfamily of rodents. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO PET reflects density of inflammatory cells rather than their activation state.
The proinflammatory role of guanylate binding protein 5 in inflammatory bowel diseases
Authors: Li Yichen , Lin Xutao , Gao Sheng , Wang Wenyu , Cheng Sijing , Wang Wenxia , Huang Yibo , Zou Yifeng , Zhu Ruixin , Ke Jia , Zhu Lixin
Published: March 2022

Background: NLRP3 inflammasome is implicated in the pathogenesis of inflammatory bowel diseases (IBD). Since guanylate binding protein 5 (GBP5) induces the NLRP3 inflammasome activity, we aim to investigate the potential role of GBP5 in IBD pathogenesis. Results: The expression of GBP5, NLRP3 inflammasome and related cytokines and chemokines were examined in two cohorts of IBD patients and healthy controls, by microarray transcriptome analysis and quantitative real time PCR. Cellular localization of GBP5 in colonic biopsies were examined by immunohistochemistry and immunofluorescence with confocal microscopy. For functional studies, GBP5 was induced by interferon γ or silenced by siRNA or CRISPR/CAS9 technique, and inflammatory activities were evaluated at mRNA and protein levels. We found that expression of GBP5 was elevated in colonic mucosa in two geographically and culturally distinct IBD cohorts. In colonic tissues of IBD patients, GBP5 expression was mainly confined to immune cells and the levels of GBP5 expression were correlated with those of the inflammatory cytokines and chemokines. In cultured T and macrophage cells, expression of proinflammatory cytokines and chemokines were increased when GBP5 was induced, while GBP5 deficiency leads to decreased expression of proinflammatory mediators including gasdermin D, caspase 1, cytokines and chemokines.Conclusions: GBP5 is required in the expression of many pro-inflammatory cytokines and chemokines in intestinal immune cells. In addition, GBP5 may up-regulate inflammatory reactions through an inflammasome mediated mechanism. Since GBP5 plays a pro-inflammatory role at the early steps of the inflammatory cascades of IBD pathogenesis, and is implicated in IBD patients of distinct genetic and environmental backgrounds, targeting GBP5 could be an effective strategy for the management of IBD.
A multi-immune gene prognostic model for evaluation of survival and prognosis of colorectal cancer
Authors: Wen Hexin , Chen Shuran , Qiu Quanwei , Wang Yitong , Zuo Lugen , Liu Mulin , Hao Bo , Dong Rui
Published: March 2022

Objective: We aimed to construct a multi-immune gene model for the prognosis of colorectal cancer. This study would not only provide important clinical data for the evaluation of survival and prognosis of colorectal cancer, but provide insights into the tumor immune mechanisms.Methods: Colorectal cancer gene expression and clinicopathological data were downloaded from the TCGA database, and then we performed gene expression analysis to obtain differentially expressed genes. In addition, we downloaded immune genes from the ImmPort immune gene database, and obtained differentially expressed immune genes after intersection with the differentially expressed colorectal cancer genes. We further performed survival analysis of the differential immune genes to obtain prognosis-related genes, which were used to construct a multi-immune gene prognostic model. We then analyzed the impact of the prognostic model risk score on the survival of colorectal cancer patients through survival analysis, using ROC analysis. In addition, we performed risk curve analysis to validate the accuracy of the prognostic model risk score in assessing the prognosis of colorectal cancer, and also conducted independent prognostic analysis. Finally, we analyzed the correlation between the immune genes, and transcription factors as well as immune cells.Results: Our analysis showed that prognosis of the high-risk group as evaluated by the immune gene prognosis model risk score was poor (P<0.001). The prognostic model risk score could accurately classify the colorectal patients and has high accuracy in the analysis of prognosis of colorectal cancer (AUC=0.861). Our data demonstrated a certain correlation between the immune genes, transcription factors and immune cells.Conclusions: The constructed prognostic model could accurately assess the prognosis and survival of patients with colorectal cancer. Immune genes might regulate malignant progression of tumors by modulating the production of transcription factors and immune cells. This study demonstrated the influence of immune factors on the prognosis of colorectal cancer and provided a reference for further studies evaluating the role of immunity in the development of colorectal cancer.
The Prognostic Value of Diabetes in Patients Underwent Radical Cystectomy: A Meta- analysis
Authors: LV Dong , XIANG Ying , SONG Tao , ZHOU Guang-Peng , SHEN Tai-Ming
Published: March 2022

Objective
To systematically evaluate the impact of diabetes on the prognosis of bladder cancer patients after radical cystectomy (RC).
Methods
PubMed, Embase, Cochrane Library database were selected from the inception to the October 2021. The studies on the effects of diabetes on bladder cancer patients after RC were included for analysis. The inclusion and exclusion criteria were independently selected for literature screening, the quality of the included studies was evaluated and data were extracted.
Results
A total of 5 cohort studies were included, with a total of 2 661 subjects, including 391 cases in the diabetic group, non-diabetes. Meta-analysis results show that diabetes increases the overall risk of death in patients after RC (HR = 1.36, 95%CI: 1.30 ~ 1.43, P < 0.001) and the risk of tumor-specific death (HR = 1.59, 95%CI: 1.29 ~ 1.95, P < 0.001). Sensitivity analysis shows that the stability of this study is well.
Conclusion
Diabetes was an independent risk factor in terms of overall and cancer-specific survival in patients underwent RC.
Activation of KYN-AHR axis impairs the chondrogenic and chondroprotective effects of human umbilical cord-derived mesenchymal stem cells on osteoarthritis
Authors: Chang Yan , Wang Xinwei , Li Susu , Wang Yueye , Jia Chengyan , Yang Xuezhi , Li Siyu , Zhang Bingjie , Zhao Yingjie , Wei Wei
Published: March 2022

Background: It has been proved that intra-articular injection of mesenchymal stem cells (MSCs) could alleviate cartilage damage of osteoarthritis (OA) via differentiating into chondrocytes or protecting inherent cartilage. However, how OA articular microenvironment could affect MSCs’ chondrogenic and chondroprotective efficiency has yet to be fully demonstrated. Tryptophan (Trp) metabolites, most of which are endogenous ligand for aryl hydrocarbon receptor (AHR), are abnormally increased in synovial fluid (SF) of OA patient. In this study, the effects of kynurenine (KYN), one of the most important metabolites of Trp, were evaluated on the chondrogenic and chondroprotective effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). Methods: hUC-MSCs were cultured with conditioned medium containing different proportions of OA SF, then AHR activation, proliferation and chondrogenesis of hUC-MSCs were measured. In order to determine whether the chondrogenic differentiation of hUC-MSCs were regulated by AHR, hUC-MSCs were stimulated with KYN before detecting their chondrogenesis. In vitro AHR-konck down hUC-MSCs stable cell line (shAHR-UC-MSC) was generated using lentivirus transfection. Moreover, the chondroprotective effiency of shAHR-UC-MSC was determined in OA rat model.Results: OA SF could activate AHR signaling in hUC-MSCs in a concentration-dependent manner and inhibit the chondrogenic differentiation and proliferation ability of hUC-MSCs. Similar results were observed in hUC-MSCs stimulated with KYN in vitro. AHR knockdown could remarkably eliminate the suppression effects of KYN on hUC-MSCs’ chondrogenic differentiation and proliferation ability. Notably, hUC-MSCs with AHR knockdown exhibited superior therapeutic effiency in OA rat upon intra-articular injection. Conclusion: Taken together, this study indicates that OA articular microenvironment is not conducive to the therapeutic effect of hUC-MSCs, which is related to the activation of the AHR pathway by tryptophan metabolites, thus impairs the chondrogenic and chondroprotective effects of hUC-MSCs. AHR might be a promising modification target for further improving the therapeutic efficacy of hUC-MSCs on treatment of cartilage-related diseases such as OA.
When the world stops: The impact of COVID-19 on physical activity and physical literacy
Authors: Houser Natalie , Humbert Louise , Kriellaars Dean , Erlandson Marta
Published: March 2022

Matched pre-during pandemic comparison (160 children) revealed a substantial reduction in physical activity (p < 0.001, rrb=0.83), environmental participation (p = 0.046, rrb=0.16), movement valuation (p < 0.001, rrb=0.61), and parent perceptions of children’s physical literacy (p < 0.001, rrb=0.56,). Examining physical activity trajectories, higher pre-pandemic physical literacy protected children from pandemic related activity decline. Emerging from the pandemic, interventions should address children’s eroded belief in movement, and consider physical literacy levels of children in individualizing movement opportunities for restoration of activity levels.
Electrodeposited Magnetic Nanoporous Membrane (MNM) with a Multi-Edge Superparamagnetic Heterogeneous Wedge Junction for High-Yield and High-Throughput Immunocapture of Specific Extracellular Vesicles and Lipoproteins
Authors: Zhang Chenguang , Huo Xiaoye , Zhu Yini , Higginbotham James , Lu Xin , Franklin Jeffrey , Vickers Kasey C. , Coffey Robert , Senapati Satyajyoti , Wang Ceming , Chang Hsueh-Chia
Published: March 2022

Superparamagnetic nanobeads offer several advantages over microbeads for immunocapture of specifc molecular nanocarriers (extracellular vesicles, lipoproteins, and viruses) in a bioassay: high-yield capture, reduction in incuba-tion time and higher capture capacity. However, nanobeads are difficult to “pull down” because their superparamag-netic feature requires high nanoscale magnetic field gradients in addition to high magnetic fields. Here, electroplated track-etched membrane is shown to produce a unique superparamagnetic nanowedge ring with multiple edges around each nanopore. With a uniform external magnetic field, the induced monopole and dipole of this nanowedge junction combine to produce a 10x higher nanobead trapping force. A dense nanobead suspension can be filtered through the magnetic nanoporous membrane (MNM) at a high-throughput with 99% bead capture rate. The capture yield of specific nanocarriers in heterogeneous media (filtered plasma and conditioned cell media) by nanobeads/MNM ex-ceeds 80%. Quantification of RNA cargo in captured extracellular vesicles demonstrate 60x increase in capture rate of a specific microRNA relative to magnetic bead columns. Reproducibility, low loss, and concentration-independent capture rates are also demonstrated. This new MNM material hence significantly expands the application of nano-bead immunocapture to heterogeneous physiological samples, such as blood and saliva, whose molecular analytes are cargoes of nanocarriers.
Upregulation of miR-1199-5p is associated with reduced type 2 5-α reductase in benign prostatic hyperplasia
Authors: Liu Zhanliang , Lin Zhemin , Cao Fang , Jiang Mingxin , jin Song , Cui Yun , Niu YN
Published: March 2022

Background
The 5-α reductase inhibitors (5-ARIs) are the first-line drug managing benign prostatic hyperplasia (BPH). Unfortunately, some patients showed no responses to 5-ARIs therapy, even suffering from worse symptoms. Although the decreased expression of 5-α reductase type 2(SRD5A2) in BPH tissues might explain the 5-ARIs therapy failure, the mechanisms underlying SRD5A2 decreased remained unelucidated.
Objectives
To investigate the mechanisms of microRNA regulating the variable expression of SRD5A2 resulting in treatment failure of 5-ARIs.
Materials and methods
The expression of SRD5A2 and microRNAs in BPH tissues and prostate cells were detected by immunohistochemistry, western blotting, and quantitative real-time PCR (qRT-PCR). Dual-luciferase reporter assay was performed to confirm that microRNA directly combine to SRD5A2 mRNA. The apoptosis of prostatic cells was detected by flow cytometry.
Results
13.6%, 28.8%, and 57.6% of BPH tissues showed negative, weak, and strong positive SRD5A2 expression, respectively. Normal human prostatic epithelial cell line RWPE-1 strongly expressed SRD5A2, whereas the immortalized human prostatic epithelial cell line BPH-1 weakly expressed SRD5A2. miR-1199-5p expression level in BPH-1 was remarkably higher than that in RWPE-1(P༜0.001), and miR-1199-5p expression was significantly upregulated in BPH tissues with negative SRD5A2 expression than those with positive SRD5A2 expression. After miR-1199-5p mimics transfection, SRD5A2 expression was decreased markedly in RWPE-1 cells, whereas after miR-1199-5p inhibitor transfection, SRD5A2 expression increased in BPH-1 cells. Dual-luciferase reporter assay showed that miR-1199-5p could bind the 3’ untranslated region of SRD5A2. Additionally, miR-1199-5p could decrease the sensibility of finasteride (100 µM) on RWPE-1 cells.
Conclusion
Our results demonstrate that SRD5A2 expression varied in BPH tissues and miR-1199-5p might be one of the several factors contributing to differential SRD5A2 expression in BPH patients.
The filamentary internal structure of the 3C279 blazar jet
Authors: Fuentes Antonio , Gomez Jose , Martí José María , Perucho Manel , Zhao Guang-Yao , Lico Rocco , Lobanov Andrei , Bruni Gabriele , Kovalev Yuri , Chael Andrew , Akiyama Kazunori , Bouman Katherine , Sun He , Cho Ilje , Traianou Efthalia , Toscano Teresa , Dahale Rohan , Gurvits Leonid , Jorstad Svetlana , Kim Jae-Young , Marscher Alan , Mizuno Yosuke , Ros Eduardo , Savolainen Tuomas
Published: March 2022

Supermassive black holes at the centre of active galactic nuclei power some of the most luminous objects in the Universe. Typically, very long baseline interferometric (VLBI) observations of blazars have revealed only funnel-like morphologies with little information of the ejected plasma internal structure. Here we show extremely-high angular resolution images of the blazar 3C279 obtained with the space VLBI mission RadioAstron, which allowed us to resolve the jet transversely and reveal several filaments produced by Kelvin–Helmholtz instabilities in a kinetically dominated flow that originate from the VLBI core and extend up to 175 parsecs (de-projected) downstream the jet. The VLBI core appears to be elongated, in agreement with recent Event Horizon Telescope results, but thanks to our higher dynamic range and increased field of view we are able to connect the immediate environment of the supermassive black hole with the large-scale jet. From the observed linear polarization and strong cross-section emission asymmetry we can infer that the filaments are threaded by a helical magnetic field rotating clockwise, as seen in the direction of the flow motion, with an intrinsic helix pitch angle of ~45 degrees in a jet with a Lorentz factor of ~13.
Bone-Marrow Derived Stem Cells Protocol for Premature Ovarian Failure – A case study with successful spontaneous pregnancy and delivery after treatment.
Authors: Naimat Ihsan , Alaomar Salma , Aljarrah Majed , Alkraimeen Leen , Alayan Sara , Mihai Diana , Mishra Prabhu
Published: March 2022

OBJECTIVES Stem cell-based therapies are emerging enormously as a ray of hope and therapeutic alternative for ovarian rejuvenation, regeneration and follicular development in women with impaired ovaries mainly due to primary ovarian insufficiency or premature ovarian failures, the conditions which cannot be improved much medically or surgically. In the modern society, the childbearing age is being delayed by women due to profound socio-economic changes making ovarian aging a key challenge for reproductive medicine. Based on the current scenario, the need of the hour is novel methods to restore fertility for all cases of ovarien impairement like poor ovarian reserve or primary ovarian insufficiency. As per the studies reported, the infusion of the whole population of human bone marrow-derived stem cells promote ovarian local vascularization, human follicle growth, increase follicle and stromal cell proliferation, and lead to reduction in apoptosis and atresia thereby, providing an adequate ovarian niche for follicular rescue in patients. MATERIAL AND METHOD Based on the previous reports, we aimed to evaluate the effects of autologous bone marrow derived stem cell transplantation into ovary on the ovarian reserve of women with impaired ovarian functions. We, therefore, designed a method to deliver bone marrow derived stem cells directly to human ovaries. RESULTS This study showed that autologous bone marrow derived stem cell ovarian transplant led to the improvement in ovarian reserve biomarkers and reproductive outcomes which results in more follicles and oocytes developed after ovarian stimulation. This technique allows successful pregnancies in women with impaired ovarian functions, however, further research is still needed as the embryo euploidy is not modified by the stem cells therapy. Diagnostic hormonal levels improved post procedure; there was a reduction in FSH and increase in AMH and estradiol levels.CONCLUSIONS Stem cells are foundation cells of the body with the remarkable abilities of self-renewal and differentiation into other cell types and this treatment bring hope to a lot of couples dealing with infertility.
Escape box and puzzle design as educational methods for engagement and satisfaction of medical student learners in emergency medicine: Survey study
Authors: Cantwell Christina , Saadat Soheil , Sakaria Sangeeta , Wiechmann Warren , Sudario Gabriel
Published: March 2022

Background: Gamification in medical education has gained popularity over the past several years. We describe a virtual escape box in emergency medicine clerkship didactics to teach chest pain and abdominal pain and compare this instructional method to a traditional flipped classroom format. Methods: A virtual escape box was designed at our institution and incorporated into the mandatory two-week emergency medicine clerkship. The game consisted of a PDF with four cases containing puzzles to unlock a final clue. Likert scale surveys were administered to assess participants’ perceptions of the escape box format; of clerkship didactics as a whole; and of the clerkship overall. These responses were compared to the prior year’s evaluations on flipped classroom didactics and clerkship. Results: 134 learners participated in the escape box and completed the survey. Eighty-six percent strongly agreed with feeling more engaged with the escape box, 84% strongly agreed with learning something new, 81% strongly agreed with finding the escape box to be satisfying, 78% strongly agreed with being able to apply knowledge gained, and 74% strongly agreed with wanting more escape boxes incorporated into medical education. The escape box showed a higher average score (3.6±0.63) compared to chest pain (3.5±0.67) and abdominal pain (3.2±0.77) flipped classroom sessions (p=0.0491) for the category of “lecturer explaining content clearly and at the proper level of complexity.” For the category of “lecturer provided effective instructional materials,” the escape box showed higher scores (3.6±0.63) compared to flipped classroom for chest pain (3.4±0.77) and abdominal pain (3.1±0.80) (p<0.001). Conclusions: Escape boxes are adaptable to a virtual format and can teach abstract concepts such as teamwork and communication in addition to traditional lecture content. Ratings of didactics were higher for the escape box compared to the flipped classroom, while ratings of overall clerkship experience were not found to change significantly.
Positive lymph nodes predict distant metastasis of salivary duct carcinoma after postoperative radiotherapy
Authors: Yan Wenbin , Ou Xiaomin , shen chunying , Hu Chaosu
Published: March 2022

Purpose
Salivary duct carcinoma (SDC) is a high-grade subtype of salivary gland malignancy. Distant metastasis was the common pattern of failure for patients receiving surgery and adjuvant radiotherapy. We are aimed to analyze the prognostic value of positive lymph nodes for distant metastasis in the SDC following postoperative radiotherapy.
Patients and Methods
: We reviewed the data of patients with SDC receiving surgical resection and radiotherapy. The univariate analysis was conducted using Log-rank method for the clinicopathological features with distant-metastasis-free survival (DMFS). The multivariable analysis was performed by Cox regression hazards method. A risk stratification model was established by the score calculated with the variables qualified by multivariate P < 0.05.
Results
91 patients were enrolled, and the median age at diagnosis was 58.5 years. 53.8%(n = 49) of the patients appeared with the involvement of neck lymph nodes after surgery. The advanced T stage (95% CI 1.325–5.38; P = 0.006), number of positive lymph nodes (PLN ≥ 8) (95% CI 1.241–6.58; P = 0.013), and peripheral invasion (PNI) (95% CI 1.059–4.65; P = 0.034) were significantly associated with DMFS for the SDC in the multivariate analysis. Patients were divided into two subgroups based on the risk factors, while significant differences of DMFS and OS were observed between the risk cohorts (5-year DMFS:35% vs.64.4%, P = 0.0001; 5-year OS:53.6% vs.70.4%; P = 0.048).
Conclusion
Higher number of positive lymph nodes was associated with worse DMFS in SDC following PORT. The patients at high risk appeared with significantly poor DMFS and survival, and clinical trials on adjuvant therapy are warranted for this subgroup.
An experimental electro-thermo-mechanical characterization of plastic deformation of quenched and tempered pipe steel for oil country tubular goods
Authors: Saberi Saeid , Weiss Helmut , Winter Gerald , Klarner Jürgen , Stockinger Martin
Published: March 2022

Development, manufacturing, and optimization of Oil Country Tubular Goods (OCTG) are strongly related to thermo-mechanical behavior of quenched and tempered pipe steels. Threaded pipe connections consist of a pipe end with external thread (pin) and coupling with the internal thread (box). They are manufactured on seamless pipes made of typical OCTG steel grades like P110. Introduced residual stresses in the threaded connections due to cold preforming process as well as tension/ compression and torsion make-up tests lead to material degradation of the pipe steel. The complex geometry of thread and difficult access to the thread surface make conventional methods for residual stress measurement impossible. In this study, in-situ measurement of the strain, the temperature and the electrical resistivity of steel P110 during electro-mechanical coupled uniaxial tensile test was performed. The electro-thermo-mechanical properties of the investigated material were determined using a Matlab® code. The presented experimental method could be used for the experimental in-situ measurement of local plastic strains in threaded connections under make- up tests. Inanition, the obtained results of this research such as electro-thermo-mechanical properties of investigated pipe steel could be applied for material modelling of pipe steels.
Taxonomic study of polymorphic basidiomycetous fungi Sirobasidium and Sirotrema: Sirobasidium apiculatum sp. nov., Phaeotremella translucens comb. nov. and rediscovery of Sirobasidium japonicum in Japan
Authors: Degawa Yousuke , Endoh Rikiya , Masumoto Hiroshi , Yoshihashi Yuma , Ohkuma Moriya , Degawa Yousuke
Published: March 2022

Species in the genera Sirobasidium and Sirotrema (Tremellales, Tremellomycetes, Agaricomycotina, Basidiomycota) were described based on the morphology of teleomorph, and many of them lack both isolates of anamorphic yeast state and nucleotide sequence data. Strains of Sirotrema translucens and Sirobasidium japonicum were established for the first time from basidiocarps collected in Japan. Also, an undescribed species in the genus Sirobasidium was isolated. Molecular phylogenetic analysis based on the sequences of D1/D2 region of large subunit ribosomal RNA gene (LSU D1/D2), ITS-5.8S ribosomal RNA gene (ITS), and small subunit ribosomal RNA gene (SSU) showed that St. translucens, which has been considered to be related to the genus Sirobasidium based on its basidial ontogeny, was placed in a phylogenetically separated clade including the genus Phaeotremella. The analysis also revealed that Sirobasidium sp. and Sb. japonicum, previously assumed to have a close affinity to the order Auriculariales, were members in the Tremellales. Sirobasidium sp. was characterised by its apiculate epibasidia and 2-celled basidia, which is a unique combination of characteristics in the genus. In conclusion, we keep Sirobasidium japonicum in the Tremellales and propose Sirobasidium apiculatum sp. nov. and Phaeotremella translucens comb. nov.
The effect of goal-directed crystalloid versus colloid administration on postoperative pulmonary function: A substudy of a randomized controlled clinical trial
Authors: Obradovic Mina , Luf Florian , Reiterer Christian , Schoppmann Sebastian , Kurz Andrea , Fleischmann Edith , Kabon Barbara
Published: March 2022

Background: Pulmonary function is impaired after major abdominal surgery and might be improved by restrictive fluid administration. Under the assumption of a fluid sparing effect of colloids we tested the hypothesis that an intraoperative colloid-based goal-directed fluid management strategy improves postoperative pulmonary function parameters compared to goal-directed crystalloid administration. Methods: We performed a preplanned, single-center substudy within a recently published trial evaluating the effect of goal-directed crystalloids versus colloids on a composite of major complications. 60 patients undergoing major open abdominal surgery were randomized to Doppler-guided intraoperative fluid replacement therapy with lactated Ringer’s solution (n = 31) or 6% hydroxyethyl starch 130/0.4 (n = 29). A blinded investigator performed bedside spirometry (Spirobank-G, Medical International Research; Rome, Italy) preoperatively as well as 6-, 24-, and 48 hours postoperatively. Results: Median total intraoperative fluid requirements were significantly higher during crystalloid administration compared to patients receiving colloids (4567 ml vs. 3044 ml, p = 0.01). 6 hours after surgery pulmonary function parameters did not differ significantly between the crystalloid - and the colloid group: forced vital capacity (FVC): 1.6 l (1.2 - 2 l) vs.1.9 l (1.5 - 2.4 l), p = 0.15; forced expiratory volume in 1 second (FEV1): 1.1 l (0.9 - 1.6 l) vs. 1.4 l (1.2 - 1.7 l), p = 0.18; peak expiratory flow (PEF): 2 l.sec -1 (1.5 - 3.6 l.sec -1) vs. 2.3 l.sec -1 (1.8 - 3.4 l.sec -1 ), p = 0.23. Similarly, postoperative time weighted averages of FVC (p = 0.50), FEV1 (p = 0.96) and PEF (p = 0.39) did not differ significantly. Conclusion: Intraoperative goal-directed colloid administration did not significantly improve postoperative pulmonary function parameters in patients undergoing open abdominal surgery compared to goal-directed crystalloid administration.Trial Registration: ClinicalTrials.gov (NCT00517127, registered on August 16th, 2007, https://clinicaltrials.gov/ct2/show/NCT00517127) and EudraCT (2005-004602-86)
Nonparametric inference for the reproductive rate in generalized compartmental models
Authors: Trejo Imelda , Lin Yen Ting , Patrick Amanda Louise , Hengartner Nicolas
Published: March 2022

We develop a tractable non-parametric model for the time-varying reproductive rate of infectious diseases that combines the structure of a deterministic compartmental model and a stochastic model for incidence data. We use Bayesian inference to estimate, with uncertainty, the reproductive rate of the Coronavirus 2019 outbreak in the U.S. states of California, Florida, Michigan, New Mexico, New York, and Texas from January 2020 to March 2022. We use the inferred reproductive rates to estimate the posterior distribution of the time-varying reproduction numbers for each state. Compering the time-varying reproduction numbers across the states, we identify some epidemic waves, potentially driven from changes in human behavior and virus mutations.
Analysis of palmar hyperhidrosis using thermal image-based heat of evaporation
Authors: Lee Jiwon , Lee Onseok
Published: March 2022

The condition of hyperhidrosis, which may impair one's quality of life depending on the degree of discomfort, is characterized by excessive sweating. Clinicians mainly use patient histories and questionnaires to diagnose palmar hyperhidrosis. In cases of high severity, hyperhidrosis is diagnosed through infrared thermal imaging; however, it is evaluated based on the clinician's knowledge and experience. Therefore, we intend to present an objective diagnostic method that uses a quantitative approach as an alternative to the subjective evaluation for diagnosing diseases such as hyperhidrosis. In this study, the heat of palmar evaporation was quantified and analyzed from thermal images. The higher the water in the evaporating process of residual heat from body temperature and sweat, the slower is the diffusion, and hyperhidrosis can be diagnosed depending on the degree of diffusion. The analyzed data were used as classifier training data to diagnose the state of sweating. K-nearest neighbors, one of the classifiers used, showed the best performance with 98% accuracy. This study quantitatively presents the criteria for determining the injection site for drug treatment of palmar hyperhidrosis, and can be presented as a new diagnostic evaluation method for thermal imaging-based palmar hyperhidrosis based on the phenomenon of evaporation.
Spatial epitranscriptomics reveals A-to-I editome specific to cancer stem cell microniches
Authors: Kwon Sunghoon , Lee Amos , Lee Yongju , Choi Ahyoun , Lee Han-Byoel , Shin Kyoungseob , Lee Hyunho , Kim Ji Young , Ryu Han Suk , Kim Hoe Suk , Ryu Seung Yeon , Lee Sangeun , Cheun Jong-Ho , Yoo Duck Kyun , Lee Sumin , Choi Hansol , Ryu Taehoon , Yeom Huiran , Kim Namphil , Noh Jinsung , Lee Yonghee , Kim Inyoung , Bae Sangwook , Kim Jinhyun , Lee Wooseok , Kim Okju , Jung Yushin , Kim Changhoe , Song Seo Woo , Choi Yeongjae , Chung Junho , Kim Byung Gee , Han Wonshik
Published: March 2022

Epitranscriptomic features, such as single-base RNA editing, are sources of transcript diversity in cancer, but little is understood in terms of their spatial context in the tumour microenvironment. Here, we introduce spatial-histopathological examination-linked epitranscriptomics converged to transcriptomics with sequencing (Select-seq), which isolates regions of interest from immunofluorescence-stained tissue and obtains transcriptomic and epitranscriptomic data. With Select-seq, we were able to analyse the cancer stem cell-like microniches in relation to the tumour microenvironment of triple-negative breast cancer (TNBC) patients. We identified alternative splice variants, performed complementarity-determining region analysis of infiltrating T cells and B cells, and assessed adenosine-to-inosine (A-to-I) base editing in tumour tissue sections. Especially, in TNBC microniches, A-to-I editome specific to different microniche groups was identified.