bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization Design of the Inner Structure for a Bioinspired Heel Pad with Distinct Cushioning Property
Authors: Jin Jianqiao , Wang Kunyang , Ren Lei , Qian Zhihui , Lu Xuewei , Liang Wei , Xu Xiaohan , Zhao Shun , Zhao Di , Wang Xu , Ren Luquan
Published: December 2022

In the existing research on prosthetic footplates, rehabilitation insoles, and robot feet, the cushioning parts are basically based on simple mechanisms and elastic pads. Most of them are unable to provide adequate impact resistance especially during contact with the ground. This paper developed a bioinspired heel pad by optimizing the inner structures inspired from human heel pad which has great cushioning performance. The distinct structures of the human heel pad were determined through magnetic resonance imaging (MRI) technology and related literatures. Five-layer pads with and without inner structures by using two materials (soft rubber and resin) were obtained, resulting in four bionic heel pads. Three finite element simulations (static, impact, and walking) were conducted to compare the cushioning effects in terms of deformations, ground reactions, and principal stress. The optimal pad with bionic structures and soft rubber material reduced 28.0% peak vertical ground reaction force (GRF) during walking compared with the unstructured resin pad. Human walking tests by a healthy subject wearing the 3D printed bionic pads also showed similar findings, with an almost 20% decrease in peak vertical GRF at normal speed. The soft rubber heel pad with bionic structures has the best cushioning performance, while the unstructured resin pad depicts the poorest. This study proves that with proper design of the inner structures and materials, the bionic pads will demonstrate distinct cushioning properties, which could be applied to the engineering fields, including lower limb prosthesis, robotics, and rehabilitations.
Caffeine Delays Ethanol-Induced Sedation in Drosophila
Authors: Tremblay Sonia , Zeng Yanqiqi , Yue Aixin , Chabot Kiana , Mynahan Abigail , Desrochers Stephanie , Bridges Sarra , Ahmad S. Tariq
Published: December 2022

Caffeine and ethanol are among the most widely available and commonly consumed psychoactive substances. Both interact with adenosine receptor-mediated signaling which regulates numerous neurological processes including sleep and waking behaviors. In mammals, caffeine is an adenosine receptor antagonist and thus acts as a stimulant. Conversely, ethanol is a sedative because it promotes GABAergic neurotransmission, inhibits glutamatergic neurotransmission, and increases the amount of adenosine in the brain. Despite seemingly overlapping interactions, not much is known about the effect of caffeine on ethanol-induced sedation in Drosophila. In this study, using Drosophila melanogaster as a model, we show that caffeine supplementation in food delays the onset of ethanol-induced sedation in males and females of different strains. The resistance to sedation reverses upon caffeine withdrawal. Heterozygous adenosine receptor mutant flies are resistant to sedation. These findings suggest that caffeine and adenosine receptors modulate the sedative effects of ethanol in Drosophila.
Effect of Sox18 on the Induction Ability of Dermal Papilla Cells in Hu Sheep
Authors: Hu Tingyan , Lv Xiaoyang , Getachew Tesfaye , Mwacharo Joram M. , Haile Aynalem , Quan Kai , Li Yutao , Wang Shanhe , Sun Wei
Published: December 2022

Sox18 is a developmental gene that encodes transcription factors. It has been indicated as be a key gene affecting the growth and development of hair follicles, in which dermal papilla cells (DPCs) have been demonstrated to play an important role through their ability to induce the formation of hair follicles. Pre-laboratory studies have found that Sox18 is differentially expressed in the dermal papilla cells of different pattern types of Hu sheep. We speculated that Sox18 plays an important role in the dermal papilla cells of Hu sheep. In our study, we analyzed the effect of Sox18 on the induction ability of DPCs in order to elucidate the function and molecular mechanism of Sox18 in the DPCs of Hu sheep. We first identified the expression of Sox18 in the DPCs of Hu sheep by immunofluorescence staining. We then used alkaline phosphatase staining, cell morphology observations and RT-PCR to detect the effect of Sox18 on the induction of DPCs after overexpression of or interference with Sox18. We also used RT-PCR, WB and immunofluorescence staining to detect the effect of Sox18 on the Wnt/β-catenin signal pathway in DPCs. We found that Sox18 was specifically expressed in the DPCs of Hu sheep, and that Sox18 could enhance the alkaline phosphatase activity in the DPCs of Hu sheep and accelerate cell agglutination. The results of RT-PCR revealed that Sox18 promoted the mRNA expression of Versican, HHIP and FGFRI, and inhibited the mRNA expression of BMP4 and WIF1. Further studies showed that Sox18 promoted the expression of β-catenin and activated the Wnt/β-catenin signal pathway in DPCs. When the Wnt/β-catenin signal pathway of DPCs was activated, the induction ability of DPCs was enhanced. Overall, we believe that Sox18 could enhance the induction ability of DPCs in Hu sheep and regulate the induction ability of DPCs through the Wnt/β-catenin signal pathway.
Metabolic Maturation Exaggerates Abnormal Calcium Handling in a Lamp2 Knockout Human Pluripotent Stem Cell-Derived Cardiomyocyte Model of Danon Disease
Authors: Barndt Robert J. , Liu Qing , Tang Ying , Haugh Michael P. , Cui Jeffery , Chan Stephen Y. , Wu Haodi
Published: December 2022

Danon disease (DD) is caused by mutations of the gene encoding lysosomal-associated membrane protein type 2 (LAMP2), which lead to impaired autophagy, glycogen accumulation, and cardiac hypertrophy. However, it is not well understood why a large portion of DD patients develop arrhythmia and sudden cardiac death. In the current study, we generated LAMP2 knockout (KO) human iPSC-derived cardiomyocytes (CM), which mimic the LAMP2 dysfunction in DD heart. Morphologic analysis demonstrated the sarcomere disarrangement in LAMP2 KO CMs. In functional studies, LAMP2 KO CMs showed near-normal calcium handling at base level. However, treatment of pro-maturation medium (MM) exaggerated the disease phenotype in the KO cells as they exhibited impaired calcium recycling and increased irregular beating events, which recapitulates the pro-arrhythmia phenotypes of DD patients. Further mechanistic study confirmed that MM treatment significantly enhanced the autophagic stress in the LAMP2 KO CMs, which was accompanied by an increase of both cellular and mitochondrial reactive oxygen species (ROS) levels. Excess ROS accumulation in LAMP2 KO CMs resulted in the over-activation of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and arrhythmogenesis, which was partially rescued by the treatment of ROS scavenger. In summary, our study has revealed ROS induced CaMKIIδ overactivation as a key mechanism that promotes cardiac arrhythmia in DD patients.
Iron Deprivation by Oral Deferoxamine Application Alleviates Acute Campylobacteriosis in a Clinical Murine Campylobacter jejuni Infection Model
Authors: Bereswill Stefan , Mousavi Soraya , Weschka Dennis , Buczkowski Agnes , Schmidt Sebastian , Heimesaat Markus M.
Published: December 2022

The progressively rising food-borne Campylobacter jejuni infections pose serious health problems and socioeconomic burdens. Given that antibiotic therapy is not recommended for most campylobacteriosis patients, novel treatment options include strategies targeting iron homeostasis that impacts both C. jejuni virulence and inflammatory cell damage caused by toxic oxygen species. In our preclinical intervention study, we tested potential disease-alleviating effects upon prophylactic oral application of the iron-chelating compound desferoxamine (DESF) in acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10−/− mice received synthetic DESF via the drinking water starting seven days before oral infection with C. jejuni strain 81-176. Results revealed that the DESF application did not reduce gastrointestinal pathogen loads but significantly improved the clinical outcome of infected mice at day 6 post-infection. This was accompanied by less pronounced colonic epithelial cell apoptosis, attenuated accumulation of neutrophils in the infected large intestines and abolished intestinal IFN-γ and even systemic MCP-1 secretion. In conclusion, our study highlights the applied murine campylobacteriosis model as suitable for investigating the role of iron in C. jejuni infection in vivo as demonstrated by the disease-alleviating effects of specific iron binding by oral DESF application in acute C. jejuni induced enterocolitis.
Understanding Calmodulin Variants Affecting Calcium-Dependent Inactivation of L-Type Calcium Channels through Whole-Cell Simulation of the Cardiac Ventricular Myocyte
Authors: McCoy Matthew D. , Ullah Aman , Lederer W. Jonathan , Jafri M. Saleet
Published: December 2022

Mutations in the calcium-sensing protein calmodulin (CaM) have been linked to two cardiac arrhythmia diseases, Long QT Syndrome 14 (LQT14) and Catecholaminergic Polymorphic Ventricular Tachycardia Type 4 (CPVT4), with varying degrees of severity. Functional characterization of the CaM mutants most strongly associated with LQT14 show a clear disruption of the calcium-dependent inactivation (CDI) of the L-Type calcium channel (LCC). CPVT4 mutants on the other hand are associated with changes in their affinity to the ryanodine receptor. In clinical studies, some variants have been associated with both CPVT4 and LQT15. This study uses simulations in a model for excitation–contraction coupling in the rat ventricular myocytes to understand how LQT14 variant might give the functional phenotype similar to CPVT4. Changing the CaM-dependent transition rate by a factor of 0.75 corresponding to the D96V variant and by a factor of 0.90 corresponding to the F142L or N98S variants, in a physiologically based stochastic model of the LCC prolonger, the action potential duration changed by a small amount in a cardiac myocyte but did not disrupt CICR at 1, 2, and 4 Hz. Under beta-adrenergic simulation abnormal excitation–contraction coupling was observed above 2 Hz pacing for the mutant CaM. The same conditions applied under beta-adrenergic stimulation led to the rapid onset of arrhythmia in the mutant CaM simulations. Simulations with the LQT14 mutations under the conditions of rapid pacing with beta-adrenergic stimulation drives the cardiac myocyte toward an arrhythmic state known as Ca2+ overload. These simulations provide a mechanistic link to a disease state for LQT14-associated mutations in CaM to yield a CPVT4 phenotype. The results show that small changes to the CaM-regulated inactivation of LCC promote arrhythmia and underscore the significance of CDI in proper heart function.
Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro
Authors: Poggio Fabio , Brofiga Martina , Tedesco Mariateresa , Massobrio Paolo , Adriano Enrico , Balestrino Maurizio
Published: December 2022

The creatine precursor Guanidinoacetic Acid (GAA) accumulates in the genetic deficiency of the GuanidinoAcetate Methyl Transferase (GAMT) enzyme and it is believed to cause the seizures that often occur in this condition. However, evidence that it is indeed epileptogenic is scarce and we previously found that it does not cause neuronal hyperexcitation in in vitro brain slices. Here, we used Micro-Electrode Arrays (MEAs) to further investigate the electrophysiological effects of its acute and chronic administration in the networks of cultured neurons, either neocortical or hippocampal. We found that: (1) GAA at the 1 µM concentration, comparable to its concentration in normal cerebrospinal fluid, does not modify any of the parameters we investigated in either neuronal type; (2) at the 10 µM concentration, very similar to that found in the GAMT deficiency, it did not affect any of the parameters we tested except the bursting rate of neocortical networks and the burst duration of hippocampal networks, both of which were decreased, a change pointing in a direction opposite to epileptogenesis; (3) at the very high and unphysiological 100 µM concentration, it caused a decrease in all parameters, a change that again goes in the direction opposite to epileptogenesis. Our results confirm that GAA is not epileptogenic.
3α,7-Dihydroxy-14(13→12)abeo-5β,12α(H),13β(H)-cholan-24-oic Acids Display Neuroprotective Properties in Common Forms of Parkinson’s Disease
Authors: Luxenburger Andreas , Clemmens Hannah , Hastings Christopher , Harris Lawrence D. , Ure Elizabeth M. , Cameron Scott A. , Aasly Jan , Bandmann Oliver , Weymouth-Wilson Alex , Furneaux Richard H. , Mortiboys Heather
Published: December 2022

Parkinson’s Disease is the most common neurodegenerative movement disorder globally, with prevalence increasing. There is an urgent need for new therapeutics which are disease-modifying rather than symptomatic. Mitochondrial dysfunction is a well-documented mechanism in both sporadic and familial Parkinson’s Disease. Furthermore, ursodeoxycholic acid (UDCA) has been identified as a bile acid which leads to increased mitochondrial function in multiple in vitro and in vivo models of Parkinson’s Disease. Here, we describe the synthesis of novel C-nor-D-homo bile acid derivatives and the 12-hydroxy-methylated derivative of lagocholic acid (7) and their biological evaluation in fibroblasts from patients with either sporadic or LRRK2 mutant Parkinson’s Disease. These compounds boost mitochondrial function to a similar level or above that of UDCA in many assays; notable, however, is their ability to boost mitochondrial function to a higher level and at lower concentrations than UDCA specifically in the fibroblasts from LRRK2 patients. Our study indicates that novel bile acid chemistry could lead to the development of more efficacious bile acids which increase mitochondrial function and ultimately cellular health at lower concentrations proving attractive potential novel therapeutics for Parkinson’s Disease.
Impact of Liver Metastases and Number of Metastatic Sites on Immune-Checkpoint Inhibitors Efficacy in Patients with Different Solid Tumors: A Retrospective Study
Authors: Maugeais Madeleine , Péron Julien , Dalle Stéphane , Boespflug Amélie , Duruissaux Michaël , Corbaux Pauline , Reverdy Thibault , Sahin Gulsum , Rabier Aurélie , Lopez Jonathan , Freymond Nathalie , Maillet Denis
Published: December 2022

Background: ICIs have dramatically improved patient outcomes in different malignancies. However, the impact of liver metastases (LM) and number of metastatic sites (MS) remains unclear in patients treated with single-agent anti-PD(L)1. Methods: We aimed to assess the prognostic impact of LM and MS number on progression-free survival (PFS) and overall survival (OS) in a large single-arm retrospective multicentric cohort (IMMUCARE) of patients treated with anti-PD(L)-1 for different solid tumors. Results: A total of 759 patients were enrolled from January 2012 to October 2018. The primary tumor types were non-small cell lung cancer (71%), melanoma (19%), or urologic cancer (10%). At the time of ICI initiation, 167 patients (22%) had LM and 370 patients (49%) had more than MS. LM was associated with a shorter median PFS of 1.9 months (95% CI: 1.8–2.5) vs. 4.0 months (95% CI: 3.6–5.4) in patients without LM (p < 0.001). The median OS of patients with LM was of 5.2 months (95% CI: 4.0–7.7) compared with 12.8 months (95% CI: 11.2–15.1) (p < 0.001). Interestingly, LM were not associated with shorter PFS, or OS compared to other MS types (brain, bone, or lung) in patients with only one MS. Patients with multiple MS also had poor clinical outcomes compared to patients with only one MS. The presence of LM and MS number were independent prognostic factors on overall survival. Conclusion: The presence of LM or multiple MS were associated with poorer survival outcomes in patients treated with anti-PD(L)-1.
Central Sensitization and Psychological State Distinguishing Complex Regional Pain Syndrome from Other Chronic Limb Pain Conditions: A Cluster Analysis Model
Authors: Karpin Hana , Vatine Jean-Jacques , Bachar Kirshenboim Yishai , Markezana Aurelia , Weissman-Fogel Irit
Published: December 2022

Complex regional pain syndrome (CRPS) taxonomy has been updated with reported subtypes and is defined as primary pain alongside other chronic limb pain (CLP) conditions. We aimed at identifying CRPS clinical phenotypes that distinguish CRPS from other CLP conditions. Cluster analysis was carried out to classify 61 chronic CRPS and 31 CLP patients based on evoked pain (intensity of hyperalgesia and dynamic allodynia, allodynia area, and after-sensation) and psychological (depression, kinesiophobia, mental distress, and depersonalization) measures. Pro-inflammatory cytokine IL-6 and TNF-α serum levels were measured. Three cluster groups were created: ‘CRPS’ (78.7% CRPS; 6.5% CLP); ‘CLP’ (64.5% CLP; 4.9% CRPS), and ‘Mixed’ (16.4% CRPS; 29% CLP). The groups differed in all measures, predominantly in allodynia and hyperalgesia (p < 0.001, η² > 0.58). ‘CRPS’ demonstrated higher psychological and evoked pain measures vs. ‘CLP’. ‘Mixed’ exhibited similarities to ‘CRPS’ in psychological profile and to ‘CLP’ in evoked pain measures. The serum level of TNF-αwas higher in the ‘CRPS’ vs. ‘CLP’ (p < 0.001) groups. In conclusion, pain hypersensitivity reflecting nociplastic pain mechanisms and psychological state measures created different clinical phenotypes of CRPS and possible CRPS subtypes, which distinguishes them from other CLP conditions, with the pro-inflammatory TNF-α cytokine as an additional potential biomarker.
Renal Papillary Necrosis (RPN) in an African Population: Disease Patterns, Relevant Pathways, and Management
Authors: Gaudji Guy Roger , Bida Meshack , Conradie Marius , Damane Botle Precious , Bester Megan Jean
Published: December 2022

Renal papillary necrosis (RPN) is characterized by coagulative necrosis of the renal medullary pyramids and papillae. Multiple conditions and toxins are associated with RPN. Several RPN risk factors, or POSTCARDS, have been identified, with most patients presenting with RPN having at least two contributing risk factors. Currently, there is no specific test to diagnose and confirm RPN; however, several imaging tools can be used to diagnose the condition. RPN is currently underdiagnosed in African populations, often with fatal outcomes. In African clinical settings, there is a lack of consensus on how to define and describe RPN in terms of kidney anatomy, pathology, endourology, epidemiology, the identification of African-specific risk factors, the contribution of oxidative stress, and lastly an algorithm for managing the condition. Several risk factors are unique to African populations including population-specific genetic factors, iatrogenic factors, viral infections, antimicrobial therapy, schistosomiasis, substance abuse, and hypertension (GIVASSH). Oxidative stress is central to both GIVASSH and POSTCARDS-associated risk factors. In this review, we present information specific to African populations that can be used to establish an updated consensual definition and practical grading system for radiologists, urologists, nephrologists, nuclear physicians, and pathologists in African clinical settings.
Modeling Central Nervous System Injury In Vitro: Current Status and Promising Future Strategies
Authors: Pilipović Kristina , Harej Hrkać Anja , Kučić Natalia , Mršić-Pelčić Jasenka
Published: December 2022

The central nervous system (CNS) injury, which occurs because of mechanical trauma or ischemia/hypoxia, is one of the main causes of mortality and morbidity in the modern society. Until know, despite the fact that numerous preclinical and clinical studies have been undertaken, no significant neuroprotective strategies have been discovered that could be used in the brain trauma or ischemia treatment. Although there are many potential explanations for the failure of those studies, it is clear that there are questions regarding the use of experimental models, both in vivo and in vitro, when studying CNS injury and searching new therapeutics. Due to some ethical issues with the use of live animals in biomedical research, implementation of experimental strategies that prioritize the use of cells and tissues in the in vitro environment has been encouraged. In this review, we examined some of the most commonly used in vitro models and the most frequently utilized cellular platforms in the research of traumatic brain injury and cerebral ischemia. We also proposed some future strategies that could improve the usefulness of these studies for better bench-to-bedside translational outcomes.
Hyperandrogenic Symptoms Are a Persistent Suffering in Midlife Women with PCOS; a Prospective Cohort Study in Sweden
Authors: Persson Sofia , Ubhayasekera Kumari A. , Bergquist Jonas , Turkmen Sahruh , Poromaa Inger Sundström , Elenis Evangelia
Published: December 2022

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women, and the majority suffers from hyperandrogenism. Hyperandrogenism causes psychological morbidity and impaired quality of life in women with PCOS during the reproductive years, but data on prevalence and impact during midlife are lacking. Thus, this study aimed to address whether hyperandrogenism persists into midlife and, if so, what impact it has on quality of life. In order to answer this question, we performed a multicenter prospective cohort study, where we included women already diagnosed with PCOS who had reached the age of 45 years or more and age-matched controls. All participants underwent a physical exam, structured medical interview, biochemical testing and filled out self-assessment questionnaires. More than 40% of the women with PCOS and 82% of those who presented with the hyperandrogenic phenotype at the diagnostic work-up still suffered from hirsutism. Circulating testosterone levels were similar between women with PCOS and controls while free androgen index was higher in women with PCOS, independent of weight. Women with hyperandrogenic PCOS expressed persisting concerns regarding hirsutism at the follow-up assessment. In conclusion, women with PCOS who present with hyperandrogenic symptoms at the time they are diagnosed with PCOS have a higher risk of persistent androgenic symptoms and impaired quality of life in midlife.
The Prognostic and Predictive Value of Genomic Assays in Guiding Adjuvant Breast Radiation Therapy
Authors: Beyer Sasha J. , Tallman Miranda , Jhawar Sachin R. , White Julia R. , Bazan Jose G.
Published: December 2022

Many patients with non-metastatic breast cancer benefit from adjuvant radiation therapy after lumpectomy or mastectomy on the basis of many randomized trials. However, there are many patients that have such low risks of recurrence after surgery that de-intensification of therapy by either reducing the treatment volume or omitting radiation altogether may be appropriate options. On the other hand, dose intensification may be necessary for more aggressive breast cancers. Until recently, these treatment decisions were based solely on clinicopathologic factors. Here, we review the current literature on the role of genomic assays as prognostic and/or predictive biomarkers to help guide adjuvant radiation therapy decision-making.
Association between Immunosuppressive Therapy Utilized in the Treatment of Autoimmune Disease or Transplant and Cancer Progression
Authors: Reyes Amanda , Mohanty Atish , Pharaon Rebecca , Massarelli Erminia
Published: December 2022

Autoimmunity and cancer rates have both been on the rise in Western civilization prompting many to investigate the link between the two entities. This review will investigate the complex interactions between the activation and deactivation of the immune system and the development of malignancy. Additional focus will be placed on the main classes of immune inhibitor therapy utilized in transplant patients and in autoimmune disease including TNF-alpha, Calcineurin, mTOR, purine synthesis antagonists and IMPDH inhibitors.
Synergistic Effect of Composite Nickel Phosphide Nanoparticles and Carbon Fiber on the Enhancement of Salivary Enzyme-Free Glucose Sensing
Authors: Brito Tania P. , Butto-Miranda Nicole , Neira-Carrillo Andrónico , Bollo Soledad , Ruíz-León Domingo
Published: December 2022

An electrospinning method was used for the preparation of an in situ composite based on Ni2P nanoparticles and carbon fiber (FC). The material was tested for the first time against direct glucose oxidation reaction. The Ni2P nanoparticles were distributed homogeneously throughout the carbon fibers with a composition determined by thermogravimetric analysis (TGA) of 40 wt% Ni2P and 60 wt% carbon fiber without impurities in the sample. The electrochemical measurement results indicate that the GCE/FC/Ni2P in situ sensor exhibits excellent catalytic activity compared to the GCE/Ni2P and GCE/FC/Ni2P ex situ electrodes. The GCE/FC/Ni2P in situ sensor presents a sensitivity of 1050 µAmM−1cm−2 in the range of 5–208 µM and a detection limit of 0.25 µM. The sensor was applied for glucose detection in artificial saliva, with a low interference observed from normally coexisting electroactive species. In conclusion, our sensor represents a novel and analytical competitive alternative for the development of non-enzymatic glucose sensors in the future.
Optimized Design and Preparation of Ag Nanoparticle Multilayer SERS Substrates with Excellent Sensing Performance
Authors: Wen Ping , Yang Feng , Hu Xiaoling , Xu Yi , Wan Shu , Chen Li
Published: December 2022

Nanoparticle multilayer substrates usually exhibit excellent SERS activity due to multi-dimensional plasmon coupling. However, simply increasing the layers will lead to several problems, such as complex manufacturing procedures, reduced uniformity and poor reproducibility. In this paper, the local electric field (LEF) characteristics of a Ag nanoparticle (AgNP) multilayer were systematically studied through finite element simulations. We found that, on the glass support, the LEF intensity improved with the increase in the layers of AgNPs. However, the maximum LEF could be obtained with only two layers of AgNPs on the Au film support, and it was much stronger than the optimal value of the former. To verify the simulation results, we have successfully prepared one to four layers of AgNPs on both supports with a liquid–liquid interface self-assembly method, and carried out a series of SERS measurements. The experimental results were in good agreement with the simulations. Finally, the optimized SERS substrate, the 2-AgNP@Au film, showed an ultra-high SERS sensitivity, along with an excellent signal uniformity, which had a detection ability of 1 × 10−15 M for the Rhodamine 6G (R6G) and a relative standard deviation (RSD) of 11% for the signal intensity. Our study provides important theoretical guidance and a technical basis for the optimized design and application of high-performance SERS substrates.
Biofunctionalization of Multiplexed Silicon Photonic Biosensors
Authors: Puumala Lauren S. , Grist Samantha M. , Morales Jennifer M. , Bickford Justin R. , Chrostowski Lukas , Shekhar Sudip , Cheung Karen C.
Published: December 2022

Silicon photonic (SiP) sensors offer a promising platform for robust and low-cost decentralized diagnostics due to their high scalability, low limit of detection, and ability to integrate multiple sensors for multiplexed analyte detection. Their CMOS-compatible fabrication enables chip-scale miniaturization, high scalability, and low-cost mass production. Sensitive, specific detection with silicon photonic sensors is afforded through biofunctionalization of the sensor surface; consequently, this functionalization chemistry is inextricably linked to sensor performance. In this review, we first highlight the biofunctionalization needs for SiP biosensors, including sensitivity, specificity, cost, shelf-stability, and replicability and establish a set of performance criteria. We then benchmark biofunctionalization strategies for SiP biosensors against these criteria, organizing the review around three key aspects: bioreceptor selection, immobilization strategies, and patterning techniques. First, we evaluate bioreceptors, including antibodies, aptamers, nucleic acid probes, molecularly imprinted polymers, peptides, glycans, and lectins. We then compare adsorption, bioaffinity, and covalent chemistries for immobilizing bioreceptors on SiP surfaces. Finally, we compare biopatterning techniques for spatially controlling and multiplexing the biofunctionalization of SiP sensors, including microcontact printing, pin- and pipette-based spotting, microfluidic patterning in channels, inkjet printing, and microfluidic probes.
Ultrasensitive Electrochemiluminescence Immunoassay Based on Signal Amplification of 0D Au—2D WS2 Nano-Hybrid Materials
Authors: Li Qile , Xu Ke , Zhang Haipeng , Huang Zengguang , Xu Chao , Zhou Zhen , Peng Huaping , Shi Linxing
Published: December 2022

In this study, we proposed a novel Ru(bpy)32+-Au-WS2 nanocomposite (Ru-Au-WS2 NCs) nano-hybrid electrochemiluminescence (ECL) probe for the highly sensitive detection of carcinoembryonic antigen (CEA). This system utilizes Au nanoparticles (Au NPs) as a bridge to graft the high-performance of a Ru(bpy)32+ ECL emitter and WS2 nanosheet with excellent electrochemical performance into an ECL platform, which shows outstanding anodic ECL performance and biosensing platform due to the synergetic effect and biocompatibility of Au NPs and WS2 nanosheet. Because the ECL intensity of Ru(bpy)32+ is sensitively affected by the antibody-antigen insulator, a preferable linear dependence was obtained in the concentration range of CEA from 1 pg·mL−1 to 350 ng·mL−1 with high selectivity (LOD of 0.3 pg·mL−1, S/N = 3). Moreover, the ECL platform had good reproducibility and stability and exhibited excellent anti-interference performance in the detection process of CEA. We believe that the platform we have developed can expand the opportunities for the detection of additional high specificity-related antibodies/antigens and demonstrate broad prospects for disease diagnosis and biochemical research.
Alterations in Corticocortical Vestibular Network Functional Connectivity Are Associated with Decreased Balance Ability in Elderly Individuals with Mild Cognitive Impairment
Authors: Xia Rui , Ren Jinxin , Li Xingjie , Liu Jun , Dai Yalan , Kuang Yuxing , Wu Zhuguo , Chen Shangjie
Published: December 2022

The corticocortical vestibular network (CVN) plays an important role in maintaining balance and stability. In order to clarify the specific relationship between the CVN and the balance ability of patients with mild cognitive impairment (MCI), we recruited 30 MCI patients in the community. According to age and sex, they were 1:1 matched to 30 older adults with normal cognitive function. We evaluated balance ability and performed MRI scanning in the two groups of participants. We analyzed functional connectivity within the CVN based on the region of interest. Then, we performed a Pearson correlation analysis between the functional connection and the Berg Balance Scale scores. The research results show that compared with the control group, there were three pairs of functional connections (hMST_R–Premotor_R, PFcm_R–SMA_L, and hMST_L–VIP_R) that were significantly decreased in the CVNs of the MCI group (p < 0.05). Further correlation analysis showed that there was a significant positive correlation between hMST_R–Premotor_R functional connectivity and BBS score (r = 0.364, p = 0.004). The decline in balance ability and increase in fall risk in patients with MCI may be closely related to the change in the internal connection mode of the corticocortical vestibular network.
Correction: Valcic et al. Determining Whether Sex and Zygosity Modulates the Association between APOE4 and Psychosis in a Neuropathologically-Confirmed Alzheimer’s Disease Cohort. Brain Sci. 2022, 12, 1266
Authors: Valcic Mila , Khoury Marc A. , Kim Julia , Fornazzari Luis , Churchill Nathan W. , Ismail Zahinoor , De Luca Vincenzo , Tsuang Debby , Schweizer Tom A. , Munoz David G. , Fischer Corinne E.
Published: December 2022

In the original publication [...]
Multisensory Enhancement of Cognitive Control over Working Memory Capture of Attention in Children with ADHD
Authors: Cai Biye , Cai Shizhong , He Hua , He Lu , Chen Yan , Wang Aijun
Published: December 2022

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school-age children. Although it has been well documented that children with ADHD are associated with impairment of executive functions including working memory (WM) and inhibitory control, there is not yet a consensus as to the relationship between ADHD and memory-driven attentional capture (i.e., representations in WM bias attention toward the WM-matched distractors). The present study herein examined whether children with ADHD have sufficient cognitive control to modulate memory-driven attentional capture. 73 school-age children (36 with ADHD and 37 matched typically developing (TD) children) were instructed to perform a visual search task while actively maintaining an item in WM. In such a paradigm, the modality and the validity of the memory sample were manipulated. The results showed that under the visual WM encoding condition, no memory-driven attentional capture was observed in TD children, but significant capture was found in children with ADHD. In addition, under the audiovisual WM encoding condition, memory-matched distractors did not capture the attention of both groups. The results indicate a deficit of cognitive control over memory-driven attentional capture in children with ADHD, which can be improved by multisensory WM encoding. These findings enrich the relationship between ADHD and cognitive control and provide new insight into the influence of cross-modal processing on attentional guidance.
Precise Spiking Motifs in Neurobiological and Neuromorphic Data
Authors: Grimaldi Antoine , Gruel Amélie , Besnainou Camille , Jérémie Jean-Nicolas , Martinet Jean , Perrinet Laurent U.
Published: December 2022

Why do neurons communicate through spikes? By definition, spikes are all-or-none neural events which occur at continuous times. In other words, spikes are on one side binary, existing or not without further details, and on the other, can occur at any asynchronous time, without the need for a centralized clock. This stands in stark contrast to the analog representation of values and the discretized timing classically used in digital processing and at the base of modern-day neural networks. As neural systems almost systematically use this so-called event-based representation in the living world, a better understanding of this phenomenon remains a fundamental challenge in neurobiology in order to better interpret the profusion of recorded data. With the growing need for intelligent embedded systems, it also emerges as a new computing paradigm to enable the efficient operation of a new class of sensors and event-based computers, called neuromorphic, which could enable significant gains in computation time and energy consumption—a major societal issue in the era of the digital economy and global warming. In this review paper, we provide evidence from biology, theory and engineering that the precise timing of spikes plays a crucial role in our understanding of the efficiency of neural networks.
Repetitive Transcranial Magnetic Stimulation of the Brain Region Activated by Motor Imagery Involving a Paretic Wrist and Hand for Upper-Extremity Motor Improvement in Severe Stroke: A Preliminary Study
Authors: Gao Tianhao , Hu Yiqian , Zhuang Jie , Bai Yulong , Lu Rongrong
Published: December 2022

Approximately two-thirds of stroke survivors experience chronic upper-limb paresis; however, treatment options are limited. Repetitive transcranial magnetic stimulation (rTMS) can enhance motor function recovery in stroke survivors, but its efficacy is controversial. We compared the efficacy of stimulating different targets in 10 chronic stroke patients with severe upper-limb motor impairment. Motor imagery-based brain–computer interface training augmented with virtual reality was used to induce neural activity in the brain region during an imagery task. Participants were then randomly assigned to two groups: an experimental group (received high-frequency rTMS delivered to the brain region activated earlier) and a comparison group (received low-frequency rTMS delivered to the contralesional primary motor cortex). Behavioural metrics and diffusion tensor imaging were compared pre- and post rTMS. After the intervention, participants in both groups improved somewhat. This preliminary study indicates that in chronic stroke patients with severe upper-limb motor impairment, inducing activation in specific brain regions during motor imagery tasks and selecting these regions as a target is feasible. Further studies are needed to explore the efficacy of this intervention.
Effectiveness of Anodal otDCS Following with Anodal tDCS Rather than tDCS Alone for Increasing of Relative Power of Intrinsic Matched EEG Bands in Rat Brains
Authors: Al-Tawarah Nafe M. , Kaptan Zulal , Abu-Harirah Hashem A. , Nofal Mohammad , Almajali Belal , Jarrar Sultan , Bayraktaroğlu Zubeyir , Qaralleh Haitham , Khleifat Khaled M. , Ziylan Ziya Y. , Al dmour Rawand H. , Alqaraleh Moath , Karamursel Sacit
Published: December 2022

Background: This study sought to determine whether (1) evidence is available of interactions between anodal tDCS and oscillated tDCS stimulation patterns to increase the power of endogenous brain oscillations and (2) the frequency matching the applied anodal otDCS’s frequency and the brain’s dominant intrinsic frequency influence power shifting during stimulation pattern sessions by both anodal DCS and anodal oscillated DCS. Method: Rats received different anodal tDCS and otDCS stimulation patterns using 8.5 Hz and 13 Hz state-related dominant intrinsic frequencies of anodal otDCS. The rats were divided into groups with specific stimulation patterns: group A: tDCS–otDCS (8.5 Hz)–otDCS (13 Hz); group B: otDCS (8.5 Hz)–tDCS–otDCS (13 Hz); group C: otDCS (13 Hz)–tDCS–otDCS (8.5 Hz). Acute relative power changes (i.e., following 10 min stimulation sessions) in six frequency bands—delta (1.5–4 Hz), theta (4–7 Hz), alpha-1 (7–10 Hz), alpha-2 (10–12 Hz), beta-1 (12–15 Hz) and beta-2 (15–20 Hz)—were compared using three factors and repeated ANOVA measurement. Results: For each stimulation, tDCS increased theta power band and, above bands alpha and beta, a drop in delta power was observed. Anodal otDCS had a mild increasing power effect in both matched intrinsic and delta bands. In group pattern stimulations, increased power of endogenous frequencies matched exogenous otDCS frequencies—8.5 Hz or 13 Hz—with more potent effects in upper bands. The power was markedly more potent with the otDCS–tDCS stimulation pattern than the tDCS–otDCS pattern. Significance: The findings suggest that the otDCS–tDCS pattern stimulation increased the power in matched intrinsic oscillations and, significantly, in the above bands in an ascending order. We provide evidence for the successful corporation between otDCS (as frequency-matched guidance) and tDCS (as a power generator) rather than tDCS alone when stimulating a desired brain intrinsic band (herein, tES specificity).
Hemispherotomy in Infants with Hemimegalencephaly: Long-Term Seizure and Developmental Outcome in Early Treated Patients
Authors: Pepi Chiara , De Benedictis Alessandro , Rossi-Espagnet Maria Camilla , Cappelletti Simona , Da Rold Martina , Falcicchio Giovanni , Vigevano Federico , Marras Carlo Efisio , Specchio Nicola , De Palma Luca
Published: December 2022

Hemimegalencephaly (HME) is a rare brain congenital malformation, consisting in altered neuronal migration and proliferation within one hemisphere, which is responsible for early onset drug-resistant epilepsy. Hemispherotomy is an effective treatment option for patients with HME and drug-resistant epilepsy. Surgical outcome may be variable among different surgical series, and the long-term neuropsychological trajectory has been rarely defined using a standardized neurocognitive test. We report the epileptological and neuropsychological long-term outcomes of four consecutive HME patients, operated on before the age of three years. All patients were seizure-free and drug-free, and the minimum follow-up duration was of five years. Despite the excellent post-surgical seizure outcome, the long-term developmental outcome is quite variable between patients, ranging from mild to severe intellectual disabilities. Patients showed improvement mainly in communication skills, while visuo-perceptive and coordination abilities were more impaired. Epileptological outcome seems to be improved in early treated patients; however, neuropsychological outcome in HME patients may be highly variable despite early surgery.
The Relationship between Corporate Social Responsibility on Social Media and Brand Advocacy Behavior of Customers in the Banking Context
Authors: Huang Shijiao , Hai Xu , Adam Nawal Abdalla , Fu Qinghua , Ahmad Aqeel , Zapodeanu Daniela , Badulescu Daniel
Published: December 2022

This research study aims to investigate the relationship between corporate social responsibility (CSR)-related communication on social media and brand advocacy behavior of retail banking customers in a developing country. This study also proposes a dual mediating mechanism of customer engagement and customer-company identification in the above-proposed relationship. The data were collected from retail banking customers with the help of a self-administered questionnaire (n = 356). To test the hypothesized relationships, a theoretical model was developed in this study. For hypothesis testing, we used the structural equation modeling (SEM) technique in AMOS software. The empirical analysis results confirmed our theoretical assumption that the manifestation of CSR-related communication on social media by a bank significantly influenced the advocacy behavior of retail banking customers. Our study also confirmed the mediating function of customer engagement and customer-company identification. The findings of this study offer different implications for the banking sector. For example, our study highlights the critical role of CSR-related communication on social media for meaningful customer–brand relationships by promoting the advocacy behavior of customers.
An Effective Metaheuristic Approach for Building Energy Optimization Problems
Authors: Yuan Xinzhe , Karbasforoushha Mohammad , Syah Rahmad , Khajehzadeh Mohammad , Keawsawasvong Suraparb , Nehdi Moncef
Published: December 2022

Mathematical optimization can be a useful strategy for minimizing energy usage while designing low-energy buildings. To handle building energy optimization challenges, this study provides an effective hybrid technique based on the pelican optimization algorithm (POA) and the single candidate optimizer (SCO). The suggested hybrid algorithm (POSCO) benefits from both the robust local search power of the single candidate method and the efficient global search capabilities of the pelican optimization. To conduct the building optimization task, the optimization method was developed and integrated with the EnergyPlus codes. The effectiveness of the proposed POSCO method was verified using mathematical test functions, and the outcomes were contrasted with those of conventional POA and other effective optimization techniques. Application of POSCO for global function optimization reveals that, among the thirteen considered functions, the proposed method was best at finding the global solution for seven functions, while providing superior results for the other functions when compared with competitive techniques. The suggested POSCO is applied for reducing an office buildings’ annual energy use. Comparing POSCO to POA procedures, the building energy usage is reduced. Furthermore, POSCO is compared to simple POA and other algorithms, with the results showing that, at specific temperatures and lighting conditions, the POSCO approach outperforms selected state-of-the-art methods and reduces building energy usage. As a result, all data suggests that POSCO is a very promising, dependable, and feasible optimization strategy for dealing with building energy optimization models. Finally, the building energy optimization findings for various climatic conditions demonstrate that the changes to the weather dataset had limited effect on the efficiency of the optimization procedure.
Numerical Simulation of Concrete Attacked by Sulfate under Drying–Wetting Cycles Coupled with Alternating Loads
Authors: Guan Bowen , Zhang Shuowen , Wang Faping , Wu Jiayu , Li Lingyun
Published: December 2022

Concrete structures such as rigid pavements, tunnels, and runways at airports are usually subject to fatigue traffic loading during their service life. Research on the aftereffects of drying–wetting cycles coupled with alternating loads on concrete erosion in saline–alkali and coastal areas is of considerable practical importance. For this study, we utilized specimens of dimensions 100 mm × 100 mm × 400 mm with strength ratios of C30, C40, and C50. We incubated the concrete samples in a 24 h/24 h drying–wetting cycle with sodium sulfate solutions of different concentrations as we applied alternating loads. We conducted ultrasonic wave velocity tests every 30 days from the 60th day of the experiment to determine the change in the sound velocity of the concrete over the course of 360 days. In addition, we examined the invasion depth of SO42− with time. Based on the change in sound velocity, we developed the damage degree function, and we modified the diffusion coefficient of SO42− in concrete in accordance with the coupling of drying–wetting cycles and alternating loads. We conducted a simulation on SO42− penetration depth, and the results were in reasonable agreement with those obtained by experimental testing.
Study on Group Movement Characteristics in Stairwell of High-Rise Buildings
Authors: Wei Xiaoge , Zhao Yinlong , Lian Liping , Yao Haowei , Song Huaitao , Qin Hengjie
Published: December 2022

In order to cope with limited land availability and the increasing urban population, more high-rise buildings are being built throughout cities, but this has also led to new challenges in the emergency evacuation of people. Therefore, we conducted an evacuation experiment of a group of people in the stairwells of high-rise buildings to explore the movement law of groups in stairwells. The experiment had 18 scenes, including the evacuation movement of an independent group and the crowd evacuation movement of different groups. Analyzing the independent groups’ movement showed that regardless of the type of group, the average speed of the crowd was more than 1.2 m/s, which was longer than that of previous studies. The more constraints in the evacuation process, the smaller the speed difference between males and females. Group cohesion was mostly concentrated at about 1 s. Moreover, group velocity and cohesion were found to have no significant correlation in stairwell movement. Analyzing the crowd evacuation time of eight different scenes showed that it took longer for crowds bearing weight to evacuate than those not bearing weight. According to the spatiotemporal evolution of crowd evacuation in stairwells, the crowd moves intermittently in the evacuation process, especially in the early and middle stages of evacuation, and the influence of group factors on this process was not obvious. Regardless of the kind of scene or stairwell, the number of pedestrians generally first increased and then decreased to a significantly low value, and the number of pedestrians reached about 30 in the scenario of people without any load. Additionally, the speed of the pedestrians entering the stairwell in the back of the group was not faster than that of the pedestrians in the front, which showed that pedestrians rarely engaged in overtaking behavior. The research results of this paper not only enrich evacuation research but also provide support for the design of high-rise stairs.