bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-like growth factor 1 signaling in the placenta requires endothelial nitric oxide synthase to support trophoblast function and normal fetal growth
Authors: Wilson Rebecca L. , Troja Weston , Sumser Emily K. , Maupin Alec , Lampe Kristin , Jones Helen N.
Published: February 2021

Currently, there is no effective treatment for placental dysfunction in utero. In a ligated mouse model of fetal growth restriction (FGR), nanoparticle-mediated human insulin-like 1 growth factor ( hIGF1) gene delivery (NP-Plac1-hIGF1) increased hIGF1 expression and maintained fetal growth. However, whether it can restore fetal growth remains to be determined. Using the endothelial nitric oxide synthase knockout (eNOS−/−) mouse model, a genetic model of FGR, we found that despite inducing expression of hIGF1 in the placentas treated with NP-Plac1-hIGF1 ( P = 0.0425), FGR did not resolve. This was associated with no change to the number of fetal capillaries in the placental labyrinth; an outcome which was increased with NP-Plac1-hIGF1 treatment in the ligated mouse model, despite increased expression of angiopoietin 1 ( P = 0.05), and suggested IGF1 signaling in the placenta requires eNOS to modulate placenta angiogenesis. To further assess this hypothesis, BeWo choriocarcinoma cell line and human placental explant cultures were treated with NP-Plac1-hIGF1, oxidative stress was induced with hydrogen peroxide (H2O2), and NOS activity was inhibited using the inhibitor NG-monomethyl-l-arginine (l-NMMA). In both BeWo cells and explants, the protective effect of NP-Plac1-hIGF1 treatment against H2O2-induced cell death/lactate dehydrogenase release was prevented by eNOS inhibition ( P = 0.003 and P < 0.0001, respectively). This was associated with an increase in mRNA expression of oxidative stress markers hypoxia inducing factor 1α ( HIF1α; P < 0.0001) and ADAM10 ( P = 0.0002) in the NP-Plac1-hIGF1 + H2O2 + l-NMMA-treated BeWo cells. These findings show for the first time the requirement of eNOS/NOS in IGF1 signaling in placenta cells that may have implications for placental angiogenesis and fetal growth.
Time course of changes in V̇o2peak and O2 extraction during ramp cycle exercise following HIIT versus moderate-intensity continuous training in type 2 diabetes
Authors: Gildea Norita , McDermott Adam , Rocha Joel , O’Shea Donal , Green Simon , Egaña Mikel
Published: February 2021

In the present study, we assessed the time course of adaptations in peak oxygen uptake (V̇o2peak) and muscle fractional oxygen (O2) extraction (using near-infrared spectroscopy) following 12 wk of low-volume high-intensity interval training (HIIT) versus moderate-intensity continuous endurance training (MICT) in adults with uncomplicated type 2 diabetes (T2D). Participants with T2D were randomly assigned to MICT ( n = 12, 50 min of moderate-intensity cycling) or HIIT ( n = 9, 10 × 1 min at ∼90% maximal heart rate) or to a nonexercising control group ( n = 9). Exercising groups trained three times per week and measurements were taken every 3 wk. The rate of muscle deoxygenation (i.e., deoxygenated hemoglobin and myoglobin concentration, Δ[HHb + Mb]) profiles of the vastus lateralis muscle were normalized to 100% of the response, plotted against % power output (PO), and fitted with a double linear regression model. V̇o2peak increased ( P < 0.05) by week 3 of MICT (+17%) and HIIT (+8%), with no further significant changes thereafter. Total increases in V̇o2peak posttraining ( P < 0.05) were 27% and 14%, respectively. The %Δ[HHb + Mb] versus %PO slope of the first linear segment ( slope1) was reduced ( P < 0.05) beyond 3 wk of HIIT and MICT, with no further significant changes thereafter. No changes in V̇o2peak or slope1 were observed in the control group. Low-volume HIIT and MICT induced improvements in V̇o2peak following a similar time course, and these improvements were likely, at least in part, due to an improved microvascular O2 delivery.
Interjoint coordination between the ankle and hip joints during quiet standing in individuals with motor incomplete spinal cord injury
Authors: Lee Jae W. , Chan Katherine , Unger Janelle , Yoo Jaeeun , Musselman Kristin E. , Masani Kei
Published: February 2021

There are limited studies investigating the biomechanics of standing balance for individuals with motor incomplete spinal cord injury (iSCI). Through our study, we found that these individuals with iSCI demonstrated increased postural sway primarily due to increased ankle joint accelerations. In addition, the ankle-hip coordination was equivalent between able-bodied individuals and those with motor incomplete spinal cord injury, which was not able to reduce the large body acceleration.
Medial olivocochlear reflex effects on amplitude growth functions of long- and short-latency components of click-evoked otoacoustic emissions in humans
Authors: Goodman Shawn S. , Boothalingam Sriram , Lichtenhan Jeffery T.
Published: February 2021

The auditory efferent system, operating at moderate to high sound levels, may improve hearing in background noise and provide protection from noise damage. We used otoacoustic emissions to measure these efferent effects across a wide range of sound levels and identified level-dependent and independent effects. Previous reports have focused on level-dependent measures. The level-independent effects identified here may provide new insights into the functional relevance of auditory efferent activity in humans.
Operculo-insular and anterior cingulate plasticity induced by transcranial magnetic stimulation in the human motor cortex: a dynamic casual modeling study
Authors: Hodkinson Duncan J. , Bungert Andreas , Bowtell Richard , Jackson Stephen R. , Jung JeYoung
Published: February 2021

Transcranial magnetic stimulation of the primary motor cortex (M1) is a promising treatment for chronic pain, but its mechanism of action remains unclear. Competing dynamic causal models of effective connectivity between M1 and medial and lateral pain systems suggest direct input into the insular, anterior cingulate cortex, and parietal operculum. This supports the hypothesis that analgesia produced from M1 stimulation most likely acts through the activation of top-down processes associated with intracortical modulation.
Anti‐Enterococcus Faecalis, Cytotoxicity, Phytotoxicity, and Anticancer Studies on Clausena excavata Burum. f. (Rutaceae) Leaves
Authors: Albaayit Shaymaa Fadhel Abbas , Maharjan Rukesh , Abdullah Rasedee , Noor Mohd Hezmee Mohd
Published: February 2021

Background. Clausena excavata Burum. f. has long been applied in ethnomedicine for the treatment of various disorders like rhinitis, headache, cough, wound healing, fever, and detoxification. This study is aimed at investigating the antibacterial activity against Enterococcus faecalis ATCC 49532 using AlamarBlue assay and atomic force microscopy (AFM) as well as the cytotoxicity, anticancer, and phytotoxicity of C. excavata. Method. Bacterial cell viability was performed by using microplate AlamarBlue assay. Atomic force microscopy was used to determine morphological changes in the surface of bacterial cells. Cytotoxicity and phytotoxicity were determined by brine shrimp lethality and Lemna minor bioassay. Caco‐2 (colorectal adenocarcinoma) cell line was used for the evaluation of the anticancer effects. Result. Among the fractions tested, ethyl acetate (EA) fraction was found to be active with minimum inhibitory concentration (MIC) of 750 μg/mL against E. faecalis, but other fractions were found to be insensitive to bacterial growth. Microscopically, the EA fraction‐treated bacteria showed highly damaged cells with their cytoplasmic content scattered all over. The LC50 value of the EA fraction against brine shrimp was more than 1000 μg/mL showing the nontoxic nature of this fraction. Chloroform (CH), EA, and methanol (MOH) fractions of C. excavata were highly herbicidal at the concentration of 1000 μg/mL. EA inhibited Caco‐2 cell line with an IC50 of 20 μg/mL. Conclusions. This study is the first to reveal anti‐E. faecalis property of EA fraction of C. excavata leaves, natural herbicidal, and anticancer agents thus highlight the potential compound present in its leaf which needs to be isolated and tested against multidrug‐resistant E. faecalis.
Massive Blood Transfusion for Trauma Score to Predict Massive Blood Transfusion in Trauma
Authors: Akaraborworn Osaree , Siribumrungwong Boonying , Sangthong Burapat , Thongkhao Komet
Published: February 2021

Background. Massive blood loss is the most common cause of immediate death in trauma. A massive blood transfusion (MBT) score is a prediction tool to activate blood banks to prepare blood products. The previously published scoring systems were mostly developed from settings that had mature prehospital systems which may lead to a failure to validate in settings with immature prehospital systems. This research aimed to develop a massive blood transfusion for trauma (MBTT) score that is able to predict MBT in settings that have immature prehospital care. Methods. This study was a retrospective cohort that collected data from trauma patients who met the trauma team activation criteria. The predicting parameters included in the analysis were retrieved from the history, physical examination, and initial laboratory results. The significant parameters from a multivariable analysis were used to develop a clinical scoring system. The discrimination was evaluated by the area under a receiver operating characteristic (AuROC) curve. The calibration was demonstrated with Hosmer–Lemeshow goodness of fit, and an internal validation was done. Results. Among 867 patients, 102 (11.8%) patients received MBT. Four factors were associated with MBT: a score of 3 for age ≥60 years; 2.5 for base excess ≤–10 mEq/L; 2 for lactate >4 mmol/L; and 1 for heart rate ≥105 /min. The AuROC was 0.85 (95% CI: 0.78–0.91). At the cut point of ≥4, the positive likelihood ratio of the score was 6.72 (95% CI: 4.7–9.6,

p

 < 0.001), the sensitivity was 63.6%, and the specificity was 90.5%. Internal validation with bootstrap replications had an AuROC of 0.83 (95% CI: 0.75–0.91). Conclusions. The MBTT score has good discrimination to predict MBT with simple and rapidly obtainable parameters.
Dip Angle Effect on the Main Roof First Fracture and Instability in a Fully‐Mechanized Workface of Steeply Dipping Coal Seams
Authors: Wei Zhen , Yang Ke , Chi Xiaolou , Liu Wenjie , Zhao Xinyuan
Published: February 2021

The fracture instability mechanism of the basic roof is the key to support selection and surrounding rock stability control, and it is also the guarantee of safe and efficient coal mining. By means of theoretical analysis and numerical calculation, the calculation model of basic roof of steeply dipping coal seams (SDCS) under linear load is established, the stress distribution expression of basic roof plate is deduced, the inclination effect of stress evolution of steeply dipping coal seams (SDCS) workface is analyzed, and the “sequential” weighting mechanism of workface is revealed. Based on the numerical simulation test, the evolution laws of vertical stress release and shear stress concentration of overlying strata in workface with different coal seam dip angles are obtained. The results show that there is shear stress arch in the overlying strata. With the increase of coal seam dip angle, the overlying strata are suddenly damaged under the action of shear stress. The roof is in the state of discontinuous movement due to its self‐weight and overburden pressure. Support is affected by the discontinuous movement and moved along with the roof. The results of this study can be of theoretical reference to the control of SDCS.
Evaluation of Urban Industry-Education Integration Based on Improved Fuzzy Linguistic Approach
Authors: Chen Zhenbin , Zhang Wanhong , Li Lian , He Mengxing , Wang Jian
Published: February 2021

Integration of industry and education is a strategic measure to address the structural imbalance issues in the scientific and technological development and industrial transformation, as well as educational system. Currently, joint efforts of governments, universities, and enterprises have achieved improvements in integrating education and various related industries. However, the evaluation of industry-education integration has not received sufficient attention it deserves. Based on the context-input-process-product (CIPP) evaluation model, this paper proposes an evaluation index system for urban industry-education integration. Considering the vagueness and uncertainty of the indexes, the evaluation model is established using intuitionistic fuzzy analytic hierarchy process (IFAHP) method and 2-tuple linguistic information representation approach. A case study indicates that industry-education integration environment is the most important division of evaluation, with local regulation being the most important evaluation index. The evaluation model is proven to be effective in improving the urban industry-education integration.
Anterolateral Bone Window for Revision Broken Cemented Stem of Unipolar Hemiarthroplasty
Authors: Mohamed Mahmoud Mohamed Mosa , Ibrahim Bahaaeldin , Amr Amr Abdelhalem , Bayoumy Maysara Abdelhalem
Published: February 2021

Background. Fractured stem of the hip prosthesis is well documented in the literature. Although it is rare, it is considered as a challenging problem. Many techniques have been described to solve this problem. Purpose of the Study. Evaluation of the effect of anterolateral bone window for extraction of the cemented femoral stem of hemiarthroplasty in revision total hip replacement. Methods. The study included eight revision hip arthroplasties in eight patients, with a broken stem of cemented (Thompson) hemiarthroplasty, which has been revised by the anterolateral proximal femoral window. All cases received cemented cups and cement-in-cement stems, except one case who received cementless long stem. Clinical follow-up of cases by Harries hip score (HHS) and X-ray. Results. Functional improvement of HHS of all cases, with no signs of loosening, after a mean follow-up period of 1.5 years. Conclusion. Extraction of broken stem is a challenging procedure. Many techniques have been described for revision of cases with a fractured stem of hip prosthesis, but we think that the anterolateral femoral bone window is a reproducible technique due to the characteristics of simplicity, short-time procedure, less invasive, not requiring extra instruments, and can be successful for most patients.
Dynamics of a Large-Scale Spiking Neural Network with Quadratic Integrate-and-Fire Neurons
Authors: Ye Weijie
Published: February 2021

Since the high dimension and complexity of the large-scale spiking neural network, it is difficult to research the network dynamics. In recent decades, the mean-field approximation has been a useful method to reduce the dimension of the network. In this study, we construct a large-scale spiking neural network with quadratic integrate-and-fire neurons and reduce it to a mean-field model to research the network dynamics. We find that the activity of the mean-field model is consistent with the network activity. Based on this agreement, a two-parameter bifurcation analysis is performed on the mean-field model to understand the network dynamics. The bifurcation scenario indicates that the network model has the quiescence state, the steady state with a relatively high firing rate, and the synchronization state which correspond to the stable node, stable focus, and stable limit cycle of the system, respectively. There exist several stable limit cycles with different periods, so we can observe the synchronization states with different periods. Additionally, the model shows bistability in some regions of the bifurcation diagram which suggests that two different activities coexist in the network. The mechanisms that how these states switch are also indicated by the bifurcation curves.
Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in BBS2 in a Kashmiri Family with Bardet‐Biedl Syndrome
Authors: Ali Ghazanfar , Sadia  , Foo Jia Nee , Nasir Abdul , Chang Chu-Hua , Chew Elaine GuoYan , Latif Zahid , Azeem Zahid , Ain-ul-Batool Syeda , Kazmi Syed Akif Raza , Awan Naheed Bashir , Khan Abdul Hameed , Rehman Fazal-Ur- , Khalid Madiha , Wali Abdul , Sarwar Samina , Akhtar Wasim , Ahmed Abbasi Ansar , Nisar Rameez
Published: February 2021

Background. Bardet‐Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease‐causing variant/s in patients exhibiting clinical features of BBS. Methods. The identification of disease‐causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. Results. WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in‐silico softwares. Conclusion. Clinical and genetic spectrum of BBS and BBS‐like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype‐phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.
Recursive Identification for Fractional Order Hammerstein Model Based on ADELS
Authors: Jin Qibing , Ye Youliang , Cai Wu , Wang Zeyu
Published: February 2021

This paper deals with the identification of the fractional order Hammerstein model by using proposed adaptive differential evolution with the Local search strategy (ADELS) algorithm with the steepest descent method and the overparameterization based auxiliary model recursive least squares (OAMRLS) algorithm. The parameters of the static nonlinear block and the dynamic linear block of the model are all unknown, including the fractional order. The initial value of the parameter is obtained by the proposed ADELS algorithm. The main innovation of ADELS is to adaptively generate the next generation based on the fitness function value within the population through scoring rules and introduce Chebyshev mapping into the newly generated population for local search. Based on the steepest descent method, the fractional order identification using initial values is derived. The remaining parameters are derived through the OAMRLS algorithm. With the initial value obtained by ADELS, the identification result of the algorithm is more accurate. The simulation results illustrate the significance of the proposed algorithm.
Quantum Inequalities of Hermite–Hadamard Type for
r
-Convex Functions
Authors: You Xuexiao , Kara Hasan , Budak Hüseyin , Kalsoom Humaira
Published: February 2021

In this present study, we first establish Hermite–Hadamard type inequalities for

r

-convex functions via

q

κ

2

-definite integrals. Then, we prove some quantum inequalities of Hermite–Hadamard type for product of two

r

-convex functions. Finally, by using these established inequalities and the results given by (Brahim et al. 2015), we prove several quantum Hermite–Hadamard type inequalities for coordinated

r

-convex functions and for the product of two coordinated

r

-convex functions.
[Retracted] An Educational Web‐Based Expert System for Novice Highway Technology in Flexible Pavement Maintenance
Authors: Milad Abdalrhman , Yusoff Nur Izzi Md. , Majeed Sayf A. , Ali Zainab Hasan , Solla Mohmed , Al-Ansari Nadhir , Rahmat Riza Atiq , Yaseen Zaher Mundher
Published: February 2021

Nowadays, higher education worldwide is affected by the COVID‐19 pandemic. It has affected students’ attendance in the universities and causes universities to close down in more than 190 countries. On the other hand, novice engineers studied only a few lectures related to highway engineering. Their lectures have included very little knowledge about asphalt pavement construction as highway engineering consists of many areas that are not studied in detail during their studying years subject to their traditional education. Due to all mentioned, a new drive to promote online learning paves the way to evaluate our future approach to curriculum development and delivery of educational materials for engineering courses. However, experts can offer solutions to these problems using their past experience. Hence, a system that allows experts to share their experience with other engineers after completing a project is needed. Nevertheless, the web‐based expert system for maintaining flexible pavement problems in tropical regions (ESTAMPSYS) designed in this study is a novel concept. Prior to developing this system, the need for such a system was determined through literature review and validated through a questionnaire survey. Experts were interviewed, and a questionnaire survey was conducted to construct the knowledge base of the system. Knowledge was presented as rules and coded in software through PHP programming. Web pages that support the user interface were designed using a framework that consists of CSS, HTML, and J‐Query. Furthermore, the system was tested by an array of users engaged in highway engineering, namely, experts, teaching experts, novice engineers, and students. The mean values of the overall system evaluation performed by 20 users using a five‐point Likert scale were 4, 4.5, 3.75, 4.25, 5, 4, and 3.5. Expert and user satisfaction prove the effectiveness of the proposed system.
Supply Chain Inventory Collaborative Management and Information Sharing Mechanism Based on Cloud Computing and 5G Internet of Things
Authors: Zhang Fuan , Gong Zhenzhi
Published: February 2021

With the development of economic globalization, the competition among enterprises is increasingly fierce. Therefore, companies need close information sharing to realize the integration of supply chain. This article aims to study the collaborative management and information sharing mechanism of supply chain inventory based on cloud computing and 5G Internet of Things. This article first introduces the theory and methods of collaborative supply chain management and the information exchange mechanism and then discusses the problem of information sharing in the supply chain, that is, the bullwhip phenomenon, and then from the demand forecast, supply chain structure, time lag, and shortage game, six aspects are analyzed. The cause of the bullwhip phenomenon is analyzed. Secondly, this article proposes a quantitative analysis of the bullwhip effect, establishes a mathematical model of the bullwhip effect in the supply chain, and uses quantitative analysis to analyze the value of information sharing in the supply chain. Finally, this article uses cloud computing technology to build a supply chain information collaboration system architecture and uses EPC Internet of Things to build a supply chain information sharing model and describes the entire operation process of the supply chain. The experimental results of this paper show that the application of cloud computing technology to supply chain management establishes a system platform for supply chain information sharing, improves the overall operational efficiency of supply chain management, and realizes supply chain information sharing and business collaboration. In addition, the operating costs and risks of each node enterprise in the supply chain are reduced by 12% compared with the nonsharing situation, which also shows that the overall benefits of the supply chain have been correspondingly improved and market competitiveness has been enhanced.
Interrelationships between Acoustic Emission and Cutting Force in Rock Cutting
Authors: Liu Sifei , Shi Peng , Wan Zhijun , Lu Shuaifeng , Lv Jiakun , Meng Fanfei
Published: February 2021

Cutting force is the key signal to realize intelligent control of shearer and mastering the change process of cutting force is helpful to improve the adaptive cutting of shearer. In this paper, full scale rock cutting tests are used to carry out single pick cutting experiments on three kinds of coal, and the acoustic emission (AE) signals of coal and rock cutting are monitored in the whole process. The relationship between AE and cutting force is also discussed. The results show that the development of AE energy can represent the different stages of the cutting process, and the time fractal dimension of AE energy can reveal the change law of coal structure stability. In addition, the acoustic emission waveform at the peak cutting force of the same kind of coal has the same main frequency, power spectrum density (PSD) variation law, and the area under PSD curve; for different types of coal, the area under PSD curve at peak cutting force increases with the increase of USC. In the cutting process, the AE signal has obvious characteristics and internal evolution law in energy amplitude, fractal dimension, and PSD index. The change characteristics of AE energy can be used as the precursor information of the peak cutting force, and the coal failure at the peak cutting force has the identity. The above conclusions are of great significance for intelligent control of shearer and intelligent mining of coal mine.
Advances in Imaging Technology of Anterior Segment of the Eye
Authors: Han Sang Beom , Liu Yu-Chi , Mohamed-Noriega Karim , Mehta Jodhbir S.
Published: February 2021

Advances in imaging technology and computer science have allowed the development of newer assessment of the anterior segment, including Corvis ST, Brillouin microscopy, ultrahigh-resolution optical coherence tomography, and artificial intelligence. They enable accurate and precise assessment of structural and biomechanical alterations associated with anterior segment disorders. This review will focus on these 4 new techniques, and a brief overview of these modalities will be introduced. The authors will also discuss the recent advances in research regarding these techniques and potential application of these techniques in clinical practice. Many studies on these modalities have reported promising results, indicating the potential for more detailed comprehensive understanding of the anterior segment tissues.
ПРОГНОСТИЧНЕ ЗНАЧЕННЯ ІНТЕГРАЛЬНОЇ ОЦІНКИ ТЯЖКОСТІ УРАЖЕННЯ ЦЕРЕБРАЛЬНИХ СТРУКТУР У ПАЦІЄНТІВ У ГОСТРОМУ ПЕРІОДІ СПОНТАННОГО СУПРАТЕНТОРІАЛЬНОГО ВНУТРІШНЬОМОЗКОВОГО КРОВОВИЛИВУ
Authors: Kozyolkin О. А. , Kuznietsov А. А.
Published: February 2021

РЕЗЮМЕ. Мета роботи – удосконалити діагностичні заходи у хворих на спонтанний супратенторіальний внутрішньомозковий крововилив (ССВМК) шляхом розробки критеріїв прогнозування перебігу та виходу гострого періоду захворювання на підставі інтегральної кількісної оцінки ініціальної тяжкості ураження церебральних структур за даними нейровізуалізаційного дослідження.

Матеріал і методи. Проведено проспективне когортне порівняльне дослідження 344 пацієнтів з гіпертензивним ССВМК, що розвинувся вперше. Діагноз встановлювали за даними комп’ютерно-томографічного дослідження, яке проводили в перші 24 години від дебюту захворювання, визначали наступні кількісні показники: обсяг внутрішньомозкового крововиливу (ОВМК), вираженість латеральної дислокації (ЛД), обсяг вторинного внутрішньошлуночкового крововиливу (ОВВШК), загальний обсяг інтракраніальної геморагії (ЗОІКГ). Клініко-неврологічне дослідження містило оцінку рівня неврологічного дефіциту за National Institute of Health Stroke Scale та шкалою коми Full Outline of UnResponsiveness. В якості кінцевих точок реєстрували несприятливі варіанти перебігу (раннє клініко-неврологічне погіршення (РКНП) протягом 48 годин з моменту госпіталізції) та виходу гострого періоду ССВМК на тлі консервативної терапії (летальний вихід, несприятливий функціональний вихід у вигляді значення 4–5 балів за модифікованою шкалою Ренкіна на 21 добу захворювання). Оперативне лікування було проведено 30 пацієнтам. Ідентифікацію інтегральних нейровізуалізаційних патернів (НП) здійснювали інструментами кластерного аналізу. Розраховували показники відносного ризику (ВР).

Результати. Розроблені діагностичні критерії 5 типів НП, які враховують сукупність комп’ютерно-томографічних показників (ОВМК, вираженість ЛД, ОВВШК, ЗОІКГ) і відповідають градаціям інтегральної кількісної оцінки тяжкості ураження церебральних структур у хворих на ССВМК. Вказані НП були ранжовані в порядку збільшення ЗОІКГ. Групи пацієнтів з різними НП відрізнялися за питомою вагою РКНП (критерій c2 Пірсона=129,7, p<0,0001) та структурою градацій виходу гострого періоду захворювання на тлі консервативної терапії (критерій c2 Пірсона=241,2, p<0,0001). В субкогорті пацієнтів з НП І типу (n=158) найбільшою була питома вага сприятливого функціонального виходу (72,2 %), в субкогорті хворих з НП ІІ типу (n=67) більш поширеним був несприятливий функціональний вихід (64,2 %). Доведено, що наявність НП ІІІ–V типів є діагностичним маркером підвищеного ризику РКНП (ВР (95 % ДІ)=5,32 (3,81–7,42), р<0,0001) та летального виходу (ВР (95 % ДІ)=9,71 (6,25–15,10), р<0,0001).

Висновки. Запропоновані градації інтегральної нейровізуалізаційної оцінки тяжкості ураження церебральних структур у хворих на ССВМК асоційовані з клініко-неврологічними даними і є інформативними критеріями прогнозування перебігу та виходу гострого періоду захворювання.
ЕЛЕКТРОСТИМУЛЯЦІЯ В ЛІКУВАННІ НЕЙРОГЕННИХ РОЗЛАДІВ СЕЧОВИПУСКАННЯ
Authors: Vozianov S. O. , Zakharash M. P. , Chabanov P. V. , Zakharash Yu. M. , Sevastyanova N. A. , Ugarov V. Yu. , Reprintseva A. S.
Published: February 2021

РЕЗЮМЕ. Мета – підвищення ефективності лікування хворих із нейрогенними розладами сечовипускання.

Матеріал і методи. Обстежено 56 хворих із нейрогенними порушеннями сечовипускання. Функціональний стан детрузора, внутрішнього сфінктера сечового міхура, зовнішнього сфінктера уретри визначали за допомогою електроміографічного дослідження. Електростимуляцію сечового міхура проводили за стимулювальною методикою з частотою 70 Гц, модуляцією 100 %, посилка-пауза 4–6 с, протягом 15 хв, курсом 2 тижні.

Результати. Встановлено, що електроміографія відображає функціональний стан сечовивідних шляхів. Призначення електростимуляції дозволило досягти достовірної позитивної динаміки в клініко-функціональному стані пацієнтів.

Висновки. Лікування пацієнтів із нейрогенними розладами сечовипускання за допомогою електростимуляції є ефективним.
ДОКЛІНІЧНЕ ДОСЛІДЖЕННЯ НАНОЧАСТИНОК ФЕРУМУ
Authors: Stravskyy Y. S. , Fedoniuk L. Ya. , Yarema O. M. , Skyba E. І. , Reznichenko L. S.
Published: February 2021

Вступ. Доклінічне вивчення лікарських препаратів – невід’ємна частина процесу створення лікарського засобу. Доклінічне дослідження є найбільш тривалим та відповідальним етапом розробки лікарського засобу, який вимагає особливих підходів до планування і забезпечення якості при плануванні вимірювальних експериментів, проведенні випробування та оцінки його результатів.

Мета дослідження – визначити біобезпечність, гостру токсичність, протимікробну та фунгіцидну дії наночастинок Феруму.

Методи дослідження. Біобезпечність синтезованої субстанції наночастинок у тестах in vitro визначали з використанням показників цитотоксичності, мутагенності, молекулярно-генетичного (показник генотоксичності), фізіологічного (стан мікрофлори шлунково-кишкового тракту людини) та біохімічних (ATФ-aзна і лактатдегідрогеназна активність) маркерів. Протимікробну дію нуль-валентного Феруму (Fe0NP) щодо тест-штамів мікроорганізмів визначали методом серійних розведень у бульйоні відповідно до Методичних вказівок 4.2.1890-04, 2004. Використовували такі тест-штами мікроорганізмів, як Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Candida albicans, із колекції Державного науково-контрольного інституту біотехнології і штамів мікро­організмів.

Результати й обговорення. Синтезовані наночастинки є частинками Fe0NP. Взаємодія синтезованих наночастинок Феруму з тестовими еукаріотичними клітинами не призводила до появи первинних ДНК‑ушко­джень порівняно з впливом N-нітрозометилсечовини, яка є відомим генотоксикантом. Синтезовані наночастинки характеризувались як біобезпечні у тестах на мутагенність з використанням поліхроматофільних еритроцитів кісткового мозку тварин. Аналіз показав, що експериментальна субстанція Fe0NP у досліджуваному концентраційному діапазоні проявила помірну протимікробну активність у тестах in vitro відносно як грамнегативних (S. typhimurium, S. sonnei, P. aeruginosa, P. vulgaris, P. mirabilis), так і грампозитивних (S. aureus) мікроорганізмів. Однак гриби Candida albicans виявилися нечутливими до наночастинок Феруму в досліджуваних концентраціях.

Висновки. Фізико-хімічна характеристика й оцінка критеріїв біобезпечності в тестах in vitro та in vivo свідчать про те, що синтезованим сферичним наночастинкам нуль-валентного Феруму властивий низький рівень потенційної небезпеки: виявлено відсутність генотоксичної, цитотоксичної, мутагенної дій, негативного впливу на ключові біохімічні параметри і загальний фізіологічний стан живого організму. Це дозволяє рекомендувати синтезовану субстанцію наночастинок Феруму для подальших досліджень з метою їх застосування як потенційної біологічно активної субстанції.
QSAR-АНАЛІЗ БІБЛІОТЕК 4-ТІАЗОЛІДИНОН-СПОРІДНЕНИХ ГЕТЕРОЦИКЛІВ ДЛЯ ПРОГНОЗУВАННЯ ПРОТИТРИПАНОСОМНИХ ВЛАСТИВОСТЕЙ НОВИХ ПОХІДНИХ
Authors: Kryshchyshyn-Dylevych A. P.
Published: February 2021

Вступ. Похідні тіазолідинону та споріднених гетероциклів є джерелом нових протипаразитарних агентів, у тому числі молекул із протитрипаносомними властивостями. В актуальних наукових джерелах знайдено ряд досліджень про кількісний взаємозв’язок структура – протитрипаносомна активність, що включає різні підходи комп’ютерної хімії. Більшість досліджень належить до так званих мультитаргетних, коли до вибірки включають результати інших видів протипаразитарних активностей. Розробка нових QSAR-моделей похідних тіазолідинону з протитрипаносомними властивостями дозволить окреслити напрямки спрямованого дизайну нових протипаразитарних агентів на основі циклів тіазолу та тіазолідинону.

Мета дослідження – встановити кількісний взаємозв’язок структура – протитрипаносомна активність у межах бібліотек тіазолідинонів та споріднених гетероциклів.

Методи дослідження. Побудову математичних моделей на основі QSAR-аналізу здійснювали за допомогою онлайн-платформи Online Chemical Database.

Результати й обговорення. Аналіз кількісного взаємозв’язку структура – протитрипаносомна активність проводили із застосуванням математичної моделі асоціативних нейронних мереж (ASNN: Associative Neural Networks) та методу регресії Random Forest (RFR: Random Forest regression) на основі вибірок, що включали похідні ізотіокумарин-3-карбонових кислот, тіопіранотіазолів і 4-тіазолідинон-імідазотіадіазолів із встановленою трипаноцидною активністю щодо Trypanosoma brucei brucei та Trypanosoma brucei gambiense. Кращу прогнозувальну здатність для групи ізотіокумарин-3-карбонових кислот і тіопірано[2,3-d][1,3]тіазол-2-онів обчислено за допомогою алгоритму Random Forest. Модель, обчислена на основі алгоритму Random Forest для групи імідазотіадіазолів, володіє найвищою прогнозувальною здатністю зі значенням R2=0,96.

Висновок. На основі методів асоціативних нейронних мереж та регресії Random Forest розроблено прогностичні моделі для прогнозування протипаразитарної активності диверсифікованих похідних ­4-тіазолідинонів і подальшого фокусування напрямків оптимізації нових біологічно активних молекул із трипаноцидними властивостями.
System Genetics Including Causal Inference Identify Immune Targets for Coronary Artery Disease and the Lifespan
Authors: Bon-Baret Valentin , Chignon Arnaud , Boulanger Marie-Chloé , Li Zhonglin , Argaud Deborah , Arsenault Benoit J. , Thériault Sébastien , Bossé Yohan , Mathieu Patrick
Published: February 2021

Background:

Randomized clinical trials indicate that the immune response plays a significant role in coronary artery disease (CAD), a disorder impacting the lifespan potential. However, the identification of targets critical to the immune response in atheroma is still hampered by a lack of solid inference.

Methods:

Herein, we implemented a system genetics approach to identify causally associated immune targets implicated in atheroma. We leveraged genome-wide association studies to perform mapping and Mendelian randomization to assess causal associations between gene expression in blood cells with CAD and the lifespan. Expressed genes (eGenes) were prioritized in network and in single-cell expression derived from plaque immune cells.

Results:

Among 840 CAD-associated blood eGenes, 37 were predicted causally associated with CAD and 6 were also associated with the parental lifespan in Mendelian randomization. In multivariable Mendelian randomization, the impact of eGenes on the lifespan potential was mediated by the CAD risk. Predicted causal eGenes were central in network.
FLT1
and
CCR5
were identified as targets of approved drugs, whereas 22 eGenes were deemed tractable for the development of small molecules and antibodies. Analyses of plaque immune single-cell expression identified predicted causal eGenes enriched in macrophages (
GPX1
,
C4orf3
) and involved in ligand-receptor interactions (
CCR5
).

Conclusions:

We identified 37 blood eGenes predicted causally associated with CAD. The predicted expression for 6 eGenes impacted the lifespan potential through the risk of CAD. Prioritization based on network, annotations, and single-cell expression identified targets deemed tractable for the development of drugs and for drug repurposing.
CARMN
Loss Regulates Smooth Muscle Cells and Accelerates Atherosclerosis in Mice
Authors: Vacante Francesca , Rodor Julie , Lalwani Mukesh K. , Mahmoud Amira D. , Bennett Matthew , De Pace Azzurra L. , Miller Eileen , Van Kuijk Kim , de Bruijn Jenny , Gijbels Marion , Williams Thomas C. , Clark Michael B. , Scanlon Jessica P. , Doran Amanda C. , Montgomery Rusty , Newby David E. , Giacca Mauro , O’Carroll Dónal , Hadoke Patrick W.F. , Denby Laura , Sluimer Judith C. , Baker Andrew H.
Published: February 2021

Rationale:

In the microenvironment of atherosclerotic lesions, vascular smooth muscle cells (vSMCs) switch to a dedifferentiated state but the underlying molecular mechanisms driving this switch are not fully understood. Long noncoding RNAs (lncRNAs) are dysregulated during vascular pathology, but relatively little is known about their involvement in controlling vSMCs function. Cardiac mesoderm enhancer-associated noncoding RNA (CARMN) is a lncRNA located immediately upstream of the
microRNAs-143
and
-145 (miR-143
and
miR-145
), both involved in vSMCs function.

Objective:

We investigated the role of the lncRNA CARMN, independent from miR-143 and miR-145, as a potential regulator of vSMC phenotypes in vitro and the consequences of its loss during the development of atherosclerosis in vivo. We hypothesized that loss of CARMN is a primary event controlling the functional switch towards proatherogenic vSMC phenotype and accelerates the development of the plaques in vivo.

Method and Results:

Expression of CARMN lncRNA was silenced using locked nucleic acids antisense oligonucleotides (GapmeRs) in human coronary arterial smooth muscle cells, revealing that GapmeR-mediated loss of CARMN negatively affects miR-143 and miR-145 microRNA expression. RNA sequencing of CARMN-depleted human coronary arterial smooth muscle cells revealed large transcriptomic changes, associated with vSMC proliferation, migration, inflammation, lipid metabolism, and dedifferentiation. The use of miR-143 and miR-145 mimics revealed that CARMN regulates human coronary arterial smooth muscle cell proliferation in a microRNA-independent manner. In humans and mice, CARMN and associated microRNAs were downregulated in advanced versus early atherosclerotic lesions. Using a CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) knockout approach, we explored the implications of
CARMN
depletion during atherosclerosis in vivo. Consistent with in vitro results, the knockout of
CARMN
impaired the expression of miR-143 and miR-145 under homeostatic conditions. Importantly, when atherosclerosis was induced in these mice, CARMN knockout increased the volume, size, proinflammatory Lgals3 (galectin 3)-expressing cells content, and altered plaque composition, yielding an advanced phenotype.

Conclusions:

We identified the early loss of CARMN lncRNA as critical event which primes vSMCs towards a proatherogenic phenotype in vitro and accelerates the development of atherosclerosis in vivo.
Studies on Longidorus iberis (Escuer & Arias, 1997) n. comb. (Nematoda: Longidoridae) from Spain
Authors: Clavero-Camacho Ilenia , Liébanas Gracia , Escuer Miguel , Cantalapiedra-Navarrete Carolina , Archidona-Yuste Antonio , Castillo Pablo , Palomares-Rius Juan E.
Published: February 2021

Specimens of a thin longidorid species collected in Peñalba (Huesca), north-west Spain, were previously described as Paralongidorus iberis. However, we conclude, through scanning electron microscopy and molecular studies on a population from about 15 km from the type locality and on paratype specimens, that this species was originally placed in the wrong genus. Both populations have pore-like amphidial apertures, not slit-like as in Paralongidorus, and the species is therefore transferred to Longidorus. Longidorus iberis n. comb. is regarded as a valid species and is clearly different from closely related species such as L. tabernensis, L. iliturgiensis, L. alvegus and L. indalus in morphometrics and molecular markers. Molecular data are reported for the first time, including the D2-D3 expansion segments of 28S rRNA, ITS1 rRNA, partial 18S rRNA and partial mitochondrial coxI regions. These molecular markers were used for inferring the phylogenetic relationships with other species within Longidorus and Paralongidorus, all clearly separating L. iberis n. comb. from other related taxa and placing the species in the Longidorus clade, rather than with Paralongidorus.
Material Culture and Healing Practice
Authors: Winterbottom Anna Elizabeth
Published: February 2021

The practice of medicine and healing is always accompanied by a range of paraphernalia, from pillboxes to instruments to clothing. Yet such things have rarely attracted the attention of historians of medicine. Here, I draw on perspectives from art history and religious studies to ask how these objects relate, in practical and symbolic terms, to practices of healing. In other words, what is the connection between medical culture and material culture? I focus on craft objects relating to medicine and healing in Lanka during the Kandyan period (ca. 1595–1815) in museum collections in Canada and Sri Lanka. I ask what the objects can tell us, first, about early modern Lankan medicine and healing and, second, about late nineteenth- and twentieth-century efforts to reconstruct tradition. Finally, I explore what studying these objects might add to current debates about early modern globalization in the context of both material culture and medicine.
Ichiro the Public Diplomat: Professional Sport as Cultural Intermediary in Configuring US-Japan Relations
Authors: Moscato Derek
Published: February 2021

This study examines the confluence of sport and soft power within public diplomacy. It analyses professional baseball player Ichiro Suzuki’s role in the United States as a sporting ambassador from Japan — potentially catalysing goodwill, cultural interest, perceptions of national personality traits and even views of policy issues such as international trade and country relations. In doing so, this research draws from non-state public diplomacy, which considers the transnational impacts of non-traditional communication vehicles such as cultural and sporting exchanges. It measures US public sentiment towards Japan through quantitative analysis of survey responses collected by Pew Research Center in conjunction with the Sasakawa Peace Foundation. The success of Japan’s cultural and sporting exports highlights their potential and realised role in binding national ties. Furthermore, Tokyo’s hosting of the Summer Olympiad emphasises the role of sport not only as a vehicle for competition and entertainment but also its utility in global engagement.
Acrocordiella yunnanensis sp. nov. (Requienellaceae, Xylariales) from Yunnan, China

Authors: DISSANAYAKE LAKMALI S. , MAHARACHCHIKUMBURA SAJEEWA S.N. , MORTIMER PETER E. , HYDE KEVIN D. , KANG JI-CHUAN
Published: February 2021

Acrocordiella yunnanensis sp. nov. is introduced here from dead twigs of an unidentified dicotyledonous host from Xishuangbanna Prefecture, Yunnan Province, China. Phylogenetic analyses based on LSU and ITS sequence data revealed that this new species with a distinct sexual morph belongs to Requienellaceae (Sordariomycetes, Ascomycota). Acrocordiella yunnanensis is closely related to Acrocordiella omanensis in Requienellaceae. This novel taxon is illustrated, described, and a morphology-based key is provided to facilitate the identification of species in Acrocordiella.
The genus Gasteruption Latreille, 1796 (Hymenoptera: Gasteruptiidae) in the Czech Republic and Slovakia: distribution, checklist, ecology, and conservation status
Authors: BOGUSCH PETR
Published: February 2021

The genus Gasteruption (Gasteruptiidae) is represented in Europe by more than 30 species. Of these, twenty-one are recorded from the Czech Republic and Slovakia, with six being new records for the Czech Republic and eight for Slovakia. Three species are recorded as new for Bohemia (western part of the Czech Republic). Gasteruption goberti is excluded from the fauna of the Czech Republic because specimens previously identified as G. goberti belong to G. caucasicum. Four species (G. assectator, G. caucasicum, G. jaculator and G. nigritarse) are common and widespread in both countries, G. tournieri is very common but prefers warmer regions. Only G, subtile occurs predominantly in higher altitudes of mountain ranges, while the other species are usually restricted to or are more common in warmer regions. Gasteruption opacum and G. subtile are regionally extinct from the Czech Republic and G. paternum from Slovakia, with the the most recent records of these species are pre-1990. Gasteruption freyi, G. hastator and G. hungaricum are considered very endangered thermophilous species of loess walls and steppe habitats with a marked loss of occurrence records post-1990. Locally common but much rarer than in the past are G. erythrostomum and G. boreale. Due to the fact that recent determination keys are focused on other regions, a determination key for all species recorded in central Europe is presented.