bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Characterization of Human Pluripotent Stem Cell-Derived Models of the Brain with Microelectrode Arrays
Authors: Pelkonen Anssi , Pistono Cristiana , Klecki Pamela , Gómez-Budia Mireia , Dougalis Antonios , Konttinen Henna , Stanová Iveta , Fagerlund Ilkka , Leinonen Ville , Korhonen Paula , Malm Tarja
Published: December 2021

Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.
Successful Multidisciplinary Repair of Severe Bilateral Uretero-Enteric Stricture with Inflammatory Reaction Extending to the Left Iliac Artery, after Robotic Radical Cystectomy and Intracorporeal Ileal Neobladder
Authors: Mancini Mariangela , Nguyen Alex Anh Ly , Taverna Alessandra , Beltrami Paolo , Zattoni Filiberto , Dal Moro Fabrizio
Published: December 2021

Uretero-enteric anastomotic strictures (UES) after robot-assisted radical cystectomy (RARC) represent the main cause of post-operative renal dysfunction. The gold standard for treatment of UES is open uretero-ileal reimplantation (UIR), which is often a challenging and complex procedure associated with significant morbidity. We report a challenging case of long severe bilateral UES (5 cm on the left side, 3 cm on the right side) after RARC in a 55 years old male patient who was previously treated in another institution and who came to our attention with kidney dysfunction and bilateral ureteral stents from the previous two years. Difficult multiple ureteral stent placement and substitutions had been previously performed in another hospital, with resulting urinary leakage. An open surgical procedure via an anterior transperitoneal approach was performed at our hospital, which took 10 h to complete, given the massive intestinal and periureteral adhesions, which required very meticulous dissection. A vascular surgeon was called to repair an accidental rupture that had occurred during the dissection of the external left iliac artery, involved in the extensive periureteral inflammatory process. Excision of a segment of the external iliac artery was accomplished, and an interposition graft using a reversed saphenous vein was performed. Bilateral ureteroneocystostomy followed, which required, on the left side, the interposition of a Casati-Boari flap harvested from the neobladder, and on the right side a neobladder-psoas-hitching procedure with intramucosal direct ureteral reimplantation. The patient recovered well and is currently in good health, as determined at his recent 24-month follow-up visit. No signs of relapse of the strictures or other complications were detected. Bilateral ureteral reimplantation after robotic radical cystectomy is a complex procedure that should be restricted to high-volume centers, where multidisciplinary teams are available, including urologists, endourologists, and general and vascular surgeons.
Determinant of Covariance Matrix Model Coupled with AdaBoost Classification Algorithm for EEG Seizure Detection
Authors: Al-Hadeethi Hanan , Abdulla Shahab , Diykh Mohammed , Green Jonathan H.
Published: December 2021

Experts usually inspect electroencephalogram (EEG) recordings page-by-page in order to identify epileptic seizures, which leads to heavy workloads and is time consuming. However, the efficient extraction and effective selection of informative EEG features is crucial in assisting clinicians to diagnose epilepsy accurately. In this paper, a determinant of covariance matrix (Cov–Det) model is suggested for reducing EEG dimensionality. First, EEG signals are segmented into intervals using a sliding window technique. Then, Cov–Det is applied to each interval. To construct a features vector, a set of statistical features are extracted from each interval. To eliminate redundant features, the Kolmogorov–Smirnov (KST) and Mann–Whitney U (MWUT) tests are integrated, the extracted features ranked based on KST and MWUT metrics, and arithmetic operators are adopted to construe the most pertinent classified features for each pair in the EEG signal group. The selected features are then fed into the proposed AdaBoost Back-Propagation neural network (AB_BP_NN) to effectively classify EEG signals into seizure and free seizure segments. Finally, the AB_BP_NN is compared with several classical machine learning techniques; the results demonstrate that the proposed mode of AB_BP_NN provides insignificant false positive rates, simpler design, and robustness in classifying epileptic signals. Two datasets, the Bern–Barcelona and Bonn datasets, are used for performance evaluation. The proposed technique achieved an average accuracy of 100% and 98.86%, respectively, for the Bern–Barcelona and Bonn datasets, which is considered a noteworthy improvement compared to the current state-of-the-art methods.
The Estimation of the Potential for Using Smart-Trackers as a Part of a Medical Indoor-Positioning System
Authors: Pospelova Irina V. , Cherepanova Irina V. , Bragin Dmitry S. , Sidorov Ivan A. , Kostyuchenko Evgeny Y. , Serebryakova Victoriya N.
Published: December 2021

This research aims to estimate the feasibility of using smart-bracelets as a part of a medicine indoor-positioning system, to monitor the health status and location of patients in a hospital. The smart-bracelet takes on the role of a token of the system and can measure pulse, blood pressure and saturation and provide data transmission over the BLE. The distance between token and anchor was calculated by the RSSI. The position of a token and anchor relative to each other was determined by the trilateration method. The results of the research showed that the accuracy of the developed system in a static position is 1.46 m and exceeds 3 m in a dynamic position. Results of experiments showed that measurements from the smart bracelets are transmitted to the server of the system without distortion. The study results indicated that smart-bracelets could be used to locate patients inside a hospital or estimate their current health state. Given the low accuracy of systolic pressure measurement, it is recommended to develop an algorithm that will allow smooth measuring error for higher-precision estimation of the patient’s general health state. In addition, it is planned to improve the positioning algorithm.
The Possibility of Enhanced Power Transfer in a Multi-Terminal Power System through Simultaneous AC–DC Power Transmission
Authors: Parveen Shaista , Hameed Salman , Rahman Hafizur , Rahman Khaliqur , Tariq Mohd , Alamri Basem , Ahmad Akbar
Published: December 2021

The feasibility of power transfer enhancement, through simultaneous AC–DC power transmission in a two-terminal transmission network, has been proposed earlier by the authors, and the concept is well established. To meet the increase in demand for electricity, a new technique is proposed in this article to increase the use of existing transmission lines in addition to independent control of AC and DC power flow. This paper extends the concept to a three-terminal transmission network by considering a power tapping from the middle of the line. DC is also superimposed in the already existing three-terminal AC transmission system. In the proposed topology, a multi-terminal simultaneous AC–DC system is used, which is integrated with a zig-zag transformer and more than two voltage source converter (VSC) stations. Each terminal may represent an area of the power system. Anyone/two-terminal(s) may act as sending end, whereas the remaining two/one terminal(s) may act as receiving end. Power can flow in either direction through each segment of the transmission system. At sending end, VSC converts a part of AC to DC and injects it into the neutral of the zig-zag transformer. On receiving terminal, DC power is tapped from neutral of zig-zag transformer and fed to VSC for conversion back to AC. The concept is verified in the digital simulation software PSCAD/EMTDC.
Study on Structural Performance of Horizontal Axis Wind Turbine with Air Duct for Coal Mine
Authors: Gui Xiaohong , Xue Haiteng , Gao Ripeng , Zhan Xingrui , Zhao Fupeng
Published: December 2021

Considering the characteristics of narrow underground space and energy distribution, based on blade element momentum theory, Wilson optimization model and MATLAB programming calculation results, the torsion angle and chord length of wind turbine blade under the optimized conditions were obtained. Through coordinate transformation, the data were transformed into three-dimensional form. The three-dimensional model of the blade was constructed, and the horizontal axis wind turbine blade under the underground low wind speed environment was designed. The static structural analysis and modal analysis were carried out. Structural design, optimization calculation and aerodynamic analysis were carried out for three kinds of air ducts: external convex, internal concave and linear. The results show that the velocity distribution in the throat of linear air duct is relatively uniform and the growth rate is large, so it should be preferred. When the tunnel wind speed is 4.3 m/s and the rated speed is 224 rad/s, the maximum displacement of the blade is in the blade tip area and the maximum stress is at the blade root, which is not easy to resonate. The change rate of displacement, stress and strain of blade is positively correlated with speed. The energy of blade vibration is mainly concentrated in the swing vibration of the first and second modes. With the increase in vibration mode order, the amplitude and shape of the blade gradually transition to the coupling vibration of swing, swing and torsion. The stress and strain of the blade are lower than the allowable stress and strain of glass fiber reinforced plastics (FRP), and resonance is not easy to occur in the first two steps. The blade is generally safe and meets the design requirements.
Tieguanyin Oolong Tea Extracts Alleviate Behavioral Abnormalities by Modulating Neuroinflammation in APP/PS1 Mouse Model of Alzheimer’s Disease
Authors: Kang Hyunuk , Zhou Hui , Ye Yushan , Yang Jiangfan , Liu Zhonghua , He Puming , Li Bo , Wu Yuanyuan , Wang Yaomin , Tu Youying
Published: December 2021

Alzheimer’s disease (AD) is a common neurodegenerative disease; tea components have important neuroprotective effects. This article explores the effects and mechanisms of Qingxiang Tiguanyin (Tgy-Q), Nongxiang Tieguanyin (Tgy-N), and Chenxiang Tieguanyin (Tgy-C) extracts on APP/PS1 AD model mice. Morris water maze and new object recognition experiments show that Tieguanyin extracts can effectively enhance the cognitive ability of APP/PS1 mice. H&E staining, Nissl staining, and immunohistochemical staining show that Tieguanyin extracts make nerve cell boundaries and nucleoli become clearer, relieve nucleus pyknosis, and effectively reduce Aβ1-40 and Aβ1-42 in the hippocampus and cortex. They also restore the morphology of microglia and astrocytes. In addition, Tieguanyin extracts can balance the oxidative stress level in the brain of APP/PS1 mice by improving the antioxidant capacity. Western blot results show that Tieguanyin extracts can reduce the expression of NF-κB p65, TNF-α, IL-1β, IL-6, COX-2, and iNOS in mouse brain, which demonstrates that Tieguanyin extracts improves cognitive ability by alleviating inflammation. This article demonstrates for the first time that Tieguanyin extracts can inhibit the excessive activation of the NF-κB p65 signaling pathway and improve the antioxidant capacity in the cerebral cortex and hippocampus, to improve the cognitive ability of APP/PS1 mice. Our results shed light into the beneficial of Tieguanyin tea extracts on preventing and alleviating AD diseases.
Lactiplantibacillus plantarum 1201 Inhibits Intestinal Infection of Salmonella enterica subsp. enterica Serovar Typhimurium Strain ATCC 13311 in Mice with High-Fat Diet
Authors: Ren Zhongyue , Peng Lingling , Chen Shufang , Pu Yi , Lv Huihui , Wei Hua , Wan Cuixiang
Published: December 2021

Salmonella Typhimurium is widely distributed in food. It can colonise the gastrointestinal tract after ingestion, causing lamina propria edema, inflammatory cell infiltration, and mucosal epithelial decomposition. A high-fat diet (HFD) can induce an inflammatory response, but whether HFD can increase the infection level of S. Typhimurium is unknown. We established a model of Salmonella enterica subsp. enterica serovar Typhimurium strain ATCC 13311 ATCC 13311 infection in healthy adult mice with a maintenance diet (MD) or HFD to explore the effect of Lactiplantibacillus plantarum 1201 intervention on S. Typhimurium ATCC 13311 colonization and its protective effects on mice. HFD exacerbated the infection of S. Typhimurium ATCC 13311, while the intervention of L. plantarum 1201 effectively mitigated this process. L. plantarum 1201 can reduce the colonies of S. ATCC 13311 in the intestines and tissues; and reduce intestinal inflammation by down-regulating the level of TLR4/NF-κB pathway related proteins in serum and the expression of related inflammatory factors in the colon and jejunum. Since L. plantarum 1201 can inhibit the colonization of S. Typhimurium ATCC 13311 and relieve inflammation in HFD, current research may support the use of L. plantarum 1201 to prevent S. Typhimurium infection.
Development of Selection Indices for Improvement of Seed Yield and Lipid Composition in Bambara Groundnut (Vigna subterranea (L.) Verdc.)
Authors: Azman Halimi Razlin , Raymond Carolyn A. , Barkla Bronwyn J. , Mayes Sean , King Graham J.
Published: December 2021

The underutilised grain legume bambara groundnut (Vigna subterranea) has the potential to contribute significantly to nutritional security. However, the lack of commercial cultivars has hindered its wider adoption and utilisation as a food source. The development of competitive cultivars is impeded by (1) lack of systematic data describing variation in nutritional composition within the gene pool, and (2) a poor understanding of how concentrations of different nutritional components interact. In this study, we analysed seed lipid and protein concentration and lipid composition within a collection of 100 lines representing the global gene pool. Seed protein and lipid varied over twofold with a normal distribution, but no significant statistical correlation was detected between the two components. Seed lipid concentration (4.2–8.8 g/100 g) is primarily determined by the proportion of oleic acid (r2 = 0.45). Yield and composition data for a subset of 40 lines were then used to test selection parameters for high yielding, high lipid breeding lines. From five selection indices tested using 15 scenarios, an index based on the seed number, seed weight, and oleic acid yielded a >50% expected increase in each of the mean values of seed number, pod dry weight, seed dry weight, and seed size, as well as an expected 7% increase in seed lipid concentration.
Quantitative Methods for the Prioritization of Foods Implicated in the Transmission of Hepatititis E to Humans in Italy
Authors: Moro Ornella , Suffredini Elisabetta , Isopi Marco , Tosti Maria Elena , Schembri Pietro , Scavia Gaia
Published: December 2021

Hepatitis E is considered an emerging foodborne disease in Europe. Several types of foods are implicated in the transmission of the hepatitis E virus (HEV) to humans, in particular, pork and wild boar products. We developed a parametric stochastic model to estimate the risk of foodborne exposure to HEV in the Italian population and to rank the relevance of pork products with and without liver (PL and PNL, respectively), leafy vegetables, shellfish and raw milk in HEV transmission. Original data on HEV prevalence in different foods were obtained from a recent sampling study conducted in Italy at the retail level. Other data were obtained by publicly available sources and published literature. The model output indicated that the consumption of PNL was associated with the highest number of HEV infections in the population. However, the sensitivity analysis showed that slight variations in the consumption of PL led to an increase in the number of HEV infections much higher than PNL, suggesting that PL at an individual level are the top risky food. Uncertainty analysis underlined that further characterization of the pork products preparation and better assessment of consumption data at a regional level is critical information for fine-tuning the most risky implicated food items in Italy.
Antigenicity and Safety Evaluation of Lactiplantibacillus plantarum 7-2 Screened to Reduce α-Casein Antigen
Authors: Mu Guangqing , Zhang Zhao , Wang Jiayi , Jiang Shujuan , Wang Hongxin , Xu Yunpeng , Li Xinling , Chi Lei , Li Yue , Tuo Yanfeng , Zhu Xuemei
Published: December 2021

α-Casein (α-CN) is considered the main allergen in bovine milk. Lactic acid bacteria (LAB) fermentation can hydrolyze milk protein and therefore reduce the antigenicity. In this paper, a LAB reducing the antigenicity of casein, identified as LactiplantibacillusPlantarum 7-2 (L. plantarum 7-2), was primarily identified by screening for protein hydrolysis ability using a method involving the determination of released free amino acid with further selection for the ideal antigenicity-reducing capability by enzyme-linked immunosorbent assay (ELISA). In order to verify the capability of L. plantarum 7-2 in inhibiting antigenicity, the standard milk proteins α-LA, β-LG, α-CN, β-CN and κ-CN were cultured with L. plantarum 7-2 for 18 h; The results of SDS-PAGE show that all the bands corresponding to the full length tested proteins became unclear or completely disappeared indicating that these proteins were hydrolyzed by L. plantarum 7-2. Correspondingly, the antigenicities of α-CN and β-LG were significantly reduced. L. plantarum 7-2 demonstrated negative hemolysis and nitrate reductase capabilities and was sensitive to the commonly used antibiotics ampicillin clindamycin tetracycline chloramphenicol, and erythromycin, demonstrating that L. plantarum 7-2 could be used in dairy product fermentation to reduce the antigenicity of milk protein.
Fixed Point Results for F-Contractions in Cone Metric Spaces over Topological Modules and Applications to Integral Equations
Authors: Branga Adrian Nicolae
Published: December 2021

In this paper, the concept of F-contraction was generalized for cone metric spaces over topological left modules and some fixed point results were obtained for self-mappings satisfying a contractive condition of this type. Some applications of the main result to the study of the existence and uniqueness of the solutions for certain types of integral equations were presented in the last part of the article, one of them being a fractional integral equation.
Lipid-Associated Variants near ANGPTL3 and LPL Show Parent-of-Origin Specific Effects on Blood Lipid Levels and Obesity
Authors: Lessmark Anna , Hatem Gad , Kovacs Györgyi , Vitai Marta , Ahlqvist Emma , Tuomi Tiinamaija , Koranyi Laszlo , Groop Leif , Prasad Rashmi B.
Published: December 2021

Parent-of-origin effects (POE) and sex-specific parental effects have been reported for plasma lipid levels, and a strong relationship exists between dyslipidemia and obesity. We aim to explore whether genetic variants previously reported to have an association to lipid traits also show POE on blood lipid levels and obesity. Families from the Botnia cohort and the Hungarian Transdanubian Biobank (HTB) were genotyped for 12 SNPs, parental origin of alleles were inferred, and generalized estimating equations were modeled to assess parental-specific associations with lipid traits and obesity. POE were observed for the variants at the TMEM57, DOCK7/ANGPTL3, LPL, and APOA on lipid traits, the latter replicated in HTB. Sex-specific parental effects were also observed; variants at ANGPTL3/DOCK7 showed POE on lipid traits and obesity in daughters only, while those at LPL and TMEM57 showed POE on lipid traits in sons. Variants at LPL and DOCK7/ANGPTL3 showed POE on obesity-related traits in Botnia and HTB, and POE effects on obesity were seen to a higher degree in daughters. This highlights the need to include analysis of POEs in genetic studies of complex traits.
The Experiences of People with Diabetes during COVID-19 Pandemic Lockdown
Authors: Al-Moteri Modi , Plummer Virginia , Youssef Hanan A. M. , Yaseen Ruba W. H. , Al Malki Mohammed , Elryah Ahmed AbdElbagy Ibrahim , Karani Ahmed Al
Published: December 2021

Little is known about the theoretical foundation underling the response of people with diabetes managing their everyday routines during COVID-19 pandemic lockdown. Aim: To explore the experience of people with diabetes during COVID-19 pandemic lockdown in light of the risk perception, response and behavioral change theories. Method: A qualitative descriptive design was employed, and Braun and Clark’s six step analysis were used for thematic analysis. Semi-structured interviews were conducted online using Zoom Videos Communication. Result: Five themes were defined as follows: (1) perceived the threat and faced their fears, (2) appraised the damage, (3) identified the challenges, (4) modified their routine, and (5) identified the strengths that facilitate the efficacy of their response. There were eight sub-themes within the themes. Conclusion: The results of this study may provide an opportunity for nurses to reflect on issues highlighted by the patients regarding more effective communication, knowledge and skill development for people to support self-care during national emergencies.
Mental Health in Women Victims of Gender Violence: Descriptive and Multivariate Analysis of Neuropsychological Functions and Depressive Symptomatology
Authors: Torres García Ana Victoria , Vega-Hernández María Concepción , Antón Rubio Concha , Pérez-Fernández Miguel
Published: December 2021

Female victims of abuse, as well as suffering from psychopathological disorders such as depression, can have neuropsychological sequelae affecting memory and attention, with serious consequences, both physical and psychological, in their daily lives. Therefore, the objective of this study is to analyse these sequelae that affect attention and memory, as well as the possible association of these sequelae to depression. A total of 68 women, victims of gender-based violence, between the ages of 15 and 62 participated in this study. The Luria DNA Battery (Neuropsychological Diagnosis of Adults) by Manga and Ramos (2000); and the Beck Depression Inventory (2011) were applied. It is shown that female victims of gender-based violence present poor short-term memory, attentional control, and score low on the Luria-DNA battery. Of these women, 60% suffer from some relevant type of depression. Through HJ-Biplot analysis, a direct relationship was found between memory and attentional control with the total score of the Luria battery. However, an inverse relationship was found between short-term memory and depression. In addition, three well-differentiated clusters of female victims of gender-based violence were identified. It is concluded that a lower rate of depression is observed in female victims of abuse when they have a more intact short-term memory.
Health Equity and a Paradigm Shift in Occupational Safety and Health
Authors: Flynn Michael A. , Check Pietra , Steege Andrea L. , Sivén Jacqueline M. , Syron Laura N.
Published: December 2021

Despite significant improvements in occupational safety and health (OSH) over the past 50 years, there remain persistent inequities in the burden of injuries and illnesses. In this commentary, the authors assert that addressing these inequities, along with challenges associated with the fundamental reorganization of work, will require a more holistic approach that accounts for the social contexts within which occupational injuries and illnesses occur. A biopsychosocial approach explores the dynamic, multidirectional interactions between biological phenomena, psychological factors, and social contexts, and can be a tool for both deeper understanding of the social determinants of health and advancing health equity. This commentary suggests that reducing inequities will require OSH to adopt the biopsychosocial paradigm. Practices in at least three key areas will need to adopt this shift. Research that explicitly examines occupational health inequities should do more to elucidate the effects of social arrangements and the interaction of work with other social determinants on work-related risks, exposures, and outcomes. OSH studies regardless of focus should incorporate inclusive methods for recruitment, data collection, and analysis to reflect societal diversity and account for differing experiences of social conditions. OSH researchers should work across disciplines to integrate work into the broader health equity research agenda.
Inventory and Distribution Characteristics of Large-Scale Landslides in Baoji City, Shaanxi Province, China
Authors: Li Lei , Xu Chong , Xu Xiwei , Zhang Zhongjian , Cheng Jia
Published: December 2021

Inventories of historical landslides play an important role in the assessment of natural hazards. In this study, we used high-resolution satellite imagery from Google Earth to interpret large landslides in Baoji city, Shaanxi Province on the southwestern edge of the Loess Plateau. Then, a comprehensive and detailed map of the landslide distribution in this area was prepared in conjunction with the historical literature, which includes 3440 landslides. On this basis, eight variables, including elevation, slope, aspect, slope position, distance to the fault, land cover, lithology and distance to the stream were selected to examine their influence on the landslides in the study area. Landslide number density (LND) and landslide area percentage (LAP) were used as evaluation indicators to analyze the spatial distribution characteristics of the landslides. The results show that most of the landslides are situated at elevations from 500 to 1400 m. The LND and LAP reach their peaks at slopes of 10–20°. Slopes facing WNW and NW directions, and middle and lower slopes are more prone to sliding with higher LND and LAP. LND and LAP show a decreasing trend as the distance to the fault or stream increases, followed by a slow rise. Landslides occur primarily in the areas covered by crops. Regarding lithology, the regions covered by the Quaternary loess and Cretaceous gravels are the main areas where landslides occur. The results would be helpful for further understanding the developmental characteristics and spatial distribution of landslides on the Loess Plateau, and also provide a support to subsequent landslide susceptibility mapping in this region.
Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer’s Disease
Authors: Bonfili Laura , Gong Chunmei , Lombardi Francesca , Cifone Maria Grazia , Eleuteri Anna Maria
Published: December 2021

Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in neurodegenerative pathologies. We report evidence that chronic supplementation with SLAB51 enhanced cerebral expression of HIF-1α and decreased levels of prolyl hydroxylase 2 (PHD2), an oxygen dependent regulator of HIF-1α degradation; moreover, it successfully counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels in AD mice. Altogether, the results demonstrate an additional mechanism through which SLAB51 exerts neuroprotective and anti-inflammatory effects in this model of AD.
Facilitating GL13K Peptide Grafting on Polyetheretherketone via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide: Surface Properties and Antibacterial Activity
Authors: Hu Chih-Chien , Kumar Selvaraj Rajesh , Vi Truong Thi Tuong , Huang Yu-Tzu , Chen Dave W. , Lue Shingjiang Jessie
Published: December 2021

In the present work, the antimicrobial peptide (AMP) of GL13K was successfully coated onto a polyetheretherketone (PEEK) substrate to investigate its antibacterial activities against Staphylococcus aureus (S. aureus) bacteria. To improve the coating efficiency, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) was mixed with a GL13K solution and coated on the PEEK surface for comparison. Both energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) data confirmed 30% greater peptide coating on PEEK/GL13K-EDC than PEEK without EDC treatment. The GL13K graft levels are depicted in the micrograms per square centimeter range. The PEEK/GL13K-EDC sample showed a smoother and lower roughness (Rq of 0.530 µm) than the PEEK/GL13K (0.634 µm) and PEEK (0.697 µm) samples. The surface of the PEEK/GL13K-EDC was more hydrophilic (with a water contact angle of 24°) than the PEEK/GL13K (40°) and pure PEEK (89°) samples. The pure PEEK disc did not exhibit any inhibition zone against S. aureus. After peptide coating, the samples demonstrated significant zones of inhibition: 28 mm and 25 mm for the PEEK/GL13K-EDC and PEEK/GL13K samples, respectively. The bacteria-challenged PEEK sample showed numerous bacteria clusters, whereas PEEK/GL13K contained a little bacteria and PEEK/GL13K-EDC had no bacterial attachment. The results confirm that the GL13K peptide coating was able to induce antibacterial and biofilm-inhibitory effects. To the best of our knowledge, this is the first report of successful GL13K peptide grafting on a PEEK substrate via EDC coupling. The present work illustrates a facile and promising coating technique for a polymeric surface to provide bactericidal activity and biofilm resistance to medical implantable devices.
Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells
Authors: Wang Shuo-Yu , Shih Yin-Hwa , Shieh Tzong-Ming , Tseng Yu-Hsin
Published: December 2021

Over half of older patients with acute myeloid leukemia (AML) do not respond to cytotoxic chemotherapy, and most responders relapse because of drug resistance. Cytarabine is the main drug used for the treatment of AML. Intensive treatment with high-dose cytarabine can increase the overall survival rate and reduce the relapse rate, but it also increases the likelihood of drug-related side effects. To optimize cytarabine treatment, understanding the mechanism underlying cytarabine resistance in leukemia is necessary. In this study, the gene expression profiles of parental HL60 cells and cytarabine-resistant HL60 (R-HL60) cells were compared through gene expression arrays. Then, the differential gene expression between parental HL60 and R-HL60 cells was measured using KEGG software. The expression of numerous genes associated with the nuclear factor κB (NF-κB) signaling pathway changed during the development of cytarabine resistance. Proteasome inhibitors inhibited the activity of non-canonical NF-κB signaling pathway and induced the apoptosis of R-HL60 cells. The study results support the application and possible mechanism of proteasome inhibitors in patients with relapsed or refractory leukemia.
Structure–Function Relationships in the Human P-Glycoprotein (ABCB1): Insights from Molecular Dynamics Simulations
Authors: Mora Lagares Liadys , Pérez-Castillo Yunierkis , Minovski Nikola , Novič Marjana
Published: December 2021

P-Glycoprotein (P-gp) is a transmembrane protein belonging to the ATP binding cassette superfamily of transporters, and it is a xenobiotic efflux pump that limits intracellular drug accumulation by pumping compounds out of cells. P-gp contributes to a reduction in toxicity, and has broad substrate specificity. It is involved in the failure of many cancer and antiviral chemotherapies due to the phenomenon of multidrug resistance (MDR), in which the membrane transporter removes chemotherapeutic drugs from target cells. Understanding the details of the ligand–P-gp interaction is therefore critical for the development of drugs that can overcome the MDR phenomenon, for the early identification of P-gp substrates that will help us to obtain a more effective prediction of toxicity, and for the subsequent outdesign of substrate properties if needed. In this work, a series of molecular dynamics (MD) simulations of human P-gp (hP-gp) in an explicit membrane-and-water environment were performed to investigate the effects of binding different compounds on the conformational dynamics of P-gp. The results revealed significant differences in the behaviour of P-gp in the presence of active and non-active compounds within the binding pocket, as different patterns of movement were identified that could be correlated with conformational changes leading to the activation of the translocation mechanism. The predicted ligand–P-gp interactions are in good agreement with the available experimental data, as well as the estimation of the binding-free energies of the studied complexes, demonstrating the validity of the results derived from the MD simulations.
High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling
Authors: Øvestad Irene Tveiterås , Engesæter Birgit , Halle Mari Kyllesø , Akbari Saleha , Bicskei Beatrix , Lapin Morten , Austdal Marie , Janssen Emiel A. M. , Krakstad Camilla , Lillesand Melinda , Nordhus Marit , Munk Ane Cecilie , Gudlaugsson Einar G.
Published: December 2021

Implementation of high-risk human papilloma virus (HPV) screening and the increasing proportion of HPV vaccinated women in the screening program will reduce the percentage of HPV positive women with oncogenic potential. In search of more specific markers to identify women with high risk of cancer development, we used RNA sequencing to compare the transcriptomic immune-profile of 13 lesions with cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) and 14 normal biopsies from women with detected HPV infections. In CIN3/AIS lesions as compared to normal tissue, 27 differential expressed genes were identified. Transcriptomic analysis revealed significantly higher expression of a number of genes related to proliferation, (CDKN2A, MELK, CDK1, MKI67, CCNB2, BUB1, FOXM1, CDKN3), but significantly lower expression of genes related to a favorable immune response (NCAM1, ARG1, CD160, IL18, CX3CL1). Compared to the RNA sequencing results, good correlation was achieved with relative quantitative PCR analysis for NCAM1 and CDKN2A. Quantification of NCAM1 positive cells with immunohistochemistry showed epithelial reduction of NCAM1 in CIN3/AIS lesions. In conclusion, NCAM1 and CDKN2A are two promising candidates to distinguish whether women are at high risk of developing cervical cancer and in need of frequent follow-up.
Novel Tetrazole-Based Antimicrobial Agents Targeting Clinical Bacteria Strains: Exploring the Inhibition of Staphylococcus aureus DNA Topoisomerase IV and Gyrase
Authors: Roszkowski Piotr , Szymańska-Majchrzak Jolanta , Koliński Michał , Kmiecik Sebastian , Wrzosek Małgorzata , Struga Marta , Szulczyk Daniel
Published: December 2021

Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1–3 were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds 1, 2, 3 were within the range of 0.8–3.2 μg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical Staphylococci panels: Staphylococcus aureus (T5592; T5591) and Staphylococcus epidermidis (5253; 4243) with MIC values of 0.8 μg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds 1–3 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates.
Evaluation of the Effect of Fungatol and Gamma-T-ol on the Emergence and Adult Parasitoid Survival of Mummies of Cotton Aphids Parasitized by Aphidius colemani
Authors: Hassan Errol , Mostafiz Md Munir , Iramu Ellen Talairamo , George Doug , Lee Kyeong-Yeoll
Published: December 2021

Beneficial insects play a major role in controlling pest populations. In sustainable agricultural production systems, control methods compatible with integrated pest management (IPM) are preferred over broad-spectrum pesticides. EOs from aromatic plants may provide a new and safe alternative to synthetic chemicals. In this research, the efficacy of Fungatol, Gamma-T-ol, Fungatol plus neem, and Gamma-T-ol plus neem was evaluated against Aphidius colemani Viereck (Hymenoptera: Braconidae; Aphidiidae), the parasitoid of the cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae). Under laboratory and greenhouse conditions, five different concentrations of each formulation were applied to parasitized mummies and adult parasitoids. Results for parasitoid emergence from aphid mummies sprayed with different concentrations of Fungatol, Gamma-T-ol, Fungatol plus neem, and Gamma-T-ol plus neem in the laboratory and glasshouse showed that the formulations did not adversely affect adult emergence as rates above 60% were observed. For residual toxicity tests done by exposing adult parasitoids to a fresh, dry biopesticide film sprayed on glass plates, less than 20% mortality was observed after 48 h of exposure. Adult longevity tests revealed that the highest concentrations of some of the formulations evaluated were slightly toxic to A. colemani. According to the IOBC rating, our results indicated that most of the tested concentrations for each formulation were harmless to A. colemani. Based on the above results, it may be proposed that the formulations evaluated in this study are potential botanical pesticide candidates for incorporation into an IPM program.
Laser Fiber Displacement Velocity during Tm-Fiber and Ho:YAG Laser Lithotripsy: Introducing the Concept of Optimal Displacement Velocity
Authors: Panthier Frederic , Germain Thibault , Gorny Cyril , Berthe Laurent , Doizi Steeve , Traxer Olivier
Published: December 2021

Background: Endocorporeal laser lithotripsy (EL) during flexible ureteroscopy (URS-f) often uses “dusting” settings with “painting” technique. The displacement velocity of the laser fiber (LF) at the stone surface remains unknown and could improve EL’s ablation rates. This in vitro study aimed to define the optimal displacement velocity (ODV) for both holmium:yttrium-aluminium-garnet (Ho:YAG) and thulium fiber laser (Tm-Fiber). Methods: A 50W-TFL (IRE Polus®, Moscow, Russia) and a 30W-MH1-Ho:YAG laser (Rocamed®, Signes, Provence-Alpes-Côte d’Azur, France), were used with 272 µm-Core-Diameter LF (Sureflex, Boston Scientific©, San Jose, CA, USA), comparing three TFL modes, “fine dusting” (FD: 0.05–0.15 J/100–600 Hz); “dusting” (D: 0.5 J/30–60 Hz); “fragmentation” (Fr: 1 J/15–30 Hz) and two Ho:YAG modes (D: 0.5 J/20 Hz, Fr: 1 J/15 Hz). An experimental setup consisting of immerged cubes of calcium oxalate monohydrate (COM) stone phantoms (Begostone Plus, Bego©, Lincoln, RI, USA) was used with a 2 s’ laser operation time. LF were in contact with the stones, static or with a displacement of 5, 10 or 20 mm. Experiments were repeated four times. Stones were dried and µ-scanned. Ablation volumes (mm3) were measured by 3D-segmentation. Results: ODV was higher in dusting compared to fragmentation mode during Ho:YAG lithotripsy (10 mm/s vs. 5 mm/s, respectively). With Tm-Fiber, dusting and fragmentation OVDs were similar (5 mm/s). Tm-Fiber ODV was lower than Ho:YAGs in dusting settings (5 mm/s vs. 10 mm/s, respectively). Without LF displacement, ablation volumes were at least two-fold higher with Tm-Fiber compared to Ho:YAG. Despite the LF-DV, we report a 1.5 to 5-fold higher ablation volume with Tm-Fiber compared to Ho:YAG. Conclusions: In dusting mode, the ODVTm-Fiber is lower compared to ODVHo:YAG, translating to a potential easier Tm-Fiber utilization for “painting” dusting technique. The ODV determinants remain unknown. Dynamic ablation volumes are higher to static ones, regardless of the laser source, settings or LF displacement velocity.
Weakening or Structural Strengthening? An Evaluation of Bone Density after MRgFUS Ablation for Treatment of Benign Bone Lesions
Authors: de Cataldo Camilla , Bruno Federico , Necozione Stefano , Novello Mariangela , Palumbo Pierpaolo , Zugaro Luigi , Barile Antonio , Masciocchi Carlo , Arrigoni Francesco
Published: December 2021

Previous studies suggest that interventional ablative procedures on bone lesions may weaken the bone, especially when performed through the needle approach. Our purpose was to evaluate, through Computed Tomography (CT), the effects of Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) ablation on painful osteoid osteomas and osteoblastomas in terms of bone density and morphological changes. We retrospectively evaluated patients treated at our institution with MRgFUS for superficial, painful osteoid osteoma or osteoblastoma during the last 9 years. Inclusion criteria were procedural and clinical success, as well as the availability of pre- and postprocedural CT examinations. Imaging features assessed were perilesional/nidus density changes and the occurrence of pathological fractures during the follow-up period. Our study population included 31 osteoid osteomas and 5 intra-articular osteoblastomas in 36 treated patients. We found an increased bone density of the lesions when pre and post-treatment CT- values were compared: these differences were statistically significant, and this finding is consistent with significant bone densification at the post-treatment imaging follow-up. No pathological fractures were observed after ablation during the follow-up. MRgFUS can be considered to be the treatment of choice for benign superficial bone lesions, thanks to its minimal invasiveness, excellent effectiveness, and safety. Pathological fractures, reported in literature as a rare event using needle ablation, never occurred in our MRgFUS treatment series.
Conservative Surgery in Endometrial Cancer
Authors: Gallo Alessandra , Catena Ursula , Saccone Gabriele , Di Spiezio Sardo Attilio
Published: December 2021

Endometrial cancer (EC) is the sixth most common female cancer worldwide. The median age of diagnosis is 65 years. However, 4% of women diagnosed with EC are younger than 40 years old, and 70% of these women are nulliparous. These data highlight the importance of preserving fertility in these patients, at a time when the average age of the first pregnancy is significantly delayed and is now firmly established at over 30 years of age. National Comprehensive Cancer Network (NCCN guidelines state that the primary treatment of endometrial endometrioid carcinoma, limited to the uterus, is a total hysterectomy, bilateral salpingo-oophorectomy and surgical staging. Fertility-sparing treatment is not the standard of care, and patients eligible for this treatment always have to undergo strict counselling. Nowadays, a combined approach consisting of hysteroscopic resection, followed by oral or intrauterine-released progestins, has been reported to be an effective fertility-sparing option. Hysteroscopic resection followed by progestins achieved a complete response rate of 95.3% with a recurrence rate of 14.1%. The pregnancy rate in women undergoing fertility-sparing treatment is 47.8%, but rises to 93.3% when only considering women who tried to conceive during the study period. The aim of the present review is to provide a literature overview reflecting the current state of fertility-sparing options for the management of EC, specific criteria for considering such options, their limits, the implications for reproductive outcomes and the latest research trends in this direction.
Synergistic Impact of Bioactive Byproduct Extract Leads to Anti-Fusarium and Anti-Mycotoxin Secretion
Authors: Badr Ahmed Noah , Stepien Lukasz , Drzewiecka Kinga , Alharthi Salman S. , Selim Khaled , Abdel-Razek Adel Gabr
Published: December 2021

Fruit byproducts are considered a high source of bioactive molecules, which possess antioxidant activities. These antioxidants play principal functions in mycotoxin reduction. This study aimed to evaluate crude mandarin byproduct extract for its chemical interaction with fungal growth and suppression of mycotoxin production, and to illustrate whether the impact was regarding individual molecules or a synergistic antioxidation process. Extract contents were analyzed for their phenolic, flavonoids, and antioxidant activity. The fatty acid composition and volatile components were determined using the GC apparatus. The influence of the extract evaluated versus the standard phenolics of trans-ferulic and hesperidin were evaluated. The liposome technique was applied to prevent the antioxidant properties of the bioactive extract. The anti-mycotoxigenic effects of the liposomal and non-liposomal extract were determined in fungal media against the standard phenolics. The results manifested ferulic (235.54 ± 3.34 mg/100 g) and hesperidin (492.11 ± 1.15 mg/100 g) as high phenolics in the extract. Limonene was the main volatile (67.54 ± 1.74%), as well antioxidant activities determined in considerable values. The crude extract recorded efficiency as an anti-Fusarium agent, but less than the standard hesperidin applied in fungal media. The bioactive extract recorded possessed a reduction influence on mycotoxin production. The impact may be joining with its fungal inhibition or its component activity with the active groups on the mycotoxin molecule. The formation of liposomal extract enhanced its efficacy in mycotoxin reduction. This enhancement may illustrate its protective properties for antioxidant components of the bioactive extract.