bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Combination of Lime and Plant Species Effects on Trace Metals (Copper and Cadmium) in Soil Exchangeable Fractions and Runoff in the Red Soil Region of China
Authors: Xu Lei , Xing Xiangyu , Cui Hongbiao , Zhou Jing , Zhou Jun , Peng Jianbiao , Bai Jingfeng , Zheng Xuebo , Ji Mingfei 
Published: July 2021

The water-soluble heavy metal ions in contaminated soil may enter aquatic ecosystem through runoff, thus causing negative impact on the water environment. In this study, a two-year in situ experiment was carried out to explore an effective way to reduce the runoff erosion and water-soluble copper (Cu) and cadmium (Cd) in a contaminated soil (Cu: 1,148 mg kg−1, Cd: 1.31 mg kg−1) near a large Cu smelter. We evaluated the ability to influence soil properties by four Cu-tolerance plant species (Pennisetum sp., Elsholtzia splendens, Vetiveria zizanioides, Setaria pumila) grown in a contaminated acidic soil amended with lime. The results show that the addition of lime can significantly reduce the exchangeable fraction (EXC) of Cu and Cd in soil (81.1–85.6% and 46.3–55.9%, respectively). Plant species cannot change the fraction distributions of Cu and Cd in the lime-amended soils, but they can reduce the runoff generation by 8.39–77.0%. Although water-soluble Cu concentrations in the runoff were not significantly differed and water-soluble Cd cannot be detected among the four plant species, the combined remediation can significantly reduce 35.9–63.4% of Cu erosion to aquatic ecosystem, following the order: Pennisetum sp. &gt; Elsholtzia splendens &gt; Vetiveria zizanioides &gt; Setaria pumila. The implication of this study would provide valuable insights for contaminated soil management and risk reduction in the Cu and Cd contaminated regions.
A Web Screening on Educational Initiatives to Increase Citizens’ Literacy on Genomics and Genetics
Authors: Sassano Michele , Calabrò Giovanna Elisa , Boccia Stefania 
Published: July 2021

IntroductionPopulation awareness and empowerment in omics sciences represent a fundamental driver to increase the adoption of evidence-based approaches in personalized medicine. In this context, a pivotal role is played by citizens’ literacy, and educational initiatives carried out in this context are key assets to drive future effective interventions. With the present study, we summarized the educational initiatives conducted worldwide aimed at increasing citizens’ literacy in omics sciences.Materials and MethodsWe conducted a web search of the educational initiatives aimed at improving citizens’ literacy in omics sciences undertaken worldwide, by using three search engines (Google, Bing, and Yahoo Search), in English and in Italian languages.ResultsWe identified five initiatives in Europe, 22 in non-European countries, and 13 in Italy. Overall, the majority (69%) were web-based initiatives, while 31% required in-person attendance. The online initiatives included web pages for reading, online lessons/courses, web portals, videos/short movies, animations, and apps for mobile devices. The residential initiatives, on the other hand, included exhibitions, seminars, courses, symposia, information stands in public places, guided visits to research laboratories, and interactive laboratories. All the initiatives were highly heterogeneous in terms of methodologies and the topics addressed.Discussion and ConclusionOverall, we identified a variety of initiatives aimed at improving citizens’ literacy in omics sciences, with the largest majority carried out in the United States and being web-based. Our results showed heterogeneity among the initiatives as to the dealt topics and the adopted methods. Further research is needed, however, to quantitatively assess the effectiveness of educational initiatives to improve citizens’ literacy in omics sciences.
The Effect of Immunosuppressive Adjuvant Kynurenine on Type 1 Diabetes Vaccine
Authors: Sun Jing , Shi Jiandong , Li Jianfang , Wu Meini , Li Yanhan , Jia Sengquan , Ma Chunli , Wang Xinyi , Li Zhiyuan , Hu Ningzhu , Hu Yunzhang 
Published: July 2021

Inducing antigen-specific tolerance is a promising treatment for preventing or reversing Type 1 diabetes (T1D). In contrast to a vaccine that induces immune responses against pathogens, a tolerogenic vaccine can suppress immunity against antigens causing diseases by administrating a mixture of self-antigens with an adjuvant that decreases the strength of antigen-specific response. Kynurenine (Kyn) is an endogenous substance that can inhibit the natural killer cell and T cell proliferation and promote the differentiation of naïve T cells into regulatory T cells (Tregs). In this study, we evaluated the efficacy of Kyn as a novel suppressive adjuvant. Kyn was co-immunized with GAD65 phage vaccine to induce Tregcells and tolerogenic responses for the prevention of T1D in NOD mouse model. Mice were subcutaneously immunized two times with 1011Pfu (100μL,1012Pfu/ml) GAD65 phage vaccine doses mixed with 200 μg of Kyn. Serum antibodies and cytokines were detected by ELISA and electrochemiluminescence, respectively. Flow cytometry assay was used to analyze DC and Treg. MTS was used for the analysis of spleen lymphocyte proliferation. RNA sequencing was used to investigate mRNA and miRNA expression profiles in spleen lymphocytes. Compared to GAD65 phage vaccine alone, co-immunization of Kyn and GAD65 phage vaccine resulted in the prevention of hyperglycemia in 60% of mice for at least one month. Further, Kyn enhances GAD65-specific Th2-mediated immune responses; regulates the Th1/Th2 imbalance and increases the secretion of Th2 cytokines and the number of CD4+CD25+Foxp3+T cells; suppresses DC maturation and GAD65-specific T lymphocyte proliferation. Moreover, we integrated Kyn related miRNA and mRNA expression profiles obtained from the spleen lymphocyte RNA-sequencing which was stimulated by Kynin vitro. These data provide an important basis for understanding the mechanisms underlying Kyn as an immunosuppressive adjuvant which regulated the immune response. These findings suggest that Kyn can serve as an effective suppressive adjuvant candidate for Type 1 diabetes vaccines.
Vagus Nerve Stimulation Promotes Epithelial Proliferation and Controls Colon Monocyte Infiltration During DSS-Induced Colitis
Authors: Meroni Elisa , Stakenborg Nathalie , Gomez-Pinilla Pedro J. , Stakenborg Michelle , Aguilera-Lizarraga Javier , Florens Morgane , Delfini Marcello , de Simone Veronica , De Hertogh Gert , Goverse Gera , Matteoli Gianluca , Boeckxstaens Guy E. 
Published: July 2021

Background: We previously showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis in vagotomized mice. Here, we evaluated whether vagus nerve stimulation (VNS) is able to reduce the severity of DSS colitis and aimed to unravel the mechanism involved.Methods: Colitis was induced in wild type mice by 2.5% DSS administration in drinking water for 5 days. VNS (5 Hz, 1 ms, 1 mA) was applied 1 day prior to and after 4 days of DSS administration to evaluate changes in epithelial integrity and inflammatory response, respectively. Epithelial integrity was assessed using TUNEL and Ki67 staining. Monocytes, immature and mature macrophages were sorted from colonic samples and gene expression levels of pro-inflammatory cytokines were studied.Results: VNS applied prior to DSS administration (i.e., prophylactic VNS) reduced disease activity index (VNS 0.8 ± 0.6 vs. sham 2.8 ± 0.7, p &lt; 0.001, n = 5) and tended to improve histology score. Prophylactic VNS significantly increased epithelial cell proliferation and diminished apoptosis compared to sham stimulation. VNS applied at day 4 during DSS administration (i.e., therapeutic VNS) decreased the influx of monocytes, monocyte-derived macrophages and neutrophils, and significantly reduced pro-inflammatory cytokine expression (i.e., Tnfα and Cxcl1) in immature macrophages compared to sham stimulation.Conclusions: A single period of VNS applied prior to DSS exposure reduced DSS-induced colitis by an improvement in epithelial integrity. On the other hand, VNS applied during the inflammatory phase of DSS colitis reduced cytokine expression in immature macrophages. Our data further underscores the potential of VNS as novel therapeutic approach for inflammatory bowel diseases.
Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Modulates Electroencephalographic Functional Connectivity in Alzheimer’s Disease
Authors: Guo Yi , Dang Ge , Hordacre Brenton , Su Xiaolin , Yan Nan , Chen Siyan , Ren Huixia , Shi Xue , Cai Min , Zhang Sirui , Lan Xiaoyong 
Published: July 2021

Background: Increasing evidence demonstrates that repetitive transcranial magnetic stimulation (rTMS) treatment of the dorsolateral prefrontal cortex is beneficial for improving cognitive function in patients with Alzheimer’s disease (AD); however, the underlying mechanism of its therapeutic effect remains unclear.Objectives/Hypothesis: The aim of this study was to investigate the impact of rTMS to the dorsolateral prefrontal cortex on functional connectivity along with treatment response in AD patients with different severity of cognitive impairment.Methods: We conducted a 2-week treatment course of 10-Hz rTMS over the left dorsolateral prefrontal cortex in 23 patients with AD who were split into the mild or moderate cognitive impairment subgroup. Resting state electroencephalography and general cognition was assessed before and after rTMS. Power envelope connectivity was used to calculate functional connectivity at the source level. The functional connectivity of AD patients and 11 cognitively normal individuals was compared.Results: Power envelope connectivity was higher in the delta and theta bands but lower in the beta band in the moderate cognitive impairment group, compared to the cognitively normal controls, at baseline (p &lt; 0.05). The mild cognitive impairment group had no significant abnormities. Montreal Cognitive Assessment scores improved after rTMS in the moderate and mild cognitive impairment groups. Power envelope connectivity in the beta band post-rTMS was increased in the moderate group (p &lt; 0.05) but not in the mild group. No significant changes in the delta and theta band were found after rTMS in both the moderate and mild group.Conclusion: High-frequency rTMS to the dorsolateral prefrontal cortex modulates electroencephalographic functional connectivity while improving cognitive function in patients with AD. Increased beta connectivity may have an important mechanistic role in rTMS therapeutic effects.
Visualizing Neuropharmacological Effects of Guanfacine Extended Release in Attention Deficit Hyperactivity Disorder Using Functional Near-Infrared Spectroscopy
Authors: Ikeda Takahiro , Inoue Akari , Tanaka Daisuke , Hashimoto Tamao , Sutoko Stephanie , Tokuda Tatsuya , Kyutoku Yasushi , Maki Atsushi , Yamagata Takanori , Dan Ippeita , Monden Yukifumi 
Published: July 2021

Objective: In the current study, we explored the neural substrate for acute effects of guanfacine extended release (GXR) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD), using functional near-infrared spectroscopy (fNIRS).Methods: Following a GXR washout period, 12 AD HD children (6–10 years old) performed a go/no-go task before and 3 h after GXR or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design study. In the primary analysis, fNIRS was used to monitor the right prefrontal cortical hemodynamics of the participants, where our former studies showed consistent dysfunction and osmotic release oral system-methylphenidate (OROS-MPH) and atomoxetine hydrochloride (ATX) elicited recovery. We examined the inter-medication contrast, comparing the effect of GXR against the placebo. In the exploratory analysis, we explored neural responses in regions other than the right prefrontal cortex (PFC).Results: In the primary analysis, we observed no significant main effects or interactions of medication type and age in month (two-way mixed ANCOVA, Fs &lt; 0.20, all ps &gt; .05). However, in the post-hoc analysis, we observed significant change in the oxy-Hb signal in the right angular gyrus (AG) for inter-medication (one sample t-test, p &lt; 0.05, uncorrected, Cohen's d = 0.71).Conclusions: These results are different from the neuropharmacological effects of OROS-MPH and ATX, which, in an upregulated manner, reduced right PFC function in ADHD children during inhibitory tasks. This analysis, while limited by its secondary nature, suggested that the improved cognitive performance was associated with activation in the right AG, which might serve as a biological marker to monitor the effect of GXR in the ADHD children.
Multiple Extramedullary-Bone Related and/or Extramedullary Extraosseous Are Independent Poor Prognostic Factors in Patients With Newly Diagnosed Multiple Myeloma
Authors: He JingSong , Yue XiaoYan , He DongHua , Zhao Yi , Yang Yang , Zheng GaoFeng , Zhang Enfan , Han XiaoYan , Wu WenJun , Yang Li , Chen Jing , Cai Zhen 
Published: July 2021

BackgroundExtramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood.MethodsIn this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen.ResultsThe overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (&gt;1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, &gt;245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients.ConclusionsThis study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.
Comparative Study of Qualitative and Quantitative Analyses of Contrast-Enhanced Ultrasound and the Diagnostic Value of B-Mode and Color Doppler for Common Benign Tumors in the Parotid Gland
Authors: Yan Meiying , Xu Dong , Chen Liyu , Zhou Lingyan 
Published: July 2021

PurposeTo preliminarily identify three common benign parotid gland tumors: pleomorphic adenomas (PA), Warthin tumors (WT), and basal cell adenomas (BCA) by qualitative and quantitative analyses using contrast-enhanced ultrasound (CEUS).MethodsPreoperative images of parotid gland masses were analyzed, including 129 cases of ultrasonography (US) and color Doppler sonography (CDS) and 110 cases of qualitative and quantitative CEUS. The diagnosis was confirmed by postsurgical pathology outcomes.ResultsPA presented low and heterogeneous enhancement and echo-free area, whereas most WT and BCA presented with high and relatively homogeneous enhancement. Compared with WT and BCA groups, a “slow in” pattern was more common in the PA group and a “slow out” pattern was more frequently noted in the WT group than in the PA and BCA groups. The unique features of qualitative CEUS in the PA group enable distinguishing PA from the 2 other groups. The further distinction among the groups was made based on quantitative parameters of time-intensity curves (TICs), which revealed that the mean peak intensity (PI), mean transit time (MTT), the area under the curve (AUC), and time from peak to one half (HT) exhibited significant differences. ROC analysis was next applied to determine the optimal cutoff points to predict the diagnostic tendency among the groups. When the rising slope (RS) was &gt;2.145, the possibility of BCA was greater than WT.ConclusionsCEUS ultrasound is of significant value in the differential diagnosis of the 3 common benign parotid gland masses.
Impact of Examined Lymph Node Count and Lymph Node Density on Overall Survival of Penile Cancer
Authors: Gao Pan , Zhu Tianle , Gao Jingjing , Li Hu , Liu Xi , Zhang Xiansheng 
Published: July 2021

BackgroundFew studies have explored the optimal examined lymph node count and lymph node density cutoff values that could be used to predict the survival of patients with penile cancer. We further clarify the prognostic value of lymph node density and examined lymph node count in penile cancer.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was explored to recruit penile cancer patients from 2010 to 2015. A retrospective analysis of penile cancer patients’ data from the First Affiliated Hospital of Anhui Medical University was performed for verification (2006–2016). The cutoff values of examined lymph node count and lymph node density were performed according to the ROC curve. Kaplan-Meier survival analysis was used to compare survival differences among different groups. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the significant variables. On the basis of Cox proportional hazards regression model, a nomogram was established and validated by calibration plot diagrams and concordance index (C-index).ResultsA total of 528 patients in the Surveillance, Epidemiology, and End Results cohort and 156 patients in the Chinese cohort were included in this study. Using the ROC curve, we found that the recommended cutoff values of ELN and LND were 13 and 9.3%, respectively (P &lt;0.001). Kaplan–Meier curves suggested the significant differences of overall survival among different examined lymph nodes and lymph node density. Multivariate analysis indicated ELN and LND were independent prognostic factor for OS of penile cancer patients. Nomogram showed the contribution of ELN and LND to predicting OS was large. The C-index at 3-, and 5-year were 0.744 for overall survival (95% CI 0.711–0.777).ConclusionsThe more lymph nodes examined, the lower the density of lymph nodes, and the higher the long-term survival rate of penile cancer. We recommended 13 examined lymph nodes and lymph node density &gt;9.3% as the cutoff value for evaluating the prognosis of penile cancer patients.
Anxiety, Loneliness, Drug Craving, and Depression Among Substance Abusers in Sichuan Province, China
Authors: Chen Xin , Qiu Nan , Zhai Liang , Ren Gui 
Published: July 2021

Studies have reported that anxiety had a positive effect on depression among substance abusers in males. However, little is known about the mechanism underlying this relationship in substance abusers in males. The purpose of this study was to investigate the mediating effect of loneliness and drug craving between anxiety and depression in substance abusers in males. State-Trait Anxiety Inventory, The UCLA Loneliness Scale, Drug Craving Scale, and The Center for Epidemiologic Studies Depression Scale were employed into this study to investigate 585 substance abusers in males (age range of 20–58 years: M = 33.21, SD = 6.97). Structural equation modeling and the bootstrap approach were used to analyze the mediating effect of loneliness and drug craving on the relationship between anxiety and depression. The results indicated that: Loneliness had a significant positive correlation with anxiety (r = 0.37, p &lt; 0.001) and depression (r = 0.49, p &lt; 0.001); Drug craving had a significant positive correlation with anxiety (r = 0.28, p &lt; 0.001) and depression (r = 0.39, p &lt; 0.001). Loneliness and drug craving mediated the link between anxiety and depression. There was a significant positive correlation between substance abusers in male’s anxiety, loneliness, drug craving, and depression. Loneliness and drug craving had a significant mediating effect on the relationship between anxiety and depression. Therefore, it was suggested that substance abusers in male’s anxiety and depression might be improved and driven by decreasing loneliness and drug craving. Targeted interventions to decrease substance abusers in male’s loneliness and drug craving should be developed, implemented, and help them to recover.
Non-invasive Biomarkers of Liver Inflammation and Cell Death in Response to Alcohol Detoxification
Authors: Neuman Manuela G. , Mueller Johannes , Mueller Sebastian 
Published: July 2021

IntroductionAlcohol-related liver disease (ALD) represents the most common liver disease worldwide, however, the underlying molecular mechanisms are still poorly understood. Namely centrilobular inflammation and programmed cell death are characteristic to ALD and it remains to be elucidated why they persist despite the absence of alcohol.AimsTo study the effects of alcohol withdrawal in a cohort of heavy drinkers and the role of cirrhosis by using non-invasive biomarkers such as cytokines, apoptotic and angiogenic markers.MethodsCaspase 3-cleaved M30, M65, cytokines (IL-6, IL-8), tumor necrosis factor alpha (TNF-α), transforming growth factor (TGF-β) and vascular endothelial growth factor (VEGF) were measured in 114 heavy drinkers. The role of alcohol detoxification was investigated in 45 patients. The liver histology was available in 23 patients. Fibrosis stage and steatosis were assessed by measuring liver stiffness (LS) and controlled attenuation parameter (CAP) in all patients using transient elastography (FibroScan, Echosens, Paris). Mean observation interval between the measurements was 5.7 ± 1.4 days (mean + –SD).ResultsPatients consumed a mean of 204 ± 148 g/day alcohol with a heavy drinking duration of 15.3 ± 11.0 years. Mean LS was 20.7 ± 24.4 kPa and mean CAP was 303 ± 51 dB/m. Fibrosis distribution was F0–38.1%, F1-2–31%, F3–7.1 and F4–23.9%. Apoptotic markers M30 and M65 were almost five times above normal. In contrast, TNF- α a, IL-8 and VEGF were only slightly elevated. Patients with manifest liver cirrhosis (F4) had significantly higher levels of M30, M65, IL-6 and IL-8. Histology features such as hepatocyte ballooning, Mallory-Denk bodies, inflammation and fibrosis were all significantly associated with elevated LS, and serum levels of TNF-alpha, M30 and M65 but not with CAP and other cytokines. During alcohol detoxification, LS, transaminases, TGF- β, IL-6, IL-8 and VEGF decreased significantly. In contrast, no significant changes were observed for M30, M65 and TNF- α and M30 even increased during detoxification in non-cirrhotic patients. Profibrogenic cytokine TGF-beta and pro-angiogenic cytokine VEGF showed a delayed decrease in patients with manifest cirrhosis.ConclusionPatients with alcohol-related cirrhosis have a pronounced apoptotic activity and a distinct inflammatory response that only partly improves after 1 week of alcohol detoxification. Alcohol withdrawal may represent an important approach to better dissect the underlying mechanisms in the setting of alcohol metabolism.