bluuebunny/crossref_metadata_2025 huggingface dataset:
Dam Deformation Interpretation and Prediction Based on a Long Short-Term Memory Model Coupled with an Attention Mechanism
Authors: Su Yan , Weng Kailiang , Lin Chuan , Chen Zeqin
Published: July 2021

An accurate dam deformation prediction model is vital to a dam safety monitoring system, as it helps assess and manage dam risks. Most traditional dam deformation prediction algorithms ignore the interpretation and evaluation of variables and lack qualitative measures. This paper proposes a data processing framework that uses a long short-term memory (LSTM) model coupled with an attention mechanism to predict the deformation response of a dam structure. First, the random forest (RF) model is introduced to assess the relative importance of impact factors and screen input variables. Secondly, the density-based spatial clustering of applications with noise (DBSCAN) method is used to identify and filter the equipment based abnormal values to reduce the random error in the measurements. Finally, the coupled model is used to focus on important factors in the time dimension in order to obtain more accurate nonlinear prediction results. The results of the case study show that, of all tested methods, the proposed coupled method performed best. In addition, it was found that temperature and water level both have significant impacts on dam deformation and can serve as reliable metrics for dam management.
Enhancing Design for Additive Manufacturing Workflow: Optimization, Design and Simulation Tools
Authors: Sbrugnera Sotomayor Nicolas Alberto , Caiazzo Fabrizia , Alfieri Vittorio
Published: July 2021

In the last few decades, complex light-weight designs have been successfully produced via additive manufacturing (AM), launching a new era in the thinking–design process. In addition, current software platforms provide design tools combined with multi-scale simulations to exploit all the technology benefits. However, the literature highlights that several stages must be considered in the design for additive manufacturing (DfAM) process, and therefore, performing holistic guided-design frameworks become crucial to efficiently manage the process. In this frame, this paper aims at providing the main optimization, design, and simulation tools to minimize the number of design evaluations generated through the different workflow assessments. Furthermore, DfAM phases are described focusing on the implementation of design optimization strategies as topology optimization, lattice infill optimization, and generative design in earlier phases to maximize AM capabilities. In conclusion, the current challenges for the implementation of the workflow are hence described.
Actin-Related Protein 6 (Arp6) Influences Double-Strand Break Repair in Yeast
Authors: Hooshyar Mohsen , Burnside Daniel , Hajikarimlou Maryam , Omidi Katayoun , Jesso Alexander , Vanstone Megan , Young Adamo , Cherubini Pedro Matilha , Jessulat Matthew , Potter Taylor , Schoenrock Andrew , Bhojoo Urvi , Silva Eshan , Moteshareie Houman , Babu Mohan , Diallo Jean-Simon , Dehne Frank , Samanfar Bahram , Golshani Ashkan
Published: July 2021

DNA double-strand breaks (DSBs) are the most deleterious form of DNA damage and are repaired through non-homologous end-joining (NHEJ) or homologous recombination (HR). Repair initiation, regulation and communication with signaling pathways require several histone-modifying and chromatin-remodeling complexes. In budding yeast, this involves three primary complexes: INO80-C, which is primarily associated with HR, SWR1-C, which promotes NHEJ, and RSC-C, which is involved in both pathways as well as the general DNA damage response. Here we identify ARP6 as a factor involved in DSB repair through an RSC-C-related pathway. The loss of ARP6 significantly reduces the NHEJ repair efficiency of linearized plasmids with cohesive ends, impairs the repair of chromosomal breaks, and sensitizes cells to DNA-damaging agents. Genetic interaction analysis indicates that ARP6, MRE11 and RSC-C function within the same pathway, and the overexpression of ARP6 rescues rsc2∆ and mre11∆ sensitivity to DNA-damaging agents. Double mutants of ARP6, and members of the INO80 and SWR1 complexes, cause a significant reduction in repair efficiency, suggesting that ARP6 functions independently of SWR1-C and INO80-C. These findings support a novel role for ARP6 in DSB repair that is independent of the SWR1 chromatin remodeling complex, through an apparent RSC-C and MRE11-associated DNA repair pathway.
Urban Heat Islands and Vulnerable Populations in a Mid-Size Coastal City in an Arid Environment
Authors: Quintana-Talvac Carolina , Corvacho-Ganahin Oscar , Smith Pamela , Sarricolea Pablo , Prieto Manuel , Meseguer-Ruiz Oliver
Published: July 2021

Arica is a coastal city located in northern Chile, in the Atacama Desert. The behavior of surface temperatures in the city between 1985 and 2019 was studied using Landsat satellite images, leading to the identification of surface urban heat islands (SUHI), surface urban cold islands (SUCI), and average temperature zones. The higher intensities of the SUHI reach values of almost 45 °C and the SUCI lower values are below 13 °C. From the socioeconomic characterisation of the population based on indicators retrieved from the 2012 and 2017 population censuses, we identified that during the study period there was a lower presence of SUHI, but these were linked to spaces of lower socioeconomic level and, for the most part, would form new urban spaces within the city. On the other hand, SUCI had a greater spatial presence in the study area and in the urban morphology, being found mostly in areas of high socioeconomic level and in consolidated spaces with few possibilities of generating new constructions.
Association between Polycyclic Aromatic Hydrocarbon Exposure and Diarrhea in Adults
Authors: Wu Chia-Che , Fang Wen-Hui , Wang Chung-Ching , Lai Ching-Huang , Chen Wei-Liang
Published: July 2021

Objective: Polycyclic aromatic hydrocarbons (PAHs) are not only natural but also anthropogenic contaminants that exist in many places in the environment. Human beings often accidentally ingest PAHs via smoking. Furthermore, smoking may increase the risk of bowel disorder, including diarrhea and other gastrointestinal problems. Therefore, PAH exposure is hypothesized to be related to diarrhea risk. This study discusses the association between diarrhea and PAH exposure in the United States adult population. Method: 10,537 participants from the National Health and Nutrition Examination Survey (NHANES 2001–2006) were involved in this cross-sectional analysis. Bowel disorders were assessed via examination of stool frequency and stool type. The concentrations of urinary PAH metabolites were used to evaluate PAH exposure. The association between bowel habits and PAH exposure was assessed using a multivariate logistic regression model with covariate assessment of gender, age, race, liver function, kidney function, and common chronic health diseases. Results: All PAH metabolites except 1-hydroxynaphthalene, 1-hydroxypyrene, and 9-hydroxyfluorene were substantially correlated with an increased risk of diarrhea (p < 0.05) after modification of relevant covariables. This study also revealed significant association in the group of females (p < 0.05). Furthermore, all PAH metabolites except 1-hydroxynaphthalene, 2-hydroxyphenanthrene, 1-hydroxypyrene, and 9-hydroxyfluorene show significantly positive association in the non-obesity group (BMI < 30, p < 0.05). Conclusions: PAH exposure is highly associated with risk of bowel disorders among the adult population in the United States, especially in female and non-obesity populations. More research is necessary to shed light on the pathophysiological mechanisms associated to PAH exposure and diarrhea.
High-Speed Visualization of Very Large High-Resolution Simulations for Air Hazard Transport and Dispersion
Authors: Oldrini Olivier , Perdriel Sylvie , Armand Patrick , Duchenne Christophe
Published: July 2021

In the case of an atmospheric release of a noxious substance, modeling remains an essential tool to assess and forecast the impact of the release. The impact of such situations on populated, and hence built-up, areas is of the uttermost importance. However, modeling on such areas requires specific high-resolution approaches, which are complex to set up in emergency situations. Various approaches have been tried and evaluated: The EMERGENCIES and EMED project demonstrated an effective strategy using intensive parallel computing. Large amounts of data were produced that proved initially to be difficult to visualize, especially in a crisis management framework. A dedicated processing has been set up to allow for rapid and effective visualization of the modeling results. This processing relies on a multi-level tiled approach initiated in web cartography. The processing is using a parallel approach whose performances were evaluated using the large amounts of data produced in the EMERGENCIES and EMED projects. The processing proved to be very effective and compatible with the requirements of emergency situations.
The Impact of Large-Scale Social Restriction Phases on the Air Quality Index in Jakarta
Authors: Pardamean Bens , Rahutomo Reza , Cenggoro Tjeng Wawan , Budiarto Arif , Perbangsa Anzaludin Samsinga
Published: July 2021

We reported the result of our study on the impact of Large-Scale Social Restriction (LSSR) phases due to the COVID-19 outbreak on the air quality in Jakarta. Specifically, this study covered the change of Air Quality Index (AQI) based on five pollutants, PM10, SO2, CO, O3, and NO2, contained in Jakarta’s air before and during LSSR. The AQI data were provided by the Ministry of Environment and Forestry, Indonesia, from January 2019 to December 2020 at five different locations in Jakarta, with missing data for March and September 2020 due to unknown reasons. These data were grouped into the period before the LSSR from January 2019 to February 2020 and the period during LSSR from April 2020 to December 2020. In order to measure the change in the air quality of Jakarta before and during LSSR, we ran a chi-squared test to the AQI for each location and LSSR phase as well as paired one-sided t-test for the seasonal trend. The result of this study showed that, in general, LSSR improved the air quality of Jakarta. The improvement was mainly contributed by reduced transportation activities that were induced by LSSR. Further analysis on the seasonal pollutants trend showed a variation of AQI improvement in each phase due to their unique characteristics.
Application of Rough and Fuzzy Set Theory for Prediction of Stochastic Wind Speed Data Using Long Short-Term Memory
Authors: Imani Moslem , Fakour Hoda , Lan Wen-Hau , Kao Huan-Chin , Lee Chi Ming , Hsiao Yu-Shen , Kuo Chung-Yen
Published: July 2021

Despite the great significance of precisely forecasting the wind speed for development of the new and clean energy technology and stable grid operators, the stochasticity of wind speed makes the prediction a complex and challenging task. For improving the security and economic performance of power grids, accurate short-term wind power forecasting is crucial. In this paper, a deep learning model (Long Short-term Memory (LSTM)) has been proposed for wind speed prediction. Knowing that wind speed time series is nonlinear stochastic, the mutual information (MI) approach was used to find the best subset from the data by maximizing the joint MI between subset and target output. To enhance the accuracy and reduce input characteristics and data uncertainties, rough set and interval type-2 fuzzy set theory are combined in the proposed deep learning model. Wind speed data from an international airport station in the southern coast of Iran Bandar-Abbas City was used as the original input dataset for the optimized deep learning model. Based on the statistical results, the rough set LSTM (RST-LSTM) model showed better prediction accuracy than fuzzy and original LSTM, as well as traditional neural networks, with the lowest error for training and testing datasets in different time horizons. The suggested model can support the optimization of the control approach and the smooth procedure of power system. The results confirm the superior capabilities of deep learning techniques for wind speed forecasting, which could also inspire new applications in meteorology assessment.
An Empirical Atmospheric Density Calibration Model Based on Long Short-Term Memory Neural Network
Authors: Zhang Yan , Yu Jinjiang , Chen Junyu , Sang Jizhang
Published: July 2021

The accuracy of the atmospheric mass density is one of the most important factors affecting the orbital precision of spacecraft at low Earth orbits (LEO). Although there are a number of empirical density models available to use in the orbit determination and prediction of LEO spacecraft, all of them suffer from errors of various degrees. A practical way to reduce the error of a particular model is to calibrate the model using precise density data or tracking data. In this paper, a long short-term memory (LSTM) neural network is proposed to calibrate the NRLMSISE-00 density model, in which the densities derived from spaceborne accelerometer data are the main input. The resulted LSTM-NRL model, calibrated using the accelerometer data from Challenging Minisatellite Payload (CHAMP) satellite, is extensively experimented to evaluate the calibration performance. With data in one month to train the LSTM-NRL model, the model is shown to effectively reduce the root mean square error of the model densities outside the training window by more than 40% in various time spans and space weather environment. The LSTM-NRL model is also shown to have remarkable transferring performance when it is applied along the GRACE satellite orbits.
Characterization of Ambient Particulate Matters in an Industry-Intensive Area in Central Taiwan
Authors: Li Hsing-Wang , Chen Kang-Shin , Lai Chia-Hsiang , Chen Ting-Yu , Lin Yi-Ching , Lin Yung-Chang , Chen Chia-Hung , Peng Yen-Ping , Lin Ming-Hsun
Published: July 2021

Atmospheric particulate matters (PMs) were measured in an industry-intensive region in central Taiwan in order to investigate the characteristics and possible sources of PMs. The samplings were simultaneously conducted using a 10- and 3-stage Micro Orifice Uniform Deposit Impactor (MOUDI) from 2017 to 2018. In this study, the characteristics of PMs in this region were evaluated by measuring the mass concentration of PMs and analyzing water-soluble ions and metallic elements, as well as dioxins. Additionally, principal component analysis (PCA) was used to identify the potential sources of PMs. The results showed that the mean concentration of coarse (>1.8 μm), fine (0.1–1.8 μm), and ultrafine (<0.1 μm) particles were 13.60, 14.38, and 3.44 μg/m3, respectively. In the industry-intensive region, the size distribution of ambient particles showed a bi-modal distribution with a high concentration of coarse particles in the spring and summer, while fine particles were dominant in the autumn and winter. The most abundant water-soluble ions of PMs were NO3−, Cl−, and SO42−, while the majority of metallic elements were Na, Fe, Ca, Al, and Mg in different particle sizes. The results of Pearson’s correlation analysis for metals indicated that the particles in the collected air samples were related to the iron and steelmaking industries, coal burning, vehicle exhausts, and high-tech industries. The dioxin concentration ranged from 0.0006 to 0.0017 pg I-TEQ/Nm3. Principal component analysis (PCA) revealed that the contribution to PMs was associated with sea salt, secondary pollutants, and industrial process.
Effect of Temperature on Sowing Dates of Wheat under Arid and Semi-Arid Climatic Regions and Impact Quantification of Climate Change through Mechanistic Modeling with Evidence from Field
Authors: Hussain Jamshad , Khaliq Tasneem , Rahman Muhammad Habib ur , Ullah Asmat , Ahmed Ishfaq , Srivastava Amit Kumar , Gaiser Thomas , Ahmad Ashfaq
Published: July 2021

Rising temperature from climate change is the most threatening factor worldwide for crop production. Sustainable wheat production is a challenge due to climate change and variability, which is ultimately a serious threat to food security in Pakistan. A series of field experiments were conducted during seasons 2013–2014 and 2014–2015 in the semi-arid (Faisalabad) and arid (Layyah) regions of Punjab-Pakistan. Three spring wheat genotypes were evaluated under eleven sowing dates from 16 October to 16 March, with an interval of 14–16 days in the two regions. Data for the model calibration and evaluation were collected from field experiments following the standard procedures and protocols. The grain yield under future climate scenarios was simulated by using a well-calibrated CERES-wheat model included in DSSAT v4.7. Future (2051–2100) and baseline (1980–2015) climatic data were simulated using 29 global circulation models (GCMs) under representative concentration pathway (RCP) 8.5. These GCMs were distributed among five quadrants of climatic conditions (Hot/Wet, Hot/Dry, Cool/Dry, Cool/Wet, and Middle) by a stretched distribution approach based on temperature and rainfall change. A maximum of ten GCMs predicted the chances of Middle climatic conditions during the second half of the century (2051–2100). The average temperature during the wheat season in a semi-arid region and arid region would increase by 3.52 °C and 3.84 °C, respectively, under Middle climatic conditions using the RCP 8.5 scenario during the second half-century. The simulated grain yield was reduced by 23.5% in the semi-arid region and 35.45% in the arid region under Middle climatic conditions (scenario). Mean seasonal temperature (MST) of sowing dates ranged from 16 to 27.3 °C, while the mean temperature from the heading to maturity (MTHM) stage was varying between 12.9 to 30.4 °C. Coefficients of determination (R2) between wheat morphology parameters and temperature were highly significant, with a range of 0.84–0.96. Impacts of temperature on wheat sown on 15 March were found to be as severe as to exterminate the crop before heading. The spikes and spikelets were not formed under a mean seasonal temperature higher than 25.5 °C. In a nutshell, elevated temperature (3–4 °C) till the end-century can reduce grain yield by about 30% in semi-arid and arid regions of Pakistan. These findings are crucial for growers and especially for policymakers to decide on sustainable wheat production for food security in the region.
Long Colimits of Topological Groups III: Homeomorphisms of Products and Coproducts
Authors: Dahmen Rafael , Lukács Gábor
Published: July 2021

The group of compactly supported homeomorphisms on a Tychonoff space can be topologized in a number of ways, including as a colimit of homeomorphism groups with a given compact support or as a subgroup of the homeomorphism group of its Stone-Čech compactification. A space is said to have the Compactly Supported Homeomorphism Property (CSHP) if these two topologies coincide. The authors provide necessary and sufficient conditions for finite products of ordinals equipped with the order topology to have CSHP. In addition, necessary conditions are presented for finite products and coproducts of spaces to have CSHP.
Programmed Cell Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor of Treatment Response in Patients with Urothelial Carcinoma
Authors: Chiang Pei-Jhang , Xu Ting , Cha Tai-Lung , Tsai Yi-Ta , Liu Shu-Yu , Wu Sheng-Tang , Meng En , Tsao Chih-Wei , Kao Chien-Chang , Chen Chin-Li , Sun Guang-Huan , Yu Dah-Shyong , Chang Sun-Yran , Yang Ming-Hsin
Published: July 2021

Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.
Suspension of Amorphous Calcium Phosphate Nanoparticles Impact Commitment of Human Adipose-Derived Stem Cells In Vitro
Authors: Wolint Petra , Näf Lukas , Schibler Désirée , Hild Nora , Stark Wendelin J. , Giovanoli Pietro , Calcagni Maurizio , Buschmann Johanna
Published: July 2021

Amorphous calcium phosphate (aCaP) nanoparticles may trigger the osteogenic commitment of adipose-derived stem cells (ASCs) in vitro. The ASCs of three human donors are investigated using basal culture medium DMEM to either 5 or 50 µg/mL aCaP nanoparticles suspension (control: no nanoparticles). After 7 or 14 days, stem cell marker genes, as well as endothelial, osteogenic, chondrogenic, and adipogenic genes, are analyzed by qPCR. Free calcium and phosphate ion concentrations are assessed in the cell culture supernatant. After one week and 5 µg/mL aCaP, downregulation of osteogenic markers ALP and Runx2 is found, and averaged across the three donors. Our results show that after two weeks, ALP is further downregulated, but Runx2 is upregulated. Endothelial cell marker genes, such as CD31 and CD34, are upregulated with 50 µg/mL aCaP and a 2-week exposure. Inter-donor variability is high: Two out of three donors show a significant upregulation of ALP and Runx2 at day 14 with 50 µg/mL aCaP compared to 5 µg/mL aCaP. Notably, all changes in stem cell commitment are obtained in the absence of an osteogenic medium. While the chemical composition of the culture medium and the saturation status towards calcium phosphate phases remain approximately the same for all conditions, gene expression of ASCs changes considerably. Hence, aCaP nanoparticles show the potential to trigger osteogenic and endothelial commitment in ASCs.
Knowledge Gaps in the Definition of Threats for the Red List Assessment of European Freshwater-Dependent Fish Species
Authors: Branco Paulo , Segurado Pedro , Costa Maria João , Teixeira Afonso , Santos José Maria , Ferreira Maria Teresa , Duarte Gonçalo
Published: July 2021

Freshwater ecosystems are disproportionally important for biodiversity conservation, as they support more than 9% of known animal species while representing less than 1% of the Earth’s surface. However, the vast majority of the threats (99%, or 826 out of 837) identified by the International Union for Conservation of Nature Red List of Threatened Species known to affect the 434 known freshwater-dependent fish and lampreys of Europe are not supported by validated published scientific knowledge. This general lack of information about freshwater-dependent fish and lamprey species may have deleterious effects on species conservation, and additional funding is required to fill baseline knowledge gaps.
Mitochondria and Antibiotics: For Good or for Evil?
Authors: Suárez-Rivero Juan M. , Pastor-Maldonado Carmen J. , Povea-Cabello Suleva , Álvarez-Córdoba Mónica , Villalón-García Irene , Talaverón-Rey Marta , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Sánchez-Alcázar José A.
Published: July 2021

The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed.
Combined Beneficial Effect of Genistein and Atorvastatin on Adipogenesis in 3T3-L1 Adipocytes
Authors: Lee Dahae , Kim Ji-Youn , Kim Hae-Won , Yoo Jeong-Eun , Kang Ki Sung
Published: July 2021

Genistein (4,5,7-trihydroxyisoflavone) is abundant in various dietary vegetables, especially soybeans, and is known to have not only an estrogenic effect but also an antiadipogenic effect. Atorvastatin (dihydroxy monocarboxylic acid) is a statin used to prevent heart disease. Although genistein and atorvastatin have been reported to possess antiadipogenic effects, their combined effects are still unclear. The aim of the current study was to explore whether the combination of genistein and atorvastatin at low concentrations significantly suppresses adipogenesis in a murine preadipocyte cell line (3T3-L1) compared to treatment with genistein or atorvastatin alone. Our results showed that cotreatment with 50 µM genistein and 50 nM atorvastatin significantly suppressed preadipocyte differentiation, whereas when each compound was used alone, there was no inhibitory effect. Additionally, cotreatment with genistein and atorvastatin significantly downregulated adipogenic marker proteins, including mitogen-activated protein kinases (MAPKs), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), glucocorticoid receptor (GR), and CCAAT/enhancer-binding protein β (C/EBPβ). This is the first evidence of the combined antiadipogenic effects of genistein and atorvastatin. Although additional experiments are required, combinational treatment with genistein and atorvastatin may be an alternative treatment for menopause-associated lipid metabolic disorders and obesity.
Can Glycosylation Mask the Detection of MHC Expressing p53 Peptides by T Cell Receptors?
Authors: Nguyen Thanh Binh , Lane David P. , Verma Chandra S.
Published: July 2021

Proteins of the major histocompatibility complex (MHC) class I, or human leukocyte antigen (HLA) in humans interact with endogenous peptides and present them to T cell receptors (TCR), which in turn tune the immune system to recognize and discriminate between self and foreign (non-self) peptides. Of especial importance are peptides derived from tumor-associated antigens. T cells recognizing these peptides are found in cancer patients, but not in cancer-free individuals. What stimulates this recognition, which is vital for the success of checkpoint based therapy? A peptide derived from the protein p53 (residues 161–169 or p161) was reported to show this behavior. T cells recognizing this unmodified peptide could be further stimulated in vitro to create effective cancer killing CTLs (cytotoxic T lymphocytes). We hypothesize that the underlying difference may arise from post-translational glycosylation of p161 in normal individuals, likely masking it against recognition by TCR. Defects in glycosylation in cancer cells may allow the presentation of the native peptide. We investigate the structural consequences of such peptide glycosylation by investigating the associated structural dynamics.
A Sarcopenia Detection System Using an RGB-D Camera and an Ultrasound Probe: Eye-in-Hand Approach
Authors: Kim Yeoun-Jae , Choi Jueun , Moon Jungwoo , Sung Kyung Rim , Choi Jaesoon
Published: July 2021

Skeletal muscle mass deficiency and quality degradation constitute sarcopenia for elderly people. Sarcopenia can result in musculoskeletal damage and accompany various metabolic problems, which make early sarcopenia diagnosis important. Various modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), have been developed for screening sarcopenia. Recently, ultrasound scanning was suggested for screening sarcopenia because of its safety, usability, and cost effectiveness. However, there has been no standardized assessment methodology for screening sarcopenia with ultrasound scanning. Therefore, prior to this study, we developed a four-degrees-of-freedom (DOF) sarcopenia detection system using an RGB-D camera and an ultrasound probe to automatically scan the human thigh without operator dependency. However, due to the eye-to-hand approach with the RGB-D camera, the system has limited usability for clinical trials. Therefore, in this study we modified the system such that it became eye-in-hand by attaching the RGB-D camera to the upper part of the system with an enhanced arc fitting algorithm. The modified system and enhanced algorithm were verified by an in-vitro test with bean curd-gelatin phantom. The results showed that the thickness of bean curd in the gelatin phantom was maintained at approximately 12.7 ± 0.35 mm over the 71.5∘ scanning range with 2.49 ± 0.15 N radial force at various thickness measuring points.
Disrupted Functional Rich-Club Organization of the Brain Networks in Children with Attention-Deficit/Hyperactivity Disorder, a Resting-State EEG Study
Authors: Ahmadi Maliheh , Kazemi Kamran , Kuc Katarzyna , Cybulska-Klosowicz Anita , Helfroush Mohammad Sadegh , Aarabi Ardalan
Published: July 2021

Growing evidence indicates that disruptions in the brain’s functional connectivity play an important role in the pathophysiology of ADHD. The present study investigates alterations in resting-state EEG source connectivity and rich-club organization in children with inattentive (ADHDI) and combined (ADHDC) ADHD compared with typically developing children (TD) under the eyes-closed condition. EEG source analysis was performed by eLORETA in different frequency bands. The lagged phase synchronization (LPS) and graph theoretical metrics were then used to examine group differences in the topological properties and rich-club organization of functional networks. Compared with the TD children, the ADHDI children were characterized by a widespread significant decrease in delta and beta LPS, as well as increased theta and alpha LPS in the left frontal and right occipital regions. The ADHDC children displayed significant increases in LPS in the central, temporal and posterior areas. Both ADHD groups showed small-worldness properties with significant increases and decreases in the network degree in the θ and β bands, respectively. Both subtypes also displayed reduced levels of network segregation. Group differences in rich-club distribution were found in the central and posterior areas. Our findings suggest that resting-state EEG source connectivity analysis can better characterize alterations in the rich-club organization of functional brain networks in ADHD patients.
Brain Structural Connectivity Differences in Patients with Normal Cognition and Cognitive Impairment
Authors: Zdanovskis Nauris , Platkājis Ardis , Kostiks Andrejs , Karelis Guntis , Grigorjeva Oļesja
Published: July 2021

Advances in magnetic resonance imaging, particularly diffusion imaging, have allowed researchers to analyze brain connectivity. Identification of structural connectivity differences between patients with normal cognition, cognitive impairment, and dementia could lead to new biomarker discoveries that could improve dementia diagnostics. In our study, we analyzed 22 patients (11 control group patients, 11 dementia group patients) that underwent 3T MRI diffusion tensor imaging (DTI) scans and the Montreal Cognitive Assessment (MoCA) test. We reconstructed DTI images and used the Desikan–Killiany–Tourville cortical parcellation atlas. The connectivity matrix was calculated, and graph theoretical analysis was conducted using DSI Studio. We found statistically significant differences between groups in the graph density, network characteristic path length, small-worldness, global efficiency, and rich club organization. We did not find statistically significant differences between groups in the average clustering coefficient and the assortativity coefficient. These statistically significant graph theory measures could potentially be used as quantitative biomarkers in cognitive impairment and dementia diagnostics.
Distinct Cellular Profiles of Hif1a and Vegf mRNA Localization in Microglia, Astrocytes and Neurons during a Period of Vascular Maturation in the Auditory Brainstem of Neonate Rats
Authors: Chang Daphne , Brown Quetanya , Tsui Grace , He Ye , Liu Jia , Shi Lingyan , Rodríguez-Contreras Adrián
Published: July 2021

Defining the relationship between vascular development and the expression of hypoxia-inducible factors (Hifs) and vascular endothelial growth factor (Vegf) in the auditory brainstem is important to understand how tissue hypoxia caused by oxygen shortage contributes to sensory deficits in neonates. In this study, we used histology, molecular labeling, confocal microscopy and 3D image processing methods to test the hypothesis that significant maturation of the vascular bed in the medial nucleus of the trapezoid body (MNTB) occurs during the postnatal period that precedes hearing onset. Isolectin-B4 histochemistry experiments suggested that the MNTB vasculature becomes more elaborate between P5 and P10. When combined with a cell proliferation marker and immunohistochemistry, we found that vascular growth coincides with a switch in the localization of proliferating cells to perivascular locations, and an increase in the density of microglia within the MNTB. Furthermore, microglia were identified as perivascular cells with proliferative activity during the period of vascular maturation. Lastly, combined in situ hybridization and immunohistochemistry experiments showed distinct profiles of Hif1a and Vegf mRNA localization in microglia, astrocytes and MNTB principal neurons. These results suggest that different cells of the neuro-glio-vascular unit are likely targets of hypoxic insult in the auditory brainstem of neonate rats.
Minor Non-Disabling Stroke Patients with Large Vessel Severe Stenosis or Occlusion Might Benefit from Thrombolysis
Authors: Zhong Wansi , Zhou Ying , Zhang Kemeng , Yan Shenqiang , Sun Jianzhong , Lou Min
Published: July 2021

Background: The benefit of alteplase in minor non-disabling acute ischemic stroke (AIS) is unknown. We aimed to explore the clinical efficacy of alteplase-treatment in minor non-disabling stroke in clinical practice. Methods: We used a prospectively collected database of AIS patients who were being assessed for thrombolysis with alteplase. Minor non-disabling AIS was identified as patients with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 and a score 0 or 1 on each baseline NIHSS score item (items 1a to 1c being 0). Results: A total of 461 patients with minor non-disabling AIS were included and among them 240 (52.1%) patients were treated with alteplase and 113 (24.5%) patients had severe stenosis/occlusion of large vessels. No significant association of 90-day excellent outcome was found with alteplase-treatment (77.1% vs. 80.5%, p 1 = 0.425; OR 0.911, 95% CI 0.428 to 1.940; p 2 = 0.808). However, among patients with severe stenosis/occlusion of large vessels, alteplase-treatment was independently associated with excellent outcome (74.4% vs. 45.7%, p 1 = 0.005; OR 4.709, 95% CI 1.391 to 11.962; p 2 = 0.010). Conclusion: Although alteplase-treatment did not result in an excellent outcome in general minor non-disabling stroke patients, it may work in those specific patients who had severe stenosis/occlusion of large vessels.
Enhanced Expectation of External Sensations of the Chest Regulates the Emotional Perception of Fearful Faces
Authors: Jung Won-Mo , Lee In-Seon , Lee Ye-Seul , Ryu Yeonhee , Park Hi-Joon , Chae Younbyoung
Published: July 2021

Emotional perception can be shaped by inferences about bodily states. Here, we investigated whether exteroceptive inferences about bodily sensations in the chest area influence the perception of fearful faces. Twenty-two participants received pseudo-electrical acupuncture stimulation at three different acupoints: CV17 (chest), CV23 (chin), and PC6 (left forearm). All stimuli were delivered with corresponding visual cues, and the control condition included visual cues that did not match the stimulated body sites. After the stimulation, the participants were shown images with one of five morphed facial expressions, ranging from 100% fear to 100% disgust, and asked to classify them as fearful or disgusted. Brain activity was measured using functional magnetic resonance imaging during the facial expression classification task. When the participants expected that they would receive stimulation of the chest (CV17), the ratio of fearful to non-fearful classifications decreased compared to the control condition, and brain activities within the periaqueductal gray and the default mode network decreased when they viewed fearful faces. Our findings suggest that bodily sensations around the chest, but not the other tested body parts, were selectively associated with fear perception and that altering external inferences inhibited the perception of fearful faces.
Transcranial Direct Current Stimulation (tDCS) for Depression during Pregnancy: Results from an Open-Label Pilot Study
Authors: Kurzeck Anna Katharina , Dechantsreiter Esther , Wilkening Anja , Kumpf Ulrike , Nenov-Matt Tabea , Padberg Frank , Palm Ulrich
Published: July 2021

Introduction: Depression is the most common morbidity during pregnancy. Available first-line therapy options are limited and depressive disorders in pregnant women are often untreated, leading to negative effects on maternal and fetal health. Objectives: The aim of this open-label pilot study is to extend evidence on the use of transcranial direct current stimulation (tDCS) as a treatment of antenatal depression and to point out options for the use of tDCS in this population. Methods: Six drug-free female patients with major depressive disorder during pregnancy (later than 10th gestational week) were included in this pilot study. Patients were treated with twice-daily tDCS (2 mA, 30 min, anode: F3, cathode: F4) over ten days during inpatient stay (Phase 1) and with once-daily tDCS over 10 days during an optional outpatient stay (Phase 2). Clinical (HAMD-21, BDI) and neuropsychological ratings (Trail Making Test A/B) were performed at baseline, after two and four weeks as well as an obstetric examination. Results: Six right-handed females (23–43 years, 12–33. gestational week) completed Phase 1; four patients additionally joined in Phase 2. tDCS was well tolerated and no adverse effects occurred. Clinical ratings showed an improvement of mean baseline HAMD-21 from 22.50 ± 7.56 to 13.67 ± 3.93 after week 2, and to 8.75 ± 4.99 after week 4. The mean baseline BDI was 26.00 ± 13.90 and declined to 11.17 ± 5.46 after week 2, and to 9.25 ± 3.30 after week 4. Conclusions: Statistically significant changes in HAMD-21 and BDI were observed after Phase 1. One patient achieved remission in terms of HAMD in Phase 1. Although this small-scale study lacks sham control, it shows clinical improvement and absence of adverse events in this critical population.
Oxcarbazepine for Behavioral Disorders after Brain Injury: Factors Influencing Efficacy
Authors: Pozzi Marco , Avantaggiato Paolo , Pastore Valentina , Carnovale Carla , Clementi Emilio , Strazzer Sandra
Published: July 2021

Carbamazepine and oxcarbazepine are used for behavioral disorders following organic diseases. After severe acquired brain injury, patients may develop frontal symptoms. In our neurological rehabilitation routine, oxcarbazepine is used for better safety over carbamazepine, although its efficacy is not clarified. We aimed to improve knowledge on this use of oxcarbazepine, by probing clinical factors associated with response. We retrospectively examined the clinical records of our patients, collecting clinical variables and outcomes of efficacy, both clinician-rated and caregiver/self-rated. We described the distribution of clinical variables and examined their associations via logistic regressions. Patients in our cohort were predominantly pediatric, with frontal lobe damage and irritable/reactive. With an oxcarbazepine median dose of 975 mg, almost half of patients improved. We found several clinical factors associated with clinician-rated efficacy: absence of frontal damage and absence of irritability/reactivity symptoms; clinical factors associated with caregivers/patients-rated efficacy were: higher DRS score at baseline and higher patient age. In this retrospective study, we observed that oxcarbazepine was differentially efficacious in patients with specific characteristics. Our study could not examine drug therapy separately from neuropsychological therapy, nor the influence of dose. Our associative results should be verified experimentally, also assessing causality and establishing dose-related efficacy and safety.
Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma
Authors: Dasgupta Shatavisha , Ewing-Graham Patricia C. , Swagemakers Sigrid M. A. , van den Bosch Thierry P. P. , Atmodimedjo Peggy N. , Verbiest Michael M. P. J. , de Haan Marit , van Doorn Helena C. , van der Spek Peter J. , Koljenović Senada , van Kemenade Folkert J.
Published: July 2021

DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ±0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.
Occupational Exposure to Carcinogens and Occupational Epidemiological Cancer Studies in Iran: A Review
Authors: Hosseini Bayan , Hall Amy L. , Zendehdel Kazem , Kromhout Hans , Onyije Felix M. , Moradzadeh Rahmatollah , Zamanian Maryam , Schüz Joachim , Olsson Ann
Published: July 2021

Introduction: The extent of exposure to occupational carcinogens is not well characterized in Iran, and little is known about the burden of occupational cancer. Objectives: This study aimed to describe exposure to occupational carcinogens and occupational epidemiology studies in Iran. Methods: Relevant studies up to January 2021 in Iran were identified through three databases (PubMed, Web of Science, and Google Scholar). Results: Forty-nine publications from 2009 to 2020 (one cohort, 11 case-control, 34 exposure monitoring studies, and three cancer burden studies) were included. The exposure monitoring studies were conducted mainly in the petroleum industry, metal industry, manufacturing of electronics, manufacturing of plastics, construction industry, and service industry. A few of the case-control studies also reported increased risk of cancers in relation to work in those industries. Conclusions: Occupational cancer epidemiology in Iran is at an early stage. Both epidemiological and exposure monitoring studies are generally limited in size to provide robust evidence of occupational cancer risks. A coherent strategy to estimate the occupational cancer burden in Iran should start with conducting epidemiological studies along with systematic monitoring of occupational carcinogens for use in hazard control and research.
Allele-Specific MicroRNA-Mediated Regulation of a Glycolysis Gatekeeper PDK1 in Cancer Metabolism
Authors: Subramaniam Sugarniya , Jeet Varinder , Gunter Jennifer H. , Clements Judith A. , Batra Jyotsna
Published: July 2021

Background: Emerging evidence has revealed that genetic variations in microRNA (miRNA) binding sites called miRSNPs can alter miRNA binding in an allele-specific manner and impart prostate cancer (PCa) risk. Two miRSNPs, rs1530865 (G > C) and rs2357637 (C > A), in the 3′ untranslated region of pyruvate dehydrogenase kinase 1 (PDK1) have been previously reported to be associated with PCa risk. However, these results have not been functionally validated. Methods: In silico analysis was used to predict miRNA–PDK1 interactions and was tested using PDK1 knockdown, miRNA overexpression and reporter gene assay. Results: PDK1 expression was found to be upregulated in PCa metastasis. Further, our results show that PDK1 suppression reduced the migration, invasion, and glycolysis of PCa cells. Computational predictions showed that miR-3916, miR-3125 and miR-3928 had a higher binding affinity for the C allele than the G allele for the rs1530865 miRSNP which was validated by reporter gene assays. Similarly, miR-2116 and miR-889 had a higher affinity for the A than C allele of the rs2357637 miRSNP. Overexpression of miR-3916 and miR-3125 decreased PDK1 protein levels in cells expressing the rs1530865 SNP C allele, and miR-2116 reduced in cells with the rs2357637 SNP A allele. Conclusions: The present study is the first to report the regulation of the PDK1 gene by miRNAs in an allele-dependent manner and highlights the role of PDK1 in metabolic adaption associated with PCa progression.