bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a Silk Sericin and Methylsulfonylmethane (MSM) Blends on Inflammatory Response and Wound Healing
Authors: Jeong Hyun-Lyung , Kang Eun-Bin , Yun Seung-Geun , Park Dan-bi , Lim Jeong-Ok , Suh Jang-Soo
Published: December 2022

The natural product silk sericin has excellent biological properties, such as biocompatibility, biodegradability, and antioxidant activity, and it also facilitates cell proliferation, collagen type 1 production, and wound healing. Methylsulfonylmethane (MSM) is a natural organic sulfur compound known to relieve pain and inflammation. In this study, we formulated sericin and MSM blends in various ratios, and investigated their effects on the inflammatory response and subsequent healing of a wound in vitro using macrophages and fibroblasts. The experimental findings, derived from cell viability analyses and nuclear factor kappa B (NFκB)/cyclooxygenase-2 (COX-2)/inducible nitric oxide synthase (iNOS) pathway assays, demonstrated that the anti-inflammatory activity of MSM was more effective when it was blended with sericin. In contrast, MSM alone did not enhance wound healing but rather delayed it at higher concentrations. We confirmed that the blend of sericin and MSM exhibited a synergistic effect on suppressing inflammatory responses and promoting subsequent wound healing when the two materials were optimally blended.
Predicting the Onset of Freezing of Gait Using EEG Dynamics
Authors: John Alka Rachel , Cao Zehong , Chen Hsiang-Ting , Martens Kaylena Ehgoetz , Georgiades Matthew , Gilat Moran , Nguyen Hung T. , Lewis Simon J. G. , Lin Chin-Teng
Published: December 2022

Freezing of gait (FOG) severely incapacitates the mobility of patients with advanced Parkinson’s disease (PD). An accurate prediction of the onset of FOG could improve the quality of life for PD patients. However, it is imperative to distinguish the possibility of the onset of FOG from that of voluntary stopping. Our previous work demonstrated the neurological differences between the transition to FOG and voluntary stopping using electroencephalogram (EEG) signals. We employed a timed up-and-go (TUG) task to elicit FOG in PD patients. Some of these TUG tasks had an additional voluntary stopping component, where participants stopped walking based on verbal instruction to “stop”. The performance of the convolutional neural network (CNN) in identifying the transition to FOG from normal walking and the transition to voluntary stopping was explored. To the best of our knowledge, this work is the first study to propose a deep learning method to distinguish the transition to FOG from the transition to voluntary stop in PD patients. The models, trained on the EEG data from 17 PD patients who manifested FOG episodes, considering a short two-second transition window for FOG occurrence or voluntary stopping, achieved close to 75% classification accuracy in distinguishing transition to FOG from the transition to voluntary stopping or normal walking. Our results represent an important step toward advanced EEG-based cueing systems for smart FOG intervention, excluding the potential confounding of voluntary stopping.
Dynamic Characteristics of Post-Cyclic Saturated Loess
Authors: Wang Qian , Wang Yan , Ma Wenguo , Tao Dongwang
Published: December 2022

Damage to soil structure caused by strong earthquakes is one of the main reasons for post-earthquake geohazard development. To investigate the nonlinear dynamic behaviors of the post-earthquake loess, a pre-shock reconsolidation test was designed to simulate the process of the loess undergoing earthquake and post-earthquake reconsolidation in a natural state. Furthermore, dynamic triaxial tests of the specimens before and after pre-shock action and consolidation stabilization with different over-consolidation ratios (OCR) were conducted to investigate the variety of the dynamic modulus and damping ratio of the saturated loess. The influence of pre-shock and reconsolidation on the dynamic behaviors was determined. Moreover, the mechanism of the changes after pre-shock and consolidation was discussed by combining the microstructure test results of soil samples before and after pre-shock and reconsolidation. The results suggest that the kinetic stiffness of the pre-shock saturated loess decreases significantly under the same consolidation conditions. The growth of the damping ratio-dynamic strain curve increases, and the deformation potential of the loess has a remarkable growth. With an increase in OCR, the dynamic elastic modulus after pre-shock increases continuously; however, the damping ratio decreases significantly. The dynamic stiffness increases and the deformation potential weakens significantly. The strong earthquake leads to the weakening of interparticle cementation, pore penetration, and structural reorganization in the local area, causes connecting of the macropores, and produces microfractures in the soil, which makes a significant decrease in the dynamic shear modulus ratio and an increase in the damping ratio of the loess, leading to the enhancement of soil dynamic nonlinearity and the attenuation of the dynamic strength. Moreover, the compaction effect of reconsolidation on the soil increases the interparticle friction and heals some microfractures, which leads to an increase in soil stiffness. This makes the maximum dynamic shear modulus and the maximum dynamic shear stress amplitude of the post-cyclic saturated loess perform at the same level compared with the natural loess without shock when the OCR equals three. However, the dynamic shear modulus and the damping ratio of the post-cyclic saturated loess are close to the natural loess when the OCR equals two.
The Importance of the Microbiota in Shaping Women’s Health—The Current State of Knowledge
Authors: Krupa-Kotara Karolina , Helisz Paulina , Gwioździk Weronika , Grajek Mateusz
Published: December 2022

According to current knowledge, a properly colonized human microbiota contributes to the proper functioning of the body. The composition of the natural flora changes depending on age, health, living conditions, and the use of antimicrobial agents: antibiotics, disinfectants, and some cosmetics. The human body is diversely populated with microorganisms and undergoes constant changes under the influence of various factors, and its proper composition is extremely important for the proper functioning of the body. Given the above, it was decided that we would review current scientific research that explains the cause–effect relationship between the composition of microorganisms populating the human body and health, focusing on women’s health. As a result, an overview paper was prepared based on 109 scientific sources from 2009–2022. Special attention was paid to the most recent scientific studies of the last five years, which account for more than 75% of the cited sources.
The Image of Women Architects in Films, 1912–1943: New Careers and Stereotyped Femininities
Authors: Pérez-Moreno Lucía C. , Lus-Arana Luis M.
Published: December 2022

Contrary to what might be expected, portrayals of women architects in films can be found as far back as the early decades of the twentieth century. In this article, the authors review a few films released between 1912 and 1943 in which one of the characters is a woman architect, focusing on three of them: Dr. Monica (1934), Woman Chases Man (1937) and The Lamp Still Burns (1943). The article explores the ways in which architecture was used by screenwriters and directors as a suitable vehicle to portray the ‘new woman’, as well as the conflicts that arise when a woman practices a traditionally male profession. It analyses the differences and limitations of these depictions, and the stereotypes regarding femininity that permeated these works of fiction.
Decision-Support System for Estimating Resource Consumption in Bridge Construction Based on Machine Learning
Authors: Kovačević Miljan , Ivanišević Nenad , Stević Dragan , Marković Ljiljana Milić , Bulajić Borko , Marković Ljubo , Gvozdović Nikola
Published: December 2022

The paper presents and analyzes the state-of-the-art machine learning techniques that can be applied as a decision-support system in the estimation of resource consumption in the construction of reinforced concrete and prestressed concrete road bridges. The formed database on the consumption of concrete in the construction of bridges, along with their project characteristics, was the basis for the formation of the assessment model. The models were built using information from 181 reinforced concrete bridges in the eastern and southern branches of Corridor X in Serbia, with a value of more than 100 million euros. The application of artificial neural network models (ANNs), models based on regression trees (RTs), models based on support vector machines (SVM), and Gaussian processes regression (GPR) were analyzed. The accuracy of each model is determined by multi-criterion evaluation against four accuracy criteria root mean square error (RMSE), mean absolute error (MAE), Pearson’s linear correlation coefficient (R), and mean absolute percentage error (MAPE). According to all established criteria, the model based on GPR demonstrated the greatest accuracy in calculating the concrete consumption of bridges. According to the study, using automatic relevance determination (ARD) covariance functions results in the most accurate and optimal models and also makes it possible to see how important each input variable is to the model’s accuracy.
Particle Contamination in Commercial Lithium-Ion Cells—Risk Assessment with Focus on Internal Short Circuits and Replication by Currently Discussed Trigger Methods
Authors: Grabow Jens , Klink Jacob , Benger Ralf , Hauer Ines , Beck Hans-Peter
Published: December 2022

A possible contamination with impurities or material weak points generated in cell production of lithium-ion batteries increases the risk of spontaneous internal short circuits (ISC). An ISC can lead to a sudden thermal runaway (TR) of the cell, thereby making these faults especially dangerous. Evaluation regarding the criticality of an ISC, the development of detection methods for timely fault warning and possible protection concepts require a realistic failure replication for general validation. Various trigger methods are currently discussed to reproduce these ISC failure cases, but without considering a valid basis for the practice-relevant particle properties. In order to provide such a basis for the evaluation and further development of trigger methods, in this paper, the possibilities of detecting impurity particles in production were reviewed and real particles from pouch cells of an established cell manufacturer were analysed. The results indicate that several metallic particles with a significant size up to 1 mm × 1.7 mm could be found between the cell layers. This evidence shows that contamination with impurity particles cannot be completely prevented in cell production, as a result of which particle-induced ISC must be expected and the need for an application-oriented triggering method currently exists. The cause of TR events in the field often cannot be identified. However, it is noticeable that such faults often occur during the charging process. A new interesting hypothesis for this so-far unexplained phenomenon is presented here. Based on all findings, the current trigger methods for replicating an external particle-induced ISC were evaluated in significant detail and specific improvements are identified. Here, it is shown that all current trigger methods for ISC replication exhibit weaknesses regarding reproducibility, which results mainly from the scattering random ISC contact resistance.
Elucidating Spatial Distribution of Electrochemical Reaction in a Porous Electrode by Electrochemical Impedance Spectra for Flow Batteries
Authors: Zhang Jie , Gan Qilong , Yuan Xianzhi , Xiang Zhipeng , Fu Zhiyong , Liang Zhenxing
Published: December 2022

A porous electrode is an essential component in a flow battery, and its structure determines the battery’s performance. The coupling of the multi-temporal-spatial-scale processes (e.g., electrochemical reaction, mass transfer, charge transfer) makes the recognition of each process complicated. Herein, a symmetric flow cell device is developed, and the electrochemical impedance measurement (two- or three-electrode configuration) is realized to elucidate the electrochemical processes. First, the effect of flow rate and concentration on the impedance spectra is investigated to identify the electrochemical processes. Second, the distributed resistance is quantified to describe the spatial distribution of the electrochemical reaction. It is found that the electrochemical reaction occurs near the membrane side at a low polarization current, and the reaction zones spatially extend from the membrane side to the current collector with the increase of imposed polarization. Such an evolution of the spatial distribution stems from the trade-off between the mass transfer and the ion conduction in the porous electrode. This work provides an experimental method to nondestructively probe the electrochemical processes, and the result provides guidance for developing innovative electrode structures for flow batteries.
Multiomics Approach Captures Hepatic Metabolic Network Altered by Chronic Ethanol Administration
Authors: Sakallioglu Isin Tuna , Tripp Bridget , Kubik Jacy , Casey Carol A. , Thomes Paul , Powers Robert
Published: December 2022

Using a multiplatform and multiomics approach, we identified metabolites, lipids, proteins, and metabolic pathways that were altered in the liver after chronic ethanol administration. A functional enrichment analysis of the multiomics dataset revealed that rats treated with ethanol experienced an increase in hepatic fatty acyl content, which is consistent with an initial development of steatosis. The nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC-MS) metabolomics data revealed that the chronic ethanol exposure selectively modified toxic substances such as an increase in glucuronidation tyramine and benzoyl; and a depletion in cholesterol-conjugated glucuronides. Similarly, the lipidomics results revealed that ethanol decreased diacylglycerol, and increased triacylglycerol, sterol, and cholesterol biosynthesis. An integrated metabolomics and lipidomics pathway analysis showed that the accumulation of hepatic lipids occurred by ethanol modulation of the upstream lipid regulatory pathways, specifically glycolysis and glucuronides pathways. A proteomics analysis of lipid droplets isolated from control EtOH-fed rats and a subsequent functional enrichment analysis revealed that the proteomics data corroborated the metabolomic and lipidomic findings that chronic ethanol administration altered the glucuronidation pathway.
Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective of Chronological Age
Authors: Jiménez-Balado Joan , Giralt-Steinhauer Eva , Fernández-Pérez Isabel , Rey Lucía , Cuadrado-Godia Elisa , Ois Ángel , Rodríguez-Campello Ana , Soriano-Tárraga Carolina , Lazcano Uxue , Macias-Gómez Adrià , Suárez-Pérez Antoni , Revert Anna , Estragués Isabel , Beltrán-Mármol Brigitte , Medrano-Martorell Santiago , Capellades Jaume , Roquer Jaume , Jiménez-Conde Jordi
Published: December 2022

In this manuscript we studied the relationship between WMH and biological age (B-age) in patients with acute stroke. We included in this study 247 patients with acute stroke recruited at Hospital del Mar having both epigenetic (DNA methylation) and magnetic resonance imaging data. WMH were measured using a semi-automated method. B-age was calculated using two widely used methods: the Hannum and Horvath formulas. We used multiple linear regression models to interrogate the role of B-age on WMH volume after adjusting for chronological age (C-age) and other covariables. Average C-age of the sample was 68.4 (±11.8) and we observed a relatively high median WMH volume (median = 8.8 cm3, Q1–Q3 = 4.05–18.8). After adjusting for potential confounders, we observed a significant effect of B-ageHannum on WMH volume (βHannum = 0.023, p-value = 0.029) independently of C-age, which remained significant (βC-age = 0.021, p-value = 0.036). Finally, we performed a mediation analysis, which allowed us to discover that 42.7% of the effect of C-age on WMH is mediated by B-ageHannum. On the other hand, B-ageHoarvath showed no significant associations with WMH after being adjusted for C-age. In conclusion, we show for the first time that biological age, measured through DNA methylation, contributes substantially to explain WMH volumetric burden irrespective of chronological age.
Circulating Fibroblast Growth Factor-23 Levels Can Predict Rapid Kidney Function Decline in a Healthy Population: A Community-Based Study
Authors: Chen Hsing-Yu , Fang Wei-Ching , Chu Shao-Chi , Wang Po-Hsi , Lee Chin-Chan , Wu I-Wen , Sun Chiao-Yin , Hsu Heng-Jung , Chen Chun-Yu , Chen Yung-Chang , Wu Vin-Cent , Pan Heng-Chih
Published: December 2022

Background: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. Methods: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD—a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. Results: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Conclusions: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.
First Evidence of the Protective Effects of 2-Pentadecyl-2-Oxazoline (PEA-OXA) in In Vitro Models of Acute Lung Injury
Authors: Schiano Moriello Aniello , Roviezzo Fiorentina , Iannotti Fabio Arturo , Rea Giuseppina , Allarà Marco , Camerlingo Rosa , Verde Roberta , Di Marzo Vincenzo , Petrosino Stefania
Published: December 2022

Acute respiratory distress syndrome (ARDS) is a serious inflammatory lung disorder and a complication of SARS-CoV-2 infection. In patients with severe SARS-CoV-2 infection, the transition to ARDS is principally due to the occurrence of a cytokine storm and an exacerbated inflammatory response. The effectiveness of ultra-micronized palmitoylethanolamide (PEA-um) during the earliest stage of COVID-19 has already been suggested. In this study, we evaluated its protective effects as well as the effectiveness of its congener, 2-pentadecyl-2-oxazoline (PEA-OXA), using in vitro models of acute lung injury. In detail, human lung epithelial cells (A549) activated by polyinosinic–polycytidylic acid (poly-(I:C)) or Transforming Growth Factor-beta (TGF-β) were treated with PEA-OXA or PEA. The release of IL-6 and the appearance of Epithelial–Mesenchymal Transition (EMT) were measured by ELISA and immunofluorescence assays, respectively. A possible mechanism of action for PEA-OXA and PEA was also investigated. Our results showed that both PEA-OXA and PEA were able to counteract poly-(I:C)-induced IL-6 release, as well as to revert TGF-β-induced EMT. In addition, PEA was able to produce an “entourage” effect on the levels of the two endocannabinoids AEA and 2-AG, while PEA-OXA only increased PEA endogenous levels, in poly-(I:C)-stimulated A549 cells. These results evidence for the first time the superiority of PEA-OXA over PEA in exerting protective effects and point to PEA-OXA as a new promising candidate in the management of acute lung injury.
Short-Term Consequences of Single Social Defeat on Accumbal Dopamine and Behaviors in Rats
Authors: Nemets Vsevolod V. , Deal Alex L. , Sobolev Vladislav E. , Grinevich Vladimir P. , Gainetdinov Raul R. , Budygin Evgeny A.
Published: December 2022

The present study aimed to explore the consequences of a single exposure to a social defeat on dopamine release in the rat nucleus accumbens measured with a fast-scan cyclic voltammetry. We found that 24 h after a social defeat, accumbal dopamine responses, evoked by a high frequency electrical stimulation of the ventral tegmental area, were more profound in socially defeated rats in comparison with non-defeated control animals. The enhanced dopamine release was associated with the prolonged immobility time in the forced swim test. The use of the dopamine depletion protocol revealed no alteration in the reduction and recovery of the amplitude of dopamine release following social defeat stress. However, administration of dopamine D2 receptor antagonist, raclopride (2 mg/kg, i.p.), resulted in significant increase of the electrically evoked dopamine release in both groups of animals, nevertheless exhibiting less manifested effect in the defeated rats comparing to control animals. Taken together, our data demonstrated profound alterations in the dopamine transmission in the association with depressive-like behavior following a single exposure to stressful environment. These voltammetric findings pointed to a promising path for the identification of neurobiological mechanisms underlying stress-promoted behavioral abnormalities.
CISD1 Is a Breast Cancer Prognostic Biomarker Associated with Diabetes Mellitus
Authors: Liu Fangfang , Dong Yifeng , Zhong Fuyu , Guo Haodan , Dong Pengzhi
Published: December 2022

Women with diabetes mellitus are believed to have increased risk of developing breast cancer and lower life expectancies. This study aims to depict the association between the CISD1, the co-expressed genes, and diabetes mellitus to offer potential therapeutic targets for further mechanical research. The TCGA-BRCA RNAseq data is acquired. All the data and analyzed using R packages and web-based bioinformatics tools. CISD1 gene expression was evaluated between tumor bulk and adjacent tissue. Immune cell infiltration evaluation was performed. CISD1 expressed significantly higher in tumor tissue than that of the normal tissue, indicating poor overall survival rates. High expression level of CISD1 in tumor shows less pDC and NK cells penetration. There are 138 genes shared between CISD1 co-expressed gene pool in BRCA and diabetes mellitus related genes using “diabetes” as the term for text mining. These shared genes enrich in “cell cycle” and other pathways. MCODE analysis demonstrates that p53-independent G1/S DNA damage checkpoint, p53-independent DNA damage response, and ubiquitin mediated degradation of phosphorylated cdc25A are top-ranked than other terms. CISD1 and co-expressed genes, especially shared ones with diabetes mellitus, can be the focused genes considered when addressing clinical problems in breast cancer with a diabetes mellitus background.
Pan-Cancer Analysis of the Roles and Driving Forces of RAB42
Authors: Zheng Mingzhu , Wang Wenhao , Bu Yulan , Liu Jing , Ma Jingang , Wang Rui , Ren Xiaomin , Lu Zhong , Li Jiaqiu , Cai Jinwei
Published: December 2022

RAB42 is a member of the RAS family. However, the roles and driving forces for RAB42 in tumors remain elusive. In this study, we performed a comprehensive pan-cancer analysis of the roles and regulatory mechanisms of RAB42 using bioinformatics and experiments. Online databases such as Sanger Box, ACLBI and TIDE were used to search for the expression levels, prognostic value and immune features of RAB42. We observed that RAB42 expression was upregulated in most tumors and was closely associated with poor prognosis. Enrichment analysis indicated that RAB42 was related to multiple biological functions, especially the immune process. RAB42 expression had a positive correlation with immune cell infiltration and immune checkpoint gene expression. RAB42 had a high predictive value for immunotherapy efficiency. Our study screened out susceptible drugs for the RAB42 protein by sensitivity analysis and virtual screening. Many key driver genes such as TP53 contributed to RAB42 expression. DNA methylation, super-enhancer and non-coding RNAs were the epigenetic factors responsible for RAB42 expression. In brief, RAB42 could serve as a diagnostic and prognostic biomarker in many tumor types. RAB42 might be a predictive biomarker and a new target for immunotherapy. Genetic and epigenetic factors were essential for RAB42 overexpression in tumors.
Integrating Transcriptomic and ChIP-Seq Reveals Important Regulatory Regions Modulating Gene Expression in Myometrium during Implantation in Pigs
Authors: Wang Weiwei , Cao Caiqin , Zhang Botao , Wang Feiyu , Deng Dadong , Cao Jianhua , Li Hua , Yu Mei
Published: December 2022

The myometrium is the outer layer of the uterus. Its contraction and steroidogenic activities are required for embryo implantation. However, the molecular mechanisms underlying its functions remain unknown in pigs. The myometrium includes the inner circular muscle (CM) and the outer longitudinal muscle (LM) layers. In this study, we collected the CM and LM samples from the mesometrial side (named M) of the uterus on days 12 (pre-implantation stage) and 15 (implantation stage) of pregnancy and day 15 of the estrous cycle. The transcriptomic results revealed distinct differences between the uterine CM and LM layers in early pregnancy: the genes expressed in the LM layer were mainly related to contraction pathways, whereas the transcriptional signatures in the CM layer on day 15 of pregnancy were primarily involved in the immune response processes. Subsequent comparisons in the CM layer between pregnant and cyclic gilts show that the transcriptional signatures of the CM layer are implantation-dependent. Next, we investigated the genome-wide profiling of histone H3 lysine 27 acetylation (H3K27ac) and histone H3 lysine 4 trimethylation (H3K4me3) in pig uterine CM and LM layers. The genomic regions that had transcriptional activity and were associated with the expression of genes in the two layers were characterized. Taken together, the regulatory regions identified in the study may contribute to modulating the gene expression in pig uterine CM and LM layers during implantation.
Relationship among Body Composition, Adipocytokines, and Irisin on Exercise Capacity and Quality of Life in COPD: A Pilot Study
Authors: Cuttitta Giuseppina , Ferraro Maria , Cibella Fabio , Alfano Pietro , Bucchieri Salvatore , Patti Angelo Maria , Muratori Rosalba , Pace Elisabetta , Bruno Andreina
Published: December 2022

Adipose tissue is an endocrine organ that interferes with the severity of chronic obstructive pulmonary disease (COPD). Although inflammatory markers, body composition, and nutritional status have a significant impact on pulmonary function, the real contribution of adipocytokines and myokines in COPD is still controversial. We aimed to evaluate the role played by the body composition, leptin, adiponectin, haptoglobin, and irisin on the functional exercise capacity, respiratory function, and quality of life (QoL) in COPD. In 25 COPD (20% GOLD-1; 60% GOLD-2; 20% GOLD-3) patients and 26 matched control subjects, we find that leptin, total adiponectin and haptoglobin are significantly increased whereas the 6 min walk test (6MWT) and physical functioning scores are significantly decreased in COPD versus controls. A significant positive relationship is found between leptin and fat mass and between 6MWT and the good health indicators of nutritional status. A significant inverse relationship is found between 6MWT and leptin and fat mass, FEV1 and haptoglobin, and irisin and haptoglobin. Phase angle and leptin level are significant predictors for functional exercise capacity assessed with 6MWT. Taken altogether, the results of this pilot study further support the role played by body composition and adipocytokines on exercise capacity respiratory function and QoL in COPD.
Hyperoxia Induced Hypomyelination
Authors: Song Weilin , Hoppe George , Hanna Demiana , DeSilva Tara M. , Sears Jonathan E.
Published: December 2022

We asked whether hyperoxia might induce hypomyelination of the corpus callosum, clinically described as periventricular leukomalacia (PVL) of the severely preterm infant. Mouse pups and their nursing dams were placed in 80% oxygen from P4-P8, then removed to room air until P11. Corpus callosal sections were probed myelin immunofluorescence, tested for myelin basic protein concentration by Western blot, and both glial fibrillary acidic protein levels and apoptosis quantified. Density of corpus callosal capillaries were measured after lectin staining and hypoxia measured by Hypoxyprobe. Numbers of oligodendrocytes were quantified by immunohistochemistry. We next used hypoxiamimesis as a surrogate to hypoxia by comparing cerebral hypoxia inducible factor (HIF) stabilization to hepatic HIF stabilization. Hyperoxia induced hypomyelination and a reduction of corpus callosal capillaries. Hyperoxia decreased numbers of oligodendrocytes with an increase in corpus callosal fibrosis and apoptosis. Cerebral hypoxiamimesis induced hypomyelination whereas hepatic hypoxiamimesis alone increased myelination, oligodendrocyte numbers, and corpus callosal capillary density. Hepatic HIF-1 dependence on myelination was confirmed using the cre/lox hepatic HIF-1 knockout. These findings suggest that hyperoxia can induce hypomyelination through vasoobliteration and subsequent ischemia, adding a potential oxygen induced mechanism to the diverse causes of periventricular leukomalacia of the severely preterm infant. Targeting hepatic HIF-1 alone led to increased myelination.
Necessity of Pelvic Lymph Node Irradiation in Patients with Recurrent Prostate Cancer after Radical Prostatectomy in the PSMA PET/CT Era: A Narrative Review
Authors: Nabian Naeim , Ghalehtaki Reza , Couñago Felipe
Published: December 2022

The main prostate cancer (PCa) treatments include surgery or radiotherapy (with or without ADT). However, none of the suggested treatments eliminates the risk of lymph node metastases. Conventional imaging methods, including MRI and CT scanning, are not sensitive enough for the diagnosis of lymph node metastases; however, the novel imaging method, PSMA PET/CT scanning, has provided valuable information about the pelvic LN involvement in patients with recurrent PCa (RPCa) after radical prostatectomy. The high sensitivity and negative predictive value enable accurate N staging in PCa patients. In this narrative review, we summarize the evidence on the treatment and extent of radiation in prostate-only or whole-pelvis radiation in patients with positive and negative LN involvement on PSMA PET/CT scans.
Rapid and Accurate Discrimination of Mycobacterium abscessus Subspecies Based on Matrix-Assisted Laser Desorption Ionization-Time of Flight Spectrum and Machine Learning Algorithms
Authors: Wang Hsin-Yao , Kuo Chi-Heng , Chung Chia-Ru , Lin Wan-Ying , Wang Yu-Chiang , Lin Ting-Wei , Yu Jia-Ruei , Lu Jang-Jih , Wu Ting-Shu
Published: December 2022

Mycobacterium abscessus complex (MABC) has been reported to cause complicated infections. Subspecies identification of MABC is crucial for adequate treatment due to different antimicrobial resistance properties amid subspecies. However, long incubation days are needed for the traditional antibiotic susceptibility testing (AST). Delayed effective antibiotics administration often causes unfavorable outcomes. Thus, we proposed a novel approach to identify subspecies and potential antibiotic resistance, guiding early and accurate treatment. Subspecies of MABC isolates were determined by secA1, rpoB, and hsp65. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI–TOF MS) spectra were analyzed, and informative peaks were detected by random forest (RF) importance. Machine learning (ML) algorithms were used to build models for classifying MABC subspecies based on spectrum. The models were validated by repeated five-fold cross-validation to avoid over-fitting. In total, 102 MABC isolates (52 subspecies abscessus and 50 subspecies massiliense) were analyzed. Top informative peaks including m/z 6715, 4739, etc. were identified. RF model attained AUROC of 0.9166 (95% CI: 0.9072–0.9196) and outperformed other algorithms in discriminating abscessus from massiliense. We developed a MALDI–TOF based ML model for rapid and accurate MABC subspecies identification. Due to the significant correlation between subspecies and corresponding antibiotics resistance, this diagnostic tool guides a more precise and timelier MABC subspecies-specific treatment.
High-Dose Intravenous Ascorbate in Sepsis, a Pro-Oxidant Enhanced Microbicidal Activity and the Effect on Neutrophil Functions
Authors: Sae-khow Kritsanawan , Charoensappakit Awirut , Chiewchengchol Direkrit , Leelahavanichkul Asada
Published: December 2022

Vitamin C (ascorbic acid), a water-soluble essential vitamin, is well-known as an antioxidant and an essential substrate for several neutrophil functions. Because of (i) the importance of neutrophils in microbial control and (ii) the relatively low vitamin C level in neutrophils and in plasma during stress, vitamin C has been studied in sepsis (a life-threatening organ dysfunction from severe infection). Surprisingly, the supraphysiologic blood level of vitamin C (higher than 5 mM) after the high-dose intravenous vitamin C (HDIVC) for 4 days possibly induces the pro-oxidant effect in the extracellular space. As such, HDIVC demonstrates beneficial effects in sepsis which might be due to the impacts on an enhanced microbicidal activity through the improved activity indirectly via enhanced neutrophil functions and directly from the extracellular pro-oxidant effect on the organismal membrane. The concentration-related vitamin C properties are also observed in the neutrophil extracellular traps (NETs) formation as ascorbate inhibits NETs at 1 mM (or less) but facilitates NETs at 5 mM (or higher) concentration. The longer duration of HDIVC administration might be harmful in sepsis because NETs and pro-oxidants are partly responsible for sepsis-induced injuries, despite the possible microbicidal benefit. Despite the negative results in several randomized control trials, the short course HDIVC might be interesting to use in some selected groups, such as against anti-biotic resistant organisms. More studies on the proper use of vitamin C, a low-cost and widely available drug, in sepsis are warranted.
Will Omics Biotechnologies Save Us from Future Pandemics? Lessons from COVID-19 for Vaccinomics and Adversomics
Authors: Ferraresi Alessandra , Isidoro Ciro
Published: December 2022

The COVID-19 pandemic had cross-cutting impacts on planetary health, quotidian life, and society. Mass vaccination with the current gene-based vaccines has helped control the pandemic but unfortunately it has not shown effectiveness in preventing the spread of the virus. In addition, not all individuals respond to these vaccines, while others develop adverse reactions that cannot be neglected. It is also a fact that some individuals are more susceptible to infection while others develop effective immunization post-infection. We note here that the person-to-person and population variations in vaccine efficacy and side effects have been studied in the field of vaccinomics long before the COVID-19 pandemic. Additionally, the field of adversomics examines the mechanisms of individual differences in the side effects of health interventions. In this review, we discuss the potential of a multi-omics approach for comprehensive profiling of the benefit/risk ratios of vaccines. Vaccinomics and adversomics stand to benefit planetary health and contribute to the prevention of future pandemics in the 21st century by offering precision guidance to clinical trials as well as promoting precision use of vaccines in ways that proactively respond to individual and population differences in their efficacy and safety. This vision of pandemic prevention based on personalized instead of mass vaccination also calls for equity in access to precision vaccines and diagnostics that support a vision and practice of vaccinomics and adversomics in planetary health.
Prevalence and Virulence of Commensal Pseudomonas Aeruginosa Isolates from Healthy Individuals in Southern Vietnam (2018–2020)
Authors: Tran Nguyen Bao Vy , Truong Quang Minh , Nguyen Lam Que Anh , Nguyen Ngoc My Huong , Tran Quang Hung , Dinh Thi Tuyet Phuong , Hua Vinh Son , Nguyen Van Dung , Lambert Peter A. , Nguyen Thi Thu Hoai
Published: December 2022

Understanding the colonization of Pseudomonas aeruginosa (P. aeruginosa) in healthy humans is useful for future prevention and treatment of P. aeruginosa infection. This study aimed to investigate the prevalence and risk factors of of P. aeruginosa colonization in healthy humans. At the same time, the virulence of the isolated P. aeruginosa was also studied. In the study, 609 Vietnamese volunteers (310 females and 299 males, age range of 2 to 73 years), who had no acute infection or disease symptoms participated at the time of sample collection. Samples were taken from the throat, nostrils, and outer ears. P. aeruginosa was found in 19 participants (3.12%, 95% CI: 0.017–0.045), mainly from the throat (11/19, 57.89%). Participants with a history of sinusitis were 11.57 times more likely to be colonized with P. aeruginosa than participants without a history of sinusitis (OR: 11.57, 95% CI: 4.08–32.76, p-value < 0.0001, Fisher’s Exact test). Age and sex were not significantly associated with P. aeruginosa colonization. Among 16 P. aeruginosa isolates used in virulence tests, 100% (16/16) were positive for the synthesis of biofilm, pyocyanin, and siderophores; 93.75% (15/16) isolates were positive for the synthesis of gelatinase and protease; and 50% (8/16) isolates were positive for lipase. There were no differences in the pattern and range of virulence factors of P. aeruginosa isolates taken from participants with and without sinusitis history. P. aeruginosa colonized 3.12% of participants, and its presence was associated with sinusitis history.
The Role of LINC01564, RAMS11, CBX4 and TOP2A in Hepatocellular Carcinoma
Authors: Badr Eman A. E. , Elmongy Elshaymaa I. , Mostafa Rasha Galal , El-Sayed Ibrahim El-Tantawy , Abd El-Ati Gad Allah Abd El-Naser , Khairy Ahmed Asmaa , Elghobashy Yasser A. S.
Published: December 2022

Background: Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancers worldwide. Hepatitis C virus (HCV) infection remains a major risk factor for chronic liver disease, cirrhosis, and HCC. To understand the molecular pathogenesis of HCC in chronic HCV infection, many molecular markers are extensively studied, including long noncoding RNAs (lncRNA). Objective: To evaluate the expression levels of lncRNAs (LINC01564, RAMS11), CBX4, and TOP2A in patients with chronic HCV infection and patients with HCC on top of chronic HCV infection and correlate these levels with the clinicopathological features of HCC. Subjects and Methods: One hundred and fifty subjects were enrolled in this study and divided into three groups: group I included 50 patients with HCC on top of chronic hepatitis C (CHC), group II included 50 patients with CHC only, and group III included 50 healthy individuals as a control group. LncRNAs relative expression level was determined by RT-PCR. Results: lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in both patient groups compared to controls (p < 0.001*), with the highest levels in the HCC group compared with the CHC group. Additionally, these levels were significantly positively correlated with the clinicopathological features of HCC. Conclusions: The lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in CHC patients—in particular, patients with HCC. Thus, these circulatory lncRNAs may be able to serve as promising noninvasive diagnostic markers for HCC associated with viral C hepatitis.
The Effect of Earthing Mat on Stress-Induced Anxiety-like Behavior and Neuroendocrine Changes in the Rat
Authors: Park Hyun-Jung , Jeong Woojin , Yu Hyo Jeong , Ye Minsook , Hong Yunki , Kim Minji , Kim Ji Youn , Shim Insop
Published: December 2022

Grounding is a therapeutic technique that involves doing activities that “ground” or electrically reconnect us to the earth. The physiological effects of grounding have been reported from a variety of perspectives such as sleep or pain. However, its anti-stress efficacy is relatively unknown. The present study investigated the stress-related behavioral effects of earthing mat and its neurohormonal mechanisms in the Sprague–Dawley male rat. Rats were randomly divided into four groups: the naïve normal (Normal), the 21 days immobilization stressed (Control), the 21 days stressed + earthing mat for 7 days (A7) or 21 days (A21) group. The depressive-and anxiety like behaviors were measured by forced swimming test (FST), tail suspension test (TST) and elevated plus maze (EPM). Using immunohistochemistry, the expression of corticotrophin-releasing factor (CRF) and c-Fos immunoreactivity were analyzed in the brain. In the EPM, time spent in the open arm of the earthing mat groups was significantly increased compared to the Control group (p < 0.001), even though there were without effects among groups in the FST and TST. The expression of CRF immunoreactive neurons in the earthing mat group was markedly decreased compared to the Control group. Overall, the earthing mat reduced stress-induced behavioral changes and expression of c-Fos and CRF immunoreactivity in the brain. These results suggest that the earthing mat may have the potential to improve stress-related responses via the regulation of the corticotrophinergic system.
Preparation, Characterization, and Drug Delivery of Hexagonal Boron Nitride-Borate Bioactive Glass Biomimetic Scaffolds for Bone Tissue Engineering
Authors: Ensoylu Mertcan , Deliormanlı Aylin M. , Atmaca Harika
Published: December 2022

In this study, biomimetic borate-based bioactive glass scaffolds containing hexagonal boron nitride hBN nanoparticles (0.1, 0.2, 0.5, 1, and 2% by weight) were manufactured with the polymer foam replication technique to be used in hard tissue engineering and drug delivery applications. To create three-dimensional cylindrical-shaped scaffolds, polyurethane foams were used as templates and covered using a suspension of glass and hBN powder mixture. Then, a heat treatment was applied at 570 °C in an air atmosphere to remove the polymer foam from the structure and to sinter the glass structures. The structural, morphological, and mechanical properties of the fabricated composites were examined in detail. The in vitro bioactivity of the prepared composites was tested in simulated body fluid, and the release behavior of gentamicin sulfate and 5-fluorouracil from glass scaffolds were analyzed separately as a function of time. The cytotoxicity was investigated using osteoblastic MC3T3-E1 cells. The findings indicated that the hBN nanoparticles, up to a certain concentration in the glass matrix, improved the mechanical strength of the glass scaffolds, which mimic the cancellous bone. Additionally, the inclusion of hBN nanoparticles enhanced the in vitro hydroxyapatite-forming ability of bioactive glass composites. The presence of hBN nanoparticles accelerated the drug release rates of the system. It was concluded that bioactive glass/hBN composite scaffolds mimicking native bone tissue could be used for bone tissue repair and regeneration applications.
MoCLORA—An Architecture for Legged-and-Climbing Modular Bio-Inspired Robotic Organism
Authors: Prados Carlos , Hernando Miguel , Gambao Ernesto , Brunete Alberto
Published: December 2022

MoCLORA (Modular Climbing-and-Legged Robotic Organism Architecture) is a software framework for climbing bio-inspired robotic organisms composed of modular robots (legs). It is presented as a modular low-level architecture that coordinates the modules of an organism with any morphology, at the same time allowing exchanges between the physical robot and its digital twin. It includes the basic layers to control and coordinate all the elements, while allowing adding new higher-level components to improve the organism’s behavior. It is focused on the control of both the body and the legs of the organism, allowing for position and velocity control of the whole robot. Similarly to insects, which are able to adapt to new situations after the variation on the capacity of any of their legs, MoCLORA allows the control of organisms composed of a variable number of modules, arranged in different ways, giving the overall system the versatility to tackle a wide range of tasks in very diverse environments. The article also presents ROMERIN, a modular climbing and legged robotic organism, and its digital twin, which allows the creation of different module arrangements for testing. MoCLORA has been tested and validated with both the physical robot and its digital twin.
Fluorescent Sensing of Glutathione and Related Bio-Applications
Authors: Sun Xiaohuan , Guo Fei , Ye Qianyun , Zhou Jinfeng , Han Jie , Guo Rong
Published: December 2022

Glutathione (GSH), as the most abundant low-molecular-weight biological thiol, plays significant roles in vivo. Abnormal GSH levels have been demonstrated to be related to the dysfunction of specific physiological activities and certain kinds of diseases. Therefore, the sensing of GSH is emerging as a critical issue. Cancer, with typical high morbidity and mortality, remains one of the most serious diseases to threaten public health. As it is clear that much more concentrated GSH is present at tumor sites than at normal sites, the in vivo sensing of GSH offers an option for the early diagnosis of cancer. Moreover, by monitoring the amounts of GSH in specific microenvironments, effective diagnosis of ROS levels, neurological diseases, or even stroke has been developed as well. In this review, we focus on the fluorescent methodologies for GSH detection, since they can be conveniently applied in living systems. First, the fluorescent sensing methods are introduced. Then, the principles for fluorescent sensing of GSH are discussed. In addition, the GSH-sensing-related biological applications are reviewed. Finally, the future opportunities in in the areas of fluorescent GSH sensing—in particular, fluorescent GSH-sensing-prompted disease diagnosis—are addressed.