bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Genomic Profile in TERT, DSP, and FAM13A Between COPD Patients With Emphysema, IPF, and CPFE Syndrome
Authors: Guzmán-Vargas Javier , Ambrocio-Ortiz Enrique , Pérez-Rubio Gloria , Ponce-Gallegos Marco Antonio , Hernández-Zenteno Rafael de Jesus , Mejía Mayra , Ramírez-Venegas Alejandra , Buendia-Roldan Ivette , Falfán-Valencia Ramcés
Published: August 2021

Background: Genetic association studies have identified single nucleotide polymorphisms (SNPs) associated with lasting lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF), as well as the simultaneous presentation, known as Combined Pulmonary Fibrosis and Emphysema (CPFE) Syndrome. It is unknown if these diseases share genetic variants previously described in an independent way. This study aims to identify common or differential variants between COPD, IPF, and CPFE.

Materials and methods: The association analysis was carried out through a case-control design in a Mexican mestizo population (n = 828); three patients' groups were included: COPD smokers (COPD-S, n = 178), IPF patients (n = 93), and CPFE patients (n = 16). Also, two comparison groups were analyzed: smokers without COPD (SWOC, n = 367) and healthy subjects belonging to the Mexican Pulmonary Aging Cohort (PAC, n = 174). Five SNPs in four genes previously associated to interstitial and obstructive diseases were selected: rs2609255 (FAM13A), rs2736100 (TERT), rs2076295 (DSP) rs5743890, and rs111521887 (TOLLIP). Genotyping was performed by qPCR using predesigned Taqman probes.

Results: In comparing IPF vs. PAC, significant differences were found in the frequency of the rs260955 G allele associated with the IPF risk (OR = 1.68, p = 0.01). Also, the genotypes, GG of rs260955 (OR = 2.86, p = 0.01) and TT of rs2076295 (OR = 1.79, p = 0.03) were associated with an increased risk of IPF; after adjusting by covariables, only the rs260955 G allele remain significant (p = 0.01). For the CPFE vs. PAC comparison, an increased CPFE risk was identified since there is a difference in the rs2736100 C allele (OR = 4.02, p < 0.01; adjusted p < 0.01). For COPD-S, the rs2609255 TG genotype was associated with increased COPD risk after adjusting by covariables.

Conclusion: The rs2736100 C allele is associated with decreased IPF risk and confers an increased risk for CPFE. Also, the rs2076295 TT genotype is associated with increased IPF risk, while the GG genotype is associated with CFPE susceptibility. The rs2609255 G allele and GG genotype are associated with IPF susceptibility, while the TG genotype is present in patients with emphysema.
Epidemiology and Clinical Management of Rheumatic Autoimmune Diseases in the COVID-19 Pandemic: A Review
Authors: Zhu Yingzi , Zhong Jixin , Dong Lingli
Published: August 2021

The coronavirus disease 2019 (COVID-19) has been in pandemic for more than 1 year, with serious negative effects produced worldwide. During this period, there have been a lot of studies on rheumatic autoimmune diseases (RADs) combined with COVID-19. The purpose of this study is to review and summarize these experiences. Pubmed, Web of science, Embase and the Cochrane library were searched from January 15, 2020 to July 15, 2021 using RADs and COVID-19 related keywords. Based on a comprehensive review of studies covering 16 countries, the prevalence of COVID-19 does not necessarily increase in RADs patients compared to the general population. In RADs population infected with COVID-19, a high proportion of female patients (54.44~95.2%), elderly patients (≥50y, 48~75.88%), and patients with pre-existing comorbidities (respiratory, 4.8~60.4%; endocrine, 8.52~44.72%; cardiovascular, 15.7~64.73%) were observed, although, this does not appear to have a decisive effect on disease severity. Many anti-rheumatic treatments have been extensively evaluated for their efficacy of treating COVID-19 in RADs patients, with TNF-α inhibitors and IL-6 receptor antagonist receiving more positive reviews. However, there is no conclusive information for most of the therapeutic regimens due to the lack of high-level evidence. Inflammatory markers or neutrophil-lymphocyte-ratio may be applied as indicators for clinical prognosis or therapeutic regimens adjustment. Thus, more research is still needed to address the prevalence, treatment, and clinical monitoring of RADs patients in COVID-19 pandemic.
Gestational Diabetes Mellitus in Pregnancy Increased Erythropoietin Level Affecting Differentiation Potency of Haematopoietic Stem Cell of Umbilical Cord Blood
Authors: Mohd Idris Mohd Razif , Nordin Fazlina , Mahdy Zaleha Abdullah , Abd Wahid S. Fadilah
Published: August 2021

Background: The in utero environment has many factors that can support cell differentiation. Cytokines, chemokines and growth factors play big roles in haematopoietic mechanisms. Some diseases like gestational diabetes mellitus (GDM) might affect the environment and haematopoietic stem cell (HSC) quality. The aim of this study is to investigate the adverse effects of GDM on umbilical cord blood (UCB) HSC in terms of differentiation potency including the UCB parameters used for banking and transplantation purposes.

Methods: UCB-HSC was collected from 42 GDM and 38 normal pregnancies. UCB-HSC was isolated and further enriched using immuno-magnetic separation beads (MACS). The UCB-HSC were cultured in methylcellulose media to investigate the differentiation potency. The level of erythropoietin (EPO) and insulin in the UCB plasma was measured using enzyme linked immunoassay (ELISA) technique.

Result: The UCB parameters; volume, total nucleated count (TNC) and total CD34+ cells were significantly reduced in the GDM group compared to the control group. The number of HSC progenitors' colonies were significantly reduced in the GDM group except for progenitor BFU-E, which was significantly increased (GDM = 94.19 ± 6.21, Control = 73.61 ± 2.73, p = 0.010). This data was associated with higher EPO level in GDM group. However, the insulin level in the GDM group was comparable to the Control group.

Conclusion: Our results suggest that the changes in the in utero environment due to abnormalities during pregnancy such as GDM might affect the differentiation potency of UCB-HSC. These findings can be considered as an additional parameter for the inclusion and exclusion criteria for UCB banking, particularly for mothers with GDM.
Gut and Vagina Microbiota Associated With Estrus Return of Weaning Sows and Its Correlation With the Changes in Serum Metabolites
Authors: Zhang Jia , Liu Min , Ke Shanlin , Huang Xiaochang , Fang Shaoming , He Maozhang , Fu Hao , Chen Congying , Huang Lusheng
Published: August 2021

More and more studies have indicated that gut microbiota takes part in the biosynthesis and metabolism of sex hormones. Inversely, sex hormones influence the composition of gut microbiota. However, whether microbiota in the gut and vagina is associated with estrus return of weaning sows is largely unknown. Here, using 16S rRNA gene sequencing in 158 fecal and 50 vaginal samples, we reported the shifts in the gut and vaginal microbiota between normal return and non-return sows. In fecal samples, Lactobacillus and S24-7 were enriched in normal return sows, while Streptococcus luteciae, Lachnospiraceae, Clostridium, and Mogibacterium had higher abundance in non-return sows. In vaginal swabs, the operational taxonomic units (OTUs) annotated to Clostridiales, Ruminoccaceae, and Oscillospira were enriched in normal return sows, while those OTUs annotated to Campylobacter, Anaerococcus, Parvimonas, Finegoldia, and Dorea had higher abundances in non-return sows. Co-abundance group (CAG) analysis repeated the identification of the bacterial taxa associated with the estrus return of weaning sows. The predicted functional capacities in both gut and vaginal microbiome were changed between normal return and non-return sows. Serum metabolome profiles were determined by non-targeted metabolome analysis in seven normal return and six non-return sows. The metabolite features having higher abundance in normal return sows were enriched in the pathways Steroid hormone biosynthesis, Starch and sucrose metabolism, Galactose metabolism, and Vitamin B6 metabolism, while the metabolite features belonging to organic acids and derivatives, indoles and derivatives, sulfoxides, and lignans and neolignans had significantly higher abundance in non-return sows. Correlation analysis found that the changes in gut microbiota were associated with the shifts of serum metabolites and suggested that certain bacteria might affect estrus return of weaning sow through serum metabolites. These findings may provide new insights for understanding the role of the gut and vaginal microbiota in sow return to estrus after weaning.
Preliminary Study on Antifungal Mechanism of Aqueous Extract of Cnidium monnieri Against Trichophyton rubrum
Authors: Yanyun Cao , Ying Tang , Wei Kong , Hua Fang , Haijun Zhu , Ping Zheng , Shunming Xu , Jian Wan
Published: August 2021

Trichoderma rubrum (T. rubrum) is one of the important pathogens because it is the cause of most dermatomycosis. The treatment of Trichophyton rubrum infection is time-consuming and very expensive; it is easy for the infections to reoccur, leading to therapeutic failures, persistence, and chronic infection. These issues have inspired researchers to study natural alternative therapies instead. Cnidium monnieri (L.), as a kind of traditional Chinese medicine, has a variety of pharmacological activities and a wide range of applications, so it has a high potential for researching and economic value. We detected the effect of aqueous extract of C. monnieri (L.) on the activity of T. rubrum by Cell Count Kit-8 assay (CCK-8), and we found that 128 and 256 μg/ml of aqueous extracts of C. monnieri (L.) co-cultured with T. rubrum for 24 h showed the inhibitory effect on T. rubrum. The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed that aqueous extract of C. monnieri (L.) damaged the T. rubrum. At the same time, mass spectrometry screening with T. rubrum before and after the treatment of 256 μg/ml of aqueous extracts of C. monnieri (L.) showed that 966 differentially expressed proteins were detected, including 524 upregulated differentially expressed genes (DEGs) and 442 downregulated DEGs. The most significantly downregulated protein was chitin synthase (CHS); and the results of qRT-PCR and Western blotting demonstrated that the expression level of CHS was downregulated in the 256 μg/ml group compared with the control group. The study showed that the aqueous extract of C. monnieri (L.) could destroy the morphology of mycelia and the internal structure of T. rubrum, and it could inhibit the growth of T. rubrum. The antifungal effect of aqueous extract of C. monnieri (L.) may be related to the downregulation of the expression of CHS in T. rubrum, and CHS may be one of the potential targets of its antifungal mechanism. We concluded that aqueous extract from C. monnieri (L.) may be a potential candidate for antifungal agents.
Deciphering the Antibacterial Role of Peptide From Bacillus subtilis subsp. spizizenii Ba49 Against Staphylococcus aureus
Authors: Taggar Ramita , Singh Sanpreet , Bhalla Vijayender , Bhattacharyya Mani Shankar , Sahoo Debendra K.
Published: August 2021

An increase in antibiotic resistance has led to escalating the need for the development of alternate therapy. Antimicrobial peptides (AMPs) are at the forefront of replacing conventional antibiotics, showing slower development of drug resistance, antibiofilm activity, and the ability to modulate the host immune response. The ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens that jeopardize most conventional antibiotics are known to be involved in severe respiratory tract, bloodstream, urinary tract, soft tissue, and skin infections. Among them, S. aureus is an insidious microbe and developed resistance against conventional antibiotics. In the present study, an AMP (named as peptide-Ba49) isolated from Bacillus subtilis subsp. spizizenii strain from Allium cepa (the common onion) exhibited strong antibacterial efficacy against S. aureus ATCC 25923. The mode of action of this peptide-Ba49 on S. aureus was deciphered through various sensitive probes, i.e., DiSC3 (5) and H2DCFDA, suggesting the peptide-Ba49 to be acting upon through change in membrane potential and by triggering the production of reactive oxygen species (ROS). This induced disruption of the cell membrane was further supported by morphological studies using scanning electron microscopy (SEM). Investigations on a possible post-antibiotic effect (PAE) of peptide-Ba49 showed prolonged PAE against S. aureus. Furthermore, the peptide-Ba49 prevented the formation of S. aureus biofilm at low concentration and showed its potential to degrade the mature biofilm of S. aureus. The peptide-Ba49 also exhibited intracellular killing potential against S. aureus ATCC 25923 in the macrophage cells, and moreover, peptide-Ba49 was found to bolster the fibroblast cell migration in the scratch assay at low concentration, exhibiting a wound healing efficacy of this peptide. These studies demonstrated that peptide-Ba49 isolated from the strain B. subtilis subsp. spizizenii could be a therapeutic candidate to combat the pathogenic S. aureus infections.
Adaptive Response of Listeria monocytogenes to the Stress Factors in the Food Processing Environment
Authors: Wiktorczyk-Kapischke Natalia , Skowron Krzysztof , Grudlewska-Buda Katarzyna , Wałecka-Zacharska Ewa , Korkus Jakub , Gospodarek-Komkowska Eugenia
Published: August 2021

Listeria monocytogenesare Gram-positive, facultatively anaerobic, non-spore-forming bacteria that easily adapt to changing environmental conditions. The ability to grow at a wide range of temperatures, pH, and salinity determines the presence of the pathogen in water, sewage, soil, decaying vegetation, and animal feed.L. monocytogenesis an etiological factor of listeriosis, especially dangerous for the elderly, pregnant women, and newborns. The major source ofL. monocytogenesfor humans is food, including fresh and smoked products. Its high prevalence in food is associated with bacterial adaptation to the food processing environment (FPE). Since the number of listeriosis cases has been progressively increasing an efficient eradication of the pathogen from the FPE is crucial. Understanding the mechanisms of bacterial adaptation to environmental stress will significantly contribute to developing novel, effective methods of controllingL. monocytogenesin the food industry.
Corticothalamic Pathways in Auditory Processing: Recent Advances and Insights From Other Sensory Systems
Authors: Antunes Flora M. , Malmierca Manuel S.
Published: August 2021

The corticothalamic (CT) pathways emanate from either Layer 5 (L5) or 6 (L6) of the neocortex and largely outnumber the ascending, thalamocortical pathways. The CT pathways provide the anatomical foundations for an intricate, bidirectional communication between thalamus and cortex. They act as dynamic circuits of information transfer with the ability to modulate or even drive the response properties of target neurons at each synaptic node of the circuit. L6 CT feedback pathways enable the cortex to shape the nature of its driving inputs, by directly modulating the sensory message arriving at the thalamus. L5 CT pathways can drive the postsynaptic neurons and initiate a transthalamic corticocortical circuit by which cortical areas communicate with each other. For this reason, L5 CT pathways place the thalamus at the heart of information transfer through the cortical hierarchy. Recent evidence goes even further to suggest that the thalamus via CT pathways regulates functional connectivity within and across cortical regions, and might be engaged in cognition, behavior, and perceptual inference. As descending pathways that enable reciprocal and context-dependent communication between thalamus and cortex, we venture that CT projections are particularly interesting in the context of hierarchical perceptual inference formulations such as those contemplated in predictive processing schemes, which so far heavily rely on cortical implementations. We discuss recent proposals suggesting that the thalamus, and particularly higher order thalamus via transthalamic pathways, could coordinate and contextualize hierarchical inference in cortical hierarchies. We will explore these ideas with a focus on the auditory system.
Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration
Authors: Anand Praveen , Privitera Rosario , Donatien Philippe , Misra V. Peter , Woods David R.
Published: August 2021

Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application.

Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment.

Results: Participants showed significant decrease in spontaneous pain (mean NPRS: −1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (−1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001).

Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019).

Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.
Stress Assessment of Vestibular Endurance Training for Civil Aviation Flight Students Based on EEG
Authors: Hu Haixu , Fang Zhou , Qian Zhiyu , Yao Liuye , Tao Ling , Qin Bing
Published: August 2021

Objective: The main goal of this study is to clarify the electroencephalogram (EEG) characteristics of the stress response caused by vestibular endurance training under real conditions.

Methods: Ten pilot trainees received a series of acute anti-vertigo training stimulations on the rotary ladder while recording electroencephalographic data (64 electrodes). Afterward, the anti-vertigo ability of the subject was tested for the best performance after 1 month of training and verified whether it is related to the EEG signals we collected before.

Results: (1) The absolute power of α waves in the C3 and C4 regions is the same as the difference between 1 min before and 2 min after stimulation, and their activity is enhanced by stimulation. Otherwise, the activation of the C3 region after 5 min of stimulation is still significantly changed. (2) Through Spearman's correlation analysis, we found that the α waves in the C3 and C4 the greater the power change, the better the performance of the subject in the proficient stage.

Conclusion: C3 and C4 areas are specific brain regions of the stress response of anti-vertigo endurance training, and the absolute power of the α wave can be used as a parameter for identifying the degree of motion sickness (MS). The absolute power changes of α waves in the C3 and C4 areas are positively correlated with their anti-vertigo potential.

Significance: Increasing the absolute power of α wave in the C3 and C4 is a manifestation of MS stress adaptability.
A Narrative Review of Methodological Considerations in Magnetic Resonance Imaging of Offspring Brain Development and the Influence of Parenting
Authors: Bhanot Shiv , Bray Signe , McGirr Alexander , Lee Kate , Kopala-Sibley Daniel C.
Published: August 2021

Parenting has been robustly associated with offspring psychosocial development, and these effects are likely reflected in brain development. This hypothesis is being tested with increasingly rigorous methods and the use of magnetic resonance imaging, a powerful tool for characterizing human brain structure and function. The objective of this narrative review was to examine methodological issues in this field that impact the conclusions that can be drawn and to identify future directions in this field. Studies included were those that examined associations between parenting and offspring brain structure or function. Results show four thematic features in this literature that impact the hypotheses that can be tested, and the conclusions drawn. The first theme is a limited body of studies including repeated sampling of offspring brain structure and function, and therefore an over-reliance on cross-sectional or retrospective associations. The second involves a focus on extremes in early life caregiving, limiting generalizability. The third involves the nature of parenting assessment, predominantly parent- or child-report instead of observational measures which may be more ecologically valid measures of parenting. A closely related fourth consideration is the examination of detrimental versus positive parenting behaviors. While studies with one or more of these thematic limitations provide valuable information, future study design should consider addressing these limitations to determine how parenting shapes offspring brain development.
Epigenetics Is Implicated in the Basis of Gender Incongruence: An Epigenome-Wide Association Analysis
Authors: Ramirez Karla , Fernández Rosa , Collet Sarah , Kiyar Meltem , Delgado-Zayas Enrique , Gómez-Gil Esther , Van Den Eynde Tibbert , T’Sjoen Guy , Guillamon Antonio , Mueller Sven C. , Pásaro Eduardo
Published: August 2021

Introduction

The main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population.

Methods

A global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program by a 2-way ANOVA test comparing populations by group and their sex assigned at birth.

Results

The principal components analysis (PCA) showed that both populations (cis and trans) differ in the degree of global CpG methylation prior to GAHT. The 2-way ANOVA test showed 71,515 CpGs that passed the criterion FDR p < 0.05. Subsequently, in male assigned at birth population we found 87 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2) of which 22 were located in islands. The most significant CpGs were related to genes: WDR45B, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP, and NCOA6. Regarding the female assigned at birth populations, we found 2 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2), but none were located in islands. One of these CpGs, related to the MPPED2 gene, is shared by both, trans men and trans women. The enrichment analysis showed that these genes are involved in functions such as negative regulation of gene expression (GO:0010629), central nervous system development (GO:0007417), brain development (GO:0007420), ribonucleotide binding (GO:0032553), and RNA binding (GO:0003723), among others.

Strengths and Limitations

It is the first time that a global CpG methylation analysis has been carried out in a population with gender incongruence before GAHT. A prospective study before/during GAHT would provide a better understanding of the influence of epigenetics in this process.

Conclusion

The main finding of this study is that the cis and trans populations have different global CpG methylation profiles prior to GAHT. Therefore, our results suggest that epigenetics may be involved in the etiology of gender incongruence.
A Brain-Inspired Homeostatic Neuron Based on Phase-Change Memories for Efficient Neuromorphic Computing
Authors: Muñoz-Martin Irene , Bianchi Stefano , Hashemkhani Shahin , Pedretti Giacomo , Melnic Octavian , Ielmini Daniele
Published: August 2021

One of the main goals of neuromorphic computing is the implementation and design of systems capable of dynamic evolution with respect to their own experience. In biology, synaptic scaling is the homeostatic mechanism which controls the frequency of neural spikes within stable boundaries for improved learning activity. To introduce such control mechanism in a hardware spiking neural network (SNN), we present here a novel artificial neuron based on phase change memory (PCM) devices capable of internal regulation via homeostatic and plastic phenomena. We experimentally show that this mechanism increases the robustness of the system thus optimizing the multi-pattern learning under spike-timing-dependent plasticity (STDP). It also improves the continual learning capability of hybrid supervised-unsupervised convolutional neural networks (CNNs), in terms of both resilience and accuracy. Furthermore, the use of neurons capable of self-regulating their fire responsivity as a function of the PCM internal state enables the design of dynamic networks. In this scenario, we propose to use the PCM-based neurons to design bio-inspired recurrent networks for autonomous decision making in navigation tasks. The agent relies on neuronal spike-frequency adaptation (SFA) to explore the environment via penalties and rewards. Finally, we show that the conductance drift of the PCM devices, contrarily to the applications in neural network accelerators, can improve the overall energy efficiency of neuromorphic computing by implementing bio-plausible active forgetting.
Reliability and Reproducibility of Hadamard Encoded Pseudo-Continuous Arterial Spin Labeling in Healthy Elderly
Authors: Neumann Katja , Schidlowski Martin , Günther Matthias , Stöcker Tony , Düzel Emrah
Published: August 2021

The perfusion parameters cerebral blood flow (CBF) and arterial transit time (ATT) measured with arterial spin labeling (ASL) magnetic resonance imaging (MRI) provide valuable essentials to assess the integrity of cerebral tissue. Brain perfusion changes, due to aging, an intervention, or neurodegenerative diseases for example, could be investigated in longitudinal ASL studies with reliable ASL sequences. Generally, pseudo-continuous ASL (pCASL) is preferred because of its larger signal-to-noise ratio (SNR) compared to pulsed ASL (PASL) techniques. Available pCASL versions differ regarding their feature details. To date only little is known about the reliability and reproducibility of CBF and ATT measures obtained with the innovative Hadamard encoded pCASL variant, especially if applied on participants in old age. Therefore, we investigated an in-house developed Hadamard encoded pCASL sequence on a group of healthy elderly at two different 3 Tesla Siemens MRI systems (Skyra and mMR Biograph) and evaluated CBF and ATT reliability and reproducibility for several regions-of-interests (ROI). Calculated within-subject coefficients of variation (wsCV) demonstrated an excellent reliability of perfusion measures, whereas ATT appeared to be even more reliable than CBF [e.g., wsCV(CBF) = 2.9% vs. wsCV(ATT) = 2.3% for a gray matter (GM) ROI on Skyra system]. Additionally, a substantial agreement of perfusion values acquired on both MRI systems with an inter-session interval of 78 ± 17.6 days was shown by high corresponding intra-class correlation (ICC) coefficients [e.g., ICC(CBF) = 0.704 and ICC(ATT) = 0.754 for a GM ROI]. The usability of this novel Hadamard encoded pCASL sequence might improve future follow-up perfusion studies of the aging and/or diseased brain.
Enhancing Performance of SSVEP-Based Visual Acuity via Spatial Filtering
Authors: Zheng Xiaowei , Xu Guanghua , Han Chengcheng , Tian Peiyuan , Zhang Kai , Liang Renghao , Jia Yaguang , Yan Wenqiang , Du Chenghang , Zhang Sicong
Published: August 2021

The purpose of this study was to enhance the performance of steady-state visual evoked potential (SSVEP)-based visual acuity assessment with spatial filtering methods. Using the vertical sinusoidal gratings at six spatial frequency steps as the visual stimuli for 11 subjects, SSVEPs were recorded from six occipital electrodes (O1, Oz, O2, PO3, POz, and PO4). Ten commonly used training-free spatial filtering methods, i.e., native combination (single-electrode), bipolar combination, Laplacian combination, average combination, common average reference (CAR), minimum energy combination (MEC), maximum contrast combination (MCC), canonical correlation analysis (CCA), multivariate synchronization index (MSI), and partial least squares (PLS), were compared for multielectrode signals combination in SSVEP visual acuity assessment by statistical analyses, e.g., Bland–Altman analysis and repeated-measures ANOVA. The SSVEP signal characteristics corresponding to each spatial filtering method were compared, determining the chosen spatial filtering methods of CCA and MSI with a higher performance than the native combination for further signal processing. After the visual acuity threshold estimation criterion, the agreement between the subjective Freiburg Visual Acuity and Contrast Test (FrACT) and SSVEP visual acuity for the native combination (0.253 logMAR), CCA (0.202 logMAR), and MSI (0.208 logMAR) was all good, and the difference between FrACT and SSVEP visual acuity was also all acceptable for the native combination (−0.095 logMAR), CCA (0.039 logMAR), and MSI (−0.080 logMAR), where CCA-based SSVEP visual acuity had the best performance and the native combination had the worst. The study proved that the performance of SSVEP-based visual acuity can be enhanced by spatial filtering methods of CCA and MSI and also recommended CCA as the spatial filtering method for multielectrode signals combination in SSVEP visual acuity assessment.
A Review on Signal Processing Approaches to Reduce Calibration Time in EEG-Based Brain–Computer Interface
Authors: Huang Xin , Xu Yilu , Hua Jing , Yi Wenlong , Yin Hua , Hu Ronghua , Wang Shiyi
Published: August 2021

In an electroencephalogram- (EEG-) based brain–computer interface (BCI), a subject can directly communicate with an electronic device using his EEG signals in a safe and convenient way. However, the sensitivity to noise/artifact and the non-stationarity of EEG signals result in high inter-subject/session variability. Therefore, each subject usually spends long and tedious calibration time in building a subject-specific classifier. To solve this problem, we review existing signal processing approaches, including transfer learning (TL), semi-supervised learning (SSL), and a combination of TL and SSL. Cross-subject TL can transfer amounts of labeled samples from different source subjects for the target subject. Moreover, Cross-session/task/device TL can reduce the calibration time of the subject for the target session, task, or device by importing the labeled samples from the source sessions, tasks, or devices. SSL simultaneously utilizes the labeled and unlabeled samples from the target subject. The combination of TL and SSL can take advantage of each other. For each kind of signal processing approaches, we introduce their concepts and representative methods. The experimental results show that TL, SSL, and their combination can obtain good classification performance by effectively utilizing the samples available. In the end, we draw a conclusion and point to research directions in the future.
Vitamin D Status and Its Correlation With Anthropometric and Biochemical Indicators of Cardiometabolic Risk in Serbian Underground Coal Miners in 2016
Authors: Šarac Ivana , Jovanović Jovica , Zec Manja , Pavlović Zoran , Debeljak-Martačić Jasmina , Zeković Milica , Milešević Jelena , Gurinović Mirjana , Glibetić Maria
Published: August 2021

The status of vitamin D in underground working coal miners and its association with their cardiometabolic health is rarely studied. This study aimed to examine vitamin D (VitD) status in Serbian underground coal miners and to correlate it with anthropometric and laboratory indicators of cardiometabolic risk. Nutritional data (food frequency questionnaire, FFQ, and two times repeated 24 h recall), anthropometric data (including segmental analysis by bio-impedance analyzer TANITA BC-545N), arterial tension, and biochemical and hematological data of 103 coal miners (aged 22–63 years) were correlated with their late summer (early September) serum 25 (OH)D levels (measured by HPLC). 68.9% of the studied coal miners were overweight/obese, and 48.5% had metabolic syndrome. Their mean VitD nutritional intakes were low: 5.3 ± 3.8 μg/day (FFQ) and 4.9 ± 8 μg/day (24 h recalls), but their mean serum 25 (OH)D levels were surprisingly high (143.7 ± 41.4 nmol/L). Only 2.9% of the coal miners had 25(OH)D levels lower than 75 nmol/L (indicating an insufficient/deficient status), while 63.2% had values above 125 nmol/L (upper optimal limit), and even 10.7% had values above 200 nmol/L. There were no statistical differences in 25 (OH)D levels in the coal miners with or without metabolic syndrome (or overweight/obesity). Interestingly, 25(OH)D levels had significant positive correlations with body mass index (BMI), fat mass (FM), fat mass percentage (FM%), limbs FM%, serum triglycerides, GGT, AST, ALT, and ALT/AST ratio, and had significant negative correlations with serum HDL-cholesterol and age. All these correlations were lost after corrections for age, FM, FM%, and legs FM%. In Serbian coal miners, high levels of early September VitD levels were observed, indicating sufficient non-working-hour sun exposure during the summer period. Furthermore, the unexpected positive correlations of VitD levels with anthropometric and biochemical parameters indicative of obesity, metabolic syndrome, and fatty liver disease were found. More research is needed on the VitD status of coal miners (particularly in the winter period) and its relationship with their cardiometabolic status.
A Soybean Resistant Protein-Containing Diet Increased the Production of Reg3γ Through the Regulation of the Gut Microbiota and Enhanced the Intestinal Barrier Function in Mice
Authors: Ogita Tasuku , Namai Fu , Mikami Ayane , Ishiguro Takahiro , Umezawa Koji , Uyeno Yutaka , Shimosato Takeshi
Published: August 2021

The maintenance of intestinal homeostasis is necessary for a good quality of life, and strengthening of the intestinal barrier function is thus an important issue. Therefore, we focused on soybean resistant protein (SRP) derived from kori-tofu (freeze-dried tofu), which is a traditional Japanese food, as a functional food component. In this study, to investigate the effect of SRP on the intestinal barrier function and intestinal microbiota, we conducted an SRP free intake experiment in mice. Results showed that ingestion of SRP decreased the serum level of lipopolysaccharide-binding protein and induced the expression of Reg3γ, thereby improving the intestinal barrier function. In addition, SRP intake induced changes in the cecal microbiota, as observed by changes in β-diversity. In particular, in the microbiota, the up-regulation of functional gene pathways related to the bacterial invasion of epithelial cells (ko05100) was observed, suggesting that Reg3γ expression was induced by the direct stimulation of epithelial cells. The results of this study suggest that SRP is a functional food component that may contribute to the maintenance of intestinal homeostasis.
Combination of the Distance From Tumor Edge to Subventricular Zone and IDH Mutation Predicts Prognosis of Patients With Glioma
Authors: Zhang Shuixian , Zhao Fengchun , Zhou Tengyuan , Liu Dan , Yao Xiaohong , Fu Wenjuan , Liu Zhi , Lan Chuan , Lai Zhaopan , Liu Chen , Li Haitao , Li Yuhong , Hu Shengli , Yin Yi , Tan Liang , Li Wenyan , Li Fei , Hu Rong , Feng Hua
Published: August 2021

Both subventricular zone (SVZ) contact and isocitrate dehydrogenase 1 (IDH1) mutation have been reported to be related to the outcome of glioma, respectively. However, far too little attention has been paid to the role of tumor edge-SVZ distance in the outcome of glioma. We aim to assess the value of tumor-SVZ distance, as well as combined tumor-SVZ distance and IDH status, in predicting the outcome of gliomas (WHO grade II–IV). Here, the MR images and clinical data from 146 patients were included in the current study. The relationship between survival and the tumor-SVZ distance as well as survival and combination of tumor-SVZ distance and IDH status were determined via univariate and multivariate analyses. In univariate analysis of tumor-SVZ distance, the patients were divided into three types (SVZ involvement, tumor-SVZ distance from 0 to 10 mm, and tumor-SVZ distance >10 mm). The results showed that the OS (p = 0.02) and PFS (p = 0.002) for the patients had a positive correlation with the tumor-SVZ distance. In addition, simple linear correlation found a significant relationship between the two parameters (OS and PFS) and tumor-SVZ distance in patients with non-SVZ-contacting glioma. Combination analysis of the tumor-SVZ distance and IDH status showed that IDH1 mutation and SVZ non-involvement enable favorable outcomes, whereas IDH1 wild type with SVZ involvement indicates a significantly worse prognosis in all patients. Moreover, in patients with non-SVZ-contacting glioma, IDH1 mutation concurrent with tumor-SVZ distance >10 mm has better OS and PFS. IDH1 wild type and tumor-SVZ distance from 0 to 10 mm suggest poorer OS and PFS. Multivariate analysis showed WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, gross total resection, and chemotherapy serve as independent predictors of OS. WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, and chemotherapy serve as independent predictors of PFS of patients with glioma. In conclusion, tumor-SVZ distance and IDH1 mutation status are the determinants affecting patient outcome.
The Role of the Metabolic Parameters of 18F-FDG PET/CT in Patients With Locally Advanced Cervical Cancer
Authors: Wang Dunhuang , Liu Xiaoliang , Wang Weiping , Huo Li , Pan Qingqing , Ren Xue , Zhang Fuquan , Hu Ke
Published: August 2021

Purpose

To evaluate the role of the pre-treatment cervical and lymph node (LN) metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) for locally advanced cervical cancer (LACC) patients receiving concurrent chemoradiotherapy or radiotherapy.

Methods

we reviewed 125 consecutive patients with LACC who underwent pre-treatment 18F-FDG PET/CT examination and concurrent chemoradiotherapy or radiotherapy from February 2010 to December 2015 at our institute. The mean standardized uptake value (SUVmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of cervical lesion and lymph node (LN) were recorded. Receiver operator characteristic curve, C-index, Kaplan-Meier method, and Cox proportional hazards models were performed.

Results

The median follow-up was 62 months (range, 4-114 months). For 125 included patients with cervical cancer, the 5-year overall survival (OS), disease-free survival (DFS), local control (LC) and distant metastasis-free survival (DMFS) rates were 83.6%, 75.1%, 92.3% and 79.9%, respectively. Cervical MTV (c-index 0.59-0.61) and cervical TLG (c-index 0.60-0.62) values calculated with a threshold of 40% SUVmax presented stronger prediction capability than cervical SUVmean (c-index 0.51-0.58) and cervical SUVmax (c-index 0.53-0.57) for OS, DFS, LC, and DMFS. In univariate analysis, cervical TLG ≥ 113.4 had worse DFS and DMFS. Cervical MTV ≥ 18.3 cm3 had worse OS and DMFS. In multivariate analysis, cervical TLG ≥ 113.4 implied worse OS, DFS, and DMFS. In either univariate or multivariate analyses, cervical SUVmean and cervical SUVmax had no statistically significant correlation with OS, DFS, LC and DMFS. For 55 cervical cancer patients with positive LN, LN SUVmax presented strongest prediction capability for OS (c-index = 0.79), DFS (c-index = 0.72), LC (c-index = 0.62), and DMFS (c-index = 0.79). In multivariate analysis, LN SUVmax remained significant biomarker linked to OS, DFS, and DMFS.

Conclusion

Pre-treatment cervical and LN metabolic parameters were associated with survival outcomes in patients with LACC. In our study, we found that pre-treatment cervical TLG and LN SUVmax may be important prognostic biomarkers for OS, DFS, and DMFS. However, further prospective studies with a large number of patients are required to evaluate the value of the metabolic parameters in survival outcomes prediction.
Identification of a Hypoxia-Related Molecular Classification and Hypoxic Tumor Microenvironment Signature for Predicting the Prognosis of Patients with Triple-Negative Breast Cancer
Authors: Sun Xiaoli , Luo Huan , Han Chenbo , Zhang Yu , Yan Cunli
Published: August 2021

Purpose

The hypoxic tumor microenvironment was reported to be involved in different tumorigenesis mechanisms of triple-negative breast cancer (TNBC), such as invasion, immune evasion, chemoresistance, and metastasis. However, a systematic analysis of the prognostic prediction models based on multiple hypoxia-related genes (HRGs) has not been established in TNBC before in the literature. We aimed to develop and verify a hypoxia gene signature for prognostic prediction in TNBC patients.

Methods

The RNA sequencing profiles and clinical data of TNBC patients were generated from the TCGA, GSE103091, and METABRIC databases. The TNBC-specific differential HRGs (dHRGs) were obtained from differential expression analysis of hypoxia cultured TNBC cell lines compared with normoxic cell lines from the GEO database. Non-negative matrix factorization (NMF) method was then performed on the TNBC patients using the dHRGs to explore a novel molecular classification on the basis of the dHRG expression patterns. Prognosis-associated dHRGs were identified by univariate and multivariate Cox regression analysis to establish the prognostic risk score model.

Results

Based on the expressions of 205 dHRGs, all the patients in the TCGA training cohort were categorized into two subgroups, and the patients in Cluster 1 demonstrated worse OS than those in Cluster 2, which was validated in two independent cohorts. Additionally, the effects of somatic copy number variation (SCNV), somatic single nucleotide variation (SSNV), and methylation level on the expressions of dHRGs were also analyzed. Then, we performed Cox regression analyses to construct an HRG-based risk score model (3-gene dHRG signature), which could reliably discriminate the overall survival (OS) of high-risk and low-risk patients in TCGA, GSE103091, METABRIC, and BMCHH (qRT-PCR) cohorts.

Conclusions

In this study, a robust predictive signature was developed for patients with TNBC, indicating that the 3-gene dHRG model might serve as a potential prognostic biomarker for TNBC.
STK3-ALK, a Novel ALK Rearrangement in Non-Small Cell Lung Cancer With Sensitivity to Tyrosine Kinase Inhibitors: A Case Report
Authors: Feng Chunlai , Zhou Rong , Liu Feng , Wang Tingting , Liu Sisi , Shao Yang
Published: August 2021

Anaplastic lymphoma kinase (ALK) rearrangement occurs in 5% to 8% of patients with non-small cell lung cancer (NSCLC). More than 90 different ALK fusion partners have been discovered in NSCLC patients, and ALK tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib have achieved tumor responses in patients with advanced ALK-positive NSCLC. Here, we report the case of a patient with an advanced NSCLC carrying a novel serine/threonine kinase 3 (STK3)-ALK rearrangement, which was identified by targeted next-generation sequencing (NGS) and was confirmed by RNA sequencing. Anti-ALK immunohistochemistry (IHC) staining also revealed the high expression of ALK. The patient benefitted from alectinib treatment after experiencing crizotinib resistance and achieved an overall response to TKI of over 14 months. At the timepoint of submission of this manuscript, this patient is still receiving alectinib treatment with a good tolerance. This study provides meaningful insights into the potential treatment option for NSCLC patients with brain metastases harboring STK3-ALK fusions and highlights the advantages of NGS in rapidly identifying novel molecular targets.
Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology
Authors: Petropoulos Ioannis N. , Bitirgen Gulfidan , Ferdousi Maryam , Kalteniece Alise , Azmi Shazli , D'Onofrio Luca , Lim Sze Hway , Ponirakis Georgios , Khan Adnan , Gad Hoda , Mohammed Ibrahim , Mohammadi Yacob E. , Malik Ayesha , Gosal David , Kobylecki Christopher , Silverdale Monty , Soran Handrean , Alam Uazman , Malik Rayaz A.
Published: August 2021

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases.
Medication Adherence and the Role of Pictograms in Medication Counselling of Chronic Patients: a Review
Authors: Merks Piotr , Cameron Jameason , Bilmin Krzysztof , Świeczkowski Damian , Chmielewska-Ignatowicz Tomira , Harężlak Tomasz , Białoszewska Katarzyna , Sola Katarina Fehir , Jaguszewski Miłosz J , Vaillancourt Regis
Published: August 2021

Pharmaceutical care requires a patient-centered approach, focusing on the ability of patients to understand drug-related information and follow the instructions delivered by pharmacists as well as other health-care providers included in the circle of care. With the goal of ensuring the prescribed use of medications, called medication adherence, health-care providers have to consider many risk factors such as geography (culture), social economic status, age, and low literacy that may predispose patients to non-adherence, and considerations have to be made for chronic patients living with life-long disease states. The aim of this review is to provide a balanced and comprehensive review outlining a number of different medication counselling and education approaches that have been used to try to improve medication adherence and health outcomes with the use of clear and concise graphic illustrations—called pictograms. By highlighting the current landscape of the general use and efficacy of pharmaceutical pictograms to aid in the knowledge and recall of drug-related information, as well as outlining specific medication adherence outcomes with pharmaceutical pictograms in chronic patients, the current review describes the need for health-care providers to move beyond the traditional didactic methods of oral and verbal communication with patients regarding medication-taking behavior.