bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Covid-19 in Multiple Sclerosis Patients Treated With Ocrelizumab: A Case Series
Authors: De Mercanti Stefania F. , Vercellino Marco , Bosa Chiara , Alteno Anastasia , Schillaci Valentina , Clerico Marinella , Cavalla Paola 
Published: October 2021

Introduction: Limited data are available on the course of Coronavirus disease 2019 (COVID-19) in people with Multiple Sclerosis (MS). More real-world data are needed to help the MS community to manage MS treatment properly. In particular, it is important to understand the impact of immunosuppressive therapies used to treat MS on the outcome of COVID-19.Methods: We retrospectively collected data on all confirmed cases of COVID-19 in MS patients treated with ocrelizumab, followed in two MS Centers based in University Hospitals in Northern Italy from February 2020 to June 2021.Results: We identified 15 MS patients treated with ocrelizumab with confirmed COVID-19 (mean age, 50.47 ± 9.1 years; median EDSS, 3.0; range 1.0–7.0). Of these, 14 were confirmed by nasal swab and 1 was confirmed by a serological test. COVID-19 severity was mild to moderate in the majority of patients (n = 11, 73.3%; mean age, 49.73; median EDSS 3.0). Four patients (26.7%; mean age, 52.5 years; median EDSS, 6) had severe disease and were hospitalized; one of them died (age 50, EDSS 6.0, no other comorbidities). None of them had underlying respiratory comorbidities.Conclusion: This case series highlights the large variability of the course of COVID-19 in ocrelizumab-treated MS patients. The challenges encountered by the healthcare system in the early phase of the COVID-19 pandemic might have contributed to the case fatality ratio observed in this series. Higher MS-related disability was associated with a more severe COVID-19 course.
Efficacy of Cyproheptadine Monotherapy in Hepatocellular Carcinoma With Bone Metastasis: A Case Report
Authors: Feng Yu-Min , Chen Tsung-Hsien , Berman Dara , Chou Chu-Kuang , Liao Kai-Sheng , Hsieh Ming-Chih , Chen Chi-Yi 
Published: October 2021

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. Particularly, cases of bone metastasis have poorer prognoses.Case PresentationA 62-year-old woman with suspected advanced HCC accompanied by bone metastasis with severe back pain and sciatica showed disease remission after cyproheptadine monotherapy. Initially, her serum alpha fetal protein (AFP) level was high, reaching up to 17697.62 ng/ml. A dose of 4 mg cyproheptadine, 3 times a day for 17 months was prescribed as the only treatment. Within 3 months, the serum AFP level gradually normalized down to 4.3 ng/ml. Both liver biopsy and bone biopsies were subsequently performed after 2 weeks of cyproheptadine. The results showed no malignancy. During the 34 months of follow-ups, the serum AFP remained normal in the range of 1.05 to 2.86 ng/ml. The patient has survived for 5 years without back pain and sciatica thus far.ConclusionsThis is the first report to investigate a successful clinical approach in cyproheptadine monotherapy for an advanced HCC patient with bone metastasis. We recommend cyproheptadine as a potential anti-HCC agent for the treatment of HCC with bone metastasis, but more related studies such as prospectively clinical trials, and ideally randomized trials are still needed.
Recombinant Human Adenovirus-p53 Therapy for the Treatment of Cervical Cancer: A Meta-Analysis
Authors: Guo Yaru , Chen Jiuzhou , Zhang Xiwen , Fang Miao , Xu Mingna , Zhang Longzhen , Rao Enyu , Xin Yong 
Published: October 2021

ObjectivesTo evaluate the clinical curative effects and toxicity of recombinant human adenovirus-p53 injection (rAd-p53) plus chemotherapy (CT), radiotherapy (RT), or concurrent chemoradiotherapy (CRT) for the treatment of cervical cancer.MethodsWe identified 14 eligible studies in the PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wangfangdate, CBM, and VIP databases from their inception to May 2021 and performed meta-analyses using RevMan version 5.3.ResultsThis analysis included 14 studies involving 737 patients. The results of the meta-analysis results showed significantly improved complete remission (odds ratio [OR] = 2.54, 95% confidence interval [CI]: 1.74–3.70, p &lt; 0.00001), partial remission (OR = 1.56, 95% CI: 1.14–2.14, p = 0.006), and object response (OR = 4.47, 95% CI: 3.02–6.60, p &lt; 0.00001) rates in the rAd-p53 combination therapy group compared to those in the CT/RT/CRT group. The results of subgroup analyses of CT/RT/CRT were consistent with the overall results. Regarding the incidence of adverse reactions, only the occurrence rate of fever (OR = 18.21, 95% CI: 10.54–31.47, p &lt; 0.00001) in the rAd-p53 combination group was higher than that in the CT/RT/CRT group. No other significant differences were observed in other adverse reactions.ConclusionRAd-p53 combined with CT/RT/CRT for the treatment of cervical cancer showed significant advantages in efficacy and safety compared to those in the CT/RT/CRT group. Therefore, rAd-p53 has great potential as an effective therapy for cervical cancer.Systematic Review Registrationhttps://inplasy.com/inplasy-2021-5-0058/.
Choroidal Vascularity Index in CHM Carriers
Authors: Mucciolo Dario Pasquale , Giorgio Dario , Lippera Myrta , Passerini Ilaria , Pelo Elisabetta , Cipollini Francesca , Sodi Andrea , Virgili Gianni , Giansanti Fabrizio , Murro Vittoria 
Published: October 2021

PurposeTo assess the choroidal structure using the Choroidal Vascularity Index (CVI) and analyse choroidal changes in choroideremia (CHM) carriers.Material and MethodsFemale CHM carriers, genetically characterized, and a control group were recruited at the Eye Clinic of Careggi Teaching Hospital, Florence. The patients underwent a complete ophthalmic evaluation and retinal imaging. In particular, the Stromal Area (SA), Luminal Area (LA), Total Choroidal Area (TCA), CVI, and Subfoveal Choroidal Thickness (SFCT) were calculated for each eye using Optical Coherence Tomography (OCT) examinations.ResultsTwelve eyes of 6 CHM carriers and 14 eyes of 7 age-matched controls were analysed. The mean SFCT was 270.9 ± 54.3μm in carriers and 281.4 ± 36.8μm in controls (p = 0.564); LA was 0.99 ± 0.25mm2 and 1.01 ± 0.13mm2 (p = 0.172); SA was 0.53 ± 0.09mm2 and 0.59 ± 0.07mm2 (p = 0.075), and TCA was 1.53 ± 0.34mm2 and 1.69 ± 0.19mm2 respectively (p = 0.146). Mean CVI measured 64.03 ± 3.98% in the CHM carriers and 65.25 ± 2.55% in the controls (p = 0.360).ConclusionsThe CVI and CVI-related parameters (SA, LA, and TCA) do not differ between CHM female carriers and controls. These findings reveal a preserved choroidal vasculature in eyes with RPE impairment and support the primary role of RPE in the pathogenesis of CHM disease.
Mechanistic Modeling of Placental Drug Transfer in Humans: How Do Differences in Maternal/Fetal Fraction of Unbound Drug and Placental Influx/Efflux Transfer Rates Affect Fetal Pharmacokinetics?
Authors: Liu Xiaomei I. , Green Dionna J. , van den Anker John N. , Rakhmanina Natella Y. , Ahmadzia Homa K. , Momper Jeremiah D. , Park Kyunghun , Burckart Gilbert J. , Dallmann André 
Published: October 2021

Background: While physiologically based pharmacokinetic (PBPK) models generally predict pharmacokinetics in pregnant women successfully, the confidence in predicting fetal pharmacokinetics is limited because many parameters affecting placental drug transfer have not been mechanistically accounted for.Objectives: The objectives of this study were to implement different maternal and fetal unbound drug fractions in a PBPK framework; to predict fetal pharmacokinetics of eight drugs in the third trimester; and to quantitatively investigate how alterations in various model parameters affect predicted fetal pharmacokinetics.Methods: The ordinary differential equations of previously developed pregnancy PBPK models for eight drugs (acyclovir, cefuroxime, diazepam, dolutegravir, emtricitabine, metronidazole, ondansetron, and raltegravir) were amended to account for different unbound drug fractions in mother and fetus. Local sensitivity analyses were conducted for various parameters relevant to placental drug transfer, including influx/efflux transfer clearances across the apical and basolateral membrane of the trophoblasts.Results: For the highly-protein bound drugs diazepam, dolutegravir and ondansetron, the lower fraction unbound in the fetus vs. mother affected predicted pharmacokinetics in the umbilical vein by ≥10%. Metronidazole displayed blood flow-limited distribution across the placenta. For all drugs, umbilical vein concentrations were highly sensitive to changes in the apical influx/efflux transfer clearance ratio. Additionally, transfer clearance across the basolateral membrane was a critical parameter for cefuroxime and ondansetron.Conclusion: In healthy pregnancies, differential protein binding characteristics in mother and fetus give rise to minor differences in maternal-fetal drug exposure. Further studies are needed to differentiate passive and active transfer processes across the apical and basolateral trophoblast membrane.
Experience of a Strategy Including CYP2C19 Preemptive Genotyping Followed by Therapeutic Drug Monitoring of Voriconazole in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation
Authors: García-García Irene , Dapía Irene , Montserrat Jaime , Martinez de Soto Lucía , Bueno David , Díaz Lucía , Queiruga Javier , Rodriguez Mariblanca Amelia , Guerra-García Pilar , Ramirez Elena , Frías Jesus , Pérez Martínez Antonio , Carcas-Sansuan Antonio J. , Borobia Alberto M. 
Published: October 2021

Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype. In 2017, in our hospital, a clinical protocol was developed for individualization of VCZ in immunocompromised patients based on preemptive genotyping of CYP2C19 and dosing proposed by Hicks et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) clinical guidelines, and routine therapeutic drug monitoring (TDM). We made a retrospective review of a cohort of 28 immunocompromised pediatric patients receiving VCZ according to our protocol. CYP2C19 gene molecular analysis was preemptively performed using PharmArray®. Plasma trough concentrations were measured by immunoassay analysis until target concentrations (1–5.5 μg/ml) were reached. Sixteen patients (57.14%) achieved VCZ trough target concentrations in the first measure after the initial dose based on PGx. This figure is similar to estimations made by Hicks et al. in their simulation (60%). Subdividing by phenotype, our genotyping and TDM-combined strategy allow us to achieve target concentrations during treatment/prophylaxis in 90% of the CYP2C19 Normal Metabolizers (NM)/Intermediate Metabolizers (IM) and 100% of the Rapid Metabolizers (RM) and Ultrarapid Metabolizers (UM) of our cohort. We recommended modifications of the initial dose in 29% (n = 8) of the patients. In RM ≥12 years old, an increase of the initial dose resulted in 50% of these patients achieving target concentrations in the first measure after initial dose adjustment based only on PGx information. Our experience highlights the need to improve VCZ dose predictions in children and the potential of preemptive genotyping and TDM to this aim. We are conducting a multicenter, randomized clinical trial in patients with risk of aspergillosis in order to evaluate the effectiveness and efficiency of VCZ individualization: VORIGENIPHARM (EudraCT: 2019-000376-41).
Analysis of Psychological Trends and Policy Recommendations of Medical Staff in Northern China in the Latter Stages of the COVID-19 Pandemic
Authors: Yang Xueping , Miao Junxiao , Fan Weizhong , Wang Lili , Sun Shuning , Li Hongshi , Wang Na , Wang Xuesong , Lin Muhui , He Ru 
Published: October 2021

Aim: Since the 2019 coronavirus disease (COVID-19) outbreak, medical staff have faced greater psychological stress and are prone to psychological problems such as anxiety and depression, as confirmed by several studies. This study further clarifies the psychological status of Chinese medical staff during the stable phase of the pandemic through a cross-sectional investigation in a large population sample in northern China.Methods: Subjects: Clinical frontline medical staff from seven hospitals in Liaoning Province were recruited from November 2020 to February 2021.Research Tools: The research tools used were the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Simplified Coping Style Questionnaire (SCSQ), and General Status Questionnaire.Statistical Analysis: SPSS 22.0, ANOVA variance analysis, and multiple logistics regression were used for statistical analysis. P-values of &lt;0.05 indicated significant statistical differences.Results: A total of 3,144 medical staff completed the survey (599 men [19.1%] and 2,545 women [80.9%]; 1,020 doctors [32.4%] and 2,124 nurses [67.6%]). Among all subjects, the rates of anxiety and depression were 21.1% (663/3, 144) and 43.9% (1,381/3,144), respectively. Multiple logistic comparative analysis revealed that age (OR = 1.272, 95% CI = 1.036–1.561, P = 0.022), the need for psychological counseling (OR = 1.566, 95% CI = 1.339–1.830, P &lt; 0.001), and the coexistence of depression (OR = 0.050, 95% CI = 0.038–0.066, P &lt; 0.001) were significantly associated with anxiety. Coexisting anxiety was also associated with the occurrence of depression (OR = 0.050, 95% CI = 0.038–0.065, P &lt; 0.001).Conclusions: In the later stages of the pandemic in China, the occurrence rates of anxiety and depression among medical staff remain high. In addition to age, there is little correlation between anxiety or depression and general factors such as gender and profession. As a special group, medical staff show different psychological changes at various times during a stressful event. Concerning for the psychological needs of medical staff and different psychologically oriented policy implementation are needed.
The Story of a Re-Operating Windmill
Authors: Bitay Enikő , Márton László , Talpas János 
Published: October 2021

Abstract
Research on the history of the development of grain milling structures is a priority topic of the Department of Technical Sciences of the Transylvanian Museum Association. Quite a few publications and study volumes contain the results of the research. The present dissertation presents another grinding structure, the windmill, its reconstruction, creating a connection between the theoretical foundations and the practical implementation. Although it was built as a museum and tourist object, it is also a significant work from the point of view of technical history.
The Felsőszentiván windmill is powered by a 14-meter-diameter windmill. The mill has a two-stage accelerator gear that increases the low, non-grinding speed of the wind turbine for the rotation typical of grindstone mills.
The upper stones of a pair of grindstones rest on a vertical axis, and by raising this the gap between the stones can be adjusted. This determines the particle size of the grind. The windmill consists of three functional parts: a windmill, an accelerator gear and a grain mill made up of a pair of grindstones.
Industry and Research: New Collaborative Perspectives in the Industry 4.0 Era
Authors: Forgó Zoltán , Bakos Levente 
Published: October 2021

Abstract
The paper presents some challenges of developing DIHs (Digital Innovation Hubs) based on the Industry 4.0 principles in Transylvania (Romania). DIHs have proven to be successful as knowledge transfer centers especially in information technologies, but they are still a novelty in the field of manufacturing technologies and industrial engineering in many regions. The paper presents conceptual possibilities of developing a manufacturing technology based DIH in Romania, based on cooperation among local organizations.
An Analysis of Manufacturing Precision of Involute Worms Using a Kinematical Model
Authors: Kelemen Csongor , Máté Márton 
Published: October 2021

Abstract
The manufacturing precision of involute worms constitutes a major requirement. On the one hand, the worm constitutes the input element of the worm drive; secondly, the involute helical surface is the basic surface of an involute worm-hob. This paper presents an analytic comparison between the involute surfaces obtained using theoretical equations, kinematic simulation of the cutting and the surface charged with errors. The surface error is considered the distance along the normal direction to the theoretical surface, measured between this and the surface charged with simulated manufacturing errors. The main sources of errors are considered the center-error of the edge plane, the edge profile error and deviation of the axial feed direction from the axis of the worm. The theoretical results allow us to conclude that the influence of the edge profile error is the largest. It is followed by the parallelism error between the feed direction and the axis of the worm, and finally, the center error of the tool edge.
Cутність адміністративних процедур в діяльності Служби безпеки України як суб’єкта забезпечення критичної інфраструктури
Authors: Безпалова О. , Осипчук І. 
Published: October 2021

Доведено, що адміністративна процедура в діяльності СБУ щодо забезпечення критичної інфраструктури – це законодавчо визначена юридична конструкція послідовно здійснюваних дій, що закріплена адміністративно-процедурними нормами і спрямована на виконання позитивної діяльності щодо запобігання посяганням на об’єкти критичної інфраструктури. Сформульовано особливості зазначеної категорії з урахуванням суб’єкта її здійснення.
Наголошено, що при здійсненні адміністративно-процедурної діяльності СБУ щодо охорони об’єктів критичної інфраструктури остання здебільшого є правообмежувальною та такою, що сьогодні не завжди має нормативно визначений стадійний характер, що пов’язано з необхідністю оперативно, без зволікань виявляти загрози і ризики, які впливають на функціональність та безпечність об’єктів критичної інфраструктури.
Доведено, що сьогодні нормативного закріплення отримали лише адміністративні процедури охорони об’єктів інформаційної критичної інфраструктури СБУ. Це свідчить про те, що перелік об’єктів критичної інфраструктури, який наразі визначений проєктом Закону України «Про критичну інфраструктуру та її захист», є неповним, оскільки, по-перше, поза увагою залишився об’єкт інформаційної критичної інфраструктури, а по-друге – вимагає розширення кола повноважень СБУ щодо забезпечення охорони об’єктів критичної інфраструктури, особливо в діяльності, що стосується надання послуг у галузі енергетики, у сфері використання ядерної енергії, хімічної промисловості, оборонно-промислового комплексу, електронних комунікацій, у банківському та фінансовому секторах.
Quantitative control of plasma and surface reactions for dielectric film etching
Authors: Tatsumi Tetsuya 
Published: October 2021

Abstract
This paper reviews reaction control in the dry etching of insulating films. High ion fluxes are required for high-speed SiO2 processing. However, because atomic F generation due to excessive fluorocarbon gas dissociation causes reduced selectivity, the number of electron collisions should be reduced by using short residence times. The C–F-based polymer thickness formed during processing varies based on the oxygen content of the material to be etched. To achieve high etch selectivity, the incident flux balance must be adjusted quantitatively to ensure that the polymer becomes thinner during etching and thicker as the underlying material is exposed. Even under high selectivity conditions, incident ions cause damage at the moment the underlying material is exposed. To suppress this damage, the ion penetration depth, which depends on both ion energy distribution and ion composition, must be reduced. Recently, atomic layer etching combined with C–F polymer deposition and removal using Ar ion irradiation has been studied. To improve the accuracy of such cyclic etching processes, it is important to understand and control the transient states of both plasma and surface reactions quantitatively.
RANDOM MULTI-MODAL DEEP LEARNING IN THE PROBLEM OF IMAGE RECOGNITION
Authors: Паршин А.И. , Аралов М.Н. , Барабанов В.Ф. , Гребенникова Н.И. 
Published: October 2021

Задача распознавания изображений - одна из самых сложных в машинном обучении, требующая от исследователя как глубоких знаний, так и больших временных и вычислительных ресурсов. В случае использования нелинейных и сложных данных применяются различные архитектуры глубоких нейронных сетей, но при этом сложным вопросом остается проблема выбора нейронной сети. Основными архитектурами, используемыми повсеместно, являются свёрточные нейронные сети (CNN), рекуррентные нейронные сети (RNN), глубокие нейронные сети (DNN). На основе рекуррентных нейронных сетей (RNN) были разработаны сети с долгой краткосрочной памятью (LSTM) и сети с управляемыми реккурентными блоками (GRU). Каждая архитектура нейронной сети имеет свою структуру, свои настраиваемые и обучаемые параметры, обладает своими достоинствами и недостатками. Комбинируя различные виды нейронных сетей, можно существенно улучшить качество предсказания в различных задачах машинного обучения. Учитывая, что выбор оптимальной архитектуры сети и ее параметров является крайне трудной задачей, рассматривается один из методов построения архитектуры нейронных сетей на основе комбинации свёрточных, рекуррентных и глубоких нейронных сетей. Показано, что такие архитектуры превосходят классические алгоритмы машинного обучения
The image recognition task is one of the most difficult in machine learning, requiring both deep knowledge and large time and computational resources from the researcher. In the case of using nonlinear and complex data, various architectures of deep neural networks are used but the problem of choosing a neural network remains a difficult issue. The main architectures used everywhere are convolutional neural networks (CNN), recurrent neural networks (RNN), deep neural networks (DNN). Based on recurrent neural networks (RNNs), Long Short Term Memory Networks (LSTMs) and Controlled Recurrent Unit Networks (GRUs) were developed. Each neural network architecture has its own structure, customizable and trainable parameters, and advantages and disadvantages. By combining different types of neural networks, you can significantly improve the quality of prediction in various machine learning problems. Considering that the choice of the optimal network architecture and its parameters is an extremely difficult task, one of the methods for constructing the architecture of neural networks based on a combination of convolutional, recurrent and deep neural networks is considered. We showed that such architectures are superior to classical machine learning algorithms