bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Segmentation Method and Target Lesion Selection on Radiomic Analysis of 18F-FDG PET Images in Diffuse Large B-Cell Lymphoma
Authors: Botta Francesca , Ferrari Mahila , Raimondi Sara , Corso Federica , Lo Presti Giuliana , Mazzara Saveria , Airò Farulla Lighea Simona , Radice Tommaso , Vanazzi Anna , Derenzini Enrico , Travaini Laura Lavinia , Ceci Francesco
Published: September 2022

Radiomic analysis of 18F[FDG] PET/CT images might identify predictive imaging biomarkers, however, the reproducibility of this quantitative approach might depend on the methodology adopted for image analysis. This retrospective study investigates the impact of PET segmentation method and the selection of different target lesions on the radiomic analysis of baseline 18F[FDG] PET/CT images in a population of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients. The whole tumor burden was segmented on PET images applying six methods: (1) 2.5 standardized uptake value (SUV) threshold; (2) 25% maximum SUV (SUVmax) threshold; (3) 42% SUVmax threshold; (4) 1.3∙liver uptake threshold; (5) intersection among 1, 2, 4; and (6) intersection among 1, 3, 4. For each method, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG) were assessed, and their association with survival outcomes (progression-free survival PFS and overall survival OS) was investigated. Methods 1 and 2 provided stronger associations and were selected for the next steps. Radiomic analysis was then performed on two target lesions for each patient: the one with the highest SUV and the largest one. Fifty-three radiomic features were extracted, and radiomic scores to predict PFS and OS were obtained. Two proportional-hazard regression Cox models for PFS and OS were developed: (1) univariate radiomic models based on radiomic score; and (2) multivariable clinical–radiomic model including radiomic score and clinical/diagnostic parameters (IPI score, SUVmax, TMTV, WTLG, lesion volume). The models were created in the four scenarios obtained by varying the segmentation method and/or the target lesion; the models’ performances were compared (C-index). In all scenarios, the radiomic score was significantly associated with PFS and OS both at univariate and multivariable analysis (p < 0.001), in the latter case in association with the IPI score. When comparing the models’ performances in the four scenarios, the C-indexes agreed within the confidence interval. C-index ranges were 0.79–0.81 and 0.80–0.83 for PFS radiomic and clinical–radiomic models; 0.82–0.87 and 0.83–0.90 for OS radiomic and clinical–radiomic models. In conclusion, the selection of either between two PET segmentation methods and two target lesions for radiomic analysis did not significantly affect the performance of the prognostic models built on radiomic and clinical data of DLBCL patients. These results prompt further investigation of the proposed methodology on a validation dataset.
Electrification of a Class 8 Heavy-Duty Truck Considering Battery Pack Sizing and Cargo Capacity
Authors: Leonard Aiden Thomas , Salek Farhad , Azizi Aydin , Resalati Shahaboddin
Published: September 2022

The design and performance optimization of fully electric trucks constitute an integral goal of the transport sector to meet climate emergency measures and local air quality requirements. Most studies in the literature have determined the optimum pack size based on economic factors, without accounting for the details of pack behavior when varying the size. In this paper, the effect of battery pack sizing and cargo capacity of a class 8, 41-ton truck on its overall energy performance and technical parameters of its powertrain is investigated. For this purpose, the proposed electric truck is designed and mathematically modelled using AVL CRUISE M software. The second-order equivalent circuit model is developed to predict the battery packs’ parameters. The proposed battery pack model is extracted from experimental analysis on SONY VTC6 lithium-ion batteries performed in the lab. The weight changes due to adding the battery packs to the truck are also estimated and have been taken into account. The mathematical model of the powertrain is simulated in the long-haul driving cycle considering different cargo capacities and battery pack sizes. The results of this study revealed that the battery pack voltage reached its minimum value when the maximum cargo capacity was applied for the 399 kWh battery pack. In addition, increasing the occupied cargo capacity from 10% to 100% resulted in an increase in the regenerative brake energy of up to 9.87 kWh, while changing the battery size imposed minimal impacts on regenerative brake energy recovery as well as energy consumption.
Entropy-Based Dynamic Rescoring with Language Model in E2E ASR Systems
Authors: Gong Zhuo , Saito Daisuke , Minematsu Nobuaki
Published: September 2022

Language models (LM) have played crucial roles in automatic speech recognition (ASR), whether as an essential part of a conventional ASR system composed of an acoustic model and LM, or as an integrated model to enhance the performance of novel end-to-end ASR systems. With the development of machine learning and deep learning, language modeling has made great progress in natural language processing applications. In recent years, efforts have been made to leverage the advantages of novel LM to ASR. The most common way to apply an integration is still shallow fusion because it can be easily implemented by zero-overhead while obtaining significant improvement. Our method can further enhance the applicability of shallow fusion without hyperparameter tuning while maintaining similar performance.
The Role of Privacy Fatigue in Privacy Paradox: A PSM and Heterogeneity Analysis
Authors: Tian Xinluan , Chen Lina , Zhang Xiaojuan
Published: September 2022

Powerful rising trends of mobile media platforms have also resulted in the escalation of users’ privacy concerns. However, there is a paradox between users’ attitudes towards privacy and their actual privacy disclosure behaviors. This study attempts to explain the phenomenon of privacy paradox in the mobile social media context from the privacy fatigue perspective. Based on the Elaboration Likelihood Model (ELM) and employing the method of Propensity Score Matching (PSM), this paper confirmed that privacy fatigue could directly explain the privacy paradox. Among the findings, cynicism turned the relationship between privacy concern and privacy protection behaviors from positive influence to negative influence, while emotional exhaustion would weaken the positive influence relationship between privacy concern and the intention to undertake privacy protection behaviors. In addition, the study also revealed the heterogeneous effects of individual characteristics and usage characteristics variables on how the privacy fatigue influences privacy paradox.
Photocatalytic Properties of Immobilised Graphitic Carbon Nitride on the Alumina Substrate
Authors: Vukšić Milan , Kocijan Martina , Ćurković Lidija , Radošević Tina , Vengust Damjan , Podlogar Matejka
Published: September 2022

Textile industries significantly impact the contamination of wastewater. Conventional wastewater treatment methods consider the most common pollutants; however, they are very expensive and commonly produce toxic by-products. In the scientific community, advanced oxidation processes appear to be the most appealing, and a majority of the published work considers heterogeneous photocatalysis for the degradation of various toxic chemicals. For convenience, the reaction is performed directly in the water environment. In this work, a metal-free graphitic carbon nitride (g-C3N4) was prepared through a simple thermal method using urea as a precursor. Prepared g-C3N4 was deposited on the surface of the alumina ceramic ring by the dip-coating method using ethylene glycol as binder. The alumina ceramic ring, as substrate, was prepared by the slip casting method. Photocatalytic properties of immobilised graphitic carbon nitride were used for degradation of methylene blue as a model pollutant under simulated solar light irradiation. The photocatalyst was characterised by XRD, FTIR, UV-Vis DRS, TGA, BET and SEM/EDX analyses. The photocatalytic degradation of MB from an aqueous solution was found to increase with increasing irradiation time. It was found that the graphitic carbon nitride immobilised on alumina ceramic is convenient for largescale environmental applications because the whole setup is cheap, nontoxic, easy to operate and offers reusability with a high removal rate of MB after three consecutive cycles.
Factors Influencing Student Satisfaction toward STEM Education: Exploratory Study Using Structural Equation Modeling
Authors: Zhao Jingbo , Wijaya Tommy Tanu , Mailizar Mailizar , Habibi Akhmad
Published: September 2022

Learning satisfaction has a relationship with student outcomes. Furthermore, this has prompted many governments to increasingly implement STEM education-based learning. Many studies have examined the improvement of STEM education by teachers. However, the studies have not analyzed STEM education’s effect on students’ learning satisfaction. Extending the planned behavior theory, this study aimed to predict high school students’ learning satisfaction with STEM education. The questionnaire developed from the TPB model was filled out by 174 high school students in Indonesia. Furthermore, AMOS and SPSS 23 software were used for structural equation model analysis. The results showed that seven of twelve hypotheses were supported. Subjective norm and playfulness factors of STEM education positively relate to students’ attitudes toward STEM education. Attitude is the most important factor influencing student satisfaction and acceptance toward STEM education. Therefore, this study provides a theoretical and practical contribution to improving learning satisfaction in technology-based STEM education.
Augmentation of Deep Learning Models for Multistep Traffic Speed Prediction
Authors: Riaz Adnan , Rahman Hameedur , Arshad Muhammad Ali , Nabeel Muhammad , Yasin Affan , Al-Adhaileh Mosleh Hmoud , Eldin Elsayed Tag , Ghamry Nivin A.
Published: September 2022

Traffic speed prediction is a vital part of the intelligent transportation system (ITS). Predicting accurate traffic speed is becoming an important and challenging task with the rapid development of deep learning and increasing traffic data size. In this study, we present a deep-learning-based architecture for network-wide traffic speed prediction. We propose a deep-learning-based model consisting of a fully convolutional neural network, bidirectional long short-term memory, and attention mechanism. Our design aims to consider both backward and forward dependencies of traffic data to predict multistep network-wide traffic speed. Thus, we propose a model named AttBDLTSM-FCN for multistep traffic speed prediction. We augmented the attention-based bidirectional long short-term memory recurrent neural network with the fully convolutional network to predict the network-wide traffic speed. In traffic speed prediction, this is the first time that augmentation of AttBDLSTM and FCN have been exploited to measure the backward dependency of traffic data, as a building block for a deep architecture model. We conducted comprehensive experiments, and the experimental evaluations illustrated that the proposed architecture achieved better performance compared to state-of-the-art models when considering the short and long traffic speed prediction, e.g., 15, 30, and 60 min, in multistep traffic speed prediction.
Parametric Optimization of Nozzle Turbine Vane Modal Characteristics by Means of Artificial System
Authors: Robak Rafał , Szczepanik Mirosław , Rulik Sebastian
Published: September 2022

Modal analysis is a fundamental assessment in the design phase of a nozzle guide vane in a low pressure turbine system. Evaluation is crucial for new concept design but also in case of design modification. The technical requirement is to ensure appropriate durability level (number of flight cycles) and the reliability of the system. An understanding of dynamic behavior is one of the key elements in the high cycle fatigue (HCF) evaluation. Finite element method (FEM) analyses are widely used in new product introduction phases to verify modal characteristics with respect to operating range and engine orders (forcing function, excitation). In the process used 2D representation of the nozzle guide vane approximated by axisymmetric and plane stress with thickness FEM plain elements. The optimization process used geometrical parameters (nozzle outer band and casing shell) and surrogate models to find optimal solutions from a frequency placement perspective. A sensitivity analysis and optimization process revealed casing shell thickness to be a major contribution in the modal response and weight. Excluding casing shell parameters led to a lower frequency shift with respect to the reference configuration. The presented optimization framework is very robust and time effective in completing the optimization task together with a sensitivity analysis for the defined design domain. An FEM model validation of the surrogate model showed consistency in the modal analysis results. A promising solution from the component weight standpoint is the optimization with hook position and leaning only. A future research recommendation is to study an extended parameter range to reduce weight impact for this set.
Multidisciplinary Design Optimization of a Re-Entry Spacecraft via Radau Pseudospectral Method
Authors: Kabganian Masoud , Hashemi Seyed M. , Roshanian Jafar
Published: September 2022

The design and optimization of re-entry spacecraft or its subsystems is a multidisciplinary or multiobjective optimization problem by nature. Multidisciplinary design optimization (MDO) focuses on using numerical optimization in designing systems with several subsystems or disciplines that have interactions and independent actions. In the present paper, the system-level optimizer, trajectory, geometry and shape, aerodynamics, and aerothermodynamics differential equations, are converted to algebraic equations using the Radau pseudospectral method (RPM) since a spacecraft is a nonlinear, extensive, and sparse system. The solution to the problem with the help of MDO is reached by iterating all the disciplines together; one can simultaneously enhance the design, decrease the time and cost of the entire design cycle, and minimize the structural mass of a re-entry spacecraft. Considering various methods presented in earlier research works, a combined and innovative all-at-once (AAO), RPM-based MDO method, including the key subsystems in the design process of a re-entry capsule-shape spacecraft with a low lift-to-drag ratio (L/D), is presented. Considering the applicable state and control variables, various constraints, and parameters applied to several geometric shapes of a blunt capsule and using Apollo’s aerodynamic and aerothermodynamic coefficients, the optimized dimensions for a re-entry spacecraft are presented. The introduced optimization scheme led to a 17% mass reduction compared to the original mass of the Apollo vehicle. Fast computing and simplified models are used together in this method to analyze a wide range of vehicle shapes and entry types during conceptual design.
An Evaluation of Precipitation in Dongting Lake Basin on CMIP5 Models
Authors: Yin Yiwen , Jiang Shuai , Peng Jie , Zhu Hao , Ruan Neng , Wang Wei
Published: September 2022

The rainfall in the Dongting Lake Basin influences tens of millions of people, and its long-term change remains uncertain. In this paper, 15 CMIP5 models with precipitation data for the time period of 2006–2019 for which reliable observations are available under the RCP4.5 scenario were evaluated for their applicability, and the models with better simulation results were selected for predicting the precipitation in the Dongting Lake Basin during the flood season (April–September) in the mid-21st century (2020–2049). The results of the study show that (i) most models behaved reasonably consistent with the observation in the Dongting Lake Basin, and predicted an upward trend for the future precipitation while the multi-model ensemble (MME) showed a relatively slow increasing trend of 0.8 mm/year; (ii) the future precipitation in Dongting Lake Basin presented a variation form of “peak–valley–peak–valley”, suggesting strong interannual and interdecadal variations; (iii) the interannual variability showed great agreement with large-scale circulation, implying that the rainfall is controlled by the circulation. The analysis of the wind fields at 200 hPa and 850 hPa in the peak and valley years showed that the characteristics of low-level convergence and high-level divergence were significantly stronger in the peak precipitation years than in the weak years; moreover, the teleconnection pattern of “+ − +” from Europe, the Ural Mountains, and East Asia was clearly manifested in the 500 hPa height field of the Dongting Lake Basin, which can influence the intensity of the trough ridge over East Asia and change the low-level water vapor convergence and divergence, thus affecting the source of water vapor in the Dongting Lake Basin.
System of Imaging Photometers for Upper Atmospheric Phenomena Study in the Arctic Region
Authors: Klimov Pavel , Sharakin Sergei , Belov Alexander , Kozelov Boris , Murashov Alexei , Saraev Roman , Trofimov Daniil , Roldugin Alexei , Lubchich Vladimir
Published: September 2022

A Pulsating Aurora Imaging Photometers Stereoscopic System (PAIPS) is suggested and described in the paper. The system is based on two lens telescopes with a matrix of multianode photomultiplier tubes as photodetectors placed in two high latitude observatories of the Polar Geophysical Institute. Telescopes provide simultaneous observations of a large volume of the atmosphere at altitudes in the range 50–100 km with high temporal resolution (up to 2.5 μs) and a spatial resolution of about 2 km. This is a novel system for pulsating aurora study aimed to determine the energies of precipitating electrons responsible for the pulsating aurora occurrence. The system can be used for other atmospheric phenomena studies: meteors, transient luminous events, etc. One telescope has been operating since September 2021 and has measured a variety of optical phenomena.
Present and Future Changes in Winter Cyclonic Activity in the Mediterranean–Black Sea Region in the 21st Century Based on an Ensemble of CMIP6 Models
Authors: Voskresenskaya Elena N. , Maslova Veronika N. , Lubkov Andrey S. , Zhuravskiy Viktor Y.
Published: September 2022

A better understanding of expected future cyclonic activity, especially in winter in the Mediterranean basin, is essential in developing scientifically based adaptation and mitigation methods to study extreme precipitation and wind anomalies. The aim of this study was to analyze the changes in winter cyclonic activity in the Mediterranean–Black Sea region, as part of the North Atlantic–European sector, at three 15 year periods: the beginning, middle, and end of the 21st century. Our projections were based on an ensemble of seven Coupled Model Intercomparison Project (CMIP), phase 6, models, which showed the best agreement with NCEP/NCAR and ERA5 reanalyses under the intermediate SSP2-4.5 and highest-emission SSP5-8.5 scenarios. The results showed a consistent increase in the frequency of cyclones over Central Europe and the British Isles, which was associated with shifts in cyclone tracks: northward from the western Mediterranean region and southward from the Icelandic Low region. The latter shift led to a decrease in the frequency in the northern Atlantic–European region. At the same time, there was a reduction in the frequency of cyclones over the eastern region of the Mediterranean Sea, consistent with the decrease in cyclogenesis events. Area-averaged cyclone numbers in the western and eastern Mediterranean and Black Sea subregions reduced at the end of the century under the highest-emission scenario, but not constantly. There was a rise in the middle of the 21st century under both scenarios, which may be linked to long-term multidecadal variability or regional features. In general, our study showed that the future winter cyclonic activity in the Mediterranean–Black Sea region will respond unevenly to global climate changes, due to regional and monthly features and long-term quasiperiodic variability.
Particulate Matter versus Airborne Viruses—Distinctive Differences between Filtering and Inactivating Air Cleaning Technologies
Authors: Burdack-Freitag Andrea , Buschhaus Michael , Grün Gunnar , Hofbauer Wolfgang Karl , Johann Sabine , Nagele-Renzl Anna Maria , Schmohl Andreas , Scherer Christian Rudolf
Published: September 2022

The current pandemic of the SARS-CoV-2 virus requires measures to reduce the risk of infection. In addition to the usual hygiene measures, air cleaners are a recommended solution to decrease the viral load in rooms. Suitable technologies range from pure filters to inactivating units, such as cold plasma or UVC irradiation. Such inactivating air cleaners, partly combined with filter technology, are available on the market in various designs, dimensions and technical specifications. Since it is not always clear whether they may produce undesirable by-products, and the suitability for particular applications cannot be assessed on the basis of the principle of operation, the effectivity of six inactivating devices was investigated in a near-real environment. The investigations were based on a standard method published by the VDI. The procedure was extended in such a way that a permanent virus source was simulated, which corresponds to the presence of a person suffering from COVID-19 in a room. The study addresses the difference of the mere presence of viruses to the determination of the virulence. As a result, a deep understanding is provided between the behavior of a virus as a pure aerosolized particle and its real infectivity in order to enable the assessment of suitable air cleaners.
The Spatio-Temporal Onset Characteristics of Indian Summer Monsoon Rainfall and Their Relationship with Climate Indices
Authors: Saini Atul , Sahu Netrananda , Mishra Saroj K. , Jain Shipra , Behera Swadhin , Dash Sushil K.
Published: September 2022

Regional variations of monsoon onset dates across India were analyzed for 67 years (1951–2017) under different modes of climate variations, i.e., El Niño, La Niña, and the Indian Ocean Dipole (IOD), along with flood and drought years using the objective method and statistical techniques. Monsoon onset analysis revealed that the northern, northeastern, and southern parts were highly susceptible to the early onset of La Niña, and the northern and northern northwest parts were highly susceptible to the early onset of El Niño. The onset dates were early (late) in the sub-regions of the central, southern, and northeastern (northern, northwestern, and western) parts of India during flood (drought) years. Further, onset dates in flood years occurred earlier than those in La Niña years, and onset dates in drought years were later than those in El Niño years. The onset occurrence probability and influence of the synoptic events are discussed. This research could help in understanding the onset of monsoon and its predictability for societal applications.
An Efficient and Secure Big Data Storage in Cloud Environment by Using Triple Data Encryption Standard
Authors: Ramachandra Mohan Naik , Srinivasa Rao Madala , Lai Wen Cheng , Parameshachari Bidare Divakarachari , Ananda Babu Jayachandra , Hemalatha Kivudujogappa Lingappa
Published: September 2022

In recent decades, big data analysis has become the most important research topic. Hence, big data security offers Cloud application security and monitoring to host highly sensitive data to support Cloud platforms. However, the privacy and security of big data has become an emerging issue that restricts the organization to utilize Cloud services. The existing privacy preserving approaches showed several drawbacks such as a lack of data privacy and accurate data analysis, a lack of efficiency of performance, and completely rely on third party. In order to overcome such an issue, the Triple Data Encryption Standard (TDES) methodology is proposed to provide security for big data in the Cloud environment. The proposed TDES methodology provides a relatively simpler technique by increasing the sizes of keys in Data Encryption Standard (DES) to protect against attacks and defend the privacy of data. The experimental results showed that the proposed TDES method is effective in providing security and privacy to big healthcare data in the Cloud environment. The proposed TDES methodology showed less encryption and decryption time compared to the existing Intelligent Framework for Healthcare Data Security (IFHDS) method.
A Multi-Specific DARPin Potently Neutralizes Shiga Toxin 2 via Simultaneous Modulation of Both Toxin Subunits
Authors: Zeng Yu , Jiang Mengqiu , Robinson Sally , Peng Zeyu , Chonira Vikas , Simeon Rudo , Tzipori Saul , Zhang Junjie , Chen Zhilei
Published: September 2022

Shiga toxin-producing E. coli (STEC) is a common cause of bloody diarrhea. The pathology of STEC infection derives from two exotoxins—Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2)—that are secreted by STEC in the gut, from where they are systemically absorbed, causing severe kidney damage leading to hemolytic uremic syndrome (HUS). Currently, there is no effective treatment for HUS, and only supportive care is recommended. We report the engineering of a panel of designed ankyrin repeat proteins (DARPin) with potent neutralization activity against Stx2a, the major subtype associated with HUS. The best dimeric DARPin, SD5, created via a combination of directed evolution and rational design, neutralizes Stx2a with a half maximal effective concentration (EC50) of 0.61 nM in vitro. The two monomeric DARPin constituents of SD5 exhibit complementary functions—SHT targets the enzymatic A subunit of Stx2a and inhibits the toxin’s catalytic activity, while DARPin #3 binds the B subunit, based on the cryo-EM study, and induces a novel conformational change in the B subunit that distorts its five-fold symmetry and presumably interferes with toxin attachment to target cells. SD5 was fused to an albumin-binding DARPin, and the resulting trimeric DARPin DA1-SD5 efficiently protects mice in a toxin challenge model, pointing to a high potential of this DARPin as a therapeutic for STEC infection. Finally, the unprecedented toxin conformational change induced by DARPin #3 represents a novel mode of action for neutralizing Stx2 toxicity and reveals new targets for future drug development.
Role of Cell-Cell Junctions in Oesophageal Squamous Cell Carcinoma
Authors: Xu Qian-Rui , Du Xiao-Hui , Huang Ting-Ting , Zheng Yu-Chun , Li Yu-Ling , Huang Dan-Yi , Dai Hao-Qiang , Li En-Min , Fang Wang-Kai
Published: September 2022

Cell–cell junctions comprise various structures, including adherens junctions, tight junctions, desmosomes, and gap junctions. They link cells to each other in tissues and regulate tissue homeostasis in critical cellular processes. Recent advances in cell–cell junction research have led to critical discoveries. Cell–cell adhesion components are important for the invasion and metastasis of tumour cells, which are not only related to cell–cell adhesion changes, but they are also involved in critical molecular signal pathways. They are of great significance, especially given that relevant molecular mechanisms are being discovered, there are an increasing number of emerging biomarkers, targeted therapies are becoming a future therapeutic concern, and there is an increased number of therapeutic agents undergoing clinical trials. Oesophageal squamous cell carcinoma (ESCC), the most common histological subtype of oesophageal cancer, is one of the most common cancers to affect epithelial tissue. ESCC progression is accompanied by the abnormal expression or localisation of components at cell–cell junctions. This review will discuss the recent scientific developments related to the molecules at cell–cell junctions and their role in ESCC to offer valuable insights for readers, provide a global view of the relationships between position, construction, and function, and give a reference for future mechanistic studies, diagnoses, and therapeutic developments.
Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy
Authors: Hosoya Tomohiro , Takahashi Masamichi , Davey Calvin , Sese Jun , Honda-Kitahara Mai , Miyakita Yasuji , Ohno Makoto , Yanagisawa Shunsuke , Omura Takaki , Kawauchi Daisuke , Ozeki Yukie , Kikuchi Miyu , Nakano Tomoyuki , Yoshida Akihiko , Igaki Hiroshi , Matsushita Yuko , Ichimura Koichi , Narita Yoshitaka
Published: September 2022

The aim of the present study was to determine which individual or combined CpG sites among O6-methylguanine DNA methyltransferase CpG 74–89 in glioblastoma mainly affects the response to temozolomide resulting from CpG methylation using statistical analyses focused on the tumor volume ratio (TVR). We retrospectively examined 44 patients who had postoperative volumetrically measurable residual tumor tissue and received adjuvant temozolomide therapy for at least 6 months after initial chemoradiotherapy. TVR was defined as the tumor volume 6 months after the initial chemoradiotherapy divided by that before the start of chemoradiotherapy. Predictive values for TVR as a response to adjuvant therapy were compared among the averaged methylation percentages of individual or combined CpGs using the receiver operating characteristic curve. Our data revealed that combined CpG 78 and 79 showed a high area under the curve (AUC) and a positive likelihood ratio and that combined CpG 76–79 showed the highest AUC among all combinations. AUCs of consecutive CpG combinations tended to be higher for CpG 74–82 in exon 1 than for CpG 83–89 in intron 1. In conclusion, the methylation status at CpG sites in exon 1 was strongly associated with TVR reduction in glioblastoma.
Validation of a Commercial Enzyme-Linked Immunosorbent Assay for Allopregnanolone in the Saliva of Healthy Pregnant Women
Authors: Grötsch Maria Katharina , Wietor Denise Margret , Hettich Timm , Ehlert Ulrike
Published: September 2022

Enzyme-linked immunosorbent assays (ELISAs) for saliva are simple, non-invasive methods for hormone detection. Allopregnanolone (ALLO) is a neuroactive steroid hormone that plays a crucial role in the aetiology of reproductive mood disorders. To better understand the relationship between ALLO and mood, a validated method to measure peripheral hormone levels is required. Currently, there is no commercially available ELISA with which to measure ALLO in saliva. We validated two ELISAs, developed for use with blood, with the saliva samples of 25 pregnant women, examining the range and sensitivity, intra- and inter-assay precision, parallelism, linearity of dilution, and recovery. The samples were simultaneously analysed using the liquid-chromatography–mass-spectrometry (LC-MS) method. The kits differed in range (31.2–2000 pg/mL vs. 1.6–100 ng/mL) and sensitivity (<9.5 pg/mL vs. 0.9 ng/mL), with the latter showing significant matrix effects and the former fulfilling the acceptance criteria of all the parameters. The concentrations measured with LC–MS were below the lower limit of quantification (<1.0 ng/mL) and no signal was detected. One of the tested ELISAs is a valid method for detecting ALLO in the saliva of pregnant women. It has a suitable measurement range and higher sensitivity than the conventional LC–MS method.
Heterogeneous Clinical Phenotypes of dHMN Caused by Mutation in HSPB1 Gene: A Case Series
Authors: Shen Xiya , Zhang Jiawei , Zhan Feixia , Tian Wotu , Jiang Qingqing , Luan Xinghua , Zhang Xiaojie , Cao Li
Published: September 2022

Mutations in HSPB1 are known to cause Charcot-Marie-Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). In this study, we presented three patients with mutation in HSPB1 who were diagnosed with dHMN. Proband 1 was a 14-year-old male with progressive bilateral lower limb weakness and walking difficulty for four years. Proband 2 was a 65-year-old male with chronic lower limb weakness and restless legs syndrome from the age of 51. Proband 3 was a 50-year-old female with progressive weakness, lower limbs atrophy from the age of 44. The nerve conduction studies (NCS) suggested axonal degeneration of the peripheral motor nerves and needle electromyography (EMG) revealed chronic neurogenic changes in probands. Open sural nerve biopsy for proband 2 and the mother of proband 1 showed mild to moderate loss of myelinated nerve fibers with some nerve fiber regeneration. A novel p.V97L in HSPB1 was identified in proband 3, the other two variants (p.P182A and p.R127W) in HSPB1 have been reported previously. The functional studies showed that expressing mutant p.V97L HSPB1 in SH-SY5Y cells displayed a decreased cell activity and increased apoptosis under stress condition. Our study expands the clinical phenotypic spectrum and etiological spectrum of HSPB1 mutation.
Selecting Multitarget Peptides for Alzheimer’s Disease
Authors: Kasus-Jacobi Anne , Washburn Jennifer L. , Laurence Riley B. , Pereira H. Anne
Published: September 2022

Alzheimer’s disease (AD) is a multifactorial disease with a complex pathogenesis. Developing multitarget drugs could be a powerful strategy to impact the progressive loss of cognitive functions in this disease. The purpose of this study is to select a multitarget lead peptide candidate among a series of peptide variants derived from the neutrophil granule protein cathepsin G. We screened eight peptide candidates using the following criteria: (1) Inhibition and reversion of amyloid beta (Aβ) oligomers, quantified using an enzyme-linked immunosorbent assay (ELISA); (2) direct binding of peptide candidates to the human receptor for advanced glycation end-products (RAGE), the Toll-like receptor 4 (TLR4) and the S100 calcium-binding protein A9 (S100A9), quantified by ELISA; (3) protection against Aβ oligomer-induced neuronal cell death, using trypan blue to measure cell death in a murine neuronal cell line; (4) inhibition of TLR4 activation by S100A9, using a human TLR4 reporter cell line. We selected a 27-mer lead peptide that fulfilled these four criteria. This lead peptide is a privileged structure that displays inherent multitarget activity. This peptide is expected to significantly impact cognitive decline in mouse models of Alzheimer’s disease, by targeting both neuroinflammation and neurodegeneration.
Next-Generation SINE Compound KPT−8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD
Authors: English Katherine G. , Reid Andrea L. , Samani Adrienne , Coulis Gerald J. F. , Villalta S. Armando , Walker Christopher J. , Tamir Sharon , Alexander Matthew S.
Published: September 2022

Duchenne muscular dystrophy (DMD) is a progressive, X-linked childhood neuromuscular disorder that results from loss-of-function mutations in the DYSTROPHIN gene. DMD patients exhibit muscle necrosis, cardiomyopathy, respiratory failure, and loss of ambulation. One of the major driving forces of DMD disease pathology is chronic inflammation. The current DMD standard of care is corticosteroids; however, there are serious side effects with long-term use, thus identifying novel anti-inflammatory and anti-fibrotic treatments for DMD is of high priority. We investigated the next-generation SINE compound, KPT−8602 (eltanexor) as an oral therapeutic to alleviate dystrophic symptoms. We performed pre-clinical evaluation of the effects of KPT−8602 in DMD zebrafish (sapje) and mouse (D2-mdx) models. KPT−8602 improved dystrophic skeletal muscle pathologies, muscle architecture and integrity, and overall outcomes in both animal models. KPT−8602 treatment ameliorated DMD pathology in D2-mdx mice, with increased locomotor behavior and improved muscle histology. KPT−8602 altered the immunological profile of the dystrophic mice, and reduced circulating osteopontin serum levels. These findings demonstrate KPT−8602 as an effective therapeutic in DMD through by promotion of an anti-inflammatory environment and overall improvement of DMD pathological outcomes.
Noninvasive Hemodynamic Monitoring in Advanced Heart Failure Patients: New Approach for Target Treatments
Authors: Piccirillo Gianfranco , Moscucci Federica , Corrao Andrea , Carnovale Myriam , Di Diego Ilaria , Lospinuso Ilaria , Caltabiano Cristina , Mezzadri Martina , Rossi Pietro , Magrì Damiano
Published: September 2022

Using bio-impedance to deduce some hemodynamic parameters combined with some short-term ECG temporal dispersion intervals, and measuring myocardial depolarization, intraventricular conduction, and repolarization. A total of 65 in-hospital patients (M/F:35/30) were enrolled, 39 with HFrEF and 26 HFpEF, in New York Heart Association (NYHA) class IV. Stroke volume (SVI), cardiac indexes (CI), left ventricular ejection fraction (LVEFBIO), end diastolic volume (LV-EDV), and other systolic and diastolic parameters were noninvasively obtained at enrollment and at hospital discharge. At the same time, QR, QRS, QT, ST, Tpeak-Tend (Te) interval mean, and standard deviation (SD) from 5 min ECG recordings were obtained. At baseline, HFrEF patients reported significantly lower SVI (p < 0.05), CI (p < 0.05), and LVEF (p < 0.001) than HFpEF patients; moreover, HFrEF patients also showed increased LV-EDV (p < 0.05), QR, QRS, QT, ST, and Te means (p < 0.05) and standard deviations (p < 0.05) in comparison to HFpEF subjects. Multivariable logistic regression analysis reported a significant correlation between hospital mortality and Te mean (odds ratio: 1.03, 95% confidence limit: 1.01–1.06, p: 0.01). Fifty-seven percent of patients were considered responders to optimal medical therapy and, at discharge, they had significantly reduced NT-proBNP, (p < 0.001), heart rate (p < 0.05), and TeSD (p < 0.001). LVEF, obtained by transthoracic echocardiography, and LVEFBIO were significantly related (r: 0.781, p < 0.001), but these two parameters showed a low agreement limit. Noninvasive hemodynamic and ECG-derived parameters were useful to highlight the difference between HFrEF and HFpEF and between responders and nonresponders to the optimal medical therapy. Short-period bioimpedance and electrocardiographic data should be deeply evaluated to determine possible advantages in the therapeutic and prognostic approach in severe CHF.
T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients
Authors: Reverchon Flora , Guillard Colleen , Mollet Lucile , Auzou Pascal , Gosset David , Madouri Fahima , Valéry Antoine , Menuet Arnaud , Ozsancak Canan , Pallix-Guyot Maud , Morisset-Lopez Séverine
Published: September 2022

Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT7 receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far. In this study, we collected blood sample from three groups: acute relapsing MS patients (ARMS), natalizumab-treated MS patients (NTZ), and control subjects. We investigated the 5-HT7 expression on circulating lymphocytes and evaluated the effects of its activation on cytokine production with peripheral blood mononuclear cell (PBMC) cultures. We found a significant increase in the 5-HT7 surface expression on T lymphocytes and on the different CD4+ T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT7R activation significantly promotes the production of IL-10, a potent immunosuppressive cytokine in PBMCs. This study provides for the first time a dysregulation of 5-HT7 expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT7 may play a role in the immuno-protective mechanisms of NTZ in MS disease and could be considered as an interesting therapeutic target in MS.
State-of-the-Art Advances of Nanomedicine for Diagnosis and Treatment of Bladder Cancer
Authors: Kong Chenfan , Zhang Shaohua , Lei Qifang , Wu Song
Published: September 2022

Bladder cancer is a common malignant tumor of the urinary system. Cystoscopy, urine cytology, and CT are the routine diagnostic methods. However, there are some problems such as low sensitivity and difficulty in staging, which must be urgently supplemented by novel diagnostic methods. Surgery, intravesical instillation, systemic chemotherapy, and radiotherapy are the main clinical treatments for bladder cancer. It is difficult for conventional treatment to deal with tumor recurrence, progression and drug resistance. In addition, the treatment agents usually have the defects of poor specific distribution ability to target tumor tissues and side effects. The rapid development of nanomedicine has brought hope for the treatment of bladder cancer in reducing side effects, enhancing tumor inhibition effects, and anti-drug resistance. Overall, we review the new progression of nano-platforms in the diagnosis and treatment of bladder cancer.
Reversibly Migratable Fluorescent Probe for Precise and Dynamic Evaluation of Cell Mitochondrial Membrane Potentials
Authors: Song Guofen , He Haiwei , Chen Wanling , Lv Yuanliang , Chu Paul K. , Wang Huaiyu , Li Penghui
Published: September 2022

The mitochondrial membrane potential (MMP, ΔΨmito) provides the charge gradient required for mitochondrial functions and is a key indicator of cellular health. The changes in MMP are closely related to diseases and the monitoring of MMP is thus vital for pathological study and drug development. However, most of the current fluorescent probes for MMP rely solely on the cell fluorescence intensity and are thus restricted by poor photostability, rendering them not suitable for long-term dynamic monitoring of MMP. Herein, an MMP-responsive fluorescent probe pyrrolyl quinolinium (PQ) which is capable of reversible migration between mitochondria and nucleolus is developed and demonstrated for dynamic evaluation of MMP. The fluorescence of PQ translocates from mitochondria to nucleoli when MMP decreases due to the intrinsic RNA-specificity and more importantly, the translocation is reversible. The cytoplasm to nucleolus fluorescence intensity ratio is positively correlated with MMP so that this method avoids the negative influence of photostability and imaging parameters. Various situations of MMP can be monitored in real time even without controls. Additionally, long-term dynamic evaluation of MMP is demonstrated for HeLa cells using PQ in oxidative environment. This study is expected to give impetus to the development of mitochondria-related disease diagnosis and drug screening.
Postoperative Hematoma Expansion in Patients Undergoing Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage
Authors: Vychopen Martin , Wach Johannes , Lampmann Tim , Asoglu Harun , Borger Valeri , Hamed Motaz , Vatter Hartmut , Güresir Erdem
Published: September 2022

Introduction: The aim of the study was to analyze risk factors for hematoma expansion (HE) in patients undergoing decompressive hemicraniectomy (DC) in patients with elevated intracranial pressure due to spontaneous intracerebral hematoma (ICH). Methods: We retrospectively evaluated 72 patients with spontaneous ICH who underwent DC at our institution. We compared the pre- and postoperative volumes of ICH and divided the patients into two groups: first, patients with postoperative HE > 6 cm3 (group 1), and second, patients without HE (group 2). Additionally, we screened the medical history for anticoagulant and antiplatelet medication (AC/AP), bleeding-related comorbidities, age, admission Glasgow coma scale and laboratory parameters. Results: The rate of AC/AP medication was higher in group 1 versus group 2 (15/16 vs. 5/38, p < 0.00001), and patients were significantly older in group 1 versus group 2 (65.1 ± 16.2 years vs. 54.4 ± 14.3 years, p = 0.02). Furthermore, preoperative laboratory tests showed lower rates of hematocrit (34.1 ± 5.4% vs. 38.1 ± 5.1%, p = 0.01) and hemoglobin (11.5 ± 1.6 g/dL vs. 13.13 ± 1.8 g/dL, p = 0.0028) in group 1 versus group 2. In multivariate analysis, the history of AC/AP medication was the only independent predictor of HE (p < 0.0001, OR 0.015, CI 95% 0.001–0.153). Conclusion: We presented a comprehensive evaluation of risk factors for hematoma epansion by patients undergoing DC due to ICH.
Different Music Training Modulates Theta Brain Oscillations Associated with Executive Function
Authors: Wang Junce , Xu Ruijie , Guo Xiaolong , Guo Sijia , Zhou Junchen , Lu Jing , Yao Dezhong
Published: September 2022

Different music training involves different hand coordination levels and may have a significant influence on brain oscillation for the executive function. However, few research has focused on the plasticity of executive function and the brain oscillation modulated by different musical instrument training modules. In this study, we recruited 18 string musicians, 20 pianists, and 19 non-musicians to perform a bimanual key pressing task during EEG recording. Behavioral results revealed that pianists have the highest accuracy and the shortest response time, followed by string musicians and non-musicians (p < 0.05). Time-frequency analyses of EEG revealed that pianists generated significantly greater theta power than the other groups from 500 ms to 800 ms post-stimulus in mid-central, frontal brain areas, and motor control areas. Functional connectivity analyses found that the pianists showed significantly greater connectivity in the frontal-parietal area in theta band based on phase-locking value analysis, which suggests that piano training improves executive function and enhances the connectivity between prefrontal and mid-central regions. These findings contribute to a better understanding of the effects of different music training on executive function.
A Scientific Approach to Conscious Experience, Introspection, and Unconscious Processing: Vision and Blindsight
Authors: Werth Reinhard
Published: September 2022

Although subjective conscious experience and introspection have long been considered unscientific and banned from psychology, they are indispensable in scientific practice. These terms are used in scientific contexts today; however, their meaning remains vague, and earlier objections to the distinction between conscious experience and unconscious processing, remain valid. This also applies to the distinction between conscious visual perception and unconscious visual processing. Damage to the geniculo-striate pathway or the visual cortex results in a perimetrically blind visual hemifield contralateral to the damaged hemisphere. In some cases, cerebral blindness is not absolute. Patients may still be able to guess the presence, location, shape or direction of movement of a stimulus even though they report no conscious visual experience. This “unconscious” ability was termed “blindsight”. The present paper demonstrates how the term conscious visual experience can be introduced in a logically precise and methodologically correct way and becomes amenable to scientific examination. The distinction between conscious experience and unconscious processing is demonstrated in the cases of conscious vision and blindsight. The literature on “blindsight” and its neurobiological basis is reviewed. It is shown that blindsight can be caused by residual functions of neural networks of the visual cortex that have survived cerebral damage, and may also be due to an extrastriate pathway via the midbrain to cortical areas such as areas V4 and MT/V5.