bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Primary RPE Cells in a Porcine Organotypic Co-Cultivation Model
Authors: Wagner Natalie , Safaei Armin , Hurst José , Vogt Pia A. , Dick H. Burkhard , Joachim Stephanie C. , Schnichels Sven
Published: July 2022

The pathological events of age-related macular degeneration are characterized by degenerative processes involving the photoreceptor cells, retinal pigment epithelium (RPE), and the Bruch’s membrane as well as choroidal alterations. To mimic in vivo interactions between photoreceptor cells and RPE cells ex vivo, complex models are required. Hence, the aim of this study was to establish a porcine organotypic co-cultivation model and enlighten the interactions of photoreceptor and RPE cells, with a special emphasis on potential neuroprotective effects. Porcine neuroretina explants were cultured with primary porcine RPE cells (ppRPE) or medium derived from these cells (=conditioned medium). Neuroretina explants cultured alone served as controls. After eight days, RT-qPCR and immunohistology were performed to analyze photoreceptors, synapses, macroglia, microglia, complement factors, and pro-inflammatory cytokines (e.g., IL1B, IL6, TNF) in the neuroretina samples. The presence of ppRPE cells preserved photoreceptors, whereas synaptical density was unaltered. Interestingly, on an immunohistological as well as on an mRNA level, microglia and complement factors were comparable in all groups. Increased IL6 levels were noted in ppRPE and conditioned medium samples, while TNF was only upregulated in the ppRPE group. IL1B was elevated in conditioned medium samples. In conclusion, a co-cultivation of ppRPE cells and neuroretina seem to have beneficial effects on the neuroretina, preserving photoreceptors and maintaining synaptic vesicles in vitro. This organotypic co-cultivation model can be used to investigate the complex interactions between the retina and RPE cells, gain further insight into neurodegenerative pathomechanisms occurring in retinal diseases, and evaluate potential therapeutics.
α-Synuclein Conformational Plasticity: Physiologic States, Pathologic Strains, and Biotechnological Applications
Authors: Li Amanda , Rastegar Cyrus , Mao Xiaobo
Published: July 2022

α-Synuclein (αS) is remarkable for both its extensive conformational plasticity and pathologic prion-like properties. Physiologically, αS may populate disordered monomeric, helically folded tetrameric, or membrane-bound oligomeric states. Pathologically, αS may assemble into toxic oligomers and subsequently fibrils, the prion-like transmission of which is implicated in a class of neurodegenerative disorders collectively termed α-synucleinopathies. Notably, αS does not adopt a single “amyloid fold”, but rather exists as structurally distinct amyloid-like conformations referred to as “strains”. The inoculation of animal models with different strains induces distinct pathologies, and emerging evidence suggests that the propagation of disease-specific strains underlies the differential pathologies observed in patients with different α-synucleinopathies. The characterization of αS strains has provided insight into the structural basis for the overlapping, yet distinct, symptoms of Parkinson’s disease, multiple system atrophy, and dementia with Lewy bodies. In this review, we first explore the physiological and pathological differences between conformational states of αS. We then discuss recent studies on the influence of micro-environmental factors on αS species formation, propagation, and the resultant pathological characteristics. Lastly, we review how an understanding of αS conformational properties has been translated to emerging strain amplification technologies, which have provided further insight into the role of specific strains in distinct α-synucleinopathies, and show promise for the early diagnosis of disease.
Enhancer-LSTMAtt: A Bi-LSTM and Attention-Based Deep Learning Method for Enhancer Recognition
Authors: Huang Guohua , Luo Wei , Zhang Guiyang , Zheng Peijie , Yao Yuhua , Lyu Jianyi , Liu Yuewu , Wei Dong-Qing
Published: July 2022

Enhancers are short DNA segments that play a key role in biological processes, such as accelerating transcription of target genes. Since the enhancer resides anywhere in a genome sequence, it is difficult to precisely identify enhancers. We presented a bi-directional long-short term memory (Bi-LSTM) and attention-based deep learning method (Enhancer-LSTMAtt) for enhancer recognition. Enhancer-LSTMAtt is an end-to-end deep learning model that consists mainly of deep residual neural network, Bi-LSTM, and feed-forward attention. We extensively compared the Enhancer-LSTMAtt with 19 state-of-the-art methods by 5-fold cross validation, 10-fold cross validation and independent test. Enhancer-LSTMAtt achieved competitive performances, especially in the independent test. We realized Enhancer-LSTMAtt into a user-friendly web application. Enhancer-LSTMAtt is applicable not only to recognizing enhancers, but also to distinguishing strong enhancer from weak enhancers. Enhancer-LSTMAtt is believed to become a promising tool for identifying enhancers.
Amylin and Secretases in the Pathology and Treatment of Alzheimer’s Disease
Authors: Singh Som , Yang Felix , Sivils Andy , Cegielski Victoria , Chu Xiang-Ping
Published: July 2022

Alzheimer’s disease remains a prevailing neurodegenerative condition which has an array physical, emotional, and financial consequences to patients and society. In the past decade, there has been a greater degree of investigation on therapeutic small peptides. This group of biomolecules have a profile of fundamentally sound characteristics which make them an intriguing area for drug development. Among these biomolecules, there are four modulatory mechanisms of interest in this review: alpha-, beta-, gamma-secretases, and amylin. These protease-based biomolecules all have a contributory role in the amyloid cascade hypothesis. Moreover, the involvement of various biochemical pathways intertwines these peptides to have shared regulators (i.e., retinoids). Further clinical and translational investigation must occur to gain a greater understanding of its potential application in patient care. The aim of this narrative review is to evaluate the contemporary literature on these protease biomolecule modulators and determine its utility in the treatment of Alzheimer’s disease.
Zinc in Cognitive Impairment and Aging
Authors: Sun Ruize , Wang Jue , Feng Juan , Cao Bin
Published: July 2022

Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes in normal mammalian brain development, especially in the development of the central nervous system. Zinc deficiency can lead to neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular diseases, and other pathological conditions, which can cause cognitive impairment and premature aging. This study aimed to review the important effects of zinc and zinc-associated proteins in cognitive impairment and aging, to reveal its molecular mechanism, and to highlight potential interventions for zinc-associated aging and cognitive impairments.
Comparison of Tau and Amyloid-β Targeted Immunotherapy Nanoparticles for Alzheimer’s Disease
Authors: Mashal Yara , Abdelhady Hosam , Iyer Arun K.
Published: July 2022

Alzheimer’s disease (AD) is a rapidly growing global concern associated with the accumulation of amyloid-β plaques and intracellular neurofibrillary tangles in the brain combined with a high acetylcholinesterase activity. AD diagnosis is usually made too late, when patients have an extensive neuronal death, and brain damage is irreversible. Several therapeutic targets have been defined mainly related to two hypotheses of AD: the tau hypothesis and the amyloid-β hypothesis. Here, we intend to investigate and to compare different therapeutic approaches for AD, mainly based on nanoparticles (NPs) targeted at the brain and at the pathological hallmarks of the disease. We analyzed preclinical trials that have successfully improved drug bioavailability in the brain by using targeted nanocarriers towards either tau, amyloid-β, or both. We then compared these trials to find out which protein is more efficient in therapeutic targeting. We found that the search for a cure was mostly based on the amyloid-β hypothesis, with Aβ dysplasia emerging as the most confirmed and convincing therapeutic target. Targeted NPs have proven useful to enhance both the bioavailability and the performance of therapies against AD in animal models. A better understanding of AD mechanisms will help the successful application of targeted NPs for combined therapies.
Can Slight Variations to Lateral Wedge Insoles Induce Significant Biomechanical Changes in Patients with Knee Osteoarthritis?
Authors: Ferreira Vitor , Machado Leandro , Vilaça Adélio , Xará-Leite Francisco , Roriz Paulo
Published: July 2022

Lateral wedge insoles are recommended in order to minimize the impacts of osteoarthritis of the knee. The amount of wedging required to induce a biomechanical response with clinical significance is still controversial. This study aimed to investigate the immediate biomechanical effects of different amounts of wedging in symptomatic medial knee OA. A 3D motion capture system and five force platforms were used to acquire walking kinematic and kinetic data along a 10 m walkway. Each participant was tested for six different lateral wedge insoles (0, 2, 4, 6, 8, and 10°) in a randomized order. Thirty-eight patients with medial osteoarthritis of the knee were recruited. The application of insoles resulted in an incremental reduction of the first peak of the external knee adduction moment under all experimental conditions in comparison with the control condition (0° insole). A significant increase (p < 0.05) was observed in peak ankle eversion and in ankle eversion at the first peak of the external knee adduction moment with insoles higher than 8° and 6°, respectively. Slight variations to lateral wedge insoles, greater than 2°, appear to induce significant biomechanical changes in patients with knee osteoarthritis.
Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia
Authors: Khalaf Guy , Mattern Claudia , Begou Mélina , Boespflug-Tanguy Odile , Massaad Charbel , Massaad-Massade Liliane
Published: July 2022

Pelizaeus–Merzbacher Disease (PMD) is an inherited leukodystrophy affecting the central nervous system (CNS)—a rare disorder that especially concerns males. Its estimated prevalence is 1.45–1.9 per 100,000 individuals in the general population. Patients affected by PMD exhibit a drastic reduction or absence of myelin sheaths in the white matter areas of the CNS. The Proteolipid Protein 1 (PLP1) gene encodes a transmembrane proteolipid protein. PLP1 is the major protein of myelin, and it plays a key role in the compaction, stabilization, and maintenance of myelin sheaths. Its function is predominant in oligodendrocyte development and axonal survival. Mutations in the PLP1 gene cause the development of a wide continuum spectrum of leukopathies from the most severe form of PMD for whom patients exhibit severe CNS hypomyelination to the relatively mild late-onset type 2 spastic paraplegia, leading to the concept of PLP1-related disorders. The genetic diversity and the biochemical complexity, along with other aspects of PMD, are discussed to reveal the obstacles that hinder the development of treatments. This review aims to provide a clinical and mechanistic overview of this spectrum of rare diseases.
Adipose-Derived Stem Cell Exosomes as a Novel Anti-Inflammatory Agent and the Current Therapeutic Targets for Rheumatoid Arthritis
Authors: Chang Ting-Hui , Wu Chien-Sheng , Chiou Shih-Hwa , Chang Chih-Hung , Liao Hsiu-Jung
Published: July 2022

Patients with rheumatoid arthritis (RA), a chronic inflammatory joint disorder, may not respond adequately to current RA treatments. Mesenchymal stem cells (MSCs) elicit several immunomodulatory and anti-inflammatory effects and, thus, have therapeutic potential. Specifically, adipose-derived stem cell (ADSC)-based RA therapy may have considerable potency in modulating the immune response, and human adipose tissue is abundant and easy to obtain. Paracrine factors, such as exosomes (Exos), contribute to ADSCs’ immunomodulatory function. ADSC-Exo-based treatment can reproduce ADSCs’ immunomodulatory function and overcome the limitations of traditional cell therapy. ADSC-Exos combined with current drug therapies may provide improved therapeutic effects. Using ADSC-Exos, instead of ADSCs, to treat RA may be a promising cell-free treatment strategy. This review summarizes the current knowledge of medical therapies, ADSC-based therapy, and ADSC-Exos for RA and discusses the anti-inflammatory properties of ADSCs and ADSC-Exos. Finally, this review highlights the expanding role and potential immunomodulatory activity of ADSC-Exos in patients with RA.
Probing Denaturation of Protein A via Surface-Enhanced Infrared Absorption Spectroscopy
Authors: Di Meo Valentina , Moccia Massimo , Sanità Gennaro , Crescitelli Alessio , Lamberti Annalisa , Galdi Vincenzo , Rendina Ivo , Esposito Emanuela
Published: July 2022

We apply surface-enhanced infrared absorption (SEIRA) spectroscopy to monitor the denaturation process of a surface-bound protein A monolayer. Our proposed platform relies on a plasmonic metasurface comprising different spatial subregions (“pixels”) that are engineered to exhibit different resonances covering the infrared region of the electromagnetic spectrum that is matched to the vibrational modes of the Amide groups. Specifically, we are able to determine changes in the Amide I and Amide II vibration coupled modes, by comparing the SEIRA reflectance spectra pertaining to the native state and a denatured state induced by a pH variation. In particular, we observe some evident red-shifts in the principal Amide I mode and the Amide II vibration coupled modes (attributable to the breaking of hydrogen bonds), which result in insurmountable barriers for refolding. Thanks to the strong field localization, and consequent enhancement of the light-matter interactions, our proposed sensing platform can operate with extremely small amounts of an analyte, with an estimated detection limit of about 3 femtomoles of molecules.
Ratiometric Fluorescence Detection of Colorectal Cancer-Associated Exosomal miR-92a-3p with DSN-Assisted Signal Amplification by a MWCNTs@Au NCs Nanoplatform
Authors: Sun Zhiwei , Li Juan , Tong Yao , Zhao Li , Zhou Xiaoyu , Li Hui , Wang Chuanxin , Du Lutao , Jiang Yanyan
Published: July 2022

The detection of miRNA shows great promise in disease diagnosis. In this work, a ratiometric fluorescent biosensor based on multi-walled carbon nanotubes@gold nanoclusters (MWCNTs@Au NCs) and duplex-specific nuclease (DSN)-assisted signal amplification was fabricated for miRNA detection. Colorectal cancer (CRC)-associated miR-92a-3p extracted from exosomes was selected as the target. MWCNTs@Au NCs performs the dual functions of fluorescence quencher and internal fluorescence reference. In the absence of miR-92a-3p, an Atto-425-modified single-stranded DNA probe is adsorbed on MWCNTs@Au NCs, resulting in the quenching of Atto-425. In the presence of miR-92a-3p, the duplex is formed by hybridization of the probe and miR-92a-3p and leaves the MWCNTs@Au NCs, resulting in the fluorescence recovery of Atto-425. DSN can cleave the probe and result in the release of miR-92a-3p. The released miR-92a-3p can hybridize with other probes to form a signal amplification cycle. The fluorescence of MWCNTs@Au NCs remains stable and constitutes a ratiometric fluorescence system with that of Atto-425. A detection concentration interval of 0.1–10 pM and a limit of detection of 31 fM was obtained under optimized measurement conditions. In addition, the accuracy of the biosensor was validated by detecting the concentration of miR-92a-3p extracted from clinical exosome samples.
Highly Sensitive Love Mode Acoustic Wave Platform with SiO2 Wave-Guiding Layer and Gold Nanoparticles for Detection of Carcinoembryonic Antigens
Authors: Li Chong , Zhang Jikai , Xie Haiyu , Luo Jingting , Fu Chen , Tao Ran , Li Honglang , Fu Yongqing
Published: July 2022

A highly sensitive and precise Love wave mode surface acoustic wave (SAW) immunosensor based on an ST-cut 90°X quartz substrate and an SiO2 wave-guiding layer was developed to detect cancer-related biomarkers of carcinoembryonic antigens (CEAs). A delay line structure of the SAW device with a resonant frequency of 196 MHz was designed/fabricated, and its surface was functionalized through CEA antibody immobilization. The CEA antibodies were bound with gold nanoparticles and CEA antibodies to form a sandwich structure, which significantly amplified the mass loading effect and enhanced the maximum responses by 30 times. The center frequency of the Love wave immunosensor showed a linear response as a function of the CEA concentration in the range of 0.2–5 ng/mL. It showed a limit of detection of 0.2 ng/mL, and its coefficient of determination was 0.983. The sensor also showed minimal interference from nonspecific adsorptions, thus demonstrating its promise for point-of-care applications for cancer biomarkers.
Mechanical Properties of the Extracellular Environment of Human Brain Cells Drive the Effectiveness of Drugs in Fighting Central Nervous System Cancers
Authors: Cieśluk Mateusz , Pogoda Katarzyna , Piktel Ewelina , Wnorowska Urszula , Deptuła Piotr , Bucki Robert
Published: July 2022

The evaluation of nanomechanical properties of tissues in health and disease is of increasing interest to scientists. It has been confirmed that these properties, determined in part by the composition of the extracellular matrix, significantly affect tissue physiology and the biological behavior of cells, mainly in terms of their adhesion, mobility, or ability to mutate. Importantly, pathophysiological changes that determine disease development within the tissue usually result in significant changes in tissue mechanics that might potentially affect the drug efficacy, which is important from the perspective of development of new therapeutics, since most of the currently used in vitro experimental models for drug testing do not account for these properties. Here, we provide a summary of the current understanding of how the mechanical properties of brain tissue change in pathological conditions, and how the activity of the therapeutic agents is linked to this mechanical state.
Repetitive Neuromuscular Magnetic Stimulation for Pediatric Headache Disorders: Muscular Effects and Factors Affecting Level of Response
Authors: Börner Corinna , Staisch Jacob , Lang Magdalena , Hauser Ari , Hannibal Iris , Huß Kristina , Klose Birgit , Lechner Matthias F. , Sollmann Nico , Heinen Florian , Landgraf Mirjam N. , Bonfert Michaela V.
Published: July 2022

Repetitive neuromuscular magnetic stimulation (rNMS) for pediatric headache disorders is feasible, safe, and alleviates headache symptoms. This study assesses muscular effects and factors affecting response to rNMS. A retrospective chart review included children with headaches receiving six rNMS sessions targeting the upper trapezius muscles. Pressure pain thresholds (PPT) were measured before and after rNMS, and at 3-month follow-up (FU). Mean headache frequency, duration, and intensity within the last 3 months were documented. In 20 patients (14.1 ± 2.7 years), PPT significantly increased from pre- to post-treatment (p < 0.001) sustaining until FU. PPT changes significantly differed between primary headache and post-traumatic headache (PTH) (p = 0.019–0.026). Change in headache frequency was significantly higher in patients with than without neck pain (p = 0.032). A total of 60% of patients with neck pain responded to rNMS (≥25%), while 20% of patients without neck pain responded (p = 0.048). 60% of patients receiving rNMS twice a week were responders, while 33% of patients receiving rNMS less or more frequently responded to treatment, respectively. Alleviation of muscular hyperalgesia was demonstrated sustaining for 3 months, which was emphasized in PTH. The rNMS sessions may positively modulate headache symptoms regardless of headache diagnosis. Patients with neck pain profit explicitly well. Two rNMS sessions per week led to the highest reduction in headache frequency.
Dynamic Prediction of Mechanical Thrombectomy Outcome for Acute Ischemic Stroke Patients Using Machine Learning
Authors: Hu Yixing , Yang Tongtong , Zhang Juan , Wang Xixi , Cui Xiaoli , Chen Nihong , Zhou Junshan , Jiang Fuping , Zhu Junrong , Zou Jianjun
Published: July 2022

The unfavorable outcome of acute ischemic stroke (AIS) with large vessel occlusion (LVO) is related to clinical factors at multiple time points. However, predictive models used for dynamically predicting unfavorable outcomes using clinically relevant preoperative and postoperative time point variables have not been developed. Our goal was to develop a machine learning (ML) model for the dynamic prediction of unfavorable outcomes. We retrospectively reviewed patients with AIS who underwent a consecutive mechanical thrombectomy (MT) from three centers in China between January 2014 and December 2018. Based on the eXtreme gradient boosting (XGBoost) algorithm, we used clinical characteristics on admission (“Admission” Model) and additional variables regarding intraoperative management and the postoperative National Institute of Health stroke scale (NIHSS) score (“24-Hour” Model, “3-Day” Model and “Discharge” Model). The outcome was an unfavorable outcome at the three-month mark (modified Rankin scale, mRS 3–6: unfavorable). The area under the receiver operating characteristic curve and Brier scores were the main evaluating indexes. The unfavorable outcome at the three-month mark was observed in 156 (62.0%) of 238 patients. These four models had a high accuracy in the range of 75.0% to 87.5% and had a good discrimination with AUC in the range of 0.824 to 0.945 on the testing set. The Brier scores of the four models ranged from 0.122 to 0.083 and showed a good predictive ability on the testing set. This is the first dynamic, preoperative and postoperative predictive model constructed for AIS patients who underwent MT, which is more accurate than the previous prediction model. The preoperative model could be used to predict the clinical outcome before MT and support the decision to perform MT, and the postoperative models would further improve the predictive accuracy of the clinical outcome after MT and timely adjust therapeutic strategies.
Quality of Life and Mental Health Status in Recovered COVID-19 Subjects at Two Years after Infection in Taizhou, China: A Longitudinal Cohort Study
Authors: Pan Juan , Zhou Kai , Wang Jing , Zheng Yufen , Yu Die , Kang Haixin , Zhang Yanjie , Peng Shuotao , Tung Tao-Hsin , Shen Bo
Published: July 2022

According to previous studies, mental status in 1-year COVID-19 survivors might range from 6–43%. Longer-term psychological consequences in recovered COVID-19 subjects are unknown, so we analyzed longer-term quality of life and mental status in recovered COVID-19 subjects at 2 years after infection. Among 144 recovered COVID-19 subjects in the Taizhou region, 73 and 45 completed face-to-face follow-ups at the first year and second year after infection, respectively, with a 61.7% follow-up rate. The questionnaire, which was administered at both follow-ups, included questions about quality of life, psychological health, and post-traumatic stress disorder (PTSD). The Mann-Whitney U test was used to the differences of each scale between the first and second year. Among the 45 people who completed both follow-up visits, the incidence of psychological problems was 4.4% (2/45) in the first year, and no new psychological abnormalities were observed in the second year. Quality of life improved, while the General Health Questionnaire (GHQ-12) and Impact of Event Scale-Revised (IES-R) scores did not improve over time. The incidence of mental disorders was lower than those in previous studies. Multidisciplinary management for COVID-19 in this study hospital may have reduced the frequency to a certain extent. However, among those with mental health problems, such problems may exist for a long time, and long-term attention should be given to the psychological status of recovered COVID-19 subjects.
The Impact of Core Self-Evaluations on Job Satisfaction and Turnover Intention among Higher Education Academic Staff: Mediating Roles of Intrinsic and Extrinsic Motivation
Authors: Akosile Abisola Leah , Ekemen Mehmet Ali
Published: July 2022

Job satisfaction and turnover intention among academic staff remains a challenge in higher education institutions. To aid understanding of the factors that can reduce intention to leave and increase job satisfaction among academic staff, the present research investigated the impact of core self-evaluations (CSEs) on job satisfaction and turnover intention by proposing a parallel mediation model. The researcher used quantitative approach. The sample consisted of (n = 305) academic staff working in higher education institutions in Nigeria, with a total of 80 females and 225 males. The study attempted to investigate the connection between core self-evaluations, job satisfaction, and turnover intention using self-determination theory to investigate the parallel mediating role of intrinsic and extrinsic motivation on the relationship. Through application of structural equation modeling, the findings showed that CSEs had an impact on job satisfaction and turnover intention, mainly through the mediating role of intrinsic and extrinsic motivation. The mediating role of intrinsic and extrinsic motivation provided new insight into the connections between core self-evaluations, job satisfaction, and turnover expectations.
Changes in Human Electroencephalographic Activity in Response to Agastache rugosa Essential Oil Exposure
Authors: Hong Minji , Jang Hyejeong , Bo Sela , Kim Minju , Deepa Ponnuvel , Park Jiyea , Sowndhararajan Kandhasamy , Kim Songmun
Published: July 2022

Agastache rugosa (Korean mint) is an important medicinal and aromatic plant and its aerial parts have a pleasant fragrance. A. rugosa leaves are used as an ingredient in salads and soups for enhancing the aroma and taste of foods in Korea. However, there is no report on the influence of the aroma of A. rugosa on human psychophysiological activity. Therefore, the present study aimed to investigate the effect of exposure to the essential oil of Korean A. rugosa on human electroencephalographic (EEG) activity. The essential oil of A. rugosa was isolated using steam distillation extraction and its composition was determined by gas chromatography and mass spectrometry (GC–MS) analysis. In the EEG study, 38 healthy volunteers (19 men and 19 women) participated. The EEG readings were analyzed for 25 EEG indices from 29 electrodes placed on the scalp according to the international 10–20 system. The major component in the essential oil of A. rugosa was estragole (89.49%) followed by D-limonene (3.40%), menthone (1.80%), and pulegone (1.86%). In the EEG study, significant decreases in absolute theta (AT) and relative theta (RT) power spectra were observed during the exposure to A. rugosa essential oil when compared to that of no odor exposure. Whereas relative alpha (RA), relative slow alpha (RSA), spectral edge frequency 50% (SEF50), and spectral edge frequency 50% of alpha (ASEF) power spectra values significantly increased. These results reveal that the EEG power spectra changes incurred during the exposure to the essential oil of A. rugosa may be associated with the enhancement of freshness and concentration states of the human brain.
Effects of Ground Motion Duration on the Seismic Performance of a Two-Storey Balloon-Type CLT Building
Authors: Jafari Maral , Pan Yuxin , Shahnewaz Md , Tannert Thomas
Published: July 2022

The effects of long duration ground motions on the seismic performance of a newly constructed two-storey balloon-type cross-laminated timber (CLT) building located in Vancouver, Canada, was studied. A three-dimensional numerical model of the building was developed in OpenSees. The connection and shear wall models were validated with test data. Twenty-four pairs of long and short duration records with approximately the same amplitude, frequency content, and rate of energy build-up were used for nonlinear dynamic analyses. Fragility curves were developed based on the results of incremental dynamic analysis to assess the building’s collapse capacity. At design intensity level, ground motion duration was shown not to be a critical factor as the difference in inter-storey drift ratio between the two sets of records was negligible. However, due to the larger number of inelastic cycles, the long duration motions increased the median probability of collapse by 9% when compared with the short duration motions. Further research is required to evaluate the duration effects on taller and platform-type CLT buildings.
Dynamic Properties of Soil Cements for Numerical Modelling of the Foundation’s Basis Transformed under the Technology of Deep Soil Mixing: A Determination Method
Authors: Ter-Martirosyan Armen , Sidorov Vitalii , Sobolev Evgeny
Published: July 2022

This research investigates the mechanical properties of soil-cement specimens ranging from ultrasmall to large values of shear strain at dynamic loading. The nonlinear behavior of soil cement exposed to dynamic loading in a wide range of changing shear strains was examined on the basis of two mechanical models. All soil-cement specimens were collected from under an existing building and modified with deep soil mixing (DSM.). Soil-cement samples were examined using low-amplitude oscillations in the resonant column and the dynamic triaxial compression method. Additionally, the stress–strain state for modified footings exposed to dynamic loading, and the approximation of soil stiffness and damping coefficient was analyzed. Dependencies on the basis of the resilient elastic models of Ramberg–Osgood and Hardin–Drnevich are proposed for application. Results reveal that the empirical graphs of the dependency soil stiffness–shear strain based on various methods exhibited the distinctive S-shape of decreased stiffness. The stiffness of the soil cement was reduced by 50% of the maximal value at shear strains of the 10−3 decimal order. The method presented in this study enables the drawing of stiffness change and damping–shear strain dependency where the range of shear strains changes from ultrasmall to large strains. The normalized modulus of shearing and the damping coefficient on shear strains for soil cement could be obtained under the proposed method. This method can be used for the preliminary calculations of structures on the footing modified by mathematical modelling or when field research data from site investigation are not available.
Research on the Relationship between Thermal Insulation Thickness and Summer Overheating Risk: A Case Study in Severe Cold and Cold Regions of China
Authors: Bo Rui , Shao Yu , Xu Yitong , Yu Yang , Guo Haibo , Chang Wen-Shao
Published: July 2022

Given the prediction of global warming, there is a growing concern about overheating in the severe cold and cold regions of China. In the past decades, indoor thermal comfort has been neglected in building practice, while efficiency-oriented improvements have been developed, such as increased insulation of building envelope. An extensive literature review shows contradictory conclusions about whether increased insulation can alleviate overheating. The aim of this research is to conduct simulations based on measured data to reveal the influence of insulation on overheating in dwellings in these regions of China. An unoccupied residential flat was monitored to determine the extent of overheating while eliminating the effects of other contributors, such as natural ventilation. Validated building performance simulations were carried out with altered insulation layer thickness in Integrated Environmental Solutions-Virtual Environment IESVE software to examine its influence on overheating during summertime in five representative cities. The results showed clear evidence of summer overheating in these regions. In Yichun, Harbin, Shenyang, Dalian and Beijing, walls with increased insulation were found to exacerbate overheating in the bedrooms without natural ventilation by 22.5%, 16.6%, 20.3%, 11.8% and 6.9%, respectively, compared to the uninsulated walls. This study provides useful information for building regulations on energy efficiency and thermal comfort.
Identification of Urban Functional Areas and Governance Measures Based on Point of Interest Data: A Case Study of the Shenyang Railway Station Area in Shenyang City
Authors: Liu Shengjun , Su Lihong , Guo Hongqian , Chen Yijing
Published: July 2022

Inventory extraction and governance measures in urban land use have become important topics in urban regeneration research. This study aimed to inform design governance in urban regeneration through a point of interest (POI) data-based case study. An approximately 15 km2 rectangular development area was assessed for its characteristics and deficiencies. Frequency density analysis was conducted based on data identification of urban built environments and governance from an integrated planning perspective, using field research, spatial autocorrelation, Getis–Ord Gi* analysis, and SPSS. We (1) applied POI data to assess the frequency ratios of the function types for the 6008 buildings in the study area; (2) analysed layouts of POI densities in hotspots for different formats; and (3) applied an evidence-based approach and overlay analysis to identify the area’s functional morphological zones. Finally, the urban physical and morphological properties were identified and compared with the identification result of the urban functional areas to qualitatively evaluate the differences. Global Moran’s I of the POI density of Retail Business (B11), Restaurants (B13), Hotels (B14), Entertainment and Recreation (B3), and Residential Services (R22) were 0.35, 0.35, 0.06, 0.20, and 0.15, respectively, displaying a significant spatial clustering feature. However, for land types including Administrative Offices (A1), Finance and Insurance (B21), and Other Business Facilities (B29), the p-values between the POI density and the random pattern were 0.23, 0.71, 0.56, respectively, showing no significant difference. Our study provides recommendations for governance and integrated urban redevelopment planning to coordinate and guide further regeneration.
A Bayesian Approach towards Modelling the Interrelationships of Pavement Deterioration Factors
Authors: Philip Babitha , Jassmi Hamad Al
Published: July 2022

In this study, Bayesian Belief Networks (BBN) are proposed to model the relationships between factors contributing to pavement deterioration, where their values are probabilistically estimated based on their interdependencies. Such probabilistic inferences are deemed to provide a reasonable alternative over costly data collection campaigns and assist in road condition diagnoses and assessment efforts in cases where data are only partially available. The BBN models examined in this study are based on a vast database of pavement deterioration factors including road distress data, namely cracking, deflection, the International Roughness Index (IRI) and rutting, from major road sections in the United Arab Emirates (UAE) along with the corresponding traffic and climatic factors. The dataset for the analysis consisted of 3272 road sections, each of 10 m length. The test results showed that the most critical parameter representing the whole process of road deterioration is the IRI with the highest nodal force. Additionally, IRI is strongly correlated with rutting and deflection, with mutual information of 0.147 and 0.143, respectively. Furthermore, a Bayesian network structure with a contingency table fit of over 90% illustrates how the road distress parameters change in the presence of external factors, such as traffic and climatic conditions.
A Novel ALDH1A1 Inhibitor Blocks Platinum-Induced Senescence and Stemness in Ovarian Cancer
Authors: Muralikrishnan Vaishnavi , Fang Fang , Given Tyler C. , Podicheti Ram , Chtcherbinine Mikhail , Metcalfe Tara X. , Sriramkumar Shruthi , O’Hagan Heather M. , Hurley Thomas D. , Nephew Kenneth P.
Published: July 2022

Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and the development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for the emergence of chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size and number of tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that aldehyde dehydrogenase 1A1 (ALDH1A1) is essential for the survival of OCSCs. We identified a first-in-class ALDH1A1 inhibitor, compound 974, and used 974 as a tool to decipher the mechanism of stemness regulation by ALDH1A1. The treatment of OCSCs with 974 significantly inhibited ALDH activity, the expression of stemness genes, and spheroid and colony formation. An in vivo limiting dilution assay demonstrated that 974 significantly inhibited CSC frequency. A transcriptomic sequencing of cells treated with 974 revealed a significant downregulation of genes related to stemness and chemoresistance as well as senescence and the senescence-associated secretory phenotype (SASP). We confirmed that 974 inhibited the senescence and stemness induced by platinum-based chemotherapy in functional assays. Overall, these data establish that ALDH1A1 is essential for OCSC survival and that ALDH1A1 inhibition suppresses chemotherapy-induced senescence and stemness. Targeting ALDH1A1 using small-molecule inhibitors in combination with chemotherapy therefore presents a promising strategy to prevent ovarian cancer recurrence and has the potential for clinical translation.
Radiomic Cancer Hallmarks to Identify High-Risk Patients in Non-Metastatic Colon Cancer
Authors: Caruso Damiano , Polici Michela , Zerunian Marta , Del Gaudio Antonella , Parri Emanuela , Giallorenzi Maria Agostina , De Santis Domenico , Tarantino Giulia , Tarallo Mariarita , Dentice di Accadia Filippo Maria , Iannicelli Elsa , Garbarino Giovanni Maria , Canali Giulia , Mercantini Paolo , Fiori Enrico , Laghi Andrea
Published: July 2022

The study was aimed to develop a radiomic model able to identify high-risk colon cancer by analyzing pre-operative CT scans. The study population comprised 148 patients: 108 with non-metastatic colon cancer were retrospectively enrolled from January 2015 to June 2020, and 40 patients were used as the external validation cohort. The population was divided into two groups—High-risk and No-risk—following the presence of at least one high-risk clinical factor. All patients had baseline CT scans, and 3D cancer segmentation was performed on the portal phase by two expert radiologists using open-source software (3DSlicer v4.10.2). Among the 107 radiomic features extracted, stable features were selected to evaluate the inter-class correlation (ICC) (cut-off ICC > 0.8). Stable features were compared between the two groups (T-test or Mann–Whitney), and the significant features were selected for univariate and multivariate logistic regression to build a predictive radiomic model. The radiomic model was then validated with an external cohort. In total, 58/108 were classified as High-risk and 50/108 as No-risk. A total of 35 radiomic features were stable (0.81 ≤ ICC <  0.92). Among these, 28 features were significantly different between the two groups (p < 0.05), and only 9 features were selected to build the radiomic model. The radiomic model yielded an AUC of 0.73 in the internal cohort and 0.75 in the external cohort. In conclusion, the radiomic model could be seen as a performant, non-invasive imaging tool to properly stratify colon cancers with high-risk disease.
Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors
Authors: Kim Hye Ryeon , Kang Jung Hun , Kim Sung Hyun , Kim Seung Tae , Kim Ilhwan , Min Young Joo , Shin Seong Hoon , Oh Sung Yong , Lee Gyeong-Won , Lee Ji Hyun , Ji Jun Ho , Huh Seok Jae , Lee Suee
Published: July 2022

Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1–8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6–22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.
Impact of Anti-Angiogenic Treatment on Bone Vascularization in a Murine Model of Breast Cancer Bone Metastasis Using Synchrotron Radiation Micro-CT
Authors: Xu Hao , Lafage-Proust Marie-Hélène , Bouazza Lamia , Geraci Sandra , Clezardin Philippe , Roche Bernard , Peyrin Françoise , Langer Max
Published: July 2022

Bone metastases are frequent complications of breast cancer, facilitating the development of anarchic vascularization and induce bone destruction. Therefore, anti-angiogenic drugs (AAD) have been tested as a therapeutic strategy for the treatment of breast cancer bone metastasis. However, the kinetics of skeletal vascularization in response to tumor invasion under AAD is still partially understood. Therefore, the aim of this study was to explore the effect of AAD on experimental bone metastasis by analyzing the three-dimensional (3D) bone vasculature during metastatic formation and progression. Seventy-three eight-week-old female mice were treated with AAD (bevacizumab, vatalanib, or a combination of both drugs) or the vehicle (placebo) one day after injection with breast cancer cells. Mice were sacrificed eight or 22 days after tumor cell inoculation (time points T1 and T2, respectively). Synchrotron radiation microcomputed tomography (SR-μCT) was used to image bone and blood vessels with a contrast agent. Hence, 3D-bone and vascular networks were simultaneously visualized and quantitatively analyzed. At T1, the trabecular bone volume fraction was significantly increased (p < 0.05) in the combined AAD-treatment group, compared to the placebo- and single AAD-treatment groups. At T2, only the bone vasculature was reduced in the combined AAD-treatment group (p < 0.05), as judged by measurement of the blood vessel thickness. Our data suggest that, at the early stage, combined AAD treatment dampens tumor-induced bone resorption with no detectable effects on bone vessel organization while, at a later stage, it affects the structure of bone microvascularization.
Assessment of a Size-Based Method for Enriching Circulating Tumour Cells in Colorectal Cancer
Authors: Vasantharajan Sai Shyam , Barnett Edward , Gray Elin S. , McCall John L. , Rodger Euan J. , Eccles Michael R. , Munro Fran , Pattison Sharon , Chatterjee Aniruddha
Published: July 2022

Circulating tumour cells (CTC) from solid tumours are a prerequisite for metastasis. Isolating CTCs and understanding their biology is essential for developing new clinical tests and precision oncology. Currently, CellSearch is the only FDA (U.S. Food and Drug Administration)-approved method for CTC enrichment but possesses several drawbacks owing to a reliance on the epithelial cell adhesion molecule (EpCAM) and a resource-intensive nature. Addressing these shortcomings, we optimised an existing size-based method, MetaCell, to enrich CTCs from blood of colorectal cancer (CRC) patients. We evaluated the ability of MetaCell to enrich CTCs by spiking blood with CRC cell lines and assessing the cell recovery rates and WBC depletion via immunostaining and gene expression. We then applied MetaCell to samples from 17 CRC patients and seven controls. Recovery rates were >85% in cell lines, with >95% depletion in WBCs. MetaCell yielded CTCs and CTC clusters in 52.9% and 23.5% of the patients, respectively, without false positives in control patients. CTCs and cluster detection did not correlate with histopathological parameters. Overall, we demonstrated that the MetaCell platform enriched CRC cells with high recovery rates and high purity. Our pilot study also demonstrated the ability of MetaCell to detect CTCs in CRC patients.
Factors Predicting Surgical Effort Using Explainable Artificial Intelligence in Advanced Stage Epithelial Ovarian Cancer
Authors: Laios Alexandros , Kalampokis Evangelos , Johnson Racheal , Munot Sarika , Thangavelu Amudha , Hutson Richard , Broadhead Tim , Theophilou Georgios , Leach Chris , Nugent David , De Jong Diederick
Published: July 2022

(1) Background: Surgical cytoreduction for epithelial ovarian cancer (EOC) is a complex procedure. Encompassed within the performance skills to achieve surgical precision, intra-operative surgical decision-making remains a core feature. The use of eXplainable Artificial Intelligence (XAI) could potentially interpret the influence of human factors on the surgical effort for the cytoreductive outcome in question; (2) Methods: The retrospective cohort study evaluated 560 consecutive EOC patients who underwent cytoreductive surgery between January 2014 and December 2019 in a single public institution. The eXtreme Gradient Boosting (XGBoost) and Deep Neural Network (DNN) algorithms were employed to develop the predictive model, including patient- and operation-specific features, and novel features reflecting human factors in surgical heuristics. The precision, recall, F1 score, and area under curve (AUC) were compared between both training algorithms. The SHapley Additive exPlanations (SHAP) framework was used to provide global and local explainability for the predictive model; (3) Results: A surgical complexity score (SCS) cut-off value of five was calculated using a Receiver Operator Characteristic (ROC) curve, above which the probability of incomplete cytoreduction was more likely (area under the curve [AUC] = 0.644; 95% confidence interval [CI] = 0.598–0.69; sensitivity and specificity 34.1%, 86.5%, respectively; p = 0.000). The XGBoost outperformed the DNN assessment for the prediction of the above threshold surgical effort outcome (AUC = 0.77; 95% [CI] 0.69–0.85; p < 0.05 vs. AUC 0.739; 95% [CI] 0.655–0.823; p < 0.95). We identified “turning points” that demonstrated a clear preference towards above the given cut-off level of surgical effort; in consultant surgeons with <12 years of experience, age <53 years old, who, when attempting primary cytoreductive surgery, recorded the presence of ascites, an Intraoperative Mapping of Ovarian Cancer score >4, and a Peritoneal Carcinomatosis Index >7, in a surgical environment with the optimization of infrastructural support. (4) Conclusions: Using XAI, we explain how intra-operative decisions may consider human factors during EOC cytoreduction alongside factual knowledge, to maximize the magnitude of the selected trade-off in effort. XAI techniques are critical for a better understanding of Artificial Intelligence frameworks, and to enhance their incorporation in medical applications.