bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural correlates of integration processes during dynamic face perception
Authors: Alp Nihan , Ozkan Huseyin
Published: January 2022

Integrating the spatiotemporal information acquired from the highly dynamic world around us is essential to navigate, reason, and decide properly. Although this is particularly important in a face-to-face conversation, very little research to date has specifically examined the neural correlates of temporal integration in dynamic face perception. Here we present statistically robust observations regarding the brain activations measured via electroencephalography (EEG) that are specific to the temporal integration. To that end, we generate videos of neutral faces of individuals and non-face objects, modulate the contrast of the even and odd frames at two specific frequencies ($$f_1$$

f
1

and $$f_2$$

f
2

) in an interlaced manner, and measure the steady-state visual evoked potential as participants view the videos. Then, we analyze the intermodulation components (IMs: ($$nf_1\pm mf_2$$

n

f
1

±
m

f
2

), a linear combination of the fundamentals with integer multipliers) that consequently reflect the nonlinear processing and indicate temporal integration by design. We show that electrodes around the medial temporal, inferior, and medial frontal areas respond strongly and selectively when viewing dynamic faces, which manifests the essential processes underlying our ability to perceive and understand our social world. The generation of IMs is only possible if even and odd frames are processed in succession and integrated temporally, therefore, the strong IMs in our frequency spectrum analysis show that the time between frames (1/60 s) is sufficient for temporal integration.
Hydrogen peroxide can be a plausible biomarker in cyanobacterial bloom treatment
Authors: Asaeda Takashi , Rahman Mizanur , Abeynayaka Helayaye Damitha Lakmali
Published: January 2022

The effect of combined stresses, photoinhibition, and nutrient depletion on the oxidative stress of cyanobacteria was measured in laboratory experiments to develop the biomass prediction model. Phormidium ambiguum was exposed to various photosynthetically active radiation (PAR) intensities and phosphorous (P) concentrations with fixed nitrogen concentrations. The samples were subjected to stress assays by detecting the hydrogen peroxide (H2O2) concentration and antioxidant activities of catalase (CAT) and superoxide dismutase (SOD). H2O2 concentrations decreased to 30 µmol m−2 s−1 of PAR, then increased with higher PAR intensities. Regarding P concentrations, H2O2 concentrations (nmol L−1) generally decreased with increasing P concentrations. SOD and CAT activities were proportionate to the H2O2 protein−1. No H2O2 concentrations detected outside cells indicated the biological production of H2O2, and the accumulated H2O2 concentration inside cells was parameterized with H2O2 concentration protein−1. With over 30 µmol m−2 s−1 of PAR, H2O2 concentration protein−1 had a similar increasing trend with PAR intensity, independently of P concentration. Meanwhile, with increasing P concentration, H2O2 protein−1 decreased in a similar pattern regardless of PAR intensity. Protein content decreased with gradually increasing H2O2 up to 4 nmol H2O2 mg−1 protein, which provides a threshold to restrict the growth of cyanobacteria. With these results, an empirical formula—protein (mg L−1) = − 192*Log((H2O2/protein)/4.1), where H2O2/protein (nmol mg−1) = − 0.312*PAR2/(502 + PAR2)*((25/PAR)4 + 1)*Log(P/133,100), as a function of total phosphorus concentration, P (µg L−1)—was developed to obtain the cyanobacteria biomass.
Induced magnetic field and viscous dissipation on flows of two immiscible fluids in a rectangular channel
Authors: Shah Nehad Ali , Alrabaiah Hussam , Vieru Dumitru , Yook Se-Jin
Published: January 2022

The unsteady, magneto-hydrodynamic generalized Couette flows of two immiscible fluids in a rectangular channel with isothermal walls under the influence of an inclined magnetic field and an axial electric field have been investigated. Both fluids are considered electrically conducting and the solid boundaries are electrically insulated. Approximate analytical solutions for the velocity, induced magnetic, and temperature fields have been determined using the Laplace transform method along with the numerical Stehfest's algorithm for the inversion of the Laplace transforms. Also, for the nonlinear differential equation of energy, a numerical scheme based on the finite differences has been developed. A particular case has been numerically and graphically studied to show the evolution of the fluid velocity, induced magnetic field, and viscous dissipation in both flow regions.
Plant canopy may promote seed dispersal by wind
Authors: Qin Xuanping , Liang Wei , Liu Zhimin , Liu Minghu , Baskin Carol C. , Baskin Jerry M. , Xin Zhiming , Wang Zhigang , Zhou Quanlai
Published: January 2022

Seed dispersal has received much research attention. The plant canopy can intercept diaspores, but the effect of the plant canopy (the aboveground portion of a plant consisting of branches and leaves) on dispersal distance has not been explored empirically. To determine the effect of plant canopy on seed dispersal distance, a comparison of diaspores falling through open air and through plant canopy was made in a wind tunnel using three wind speeds and diaspores with various traits. Compared with diaspores falling through open air, the dispersal distance of diaspores falling through plant canopy was decreased or increased, depending on wind speed and diaspore traits. When falling through a plant canopy, dispersal distance of diaspores with thorns or those without appendages was promoted at low wind speed (2 m s−1), while that of diaspores with low wing loading (0.5 mg mm−2) and terminal velocity (2.5 m s−1) was promoted by relatively high (6 m s−1) wind speed. A plant canopy could increase seed dispersal distance, which may be due to the complicated updraft generated by canopy. The effect of maternal plants on seed dispersal regulates the distribution pattern and the species composition of the community.
Three-state majority-vote model on small-world networks
Authors: Zubillaga Bernardo J. , Vilela André L. M. , Wang Minggang , Du Ruijin , Dong Gaogao , Stanley H. Eugene
Published: January 2022

In this work, we study the opinion dynamics of the three-state majority-vote model on small-world networks of social interactions. In the majority-vote dynamics, an individual adopts the opinion of the majority of its neighbors with probability 1-q, and a different opinion with chance q, where q stands for the noise parameter. The noise q acts as a social temperature, inducing dissent among individual opinions. With probability p, we rewire the connections of the two-dimensional square lattice network, allowing long-range interactions in the society, thus yielding the small-world property present in many different real-world systems. We investigate the degree distribution, average clustering coefficient and average shortest path length to characterize the topology of the rewired networks of social interactions. By employing Monte Carlo simulations, we investigate the second-order phase transition of the three-state majority-vote dynamics, and obtain the critical noise $$q_c$$

q
c

, as well as the standard critical exponents $$\beta /\nu$$

β
/
ν

, $$\gamma /\nu$$

γ
/
ν

, and $$1/\nu$$

1
/
ν

for several values of the rewiring probability p. We conclude that the rewiring of the lattice enhances the social order in the system and drives the model to different universality classes from that of the three-state majority-vote model in two-dimensional square lattices.
RETRACTED ARTICLE: Performance of
graphene-zinc oxide nanocomposite coated-glassy carbon electrode in the sensitive
determination of para-nitrophenol
Authors: Dar Riyaz Ahmad , Naikoo Gowhar Ahmad , Srivastava Ashwini Kumar , Hassan Israr Ul , Karna Shashi P. , Giri Lily , Shaikh Ahamad M. H. , Rezakazemi Mashallah , Ahmed Waqar
Published: January 2022

Graphene: zinc oxide nanocomposite (GN:ZnO NC) platform was tried for
the sensitive determination of para-nitrophenol (p-NP) through the electrochemical
method. ZnO nanoparticles (NPs) were synthesized by the modified wet-chemical method
where in potassium hydroxide and zinc nitrate were used as precursors and starch as
a stabilizing agent. A green and facile approach was applied to synthesize GN:ZnO NC
in which glucose was employed as a reductant to reduce graphene-oxide to graphene in
the presence of ZnO NPs. The synthesized NC was characterized using scanning and
high-resolution transmission electron microscopy, energy dispersive x-ray analysis,
X-ray diffraction and Raman spectroscopic techniques to examine the crystal phase,
crystallinity, morphology, chemical composition and phase structure. GN:ZnO NC layer
deposited over the glassy carbon electrode (GCE) was initially probed for its
electrochemical performance using the standard 1 mM
K3[Fe(CN)6] model complex. GN:ZnO
NC modified GCE was monitored based on p-NP concentration. An enhanced current
response was observed in 0.1 M phosphate buffer of pH 6.8 for the determination of
p-NP in a linear working range of 0.09 × 10–6 to
21.80 × 10–6 M with a lower detection limit of
8.8 × 10–9 M employing square wave adsorptive
stripping voltammetric technique at a deposition-potential and deposition-time of
− 1.0 V and 300 s, respectively. This electrochemical sensor displayed very high
specificity for p-NP with no observed interference from some other possible
interfering substances such as 2, 4-di-NP, ortho-NP, and meta-NP. The developed
strategy was useful for sensitive detection of p-NP quantity in canals/rivers and
ground H2O samples with good recoveries.
Model-free detection of unique events in time series
Authors: Benkő Zsigmond , Bábel Tamás , Somogyvári Zoltán
Published: January 2022

Recognition of anomalous events is a challenging but critical task in many scientific and industrial fields, especially when the properties of anomalies are unknown. In this paper, we introduce a new anomaly concept called “unicorn” or unique event and present a new, model-free, unsupervised detection algorithm to detect unicorns. The key component of the new algorithm is the Temporal Outlier Factor (TOF) to measure the uniqueness of events in continuous data sets from dynamic systems. The concept of unique events differs significantly from traditional outliers in many aspects: while repetitive outliers are no longer unique events, a unique event is not necessarily an outlier; it does not necessarily fall out from the distribution of normal activity. The performance of our algorithm was examined in recognizing unique events on different types of simulated data sets with anomalies and it was compared with the Local Outlier Factor (LOF) and discord discovery algorithms. TOF had superior performance compared to LOF and discord detection algorithms even in recognizing traditional outliers and it also detected unique events that those did not. The benefits of the unicorn concept and the new detection method were illustrated by example data sets from very different scientific fields. Our algorithm successfully retrieved unique events in those cases where they were already known such as the gravitational waves of a binary black hole merger on LIGO detector data and the signs of respiratory failure on ECG data series. Furthermore, unique events were found on the LIBOR data set of the last 30 years.
In vitro characterization of a small molecule PD-1 inhibitor that targets the PD-l/PD-L1 interaction
Authors: Lu Chih-Hao , Chung Wei-Min , Tsai Chun-Hao , Cheng Ju-Chien , Hsu Kai-Cheng , Tzeng Huey-En
Published: January 2022

Targeting the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis with monoclonal antibodies (mAbs) represents a crucial breakthrough in anticancer therapy, but mAbs are limited by their poor oral bioavailability, adverse events in multiple organ systems, and primary, adaptive, and acquired resistance, amongst other issues. More recently, the advent of small molecule inhibitors that target the PD-1/PD-L1 axis have shown promising cellular inhibitory activity and the potential to counteract the disadvantages of mAbs. In this study, structure-based virtual screening identified small molecule inhibitors that effectively inhibited the PD-1/PD-L1 interaction. Six of those small molecule inhibitors were applied to cell-based experiments targeting PD-1: CH-1, CH-2, CH-3, CH-4, CH-5, and CH-6. Of all 6, CH-4 displayed the lowest cytotoxicity and strongest inhibitory activity towards the PD-1/PD-L1 interaction. The experiments revealed that CH-4 inhibited the interaction of soluble form PD-L1 (sPD-L1) with PD-1 surface protein expressed by KG-1 cells. Investigations into CH-4 analogs revealed that CH-4.7 effectively blocked the PD-1/sPD-L1 interaction, but sustained the secretion of interleukin-2 and interferon-γ by Jurkat cells. Our experiments revealed a novel small molecule inhibitor that blocks the interaction of PD-1/sPD-L1 and potentially offers an alternative PD-1 target for immune checkpoint therapy.
The embryonic transcriptome of Parhyale hawaiensis reveals different dynamics of microRNAs and mRNAs during the maternal-zygotic transition
Authors: Calvo Llilians , Birgaoanu Maria , Pettini Tom , Ronshaugen Matthew , Griffiths-Jones Sam
Published: January 2022

Parhyale hawaiensis has emerged as the crustacean model of choice due to its tractability, ease of imaging, sequenced genome, and development of CRISPR/Cas9 genome editing tools. However, transcriptomic datasets spanning embryonic development are lacking, and there is almost no annotation of non-protein-coding RNAs, including microRNAs. We have sequenced microRNAs, together with mRNAs and long non-coding RNAs, in Parhyale using paired size-selected RNA-seq libraries at seven time-points covering important transitions in embryonic development. Focussing on microRNAs, we annotate 175 loci in Parhyale, 88 of which have no known homologs. We use these data to annotate the microRNAome of 37 crustacean genomes, and suggest a core crustacean microRNA set of around 61 sequence families. We examine the dynamic expression of microRNAs and mRNAs during the maternal-zygotic transition. Our data suggest that zygotic genome activation occurs in two waves in Parhyale with microRNAs transcribed almost exclusively in the second wave. Contrary to findings in other arthropods, we do not predict a general role for microRNAs in clearing maternal transcripts. These data significantly expand the available transcriptomics resources for Parhyale, and facilitate its use as a model organism for the study of small RNAs in processes ranging from embryonic development to regeneration.
A novel 14-gene signature for overall survival in lung adenocarcinoma based on the Bayesian hierarchical Cox proportional hazards model
Authors: Sun Na , Chu Jiadong , Hu Wei , Chen Xuanli , Yi Nengjun , Shen Yueping
Published: January 2022

There have been few investigations of cancer prognosis models based on Bayesian hierarchical models. In this study, we used a novel Bayesian method to screen mRNAs and estimate the effects of mRNAs on the prognosis of patients with lung adenocarcinoma. Based on the identified mRNAs, we can build a prognostic model combining mRNAs and clinical features, allowing us to explore new molecules with the potential to predict the prognosis of lung adenocarcinoma. The mRNA data (n = 594) and clinical data (n = 470) for lung adenocarcinoma were obtained from the TCGA database. Gene set enrichment analysis (GSEA), univariate Cox proportional hazards regression, and the Bayesian hierarchical Cox proportional hazards model were used to explore the mRNAs related to the prognosis of lung adenocarcinoma. Multivariate Cox proportional hazard regression was used to identify independent markers. The prediction performance of the prognostic model was evaluated not only by the internal cross-validation but also by the external validation based on the GEO dataset (n = 437). With the Bayesian hierarchical Cox proportional hazards model, a 14-gene signature that included CPS1, CTPS2, DARS2, IGFBP3, MCM5, MCM7, NME4, NT5E, PLK1, POLR3G, PTTG1, SERPINB5, TXNRD1, and TYMS was established to predict overall survival in lung adenocarcinoma. Multivariate analysis demonstrated that the 14-gene signature (HR 3.960, 95% CI 2.710–5.786), T classification (T1, reference; T3, HR 1.925, 95% CI 1.104–3.355) and N classification (N0, reference; N1, HR 2.212, 95% CI 1.520–3.220; N2, HR 2.260, 95% CI 1.499–3.409) were independent predictors. The C-index of the model was 0.733 and 0.735, respectively, after performing cross-validation and external validation, a nomogram was provided for better prediction in clinical application. Bayesian hierarchical Cox proportional hazards models can be used to integrate high-dimensional omics information into a prediction model for lung adenocarcinoma to improve the prognostic prediction and discover potential targets. This approach may be a powerful predictive tool for clinicians treating malignant tumours.
Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration
Authors: Roberts Philipp K. , Schranz Markus , Motschi Alice , Desissaire Sylvia , Hacker Valentin , Pircher Michael , Sacu Stefan , Buehl Wolf , Hitzenberger Christoph K. , Schmidt-Erfurth Ursula M.
Published: January 2022

To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.
Statistical analysis for explosives detection system test and evaluation
Authors: Lukow Stefan , Weatherall James C.
Published: January 2022

The verification of trace explosives detection systems is often constrained to small sample sets, so it is important to support the significance of the results with statistical analysis. As binary measurements, the trials are assessed using binomial statistics. A method is described based on the probability confidence interval and expressed in terms of the upper confidence interval bound that reports the probability of successful detection and its level of statistical confidence. These parameters provide useful measures of the system’s performance. The propriety of combining statistics for similar tests—for example in trace detection trials of an explosive on multiple surfaces—is examined by statistical tests. The use of normal statistics is commonly applied to binary testing, but the confidence intervals are known to behave poorly in many circumstances, including small sample numbers. The improvement of the normal approximation with increasing sample number is shown not to be substantial for the typical numbers used in this type of explosives detection system testing, and binary statistics are preferred. The methods and techniques described here for testing trace detection can be applied as well to performance testing of explosives detection systems in general.
Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults
Authors: Hong Yun Soo , Jung Kyung Uk , Rampal Sanjay , Zhao Di , Guallar Eliseo , Ryu Seungho , Chang Yoosoo , Kim Hyung Ook , Kim Hungdai , Chun Ho-Kyung , Sohn Chong Il , Shin Hocheol , Cho Juhee
Published: January 2022

Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011–2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P < 0.001). Compared to men, the prevalence of hemorrhoidal disease was higher in parous women (adjusted odds ratio [OR] 1.06; 95% confidence interval [CI] 1.02–1.10), and lower in nulliparous women (adjusted OR 0.92; 95% CI 0.86–0.98). In the adjusted analyses, older age, female sex, smoking, overweight, and being hypertensive were independently associated with the presence of hemorrhoidal disease. The prevalence of hemorrhoidal disease was positively associated with body mass index and waist circumference in parous women. The prevalence of hemorrhoidal disease was higher in older age, females, ever-smokers, and hypertensive participants. The association of excess adiposity with the prevalence of hemorrhoidal disease differed by sex and parity.
Field deployable impedance-based corrosion sensor
Authors: Li Jiajun , Jiang Xiaoxue , Khan Faheem , Ye Xuanjie , Wang Shuren , Chen Jie
Published: January 2022

Electrochemical impedance spectroscopy (EIS) has been used in various applications, such as metal corrosion monitoring. However, many conventional corrosion monitoring setups are bulky and inconvenient for in-situ testing. The purpose of this work is to reduce the size of the whole corrosion monitoring system. We utilized EIS to design a field deployable impedance-based corrosion sensor (FDICS), capable of performing in-situ EIS analysis. Experiments verified the sensor’s accuracy, and the results showed that the sensor performed similarly to a bench-top EIS machine when we tested on circuit models. Furthermore, we used the proposed FDICS to monitor a metal corrosion experiment and performed EIS. The result showed that the proposed FDICS is able to obtain the sample’s impedance spectroscopy, which could help researchers test its corrosion severity on a metallic sample in-situ. Compared to other bulky conventional setups, our device eliminates the design complexity while still showing insights into the corrosion reaction.
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity
Authors: Berdyński Mariusz , Miszta Przemysław , Safranow Krzysztof , Andersen Peter M. , Morita Mitsuya , Filipek Sławomir , Żekanowski Cezary , Kuźma-Kozakiewicz Magdalena
Published: January 2022

Mutations in superoxide dismutase 1 gene (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper and lower motor neurons. The clinical phenotype of ALS shows inter- and intrafamilial heterogeneity. The aim of the study was to analyze the relations between individual SOD1 mutations and the clinical presentation using in silico methods to assess the SOD1 mutations severity. We identified SOD1 causative variants in a group of 915 prospectively tested consecutive Polish ALS patients from a neuromuscular clinical center, performed molecular modeling of mutated SOD1 proteins and in silico analysis of mutation impact on clinical phenotype and survival analysis of associations between mutations and hazard of clinical end-points. Fifteen SOD1 mutations were identified in 21.1% familial and 2.3% sporadic ALS cases. Their effects on SOD1 protein structure and functioning inferred from molecular modeling and in silico analyses correlate well with the clinical data. Molecular modeling results support the hypothesis that folding intermediates rather than mature SOD1 protein give rise to the source of cytotoxic conformations in ALS. Significant associations between type of mutation and clinical end-points were found.
Interrelationship between 2019-nCov receptor DPP4 and diabetes mellitus targets based on protein interaction network
Authors: Gao Qian , Zhang Wenjun , Li Tingting , Yang Guojun , Zhu Wei , Chen Naijun , Jin Huawei
Published: January 2022

Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.
Artificial intelligence predicts clinically relevant atrial high-rate episodes in patients with cardiac implantable electronic devices
Authors: Kim Min , Kang Younghyun , You Seng Chan , Park Hyung-Deuk , Lee Sang-Soo , Kim Tae-Hoon , Yu Hee Tae , Choi Eue-Keun , Park Hyoung-Seob , Park Junbeom , Lee Young Soo , Kang Ki-Woon , Shim Jaemin , Sung Jung-Hoon , Oh Il-Young , Park Jong Sung , Joung Boyoung
Published: January 2022

To assess the utility of machine learning (ML) algorithms in predicting clinically relevant atrial high-rate episodes (AHREs), which can be recorded by a pacemaker. We aimed to develop ML-based models to predict clinically relevant AHREs based on the clinical parameters of patients with implanted pacemakers in comparison to logistic regression (LR). We included 721 patients without known atrial fibrillation or atrial flutter from a prospective multicenter (11 tertiary hospitals) registry comprising all geographical regions of Korea from September 2017 to July 2020. Predictive models of clinically relevant AHREs were developed using the random forest (RF) algorithm, support vector machine (SVM) algorithm, and extreme gradient boosting (XGB) algorithm. Model prediction training was conducted by seven hospitals, and model performance was evaluated using data from four hospitals. During a median follow-up of 18 months, clinically relevant AHREs were noted in 104 patients (14.4%). The three ML-based models improved the discrimination of the AHREs (area under the receiver operating characteristic curve: RF: 0.742, SVM: 0.675, and XGB: 0.745 vs. LR: 0.669). The XGB model had a greater resolution in the Brier score (RF: 0.008, SVM: 0.008, and XGB: 0.021 vs. LR: 0.013) than the other models. The use of the ML-based models in patient classification was associated with improved prediction of clinically relevant AHREs after pacemaker implantation.
Genomic studies controvert the existence of the CUX1 p75 isoform
Authors: Krishnan Manisha , Senagolage Madhavi D. , Baeten Jeremy T. , Wolfgeher Donald J. , Khan Saira , Kron Stephen J. , McNerney Megan E.
Published: January 2022

CUX1, encoding a homeodomain-containing transcription factor, is recurrently deleted or mutated in multiple tumor types. In myeloid neoplasms, CUX1 deletion or mutation carries a poor prognosis. We have previously established that CUX1 functions as a tumor suppressor in hematopoietic cells across multiple organisms. Others, however, have described oncogenic functions of CUX1 in solid tumors, often attributed to truncated CUX1 isoforms, p75 and p110, generated by an alternative transcriptional start site or post-translational cleavage, respectively. Given the clinical relevance, it is imperative to clarify these discrepant activities. Herein, we sought to determine the CUX1 isoforms expressed in hematopoietic cells and find that they express the full-length p200 isoform. Through the course of this analysis, we found no evidence of the p75 alternative transcript in any cell type examined. Using an array of orthogonal approaches, including biochemistry, proteomics, CRISPR/Cas9 genomic editing, and analysis of functional genomics datasets across a spectrum of normal and malignant tissue types, we found no data to support the existence of the CUX1 p75 isoform as previously described. Based on these results, prior studies of p75 require reevaluation, including the interpretation of oncogenic roles attributed to CUX1.
Spontaneous mutation rate estimates for the principal malaria vectors Anopheles coluzzii and Anopheles stephensi
Authors: Rashid Iliyas , Campos Melina , Collier Travis , Crepeau Marc , Weakley Allison , Gripkey Hans , Lee Yoosook , Schmidt Hanno , Lanzaro Gregory C.
Published: January 2022

Using high-depth whole genome sequencing of F0 mating pairs and multiple individual F1 offspring, we estimated the nuclear mutation rate per generation in the malaria vectors Anopheles coluzzii and Anopheles stephensi by detecting de novo genetic mutations. A purpose-built computer program was employed to filter actual mutations from a deep background of superficially similar artifacts resulting from read misalignment. Performance of filtering parameters was determined using software-simulated mutations, and the resulting estimate of false negative rate was used to correct final mutation rate estimates. Spontaneous mutation rates by base substitution were estimated at 1.00 × 10−9 (95% confidence interval, 2.06 × 10−10—2.91 × 10−9) and 1.36 × 10−9 (95% confidence interval, 4.42 × 10−10—3.18 × 10−9) per site per generation in A. coluzzii and A. stephensi respectively. Although similar studies have been performed on other insect species including dipterans, this is the first study to empirically measure mutation rates in the important genus Anopheles, and thus provides an estimate of µ that will be of utility for comparative evolutionary genomics, as well as for population genetic analysis of malaria vector mosquito species.
Genome-wide association study identifies tumor anatomical site-specific risk variants for colorectal cancer survival
Authors: Labadie Julia D. , Savas Sevtap , Harrison Tabitha A. , Banbury Barb , Huang Yuhan , Buchanan Daniel D. , Campbell Peter T. , Gallinger Steven J. , Giles Graham G. , Gunter Marc J. , Hoffmeister Michael , Hsu Li , Jenkins Mark A. , Lin Yi , Ogino Shuji , Phipps Amanda I. , Slattery Martha L. , Steinfelder Robert S. , Sun Wei , Van Guelpen Bethany , Hua Xinwei , Figuieredo Jane C. , Pai Rish K. , Nassir Rami , Qi Lihong , Chan Andrew T. , Peters Ulrike , Newcomb Polly A.
Published: January 2022

Identification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies. Approximately 7.5 million SNPs were examined under the log-additive model using Cox proportional hazards models, adjusting for clinical factors and principal components. Additionally, we ran secondary analyses stratifying by tumor site and disease stage. We used a genome-wide p-value threshold of 5 × 10–8 to assess statistical significance. No variants were statistically significantly associated with disease-specific survival in the full case analysis or in the stage-stratified analyses. Three SNPs were statistically significantly associated with disease-specific survival for cases with tumors located in the distal colon (rs698022, HR = 1.48, CI 1.30–1.69, p = 8.47 × 10–9) and the proximal colon (rs189655236, HR = 2.14, 95% CI 1.65–2.77, p = 9.19 × 10–9 and rs144717887, HR = 2.01, 95% CI 1.57–2.58, p = 3.14 × 10–8), whereas no associations were detected for rectal tumors. Findings from this large genome-wide association study highlight the potential for anatomical-site-stratified genome-wide studies to identify germline genetic risk variants associated with colorectal cancer-specific survival. Larger sample sizes and further replication efforts are needed to more fully interpret these findings.
Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioon spinulosum extract: in vitro and in vivo approach
Authors: Elekhnawy Engy , Negm Walaa A. , El-Aasr Mona , Kamer Amal Abo , Alqarni Mohammed , Batiha Gaber El-Saber , Obaidullah Ahmad J. , Fawzy Heba M.
Published: January 2022

Pseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.
DNA binding by the antimalarial compound artemisinin
Authors: Slavkovic Sladjana , Shoara Aron A. , Churcher Zachary R. , Daems Elise , de Wael Karolien , Sobott Frank , Johnson Philip E.
Published: January 2022

Artemisinin (ART) is a vital medicinal compound that is used alone or as part of a combination therapy against malaria. ART is thought to function by attaching to heme covalently and alkylating a range of proteins. Using a combination of biophysical methods, we demonstrate that ART is bound by three-way junction and duplex containing DNA molecules. Binding of ART by DNA is first shown for the cocaine-binding DNA aptamer and extensively studied using this DNA molecule. Isothermal titration calorimetry methods show that the binding of ART is both entropically and enthalpically driven at physiological NaCl concentration. Native mass spectrometry methods confirm DNA binding and show that a non-covalent complex is formed. Nuclear magnetic resonance spectroscopy shows that ART binds at the three-way junction of the cocaine-binding aptamer, and that binding results in the folding of the structure-switching variant of this aptamer. This structure-switching ability was exploited using the photochrome aptamer switch assay to demonstrate that ART can be detected using this biosensing assay. This study is the first to demonstrate the DNA binding ability of ART and should lay the foundation for further work to study implications of DNA binding for the antimalarial activity of ART.
Genome-wide aberrant methylation in primary metastatic UM and their matched metastases
Authors: Smit Kyra N. , Boers Ruben , Vaarwater Jolanda , Boers Joachim , Brands Tom , Mensink Hanneke , Verdijk Robert M. , van IJcken Wilfred F. J. , Gribnau Joost , de Klein Annelies , Kilic Emine
Published: January 2022

Uveal melanoma (UM) is an aggressive intra-ocular cancer with a strong tendency to metastasize. Metastatic UM is associated with mutations in BAP1 and SF3B1, however only little is known about the epigenetic modifications that arise in metastatic UM. In this study we aim to unravel epigenetic changes contributing to UM metastasis using a new genome-wide methylation analysis technique that covers over 50% of all CpG’s. We identified aberrant methylation contributing to BAP1 and SF3B1-mediated UM metastasis. The methylation data was integrated with expression data and surveyed in matched UM metastases from the liver, skin and bone. UM metastases showed no commonly shared novel epigenetic modifications, implying that epigenetic changes contributing to metastatic spreading and colonization in distant tissues occur early in the development of UM and epigenetic changes that occur after metastasis are mainly patient-specific. Our findings reveal a plethora of epigenetic modifications in metastatic UM and its metastases, which could subsequently result in aberrant repression or activation of many tumor-related genes. This observation points towards additional layers of complexity at the level of gene expression regulation, which may explain the low mutational burden of UM.
Observation of ionic conductivity on PUA-TBAI-I2 gel polymer electrolyte
Authors: Chai K. L. , Aung Min Min , Noor I. M. , Lim H N , Abdullah L C
Published: January 2022

Jatropha oil-based polyurethane acylate gel polymer electrolyte was mixed with different concentrations of tetrabutylammonium iodide salt (TBAI). The temperature dependences of ionic conductivity, dielectric modulus and relaxation time were studied in the range of 298 to 393 K. The highest ionic conductivity of (1.88 ± 0.020) × 10–4 Scm−1 at 298 K was achieved when the gel contained 30 wt% of TBAI and 2.06 wt% of I2. Furthermore, the study found that conductivity-temperature dependence followed the Vogel-Tammann Fulcher equation. From that, it could be clearly observed that 30 wt% TBAI indicated the lowest activation energy of 6.947 kJ mol−1. By using the fitting method on the Nyquist plot, the number density, mobility and diffusion coefficient of the charge carrier were determined. The charge properties were analysed using the dielectric permittivity, modulus and dissipation factor. Apart from this, the stoke drag and capacitance were determined.
The H2FPEF and HFA-PEFF algorithms for predicting exercise intolerance and abnormal hemodynamics in heart failure with preserved ejection fraction
Authors: Amanai Shiro , Harada Tomonari , Kagami Kazuki , Yoshida Kuniko , Kato Toshimitsu , Wada Naoki , Obokata Masaru
Published: January 2022

Exercise intolerance is a primary manifestation in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with abnormal hemodynamics and a poor quality of life. Two multiparametric scoring systems have been proposed to diagnose HFpEF. This study sought to determine the performance of the H2FPEF and HFA-PEFF scores for predicting exercise capacity and echocardiographic findings of intracardiac pressures during exercise in subjects with dyspnea on exertion referred for bicycle stress echocardiography. In a subset, simultaneous expired gas analysis was performed to measure the peak oxygen consumption (VO2). Patients with HFpEF (n = 83) and controls without HF (n = 104) were enrolled. The H2FPEF score was obtainable for all patients while the HFA-PEFF score could not be calculated for 23 patients (feasibility 88%). Both H2FPEF and HFA-PEFF scores correlated with a higher E/e′ ratio (r = 0.49 and r = 0.46), lower systolic tricuspid annular velocity (r =  − 0.44 and =  − 0.24), and lower cardiac output (r =  − 0.28 and r =  − 0.24) during peak exercise. Peak VO2 and exercise duration decreased with an increase in H2FPEF scores (r =  − 0.40 and r =  − 0.32). The H2FPEF score predicted a reduced aerobic capacity (AUC 0.71, p = 0.0005), but the HFA-PEFF score did not (p = 0.07). These data provide insights into the role of the H2FPEF and HFA-PEFF scores for predicting exercise intolerance and abnormal hemodynamics in patients presenting with exertional dyspnea.
Identifying gene expression profiles associated with neurogenesis and inflammation in the human subependymal zone from development through aging
Authors: Bitar Mainá , Weissleder Christin , North Hayley F. , Clearwater Misaki S. , Zalucki Oressia , Halliday Glenda M. , Webster Maree J. , Piper Michael , Weickert Cynthia Shannon , Barry Guy
Published: January 2022

The generation of new neurons within the mammalian forebrain continues throughout life within two main neurogenic niches, the subgranular zone (SGZ) of the hippocampal dentate gyrus, and the subependymal zone (SEZ) lining the lateral ventricles. Though the SEZ is the largest neurogenic niche in the adult human forebrain, our understanding of the mechanisms regulating neurogenesis from development through aging within this region remains limited. This is especially pertinent given that neurogenesis declines dramatically over the postnatal lifespan. Here, we performed transcriptomic profiling on the SEZ from human post-mortem tissue from eight different life-stages ranging from neonates (average age ~ 2 months old) to aged adults (average age ~ 86 years old). We identified transcripts with concomitant profiles across these decades of life and focused on three of the most distinct profiles, namely (1) genes whose expression declined sharply after birth, (2) genes whose expression increased steadily with age, and (3) genes whose expression increased sharply in old age in the SEZ. Critically, these profiles identified neuroinflammation as becoming more prevalent with advancing age within the SEZ and occurring with time courses, one gradual (starting in mid-life) and one sharper (starting in old age).
The role of neutrophil gelatinase-associated lipocalin and iron homeostasis in object recognition impairment in aged sepsis-survivor rats
Authors: Nikaido Yoshikazu , Midorikawa Yoko , Furukawa Tomonori , Shimoyama Shuji , Takekawa Daiki , Kitayama Masato , Ueno Shinya , Kushikata Tetsuya , Hirota Kazuyoshi
Published: January 2022

Older adult patients with sepsis frequently experience cognitive impairment. The roles of brain neutrophil gelatinase-associated lipocalin (NGAL) and iron in older sepsis patients remain unknown. We investigated the effects of lipopolysaccharide-induced sepsis on novel object recognition test, NGAL levels, an inflammatory mediator tumor necrosis factor-α (TNFα) levels, and iron ion levels in the hippocampus and cortex of young and aged rats. The effect of an iron chelator deferoxamine pretreatment on aged sepsis rats was also examined. Young sepsis-survivor rats did not show impaired novel object recognition, TNFα responses, or a Fe2+/Fe3+ imbalance. They showed hippocampal and cortical NGAL level elevations. Aged sepsis-survivor rats displayed a decreased object discrimination index, elevation of NGAL levels and Fe2+/Fe3+ ratio, and no TNFα responses. Pretreatment with deferoxamine prevented the reduction in the object recognition of aged sepsis-survivor rats. The elevation in hippocampal and cortical NGAL levels caused by lipopolysaccharide was not influenced by deferoxamine pretreatment. The lipopolysaccharide-induced Fe2+/Fe3+ ratio elevation was blocked by deferoxamine pretreatment. In conclusion, our findings suggest that iron homeostasis in the cortex and hippocampus contributes to the maintenance of object recognition ability in older sepsis survivors.
Establishment and characterization of immortalized sweat gland myoepithelial cells
Authors: Hayakawa Tomohisa , Fujita Fumitaka , Okada Fumihiro , Sekiguchi Kiyotoshi
Published: January 2022

Sweat glands play an important role in thermoregulation via sweating, and protect human vitals. The reduction in sweating may increase the incidence of hyperthermia. Myoepithelial cells in sweat glands exhibit stemness characteristics and play a major role in sweat gland homeostasis and sweating processes. Previously, we successfully passaged primary myoepithelial cells in spheroid culture systems; however, they could not be maintained for long under in vitro conditions. No myoepithelial cell line has been established to date. In this study, we transduced two immortalizing genes into primary myoepithelial cells and developed a myoepithelial cell line. When compared with primary sweat gland cells, the immortalized myoepithelial cells (designated "iEM") continued to form spheroids after the 4th passage and expressed α-smooth muscle actin and other proteins that characterize myoepithelial cells. Furthermore, treatment with small compounds targeting the Wnt signaling pathways induced differentiation of iEM cells into luminal cells. Thus, we successfully developed an immortalized myoepithelial cell line having differentiation potential. As animal models are not useful for studying human sweat glands, our cell line will be helpful for studying the mechanisms underlying the pathophysiology of sweating disorders.
Relationship between muscle strength and rehospitalization in ventricular assist device patients
Authors: Kobayashi Kiyonori , Mutsuga Masato , Usui Akihiko
Published: January 2022

We examined the relationship between leg extensor muscle strength (LEMS) at discharge and rehospitalization within 1 year in patients with a newly implanted ventricular assist device (VAD). This study included 28 patients who had received a VAD at our institution between October 2013 and February 2019, all of whom had been discharged for 1 year. The patients were divided into two groups according to their LEMS at discharge (higher strength [group H] and lower strength [group L]), based on the median value of the 55.2 kg-force (kgf)/body weight (BW) equation. Exercise performance parameters (e.g., grip strength, 6-min walk distance, and peak VO2) and laboratory data concerning nutritional status were also collected. Nine patients (64.3%) in group L were rehospitalized within 1 year after discharge. The rehospitalization rate was significantly higher in group L than group H (p = 0.020). Compared with discharge, patients exhibited higher grip strength (56.3 vs. 48.6 kg/BW, respectively; p = 0.011), 6-min walk distances (588 vs. 470 m, respectively; p = 0.002), and peak VO2 (15.4 vs. 11.9 mL/min/kg, respectively; p < 0.001) at 1 year after discharge. However, the LEMS (57.4 vs. 58.0 kgf/BW, respectively; p = 0.798) did not increase after discharge in VAD patients who avoided rehospitalization. LEMS at discharge was associated with rehospitalization after VAD surgery; a high LEMS improves the likelihood of avoiding rehospitalization.