bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaf Extracts of Cistus ladanifer Exhibit Potent Antioxidant and Antiproliferative Activities against Liver, Prostate and Breast Cancer Cells
Authors: Bouothmany Kaoutar , Bourhia Mohammed , Aoussar Noura , Attaleb Mohammed , Salamatullah Ahmad , Nafidi Hiba-Allah , Mellouki Fouad , El Mzibri Mohammed , Aboul-Soud Mourad , Benbacer Laila
Published: August 2022

Chemical composition, antioxidant, and antiproliferative properties of C. ladanifer crude extracts, including hexane (Hex), dichloromethane (DCM), ethyl acetate (E.A) and ethanol (EtOH) were investigated. The chemical composition of C. ladanifer crude extracts was determined by use of GC-MS, whereas DPPH and FRAP assays were employed to determine its antioxidant capacity. The obtained results showed that the ethanolic extract exhibited a significant antioxidant effect recording an IC50 value of 266.6 ± 0.828 μg/mL with DPPH assay, and a higher reducing power 0.494 ± 0.035 using the FRAP test. The extracts exhibited significant antiproliferative activity against three cancer cell lines. The DCM extract exhibited the highest total polyphenol content (76.066 ± 9.978 μg AGE/mg) and was revealed to be more effective against HepG2 (31.54 ± 0.242 μg/mL). The Hex extract that presented the highest flavonoid content (50.209 ± 3.805 μg CE/mg) exhibited the highest antiproliferative activity against 22Rv1 and MDA-MB-231 recording IC50 values 11.32 ± 2.126 μg/mL and 82.4 ± 1.124 μg/mL, respectively. All four extracts exhibited minimal toxicity against human skin-derived fibroblast cells indicating the specificity of their observed anticancer activity. GC-MS analysis identified interesting phytochemicals underlying the obtained antioxidant and cytotoxic activities. Taken together, results of the current study highlight the significance of C. ladanifer as a valuable source of antioxidant and anticancer bioactive compounds, thereby warranting further detailed investigation.
Domiciliary Management of Periodontal Indexes and Glycosylated Hemoglobin (HbA1c) in Type 1 Diabetic Patients with Paraprobiotic-Based Toothpaste and Mousse: Randomized Clinical Trial
Authors: Butera Andrea , Pascadopoli Maurizio , Gallo Simone , Alovisi Mario , Lovati Elisabetta , Mutti Elisa , Scribante Andrea
Published: August 2022

Background: Periodontal disease is a chronic inflammation of periodontal tissues. Several systemic diseases are related to this condition. One of the strongest associations is that of periodontitis and type 2 diabetes mellitus (T2DM). On the contrary, the link with type 1 diabetes mellitus (T1DM) has not been extensively investigated. The objective of the present report is to evaluate and compare the effect of two domiciliary oral hygiene protocols on the periodontal clinical status as well as on the metabolic control in patients affected by T1DM. Methods: Sample size calculation required 20 patients per group, therefore 40 patients were equally and randomly assigned to the following home oral care protocols: a probiotic-based one (trial group) and a natural extracts-based one (control group). At the beginning of the study, after 3 and 6 months, the following periodontal indexes were collected: Probing Pocket Depth (PPD), Plaque Index (PI), Clinical Attachment Level (CAL), Bleeding on Probing (BoP), and Glycosylated Hemoglobin (HbA1c). Data underwent statistical analysis (significance threshold: p < 0.05). Results: In both groups, significant decreases in the periodontal clinical indexes were found at various time frames, whereas the levels of HbA1c significantly decreased only in the control group. Conclusions: Both the domiciliary treatments administered can significantly improve PPD, PI, CAL, and BOP parameters, whereas only the natural extracts-based gel seems to decrease HbA1c levels of T1DM patients.
Correlation between Acoustic Analysis and Psycho-Acoustic Evaluation of Violins
Authors: Nastac Silviu Marian , Gliga Vasile Ghiorghe , Mihalcica Mircea , Nauncef Alina Maria , Dinulica Florin , Campean Mihaela
Published: August 2022

This paper presents the results of an experimental study performed on seven violins obtained from a top plate made of resonance spruce and a back plate made of curly maple. Each pair of plates had a different modification to its thickness profile. Some were thickened and others were thinned compared to the classical thickness profile. Then, a soloist played a musical sequence on each violin and the acoustic signals were recorded. The sound quality of the signals was evaluated with a psycho-acoustic evaluation based on a blind questionnaire completed by listeners. It turned out that: (1) respondents with more musical experience (especially those with over 26 years of experience) were more demanding in assessing sound clarity and offered the widest range of scores in assessing this quality; (2) the musical experience of the respondents influenced to the highest degree the appreciation of the warm sound quality; (3) the scores for the violins with thinned plates were weaker, especially according to the psycho-acoustic analysis; and (4) the highest score was obtained by the violin with the thickest plates, which can be correlated with the two dominant frequencies extracted from the FFT analysis, whose values coincide with the frequencies of the B1− and B1+ modes.
Qualifying and Quantifying the Emissions of Volatile Organic Compounds from the Coking Process in a Steel Plant Using an Innovative Sampling Technique
Authors: Shao Cheng-Tsung , Cheng Wen-Hsi , Lin Yuan-Chung , Chang Ken-Lin , Chen Kang-Shin , Yuan Chung-Shin
Published: August 2022

The aim of this paper is to quantify the amounts of volatile organic compounds (VOCs) emitted from a coke oven in a steel plant in Taiwan and estimate the emission factors of VOCs using an innovative sampling technique. The identification of VOCs emissions was referred to in the AP-42 report issued by the USEPA and the field measurement data of fugitive emissions. VOCs were sampled using a self-designed closed sampling system. A total of six emission points, including quenching emissions, charge lid emissions, combustion stack emissions, door emissions, charging emissions, and coke pushing emissions, were identified in the coking process after comparing with the report of AP-42, and the emission factor of VOCs was 0.030 kg/ton-coke. It showed that the emission factor of VOCs via field measurement was approximately 56% of that reported by Taiwan EPA. Therefore, VOCs emissions estimated by the Taiwan EPA would be highly overestimated than those from the coke oven in the site.
The AtmChile Open-Source Interactive Application for Exploring Air Quality and Meteorological Data in Chile
Authors: Catalán Francisco , Chandia Damián , Toro Araya Richard , Leiva Guzman Manuel A.
Published: August 2022

AtmChile is an R package that permits the download and management of data from the National Air Quality Information System (SINCA, Spanish acronyms) and the Chilean Meteorological Directorate (DMC, Spanish acronyms) for multiple air quality and climatological parameters in a simple and intuitive platform. The AtmChile package includes the ChileAirQualityApp, a dashboard for enhancing the data download functions of this package with analysis, visualization, and descriptive statistics tools in a user-friendly manner. The AtmChile offers researchers and the public a highly intuitive open access package to download, validate, visualize, and preliminarily analyze air quality and climatological data available in Chile.
Characteristics of Low-Latitude Ionosphere Activity and Deterioration of TEC Model during the 7–9 September 2017 Magnetic Storm
Authors: Li Jianfeng , Wang Yongqian , Yang Shiqi , Wang Fang
Published: August 2022

Under the influence of space weather, abnormal disturbances in the ionosphere will distort the ionosphere model seriously and affect the global navigation satellite system negatively. This study analyzes the ionospheric activity characteristics and the ionospheric model performance in low latitude during a strong geomagnetic storm from 7 to 9 September 2017. The research goals are to determine the abnormal behavior of the ionosphere during the geomagnetic storm and to refine the ionosphere model in the low latitude. In the experiment, the vertical total electron content (VTEC) peak value at low latitudes caused by this geomagnetic storm was significantly higher than that on the geomagnetic quiet day, and the VTEC peak value increased by approximately 75%. In the main phase of the geomagnetic storm, the degree of VTEC variation with longitude is significantly higher than that of the geomagnetic quiet day. The VTEC variation trend in the northern hemisphere is more severe than that in the southern hemisphere. In the region where VTEC decreases with longitude, the VTEC in the northern hemisphere is higher than that in the southern hemisphere on the same longitude at low latitudes, and this phenomenon is not significantly affected by the geomagnetic disturbance of the recovery phase. During the geomagnetic storm, the daily minimum value of VTEC at different latitudes was basically the same, approximately 5 TECU, indicating that the nighttime VTEC of the ionosphere in low latitudes was weakly affected by latitude and geomagnetic storms. Geomagnetic disturbances during geomagnetic storms will lead to anomalous features of the “Fountain effect” in the ionosphere at low latitudes. In addition, this geomagnetic storm event caused the accuracy of spherical harmonics (SH), polynomial, and ICE models to decrease by 7.12%, 27.87%, and 48.56%, respectively, and caused serious distortion, which is negative VTEC values fitted by the polynomial model.
Variation of Moisture and Soil Water Retention in a Lowland Area of Central Poland—Solec Site Case Study
Authors: Oleszczuk Ryszard , Jadczyszyn Jan , Gnatowski Tomasz , Brandyk Andrzej
Published: August 2022

Soil moisture monitoring is crucial for a variety of activities involving soil water regime estimation. Different phenomena such as drought, exhibit impacts of a variable extent in the soil profile, requiring moisture content monitoring as well as reliable analyses of the soil properties. In the village of Solec, located in central Poland, monitoring of the moisture content was attempted for a sandy soil in order to estimate soil moisture distributions for two dry years (2015, 2016) and a wet one (2017). Simple and easily obtainable drought indices, such as dry spells, climatic water balance, groundwater table depth, soil water content and potential were estimated and related with spatiotemporal evolution of soil water conditions. Soil layers subject to drought were found to be different either from a moisture (15–45 cm) or soil water potential (10–25 cm), showing diverse physical properties and relations with the ground water table. The coherence of the analysed drought indices was proven for a light, sandy soil, which has national significance for the state, drought monitoring network. Knowledge obtained during previous studies, which omitted soil water conditions for this type of the soil was supplemented. Based on its own water content, the profile of the analysed soil (Stagnic Folic Gleysols–Arenic) exhibits a negative climatic water balance and requires irrigation practices to mitigate drought effects.
Monitoring the Spring 2021 Drought Event in Taiwan Using Multiple Satellite-Based Vegetation and Water Indices
Authors: Chou Chien-Ben , Weng Min-Chuan , Huang Huei-Ping , Chang Yu-Cheng , Chang Ho-Chin , Yeh Tzu-Ying
Published: August 2022

The monitoring of droughts is practically important yet challenging due to the complexity of the phenomena. The occurrence of drought involves changes in meteorological conditions, vegetation coverage and soil moisture. To advance the techniques for detecting and monitoring droughts, this study explores the usage of a suite of vegetation and water indices derived from high-resolution images produced by geostationary satellite Himawari-8. The technique is tested on the detection of the drought event in Spring 2021 across Taiwan due to deficit of precipitation in that season. It is found that the time series analysis of green chlorophyll index (CIgreen) and normalized difference vegetation index (NDVI) helps detect the initiation of drought before its severity intensifies. The vegetation condition index (VCI) and vegetation health index (VHI) derived from GIgreen and NDVI are similarly useful for the early warning of a drought event. In addition to vegetation indices, the normalized difference water index (NDWI) is adopted for quantifying the deficit in precipitation. It is found that NDWI provides a better early warning system of drought compared to the vegetation indices. Combining the vegetation and water indices allows a more complete description of the evolution of drought for the Spring 2021 event. The potential for using the new framework for the early warning of future drought events is discussed.
Monitoring the Influence of Industrialization and Urbanization on Spatiotemporal Variations of AQI and PM2.5 in Three Provinces, China
Authors: Chen Hu , Deng Guoqu , Liu Yiwen
Published: August 2022

With the rapid development of industrialization and urbanization, atmospheric pollution research is vital for regional sustainable development and related policies formulated by the government. Previous studies have mainly studied a single evaluation method to analyze the air quality index (AQI) or single air pollutant. This research integrated the Spearman coefficient (SC) correlation analysis, a random search (RS) algorithm and an excellent extreme gradient boosting (XGBoost) algorithm to evaluate the air pollution influence of industrialization and urbanization (APIIU). Industrialization, urbanization and meteorological indicators were used to measure the influence degree of APIIU on AQI and particulate matter 2.5 (PM2.5), respectively. The main findings were: (1) the APIIU-AQI and APIIU-PM2.5 of Henan Province, Hubei Province and Hunan Province had significant changes from 2017 to 2019; (2) the value of square of determination coefficient of real value (R2), the root mean square error (RMSE) and the mean absolute percentage error (MAPE) of APIIU-AQI and APIIU-PM2.5 in three provinces predicted by the SC-RS-XGBoost were 0.945, 0.103, 4.25% and 0.897, 0.205, 4.84%, respectively; (3) the predicted results were more accurate than using a SC-XGBoost, RS-XGBoost, traditional XGBoost, support vector regression (SVR) and extreme learning machine (ELM).
A Southern Portuguese Margin Perspective of Marine Isotope Stage 47—An Interglacial in the 41 kyr World
Authors: Voelker Antje H. L. , Rodrigues Teresa , Trotta Samanta , Marino Maria , Kuhnert Henning
Published: August 2022

In order to better understand interglacial climate variability within the 41 kyr world, we produced high-resolution climate records for interglacial Marine Isotope Stage (MIS) 47 (1424–1452 ka) at IODP Site U1387 (36°48′ N, 7°43′ W) on the southern Portuguese margin. Using benthic and planktonic foraminifera stable isotope records, Uk’37 sea-surface temperature (SST), and plankton assemblage data we investigated Mediterranean Outflow Water (MOW) and surface water conditions. The MOW-level records indicate a poorly ventilated and sluggish bottom current during the MIS 48/MIS 47 transition in association with the insolation maximum, whereas a well-ventilated MOW formed a contourite layer during the second insolation maximum. The benthic δ18O record shows a fairly abrupt change during the deglaciation of MIS 48, while the surface waters experienced a terminal stadial event that was associated with initial cooling and freshening followed by stepwise warming until interglacial SST was reached at 1450 ka. Interglacial conditions with SST of 24 °C or higher persisted until 1427 ka, although warm SST prevailed into MIS 46. The persistent and prolonged warmth is attributed to a northward expansion of the subtropical gyre during MIS 47 as reflected by the dominance of subtropical-tropical planktonic foraminifera species and the presence of warm water coccolithophores taxa.
Relaxed Indistinguishability Relations and Relaxed Metrics: The Aggregation Problem
Authors: González-Hedström Juan-De-Dios , Miñana Juan-José , Valero Oscar
Published: August 2022

The main purpose of this paper is to study the relationship between those functions that aggregate relaxed indistinguishability fuzzy relations with respect to a collection of t-norms and those functions that merge relaxed pseudo-metrics, extending the classical approach explored for pseudo-metrics and indistinguishability fuzzy relations. Special attention is paid to the distinguished class of SSI-relaxed indistinguishability fuzzy relations showing that functions merging this special type of relaxed indistinguishability fuzzy relations can be expressed through functions aggregating SSD-relaxed pseudo-metrics. Outstanding differences between those functions aggregating indistinguishability fuzzy relations and those that aggregate their counterpart separating points are shown.
Early Diagnosis of Intracranial Internal Carotid Artery Stenosis Using Extracranial Hemodynamic Indices from Carotid Doppler Ultrasound
Authors: Zhang Xiangdong , Wu Dan , Li Hongye , Fang Yonghan , Xiong Huahua , Li Ye
Published: August 2022

Atherosclerotic intracranial internal carotid artery stenosis (IICAS) is a leading cause of strokes. Due to the limitations of major cerebral imaging techniques, the early diagnosis of IICAS remains challenging. Clinical studies have revealed that arterial stenosis may have complicated effects on the blood flow’s velocity from a distance. Therefore, based on a patient-specific one-dimensional hemodynamic model, we quantitatively investigated the effects of IICAS on extracranial internal carotid artery (ICA) flow velocity waveforms to identify sensitive hemodynamic indices for IICAS diagnoses. Classical hemodynamic indices, including the peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI), were calculated on the basis of simulations with and without IICAS. In addition, the first harmonic ratio (FHR), which is defined as the ratio between the first harmonic amplitude and the sum of the amplitudes of the 1st–20th order harmonics, was proposed to evaluate flow waveform patterns. To investigate the diagnostic performance of the indices, we included 52 patients with mild-to-moderate IICAS (<70%) in a case–control study and considered 24 patients without stenosis as controls. The simulation analyses revealed that the existence of IICAS dramatically increased the FHR and decreased the PSV and EDV in the same patient. Statistical analyses showed that the average PSV, EDV, and RI were lower in the stenosis group than in the control group; however, there were no significant differences (p > 0.05) between the two groups, except for the PSV of the right ICA (p = 0.011). The FHR was significantly higher in the stenosis group than in the control group (p < 0.001), with superior diagnostic performance. Taken together, the FHR is a promising index for the early diagnosis of IICAS using carotid Doppler ultrasound methods.
Multiscale Analysis of Cellular Composition and Morphology in Intact Cerebral Organoids
Authors: Ma Haihua , Chen Juan , Deng Zhiyu , Sun Tingting , Luo Qingming , Gong Hui , Li Xiangning , Long Ben
Published: August 2022

Cerebral organoids recapitulate in vivo phenotypes and physiological functions of the brain and have great potential in studying brain development, modeling diseases, and conducting neural network research. It is essential to obtain whole-mount three-dimensional (3D) images of cerebral organoids at cellular levels to explore their characteristics and applications. Existing histological strategies sacrifice inherent spatial characteristics of organoids, and the strategy for volume imaging and 3D analysis of entire organoids is urgently needed. Here, we proposed a high-resolution imaging pipeline based on fluorescent labeling by viral transduction and 3D immunostaining with fluorescence micro-optical sectioning tomography (fMOST). We were able to image intact organoids using our pipeline, revealing cytoarchitecture information of organoids and the spatial localization of neurons and glial fibrillary acidic protein positive cells (GFAP+ cells). We performed single-cell reconstruction to analyze the morphology of neurons and GFAP+ cells. Localization and quantitative analysis of cortical layer markers revealed heterogeneity of organoids. This pipeline enabled acquisition of high-resolution spatial information of millimeter-scale organoids for analyzing their cell composition and morphology.
Making the Most of Its Short Reads: A Bioinformatics Workflow for Analysing the Short-Read-Only Data of Leishmania orientalis (Formerly Named Leishmania siamensis) Isolate PCM2 in Thailand
Authors: Anuntasomboon Pornchai , Siripattanapipong Suradej , Unajak Sasimanas , Choowongkomon Kiattawee , Burchmore Richard , Leelayoova Saovanee , Mungthin Mathirut , E-kobon Teerasak
Published: August 2022

Background: Leishmania orientalis (formerly named Leishmania siamensis) has been neglected for years in Thailand. The genomic study of L. orientalis has gained much attention recently after the release of the first high-quality reference genome of the isolate LSCM4. The integrative approach of multiple sequencing platforms for whole-genome sequencing has proven effective at the expense of considerably expensive costs. This study presents a preliminary bioinformatic workflow including the use of multi-step de novo assembly coupled with the reference-based assembly method to produce high-quality genomic drafts from the short-read Illumina sequence data of L. orientalis isolate PCM2. Results: The integrating multi-step de novo assembly by MEGAHIT and SPAdes with the reference-based method using the L. enriettii genome and salvaging the unmapped reads resulted in the 30.27 Mb genomic draft of L. orientalis isolate PCM2 with 3367 contigs and 8887 predicted genes. The results from the integrated approach showed the best integrity, coverage, and contig alignment when compared to the genome of L. orientalis isolate LSCM4 collected from the northern province of Thailand. Similar patterns of gene ratios and frequency were observed from the GO biological process annotation. Fifty GO terms were assigned to the assembled genomes, and 23 of these (accounting for 61.6% of the annotated genes) showed higher gene counts and ratios when results from our workflow were compared to those of the LSCM4 isolate. Conclusions: These results indicated that our proposed bioinformatic workflow produced an acceptable-quality genome of L. orientalis strain PCM2 for functional genomic analysis, maximising the usage of the short-read data. This workflow would give extensive information required for identifying strain-specific markers and virulence-associated genes useful for drug and vaccine development before a more exhaustive and expensive investigation.
DNA Barcode Gap Analysis for Multiple Marker Genes for Phytoplankton Species Biodiversity in Mediterranean Aquatic Ecosystems
Authors: Tzafesta Eftychia , Saccomanno Benedetta , Zangaro Francesco , Vadrucci Maria Rosaria , Specchia Valeria , Pinna Maurizio
Published: August 2022

The implementation of DNA metabarcoding and environmental DNA (eDNA) to the biodiversity assessment and biomonitoring of aquatic ecosystems has great potential worldwide. However, DNA metabarcoding and eDNA are highly reliant on the coverage of the DNA barcode reference libraries that are currently hindered by the substantial lack of reference sequences. The main objective of this study was to analyze the current coverage of DNA barcode reference libraries for phytoplankton species of the aquatic Mediterranean ecoregion in the southeast of Italy (Apulia Region) in order to assess the applicability of DNA metabarcoding and eDNA in this area. To do so, we investigated three main DNA barcode reference libraries, BOLD Systems, GenBank and SILVA, for the availability of DNA barcodes of the examined phytoplankton species. The gap analysis was conducted for three molecular gene markers, 18S, 16S and COI. The results showed a considerable lack of barcodes for all three markers. However, among the three markers, 18S had a greater coverage in the reference libraries. For the 18S gene marker, the barcode coverage gap across the three types of ecosystems examined was 32.21–39.68%, 60.12–65.19% for the 16S marker gene, and 72.44–80.61 for the COI marker gene. Afterwards, the interspecific genetic distance examined on the most represented molecular marker, 18S, was able to distinguish 80% of the species mined for lakes and 70% for both marine and transitional waters. Conclusively, this work highlights the importance of filling the gaps in the reference libraries, and constitutes the basis towards the advancement of DNA metabarcoding and eDNA application for biodiversity assessment and biomonitoring.
Comparative Chloroplast Genomes of Six Magnoliaceae Species Provide New Insights into Intergeneric Relationships and Phylogeny
Authors: Yang Lin , Tian Jinhong , Xu Liu , Zhao Xueli , Song Yuyang , Wang Dawei
Published: August 2022

Magnoliaceae plants are industrial tree species with high ornamental and medicinal value. We published six complete chloroplast genomes of Magnoliaceae by using Illumina sequencing. These showed a typical quadripartite structure of angiosperm and were 159,901–160,008 bp in size. A total of 324 microsatellite loci and six variable intergenic regions (Pi > 0.01) were identified in six genomes. Compared with five other genomes, the contraction and expansion of the IR regions were significantly different in Manglietia grandis. To gain a more thorough understanding of the intergeneric relationships in Magnoliaceae, we also included 31 published chloroplast genomes of close relative species for phylogenetic analyses. New insights into the intergeneric relationships of Magnoliaceae are provided based on our results and previous morphological, phytochemical and anatomical information. We suggest that the genus Yulania should be separated from the genus Michelia and its systematic position of should be restored; the genera Paramichelia and Tsoongiodendron should be merged into the genus Michelia; the genera Pachylarnax and Parakmeria should be combined into one genus. These findings will provide a theoretical basis for adjusting the phylogenetic position of Magnoliaceae at the molecular level.
Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases
Authors: Sajeev Anjana , Hegde Mangala , Girisa Sosmitha , Devanarayanan Thulasidharan Nair , Alqahtani Mohammed S. , Abbas Mohamed , Sil Samir Kumar , Sethi Gautam , Chen Jen-Tsung , Kunnumakkara Ajaikumar B.
Published: August 2022

There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing several disastrous and fatal diseases. Oroxylin A (OA) is a flavonoid obtained from the plants Oroxylum indicum, Scutellaria baicalensis, and S. lateriflora, which have distinctive pharmacological properties. OA modulates the important signaling pathways, including NF-κB, MAPK, ERK1/2, Wnt/β-catenin, PTEN/PI3K/Akt, and signaling molecules, such as TNF-α, TGF-β, MMPs, VEGF, interleukins, Bcl-2, caspases, HIF-1α, EMT proteins, Nrf-2, etc., which play a pivotal role in the molecular mechanism of chronic diseases. Overwhelming pieces of evidence expound on the anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer potentials of this flavonoid, which makes it an engrossing compound for research. Numerous preclinical and clinical studies also displayed the promising potential of OA against cancer, cardiovascular diseases, inflammation, neurological disorders, rheumatoid arthritis, osteoarthritis, etc. Therefore, the current review focuses on delineating the role of OA in combating different chronic diseases and highlighting the intrinsic molecular mechanisms of its action.
Effect of Curcumin as Feed Supplement on Immune Response and Pathological Changes of Broilers Exposed to Aflatoxin B1
Authors: Li Sihong , Han Meiyu , Zhang Yixin , Ishfaq Muhammad , Liu Ruimeng , Wei Gaoqiang , Zhang Xiuying , Zhang Xiuying
Published: August 2022

In this study, we examined the protective effects of curcumin against the AFB1-induced immune response of and pathological changes in broilers. Histopathology examinations showed that at day 28, AFB1 (5 mg/kg) exposure leads to severe histological changes in the spleen, thymus and bursa of Fabricius with a decrease in the number and karyoplasmic area ratio of plasma cells. Curcumin alleviated the AFB1-induced immune organs’ damage as well as the changes in plasma cells in a dose-dependent manner. RT-PCR data showed that AFB1 significantly downregulated the IL-2 and IFN-γ mRNA expression levels in the thymus, spleen and bursa of Fabricius. However, curcumin supplementation improved the AFB1-induced immune organs’ damage via upregulated cytokines’ expression. Intriguingly, similar trends were noticed in abnormal morphological changes and the immune response at day 35 after the withdrawal of AFB1 and curcumin from the diet, suggesting the protective effects and immunomodulatory function against AFB1 in broilers. The current study provides a scientific experimental basis for the application of curcumin as a therapeutic drug or additive in animal husbandry productive practice.
Association between Vitamin C Deficiency and Mortality in Patients with Septic Shock
Authors: Park Jong Eun , Shin Tae Gun , Jeong Daun , Lee Gun Tak , Ryoo Seung Mok , Kim Won Young , Jo You Hwan , Suh Gil Joon , Hwang Sung Yeon
Published: August 2022

The prognostic value of low vitamin C levels has not been well investigated in patients with septic shock. We aimed to evaluate the association of vitamin C deficiency with mortality in patients with septic shock. We conducted a retrospective analysis of 165 patients with septic shock from a prospective multicenter trial and institutional sepsis registry between April 2018 and January 2020. The primary outcome was 28-day mortality. The patients were categorized into vitamin C deficiency and normal groups based on a vitamin C cutoff level of 11.4 mmol/L. Multivariable Cox regression analysis was performed to examine the association between vitamin C levels and 28-day mortality. A total of 165 patients was included for analysis and 77 (46.7%) had vitamin C deficiency. There was no significant difference in the 28-day mortality rate between the vitamin C deficiency group and the normal group (23.4% (n = 18/77) vs. 13.6% (n = 12/88), p = 0.083). Multivariable Cox proportional hazard analysis showed vitamin C deficiency to be associated with increased risk of 28-day mortality (adjusted hazard ratio, 2.65, 95% confidence interval (CI), 1.08–6.45; p = 0.032). Initial vitamin C deficiency was associated with a higher risk of 28-day mortality in patients with septic shock after adjusting for intravenous administration of vitamin C and thiamine, baseline characteristics, laboratory findings, and severity of illness.
Effects of Achieving Sustained Virologic Response after Direct-Acting Antiviral Agents on Long-Term Liver Fibrosis in Diabetics vs. in Non-Diabetic Patients with Chronic Hepatitis C Infection
Authors: Popescu Marian-Sorin , Firu Dan-Mihai , Pădureanu Vlad , Mărginean Cristina Maria , Mitruț Radu , Arsene Andreea Letitia , Mărgăritescu Dragoș Nicolae , Calina Daniela , Docea Anca Oana , Mitruț Paul
Published: August 2022

Because of the prevalence of HCV worldwide as well as its undiagnosed population due to a lack of screening, HCV can be considered a modern pandemic disease. In 2016, the World Health Organization (WHO) set goals for HCV’s elimination that included a 65 percent reduction in mortality and an 80 percent reduction in newly infected cases by 2030. This study is a follow-up evaluation of 80 patients who received interferon-free treatment with direct-acting agents (DAA) for chronic HCV infection between the second half of 2017 and the end of 2018. They were assessed using a FibroMax test prior to DAA administration. Two pills/day of Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg and two pills/day of Dasabuvir 250 mg were given to the patients for 8 weeks. After treatment, all 80 patients in this study achieved an SVR (sustained virologic response), and the FibroMax test was performed three years later. Our study found that successfully treating HCV infection can play a significant role in reducing fibrosis in T2DM patients. In comparison to those of ActiTest and SteatoTest, FibroMax scores showed a significantly greater reduction in T2DM patients than in treatment-naive patients.
Effect of Fluoxetine and Acacetin on Central Vestibular Compensation in an Animal Model of Unilateral Peripheral Vestibulopathy
Authors: Hatat Bérénice , Boularand Romain , Bringuier Claire , Chanut Nicolas , Chabbert Christian , Tighilet Brahim
Published: August 2022

Damage to the peripheral vestibular system is known to generate a syndrome characterized by postural, locomotor, oculomotor, perceptual and cognitive deficits. Current pharmacological therapeutic solutions for these pathologies lack specificity and efficacy. Recently, we demonstrated that apamin, a specific SK channel blocker, significantly reduced posturo-locomotor and oculomotor deficits in the cat and the rat. The aim of the present study was to test the antivertigo potential of compounds belonging to the SK antagonists family, such as Acacetin and Fluoxetine. Young rats were subjected to unilateral ototoxic lesions of the vestibular organ using transtympanic administration of arsanilic acid (TTA) to evoke unilateral vestibular loss (UVL). Vestibular syndrome was monitored using behavioural evaluation allowing appreciation of the evolution of static and dynamic posturo-locomotor deficits. A significant effect of the TTA insult was only found on the distance moved, the mean body velocity and the not moving time. From day 2 to week 2 after TTA, the distance moved and the mean body velocity were significantly decreased, while the not moving time was significantly increased. Acacetin does not evoke any significant change in the vestibular posturo-locomotor parameters’ kinetics. Administration of Fluoxetine two weeks before TTA and over three weeks after TTA (preventive group) does not evoke any significant change in the vestibular posturo-locomotor parameters’ kinetics. Administration of Fluoxetine from three weeks after TTA significantly delayed the functional recovery. This study demonstrates that Acacetin or Fluoxetine in TTA vestibulo-injured rats does not bring any significant benefit on the posture and locomotor balance deficits.
Targeted Protein Degradation to Overcome Resistance in Cancer Therapies: PROTAC and N-Degron Pathway
Authors: Kim Hanbyeol , Park Jeongbae , Kim Jeong-Mok
Published: August 2022

Extensive progress in understanding the molecular mechanisms of cancer growth and proliferation has led to the remarkable development of drugs that target cancer-driving molecules. Most target molecules are proteins such as kinases and kinase-associated receptors, which have enzymatic activities needed for the signaling cascades of cells. The small molecule inhibitors for these target molecules greatly improved therapeutic efficacy and lowered the systemic toxicity in cancer therapies. However, long-term and high-dosage treatment of small inhibitors for cancer has produced other obstacles, such as resistance to inhibitors. Among recent approaches to overcoming drug resistance to cancers, targeted protein degradation (TPD) such as proteolysis-targeting chimera (PROTAC) technology adopts a distinct mechanism of action by which a target protein is destroyed through the cellular proteolytic system, such as the ubiquitin–proteasome system or autophagy. Here, we review the currently developed PROTACs as the representative TPD molecules for cancer therapy and the N-degrons of the N-degron pathways as the potential TPD ligands.
A Review of the Systemic Treatment of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis
Authors: Chang Hua-Ching , Wang Tsung-Jen , Lin Ming-Hsiu , Chen Ting-Jui
Published: August 2022

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon but life-threatening diseases mostly caused by drugs. Although various systemic immunomodulating agents have been used, their therapeutic efficacy has been inconsistent. This study aimed to provide an evidence-based review of systemic immunomodulating treatments for SJS/TEN. We reviewed 13 systematic review and meta-analysis articles published in the last 10 years. The use of systemic corticosteroids and IVIg is still controversial. An increasing number of studies have suggested the effectiveness of cyclosporine and biologic anti-TNF-α in recent years. There were also some promising results of combination treatments. Further large-scale randomized controlled trials are required to provide more definitive evidence of the effectiveness of these treatments. The pathogenesis of SJS/TEN has been elucidated in recent years and advances in the understanding of SJS/TEN may inspire the discovery of potential therapeutic targets.
Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System
Authors: Priester Jasmin , Dreute Jan , Kracht Michael , Schmitz M. Lienhard
Published: August 2022

The NF-κB system is a key transcriptional pathway that regulates innate and adaptive immunity because it triggers the activation and differentiation processes of lymphocytes and myeloid cells during immune responses. In most instances, binding to cytoplasmic inhibitory IκB proteins sequesters NF-κB into an inactive state, while a plethora of external triggers activate three complex signaling cascades that mediate the release and nuclear translocation of the NF-κB DNA-binding subunits. In addition to these cytosolic steps (level 1 of NF-κB regulation), NF-κB activity is also controlled in the nucleus by signaling events, cofactors and the chromatin environment to precisely determine chromatin recruitment and the specificity and timing of target gene transcription (level 2 of NF-κB regulation). Here, we discuss an additional layer of the NF-κB system that manifests in various steps of post-transcriptional gene expression and protein secretion. This less-studied regulatory level allows reduction of (transcriptional) noise and signal integration and endows time-shifted control of the secretion of inflammatory mediators. Detailed knowledge of these steps is important, as dysregulated post-transcriptional NF-κB signaling circuits are likely to foster chronic inflammation and contribute to the formation and maintenance of a tumor-promoting microenvironment.
Velopharyngeal Insufficiency Treatment in Cleft Palate Patients: Umbrella Review
Authors: Vale Francisco , Paula Anabela Baptista , Travassos Raquel , Nunes Catarina , Ribeiro Madalena Prata , Marques Filipa , Pereira Flávia , Carrilho Eunice , Marto Carlos Miguel , Francisco Inês
Published: August 2022

Velopharyngeal insufficiency may occur as a result of an anatomical or structural defect and may be present in patients with cleft lip and palate. The treatment options presented in the literature are varied, covering invasive and non-invasive methods. However, although these approaches have been employed and their outcomes reviewed, no conclusions have been made about which approach is the gold-standard. This umbrella review aimed to synthesize the current literature regarding velopharyngeal insufficiency treatments in cleft lip and palate patients, evaluating their effectiveness based on systematic reviews. A standardized search was carried out in several electronic databases, namely PubMed via Medline, Web of Science, Cochrane Library, and Embase. The quality of the included studies was evaluated using AMSTAR2 and degree of overlap was analyzed using Corrected Covered Area. Thirteen articles were included in the qualitative review, with only 1 in the non-invasive method category, and 12 in the invasive method category. All reviewed articles were judged to be of low quality. In symptomatic patients, treatment did not solely comprise speech therapy, as surgical intervention was often necessary. Although there was no surgical technique considered to be the gold standard for the correction of velopharyngeal insufficiency, the Furlow Z-plasty technique and minimal incision palatopharyngoplasty were the best among reported techniques.
Use of Deep Learning to Detect the Maternal Heart Rate and False Signals on Fetal Heart Rate Recordings
Authors: Boudet Samuel , Houzé de l’Aulnoit Agathe , Peyrodie Laurent , Demailly Romain , Houzé de l’Aulnoit Denis
Published: August 2022

We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU, and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.
Application of Micro-Western Array for Identifying Different Serum Protein Expression Profile among Healthy Control, Alzheimer’s Disease Patients and Patients’ Adult Children
Authors: Huo Chieh , Chen Ming-Hui , Hour Tzyh-Chyuan , Huang Ling-Chun , Fong Yi-On , Kuo Ying-Yu , Yang Yuan-Han , Chuu Chih-Pin
Published: August 2022

(1) Background: Alzheimer’s disease (AD) is the most common form of dementia. Increased levels of inflammatory proteins have been observed in brain and plasma samples of AD patients; however, it is not clear if other serum proteins correlate to the development or disease progression of AD. (2) Methods: Micro-Western Array (MWA) is a high-throughput antibody-based proteomics system which allows detection of the expression levels of 24–96 different proteins within 6–30 samples simultaneously. We applied MWA to explore potential serum protein biomarkers correlated to the development and progression of AD by examining the difference in serum protein profile of 31 healthy control (HC), 30 patients with AD and 30 patients’ adult children (ACS). (3) Results: Compared to HC, AD and ACS express similar pattern of serum proteins, including higher protein levels of ABCA1, ABCG1, SREBP1 and LXRβ but lower protein levels of ApoD, ApoE, ApoH, c_Myc, COX2 and Hippo-YAP signaling proteins. AD patients had higher serum levels of ABCG1, ApoD, ApoH, COX2, LXRα and YAP, but lower levels of ABCA1, ApoE, c_Myc, LATS1, MST1, MST2, Nanog, NFκB_p50, PPARγ and SREBP2, as compared to ACS. Pearson’s correlation analysis revealed that the protein expression level of ApoE, c_Myc, LATS1, MST2, NFκB p50, PPARγ and SREBP1 was negatively correlated to age, while that of ApoE, c_Myc, LATS1, MST1, MST2, Nanog, NFκB p50 and PPARγ was positively correlated to age. (4) Conclusions: We identified a group of serum proteins which may correlate to disease progression of AD and can be potential diagnostic serum protein biomarkers.
What Are the Neural Correlates of Impaired Awareness of Social Cognition and Function in Dementia? A Systematic Review
Authors: Hengstschläger Anna , Sommerlad Andrew , Huntley Jonathan
Published: August 2022

Deficits in social cognition and function are characteristic of dementia, commonly accompanied by a loss of awareness of the presence or extent of these deficits. This lack of awareness can impair social relationships, increase patients’ and carers’ burden, and contribute to increased rates of institutionalization. Despite clinical importance, neural correlates of this complex phenomenon remain unclear. We conducted a systematic search of five electronic databases to identify functional and structural neuroimaging studies investigating the neural correlates of impaired awareness of social cognition and function in any dementia type. We rated study quality and conducted a narrative synthesis of the results of the eight studies that met the predefined eligibility criteria. Across these studies, deficits in awareness of impairments in social cognition and function were associated with structural or functional abnormalities in the frontal pole, orbitofrontal cortex, temporal pole, middle temporal gyrus, inferior temporal gyrus, fusiform gyrus, amygdala, hippocampus, parahippocampal gyrus, and insula. Several identified regions overlap with established neural correlates of social cognition. More research is needed to understand awareness of social cognition and function and how this becomes impaired in dementia to improve neuroscientific understanding, aid the identification of this problematic symptom, and target interventions to reduce burden and improve care.