bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Stress Response during Vaginal Delivery and Elective Cesarean Section through Assessment of Levels of Cortisol, Interleukin 6 (IL-6), Growth Hormone (GH) and Insulin-Like Growth Factor 1 (IGF-1)
Authors: Kiriakopoulos Nikolaos , Grigoriadis Sokratis , Maziotis Evangelos , Philippou Anastasios , Rapani Anna , Giannelou Polina , Tsioulou Petroula , Sfakianoudis Konstantinos , Kontogeorgi Adamantia , Bakas Panagiotis , Mastorakos George , Koutsilieris Michael , Simopoulou Mara
Published: July 2019

Background: How do stress related phenomena during labor differ between vaginal delivery (VD) and elective cesarean section (CS), remains of heightened interest. The purpose of this study is to investigate discrepancies regarding the stress response during VD and CS. Methods: Cortisol, interleukin 6 (IL-6), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels from parturients’ peripheral blood were evaluated on three time-points, namely during the first stage of labor (TP1), two hours post labor (TP2) and 48 h post labor (TP3). Levels were also evaluated from the umbilical cord blood. A total of 50 women were enrolled in this prospective cohort study, with 24 and 26 subjected to CS and VD, respectively. Results: No statistically significant differences were observed between the two groups at TP1. Only GH levels presented the same pattern during the three time-points among both groups. In the umbilical cord blood, the CS group presented statistically significant higher IGF-1 and GH levels. In the umbilical cord blood, IGF-1 and GH levels were positively correlated, while GH and cortisol levels were negatively correlated. Conclusion: CS is a less stressful procedure than VD and is further associated with less intense inflammation, albeit with a longer inflammatory response period. Labor physiology during CS differs considerably regarding respective observations during VD. This merits extensive investigation in order to decipher these data for optimal clinical practice and guidelines.
The Off-Label Use of Inhaled Nitric Oxide as a Rescue Therapy in Neonates with Refractory Hypoxemic Respiratory Failure: Therapeutic Response and Risk Factors for Mortality
Authors: Hsiao Hsiu-Feng , Yang Mei-Chin , Lai Mei-Yin , Chu Shih-Ming , Huang Hsuan-Rong , Chiang Ming-Chou , Fu Ren-Huei , Hsu Jen-Fu , Tsai Ming-Horng
Published: July 2019

Objectives: The indication of inhaled nitric oxide (iNO) used in preterm infants has not been well defined. Neonates with refractory hypoxemia may benefit from the pulmonary vasodilatory effects of iNO. The aim of this study was to investigate the off-label use of iNO as a rescue therapy. Methods: Between January 2010 and December 2017, all neonates who received iNO as a rescue therapy from a tertiary-level medical center were enrolled, and those who were not diagnosed with persistent pulmonary hypertension of newborn (PPHN) were defined as having received off-label use of iNO. The controls were 636 neonates with severe respiratory failure requiring high-frequency oscillatory ventilation but no iNO. Results: A total of 206 neonates who received iNO as a rescue therapy were identified, and 84 (40.8%) had off-label use. The median (interquartile) gestational age was 30.5 (26.3–37.0) weeks. Neonates receiving iNO had significantly more severe respiratory failure and a higher oxygenation index than the controls (p < 0.001). Respiratory distress syndrome and secondary pulmonary hypertension after severe bronchopulmonary dysplasia (BPD) were the most common causes of the off-label iNO prescription. Of the 84 neonates with off-label use of iNO, 53 (63.1%) had initial improvement in oxygenation, but 44 (52.4%) eventually died. The overall mortality rate was 41.7% (86/206). After multivariate logistic regression, extremely preterm (odds ratio [OR] 5.51; p < 0.001), presence of pulmonary hemorrhage (OR 2.51; p = 0.036) and severe hypotension (OR 2.78; p = 0.008) were the independent risk factors for final mortality. Conclusions: iNO is applicable to be an off-label rescue therapy for premature neonates with refractory hypoxemia due to severe pulmonary hypertension and bronchopulmonary dysplasia.
Long-Term Risk Factor Control After Myocardial Infarction—A Need for Better Prevention Programmes
Authors: Osteresch Rico , Fach Andreas , Schmucker Johannes , Eitel Ingo , Langer Harald , Hambrecht Rainer , Wienbergen Harm
Published: July 2019

Introduction: Long-term prognosis of myocardial infarction (MI) is still serious, especially in patients with MI and cardiogenic shock. To improve long-term prognosis and prevent recurrent events, sustainable cardiovascular risk factor control (RFC) after MI is crucial. Methods: The article gives an overview on health care data regarding RFC after MI and presents recent trials on modern preventive strategies that support patients to achieve risk factor targets during long-term course. Results: International registry studies, such as EUROASPIRE, observed alarming deficiencies in RFC after MI. As data of the German Bremen ST-segment elevation myocardial infarction (STEMI)-Registry show, most deficiencies are found in socially disadvantaged city districts and in young patients. Several studies on prevention programmes to improve RFC after MI reported inconsistent data; however, in the recently published IPP trial a 12-months intensive prevention programme that included both repetitive personal contacts with non-physician prevention assistants and telemetric risk factor control, was associated with significant improvements of numerous risk factors (smoking, LDL and total cholesterol, systolic blood pressure and physical inactivity). Conclusions: There is a strong need of action to improve long-term risk RFC after MI, especially in socially disadvantaged patients. Modern prevention programmes, using personal and telemetric contacts, have large potential to support patients in achieving long-term risk factor targets after coronary events.
Postoperative Imaging and Tumor Marker Surveillance in Resected Pancreatic Cancer
Authors: Wu Hsu , Guo Jhe-Cyuan , Yang Shih-Hung , Tien Yu-Wen , Kuo Sung-Hsin
Published: July 2019

Background: Pancreatic cancer is a catastrophic disease with high recurrence and death rates, even in early stages. Early detection and early treatment improve survival in many cancer types but have not yet been clearly documented to do so in pancreatic cancer. In this study, we assessed the benefit on survival resulting from different patterns of surveillance in daily practice after curative surgery of early pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who had received curative surgery between January 2000 and December 2013 at our institute were retrospectively reviewed. Patients were classified into one of four groups, based on surveillance strategy: the symptom group, the imaging group, the marker group (carbohydrate antigen 19-9 and/or carcinoembryonic antigen), and the intense group (both imaging and tumor marker assessment). Overall survival (OS), relapse-free survival (RFS), and post-recurrence overall survival (PROS) were evaluated. Results: One hundred and eighty-one patients with documented recurrence or metastasis were included in our analysis. The median OS for patients in the symptom group, imaging group, marker group, and intense group were 21.4 months, 13.9 months, 20.5 months, and 16.5 months, respectively (p = 0.670). Surveillance with imaging, tumor markers, or both was not an independent risk factor for OS in univariate and multivariate analyses. There was no significant difference in median RFS (symptom group, 11.7 months; imaging group, 6.3 months; marker group, 9.3 months; intense group, 6.9 months; p = 0.259) or median PROS (symptom group, 6.9 months; imaging group, 7.5 months; marker group, 5.0 months; intense group, 7.8 months; p = 0.953) between the four groups. Multivariate analyses identified poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (≥1), primary tumor site (tail), and tumor grade (poor differentiation) were poor prognostic factors for OS. Conclusions: Surveillance with regular imaging, tumor marker, or both was not an independent risk factor for OS of pancreatic cancer patients who undergo curative tumor resection.
Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease
Authors: Piscaer Ianthe , van den Ouweland Jody M. W. , Vermeersch Kristina , Reynaert Niki L. , Franssen Frits M. E. , Keene Spencer , Wouters Emiel F. M. , Janssens Wim , Vermeer Cees , Janssen Rob
Published: July 2019

Elastin degradation is accelerated in chronic obstructive pulmonary disease (COPD) and is partially regulated by Matrix Gla Protein (MGP), via a vitamin K-dependent pathway. The aim was to assess vitamin K status in COPD as well as associations between vitamin K status, elastin degradation, lung function parameters and mortality. A total of 192 COPD patients and 186 age-matched controls were included. In addition to this, 290 COPD patients from a second independent longitudinal cohort were also included. Vitamin K status was assessed by measuring plasma inactive MGP levels and rates of elastin degradation by measuring plasma desmosine levels. Reduced vitamin K status was found in COPD patients compared to smoking controls (p < 0.0005) and controls who had never smoked (p = 0.001). Vitamin K status was inversely associated with desmosine (cohort 1: p = 0.001; cohort 2: p = 0.004). Only few significant associations between vitamin K status and lung function parameters were found. Mortality was higher in COPD patients within the quartile with the lowest vitamin K status compared to those within the other quartiles (hazard ratio 1.85, 95% confidence interval (CI), 1.21–2.83, p = 0.005). In conclusion, we demonstrated reduced vitamin K status in COPD and an inverse association between vitamin K status and elastin degradation rate. Our results therefore suggest a potential role of vitamin K in COPD pathogenesis.
The Effect of Positive End-Expiratory Pressure on Lung Micromechanics Assessed by Synchrotron Radiation Computed Tomography in an Animal Model of ARDS
Authors: Scaramuzzo Gaetano , Broche Ludovic , Pellegrini Mariangela , Porra Liisa , Derosa Savino , Tannoia Angela Principia , Marzullo Andrea , Borges João Batista , Bayat Sam , Bravin Alberto , Larsson Anders , Perchiazzi Gaetano
Published: July 2019

Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH2O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 ± 2.0 at PEEP 12 to 7.6 ± 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 ± 52 at PEEP 12 to 146.4 ± 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.
Negative Self-Perception and Self-Attitude of Sexuality Is a Risk Factor for Patient Dissatisfaction Following Penile Surgery with Small Intestinal Submucosa Grafting for the Treatment of Severe Peyronie’s Disease
Authors: Soave Armin , Laurich Sebastian , Dahlem Roland , Vetterlein Malte W. , Engel Oliver , Nieder Timo O. , Briken Peer , Rink Michael , Fisch Margit , Reiss Philip
Published: July 2019

Objective: To assess patient satisfaction with surgical outcome, body related self-perceptions, self-attitudes of sexuality, and health related quality of life after penile surgery with small intestinal submucosa (SIS) grafting for the treatment of severe Peyronie’s disease (PD). Material and methods: This retrospective study included 82 patients, who were treated with SIS grafting for severe PD between 2009 and 2013 at the University Medical Center Hamburg-Eppendorf. Patients were asked to complete standardized questionnaires including the International Index of Erectile Function Erectile Function domain (IIEF-EF), Short-Form (SF)-8 Health Survey, and Frankfurt Body Concept Scale-Sexuality (FKKS-SEX). Results: Follow-up was available in 58 (69.9%) patients. SIS grafting resulted in subjective straightening of the penis in 53 (91.3%) patients. After a mean follow-up of 28.9 ± 16.5 months, 24 (41.4%) patients were satisfied or very satisfied with surgical outcome. Postoperatively, the mean FKKS-SEX was 23.5 ± 5.9. In total, 36 (62.1%), 18 (31%), and four (6.9%) patients had FKKS-SEX scores corresponding to positive, neutral, and negative self-perception and self-attitude of sexuality, respectively. The mean postoperative SF-8 was 15.2 ± 6.4. Compared to the mean for German controls, patients achieved lower mean scores in the domains social functioning (50.4 ± 7.1), mental health (49.5 ± 9.2), and emotional roles (48.5 ± 6.8). Subjective shortening of the penis (Odds ratio (OR): 2.0), negative body related self-perceptions, and self-attitudes of sexuality (OR: 3.6) as well as IIEF-EF score (OR: 0.9) were risk factors for patient dissatisfaction (p-values ≤ 0.02). Conclusion: A relevant number of patients is not satisfied with surgical outcome after SIS grafting for the treatment of severe PD. Subjective shortening of the penis, negative body related self-perceptions, and self-attitudes of sexuality as well as IIEF-EF score were risk factors for patient dissatisfaction.
Is Peri-Implant Probing Causing Over-Diagnosis and Over-Treatment of Dental Implants?
Authors: Coli Pierluigi , Sennerby Lars
Published: July 2019

Pocket probing depth (PPD) and bleeding on probing (BOP) measurements are useful indices for the assessment of periodontal conditions. The same periodontal indices are commonly recommended to evaluate the dental implant/tissue interface to identify sites with mucositis and peri-implantitis, which, if not treated, are anticipated to lead to implant failure. The aim of the present narrative review is to discuss the available literature on the effectiveness of probing at dental implants for identification of peri-implant pathology. There is substantial clinical evidence that PPD and BOP measurements are very poor indices of peri-implant tissue conditions and are questionable surrogate endpoints for implant failure. On the contrary, the literature suggests that frequent disturbance of the soft tissue barrier at implants may instead induce inflammation and bone resorption. Moreover, over-diagnosis and subsequent unnecessary treatment may lead to iatrogenic damage to the implant-tissue interface. Despite this, the recommendations from recent consensus meetings are still promoting the use of probing at dental implants. For evaluation of implants, for instance at annual check-ups, the present authors recommend a clinical examination that includes (i) a visual inspection of the peri-implant tissues for the assessment of oral hygiene and the detection of potential redness, swelling, (ii) palpation of the peri-implant tissues for assessment of the potential presence of swelling, bleeding, suppuration. In addition, (iii) radiography is recommended for the assessment of crestal bone level for comparison with previous radiographs to evaluate potential progressive bone loss even if there is a need for more scientific evidence of the true value of the first two clinical testing modes.
Subclinical Atherosclerosis Imaging in People Living with HIV
Authors: Schoepf Isabella C. , Buechel Ronny R. , Kovari Helen , Hammoud Dima A. , Tarr Philip E.
Published: July 2019

In many, but not all studies, people living with HIV (PLWH) have an increased risk of coronary artery disease (CAD) events compared to the general population. This has generated considerable interest in the early, non-invasive detection of asymptomatic (subclinical) atherosclerosis in PLWH. Ultrasound studies assessing carotid artery intima-media thickness (CIMT) have tended to show a somewhat greater thickness in HIV+ compared to HIV−, likely due to an increased prevalence of cardiovascular (CV) risk factors in PLWH. Coronary artery calcification (CAC) determination by non-contrast computed tomography (CT) seems promising to predict CV events but is limited to the detection of calcified plaque. Coronary CT angiography (CCTA) detects calcified and non-calcified plaque and predicts CAD better than either CAC or CIMT. A normal CCTA predicts survival free of CV events over a very long time-span. Research imaging techniques, including black-blood magnetic resonance imaging of the vessel wall and 18F-fluorodeoxyglucose positron emission tomography for the assessment of arterial inflammation have provided insights into the prevalence of HIV-vasculopathy and associated risk factors, but their clinical applicability remains limited. Therefore, CCTA currently appears as the most promising cardiac imaging modality in PLWH for the evaluation of suspected CAD, particularly in patients <50 years, in whom most atherosclerotic coronary lesions are non-calcified.
Memristor-Based Loop Filter Design for Phase Locked Loop
Authors: Adesina Naheem Olakunle , Srivastava Ashok
Published: July 2019

The main challenge in designing a loop filter for a phase locked loop (PLL) is the physical dimensions of the passive elements used in the circuit that occupy large silicon area. In this paper, the basic features of a charge-controlled memristor are studied and the design procedures for various components of a PLL are examined. Following this, we propose a memristor-based filter design which has its resistance being replaced by a memristor in order to reduce the die area and achieve a low power consumption. We obtained a tuning range of 741–994 MHz, a stable output frequency of 1 GHz from the transfer characteristics of voltage-controlled oscillator (VCO), and an improved settling time. In addition to reduced power consumption and area occupied on the chip, our design shows a high reliability over wider range of temperature variations.
A Fuzzy-Based Decision-Making Model for Improving the Carrying Capacity of Ship Locks: A Three Gorges Dam Case
Authors: Shi Shaoyue , Zhang Danhong , Su Yixin , Wan Chengpeng , Zhang Mingyang , Liu Cong
Published: July 2019

This paper develops a decision-making model to assist the improvement of the carrying capacity of ship locks by combing fuzzy logic, the analytic hierarchy process (AHP) method, and the technique for order preference by similarity to an ideal solution (TOPSIS). A three-level hierarchical structure is constructed to identify the key factors influencing the carrying capacity of ship locks from the aspects of ship locks, vessels, environment, and administration. On this basis, a series of targeted strategies have been put forward to improve the carrying capacity of ship locks, and the TOPSIS method is applied to rank these strategies in terms of their performance. A case study of the five-stage dual-track ship lock of the Three Gorges Dam in China has been conducted to demonstrate the feasibility and rationality of the proposed model, and correlation analysis is conducted to verify the identified influencing factors in order to eliminate potential bias which may be generated from using AHP. The results obtained from the proposed methods are consistent with the real-life situation to a certain extent, indicating that the proposed method can provide a useful reference for improving the carrying capacity of ship locks.
Non-Intrusive Presence Detection and Position Tracking for Multiple People Using Low-Resolution Thermal Sensors
Authors: Singh Saipriyati , Aksanli Baris
Published: July 2019

This paper presents a framework to accurately and non-intrusively detect the number of people in an environment and track their positions. Different from most of the previous studies, our system setup uses only ambient thermal sensors with low-resolution, using no multimedia resources or wearable sensors. This preserves user privacy in the environment, and requires no active participation by the users, causing no discomfort. We first develop multiple methods to estimate the number of people in the environment. Our experiments demonstrate that algorithm selection is very important, but with careful selection, we can obtain up to 100% accuracy when detecting user presence. In addition, we prove that sensor placement plays a crucial role in the system performance, where placing the sensor on the room ceiling yields to the best results. After accurately finding the number of people in the environment, we perform position tracking on the collected ambient data, which are thermal images of the space where there are multiple people. We consider position tracking as static activity detection, where the user’s position does not change while performing activities, such as sitting, standing, etc. We perform efficient pre-processing on the data, including normalization and resizing, and then feed the data into well-known machine learning methods. We tested the efficiency of our framework (including the hardware and software setup) by detecting four static activities. Our results show that we can achieved up to 97.5% accuracy when detecting these static activities, with up to 100% class-wise precision and recall rates. Our framework can be very beneficial to several applications such as health-care, surveillance, and home automation, without causing any discomfort or privacy issues for the users.
Productivity and Community Composition of Low Biomass/High Silica Precipitation Hot Springs: A Possible Window to Earth’s Early Biosphere?
Authors: Havig Jeff R. , Hamilton Trinity L.
Published: July 2019

Terrestrial hot springs have provided a niche space for microbial communities throughout much of Earth’s history, and evidence for hydrothermal deposits on the Martian surface suggest this could have also been the case for the red planet. Prior to the evolution of photosynthesis, life in hot springs on early Earth would have been supported though chemoautotrophy. Today, hot spring geochemical and physical parameters can preclude the occurrence of oxygenic phototrophs, providing an opportunity to characterize the geochemical and microbial components. In the absence of the photo-oxidation of water, chemoautotrophy in these hot springs (and throughout Earth’s history) relies on the delivery of exogenous electron acceptors and donors such as H2, H2S, and Fe2+. Thus, systems fueled by chemoautotrophy are likely energy substrate-limited and support low biomass communities compared to those where oxygenic phototrophs are prevalent. Low biomass silica-precipitating systems have implications for preservation, especially over geologic time. Here, we examine and compare the productivity and composition of low biomass chemoautotrophic versus photoautotrophic communities in silica-saturated hot springs. Our results indicate low biomass chemoautotrophic microbial communities in Yellowstone National Park are supported primarily by sulfur redox reactions and, while similar in total biomass, show higher diversity in anoxygenic phototrophic communities compared to chemoautotrophs. Our data suggest productivity in Archean terrestrial hot springs may be directly linked to redox substrate availability, and there may be high potential for geochemical and physical biosignature preservation from these communities.
N-Benzo[c][1,2,5]thiazol-4-yl-3-trifluoromethylbenzamide
Authors: Al Mamari Hamad H. , Al Awaimri Nasser , Al Lawati Yousuf
Published: July 2019

The title compound, N-benzo[c][1,2,5]thiazol-4-yl-3-trifluoromethylbenzamide (1) was synthesized by reacting 3-trifluoromethylbenzoyl chloride (4) and 4-aminobenzo[c][1,2,5]thiadiazole (5). The compound was characterized by various spectroscopic methods (1H NMR, 13C NMR, IR, GC-MS) and its composition confirmed by elemental analysis. The importance of this compound lies in its possession of an N,N-bidentate directing group. Such a structural motif is potentially suitable for metal-catalyzed C-H bond functionalization reactions.
Effects of Epoxy Adhesive Layer Thickness on Bond Strength of Joints in Concrete Structures
Authors: Yeon Jaeheum , Song Yooseob , Kim Kwan Kyu , Kang Julian
Published: July 2019

In the construction field, adhesives are frequently used to improve adhesion between two objects. Epoxy adhesives are applied as long-term solutions, improving the bond between repair materials and existing concrete structures. Experimental investigations of the relationship between the thickness of an adhesive layer and its shear strength have been conducted by a number of industries outside of the construction sector. However, that research used metal plates as adherends when determining the shear strengths of epoxy adhesives. Therefore, this study examines epoxy adhesives’ shear strength development when applied to concrete adherends. The test results show that the thickness of the bond layer did affect shear strength development in the epoxy adhesives examined.
Printability and Microstructure of Selective Laser Melting of WC/Co/Cr Powder
Authors: Campanelli Sabina Luisa , Contuzzi Nicola , Posa Paolo , Angelastro Andrea
Published: July 2019

The selective laser melting process is a growing technology for the manufacture of parts with very complex geometry. However, not all materials are suitable for this process, involving rapid localized melting and solidification. Tungsten has difficulties due to the high melting temperature. This study focuses on the possibility of processing a WC/Co/Cr composite powder using selective laser melting. Samples were fabricated and characterized in terms of density, defects, microstructure and hardness. Tests were conducted with hatch spacing of 120 μm and process speed of 40 mm/s. A constant laser power of 100 W and a powder layer thickness of 30 μm were used. A relative density of 97.53%, and therefore a low porosity, was obtained at an energy density of 12.5 J/mm2. Microscopic examination revealed the presence of small cracks and a very heterogeneous distribution of the grain size.
Strengthening Mechanism of Titanium Boride Whisker-Reinforced Ti-6Al-4V Alloy Matrix Composites with the TiB Orientation Perpendicular to the Loading Direction
Authors: Kurita Hiroki , Suzuki Shiori , Kikuchi Shoichi , Yodoshi Noriharu , Gourdet Sophie , Narita Fumio
Published: July 2019

We fabricated fully dense titanium boride (TiB) whisker-reinforced Ti-6Al-4V alloy matrix (Ti6Al4V-TiB) composites, with a homogeneous dispersion, a TiB orientation perpendicular to the loading direction (; two-dimensional random direction) and an intimate Ti/TiB interface without an intermediate interfacial layer in the Ti-6Al-4V alloy matrix, by spark plasma sintering. Microstructural analysis allows us to present the tensile properties of the Ti6Al4V-TiB composites with the theories for discontinuous fiber-reinforced composites. The Ti6Al4V-TiB 10 vol.% composite yielded a Young’s modulus of 130 GPa, an ultimate tensile strength (UTS) of 1193 MPa and an elongation of 2.8%. The obtained experimental Young’s modulus and UTS of the Ti6Al4V-TiB composites were consistent with the theoretical values estimated by the Halpin-Tsai and Shear-lag models. The good agreement between our experimental results and these models indicates that the TiB whiskers behave as discontinuous fibers in the Ti-6Al-4V alloy matrix.
The Influence of Astaxanthin on the Proliferation of Adipose-derived Mesenchymal Stem Cells in Gelatin-Methacryloyl (GelMA) Hydrogels
Authors: Choi Bo Young , Chalisserry Elna Paul , Kim Myoung Hwan , Kang Hyun Wook , Choi Il-Whan , Nam Seung Yun
Published: July 2019

Recently, astaxanthin, a red lipophilic pigment belonging to the xanthophyllic family of carotenoids, has shown the feasibility of its uses in tissue engineering and regenerative medicine, due to its excellent antioxidant activities and its abilities to enhance the self-renewal potency of stem cells. In this study, we demonstrate the influence of astaxanthin on the proliferation of adipose-derived mesenchymal stem cells in tissue-engineered constructs. The tissue engineered scaffolds were fabricated using photopolymerizable gelatin methacryloyl (GelMA) with different concentrations of astaxanthin. The effects of astaxanthin on cellular proliferation in two-dimensional environments were assessed using alamar blue assay and reverse transcription polymerase chain reaction (RT-PCR). Then, rheological properties, chemical structures and the water absorption of the fabricated astaxanthin-incorporated GelMA hydrogels were characterized using NMR analysis, rheological analysis and a swelling ratio test. Finally, the influence in three-dimensional environments of astaxanthin-incorporated GelMA hydrogels on the proliferative potentials of adipose-derived stem cells was assessed using alamar blue assay and the confocal imaging with Live/dead staining. The experimental results of the study indicate that an addition of astaxanthin promises to induce stem cell potency via proliferation, and that it can be a useful tool for a three-dimensional culture system and various tissue engineering applications.
Overview of Current Targeted Anti-Cancer Drugs for Therapy in Onco-Hematology
Authors: Crisci Stefania , Amitrano Filomena , Saggese Mariangela , Muto Tommaso , Sarno Sabrina , Mele Sara , Vitale Pasquale , Ronga Giuseppina , Berretta Massimiliano , Di Francia Raffaele
Published: July 2019

The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells’ inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.
Validation of a New Quality Assessment Procedure for Ductile Irons Production Based on Strain Hardening Analysis
Authors: Angella Giuliano , Zanardi Franco
Published: July 2019

A mathematical procedure based on the analysis of tensile flow curves has been proposed to assess the microstructure quality of several ductile irons (DIs). The procedure consists of a first diagram for the assessment of the ideal microstructure of DIs, that is, the matrix where mobile dislocations move, and a second diagram for the assessment of the casting integrity because of potential metallurgical discontinuities and defects in DIs. Both diagrams are based on the dislocation-density-related constitutive Voce equation that is used for modeling the tensile plastic behavior of DIs. The procedure stands on the fundamental assumption that the strain hardening behavior of DIs is not affected by the nature and the density of the potential metallurgical discontinuities and defects, which are expected to affect only the elongations to fracture. However, this fundamental assumption is not obvious, and so its validity was evaluated through tensile testing Isothermed Ductile Irons (IDIs) 800, showing a wide scatter of elongations to rupture. The analysis of the strain hardening behaviors supported by strain energy density calculations of IDIs tensile tests proved that the fundamental assumption was valid and the quality assessment procedure could be applied to IDIs. A modified Voce equation was also introduced to improve the fitting of the experimental tensile flow curves and the strain energy density calculations.
A New S-Shape Specimen for Studying the Dynamic Shear Behavior of Metals
Authors: Arab Ali , Guo Yansong , Zhou Qiang , Chen Pengwan
Published: July 2019

A new S-shaped specimen geometry is developed in this study to investigate the shear behavior of materials under dynamic shear condition. Traditionally, hat-shaped geometry is used to study the dynamic shear of materials by a conventional split Hopkinson pressure bar apparatus. However, in this geometry, the force equilibrium on the two sides of the sample is difficult to fulfill, and the stress field in the shear region is not homogeneous. Hence, the calculated shear stress–strain curve from this geometry is not precise. To overcome this problem, the new S-shaped specimen is designed to achieve accurate shear stress–strain curve. This geometry can be used in a wide range of strain rates and does not require additional machining process for microstructure observation. The new S-shaped specimen is successfully coupled with digital image correlation method because of the flat surface. Digital image correlation results indicate that the fracture patterns of the new S-shaped specimen occur with maximum shear strains in the shear region in the middle of the sample. This result is also validated by finite element model simulation. The new S-shaped specimen geometry can be used to study the dynamic shear behavior of various metals.
The Genetic Basis of Toxin Biosynthesis in Dinoflagellates
Authors: Verma Arjun , Barua Abanti , Ruvindy Rendy , Savela Henna , Ajani Penelope A. , Murray Shauna A.
Published: July 2019

In marine ecosystems, dinoflagellates can become highly abundant and even dominant at times, despite their comparatively slow growth rates. One factor that may play a role in their ecological success is the production of complex secondary metabolite compounds that can have anti-predator, allelopathic, or other toxic effects on marine organisms, and also cause seafood poisoning in humans. Our knowledge about the genes involved in toxin biosynthesis in dinoflagellates is currently limited due to the complex genomic features of these organisms. Most recently, the sequencing of dinoflagellate transcriptomes has provided us with valuable insights into the biosynthesis of polyketide and alkaloid-based toxin molecules in dinoflagellate species. This review synthesizes the recent progress that has been made in understanding the evolution, biosynthetic pathways, and gene regulation in dinoflagellates with the aid of transcriptomic and other molecular genetic tools, and provides a pathway for future studies of dinoflagellates in this exciting omics era.
A Statistical Approach for Analysis of Dissolution Rates Including Surface Morphology
Authors: Trindade Pedrosa Elisabete , Kurganskaya Inna , Fischer Cornelius , Luttge Andreas
Published: July 2019

Understanding mineral dissolution is relevant for natural and industrial processes that involve the interaction of crystalline solids and fluids. The dissolution of slow dissolving minerals is typically surface controlled as opposed to diffusion/transport controlled. At these conditions, the dissolution rate is no longer constant in time or space, an outcome observed in rate maps and correspondent rate spectra. The contribution and statistical prevalence of different dissolution mechanisms is not known. Aiming to contribute to close this gap, we present a statistical analysis of the variability of calcite dissolution rates at the nano- to micrometer scale. A calcite-cemented sandstone was used to perform flow experiments. Dissolution of the calcite-filled rock pores was measured using vertical scanning interferometry. The resultant types of surface morphologies influenced the outcome of dissolution. We provide a statistical description of these morphologies and show their temporal evolution as an alternative to the lack of rate spatial variability in rate constants. Crystal size impacts dissolution rates most probably due to the contribution of the crystal edges. We propose a new methodology to analyze the highest rates (tales of rate spectra) that represent the formation of deeper etch pits. These results have application to the parametrization and upscaling of geochemical kinetic models, the characterization of industrial solid materials and the fundamental understanding of crystal dissolution.
Atomistic View of Mercury Cycling in Polar Snowpacks: Probing the Role of Hg2+ Adsorption Using Ab Initio Calculations
Authors: Yi Yoo Soo , Han Yeongcheol , Lee Sung Keun , Hur Soon Do
Published: July 2019

Photochemical oxidation of atmospheric elemental mercury (Hg0) promotes reactive oxidized Hg (HgII) adsorption on particles and deposition to the polar snowpack. The deposited Hg either returns to the atmosphere via photochemical reduction or remains in the snowpack depending on the strength of adsorption. In this study, we performed ab initio calculations to understand the atomic-level cause of the fate of adsorbed Hg by determining the adsorption affinity for Hg2+, the simplest form of HgII, of barite, halite, muscovite, illite, and ice-Ih as potential adsorbents. The adsorption affinity was estimated by calculating the energy required to dissociate adsorbed Hg2+ from the adsorbents. The results reveal that Hg2+ is stable on the surfaces of the selected adsorbents, except barite, but is prone to photodissociation under solar ultraviolet radiation. This mild adsorption is expected to contribute to the bidirectional exchange of Hg between the atmosphere and the polar snowpack. Thus, this theoretical approach can provide complementary perspectives on polar Hg dynamics beyond the limitations of field and laboratory experiments. Further studies on more complicated and realistic adsorption models with different HgII species and adsorbent surfaces having diverse defective structures are required to better comprehend air–snow Hg cycling in the polar regions.
A Clean Process to Prepare High-Quality Acid-Soluble Titanium Slag from Titanium Middling Ore
Authors: Han Jiqing , Zhang Jing , Feng Wei , Chen Xiao , Zhang Li , Tu Ganfeng
Published: July 2019

A direct reduction-magnetic separation-alkali leaching-dilute acid washing method was proposed to prepare high-quality acid-soluble titanium slag (HQASTS) from titanium middling ore. The relevant potential pH diagrams were built, and the analysis results showed that the pH values for alkali leaching and dilute acid washing should be higher than 13.50 and lower than 1.00, respectively. Increasing temperature was beneficial to alkali leaching but not to dilute acid washing. The effects of operating parameters on the TiO2 content and impurity oxides extraction ratios of titanium slag were investigated, and the optimal experimental conditions were obtained. The HQASTS was obtained with TiO2 and Fe2O3 content of 75.37 wt % and 0.96 wt %, respectively, under the above conditions. Furthermore, the leaching mechanism was studied by chemical analysis and X-ray diffraction (XRD) technology, and it was found that the alkali leaching-dilute acid washing process presented in this work could avoid the encapsulation of the unreacted anorthite by the calcium aluminum spinel generated in alkali leaching.
Hydrothermal Aluminum-Phosphate-Sulfates in Ash from the 2014 Hydrothermal Eruption at Ontake Volcano, Central Honshu, Japan
Authors: Imura Takumi , Minami Yusuke , Ohba Tsukasa , Matsumoto Akiko , Arribas Antonio , Nakagawa Mitsuhiro
Published: July 2019

Aluminum-phosphate-sulfates (APS) of the alunite supergroup occur in igneous rocks within zones of advanced argillic and silicic alteration in porphyry and epithermal ore environments. In this study we report on the presence of woodhouseite-rich APS in ash from the 27 September 2014 hydrothermal eruption of Ontake volcano. Scanning electron microscope coupled with energy dispersive X-ray spectrometer (SEM-EDS) and field emission (FE)-SEM-EDS observations show two types of occurrence of woodhouseite: (a) as cores within chemically zoned alunite-APS crystals (Zoned-alunite-woodhouseite-APS), and (b) as a coherent single-phase mineral in micro-veinlets intergrown with similar micro-veinlets of silica minerals (Micro-wormy-vein woodhouseite-APS). The genetic environment of APS minerals at Ontake volcano is that of a highly acidic hydrothermal system existing beneath the volcano summit, formed by condensation in magmatic steam and/or ground waters of sulfur-rich magmatic volatiles exsolved from the magma chamber beneath Mt. Ontake. Under these conditions, an advanced argillic alteration assemblage forms, which is composed of silica, pyrophyllite, alunite and kaolinite/dickite, plus APS, among other minerals. The discovery of woodhouseite in the volcanic ash of the Ontake 2014 hydrothermal eruption represents the first reported presence of APS within an active volcano. Other volcanoes in Japan and elsewhere with similar phreatic eruptions ejecting altered ash fragments will likely contain APS minerals derived from magmatic-hydrothermal systems within the subvolcanic environment. The presence of APS minerals within the advanced argillic zone below the summit vent of Ontake volcano, together with the prior documentation of phyllic and potassically altered ash fragments, provides evidence for the existence within an active volcano in Japan of an alteration column comparable to that of porphyry copper systems globally.
A Rapid Chemiluminescence Assay for Measurement of Folate in Small Volumes of Breast Milk
Authors: Guignard Laurence , Nembrini Chiara , Moulin Julie , Meisser Karine , Silva-Zolezzi Irma , Kratzsch Jürgen , Vogel Mandy , Kiess Wieland , Eckhardt Erik
Published: July 2019

Early life exposure to folate has long lasting effects on development and health. Newborns obtain part of their folate from maternal milk. Studies on health effects of milk folate require rapid, affordable and reliable measurements in large numbers of samples from cohort studies. Recently, a competitive chemiluminescence assay for quantification of folate has become available for automated diagnostic measurement of folate in human serum or plasma. We tested if this method (“FOLA” from Siemens Healthcare) could also be used for human milk. To minimize interference and matrix effects, samples had to be skimmed, diluted seven times with demineralized water, and heated for 5 min at 90 °C. Folate could thus be measured in a linear range between 8.4 and 111.7 nM, with recoveries for the most relevant form, 5-methyltetrahydrofolate (5-MeTHF), of 96%–107%. Results were comparable to those with a recently validated Liquid Chromatography/Mass Spectrometry method (Y = 0.998X − 0.2; R2 = 0.807). The FOLA method was subsequently used for samples from the LIFE Child cohort in Germany, providing first data of breast milk folate in this country (range: 6.2–100.7 nM). This technique could indeed prove useful for large cohorts with multiple samplings.
Supersaturation Potential of Amorphous Active Pharmaceutical Ingredients after Long-Term Storage
Authors: Edueng Khadijah , Mahlin Denny , Gråsjö Johan , Nylander Olivia , Thakrani Manish , Bergström Christel A.S.
Published: July 2019

This study explores the effect of physical aging and/or crystallization on the supersaturation potential and crystallization kinetics of amorphous active pharmaceutical ingredients (APIs). Spray-dried, fully amorphous indapamide, metolazone, glibenclamide, hydrocortisone, hydrochlorothiazide, ketoconazole, and sulfathiazole were used as model APIs. The parameters used to assess the supersaturation potential and crystallization kinetics were the maximum supersaturation concentration (Cmax,app), the area under the curve (AUC), and the crystallization rate constant (k). These were compared for freshly spray-dried and aged/crystallized samples. Aged samples were stored at 75% relative humidity for 168 days (6 months) or until they were completely crystallized, whichever came first. The solid-state changes were monitored with differential scanning calorimetry, Raman spectroscopy, and powder X-ray diffraction. Supersaturation potential and crystallization kinetics were investigated using a tenfold supersaturation ratio compared to the thermodynamic solubility using the µDISS Profiler. The physically aged indapamide and metolazone and the minimally crystallized glibenclamide and hydrocortisone did not show significant differences in their Cmax,app and AUC when compared to the freshly spray-dried samples. Ketoconazole, with a crystalline content of 23%, reduced its Cmax,app and AUC by 50%, with Cmax,app being the same as the crystalline solubility. The AUC of aged metolazone, one of the two compounds that remained completely amorphous after storage, significantly improved as the crystallization kinetics significantly decreased. Glibenclamide improved the most in its supersaturation potential from amorphization. The study also revealed that, besides solid-state crystallization during storage, crystallization during dissolution and its corresponding pathway may significantly compromise the supersaturation potential of fully amorphous APIs.
Prediction of Transformation Products of Monensin by Electrochemistry Compared to Microsomal Assay and Hydrolysis
Authors: Kotthoff Lisa , Lisec Jan , Schwerdtle Tanja , Koch Matthias
Published: July 2019

The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation.