bluuebunny/crossref_metadata_2025 huggingface dataset:
Elements to assess the quality of information of case reports in pregnancy pharmacovigilance data—a ConcePTION project
Authors: van Rijt-Weetink Yrea R. J. , Chamani Khoezik , Egberts Antoine C. G. , van Hunsel Florence P. A. M. , Lewis David J. , Yates Laura M. , Winterfeld Ursula , van Puijenbroek Eugène P.
Published: June 2023

To assess the risk of exposure to a medicinal product during pregnancy in an individual case report, the necessary information should be present, complete and clearly described. Previously designed grading tools were not developed for pregnancy pharmacovigilance data. This study aims to identify the elements that are necessary to assess of the quality of information for risk assessment of medicinal products used during pregnancy. This is a first step in the development of a validated method to assess the clinical quality of case reports in pregnancy pharmacovigilance data. Potential information elements were determined by means of an expert focus group discussion and a survey based on its outcome. This provided an overview of possible information elements to be selected. For the final selection of the elements, a second survey and subsequent focus group discussion was used. Twenty-one information elements within seven categories were identified: information related to the association itself, the event, exposure to the medicinal product, maternal factors, pregnancy, labour, and the child. This study identified elements considered necessary in the assessment of quality of information of case reports in pregnancy pharmacovigilance data, via an extensive four-step process.
The spectrum of in vitro maturation in clinical practice: the current insight
Authors: Ahmad Mohd Faizal , Elias Marjanu Hikmah , Mat Jin Norazilah , Abu Muhammad Azrai , Syafruddin Saiful Effendi , Zainuddin Ani Amelia , Suzuki Nao , Abdul Karim Abdul Kadir
Published: June 2023

In vitro oocyte maturation (IVM) has been used worldwide. Despite the long-term implementation, the uptake of this procedure to complement current in vitro fertilization (IVF) remains low. The main reason is likely due to the non-synchronization of protocol and definition criteria, leading to difficulty in collective proper outcome data worldwide and, thus, lack of understanding of the exact IVM procedure. The review aims to consolidate the current clinical practice of IVM by dissecting relevant publications to be tailored for a current spectrum of clinical practice. Nevertheless, the background theories of oocyte maturation were also explored to provide a comprehensive understanding of the basis of IVM theories. Additional discussion of other potential uses of IVM in the future, such as in ovarian tissue cryopreservation known as OTO-IVM for fertility preservation and among women with diminished ovarian reserve, was also explored. Otherwise, future collaboration among all IVM centers is paramount for better collection of clinical data to provide valid recommendations for IVM in clinical practice, especially in molecular integrity and possible DNA alteration if present for IVM offspring outcome safety purposes.
A comprehensive overview of exosome lncRNAs: emerging biomarkers and potential therapeutics in endometriosis
Authors: Wang Min , Zheng Lianwen , Lin Ruixin , Ma Shuai , Li Jiahui , Yang Shuli
Published: June 2023

Endometriosis is a gynecological condition that significantly impacting women’s daily lives. In recent years, the incidence of endometriosis has been rising yearly and is now an essential contributor to female infertility. Exosomes are extracellular vesicles (EVs) that carry long noncoding RNA (lncRNA) and shield lncRNA from the outside environment thanks to their vesicle-like structure. The role of exosome-derived lncRNAs in endometriosis is also receiving more study as high-throughput sequencing technology develops. Several lncRNAs with variable expression may be crucial to the emergence and growth of endometriosis. The early diagnosis of endometriosis will be considerably improved by further high specificity and sensitivity Exosome lncRNA screening. Exosomes assist lncRNAs in carrying out their roles, offering a new target for creating endometriosis-specific medications. In order to serve as a reference for clinical research on the pathogenesis, diagnosis, and treatment options of endometriosis, this paper covers the role of exosome lncRNAs in endometriosis and related molecular mechanisms.
Synchronous rectification of LLC resonant converters based on resonant inductor voltage
Authors: Luo Zuohao , Wu Zaijun , Quan Xiangjun , Xie Xingfeng , Dou Xiaobo , Hu Qinran
Published: June 2023

Synchronous rectification (SR) technology has been a critical technology for LLC converters to achieve high efficiency and power density. However, conventional SR driving methods face challenges in terms of light-load condition, module size, switching accuracy, and circuit complexity. This paper proposes an SR driving strategy based on resonant inductor voltage (RLV) to address those issues. This RLV-SR driving strategy does not require current sensors and is insensitive to rectifier parasitic parameters. In addition, the RLV-SR driving strategy can be applied in a relatively wide operating frequency range and load conditions. Experimental results based on a 100-W/24-V LLC converter are presented to verify the effectiveness of the proposed RLV-SR driving strategy. Furthermore, the error of turn-on time caused by stray inductance is significantly reduced compared with the conventional VDS-ON sensing method, which improves the power converter’s efficiency.
Material balance principle to estimate eco-efficiency of saffron-producers aiming reduction in greenhouse gas emissions in Iran
Authors: Mardani Najafabadi M. , Rastegaripour F. , Yavari F. , Ahani E.
Published: June 2023

Introduction: During the last decades, environmental pollution has been considered one of the challenges of the agricultural sector, which has affected the relationship between the ecological and economic performance of agricultural products.

Methods: In this study, the DEA-MBP approach based on the SBM model has been used to investigate the eco-efficiency of saffron farms in Iran. The main purpose of this approach is to decrease GHG emissions by mitigating the use of highly polluting production inputs.

Results: The results showed that the average eco-efficiency is estimated at 74% and is 12% lower than technical efficiency without considering environmental issues. Therefore, saffron producers are 26% far from full efficiency, and they must change their consumption of inputs and production of inputs according to environmental issues in order to achieve it. Excessive use of diesel fuel and fungicides is cause of GHG emissions in these farms.

Discussion: The use of sustainable and ecological cultivation methods in farms in order to reduce the consumption of chemical fertilizers and fungicides should be considered. Replacing old machinery and repairing them can also considerably reduce fuel consumption and GHG emissions.
Bismuth exposure affects morpho-physiological performances and the ionomic profile in garden cress (Lepidium sativum L.) plants
Authors: Pietrini Fabrizio , Passatore Laura , Carloni Serena , Massimi Lorenzo , Astolfi Maria Luisa , Giusto Chiara , Zacchini Massimo
Published: June 2023

Environmental pollution caused by heavy metals has long been considered a relevant threat to ecosystem survival and human health. The use of safer substitutes for the most toxic heavy metals in many industrial applications is discussed as a potential way to face this issue. In this regard, Bi has been proposed for replacing Pb in several production processes. However, few literature records reported on the effects of Bi on living organisms, particularly on plants. In this study, garden cress (Lepidium sativum L.) plants were exposed to different concentrations of Bi nitrate added to soil in growth chambers for 21 days. Results evidenced the toxic effect of Bi on shoot growth, regardless of the Bi nitrate concentration in the soil, paralleled by a similar reduction in the chlorophyll and carotenoid content, a decrease in the nitrogen balance index values, and an impairment of the photosynthetic machinery evaluated by chlorophyll fluorescence image analysis. The presence of Bi in the soil was shown to affect element accumulation in roots and translocation to shoots, with micronutrient content particularly reduced in the leaves of Bi-treated plants. A dose-dependent plant accumulation of Bi to metal concentration in the soil was observed, even if very low metal bioconcentration ability was highlighted. The reduced Bi translocation from roots to shoots in plants exposed to increasing Bi concentrations in the soil is discussed as a possible defense mechanism likely associated with the observed increase of anthocyan and flavonol contents and the activation of photoprotection mechanisms preventing higher damages to the photosynthetic apparatus.
A novel PKHD1 splicing variant identified in a fetus with autosomal recessive polycystic kidney disease
Authors: Miao Mingzhu , Feng Liqun , Wang Jue , Xu Cheng , Su Xiaotian , Zhang Guoying , Lu Shoulian
Published: June 2023

Objective: Variants of the polycystic kidney and hepatic disease 1 (PKHD1) gene are associated with autosomal recessive polycystic kidney disease (ARPKD). This study aimed to identify the genetic causes in a Chinese pedigree with ARPKD and design a minigene construct of the PKHD1 gene to investigate the impact of its variants on splicing.

Methods: Umbilical cord samples from the proband and peripheral blood samples from his parents were collected, and genomic DNA was extracted for whole-exome sequencing (WES). Bioinformatic analysis was used to identify potential genetic causes, and Sanger sequencing confirmed the existence of variants within the pedigree. A minigene assay was performed to validate the effects of an intronic variant on mRNA splicing.

Results: Two variants, c.9455del (p.N3152Tfs*10) and c.2408-13C>G, were identified in the PKHD1 gene (NM_138694.4) by WES; the latter has not been previously reported. In silico analysis predicted that this intronic variant is potentially pathogenic. Bioinformatic splice prediction tools revealed that the variant is likely to strongly impact splice site function. An in vitro minigene assay revealed that c.2408-13C>G can cause aberrant splicing, resulting in the retention of 12 bp of intron 23.

Conclusion: A novel pathogenic variant of PKHD1, c.2408-13C>G, was found in a fetus with ARPKD, which enriches the variant spectrum of the PKHD1 gene and provides a basis for genetic counseling and the diagnosis of ARPKD. Minigenes are optimal to determine whether intron variants can cause aberrant splicing.
Identification and prediction of immune checkpoint inhibitors-related pneumonitis by machine learning
Authors: Gong Li , Gong Jun , Sun Xin , Yu Lin , Liao Bin , Chen Xia , Li Yong-sheng
Published: June 2023

Background

Immune checkpoint inhibitor (ICI)-related pneumonitis (IRP) is a common and potentially fatal clinical adverse event. The identification and prediction of the risk of ICI-related IRP is a major clinical issue. The objective of this study was to apply a machine learning method to explore risk factors and establish a prediction model.

Methods

We retrospectively analyzed 48 patients with IRP (IRP group) and 142 patients without IRP (control group) who were treated with ICIs. An Elastic Net model was constructed using a repeated k-fold cross-validation framework (repeat = 10; k = 3). The prediction models were validated internally and the final prediction model was built on the entire training set using hyperparameters with the best interval validation performance. The generalizability of the final prediction model was assessed by applying it to an independent test set. The overall performance, discrimination, and calibration of the prediction model were evaluated.

Results

Eleven predictors were included in the final predictive model: sindillizumab, number of ≥2 underlying diseases, history of lung diseases, tirelizumab, non-small cell lung cancer (NSCLC), percentage of CD4+ lymphocytes, body temperature, KPS score ≤70, hemoglobin, cancer stage IV, and history of antitumor therapy. The external validation of the risk prediction model on an independent test set of 37 patients and showed good discrimination and acceptable calibration ability: with AUC of 0.81 (95% CI 0.58–0.90), AP of 0.76, scaled Brier score of 0.31, and Spiegelhalter-z of −0.29 (P-value:0.77). We also designed an online IRP risk calculator for use in clinical practice.

Conclusion

The prediction model of ICI-related IRP provides a tool for accurately predicting the occurrence of IRP in patients with cancer who received ICIs.
Airway macrophages display decreased expression of receptors mediating and regulating scavenging in early cystic fibrosis lung disease
Authors: Slimmen Lisa J. M. , Giacalone Vincent D. , Schofield Craig , Horati Hamed , Manaï Badies H. A. N. , Estevão Silvia C. , Garratt Luke W. , Peng Limin , Tirouvanziam Rabindra , Janssens Hettie M. , Unger Wendy W. J.
Published: June 2023

Background

Cystic fibrosis (CF) airway disease is characterized by chronic inflammation, featuring neutrophil influx to the lumen. Airway macrophages (AMs) can promote both inflammation and resolution, and are thus critical to maintaining and restoring homeostasis. CF AM functions, specifically scavenging activity and resolution of inflammation, have been shown to be impaired, yet underlying processes remain unknown. We hypothesized that impaired CF AM function results from an altered expression of receptors that mediate or regulate scavenging, and set out to investigate changes in expression of these markers during the early stages of CF lung disease.

Methods

Bronchoalveolar lavage fluid (BALF) was collected from 50 children with CF aged 1, 3 or 5 years. BALF cells were analyzed using flow cytometry. Expression levels of surface markers on AMs were expressed as median fluorescence intensities (MFI) or percentage of AMs positive for these markers. The effect of age and neutrophilic inflammation, among other variables, on marker expression was assessed with a multivariate linear regression model.

Results

AM expression of scavenger receptor CD163 decreased with age (p = 0.016) and was negatively correlated with BALF %neutrophils (r = -0.34, p = 0.016). AM expression of immune checkpoint molecule SIRPα also decreased with age (p = 0.0006), but did not correlate with BALF %neutrophils. Percentage of AMs expressing lipid scavenger CD36 was low overall (mean 20.1% ± 16.5) and did not correlate with other factors. Conversely, expression of immune checkpoint PD-1 was observed on the majority of AMs (mean PD-1pos 72.9% ± 11.8), but it, too, was not affected by age or BALF %neutrophils. Compared to matched blood monocytes, AMs had a higher expression of CD16, CD91, and PD-1, and a lower expression of CD163, SIRPα and CD36.

Conclusion

In BALF of preschool children with CF, higher age and/or increased neutrophilic inflammation coincided with decreased expression of scavenger receptors on AMs. Expression of scavenging receptors and regulators showed a distinctly different pattern in AMs compared to blood monocytes. These findings suggest AM capacity to counter inflammation and promote homeostasis reduces during initiation of CF airway disease and highlight new avenues of investigation into impaired CF AM function.
Deconstructing the causes of July sea level variability in the East Sea from 1994 to 2021
Authors: Han MyeongHee , Chang Yeon S. , Yoo Jeseon
Published: June 2023

In 2021 the East Sea experienced its highest July sea level (65.09 cm), as well as the highest July sea surface and atmospheric temperatures, in the 29 years between 1993 and 2021. We present several methodologies to identify the more important causes of sea level change (SLC) in a semi-enclosed sea and explore the critical fluctuation of ocean mass transport divergence during a period of rapid sea level rise. Based on satellite altimeter data in the East Sea, the SLC, as reflected in the absolute dynamic topography (ADT), which is the ADT difference between the last and first days of a month, was 7.18 cm in July 2021. This may reflect a combination of oceanic and atmospheric factors: ocean heat transport divergence among the Korea, Tsugaru, and Soya Straits was found to contribute 2.32 cm of SLC, atmospheric heat flux at the sea surface contributed 2.87 cm of SLC, and mass divergence (including errors) accounted for 1.98 cm of SLC. The monthly mean sea level (ADT) variation in the East Sea should be examined in terms of the oceanic and atmospheric fluxes, and the SLC sources can additionally be divided into heat and others (mass + errors). The proportional contribution of heat to SLC from 1994 to 2021 was 97.4%. Although the contributions of mass and errors were small, there were substantial temporal fluctuations, as their standard deviation reached up to 96.7% of that of SLC in ADT. In the near future, a more precise analysis of the contributions of mass and errors to SLC is required.
Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL
Authors: Zhang Xujuan , Zhao Pengxiang , Ma Mingshen , Wu Hao , Liu Rui , Liu Ziyi , Cai Zisong , Liu Mengyu , Xie Fei , Ma Xuemei
Published: June 2023

Purpose

Lacrimal gland benign lymphoepithelial lesion (LGBLEL) is an IgG4-related disease of unknown etiology with a risk for malignant transformation. Estrogen is considered to be related to LGBLEL onset.

Methods

Seventy-eight LGBLEL and 13 control clinical samples were collected and studied to determine the relationship between estrogen and its receptors and LGBLEL development.

Results

The serological analysis revealed no significant differences in the levels of three estrogens be-tween the LGBLEL and control groups. However, immunohistochemical analyses indicated that the expression levels of ERβ and its downstream receptor RERG were relatively lower in LGBLEL samples than in control samples, with higher expression in the lacrimal gland and lower expression in the lymphocyte infiltration region. However, low expression of ERα was detected. The transcriptome sequence analysis revealed upregulated genes associated with LGBLEL enriched in lymphocyte proliferation and activation function; downregulated genes were enriched in epithelial and vascular proliferation functions. The key genes and gene networks were further analyzed. Interactions between B cells and epithelial cells were analyzed due to the identified involvement of leukocyte subsets and epithelial cells. B cell proliferation was found to potentially contribute to lacrimal gland apoptosis.

Conclusion

Therefore, the tissue-heterogeneous expression pattern of ERβ is potentially related to the clinical manifestations and progression of LGBLEL, although further investigations are required to confirm this finding.
sTREM-1 and TNF-α levels are associated with the clinical outcome of leprosy patients
Authors: Bezerra-Santos Márcio , Bomfim Lays G. Santos , Santos Camilla N. Oliveira , Cunha Maria Wiliane N. , de Moraes Eduardo J. Rocha , Cazzaniga Rodrigo A. , Tenório Martha D. L. , Araujo Jonnia M. Sherlock , Menezes-Silva Lucas , Magalhães Lucas Sousa , Barreto Aline S. , Reed Steven G. , Duthie Malcolm S. , Lipscomb Michael W. , de Almeida Roque Pacheco , de Moura Tatiana Rodrigues , de Jesus Amélia Ribeiro
Published: June 2023

Leprosy reaction (LR) and physical disability (PD) are the most significant clinical complications of leprosy. Herein, we assessed the circulating serum-sTREM-1 and TNF-α levels and their genetic polymorphisms in leprosy. Serum-sTREM-1 and TNF-α levels were measured in leprosy patients (LP) before treatment (n = 51) and from their household contacts (HHCs; n = 25). DNA samples were genotyped using TREM-1 rs2234246 and TNF-α rs1800629-SNP in 210 LPs and 168 endemic controls. The circulating sTREM-1 and TNF-α levels are higher in the multibacillary form. The ROC curve of the serum-sTREM-1 levels was able to differentiate LR from non-LR and PD from non-PD. Similarly, LPs with serum-sTREM-1 levels >210 pg/ml have 3-fold and 6-fold higher chances of presenting with LR and PD, respectively. Genotypes CC+CT of the TREM-1 were associated with leprosy. Taken together, our analyses indicated that sTREM-1 and TNF-α play an important role in the pathogenesis of leprosy and provide promising biomarkers to assist in the diagnosis of leprosy complications.
BALF metagenomic next-generation sequencing analysis in hematological malignancy patients with suspected pulmonary infection: clinical significance of negative results
Authors: Deng Zuqun , Tang Yishu , Tu Yixuan , Liu Mei , Cheng Qian , Zhang Jian , Liu Feiyang , Li Xin
Published: June 2023

Purpose

Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) is gradually being used in hematological malignancy (HM) patients with suspected pulmonary infections. However, negative results are common and the clinical value and interpretation of such results in this patient population require further analysis.

Methods

Retrospective analysis of 112 HM patients with suspected pulmonary infection who underwent BALF mNGS and conventional microbiological tests. The final diagnosis, imaging findings, laboratory results and treatment regimen of 29 mNGS-negative patients were mainly analyzed.

Results

A total of 83 mNGS positive and 29 negative patients (15 true-negatives and 14 false-negatives) were included in the study. Compared to false-negative patients, true-negative patients showed more thickening of interlobular septa on imaging (p < 0.05); fewer true-negative patients had acute respiratory symptoms such as coughing or sputum production (p < 0.05) clinically; On the aspect of etiology, drug-related interstitial pneumonia (6/15, 40%) was the most common type of lung lesion in true-negative patients; on the aspect of pathogenesis, false-negative patients mainly missed atypical pathogens such as fungi and tuberculosis (8/14, 57.1%). Regarding treatment, delayed anti-infection treatment occurred after pathogen missing in mNGS false-negative patients, with the longest median time delay observed for anti-tuberculosis therapy (13 days), followed by antifungal therapy (7 days), and antibacterial therapy (1.5 days); the delay in anti-tuberculosis therapy was significantly longer than that in antibacterial therapy (p < 0.05).

Conclusion

For HMs patients with imaging showing thickening of interlobular septa and no obvious acute respiratory symptoms, lung lesions are more likely caused by drug treatment or the underlying disease, so caution should be exercised when performing BALF mNGS. If BALF mNGS is negative but infection is still suspected, atypical pathogenic infections should be considered.
Soil amendment and rhizobacterial inoculation improved Cu phytostabilization, plant growth and microbial activity in a bench-scale experiment
Authors: Romero-Estonllo Marc , Ramos-Castro Judith , San Miguel del Río Yaiza , Rodríguez-Garrido Beatriz , Prieto-Fernández Ángeles , Kidd Petra S. , Monterroso Carmen
Published: June 2023

Mine driven trace elements’ pollution entails environmental risks and causes soil infertility. In the last decades, in situ techniques such as phytostabilization have become increasingly important as ways to tackle these negative impacts. The aim of this study was to test the individual and combined effects of different aided phytostabilization techniques using substrate from barren tailings of a Cu mine, characterized by extreme infertility (high acidity and deficiency of organic matter and nutrients). The experiment analyzed the growth of Populus nigra L. planted alone (P) or in co-cropping with Trifolium repens L. (PT), in pots containing mine soil amended with compost (1, 10, compost, soil, w/w) non inoculated (NI) or inoculated with plant growth promoting rhizobacteria (PGP), mycorrhizae (MYC) or a combination of bacterial and fungal inocula (PGPMYC). Non-amended, non-planted and non-inoculated reference ports were also prepared. Plants were harvested after 110 days of plant development and several biometric and phytopathological parameters (stem height, aerial biomass, root biomass, wilting, chlorosis, pest and death) and macro and micronutrient composition were determined. The growth substrate was analyzed for several physicochemical (pH, CECe, and exchangeable cations, total C and N, P Olsen and availability of trace elements) and microbiological (community level physiological profiles: activity, richness and diversity) parameters. The use of the amendment, P. nigra plantation, and inoculation with rhizobacteria were the best techniques to reduce toxicity and improve soil fertility, as well as to increase the plant survival and growth. Soil bacterial functional diversity was markedly influenced by the presence of plants and the inoculation with bacteria, which suggests that the presence of plant regulated the configuration of a microbial community in which the inoculated bacteria thrive comparatively better. The results of this study support the use of organic amendments, tolerant plants, and plant growth promoting rhizobacteria to reduce environmental risk and improve fertility of soils impacted by mining.
Substrate-independent expression of key functional genes in Cycloclasticus pugetii strain PS-1 limits their use as markers for PAH biodegradation
Authors: Vogel Anjela L. , Thompson Katharine J. , Straub Daniel , App Constantin B. , Gutierrez Tony , Löffler Frank E. , Kleindienst Sara
Published: June 2023

Microbial degradation of petroleum hydrocarbons is a crucial process for the clean-up of oil-contaminated environments. Cycloclasticus spp. are well-known polycyclic aromatic hydrocarbon (PAH) degraders that possess PAH-degradation marker genes including rhd3α, rhd2α, and pahE. However, it remains unknown if the expression of these genes can serve as an indicator for active PAH degradation. Here, we determined transcript-to-gene (TtG) ratios with (reverse transcription) qPCR in cultures of Cycloclasticus pugetii strain PS-1 grown with naphthalene, phenanthrene, a mixture of these PAHs, or alternate substrates (i.e., no PAHs). Mean TtG ratios of 1.99 × 10−2, 1.80 × 10−3, and 3.20 × 10−3 for rhd3α, rhd2α, and pahE, respectively, were measured in the presence or absence of PAHs. The TtG values suggested that marker-gene expression is independent of PAH degradation. Measurement of TtG ratios in Arctic seawater microcosms amended with water-accommodated crude oil fractions, and incubated under in situ temperature conditions (i.e., 1.5°C), only detected Cycloclasticus spp. rhd2α genes and transcripts (mean TtG ratio of 4.15 × 10−1). The other marker genes—rhd3α and pahE—were not detected, suggesting that not all Cycloclasticus spp. carry these genes and a broader yet-to-be-identified repertoire of PAH-degradation genes exists. The results indicate that the expression of PAH marker genes may not correlate with PAH-degradation activity, and transcription data should be interpreted cautiously.
Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation
Authors: Akash Shopnil , Bayıl Imren , Rahman Md. Anisur , Mukerjee Nobendu , Maitra Swastika , Islam Md. Rezaul , Rajkhowa Sanchaita , Ghosh Arabinda , Al-Hussain Sami A. , Zaki Magdi E. A. , Jaiswal Vikash , Sah Sanjit , Barboza Joshuan J. , Sah Ranjit
Published: June 2023

Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus’s ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from −7.4 to −8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from −6.2 to −8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical.
Lactobacillus rhamnosus GG ATCC53103 and Lactobacillus plantarum JL01 improved nitrogen metabolism in weaned piglets by regulating the intestinal flora structure and portal vein metabolites
Authors: He Feng , Jin Xueying , Wang Chunfeng , Hu Jingtao , Su Shuai , Zhao Lei , Geng Tingting , Zhao Yuan , Pan Li , Bao Nan , Sun Hui
Published: June 2023

At present, most studies have shown that probiotics have a positive regulatory effect on the nutritional metabolism of the body, but the mechanism is still unclear. Here, 48 piglets were divided into four groups. The control group was not fed probiotics, the Lac group was fed L. Rhamnosus GG ATCC53103, the Rha group was fed L. Plantarum JL01, and the mix group was fed two types of probiotics. Nitrogen metabolism and mRNA levels of mTOR and S6K in skeletal muscle were observed in each group. Then, metagenome and non-targeted metabonomics were used to observe the changes of intestinal microorganisms and plasma metabolites in portal channels after probiotics feeding. Finally, we combined the results of omics analysis to reveal the mechanism of probiotics on nitrogen metabolism in weaned piglets. The results showed that L. Rhmnosus GG ATCC53103 and L. Plantarum JL01 increased nitrogen apparent digestibility, nitrogen deposition rate, and nitrogen utilization rate of weaned piglets (P < 0.05); the relative expression of mTOR and SK6 mRNA in skeletal muscle increased significantly (P < 0.05). When L. rhamnosus GG ATCC53103 and L. plantarum JL01 were combined, we found that Clostridium and Prevotella significantly increased in the jejunum (P < 0.05). The relative abundance of Lactobacillus, Ruminococcus, Streptococcus, and Prevotella in the ileum increased significantly (P < 0.05). Compared with the control group, L-Tryptophan, 3-Phosphonyloxypyruvate, cis-Aconitate, and Carbamoyl phosphate were significantly increased in the mixed group portal vein. The result of the combinatorial analysis showed that the significantly increased microorganisms could encode the enzyme genes for the synthesis of L-Tryptophan, 3-Phosphonooxypyruvate, cis-Aconitate, and Carbamoyl phosphate. In summary, our results demonstrated that L. Rhamnosus GG ATCC53103 and L. Plantarum JL01 could stimulate the expression of skeletal muscle protein synthesis genes of weaned piglets by modulating the structure of the gut microbiota and its metabolites, thereby improving nitrogen metabolism in weaned piglets.
Genomic insights into Aspergillus sydowii 29R-4-F02: unraveling adaptive mechanisms in subseafloor coal-bearing sediment environments
Authors: Jiang Jun-Peng , Liu Xuan , Liao Yi-Fan , Shan Jun , Zhu Yu-Ping , Liu Chang-Hong
Published: June 2023

Introduction

Aspergillussydowii is an important filamentous fungus that inhabits diverse environments. However, investigations on the biology and genetics of A. sydowii in subseafloor sediments remain limited.

Methods

Here, we performed de novo sequencing and assembly of the A. sydowii 29R-4-F02 genome, an isolate obtained from approximately 2.4 km deep, 20-million-year-old coal-bearing sediments beneath the seafloor by employing the Nanopore sequencing platform.

Results and Discussion

The generated genome was 37.19 Mb with GC content of 50.05%. The final assembly consisted of 11 contigs with N50 of 4.6 Mb, encoding 12,488 putative genes. Notably, the subseafloor strain 29R-4-F02 showed a higher number of carbohydrate-active enzymes (CAZymes) and distinct genes related to vesicular fusion and autophagy compared to the terrestrial strain CBS593.65. Furthermore, 257 positively selected genes, including those involved in DNA repair and CAZymes were identified in subseafloor strain 29R-4-F02. These findings suggest that A. sydowii possesses a unique genetic repertoire enabling its survival in the extreme subseafloor environments over tens of millions of years.
A novel framework of MOPSO-GDM in recognition of Alzheimer's EEG-based functional network
Authors: Wang Ruofan , Wang Haodong , Shi Lianshuan , Han Chunxiao , He Qiguang , Che Yanqiu , Luo Li
Published: June 2023

Background

Most patients with Alzheimer's disease (AD) have an insidious onset and frequently atypical clinical symptoms, which are considered a normal consequence of aging, making it difficult to diagnose AD medically. But then again, accurate diagnosis is critical to prevent degeneration and provide early treatment for AD patients.

Objective

This study aims to establish a novel EEG-based classification framework with deep learning methods for AD recognition.

Methods

First, considering the network interactions in different frequency bands (δ, θ, α, β, and γ), multiplex networks are reconstructed by the phase synchronization index (PSI) method, and fourteen topology features are extracted subsequently, forming a high-dimensional feature vector. However, in feature combination, not all features can provide effective information for recognition. Moreover, combining features by manual selection is time-consuming and laborious. Thus, a feature selection optimization algorithm called MOPSO-GDM was proposed by combining multi-objective particle swarm optimization (MOPSO) algorithm with Gaussian differential mutation (GDM) algorithm. In addition to considering the classification error rates of support vector machine, naive bayes, and discriminant analysis classifiers, our algorithm also considers distance measure as an optimization objective.

Results

Finally, this method proposed achieves an excellent classification error rate of 0.0531 (5.31%) with the feature vector size of 8, by a ten-fold cross-validation strategy.

Conclusion

These findings show that our framework can adaptively combine the best brain network features to explore network synchronization, functional interactions, and characterize brain functional abnormalities, which can improve the recognition efficiency of diseases. While improving the classification accuracy of application algorithms, we aim to expand our understanding of the brain function of patients with neurological disorders through the analysis of brain networks.
Three potential neurovascular pathways driving the benefits of mindfulness meditation for older adults
Authors: Pommy Jessica , Smart Colette M. , Bryant Andrew M. , Wang Yang
Published: June 2023

Mindfulness meditation has been shown to be beneficial for a range of different health conditions, impacts brain function and structure relatively quickly, and has shown promise with aging samples. Functional magnetic resonance imaging metrics provide insight into neurovascular health which plays a key role in both normal and pathological aging processes. Experimental mindfulness meditation studies that included functional magnetic resonance metrics as an outcome measure may point to potential neurovascular mechanisms of action relevant for aging adults that have not yet been previously examined. We first review the resting-state magnetic resonance studies conducted in exclusively older adult age samples. Findings from older adult-only samples are then used to frame the findings of task magnetic resonance imaging studies conducted in both clinical and healthy adult samples. Based on the resting-state studies in older adults and the task magnetic resonance studies in adult samples, we propose three potential mechanisms by which mindfulness meditation may offer a neurovascular therapeutic benefit for older adults: (1) a direct neurovascular mechanism via increased resting-state cerebral blood flow; (2) an indirect anti-neuroinflammatory mechanism via increased functional connectivity within the default mode network, and (3) a top-down control mechanism that likely reflects both a direct and an indirect neurovascular pathway.
Regional contributions of D-serine to Alzheimer’s disease pathology in male AppNL–G–F/NL–G–F mice
Authors: Ni Xiance , Inoue Ran , Wu Yi , Yoshida Tomoyuki , Yaku Keisuke , Nakagawa Takashi , Saito Takashi , Saido Takaomi C. , Takao Keizo , Mori Hisashi
Published: June 2023

Background

Neurodegenerative processes in Alzheimer’s disease (AD) are associated with excitotoxicity mediated by the N-methyl-D-aspartate receptor (NMDAR). D-Serine is an endogenous co-agonist necessary for NMDAR-mediated excitotoxicity. In the mammalian brain, it is produced by serine racemase (SRR) from L-serine, suggesting that dysregulation of L-serine, D-serine, or SRR may contribute to AD pathogenesis.

Objective and methods

We examined the contributions of D-serine to AD pathology in the AppNL–G–F/NL–G–F gene knock-in (APPKI) mouse model of AD. We first examined brain SRR expression levels and neuropathology in APPKI mice and then assessed the effects of long-term D-serine supplementation in drinking water on neurodegeneration. To further confirm the involvement of endogenous D-serine in AD progression, we generated Srr gene-deleted APPKI (APPKI-SRRKO) mice. Finally, to examine the levels of brain amino acids, we conducted liquid chromatography–tandem mass spectrometry.

Results

Expression of SRR was markedly reduced in the retrosplenial cortex (RSC) of APPKI mice at 12 months of age compared with age-matched wild-type mice. Neuronal density was decreased in the hippocampal CA1 region but not altered significantly in the RSC. D-Serine supplementation exacerbated neuronal loss in the hippocampal CA1 of APPKI mice, while APPKI-SRRKO mice exhibited attenuated astrogliosis and reduced neuronal death in the hippocampal CA1 compared with APPKI mice. Furthermore, APPKI mice demonstrated marked abnormalities in the cortical amino acid levels that were partially reversed in APPKI-SRRKO mice.

Conclusion

These findings suggest that D-serine participates in the regional neurodegenerative process in the hippocampal CA1 during the amyloid pathology of AD and that reducing brain D-serine can partially attenuate neuronal loss and reactive astrogliosis. Therefore, regulating SRR could be an effective strategy to mitigate NMDAR-dependent neurodegeneration during AD progression.
Altered brain functional connectivity in vegetative state and minimally conscious state
Authors: Yang Yi , Dai Yangyang , He Qiheng , Wang Shan , Chen Xueling , Geng Xiaoli , He Jianghong , Duan Feng
Published: June 2023

Objectives

The pathological mechanism for a disorder of consciousness (DoC) is still not fully understood. Based on traditional behavioral scales, there is a high rate of misdiagnosis for subtypes of DoC. We aimed to explore whether topological characterization may explain the pathological mechanisms of DoC and be effective in diagnosing the subtypes of DoC.

Methods

Using resting-state functional magnetic resonance imaging data, the weighted brain functional networks for normal control subjects and patients with vegetative state (VS) and minimally conscious state (MCS) were constructed. Global and local network characteristics of each group were analyzed. A support vector machine was employed to identify MCS and VS patients.

Results

The average connection strength was reduced in DoC patients and roughly equivalent in MCS and VS groups. Global efficiency, local efficiency, and clustering coefficients were reduced, and characteristic path length was increased in DoC patients (p < 0.05). For patients of both groups, global network measures were not significantly different (p > 0.05). Nodal efficiency, nodal local efficiency, and nodal clustering coefficient were reduced in frontoparietal brain areas, limbic structures, and occipital and temporal brain areas (p < 0.05). The comparison of nodal centrality suggested that DoC causes reorganization of the network structure on a large scale, especially the thalamus. Lobal network measures emphasized that the differences between the two groups of patients mainly involved frontoparietal brain areas. The accuracy, sensitivity, and specificity of the classifier for identifying MCS and VS patients were 89.83, 78.95, and 95%, respectively.

Conclusion

There is an association between altered network structures and clinical symptoms of DoC. With the help of network metrics, it is feasible to differentiate MCS and VS patients.
Controlling neocortical epileptic seizures using forced temporal spike-time stimulation: an in silico computational study
Authors: Schmalz Joseph , Quinarez Rachel V. , Kothare Mayuresh V. , Kumar Gautam
Published: June 2023

Epileptic seizure is typically characterized by highly synchronized episodes of neural activity. Existing stimulation therapies focus purely on suppressing the pathologically synchronized neuronal firing patterns during the ictal (seizure) period. While these strategies are effective in suppressing seizures when they occur, they fail to prevent the re-emergence of seizures once the stimulation is turned off. Previously, we developed a novel neurostimulation motif, which we refer to as “Forced Temporal Spike-Time Stimulation” (FTSTS) that has shown remarkable promise in long-lasting desynchronization of excessively synchronized neuronal firing patterns by harnessing synaptic plasticity. In this paper, we build upon this prior work by optimizing the parameters of the FTSTS protocol in order to efficiently desynchronize the pathologically synchronous neuronal firing patterns that occur during epileptic seizures using a recently published computational model of neocortical-onset seizures. We show that the FTSTS protocol applied during the ictal period can modify the excitatory-to-inhibitory synaptic weight in order to effectively desynchronize the pathological neuronal firing patterns even after the ictal period. Our investigation opens the door to a possible new neurostimulation therapy for epilepsy.
Association between intraoperative steroid and postoperative mortality in patients undergoing craniotomy for brain tumor
Authors: He Jialing , He Shuanghong , Zhang Yu , Tian Yixin , Hao Pengfei , Li Tiangui , Xiao Yangchun , Peng Liyuan , Feng Yuning , Cheng Xin , Deng Haidong , Wang Peng , Chong Weelic , Hai Yang , Chen Lvlin , You Chao , Jia Lu , Chen Dengkui , Fang Fang
Published: June 2023

Background

Despite the widespread use of intraoperative steroids in various neurological surgeries to reduce cerebral edema and other adverse symptoms, there is sparse evidence in the literature for the optimal and safe usage of intraoperative steroid administration in patients undergoing craniotomy for brain tumors. We aimed to investigate the effects of intraoperative steroid administration on postoperative 30-day mortality in patients undergoing craniotomy for brain tumors.

Methods

Adult patients who underwent craniotomy for brain tumors between January 2011 to January 2020 were included at West China Hospital, Sichuan University in this retrospective cohort study. Stratified analysis based on the type of brain tumor was conducted to explore the potential interaction.

Results

This study included 8,663 patients undergoing craniotomy for brain tumors. In patients with benign brain tumors, intraoperative administration of steroids was associated with a higher risk of postoperative 30-day mortality (adjusted OR 1.98, 95% CI 1.09–3.57). However, in patients with malignant brain tumors, no significant association was found between intraoperative steroid administration and postoperative 30-day mortality (adjusted OR 0.86, 95% CI 0.55–1.35). Additionally, administration of intraoperative steroids was not associated with acute kidney injury (adjusted OR 1.11, 95% CI 0.71–1.73), pneumonia (adjusted OR 0.89, 95% CI 0.74–1.07), surgical site infection (adjusted OR 0.78, 95% CI 0.50–1.22) within 30 days, and stress hyperglycemia (adjusted OR 1.05, 95% CI 0.81–1.38) within 24 h after craniotomy for brain tumor.

Conclusion

In patients undergoing craniotomy for benign brain tumors, intraoperative steroids were associated with 30-day mortality, but this association was not significant in patients with malignant brain tumors.
Seasonal variation in the incidence of primary intracerebral hemorrhage: a 16-year nationwide analysis
Authors: Baig Eman , Tannous Jonika , Potter Thomas , Pan Alan , Prince Taya , Britz Gavin , Vahidy Farhaan S. , Bako Abdulaziz T.
Published: June 2023

Introduction

Data on nationwide trends and seasonal variations in the incidence of Intracerebral Hemorrhage (ICH) in the United States (US) are lacking.

Methods

We used the Nationwide Inpatient Sample (2004–2019) and Census Bureau data to calculate the quarterly (Q1:January-March; Q2:April-June; Q3:July-September; Q4:October-December) incidence rates (IR) of adult (≥18 years) ICH hospitalizations, aggregated across Q1–Q4 and Q2–Q3. We report adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) for differences in the quarterly incidence of ICH, as compared to acute ischemic stroke (AIS), between Q1Q4 and Q2Q3 using a multivariable Poisson regression model. We additionally performed stratified analyses across the four US regions.

Results

Among 822,143 (49.0% female) ICH and 6,266,234 (51.9% female) AIS hospitalizations, the average quarterly crude IR of ICH was consistently higher in Q1Q4 compared to Q2Q3 (5.6 vs. 5.2 per 100,000) (aIRR, CI: 1.09, 1.08–1.11)—this pattern was similar across all four US regions. However, a similar variation pattern was not observed for AIS incidence. The incidence (aIRR, CI) of both ICH (1.01, 1.00–1.02) and AIS (1.03, 1.02–1.03) is rising.

Conclusion

Unlike AIS, ICH incidence is consistently higher in colder quarters, underscoring the need for evaluation and prevention of factors driving seasonal variations in ICH incidence.