bluuebunny/crossref_metadata_2025 huggingface dataset:
Sampling of fluid through skin with magnetohydrodynamics for noninvasive glucose monitoring
Authors: Hakala Tuuli A. , García Pérez Alejandro , Wardale Melissa , Ruuth Ida A. , Vänskä Risto T. , Nurminen Teemu A. , Kemp Emily , Boeva Zhanna A. , Alakoskela Juha-Matti , Pettersson-Fernholm Kim , Hæggström Edward , Bobacka Johan
Published: April 2021

Out of 463 million people currently with diabetes, 232 million remain undiagnosed. Diabetes is a threat to human health, which could be mitigated via continuous self-monitoring of glucose. In addition to blood, interstitial fluid is considered to be a representative sample for glucose monitoring, which makes it highly attractive for wearable on-body sensing. However, new technologies are needed for efficient and noninvasive sampling of interstitial fluid through the skin. In this report, we introduce the use of Lorentz force and magnetohydrodynamics to noninvasively extract dermal interstitial fluid. Using porcine skin as an ex-vivo model, we demonstrate that the extraction rate of magnetohydrodynamics is superior to that of reverse iontophoresis. This work seeks to provide a safe, effective, and noninvasive sampling method to unlock the potential of wearable sensors in needle-free continuous glucose monitoring devices that can benefit people living with diabetes.
Effective Hamiltonian for silicene under arbitrary strain from multi-orbital basis
Authors: Siu Zhuo Bin , Jalil Mansoor B. A.
Published: April 2021

A tight-binding (TB) Hamiltonian is derived for strained silicene from a multi-orbital basis. The derivation is based on the Slater–Koster coupling parameters between different orbitals across the silicene lattice and takes into account arbitrary distortion of the lattice under strain, as well as the first and second-order spin–orbit interactions (SOI). The breaking of the lattice symmetry reveals additional SOI terms which were previously neglected. As an exemplary application, we apply the linearized low-energy TB Hamiltonian to model the current-induced spin accumulation in strained silicene coupled to an in-plane magnetization. The interplay between symmetry-breaking and the additional SOI terms induces an out-of-plane spin accumulation. This spin accumulation remains unbalanced after summing over the Fermi surfaces of the occupied bands and the two valleys, and can thus be utilized for spin torque switching.
Older adults use a motor plan that is detrimental to endpoint control
Authors: Delmas Stefan , Choi Yoon Jin , Komer Marcel , Weintraub Michelle , Yacoubi Basma , Christou Evangelos A.
Published: April 2021

Here, we aimed to understand if older adults (OA) use a unique motor plan that is detrimental to endpoint control. We performed two experiments that used ankle ballistic contractions that reversed at the target. In Experiment 1, eight young adults (YA; 27.1 ± 4.2) and eight OA (73.3 ± 4.5) aimed to perform an ankle dorsiflexion–plantarflexion movement that reversed at 9° in 180 ms (target). We found that the coordination pattern (motor plan) differed for the two groups. OA used significantly greater soleus (SOL) activity to reverse the ankle movement than YA and exhibited greater tibialis anterior (TA) muscle activity variability (p < 0.05). OA exhibited worse endpoint control than YA, which associated with the exacerbated TA variability (R2 > 0.2; p < 0.01). Experiment 2 aimed to confirm that the OA motor plan was detrimental to endpoint control. Fifteen YA (20.5 ± 1.4) performed an ankle dorsiflexion–plantarflexion contraction that reversed at 30% MVC in 160 ms by using either a pattern that mimicked OA (High SOL) or YA (Low SOL). With the High SOL coordination pattern, YA exhibited impaired endpoint control and greater TA activation variability. These findings provide strong evidence that OA select a unique motor plan that is detrimental to endpoint control.
Maintaining higher leaf photosynthesis after heading stage could promote biomass accumulation in rice
Authors: Honda Sotaro , Ohkubo Satoshi , San Nan Su , Nakkasame Anothai , Tomisawa Kazuki , Katsura Keisuke , Ookawa Taiichiro , Nagano Atsushi J. , Adachi Shunsuke
Published: April 2021

Leaf photosynthetic rate changes across the growing season as crop plants age. Most studies of leaf photosynthesis focus on a specific growth stage, leaving the question of which pattern of photosynthetic dynamics maximizes crop productivity unanswered. Here we obtained high-frequency data of canopy leaf CO2 assimilation rate (A) of two elite rice (Oryza sativa) cultivars and 76 inbred lines across the whole growing season. The integrated A value after heading was positively associated with crop growth rate (CGR) from heading to harvest, but that before heading was not. A curve-smoothing analysis of A after heading showed that accumulated A at > 80% of its maximum (A80) was positively correlated with CGR in analyses of all lines mixed and of lines grouped by genetic background, while the maximum A and accumulated A at ≤ 80% were less strongly correlated with CGR. We also found a genomic region (~ 12.2 Mb) that may enhance both A80 and aboveground biomass at harvest. We propose that maintaining a high A after heading, rather than having high maximum A, is a potential target for enhancing rice biomass accumulation.
Investigation of the Wilson gene ATP7B transcriptional start site and the effect of core promoter alterations
Authors: Höflich Clemens , Brieger Angela , Zeuzem Stefan , Plotz Guido
Published: April 2021

Pathogenic genetic variants in the ATP7B gene cause Wilson disease, a recessive disorder of copper metabolism showing a significant variability in clinical phenotype. Promoter mutations have been rarely reported, and controversial data exist on the site of transcription initiation (the core promoter). We quantitatively investigated transcription initiation and found it to be located in immediate proximity of the translational start. The effects human single-nucleotide alterations of conserved bases in the core promoter on transcriptional activity were moderate, explaining why clearly pathogenic mutations within the core promoter have not been reported. Furthermore, the core promoter contains two frequent polymorphisms (rs148013251 and rs2277448) that could contribute to phenotypical variability in Wilson disease patients with incompletely inactivating mutations. However, neither polymorphism significantly modulated ATP7B expression in vitro, nor were copper household parameters in healthy probands affected. In summary, the investigations allowed to determine the biologically relevant site of ATP7B transcription initiation and demonstrated that genetic variations in this site, although being the focus of transcriptional activity, do not contribute significantly to Wilson disease pathogenesis.
A new reduced-morphology model for CA1 pyramidal cells and its validation and comparison with other models using HippoUnit
Authors: Tomko Matus , Benuskova Lubica , Jedlicka Peter
Published: April 2021

Modeling long-term neuronal dynamics may require running long-lasting simulations. Such simulations are computationally expensive, and therefore it is advantageous to use simplified models that sufficiently reproduce the real neuronal properties. Reducing the complexity of the neuronal dendritic tree is one option. Therefore, we have developed a new reduced-morphology model of the rat CA1 pyramidal cell which retains major dendritic branch classes. To validate our model with experimental data, we used HippoUnit, a recently established standardized test suite for CA1 pyramidal cell models. The HippoUnit allowed us to systematically evaluate the somatic and dendritic properties of the model and compare them to models publicly available in the ModelDB database. Our model reproduced (1) somatic spiking properties, (2) somatic depolarization block, (3) EPSP attenuation, (4) action potential backpropagation, and (5) synaptic integration at oblique dendrites of CA1 neurons. The overall performance of the model in these tests achieved higher biological accuracy compared to other tested models. We conclude that, due to its realistic biophysics and low morphological complexity, our model captures key physiological features of CA1 pyramidal neurons and shortens computational time, respectively. Thus, the validated reduced-morphology model can be used for computationally demanding simulations as a substitute for more complex models.
Proteomic comparison between different tissue preservation methods for identification of promising biomarkers of urothelial bladder cancer
Authors: Valdés Alberto , Bitzios Athanasios , Kassa Eszter , Shevchenko Ganna , Falk Alexander , Malmström Per-Uno , Dragomir Anca , Segersten Ulrika , Lind Sara Bergström
Published: April 2021

Samples in biobanks are generally preserved by formalin-fixation and paraffin-embedding (FFPE) and/or optimal cutting temperature compound (OCT)-embedding and subsequently frozen. Mass spectrometry (MS)-based analysis of these samples is now available via developed protocols, however, the differences in results with respect to preservation methods needs further investigation. Here we use bladder urothelial carcinoma tissue of two different tumor stages (Ta/T1—non-muscle invasive bladder cancer (NMIBC), and T2/T3—muscle invasive bladder cancer (MIBC)) which, upon sampling, were divided and preserved by FFPE and OCT. Samples were parallel processed from the two methods and proteins were analyzed with label-free quantitative MS. Over 700 and 1200 proteins were quantified in FFPE and OCT samples, respectively. Multivariate analysis indicates that the preservation method is the main source of variation, but also tumors of different stages could be differentiated. Proteins involved in mitochondrial function were overrepresented in OCT data but missing in the FFPE data, indicating that these proteins are not well preserved by FFPE. Concordant results for proteins such as HMGCS2 (uniquely quantified in Ta/T1 tumors), and LGALS1, ANXA5 and plastin (upregulated in T2/T3 tumors) were observed in both FFPE and OCT data, which supports the use of MS technology for biobank samples and encourages the further evaluation of these proteins as biomarkers.
Mining the plasma-proteome associated genes in patients with gastro-esophageal cancers for biomarker discovery
Authors: Vizeacoumar Frederick S. , Guo Hongyu , Dwernychuk Lynn , Zaidi Adnan , Freywald Andrew , Wu Fang-Xiang , Vizeacoumar Franco J. , Ahmed Shahid
Published: April 2021

Gastro-esophageal (GE) cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of GE cancers, to yield predictive response to the available therapies. Our study aims to identify leading genes that are differentially regulated in patients with these cancers. We explored the expression data for those genes whose protein products can be detected in the plasma using the Cancer Genome Atlas to identify leading genes that are differentially regulated in patients with GE cancers. Our work predicted several candidates as potential biomarkers for distinct stages of GE cancers, including previously identified CST1, INHBA, STMN1, whose expression correlated with cancer recurrence, or resistance to adjuvant therapies or surgery. To define the predictive accuracy of these genes as possible biomarkers, we constructed a co-expression network and performed complex network analysis to measure the importance of the genes in terms of a ratio of closeness centrality (RCC). Furthermore, to measure the significance of these differentially regulated genes, we constructed an SVM classifier using machine learning approach and verified these genes by using receiver operator characteristic (ROC) curve as an evaluation metric. The area under the curve measure was > 0.9 for both the overexpressed and downregulated genes suggesting the potential use and reliability of these candidates as biomarkers. In summary, we identified leading differentially expressed genes in GE cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted treatment.
Genetic analysis and selection of Bambara groundnut (Vigna subterranea [L.] Verdc.) landraces for high yield revealed by qualitative and quantitative traits
Authors: Khan Md Mahmudul Hasan , Rafii Mohd Y. , Ramlee Shairul Izan , Jusoh Mashitah , Al Mamun Md
Published: April 2021

As a crop for the new millennium Bambara groundnut (Vigna subterranea [L.] Verdc.) considered as leading legumes in the tropical regions due to its versatile advantages. The main intent of this study was to find out the high yielding potential genotypes and considering these genotypes to develop pure lines for commercial cultivation in Malaysia. Considering the 14 qualitative and 27 quantitative traits of fifteen landraces the variation and genetic parameters namely, variability, heritability, genetic advance, characters association, and cluster matrix were determined. ANOVA revealed significant variation for all the agronomic traits (except plant height). Among the accessions, highly significant differences (P ≤ 0.01) were found for almost all the traits excluding fifty percent flowering date, seed length, seed width. The 16 traits out of the 27 quantitative traits had a coefficient of variation (CV) ≥ 20%. A positive and intermediate to perfect highly significant association (r = 0.23 to 1.00; P < 0.00) was found between yield and its related traits. The trait dry seed weight per plant (g) had the highest GCV = 59.91% and PCV = 59.57% whereas the trait fresh pod weight (99.55%), dry seed weight (98.86%), and yield (98.10%) were highly heritable. The genetic advance recorded the highest for dry seed weight (122.01%) and lowest (3.97%) for plant height. To validate the genetic disparity, an unweighted pair-group produce with arithmetic mean (UPGMA), principal component analysis (PCA), heatmap, and H’-index was performed considering 27 quantitative traits. The constructed dendrogram showed five distinct groups of accessions. Genotypes G2, G3, and G9 from Group IV consider as promising lines which gave 70.05% higher mean yield compared to grand mean yield (1180 kg ha−1) with desirable traits. Group II had a maximum number of accessions while group III and group V had one of each. However, findings declared that the availability of genetic variance will be beneficial for this crop improvement through cross breeding as well as the plant breeders to prefer desirable traits in V. subterranea L. Verdc. for further breeding purposes.
Tracing local sources and long-range transport of PM10 in central Taiwan by using chemical characteristics and Pb isotope ratios
Authors: Wu Po-Chao , Huang Kuo-Fang
Published: April 2021

Central Taiwan is among the most heavily polluted regions in Taiwan because of a complex mixing of local emissions from intense anthropogenic activities with natural dust. Long-range transport (LRT) of pollutants from outside Taiwan also contributes critically to the deterioration of air quality, especially during the northeast monsoon season. To identify the sources of particulate matter < 10 μm (PM10) in central Taiwan, this study performed several sampling campaigns, including three local events, one LRT event, and one dust storm event, during the northeast monsoon season of 2018/2019. The PM10 samples were analyzed for water-soluble ion and trace metal concentrations as well as Pb isotope ratios. Local sediments were also collected and analyzed to constrain chemical/isotopic signatures of natural sources. The Pb isotope data were interpreted together with the enrichment factors and elemental ratios of trace metals in PM10, and reanalysis data sets were used to delineate the sources of PM10 in central Taiwan. Our results suggested that Pb in PM10 was predominantly contributed by oil combustion and oil refineries during the local events (48–88%), whereas the lowest contributions were from coal combustion (< 21%). During periods of high wind speed, the contribution from natural sources increased significantly from 13 to 31%. Despite Pb represented only a small portion of PM10, a strong correlation (r = 0.89, p  < 0.001, multiple regression analysis) between PM10 mass and the concentrations of Pb, V, and Al was observed in the study area, suggesting that the sources of PM10 in central Taiwan can be possibly tracked by using chemical characteristics and Pb isotopes in PM10. Moreover, the Pb isotopic signals of PM10 collected during the LRT event confirmed the impact of LRT from Mainland China, and the chemical characteristics of the PM10 significantly differed from those of the PM10 collected during local events. This study demonstrates the robustness of using a combination of Pb isotopic compositions and chemical characteristics in PM10 for source tracing in complex and heavily polluted areas.
Crowdsourced privacy-preserved feature tagging of short home videos for machine learning ASD detection
Authors: Washington Peter , Tariq Qandeel , Leblanc Emilie , Chrisman Brianna , Dunlap Kaitlyn , Kline Aaron , Kalantarian Haik , Penev Yordan , Paskov Kelley , Voss Catalin , Stockham Nathaniel , Varma Maya , Husic Arman , Kent Jack , Haber Nick , Winograd Terry , Wall Dennis P.
Published: April 2021

Standard medical diagnosis of mental health conditions requires licensed experts who are increasingly outnumbered by those at risk, limiting reach. We test the hypothesis that a trustworthy crowd of non-experts can efficiently annotate behavioral features needed for accurate machine learning detection of the common childhood developmental disorder Autism Spectrum Disorder (ASD) for children under 8 years old. We implement a novel process for identifying and certifying a trustworthy distributed workforce for video feature extraction, selecting a workforce of 102 workers from a pool of 1,107. Two previously validated ASD logistic regression classifiers, evaluated against parent-reported diagnoses, were used to assess the accuracy of the trusted crowd’s ratings of unstructured home videos. A representative balanced sample (N = 50 videos) of videos were evaluated with and without face box and pitch shift privacy alterations, with AUROC and AUPRC scores > 0.98. With both privacy-preserving modifications, sensitivity is preserved (96.0%) while maintaining specificity (80.0%) and accuracy (88.0%) at levels comparable to prior classification methods without alterations. We find that machine learning classification from features extracted by a certified nonexpert crowd achieves high performance for ASD detection from natural home videos of the child at risk and maintains high sensitivity when privacy-preserving mechanisms are applied. These results suggest that privacy-safeguarded crowdsourced analysis of short home videos can help enable rapid and mobile machine-learning detection of developmental delays in children.
Assessment of water resource security in karst area of Guizhou Province, China
Authors: Liu Liying
Published: April 2021

This paper presents the assessment of water resource security in the Guizhou karst area, China. A mean impact value and back-propagation (MIV-BP) neural network was used to understand the influencing factors. Thirty-one indices involving five aspects, the water quality subsystem, water quantity subsystem, engineering water shortage subsystem, water resource vulnerability subsystem, and water resource carrying capacity subsystem, were selected to establish an evaluation index of water resource security. In addition, a genetic algorithm and back-propagation (GA-BP) neural network was constructed to assess the water resource security of Guizhou Province from 2001 to 2015. The results show that water resource security in Guizhou was at a moderate warning level from 2001 to 2006 and a critical safety level from 2007 to 2015, except in 2011 when a moderate warning level was reached. For protection and management of water resources in a karst area, the modes of development and utilization of water resources must be thoroughly understood, along with the impact of engineering water shortage. These results are a meaningful contribution to regional ecological restoration and socio-economic development and can promote better practices for future planning.
A refined medium to enhance the antimicrobial activity of postbiotic produced by Lactiplantibacillus plantarum RS5
Authors: Ooi May Foong , Foo Hooi Ling , Loh Teck Chwen , Mohamad Rosfarizan , Rahim Raha Abdul , Ariff Arbakariya
Published: April 2021

Postbiotic RS5, produced by Lactiplantibacillus plantarum RS5, has been identified as a promising alternative feed supplement for various livestock. This study aimed to lower the production cost by enhancing the antimicrobial activity of the postbiotic RS5 by improving the culture density of L. plantarum RS5 and reducing the cost of growth medium. A combination of conventional and statistical-based approaches (Fractional Factorial Design and Central Composite Design of Response Surface Methodology) was employed to develop a refined medium for the enhancement of the antimicrobial activity of postbiotic RS5. A refined medium containing 20 g/L of glucose, 27.84 g/L of yeast extract, 5.75 g/L of sodium acetate, 1.12 g/L of Tween 80 and 0.05 g/L of manganese sulphate enhanced the antimicrobial activity of postbiotic RS5 by 108%. The cost of the production medium was reduced by 85% as compared to the commercially available de Man, Rogosa and Sharpe medium that is typically used for Lactobacillus cultivation. Hence, the refined medium has made the postbiotic RS5 more feasible and cost-effective to be adopted as a feed supplement for various livestock industries.
Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity
Authors: Ottolenghi Aner , Bolel Priyanka , Sarkar Rhitajit , Greenshpan Yariv , Iraqi Muhammed , Ghosh Susmita , Bhattacharya Baisali , Taylor Zoe V. , Kundu Kiran , Radinsky Olga , Gazit Roi , Stepensky David , Apte Ron N. , Voronov Elena , Porgador Angel
Published: April 2021

IL-2 is the master-regulator cytokine for T cell dependent responses and is crucial for proliferation and survival of T cells. However, IL-2-based treatments remained marginal, in part due to short half-life. Thus, we aimed to extend IL-2 half-life by flanking the IL-2 core with sequences derived from the extensively glycosylated hinge region of the NCR2 receptor. We termed this modified IL-2: “S2A”. Importantly, S2A blood half-life was extended 14-fold compared to the clinical grade IL-2, Proleukin. Low doses inoculation of S2A significantly enhanced induction of Tregs (CD4+ Regulatory T cells) in vivo, as compared to Proleukin, while both S2A and Proleukin induced low levels of CD8+ T cells. In a B16 metastatic melanoma model, S2A treatment was unable to reduce the metastatic capacity of B16 melanoma, while enhancing induction and recruitment of Tregs, compared to Proleukin. Conversely, in two autoimmune models, rheumatoid arthritis and DSS-induced colitis, S2A treatment significantly reduced the progression of disease compared to Proleukin. Our results suggest new avenues for generating long-acting IL-2 for long-standing treatment and a new technique for manipulating short-life proteins for clinical and research uses.
Characterization of a new natural fiber extracted from Corypha taliera fruit
Authors: Tamanna Taslima Ahmed , Belal Shah Alimuzzaman , Shibly Mohammad Abul Hasan , Khan Ayub Nabi
Published: April 2021

This study deals with the determination of new natural fibers extracted from the Corypha taliera fruit (CTF) and its characteristics were reported for the potential alternative of harmful synthetic fiber. The physical, chemical, mechanical, thermal, and morphological characteristics were investigated for CTF fibers. X-ray diffraction and chemical composition characterization ensured a higher amount of cellulose (55.1 wt%) content and crystallinity (62.5%) in the CTF fiber. The FTIR analysis ensured the different functional groups of cellulose, hemicellulose, and lignin present in the fiber. The Scherrer’s equation was used to determine crystallite size 1.45 nm. The mean diameter, specific density, and linear density of the CTF fiber were found (average) 131 μm, 0.86 g/cc, and 43 Tex, respectively. The maximum tensile strength was obtained 53.55 MPa for GL 20 mm and Young’s modulus 572.21 MPa for GL 30 mm. The required energy at break was recorded during the tensile strength experiment from the tensile strength tester and the average values for GL 20 mm and GL 30 mm are 0.05381 J and 0.08968 J, respectively. The thermal analysis ensured the thermal sustainability of CTF fiber up to 230 °C. Entirely the aforementioned outcomes ensured that the new CTF fiber is the expected reinforcement to the fiber-reinforced composite materials.
Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival
Authors: Gentiluomo Manuel , Corradi Chiara , Vanella Giuseppe , Johansen Astrid Z. , Strobel Oliver , Szentesi Andrea , Milanetto Anna Caterina , Hegyi Péter , Kupcinskas Juozas , Tavano Francesca , Neoptolemos John P. , Bozzato Dania , Hackert Thilo , Pezzilli Raffaele , Johansen Julia S. , Costello Eithne , Mohelnikova-Duchonova Beatrice , van Eijck Casper H. J. , Talar-Wojnarowska Renata , Hansen Carsten Palnæs , Darvasi Erika , Chen Inna M. , Cavestro Giulia Martina , Soucek Pavel , Piredda Liliana , Vodicka Pavel , Gazouli Maria , Arcidiacono Paolo Giorgio , Canzian Federico , Campa Daniele , Capurso Gabriele
Published: April 2021

Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients’ response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58–15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.
Assessing the relationship between pregravid body mass index and risk of adverse maternal pregnancy and neonatal outcomes: prospective data in Southwest China
Authors: Chen Yue , Wan Ke , Gong Yunhui , Zhang Xiao , Liang Yi , Wang Xiaoyu , Feng Ping , He Fang , Zhou Rong , Yang Dagang , Jia Hong , Cheng Guo , Shimokawa Toshio
Published: April 2021

The relevance of pregestational body mass index (BMI) on adverse pregnancy outcomes remained unclear in Southwest China. This study aimed to investigate the overall and age-category specific association between pre-gestational BMI and gestational diabetes mellitus (GDM), preeclampsia, cesarean delivery, preterm delivery, stillbirth, macrosomia, and small-for-gestational age (SGA) or large-for-gestational age (LGA) neonates in Southwest China. Furthermore, it explores the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. 51,125 Chinese singleton pregnant women were recruited as study subjects. Multiple logistic regression models were used to examine the influence of pre-pregnancy BMI on adverse pregnancy outcomes. Gradient boosting machine was used to evaluate the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. It is found that women who were overweight or obese before pregnancy are at higher risk of adverse pregnancy outcomes except for SGA neonates, while pre-pregnancy underweight is a protective factor for GDM, preeclampsia, cesarean delivery, macrosomia and LGA, but not SGA. Younger mothers are more susceptible to GDM and macrosomia neonates, while older mothers are more prone to preeclampsia. Pre-pregnancy BMI has more influence on various pregnancy outcomes than maternal age. To improve pregnancy outcomes, normal BMI weight as well as relatively young maternal ages are recommended for women in child-bearing age.
MiR-485 targets the DTX4 gene to regulate milk fat synthesis in bovine mammary epithelial cells
Authors: Liu Juan , Jiang Ping , Iqbal Ambreen , Ali Shaokat , Gao Zhen , Pan Ziyi , Xia Lixin , Yin Fuquan , Zhao Zhihui
Published: April 2021

MicroRNAs (miRNAs) are mRNA suppressors that regulate a variety of cellular and physiological processes, including cell proliferation, apoptosis, triglyceride synthesis, fat formation, and lipolysis, by post-transcriptional processing. In previous studies, we isolated and sequenced miRNAs from mammary epithelial cells from Chinese Holstein cows with high and low milk fat percentages. MiR-485 was one of the significantly differentially expressed miRNAs that were identified. In the present study, the relationship between the candidate target gene DTX4 and miR-485 was validated by bioinformatics and real-time fluorescent quantitative PCR (qRT-PCR) and Western blot (WB) analyses in bovine mammary epithelial cells (bMECs). The results indicated that miR-485 negatively regulated the mRNA expression of the target gene DTX4. Furthermore, an shRNA interference vector for the target gene DTX4 was constructed successfully, and it increased the triglyceride content and reduced the cholesterol content of transfected cells. These results suggest that miR-485 may affect the contents of triglycerides (TGs) and cholesterol (CHOL) by targeting the DTX4 gene. This study indicates that miR-485 has a role in regulating milk fat synthesis and that miR-485 targets the DTX4 gene to regulate lipid metabolism in bMECs. These findings contribute to the understanding of the functional significance of miR-485 in milk fat synthesis.
CGRP protects bladder smooth muscle cells stimulated by high glucose through inhibiting p38 MAPK pathway in vitro
Authors: Xue Jun , Liu Yadong , Zhang Sichong , Ding Liucheng , Shen Baixin , Shao Yunpeng , Wei Zhongqing
Published: April 2021

This study aimed to explore the effect of calcitonin gene-related peptide (CGRP) on bladder smooth muscle cells (BSMCs) under high glucose (HG) treatment in vitro. BSMCs from Sprague–Dawley rat bladders were cultured and passaged in vitro. The third-generation cells were cultured and divided into control group, HG group, HG + CGRP group, HG + CGRP + asiatic acid (AA, p-p38 activator) group, CGRP group, AA group, HG + CGRP + CGRP-8-37 (CGRP receptor antagonist) group and HG + LY2228820 (p38 MAPK inhibitor) group. The cell viability, apoptosis, malondialdehyde (MDA) and superoxide dismutase (SOD) levels of BSMCs were observed by the relevant detection kits. The expressions of α-SM-actin, p38 and p-p38 were detected by qRT-PCR or Western blot analysis. Compared with the control group, the cell viability, SOD and α-SM-actin levels of BSMCs were decreased and apoptotic cells, MDA and p-p38 levels were increased after HG treatment, while these changes could be partly reversed when BSMCs were treated with HG and CGRP or LY2228820 together. Moreover, AA or CGRP-8-37 could suppress the effect of CGRP on BSMCs under HG condition. Our data indicate that CGRP protects BSMCs from oxidative stress induced by HG in vitro, and inhibit the α-SM-actin expression decrease through inhibiting the intracellular p38 MAPK signaling pathway.
Deep learning approach for automatic landmark detection and alignment analysis in whole-spine lateral radiographs
Authors: Yeh Yu-Cheng , Weng Chi-Hung , Huang Yu-Jui , Fu Chen-Ju , Tsai Tsung-Ting , Yeh Chao-Yuan
Published: April 2021

Human spinal balance assessment relies considerably on sagittal radiographic parameter measurement. Deep learning could be applied for automatic landmark detection and alignment analysis, with mild to moderate standard errors and favourable correlations with manual measurement. In this study, based on 2210 annotated images of various spinal disease aetiologies, we developed deep learning models capable of automatically locating 45 anatomic landmarks and subsequently generating 18 radiographic parameters on a whole-spine lateral radiograph. In the assessment of model performance, the localisation accuracy and learning speed were the highest for landmarks in the cervical area, followed by those in the lumbosacral, thoracic, and femoral areas. All the predicted radiographic parameters were significantly correlated with ground truth values (all p < 0.001). The human and artificial intelligence comparison revealed that the deep learning model was capable of matching the reliability of doctors for 15/18 of the parameters. The proposed automatic alignment analysis system was able to localise spinal anatomic landmarks with high accuracy and to generate various radiographic parameters with favourable correlations with manual measurements.
Rapid eye movement sleep and slow wave sleep rebounded and related factors during positive airway pressure therapy
Authors: Cheng Jin-Xiang , Ren Jiafeng , Qiu Jian , Jiang Yingcong , Zhao Xianchao , Sun Shuyu , Su Changjun
Published: April 2021

This study aimed to investigate the clinical characteristics and predictors of increased rapid eye movement (REM) sleep or slow wave sleep (SWS) in patients with obstructive sleep apnea (OSA) following positive airway pressure (PAP) therapy. The study retrospectively analyzed data from patients with OSA who underwent both diagnostic polysomnography (PSG) and pressure titration PSG at the Tangdu Hospital Sleep Medicine Center from 2011–2016. Paired diagnostic PSG and pressure titration studies from 501 patients were included. REM rebound was predicted by a higher oxygen desaturation index, lower REM proportion, higher arousal index, lower mean pulse oxygen saturation (SpO2), higher Epworth sleepiness score and younger age (adjusted R2 = 0.482). The SWS rebound was predicted by a longer total duration of apneas and hypopneas, lower N3 duration, lower SpO2 nadir, lower REM proportion in diagnostic PSG and younger age (adjusted R2 = 0.286). Patients without REM rebound or SWS rebound had a high probability of comorbidities with insomnia and mood complaints. Some parameters (subjective and objective insomnia, excessive daytime sleepiness, age and OSA severity) indicate changes in REM sleep and SWS between diagnostic and titration PSG tests. Treatment of insomnia and mood disorders in patients with OSA may helpful to improve the use PAP.
Postnatal structural development of mammalian Basilar Membrane provides anatomical basis for the maturation of tonotopic maps and frequency tuning
Authors: Tani Tomomi , Koike-Tani Maki , Tran Mai Thi , Shribak Michael , Levic Snezana
Published: April 2021

The basilar membrane (BM) of the mammalian cochlea constitutes a spiraling acellular ribbon that is intimately attached to the organ of Corti. Its graded stiffness, increasing from apex to the base of the cochlea provides the mechanical basis for sound frequency analysis. Despite its central role in auditory signal transduction, virtually nothing is known about the BM’s structural development. Using polarized light microscopy, the present study characterized the architectural transformations of freshly dissected BM at time points during postnatal development and maturation. The results indicate that the BM structural elements increase progressively in size, becoming radially aligned and more tightly packed with maturation and reach the adult structural signature by postnatal day 20 (P20). The findings provide insight into structural details and developmental changes of the mammalian BM, suggesting that BM is a dynamic structure that changes throughout the life of an animal.
Toughening and polymerization stress control in composites using thiourethane-treated fillers
Authors: Fugolin Ana Paula Piovezan , Costa Ana Rosa , Correr-Sobrinho Lourenco , Crystal Chaw R. , Lewis Steven , Ferracane Jack Liborio , Pfeifer Carmem Silvia
Published: April 2021

Filler particle functionalization with thiourethane oligomers has been shown to increase fracture toughness and decrease polymerization stress in dental composites, though the mechanism is poorly understood. The aim of this study was to systematically characterize the effect of the type of filler surface functionalization on the physicochemical properties of experimental resin composites containing fillers of different size and volume fraction. Barium glass fillers (1, 3 and 10 µm) were functionalized with 2 wt% thiourethane-silane (TU-Sil) synthesized de novo and characterized by thermogravimetric analysis. Fillers treated with 3-(Trimethoxysilyl)propyl methacrylate (MA-Sil) and with no surface treatment (No-Sil) served as controls. Fillers (50, 60 and 70 wt%) were incorporated into BisGMA-UDMA-TEGDMA (5:3:2) containing camphorquinone/ethyl-4-dimethylaminobenzoate (0.2/0.8 wt%) and 0.2 wt% di-tert-butyl hydroxytoluene. The functionalized particles were characterized by thermogravimetric analysis and a representative group was tagged with methacrylated rhodamine B and analyzed by confocal laser scanning microscopy. Polymerization kinetics were assessed by near-IR spectroscopy. Polymerization stress was tested in a cantilever system, and fracture toughness was assessed with single edge-notched beams. Fracture surfaces were characterized by SEM. Data were analyzed with ANOVA/Tukey's test (α = 0.05). The grafting of thiourethane oligomer onto the surface of the filler particles led to reductions in polymerization stress ranging between 41 and 54%, without affecting the viscosity of the composite. Fracture toughness increased on average by 35% for composites with the experimental fillers compared with the traditional methacrylate-silanized groups. SEM and confocal analyses demonstrate that the coverage of the filler surface was not homogeneous and varied with the size of the filler. The average silane layer for the 1 µm particle functionalized with the thiourethane was 206 nm, much thicker than reported for traditional silanes. In summary, this study systematically characterized the silane layer and established structure–property relationships for methacrylate and thiourethane silane-containing materials. The results demonstrate that significant stress reductions and fracture toughness increases are obtained by judiciously tailoring the organic–inorganic interface in dental composites.
Discovery of CASP8 as a potential biomarker for high-risk prostate cancer through a high-multiplex immunoassay
Authors: Liu Shiqin , Garcia-Marques Fernando , Zhang Chiyuan Amy , Lee Jordan John , Nolley Rosalie , Shen Michelle , Hsu En-Chi , Aslan Merve , Koul Kashyap , Pitteri Sharon J. , Brooks James D. , Stoyanova Tanya
Published: April 2021

Prostate cancer remains the most common non-cutaneous malignancy among men in the United States. To discover potential serum-based biomarkers for high-risk prostate cancer, we performed a high-multiplex immunoassay utilizing patient-matched pre-operative and post-operative serum samples from ten men with high-grade and high-volume prostate cancer. Our study identified six (CASP8, MSLN, FGFBP1, ICOSLG, TIE2 and S100A4) out of 174 proteins that were significantly decreased after radical prostatectomy. High levels of CASP8 were detected in pre-operative serum samples when compared to post-operative serum samples and serum samples from patients with benign prostate hyperplasia (BPH). By immunohistochemistry, CASP8 protein was expressed at higher levels in prostate cancer tissues compared to non-cancerous and BPH tissues. Likewise, CASP8 mRNA expression was significantly upregulated in prostate cancer when compared to benign prostate tissues in four independent clinical datasets. In addition, mRNA levels of CASP8 were higher in patients with recurrent prostate cancer when compared to patients with non-recurrent prostate cancer and high expression of CASP8 was associated with worse disease-free survival and overall survival in renal cancer. Together, our results suggest that CASP8 may potentially serve as a biomarker for high-risk prostate cancer and possibly renal cancer.
Reference gene selection for expression studies in the reproductive axis tissues of Magang geese at different reproductive stages under light treatment
Authors: Zhang Bei-Bei , Shen Xu , Li Xiu-Jin , Tian Yun-Bo , Ouyang Hong-Jia , Huang Yun-Mao
Published: April 2021

In quantitative PCR research, appropriate reference genes are key to determining accurate mRNA expression levels. In order to screen the reference genes suitable for detecting gene expression in tissues of the reproductive axis, a total of 420 (males and females = 1:5) 3-year-old Magang geese were selected and subjected to light treatment. The hypothalamus, pituitary and testicular tissues were subsequently collected at different stages. Ten genes including HPRT1, GAPDH, ACTB, LDHA, SDHA, B2M, TUBB4, TFRC, RPS2 and RPL4 were selected as candidate reference genes. The expression of these genes in goose reproductive axis tissues was detected by real-time fluorescent quantitative PCR. The ΔCT, geNorm, NormFinder and BestKeeper algorithms were applied to sort gene expression according to stability. The results showed that ACTB and TUBB4 were the most suitable reference genes for the hypothalamic tissue of Magang goose in the three breeding stages; HPRT1 and RPL4 for pituitary tissue; and HPRT1 and LDHA for testicular tissue. For all three reproductive axis tissues, ACTB was the most suitable reference gene, whereas the least stable reference gene was GAPDH. Altogether, these results can provide references for tissue expression studies in geese under light treatment.
Development of machine learning model for diagnostic disease prediction based on laboratory tests
Authors: Park Dong Jin , Park Min Woo , Lee Homin , Kim Young-Jin , Kim Yeongsic , Park Young Hoon
Published: April 2021

The use of deep learning and machine learning (ML) in medical science is increasing, particularly in the visual, audio, and language data fields. We aimed to build a new optimized ensemble model by blending a DNN (deep neural network) model with two ML models for disease prediction using laboratory test results. 86 attributes (laboratory tests) were selected from datasets based on value counts, clinical importance-related features, and missing values. We collected sample datasets on 5145 cases, including 326,686 laboratory test results. We investigated a total of 39 specific diseases based on the International Classification of Diseases, 10th revision (ICD-10) codes. These datasets were used to construct light gradient boosting machine (LightGBM) and extreme gradient boosting (XGBoost) ML models and a DNN model using TensorFlow. The optimized ensemble model achieved an F1-score of 81% and prediction accuracy of 92% for the five most common diseases. The deep learning and ML models showed differences in predictive power and disease classification patterns. We used a confusion matrix and analyzed feature importance using the SHAP value method. Our new ML model achieved high efficiency of disease prediction through classification of diseases. This study will be useful in the prediction and diagnosis of diseases.
Real-time coronary artery stenosis detection based on modern neural networks
Authors: Danilov Viacheslav V. , Klyshnikov Kirill Yu. , Gerget Olga M. , Kutikhin Anton G. , Ganyukov Vladimir I. , Frangi Alejandro F. , Ovcharenko Evgeny A.
Published: April 2021

Invasive coronary angiography remains the gold standard for diagnosing coronary artery disease, which may be complicated by both, patient-specific anatomy and image quality. Deep learning techniques aimed at detecting coronary artery stenoses may facilitate the diagnosis. However, previous studies have failed to achieve superior accuracy and performance for real-time labeling. Our study is aimed at confirming the feasibility of real-time coronary artery stenosis detection using deep learning methods. To reach this goal we trained and tested eight promising detectors based on different neural network architectures (MobileNet, ResNet-50, ResNet-101, Inception ResNet, NASNet) using clinical angiography data of 100 patients. Three neural networks have demonstrated superior results. The network based on Faster-RCNN Inception ResNet V2 is the most accurate and it achieved the mean Average Precision of 0.95, F1-score 0.96 and the slowest prediction rate of 3 fps on the validation subset. The relatively lightweight SSD MobileNet V2 network proved itself as the fastest one with a low mAP of 0.83, F1-score of 0.80 and a mean prediction rate of 38 fps. The model based on RFCN ResNet-101 V2 has demonstrated an optimal accuracy-to-speed ratio. Its mAP makes up 0.94, F1-score 0.96 while the prediction speed is 10 fps. The resultant performance-accuracy balance of the modern neural networks has confirmed the feasibility of real-time coronary artery stenosis detection supporting the decision-making process of the Heart Team interpreting coronary angiography findings.
Design approach of perforated labyrinth-based acoustic metasurface for selective acoustic levitation manipulation
Authors: Xu Zhike , Qin Ling , Xu Wei , Fang Shuhua , Wang Jiyao
Published: April 2021

This paper proposes a metasurface design approach with perforated labyrinthine path coil structure to manipulate the acoustic transmission with inexpensive materials. The medium in the labyrinthine path coils in this design is air, but not limited to air. A systematic approach has been proposed for the unit cell design of acoustic metamaterials with adjustable resonance peak frequencies and bandgap width. The theory demonstrates that the length of pipe segments determines resonance peak frequencies and the cross-sectional area ratio adjusts the bandgap width. The proposed design approach uses an equivalent pipe circuit based analytical model to design the high transmission (high pass) and high reflection (low pass) unit cell. The simulation and experiment has been performed to evaluate the validity of the theory. Although there exists some assumptions in the theory, the theory still has enough accuracy to guide the metasurface design illustrated by the simulation and experiment results.
Analyzing effect of quadruple multiple sequence alignments on deep learning based protein inter-residue distance prediction
Authors: Jain Aashish , Terashi Genki , Kagaya Yuki , Maddhuri Venkata Subramaniya Sai Raghavendra , Christoffer Charles , Kihara Daisuke
Published: April 2021

Protein 3D structure prediction has advanced significantly in recent years due to improving contact prediction accuracy. This improvement has been largely due to deep learning approaches that predict inter-residue contacts and, more recently, distances using multiple sequence alignments (MSAs). In this work we present AttentiveDist, a novel approach that uses different MSAs generated with different E-values in a single model to increase the co-evolutionary information provided to the model. To determine the importance of each MSA’s feature at the inter-residue level, we added an attention layer to the deep neural network. We show that combining four MSAs of different E-value cutoffs improved the model prediction performance as compared to single E-value MSA features. A further improvement was observed when an attention layer was used and even more when additional prediction tasks of bond angle predictions were added. The improvement of distance predictions were successfully transferred to achieve better protein tertiary structure modeling.