bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Image Processing and Equivalent Circuit Approach for the Diagnostic of Atmospheric Pressure DBD
Authors: Rueda Vanesa , Diez Rafael , Bente Nicolas , Piquet Hubert
Published: August 2022

The framework of this paper is the study of gas treatments (NOx abatement) by dielectric barrier discharge (DBD) at atmospheric pressure. To investigate the impact of various solutions for electrical energy injection on the treatment process, two diagnostic methods are considered to evaluate the discharging ratio on the reactor surface: an image processing method and a DBD equivalent circuit analysis, both presented in this paper. For the image analysis, the discharge area is first translated into gray levels, then segmented using the Otsu’s method in order to perform the discharging ratio diagnostic. The equivalent circuit approach, derived from the classical Manley’s diagram analysis, includes the behavior of the part of the reactor in which no discharge is happening. The identification of its parameters is used to estimate the discharging ratio, which evaluates the percentage of the reactor surface covered by the discharge. Experimental results with specifically developed power supplies are presented: they show a good agreement between the two methods. To allow a quantitative comparison of the discharge uniformity according to the operating conditions, the statistical analysis of gray level distribution is performed: non-uniform discharges with intense energy channels are shown to be clearly distinguished from more diffuse ones.
Intelligent Target Design Based on Complex Target Simulation
Authors: Hao Jiaxing , Wang Xuetian , Yang Sen , Gao Hongmin , Yu Cuicui , Xing Wentao
Published: August 2022

The emergence and popularization of various fifth-generation fighter jets with supersonic cruise, super maneuverability, and stealth functionalities have raised higher and more comprehensive challenges for the tactical performance and operational indicators of air defense weapon systems. The training of air defense systems requires simulated targets; however, the traditional targets cannot simulate the radar cross-section (RCS) distribution characteristics of fifth-generation fighter aircrafts. In addition, the existing target aircrafts are expensive and cannot be mass-produced. Therefore, in this paper, a corner reflector and a Luneburg ball reflector with RCS distribution characteristics of a fifth-generation fighter in a certain spatial area are designed for target simulation. Several corner reflectors and Luneburg balls are used to form an array to realize the simulations. The RCS value and distribution characteristics of the target can be combined with fuzzy clustering and a single-chip microcomputer to design an intelligent switching system, which improves the practicability of the intelligent target design proposed in this paper.
A High-Resolution MIR Echelle Grating Spectrometer with a Three-Mirror Anastigmatic System
Authors: Wang Qingyu , Shen Honghai , Liu Weiqi , Dai Pengzhang
Published: August 2022

With the emergence of high-performance infrared detectors and the latest progress in grating manufacturing technology, high-resolution and high-sensitivity infrared spectrometers provide new methods for application to many fields, including astronomy and remote sensing detection. Spectral detection has attracted considerable attention due to its advantages of noncontact and stability. To obtain the detailed features of the missile’s tail flame spectrum, traditional plane reflection gratings are used as the main dispersive element; however, the instrument’s volume will increase with increasing resolution, which is not conducive to remote sensing detection from airborne platforms. Such spectrometers cannot meet high-resolution spectroscopy requirements. To address this problem, this paper proposes an immersion echelle spectrometer combined with a three-mirror astigmatism optical system. High resolution and compact size were achieved. In this paper, a small high-resolution infrared echelle spectrometer optical system was created by combining an off-axis three-mirror anti-astigmatism system, a Littrow structure, and a concave grating Wadsworth imaging device. The optical system operated in the 3.7–4.8 μm band; the echelle grating worked under quasi-Littrow conditions, while the concave grating was used for auxiliary dispersion to separate overlapping orders. The resolution of the optical system in the entire working band was 23,000–45,000. The optical plane size of the spectrometer was around 360 mm × 165 mm. The results show that the Mid-IR echelle spectrometer achieved high spectral resolution, better than 0.25 cm−1, meeting missile tail flame detection requirements. This device has the potential for real-time long-range target detection when warheads are destroyed. While this study focuses on the mid-wave infrared band, its approach can also be extended to other infrared bands.
Enhancing the Thermal and Kinetic Stability of Ketol-Acid Reductoisomerase, a Central Catalyst of a Cell-Free Enzyme Cascade for the Manufacture of Platform Chemicals
Authors: Lv You , Zheng Shan , Goldenzweig Adi , Liu Fengjiang , Gao Yan , Yang Xiuna , Kandale Ajit , McGeary Ross P. , Williams Simon , Kobe Bostjan , Schembri Mark A. , Landsberg Michael J. , Wu Bin , Brück Thomas B. , Sieber Volker , Boden Mikael , Rao Zihe , Fleishman Sarel J. , Schenk Gerhard , Guddat Luke W.
Published: August 2022

The branched-chain amino acids (BCAAs) leucine, isoleucine and valine are synthesized via a common biosynthetic pathway. Ketol-acid reductoisomerase (KARI) is the second enzyme in this pathway. In addition to its role in BCAA biosynthesis, KARI catalyzes two rate-limiting steps that are key components of a cell-free biofuel biosynthesis route. For industrial applications, reaction temperature and enzyme stability are key factors that affect process robustness and product yield. Here, we have solved the cryo-EM structure (2.94 Å resolution) of a homododecameric Class I KARI (from Campylobacter jejuni) and demonstrated how a triad of amino acid side chains plays a crucial role in promoting the oligomerization of this enzyme. Importantly, both its thermal and solvent stability are greatly enhanced in the dodecameric state when compared to its dimeric counterpart (apparent melting temperatures (Tm) of 83.1 °C and 51.5 °C, respectively). We also employed protein design (PROSS) for a tetrameric Class II KARI (from Escherichia coli) to generate a variant with improved thermal and solvent stabilities. In total, 34 mutations were introduced, which did not affect the oligomeric state of this enzyme but resulted in a fully functional catalyst with a significantly elevated Tm (58.5 °C vs. 47.9 °C for the native version).
Advances in Respiratory Medicine (ARM)—Past, Present, Future
Authors: Barczyk Adam
Published: August 2022

Advances in Respiratory Medicine (ARM) is the journal of the Polish Respiratory Society [...]
Model for Rating a Vanadium Redox Flow Battery Stack through Constant Power Charge–Discharge Characterization
Authors: Vudisi Pavan Kumar , Jayanti Sreenivas , Chetty Raghuram
Published: August 2022

A method for estimating the stack rating of vanadium redox flow batteries (VRFBs) through constant power characterization was developed. A stack of 22 cells, each with 1500 cm2 of nominal electrode area, was constructed and tested using constant current and constant power protocols. Typical ratios of charging to discharging power that prevail in various applications (e.g., peak shaving, wind power/solar photovoltaic power integration) were employed in the test protocols. The results showed that fractional energy storage capacity utilization and round-trip energy efficiency varied linearly with the power at which the energy was charged or discharged. A zero-dimensional electrochemical model was proposed based on the area-specific resistance to account for the energy stored/extracted during constant power discharge in the state of charge (SoC) window of 20% to 80%. It was shown that this could be used to rate a given stack in terms of charging and discharging power from the point of view of its application as a power unit. The proposed method enables stack rating based on a single polarization test and can be extended to flow battery systems in general.
A Biotechnological Approach for the Production of Pharmaceutically Active Human Interferon-α from Raphanus sativus L. Plants
Authors: Kebeish Rashad , Hamdy Emad , Al-Zoubi Omar , Habeeb Talaat , Osailan Raha , El-Ayouty Yassin
Published: August 2022

Human interferon (IFN) is a type of cytokine that regulates the immune system’s response to viral and bacterial infections. Recombinant IFN-α has been approved for use in the treatment of a variety of viral infections as well as an anticancer medication for various forms of leukemia. The objective of the current study is to produce a functionally active recombinant human IFN-α2a from transgenic Raphanus sativus L. plants. Therefore, a binary plant expression construct containing the IFN-α2a gene coding sequence, under the regulation of the cauliflower mosaic virus 35SS promoter, was established. Agrobacterium-mediated floral dip transformation was used to introduce the IFN-α2a expression cassette into the nuclear genome of red and white rooted Raphanus sativus L. plants. From each genotype, three independent transgenic lines were established. The anticancer and antiviral activities of the partially purified recombinant IFN-α2a proteins were examined. The isolated IFN-α2a has been demonstrated to inhibit the spread of the Vesicular Stomatitis Virus (VSV). In addition, cytotoxicity and cell apoptosis assays against Hep-G2 cells (Human Hepatocellular Carcinoma) show the efficacy of the generated IFN-α2a as an anticancer agent. In comparison to bacterial, yeast, and animal cell culture systems, the overall observed results demonstrated the efficacy of using Raphanus sativus L. plants as a safe, cost-effective, and easy-to-use expression system for generating active human IFN-α2a.
Isoliquiritigenin Nanoemulsion Preparation by Combined Sonication and Phase-Inversion Composition Method: In Vitro Anticancer Activities
Authors: Wang Jianman , Chen Hongjin , Guo Tao , Yue Ping , Qian Tianbao , Zeng Xiangyu , Luo Yali , Li Jiangmin , Teng Lijing , Liu Qingyu , Hong Liang , Yu Zijiang , Hu Zuquan
Published: August 2022

Isoliquiritigenin (ILQ) has a number of biological activities such as antitumor and anti-inflammatory effects. However, biomedical applications of ILQ are impeded by its poor aqueous solubility. Therefore, in this research, we prepared a novel ILQ-loaded nanoemulsion, i.e., ILQ-NE, which consisted of Labrafil® M 1944 CS (oil), Cremophor® EL (surfactant), ILQ, and phosphate-buffered saline, by employing a combined sonication (high-energy) and phase-inversion composition (low-energy) method (denoted as the SPIC method). The ILQ-NE increased the ILQ solubility ~1000 times more than its intrinsic solubility. It contained spherical droplets with a mean diameter of 44.10 ± 0.28 nm and a narrow size distribution. The ILQ loading capacity was 4%. The droplet size of ILQ-NE remained unchanged during storage at 4 °C for 56 days. Nanoemulsion encapsulation effectively prevented ILQ from degradation under ultraviolet light irradiation, and enhanced the ILQ in vitro release rate. In addition, ILQ-NE showed higher cellular uptake and superior cytotoxicity to 4T1 cancer cells compared with free ILQ formulations. In conclusion, ILQ-NE may facilitate the biomedical application of ILQ, and the SPIC method presents an attractive avenue for bridging the merits and eliminating the shortcomings of traditional high-energy methods and low-energy methods.
Circulating Irisin Levels in Patients with Chronic Plaque Psoriasis
Authors: Ambrogio Francesca , Sanesi Lorenzo , Oranger Angela , Barlusconi Chiara , Dicarlo Manuela , Pignataro Patrizia , Zerlotin Roberta , Romita Paolo , Favoino Elvira , Cazzato Gerardo , Cassano Nicoletta , Vena Gino Antonio , Foti Caterina , Grano Maria
Published: August 2022

Irisin is an adipo-myokine, mainly synthetized in skeletal muscles and adipose tissues, that is involved in multiple processes. Only a few studies have evaluated serum irisin in psoriatic patients. This study aims to analyze serum irisin levels in patients with chronic plaque psoriasis, to compare them with values in controls, and to assess whether concentration of circulating irisin correlates with the severity of psoriasis, calculated by means of Psoriasis Area and Severity Index (PASI). We enrolled 46 patients with chronic plaque psoriasis; the control group included 46 sex- and age-matched subjects without any skin or systemic diseases. Serum irisin levels were measured by competitive enzyme linked immunosorbent assay. Our results showed a non-significant increase in serum irisin concentration in psoriatic patients compared to controls. A negative non-linear correlation between PASI and irisin levels was detected in psoriatic patients. Indeed, dividing patients according to psoriasis severity, the negative association between irisin and PASI was stronger in patients with mild psoriasis than in patients with higher PASI scores. Several control variables we tested showed no significant impact on serum irisin. However, erythrocyte sedimentation rate in the normal range was associated with significantly higher irisin levels in psoriatic patients. In conclusion, although irisin levels were not significantly different between controls and psoriatic patients, irisin was found to be negatively associated with psoriasis severity, especially in subjects with low PASI scores; however, further studies are needed to clarify the role of irisin in subjects with psoriasis.
The Radial Bulging and Axial Strains of Intervertebral Discs during Creep Obtained with the 3D-DIC System
Authors: Yang Mengying , Xiang Dingding , Wang Song , Liu Weiqiang
Published: August 2022

Creep-associated changes in disc bulging and axial strains are essential for the research and development of mechano-bionic biomaterials and have been assessed in various ways in ex vivo creep studies. Nonetheless, the reported methods for measurement were limited by location inaccuracy, a lack of synchronousness, and destructiveness. To this end, this study focuses on the accurate, synchronous, and noninvasive assessment of bugling and strains using the 3D digital image correlation (3D-DIC) system and the impact of creep on them. After a preload of 30 min, the porcine cervical discs were loaded with different loads for 4 h of creep. Axial strains and lateral bulging of three locations on the discs were synchronously measured. The three-parameter solid model and the newly proposed horizontal asymptote model were used to fit the acquired data. The results showed that the load application reduced disc strains by 6.39% under 300 N, 11.28% under 400 N, and 12.59% under 500 N. Meanwhile, the largest protrusion occurred in the middle of discs with a bugling of 1.50 mm, 1.67 mm, and 1.87 mm. Comparison of the peer results showed that the 3D-DIC system could be used in ex vivo biomechanical studies with reliability and had potential in the assessment of the mechanical behavior of novel biomaterials. The phenomenon of the largest middle protrusion enlightened further the strength of spinal implants in this area. The mathematical characterizations of bulging and strains under different loads yielded various model parameters, which are prerequisites for developing implanted biomaterials.
Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered
Authors: Gonçalves-Kulik Mariane , Mier Pablo , Kastano Kristina , Cortés Juan , Bernadó Pau , Schmid Friederike , Andrade-Navarro Miguel A.
Published: August 2022

There is increasing evidence that many intrinsically disordered regions (IDRs) in proteins play key functional roles through interactions with other proteins or nucleic acids. These interactions often exhibit a context-dependent structural behavior. We hypothesize that low complexity regions (LCRs), often found within IDRs, could have a role in inducing local structure in IDRs. To test this, we predicted IDRs in the human proteome and analyzed their structures or those of homologous sequences in the Protein Data Bank (PDB). We then identified two types of simple LCRs within IDRs: regions with only one (polyX or homorepeats) or with only two types of amino acids (polyXY). We were able to assign structural information from the PDB more often to these LCRs than to the surrounding IDRs (polyX 61.8% > polyXY 50.5% > IDRs 39.7%). The most frequently observed polyX and polyXY within IDRs contained E (Glu) or G (Gly). Structural analyses of these sequences and of homologs indicate that polyEK regions induce helical conformations, while the other most frequent LCRs induce coil structures. Our work proposes bioinformatics methods to help in the study of the structural behavior of IDRs and provides a solid basis suggesting a structuring role of LCRs within them.
Plasma P-Tau181 for the Discrimination of Alzheimer’s Disease from Other Primary Dementing and/or Movement Disorders
Authors: Tzartos John S. , Boufidou Fotini , Stergiou Christos , Kuhle Jens , Willemse Eline , Palaiodimou Lina , Tsantzali Ioanna , Sideri Eleni , Bonakis Anastasios , Giannopoulos Sotirios , Voumvourakis Konstantinos I. , Tsivgoulis Georgios , Tzartos Socrates J. , Kapaki Elisabeth , Paraskevas George P.
Published: August 2022

Blood phospho-tau181 may offer a useful biomarker for Alzheimer’s disease. However, the use of either serum or plasma phospho-tau181 and their diagnostic value are currently under intense investigation. In a pilot study, we measured both serum and plasma phospho-tau181 (pT181-Tau) by single molecule array (Simoa) in a group of patients with Alzheimer’s disease and a mixed group of patients with other primary dementing and/or movement disorders. Classical cerebrospinal fluid biomarkers were also measured. Plasma (but not serum) pT181-Tau showed a significant increase in Alzheimer’s disease and correlated significantly with cerebrospinal fluid amyloid and pT181-Tau. Receiver operating curve analysis revealed a significant discrimination of Alzheimer’s from non-Alzheimer’s disease patients, with an area under the curve of 0.83 and an excellent sensitivity but a moderate specificity. Plasma pT181-Tau is not an established diagnostic biomarker for Alzheimer’s disease, but it could become one in the future, or it may serve as a screening tool for specific cases of patients or presymptomatic subjects.
Putative Complementary Compounds to Counteract Insulin-Resistance in PCOS Patients
Authors: Petrillo Tabatha , Semprini Elisa , Tomatis Veronica , Arnesano Melania , Ambrosetti Fedora , Battipaglia Christian , Sponzilli Alessandra , Ricciardiello Francesco , Genazzani Andrea R. , Genazzani Alessandro D.
Published: August 2022

Polycystic ovary syndrome (PCOS) is the most frequent endocrine-metabolic disorder among women at reproductive age. The diagnosis is based on the presence of at least two out of three criteria of the Rotterdam criteria (2003). In the last decades, the dysmetabolic aspect of insulin resistance and compensatory hyperinsulinemia have been taken into account as the additional key features in the etiopathology of PCOS, and they have been widely studied. Since PCOS is a complex and multifactorial syndrome with different clinical manifestations, it is difficult to find the gold standard treatment. Therefore, a great variety of integrative treatments have been reported to counteract insulin resistance. PCOS patients need a tailored therapeutic strategy, according to the patient’s BMI, the presence or absence of familiar predisposition to diabetes, and the patient’s desire to achieve pregnancy or not. The present review analyzes and discloses the main clinical insight of such complementary substances.
Evaluation of Morphological Changes in Retinal Vessels in Type 1 Diabetes Mellitus Patients with the Use of Adaptive Optics
Authors: Matuszewski Wojciech , Gontarz-Nowak Katarzyna , Harazny Joanna M. , Bandurska-Stankiewicz Elżbieta
Published: August 2022

Introduction. Diabetes mellitus contributes to the development of microvascular complications in the eye. Moreover, it affects multiple end organs, including brain damage, leading to premature death. The use of adaptive optics technique allows to perform non-invasive in vivo assessment of retinal vessels and to identify changes in arterioles about 100 μm in diameter. The retinal vasculature may be a model of the cerebral vessels both morphologically and functionally. Aim. To evaluate morphological parameters of retinal arterioles in patients with type 1 diabetes mellitus (DM1). Material and methods. The study included 22 DM1 patients (13 females) aged 43.00 ± 9.45 years with a mean diabetes duration of 22.55 ± 10.05 years, and 23 healthy volunteers (10 females) aged 41.09 ± 10.99 years. Blood pressure, BMI, waist circumference, and metabolic control markers of diabetes were measured in both groups. Vascular examinations were performed using an rtx1 adaptive optics retinal camera (Imagine Eyes, Orsay, France); the vessel wall thickness (WT), lumen diameter (LD), wall-to-lumen ratio (WLR), and vascular wall cross-sectional area (WCSA) were assessed. Statistical analysis was performed with the application of IMB SPSS version 23 software. Results. The DM1 group did not differ significantly in age, BMI, waist circumference, blood pressure, or axial length of the eye compared to the control group. Intraocular pressure (IOP) in both groups was normal, but in the DM1 group it was significantly higher. The DM1 group had significantly higher WT, WLR, and WCSA. These parameters correlated significantly with the duration of diabetes, but not with IOP. Conclusions. The presented study demonstrates the presence of significant morphological changes in retinal vessels in DM1 patients without previously diagnosed diabetic retinopathy. Similar changes may occur in the brain and may be early indicators of cardiovascular risk, but further investigation is required to confirm that.
Recurrent Glioblastoma Treatment: State of the Art and Future Perspectives in the Precision Medicine Era
Authors: Leone Augusto , Colamaria Antonio , Fochi Nicola Pio , Sacco Matteo , Landriscina Matteo , Parbonetti Giovanni , de Notaris Matteo , Coppola Giulia , De Santis Elena , Giordano Guido , Carbone Francesco
Published: August 2022

Current treatment guidelines for the management of recurrent glioblastoma (rGBM) are far from definitive, and the prognosis remains dismal. Despite recent advancements in the pharmacological and surgical fields, numerous doubts persist concerning the optimal strategy that clinicians should adopt for patients who fail the first lines of treatment and present signs of progressive disease. With most recurrences being located within the margins of the previously resected lesion, a comprehensive molecular and genetic profiling of rGBM revealed substantial differences compared with newly diagnosed disease. In the present comprehensive review, we sought to examine the current treatment guidelines and the new perspectives that polarize the field of neuro-oncology, strictly focusing on progressive disease. For this purpose, updated PRISMA guidelines were followed to search for pivotal studies and clinical trials published in the last five years. A total of 125 articles discussing locoregional management, radiotherapy, chemotherapy, and immunotherapy strategies were included in our analysis, and salient findings were critically summarized. In addition, an in-depth description of the molecular profile of rGBM and its distinctive characteristics is provided. Finally, we integrate the above-mentioned evidence with the current guidelines published by international societies, including AANS/CNS, EANO, AIOM, and NCCN.
Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells
Authors: Peraldi Pascal , Loubat Agnès , Chignon-Sicard Bérengère , Dani Christian , Ladoux Annie
Published: August 2022

Breast adipose tissue (AT) participates in the physiological evolution and remodeling of the mammary gland due to its high plasticity. It is also a favorable microenvironment for breast cancer progression. However, information on the properties of human breast adipose progenitor cells (APCs) involved in breast physiology or pathology is scant. We performed differential enzymatic dissociation of human breast AT lobules. We isolated and characterized two populations of APCs. Here we report that these distinct breast APC populations selectively expressed markers suitable for characterization. The population preferentially expressing ALPL (MSCA1) showed higher adipogenic potential. The population expressing higher levels of INHBA and CD142 acquired myofibroblast characteristics upon TGF-β treatment and a myo-cancer-associated fibroblast profile in the presence of breast cancer cells. This population expressed the immune checkpoint CD274 (PD-L1) and facilitated the expansion of breast cancer mammospheres compared with the adipogenic population. Indeed, the breast, as with other fat depots, contains distinct types of APCs with differences in their ability to specialize. This indicates that they were differentially involved in breast remodeling. Their interactions with breast cancer cells revealed differences in the potential for tumor dissemination and estrogen receptor expression, and these differences might be relevant to improve therapies targeting the tumor microenvironment.
The Relationship between Stress, Inflammation, and Depression
Authors: Kim Il-Bin , Lee Jae-Hon , Park Seon-Cheol
Published: August 2022

A narrative review about the relationship between stress, inflammation, and depression is made as follows: Chronic stress leads to various stress-related diseases such as depression. Although most human diseases are related to stress exposure, the common pathways between stress and pathophysiological processes of different disorders are still debatable. Chronic inflammation is a crucial component of chronic diseases, including depression. Both experimental and clinical studies have demonstrated that an increase in the levels of pro-inflammatory cytokines and stress hormones, such as glucocorticoids, substantially contributes to the behavioral alterations associated with depression. Evidence suggests that inflammation plays a key role in the pathology of stress-related diseases; however, this link has not yet been completely explored. In this study, we aimed to determine the role of inflammation in stress-induced diseases and whether a common pathway for depression exists. Recent studies support pharmacological and non-pharmacological treatment approaches significantly associated with ameliorating depression-related inflammation. In addition, major depression can be associated with an activated immune system, whereas antidepressants can exert immunomodulatory effects. Moreover, non-pharmacological treatments for major depression (i.e., exercise) may be mediated by anti-inflammatory actions. This narrative review highlights the mechanisms underlying inflammation and provides new insights into the prevention and treatment of stress-related diseases, particularly depression.
Leber Hereditary Optic Neuropathy: Molecular Pathophysiology and Updates on Gene Therapy
Authors: Chi Sheng-Chu , Cheng Hui-Chen , Wang An-Guor
Published: August 2022

Molecular pathophysiology of LHON was reviewed and the current status of gene therapy for LHON is updated.
SAR296968, a Novel Selective Na+/Ca2+ Exchanger Inhibitor, Improves Ca2+ Handling and Contractile Function in Human Atrial Cardiomyocytes
Authors: Hegner Philipp , Drzymalski Marzena , Biedermann Alexander , Memmel Bernadette , Durczok Melanie , Wester Michael , Floerchinger Bernhard , Provaznik Zdenek , Schmid Christof , Zausig York , Maier Lars S. , Wagner Stefan
Published: August 2022

Background: In reverse-mode, cardiac sodium-calcium exchanger (NCX) can increase the cytoplasmic Ca2+ concentration in response to high intracellular Na+ levels, which may contribute to diastolic contractile dysfunction. Furthermore, increased spontaneous Ca2+ release from intracellular stores can activate forward mode NCX. The resulting transient inward current causes delayed afterdepolarization (DAD)-dependent arrhythmias. Moreover, recently, NCX has been associated with impaired relaxation and reduced cardiac function in heart failure with preserved ejection fraction (HFpEF). Since NCX is upregulated in human chronic atrial fibrillation (AF) as well as heart failure (HF), specific inhibition may have therapeutic potential. Objective: We tested the antiarrhythmic, lusitropic and inotropic effects of a novel selective NCX-inhibitor (SAR296968) in human atrial myocardium. Methods and Results: Right atrial appendage biopsies of 46 patients undergoing elective cardiac surgery in a predominant HFpEF cohort (n = 24/46) were investigated. In isolated human atrial cardiomyocytes, SAR296968 reduced the frequency of spontaneous SR Ca2+ release events and increased caffeine transient amplitude. In accordance, in isolated atrial trabeculae, SAR296968 enhanced the developed tension after a 30 s pause of electrical stimulation consistent with reduced diastolic sarcoplasmic reticulum (SR) Ca2+ leak. Moreover, compared to vehicle, SAR296968 decreased steady-state diastolic tension (at 1 Hz) without impairing developed systolic tension. Importantly, SAR296968 did not affect the safety parameters, such as resting membrane potential or action potential duration as measured by patch clamp. Conclusion: The novel selective NCX-inhibitor SAR296968 inhibits atrial pro-arrhythmic activity and improves diastolic and contractile function in human atrial myocardium, which may have therapeutic implications, especially for treatment of HFpEF.
Haematological Drugs Affecting Lipid Metabolism and Vascular Health
Authors: Parrella Antonio , Iannuzzi Arcangelo , Annunziata Mario , Covetti Giuseppe , Cavallaro Raimondo , Aliberti Emilio , Tortori Elena , Iannuzzo Gabriella
Published: August 2022

Many drugs affect lipid metabolism and have side effects which promote atherosclerosis. The prevalence of cancer-therapy-related cardiovascular (CV) disease is increasing due to development of new drugs and improved survival of patients: cardio-oncology is a new field of interest and research. Moreover, drugs used in transplanted patients frequently have metabolic implications. Increasingly, internists, lipidologists, and angiologists are being consulted by haematologists for side effects on metabolism (especially lipid metabolism) and arterial circulation caused by drugs used in haematology. The purpose of this article is to review the main drugs used in haematology with side effects on lipid metabolism and atherosclerosis, detailing their mechanisms of action and suggesting the most effective therapies.
Incident Atrial Fibrillation and In-Hospital Mortality in SARS-CoV-2 Patients
Authors: Maloberti Alessandro , Giannattasio Cristina , Rebora Paola , Occhino Giuseppe , Ughi Nicola , Biolcati Marco , Gualini Elena , Rizzi Jacopo Giulio , Algeri Michela , Giani Valentina , Rossetti Claudio , Epis Oscar Massimiliano , Molon Giulio , Beltrame Anna , Bonfanti Paolo , Valsecchi Maria Grazia , Genovesi Simonetta
Published: August 2022

(1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in COVID-19 patients during hospitalization, and its occurrence strongly predicts in-hospital mortality.
Effect of Cellulose–Chitosan Hybrid-Based Encapsulation on the Viability and Stability of Probiotics under Simulated Gastric Transit and in Kefir
Authors: Afzaal Muhammad , Saeed Farhan , Ateeq Huda , Shah Yasir Abbas , Hussain Muzzamal , Javed Ahsan , Ikram Ali , Raza Muhammad Ahtisham , Nayik Gulzar Ahmad , Alfarraj Saleh , Ansari Mohammad Javed , Karabagias Ioannis K.
Published: August 2022

Encapsulation comprises a promising potential for the targeted delivery of entrapped sensitive agents into the food system. A unique combination of cellulose/chitosan (Cl-Ch)-based hybrid wall material was employed to encapsulate L. plantarum by emulsion technique. The developed beads were further subjected to morphological and in vitro studies. The viability of free and encapsulated probiotics was also evaluated in kefir during storage. The developed beads presented porous spherical structures with a rough surface. A 1.58 ± 0.02 log CFU/mL, 1.26 ± 0.01 log CFU/mL, and 1.82 ± 0.01 log CFU/mL reduction were noticed for Cl-Ch hybrid cells under simulated gastro-intestinal and thermal conditions, respectively. The encapsulated cells were found to be acidic and thermally resistant compared to the free cells. Similarly, encapsulated probiotics showed better viability in kefir at the end of the storage period compared to free cells. In short, the newly developed Cl-Ch hybrid-based encapsulation has a promising potential for the targeted delivery of probiotics, as career agents, in gastric transit, and in foods.
Retrospective Multicenter Study on Outcome Measurement for Dyskinesia Improvement in Parkinson’s Disease Patients with Pallidal and Subthalamic Nucleus Deep Brain Stimulation
Authors: Meng Fangang , Cen Shanshan , Yi Zhiqiang , Li Weiguo , Cai Guoen , Wang Feng , Quintin Stephan S. , Hey Grace E. , Hernandez Jairo S. , Han Chunlei , Fan Shiying , Gao Yuan , Song Zimu , Yi Junfei , Wang Kailiang , Zhang Liangwen , Ramirez-Zamora Adolfo , Zhang Jianguo
Published: August 2022

Deep brain stimulation (DBS) is an effective treatment for dyskinesia in patients with Parkinson’s disease (PD), among which the therapeutic targets commonly used include the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Levodopa-induced dyskinesia (LID) is one of the common motor complications arising in PD patients on chronic treatment with levodopa. In this article, we retrospectively evaluated the outcomes of LID with the Unified Dyskinesia Rating Scale (UDysRS) in patients who underwent DBS in multiple centers with a GPi or an STN target. Meanwhile, the Med off MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-Ⅲ) and the levodopa equivalent daily dose (LEDD) were also observed as secondary indicators. PD patients with a GPi target showed a more significant improvement in the UDysRS compared with an STN target (92.9 ± 16.7% vs. 66.0 ± 33.6%, p < 0.0001). Both the GPi and the STN showed similar improvement in Med off UPDRS-III scores (49.8 ± 22.6% vs. 52.3 ± 29.5%, p = 0.5458). However, the LEDD was obviously reduced with the STN target compared with the GPi target (44.6 ± 28.1% vs. 12.2 ± 45.8%, p = 0.006).
Optimal Intervention Timing for Robotic-Assisted Gait Training in Hemiplegic Stroke
Authors: Xie Lingchao , Yoon Bu Hyun , Park Chanhee , You Joshua (Sung) H.
Published: August 2022

This study was designed to determine the best intervention time (acute, subacute, and chronic stages) for Walkbot robot-assisted gait training (RAGT) rehabilitation to improve clinical outcomes, including sensorimotor function, balance, cognition, and activities of daily living, in hemiparetic stroke patients. Thirty-six stroke survivors (acute stage group (ASG), n = 11; subacute stage group (SSG), n = 15; chronic stage group (CSG), n = 10) consistently received Walkbot RAGT for 30 min/session, thrice a week, for 4 weeks. Six clinical outcome variables, including the Fugl–Meyer Assessment (FMA), Berg Balance Scale (BBS), Trunk Impairment Scale (TIS), Modified Barthel Index (MBI), Modified Ashworth Scale (MAS), and Mini-Mental State Examination, were examined before and after the intervention. Significant differences in the FMA, BBS, TIS, and MBI were observed between the ASG and the SSG or CSG. A significant time effect was observed for all variables, except for the MAS, in the ASG and SSG, whereas significant time effects were noted for the FMA, BBS, and TIS in the CSG. Overall, Walkbot RAGT was more favorable for acute stroke patients than for those with subacute or chronic stroke. This provides the first clinical evidence for the optimal intervention timing for RAGT in stroke.
The Effects of Cooperative and Competitive Situations on Statistical Learning
Authors: Si Yajie , Chen Xinyu , Guo Wei , Wang Biye
Published: August 2022

Devising cooperative or competitive situations is an important teaching strategy in educational practices. Nevertheless, there is still controversy regarding which situation is better for learning. This study was conducted to explore the effects of cooperative and competitive situations on statistical learning, through the alternating serial reaction time (ASRT) task. Individual cooperative and competitive situations were devised in this study, in which individual situation served as the control condition. Ninety recruited participants were randomly assigned to a cooperative, competitive, or individual group to perform the ASRT task. For general learning, cooperative and competitive situations could indeed make learners respond faster, and there was no significant difference in the RT between the cooperative and competitive groups. Moreover, statistical learning was observed in all three groups. An additional analysis of the early stage of the experiment showed that the learning effect of the competitive group was greater than those of the cooperative and individual groups, in terms of statistical learning. However, the final learning effect was not significantly different among the three groups. Overall, the cooperative and competitive situations had a positive impact on learning and enabled the students to acquire approximately the same learning effect in a shorter time period, compared with the individual situation. Specifically, the competitive situation accelerated the statistical learning process but not the general learning process.
Neurocognitive Artificial Neural Network Models Are Superior to Linear Models at Accounting for Dimensional Psychopathology
Authors: Haywood Darren , Baughman Frank D. , Mullan Barbara A. , Heslop Karen R.
Published: August 2022

In recent years, there has been debate about the optimal conceptualisation of psychopathology. Structural models of psychopathology have been developed to counter issues, including comorbidity and poor diagnostic stability prevalent within the traditional nosological approach. Regardless of the conceptualisation of psychological dysfunction, deficits in neurocognitive abilities have been claimed to be an aetiological feature of psychopathology. Explorations of the association between neurocognition and psychopathology have typically taken a linear approach, overlooking the potential interactive dynamics of neurocognitive abilities. Previously, we proposed a multidimensional hypothesis, where within-person interactions between neurocognitive domains are fundamental to understanding the role of neurocognition within psychopathology. In this study, we used previously collected psychopathology data for 400 participants on psychopathological symptoms, substance use, and performance on eight neurocognitive tasks and compared the predictive accuracy of linear models to artificial neural network models. The artificial neural network models were significantly more accurate than the traditional linear models at predicting actual (a) lower-level and (b) high-level dimensional psychopathology. These results provide support for the multidimensional hypothesis: that the study of non-linear interactions and compensatory neurocognitive profiles are integral to understanding the functional associations between neurocognition and of psychopathology.
The Spillover Effect of Life Satisfaction on Customer Satisfaction: The Mediating Role of Service-Oriented Organizational Citizenship and the Moderating Role of Competition Climate
Authors: Luan Yunyun , Lv Meizhen , Wang Lei
Published: August 2022

In the field of organizational management, research on employees’ life experiences is insufficient. It remains unclear how employees’ non-work experiences affect customer service quality. Building on the spillover theory (an individual’s experience in one domain can be transferred to another domain) and the conservation of resources theory (individuals are motivated to protect their current resources and to acquire new resources), we aim to examine the impact of service employee’s life satisfaction on customer satisfaction while considering service-oriented organizational citizenship behavior (the discretionary extra-role behavior demonstrated by employees) as a mediating variable. To test our hypothesis, we collected multi-wave, multilevel, multisource data of 209 customer service employees from an insurance company. The results showed that service-oriented organizational citizenship behavior was an important mechanism by which employees’ overall life satisfaction positively affected customer satisfaction. In addition, this mediating effect was weaker for employees in higher competition climate groups. The study illustrates the critical contribution of the overall well-being of personnel to organizational business results.
Construction Robotics and Human–Robot Teams Research Methods
Authors: Onososen Adetayo Olugbenga , Musonda Innocent , Ramabodu Molusiwa
Published: August 2022

Though studies in construction robotics and human–robot teams research have explored varying themes, an in-depth study of the state-of-the-art of methodological paradigms appropriate for construction robotics research is hitherto lacking, taking into consideration that several studies have highlighted conflicting methodological components such as research design, methods, data sources, data types and analytical techniques. To better understand this underexplored area, this study uses a four-stage review approach utilising a scientometric and systematic analysis method based on 112 articles. Using statistical analysis to evaluate the relationship between research components, the study reveals strong associations between components of research methods, data sources and analytical techniques. Researchers are also increasingly looking to mixed paradigms in data sources and designs, highlighting a methodological plurality in construction robotics research. Implications on what this means for the future of construction robotics, policy and stakeholders are discussed in the study.
Determining Cost and Time Performance Indexes for Diversified Investment Tasks
Authors: Konior Jarosław
Published: August 2022

The aim of the research results presented in the article was to develop a method that enables the analysis and evaluation of deviations at the stage of implementing a construction investment in various construction sectors. The new method was based on the well-known Earned Value Method (EVM). It was assumed that the monitoring of costs and the constant control of the implementation time of construction projects, with the simultaneous analysis of the level of deviations, allows for the consistent management of the investment task. Moreover, it ensures—in the required time—the adoption of appropriate improvement actions, and also enables the quantification of risk during the planning of an investment. The article attempts to prove the validity of the assumption about the necessity of the cyclical verification of the level of deviations in construction projects budget and schedule. Such an approach provides numerous perceptible benefits; such as the precise determination of the size of possible losses; an immediate reaction to risk; and the possibility of making changes at every stage of implementing an investment. On the basis of the analysis of the author’s own research carried out in three research groups of facilities (collective housing; hotels; and commercial and service facilities), an original attempt was made to determine the size of cost and time performance indexes of various investment tasks. The values of these performance indexes were determined, and are presented as quantile images in boxplots.
Multimodal Prediction of Five-Year Breast Cancer Recurrence in Women Who Receive Neoadjuvant Chemotherapy
Authors: Rabinovici-Cohen Simona , Fernández Xosé M. , Grandal Rejo Beatriz , Hexter Efrat , Hijano Cubelos Oliver , Pajula Juha , Pölönen Harri , Reyal Fabien , Rosen-Zvi Michal
Published: August 2022

In current clinical practice, it is difficult to predict whether a patient receiving neoadjuvant chemotherapy (NAC) for breast cancer is likely to encounter recurrence after treatment and have the cancer recur locally in the breast or in other areas of the body. We explore the use of clinical history, immunohistochemical markers, and multiparametric magnetic resonance imaging (DCE, ADC, Dixon) to predict the risk of post-treatment recurrence within five years. We performed a retrospective study on a cohort of 1738 patients from Institut Curie and analyzed the data using classical machine learning, image processing, and deep learning. Our results demonstrate the ability to predict recurrence prior to NAC treatment initiation using each modality alone, and the possible improvement achieved by combining the modalities. When evaluated on holdout data, the multimodal model achieved an AUC of 0.75 (CI: 0.70, 0.80) and 0.57 specificity at 0.90 sensitivity. We then stratified the data based on known prognostic biomarkers. We found that our models can provide accurate recurrence predictions (AUC > 0.89) for specific groups of women under 50 years old with poor prognoses. A version of our method won second place at the BMMR2 Challenge, with a very small margin from being first, and was a standout from the other challenge entries.