4open最新文献

{"title":"Fundamental in vitro 3D human skin equivalent tool development for assessing biological safety and biocompatibility – towards alternative for animal experiments","authors":"Ayesha Idrees, I. Schmitz, A. Zoso, Dierk Gruhn, S. Pacharra, Siegfried Shah, G. Ciardelli, R. Viebahn, V. Chiono, J. Salber","doi":"10.1051/FOPEN/2021001","DOIUrl":"https://doi.org/10.1051/FOPEN/2021001","url":null,"abstract":"Nowadays, human skin constructs (HSCs) are required for biomaterials, pharmaceuticals and cosmetics in vitro testing and for the development of complex skin wound therapeutics. In vitro three-dimensional (3D) dermal-epidermal based interfollicular, full-thickness, human skin equivalent (HSE) was here developed, recapitulating skin morphogenesis, epidermal differentiation, ultra-structure, tissue architecture, and barrier function properties of human skin. Different 3D cell culture conditions were tested to optimize HSE maturation, using various commercially available serum/animal component-free and/or fully defined media, and air-liquid interface (ALI) culture. Optimized culture conditions allowed the production of HSE by culturing normal human dermal fibroblasts (NHDFs) for 5–7 days in CELLnTEC-Prime Fibroblast (CnT-PR-F) medium and then culturing normal human epidermal keratinocytes (NHEKs) for 3 days in CELLnTEC-Prime Epithelial culture (CnT-PR) medium on them. Co-culture was then submerged overnight in CELLnTEC-Prime-3D barrier (CnT-PR-3D) medium to stimulate cell-cell contact formation and finally placed at ALI for 15–20 days using CnT-PR-3D medium. Histological analysis revealed uniform distribution of NHDFs in the dermal layer and their typical elongated morphology with filopodia. Epidermal compartment showed a multi-layered structure, consisting of stratum basale, spinosum, granulosum, and corneum. NHDFs and keratinocytes of basal layer were positive for the proliferation marker Kiel 67 (Ki-67) demonstrating their active state of proliferation. The presence of typical epidermal tissue proteins (keratins, laminins, filaggrin, loricin, involucrin, and β-tubulin) at their correct anatomical position was verified by immunohistochemistry (IHC). Moreover, transmission electron microscopy (TEM) analyses revealed basement membrane with lamina lucida, lamina densa, hemidesmosomes and anchoring fibers. The epidermal layers showed abundant intracellular keratin filaments, desmosomes, and tight junction between keratinocytes. Scanning electron microscopy (SEM) analyses showed the interwoven network of collagen fibers with embedded NHDFs and adjacent stratified epidermis up to the stratum corneum similar to native human skin. HSE physiological static contact angle confirmed the barrier function. The developed HSE represents a fundamental in vitro tool to assess biocompatibility of biomaterials, pharmacotoxicity, safety and effectiveness of cosmetics, as well as to investigate skin biology, skin disease pathogenesis, wound healing, and skin infection.","PeriodicalId":6841,"journal":{"name":"4open","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88952672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of amplitude-modulated radiofrequency electromagnetic fields in advanced hepatocellular carcinoma","authors":"Arthur W. Blackstock, A. Benson, M. Kudo, Hugo Jimenez, Preeya F. Achari, Callum McGrath, Volker Kirchner, L. Wagner, N. O’Connell, Kathy Walker, Valerie K. Pasche, R. D’Agostino, A. Barbault, B. Pasche","doi":"10.1051/fopen/2021003","DOIUrl":"https://doi.org/10.1051/fopen/2021003","url":null,"abstract":"Importance: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Despite the recent approval of several new agents, long-term disease control remains elusive for most patients. Administration of 27.12 MHz radiofrequency (RF) electromagnetic fields (EMF) by means of a spoon-shaped antenna (TheraBionic P1 device) placed on the anterior part of the tongue results in systemic delivery of low and safe levels of RF EMF from head to toe. Objective: To report treatment outcomes and adverse events associated with treatment with the TheraBionic P1 device in comparison to suitable historical placebo and actively treated controls. Design: Pooled case series with comparison to historical controls. Participants: Patients with advanced HCC receiving this treatment, 18 real-world patients and 41 patients from a previously reported phase II study. Historical controls from previously conducted clinical trials. Interventions: Three hours daily treatment with the TheraBionic P1 device compared with standard of care as received by historical controls in the previously conducted trials. Main outcomes and measures: Overall survival (OS), time to progression, response rate, and adverse events in the combined pooled patients and in appropriate subgroups comparable to the historical control groups. Results: In the pooled treatment group, median OS of patients with Child-Pugh A disease (n = 32) was 10.36 (95% CI 5.42–14.07) months, 4.44 (95% CI 1.64–7.13) months for patients with Child-Pugh B disease (n = 25), and 1.99 (95% CI 0.76–3.22) months for patients with Child-Pugh C disease (n = 2). Median OS for Child-Pugh A patients was 2.62 (33.9%) months longer than the 7.74 months OS of comparable historical controls (p = 0.036). The 4.73 (95% CI 1.18–8.28) months median OS for Child-Pugh B patients receiving TheraBionic P1 device as first line therapy is slightly higher than the 4.6 months median OS of historical controls receiving Sorafenib as first line therapy. Only grade 1 mucositis and fatigue were reported by patients using the device, even among Child-Pugh B and C patients. No patients discontinued treatment because of adverse events. Conclusions and Relevance: Treatment of advanced HCC with the TheraBionic P1 device is well tolerated, even in patients with severely impaired liver function, and results in improved overall survival compared to historical controls without any significant adverse events, even after many years of continuous treatment. This treatment modality appears to be well suited for patients who have failed or are intolerant to currently approved therapies.","PeriodicalId":6841,"journal":{"name":"4open","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75165319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The origin of the elements and other implications of gravitational wave detection for nuclear physics","authors":"D. Lunney","doi":"10.1051/fopen/2020014","DOIUrl":"https://doi.org/10.1051/fopen/2020014","url":null,"abstract":"The neutron-star collision revealed by the event GW170817 gave us a first glimpse of a possible birthplace of most of our heavy elements. The multi-messenger nature of this historical event combined gravitational waves, a gamma-ray burst and optical astronomy of a “kilonova”, bringing the first observations of rapid neutron capture (r process) nucleosynthesis after 60 years of speculation. Modeling the r process requires a prodigious amount of nuclear-physics ingredients: practically all the quantum state and interaction properties of virtually all neutron-rich nuclides, many of which may never be produced in the laboratory! Another essential contribution of nuclear physics to neutron stars (and their eventual coalescence) is the equation of state (EoS) that defines their structure and composition. The EoS, combined with the knowledge of nuclear binding energies, determines the elemental profile of the outer crust of a neutron star and the relationship between its radius and mass. In addition, the EoS determines the form of the gravitational wave signal. This article combines a tutorial presentation and bibliography with recent results that link nuclear mass spectrometry to gravitational waves via neutron stars.","PeriodicalId":6841,"journal":{"name":"4open","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74185242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The general case of cutting of Generalized Möbius-Listing surfaces and bodies","authors":"J. Gielis, I. Tavkhelidze","doi":"10.1051/fopen/2020007","DOIUrl":"https://doi.org/10.1051/fopen/2020007","url":null,"abstract":"The original motivation to study Generalized Möbius-Listing GML surfaces and bodies was the observation that the solution of boundary value problems greatly depends on the domains. Since around 2010 GML’s were merged with (continuous) Gielis Transformations, which provide a unifying description of geometrical shapes, as a generalization of the Pythagorean Theorem. The resulting geometrical objects can be used for modeling a wide range of natural shapes and phenomena. The cutting of GML bodies and surfaces, with the Möbius strip as one special case, is related to the field of knots and links, and classifications were obtained for GML with cross sectional symmetry of 2, 3, 4, 5 and 6. The general case of cutting GML bodies and surfaces, in particular the number of ways of cutting, could be solved by reducing the 3D problem to planar geometry. This also unveiled a range of connections with topology, combinatorics, elasticity theory and theoretical physics.","PeriodicalId":6841,"journal":{"name":"4open","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74062052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A survey on pseudo-Chebyshev functions","authors":"P. Ricci","doi":"10.1051/fopen/2020001","DOIUrl":"https://doi.org/10.1051/fopen/2020001","url":null,"abstract":"In recent articles, by using as a starting point the Grandi (Rhodonea) curves, sets of irrational functions, extending to the fractional degree the 1st, 2nd, 3rd and 4th kind Chebyshev polynomials have been introduced. Therefore, the resulting mathematical objects are called pseudo-Chebyshev functions. In this survey, the results obtained in the above articles are presented in a compact way, in order to make the topic accessible to a wider audience. Applications in the fields of weighted best approximation, roots of 2 × 2 non-singular matrices and Fourier series are derived.","PeriodicalId":6841,"journal":{"name":"4open","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86696572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19: Monitoring the propagation of the first waves of the pandemic","authors":"W. Knafo","doi":"10.1051/fopen/2020005","DOIUrl":"https://doi.org/10.1051/fopen/2020005","url":null,"abstract":"Introduction: A phenomenological approach is proposed to monitor the propagation of the first waves of the COVID-19 pandemic.Method: A large set of data collected during the first months of 2020 is compiled into a series of semi-logarithmic plots, for a selection of 32 countries from the five continents.Results: Three regimes are identified in the propagation of an epidemic wave: a pre-epidemic regime 1, an exponential-growth regime 2, and a resorption regime 3. A two-parameters scaling of the first-wave death variation reported in China is used to fit the first-wave data reported in other countries. Comparison is made between the propagation of the pandemic in different countries, which are classified into four groups, from Group A where the pandemic first waves were contained efficiently, to Group D where the pandemic first waves widely spread. All Asian countries considered here, where fast and efficient measures have been applied, are in Group A. Group D is composed of Western-European countries and the United States of America (USA), where late decisions and confused political communication (pandemic seriousness, protection masks, herd immunity, etc.) led to a large number of deaths.Discussion:The threat of resurging epidemic waves following a lift of lockdown measures is discussed. The results obtained in Asian countries from group A, as Hong Kong and South Korea, are highlighted, and the measures taken there are presented as examples that other countries may follow.","PeriodicalId":6841,"journal":{"name":"4open","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82174242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A copula-based quantifying of the relationship between race inequality among neighbourhoods in São Paulo and age at death","authors":"V. González-López, Rafael Rodrigues de Moraes","doi":"10.1051/fopen/2020012","DOIUrl":"https://doi.org/10.1051/fopen/2020012","url":null,"abstract":"In this paper, we combine two statistical tools with the objective of creating models that represent the dependence between (i) the proportion of the black/brown population in relation to the total population of a neighborhood (pct) and (ii) the average age at which people died in the neighborhood (age). We explore the dependence between pct and age in São Paulo city, Brazil, during 2018. The statistical tools are models of copulas and informative and non-informative settings according to the Bayesian perspective. The different scenarios and models allow us to delineate the dependence between pct and age, and, through the Bayesian Information Criterion we can indicate which of these models best represents the data. The approach implemented here allows us to define estimates of variations in life expectancy conditioned by percentage intervals of pct. With them, we can conclude that on average all the scenarios point to a decrease in life expectancy by increasing the proportion of pct. When conditioning the percentages of pct to 4 intervals (0, 0.25], (0.25, 0.5], (0.5, 0.75], (0.75, 1] respectively, we note that the expectation is reduced in average at a constant rate from one interval in comparison with the immediate and next interval from left to right in [0, 1].","PeriodicalId":6841,"journal":{"name":"4open","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89731681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19: SARS-CoV-2 susceptibility in healthcare workers – cluster study at a German Teaching Hospital","authors":"M. Scherer, Alexander von Freyburg, B. Brücher, I. Jamall, Annette Schmidt, H. Hagedorn","doi":"10.1051/fopen/2020006","DOIUrl":"https://doi.org/10.1051/fopen/2020006","url":null,"abstract":"Purpose: The local health department (in German: Gesundheitsamt) ordered a shutdown of a teaching hospital due to the severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak – one index patient and five infected healthcare workers – and put it under quarantine. For the first time, all patients plus all employees of one German hospital (healthcare providers, physicians, and nurses) were tested to detect silent or asymptomatic carriers. Methods: A serial polymerase chain reaction (PCR) test for SARS-CoV-2 was performed three times (1) between April 3rd and 5th, 2020 [n = 1171], (2) between April 8th and 9th, 2020 [n = 953] and (3) between April 14th and 17th, 2020 [n = 983]. Results: The teaching hospital’s proven coronavirus disease 2019 (COVID-19) patient load on Friday, April 3rd, 2020, was 34 patients, of whom 11 were on ventilation in the intensive care unit (ICU), one in the intermediate care unit (IMC), and 22 in the infectious disease ward. Another 32 patients in a different infectious disease ward were suspected for COVID-19 with test results pending. COVID-19 silent carrier (asymptomatic) positivity rates based on the phases of testing were (1) n = 24 (2.1%), (2) n = 25 (2.6%) and n = 9 (0.9%). The cumulative infection rate for healthcare providers, physical therapists, physicians, and nurses was 1.8%, 4.5%, 4.8%, and 11.9% which were associated with the type and extent of COVID-19 patient contact (p < 0.05). Conclusion: Despite prior proper preparation, a COVID-19 positive patient load of up to 34.8% (46 of 132 hospital beds) resulted in a 10- to 20-fold increase in risk for healthcare workers for SARS-CoV-2 compared to the general population. Because of asymptomatic carriers, a COVID-19-free hospital cannot be expected to exist. Based on our experience, repeated testing of all staff members with patient contact is necessary and is the best option to effectively contain the virus. Those having the most contact with patients had the highest risk of becoming infected (10- to 20-fold higher risk), with nurses being at the highest risk.","PeriodicalId":6841,"journal":{"name":"4open","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81192479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partition Markov Model for Covid-19 Virus","authors":"J. E. García, V. González-López, G. Tasca","doi":"10.1051/fopen/2020013","DOIUrl":"https://doi.org/10.1051/fopen/2020013","url":null,"abstract":"In this paper, we investigate a specific structure within the theoretical framework of Partition Markov Models (PMM) [see García Jesús and González-López, Entropy 19, 160 (2017)]. The structure of interest lies in the formulation of the underlying partition, which defines the process, in which, in addition to a finite memory o associated with the process, a parameter G is introduced, allowing an extra dependence on the past complementing the dependence given by the usual memory o. We show, by simulations, how algorithms designed for the classic version of the PMM can have difficulties in recovering the structure investigated here. This specific structure is efficient for modeling a complete genome sequence, coming from the newly decoded Coronavirus Covid-19 in humans [see Wu et al., Nature 579, 265–269 (2020)]. The sequence profile is represented by 13 units (parts of the state space’s partition), for each of the 13 units, their respective transition probabilities are computed for any element of the genetic alphabet. Also, the structure proposed here allows us to develop a comparison study with other genomic sequences of Coronavirus, collected in the last 25 years, through which we conclude that Covid-19 is shown next to SARS-like Coronaviruses (SL-CoVs) from bats specimens in Zhoushan [see Hu et al., Emerg Microb Infect 7, 1–10 (2018)].","PeriodicalId":6841,"journal":{"name":"4open","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85663444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of fraud classification","authors":"J. E. García, V. González-López, Hugo Helito da Silva, T. S. Silva","doi":"10.1051/fopen/2020010","DOIUrl":"https://doi.org/10.1051/fopen/2020010","url":null,"abstract":"In this article, we define consumers’ profiles of electricity who commit fraud. We also compare these profiles with users’ profiles not classified as fraudsters in order to determine which of these clients should receive an inspection. We present a statistically consistent method to classify clients/users as fraudsters or not, according to the profiles of previously identified fraudsters. We show that it is possible to use several characteristics to inspect the classification of fraud; those aspects are represented by the coding performed in the observed series of clients/users. In this way, several encodings can be used, and the client risk can be constructed to integrate complementary aspects. We show that the classification method has success rates that exceed 77%, which allows us to infer confidence in the methodology.","PeriodicalId":6841,"journal":{"name":"4open","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73443393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}