bluuebunny/crossref_metadata_2025 huggingface dataset:
Dento-Skeletal Class III Treatment with Mixed Anchored Palatal Expander: A Systematic Review
Authors: d’Apuzzo Fabrizia , Nucci Ludovica , Strangio Bruno M. , Inchingolo Alessio Danilo , Dipalma Gianna , Minervini Giuseppe , Perillo Letizia , Grassia Vincenzo
Published: May 2022

Bone-anchored appliances for the treatment of Class III malocclusions have recently been found to reduce the dentoalveolar effects caused by conventional tooth-borne devices while also improving orthopaedic outcomes in growing patients. The goal of this systematic review was to compare the outcomes of skeletal Class III interceptive treatment with dental anchoring devices to those achieved with mixed anchored palatal expanders. The inclusion criteria were as follows: patients who were treated with hybrid anchored palatal expanders and different maxillary advancement appliances. Study quality was estimated using the Newcastle–Ottawa scale. A search on the Pubmed, Scopus, Embase and Cochrane Library databases yielded 350 papers. Following the initial abstract selection, 65 potentially acceptable papers were thoroughly examined, resulting in a final selection of 9 articles. The results in the short-term showed that combined tooth-borne and bone-borne appliances for rapid maxillary expansion might be recommended in protocols of skeletal Class III treatment to obtain more skeletal effects and reduce side effects on the upper teeth.
Induction Machine-Based EV Vector Control Model Using Mamdani Fuzzy Logic Controller
Authors: Salahuddin Humayun , Imdad Kashif , Chaudhry Muhammad Umar , Nazarenko Dmitry , Bolshev Vadim , Yasir Muhammad
Published: May 2022

The substantial rise in the demand for electric vehicles (EVs) has emphasized an environment-friendly and intelligent design for speed control strategies. In this paper, a Mamdani fuzzy logic controller (MFLC) was proposed to vigorously control the speed of EVs at discrete levels. MFLC member functions (MFs) are tuned for EVs operating at three different speed modes (40, 60, and 80 km/h). The proposed speed controller operation for the speed tracking of EVs was designed and tested in MATLAB (Simulink) environment. The proposed speed controller validated a remarkable improvement in dynamic speed control compared with existing P-I, FLC, Fuzzy FOPID (ACO), Fuzzy FOPID (GA), and Fuzzy FOPID (PSO) controllers. Its stability under a user-defined drive pattern is also observed. In this proposed work, the speed controller highlights the better tracking of user-defined speed response compared to the conventional aforementioned controllers. Moreover, the speed tracking of the designed model was tested for robustness against speed transients at predefined time instants, respectively. The comparison suggests that the MFLC model removes overshoot and significantly reduces the steady-state time.
Polynomial Annuities
Authors: Rajaram Rajeev , Ritchey Nathan
Published: May 2022

We use a payment pattern of the type {1k,2k,3k,…} to generalize the standard level payment and increasing annuity to polynomial payment patterns. We derive explicit formulas for the present value of an n-year polynomial annuity, the present value of an m-monthly n-year polynomial annuity, and the present value of an n-year continuous polynomial annuity. We also use the idea to extend the annuities to payment patterns derived from analytic functions, as well as to payment patterns of the type {1r,2r,3r,…}, with r being an arbitrary real number. In the process, we develop possible approximations to k! and for the gamma function evaluated at real numbers.
Designing with the Dialogic Self: A Framework for a Polyphonic Practice of Architectural Design
Authors: Tahsiri Mina
Published: May 2022

This paper questions the degree of inclusivity and equity in the treatment of voices at play in the architectural design process and advocates for an approach whereby architecture can be realized as a harmonious and polyphonic composition of multiple voices and values. Based on a dialogic ontology, the paper examines how a designer’s sense of self can contribute to their method of practice and proposes a new methodology (Narrative-based Dialogic Design-NDD) that can allow a decentralization of the sense of self to facilitate the uptake of narrative positions of others.
Promoting Social Interaction through Participatory Architecture. Experimentation, Experience, Evaluation in a Social Housing Complex (Grand’Goule, Poitiers, 1974–2021)
Authors: Loiseau Benjamin , Safin Stéphane , Tufano Antonella
Published: May 2022

Has the increase in social life and conviviality commonly imagined by the designers and decision-makers taken place? There are few systematic post-project evaluations of the methods and tools used to answer this question. Therefore, this article wishes to draw lessons from a housing experiment from the end of the 1970s, the Grand’Goule residence in Poitiers, the objective of which was to create a dense social life through design and means of participation. Some devices consisted in the creation of Surfaces d’Activités Partagées (SAPs, shared activities surfaces), which are common spaces where residents can intervene in both the interior design and the function of space itself. In this study, we analyze the Grand’Goule project, which has been displayed as a participative experiment, with the objective of creating a dense social life through original architectural and social devices. We use different sources (interviews of the inhabitants, project owners, and architects, alongside press articles and the architects’ archives) to dissect the practices in order to lead a retrospective analysis of the participative process, its successes and failures. We show that, as a very complex and fragile process, enabling the active participation of people in the design and use of a large-scale architectural project is far from obvious and suffers from several kinds of difficulties. We highlight the gap between initial intentions, final realizations and actual uses in the Grand’Goule project, and how it can inform every participative architectural project.
Interannual Variations of Rainfall in Late Spring over Southwest China and Associated Sea Surface Temperature and Atmospheric Circulation Anomalies
Authors: Mei Shuangli , Chen Shangfeng , Li Yong , Aru Hasi
Published: May 2022

Based on rainfall data for the period of 1960–2018 from 382 stations in southwest China and multiple reanalysis datasets, interannual variation of rainfall in late spring over Southwest China and associated sea surface temperature and atmospheric circulation anomalies are examined. The first leading mode of late-spring rainfall anomalies displays a uniform-distribution pattern. The second leading mode shows a zonal dipole pattern. The leading mode is related to an atmospheric wave train over mid-high latitudes of Eurasia, with a center of action of atmospheric anomaly over Southwest China. The atmospheric anomalies over Southwest China modulate late-spring rainfall there via modulating vertical motion and water vapor transport. In addition, the leading mode of late-spring rainfall anomalies has a close relation with sea surface temperature anomalies (SSTA) in the central and eastern equatorial Pacific. SSTA in the central and eastern equatorial Pacific impacts late-spring rainfall anomalies over Southwest China via modulation of the tropical Walker and Hadley circulation. The second leading mode of late-spring rainfall variation over Southwest China is closely associated with SSTA in the tropical western Pacific and a mid-high latitude wave train. SSTA in the tropical western Pacific and the mid-high latitudes wave train together leads to out-of-phase variation of meridional wind anomalies between western and eastern parts of Southwest China, which further results in a zonal dipole rainfall anomaly over Southwest China.
Warm–Wet Climate Trend Enhances Net Primary Production of the Main Ecosystems in China during 2000–2021
Authors: Ji Yuhe , Zhou Guangsheng , Wang Shudong , Zhao Jun
Published: May 2022

A significant greening trend has been reported globally in recent decades. The greening indicates the improvement in net primary production (NPP) in vegetation. Adopting statistics-based regression models, we investigated the dynamics of NPP and its climatic drivers in main ecosystems (forest land, grass land, and unused land) over China during the period 2000–2021. The results confirmed an increasing NPP covering approximately 86% area in the main ecosystems. NPP exhibited an increase rate of 6.11 g C m−2 yr−1 in forest land, 4.77 g C m−2 yr−1 in grass land, and 1.25 g C m−2 yr−1 in unused land, respectively. Over the same period, warm–wet climate trend was observed covering approximately 90% of the main ecosystems. The warm–wet climate has had a positive effect rather than negative effect on NPP in the main ecosystems, judging by their significant positive correlation. Our results suggested that the increase in annual precipitation exerted much more important effect on the increasing NPP. The warm–wet climate trend contributes to the upward trend in NPP, even if variability in NPP might involve the influence of solar radiation, atmospheric aerosols, CO2 fertilization, nitrogen deposition, human intervention, etc.
Cheap Control in a Non-Scalarizable Linear-Quadratic Pursuit-Evasion Game: Asymptotic Analysis
Authors: Turetsky Vladimir , Glizer Valery
Published: May 2022

In this work, a finite-horizon zero-sum linear-quadratic differential game, modeling a pursuit-evasion problem, was considered. In the game’s cost function, the cost of the control of the minimizing player (the minimizer/the pursuer) was much smaller than the cost of the control of the maximizing player (the maximizer/the evader) and the cost of the state variable. This smallness was expressed by a positive small multiplier (a small parameter) of the square of the L2-norm of the minimizer’s control in the cost function. Parameter-free sufficient conditions for the existence of the game’s solution (the players’ optimal state-feedback controls and the game value), valid for all sufficiently small values of the parameter, were presented. The boundedness (with respect to the small parameter) of the time realizations of the optimal state-feedback controls along the corresponding game’s trajectory was established. The best achievable game value from the minimizer’s viewpoint was derived. A relation between solutions of the original cheap control game and the game that was obtained from the original one by replacing the small minimizer’s control cost with zero, was established. An illustrative real-life example is presented.
Gold Nanorod-Assisted Photothermal Therapy and Improvement Strategies
Authors: Taylor Mitchell Lee , Wilson Raymond Edward , Amrhein Kristopher Daniel , Huang Xiaohua
Published: May 2022

Noble metal nanoparticles have been sought after in cancer nanomedicine during the past two decades, owing to the unique localized surface plasmon resonance that induces strong absorption and scattering properties of the nanoparticles. A popular application of noble metal nanoparticles is photothermal therapy, which destroys cancer cells by heat generated by laser irradiation of the nanoparticles. Gold nanorods have stood out as one of the major types of noble metal nanoparticles for photothermal therapy due to the facile tuning of their optical properties in the tissue penetrative near infrared region, strong photothermal conversion efficiency, and long blood circulation half-life after surface modification with stealthy polymers. In this review, we will summarize the optical properties of gold nanorods and their applications in photothermal therapy. We will also discuss the recent strategies to improve gold nanorod-assisted photothermal therapy through combination with chemotherapy and photodynamic therapy.
Macroinvertebrate Assemblages along the Longitudinal Gradient of an Urban Palmiet River in Durban, South Africa
Authors: Lebepe Jeffrey , Khumalo Ntombifuthi , Mnguni Anele , Pillay Sashin , Mdluli Sphosakhe
Published: May 2022

Urban rivers are regarded as unnatural because they drain catchments characterized by impervious surfaces. The present study explored macroinvertebrate communities in relation to water and habitat quality along the longitudinal gradient of an urban Palmiet River in Durban, South Africa. Sampling was conducted across six sites along the river. The water quality has shown a significant variation (ANOVA, p < 0.05) across six sites. Good-quality water was observed at Site 6, whereas Site 5 exhibiting hypertrophic condition. Sites 4 to 1 were all eutrophic; however, nutrient levels showed to decrease from Site 4 down to Site 2 and increased again at Site 1. A similar trend was observed for habitat quality, with Site 6 showing excellent and Site 5 exhibited poor habitat. Coinciding with water and habitat quality, macroinvertebrate diversity and abundance showed significant differences across six sites. Sensitive palaemonids, notonemourids, and amphipods were only observed in the headwaters and have contributed over 50% of the variation in abundance between Site 6 and other sites. The non-metric multidimensional scaling (NMDS) plot has also shown clear discrimination (MANOVA, p < 0.001) for the Average Score Per Taxon (ASPT) across the six sites. Macroinvertebrate communities have shown a clear association between water and habitat quality. These findings affirm the ecological importance of urban rivers as they provide refuge to aquatic biodiversity, with anthropogenic litter providing additional habitats for other taxa. Despite the current conditions supporting biodiversity and the functioning of the river, it is unclear if the system could endure further disturbance.
Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells
Authors: Ye Peng , Chi Xiaoxia , Yan Xiuwen , Wu Fangqin , Liang Zhigang , Yang Wen-Hao
Published: May 2022

Liver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from spheroid cultures and performing transcriptomic analysis, we determined that alanine–glyoxylate aminotransferase (AGXT), which participates in the metabolism of serine and glycine, was significantly upregulated in spheroid cultures, and its function in LCSCs remains unknown. Through the exogenous overexpression or short hairpin RNA knockdown of AGXT in HCC cells, we observed that changes in the AGXT level did not affect the spheroid ability and population of LCSCs. The knockdown of AGXT in LCSCs reduced the number of spheroids and the population of LCSCs; this implies that AGXT is required for the maintenance of cancer stemness rather than as a driver of LCSCs. Mechanistically, AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4), two well-known master regulators of cancer stemness. Taken together, our study demonstrates the role of AGXT in supporting LCSCs; thus, AGXT merits further exploration.
Physical Activity and Sedentary Time in Pregnancy: An Exploratory Study on Oxidative Stress Markers in the Placenta of Women with Obesity
Authors: Zafaranieh Saghi , Dieberger Anna M. , Leopold-Posch Barbara , Huppertz Berthold , Granitzer Sebastian , Hengstschläger Markus , Gundacker Claudia , Desoye Gernot , van Poppel Mireille N. M. ,   DALI Core Investigator Group
Published: May 2022

Regular moderate-to-vigorous physical activity (MVPA) and reduced sedentary time (ST) improve maternal glucose metabolism in pregnancy. More MVPA and less ST outside pregnancy increase antioxidant capacity, hence, are beneficial in preventing oxidative stress. The placenta is the first line of defense for the fetus from an adverse maternal environment, including oxidative stress. However, effects of MVPA and ST on oxidative stress markers in the placenta are unknown. The purpose of this study was to assess the association of MVPA and ST in pregnancy with oxidative stress markers in placentas of overweight/obese women (BMI ≥ 29 kg/m2). MVPA and ST were objectively measured with accelerometers at <20 weeks, 24–27 and 35–37 weeks of gestation. Using linear Bayesian multilevel models, the associations of MVPA and ST (mean and changes) with mRNA expression of a panel of 11 oxidative stress related markers were assessed in 96 women. MVPA was negatively correlated with HSP70 mRNA expression in a sex-independent manner and with GCLM expression only in placentas of female fetuses. ST was positively associated with HO-1 mRNA expression in placentas of male neonates. None of the other markers were associated with MVPA or ST. We speculate that increasing MVPA and reducing ST attenuates the oxidative stress state in placentas of obese pregnant women.
Optically Coupled PtOEP and DPA Molecules Encapsulated into PLGA-Nanoparticles for Cancer Bioimaging
Authors: Vepris Olena , Eich Christina , Feng Yansong , Fuentes Gastón , Zhang Hong , Kaijzel Eric L. , Cruz Luis J.
Published: May 2022

Triplet-triplet annihilation upconversion (TTA-UC) nanoparticles (NPs) have emerged as imaging probes and therapeutic probes in recent years due to their excellent optical properties. In contrast to lanthanide ion-doped inorganic materials, highly efficient TTA-UC can be generated by low excitation power density, which makes it suitable for clinical applications. In the present study, we used biodegradable poly(lactic-co-glycolic acid) (PLGA)-NPs as a delivery vehicle for TTA-UC based on the heavy metal porphyrin Platinum(II) octaethylporphyrin (PtOEP) and the polycyclic aromatic hydrocarbon 9,10-diphenylanthracene (DPA) as a photosensitizer/emitter pair. TTA-UC-PLGA-NPs were successfully synthesized according to an oil-in-water emulsion and solvent evaporation method. After physicochemical characterization, UC-efficacy of TTA-UC-PLGA-NPs was assessed in vitro and ex vivo. TTA-UC could be detected in the tumour area 96 h after in vivo administration of TTA-UC-PLGA-NPs, confirming the integrity and suitability of PLGA-NPs as a TTA-UC in vivo delivery system. Thus, this study provides proof-of-concept that the advantageous properties of PLGA can be combined with the unique optical properties of TTA-UC for the development of advanced nanocarriers for simultaneous in vivo molecular imaging and drug delivery.
The Corpus Adiposum Infrapatellare (Hoffa’s Fat Pad)—The Role of the Infrapatellar Fat Pad in Osteoarthritis Pathogenesis
Authors: Braun Sebastian , Zaucke Frank , Brenneis Marco , Rapp Anna E. , Pollinger Patrizia , Sohn Rebecca , Jenei-Lanzl Zsuzsa , Meurer Andrea
Published: May 2022

In recent years, the infrapatellar fat pad (IFP) has gained increasing research interest. The contribution of the IFP to the development and progression of knee osteoarthritis (OA) through extensive interactions with the synovium, articular cartilage, and subchondral bone is being considered. As part of the initiation process of OA, IFP secretes abundant pro-inflammatory mediators among many other factors. Today, the IFP is (partially) resected in most total knee arthroplasties (TKA) allowing better visualization during surgical procedures. Currently, there is no clear guideline providing evidence in favor of or against IFP resection. With increasing numbers of TKAs, there is a focus on preventing adverse postoperative outcomes. Therefore, anatomic features, role in the development of knee OA, and consequences of resecting versus preserving the IFP during TKA are reviewed in the following article.
Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
Authors: D’Amico Ramona , Gugliandolo Enrico , Siracusa Rosalba , Cordaro Marika , Genovese Tiziana , Peritore Alessio Filippo , Crupi Rosalia , Interdonato Livia , Di Paola Davide , Cuzzocrea Salvatore , Fusco Roberta , Impellizzeri Daniela , Di Paola Rosanna
Published: May 2022

Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system’s dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that regard, the aim of this research was to investigate the impact of ED exposure on the neuroinflammation and oxidative stress in an experimental model of Parkinson’s disease (PD). PD was induced by intraperitoneally injections of MPTP for a total dose of 80 mg/kg for each mouse. Mice were orally exposed to EDs, starting 24 h after the first MPTP administration and continuing through seven additional days. Our results showed that ED exposure raised the loss of TH and DAT induced by the administration of MPTP, as well as increased aggregation of α-synuclein, a key marker of PD. Additionally, oral exposure to EDs induced astrocytes and microglia activation that, in turn, exacerbates oxidative stress, perturbs the Nrf2 signaling pathway and activates the cascade of MAPKs. Finally, we performed behavioral tests to demonstrate that the alterations in the dopaminergic system also reflected behavioral and cognitive alterations. Importantly, these changes are more significant after exposure to atrazine compared to other EDs. The results from our study provide evidence that exposure to EDs may play a role in the development of PD; therefore, exposure to EDs should be limited.
Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy
Authors: Lauwerys Louis , Smits Evelien , Van den Wyngaert Tim , Elvas Filipe
Published: May 2022

Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body’s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8+ T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided.
Human iPSC Modeling of Genetic Febrile Seizure Reveals Aberrant Molecular and Physiological Features Underlying an Impaired Neuronal Activity
Authors: Scalise Stefania , Zannino Clara , Lucchino Valeria , Lo Conte Michela , Scaramuzzino Luana , Cifelli Pierangelo , D’Andrea Tiziano , Martinello Katiuscia , Fucile Sergio , Palma Eleonora , Gambardella Antonio , Ruffolo Gabriele , Cuda Giovanni , Parrotta Elvira Immacolata
Published: May 2022

Mutations in SCN1A gene, encoding the voltage-gated sodium channel (VGSC) NaV1.1, are widely recognized as a leading cause of genetic febrile seizures (FS), due to the decrease in the Na+ current density, mainly affecting the inhibitory neuronal transmission. Here, we generated induced pluripotent stem cells (iPSCs)-derived neurons (idNs) from a patient belonging to a genetically well-characterized Italian family, carrying the c.434T > C mutation in SCN1A gene (hereafter SCN1AM145T). A side-by-side comparison of diseased and healthy idNs revealed an overall maturation delay of SCN1AM145T cells. Membranes isolated from both diseased and control idNs were injected into Xenopus oocytes and both GABA and AMPA currents were successfully recorded. Patch-clamp measurements on idNs revealed depolarized action potential for SCN1AM145T, suggesting a reduced excitability. Expression analyses of VGSCs and chloride co-transporters NKCC1 and KCC2 showed a cellular “dysmaturity” of mutated idNs, strengthened by the high expression of SCN3A, a more fetal-like VGSC isoform, and a high NKCC1/KCC2 ratio, in mutated cells. Overall, we provide strong evidence for an intrinsic cellular immaturity, underscoring the role of mutant NaV1.1 in the development of FS. Furthermore, our data are strengthening previous findings obtained using transfected cells and recordings on human slices, demonstrating that diseased idNs represent a powerful tool for personalized therapy and ex vivo drug screening for human epileptic disorders.
Design of a Quencher-Free Fluorescent Aptasensor for Ochratoxin A Detection in Red Wine Based on the Guanine-Quenching Ability
Authors: Yang Cheng , Abbas Fathimath , Rhouati Amina , Sun Yingying , Chu Xiaolin , Cui Shengnan , Sun Bingbing , Xue Changying
Published: May 2022

This study describes a quencher-free fluorescent aptasensor for ochratoxin A (OTA) detection using the specific quenching ability of guanine for fluorescein (FAM) molecules based on photo-induced electron transfer (PIET). In this strategy, OTA is detected by monitoring the fluorescence change induced by the conformational change of the aptamer after target binding. A new shorter OTA aptamer compromising three guanine bases at the 5′ end was used in this study. This new aptamer, named G3-OTAapt1-FAM (F1), was labeled with FAM on the 3′ end as a fluorophore. In order to increase the binding affinity of the aptamer and OTA, G3-OTAapt2-FAM (F2) was designed; this added a pair of complementary bases at the end compared with F1. To prevent the strong self-quenching of F2, a complementary chain, A13, was added. Although the F1 aptasensor was simpler to implement, the sensitivity of the F2 aptasensor with A13 was better than that of F1. The proposed F1 and F2 sensors can detect OTA with a concentration as low as 0.69 nmol/L and 0.36 nmol/L, respectively.
RT-LAMP-Based Molecular Diagnostic Set-Up for Rapid Hepatitis C Virus Testing
Authors: Sharma Sandhya , Thomas Emmanuel , Caputi Massimo , Asghar Waseem
Published: May 2022

Hepatitis C virus (HCV) infections occur in approximately 3% of the world population. The development of an enhanced and extensive-scale screening is required to accomplish the World Health Organization’s (WHO) goal of eliminating HCV as a public health problem by 2030. However, standard testing methods are time-consuming, expensive, and challenging to deploy in remote and underdeveloped areas. Therefore, a cost-effective, rapid, and accurate point-of-care (POC) diagnostic test is needed to properly manage the disease and reduce the economic burden caused by high case numbers. Herein, we present a fully automated reverse-transcription loop-mediated isothermal amplification (RT-LAMP)-based molecular diagnostic set-up for rapid HCV detection. The set-up consists of an automated disposable microfluidic chip, a small surface heater, and a reusable magnetic actuation platform. The microfluidic chip contains multiple chambers in which the plasma sample is processed. The system utilizes SYBR green dye to detect the amplification product with the naked eye. The efficiency of the microfluidic chip was tested with human plasma samples spiked with HCV virions, and the limit of detection observed was 500 virions/mL within 45 min. The entire virus detection process was executed inside a uniquely designed, inexpensive, disposable, and self-driven microfluidic chip with high sensitivity and specificity.
An Intelligent ECG-Based Tool for Diagnosing COVID-19 via Ensemble Deep Learning Techniques
Authors: Attallah Omneya
Published: May 2022

Diagnosing COVID-19 accurately and rapidly is vital to control its quick spread, lessen lockdown restrictions, and decrease the workload on healthcare structures. The present tools to detect COVID-19 experience numerous shortcomings. Therefore, novel diagnostic tools are to be examined to enhance diagnostic accuracy and avoid the limitations of these tools. Earlier studies indicated multiple structures of cardiovascular alterations in COVID-19 cases which motivated the realization of using ECG data as a tool for diagnosing the novel coronavirus. This study introduced a novel automated diagnostic tool based on ECG data to diagnose COVID-19. The introduced tool utilizes ten deep learning (DL) models of various architectures. It obtains significant features from the last fully connected layer of each DL model and then combines them. Afterward, the tool presents a hybrid feature selection based on the chi-square test and sequential search to select significant features. Finally, it employs several machine learning classifiers to perform two classification levels. A binary level to differentiate between normal and COVID-19 cases, and a multiclass to discriminate COVID-19 cases from normal and other cardiac complications. The proposed tool reached an accuracy of 98.2% and 91.6% for binary and multiclass levels, respectively. This performance indicates that the ECG could be used as an alternative means of diagnosis of COVID-19.
Label-Free Detection of the Receptor-Binding Domain of the SARS-CoV-2 Spike Glycoprotein at Physiologically Relevant Concentrations Using Surface-Enhanced Raman Spectroscopy
Authors: Sarychev Andrey K. , Sukhanova Alyona , Ivanov Andrey V. , Bykov Igor V. , Bakholdin Nikita V. , Vasina Daria V. , Gushchin Vladimir A. , Tkachuk Artem P. , Nifontova Galina , Samokhvalov Pavel S. , Karaulov Alexander , Nabiev Igor
Published: May 2022

Surface-enhanced Raman scattering (SERS) spectroscopy is a surface- or cavity-enhanced variant of Raman scattering spectroscopy that allows the detection of analytes with a sensitivity down to single molecules. This method involves the use of SERS-active surfaces or cavities capable of concentrating incident radiation into small mode volumes containing the analyte. Here, we have engineered an ultranarrow metal–dielectric nano-cavity out of a film of the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) glycoprotein and a silver surface, held together by interaction between reduced protein sulfhydryl groups and silver. The concentration of light in this nano-cavity allows the label-free recording of the characteristic Raman spectra of protein samples smaller than 1 pg. This is sufficient for the ultrasensitive detection of viral protein antigens at physiologically relevant levels. Moreover, the protein SERS signal can be increased by several orders of magnitude by coating the RBD film with a nanometer-thick silver shell, thereby raising the cavity Q-factor. This ensures a sub-femtogram sensitivity of the viral antigen detection. A simple theoretical model explaining the observed additional enhancement of the SERS signal from the silver-coated protein is proposed. Our study is the first to obtain the characteristic Raman and SERS spectra of the RBD of S glycoprotein, the key SARS-CoV-2 viral antigen, directly, without the use of Raman-reporter molecules. Thus, our approach allows label-free recording of the characteristic spectra of viral antigens at concentrations orders of magnitude lower than those required for detecting the whole virus in biological media. This makes it possible to develop a high-performance optical detection method and conformational analysis of the pathogen and its variants.
Investigation of the Therapeutic Potential of New Antidiabetic Compounds Using Islet-on-a-Chip Microfluidic Model
Authors: Sokolowska Patrycja , Jastrzebska Elzbieta , Dobrzyn Agnieszka , Brzozka Zbigniew
Published: May 2022

Nowadays, diabetes mellitus is one of the most common chronic diseases in the world. Current research on the treatment of diabetes combines many fields of science, such as biotechnology, transplantology or engineering. Therefore, it is necessary to develop new therapeutic strategies and preventive methods. A newly discovered class of lipids—Palmitic Acid Hydroxy Stearic Acid (PAHSA) has recently been proposed as an agent with potential therapeutic properties. In this research, we used an islet-on-a-chip microfluidic 3D model of pancreatic islets (pseudoislets) to study two isomers of PAHSA: 5-PAHSA and 9-PAHSA as potential regulators of proliferation, viability, insulin and glucagon expression, and glucose-stimulated insulin and glucagon secretion. Due to the use of the Lab-on-a-chip systems and flow conditions, we were able to reflect conditions similar to in vivo. In addition, we significantly shortened the time of pseudoislet production, and we were able to carry out cell culture, microscopic analysis and measurements using a multi-well plate reader at the same time on one device. In this report we showed that under microfluidic conditions PAHSA, especially 5-PAHSA, has a positive effect on pseudoislet proliferation, increase in cell number and mass, and glucose-stimulated insulin secretion, which may qualify it as a compound with potential therapeutic properties.
Delusional Severity Is Associated with Abnormal Texture in FLAIR MRI
Authors: Khoury Marc A. , Bahsoun Mohamad-Ali , Fadhel Ayad , Shunbuli Shukrullah , Venkatesh Saanika , Ghazvanchahi Abdollah , Mitha Samir , Chan Karissa , Fornazzari Luis R. , Churchill Nathan W. , Ismail Zahinoor , Munoz David G. , Schweizer Tom A. , Moody Alan R. , Fischer Corinne E. , Khademi April
Published: May 2022

Background: This study examines the relationship between delusional severity in cognitively impaired adults with automatically computed volume and texture biomarkers from the Normal Appearing Brain Matter (NABM) in FLAIR MRI. Methods: Patients with mild cognitive impairment (MCI, n = 24) and Alzheimer’s Disease (AD, n = 18) with delusions of varying severities based on Neuropsychiatric Inventory-Questionnaire (NPI-Q) (1—mild, 2—moderate, 3—severe) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed for this task. The NABM region, which is gray matter (GM) and white matter (WM) combined, was automatically segmented in FLAIR MRI volumes with intensity standardization and thresholding. Three imaging biomarkers were computed from this region, including NABM volume and two texture markers called “Integrity” and “Damage”. Together, these imaging biomarkers quantify structural changes in brain volume, microstructural integrity and tissue damage. Multivariable regression was used to investigate relationships between imaging biomarkers and delusional severities (1, 2 and 3). Sex, age, education, APOE4 and baseline cerebrospinal fluid (CSF) tau were included as co-variates. Results: Biomarkers were extracted from a total of 42 participants with longitudinal time points representing 164 imaging volumes. Significant associations were found for all three NABM biomarkers between delusion level 3 and level 1. Integrity was also sensitive enough to show differences between delusion level 1 and delusion level 2. A significant specified interaction was noted with severe delusions (level 3) and CSF tau for all imaging biomarkers (p < 0.01). APOE4 homozygotes were also significantly related to the biomarkers. Conclusion: Cognitively impaired older adults with more severe delusions have greater global brain disease burden in the WM and GM combined (NABM) as measured using FLAIR MRI. Relative to patients with mild delusions, tissue degeneration in the NABM was more pronounced in subjects with higher delusional symptoms, with a significant association with CSF tau. Future studies are required to establish potential tau-associated mechanisms of increased delusional severity.
Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms
Authors: Vivas Aisen , Mikhal Julia , Ong Gabriela M. , Eigenbrodt Anna , van der Meer Andries D. , Aquarius Rene , Geurts Bernard J. , Boogaarts Hieronymus D.
Published: May 2022

Intracranial aneurysms are pouch-like extrusions from the vessels at the base of the brain which can rupture and cause a subarachnoid hemorrhage. The pathophysiological mechanism of aneurysm formation is thought to be a consequence of blood flow (hemodynamic) induced changes on the endothelium. In this study, the results of a personalized aneurysm-on-a-chip model using patient-specific flow parameters and patient-specific cells are presented. CT imaging was used to calculate CFD parameters using an immersed boundary method. A microfluidic device either cultured with human umbilical vein endothelial cells (HUVECs) or human induced pluripotent stem cell-derived endothelial cells (hiPSC-EC) was used. Both types of endothelial cells were exposed for 24 h to either 0.03 Pa or 1.5 Pa shear stress, corresponding to regions of low shear and high shear in the computational aneurysm model, respectively. As a control, both cell types were also cultured under static conditions for 24 h as a control. Both HUVEC and hiPSC-EC cultures presented as confluent monolayers with no particular cell alignment in static or low shear conditions. Under high shear conditions HUVEC elongated and aligned in the direction of the flow. HiPSC-EC exhibited reduced cell numbers, monolayer gap formation and cells with aberrant, spread-out morphology. Future research should focus on hiPSC-EC stabilization to allow personalized intracranial aneurysm models.
Post-Stroke Asymmetric Prurigo Nodularis Responding to Dupilumab Treatment: A Case Report
Authors: Sammarra Ilaria , Bennardo Luigi , Provenzano Eugenio , Patruno Cataldo , Nisticò Steven Paul
Published: May 2022

Prurigo nodularis (PN) is a dermatological condition characterized by nodular hyperkeratotic lesions mainly on the legs and arms. Asymmetrical PN is a rare dermatological condition often associated with paralysis and stroke. In this paper, we present the case of a 77-year-old woman who developed post-ictal PN which responded to dupilumab, an anti-interleukin-4/13 drug approved for the management of AD, with an extreme reduction in itch sensation. Dupilumab and other therapies reducing Th2 inflammation may, in the future, become an alternative treatment for post-ictal pruritus/PN nonresponding to traditional therapies. Of course, larger studies will be necessary to confirm our case’s findings.
Walking Behavior in Temuco, Chile: The Contribution of Built Environment and Socio-Demographic Factors
Authors: Paydar Mohammad , Arangua Calzado Javier , Kamani Fard Asal
Published: May 2022

The increase in active travel contributes to maintaining the minimum rate of physical activity and therefore has a positive impact on inhabitants’ public health. The level of walking for daily transport has decreased significantly during the last decades in Temuco, Chile. This study examined the contribution of socio-demographic factors, active family environment, and built environment factors to walking behavior and walking level based on three types of destination in Temuco. The results of Encuesta Origin Destino (EOD 2013), geographic information system (GIS), and, finally, hierarchical multiple regression analysis were used to examine the objectives. Correlations were found between total walking behavior, walking level based on three destination types, and several socio-demographic factors such as age, gender, and access to TV and Internet. Furthermore, correlations were found between walking behavior and active family environment, as well as several built environment factors. For instance, the higher mixed land use as well as number of parks and plazas contribute towards more overall walking as well as two types of walking. Identifying that most persons who walk come from low-income families and the negative impact of network connectivity on overall walking are the major differences between this context and developed countries.
The Health of Healthcare Professionals in Italian Oncology: An Analysis of Narrations through the M.A.D.I.T. Methodology
Authors: Turchi Gian Piero , Salvalaggio Ilaria , Croce Claudio , Dalla Riva Marta Silvia , Orrù Luisa , Iudici Antonio
Published: May 2022

From the analysis of the scientific literature relating to the health of oncological patients, the need to consider the global dimension of health of individuals emerges, which subsumes the bodily dimension and involves all the actors who offer their contribution to it in different ways. In this direction, the state of the art of the health construct offered by healthcare professionals highlights a lack of scientific contributions to the specific subject although these professionals are fundamental figures in oncological diagnosis setups. Considering, therefore, the healthcare roles as an integral part of the interactive framework where the oncological patient is placed, this paper offers the results of an Italian study relating to the health of healthcare professionals who take charge of patients with a neoplasia diagnosis. In particular, through an analysis of the discursive productions of 61 participants (healthcare workers, oncological patients and citizens) by the M.A.D.I.T. methodology (Methodology for the Analysis of Computerized Textual Data), this study aimed at observing the discursive reality of health offered by healthcare workers. The collected data highlight a low degree of health expressed by the healthcare professionals, who are strongly typified by rhetoric such as “the one who is destined to suffer psychologically”. These narrations limit the possibilities of development of different narrations in depicting these professionals: critical repercussions in the interaction with the oncological patients emerged, as well as in their global health degree. In conclusion, the results show the need for deep investigation into the impact that the health degree of health professionals can have on the patients they take charge of.
Safety Risk Assessment Using a BP Neural Network of High Cutting Slope Construction in High-Speed Railway
Authors: Huang Jianling , Zeng Xiaoye , Fu Jing , Han Yang , Chen Huihua
Published: May 2022

High-speed railway construction is extending to mountainous areas, and the harsh environment and complex climate pose various risks to the slope construction. This seriously threatens human lives and causes huge economic losses. The existing research results on the construction safety risks of high cutting slope construction in HSRs are limited, and a complete set of safety risk assessment processes and methods has not yet been formed. Therefore, in this study, we aimed to develop a safety risk assessment model, including factor identification and classification and assessment data processing, to help project managers evaluate safety risks in high cutting slope construction. In this study, comprehensive identification of high cutting slope construction safety risks was carried out from three dimensions, risk technical specification, literature analysis, and case statistical analysis, and a list of risk-influencing factors was formed. Based on the historical data, a high side slope risk evaluation model was established using a BP neural network algorithm. The model was applied to the risk evaluation of HF high cutting slopes. The results show that the risk evaluation level is II; the main risks are earthwork excavation method, scaffolding equipment, slope height, slope rate, groundwater, personnel safety awareness, and construction safety risk management system. Finally, a case study was used to verify the proposed model, and control measures for safety risks were proposed. Our findings will help conduct effective safety management, add to the knowledge of construction safety risk management in terms of implementation, and offer lessons and references for future construction safety management of HSR.
Positive Effects of Advanced Daylight Supply of Buildings on Schoolchildren—A Controlled, Single-Blinded, Longitudinal, Clinical Trial with Real Constructive Implementation
Authors: Neberich Marcel , Gerner Nathalie , Romodow Carina , Freidl Johanna , Huber Daniela , Weisböck-Erdheim Renate , Pichler Christina , Hartl Arnulf
Published: May 2022

Sunlight controls endogen hormone balances and numerous health effects. Therefore, it is important to provide building users, such as schoolchildren, with sufficient daylight. Too much of it, however, leads to overheating, which is why shading systems are used. Consequently, these systems improve energy balance, but might not have positive effects on present people’s health. Within this study, shading systems were installed in classrooms of a middle school: common shading in two rooms, while two others were equipped with shading blades “Schlotterer RETROLux 80D” in an innovative design, reflecting more daylight indoors. The participating classes were divided between rooms with ordinary daylighting (n = 43) and advanced daylighting (n = 42). They spent, on average, 5 days weekly and 5–8 h daily in these classrooms. Saliva samples were collected during three semesters to detect hormonal changes. Questionnaires were collected to obtain more information about the mental alterations and, furthermore, to support the physiological results. A significant reduction in cortisol levels between 6:30 AM and 11:30 AM (p < 0.001) was observed within the group that had advanced daylighting. Questionnaires show that both groups sleep less as study duration increases (p < 0.001 time effect), but only the control group has a concurrent increase in daytime sleepiness according to relative treatment effects. The results show that increased daylight supply indoors leads to a significant greater reduction in cortisol levels of children and that those positive outcomes can be achieved by using innovative technologies for buildings.