bluuebunny/crossref_metadata_2025 huggingface dataset:
Control Strategy and Corresponding Parameter Analysis of a Virtual Synchronous Generator Considering Frequency Stability of Wind Power Grid-Connected System
Authors: Liu Yingming , Wang Hanbo , Wang Xiaodong , Guo Guoxian , Jing Hejun
Published: September 2022

The doubly-fed induction generator (DFIG) based on the control strategy of constant parameter virtual synchronous generator (VSG) can cause problems of sharp frequency variations in the grid-connected system, long adjustment times, and large overshoot of the active power output from the DFIG. Aiming at dealing with the above-mentioned problems, a VSG control strategy with an independent flexible link (IFLVSG) is proposed in this paper without changing the parameters and structure of the VSG, so that the moment of inertia and damping coefficient can be flexibly adjusted according to the change of the system frequency, so as to improve the system frequency stability. To form a complete selection scheme for control parameters in IFL, the state space equation including IFLVSG control is established, and the advantages of exponential IFL are highlighted by using the sensitivity calculation method. At the same time, in order to improve the analysis efficiency, the main control parameters affecting the frequency stability of the system are selected according to the sensitivity value. Finally, the root locus analysis method is used to reveal the influence law of the main control parameters on the frequency stability of the system. The formed scheme provides a theoretical basis for the selection of control parameters.
Prerequisites and Theoretical Foundations of the Statistical Method of Frequency Stabilization in Information and Telecommunication Systems
Authors: Safaryan Olga Alexandrovna , Alferova Irina Alexandrovna
Published: September 2022

The article deals with issues related to the manifestation of the properties of synergy and emergence, potentially inherent in systems with the same or similar properties of components. These properties can be used to increase the accuracy of estimates of the frequency of signals in the system of simultaneously and independently functioning oscillators. It makes possible to increase the stability of the frequency of the generated signals. To implement these properties, simultaneous measurement of signal phase values at a number of time intervals with subsequent processing using the likelihood function can be used. It is shown that the manifestation of the synergistic property in a system of simultaneously and independently operating oscillators reduces the error in estimating random fluctuations in the frequency of oscillators. The manifestation of the emergence property allows you to exclude a constant frequency shift from the nominal value. The conditions for obtaining unbiased effective estimates of the frequency of each of the oscillators are formulated. It is noted that from a physical point of view, an increase in the accuracy of estimating the frequency of signals corresponds to multiple non-precision indirect measurements. The results of mathematical modeling are presented.
Investigation on Flow Maldistribution and Thermo-Hydraulic Performance of PCHEs with Spoiler Perforated Boards
Authors: Wang Wei , Niu Mengke , Tan Yufei , Li Bingxi , Shuai Yong
Published: September 2022

In this study, the effects of the maldistribution coefficient on the thermo-hydraulic performance of discontinuous fin printed circuit heat exchanger (DF-PCHE) entrance head and channels are numerically investigated. To improve the flow uniformity at the entrance head, the flow in the exchanger with three types of spoiler perforated boards (SPBs) having 3 × 3, 4 × 4, and 5 × 5 holes and three kinds of hole diameters (Φd = 30, 25, and 20 mm), respectively, are compared to the flow in an exchanger with no SPB. The results show that a small maldistribution coefficient for the inlet velocity field is beneficial for the thermo-hydraulic performance of the DF-PCHE channels, and a maldistribution coefficient of 0.7 is an acceptable velocity distribution for the PCHE channel inlet. Using the 3 × 3 SPB with Φd = 30 mm, the maldistribution coefficient becomes 0.7, the fastest among all the SPB application cases at ΔL = 150 mm. Moreover, its heat transfer coefficient and pressure drop increase by 22.46% and decreases by 47.2% compared to those of the exchanger without SPB, respectively.
A Low-Storage Blockchain Framework Based on Incentive Pricing Strategies
Authors: Ko Po-Han , Hsueh Yu-Ling , Hsueh Chih-Wen
Published: September 2022

Nowadays, blockchain bloat is an endangering issue caused by inefficient transaction storage mechanisms. Based on the Distributed File System (DFS), the blockchain network can reduce the local storage to solve the blockchain bloat problem. However, storing all blocks on DFS is not durable or scalable. Hence, classifying blocks into hot and cold was adopted in previous works. The blockchain nodes can reduce the time consumption and storage consumption by storing hot blocks locally. However, the previous works are not able to periodically check block integrity and do not provide a reward mechanism to encourage DFS system nodes to store blocks. We extend previous works based on the InterPlanetary File System (IPFS) and design an innovative scheme to incentivize IPFS nodes. The IPFS nodes are regulated with smart contracts and behave under the pricing strategy controls to increase profit. By adopting proof of retrievability, we guarantee the integrity of the blocks. Further, the redundant scheme extends our pricing strategy to improve the durability of our proposed framework. A load-balancing pricing strategy and a general pricing strategy are provided in the framework to reward the DFS nodes. Extensive experiments are presented to demonstrate that the latency and throughputs of our model are competitive, while still maintaining data integrity in the system. The additional increased throughput takes only 0.167% of that produced by the original Bitcoin and the upload latency takes only 6.67% of the mining time of the Bitcoin Mainnet. Furthermore, our load-balancing pricing strategy achieves the effectiveness to ensure the redundancy of blocks and reduces the overall storage consumption up to 97% using the load-balancing pricing strategy, compared to the non-load-balancing pricing strategy.
Microwave-Assisted Extraction of Polyphenols from Blackcurrant By-Products and Possible Uses of the Extracts in Active Packaging
Authors: Alchera Federica , Ginepro Marco , Giacalone Giovanna
Published: September 2022

The design of experiment (DoE) approach was used to optimize the extraction of polyphenols from blackcurrant by-products with microwave-assisted extraction and deionized water as a green solvent. Three factors (microwave power, extraction time, and solvent/matrix ratio) were evauated, and a central composite orthogonal design (CCO) was applied in order to reduce experimental runs. Empirical models relating the response and process parameters were developed. The validity of the models was tested using an analysis of variance (ANOVA). The optimal extraction conditions were found using the highest value of microwave power (780–800 W) and the lowest extraction time (60 min) and solvent/matrix ratio (10 m/g). Compared with conventional solvent extraction, the polyphenol yield increased by 25% after applying the optimized MAE process. The obtained extract was used to realize a sustainable active maltodextrin (Glucidex 2) pad using an electrospinning technique. The antimicrobial and antioxidant activities of the pads were tested on the post-harvest storage of raspberries. Two set of experiments were carried out. The recorded results showed that the pad had antimicrobial activity on the tested fruit samples and implied the possibility of using it to extend the shelf-life of the fruits.
Microwave and Roasting Impact on Pumpkin Seed Oil and Its Application in Full-Fat Mayonnaise Formula
Authors: Rezig Leila , Harzalli Zina , Gharsallah Karima , Mahfoudhi Nesrine , Chouaibi Moncef , Majdoub Hatem , Oueslati Imen
Published: September 2022

In this study, ‘Béjaoui’ Cucurbita maxima seeds variety were exposed to both microwave and roasting prior to oil cold press extraction. In addition, full-fat mayonnaise formula from untreated and treated pumpkin seed oils was prepared and assessed for their physical stabilities and bioactive properties in 28-day storage at 25 ± 1 °C. A mayonnaise sample prepared with unrefined sunflower seed oil served as a control. The results showed that the microwave pretreatment of seeds greatly enhanced the oxidative stability of the pumpkin seed oil, which increased from 3 h 46 min ± 10 min in the untreated sample to 4 h 32 min ± 14 min in the microwave cold press pumpkin seed oil. The sterol content increased from 4735 ± 236.75 mg/kg oil in the untreated cold press pumpkin seed oil to 5989 ± 299.45 mg/kg oil and 7156 ± 357.8 mg/kg in the microwave cold press pumpkin seed oil and the roasted cold press pumpkin seed oil, respectively. The mayonnaise prepared with microwave cold press pumpkin seed oil exhibited the lowest creaming index and was more stable to droplet growth when compared to the other mayonnaise samples. All mayonnaise samples prepared with pumpkin seed oils exhibited higher total phenolic contents and antioxidant activities during storage when compared to the mayonnaise sample prepared with unrefined sunflower seed oil. Among pumpkin seed oil mayonnaise samples, the highest values were, however, observed in the one prepared with microwave cold press pumpkin seed oil. Thanks to its high nutraceuticals, the latter could be confidently regarded as a natural fat substitute for commercial stable vegetable oils mayonnaise type emulsions.
An Efficient Dissipation-Preserving Numerical Scheme to Solve a Caputo–Riesz Time-Space-Fractional Nonlinear Wave Equation
Authors: Macías-Díaz Jorge E. , Bountis Tassos
Published: September 2022

For the first time, a new dissipation-preserving scheme is proposed and analyzed to solve a Caputo–Riesz time-space-fractional multidimensional nonlinear wave equation with generalized potential. We consider initial conditions and impose homogeneous Dirichlet data on the boundary of a bounded hyper cube. We introduce an energy-type functional and prove that the new mathematical model obeys a conservation law. Motivated by these facts, we propose a finite-difference scheme to approximate the solutions of the continuous model. A discrete form of the continuous energy is proposed and the discrete operator is shown to satisfy a conservation law, in agreement with its continuous counterpart. We employ a fixed-point theorem to establish theoretically the existence of solutions and study analytically the numerical properties of consistency, stability and convergence. We carry out a number of numerical simulations to verify the validity of our theoretical results.
A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders
Authors: Mashabela Leshasha T. , Maboa Mahlako M. , Miya Ntombi F. , Ajayi Taiwo O. , Chasara Rumbidzai S. , Milne Marnus , Mokhele Shoeshoe , Demana Patrick H. , Witika Bwalya A. , Siwe-Noundou Xavier , Poka Madan S.
Published: September 2022

Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.
Study on the Hydration Reaction of Typical Clay Minerals under Alkali and Sulfate Compound Activation
Authors: Zhang Siqi , Wu Zeping , Chen Jiaming , Xu Runsheng , Wang Meina , Ni Wen
Published: September 2022

Sand, stone, tailings and other aggregates often contain a small amount of clay mineral and their hydration activity is low, thereby lowering concrete performance indexes while negatively affecting their resource utilisation. In this study, clay minerals, calcium hydroxide and desulfurised gypsum were used to prepare cementitious materials to examine kaolinite, montmorillonite, illite and chlorite clay mineral contents under compound activation. The effects of curing temperature and water reducer on clay samples were analysed. The results showed that the compressive strength of kaolinite samples cured at 25 °C and 55 °C reached 1.09 and 4.93 MPa in 28 days and increased by 43% and 12%, respectively, after adding a 0.3% water reducer. Montmorillonite was activated and its compressive strength reached 5.33 MPa after curing at 55 °C in 28 days. Illite exhibited some activity and its compressive strength reached 1.43 MPa after curing at 55 °C in 28 days and the strength increased slightly after adding a water reducer. The chlorite sample had no strength after activation under the same conditions. Furthermore, X-ray diffraction and scanning electron microscope and energy-dispersive spectroscopy microstructure analyses showed that after alkali and sulfate activation, the hydration products of activated clay minerals mainly included ettringite, hydrated calcium aluminate and hydrated calcium silicate. The increase in curing temperature accelerated the reaction speed and improved the early strength. However, the effect on chlorite minerals was not obvious.
An Observational Study Using Ultrasound to Assess Allowable Needle Insertion Range of Acupoint CV12
Authors: Chu Hongmin , Kim Jaehyo , Park Seongjun , Kim Jaehyun , Lee Jung-Han , Ha Won-Bae , Jung Hyun-Jong , Yang Seung-bum , Kim Cheol-hyun , Park Jun Yong , Kang Kyung-ho , Lee Sangkwan , Lee Sanghun
Published: September 2022

Background: Abdominal organ injuries are a rarely reported complication when deep acupuncture needling is applied to the abdomen. In order to ascertain the allowable needle insertion range (ANIR) of the abdomen region, we selected acupoint CV12, which is commonly used for treating gastric disease, and ANIR was measured with an ultrasound device. Method: Eighty-five healthy volunteers were recruited, of which 83 cases of ultrasound images were obtained. To investigate the prediction factor of ANIR, we also measured several anthropometric factors. Results: The average ANIR was 25.3 ± 10.2; generally, the ANIRs of females were thicker than those of males; and the liver was observed in 62.7% subjects’ ultrasound images. The non-observed group showed thicker ANIR and higher BMI than the liver-observed group. Conclusion: There are reliable variables that make it possible to predict the ANIR. It is advised to refer to anthropometric factors in needling acupoint CV12 to avoid complications with the acupuncture treatment. However, individual differences are not negligible when applying deep needling. Thus, if the risk is not judged before or during the procedure, practitioners could consider the patient’s ANIR on CV12 when applying acupuncture by examining the individual anatomical structures using ultrasound and considering internal organ positions to prevent adverse events due to acupuncture.
Fast Saccadic Eye Movements Contribute to the Worsened Postural Sway in Older Adults Who Have Experienced Falls
Authors: Lee Changjoon , Lee Subin , Bae Youngsook
Published: September 2022

The purpose of this study was to examine changes and between-group differences in postural sway during saccadic eye movement in older adults (n = 152). The participants were stratified into older adults who have experienced a fall (n = 58) (faller group) and those who have not (n = 94) (non-faller group). We measured postural sway during saccadic eye movement. Saccadic eye movement speed was such that the target was displayed at 0.5 Hz, 2 Hz, and 3 Hz. Postural sway was measured based on path length, velocity, and length between the maximal and minimal position of center of pressure in mediolateral and anteroposterior direction. In the faller group, path length, velocity, and mediolateral displacement of the center of pressure increased significantly during 3 Hz saccadic eye movement stimulation. However, in the non-faller group, there was no significant change in the center of pressure parameters during saccadic eye movement stimulation. Mediolateral displacement of the center of pressure increased significantly in both groups during saccadic eye movement, especially at 3 Hz. Therefore, rapid saccadic eye movement stimulation can contribute to the worsened postural sway in older adults who have experienced falls, and rapid external environmental stimuli may contribute to the deterioration of the upright standing stability in older adults.
Evaluation of Natural Stone Weathering in Heritage Building by Infrared Thermography
Authors: Pappalardo Giovanna , Mineo Simone , Caliò Davide , Bognandi Annamaria
Published: September 2022

The application of non-contact diagnostic methodologies is the current challenge in the frame of the cultural heritage, referred to as preservation, monitoring and restoration. Inspired by the potential shown by infrared thermography in rock mechanics’ non-destructive applications, this paper presents the results achieved by its use for the quick survey of different weathering types affecting natural stones at historical buildings. Infrared thermography allowed recognizing and mapping the different surface temperatures arising from the presence of efflorescence, subflorescence, alveolization, black crusts and bioweathering at limestone and basalt stones. Infrared data were sided by photogrammetric three-dimensional models of surveyed spots, which provided quantitative data on the thickness of rock affected by mechanical weathering, and key correspondence between the two techniques is highlighted. Achieved results show that infrared outcomes are related to different aspects primarily involving the stone face morphology and color, as well as the environmental conditions at the surveying time. Provided interpretations were validated by field visual inspections, which confirmed the good potential of infrared thermography as a quick weathering diagnostic tool. This study can be therefore considered a starting reference for knowledge development in this scientific field.
Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1
Authors: De Simone Ilaria , Baaten Constance C. F. M. J. , Jandrot-Perrus Martine , Gibbins Jonathan M. , ten Cate Hugo , Heemskerk Johan W. M. , Jones Chris I. , van der Meijden Paola E. J.
Published: September 2022

Platelet and coagulation activation are highly reciprocal processes driven by multi-molecular interactions. Activated platelets secrete several coagulation factors and expose phosphatidylserine, which supports the activation of coagulation factor proteins. On the other hand, the coagulation cascade generates known ligands for platelet receptors, such as thrombin and fibrin. Coagulation factor (F)Xa, (F)XIIIa and activated protein C (APC) can also bind to platelets, but the functional consequences are unclear. Here, we investigated the effects of the activated (anti)coagulation factors on platelets, other than thrombin. Multicolor flow cytometry and aggregation experiments revealed that the ‘supernatant of (hirudin-treated) coagulated plasma’ (SCP) enhanced CRP-XL-induced platelet responses, i.e., integrin αIIbβ3 activation, P-selectin exposure and aggregate formation. We demonstrated that FXIIIa in combination with APC enhanced platelet activation in solution, and separately immobilized FXIIIa and APC resulted in platelet spreading. Platelet activation by FXIIIa was inhibited by molecular blockade of glycoprotein VI (GPVI) or Syk kinase. In contrast, platelet spreading on immobilized APC was inhibited by PAR1 blockade. Immobilized, but not soluble, FXIIIa and APC also enhanced in vitro adhesion and aggregation under flow. In conclusion, in coagulation, factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors.
The Asparaginyl Endopeptidase Legumain: An Emerging Therapeutic Target and Potential Biomarker for Alzheimer’s Disease
Authors: Song Mingke
Published: September 2022

Alzheimer’s disease (AD) is incurable dementia closely associated with aging. Most cases of AD are sporadic, and very few are inherited; the pathogenesis of sporadic AD is complex and remains to be elucidated. The asparaginyl endopeptidase (AEP) or legumain is the only recognized cysteine protease that specifically hydrolyzes peptide bonds after asparagine residues in mammals. The expression level of AEPs in healthy brains is far lower than that of peripheral organs. Recently, growing evidence has indicated that aging may upregulate and overactivate brain AEPs. The overactivation of AEPs drives the onset of AD through cleaving tau and amyloid precursor proteins (APP), and SET, an inhibitor of protein phosphatase 2A (PP2A). The AEP-mediated cleavage of these peptides enhances amyloidosis, promotes tau hyperphosphorylation, and ultimately induces neurodegeneration and cognitive impairment. Upregulated AEPs and related deleterious reactions constitute upstream events of amyloid/tau toxicity in the brain, and represent early pathological changes in AD. Thus, upregulated AEPs are an emerging drug target for disease modification and a potential biomarker for predicting preclinical AD. However, the presence of the blood–brain barrier greatly hinders establishing body-fluid-based methods to measure brain AEPs. Research on AEP-activity-based imaging probes and our recent work suggest that the live brain imaging of AEPs could be used to evaluate its predictive efficacy as an AD biomarker. To advance translational research in this area, AEP imaging probes applicable to human brain and AEP inhibitors with good druggability are urgently needed.
Correction: Funk et al. Criticality of Surface Characteristics of Intravenous Iron-Carbohydrate Nanoparticle Complexes: Implications for Pharmacokinetics and Pharmacodynamics. Int. J. Mol. Sci. 2022, 23, 2140
Authors: Funk Felix , Flühmann Beat , Barton Amy E.
Published: September 2022

The authors wish to make the following corrections to this paper [...]
Amorphous and Co-Amorphous Olanzapine Stability in Formulations Intended for Wet Granulation and Pelletization
Authors: da Costa Nuno F. , Daniels Rolf , Fernandes Ana I. , Pinto João F.
Published: September 2022

The preparation of amorphous and co-amorphous systems (CAMs) effectively addresses the solubility and bioavailability issues of poorly water-soluble chemical entities. However, stress conditions imposed during common pharmaceutical processing (e.g., tableting) may cause the recrystallization of the systems, warranting close stability monitoring throughout production. This work aimed at assessing the water and heat stability of amorphous olanzapine (OLZ) and OLZ-CAMs when subject to wet granulation and pelletization. Starting materials and products were characterized using calorimetry, diffractometry and spectroscopy, and their performance behavior was evaluated by dissolution testing. The results indicated that amorphous OLZ was reconverted back to a crystalline state after exposure to water and heat; conversely, OLZ-CAMs stabilized with saccharin (SAC), a sulfonic acid, did not show any significant loss of the amorphous content, confirming the higher stability of OLZ in the CAM. Besides resistance under the processing conditions of the dosage forms considered, OLZ-CAMs presented a higher solubility and dissolution rate than the respective crystalline counterpart. Furthermore, in situ co-amorphization of OLZ and SAC during granule production with high fractions of water unveils the possibility of reducing production steps and associated costs.
Formation of Ultimate Thin 2D Crystal of Pt in the Presence of Hexamethylenetetramine
Authors: Sadikin Siti Naqiyah , Ali Umar Marjoni Imamora , Hamzah Azrul Azlan , Nurdin Muhammad , Umar Akrajas Ali
Published: September 2022

Platinum naturally crystalizes into a three-dimensional crystal due to its highly symmetrical fcc lattice, with a metallic bond which is non-directional and highly isotropic. This inherently means ultimately that 2D crystals of a few atoms thick growth are hardly available in this material. Here, we discovered that a combinative effect of formic acid reductant and hexamethylenetetramine surfactant during the reduction of their metal ions precursor can realize an ultimate thin 2D crystal growth in platinum. High-resolution transmission electron microscopy and filed-emission electron microscopy analysis have also discovered that the 2D crystal of Pt has 111 facets with a lateral dimension that can be up to more than 5 μm × 2 μm. The thickness of the 2D crystal of Pt is 1.55 nm. A mechanism for obtaining ultimate thin 2D crystal of Pt using the present approach is proposed.
Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis
Authors: Nidadavolu Prakash , Bilkei-Gorzo Andras , Effah Felix , Leidmaa Este , Schürmann Britta , Berger Moritz , Bindila Laura , Schmid Matthias , Lutz Beat , Zimmer Andreas , Bailey Alexis
Published: September 2022

Endocannabinoid (eCB) signaling is markedly decreased in the hippocampus (Hip) of aged mice, and the genetic deletion of the cannabinoid receptor type 1 (CB1) leads to an early onset of cognitive decline and age-related histological changes in the brain. Thus, it is hypothesized that cognitive aging is modulated by eCB signaling through CB1. In the present study, we detailed the changes in the eCB system during the aging process using different complementary techniques in mouse brains of five different age groups, ranging from adolescence to old age. Our findings indicate that the eCB system is most strongly affected in middle-aged mice (between 9 and 12 months of age) in a brain region-specific manner. We show that 2-arachidonoylglycerol (2-AG) was prominently decreased in the Hip and moderately in caudate putamen (CPu), whereas anandamide (AEA) was decreased in both CPu and medial prefrontal cortex along with cingulate cortex (mPFC+Cg), starting from 6 months until 12 months. Consistent with the changes in 2-AG, the 2-AG synthesizing enzyme diacylglycerol lipase α (DAGLα) was also prominently decreased across the sub-regions of the Hip. Interestingly, we found a transient increase in CB1 immunoreactivity across the sub-regions of the Hip at 9 months, a plausible compensation for reduced 2-AG, which ultimately decreased strongly at 12 months. Furthermore, quantitative autoradiography of CB1 revealed that [3H]CP55940 binding markedly increased in the Hip at 9 months. However, unlike the protein levels, CB1 binding density did not drop strongly at 12 months and at old age. Furthermore, [3H]CP55940 binding was significantly increased in the lateral entorhinal cortex (LEnt), starting from the middle age until the old age. Altogether, our findings clearly indicate a middle-age crisis in the eCB system, which could be a potential time window for therapeutic interventions to abrogate the course of cognitive aging.
Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats
Authors: Othman Zaidatul Akmal , Zakaria Zaida , Suleiman Joseph Bagi , Mustaffa Khairul Mohd Fadzli , Jalil Nur Asyilla Che , Wan Ghazali Wan Syaheedah , Zulkipli Ninie Nadia , Mohamed Mahaneem
Published: September 2022

Oxidative stress contributes to major complications of obesity. This study intended to identify whether orlistat could mitigate myocardial damage in obese animal models. The tested rats were divided into two groups and fed either with normal chow (n = 6 per group) or with a high-fat diet (HFD) for 6 weeks to induce obesity (n = 12 per group). Obese rats were further subjected to treatment either with distilled water (OB group) or orlistat 10 mg/kg/day (OB + OR group). Key indices of oxidative stress, inflammation, and apoptosis were assessed using an immunohistochemical-based technique and real-time PCR. The OB group showed significant increases of oxidative stress markers (TBARs and PCO), with significant decreases of anti-oxidant markers (Nrf2, SOD, CAT, and GPx). Furthermore, mRNA expression of pro-inflammatory markers (TNF-α and NF-κβ) and pro-apoptosis markers (Bax, Caspase-3, Caspase-8, and Caspase-9) were significantly upregulated in the OB group. Obese rats developed pathological changes of myocardial damages as evidenced by the presence of myocardial hypertrophy and inflammatory cells infiltration. Orlistat dampened the progression of myocardial damage in obese rats by ameliorating the oxidative stress, and by inhibiting NF-κβ pathway and caspase-dependent cell apoptosis. Our study proposed that orlistat could potentially mitigate oxidative stress-linked myocardial damage by mitigating inflammation and apoptosis, thus rationalizing its medical usage.
Improved Bladder Tumor RNA Isolation from Archived Tissues Using Methylene Blue for Normalization, Multiplex RNA Hybridization, Sequencing and Subtyping
Authors: Köhler Stefanie A. , Brandl Lisa , Strissel Pamela L. , Gloßner Laura , Ekici Arif B. , Angeloni Miriam , Ferrazzi Fulvia , Bahlinger Veronika , Hartmann Arndt , Beckmann Matthias W. , Eckstein Markus , Strick Reiner
Published: September 2022

Methylene blue (MB) is a dye used for histology with clinical importance and intercalates into nucleic acids. After MB staining of formalin fixed paraffin embedded (FFPE) muscle invasive bladder cancer (MIBC) and normal urothelium, specific regions could be microdissected. It is not known if MB influences RNA used for gene expression studies. Therefore, we analyzed MIBC using five different RNA isolation methods comparing patient matched FFPE and fresh frozen (FF) tissues pre-stained with or without MB. We demonstrate a positive impact of MB on RNA integrity with FF tissues using real time PCR with no interference of its chemical properties. FFPE tissues showed no improvement of RNA integrity, which we propose is due to formalin induced nucleotide crosslinks. Using direct multiplex RNA hybridization the best genes for normalization of MIBC and control tissues were identified from 34 reference genes. In addition, 5SrRNA and 5.8SrRNA were distinctive reference genes detecting <200 bp fragments important for mRNA analyses. Using these normalized RNAs from MB stained MIBC and applying multiplex RNA hybridization and mRNA sequencing, a minimal gene expression panel precisely identified luminal and basal MIBC tumor subtypes, important for diagnosis, prognosis and chemotherapy response.
Improving the Ventilation of Machinery Spaces with Direct Adiabatic Cooling System
Authors: Mihai Victor , Rusu Liliana
Published: September 2022

Machinery spaces are provided with ventilation systems that ensure the necessary airflow for combustion and cooling. In some vessels, due to space constraints, the requested air flow for cooling cannot be achieved under extreme environmental conditions, and the engine load will need to be reduced. On the other hand, the outside air temperature can increase over 35 °C in some places, and the efficiency of the ventilation will be reduced. In these cases, other solutions for cooling the engine room should be analyzed. In this paper, the environmental conditions in the Romanian Danube area are analyzed to understand whether direct adiabatic cooling can be used to improve ventilation systems and what the challenges are after increasing the relative humidity inside the machinery spaces. Based on the data recorded, it was found that outside relative humidity substantially drops when the temperature increases, which ensures good conditions for the use of adiabatic cooling. This study demonstrates that by using direct adiabatic cooling, the air flow of the ventilation system can be reduced by more than 50%, which will reduce the pressure drop across the ventilation system, together with noise and energy consumption. After adiabatic cooling, the temperature and relative humidity inside the engine room will be fine for the functionality of the equipment, but the temperature–humidity index will be high, which means high discomfort for the crew. Therefore, it is concluded that this cooling solution should only be used in unattended machinery spaces.
Transcatheter Double Valve Replacement to Treat Aortic Stenosis and Severe Tricuspid Regurgitation with 3D Printing Guidance after Mechanical Mitral Valve Replacement
Authors: Zhai Mengen , Mao Yu , Ma Yanyan , Liu Yang , Yang Jian
Published: September 2022

Background: Transcatheter treatments of tricuspid regurgitation (TR) have been emerging as alternatives for high-risk patients. In contrast to the immobilization of the common transcatheter tricuspid device, using a radial force-independent stent valve device at the native tricuspid annular site has several distinct advantages. Case summary: A 76-year-old patient with renal insufficiency who underwent mechanical mitral valve replacement in 2001 and transcatheter aortic valve replacement in 2021 due to severe aortic stenosis presented with chest pain and shortness of breath. Echocardiography suggested that the flow velocities of the mitral mechanical valve and aortic prosthetic valve were both within the normal range, with no significant paravalvular regurgitation; the tricuspid valve exhibited massive regurgitation (VMAX 258 cm/s, PGMAX 27 mmHg). Due to the high surgical risk, we simulated the procedure with a three-dimensional (3D)-printed model and performed transcatheter tricuspid valve replacement using a LuX-Valve (Ningbo Jenscare Biotechnology Co., Ningbo, China). Discussion: We describe transcatheter tricuspid valve replacement using the LuX-Valve and preprocedural guidance with 3D printing. Postprocedural TR was significantly reduced, indicating that 3D printing plays an important role in preprocedural guidance and that the LuX-Valve was safe and practicable for tricuspid valve replacement.
Prevalence, Characteristics, Management and Outcomes of Patients with Heart Failure with Preserved, Mildly Reduced, and Reduced Ejection Fraction in Spain
Authors: Escobar Carlos , Palacios Beatriz , Varela Luis , Gutiérrez Martín , Duong Mai , Chen Hungta , Justo Nahila , Cid-Ruzafa Javier , Hernández Ignacio , Hunt Phillip R. , Delgado Juan F.
Published: September 2022

Objective: To estimate the prevalence, incidence, and describe the characteristics and management of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain. Methods: Adults with ≥1 inpatient or outpatient HF diagnosis between 1 January 2013 and 30 September 2019 were identified through the BIG-PAC database. Annual incidence and prevalence by EF phenotype were estimated. Characteristics by EF phenotype were described in the 2016 and 2019 HF prevalent cohorts and outcomes in the 2016 HF prevalent cohort. Results: Overall, HF incidence and prevalence were 0.32/100 person-years and 2.34%, respectively, but increased every year. In 2019, 49.3% had HFrEF, 38.1% had HFpEF, and 4.3% had HFmrEF (in 8.3%, EF was not available). Compared with HFrEF, patients with HFpEF were largely female, older, and had more atrial fibrillation but less atherosclerotic cardiovascular disease. Among patients with HFrEF, 76.3% were taking renin-angiotensin system inhibitors, 69.5% beta-blockers, 36.8% aldosterone antagonists, 12.5% sacubitril/valsartan and 6.7% SGLT2 inhibitors. Patients with HFpEF and HFmrEF took fewer HF drugs compared to HFrEF. Overall, the event rates of HF hospitalization were 231.6/1000 person-years, which is more common in HFrEF patients. No clinically relevant differences were found in patients with HFpEF, regardless EF (50- < 60% vs. ≥60%). Conclusions: >2% of patients have HF, of which around 50% have HFrEF and 40% have HFpEF. The prevalence of HF is increasing over time. Clinical characteristics by EF phenotype are consistent with previous studies. The risk of outcomes, particularly HF hospitalization, remains high, likely related to insufficient HF treatment.
Intravitreal Dexamethasone Implant (IDI) Alone and Combined with Navigated 577 nm Subthreshold Micropulse Laser (SML) for Diabetic Macular Oedema
Authors: Toto Lisa , D’Aloisio Rossella , Quarta Alberto , Libertini Daniele , D’Onofrio Giada , De Nicola Chiara , Romano Anna , Mastropasqua Rodolfo
Published: September 2022

Background: The anatomical and functional changes after intravitreal dexamethasone implant (IDI) alone and combined with navigated subthreshold micropulse laser (NSML) in diabetic macular oedema (DMO) were compared. Methods: Patients with a clinically confirmed diagnosis of non-proliferative diabetic retinopathy (NPDR) and DMO were enrolled in this prospective study and were randomly assigned to two different treatment groups: thirty patients were treated with IDI (IDI group), and the other 30 patients received IDI combined with NSML treatment (combined IDI/NSML group). All patients during a 6-month follow-up underwent best corrected visual acuity (BCVA) evaluation and spectral domain optical coherence tomography (SD OCT). The main outcome measures were: BCVA, central macular thickness (CMT); (3) choroidal vascularity index (CVI), subfoveal choroidal thickness (SCHT); and time to retreatment between IDI at baseline and the second implant in both groups. Results: BCVA, CMT, and SCHT significantly decreased starting from the 1-month follow-up and CVI from 3 months in both groups. The between-group differences were significantly different from 1-month follow-up for BCVA, from 5-month follow-up for CMT and SCHT, and from 4-month follow-up for CVI. The Needed to Treat analysis indicated that six patients would have to be treated with SML after IDI in order for just one person to receive a benefit. Conclusions: the combined treatment showed good anatomical and functional outcomes for the treatment of DMO. In addition, IDI/SML seems to reduce injection frequency over time, improving patients’ quality of life and reducing the socio-economic burden.
Use of Electroneuromyography in the Diagnosis of Neurogenic Thoracic Outlet Syndrome: A Systematic Review and Meta-Analysis
Authors: Daley Pauline , Pomares Germain , Gross Raphael , Menu Pierre , Dauty Marc , Fouasson-Chailloux Alban
Published: September 2022

Neurogenic thoracic outlet syndrome (NTOS) is a disabling condition. Its diagnosis remains challenging and is mainly guided by examination. Yet, electrophysiological evaluations are the gold standard for diagnosis of entrapment syndromes. We aimed to assess the interest of electrophysiological evaluation to diagnose NTOS. A systematic literature research was performed using PubMed, ScienceDirect, Embase, Cochrane and Google Scholar databases to collect studies reporting results of electrophysiological assessment of patients with NTOS. Then, a meta-analysis was conducted. Nine studies were eligible and concerned two hundred and thirteen patients. Results were heterogenous among studies and the quality of evidence was very low to moderate. Data could not evaluate sensitivity or specificity of electrophysiological evaluations for NTOS. The meta-analysis found significantly decreased amplitudes of medial antebrachial cutaneous nerve SNAP (sensory nerve action potential), ulnar SNAP, median CMAP (compound motor action potential) and ulnar CMAP. Needle examination found abnormalities for the abductor pollicis brevis, first dorsal interosseous and adductor digiti minimi. Unlike most upper-limb entrapment syndromes, nerve conduction assessment only provided clues in favour of NTOS. Decreased amplitude for ulnar SNAP, medial antebrachial cutaneous SNAP, median CMAP and ulnar CMAP should be assessed, as well as needle examination. Larger studies are needed to evaluate the sensitivity and specificity of electrophysiology in NTOS diagnosis.
The Burden of Carbapenem-Resistant Acinetobacter baumannii in ICU COVID-19 Patients: A Regional Experience
Authors: Montrucchio Giorgia , Corcione Silvia , Lupia Tommaso , Shbaklo Nour , Olivieri Carlo , Poggioli Miriam , Pagni Aline , Colombo Davide , Roasio Agostino , Bosso Stefano , Racca Fabrizio , Bonato Valeria , Della Corte Francesco , Guido Stefania , Della Selva Andrea , Ravera Enrico , Barzaghi Nicoletta , Cerrano Martina , Caironi Pietro , Berta Giacomo , Casalini Cecilia , Scapino Bruno , Grio Michele , Parlanti Garbero Massimiliano , Buono Gabriella , Finessi Federico , Erbetta Simona , Sciacca Paola Federica , Fiore Gilberto , Cerutti Alessandro , Livigni Sergio , Silengo Daniela , Agostini Fulvio , Berardino Maurizio , Navarra Mauro , Vendramin Silvia , Castenetto Enzo , Liccardi Marco Maria , Manno Emilpaolo , Brazzi Luca , De Rosa Francesco Giuseppe
Published: September 2022

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028–1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572–18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team.
Treating with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Accompanying Lower Incidence of Second Primary Cancers
Authors: Chou Wen-Ru , Shia Ben-Chang , Huang Yen-Chun , Ho Chieh-Wen , Chen Mingchih
Published: September 2022

Lung cancer survivors are at risk of developing second primary cancers (SPCs). Although some risk factors for the development of SPCs have been addressed, their impacts have not been clarified. This study, based on Taiwan’s National Health Insurance Research Database (NHIRD), a nationwide database, was designed to investigate the risk factors for SPCs in patients with initial lung cancer and identify the impacts of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment on the development of SPCs. In this study, 37,954 individuals were included, of whom 2819 had SPCs. These patients were further divided into the second primary lung cancers (SPLC) and second primary extrapulmonary cancer (SPEC) groups. Among the patients with lung cancer without SPCs, those aged <65 years accounted for 53.15%. Patients aged ≥65 years accounted for 40.18% and 53.24% in the SPLC and SPEC groups, respectively. Females accounted for 50.3% of patients without SPC, 54% of the SPLC group, and 44.3% of the SPEC group. Univariate and multivariate Cox proportional hazard models showed increased hazard ratios for smoking, hypertension, and diabetes mellitus, and lower HRs for surgery, chemotherapy, radiotherapy, and TKIs. Patients undergoing surgery, chemotherapy, and radiotherapy were associated with a lower risk of SPCs. Treatment with EGFR TKIs was a significant and independent factor associated with lower incidence of SPCs. This study may encourage researchers to establish predictive models based on our results to assess the risk factors for SPCs, and therefore, early screening and intervention could be applied, and the SPCs-related mortality and relevant medical costs could be reduced.
Factors Associated with Elevated Tumor Necrosis Factor-α in Aqueous Humor of Patients with Open-Angle Glaucoma
Authors: Jung Younhea , Ohn Kyoung , Shin Heejong , Oh Si Eun , Park Chan Kee , Park Hae-Young Lopilly
Published: September 2022

Tumor necrosis factor-alpha (TNF-α) is an important modulator of neuroinflammation, secreted from activated glial cells in response to intraocular stress. The purpose of this study was to investigate the clinical factors associated with elevated TNF-α and its level in aqueous humor of patients with open-angle glaucoma (OAG). Aqueous humor was collected from 73 OAG eyes, and TNF-α level was analyzed using the singleplex bead immunoassay method. Patients were divided into TNF-α-positive and TNF-α-negative groups according to the TNF-α level of 10 pg/mL, and baseline clinical characteristics were compared. The TNF-α-positive group showed higher baseline IOP, greater IOP fluctuation, and higher systolic blood pressure than the TNF-α-negative group (p = 0.007, p < 0.001, and p = 0.009, respectively). In the multivariate logistic regression analysis, IOP fluctuation (p = 0.037) and systolic blood pressure (p = 0.016) were all independently associated with positive TNF-α level. In normal-tension glaucoma (NTG) patients, presence of central scotoma (p = 0.029) was significantly associated with positive TNF-α level. In conclusion, positive TNF-α level in OAG patients was associated with greater IOP fluctuation and higher systolic blood pressure. In NTG patients, positive TNF-α level was associated with the presence of central scotoma. IOP factors and vascular factors, including blood pressure and presence of central scotoma, may indicate glaucoma pathogenesis related to TNF-α elevation in OAG patients.