bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactor Design and Thermal Performance Analysis for Solar Thermal Energy Storage Application
Authors: Getahun Dessie Yabibal , Guene Lougou Bachirou , Qi Hong , Tan Heping , Zhang Juqi , Gao Baohai , Islam Md Arafat
Published: June 2020

Solar energy is a sustainable and low-cost renewable energy of enormous importance, especially at this time where non-renewable energy sources are unsustainable and costly. However, improving the thermal performance of a solar energy storage reactor poses some challenges. In this study, the location of fluid inlets and outlets in the given reactor design and its impact on the thermal performance were investigated. A P1 approximation radiation model coupled with shallow channel approximation of fluid flow was developed. By taking the frustum base as a reference, four fluid inlets along the edges of the frustum and two outlet locations at the base and side of the reactor were computed. Inlets located 4.81 cm from the base of the frustum and an outlet located at the side of the reactor were found to have a better thermal performance with a short conveyer energy flow system. It was also deduced that radiation applied at the edges of the frustum had better thermal performance than that applied at a quartz edge. Furthermore, increasing the laminar inflow rate from 0.36 (L/h) to 3.6 (L/h) increased the temperature distribution in the reactor. This study provides noteworthy insights of relevance to the power engineering industry and academia.
High-Temperature Geothermal Utilization in the Context of European Energy Policy—Implications and Limitations
Authors: Karlsdottir Marta Ros , Heinonen Jukka , Palsson Halldor , Palsson Olafur Petur
Published: June 2020

The European Union (EU) has made climate change mitigation a high priority though a policy framework called “Clean Energy for all Europeans “. The concept of primary energy for energy resources plays a critical role in how different energy technologies appear in the context of this policy. This study shows how the calculation methodologies of primary energy content and primary energy factors pose a possible negative implication on the future development of geothermal energy when comparing against EU’s key energy policy targets for 2030. Following the current definitions of primary energy, geothermal utilization becomes the most inefficient resource in terms of primary energy use, thus contradicting key targets of increased energy efficiency in buildings and in the overall energy use of member states. We use a case study of Hellisheidi, an existing geothermal power plant in Iceland, to demonstrate how the standard primary energy factor for geothermal in EU energy policy is highly overestimated for efficient geothermal power plants. Moreover, we combine life cycle assessment and the commonly utilized combined heat and power production allocation methods to extract the non-renewable primary energy factor for geothermal and show how it is only a minimal fraction of the total primary energy factor for geothermal. The findings of the study apply to other geothermal plants within the coverage of the European Union’s energy policy, whether from high- or low-temperature geothermal resources. Geothermal has substantial potential to aid in achieving the key energy and climate targets. Still, with the current definition of the primary energy of geothermal resources, it may not reach the potential.
Verification of Utility-Scale Solar Photovoltaic Plant Models for Dynamic Studies of Transmission Networks
Authors: Machlev Ram , Batushansky Zohar , Soni Sachin , Chadliev Vladimir , Belikov Juri , Levron Yoash
Published: June 2020

In recent years, there has been a growing need for accurate models that describe the dynamics of renewable energy sources, especially photovoltaic sources and wind turbines. In light of this gap, this work focuses on the validation of standard dynamic models developed by the Western Electricity Coordinating Council (WECC), using actual measurements from the Western Texas and Southern California transmission networks. The tests are based on the North American Electric Reliability Corporation compliance standards and include dynamic stability tests for volt-varcontrol and primary frequency response. Through an extensive set of field tests, we show that the WECC generic models can be used to simulate real dynamic phenomena in large-scale solar photovoltaic power plants, and we propose guidelines for correct usage of these models. The results show that the WECC models are especially accurate when the photovoltaic system is connected with a low impedance to the main network. We also show that the tested WECC models successfully predict the frequency response of an actual grid event that occurred in the Electric Reliability Council of Texas and which resulted in a loss of nearly 1.365 GW. This result supports the use of these models in the study of large-scale dynamic phenomena that include renewable energy sources.
Porphyridium cruentum Grown in Ultra-Filtered Swine Wastewater and Its Effects on Microalgae Growth Productivity and Fatty Acid Composition
Authors: Ulusoy Erol Humeyra B. , Menegazzo Mariana Lara , Sandefur Heather , Gottberg Emily , Vaden Jessica , Asgharpour Maryam , Hestekin Christa N. , Hestekin Jamie A.
Published: June 2020

Microalgae have been extensively tested for their ability to create bio-based fuels. Microalgae have also been explored as an alternative wastewater treatment solution due to their significant uptake of nitrogen and phosphorus, as well as their ability to grow in different water types. Recently, there has been significant interest in combining these two characteristics to create economic and environmentally friendly biofuel using wastewater. This study examined the growth and lipid production of the microalgae Porphyridium (P.) cruentum grown in swine wastewater (ultra-filtered and raw) as compared with control media (L−1, modified f/2) at two different salt concentrations (seawater and saltwater). The cultivation of P. cruentum in the treated swine wastewater media (seawater = 5.18 ± 2.3 mgL−1day−1, saltwater = 3.32 ± 1.93 mgL−1day−1) resulted in a statistically similar biomass productivity compared to the control medium (seawater = 2.61 ± 2.47 mgL−1day−1, saltwater = 6.53 ± 0.81 mgL−1day−1) at the corresponding salt concentration. Furthermore, no major differences between the fatty acid compositions of microalgae in the treated swine wastewater medium and the control medium were observed. For all conditions, saturated acids were present in the highest amounts (≥67%), followed by polyunsaturated (≤22%) and finally monounsaturated (≤12%). This is the first study to find that P. cruentum could be used to remediate wastewater and then be turned into fuel by using swine wastewater with a similar productivity to the microalgae grown in control media.
Design and Thermo-Economic Comparisons of an Absorption Air Conditioning System Based on Parabolic Trough and Evacuated Tube Solar Collectors
Authors: Al-Falahi Adil , Alobaid Falah , Epple Bernd
Published: June 2020

Solar absorption cycles for air conditioning systems have recently attracted much attention. They have some important advantages that aid in reducing greenhouse gas emissions. In this work, design and thermo-economic analyses are presented in order to compare between two different collector types (parabolic trough and evacuated tube) by water–lithium bromide absorption systems, and to select the best operating conditions. Generally, the system consists of three major parts. The first part is the solar field for thermal power conversion. The second part is the intermediate cycle, which contains a flashing tank and pumping system. The third part is the water lithium bromide absorption chiller. A case study for a sports arena with 700–800 kW total cooling load is also presented. Results reveal that a parabolic trough collector combined with H2O–LiBr (PTC/H2O–LiBr) gives lower design aspects and minimum rates of hourly costs (USD 5.2/h), while ETC/H2O–LiBr configuration give USD 5.6/h. The H2O–LiBr thermo-economic product cost is USD 0.14/GJ. The cycle coefficient of performance COP was in the range of 0.5 to 0.9.
Using Remote Sensing Data to Identify Large Bottom Objects: The Case of World War II Shipwreck of General von Steuben
Authors: Grządziel Artur
Published: June 2020

The seabed of the Baltic Sea is not yet fully searched for and investigated. In 2004 the crew of the Polish Navy hydrographic ship Arctowski discovered a new shipwreck that was not listed in the official underwater objects database nor was it marked on a chart. The identity of a new wreck is most frequently established based on artefacts found in the object by divers as a part of archaeological research, or through underwater inspection with remotely operated vehicle. The aim of this paper is to show how acoustic remote sensing data is used to identify large bottom object without having to go underwater. Bathymetric survey and sonar investigation were conducted over the study area. An appropriate methodology allowed for obtaining high-resolution imagery of the wreck. A review of literature concerning the end of World War II in the Baltic Sea was carried out. Moreover, the author presents a comparative analysis and evaluation of remote sensing data with archival photos, silhouette, and ship characteristics. The proposed approach led to the identification of a new Baltic Sea wreck as the General von Steuben, which was torpedoed in 1945 by soviet submarine. The author’s findings show that state of preservation of the shipwreck, quality data as well as historical records play a key role in establishing the wreck’s identity.
A Study of Care Workers’ Wages and Relevant Factors in South Korea
Authors: Kim Yun-Young , Kyoung Seung-Ku , Lee Yong-Gab
Published: June 2020

The purpose of this study is to analyze the wages of South Korea’s care workers as reported by the Korean national health insurance services database. We also try to identify the factors determining the wages of these 1,221,085 care workers. According to the results of the analysis, first, the wage level of care workers is fundamentally low compared to other jobs; second, the labor conditions of home care facilities (compared to those in residential care facilities) are poor, because these depend on wages, which in turn depend on the external environment, such as care institutes’ management; and third, it was verified that the locations of care institutes affect the wages of care workers. As the South Korean population continues to age, the supply of high-quality care workers has important clinical implications for improving the quality of care received by the elderly. Throughout this study, it is argued that the establishment of a social service corporation has become desirable in terms of strengthening public care institutes in Korea.
National-Scale Landslide Susceptibility Mapping in Austria Using Fuzzy Best-Worst Multi-Criteria Decision-Making
Authors: Moharrami Meisam , Naboureh Amin , Gudiyangada Nachappa Thimmaiah , Ghorbanzadeh Omid , Guan Xudong , Blaschke Thomas
Published: June 2020

Landslides are one of the most detrimental geological disasters that intimidate human lives along with severe damages to infrastructures and they mostly occur in the mountainous regions across the globe. Landslide susceptibility mapping (LSM) serves as a key step in assessing potential areas that are prone to landslides and could have an impact on decreasing the possible damages. The application of the fuzzy best-worst multi-criteria decision-making (FBWM) method was applied for LSM in Austria. Further, the role of employing a few numbers of pairwise comparisons on LSM was investigated by comparing the FBWM and Fuzzy Analytical Hierarchical Process (FAHP). For this study, a wide range of data was sourced from the Geological Survey of Austria, the Austrian Land Information System, Humanitarian OpenStreetMap Team, and remotely sensed data were collected. We used nine conditioning factors that were based on the previous studies and geomorphological characteristics of Austria, such as elevation, slope, slope aspect, lithology, rainfall, land cover, distance to drainage, distance to roads, and distance to faults. Based on the evaluation of experts, the slope conditioning factor was chosen as the best criterion (highest impact on LSM) and the distance to roads was considered as the worst criterion (lowest impact on LSM). LSM was generated for the region based on the best and worst criterion. The findings show the robustness of FBWM in landslide susceptibility mapping. Additionally, using fewer pairwise comparisons revealed that the FBWM can obtain higher accuracy as compared to FAHP. The finding of this research can help authorities and decision-makers to provide effective strategies and plans for landslide prevention and mitigation at the national level.
Measuring Accessibility of Healthcare Facilities for Populations with Multiple Transportation Modes Considering Residential Transportation Mode Choice
Authors: Zhou Xinxin , Yu Zhaoyuan , Yuan Linwang , Wang Lei , Wu Changbin
Published: June 2020

Accessibility research of healthcare facilities is developing towards multiple transportation modes (MTM), which are influenced by residential transportation choices and preferences. Due to differences in travel impact factors such as traffic conditions, origin location, distance to the destination, and economic cost, residents’ daily travel presents different residential transportation mode choices (RTMC). The purpose of our study was to measure the spatial accessibility of healthcare facilities based on MTM considering RTMC (MTM-RTMC). We selected the gravity two-step floating catchment area method (G2SFCA) as a fundamental model. Through the single transportation mode (STM), MTM, and MTM-RTMC, three aspects used to illustrate and redesign the G2SFCA, we obtained the MTM-RTMC G2SFCA model that integrates RTMC probabilities and the travel friction coefficient. We selected Nanjing as the experimental area, used route planning data of four modes (including driving, walking, public transportation, and bicycling) from a web mapping platform, and applied the three models to pediatric clinic services to measure accessibility. The results show that the MTM-RTMC mechanism is to make up for the traditional estimation of accessibility, which loses sight of the influence of residential transportation choices. The MTM-RTMC mechanism that provides a more realistic and reliable way can generalize to major accessibility models and offers preferable guidance for policymakers.
GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis
Authors: Di Pietro Lorena , Barba Marta , Prampolini Chiara , Ceccariglia Sabrina , Frassanito Paolo , Vita Alessia , Guadagni Enrico , Bonvissuto Davide , Massimi Luca , Tamburrini Gianpiero , Parolini Ornella , Lattanzi Wanda
Published: June 2020

All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients’ calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic differentiation to validate the functional implication. Our results show that GLI1 and AXIN2 are expressed in periosteal and endosteal locations within the osteogenic niche of human calvarial bones. Their expression is higher in MSC isolated from calvarial bones than in those isolated from long bones and tends to decrease upon osteogenic commitment and differentiation. In particular, AXIN2 expression was lower in cells isolated from prematurely fused sutures than in those derived from patent sutures of NCS patients. This suggests that AXIN2 could reasonably represent a marker for the stem cell population that undergoes depletion during the premature ossification process occurring in CS.
Optimization of a WGA-Free Molecular Tagging-Based NGS Protocol for CTCs Mutational Profiling
Authors: De Luca Giuseppa , Cardinali Barbara , Del Mastro Lucia , Lastraioli Sonia , Carli Franca , Ferrarini Manlio , Calin George A. , Garuti Anna , Mazzitelli Carlotta , Zupo Simona , Dono Mariella
Published: June 2020

Molecular characterization of Circulating Tumor Cells (CTCs) is still challenging, despite attempts to minimize the drawbacks of Whole Genome Amplification (WGA). In this paper, we propose a Next-Generation Sequencing (NGS) optimized protocol based on molecular tagging technology, in order to detect CTCs mutations while skipping the WGA step. MDA-MB-231 and MCF-7 cell lines, as well as leukocytes, were sorted into pools (2–5 cells) using a DEPArray™ system and were employed to set up the overall NGS procedure. A substantial reduction of reagent volume for the preparation of libraries was performed, in order to fit the limited DNA templates directly derived from cell lysates. Known variants in TP53, KRAS, and PIK3CA genes were detected in almost all the cell line pools (35/37 pools, 94.6%). No additional alterations, other than those which were expected, were found in all tested pools and no mutations were detected in leukocytes. The translational value of the optimized NGS workflow is confirmed by sequencing CTCs pools isolated from eight breast cancer patients and through the successful detection of variants. In conclusion, this study shows that the proposed NGS molecular tagging approach is technically feasible and, compared to traditional NGS approaches, has the advantage of filtering out the artifacts generated during library amplification, allowing for the reliable detection of mutations and, thus, making it highly promising for clinical use.
Potential Application of Protamine for Antimicrobial Biomaterials in Bone Tissue Engineering
Authors: Honda Michiyo , Matsumoto Morio , Aizawa Mamoru
Published: June 2020

Bacterial infection of biomaterials is a serious problem in the field of medical devices. It is urgently necessary to develop new biomaterials with bactericidal activity. Antimicrobial peptides and proteins (AMPs), alternative antibacterial agents, are expected to overcome the bacterial resistance. The aim of this study was to develop a new intelligent material in bone tissue engineering based on protamine-loaded hydroxyapatite (protamine/HAp) that uses AMPs rather than antibiotics. It was found that the adsorption of protamine to HAp followed the Langmuir adsorption model and was due to electrostatic and/or hydrophobic interactions. In vitro bacterial adhesion and growth on protamine/HAp was inhibited in a protamine dose-dependent manner. Adherent bacteria exhibited an aberrant morphology for high dosages of protamine/HAp, resulting in the formation of large aggregates and disintegration of the membrane. The released protamine from protamine/HAp also prevented the growth of planktonic bacteria in vitro. However, a high dosage of protamine from powders at loading concentrations over 1000 μg·mL−1 induced a cytotoxic effect in vitro, although those exhibited no apparent cytotoxicity in vivo. These data revealed that protamine/HAp (less than 1000 μg·mL−1) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.
Phosphodiesterase SMPDL3B Gene Expression as Independent Outcome Prediction Marker in Localized Prostate Cancer
Authors: Waldbillig Frank , Nitschke Katja , Abdelhadi Abdallah , von Hardenberg Jost , Nuhn Philipp , Nientiedt Malin , Weis Cleo-Aron , Michel Maurice Stephan , Erben Philipp , Worst Thomas Stefan
Published: June 2020

Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy (n = 40, n = 56) and benign prostate hyperplasia (BPH) controls (n = 8, n = 11) were profiled for SMPDL3B expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; n = 131, n = 29 controls) and The Cancer Genome Atlas (TCGA; n = 497, n = 53 controls)) served for validation. SMPDL3B’s impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of SMPDL3B was seen in PCa compared to BPH (p < 0.001 each). A lower expression of SMPDL3B was associated with a shorter overall survival (OS) (p = 0.005) in long term follow-up. A SMPDL3B overexpression in PCa tissue was confirmed in the validation cohorts (p < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival (p = 0.011) and progression-free interval (p < 0.001) were shorter. Knockdown of SMPDL3B impaired PC3 cell migration but not proliferation (p = 0.0081). In summary, SMPLD3B is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.
Metabolomics Analysis Reveals Tissue-Specific Metabolite Compositions in Leaf Blade and Traps of Carnivorous Nepenthes Plants
Authors: Dávila-Lara Alberto , Rodríguez-López Carlos E. , O'Connor Sarah E. , Mithöfer Axel
Published: June 2020

Nepenthes is a genus of carnivorous plants that evolved a pitfall trap, the pitcher, to catch and digest insect prey to obtain additional nutrients. Each pitcher is part of the whole leaf, together with a leaf blade. These two completely different parts of the same organ were studied separately in a non-targeted metabolomics approach in Nepenthes x ventrata, a robust natural hybrid. The first aim was the analysis and profiling of small (50–1000 m/z) polar and non-polar molecules to find a characteristic metabolite pattern for the particular tissues. Second, the impact of insect feeding on the metabolome of the pitcher and leaf blade was studied. Using UPLC-ESI-qTOF and cheminformatics, about 2000 features (MS/MS events) were detected in the two tissues. They showed a huge chemical diversity, harboring classes of chemical substances that significantly discriminate these tissues. Among the common constituents of N. x ventrata are phenolics, flavonoids and naphthoquinones, namely plumbagin, a characteristic compound for carnivorous Nepenthales, and many yet-unknown compounds. Upon insect feeding, only in pitchers in the polar compounds fraction, small but significant differences could be detected. By further integrating information with cheminformatics approaches, we provide and discuss evidence that the metabolite composition of the tissues can point to their function.
Benchmarking Data Sets from PubChem BioAssay Data: Current Scenario and Room for Improvement
Authors: Tran-Nguyen Viet-Khoa , Rognan Didier
Published: June 2020

Developing realistic data sets for evaluating virtual screening methods is a task that has been tackled by the cheminformatics community for many years. Numerous artificially constructed data collections were developed, such as DUD, DUD-E, or DEKOIS. However, they all suffer from multiple drawbacks, one of which is the absence of experimental results confirming the impotence of presumably inactive molecules, leading to possible false negatives in the ligand sets. In light of this problem, the PubChem BioAssay database, an open-access repository providing the bioactivity information of compounds that were already tested on a biological target, is now a recommended source for data set construction. Nevertheless, there exist several issues with the use of such data that need to be properly addressed. In this article, an overview of benchmarking data collections built upon experimental PubChem BioAssay input is provided, along with a thorough discussion of noteworthy issues that one must consider during the design of new ligand sets from this database. The points raised in this review are expected to guide future developments in this regard, in hopes of offering better evaluation tools for novel in silico screening procedures.
Preimplantation Genetic Testing: Where We Are Today
Authors: Greco Ermanno , Litwicka Katarzyna , Minasi Maria Giulia , Cursio Elisabetta , Greco Pier Francesco , Barillari Paolo
Published: June 2020

Background: Preimplantation genetic testing (PGT) is widely used today in in-vitro fertilization (IVF) centers over the world for selecting euploid embryos for transfer and to improve clinical outcomes in terms of embryo implantation, clinical pregnancy, and live birth rates. Methods: We report the current knowledge concerning these procedures and the results from different clinical indications in which PGT is commonly applied. Results: This paper illustrates different molecular techniques used for this purpose and the clinical significance of the different oocyte and embryo stage (polar bodies, cleavage embryo, and blastocyst) at which it is possible to perform sampling biopsies for PGT. Finally, genetic origin and clinical significance of embryo mosaicism are illustrated. Conclusions: The preimplantation genetic testing is a valid technique to evaluated embryo euploidy and mosaicism before transfer.
Molecular and Functional Phenotypes of Human Bone Marrow-Derived Mesenchymal Stromal Cells Depend on Harvesting Techniques
Authors: Walter Sebastian , Randau Thomas , Hilgers Cäcilia , Haddouti El-Mustapha , Masson Werner , Gravius Sascha , Burger Christof , Wirtz Dieter , Schildberg Frank
Published: June 2020

Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon as well. This study was therefore set up to investigate proteomic and functional properties of human bone marrow-derived MSCs (hBM-MSC). These were taken from the same tissue and donor site but harvested either as aspirate or bone chip cultures. Both MSC populations were profiled for MSC markers defined by the International Society for Cellular Therapy (ISCT), MSC markers currently under discussion and markers of particular interest. While classic ISCT MSC markers did not show any significant difference between aspirate and outgrowth hBM-MSCs, our additional characterization panel revealed distinct patterns of differentially expressed markers. Furthermore, hBM-MSCs from aspirate cultures demonstrated a significantly higher osteogenic differentiation potential than outgrowth MSCs, which could be confirmed using a transcriptional approach. Our comparison of MSC phenotypes obtained by different harvesting techniques suggests the need of future standardized harvesting, processing and phenotyping procedures in order to gain better comparability in the MSC field.
Differentiation and Establishment of Dental Epithelial-Like Stem Cells Derived from Human ESCs and iPSCs
Authors: Kim Gee-Hye , Yang Jihye , Jeon Dae-Hyun , Kim Ji-Hye , Chae Geun Young , Jang Mi , Lee Gene
Published: June 2020

Tooth development and regeneration occur through reciprocal interactions between epithelial and ectodermal mesenchymal stem cells. However, the current studies on tooth development are limited, since epithelial stem cells are relatively difficult to obtain and maintain. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) may be alternative options for epithelial cell sources. To differentiate hESCs/hiPSCs into dental epithelial-like stem cells, this study investigated the hypothesis that direct interactions between pluripotent stem cells, such as hESCs or hiPSCs, and Hertwig’s epithelial root sheath/epithelial rests of Malassez (HERS/ERM) cell line may induce epithelial differentiation. Epithelial-like stem cells derived from hES (EPI-ES) and hiPSC (EPI-iPSC) had morphological and immunophenotypic characteristics of HERS/ERM cells, as well as similar gene expression. To overcome a rare population and insufficient expansion of primary cells, EPI-iPSC was immortalized with the SV40 large T antigen. The immortalized EPI-iPSC cell line had a normal karyotype, and a short tandem repeat (STR) analysis verified that it was derived from hiPSCs. The EPI-iPSC cell line co-cultured with dental pulp stem cells displayed increased amelogenic and odontogenic gene expression, exhibited higher dentin sialoprotein (DSPP) protein expression, and promoted mineralized nodule formation. These results indicated that the direct co-culture of hESCs/hiPSCs with HERS/ERM successfully established dental epithelial-like stem cells. Moreover, this differentiation protocol could help with understanding the functional roles of cell-to-cell communication and tissue engineering of teeth.
Oncology and Cardiac Rehabilitation: An Underrated Relationship
Authors: Venturini E. , Iannuzzo G. , D’Andrea A. , Pacileo M. , Tarantini L. , Canale M.L. , Gentile M. , Vitale G. , Sarullo F.M. , Vastarella R. , Di Lorenzo A. , Testa C. , Parlato A. , Vigorito C. , Giallauria F.
Published: June 2020

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient’s cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.
Lithium Use during Pregnancy and the Risk of Miscarriage
Authors: Poels Eline M. P. , Kamperman Astrid M. , Vreeker Annabel , Gilden Janneke , Boks Marco P. , Kahn René S. , Ophoff Roel A. , Bergink Veerle
Published: June 2020

Recent studies have provided new data on the teratogenicity of lithium. Less is known about the risk of miscarriage after lithium use during pregnancy. The aim of this study was to investigate the association between lithium use during pregnancy and miscarriage. Participants were women with bipolar I disorder and one or more pregnancies, of which information on medication use and pregnancy outcome was available (n = 443). The unadjusted odds ratios for miscarriage after lithium use during pregnancy was calculated. Multilevel logistic regression was used to calculate the odds ratio, adjusted for the age at conception and the clustering of pregnancies per woman. Miscarriages occurred in 20.8% of the lithium-exposed pregnancies (16/77), compared with 10.9% of the unexposed pregnancies (40/366) (OR = 2.14; 95% CI: 1.13–4.06). The adjusted odds ratio of miscarriage after lithium use during pregnancy was 2.94 (95% CI: 1.39–6.22). Lithium use during pregnancy may increase the risk of miscarriage.
Deep Learning for Automated Detection of Cyst and Tumors of the Jaw in Panoramic Radiographs
Authors: Yang Hyunwoo , Jo Eun , Kim Hyung Jun , Cha In-ho , Jung Young-Soo , Nam Woong , Kim Jun-Young , Kim Jin-Kyu , Kim Yoon Hyeon , Oh Tae Gyeong , Han Sang-Sun , Kim Hwiyoung , Kim Dongwook
Published: June 2020

Patients with odontogenic cysts and tumors may have to undergo serious surgery unless the lesion is properly detected at the early stage. The purpose of this study is to evaluate the diagnostic performance of the real-time object detecting deep convolutional neural network You Only Look Once (YOLO) v2—a deep learning algorithm that can both detect and classify an object at the same time—on panoramic radiographs. In this study, 1602 lesions on panoramic radiographs taken from 2010 to 2019 at Yonsei University Dental Hospital were selected as a database. Images were classified and labeled into four categories: dentigerous cysts, odontogenic keratocyst, ameloblastoma, and no lesion. Comparative analysis among three groups (YOLO, oral and maxillofacial surgeons, and general practitioners) was done in terms of precision, recall, accuracy, and F1 score. While YOLO ranked highest among the three groups (precision = 0.707, recall = 0.680), the performance differences between the machine and clinicians were statistically insignificant. The results of this study indicate the usefulness of auto-detecting convolutional networks in certain pathology detection and thus morbidity prevention in the field of oral and maxillofacial surgery.
The Accuracy of Jaws Repositioning in Bimaxillary Orthognathic Surgery with Traditional Surgical Planning Compared to Digital Surgical Planning in Skeletal Class III Patients: A Retrospective Observational Study
Authors: Barone Martina , De Stefani Alberto , Baciliero Ugo , Bruno Giovanni , Gracco Antonio
Published: June 2020

Background: Technological progress has led to the transition to digital methods to perform surgical planning and to obtain surgical splints with CAD/CAM technologies. The present study aimed to compare the accuracy of jaw repositioning in bimaxillary orthognathic surgery using traditional and digital surgical planning in skeletal class III patients. Methods: This study included 60 skeletal class III patients divided into two groups based on the method used to perform surgical planning: traditional (T, n = 30) and digital (D, n = 30). For each patient, a 2D presurgical Visual Treatment Objective (VTO) was prepared and the outcome of the surgery was compared with that planned by using determined cephalometric measurements (ANB, SNA, SNB, Ar-Go-Me, S-Ar-Go). Statistical analysis showed that the measurements planned and those obtained after surgery were equivalent in Group D. For Group T, the analysis showed equivalence only for one of the considered measurements (ANB). By comparing the results of the two groups, Group D presented a lower level of error than Group T. Conclusions: Digital surgical planning performed significantly better in terms of accuracy of jaw repositioning than the traditional protocol.
Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analyses
Authors: Torrico Bàrbara , Antón-Galindo Ester , Fernàndez-Castillo Noèlia , Rojo-Francàs Eva , Ghorbani Sadaf , Pineda-Cirera Laura , Hervás Amaia , Rueda Isabel , Moreno Estefanía , Fullerton Janice M. , Casadó Vicent , Buitelaar Jan K. , Rommelse Nanda , Franke Barbara , Reif Andreas , Chiocchetti Andreas G. , Freitag Christine , Kleppe Rune , Haavik Jan , Toma Claudio , Cormand Bru
Published: June 2020

The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (c.659-660insT, p.L220Ffs*18). Here, we explored the contribution of the seven human 14-3-3 family members in ASD and other psychiatric disorders by investigating the: (i) functional impact of the 14-3-3ζ mutation p.L220Ffs*18 by assessing solubility, target binding and dimerization; (ii) contribution of common risk variants in 14-3-3 genes to ASD and additional psychiatric disorders; (iii) burden of rare variants in ASD and schizophrenia; and iv) 14-3-3 gene expression using ASD and schizophrenia transcriptomic data. We found that the mutant 14-3-3ζ protein had decreased solubility and lost its ability to form heterodimers and bind to its target tyrosine hydroxylase. Gene-based analyses using publicly available datasets revealed that common variants in YWHAE contribute to schizophrenia (p = 6.6 × 10−7), whereas ultra-rare variants were found enriched in ASD across the 14-3-3 genes (p = 0.017) and in schizophrenia for YWHAZ (meta-p = 0.017). Furthermore, expression of 14-3-3 genes was altered in post-mortem brains of ASD and schizophrenia patients. Our study supports a role for the 14-3-3 family in ASD and schizophrenia.
Comparison of Male and Female Patients in Louisiana Medical Marijuana Dispensaries
Authors: Allen H. Raymond , Boudreaux Doug , Keller Jeffrey N.
Published: June 2020

Relatively little is known in terms of patient demographics, indications, previous cannabis use, or the forms and dosages of medical marijuana (MM) dispensed for patients at MM dispensaries. Even less is known in terms of how male and female patients may differ in each of these aspects. The goal of the current study was to examine each of these variables using a retrospective analysis of deidentified patient data from MM dispensaries in Louisiana. Deidentified data were analyzed from web-based pharmacist–patient consultations at MM dispensaries throughout Louisiana. Data were collected during the first 6 months following the initiation of the MM dispensing program in Louisiana. A total of 1195 MM patients (598 male/597 female) were included in the analyses. The average age of the sample was 51.9 years (±14.8) and it was composed primarily of white patients (86.7%). Males and females were nearly identical in terms of average age, race, previous cannabis use, indication profile, and MM recommendations. Differences between males and females were observed in terms of opioid use, history of psychosis, presence of more than one indication, and the duration of previous cannabis use. Our data indicate that, in MM dispensaries of the Deep South state, there are numerous similarities—and some potentially important differences—between male and female MM patients. The importance of these differences, and the importance of continued data collection/analysis, for improving MM dispensing are discussed.
Short-Period Temporal Dispersion Repolarization Markers Predict 30-Days Mortality in Decompensated Heart Failure
Authors: Piccirillo Gianfranco , Moscucci Federica , Bertani Gaetano , Lospinuso Ilaria , Mastropietri Fabiola , Fabietti Marcella , Sabatino Teresa , Zaccagnini Giulia , Crapanzano Davide , Di Diego Ilaria , Corrao Andrea , Rossi Pietro , Magrì Damiano
Published: June 2020

Background and Objectives: Electrocardiographic (ECG) markers of the temporal dispersion of the myocardial repolarization phase have been shown able to identify chronic heart failure (CHF) patients at high mortality risk. The present prospective single-center study sought to investigate in a well-characterized cohort of decompensated heart failure (HF) patients the ability of short-term myocardial temporal dispersion ECG variables in predicting the 30-day mortality, as well as their relationship with N-terminal Pro Brain Natriuretic Peptide (NT-proBNP) plasmatic values. Method: One hundred and thirteen subjects (male: 59, 67.8%) with decompensated CHF underwent 5 min of ECG recording, via a mobile phone. We obtained QT end (QTe), QT peak (QTp) and T peak to T end (Te) and calculated the mean, standard deviation (SD), and normalized index (VN). Results: Death occurred for 27 subjects (24%) within 30 days after admission. Most of the repolarization indexes (QTe mean (p < 0.05), QTeSD (p < 0.01), QTpSD (p < 0.05), mean Te (p < 0.05), TeSD (p < 0.001) QTeVN (p < 0.05) and TeVN (p < 0.01)) were significantly higher in those CHF patients with the highest NT-proBNP (>75th percentile). In all the ECG data, only TeSD was significantly and positively related to the NT-proBNP levels (r: 0.471; p < 0.001). In the receiver operating characteristic (ROC) analysis, the highest accuracy for 30-day mortality was found for QTeSD (area under curve, AUC: 0.705, p < 0.01) and mean Te (AUC: 0.680, p < 0.01), whereas for the NT-proBNP values higher than the 75th percentile, the highest accuracy was found for TeSD (AUC: 0.736, p < 0.001) and QTeSD (AUC: 0.696, p < 0.01). Conclusion: Both mean Te and TeSD could be considered as reliable markers of worsening HF and of 30-day mortality. Although larger and possibly interventional studies are needed to confirm our preliminary finding, these non-invasive and transmissible ECG parameters could be helpful in the remote monitoring of advanced HF patients and, possibly, in their clinical management. (ClinicalTrials.gov number, NCT04127162).
Transient and Persistent Gastric Microbiome: Adherence of Bacteria in Gastric Cancer and Dyspeptic Patient Biopsies after Washing
Authors: Spiegelhauer Malene R. , Kupcinskas Juozas , Johannesen Thor B. , Urba Mindaugas , Skieceviciene Jurgita , Jonaitis Laimas , Frandsen Tove H. , Kupcinskas Limas , Fuursted Kurt , Andersen Leif P.
Published: June 2020

Helicobacter pylori is a common colonizer of the human stomach, and long-term colonization has been related to development of atrophic gastritis, peptic ulcers and gastric cancer. The increased gastric pH caused by H. pylori colonization, treatment with antibiotics or proton pump inhibitors (PPI) may allow growth of other bacteria. Previous studies have detected non-Helicobacter bacteria in stomach biopsies, but no conclusion has been made of whether these represent a transient contamination or a persistent microbiota. The aim of this study was to evaluate the transient and persistent bacterial communities of gastric biopsies. The washed or unwashed gastric biopsies were investigated by cultivation and microbiota analysis (16S rRNA gene-targeted amplicon sequencing) for the distribution of H. pylori and other non-Helicobacter bacteria. The number of cultured non-Helicobacter bacteria decreased in the washed biopsies, suggesting that they might be a transient contamination. No significant differences in the bacterial diversity were observed in the microbiome analysis between unwashed and washed biopsies. However, the bacterial diversity in biopsies shown H. pylori-positive and H. pylori-negative were significantly different, implying that H. pylori is the major modulator of the gastric microbiome. Further large-scale studies are required to investigate the transient and persistent gastric microbiota.
Cohen Syndrome Patient iPSC-Derived Neurospheres and Forebrain-Like Glutamatergic Neurons Reveal Reduced Proliferation of Neural Progenitor Cells and Altered Expression of Synapse Genes
Authors: Lee You-Kyung , Hwang Su-Kyeong , Lee Soo-Kyung , Yang Jung-eun , Kwak Ji-Hye , Seo Hyunhyo , Ahn Hyunjun , Lee Yong-Seok , Kim Janghwan , Lim Chae-Seok , Kaang Bong-Kiun , Lee Jae-Hyung , Lee Jin-A , Lee Kyungmin
Published: June 2020

Cohen syndrome (CS), a rare autosomal recessive disorder, has been associated with genetic mutations in the VPS13B gene, which regulates vesicle-mediated protein sorting and transport. However, the cellular mechanism underlying CS pathogenesis in patient-derived human neurons remains unknown. We identified a novel compound heterozygous mutation, due to homozygous variation of biparental origin and heterozygous variation inherited from the father, in the VPS13B gene in a 20-month-old female patient. To understand the cellular pathogenic mechanisms, we generated induced pluripotent stem cells (iPSCs) from the fibroblasts of the CS patient. The iPSCs were differentiated into forebrain-like functional glutamatergic neurons or neurospheres. Functional annotation from transcriptomic analysis using CS iPSC-derived neurons revealed that synapse-related functions were enriched among the upregulated and downregulated genes in the CS neurons, whereas processes associated with neurodevelopment were enriched in the downregulated genes. The developing CS neurospheres were small in size compared to control neurospheres, likely due to the reduced proliferation of SOX2-positive neural stem cells. Moreover, the number of SV2B-positive puncta and spine-like structures was significantly reduced in the CS neurons, suggesting synaptic dysfunction. Taking these findings together, for the first time, we report a potential cellular pathogenic mechanism which reveals the alteration of neurodevelopment-related genes and the dysregulation of synaptic function in the human induced neurons differentiated from iPSCs and neurospheres of a CS patient.
Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor—Rationale and Design of the IMAD Pilot Study
Authors: Stracke Sylvia , Lange Sandra , Bornmann Sarah , Kock Holger , Schulze Lara , Klinger-König Johanna , Böhm Susanne , Vogelgesang Antje , von Podewils Felix , Föel Agnes , Gross Stefan , Wenzel Katrin , Wallukat Gerd , Prüss Harald , Dressel Alexander , Kunze Rudolf , Grabe Hans J. , Langner Sönke , Dörr Marcus
Published: June 2020

Background: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease. In dementia patients, GPCR-agAABs against the α1- and ß2-adrenoceptors (α1AR- and ß2AR) were found at a prevalence of 50%. Elimination of agAABs by immunoadsorption (IA) was successfully applied in cardiovascular disease. The IMAD trial (Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor) investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer’s clinical syndrome within a one-year follow-up period. Methods: the IMAD trial is designed as an exploratory monocentric interventional trial corresponding to a proof-of-concept phase-IIa study. If cognition capacity of eligible patients scores 19–26 in the Mini Mental State Examination (MMSE), patients are tested for the presence of agAABs by an enzyme-linked immunosorbent assay (ELISA)-based method, followed by a bioassay-based confirmation test, further screening and treatment with IA and intravenous immunoglobulin G (IgG) replacement. We aim to include 15 patients with IA/IgG and to complete follow-up data from at least 12 patients. The primary outcome parameter of the study is uncorrected mean cerebral perfusion measured in mL/min/100 gr of brain tissue determined by magnetic resonance imaging with arterial spin labeling after 12 months. Conclusion: IMAD is an important pilot study that will analyze whether the removal of α1AR-agAABs by immunoadsorption in α1AR-agAAB-positive patients with suspected Alzheimer’s clinical syndrome may slow the progression of dementia and/or may improve vascular functional parameters.