bluuebunny/crossref_metadata_2025_split huggingface dataset:
Black Sea Methane Flares From the Seafloor: Tracking Outgassing by Using Passive Acoustics
Authors: Longo Manfredi , Lazzaro Gianluca , Caruso Cinzia Giuseppina , Radulescu Vlad , Radulescu Raluca , Sciré Scappuzzo Sergio Simone , Birot Dominique , Italiano Francesco 
Published: August 2021

The Black Sea bottom is well known to be earth’s largest anaerobic methane source, hosting a huge amount of cold seeps releasing significant volumes of methane of both thermogenic and biogenic origin. Taking into account the well-known effects of methane concerning global warming, including the warming up of the oceans, an effective monitoring of its output from the Black Sea is nowadays an essential target for interdisciplinary studies. We discuss the results achieved during monitoring campaigns aimed to detect and track methane flares from the seafloor of the Romanian sector of the Black Sea, in order to better constrain the possible mechanisms responsible for its injection from the marine sediments, through the water column, into the atmosphere. In the mainframe of the ENVRI-Plus project, we deployed a multidisciplinary seafloor observatory for short, mid and long time monitoring and collected samples of the water column. The multidisciplinary seafloor observatory was equipped with probes for passive acoustic signals, dissolved CH4 and chemical-physical parameters. The collected data showed a high concentration of dissolved methane up to values of 5.8 micromol/L. Passive acoustics data in the frequencies range 40–2,500 Hz allow us to discriminate different degassing mechanisms and degassing styles. The acoustic energy associated with gas bubbling is interpreted as a consequence of the gas dynamics along the water column while the acoustic range 2–20 Hz reveals vibration mechanisms generated by gas dynamic’s along the cracks and inside the sediments.
Accuracy Evaluation of Altimeter-Derived Gravity Field Models in Offshore and Coastal Regions of China
Authors: Li Qianqian , Bao Lifeng , Wang Yong 
Published: August 2021

Satellite radar altimetry has made unique contributions to global and coastal gravity field recovery. This paper starts with a general introduction followed by the progress of satellite radar altimetry technology. Then, the methods of marine gravity field recovery and dominating gravity models are described briefly. Finally, typical gravity models are compared with shipboard gravity measurements to evaluate their accuracies in offshore and coastal regions of China. The root mean squares of deviations between gravity models and shipboard gravity are all more than 7 mGal in offshore regions and within the range of 9.5–10.2 mGal in coastal regions. Further analysis in coastal regions indicates that the new gravity models with new satellite missions including Jason-2, SARAL/Altika, and Envisat data have relatively higher accuracy, especially SARAL/Altika data, significantly improving the coastal gravity field. Accuracies are low in areas with strong currents, showing that tide correction is very important for altimetry-derived marine gravity recovery as well as shipboard measurements in coastal gravity field determination. Moreover, as an external check, shipboard gravity data need more operations to improve their precision, such as higher instrument accuracy and finer data processing.
Detection of Urinary Exosomal HSD11B2 mRNA Expression: A Useful Novel Tool for the Diagnostic Approach of Dysfunctional 11β-HSD2-Related Hypertension
Authors: De Santis Domenica , Castagna Annalisa , Danese Elisa , Udali Silvia , Martinelli Nicola , Morandini Francesca , Veneri Mariangela , Bertolone Lorenzo , Olivieri Oliviero , Friso Simonetta , Pizzolo Francesca 
Published: August 2021

ObjectiveApparent mineralocorticoid excess (AME) is an autosomal recessive disorder caused by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme deficiency, traditionally assessed by measuring either the urinary cortisol metabolites ratio (tetrahydrocortisol+allotetrahydrocortisol/tetrahydrocortisone, THF+5αTHF/THE) or the urinary cortisol/cortisone (F/E) ratio. Exosomal mRNA is an emerging diagnostic tool due to its stability in body fluids and its biological regulatory function. It is unknown whether urinary exosomal HSD11B2 mRNA is related to steroid ratio or the HSD11B2 662 C&gt;G genotype (corresponding to a 221 A&gt;G substitution) in patients with AME and essential hypertension (EH).Aim of the StudyTo detect and quantify HSD11B2 mRNA from urinary exosomes in samples from family members affected by AME and EH, and to evaluate the relationship between exosomal HSD11B2 mRNA, steroid ratio, 662C&gt;G genotype, and hypertension.MethodsIn this observational case–control study, urinary steroid ratios and biochemical parameters were measured. Urinary exosomes were extracted from urine and exosomal HSD11B2 mRNA was quantified by Droplet Digital PCR (ddPCR). B2M (β-2 microglobulin) gene was selected as the reference housekeeping gene.ResultsAmong family members affected by AME, exosomal urinary HSD11B2 mRNA expression was strictly related to genotypes. The two homozygous mutant probands showed the highest HSD11B2 mRNA levels (median 169, range 118–220 copies/µl) that progressively decreased in 221 AG heterozygous with hypertension (108, range 92–124 copies/µl), 221 AG heterozygous normotensives (23.35, range 8–38.7 copies/µl), and wild-type 221 AA subjects (5.5, range 4.5–14 copies/µl). Heterozygous hypertensive subjects had more HSD11B2 mRNA than heterozygous normotensive subjects. The F/E urinary ratio correlated with HSD11B2 mRNA copy number (p &lt; 0.05); HSD11B2 mRNA strongly decreased while THF+5αTHF/THE increased in the two probands after therapy. In the AME family, HSD11B2 copy number correlated with both F/E and THF+5αTHF/THE ratios, whereas in EH patients, a high F/E ratio reflected a reduced HSD11B2 mRNA expression.ConclusionsHSD11B2 mRNA is detectable and quantifiable in urinary exosomes; its expression varies according to the 662 C&gt;G genotype with the highest levels in homozygous mutant subjects. The HSD11B2 mRNA overexpression in AME could be due to a compensatory mechanism of the enzyme impairment. Exosomal mRNA is a useful tool to investigate HSD11B2 dysregulation in hypertension.
Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus
Authors: Lee Jaeseon , Park Youngjae , Jang Se Gwang , Hong Seung-Min , Song Young-Seok , Kim Min-Jun , Baek SeungYe , Park Sung-Hwan , Kwok Seung-Ki 
Published: August 2021

ObjectiveBaricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) is recently regarded as a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and JAK/signal transducer and activator of transcription (STAT) pathway-mediated cytokines such as type I interferons. The objective of this study was to determine whether baricitinib could effectively ameliorate SLE using a murine modelMethodsTo investigate effects of baricitinib on various autoimmune features, especially renal involvements in SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used as a lupus-prone animal model and treated with baricitinib for eight weeks. Immortalized podocytes and primary podocytes and B cells isolated from C57BL/6 mice were used to determine the in vitro efficacy of baricitinib.ResultsBaricitinib remarkably suppressed lupus-like phenotypes of MRL/lpr mice, such as splenomegaly, lymphadenopathy, proteinuria, and systemic autoimmunity including circulating autoantibodies and pro-inflammatory cytokines. It also modulated immune cell populations and effectively ameliorated renal inflammation, leading to the recovery of the expression of structural proteins in podocytes. According to in vitro experiments, baricitinib treatment could mitigate B cell differentiation and restore disrupted cytoskeletal structures of podocytes under inflammatory stimulation by blocking the JAK/STAT pathway.ConclusionsThe present study demonstrated that baricitinib could effectively attenuate autoimmune features including renal inflammation of lupus-prone mice by suppressing aberrant B cell activation and podocyte abnormalities. Thus, baricitinib as a selective JAK inhibitor could be a promising therapeutic candidate in the treatment of SLE.
Multi-Strain Tropical Bacillus spp. as a Potential Probiotic Biocontrol Agent for Large-Scale Enhancement of Mariculture Water Quality
Authors: Ren Wei , Wu Haiwu , Guo Cong , Xue Bingqing , Long Hao , Zhang Xiang , Cai Xiaoni , Huang Aiyou , Xie Zhenyu 
Published: August 2021

Graphical AbstractMulti-strain tropical Bacillus spp. as a potential probiotic biocontrol agent for large-scale enhancement of mariculture water quality.
Glucotoxicity Activation of IL6 and IL11 and Subsequent Induction of Fibrosis May Be Involved in the Pathogenesis of Islet Dysfunction
Authors: Lu Liqin , Zhuang Lili , Shen Ximei , Yang Liyong 
Published: August 2021

Background: Islet dysfunction is the main pathological process of type 2 diabetes mellitus (T2DM). Fibrosis causes islet dysfunction, but the current mechanism is still unclear. Here, bioinformatics analysis identified gene clusters closely related to T2DM and differentially expressed genes related to fibrosis, and animal models verified the roles of these genes.Methods: Human islet transcriptomic datasets were obtained from the Gene Expression Omnibus (GEO), and weighted gene coexpression network analysis (WGCNA) was applied to screen the key gene modules related to T2DM and analyze the correlations between the modules and clinical characteristics. Enrichment analysis was performed to identify the functions and pathways of the key module genes. WGCNA, protein-protein interaction (PPI) analysis and receiver operating characteristic (ROC) curve analysis were used to screen the hub genes. The hub genes were verified in another GEO dataset, the islets of high-fat diet (HFD)-fed Sprague-Dawley rats were observed by H&amp;E and Masson’s trichrome staining, the fibrotic proteins were verified by immunofluorescence, and the hub genes were tested by immunohistochemistry.Results: The top 5,000 genes were selected according to the median absolute deviation, and 18 modules were analyzed. The yellow module was highly associated with T2DM, and its positive correlation with glycated hemoglobin (HbA1c) was significantly stronger than that with body mass index (BMI). Enrichment analysis revealed that extracellular matrix organization, the collagen-containing extracellular matrix and cytokine−cytokine receptor interaction might influence T2DM progression. The top three hub genes, interleukin 6 (IL6), IL11 and prostaglandin-endoperoxide synthase 2 (PTGS2), showed upregulated expression in T2DM. In the validation dataset, IL6, IL11, and PTGS2 levels were upregulated in T2DM, and IL6 and PTGS2 expression was positively correlated with HbA1c and BMI; however, IL11 was positively correlated only with HbA1c. In HFD-fed Sprague-Dawley rats, the positive of IL6 and IL11 in islets was stronger, but PTGS2 expression was not significantly altered. The extent of fibrosis, irregular cellular arrangement and positive actin alpha 2 (ACTA2) staining in islets was significantly greater in HFD-fed rats than in normal diet-fed rats.Conclusion: Glucotoxicity is a major factor leading to increased IL6 and IL11 expression, and IL6-and IL11-induced fibrosis might be involved in islet dysfunction.
Neoadjuvant Chemotherapy Versus Direct Surgery for Locally Advanced Gastric Cancer With Serosal Invasion (cT4NxM0): A Propensity Score-Matched Analysis
Authors: Xu Wei , Wang Lingquan , Yan Chao , He Changyu , Lu Sheng , Ni Zhentian , Hua Zichen , Zhu Zhenglun , Sah Birendra Kumar , Yang Zhongyin , Zheng Yanan , Feng Runhua , Li Chen , Yao Xuexin , Chen Mingmin , Liu Wentao , Yan Min , Zhu Zhenggang 
Published: August 2021

BackgroundFor locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients.MethodsPatients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups.ResultsA total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P&lt;0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P&lt;0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P&lt;0.001) and complications (P=0.037) between the two groups.ConclusionThis study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.
Elucidating the Role of Serum tRF-31-U5YKFN8DYDZDD as a Novel Diagnostic Biomarker in Gastric Cancer (GC)
Authors: Huang Yuejiao , Zhang Haiyan , Gu Xinliang , Qin Shiyi , Zheng Ming , Shi Xiangrong , Peng Chunlei , Ju Shaoqing 
Published: August 2021

BackgroundGastric cancer (GC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis combined with surgical treatment can significantly improve the prognosis of patients. Therefore, it is urgent to seek higher sensitivity and specificity biomarkers in GC. tRNA-derived small RNAs are a new non-coding small RNA that widely exists in tumor cells and body fluids. In this study, we explore the expression and biological significance of tRNA-derived small RNAs in GC.Materials and MethodsFirst of all, we screened the differentially expressed tRNA-derived small RNAs in tumor tissues by high-throughput sequencing. Agarose gel electrophoresis (AGE), Sanger sequencing, and Nuclear and Cytoplasmic RNA Separation Assay were used to screen tRF-31-U5YKFN8DYDZDD as a potential tumor biomarker for the diagnosis of GC. Then, we detected the different expressions of tRF-31-U5YKFN8DYDZDD in 24 pairs of GC and paracancerous tissues, the serum of 111 GC patients at first diagnosis, 89 normal subjects, 48 superficial gastritis patients, and 28 postoperative GC patients by quantitative real-time PCR (qRT-PCR). Finally, we used the receiver operating characteristic (ROC) curve to analyze its diagnostic efficacy.ResultsThe expression of tRF-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion. The expression of serum tRF-31-U5YKFN8DYDZDD in the GC patients decreased after the operation (P = 0.0003). Combined with ROC curve analysis, tRF-31-U5YKFN8DYDZDD has better detection efficiency than conventional markers.ConclusionsThe expressions of tRF-31-U5YKFN8DYDZDD in the tumor and paracancerous tissues, the serum of GC patients and healthy people, and the serum of GC patients before and after operation were different. tRF-31-U5YKFN8DYDZDD is not only a diagnostic biomarker of GC but also a predictor of poor prognosis.
The Effect of Severe Intraventricular Hemorrhage on the Biorhythms of Feeding in Premature Infants
Authors: Gewolb Ira H. , Sobowale Babatunde T. , Vice Frank L. , Patwardhan Abhijit , Solomonia Nino , Reynolds Eric W. 
Published: August 2021

Background: Suck-swallow rhythmicity and the integration of breathing into infant feeding are developmentally regulated. Neurological injury and breathing abnormalities can both impact feeding in preterm infants.Objective: To determine the effects of neurologic injury independent of effects of disordered breathing on feeding biorhythms in premature infants.Methods: Low-risk preterm infants (LRP), infants with Grade 3–4 Intraventricular Hemorrhage (IVH), those with bronchopulmonary dysplasia (BPD), and those with both BPD and IVH (BPD+IVH) were identified. Forty-seven infants, 32–42 weeks Postmenstrual Age (PMA) were evaluated on one or more occasions (131 studies). Of these, 39 infants (81 studies) were performed at &gt;35 weeks PMA. Coefficient of variation (COV) (=standard deviation of the inter-event (e.g., suck-suck, swallow-breath, etc.) interval divided by the mean of the interval) was used to quantify rhythmic stability.Results: To adjust for PMA, only those infants &gt;35–42 weeks were compared. Suck-suck COV was significantly lower (more rhythmically stable) in the LRP group [COV = 0.274 ± 0.051 (S.D.)] compared to all other groups (BPD = 0.325 ± 0.066; IVH = 0.342 ± 0.072; BPD + IVH = 0.314 ± 0.069; all p &lt; 0.05). Similarly, suck-swallow COV was significantly lower in LRP babies (0.360 ± 0.066) compared to the BPD group (0.475 ± 0.113) and the IVH cohort (0.428 ± 0.075) (p &lt; 0.05). The BPD+IVH group (0.424 ± 0.109), while higher, was not quite statistically significant.Conclusions: Severe IVH negatively impacts suck-suck and suck-swallow rhythms. The independent effect of neurological injury in the form of IVH on feeding rhythms suggests that quantitative analysis of feeding may reflect and predict neurological sequelae.
Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab for Advanced Non-Small-Cell Lung Cancer
Authors: Wan Xiaomin , Zeng Xiaohui , Peng Liubao , Peng Ye , Liu Qiao , Yi Lidan , Luo Xia , Deng Qijian , Tan Chongqing 
Published: August 2021

Objective: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line setting for patients with advanced non-small-cell lung cancer (NSCLC) from the US payer perspective.Materials and methods: A Markov model wasdeveloped to evaluate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line treatment of advanced NSCLC. The survival benefits of nivolumab plus ipilimumab were based on the results of the CheckMate 227 trial. The main endpoints of the model were cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Univariable and probabilistic sensitivity analyses were conducted to assess model uncertainty. Additonal subgroup analyses were also performed.Results: nivolumab plus ipilimumab produced a gain of 0.62 QALYs, at a cost of $104238 per QALY. The variables that had the greatest influence on the ICER were body weight and overall survival (OS) hazard ratio (HR). The probability of nivolumab plus ipilimumab being cost-effectiveness compared to chemotherapy is 50.7 and 66.2% when the willingness-to-pay (WTP) value is $ 100,000 and $ 150,000 per QALY. The results of subgroup analyses showed the ICER remained below $150,000/QALY regardless of the PD-L1 expression level.Conclusions: nivolumab plus ipilimumab was estimated to be cost-effective compared with chemotherapy for patients with advanced NSCLC at a WTP threshold from 100,000/QALY to 150,000/QALY.
Effects of Naringin on Cardiomyocytes From a Rodent Model of Type 2 Diabetes
Authors: Uryash A. , Mijares A. , Flores V. , Adams J. A. , Lopez J. R. 
Published: August 2021

Diabetic cardiomyopathy (DCM) is a primary disease in diabetic patients characterized by diastolic dysfunction leading to heart failure and death. Unfortunately, even tight glycemic control has not been effective in its prevention. We have found aberrant diastolic Ca2+ concentrations ([Ca2+]d), decreased glucose transport, elevated production of reactive oxygen species (ROS), and increased calpain activity in cardiomyocytes from a murine model (db/db) of type 2 diabetes (T2D). Cardiomyocytes from these mice demonstrate significant cell injury, increased levels of tumor necrosis factor-alpha and interleukin-6 and expression of the transcription nuclear factor-κB (NF-κB). Furthermore, decreased cell viability, and reduced expression of Kir6.2, SUR1, and SUR2 subunits of the ATP-sensitive potassium (KATP) channels. Treatment of T2D mice with the citrus fruit flavonoid naringin for 4 weeks protected cardiomyocytes by reducing diastolic Ca2+ overload, improving glucose transport, lowering reactive oxygen species production, and suppressed myocardial inflammation. In addition, naringin reduced calpain activity, decreased cardiac injury, increased cell viability, and restored the protein expression of Kir6.2, SUR1, and SUR2 subunits of the KATP channels. Administration of the KATP channel inhibitor glibenclamide caused a further increase in [Ca2+]d in T2D cardiomyocytes and abolished the naringin effect on [Ca2+]d. Nicorandil, a KATP channel opener, and nitric oxide donor drug mimic the naringin effect on [Ca2+]d in T2D cardiomyocyte; however, it aggravated the hyperglycemia in T2D mice. These data add new insights into the mechanisms underlying the beneficial effects of naringin in T2D cardiomyopathy, thus suggesting a novel approach to treating this cardiovascular complication.