bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of Oil Trajectory and Fate Modeling of the Deepwater Horizon Oil Spill
Authors: French-McCay Deborah P. , Spaulding Malcolm L. , Crowley Deborah , Mendelsohn Daniel , Fontenault Jeremy , Horn Matthew
Published: February 2021

Trajectory and fate modeling of the oil released during the Deepwater Horizon blowout was performed for April to September of 2010 using a variety of input data sets, including combinations of seven hydrodynamic and four wind models, to determine the inputs leading to the best agreement with observations and to evaluate their reliability for quantifying exposure of marine resources to floating and subsurface oil. Remote sensing (satellite imagery) data were used to estimate the amount and distribution of floating oil over time for comparison with the model’s predictions. The model-predicted locations and amounts of shoreline oiling were compared to documentation of stranded oil by shoreline assessment teams. Surface floating oil trajectory and distribution was largely wind driven. However, trajectories varied with the hydrodynamic model used as input, and was closest to observations when using specific implementations of the HYbrid Coordinate Ocean Model modeled currents that accounted for both offshore and nearshore currents. Shoreline oiling distributions reflected the paths of the surface oil trajectories and were more accurate when westward flows near the Mississippi Delta were simulated. The modeled movements and amounts of oil floating over time were in good agreement with estimates from interpretation of remote sensing data, indicating initial oil droplet distributions and oil transport and fate processes produced oil distribution results reliable for evaluating environmental exposures in the water column and from floating oil at water surface. The model-estimated daily average water surface area affected by floating oil >1.0 g/m2 was 6,720 km2, within the range of uncertainty for the 11,200 km2 estimate based on remote sensing. Modeled shoreline oiling extended over 2,600 km from the Apalachicola Bay area of Florida to Terrebonne Bay area of Louisiana, comparing well to the estimated 2,100 km oiled based on incomplete shoreline surveys.
Modeling of Sonotrode System of Ultrasonic Consolidation With Transfer Matrix Method
Authors: Wang Yin , Chen Ziyan , Yu Qing , Cheng Fang
Published: February 2021

To establish an efficient model for sonotrode system, a key part that continuously applies ultrasonic oscillation on metal foils to form solid state bond in ultrasonic consolidation equipment, this research presents modeling methods for sonotrode system. After an introduction to the construction of sonotrode system along with its operating principle, the transfer matrix method was adopted to build the model for the system consisting two ultrasonic transducers and one sonotrode. Simulation results of transfer matrix model were compared to that of finite element method. A prototype was fabricated and tested. A comparison of the resonance frequencies calculated by two modeling methods to the experimental result showed that the difference between transfer matrix model and prototype is 6.96% while the difference between finite element model and prototype is 9.26%. The proposed transfer matrix method is an efficient way to simulate dynamic performances for sonotrode system, which provide a better foundation for further optimization.
Antibacterial Activity and Drug Loading of Moxifloxacin-Loaded Poly(Vinyl Alcohol)/Chitosan Electrospun Nanofibers
Authors: Liu Qi , Ouyang Wen-Chong , Zhou Xiu-Hong , Jin Tao , Wu Zheng-Wei
Published: February 2021

In this study, nanofibers with different ratios of poly(vinyl alcohol) and chitosan incorporated with moxifloxacin hydrochloride (MH/PVA/CS) were fabricated through the blending electrospinning, and the morphological features were tested using scanning electron microscopy (SEM). Further characterization of the new nanofiber was accomplished by Thermogravimetric analysis (TG), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). Antibacterial activity of the MH-loaded nanofibers at different drug loading were tested and compared with the blank group. Experimental results show that the MH/PVA/CS nanofibers exhibited the good antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa due to the MH incorporation. Compared with blank nanofibers, MH/PVA/CS nanofibers have significantly better antibacterial properties, and different proportions of PVA and CS have a certain effect on the antibacterial activity of nanofibers. The conclusions in this paper show that MH/PVA/CS composite nanofibers may have great potential in antibacterial materials.
RETRACTED: Glucocorticoids Should Be Used With Caution in Patients With SARS-CoV-2
Authors: Guo Yong , Chen Yan , Li Yingchuan
Published: February 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, and the use of glucocorticoids in clinical practice is controversial. Our clinical experiences with glucocorticoid treatment suggested that, while use was effective in some cases, in other cases, glucocorticoid were ineffective and even resulted in immunosuppression that could lead to deterioration. Therefore, glucocorticoids should be used with caution in patients with SARS-CoV-2.
Unsupervised Clustering Reveals Sarcoidosis Phenotypes Marked by a Reduction in Lymphocytes Relate to Increased Inflammatory Activity on 18FDG-PET/CT
Authors: Vagts Christen , Ascoli Christian , Fraidenburg Dustin R. , Baughman Robert P. , Huang Yue , Edafetanure-Ibeh Russell , Ahmed Samreen , Levin Benjamin , Lu Yang , Perkins David L. , Finn Patricia W. , Sweiss Nadera J.
Published: February 2021

Introduction: Sarcoidosis is a T-helper cell mediated disease characterized by granulomatous inflammation. We posited that unsupervised clustering of various features in sarcoidosis would establish phenotypes associated with inflammatory activity measured by 18FDG-PET/CT. Our goal was to identify unique features capable of distinguishing clusters and subsequently examine the relationship with FDG avidity to substantiate their potential use as markers for sarcoidosis inflammation.

Methods: We performed a retrospective study of a diverse, but primarily African American, cohort of 58 subjects with biopsy proven sarcoidosis followed at the University of Illinois Bernie Mac Sarcoidosis Center and Center for Lung Health who underwent 18FDG-PET/CT scan. Demographic, therapeutic, radiographic, and laboratory data were utilized in unsupervised cluster analysis to identify sarcoidosis phenotypes. The association between clusters, their defining features, and quantitative measurements on 18FDG-PET/CT was determined. The relevance of these features as markers of 18FDG-PET/CT inflammatory activity was also investigated.

Results: Clustering determined three distinct phenotypes: (1) a predominantly African American cluster with chronic, quiescent disease, (2) a predominantly African American cluster with elevated conventional inflammatory markers, advanced pulmonary disease and extrathoracic involvement, and (3) a predominantly Caucasian cluster characterized by reduced lymphocyte counts and acute disease. In contrast to the chronic quiescent cluster, Clusters 2 and 3 were defined by significantly greater FDG avidity on 18FDG-PET/CT. Despite similarly increased inflammatory activity on 18FDG-PET/CT, Clusters 2, and 3 differed with regards to extrathoracic FDG avidity and circulating lymphocyte profiles, specifically CD4+ T-cells. Notably, absolute lymphocyte counts and CD4+ T-cell counts were found to predict 18FDG-PET/CT inflammatory activity by receiver operating curve analysis with a 69.2 and 73.42% area under the curve, respectively.

Conclusions: Utilizing cluster analysis, three distinct phenotypes of sarcoidosis were identified with significant variation in race, disease chronicity, and serologic markers of inflammation. These phenotypes displayed varying levels of circulating inflammatory cells. Additionally, reduction in lymphocytes, specifically CD4+ T-cells, was significantly related to activity on 18FDG-PET/CT. Though future studies are warranted, these findings suggest that peripheral lymphocyte counts may be considered a determinant of sarcoidosis phenotypes and an indicator of active inflammation on 18FDG-PET/CT.
Bridging the Antimicrobial Activity of Two Lactoferricin Derivatives in E. coli and Lipid-Only Membranes
Authors: Marx Lisa , Semeraro Enrico F. , Mandl Johannes , Kremser Johannes , Frewein Moritz P. , Malanovic Nermina , Lohner Karl , Pabst Georg
Published: February 2021

We coupled the antimicrobial activity of two well-studied lactoferricin derivatives, LF11-215 and LF11-324, in Escherichia coli and different lipid-only mimics of its cytoplasmic membrane using a common thermodynamic framework for peptide partitioning. In particular, we combined an improved analysis of microdilution assays with ζ-potential measurements, which allowed us to discriminate between the maximum number of surface-adsorbed peptides and peptides fully partitioned into the bacteria. At the same time, we measured the partitioning of the peptides into vesicles composed of phosphatidylethanolamine (PE), phosphatidylgylcerol (PG), and cardiolipin (CL) mixtures using tryptophan fluorescence and determined their membrane activity using a dye leakage assay and small-angle X-ray scattering. We found that the vast majority of LF11-215 and LF11-324 readily enter inner bacterial compartments, whereas only 1−5% remain surface bound. We observed comparable membrane binding of both peptides in membrane mimics containing PE and different molar ratios of PG and CL. The peptides' activity caused a concentration-dependent dye leakage in all studied membrane mimics; however, it also led to the formation of large aggregates, part of which contained collapsed multibilayers with sandwiched peptides in the interstitial space between membranes. This effect was least pronounced in pure PG vesicles, requiring also the highest peptide concentration to induce membrane permeabilization. In PE-containing systems, we additionally observed an effective shielding of the fluorescent dyes from leakage even at highest peptide concentrations, suggesting a coupling of the peptide activity to vesicle fusion, being mediated by the intrinsic lipid curvatures of PE and CL. Our results thus show that LF11-215 and LF11-324 effectively target inner bacterial components, while the stored elastic stress makes membranes more vulnerable to peptide translocation.
Fungal Communities on Standing Litter Are Structured by Moisture Type and Constrain Decomposition in a Hyper-Arid Grassland
Authors: Logan J. Robert , Jacobson Kathryn M. , Jacobson Peter J. , Evans Sarah E.
Published: February 2021

Non-rainfall moisture (fog, dew, and water vapor; NRM) is an important driver of plant litter decomposition in grasslands, where it can contribute significantly to terrestrial carbon cycling. However, we still do not know whether microbial decomposers respond differently to NRM and rain, nor whether this response affects litter decomposition rates. To determine how local moisture regimes influence decomposer communities and their function, we examined fungal communities on standing grass litter at an NRM-dominated site and a rain-dominated site 75 km apart in the hyper-arid Namib Desert using a reciprocal transplant design. Dominant taxa at both sites consisted of both extremophilic and cosmopolitan species. Fungal communities differed between the two moisture regimes with environment having a considerably stronger effect on community composition than did stage of decomposition. Community composition was influenced by the availability of air-derived spores at each site and by specialization of fungi to their home environment; specifically, fungi from the cooler, moister NRM Site performed worse (measured as fungal biomass and litter mass loss) when moved to the warmer, drier rain-dominated site while Rain Site fungi performed equally well in both environments. Our results contribute to growing literature demonstrating that as climate change alters the frequency, magnitude and type of moisture events in arid ecosystems, litter decomposition rates may be altered and constrained by the composition of existing decomposer communities.
Elevated pH Conditions Associated With Microcystis spp. Blooms Decrease Viability of the Cultured Diatom Fragilaria crotonensis and Natural Diatoms in Lake Erie
Authors: Zepernick Brittany N. , Gann Eric R. , Martin Robbie M. , Pound Helena L. , Krausfeldt Lauren E. , Chaffin Justin D. , Wilhelm Steven W.
Published: February 2021

Cyanobacterial Harmful Algal Blooms (CyanoHABs) commonly increase water column pH to alkaline levels ≥9.2, and to as high as 11. This elevated pH has been suggested to confer a competitive advantage to cyanobacteria such as Microcystis aeruginosa. Yet, there is limited information regarding the restrictive effects bloom-induced pH levels may impose on this cyanobacterium’s competitors. Due to the pH-dependency of biosilicification processes, diatoms (which seasonally both precede and proceed Microcystis blooms in many fresh waters) may be unable to synthesize frustules at these pH levels. We assessed the effects of pH on the ecologically relevant diatom Fragilaria crotonensis in vitro, and on a Lake Erie diatom community in situ. In vitro assays revealed F. crotonensis monocultures exhibited lower growth rates and abundances when cultivated at a starting pH of 9.2 in comparison to pH 7.7. The suppressed growth trends in F. crotonensis were exacerbated when co-cultured with M. aeruginosa at pH conditions and cell densities that simulated a cyanobacteria bloom. Estimates demonstrated a significant decrease in silica (Si) deposition at alkaline pH in both in vitro F. crotonensis cultures and in situ Lake Erie diatom assemblages, after as little as 48 h of alkaline pH-exposure. These observations indicate elevated pH negatively affected growth rate and diatom silica deposition; in total providing a competitive disadvantage for diatoms. Our observations demonstrate pH likely plays a significant role in bloom succession, creating a potential to prolong summer Microcystis blooms and constrain diatom fall resurgence.
From the sxtA4 Gene to Saxitoxin Production: What Controls the Variability Among Alexandrium minutum and Alexandrium pacificum Strains?
Authors: Geffroy Solène , Lechat Marc-Marie , Le Gac Mickael , Rovillon Georges-Augustin , Marie Dominique , Bigeard Estelle , Malo Florent , Amzil Zouher , Guillou Laure , Caruana Amandine M. N.
Published: February 2021

Paralytic shellfish poisoning (PSP) is a human foodborne syndrome caused by the consumption of shellfish that accumulate paralytic shellfish toxins (PSTs, saxitoxin group). In PST-producing dinoflagellates such as Alexandrium spp., toxin synthesis is encoded in the nuclear genome via a gene cluster (sxt). Toxin production is supposedly associated with the presence of a 4th domain in the sxtA gene (sxtA4), one of the core genes of the PST gene cluster. It is postulated that gene expression in dinoflagellates is partially constitutive, with both transcriptional and post-transcriptional processes potentially co-occurring. Therefore, gene structure and expression mode are two important features to explore in order to fully understand toxin production processes in dinoflagellates. In this study, we determined the intracellular toxin contents of twenty European Alexandrium minutum and Alexandrium pacificum strains that we compared with their genome size and sxtA4 gene copy numbers. We observed a significant correlation between the sxtA4 gene copy number and toxin content, as well as a moderate positive correlation between the sxtA4 gene copy number and genome size. The 18 toxic strains had several sxtA4 gene copies (9–187), whereas only one copy was found in the two observed non-toxin producing strains. Exploration of allelic frequencies and expression of sxtA4 mRNA in 11 A. minutum strains showed both a differential expression and specific allelic forms in the non-toxic strains compared with the toxic ones. Also, the toxic strains exhibited a polymorphic sxtA4 mRNA sequence between strains and between gene copies within strains. Finally, our study supported the hypothesis of a genetic determinism of toxin synthesis (i.e., the existence of several genetic isoforms of the sxtA4 gene and their copy numbers), and was also consistent with the hypothesis that constitutive gene expression and moderation by transcriptional and post-transcriptional regulation mechanisms are the cause of the observed variability in the production of toxins by A. minutum.
Recovery of Synthetic Zika Virus Based on Rio-U1 Isolate Using a Genetically Stable Two Plasmid System and cDNA Amplification
Authors: de Mello Iasmim Silva , Fernandes Déberli Ruiz , Furtado Nathália Dias , dos Santos Alexandre Araújo Cunha , dos Santos Marta Pereira , Ribeiro Ieda Pereira , Raphael Lidiane Menezes Souza , Nogueira Mônica da Silva , da Cruz Stephanie Oliveira Diaz , Rocha Adalgiza da Silva , Manso Pedro Paulo de Abreu , Pelajo-Machado Marcelo , Bonaldo Myrna Cristina
Published: February 2021

In 2016, the world experienced the unprecedented Zika epidemic. The ZIKV emerged as a major human pathogen due to its association with the impairment of perinatal development and Guillain–Barré syndrome. The occurrence of these severe cases of Zika points to the significance of studies for understanding the molecular determinants of flavivirus pathogenesis. Reverse genetics is a powerful method for studying the replication and determinants of pathogenesis, virulence, and viral attenuation of flaviviruses, facilitating the design of vaccines and therapeutics. However, the main hurdle in the development of infectious clones is the instability of full-length cDNA in Escherichia coli. Here, we described the development of a genetically stable and efficient infectious clone based on the ZIKV Rio-U1 isolated in the 2016 epidemic in Brazil. The employed strategy consisted of cloning the viral cDNA genome into two stable plasmid subclones and obtaining a high-quality cDNA template with increment in DNA mass for in vitro transcription by PCR amplification. The strategy for developing a ZIKV infectious cDNA clone designed in this study was successful, yielding a replicative and efficient clone-derived virus with high similarities with its parental virus, Rio-U1, by comparison of the proliferation capacity in mammal and insect cells. The infection of AG129 immunocompromised mice caused identical mortality rates, with similar disease progression and morbidity in the animals infected with the parental and the cDNA-derived virus. Histopathological analyses of mouse brains infected with the parental and the cDNA-derived viruses revealed a similar pathogenesis degree. We observed meningoencephalitis, cellular pyknosis, and neutrophilic invasion adjacent to the choroid plexus and perivascular cuffs with the presence of neutrophils. The developed infectious clone will be a tool for genetic and functional studies in vitro and in vivo to understand viral infection and pathogenesis better.
Analysis of Circulating Microvesicles Levels and Effects of Associated Factors in Elderly Patients With Obstructive Sleep Apnea
Authors: Tan Jin , Xing Huifang , Sha Sha , Li Jinwen , Miao Yuyang , Zhang Qiang
Published: February 2021

Background: The incidence of obstructive sleep apnea (OSA) in the elderly is high, and the disorder is associated with a variety of chronic diseases. Microvesicles (MVs) are extracellular vesicles secreted by various cells during stimulation or apoptosis that play an important role in the pathogenesis of OSA. However, concentrations of circulating MVs in elderly patients with OSA remain unclear.

Methods: Patients aged >60 years old were recruited and underwent polysomnography. Circulating plasma MV concentrations, including annexin V+MVs, endothelial MVs (EMVs), platelet MVs (PMVs), and leukocyte MVs (LMVs) levels, were measured using a flow cytometer with different labeling methods. Potential factors affecting the concentration of circulating MVs in elderly patients with OSA were determined via Spearman's correlation and multiple linear regression analysis.

Results: Levels of circulating MVs, including both single- (annexin V+MVs, CD144+EMVs, CD41a+PMVs, and CD45+LMVs) and dual-labeled MVs (annexin V+CD144+EMVs), were elevated in elderly patients with OSA. Circulating MVs were positively correlated with OSA severity (AHI, ODI, and SPO2min). To some extent, obesity affected the MV concentrations in elderly patients with OSA. In addition, age and comorbidities may be associated with MV levels, but the correlations between the MV levels and age or comorbidities were not significant.

Conclusion: Concentrations of circulating MVs in elderly patients with OSA are associated with the labeling method used, OSA severity, and obesity. The effects of age and comorbidities on circulating MV levels require further verification using a larger sample size.
Weight Change After Subthalamic Nucleus Deep Brain Stimulation in Patients With Isolated Dystonia
Authors: He Weibin , Li Hongxia , Lai Yijie , Wu Yunhao , Wu Yiwen , Ramirez-Zamora Adolfo , Yi Wei , Zhang Chencheng
Published: February 2021

Purpose: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment method for advanced Parkinson's disease (PD) and isolated dystonia and provides marked improvement of major motor symptoms. In addition, non-motor effects have been reported including weight gain (WG) in patients with PD after STN-DBS. However, it is still unclear whether patients with isolated dystonia also experience WG.

Methods: Data from 47 patients with isolated dystonia who underwent bilateral STN-DBS surgery between October 2012 and June 2019 were retrospectively collected. The severity of dystonia was assessed via the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Changes in the body mass index (BMI) and BFMDRS score were analyzed using paired Student's t-tests. Regression analysis was performed to identify factors that affected the BMI after surgery.

Results: Postoperative WG was observed in 78.7% of patients. The percentage of overweight and obese patients increased from 25.5% (before STN-DBS) to 48.9% (at the last follow-up). The mean BMI and mean percentage change in BMI increased by 1.32 ± 1.83 kg/m2 (P < 0.001) and 6.28 ± 8.34%, respectively. BMI increased more in female than in male patients. At the last follow-up, BFMDRS movement and disability scores improved by 69.76 ± 33.23% and 65.66 ± 31.41%, respectively (both P < 0.001). The final regression model analysis revealed that sex and preoperative BMI alone were independently associated with BMI change (P < 0.05).

Conclusions: STN-DBS is associated with postoperative WG with patients with isolated dystonia. WG is more prominent in female patients and is associated with preoperative weight but not with the efficacy of STN-DBS on motor symptoms.
TaSCA, an Agile Survey on Chemosensory Impairments for Self-Monitoring of COVID-19 Patients: A Pilot Study
Authors: Mucignat-Caretta Carla , Bisiacchi Patrizia , Marcazzan Gian Luigi , Calistri Arianna , Parolin Cristina , Antonini Angelo
Published: February 2021

Background/Objective: During the COVID-19 pandemic, smell and taste disorders emerged as key non-respiratory symptoms. Due to widespread presence of the disease and to difficult objective testing of positive persons, the use of short surveys became mandatory. Most of the existing resources are focused on smell, very few on taste or trigeminal chemosensation called chemesthesis. However, it is possible that the three submodalities are affected differently by COVID-19.

Methods: We prepared a short survey (TaSCA) that can be administered at the telephone or through online resources to explore chemosensation. It is composed of 11 items on olfaction, taste, and chemesthesis, in order to discriminate the three modalities. We avoided abstract terms, and the use of semiquantitative scales because older patients may be less engaged. Statistical handling included descriptive statistics, Pearson's chi-squared test and cluster analysis.

Results: The survey was completed by 83 persons (60 females and 23 males), which reported diagnosis of COVID-19 by clinical (n = 7) or molecular (n = 18) means, the others being non-COVID subjects. Cluster analysis depicted the existence of two groups, one containing mostly asymptomatic and one mostly symptomatic subjects. All swab-positive persons fell within this second group. Only one item, related to trigeminal temperature perception, did not discriminate between the two groups.

Conclusions: These preliminary results indicate that TaSCA may be used to easily track chemosensory symptoms related to COVID-19 in an agile way, giving a picture of three different chemosensory modalities.
A Deep Learning Approach for the Photoacoustic Tomography Recovery From Undersampled Measurements
Authors: Shahid Husnain , Khalid Adnan , Liu Xin , Irfan Muhammad , Ta Dean
Published: February 2021

Photoacoustic tomography (PAT) is a propitious imaging modality, which is helpful for biomedical study. However, fast PAT imaging and denoising is an exigent task in medical research. To address the problem, recently, methods based on compressed sensing (CS) have been proposed, which accede the low computational cost and high resolution for implementing PAT. Nevertheless, the imaging results of the sparsity-based methods strictly rely on sparsity and incoherence conditions. Furthermore, it is onerous to ensure that the experimentally acquired photoacoustic data meets CS’s prerequisite conditions. In this work, a deep learning–based PAT (Deep-PAT)method is instigated to overcome these limitations. By using a neural network, Deep-PAT is not only able to reconstruct PAT from a fewer number of measurements without considering the prerequisite conditions of CS, but also can eliminate undersampled artifacts effectively. The experimental results demonstrate that Deep-PAT is proficient at recovering high-quality photoacoustic images using just 5% of the original measurement data. Besides this, compared with the sparsity-based method, it can be seen through statistical analysis that the quality is significantly improved by 30% (approximately), having average SSIM = 0.974 and PSNR = 29.88 dB with standard deviation ±0.007 and ±0.089, respectively, by the proposed Deep-PAT method. Also, a comparsion of multiple neural networks provides insights into choosing the best one for further study and practical implementation.
The Role of the Kappa Opioid System in Comorbid Pain and Psychiatric Disorders: Function and Implications
Authors: Ji Miao-Jin , Yang Jiao , Gao Zhi-Qiang , Zhang Liang , Liu Chao
Published: February 2021

Both pain and psychiatric disorders, such as anxiety and depression, significantly impact quality of life for the sufferer. The two also share a strong pathological link: chronic pain-induced negative affect drives vulnerability to psychiatric disorders, while patients with comorbid psychiatric disorders tend to experience exacerbated pain. However, the mechanisms responsible for the comorbidity of pain and psychiatric disorders remain unclear. It is well established that the kappa opioid system contributes to depressive and dysphoric states. Emerging studies of chronic pain have revealed the role and mechanisms of the kappa opioid system in pain processing and, in particular, in the associated pathological alteration of affection. Here, we discuss the key findings and summarize compounds acting on the kappa opioid system that are potential candidates for therapeutic strategies against comorbid pain and psychiatric disorders.
A Meta-Analysis of Risk Factors for Transient and Permanent Hypocalcemia After Total Thyroidectomy
Authors: Qin Yuan , Sun Wei , Wang Zhihong , Dong Wenwu , He Liang , Zhang Ting , Zhang Hao
Published: February 2021

Background

As hypocalcemia is the most common complication of total thyroidectomy, identifying its risk factors should guide prevention and management. The purpose of this study was to determine the risk factors for postthyroidectomy hypocalcemia.

Methods

We searched PubMed, Web of Science and EMBASE through January 31, 2019, and assessed study quality using the Newcastle–Ottawa Scale.

Results

Fifty studies with 22,940 patients met the inclusion criteria, of which 24.92% (5716/22,940) had transient hypocalcemia and 1.96% (232/11,808) had permanent hypocalcemia. Significant (P < 0.05) predictors of transient hypocalcemia were: younger age, female, parathyroid autotransplantation (PA), inadvertent parathyroid excision (IPE), Graves’ disease (GD), thyroid cancer, central lymph node dissection, preoperative severe Vitamin D deficiency, preoperative Vitamin D deficiency and a lower postoperative 24 h parathyroid hormone (PTH) level. Preoperative magnesium, preoperative PTH and Hashimoto’s thyroiditis were not significant predictors of transient hypocalcemia. IPE, GD, and thyroid cancer were associated with an increased rate of permanent hypocalcemia, but gender and PA did not predict permanent hypocalcemia.

Conclusion

Important risk factors for transient and permanent hypocalcemia were identified. However, given the limited sample size and heterogeneity of this meta-analysis, further studies are required to confirm our preliminary findings.
Identification of Core Genes and Screening of Potential Targets in Glioblastoma Multiforme by Integrated Bioinformatic Analysis
Authors: Yang Ji’an , Yang Qian
Published: February 2021

Glioblastoma multiforme is the most common primary intracranial malignancy, but its etiology and pathogenesis are still unclear. With the deepening of human genome research, the research of glioma subtype screening based on core molecules has become more in-depth. In the present study, we screened out differentially expressed genes (DEGs) through reanalyzing the glioblastoma multiforme (GBM) datasets GSE90598 from the Gene Expression Omnibus (GEO), the GBM dataset TCGA-GBM and the low-grade glioma (LGG) dataset TCGA-LGG from the Cancer Genome Atlas (TCGA). A total of 150 intersecting DEGs were found, of which 48 were upregulated and 102 were downregulated. These DEGs from GSE90598 dataset were enriched using the overrepresentation method, and multiple enriched gene ontology (GO) function terms were significantly correlated with neural cell signal transduction. DEGs between GBM and LGG were analyzed by gene set enrichment analysis (GSEA), and the significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in synapse signaling and oxytocin signaling pathways. Then, a protein-protein interaction (PPI) network was constructed to assess the interaction of proteins encoded by the DEGs. MCODE identified 2 modules from the PPI network. The 11 genes with the highest degrees in module 1 were designated as core molecules, namely, GABRD, KCNC1, KCNA1, SYT1, CACNG3, OPALIN, CD163, HPCAL4, ANK3, KIF5A, and MS4A6A, which were mainly enriched in ionic signaling-related pathways. Survival analysis of the GSE83300 dataset verified the significant relationship between expression levels of the 11 core genes and survival. Finally, the core molecules of GBM and the DrugBank database were assessed by a hypergeometric test to identify 10 drugs included tetrachlorodecaoxide related to cancer and neuropsychiatric diseases. Further studies are required to explore these core genes for their potentiality in diagnosis, prognosis, and targeted therapy and explain the relationship among ionic signaling-related pathways, neuropsychiatric diseases and neurological tumors.
A CT-Based Radiomics Approach to Predict Nivolumab Response in Advanced Non-Small-Cell Lung Cancer
Authors: Liu Chang , Gong Jing , Yu Hui , Liu Quan , Wang Shengping , Wang Jialei
Published: February 2021

Purpose

This study aims to develop a CT-based radiomics model to predict clinical outcomes of advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab.

Methods

Forty-six stage IIIB/IV NSCLC patients without EGFR mutation or ALK rearrangement who received nivolumab were enrolled. After segmenting primary tumors depicting on the pre-anti-PD1 treatment CT images, 1,106 radiomics features were computed and extracted to decode the imaging phenotypes of these tumors. A L1-based feature selection method was applied to remove the redundant features and build an optimal feature pool. To predict the risk of progression-free survival (PFS) and overall survival (OS), the selected image features were used to train and test three machine-learning classifiers namely, support vector machine classifier, logistic regression classifier, and Gaussian Naïve Bayes classifier. Finally, the overall patients were stratified into high and low risk subgroups by using prediction scores obtained from three classifiers, and Kaplan–Meier survival analysis was conduct to evaluate the prognostic values of these patients.

Results

To predict the risk of PFS and OS, the average area under a receiver operating characteristic curve (AUC) value of three classifiers were 0.73 ± 0.07 and 0.61 ± 0.08, respectively; the corresponding average Harrell’s concordance indexes for three classifiers were 0.92 and 0.79. The average hazard ratios (HR) of three models for predicting PFS and OS were 6.22 and 3.54, which suggested the significant difference of the two subgroup’s PFS and OS (p<0.05).

Conclusion

The pre-treatment CT-based radiomics model provided a promising way to predict clinical outcomes for advanced NSCLC patients treated with nivolumab.
Systemic Immune-Inflammation Index and Changes of Neutrophil-Lymphocyte Ratio as Prognostic Biomarkers for Patients With Pancreatic Cancer Treated With Immune Checkpoint Blockade
Authors: Shang Jin , Han Xiao , Zha Haoran , Tao Haitao , Li Xiaoyan , Yuan Fang , Chen Guangying , Wang Lijie , Ma Junxun , Hu Yi
Published: February 2021

The efficacy of current treatment regimens for pancreatic cancer (PC) remains unsatisfactory. In recent years, immune checkpoint blockade (ICB) therapy has shown promising anti-tumor outcomes in many malignancies, including PC. Inexpensive and readily available biomarkers which predict therapeutic responses and prognosis are in critical need. Systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) are emerging predictors for prognosis of various tumors. We aim to investigate the prognostic significance of baseline SII, NLR, and their changes in PC patients treated with ICB. Our retrospective analysis included PC patients treated with ICB therapy in the Chinese PLA General Hospital. All demographic, biological, and clinical data were extracted from medical records. Relative changes of SII after two doses of ICB were defined as ΔSII% and calculated as (SIIafter 2 doses-SIIbaseline)/SIIbaseline, and so was the case for ΔNLR%. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier curves. The prognostic significance of baseline SII, NLR, and their changes was assessed in univariate and multivariate analyses using the Cox proportional hazard regression model. In total, 122 patients with PC treated with ICB were included in the present analysis. Elevated baseline SII (HR=3.28; 95% CI:1.98–5.27; P=0.03) and ΔNLR% (HR=2.21; 95% CI:1.03–4.74; P=0.04) were significantly correlated with an increased risk of death. For PC patients receiving ICB combined with chemotherapies or radiotherapies as the first-line treatment, increased baseline SII was a negative predictor for both OS (HR=8.06; 95% CI:1.71–37.86; P=0.01) and PFS (HR=2.84; 95%CI:1.37–10.38; P=0.04). Our study reveals the prognostic value of baseline SII and NLR changes in PC patients receiving ICB therapy. The clinical utility of these prognostic biomarkers needs to be further studied in prospective studies.
Non-Coding RNAs Participate in the Pathogenesis of Neuroblastoma
Authors: Rezaei Omidvar , Honarmand Tamizkar Kasra , Hajiesmaeili Mohammadreza , Taheri Mohammad , Ghafouri-Fard Soudeh
Published: February 2021

Neuroblastoma is one of the utmost frequent neoplasms during the first year of life. This pediatric cancer is believed to be originated during the embryonic life from the neural crest cells. Previous studies have detected several types of chromosomal aberrations in this tumor. More recent studies have emphasized on expression profiling of neuroblastoma samples to identify the dysregulated genes in this type of cancer. Non-coding RNAs are among the mostly dysregulated genes in this type of cancer. Such dysregulation has been associated with a number of chromosomal aberrations that are frequently detected in neuroblastoma. In this study, we explain the role of non-coding transcripts in the malignant transformation in neuroblastoma and their role as biomarkers for this pediatric cancer.
Transcriptomic Profiling of In Vitro Tumor-Stromal Cell Paracrine Crosstalk Identifies Involvement of the Integrin Signaling Pathway in the Pathogenesis of Mesenteric Fibrosis in Human Small Intestinal Neuroendocrine Neoplasms
Authors: Laskaratos Faidon-Marios , Levi Ana , Schwach Gert , Pfragner Roswitha , Hall Andrew , Xia Dong , von Stempel Conrad , Bretherton Josephine , Thanapirom Kessarin , Alexander Sarah , Ogunbiyi Olagunju , Watkins Jennifer , Luong Tu Vinh , Toumpanakis Christos , Mandair Dalvinder , Caplin Martyn , Rombouts Krista
Published: February 2021

Aim

Analysis of the pathophysiology of mesenteric fibrosis (MF) in small intestinal neuroendocrine tumors (SI-NETs) in an in vitro paracrine model and in human SI-NET tissue samples.

Methods

An indirect co-culture model of SI-NET cells KRJ-I and P-STS with stromal cells HEK293 was designed to evaluate the paracrine effects on cell metabolic activity, gene expression by RT2 PCR Profilers to analyse cancer and fibrosis related genes, and RNA sequencing. The integrin signaling pathway, a specific Ingenuity enriched pathway, was further explored in a cohort of human SI-NET tissues by performing protein analysis and immunohistochemistry.

Results

RT Profiler array analysis demonstrated several genes to be significantly up- or down-regulated in a cell specific manner as a result of the paracrine effect. This was further confirmed by employing RNA sequencing revealing multiple signaling pathways involved in carcinogenesis and fibrogenesis that were significantly affected in these cell lines. A significant upregulation in the expression of various integrin pathway – related genes was identified in the mesenteric mass of fibrotic SI-NET as confirmed by RT-qPCR and immunohistochemistry. Protein analysis demonstrated downstream activation of the MAPK and mTOR pathways in some patients with fibrotic SI-NETs.

Conclusion

This study has provided the first comprehensive analysis of the crosstalk of SI-NET cells with stromal cells. A novel pathway – the integrin pathway – was identified and further validated and confirmed in a cohort of human SI-NET tissue featured by a dual role in fibrogenesis/carcinogenesis within the neoplastic fibrotic microenvironment.
Eplerenone Attenuates Fibrosis in the Contralateral Kidney of UUO Rats by Preventing Macrophage-to-Myofibroblast Transition
Authors: Xiong Yunzhao , Chang Yi , Hao Juan , Zhang Cuijuan , Yang Fan , Wang Zheng , Liu Yunmeng , Wang Xiangting , Mu Shengyu , Xu Qingyou
Published: February 2021

Severe renal fibrosis often occurs in obstructive kidney disease, not only in the obstructed kidney but also in the contralateral kidney, causing renal dysfunction. Although the mechanisms of injury in obstructed kidney have been studied for years, the pathogenesis of fibrosis in the contralateral kidney remains largely unknown. Here, we examined long-term unilateral ureteral obstruction (UUO) model in male Sprague–Dawley rats and found that macrophage-to-myofibroblast transition (MMT) is contributing to renal fibrosis in the contralateral kidney of UUO rats. Interestingly, this process was attenuated by treatment of eplerenone, a specific blocker of the mineralocorticoid receptor (MR). In-vitro, stimulating MR in primary cultured or cell line macrophages enhances MMT, which were also inhibited by MR blockade. Collectively, these findings provide a plausible mechanism for UUO-induced injury in the contralateral kidney, suggesting the benefit of using MR blockage as a part of treatment to UUO to protect the contralateral kidney thereby preserve renal function.
Baseline Arterial CO2 Pressure Regulates Acute Intermittent Hypoxia-Induced Phrenic Long-Term Facilitation in Rats
Authors: Perim Raphael R. , El-Chami Mohamed , Gonzalez-Rothi Elisa J. , Mitchell Gordon S.
Published: February 2021

Moderate acute intermittent hypoxia (mAIH) elicits a progressive increase in phrenic motor output lasting hours post-mAIH, a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). mAIH-induced pLTF is initiated by activation of spinally-projecting raphe serotonergic neurons during hypoxia and subsequent serotonin release near phrenic motor neurons. Since raphe serotonergic neurons are also sensitive to pH and CO2, the prevailing arterial CO2 pressure (PaCO2) may modulate their activity (and serotonin release) during hypoxic episodes. Thus, we hypothesized that changes in background PaCO2 directly influence the magnitude of mAIH-induced pLTF. mAIH-induced pLTF was evaluated in anesthetized, vagotomized, paralyzed and ventilated rats, with end-tidal CO2 (i.e., a PaCO2 surrogate) maintained at: (1) ≤39 mmHg (hypocapnia); (2) ∼41 mmHg (normocapnia); or (3) ≥48 mmHg (hypercapnia) throughout experimental protocols. Although baseline phrenic nerve activity tended to be lower in hypocapnia, short-term hypoxic phrenic response, i.e., burst amplitude (Δ = 5.1 ± 1.1 μV) and frequency responses (Δ = 21 ± 4 bpm), was greater than in normocapnic (Δ = 3.6 ± 0.6 μV and 8 ± 4, respectively) or hypercapnic rats (Δ = 2.0 ± 0.6 μV and −2 ± 2, respectively), followed by a progressive increase in phrenic burst amplitude (i.e., pLTF) for at least 60 min post mAIH. pLTF in the hypocapnic group (Δ = 4.9 ± 0.6 μV) was significantly greater than in normocapnic (Δ = 2.8 ± 0.7 μV) or hypercapnic rats (Δ = 1.7 ± 0.4 μV). In contrast, although hypercapnic rats also exhibited significant pLTF, it was attenuated versus hypocapnic rats. When pLTF was expressed as percent change from maximal chemoreflex stimulation, all pairwise comparisons were found to be statistically significant (p < 0.05). We conclude that elevated PaCO2 undermines mAIH-induced pLTF in anesthetized rats. These findings contrast with well-documented effects of PaCO2 on ventilatory LTF in awake humans.
Head-Down Tilt Position, but Not the Duration of Bed Rest Affects Resting State Electrocortical Activity
Authors: Brauns Katharina , Friedl-Werner Anika , Maggioni Martina A. , Gunga Hanns-Christian , Stahn Alexander C.
Published: February 2021

Adverse cognitive and behavioral conditions and psychiatric disorders are considered a critical and unmitigated risk during future long-duration space missions (LDSM). Monitoring and mitigating crew health and performance risks during these missions will require tools and technologies that allow to reliably assess cognitive performance and mental well-being. Electroencephalography (EEG) has the potential to meet the technical requirements for the non-invasive and objective monitoring of neurobehavioral conditions during LDSM. Weightlessness is associated with fluid and brain shifts, and these effects could potentially challenge the interpretation of resting state EEG recordings. Head-down tilt bed rest (HDBR) provides a unique spaceflight analog to study these effects on Earth. Here, we present data from two long-duration HDBR experiments, which were used to systematically investigate the time course of resting state electrocortical activity during prolonged HDBR. EEG spectral power significantly reduced within the delta, theta, alpha, and beta frequency bands. Likewise, EEG source localization revealed significantly lower activity in a broad range of centroparietal and occipital areas within the alpha and beta frequency domains. These changes were observed shortly after the onset of HDBR, did not change throughout HDBR, and returned to baseline after the cessation of bed rest. EEG resting state functional connectivity was not affected by HDBR. The results provide evidence for a postural effect on resting state brain activity that persists throughout long-duration HDBR, indicating that immobilization and inactivity per se do not affect resting state electrocortical activity during HDBR. Our findings raise an important issue on the validity of EEG to identify the time course of changes in brain function during prolonged HBDR, and highlight the importance to maintain a consistent body posture during all testing sessions, including data collections at baseline and recovery.
Melanocortin System in Kidney Homeostasis and Disease: Novel Therapeutic Opportunities
Authors: Chang Mingyang , Chen Bohan , Shaffner James , Dworkin Lance D. , Gong Rujun
Published: February 2021

Melanocortin peptides, melanocortin receptors, melanocortin receptor accessory proteins, and endogenous antagonists of melanocortin receptors are the key components constituting the melanocortin hormone system, one of the most complex and important hormonal systems in our body. A plethora of evidence suggests that melanocortins possess a protective activity in a variety of kidney diseases in both rodent models and human patients. In particular, the steroidogenic melanocortin peptide adrenocorticotropic hormone (ACTH), has been shown to exert a beneficial effect in a number of kidney diseases, possibly via a mechanism independent of its steroidogenic activity. In patients with steroid-resistant nephrotic glomerulopathy, ACTH monotherapy is still effective in inducing proteinuria remission. This has inspired research on potential implications of the melanocortin system in glomerular diseases. However, our understanding of the role of the melanocortinergic pathway in kidney disease is very limited, and there are still huge unknowns to be explored. The most controversial among these is the identification of effector cells in the kidney as well as the melanocortin receptors responsible for conveying the renoprotective action. This review article introduces the melanocortin hormone system, summarizes the existing evidence for the expression of melanocortin receptors in the kidney, and evaluates the potential strategy of melanocortin therapy for kidney disease.
Transcription Factor: A Powerful Tool to Regulate Biosynthesis of Active Ingredients in Salvia miltiorrhiza
Authors: Wu Sijia , Zhu Bo , Qin Luping , Rahman Khalid , Zhang Lei , Han Ting
Published: February 2021

Salvia miltiorrhiza Bunge is a common Chinese herbal medicine, and its major active ingredients are phenolic acids and tanshinones, which are widely used to treat vascular diseases. However, the wild form of S. miltiorrhiza possess low levels of these important pharmaceutical agents; thus, improving their levels is an active area of research. Transcription factors, which promote or inhibit the expressions of multiple genes involved in one or more biosynthetic pathways, are powerful tools for controlling gene expression in biosynthesis. Several families of transcription factors have been reported to participate in regulating phenolic acid and tanshinone biosynthesis and influence their accumulation. This review summarizes the current status in this field, with focus on the transcription factors which have been identified in recent years and their functions in the biosynthetic regulation of phenolic acids and tanshinones. Otherwise, the new insight for further research is provided. Finally, the application of the biosynthetic regulation of active ingredients by the transcription factors in S. miltiorrhiza are discussed, and new insights for future research are explored.