bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Tumor Immune Microenvironment CD3+ and CD20+ Lymphocytes Predict a Better Prognosis in Oral Tongue Squamous Cell Carcinoma
Authors: Sales de Sá Raísa , Miranda Galvis Marisol , Mariz Bruno Augusto Linhares Almeida , Leite Amanda Almeida , Schultz Luciana , Almeida Oslei Paes , Santos-Silva Alan Roger , Pinto Clovis Antonio Lopes , Vargas Pablo Agustin , Gollob Kenneth John , Kowalski Luiz Paulo
Published: February 2021

Background: Oral tongue squamous cell carcinoma (OTSCC) causes over 350,000 cases annually and particularly impacts populations in developing countries. Smoking and alcohol consumption are major risk factors. Determining the role of the tumor immune microenvironment (TIME) in OTSCC outcomes can elucidate immune mechanisms behind disease progression, and can potentially identify prognostic biomarkers.

Methods: We performed a retrospective study of 48 OTSCC surgical specimens from patients with tobacco and alcohol exposures. A panel of immunoregulatory cell subpopulations including T (CD3, CD4, CD8) and B (CD20) lymphocytes, dendritic cells (CD1a, CD83), macrophages (CD68), and immune checkpoint molecules programmed cell death protein 1 (PD-1) and ligand 1 (PD-L1) were analyzed using immunohistochemistry. The levels of immune effector cell subpopulations and markers were analyzed in relation to overall survival.

Results: Pathological characteristics of the tumor microenvironment included inflammatory infiltrates (83.3%), desmoplasia (41.6%), and perineural invasion (50.0%). The TIME contained high levels of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+), as well as immature (CD1a) and mature (CD83) dendritic cells, PD-1, and PD-L1. Higher numbers of TIME infiltrating CD3+ T cells and CD20+ B cells were predictive of better survival, while higher levels of CD83+ mature dendritic cells predicted better survival. CD3+ T cells were identified as an independent prognostic marker for OTSCC. Lastly, CD3+ T cells were strongly correlated with the number of CD8+ cells and PD-L1 expression.

Conclusion: Our findings provide evidence that the TIME profile of OTSSC impacted prognosis. The high expression of CD3+ T cells and B cells are predictive of better overall survival and indicative of an immunologically active, inflammatory TIME in patients with better survival. The number of CD3+ T cells was an independent prognostic marker.
Neuropeptide Y/Y5 Receptor Pathway Stimulates Neuroblastoma Cell Motility Through RhoA Activation
Authors: Abualsaud Nouran , Caprio Lindsay , Galli Susana , Krawczyk Ewa , Alamri Lamia , Zhu Shiya , Gallicano G. Ian , Kitlinska Joanna
Published: February 2021

Neuropeptide Y (NPY) has been implicated in the regulation of cellular motility under various physiological and pathological conditions, including cancer dissemination. Yet, the exact signaling pathways leading to these effects remain unknown. In a pediatric malignancy, neuroblastoma (NB), high NPY release from tumor tissue associates with metastatic disease. Here, we have shown that NPY stimulates NB cell motility and invasiveness and acts as a chemotactic factor for NB cells. We have also identified the Y5 receptor (Y5R) as the main NPY receptor mediating these actions. In NB tissues and cell cultures, Y5R is highly expressed in migratory cells and accumulates in regions of high RhoA activity and dynamic cytoskeleton remodeling. Y5R stimulation activates RhoA and results in Y5R/RhoA-GTP interactions, as shown by pull-down and proximity ligation assays, respectively. This is the first demonstration of the role for the NPY/Y5R axis in RhoA activation and the subsequent cytoskeleton remodeling facilitating cell movement. These findings implicate Y5R as a target in anti-metastatic therapies for NB and other cancers expressing this receptor.
Hypoglycemic Efficacy of Rh-aFGF Variants in Treatment of Diabetes in ZDF Rats
Authors: Zhang Li , Zhou Qingde , Chen Min , Yang Xuanxin , Lu Chao , Sun Wenzhe , Hui Qi , Wang Xiaojie
Published: February 2021

Acidic fibroblast growth factor (aFGF) is a promising regulator of glucose with no adverse effects of hypoglycemia. Previous researches revealed that aFGF mediated adipose tissue remodeling and insulin sensitivity. These findings supported rh-aFGF135 would be used as a new candidate for the treatment of insulin resistance and type 2 diabetes. In this study, we aimed to investigate the hypoglycemic efficacy of recombinant human acidic fibroblast growth factor 135 (rh-aFGF135) with low mitogenic in type 2 diabetic ZDF rats. ZDF rats were treated with rh-aFGF135 at a daily dosage of 0.25 and 0.50 mg/kg by tail intravenous injection for 5 weeks. The blood glucose levels, oral glucose tolerance test, insulin tolerance test, HOMA-IR for insulin resistance, serum biochemical parameters, and the histopathological changes of adipose tissue, liver and other organs were detected at designed time point. The glucose uptake activity and anti-insulin resistance effect of rh-aFGF135 were also detected in HepG2 cells. Results revealed that rh-aFGF135 exhibited a better hypoglycemic effect compared with vehicle group and without the adverse effect of hypoglycemia in ZDF rats. Compared with vehicle group, rh-aFGF135 significantly improved the situation of hyperglycemia and insulin resistance. Rh-aFGF135 decreased ALT, AST, GSP, and FFA levels noticeably compared with vehicle control group (P < 0.01 or P < 0.001). After 5 weeks of treatment, high-dosage rh-aFGF135 could remodel adipose tissue, and has no influence on other organs. H&E staining showed that rh-aFGF135 reduced the size of adipocytes. In addition, rh-aFGF135 may improve insulin resistance partly by increasing the protein expression of p-IRS-1 (human Ser 307). As a hypoglycemic drug for long-term treatment, rh-aFGF135 would be a potentially safe candidate for the therapy of type 2 diabetes.
TULP2, a New RNA-Binding Protein, Is Required for Mouse Spermatid Differentiation and Male Fertility
Authors: Zheng Meimei , Chen Xu , Cui Yiqiang , Li Wen , Dai Haiqian , Yue Qiuling , Zhang Hao , Zheng Ying , Guo Xuejiang , Zhu Hui
Published: February 2021

Spermatogenesis requires a large number of proteins to be properly expressed at certain stages, during which post-transcriptional regulation plays an important role. RNA-binding proteins (RBPs) are key players in post-transcriptional regulation, but only a few RBPs have been recognized and preliminary explored their function in spermatogenesis at present. Here we identified a new RBP tubby-like protein 2 (TULP2) and found three potential deleterious missense mutations of Tulp2 gene in dyszoospermia patients. Therefore, we explored the function and mechanism of TULP2 in male reproduction. TULP2 was specifically expressed in the testis and localized to spermatids. Studies on Tulp2 knockout mice demonstrated that the loss of TULP2 led to male sterility; on the one hand, increases in elongated spermatid apoptosis and restricted spermatid release resulted in a decreased sperm count; on the other hand, the abnormal differentiation of spermatids induced defective sperm tail structures and reduced ATP contents, influencing sperm motility. Transcriptome sequencing of mouse testis revealed the potential target molecular network of TULP2, which played its role in spermatogenesis by regulating specific transcripts related to the cytoskeleton, apoptosis, RNA metabolism and biosynthesis, and energy metabolism. We also explored the potential regulator of TULP2 protein function by using immunoprecipitation and mass spectrometry analysis, indicating that TUPL2 might be recognized by CCT8 and correctly folded by the CCT complex to play a role in spermiogenesis. Our results demonstrated the important role of TULP2 in spermatid differentiation and male fertility, which could provide an effective target for the clinical diagnosis and treatment of patients with oligo-astheno-teratozoospermia, and enrich the biological theory of the role of RBPs in male reproduction.
A Perspective of Epigenetic Regulation in Radiotherapy
Authors: Peng Qin , Weng Kegui , Li Shitian , Xu Richard , Wang Yingxiao , Wu Yongzhong
Published: February 2021

Radiation therapy (RT) has been employed as a tumoricidal modality for more than 100 years and on 470,000 patients each year in the United States. The ionizing radiation causes genetic changes and results in cell death. However, since the biological mechanism of radiation remains unclear, there is a pressing need to understand this mechanism to improve the killing effect on tumors and reduce the side effects on normal cells. DNA break and epigenetic remodeling can be induced by radiotherapy. Hence the modulation of histone modification enzymes may tune the radiosensitivity of cancer cells. For instance, histone deacetylase (HDAC) inhibitors sensitize irradiated cancer cells by amplifying the DNA damage signaling and inhibiting double-strand DNA break repair to influence the irradiated cells’ survival. However, the combination of epigenetic drugs and radiotherapy has only been evaluated in several ongoing clinical trials for limited cancer types, partly due to a lack of knowledge on the potential mechanisms on how radiation induces epigenetic regulation and chromatin remodeling. Here, we review recent advances of radiotherapy and radiotherapy-induced epigenetic remodeling and introduce related technologies for epigenetic monitoring. Particularly, we exploit the application of fluorescence resonance energy transfer (FRET) biosensors to visualize dynamic epigenetic regulations in single living cells and tissue upon radiotherapy and drug treatment. We aim to bridge FRET biosensor, epigenetics, and radiotherapy, providing a perspective of using FRET to assess epigenetics and provide guidance for radiotherapy to improve cancer treatment. In the end, we discuss the feasibility of a combination of epigenetic drugs and radiotherapy as new approaches for cancer therapeutics.
Brain Ultrastructure: Putting the Pieces Together
Authors: Nahirney Patrick C. , Tremblay Marie-Eve
Published: February 2021

Unraveling the fine structure of the brain is important to provide a better understanding of its normal and abnormal functioning. Application of high-resolution electron microscopic techniques gives us an unprecedented opportunity to discern details of the brain parenchyma at nanoscale resolution, although identifying different cell types and their unique features in two-dimensional, or three-dimensional images, remains a challenge even to experts in the field. This article provides insights into how to identify the different cell types in the central nervous system, based on nuclear and cytoplasmic features, amongst other unique characteristics. From the basic distinction between neurons and their supporting cells, the glia, to differences in their subcellular compartments, organelles and their interactions, ultrastructural analyses can provide unique insights into the changes in brain function during aging and disease conditions, such as stroke, neurodegeneration, infection and trauma. Brain parenchyma is composed of a dense mixture of neuronal and glial cell bodies, together with their intertwined processes. Intracellular components that vary between cells, and can become altered with aging or disease, relate to the cytoplasmic and nucleoplasmic density, nuclear heterochromatin pattern, mitochondria, endoplasmic reticulum and Golgi complex, lysosomes, neurosecretory vesicles, and cytoskeletal elements (actin, intermediate filaments, and microtubules). Applying immunolabeling techniques to visualize membrane-bound or intracellular proteins in neurons and glial cells gives an even better appreciation of the subtle differences unique to these cells across contexts of health and disease. Together, our observations reveal how simple ultrastructural features can be used to identify specific changes in cell types, their health status, and functional relationships in the brain.
Regulation of the Migration of Distinct Dendritic Cell Subsets
Authors: Feng Meng , Zhou Shuping , Yu Yong , Su Qinghong , Li Xiaofan , Lin Wei
Published: February 2021

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.
SLC7A11 Reduces Laser-Induced Choroidal Neovascularization by Inhibiting RPE Ferroptosis and VEGF Production
Authors: Zhao Xiaohuan , Gao Min , Liang Jian , Chen Yuhong , Wang Yimin , Wang Yuwei , Xiao Yushu , Zhao Zhenzhen , Wan Xiaoling , Jiang Mei , Luo Xueting , Wang Feng , Sun Xiaodong
Published: February 2021

In age-related macular degeneration (AMD), one of the principal sources of vascular endothelial growth factor (VEGF) is retinal pigment epithelium (RPE) cells under hypoxia or oxidative stress. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate transporter, regulates the level of cellular lipid peroxidation, and restrains ferroptosis. In our study, we assessed the role of SLC7A11 in laser-induced choroidal neovascularization (CNV) and explored the underlying mechanism. We established a mouse model of CNV to detect the expression level of SLC7A11 and VEGF during disease progression. We found the expression of the SLC7A11 protein in RPE cells peaked at 3 days after laser treatment, which was correlated with the expression of VEGF. Intraperitoneal injection of SLC7A11 inhibitor expanded the area of CNV. We examined functional proteins related to oxidative stress and Fe2+ and found laser-induced ferroptosis accompanied by increased Fe2+ content and GPX4 expression in the RPE-choroidal complex after laser treatment. We verified the expression of SLC7A11 in the ARPE19 cell line and the effects of its inhibitors on cell viability and lipid peroxidation in vitro. Application of SLC7A11 inhibitor and SLC7A11 knockdown increased the level of lipid peroxidation and reduced the cell viability of ARPE19 which can be rescued by ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1). Conversely, SLC7A11 overexpression induced resistance to erastin or RSL3-induced ferroptosis. Moreover, we tested the possible regulatory transcription factor NF-E2-related factor 2 (NRF2) of SLC7A11 by Western blot. Knock-down of NRF2 decreased the expression of SLC7A11. Our study suggests that SLC7A11 plays a key role in the laser-induced CNV model by protecting RPE cells from ferroptosis. SLC7A11 provides a new therapeutic target for neovascular AMD patients.
TET Enzymes and 5-Hydroxymethylcytosine in Neural Progenitor Cell Biology and Neurodevelopment
Authors: MacArthur Ian C. , Dawlaty Meelad M.
Published: February 2021

Studies of tissue-specific epigenomes have revealed 5-hydroxymethylcytosine (5hmC) to be a highly enriched and dynamic DNA modification in the metazoan nervous system, inspiring interest in the function of this epigenetic mark in neurodevelopment and brain function. 5hmC is generated by oxidation of 5-methylcytosine (5mC), a process catalyzed by the ten–eleven translocation (TET) enzymes. 5hmC serves not only as an intermediate in DNA demethylation but also as a stable epigenetic mark. Here, we review the known functions of 5hmC and TET enzymes in neural progenitor cell biology and embryonic and postnatal neurogenesis. We also discuss how TET enzymes and 5hmC regulate neuronal activity and brain function and highlight their implications in human neurodevelopmental and neurodegenerative disorders. Finally, we present outstanding questions in the field and envision new research directions into the roles of 5hmC and TET enzymes in neurodevelopment.
Analytical Methods for Os Isotope Ratios and Re-PGE Mass Fractions in Geological Samples
Authors: Chu Zhuyin
Published: February 2021

The recent advances in analytical methods of Re-Os and PGE in geological materials including sample dissolution, chemical separation, mass spectrometric determinations, as well as the developments of matrix-matched reference materials for data quality control are thoroughly reviewed. Further, the in-situ measurement methods for Re-PGE mass fractions and 187Os/188Os ratios, as well as the measurement methods for stable isotope ratios of Re and PGE are also briefly reviewed. This review stands as a comprehensive reference for researchers to consider in the development of measurement methods for Re-PGE mass fractions and 187Os/188Os ratios in geological materials.
Comparison of the Inhibitory Binding Modes Between the Planar Fascaplysin and Its Nonplanar Tetrahydro-β-carboline Analogs in CDK4
Authors: Liang Yan , Quan Huili , Bu Tong , Li Xuedong , Liu Xingang , Wang Songsong , He Dian , Jia Qingzhong , Zhang Yang
Published: February 2021

Fascaplysin is a natural marine product originating from sponges, attracting widespread attention due to its potential inhibitory activities against CDK4. However, its clinical application has been largely limited because of serious adverse effects caused by planar skeleton. To reduce the serious adverse effects, 18 tetrahydro-β-carboline analogs (compounds 6a-i and 7a-i) were designed and synthesized via breaking the planarity of fascaplysin, and the biological activities of the synthesized compounds were evaluated by MTT assay and CDK4/CycD3 enzyme inhibition assay. The title compounds showed varying degrees of inhibitory activities, especially the cytotoxicity of compound 6c against HeLa cells (IC50 = 1.03 ± 0.19 μM) with quite weak cytotoxicity toward the normal cells WI-38 (IC50 = 311.51 ± 56.06 μM), and the kinase inhibition test indicated that compound 6c was a potential CDK4 inhibitor. In order to further compare the action mechanisms of planar and nonplanar molecules on CDK4, the studied complexes of CDK4 bound with fascaplysin and three representative compounds (compound 6a-c) with bioactivities gradient were constructed by molecular docking and further verified through molecular dynamic simulation, which identified the key residues contributing to the ligands’ binding. By comparing the binding modes of the constructed systems, it could be found that the residues contributing significantly to compound 6c′s binding were highly consistent with those contributing significantly to fascaplysin’s binding. Through the design, synthesis of the nonplanar fascaplysin derivatives, and binding mechanism analysis, some valuable hints for the discovery of antitumor drug candidates could be provided.
Viroporins vs. Other Pore-Forming Proteins: What Lessons Can We Take?
Authors: Žerovnik Eva
Published: February 2021

Pore-forming proteins (PFPs) exist in virtually all domains of life, and by disrupting cellular membranes, depending on the pore size, they cause ion dis-balance, small substances, or even protein efflux/influx, influencing cell’s signaling routes and fate. Such pore-forming proteins exist from bacteria to viruses and also shape host defense systems, including innate immunity. There is strong evidence that amyloid toxicity is also caused by prefibrillar oligomers making “amyloid pores” into cellular membranes. For most of the PFPs, a 2-step mechanism of protein-membrane interaction takes place on the “lipid rafts,” membrane microdomains rich in gangliosides and cholesterol. In this mini-review paper, common traits of different PFPs are looked at. Possible ways for therapy of channelopathies and/or modulating immunity relevant to the new threat of SARS-CoV-2 infections could be learnt from such comparisons.
Performance of Interferon-Gamma Release Assays in the Diagnosis of Nontuberculous Mycobacterial Diseases—A Retrospective Survey From 2011 to 2019
Authors: Yang Chi , Luo Xuejiao , Fan Lin , Sha Wei , Xiao Heping , Cui Haiyan
Published: February 2021

There is an urgent need for precise diagnosis to distinguish nontuberculous mycobacterial (NTM) diseases from pulmonary tuberculosis (PTB) and other respiratory diseases. The aim of this study is to evaluate the diagnostic performance of Interferon-gamma (IFN-γ) release assays (IGRAs), including antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT.TB) and QuantiFERON-TB-Gold-Test (QFT-G), in differentiating NTM infections (N = 1,407) from culture-confirmed PTB (N = 1,828) and other respiratory diseases (N = 2,652). At specie level, 2.56%, 10.73%, and 16.49% of NTM-infected patients were infected by Mycobacterium kansasii, M. abscessus, and with M. avmm-intracellulare complex (MAC), respectively. Valid analyses of T-SPOT.TB (ESAT-6, CFP-10) and QFT-G were available for 37.03% and 85.79% in NTM-infected patients, including zero and 100% (36/36) of M. kansasii infection, 21.85% (33/151) and 92.05% (139/151) of M. abscessus infection, and 17.67% (41/232) and 91.24% (211/232) of MAC infection. Based on means comparisons and further ROC analysis, T-SPOT.TB and QFT-G performed moderate accuracy when discriminating NTM from PTB at modified cut-off values (ESAT-6 < 4 SFCs, CFP-10 < 3 SFCs, and QFT-G < 0.667 IU/ml), with corresponding AUC values of 0.7560, 0.7699, and 0.856. At species level of NTM, QFT-G effectively distinguished between MAC (AUC=0.8778), M. kansasii (AUC=0.8834) or M. abscessus (AUC=0.8783) than T-SPOT.TB. No significant differences in discriminatory power of these three IGRA tools were observed when differentiating NTM and Controls. Our results demonstrated that T-SPOT.TB and QFT-G were both efficient methods for differentiating NTM disease from PTB, and QFT-G possessed sufficient discriminatory power to distinguish infections by different NTM species.
Effects of Berberine on the Gastrointestinal Microbiota
Authors: Zhang Lichao , Wu Xiaoying , Yang Ruibing , Chen Fang , Liao Yao , Zhu Zifeng , Wu Zhongdao , Sun Xi , Wang Lifu
Published: February 2021

The gastrointestinal microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of several diseases. Berberine has been used to treat obesity, diabetes mellitus, atherosclerosis, and metabolic diseases in China. There are also clinical trials regarding berberine use in cardiovascular, gastrointestinal, and endocrine diseases. Berberine elicits clinical benefits at standard doses and has low toxicity. The mechanism underlying the role of berberine in lipid‐lowering and insulin resistance is incompletely understood, but one of the possible mechanisms is related to its effect on the gastrointestinal microbiota. An extensive search in electronic databases (PubMed, Scopus, Embase, Web of Sciences, Science Direct) was used to identify the role of the gastrointestinal microbiota in the berberine treatment. The aim of this review was to summarize the pharmacologic effects of berberine on animals and humans by regulation of the gastrointestinal microbiota.
Toxoplasma GRA Peptide-Specific Serologic Fingerprints Discriminate Among Major Strains Causing Toxoplasmosis
Authors: Arranz-Solís David , Carvalheiro Cristina G. , Zhang Elizabeth R. , Grigg Michael E. , Saeij Jeroen P. J.
Published: February 2021

The severity of toxoplasmosis depends on a combination of host and parasite factors. Among them, the Toxoplasma strain causing the infection is an important determinant of the disease outcome. Type 2 strains dominate in Europe, whereas in North America type 2, followed by type 3 and 12 strains are commonly isolated from wildlife and patients. To identify the strain type a person is infected with, serological typing provides a promising alternative to the often risky and not always possible biopsy-based DNA methods of genotyping. However, despite recent advances in serotyping, improvements in the sensitivity and specificity are still needed, and it does not yet discriminate among the major Toxoplasma lineages infecting people. Moreover, since infections caused by non-1/2/3 strains have been associated with more severe disease, the ability to identify these is critical. In the present study we investigated the diagnostic potential of an ELISA-based assay using 28 immunogenic Toxoplasma peptides derived from a recent large-scale peptide array screen. Our results show that a discrete number of peptides, derived from Toxoplasma dense granule proteins (GRA3, GRA5, GRA6, and GRA7) was sufficient to discriminate among archetypal strains that infect mice and humans. The assay specifically relies on ratios that compare individual serum reactivities against GRA-specific polymorphic peptide variants in order to determine a “reactivity fingerprint” for each of the major strains. Importantly, nonarchetypal strains that possess a unique combination of alleles, different from types 1/2/3, showed either a non-reactive, or different combinatorial, mixed serum reactivity signature that was diagnostic in its own right, and that can be used to identify these strains. Of note, we identified a distinct “HG11/12” reactivity pattern using the GRA6 peptides that is able to distinguish HG11/12 from archetypal North American/European strain infections.
Salivary Microbiome in Pediatric and Adult Celiac Disease
Authors: Poddighe Dimitri , Kushugulova Almagul
Published: February 2021

The human salivary microbiota includes hundreds of bacterial species. Alterations in gut microbiota have been explored in Celiac Disease (CD), but fewer studies investigated the characteristics of salivary microbiome in these patients, despite the potential implications in its pathogenesis. Indeed, some recent studies suggested that the partial digestion of gluten proteins by some bacteria may affect the array of gluten peptides reaching the gut and the way by which those are presented to the intestinal immune system. The available clinical studies investigating the salivary microbiota in children and adults, are insufficient to make any reliable conclusion, even though some bacterial species/phyla differences have been reported between celiac patients and controls. However, the salivary microbiome could correlate better with the duodenal microbiota, than the fecal one. Therefore, further clinical studies on salivary microbiome by different and independent research groups and including different populations, are advisable in order to explore the usefulness of the salivary microbiome analysis and understand some aspects of CD pathogenesis with potential clinical and practical implications.
Adaptive Physics-Based Non-Rigid Registration for Immersive Image-Guided Neuronavigation Systems
Authors: Drakopoulos Fotis , Tsolakis Christos , Angelopoulos Angelos , Liu Yixun , Yao Chengjun , Kavazidi Kyriaki Rafailia , Foroglou Nikolaos , Fedorov Andrey , Frisken Sarah , Kikinis Ron , Golby Alexandra , Chrisochoides Nikos
Published: February 2021

Objective:In image-guided neurosurgery, co-registered preoperative anatomical, functional, and diffusion tensor imaging can be used to facilitate a safe resection of brain tumors in eloquent areas of the brain. However, the brain deforms during surgery, particularly in the presence of tumor resection. Non-Rigid Registration (NRR) of the preoperative image data can be used to create a registered image that captures the deformation in the intraoperative image while maintaining the quality of the preoperative image. Using clinical data, this paper reports the results of a comparison of the accuracy and performance among several non-rigid registration methods for handling brain deformation. A new adaptive method that automatically removes mesh elements in the area of the resected tumor, thereby handling deformation in the presence of resection is presented. To improve the user experience, we also present a new way of using mixed reality with ultrasound, MRI, and CT.

Materials and methods:This study focuses on 30 glioma surgeries performed at two different hospitals, many of which involved the resection of significant tumor volumes. An Adaptive Physics-Based Non-Rigid Registration method (A-PBNRR) registers preoperative and intraoperative MRI for each patient. The results are compared with three other readily available registration methods: a rigid registration implemented in 3D Slicer v4.4.0; a B-Spline non-rigid registration implemented in 3D Slicer v4.4.0; and PBNRR implemented in ITKv4.7.0, upon which A-PBNRR was based. Three measures were employed to facilitate a comprehensive evaluation of the registration accuracy: (i) visual assessment, (ii) a Hausdorff Distance-based metric, and (iii) a landmark-based approach using anatomical points identified by a neurosurgeon.

Results:The A-PBNRR using multi-tissue mesh adaptation improved the accuracy of deformable registration by more than five times compared to rigid and traditional physics based non-rigid registration, and four times compared to B-Spline interpolation methods which are part of ITK and 3D Slicer. Performance analysis showed that A-PBNRR could be applied, on average, in <2 min, achieving desirable speed for use in a clinical setting.

Conclusions:The A-PBNRR method performed significantly better than other readily available registration methods at modeling deformation in the presence of resection. Both the registration accuracy and performance proved sufficient to be of clinical value in the operating room. A-PBNRR, coupled with the mixed reality system, presents a powerful and affordable solution compared to current neuronavigation systems.
Low-Frequency Elastic Properties of a Polymineralic Carbonate: Laboratory Measurement and Digital Rock Physics
Authors: Ikeda Ken , Subramaniyan Shankar , Quintal Beatriz , Goldfarb Eric James , Saenger Erik H. , Tisato Nicola
Published: February 2021

We demonstrate that the static elastic properties of a carbonate sample, comprised of dolomite and calcite, could be accurately predicted by Digital Rock Physics (DRP), a non-invasive testing method for simulating laboratory measurements. We present a state-of-the-art algorithm that uses X-ray Computed Tomography (CT) imagery to compute the elastic properties of a lacustrine rudstone sample. The high-resolution CT-images provide a digital sample that is used for analyzing microstructures and performing quasi-static compression numerical simulations. Here, we present the modified Segmentation-Less method withOut Targets method: a combination of segmentation-based and segmentation-less DRP. This new method assigns the spatial distribution of elastic properties of the sample based on homogenization theory and overcomes the monomineralic limitation of the previous work, allowing the algorithm to be used on polymineralic rocks. The method starts by partitioning CT-images of the sample into smaller sub-images, each of which contains only two phases: a mineral (calcite or dolomite) and air. Then, each sub-image is converted into elastic property arrays. Finally, the elastic property arrays from the sub-images are combined and fed into a finite element algorithm to compute the effective elastic properties of the sample. We compared the numerical results to the laboratory measurements of low-frequency elastic properties. We find that the Young’s moduli of both the dry and the fully saturated sample fall within 10% of the laboratory measurements. Our analysis also shows that segmentation-based DRP should be used cautiously to compute elastic properties of carbonate rocks similar to our sample.
Investigating Possible Gastroliths in a Referred Specimen of Bohaiornis guoi (Aves: Enantiornithes)
Authors: Liu Shumin , Li Zhiheng , Bailleul Alida M. , Wang Min , O’Connor Jingmai
Published: February 2021

Gastroliths, where preserved, can provide indirect evidence regarding diet in extinct avian and non-avian dinosaurs. Masses of gastroliths consistent with the presence of a gastric mill are preserved in many Early Cretaceous Jehol birds mostly belonging to the Ornithuromorpha. Gastroliths are also present in basal birds Sapeornis and Jeholornis in which herbivory is supported by direct evidence these taxa consumed seeds in the form of crop or stomach contents. Although gastroliths have been correlated with herbivory in non-avian dinosaurs, the presence of gastroliths and bone together in Ambopteryx calls this association in to question. Despite being known from greater numbers of specimens than other avian lineages, no unequivocal direct or indirect evidence of diet has been recovered from Jehol deposits for the Enantiornithes. A referred specimen of Bohaiornis guoi IVPP V17963 was described as preserving a small number of gastroliths interpreted as rangle, gastroliths whose function is cleaning the stomach in extant raptorial birds. However, based on comparison with gastroliths in other Jehol birds, it has alternatively been suggested that the identified structures are not ingested stones at all but some unusual mineral precipitate. Considering the limited evidence regarding diet in Enantiornithes and the importance of accurately identifying the traces in Bohaiornis in order to understand the enantiornithine digestive system, we extracted two samples of these purported gastroliths and explored these traces using computerized laminography scanning, scanning electron microscopy, energy dispersive x-ray spectroscopy, ground sections, and body size to gastral mass regressions. Similar analyses were conducted on gastroliths extracted from undisputed gastral masses of two Jehol ornithuromorphs and the non-avian pennaraptoran Caudipteryx. The combined results contradict the hypothesis that these traces are gastroliths and supports the interpretation they are mineral precipitate, most likely authigenic quartz (chalcedony). Although authigenesis is commonly responsible for the preservation of soft tissues, it is unclear if these traces record part of the tissues of this Bohaiornis. This study highlights the importance of a multidisciplinary approach in understanding unusual traces in the fossil record and reveal a previously unidentified taphonomic phenomenon in fossils from Jehol deposits.
Organized Futures. On the Ambiguity of the Digital Absorption of Uncertainty
Authors: Wendt Thomas
Published: February 2021

Digitalization primarily takes place in and through organizations. Despite this prominent role, however, the importance of organizational structure-building processes in the digital transformation is still underexposed in discourse. The fact that ongoing digitalization is linked to an established phenomenon and its own logic, is regularly not addressed due to the attraction potential of the semantics of the digital revolution. Digital revolution and the reordering of societal relationships, though, manifest themselves primarily in processes of reorganization. Structural automation processes in the ongoing digital transformation are limiting the scope for action, necessitating forms of structural structurelessness in organizations that cultivate opportunities for chance. Since organizations realize their operations as a dual of structure and individual, and the principle of organization is therefore based on the complementarity of structural formality and unpredictable informality. The paper discusses the topicality of the classical form of modern organization in the digital age and reflects on approaches to a contemporary design of spaces of opportunity. The reflexive handling of future openness is the central task of management and leadership in order to enable variation and innovation in organizations.
Home Numeracy and Preschool Children’s Mathematical Development: Expanding Home Numeracy Models to Include Parental Attitudes and Emotions
Authors: Dowker Ann
Published: February 2021

Most studies suggest that home numeracy is correlated with preschool children’s current mathematical performance, and also predicts their mathematical performance longitudinally. However, this finding is not universal, and some studies do not suggest a close relationship between home numeracy and preschoolers’ mathematical development. There are several possible reasons for the discrepant findings, including the exact nature of numeracy activities provided, and possible unreliability of parental reports of home numeracy. However, parental attitudes might also lead to differing results: because attitudes might influence actual home numeracy provision or the ways in which it is reported; because parental attitudes and beliefs might be transmitted intergenerationally; and because parental mathematics anxiety may interact with home numeracy activities to create early negative emotional associations about mathematics, as some research suggests to be the case with regard to school-age children. There has been a significant amount of research in the first two of these areas, but very little in the third area with regard to preschoolers. It should be seen as an important area for further research.
The Role of β Cell Stress and Neo-Epitopes in the Immunopathology of Type 1 Diabetes
Authors: Piganelli Jon D. , Mamula Mark J. , James Eddie A.
Published: February 2021

Due to their secretory function, β cells are predisposed to higher levels of endoplasmic reticulum (ER) stress and greater sensitivity to inflammation than other cell types. These stresses elicit changes in β cells that alter their function and immunogenicity, including defective ribosomal initiation, post-translational modifications (PTMs) of endogenous β cell proteins, and alternative splicing. Multiple published reports confirm the presence of not only CD8+ T cells, but also autoreactive CD4+ T cells within pancreatic islets. Although the specificities of T cells that infiltrate human islets are incompletely characterized, they have been confirmed to include neo-epitopes that are formed through stress-related enzymatic modifications of β cell proteins. This article summarizes emerging knowledge about stress-induced changes in β cells and data supporting a role for neo-antigen formation and cross-talk between immune cells and β cells that provokes autoimmune attack - leading to a breakdown in tissue-specific tolerance in subjects who develop type 1 diabetes.
Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women With Polycystic Ovary Syndrome
Authors: Duică Florentina , Dănilă Cezara Alina , Boboc Andreea Elena , Antoniadis Panagiotis , Condrat Carmen Elena , Onciul Sebastian , Suciu Nicolae , Creţoiu Sanda Maria , Varlas Valentin Nicolae , Creţoiu Dragoş
Published: February 2021

Polycystic ovary syndrome (PCOS) is a complex disorder that affects around 5% to 10% of women of childbearing age worldwide, making it the most common source of anovulatory infertility. PCOS is defined by increased levels of androgens, abnormal ovulation, irregular menstrual cycles, and polycystic ovarian morphology in one or both ovaries. Women suffering from this condition have also been shown to frequently associate certain cardiovascular comorbidities, including obesity, hypertension, atherosclerosis, and vascular disease. These factors gradually lead to endothelial dysfunction and coronary artery calcification, thus posing an increased risk for adverse cardiac events. Traditional markers such as C-reactive protein (CRP) and homocysteine, along with more novel ones, specifically microRNAs (miRNAs), can accurately signal the risk of cardiovascular disease (CVD) in PCOS women. Furthermore, studies have also reported that increased oxidative stress (OS) coupled with poor antioxidant status significantly add to the increased cardiovascular risk among these patients. OS additionally contributes to the modified ovarian steroidogenesis, consequently leading to hyperandrogenism and infertility. The present review is therefore aimed not only at bringing together the most significant information regarding the role of oxidative stress in promoting CVD among PCOS patients, but also at highlighting the need for determining the efficiency of antioxidant therapy in these patients.
Sternocostoclavicular Hyperostosis: Positive Clinical and Radiological Response on Pamidronate
Authors: Leerling Anne T. , Cañete Ana Navas , Ramautar Ashna I. E. , Appelman-Dijkstra Natasha M. , Winter Elizabeth M.
Published: February 2021

Background

Sternocostoclavicular hyperostosis (SCCH) is a rare disease, constituting a chronic sterile osteomyelitis with elevated bone turnover in the axial skeleton, causing pain and shoulder dysfunction. SCCH severely interferes with daily activities, work, and quality of life. SCCH has a relapse-remitting disease course, but inflammatory-induced sclerotic transformation in the affected area is slowly progressive. Here we present two patients with clinical and radiological diagnosis of SCCH treated with intravenous pamidronate, leading to clinical remission in both, but complete resolution of sclerosis in one of them, which is a novel finding in our experience.

Case Presentation

Two adult female SCCH-patients presented with longstanding pain, swelling of the anterior chest wall, and compromised shoulder function. Subsequent single photon emission computed tomography-computed tomography (SPECT/CT) illustrated elevated bone activity and sclerosis in the SC region, with hyperostosis, confirming the diagnosis of SCCH. As symptoms in both patients were eventually refractory to standard painkillers such as non-steroidal anti-inflammatory drugs (NSAIDs), intravenous pamidronate treatment in 3-month cycles was started. Pamidronate was effective in reducing pain and improving shoulder function and also led to decreased bone turnover on skeletal scintigraphy. Sclerosis in the first patient persisted. In the second patient, however, a complete resolution of sclerosis was observed.

Conclusions

SCCH remains a rare bone disorder for which no evidence-based therapies are yet available. While disease burden is high, SCCH lacks recognition and is often diagnosed long after symptomatic presentation. As for the cases in this report, pamidronate was successful in reducing symptoms, and in the second case even led to regression of sclerotic changes on CT-imaging.
Nexus Between Carbon Emissions, Energy Consumption, Urbanization and Economic Growth in Asia: Evidence From Common Correlated Effects Mean Group Estimator (CCEMG)
Authors: Adeneye Yusuf Babatunde , Jaaffar Amar Hisham , Ooi Chai Aun , Ooi Say Keat
Published: February 2021

This study investigates the dynamic relationships between carbon emission, urbanization, energy consumption, and economic growth in a panel of 42 Asian countries for the period 2000–2014 using dynamic common correlated effects panel data modeling. This study employs second generation cross-sectional Pesaran (J. Appl. Econom., 2007, 22(2), 265-312) panel unit root, Westerlund panel cointegration tests (Econom. Stat., 2007, 69(6), 709-748), and Pesaran’s (Econometrica, 2006, 74(4), 967-1012) common correlated effects mean group estimation technique. These approaches allow for cross-sectional dependence, and are robust to the presence of common factors, serial correlation, and slope heterogeneity. The Common Correlated Effect Mean Group test reveals a high average coefficient of 0.602 between carbon emission and energy consumption while low coefficients of 0.114 and 0.184 for the pairs of carbon emission-urbanization and carbon emission-GDP, respectively for the panel as a whole, suggesting a cointegration between carbon emission, urbanization, energy consumption, and economic growth. The results indicate that there is relatively high carbon emission especially for highly populated and geopolitical risk Asian countries in the short run. Findings reveal long run relationships between the variables, which is attributed to the on-going carbon taxation and energy prices. Our results are robust to PMG-ARDL estimator. Overall, these findings cast important implications on renewable energy policy and urban planning insights for the policymakers.
How Does the Efficiency of Value Realization on a Platform Influence Sustainability Transition? A Case of the Power Industry in China
Authors: Xie Jing , Lv Tao , Tong Peng , Li Xiangong , Lu Yuduo , Sajid Muhammad Jawad , Lv Qian
Published: February 2021

In the era of the digital economy, for platform-based actors making a transition from one business field harmful for the sustainable development of society to a new field, their efficiency in value realization (EVR) has become inseparable from the digital platform used. The relationship between EVR on a platform and business transitions is a topic that has not been fully discussed, especially from the perspective of the platform service system. Also, few studies have explored transaction costs and opportunity costs using queuing theory. To fill these gaps and to inform transitions to sustainability, this paper applied a system dynamics method and proposed a framework for analyzing the relationship between EVR and the transition ratio. Findings suggest that improvements in the EVR lead to decreases in response time and may lead to an improved transition ratio. The ratio between EVR and the “entry rate” is important for predicting the transition ratio. However, preference, platform maturity, and the feedback of the transition ratio cause the effect of EVR to dynamically change. Based on this mechanism, the government can take incentive measures to maintain an acceptable transition ratio. For the power industry, the case simulated for this study, the transition can be improved by effectively transmitting a phasing-out policy for platforms and actors, and by guiding power exchange platforms to set reasonable rules, service levels, and growth rates.
Dynamic Optimization Method of Transmission Line Parameters Based on Grey Support Vector Regression
Authors: Qu Zhaoyang , Li Miao , Zhang Zhenming , Cui Mingshi , Zhou Yuguang
Published: February 2021

Aiming at the problem of insufficient accuracy and timeliness of transmission line parameters in the grid energy management system (EMS) parameter library, a dynamic optimization method of transmission line parameters based on grey support vector regression is proposed. Firstly, the influence of operating conditions and meteorological factors on the changes of parameters is analyzed. Based on this, the correlation quantification method of transmission line parameters is designed based on Pearson coefficient, and the influence coefficient value is obtained. Then, with the influence coefficient as the constraint condition, a method for selecting strong influence characteristics of line parameters based on improved Elastic Net is proposed. Finally, based on the grey prediction theory, a grey support vector regression (GM-SVR) parameter optimization model is constructed to realize the dynamic optimization of line parameter values under the power grid operation state. The effectiveness and feasibility of the proposed method is verified through the commissioning of the reactance parameters of the actual local loop network transmission line.