bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection and Validation of Reference Genes for qRT-PCR Analysis in the Oil-Rich Tuber Crop Tiger Nut (Cyperus esculentus) Based on Transcriptome Data
Authors: Bai Xue , Chen Tao , Wu Yuan , Tang Mingyong , Xu Zeng-Fu
Published: March 2021

Tiger nut (Cyperus esculentus), a perennial C4 plant of the Cyperaceae family, is an unconventional crop that is distinguished by its oil-rich tubers, which also possesses the advantages of strong resistance, wide adaptability, short life periods, and large biomass. To facilitate studies on gene expression in this species, we identified and validated a series of reference genes (RGs) based on transcriptome data, which can be employed as internal controls for qRT-PCR analysis in tiger nut. Fourteen putative candidate RGs were identified and evaluated across nine different tissues of two cultivars, and the RGs were analyzed using three different algorithms (geNorm, NormFinder, and BestKeeper). The stability rankings of the candidate RGs were merged into consensus lists with RankAggreg. For the below-ground storage organ of tiger nut, the optimal RGs were TUB4 and UCE2 in different developmental stages of tubers. UCE2 and UBL5 were the most stably expressed RGs among all tissues, while Rubisco and PGK exhibited the lowest expression stability. UCE2, UBL5 and Rubisco were compared to normalize the expression levels of the caleosin (CLO) and diacylglycerol acyltransferase 2-2 (DGAT2-2) genes across the same tissues. Our results showed that the RGs identified in this study, which exhibit more uniform expression patterns, may be utilized for the normalization of qRT-PCR results, promoting further research on gene expression in various tissues of tiger nut.
Optimal Preclinical Conditions for Using Adult Human Multipotent Neural Cells in the Treatment of Spinal Cord Injury
Authors: Won Jeong-Seob , Yeon Je Young , Pyeon Hee-Jang , Noh Yu-Jeong , Hwang Ji-Yoon , Kim Chung Kwon , Nam Hyun , Lee Kyung-Hoon , Lee Sun-Ho , Joo Kyeung Min
Published: March 2021

Stem cell-based therapeutics are amongst the most promising next-generation therapeutic approaches for the treatment of spinal cord injury (SCI), as they may promote the repair or regeneration of damaged spinal cord tissues. However, preclinical optimization should be performed before clinical application to guarantee safety and therapeutic effect. Here, we investigated the optimal injection route and dose for adult human multipotent neural cells (ahMNCs) from patients with hemorrhagic stroke using an SCI animal model. ahMNCs demonstrate several characteristics associated with neural stem cells (NSCs), including the expression of NSC-specific markers, self-renewal, and multi neural cell lineage differentiation potential. When ahMNCs were transplanted into the lateral ventricle of the SCI animal model, they specifically migrated within 24 h of injection to the damaged spinal cord, where they survived for at least 5 weeks after injection. Although ahMNC transplantation promoted significant locomotor recovery, the injection dose was shown to influence treatment outcomes, with a 1 × 106 (medium) dose of ahMNCs producing significantly better functional recovery than a 3 × 105 (low) dose. There was no significant gain in effect with the 3 × 106 ahMNCs dose. Histological analysis suggested that ahMNCs exert their effects by modulating glial scar formation, neuroprotection, and/or angiogenesis. These data indicate that ahMNCs from patients with hemorrhagic stroke could be used to develop stem cell therapies for SCI and that the indirect injection route could be clinically relevant. Moreover, the optimal transplantation dose of ahMNCs defined in this preclinical study might be helpful in calculating its optimal injection dose for patients with SCI in the future.
Exogenous Transforming Growth Factor-β in Brain-Induced Symptoms of Central Fatigue and Suppressed Dopamine Production in Mice
Authors: Lee Won Kil , Kim Yeongyeong , Jang Heejin , Sim Joo Hye , Choi Hye Jin , Shin Younmin , Choi Jeong June
Published: March 2021

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is one of the most refractory diseases in humans and is characterized by severe central fatigue accompanied with various symptoms that affect daily life, such as impaired memory, depression, and somatic pain. However, the etiology and pathophysiological mechanisms of CFS remain unknown. To investigate the pathophysiological role of transforming growth factor (TGF)-β1, we injected a cytokine into the lateral ventricle of a C57BL/6 mouse. The intracranial injection of TGF-β1 increased the immobility duration in a forced swimming test (FST) and time spent at the closed arm in elevated plus maze (EPM) analysis. The mice injected with TGF-β1 into their brain showed increased sensitivity to pain in a von Frey test, and had a decreased retention time on rotarod and latency time in a bright box in a passive avoidance test. In addition, the serum levels of muscle fatigue biomarkers, lactate dehydrogenase (LDH) and creatine kinase (CK), were significantly increased after administration of TGF-β1. Intracranial injection of TGF-β1 significantly reduced the production of tyrosine hydroxylase (TH) in the ventral tegmental area, accompanied by a decreased level of dopamine in the striatum. The suppression of TH expression by TGF-β1 was confirmed in the human neuroblastoma cell line, SH-SY5Y. These results, which show that TGF-β1 induced fatigue-like behaviors by suppressing dopamine production, suggest that TGF-β1 plays a critical role in the development of central fatigue and is, therefore, a potential therapeutic target of the disease.
The Benefits of Smart Nanoparticles in Dental Applications
Authors: Vasiliu Silvia , Racovita Stefania , Gugoasa Ionela Aurica , Lungan Maria-Andreea , Popa Marcel , Desbrieres Jacques
Published: March 2021

Dentistry, as a branch of medicine, has undergone continuous evolution over time. The scientific world has focused its attention on the development of new methods and materials with improved properties that meet the needs of patients. For this purpose, the replacement of so-called “passive” dental materials that do not interact with the oral environment with “smart/intelligent” materials that have the capability to change their shape, color, or size in response to an externally stimulus, such as the temperature, pH, light, moisture, stress, electric or magnetic fields, and chemical compounds, has received much attention in recent years. A strong trend in dental applications is to apply nanotechnology and smart nanomaterials such as nanoclays, nanofibers, nanocomposites, nanobubbles, nanocapsules, solid-lipid nanoparticles, nanospheres, metallic nanoparticles, nanotubes, and nanocrystals. Among the nanomaterials, the smart nanoparticles present several advantages compared to other materials, creating the possibility to use them in various dental applications, including preventive dentistry, endodontics, restoration, and periodontal diseases. This review is focused on the recent developments and dental applications (drug delivery systems and restoration materials) of smart nanoparticles.
Metabolome and Transcriptome Analyses Reveal the Regulatory Mechanisms of Photosynthesis in Developing Ginkgo biloba Leaves
Authors: Guo Ying , Wang Tongli , Fu Fang-Fang , El-Kassaby Yousry A. , Wang Guibin
Published: March 2021

Ginkgo (Ginkgo biloba L.) is a deciduous tree species with high timber, medicinal, ecological, ornamental, and scientific values, and is widely cultivated worldwide. However, for such an important tree species, the regulatory mechanisms involved in the photosynthesis of developing leaves remain largely unknown. Here, we observed variations in light response curves (LRCs) and photosynthetic parameters (photosynthetic capacity (Pnmax) and dark respiration rate (Rd)) of leaves across different developmental stages. We found the divergence in the abundance of compounds (such as 3-phospho-d-glyceroyl phosphate, sedoheptulose-1,7-bisphosphate, and malate) involved in photosynthetic carbon metabolism. Additionally, a co-expression network was constructed to reveal 242 correlations between transcription factors (TFs) and photosynthesis-related genes (p < 0.05, |r| > 0.8). We found that the genes involved in the photosynthetic light reaction pathway were regulated by multiple TFs, such as bHLH, WRKY, ARF, IDD, and TFIIIA. Our analysis allowed the identification of candidate genes that most likely regulate photosynthesis, primary carbon metabolism, and plant development and as such, provide a theoretical basis for improving the photosynthetic capacity and yield of ginkgo trees.
Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma
Authors: Viennois Emilie , Chassaing Benoit
Published: March 2021

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.
Paving the Way for Fertilization: The Role of the Transmitting Tract
Authors: Pereira Ana Marta , Moreira Diana , Coimbra Sílvia , Masiero Simona
Published: March 2021

Angiosperm reproduction relies on the precise growth of the pollen tube through different pistil tissues carrying two sperm cells into the ovules’ embryo sac, where they fuse with the egg and the central cell to accomplish double fertilization and ultimately initiate seed development. A network of intrinsic and tightly regulated communication and signaling cascades, which mediate continuous interactions between the pollen tube and the sporophytic and gametophytic female tissues, ensures the fast and meticulous growth of pollen tubes along the pistil, until it reaches the ovule embryo sac. Most of the pollen tube growth occurs in a specialized tissue—the transmitting tract—connecting the stigma, the style, and the ovary. This tissue is composed of highly secretory cells responsible for producing an extensive extracellular matrix. This multifaceted matrix is proposed to support and provide nutrition and adhesion for pollen tube growth and guidance. Insights pertaining to the mechanisms that underlie these processes remain sparse due to the difficulty of accessing and manipulating the female sporophytic tissues enclosed in the pistil. Here, we summarize the current knowledge on this key step of reproduction in flowering plants with special emphasis on the female transmitting tract tissue.
Novel Molecular Insights into Human Lipid-Mediated T Cell Immunity
Authors: Shahine Adam , Wegrecki Marcin , Le Nours Jérôme
Published: March 2021

T cells represent a critical arm of our immune defense against pathogens. Over the past two decades, considerable inroads have been made in understanding the fundamental principles underpinning the molecular presentation of peptide-based antigens by the Major Histocompatibility Complex molecules (MHC-I and II), and their molecular recognition by specialized subsets of T cells. However, some T cells can recognize lipid-based antigens presented by MHC-I-like molecules that belong to the Cluster of Differentiation 1 (CD1) family. Here, we will review the advances that have been made in the last five years to understand the molecular mechanisms orchestrating the presentation of novel endogenous and exogenous lipid-based antigens by the CD1 glycoproteins and their recognition by specific populations of CD1-reactive T cells.
Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee
Authors: Jang Sunhee , Lee Kijun , Ju Ji Hyeon
Published: March 2021

Osteoarthritis (OA) is a degenerative and chronic joint disease characterized by clinical symptoms and distortion of joint tissues. It primarily damages joint cartilage, causing pain, swelling, and stiffness around the joint. It is the major cause of disability and pain. The prevalence of OA is expected to increase gradually with the aging population and increasing prevalence of obesity. Many potential therapeutic advances have been made in recent years due to the improved understanding of the underlying mechanisms, diagnosis, and management of OA. Embryonic stem cells and induced pluripotent stem cells differentiate into chondrocytes or mesenchymal stem cells (MSCs) and can be used as a source of injectable treatments in the OA joint cavity. MSCs are known to be the most studied cell therapy products in cell-based OA therapy owing to their ability to differentiate into chondrocytes and their immunomodulatory properties. They have the potential to improve cartilage recovery and ultimately restore healthy joints. However, despite currently available therapies and advances in research, unfulfilled medical needs persist for OA treatment. In this review, we focused on the contents of non-cellular and cellular therapies for OA, and briefly summarized the results of clinical trials for cell-based OA therapy to lay a solid application basis for clinical research.
TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues
Authors: Bartha Áron , Győrffy Balázs
Published: March 2021

Genes showing higher expression in either tumor or metastatic tissues can help in better understanding tumor formation and can serve as biomarkers of progression or as potential therapy targets. Our goal was to establish an integrated database using available transcriptome-level datasets and to create a web platform which enables the mining of this database by comparing normal, tumor and metastatic data across all genes in real time. We utilized data generated by either gene arrays from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or RNA-seq from The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories. The altered expression within different platforms was analyzed separately. Statistical significance was computed using Mann–Whitney or Kruskal–Wallis tests. False Discovery Rate (FDR) was computed using the Benjamini–Hochberg method. The entire database contains 56,938 samples, including 33,520 samples from 3180 gene chip-based studies (453 metastatic, 29,376 tumorous and 3691 normal samples), 11,010 samples from TCGA (394 metastatic, 9886 tumorous and 730 normal), 1193 samples from TARGET (1 metastatic, 1180 tumorous and 12 normal) and 11,215 normal samples from GTEx. The most consistently upregulated genes across multiple tumor types were TOP2A (FC = 7.8), SPP1 (FC = 7.0) and CENPA (FC = 6.03), and the most consistently downregulated gene was ADH1B (FC = 0.15). Validation of differential expression using equally sized training and test sets confirmed the reliability of the database in breast, colon, and lung cancer at an FDR below 10%. The online analysis platform enables unrestricted mining of the database and is accessible at TNMplot.com.
Impact of BMI on Survival Outcomes of Immunotherapy in Solid Tumors: A Systematic Review
Authors: Indini Alice , Rijavec Erika , Ghidini Michele , Tomasello Gianluca , Cattaneo Monica , Barbin Francesca , Bareggi Claudia , Galassi Barbara , Gambini Donatella , Grossi Francesco
Published: March 2021

Growing research has focused on obesity as a prognostic factor during therapy with immune-checkpoint inhibitors (ICIs). The role of body-mass index (BMI) in predicting response and toxicity to ICIs is not clear, as studies have shown inconsistent results and significant interpretation biases. We performed a systematic review to evaluate the relationship between BMI and survival outcomes during ICIs, with a side focus on the incidence of immune-related adverse events (irAEs). A total of 17 studies were included in this systematic review. Altogether, the current evidence does not support a clearly positive association of BMI with survival outcomes. Regarding toxicities, available studies confirm a superimposable rate of irAEs among obese and normal weight patients. Intrinsic limitations of the analyzed studies include the retrospective nature, the heterogeneity of patients’ cohorts, and differences in BMI categorization for obese patients across different studies. These factors might explain the heterogeneity of available results, and the subsequent absence of a well-established role of baseline BMI on the efficacy of ICIs among cancer patients. Further prospective studies are needed, in order to clarify the role of obesity in cancer patients treated with immunotherapy.
Comparing Ligninolytic Capabilities of Bacterial and Fungal Dye-Decolorizing Peroxidases and Class-II Peroxidase-Catalases
Authors: Linde Dolores , Ayuso-Fernández Iván , Laloux Marcos , Aguiar-Cervera José E. , de Lacey Antonio L. , Ruiz-Dueñas Francisco J. , Martínez Angel T.
Published: March 2021

We aim to clarify the ligninolytic capabilities of dye-decolorizing peroxidases (DyPs) from bacteria and fungi, compared to fungal lignin peroxidase (LiP) and versatile peroxidase (VP). With this purpose, DyPs from Amycolatopsis sp., Thermomonospora curvata, and Auricularia auricula-judae, VP from Pleurotus eryngii, and LiP from Phanerochaete chrysosporium were produced, and their kinetic constants and reduction potentials determined. Sharp differences were found in the oxidation of nonphenolic simple (veratryl alcohol, VA) and dimeric (veratrylglycerol-β- guaiacyl ether, VGE) lignin model compounds, with LiP showing the highest catalytic efficiencies (around 15 and 200 s−1·mM−1 for VGE and VA, respectively), while the efficiency of the A. auricula-judae DyP was 1–3 orders of magnitude lower, and no activity was detected with the bacterial DyPs. VP and LiP also showed the highest reduction potential (1.28–1.33 V) in the rate-limiting step of the catalytic cycle (i.e., compound-II reduction to resting enzyme), estimated by stopped-flow measurements at the equilibrium, while the T. curvata DyP showed the lowest value (1.23 V). We conclude that, when using realistic enzyme doses, only fungal LiP and VP, and in much lower extent fungal DyP, oxidize nonphenolic aromatics and, therefore, have the capability to act on the main moiety of the native lignin macromolecule.
Ant Diversity and Community Composition in Alpine Tree Line Ecotones
Authors: Guariento Elia , Fiedler Konrad
Published: March 2021

Ants are crucial for the functioning of many terrestrial ecosystems, but detailed knowledge of their ecological role is often lacking. This is true for high mountains where a steep environmental gradient exists from mountainous forest, densely populated by ants, to grassland habitats above the tree line, harboring a sparse ant community. We assessed ant communities in and around the tree line ecotone on five slopes in the southern-central Alps, focusing on their species diversity, community composition, and functional dimensions. Species richness and functional diversity were highest directly at the ecotone. Ant community composition was shaped by elevation and shrub cover. Further, the abundance of the dominant mound-building red wood ants (Formica s. str.) influenced the community composition of the subordinate species. We conclude that over the tree line ecotone a shift in predominance from biotic limitations in the forest to abiotic filters in the alpine environment takes place.
Laparoscopic Pectopexy—CUSUM Learning Curve and Perioperative Complications Analysis
Authors: Szymczak Paulina , Grzybowska Magdalena Emilia , Sawicki Sambor , Wydra Dariusz Grzegorz
Published: March 2021

The study aimed to examine the learning curve and perioperative complications for laparoscopic pectopexy (LP). A total of 60 women with stage II–IV apical prolapse who underwent LP were dichotomized into groups: LSH(+) with concomitant laparoscopic supracervical hysterectomy (LSH), LSH(−) after previous supracervical/total hysterectomy. Operative time, estimated blood loss and hospitalization length were evaluated with cumulative sum (CUSUM) analysis and the Kwiatkowski–Phillips–Schmidt–Shin (KPSS) test, separately for two surgeons (A and B). Intraoperative and perioperative complications according to the Clavien–Dindo (C–D) classification were analyzed. Mean operative time, change in hemoglobin level, and postoperative hospital stay were 143.5 ± 23.1 min—1.5 ± 0.5g/dL and 2.5 ± 0.9 days, respectively. LSH during pectopexy was associated with longer operative time (p = 0.01) but not with higher intraoperative bleeding or prolonged hospital stay. Severe complications rate was low (1.7%) with one bowel injury in LSH(−) (C–D grade IIIb). No C–D grade II, IV and V complications were found. Conversion to open pectopexy, return to the operating room or blood transfusion were not required. The KPSS test showed that a steady operative time for Surgeon A was achieved after 28 procedures. A proficiency for laparoscopic pectopexy based on CUSUM analysis was observed after 38–40 procedures.
Impact of Personal Protective Equipment on the First-Pass Success of Endotracheal Intubation in the ED: A Propensity-Score-Matching Analysis
Authors: Choi Jeonghyun , Shin Tae Gun , Park Jong Eun , Lee Gun Tak , Kim Young Min , Lee Soo Ah , Kim Seonwoo , Hwang Na Young , Hwang Sung Yeon
Published: March 2021

Various types and levels of personal protective equipment (PPE) are currently available to protect health-care workers against infectious diseases. However, wearing cumbersome PPE may negatively affect their performance in life-saving procedures. This study aimed to evaluate the impact of wearing extensive PPE, including a powered air-purifying respirator with a loose-fitting hood or an N95 filtering facepiece respirator, on the first-pass success (FPS) rate of endotracheal intubation (ETI) in the emergency department (ED). This study was a single-center, observational before-and-after study of 934 adult (≥18 years old) patients who underwent ETI in the academic ED. The study period was divided into a control period (from 20 January 2019, to 30 September 2019, and from 20 January 2018, to 30 September 2018) and an intervention period (from 20 January 2020, to 30 September 2020). Extensive PPE was not donned during the control period (control group, n = 687) but was donned during the intervention period (PPE group, n = 247). The primary outcome was the FPS rate. We used propensity score matching between the PPE and control groups to reduce potential confounding. Propensity score matching identified 247 cases in the PPE group and 492 cases in the control group. In the matched cohort, no significant difference was found in the FPS rate between the PPE and control groups (83.8% (n = 207) vs. 81.9% (n = 403); p = 0.522). In multivariable analysis, wearing PPE was not associated with the FPS rate (adjusted odds ratio, 0.90; 95% confidence interval, 0.57–1.40; p = 0.629) after adjusting for the level of the intubator (junior resident, senior resident, or emergency medicine (EM) specialist). In conclusion, the FPS rate is not significantly affected by wearing extensive PPE in the ED.
The Benefits and Respective Side-Effects of PE Therapy for Intractable Kawasaki Disease
Authors: Mori Masaaki , Yamazaki Susumu , Naruto Takuya
Published: March 2021

Kawasaki disease (KD) is a vasculitis syndrome that frequently develops coronary artery lesions (CALs). In the treatment of KD, the utility of high-dose intravenous immuno-globulin (IVIG) therapy has already been clarified, and it has been established as the first-line treatment method. However, since approximately 10% of patients are refractory to this IVIG therapy and 2.6% of all patients have coronary sequelae, 500 children with KD still remain every year in Japan. In this disease, it is necessary to calm inflammation within 10 days of onset in order to suppress CALs caused by a large amount of persistent inflammatory cytokines. Indeed, the early suppression of inflammation is an effective means of suppressing the onset of CALs. Here, we describe the pathophysiology of Kawasaki disease and plasma exchange (PE), which is a therapeutic method that can calm the hyper-cytokine state of this disease. The treatment result of PE for IVIG-refractory Kawasaki disease is outstanding, and an extremely large effect can be expected if it can be started before the appearance of CALs. It seems that it should always be considered as one of the powerful additional treatments in the future.
Clinical Implications of the General Movement Optimality Score: Beyond the Classes of Rasch Analysis
Authors: Barbosa Vanessa Maziero , Einspieler Christa , Smith Everett , Bos Arend F. , Cioni Giovanni , Ferrari Fabrizio , Yang Hong , Urlesberger Berndt , Marschik Peter B. , Zhang Dajie
Published: March 2021

This article explores the clinical implications of the three different classes drawn from a Rasch analysis of the general movements optimality scores (GMOS) of 383 infants. Parametric analysis of the class membership examines four variables: age of assessment, brain injury presence, general movement patterns, and 2-year-old outcomes. GMOS separated infants with typical (class 3) from atypical development, and further separated cerebral palsy (class 2) from other neurodevelopmental disorders (class 1). Each class is unique regarding its quantitative and qualitative representations on the four variables. The GMOS has strong psychometric properties and provides a quantitative measure of early motor functions. The GMOS can be confidently used to assist with early diagnosis and predict distinct classes of developmental outcomes, grade motor behaviors, and provide a solid base to study individual general movement developmental trajectories.
Age- and Severity-Related In-Hospital Mortality Trends and Risks of Severe Traumatic Brain Injury in Japan: A Nationwide 10-Year Retrospective Study
Authors: Toida Chiaki , Muguruma Takashi , Gakumazawa Masayasu , Shinohara Mafumi , Abe Takeru , Takeuchi Ichiro , Morimura Naoto
Published: March 2021

Traumatic brain injury (TBI) is the major cause of mortality and morbidity in severely-injured patients worldwide. This retrospective nationwide study aimed to evaluate the age- and severity-related in-hospital mortality trends and mortality risks of patients with severe TBI from 2009 to 2018 to establish effective injury prevention measures. We retrieved information from the Japan Trauma Data Bank dataset between 2009 and 2018. The inclusion criteria for this study were patients with severe TBI defined as those with an Injury Severity Score ≥ 16 and TBI. In total, 31,953 patients with severe TBI (32.6%) were included. There were significant age-related differences in characteristics, mortality trend, and mortality risk in patients with severe TBI. The in-hospital mortality trend of all patients with severe TBI significantly decreased but did not improve for patients aged ≤ 5 years and with a Glasgow Coma Scale (GCS) score between 3 and 8. Severe TBI, age ≥ 65 years, fall from height, GCS score 3–8, and urgent blood transfusion need were associated with a higher mortality risk, and mortality risk did not decrease after 2013. Physicians should consider specific strategies when treating patients with any of these risk factors to reduce severe TBI mortality.
Microcomputed Tomographic Assessment of the Single Cone Root Canal Fillings Performed by Undergraduate Student, Postgraduate Student and Specialist Endodontist
Authors: Drukteinis Saulius , Bilvinaite Goda , Tusas Paulius , Shemesh Hagay , Peciuliene Vytaute
Published: March 2021

The present study evaluated the obturation quality of root canals filled with BioRoot RCS sealer and single gutta-percha point by undergraduate student (US), postgraduate student (PS) and endodontist (ED). Twenty-one plastic models of upper premolars were enlarged with HyFlex EDM instruments to a size 40/0.04 taper and randomly divided into three groups (7 teeth/14 canals per group): US, PS and ED. After the obturation of root canals with BioRoot RCS and one HyFlex EDM size 40 gutta-percha point, plastic models were scanned using micro-computed tomography scanner (µCT) SkyScan 1272 at isotropic resolution of 10 µm. The porosity distribution was evaluated separately for the apical, middle and coronal thirds. The Kruskal–Wallis, Mann–Whitney, Friedman and Wilcoxon tests with the significance level set at 5% were used for data analysis. The µCT evaluation revealed open pores being the dominant type of porosity in all experimental groups and root canal thirds, with the highest percentage of pores in the apical third of root canal fillings. The quality and homogeneity of single cone root canals fillings remained similar between the groups in the apical and middle thirds (p > 0.05). Significant differences were observed only in the coronal third (p < 0.05).
Imbalance in the Levels of Angiogenic Factors in Patients with Acute and Chronic Central Serous Chorioretinopathy
Authors: Karska-Basta Izabella , Pociej-Marciak Weronika , Chrząszcz Michał , Kubicka-Trząska Agnieszka , Dębicka-Kumela Magdalena , Gawęcki Maciej , Romanowska-Dixon Bożena , Sanak Marek
Published: March 2021

Background: The pathogenesis of central serous chorioretinopathy (CSC) remains a subject of intensive research. We aimed to determine correlations between plasma levels of selected angiogenic factors and different forms of CSC. Methods: Eighty patients were enrolled in the study including 30 with a chronic form of CSC, 30 with acute CSC, and 20 controls. Presence of active CSC was determined by fluorescein angiography (FA), indocyanine green angiography (ICGA), and swept-source optical coherence tomography (SS-OCT). Plasma concentrations of angiopoietin-1, endostatin, fibroblast growth factor, placental growth factor (PlGF), platelet-derived growth factor (PDGF-AA), thrombospondin-2, vascular endothelial growth factor (VEGF), VEGF-D, and pigment epithelium–derived factor were measured, and the results were compared between groups. Additionally, mean choroidal thickness (CT) was measured in all patients. Results: Levels of angiopoietin-1 (p = 0.008), PlGF (p = 0.045), and PDGF-AA (p = 0.033) differed significantly between the three groups. Compared with the controls, VEGF (p = 0.024), PlGF (p = 0.013), and PDGF-AA (p = 0.012) were downregulated in the whole CSC group, specifically PDGF-AA (p = 0.002) in acute CSC and angiopoietin-1 (p = 0.007) in chronic CSC. An inverse correlation between mean CT and VEGF levels was noted in CSC patients (rho = −0.27, p = 0.044). Conclusions: Downregulated angiopoietin-1, VEGF, PDGF-AA, and PlGF levels may highlight the previously unknown role of the imbalanced levels of proangiogenic and antiangiogenic factors in the pathogenesis of CSC. Moreover, downregulated VEGF levels may suggest that choroidal neovascularization in CSC is associated with arteriogenesis rather than angiogenesis.
Five-Year Outcome of Aflibercept Monotherapy for Exudative Age-Related Macular Degeneration with Good Baseline Visual Acuity
Authors: Kikushima Wataru , Sakurada Yoichi , Sugiyama Atsushi , Yoneyama Seigo , Matsubara Mio , Fukuda Yoshiko , Kashiwagi Kenji
Published: March 2021

We investigated the long-term visual and anatomical outcomes of aflibercept monotherapy for exudative age-related macular degeneration (AMD) with good baseline best-corrected visual acuity (BCVA). A medical chart review was performed for 40 consecutive patients with baseline decimal BCVA ≥ 0.6 secondary to exudative AMD. Three monthly injections were administrated, and thereafter additional injection was performed if needed over 5 years. In total, 13 eyes with neovascular AMD (nAMD) and 27 eyes with polypoidal choroidal vasculopathy (PCV) were enrolled. In both groups, the mean BCVA significantly improved at the 12-month visit (p < 0.05). However, the significant improvement in BCVA disappeared at the 24-month visit, and the final mean BCVA was equivalent to that at baseline (p = 0.17 in the nAMD group and p = 0.15 in the PCV group). The median number of injections required after the loading dose was 15.0 during the 5-year follow-up (nAMD:15.0 vs. PCV:15). During the study period, 37 (92.5%) eyes required retreatment(s). Cox regression analysis demonstrated that the protective allele of ARMS2 A69S was associated with a retreatment-free period from the initial injection (p = 0.041, repeated forward selection method). As-needed aflibercept monotherapy is a preferable treatment option for exudative AMD with good initial visual acuity regardless of nAMD or PCV during the 5-year study period.
A Model-Based Approach for Adaptable Middleware Evolution in WSN Platforms
Authors: Tiberti Walter , Cassioli Dajana , Di Marco Antinisca , Pomante Luigi , Santic Marco
Published: March 2021

Advances in technology call for a parallel evolution in the software. New techniques are needed to support this dynamism, to track and guide its evolution process. This applies especially in the field of embedded systems, and certainly in Wireless Sensor Networks (WSNs), where hardware platforms and software environments change very quickly. Commonly, operating systems play a key role in the development process of any application. The most used operating system in WSNs is TinyOS, currently at its TinyOS 2.1.2 version. The evolution from TinyOS 1.x and TinyOS 2.x made the applications developed on TinyOS 1.x obsolete. In other words, these applications are not compatible out-of-the-box with TinyOS 2.x and require a porting action. In this paper, we discuss on the porting of embedded system (i.e., Wireless Sensor Networks) applications in response to operating systems’ evolution. In particular, using a model-based approach, we report the porting we did of Agilla, a Mobile-Agent Middleware (MAMW) for WSNs, on TinyOS 2.x, which we refer to as Agilla 2. We also provide a comparative analysis about the characteristics of Agilla 2 versus Agilla. The proposed Agilla 2 is compatible with TinyOS 2.x, has full capabilities and provides new features, as shown by the maintainability and performance measurement presented in this paper. An additional valuable result is the architectural modeling of Agilla and Agilla 2, missing before, which extends its documentation and improves its maintainability.
More Reliable Land Price Index: Is There a Slope Effect?
Authors: Huang Yi , Hewings Geoffrey
Published: March 2021

This paper focuses on the physical attributes of land that intrinsically limit land use and possibly affect land values. In particular, we investigate if the slope of a land does decrease its price and investigate the role of land slope in forming more reliable constant-quality land price indices and aggregate house price indices. We find that, while land slopes do decrease the land price per unit, they have a small effect on the quality-adjusted land price indices in selected neighborhoods in Auckland, New Zealand, where sloped terrain is common.
The Emerging Roles of Antioxidant Enzymes by Dietary Phytochemicals in Vascular Diseases
Authors: Lee Seung Eun , Park Yong Seek
Published: March 2021

Vascular diseases are major causes of death worldwide, causing pathologies including diabetes, atherosclerosis, and chronic obstructive pulmonary disease (COPD). Exposure of the vascular system to a variety of stressors and inducers has been implicated in the development of various human diseases, including chronic inflammatory diseases. In the vascular wall, antioxidant enzymes form the first line of defense against oxidative stress. Recently, extensive research into the beneficial effects of phytochemicals has been conducted; phytochemicals are found in commonly used spices, fruits, and herbs, and are used to prevent various pathologic conditions, including vascular diseases. The present review aims to highlight the effects of dietary phytochemicals role on antioxidant enzymes in vascular diseases.
Longitudinal T2 Mapping and Texture Feature Analysis in the Detection and Monitoring of Experimental Post-Traumatic Cartilage Degeneration
Authors: Huppertz Marc Sebastian , Schock Justus , Radke Karl Ludger , Abrar Daniel Benjamin , Post Manuel , Kuhl Christiane , Truhn Daniel , Nebelung Sven
Published: March 2021

Background: Traumatic cartilage injuries predispose articulating joints to focal cartilage defects and, eventually, posttraumatic osteoarthritis. Current clinical-standard imaging modalities such as morphologic MRI fail to reliably detect cartilage trauma and to monitor associated posttraumatic degenerative changes with oftentimes severe prognostic implications. Quantitative MRI techniques such as T2 mapping are promising in detecting and monitoring such changes yet lack sufficient validation in controlled basic research contexts. Material and Methods: 35 macroscopically intact cartilage samples obtained from total joint replacements were exposed to standardized injurious impaction with low (0.49 J, n = 14) or high (0.98 J, n = 14) energy levels and imaged before and immediately, 24 h, and 72 h after impaction by T2 mapping. Contrast, homogeneity, energy, and variance were quantified as features of texture on each T2 map. Unimpacted controls (n = 7) and histologic assessment served as reference. Results: As a function of impaction energy and time, absolute T2 values, contrast, and variance were significantly increased, while homogeneity and energy were significantly decreased. Conclusion: T2 mapping and texture feature analysis are sensitive diagnostic means to detect and monitor traumatic impaction injuries of cartilage and associated posttraumatic degenerative changes and may be used to assess cartilage after trauma to identify “cartilage at risk”.
Resolving Differential Diagnostic Problems in von Willebrand Disease, in Fibrinogen Disorders, in Prekallikrein Deficiency and in Hereditary Hemorrhagic Telangiectasia by Next-Generation Sequencing
Authors: Gindele Réka , Kerényi Adrienne , Kállai Judit , Pfliegler György , Schlammadinger Ágota , Szegedi István , Major Tamás , Szabó Zsuzsanna , Bagoly Zsuzsa , Kiss Csongor , Kappelmayer János , Bereczky Zsuzsanna
Published: March 2021

Diagnosis of rare bleeding disorders is challenging and there are several differential diagnostics issues. Next-generation sequencing (NGS) is a useful tool to overcome these problems. The aim of this study was to demonstrate the usefulness of molecular genetic investigations by summarizing the diagnostic work on cases with certain bleeding disorders. Here we report only those, in whom NGS was indicated due to uncertainty of diagnosis or if genetic confirmation of initial diagnosis was required. Based on clinical and/or laboratory suspicion of von Willebrand disease (vWD, n = 63), hypo-or dysfibrinogenemia (n = 27), hereditary hemorrhagic telangiectasia (HHT, n = 10) and unexplained activated partial thromboplastin time (APTT) prolongation (n = 1), NGS using Illumina platform was performed. Gene panel covered 14 genes (ACVRL1, ENG, MADH4, GDF2, RASA1, F5, F8, FGA, FGB, FGG, KLKB1, ADAMTS13, GP1BA and VWF) selected on the basis of laboratory results. We identified forty-seven mutations, n = 29 (6 novel) in vWD, n = 4 mutations leading to hemophilia A, n = 10 (2 novel) in fibrinogen disorders, n = 2 novel mutations in HHT phenotype and two mutations (1 novel) leading to prekallikrein deficiency. By reporting well-characterized cases using standardized, advanced laboratory methods we add new pieces of data to the continuously developing “bleeding disorders databases”, which are excellent supports for clinical patient management.
Correlation of Electrically Evoked Compound Action Potential Amplitude Growth Function Slope and Anamnestic Parameters in Cochlear Implant Patients—Identification of Predictors for the Neuronal Health Status
Authors: Gärtner Lutz , Klötzer Katharina , Lenarz Thomas , Scheper Verena
Published: March 2021

Cochlear implants (CI) are the treatment of choice in profoundly deaf patients. Measuring the electrically evoked compound action potential (ECAP) has become an important tool for verifying the function of the spiral ganglion neurons (SGN), which are the target cells of the CI stimulation. ECAP measurement is only possible after electrode insertion. No information about the neuronal health status is available before cochlear implantation. We investigated possible correlations between the ECAP amplitude growth function (AGF) slope and anamnestic parameters to identify possible predictors for SGN health status and therefore for CI outcome. The study included patients being implanted with various electrode array lengths. Correlation analysis was performed for the mean AGF slope of the whole array, for separate electrodes as well as for grouped electrodes of the apical, medial, and basal region, with duration of deafness, age at implantation, residual hearing (grouped for electrode length), and etiology. The mean ECAP AGF slopes decreased from apical to basal. They were not correlated to the length of the electrode array or any etiology. For the mean of the full array or when grouped for the apical, middle, and basal part, the ECAP AGF slope was negatively correlated to the duration of hearing loss and the age at implantation. Since a significant negative correlation of the ECAP AGF slope and age at cochlear implantation and duration of deafness was observed, this study supports the statement that early implantation of a CI is recommended for sensorineural hearing loss. Additional factors such as the cochlear coverage and insertion angle influence the ECAP AGF slope and performance of the patient and should be included in future multifactorial analysis to study predictive parameters for the CI outcome.
Whole-Genome Sequencing in Diagnostics of Selected Slovenian Undiagnosed Patients with Rare Disorders
Authors: Bergant Gaber , Maver Aleš , Peterlin Borut
Published: March 2021

Several patients with rare genetic disorders remain undiagnosed following comprehensive diagnostic testing using whole-exome sequencing (WES). In these patients, pathogenic genetic variants may reside in intronic or regulatory regions or they may emerge through mutational mechanisms not detected by WES. For this reason, we implemented whole-genome sequencing (WGS) in routine clinical diagnostics of patients with undiagnosed genetic disorders and report on the outcome in 30 patients. Criteria for consideration included (1) negative WES, (2) a high likelihood of a genetic cause for the disorders, (3) positive family history, (4) detection of large blocks of homozygosity or (5) detection of a single pathogenic variant in a gene associated with recessive conditions. We successfully discovered a causative genetic variant in 6 cases, a retrotranspositional event in the APC gene, non-coding variants in the intronic region of the OTC gene and the promotor region of the UFM1 gene, repeat expansion in the RFC1 gene and a single exon duplication in the CNGB3 gene. We also discovered one coding variant, an indel, which was missed by variant caller during WES data analysis. Our study demonstrates the impact of WGS in the group of patients with undiagnosed genetic diseases after WES in the clinical setting and the diversity of mutational mechanisms discovered, which would remain undetected using other methods.
A Study of the Feasibility of Using Ammonium Sulfate in Copper—Nickel Ore Processing
Authors: Goryachev Andrey A. , Chernousenko Elena V. , Potapov Sergey S. , Tsvetov Nikita S. , Makarov Dmitriy V.
Published: March 2021

The possibility of applying a combined concentration and metallurgical method for processing low-grade and refractory copper–nickel ores was considered. The resulting rougher and scavenger flotation concentrate contained 2.07% nickel and 0.881% copper at a recovery of 85.44% and 89.91%, respectively. The concentrate was then roasted with ammonium sulfate, followed by aqueous leaching of clinker to dissolve nickel and copper. The roasting temperature, the ratio of concentrate to (NH4)2SO4 in the mixture, and the temperature were varied. Based on the study findings, the following process conditions were found to be optimal: roasting temperature 400 °C, rougher concentrate to ammonium sulfate ratio 1:7, and grinding size −40 μm. A roasting temperature of 400 °C is significantly lower than the temperature applied in conventional pyrometallurgical processes. The possibility of collecting off-gases allows the reagent to be regenerated and makes the process even more cost-effective. End-to-end recovery into pregnant solution was 81.42% for nickel and 82.81% for copper. The resulting solutions can be processed by known hydrometallurgical methods.
Analyzing Mass Spectrometry Imaging Data of 13C-Labeled Phospholipids in Camelina sativa and Thlaspi arvense (Pennycress) Embryos
Authors: Romsdahl Trevor B. , Kambhampati Shrikaar , Koley Somnath , Yadav Umesh P. , Alonso Ana Paula , Allen Doug K. , Chapman Kent D.
Published: March 2021

The combination of 13C-isotopic labeling and mass spectrometry imaging (MSI) offers an approach to analyze metabolic flux in situ. However, combining isotopic labeling and MSI presents technical challenges ranging from sample preparation, label incorporation, data collection, and analysis. Isotopic labeling and MSI individually create large, complex data sets, and this is compounded when both methods are combined. Therefore, analyzing isotopically labeled MSI data requires streamlined procedures to support biologically meaningful interpretations. Using currently available software and techniques, here we describe a workflow to analyze 13C-labeled isotopologues of the membrane lipid and storage oil lipid intermediate―phosphatidylcholine (PC). Our results with embryos of the oilseed crops, Camelina sativa and Thlaspi arvense (pennycress), demonstrated greater 13C-isotopic labeling in the cotyledons of developing embryos compared with the embryonic axis. Greater isotopic enrichment in PC molecular species with more saturated and longer chain fatty acids suggest different flux patterns related to fatty acid desaturation and elongation pathways. The ability to evaluate MSI data of isotopically labeled plant embryos will facilitate the potential to investigate spatial aspects of metabolic flux in situ.
Performance of Quad Mass Gyroscope in the Angular Rate Mode
Authors: Askari Sina , Asadian Mohammad , Shkel Andrei
Published: March 2021

In this paper, the characterization and analysis of a silicon micromachined Quad Mass Gyroscope (QMG) in the rate mode of operation are presented. We report on trade-offs between full-scale, linearity, and noise characteristics of QMGs with different Q-factors. Allan Deviation (ADEV) and Power Spectral Density (PSD) analysis methods were used to evaluate the performance results. The devices in this study were instrumented for the rate mode of operation, with the Open-Loop (OL) and Force-to-Rebalance (FRB) configurations of the sense mode. For each method of instrumentation, we presented constraints on selection of control parameters with respect to the Q-factor of the devices. For the high Q-factor device of over 2 million, and uncompensated frequency asymmetry of 60 mHz, we demonstrated bias instability of 0.095∘/hr and Angle Random Walk (ARW) of 0.0107∘/hr in the OL mode of operation and bias instability of 0.065∘/hr and ARW of 0.0058∘/hr in the FRB mode of operation. We concluded that in a realistic MEMS gyroscope with imperfections (nearly matched, but non-zero frequency asymmetry), a higher Q-factor would increase the frequency stability of the drive axis resulting in an improved noise performance, but has challenges in implementation of digital control loops.