bluuebunny/crossref_metadata_2025 huggingface dataset:
UAV-Based Structural Damage Mapping: A Review
Authors: Kerle Norman , Nex Francesco , Gerke Markus , Duarte Diogo , Vetrivel Anand
Published: December 2019

Structural disaster damage detection and characterization is one of the oldest remote sensing challenges, and the utility of virtually every type of active and passive sensor deployed on various air- and spaceborne platforms has been assessed. The proliferation and growing sophistication of unmanned aerial vehicles (UAVs) in recent years has opened up many new opportunities for damage mapping, due to the high spatial resolution, the resulting stereo images and derivatives, and the flexibility of the platform. This study provides a comprehensive review of how UAV-based damage mapping has evolved from providing simple descriptive overviews of a disaster science, to more sophisticated texture and segmentation-based approaches, and finally to studies using advanced deep learning approaches, as well as multi-temporal and multi-perspective imagery to provide comprehensive damage descriptions. The paper further reviews studies on the utility of the developed mapping strategies and image processing pipelines for first responders, focusing especially on outcomes of two recent European research projects, RECONASS (Reconstruction and Recovery Planning: Rapid and Continuously Updated Construction Damage, and Related Needs Assessment) and INACHUS (Technological and Methodological Solutions for Integrated Wide Area Situation Awareness and Survivor Localization to Support Search and Rescue Teams). Finally, recent and emerging developments are reviewed, such as recent improvements in machine learning, increasing mapping autonomy, damage mapping in interior, GPS-denied environments, the utility of UAVs for infrastructure mapping and maintenance, as well as the emergence of UAVs with robotic abilities.
The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats
Authors: Tsuchida Tomonori , Murata Soichiro , Matsuki Koichiro , Mori Akihiro , Matsuo Megumi , Mikami Satoshi , Okamoto Satoshi , Ueno Yasuharu , Tadokoro Tomomi , Zheng Yun-Wen , Taniguchi Hideki
Published: December 2019

In this study, we reveal that liver organoid transplantation through the portal vein is a safe and effective method for the treatment of chronic liver damage. The liver organoids significantly reconstituted the hepatocytes; hence, the liver was significantly enlarged in this group, compared to the monolayer cell transplantation group in the retrorsine/partial hepatectomy (RS/PH) model. In the liver organoid transplantation group, the bile ducts were located in the donor area and connected to the recipient bile ducts. Thus, the rate of bile reconstruction in the liver was significantly higher compared to that in the monolayer group. By transplanting liver organoids, we saw a level of 70% replacement of the damaged liver. Consequently, in the transplantation group, diminished ductular reaction and a decrease of placental glutathione S-transferase (GST-p) precancerous lesions were observed. After trans-portal injection, the human induced pluripotent stem cell (hiPSC)-derived liver organoids revealed no translocation outside the liver; in contrast, the monolayer cells had spread to the lungs. The hiPSC-derived liver organoids were attached to the liver in the immunodeficient RS/PH rats. This study clearly demonstrates that liver organoid transplantation through the portal vein is a safe and effective method for the treatment of chronic liver damage in rats.
IRE1-XBP1 Pathway of the Unfolded Protein Response Is Required during Early Differentiation of C2C12 Myoblasts
Authors: Tokutake Yukako , Yamada Keita , Hayashi Satoko , Arai Wataru , Watanabe Takafumi , Yonekura Shinichi
Published: December 2019

In skeletal muscle, myoblast differentiation results in the formation of multinucleated myofibers. Although recent studies have shown that unfolded protein responses (UPRs) play an important role in intracellular remodeling and contribute to skeletal muscle differentiation, the involvement of IRE1–XBP1 signaling, a major UPR signaling pathway, remains unclear. This study aimed to investigate the effect of the IRE1–XBP1 pathway on skeletal muscle differentiation. In C2C12 cells, knockdown of IRE1 and XBP1 in cells remarkably suppressed differentiation. In addition, apoptosis and autophagy were dramatically enhanced in the XBP1-knockdown cells, highlighting the participation of IRE1–XBP1 in cell survival maintenance with differentiation stimuli during skeletal muscle differentiation. In myogenic cells, we demonstrated that the expression of CDK5 (cyclin-dependent kinase 5) is regulated by XBP1s, and we propose that XBP1 regulates the expression of MyoD family genes via the induction of CDK5. In conclusion, this study revealed that IRE1–XBP1 signaling plays critical roles in cell viability and the expression of differentiation-related genes in predifferentiated myoblasts and during the early differentiation phase.
Lixivaptan, a New Generation Diuretic, Counteracts Vasopressin-Induced Aquaporin-2 Trafficking and Function in Renal Collecting Duct Cells
Authors: Di Mise Annarita , Venneri Maria , Ranieri Marianna , Centrone Mariangela , Pellegrini Lorenzo , Tamma Grazia , Valenti Giovanna
Published: December 2019

Vasopressin V2 receptor (V2R) antagonists (vaptans) are a new generation of diuretics. Compared with classical diuretics, vaptans promote the excretion of retained body water in disorders in which plasma vasopressin concentrations are inappropriately high for any given plasma osmolality. Under these conditions, an aquaretic drug would be preferable over a conventional diuretic. The clinical efficacy of vaptans is in principle due to impaired vasopressin-regulated water reabsorption via the water channel aquaporin-2 (AQP2). Here, the effect of lixivaptan—a novel selective V2R antagonist—on the vasopressin-cAMP/PKA signaling cascade was investigated in mouse renal collecting duct cells expressing AQP2 (MCD4) and the human V2R. Compared to tolvaptan—a selective V2R antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia—lixivaptan has been predicted to be less likely to cause liver injury. In MCD4 cells, clinically relevant concentrations of lixivaptan (100 nM for 1 h) prevented dDAVP-induced increase of cytosolic cAMP levels and AQP2 phosphorylation at ser-256. Consistent with this finding, real-time fluorescence kinetic measurements demonstrated that lixivaptan prevented dDAVP-induced increase in osmotic water permeability. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of lixivaptan and suggest that lixivaptan has the potential to become a safe and effective therapy for the treatment of disorders characterized by high plasma vasopressin concentrations and water retention.
Integration of ATAC-Seq and RNA-Seq Identifies Key Genes in Light-Induced Primordia Formation of Sparassis latifolia
Authors: Yang Chi , Ma Lu , Xiao Donglai , Ying Zhenghe , Jiang Xiaoling , Lin Yanquan
Published: December 2019

Light is an essential environmental factor for Sparassis latifolia primordia formation, but the molecular mechanism is still unclear. In this study, differential expression profiling of light-induced primordia formation (LIPF) was established by integrating the assay for transposase accessible chromatin by sequencing (ATAC-seq) and RNA-seq technology. The integrated results from the ATAC-seq and RNA-seq showed 13 down-regulated genes and 17 up-regulated genes in both the L vs. D and P vs. D groups, for both methods. According to the gene ontology (GO) annotation of these differentially expressed genes (DEGs), the top three biological process categories were cysteine biosynthetic process via cystathionine, vitamin B6 catabolic, and glycine metabolic; the top three molecular function categories were 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity, glycine binding, and pyridoxal phosphate binding; cellular component categories were significantly enriched in the glycine cleavage complex. The KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis revealed that these genes were associated with vitamin B6 metabolism; selenocompound metabolism; cysteine and methionine metabolism; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism pathways. The expression of most of the DEGs was validated by qRT-PCR. To the best of our knowledge, this study is the first integrative analysis of ATAC-seq and RNA-seq for macro-fungi. These results provided a new perspective on the understanding of key pathways and hub genes in LIPF in S. latifolia. It will be helpful in understanding the primary environmental response, and provides new information to the existing models of primordia formation in edible and medicinal fungi.
Receptor Tyrosine Kinases in Development: Insights from Drosophila
Authors: Mele Sarah , Johnson Travis K.
Published: December 2019

Cell-to-cell communication mediates a plethora of cellular decisions and behaviors that are crucial for the correct and robust development of multicellular organisms. Many of these signals are encoded in secreted hormones or growth factors that bind to and activate cell surface receptors, to transmit the cue intracellularly. One of the major superfamilies of cell surface receptors are the receptor tyrosine kinases (RTKs). For nearly half a century RTKs have been the focus of intensive study due to their ability to alter fundamental aspects of cell biology, such as cell proliferation, growth, and shape, and because of their central importance in diseases such as cancer. Studies in model organisms such a Drosophila melanogaster have proved invaluable for identifying new conserved RTK pathway components, delineating their contributions, and for the discovery of conserved mechanisms that control RTK-signaling events. Here we provide a brief overview of the RTK superfamily and the general mechanisms used in their regulation. We further highlight the functions of several RTKs that govern distinct cell-fate decisions in Drosophila and explore how their activities are developmentally controlled.
The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice
Authors: Róka Beáta , Tod Pál , Kaucsár Tamás , Vizovišek Matej , Vidmar Robert , Turk Boris , Fonović Marko , Szénási Gábor , Hamar Péter
Published: December 2019

(1) Background: Sepsis-induced acute kidney injury (AKI) is the most common form of acute kidney injury (AKI). We studied the temporal profile of the sepsis-induced renal proteome changes. (2) Methods: Male mice were injected intraperitoneally with bacterial lipopolysaccharide (LPS) or saline (control). Renal proteome was studied by LC-MS/MS (ProteomeXchange: PXD014664) at the early phase (EP, 1.5 and 6 h after 40 mg/kg LPS) and the late phase (LP, 24 and 48 h after 10 mg/kg LPS) of LPS-induced AKI. Renal mRNA expression of acute phase proteins (APP) was assessed by qPCR. (3) Results: Renal proteome change was milder in EP vs. LP. APPs dominated the proteome in LP (proteins upregulated at least 4-fold (APPs/all): EP, 1.5 h: 0/10, 6 h: 1/10; LP, 24 h: 22/47, 48 h: 17/44). Lipocalin-2, complement C3, fibrinogen, haptoglobin and hemopexin were the most upregulated APPs. Renal mRNA expression preceded the APP changes with peak effects at 24 h, and indicated renal production of the majority of APPs. (4) Conclusions: Gene expression analysis revealed local production of APPs that commenced a few hours post injection and peaked at 24 h. This is the first demonstration of a massive, complex and coordinated acute phase response of the kidney involving several proteins not identified previously.
Tonic Activation of Extrasynaptic NMDA Receptors Decreases Intrinsic Excitability and Promotes Bistability in a Model of Neuronal Activity
Authors: Gall David , Dupont Geneviève
Published: December 2019

NMDA receptors (NMDA-R) typically contribute to excitatory synaptic transmission in the central nervous system. While calcium influx through NMDA-R plays a critical role in synaptic plasticity, experimental evidence indicates that NMDAR-mediated calcium influx also modifies neuronal excitability through the activation of calcium-activated potassium channels. This mechanism has not yet been studied theoretically. Our theoretical model provides a simple description of neuronal electrical activity that takes into account the tonic activity of extrasynaptic NMDA receptors and a cytosolic calcium compartment. We show that calcium influx mediated by the tonic activity of NMDA-R can be coupled directly to the activation of calcium-activated potassium channels, resulting in an overall inhibitory effect on neuronal excitability. Furthermore, the presence of tonic NMDA-R activity promotes bistability in electrical activity by dramatically increasing the stimulus interval where both a stable steady state and repetitive firing can coexist. These results could provide an intrinsic mechanism for the constitution of memory traces in neuronal circuits. They also shed light on the way by which β -amyloids can alter neuronal activity when interfering with NMDA-R in Alzheimer’s disease and cerebral ischemia.
Diagnostic Biomarkers in Liver Injury by Drugs, Herbs, and Alcohol: Tricky Dilemma after EMA Correctly and Officially Retracted Letter of Support
Authors: Teschke Rolf , Eickhoff Axel , Brown Amy C. , Neuman Manuela G. , Schulze Johannes
Published: December 2019

Liver injuries caused by the use of exogenous compounds such as drugs, herbs, and alcohol are commonly well diagnosed using laboratory tests, toxin analyses, or eventually reactive intermediates generated during metabolic degradation of the respective chemical in the liver and subject to covalent binding by target proteins. Conditions are somewhat different for idiosyncratic drug induced liver injury (DILI), for which metabolic intermediates as diagnostic aids are rarely available. Although the diagnosis of idiosyncratic DILI can well be established using the validated, liver specific, structured, and quantitative RUCAM (Roussel Uclaf Causality Assessment Method), there is an ongoing search for new diagnostic biomarkers that could assist in and also confirm RUCAM-based DILI diagnoses. With respect to idiosyncratic DILI and following previous regulatory letters of recommendations, selected biomarkers reached the clinical focus, including microRNA-122, microRNA-192, cytokeratin analogues, glutamate dehydrogenase, total HMGB-1 (High Mobility Group Box), and hyperacetylated HMGB-1 proteins. However, the new parameters total HMGB-1, and even more so the acetylated HMGB-1, came under critical scientific fire after misconduct at one of the collaborating partner centers, leading the EMA to recommend no longer the exploratory hyperacetylated HMGB1 isoform biomarkers in clinical studies. The overall promising nature of the recommended biomarkers was considered by EMA as highly dependent on the outstanding results of the now incriminated biomarker hyperacetylated HMGB-1. The EMA therefore correctly decided to officially retract its Letter of Support affecting all biomarkers listed above. New biomarkers are now under heavy scrutiny that will require re-evaluations prior to newly adapted recommendations. With Integrin beta 3 (ITGB3), however, a new diagnostic biomarker may emerge, possibly being drug specific but tested in only 16 patients; due to substantial remaining uncertainties, final recommendations would be premature. In conclusion, most of the currently recommended new biomarkers have lost regulatory support due to scientific misconduct, requiring now innovative approaches and re-evaluation before they can be assimilated into clinical practice.
Disrupted Calcium Signaling in Animal Models of Human Spinocerebellar Ataxia (SCA)
Authors: Prestori Francesca , Moccia Francesco , D’Angelo Egidio
Published: December 2019

Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 40 autosomal-dominant genetic and neurodegenerative diseases characterized by loss of balance and motor coordination due to dysfunction of the cerebellum and its efferent connections. Despite a well-described clinical and pathological phenotype, the molecular and cellular events that underlie neurodegeneration are still poorly undaerstood. Emerging research suggests that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells. Ca2+ signaling in Purkinje cells is important for normal cellular function as these neurons express a variety of Ca2+ channels, Ca2+-dependent kinases and phosphatases, and Ca2+-binding proteins to tightly maintain Ca2+ homeostasis and regulate physiological Ca2+-dependent processes. Abnormal Ca2+ levels can activate toxic cascades leading to characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells via inhibitory signals; thus, Purkinje cell dysfunction or degeneration would partially or completely impair the cerebellar output in SCAs. In the absence of the inhibitory signal emanating from Purkinje cells, DCN will become more excitable, thereby affecting the motor areas receiving DCN input and resulting in uncoordinated movements. An outstanding advantage in studying the pathogenesis of SCAs is represented by the availability of a large number of animal models which mimic the phenotype observed in humans. By mainly focusing on mouse models displaying mutations or deletions in genes which encode for Ca2+ signaling-related proteins, in this review we will discuss the several pathogenic mechanisms related to deranged Ca2+ homeostasis that leads to significant Purkinje cell degeneration and dysfunction.
Model Calibration Methodology to Assess the Actual Lighting Conditions of a Road Infrastructure
Authors: Ogando-Martínez Ana , Troncoso-Pastoriza Francisco , Eguía-Oller Pablo , Granada-Álvarez Enrique , Erkoreka Aitor
Published: December 2019

Street lighting plays an important role in the comfort and safety of drivers and pedestrians, so the control and management of the lighting systems operation and consumption is an essential service for a city. In this document, a methodology is presented to calibrate lighting models in order to assess the lighting performance through simulation techniques. The objective of this calibration is to identify the maintenance factor of the street lamps, determine the real average luminance coefficient of the road pavement and adapt the reflection properties of the road material. The method is applied in three stages and is based on the use of Radiance and GenOpt software suits for the modeling, simulation, and calibration of lighting scenes. The proposed methodology achieves errors as low as 13% for the calculation of illuminance and luminance, evincing its potential to assess the actual lighting conditions of a road.
Resistin and Cardiac Arrest—A Prospective Study
Authors: Tat Raluca M. , Golea Adela , Rahaian Rodica , Vesa Ştefan C. , Ionescu Daniela
Published: December 2019

The systemic response to ischemia-reperfusion that occurs after a cardiac arrest (CA) followed by the return of spontaneous circulation leads to endothelial toxicity and cytokine production, both responsible for the subsequent occurrence of severe cardiocirculatory dysfunction and early death. Resistin is emerging as a biomarker of proinflammatory status and myocardial ischemic injury and as a mediator of endothelial dysfunction. The study aimed to analyze the possible associations between several clinical and biological variables and the serum levels of resistin in CA survivors. Forty patients with out-of-hospital resuscitated CA, were enrolled in the study. Demographic, clinical and laboratory data (including serum resistin measurements at admission and at 6, 12, 24, 48 and 72 h) were recorded. For resistin, we calculated the area under the curve (AUC) using the trapezoidal method with measurements from 0 to 12 h, 0 to 24 h, 0 to 48 h and 0 to 72 h. Fifteen (37.5%) patients died in the first 72 h after CA. Cardiovascular comorbidities were present in 65% of patients. The majority of patients had post-CA shock (29 (72.5%)). Resistin serum levels rose in the first 12–24 h and decreased in the next 48–72 h. In univariate analysis, advanced age, longer duration of resuscitation, high sequential organ failure assessment score, high lactate levels, presence of cardiovascular comorbidities and the post-CA shock were associated with higher resistin levels. In multivariate analysis, post-CA shock or cardiovascular comorbidities were independently associated with higher AUCs for resistin for 0–12 h and 0–24 h. The only identified variable to independently predict higher AUCs for resistin for 0–48 h and 0–72 h was the presence of post-CA shock. Our data demonstrate strong independent correlation between high serum resistin levels, cardiac comorbidities and post-CA shock. The impact of the post-CA shock on serum concentration of resistin was greater than that of cardiac comorbidities.
Ulmus parvifolia Accelerates Skin Wound Healing by Regulating the Expression of MMPs and TGF-β
Authors: Kang Min Cheol , Yumnam Silvia , Park Woo Sung , So Hae Min , Kim Ki Hyun , Shin Meong Cheol , Ahn Mi-Jeong , Kim Sun Yeou
Published: December 2019

Ulmus parvifolia is one of the medicinal plants used traditionally for treatment of wounds. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of U. parvifolia in skin and skin wound healing effects using a keratinocyte model. Animal experiments showed that the wound lesions in the mice decreased with 200 mesh U. parvifolia root bark powder and were significantly reduced with treatment by UP, compared with those treated with Ulmus macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvenation.
The Abbreviated Maslach Burnout Inventory Can Overestimate Burnout: A Study of Anesthesiology Residents
Authors: Lim Wan Yen , Ong John , Ong Sharon , Hao Ying , Abdullah Hairil Rizal , Koh Darren LK , Mok Un Sam May
Published: December 2019

The Maslach Burnout Inventory for healthcare professionals (MBI-HSS) and its abbreviated version (aMBI), are the most common tools to detect burnout in clinicians. A wide range in burnout prevalence is reported in anesthesiology, so this study aimed to ascertain which of these two tools most accurately detected burnout in our anesthesiology residents. The MBI-HSS and aMBI were distributed amongst 86 residents across three hospitals, with a total of 58 residents completing the survey (67.4% response rate; 17 male and 41 female). Maslach-recommended cut-offs for the MBI-HSS and the aMBI with standard cut-offs were used to estimate burnout prevalence, and actual prevalence was established clinically by a thorough review of multiple data sources. Burnout proportions reported by the MBI-HSS and aMBI were found to be significantly different; 22.4% vs. 62.1% respectively (p < 0.0001). Compared to the actual prevalence of burnout in our cohort, the MBI-HSS detected burnout most accurately; area under receiver operating characteristic of 0.99 (95% confidence interval (CI): 0.92–1.0). Although there was a good correlation between the MBI-HSS and aMBI subscale scores, the positive predictive value of the aMBI was poor; 33.3% (95% CI:27.5–39.8%), therefore caution and clinical correlation are advised when using the aMBI tool because of the high rates of false-positives.
Degenerative Cervical Myelopathy in Higher-Aged Patients: How Do They Benefit from Surgery?
Authors: Gembruch Oliver , Jabbarli Ramazan , Rashidi Ali , Chihi Mehdi , El Hindy Nicolai , Wetter Axel , Hütter Bernd-Otto , Sure Ulrich , Dammann Philipp , Özkan Neriman
Published: December 2019

Background: Degenerative cervical myelopathy (DCM) is the most common reason for spinal cord disease in elderly patients. This study analyzes the preoperative status and postoperative outcome of higher-aged patients in comparison to young and elderly patients in order to determine the benefit to those patients from DCM surgery. Methods: A retrospective analysis of the clinical data, radiological findings, and operative reports of 411 patients treated surgically between 2007 and 2016 suffering from DCM was performed. The preoperative and postoperative neurological functions were evaluated using the modified Japanese Orthopedic Association Score (mJOA Score), the postoperative mJOA Score improvement, the neurological recovery rate (NRR) of the mJOA Score, and the minimum clinically important difference (MCID). The Charlson Comorbidity Index (CCI) was used to evaluate the impact of comorbidities on the preoperative and postoperative mJOA Score. The comparisons were performed between the following age groups: G1: ≤50 years, G2: 51–70 years, and G3: >70 years. Results: The preoperative and postoperative mJOA Score was significantly lower in G3 than in G2 and G1 (p < 0.0001). However, the mean mJOA Score’s improvement did not differ significantly (p = 0.81) between those groups six months after surgery (G1: 1.99 ± 1.04, G2: 2.01 ± 1.04, G: 2.00 ± 0.91). Furthermore, the MCID showed a significant improvement in every age-group. The CCI was evaluated for each age-group, showing a statistically significant group effect (p < 0.0001). Analysis of variance revealed a significant group effect on the delay (weeks) between symptom onset and surgery (p = 0.003). The duration of the stay at the hospital did differ significantly between the age groups (p < 0.0001). Conclusion: Preoperative and postoperative mJOA Scores, but not the extent of postoperative improvement, are affected by the patients’ age. Therefore, patients should be considered for DCM surgery regardless of their age.
Kinetics of Tear Fluid Proteins after Endothelial Keratoplasty and Predictive Factors for Recovery from Corneal Haze
Authors: Yawata Nobuyo , Awate Sunita , Liu Yu-Chi , Yuan Shi , Woon Kaing , Siak Jay , Kawano Yoh-Ichi , Sonoda Koh-Hei , Mehta Jodhbir S. , Yawata Makoto
Published: December 2019

Endothelial keratoplasty (EK) is less invasive with faster recovery as compared to conventional penetrating keratoplasty, however, it relies on the clarity of the host corneal stroma. Corneal transplantation involves the induction of immune tolerance for allogeneic tissues as well as the corneal wound healing process, in which coordinated interactions between cytokines and growth factors are critical. In this study, we profiled the expression of 51 soluble factors in the tear fluid over the course of EK and have provided evidence of dynamic changes in cytokine expression in the ipsilateral and contralateral eyes. Cluster analyses classified the cytokine expression kinetics into five groups. Group 1 proteins included TGF-b1, IL-1b, and innate proinflammatory cytokines, which bilaterally increased after surgery, despite the use of topical corticosteroid in the transplanted eyes. Local corticosteroids suppressed cytokines involved in adaptive immunity in the transplanted eyes but not in the contralateral eyes. We found tear protein expression at baseline and one week post-surgery to be a potential predictive biomarker of delayed recovery after EK in terms of the corneal haze and visual acuity. Furthermore, Group 1 tear proteins were most associated with persistent corneal haze pre-surgery as well as visual acuity at one month-post transplant.
Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy
Authors: Dubois Clémence , Martin Fanny , Hassel Chervin , Magnier Florian , Daumar Pierre , Aubel Corinne , Guerder Sylvie , Mounetou Emmanuelle , Penault-Lorca Frédérique , Bamdad Mahchid
Published: December 2019

The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 µM), combined with fractioned irradiation (i.e., 5 × 2 Gy) on two aggressive TNBC cell lines MDA-MB-231 (BRCAness) and SUM1315 (BRCA1-mutated). In 2D cell culture and for both models, the clonogenicity drop was 95-fold higher after 5 µM Olaparib and 10 Gy irradiation than Olaparib treatment alone and was only 2-fold higher after 50 µM and 10 Gy. Similar responses were obtained on TNBC tumor-like spheroid models after 10 days of co-treatment. Indeed, the ratio of metabolic activity decrease was of 1.2 for SUM1315 and 3.3 for MDA-MB-231 after 5 µM and 10 Gy and of only 0.9 (both models) after 50 µM and 10 Gy. MDA-MB-231, exhibiting a strong proliferation profile and an overexpression of AURKA, was more sensitive to the co-treatment than SUM1315 cell line, with a stem-cell like phenotype. These results suggest that, with the studied models, the potentiation of Olaparib treatment could be reached with low-dose and long-term exposure combined with fractioned irradiation.
IgG Anti-High Density Lipoprotein Antibodies Are Elevated in Abdominal Aortic Aneurysm and Associated with Lipid Profile and Clinical Features
Authors: Rodríguez-Carrio Javier , Lindholt Jes S. , Canyelles Marina , Martínez-López Diego , Tondo Mireia , Blanco-Colio Luis M. , Michel Jean-Baptiste , Escolà-Gil Joan Carles , Suárez Ana , Martín-Ventura José Luis
Published: December 2019

High-density lipoproteins cholesterol (HDLc) levels are decreased in abdominal aortic aneurysm (AAA), which is hallmarked by autoimmunity and lipid aortic deposits. To investigate whether IgG anti-HDL antibodies were present in AAA and their potential association with clinical features, IgG anti-HDL and total IgG along with HDLc plasma levels were measured in 488 AAA patients and 184 controls from the Viborg Vascular (VIVA) study, and in tissue-conditioned media from AAA intraluminal thrombus and media layer samples compared to control aortas. Higher IgG anti-HDL levels were found in AAA compared to controls, even after correcting for total IgG, and after adjusting for potential confounders. IgG anti-HDL levels were correlated with aortic diameter in univariate and adjusted multivariate analyses. IgG anti-HDL antibodies were negatively associated with HDLc levels before and after correcting for potential confounders. Increased anti-HDL antibodies were identified in tissue-conditioned media from AAA samples compared to healthy aortas, with higher levels being observed in the media layer. In conclusion, increased IgG anti-HDL levels (both in plasma and in tissue) are linked to AAA, associated with aortic diameter and HDLc levels. These data suggest a potential immune response against HDL in AAA and support an emerging role of anti-HDL antibodies in AAA.
Design, Characterization, and Evaluation of scFvCD133/rGelonin: A CD133-Targeting Recombinant Immunotoxin for Use in Combination with Photochemical Internalization
Authors: Olsen Cathrine Elisabeth , Cheung Lawrence H. , Weyergang Anette , Berg Kristian , Vallera Daniel A. , Rosenblum Michael G. , Selbo Pål Kristian
Published: December 2019

The objective of this study was to develop and explore a novel CD133-targeting immunotoxin (IT) for use in combination with the endosomal escape method photochemical internalization (PCI). scFvCD133/rGelonin was recombinantly constructed by fusing a gene (scFvCD133) encoding the scFv that targets both non-glycosylated and glycosylated forms of both human and murine CD133/prominin-1 to a gene encoding the ribosome-inactivating protein (RIP) gelonin (rGelonin). RIP-activity was assessed in a cell-free translation assay. Selective binding and intracellular accumulation of scFvCD133/rGelonin was evaluated by flow cytometry and fluorescence microscopy. PCI of scFvCD133/rGelonin was explored in CD133high and CD133low cell lines and a CD133neg cell line, where cytotoxicity was evaluated by the MTT assay. scFvCD133/rGelonin exhibited superior binding to and a higher accumulation in CD133high cells compared to CD133low cells. No cytotoxic responses were detected in either CD133high or CD133low cells after 72 h incubation with <100 nM scFvCD133/rGelonin. Despite a severe loss in RIP-activity of scFvCD133/rGelonin compared to free rGelonin, PCI of scFvCD133/rGelonin induced log-fold reduction of viability compared to PCI of rGelonin. Strikingly, PCI of scFvCD133/rGelonin exceeded the cytotoxicity of PCI of rGelonin also in CD133low cells. In conclusion, PCI promotes strong cytotoxic activity of the per se non-toxic scFvCD133/rGelonin in both CD133high and CD133low cancer cells.
Efficacy of Low-Dose Prophylactic Quetiapine on Delirium Prevention in Critically Ill Patients: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study
Authors: Kim Youlim , Kim Hyung-Sook , Park Jong Sun , Cho Young-Jae , Yoon Ho Il , Lee Sang-Min , Lee Jae Ho , Lee Choon-Taek , Lee Yeon Joo
Published: December 2019

Purpose: To evaluate the efficacy of short-term low-dose quetiapine for delirium prevention in critically ill patients. Methods: In this prospective, a single-center, randomized, double-blind, placebo-controlled trial, adult patients who were admitted from July 2015 to July 2017 to a medical intensive care unit (ICU) of a tertiary teaching hospital affiliated to Seoul National University were included. Quetiapine (12.5 mg or 25 mg oral at night; N = 16) or placebo (N = 21) was administered according to randomization until ICU discharge or the 10th ICU day. The primary endpoint was the incidence of delirium within the first 10 ICU days. Secondary endpoints included the rate of positive Confusion Assessment Method for the ICU (CAM-ICU) (the number of positive CAM-ICU counts/the number of total CAM-ICU counts), delirium duration, successful extubation, and overall mortality. Result: The incidence of delirium during the 10 days after ICU admission was 46.7% (7/15) in the quetiapine group and 55.0% (11/20) in the placebo group (p = 0.442). In the quetiapine group, the rate of positive CAM-ICU was significantly lower than in the placebo group (14.4% vs. 37.4%, p = 0.048), delirium duration during the study period was significantly shorter (0.28 day vs. 1.83 days, p = 0.018), and more patients in the quetiapine than in the placebo group were weaned from mechanical ventilation successfully (84.6% vs. 47.1%, p = 0.040). Conclusions: Our study suggests that prophylactic use of low-dose quetiapine could be helpful for preventing delirium in critically ill patients. A further large-scale prospective study is needed.
Epidemiology and Trends of Sepsis in Young Adults Aged 20–44 Years: A Nationwide Population-Based Study
Authors: Bouza Carmen , López-Cuadrado Teresa
Published: December 2019

Background: While sepsis may have especially marked impacts in young adults, there is limited population-based information on its epidemiology and trends. Methods: Population-based longitudinal study on sepsis in adults aged 20–44 years using the 2006–2015 Spanish national hospital discharge database. Cases are identified by an ICD-9-CM coding strategy. Primary endpoints are incidence and in-hospital mortality. Trends are assessed for annual percentage change (AAPC) in rates using Joinpoint regression models. Results: 28,351 cases are identified, representing 3.06‰ of all-cause hospitalisations and a crude incidence of 16.4 cases/100,000 population aged 20–44. The mean age is 36 years, 58% of cases are men, and around 60% have associated comorbidities. Seen in one third of cases, the source of infection is respiratory. Single organ dysfunction is recorded in 45% of cases. In-hospital mortality is 24% and associated with age, comorbidity and extent of organ dysfunction. Incidence rates increase over time in women (AAPC: 3.8% (95% CI: 2.1, 5.5)), whereas case-fatality decline with an overall AAPC of −5.9% (95% CI −6.6, −5.2). Our results indicate that sepsis is common in young adults and associated with high in-hospital mortality, though it shows a decreasing trend. The substantial increase in incidence rates in women needs further research.
Benthic Species Distribution Linked to Morphological Features of a Barred Coast
Authors: Holzhauer Harriëtte , Borsje Bas W. , van Dalfsen Jan A. , Wijnberg Kathelijne M. , Hulscher Suzanne J.M.H. , Herman Peter M.J.
Published: December 2019

The composition of benthic species communities in the nearshore zone is closely related to the hydrodynamic and morphodynamic conditions. Sustainable management of the coastal ecosystem requires knowledge about the natural dynamics as well as human-induced changes on the ecosystem. To improve our knowledge of the benthic species distribution along a dissipative sandy shore with multiple breaker bars, an extensive dataset was collected in the nearshore zone of the barrier islands Ameland and Schiermonnikoog in the Dutch North Sea. From 2010 to 2014, every year, approximately 180 grab samples along 18 cross-shore transects were collected and analyzed for sediment characteristics and macrobenthic species composition. Mixed-effect-models and partial redundancy analysis were used to analyze the importance of morphological features (i.e., slopes, bar crests, and troughs) as an explanatory variable for the benthic species distribution. The results indicate that the morphological features in themselves explain three times more variation than the environmental parameters used. This demonstrates the importance of morphological features as a factor in explaining the distribution of benthic species communities in the nearshore. Detailed information on morphological features is easy to obtain from bathymetry maps or visual inspection. Incorporating morphological features in species distribution models will therefore help to improve sustainable management of our valuable sandy coastal systems.
The Preparation, Thermal Properties, and Fire Property of a Phosphorus-Containing Flame-Retardant Styrene Copolymer
Authors: Sun Yu , Wang Yazhen , Liu Li , Xiao Tianyuan
Published: December 2019

A 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO) acrylate, (6-oxidodibenzo [c,e][1,2] oxaphosphinin-6-yl) methyl acrylate (DOPOAA), has been prepared. Copolymers of styrene (St) and DOPOAA were prepared by emulsion polymerization. The chemical structures of copolymers containing levels of DOPOAA were verified using Fourier transform infrared (FT-IR) spectroscopy and 1H nuclear magnetic resonance (1H-NMR) spectroscopy. The thermal properties and flame-retardant behaviors of DOPO-containing monomers and copolymers were observed using thermogravimetric analysis and micro calorimetry tests. From thermogravimetric analysis (TGA), it was found out that the T5% for decomposition of the copolymer was lower than that of polystyrene (PS), but the residue at 700 °C was higher than that of PS. The results from micro calorimetry (MCC) tests indicated that the rate for the heat release of the copolymer combustion was lower than that for PS. The limiting oxygen index (LOI) for combustion of the copolymer rose with increasing levels of DOPOAA. These data indicate that copolymerization of the phosphorus-containing flame-retardant monomer, DOPOAA, into a PS segment can effectively improve the thermal stability and flame retardancy of the copolymer.
Optimization of the Manufacturing Strategy, Machining Conditions, and Finishing of a Radial Impeller
Authors: Stratogiannis Fotios I. , Galanis Nikolaos I. , Karkalos Nikolaos E. , Markopoulos Angelos P.
Published: December 2019

Impellers are the most crucial components of pumps, as they directly determine the velocity profile of the fluid flowing through the pump and its efficiency. Given that the impellers have a complex geometry, they pose an important challenge to the manufacturer in order to construct them with the best possible dimensional accuracy and surface quality, and also achieve short machining times. In the present paper, the machining operations for the manufacture of a radial impeller were designed and implemented for the case of a single-entry semi-closed radial flow impeller. At first, the best milling strategies, optimum cutting conditions, and appropriate cutting tools were selected for each of the three machining phases, namely, roughing, semi-finishing, and finishing. Then, an experimental investigation was conducted, especially for the optimum process conditions during finishing of impeller blades, using Taguchi L16 orthogonal array. After the analysis of surface roughness was conducted for the 16 experiments, it was found that the most important parameters were spindle speed and feed. Furthermore, the optimum settings were determined as the maximum spindle speed and the lowest feed per tooth value and a regression model correlating process parameters with surface roughness was established with a high degree of accuracy.
Quorum Quenching Properties and Probiotic Potentials of Intestinal Associated Bacteria in Asian Sea Bass Lates calcarifer
Authors: Ghanei-Motlagh Reza , Mohammadian Takavar , Gharibi Darioush , Menanteau-Ledouble Simon , Mahmoudi Esmaeil , Khosravi Mohammad , Zarea Mojtaba , El-Matbouli Mansour
Published: December 2019

Quorum quenching (QQ), the enzymatic degradation of N-acyl homoserine lactones (AHLs), has been suggested as a promising strategy to control bacterial diseases. In this study, 10 AHL-degrading bacteria isolated from the intestine of barramundi were identified by 16S rDNA sequencing. They were able to degrade both short and long-chain AHLs associated with several pathogenic Vibrio species (spp.) in fish, including N-[(RS)-3-Hydroxybutyryl]-l-homoserine lactone (3-oh-C4-HSL), N-Hexanoyl-l-homoserine lactone (C6-HSL), N-(β-Ketocaproyl)-l-homoserine lactone (3-oxo-C6-HSL), N-(3-Oxodecanoyl)-l-homoserine lactone (3-oxo-C10-HSL), N-(3-Oxotetradecanoyl)-l-homoserine lactone (3-oxo-C14-HSL). Five QQ isolates (QQIs) belonging to the Bacillus and Shewanella genera, showed high capacity to degrade both synthetic AHLs as well as natural AHLs produced by Vibrio harveyi and Vibrio alginolyticus using the well-diffusion method and thin-layer chromatography (TLC). The genes responsible for QQ activity, including aiiA, ytnP, and aaC were also detected. Analysis of the amino acid sequences from the predicted lactonases revealed the presence of the conserved motif HxHxDH. The selected isolates were further characterized in terms of their probiotic potentials in vitro. Based on our scoring system, Bacillus thuringiensis QQ1 and Bacillus cereus QQ2 exhibited suitable probiotic characteristics, including the production of spore and exoenzymes, resistance to bile salts and pH, high potential to adhere on mucus, appropriate growth abilities, safety to barramundi, and sensitivity to antibiotics. These isolates, therefore, constitute new QQ probiotics that could be used to control vibriosis in Lates calcalifer.
Extraction of Hydroxyapatite Nanostructures from Marine Wastes for the Fabrication of Biopolymer-Based Porous Scaffolds
Authors: Gheysari Hengameh , Mohandes Fatemeh , Mazaheri Mozhdeh , Dolatyar Banafsheh , Askari Masoud , Simchi Abdolreza
Published: December 2019

Three-dimensional porous nanocomposites consisting of gelatin-carboxymethylcellulose (CMC) cross-linked by carboxylic acids biopolymers and monophasic hydroxyapatite (HA) nanostructures were fabricated by lyophilization, for soft-bone-tissue engineering. The bioactive ceramic nanostructures were prepared by a novel wet-chemical and low-temperature procedure from marine wastes containing calcium carbonates. The effect of surface-active molecules, including sodium dodecyl sulfate (SDS) and hexadecyltrimethylammonium bromide (CTAB), on the morphology of HA nanostructures is shown. It is demonstrated that highly bioactive and monophasic HA nanorods with an aspect ratio > 10 can be synthesized in the presence of SDS. In vitro studies on the bioactive biopolymer composite scaffolds with varying pore sizes, from 100 to 300 μm, determine the capacity of the developed procedure to convert marine wastes to profitable composites for tissue engineering.
A Descriptive Review on the Prevalence of Gastrointestinal Disturbances and Their Multiple Associations in Autism Spectrum Disorder
Authors: Lefter Radu , Ciobica Alin , Timofte Daniel , Stanciu Carol , Trifan Anca
Published: December 2019

Background and Objectives: Gastrointestinal disturbances have been frequently, but not unanimously, reported in autism spectrum disorder (ASD) individuals. Thus, digestive symptoms, such as constipation, diarrhea, abdominal bloating, and pain have been reported to correlate to the various maladaptive behaviors in ASD children, such as irritability, social withdrawal, stereotypy, hyperactivity, and even language regression. In this context, the present study provides an overview on the prevalence of the gastrointestinal (GI) disorders in ASD and the correlation between these and ASD symptoms and comorbidities and subsequently discusses the metabolic and microbiome factors underlying the effects of GI disorders in ASD. Materials and Methods: For our analysis of GI symptoms in children with ASD, we have searched peer-reviewed journals from 2005 to 2017 in PubMed databases that addressed the specificity of GI symptoms in ASD and included correlations of GI and ASD symptoms. The criteria for inclusion were clear quantitative mentioning of GI modifications, GI symptoms correlation with specific ASD symptoms or comorbidities, an appropriate methodology for defining ASD, and larger size samples. For this topic, only studies on human patients and original research were considered. A subsequent search in PubMed databases in journals from 2000 to 2017 we analyzed 13 articles on the mechanisms underlying the impact of GI dysfunctions in ASD, including gut microbial dysbiosis, immune reactivity, genetics, and altered neurotransmitters on the gut–brain axis. Results: In the 18 original research studies that we selected out of an initial 327 studies, despite the different methodology, a predominant 83% highlighted the increased prevalence of GI symptoms in ASD patients. Constipation was most frequently cited, appearing in 12 of the studies (80%), followed by diarrhea reports in eight studies (53%). The association between cognitive and behavioral deficits and GI disorders was suggested in certain groups of ASD individuals. Conclusion: The evidence presented so far by numerous studies seems to indicate that GI dysfunctions are of particular relevance in ASD, underlined by various abnormalities along the nervous connections between the central nervous system and the gut, such as impaired parasympathetic activity and increased endocrine stress response. Sufficiently large size samples and standardized methodology are required for future studies to clarify the complex interactions between GI disturbances and ASD symptoms.