bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice
Authors: Wang Xiaolong , Li Lin , Bai Mingjian , Zhao Jiaxin , Sun Xiaojie , Gao Yu , Yu Haitao , Chen Xia , Zhang Chunjing
Published: November 2022

Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.
Investigation of the inlet layout effect on the solid waste removal in an octagonal aquaculture tank
Authors: Hu Jiajun , Zhang Hanwen , Wu Lianhui , Zhu Fang , Zhang Xuefen , Gui Fukun , Qu Xiaoyu , Feng Dejun
Published: November 2022

The optimization of the inlet layout in aquaculture systems is essential to ensure minimal solid waste discharge into the environment and improve fish production efficiency. In the present study, laboratory experiments were carried out to investigate the effects of the jetting position d/a (where d is the distance from the pipe axis to the tank side and a is the side length of the tank wall) and the jetting angle θ (the acute angle between the jetting direction and the nearest tank wall) on the solid waste removal efficiency in single-inlet and dual-inlet octagonal Recirculating Aquaculture System (RAS) tanks. To this end, three jetting positions (d/a) of 1/50, 1/8, and 1/4 and ten jetting angles (θ) of 0° to 80° were considered in the experiments. The Particle Image Velocimetry (PIV) technique was applied to measure the flow characteristics in the tank and analyze the solid waste removal under different working conditions. Residual mass of the solid waste, time of complete removal of solid waste, average velocity (vavg), and uniformity coefficient of velocity distribution (DU50) were analyzed to evaluate the solid waste removal efficiency. The obtained results indicate that adjustments of the inlet layout significantly affect the solid waste removal efficiency. It was found that a single-inlet tank with a d/a of 1/8 and θ in the range 10° to 40° has a good solid wastes removal performance, and the optimal efficiency occurs at a jetting angle of 30°. Moreover, the optimal solid waste removal efficiency in a dual-inlet tank can be achieved with a d/a ratio of 1/8 and a θ of 20°. The performed analyses reveal that from the aspect of solid waste removal efficiency, a tank with a d/a ratio of 1/8 outperforms a tank with a d/a ratio of 1/4 or 1/50. The results of this article offer novel insights in the layout of octagonal RAS tanks and provide a guideline to improve self-cleaning features of aquaculture tanks.
In-situ measurement of the meniscus at the entry and exit of grease and oil lubricated rolling bearing contacts
Authors: Gray W. A. , Dwyer-Joyce R. S.
Published: November 2022

The lubricant inlet meniscus in a rolling element bearing acts as a reservoir that feeds the elastohydrodynamic contact, resulting in a sufficiently thick film to avoid wear. A shortening and/or thinning of the inlet meniscus towards the contact centre is an indicator of bearing starvation and impaired lubricant performance. This work introduces an ultrasonic method to measure meniscus dimensions. Using in situ ultrasonic sensors on a full-scale cylindrical roller bearing test rig, we show that ultrasonic waves can cause oil films to resonate, and that the resonant frequency is directly related to the film thickness. Using a benchtop rig we validate the relationship between resonant frequency and film thickness. This allows for the measurement of meniscus thickness and length in situ during bearing operation. Menisci were measured at both the inlet and outlet of rolling bearing line contacts while lubricated with different viscosity oils and grease. All lubricants used showed they could be monitored using this approach. The implication of this paper is that it is possible to measure a critically important lubrication mechanism during operation without major component modifications.
Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 Global Burden of Disease Study
Authors: Cheng Lin-Can , Li Hao-Yang , Gong Qin-Qin , Huang Cheng-Yang , Zhang Chao , Yan Jin-Zhu
Published: November 2022

Objective

To study specific information on trends in incidence, mortality, disability-adjusted life years (DALY) and the corresponding trends among five sociodemographic index regions, 21 regions, and 204 countries for decision-making, which would enable policymakers to distribute limited resources and devise policies more rationally.

Methods

Data on uterine fibroids (UNs) from 1990 to 2019, including incidence, mortality, and DALYs, were obtained from the 2019 Global Burden of Disease Study. An estimated annual percentage change (EAPC) was calculated to assess morbidity, mortality, and DALY trends.

Results

The incident cases of UFs increased from 5,769,658 (95%UI, 7,634,3995–4,274,824) incidences in 1990 to 9,643,336 (95%UI, 7,178,053-12,714,741) incidences in 2017, and the age-standardized incidence rate was steady at 225.67/100,000 persons (95%UI, 167.33–298.87) in 1990 to 241.18/100,000 persons (95%UI, 179,45–318.02) in 2019. The incidence ratio in the high sociodemographic index (SDI) region showed a unimodal distribution, with peaks in 2005. Between 2009 and 2017, the age-standardized death rate of UFs declined globally, especially in low-SDI and low-middle SDI regions. In contrast with 860,619 DALYs (95%UI, 473,067-1,505,289) in 1990, the number of DALYs was 1,378,497 (95%UI, 710,915-2,475,244) in 2019, which had increased significantly, whereas the age-standardized DALY rate decreased expressively with an EAPC of −1.93 (95%CI, from −2.16 to −1.71).

Conclusion

The global burden of UFs increased between 1990 and 2019, and the incidences and DALYs increased prominently worldwide, while the deaths from UFs had no evident growth. Lower SDI regions carried an incremental burden of UFs, while disease reduction was observed in higher SDI regions. It is high time we paid attention to the underprivileged regional quality of life and health protection.
Intraoperative intact parathyroid hormone monitoring and frozen section diagnosis are essential for successful parathyroidectomy in secondary hyperparathyroidism
Authors: Hiramitsu Takahisa , Hasegawa Yuki , Futamura Kenta , Okada Manabu , Goto Norihiko , Narumi Shunji , Watarai Yoshihiko , Tominaga Yoshihiro , Ichimori Toshihiro
Published: November 2022

Background

Total parathyroidectomy (PTx) is often performed to treat secondary hyperparathyroidism (SHPT). Successful PTx is essential to prevent recurrent and persistent SHPT because remnant parathyroid glands (PTGs) in the neck can be stimulated and may secrete excessive parathyroid hormone (PTH) in end-stage renal disease. However, to date, few studies have investigated factors contributing to successful PTx before the completion of surgery.

Materials and methods

Between August 2010 and February 2020, 344 patients underwent total PTx, transcervical thymectomy, and forearm autograft for SHPT at our institute. Factors contributing to successful PTx before the completion of surgery were investigated. Preoperative imaging diagnoses, including computed tomography, ultrasonography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy, intraoperative intact PTH (IOIPTH) monitoring, and frozen section histologic diagnosis, were performed. Successful PTx was defined as intact PTH level < 60 pg/mL on postoperative day 1. A sufficient decrease in IOIPTH level was defined as > 70% decrease in intact PTH levels measured 10 min after total PTx and transcervical thymectomy compared to intact PTH levels measured before skin incision. Logistic regression analysis was conducted to investigate factors contributing to PTx success.

Results

Univariate analysis showed that the number of all PTGs identified preoperatively by imaging modalities and the specimens submitted for frozen section diagnosis, which surgeon presumed to be PTGs, were not significant factors contributing to successful PTx. However, multivariate analysis revealed that the number of PTGs identified by frozen section diagnosis (P < 0.001, odds ratio [OR] 4.356, 95% confidence interval [CI] 2.499–7.592) and sufficient decrease in IOIPTH levels (P = 0.001, OR 7.847, 95% CI 2.443–25.204) significantly contributed to successful PTx.

Conclusion

Sufficient intact PTH level decrease observed on IOIPTH monitoring and the number of PTGs identified by frozen section diagnosis contributed to successful PTx for SHPT. IOIPTH monitoring and frozen section diagnosis are essential for achieving successful PTx for SHPT.
A case series of dermatomyositis following SARS-CoV-2 vaccination
Authors: Chan Airiss R. , Cohen Tervaert Jan Willem , Redmond Desiree , Yacyshyn Elaine , Ferrara Giovanni , Hwang Peter M. , Osman Mohamed , Gniadecki Robert
Published: November 2022

Background/Objective

The most significant adverse events following SARS-CoV-2 vaccination are myocarditis and pericarditis. Myositis and dermatomyositis have been reported following SARS-CoV-2 infection, but vaccine-induced dermatomyositis (DM) has not been reported. Our case series aimed to characterize new onset dermatomyositis or disease-related flares following SARS-CoV-2 vaccination.

Materials and methods

A total of 53 patients from our institution with a new or pre-existing diagnosis of DM were recruited and consented. Phone interviews were conducted to obtain vaccination status and symptoms following vaccination. Electronic medical records were reviewed to extract age, sex, autoantibody profiles, comorbidities, immunomodulatory therapies, creatine kinase (CK) values, and SARS-CoV-2 vaccination dates from the provincial vaccination registry. For patients who reported disease flares, records were reviewed for the onset and nature of symptoms, extent of organ involvement and changes in immunomodulation.

Results

On average, patients received 2.62 vaccine doses (range 1–3 doses). A total of 3 of 51 patients (5.88%) experienced dermatomyositis symptoms following vaccination. Two patients were newly diagnosed with dermatomyositis, one requiring hospitalization. Reported symptom onset following vaccination ranged from 1 to 30 days. Of note, all of these patients had normal CK values, even though there was muscle biopsy-confirmed myositis in one patient. Eight patients in the cohort (15.1%) had asymptomatic CK elevation (<1.5 X ULN).

Conclusion

New onset dermatomyositis or flare up of pre-existing dermatomyositis may be a rare complication in SARS-CoV-2 vaccination although no studies can support a true correlation. Several pathophysiologic mechanisms are proposed.
Subinhibitory antibiotic concentrations promote the horizontal transfer of plasmid-borne resistance genes from Klebsiellae pneumoniae to Escherichia coli
Authors: Ding Manlin , Ye Zi , Liu Lu , Wang Wei , Chen Qiao , Zhang Feiyang , Wang Ying , Sjöling Åsa , Martín-Rodríguez Alberto J. , Hu Renjing , Chen Wenbi , Zhou Yingshun
Published: November 2022

Horizontal gene transfer plays an important role in the spread of antibiotic resistance, in which plasmid-mediated conjugation transfer is the most important mechanism. While sub-minimal inhibitory concentrations (sub-MIC) of antibiotics could promote conjugation frequency, the mechanism by which sub-MIC levels of antibiotics affect conjugation frequency is not clear. Here, we used Klebsiella pneumoniae SW1780 carrying the multi-drug resistance plasmid pSW1780-KPC as the donor strain, to investigate the effects of sub-MICs of meropenem (MEM), ciprofloxacin (CIP), cefotaxime (CTX), and amikacin (AK) on conjugational transfer of pSW1780-KPC from SW1780 to Escherichia coli J53. Our results showed that the transfer frequencies increased significantly by treating SW1780 strain with sub-MIC levels of MEM, CIP, CTX and AK. Transfer frequencies at sub-MIC conditions in a Galleria mellonella were significantly higher than in vitro. To investigate gene expression and metabolic effects, RT-qPCR and LC–MS-based metabolome sequencing were performed. Transcript levels of T4SS genes virB1, virB2, virB4, virB8, and conjugation-related genes traB, traK, traE, and traL were significantly upregulated by exposure to sub-MICs of MEM, CIP, CTX, and AK. Metabolome sequencing revealed nine differentially regulated metabolites. Our findings are an early warning for a wide assessment of the roles of sub-MIC levels of antibiotics in the spread of antibiotic resistance.
Aspartate α-decarboxylase a new therapeutic target in the fight against Helicobacter pylori infection
Authors: Ibrahim Kareem A. , Kashef Mona T. , Elkhamissy Tharwat R. , Ramadan Mohammed A. , Helmy Omneya M.
Published: November 2022

Effective eradication therapy for Helicobacter pylori is a worldwide demand. Aspartate α-decarboxylase (ADC) was reported as a drug target in H. pylori, in an in silico study, with malonic acid (MA) as its inhibitor. We evaluated eradicating H. pylori infection through ADC inhibition and the possibility of resistance development. MA binding to ADC was modeled via molecular docking. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of MA were determined against H. pylori ATCC 43504, and a clinical H. pylori isolate. To confirm selective ADC inhibition, we redetermined the MIC in the presence of products of the inhibited enzymatic pathway: β-alanine and pantothenate. HPLC was used to assay the enzymatic activity of H. pylori 6x-his tagged ADC in the presence of different MA concentrations. H. pylori strains were serially exposed to MA for 14 passages, and the MICs were determined. Cytotoxicity in different cell lines was tested. The efficiency of ADC inhibition in treating H. pylori infections was evaluated using a Sprague–Dawley (SD) rat infection model. MA spectrum of activity was determined in different pathogens. MA binds to H. pylori ADC active site with a good docking score. The MIC of MA against H. pylori ranged from 0.5 to 0.75 mg/mL with MBC of 1.5 mg/mL. Increasing β-alanine and pantothenate concentrations proportionally increased MA MIC. The 6x-his tagged ADC activity decreased by increasing MA concentration. No resistance to ADC inhibition was recorded after 14 passages; MA lacked cytotoxicity in all tested cell lines. ADC inhibition effectively eradicated H. pylori infection in SD rats. MA had MIC between 0.625 to 1.25 mg/mL against the tested bacterial pathogens. In conclusion, ADC is a promising target for effectively eradicating H. pylori infection that is not affected by resistance development, besides being of broad-spectrum presence in different pathogens. MA provides a lead molecule for the development of an anti-helicobacter ADC inhibitor. This provides hope for saving the lives of those at high risk of infection with the carcinogenic H. pylori.
Apple Endophytic fungi and their antagonism against apple scab disease
Authors: Ebrahimi Leila , Hatami Rad Sepideh , Etebarian Hassan Reza
Published: November 2022

Endophytic fungi are microorganisms with the ability to colonize plants for the entire or at least a significant part of their life cycle asymptomatically, establishing a plant-fungus association. They play an important role in balancing ecosystems, as well as benefiting host through increasing plant growth, and protecting the host plants from abiotic and biotic stresses using various strategies. In the present study, endophytic fungi were isolated from wild and endemic apple cultivars, followed by characterizing their antifungal effect against Venturia inaequalis. To characterize the endophytic fungi, 417 fungal strains were separated from 210 healthy fruit, leaf, and branch samples collected from the north of Iran. Among the purified fungal isolates, 33 fungal genera were identified based on the morphological characteristics, of which 38 species were detected according to the morphological features and molecular data of ITS, tef-1α, and gapdh genomic regions (related to the genus). The results represented that most of the endophytic fungi belonged to Ascomycota (67.8%), 31.4% of isolates were mycelia sterilia, while the others were Basidiomycota (0.48%) and Mucoromycota (0.24%). Additionally, Alternaria, Cladosporium, and Nigrospora were determined as the dominant genera. The antifungal properties of the identified isolates were evaluated against V. inaequalis in vitro to determine the release of media-permeable metabolites, Volatile Organic Compounds (VOCs), chitinase, and cellulase as antifungal mechanisms, as well as producing phosphate solubilisation as growth-promoting effect. Based on the results of metabolite and VOC tests, the six isolates of Acremonium sclerotigenum GO13S1, Coniochaeta endophytica 55S2, Fusarium lateritium 61S2, Aureobasidium microstictum 7F2, Chaetomium globosum 2S1 and Ch. globosum 3 L2 were selected for greenhouse tests. Further, Co. endophytica 55S2 and F. lateritium 61S2 could solubilize inorganic phosphate. All isolates except Ch. globosum 3 L2 exhibited cellulase activity, while chitinase activity was observed in Ch. globosum 2S1, Ch. globosum 3 L2, and F. lateritium 61S2. Finally, Co. endophytica 55S2 and Ch. globosum 2S1 completely controlled the disease on the apple seedling leaves under greenhouse conditions.
Comparative genomics study of Staphylococcus aureus isolated from cattle and humans reveals virulence patterns exclusively associated with bovine clinical mastitis strains
Authors: Rodrigues Romário Alves , Pizauro Lucas José Luduverio , Varani Alessandro de Mello , de Almeida Camila Chioda , Silva Saura Rodrigues , Cardozo Marita Vedovelli , MacInnes Janet I. , Kropinski Andrew M. , Melo Poliana de Castro , Ávila Fernando Antonio
Published: November 2022

Staphylococcus aureus causes nosocomial and intramammary infections in humans and cattle, respectively. A large number of virulence factors are thought to play important roles in the pathogenesis of this bacterium. Currently, genome-wide and data-analysis studies are being used to better understand its epidemiology. In this study, we conducted a genome wide comparison and phylogenomic analyses of S. aureus to find specific virulence patterns associated with clinical and subclinical mastitis strains in cattle and compare them with those of human origin. The presence/absence of key virulence factors such as adhesin, biofilm, antimicrobial resistance, and toxin genes, as well as the phylogeny and sequence type of the isolates were evaluated. A total of 248 genomes (27 clinical mastitis, 43 subclinical mastitis, 21 milk, 53 skin-related abscesses, 49 skin infections, and 55 pus from cellulitis) isolated from 32 countries were evaluated. We found that the cflA, fnbA, ebpS, spa, sdrC, coa, emp, vWF, atl, sasH, sasA, and sasF adhesion genes, as well as the aur, hglA, hglB, and hglC toxin genes were highly associated in clinical mastitis strains. The strains had diverse genetic origins (72 protein A and 48 sequence types with ST97, ST8 and ST152 being frequent in isolates from clinical mastitis, abscess, and skin infection, respectively). Further, our phylogenomic analyses suggested that zoonotic and/or zooanthroponotic transmission may have occurred. These findings contribute to a better understanding of S. aureus epidemiology and the relationships between adhesion mechanisms, biofilm formation, antimicrobial resistance, and toxins and could aid in the development of improved vaccines and strain genotyping methods.
Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella
Authors: Zhou Yanhong , Yong Yan , Zhu Chunyang , Yang Heng , Fang Binghu
Published: November 2022

The metabolic microenvironment of bacteria impacts drug efficacy. However, the metabolic mechanisms of drug-resistant Salmonella spp. remain largely unknown. This study characterized the metabolic mechanism of gentamicin-resistant Salmonella Choleraesuis and found that D-ribose increased the gentamicin-mediated killing of this bacteria. Non-targeted metabolomics of homologous gentamicin-susceptible Salmonella Choleraesuis (SCH-S) and gentamicin-resistant S. Choleraesuis (SCH-R) was performed using UHPLC-Q-TOF MS. The metabolic signature of SCH-R included disrupted central carbon metabolism and energy metabolism, along with dysregulated amino acid and nucleotide metabolism, vitamin and cofactor metabolism, and fatty acid synthesis. D-ribose, the most suppressed metabolite in SCH-R, was shown to strengthen gentamicin efficacy against SCH-R and a clinically isolated multidrug-resistant strain. This metabolite had a similar impact on Salmonella. Derby and Salmonella. Typhimurium. D-ribose activates central carbon metabolism including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA cycle), increases the abundance of NADH, polarizes the electron transport chain (ETC), and elevates the proton motive force (PMF) of cells, and induces drug uptake and cell death. These findings suggest that central carbon metabolism plays a critical role in the acquisition of gentamicin resistance by Salmonella, and that D-ribose may serve as an antibiotic adjuvant for gentamicin treatment of resistant bacterial infections.
A comprehensive survey on computational learning methods for analysis of gene expression data
Authors: Bhandari Nikita , Walambe Rahee , Kotecha Ketan , Khare Satyajeet P.
Published: November 2022

Computational analysis methods including machine learning have a significant impact in the fields of genomics and medicine. High-throughput gene expression analysis methods such as microarray technology and RNA sequencing produce enormous amounts of data. Traditionally, statistical methods are used for comparative analysis of gene expression data. However, more complex analysis for classification of sample observations, or discovery of feature genes requires sophisticated computational approaches. In this review, we compile various statistical and computational tools used in analysis of expression microarray data. Even though the methods are discussed in the context of expression microarrays, they can also be applied for the analysis of RNA sequencing and quantitative proteomics datasets. We discuss the types of missing values, and the methods and approaches usually employed in their imputation. We also discuss methods of data normalization, feature selection, and feature extraction. Lastly, methods of classification and class discovery along with their evaluation parameters are described in detail. We believe that this detailed review will help the users to select appropriate methods for preprocessing and analysis of their data based on the expected outcome.
WDR43 is a potential diagnostic biomarker and therapeutic target for osteoarthritis complicated with Parkinson’s disease
Authors: Heng Hongquan , Liu Jie , Hu Mingwei , Li Dazhuang , Su Wenxing , Li Jian
Published: November 2022

Osteoarthritis (OA) and Parkinson’s disease (PD) are on the rise and greatly impact the quality of individuals’ lives. Although accumulating evidence indicates a relationship between OA and PD, the particular interactions connecting the two diseases have not been thoroughly examined. Therefore, this study explored the association through genetic characterization and functional enrichment. Four datasets (GSE55235, GSE12021, GSE7621, and GSE42966) were chosen for assessment and validation from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was implemented to determine the most relevant genes for clinical features. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to explore the biological processes of common genes, and to display the interrelationships between common genes, the STRING database and the application Molecular Complex Detection Algorithm (MCODE) of Cytoscape software were leveraged to get hub genes. By intersecting the common genes with the differentially expressed genes (DEGs) acquired from GSE12021 and GSE42966, the hub genes were identified. Finally, we validated the diagnostic efficacy of hub genes and explored their correlation with 22 immune infiltrating cells. As a consequence, we discovered 71 common genes, most of which were functionally enriched in antigen processing and presentation, mitochondrial translation, the mRNA surveillance pathway, and nucleocytoplasmic transport. Furthermore, WDR43 was found by intersecting eight hub genes with 28 DEGs from the two validation datasets. Receiver Operating Characteristic (ROC) implied the diagnostic role of WDR43 in OA and PD. Immune infiltration research revealed that T-cell regulatory (Tregs), monocytes, and mast cells resting were associated with the pathogenesis of OA and PD. WDR43 may provide key insights into the relationship between OA and PD.
Diffusion kurtosis imaging in patients with tissue-negative transient ischemic attack
Authors: Zhou Jia , He Rui , Xu Xiaoyu , Wei Xiaoer , Li Minghua , Wang Feng , Li Yuehua
Published: November 2022

Approximately 50–60% of patients with a clinical transient ischemic attack (TIA) do not have diffusion-weighted imaging (DWI) evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of diffusion kurtosis imaging (DKI) in the evaluation of patients with TIA who have normal DWI findings. From September 2014 to May 2017, a total of 179 consecutive patients with suspected TIA were eligible for enrollment in our study. The inclusion criteria were a confirmed diagnosis of TIA confirmed by a stroke neurologist, MRI (including DWI and DKI) within 24 h after symptom onset, no stroke history, and no DWI lesion. A follow-up DWI was performed to establish stroke recurrence within a period of 90 days. A total of 98 patients who had no lesions on the baseline DWI were included for data analysis. Of these 98 patients, 31 (31.6%) had positive findings on the initial DKI. In 29 of the 31 (93.5%) patients, the location of the abnormality observed on DKI was consistent with the clinical symptoms. During the 90-day follow-up period, 14 (14.3%) patients developed recurrent stroke. The prevalence of recurrent stroke was higher in the DKI-positive group than in the DKI-negative group (29.0% vs. 7.5%, p = 0.01). A comparison between the patients with and without recurrent stroke showed that an abnormality on the baseline DKI was associated with stroke recurrence. Furthermore, 8 of the 9 stroke patients in the DKI-positive group developed a new ischemic lesion in the artery territory corresponding to the initial DKI abnormality. The new findings suggest the predictive value of DKI on the recurrence of stroke in the patients with TIA who have negative findings on conventional DWI.
Relationship between shift work, night work, and subsequent dementia: A systematic evaluation and meta-analysis
Authors: Wang Zhen-Zhi , Sun Zhen , Zhang Mei-Ling , Xiong Kang , Zhou Feng
Published: November 2022

Background

The association between shift work, night work, and the risk of dementia are conflicting in the literature.

Objectives

This study was performed to obtain evidence on the potential relationship between shift work, night work, and dementia.

Methods

To investigate the link between shift work, night work, and dementia, we systematically searched PubMed, Embase, and Web of Science from inception to January 1, 2022. The eligibility of the retrieved records and extracted data were independently reviewed by two researchers. The Preferred Reporting Items for Systematic Evaluations and Meta-Analyses (PRISMA) statement was followed. STATA 16.0 was used to conduct the meta-analysis.

Results

A total of four studies involving 103,104 participants were included in this meta-analysis. Pooled results indicated that night shift workers had a 12% increased risk of dementia compared to subjects without night work (HR = 1.12, 95% CI 1.03–1.23, P = 0.094). Shift work was not significantly associated with dementia risk (HR: 1.09, 95% CI: 0.83–1.43, P = 0.546), but the effect of shift work on dementia risk appeared to increase with age, with a correlation observed among workers older than 50 years (HR = 1.31; 95% CI: 1.03–1.68, P = 0.030).

Conclusion

The data presented in our study suggest that night work may be a risk factor for dementia. More prospective studies with objective exposure measurements are required to further confirm this result.

Systematic review registration

https://doi.org/10.37766/inplasy2022.6.0079, identifier: INPLASY202260079.
Neural responses to naturalistic audiovisual speech are related to listening demand in cochlear implant users
Authors: Xiu Bowen , Paul Brandon T. , Chen Joseph M. , Le Trung N. , Lin Vincent Y. , Dimitrijevic Andrew
Published: November 2022

There is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and “real-world” listening environments and stimuli. Speech in the real world is often accompanied by visual cues, background environmental noise, and is generally in a conversational context, all factors that could affect listening demand. Thus, our objectives were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high-density electroencephalogram (EEG) while CI users listened/watched a naturalistic stimulus (i.e., the television show, “The Office”). We used continuous EEG to quantify “speech neural tracking” (i.e., TRFs, temporal response functions) to the show’s soundtrack and 8–12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show, mimicking a natural noisy environment. The task also included an audio-only (no video) condition. After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they understood. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). Increasing background noise affected speech neural tracking at a group level, in addition to eliciting strong individual differences. Mixed effect modeling showed that listening demand and conversation understanding were correlated to early cortical speech tracking, such that high demand and low conversation understanding occurred with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power, where higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between clinical speech perception and quality-of-life in CI users. However, physiological responses to complex natural speech may provide an objective measure of aspects of quality-of-life measures like self-perceived listening demand.
Case report: A patient with mitochondrial neurogastrointestinal encephalomyopathy and chronic intestinal failure
Authors: Barisic Ana , Ljubas Kelecic Dina , Vranesic Bender Darija , Karas Irena , Brinar Marko , Miletic Vladimir , Krznaric Zeljko
Published: November 2022

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disorder commonly diagnosed in later disease stages when it prominently manifests as malnutrition. We report on a female patient diagnosed with MNGIE at the age of 36. She was severely malnourished due to loss of resorptive surface after several surgical procedures, gastrointestinal dysmotility, and small intestinal bacterial overgrowth. Therefore, early and aggressive total parenteral nutrition was introduced. Although no reports have shown that nutritional support can modify the clinical outcome, this case suggests that adequate nutritional support, particularly parenteral nutrition, supervised by an experienced nutritional team, may prolong the lifespan of patients with MNGIE.
Lactoferrin for COVID-19 prevention, treatment, and recovery
Authors: Bolat Ecem , Eker Furkan , Kaplan Merve , Duman Hatice , Arslan Ayşenur , Saritaş Sümeyye , Şahutoğlu Arif Sercan , Karav Sercan
Published: November 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a unique beta-coronavirus, has caused the most serious outbreak of the last century at the global level. SARS-CoV-2 infections were firstly reported in the city of Wuhan in China in 2019 and this new disease was named COVID-19 by World Health Organization (WHO). As this novel disease can easily be transmitted from one individual to another via respiratory droplets, many nations around the world have taken several precautions regarding the reduction in social activities and quarantine for the limitation of the COVID-19 transmission. SARS-CoV-2 is known to cause complications that may include pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, septic shock, and death. To prevent and treat COVID-19, some significant studies have been conducted since the outbreak. One of the most noticeable therapeutic approaches is related to a multifunctional protein, lactoferrin. Lactoferrin (Lf) is an 80 kDa cationic glycoprotein that has a great range of benefits from improving the immunity to antiviral effects due to its unique characteristics such as the iron-binding ability. This review summarizes the characteristics of SARS-CoV-2 and the potential applications of Lf for the prevention, treatment, and recovery of COVID-19.
Hydrophobicity identifies false positives and false negatives in peptide-MHC binding
Authors: Solanki Arnav , Riedel Marc , Cornette James , Udell Julia , Vasmatzis George
Published: November 2022

Major Histocompability Complex (MHC) Class I molecules allow cells to present foreign and endogenous peptides to T-Cells so that cells infected by pathogens can be identified and killed. Neural networks tools such as NetMHC-4.0 and NetMHCpan-4.1 are used to predict whether peptides will bind to variants of MHC molecules. These tools are trained on data gathered from binding affinity and eluted ligand experiments. However, these tools do not track hydrophobicity, a significant biochemical factor relevant to peptide binding, in their predictions. A previous study had concluded that the peptides predicted to bind to HLA-A*0201 by NetMHC-4.0 were much more hydrophobic than expected. This paper expands that study by also focusing on HLA-B*2705 and HLA-B*0801, which prefer binding hydrophilic and balanced peptides respectively. The correlation of hydrophobicity of 9-mer peptides with their predicted binding strengths to these various HLAs was investigated. Two studies were performed, one using the data that the two neural networks were trained on, and the other using a sample of the human proteome. NetMHC-4.0 was found to have a statistically significant bias towards predicting highly hydrophobic peptides as strong binders to HLA-A*0201 and HLA-B*2705 in both studies. Machine Learning metrics were used to identify the causes for this bias: hydrophobic false positives and hydrophilic false negatives. These results suggest that the retraining the neural networks with biochemical attributes such as hydrophobicity and better training data could increase the accuracy of their predictions. This would increase their impact in applications such as vaccine design and neoantigen identification.
Case report: EML4::NTRK3 gene fusion in a patient with metastatic lung adenocarcinoma successfully treated with entrectinib
Authors: Lazzari Chiara , Pecciarini Lorenza , Doglioni Claudio , Pedica Federica , Gajate Ana Maria Samanes , Bulotta Alessandra , Gregorc Vanesa , Cangi Maria Giulia
Published: November 2022

Rearrangements involving the neurotrophin kinase (NTRK) genes NTRK1, NTRK2 and NTRK3 with different fusion partners have been observed in both adult and pediatric solid tumors. Larotrectinib and entrectinib have been the first tumor-agnostic compounds approved for the treatment of NTRK fusion-positive tumors. Here, we report the first case of a female patient with a diagnosis of stage IV lung adenocarcinoma harboring the EML4::NTRK3 gene fusion, and successfully treated with entrectinib.
Therapeutic efficacy of 166Holmium siloxane in microbrachytherapy of induced glioblastoma in minipig tumor model
Authors: Khoshnevis Mehrdad , Brown Richard , Belluco Sara , Zahi Ilyes , Maciocco Luca , Bonnefont-Rebeix Catherine , Pillet-Michelland Elodie , Tranel Jonathan , Roger Thierry , Nennig Christophe , Oudoire Patrick , Marcon Lionel , Tillement Olivier , Louis Cédric , Gehan Hélène , Bardiès Manuel , Mariani Maurizio , Muzio Valeria , Meunier Jean-Philippe , Duchemin Charlotte , Michel Nathalie , N’Tsiba Estelle , Haddad Ferid , Buronfosse Thierry , Carozzo Claude , Ponce Frédérique
Published: November 2022

Glioblastoma is considered the most common malignant primary tumor of central nervous system. In spite of the current standard and multimodal treatment, the prognosis of glioblastoma is poor. For this reason, new therapeutic approaches need to be developed to improve the survival time of the glioblastoma patient. In this study, we performed a preclinical experiment to evaluate therapeutic efficacy of 166Ho microparticle suspension administered by microbrachytherapy on a minipig glioblastoma model. Twelve minipigs were divided in 3 groups. Minipigs had injections into the tumor, containing microparticle suspensions of either 166Ho (group 1; n = 6) or 165Ho (group 2; n = 3) and control group (group 3; n = 3). The survival time from treatment to euthanasia was 66 days with a good state of health of all minipigs in group 1. The median survival time from treatment to tumor related death were 8.6 and 7.3 days in groups 2 and control, respectively. Statistically, the prolonged life of group 1 was significantly different from the two other groups (p < 0.01), and no significant difference was observed between group 2 and control (p=0.09). Our trial on the therapeutic effect of the 166Ho microparticle demonstrated an excellent efficacy in tumor control. The histological and immunohistochemical analysis showed that the efficacy was related to a severe 166Ho induced necrosis combined with an immune response due to the presence of the radioactive microparticles inside the tumors. The absence of reflux following the injections confirms the safety of the injection device.
Initial clinical applications treating pediatric and adolescent patients using MR-guided radiotherapy
Authors: Kozak Margaret M. , Crompton David , Gross Brandie A. , Harshman Lyndsay , Dickens David , Snyder Jeffrey , Shepard Andrew , St-Aubin Joël , Dunkerley David , Hyer Daniel , Buatti John M.
Published: November 2022

Purpose

To demonstrate the clinical applications and feasibility of online adaptive magnetic resonance image guided radiotherapy (MRgRT) in the pediatric, adolescent and young adult (AYA) population.

Methods

This is a retrospective case series of patients enrolled onto a prospective study. All pediatric (age < 18) and AYA patients (age< 30), treated on the Elekta Unity MR linear accelerator (MRL) from 2019 to 2021 were enrolled onto a prospective registry. Rationale for MRgRT included improved visualization of and alignment to the primary tumor, re-irradiation in a critical area, ability to use smaller margins, and need for daily adaptive replanning to minimize dose to adjacent critical structures. Step-and-shoot intensity-modulated radiation treatment (IMRT) plans were generated for all Unity patients with a dose grid of 3 mm and a statistical uncertainty of < 1% per plan.

Results

A total of 15 pediatric and AYA patients have been treated with median age of 13 years (range: 6 mos - 27 yrs). Seven patients were <10 yo. The clinical applications of MRgRT included Wilms tumor with unresectable IVC thrombus (n=1), Ewing sarcoma (primary and metastatic, n=3), recurrent diffuse intrinsic pontine glioma (DIPG, n=2), nasopharyngeal carcinoma (n=1), clival chordoma (n=1), primitive neuroectodermal tumor of the pancreas (n=1), recurrent gluteo-sacral germ cell tumor (n=1), C-spine ependymoma (n=1), and posterior fossa ependymoma (n=1). Two children required general anesthesia. One AYA patient could not complete the MRgRT course due to tumor-related pain exacerbated by longer treatment times. Two AYA patients experienced anxiety related to treatment on the MRL, one of which required daily Ativan. No patient experienced treatment interruptions or unexpected toxicity.

Conclusion

MRgRT was well-tolerated by pediatric and AYA patients. There was no increased use of anesthesia outside of our usual practice. Dosimetric advantages were seen for patients with tumors in critical locations such as adjacent to or involving optic structures, stomach, kidney, bowel, and heart.
One potential hotspot SLC25A20 gene variants in Chinese patients with carnitine-acylcarnitine translocase deficiency
Authors: Li Xiaoli , Shen Jian
Published: November 2022

Background

Carnitine-acylcarnitine translocase deficiency (CACT deficiency) is a rare and life-threatening autosomal recessive disorder of mitochondrial fatty acid oxidation caused by variant of SLC25A20 gene. The most prevalent missense variant in the SLC25A20 gene in Asia was c.199–10T > G. Due to the c.199–10T > G variant, CACT deficiency is a severe phenotype.

Materials and Methods

Herein, we present a neonatal case with c.199–10T > G variant in China and analyze the clinical, biochemical, and genetic aspects of 78 patients previously identified with CACT deficiency.

Results

The patient presented with a series of severe metabolic crises that rapidly deteriorated and eventually died 3 days after delivery. The sequencing of the patient's genome indicated that he was homozygous for the c.199–10T > G variant. 30 patients were found to have the c.199–10T > G mutation, of which 23 were Chinese and 22 were afflicted by the c.199–10T > G splicing variation. In China, c.199–10T > G allele frequency was 82.6%.

Conclusion

In CACT deficiency, prompt recognition and treatment are critical. Our data suggested that c.199–10T > G may be a potential hotspot SLC25A20 gene mutation in the Chinese population. Detection of single nucleotide polymorphism is possible for high-risk patients and parents in China.
4D-tracking in the 10-ps range: A technological perspective
Authors: Lai Adriano
Published: November 2022

The present paper focuses on recent and ready-to-come advancements concerning high-resolution 4D-tracking with a perspective approach. Four-dimensional-tracking techniques (particle tracking with timing information for each detection point) have revealed a necessity for the next and next-to-next generations of high-energy physics experiments to cope with the increasing luminosity and consequent event pile-up in the beam collision region. Such a decisive challenge concerns both detection and processing technologies at an unprecedented level of difficulty. In addition to the high performance required in space–time measurement precision (some tens of picoseconds resolution in timing and about 10 µm resolution in space), an extremely high radiation hardness is demanded for such technologies together with an extremely high read-out and processing capability. Emerging experimental solutions for sensors and electronics against such challenges are presented here.
Trust in things: A review of social science perspectives on autonomous human-machine-team systems and systemic interdependence
Authors: Akiyoshi Mito
Published: November 2022

For Autonomous Human Machine Teams and Systems (A-HMT-S) to function in a real-world setting, trust has to be established and verified in both human and non-human actors. But the nature of “trust” itself, as established by long-evolving social interaction among humans and as encoded by humans in the emergent behavior of machines, is not self-evident and should not be assumeda priori. The social sciences, broadly defined, can provide guidance in this regard, pointing to the situational, context-driven, and sometimes other-than-rational grounds that give rise to trustability, trustworthiness, and trust. This paper introduces social scientific perspectives that illuminate the nature of trust that A-HMT-S must produce as they take root in society. It does so by integrating key theoretical perspectives: the ecological theory of actors and their tasks, theory on the introduction of social problems into the civic sphere, and the material political economy framework developed in the sociological study of markets.
Screening and characterization estrogen receptor ligands from Arnebia euchroma (Royle) Johnst. via affinity ultrafiltration LC-MS and molecular docking
Authors: Zhu Lian , Ma Sheng-jun , Liu Ming-juan , Li Kai-lin , E Shuai , Wang Zi-ming , Li Sha-ni , Zhang Sheng-lan , Cai Wei
Published: November 2022

Arnebiae Radix (dried root of Arnebia euchroma (Royle) Johnst.) is a traditional Chinese medicine (TCM) used to treat macular eruptions, measles, sore throat, carbuncles, burns, skin ulcers, and inflammations. The Arnebiae Radix extract can exert anti-breast cancer effects through various mechanisms of action. This study aimed to rapidly screen potential estrogen receptor (estrogen receptor α and estrogen receptor β) ligands from the Arnebiae Radix extract. In this study, an analytical method based on affinity ultrafiltration coupled with UHPLC-Q-Exactive Orbitrap mass spectrometry was established for rapidly screening and identifying estrogen receptor ligands. Then, bindings of the components to the active site of estrogen receptor (estrogen receptor α and estrogen receptor β) were investigated via molecular docking. Moreover, surface plasmon resonance (SPR) experiments with six compounds were performed to verify the affinity. As a result, a total of 21 ligands were screened from Arnebiae Radix using affinity ultrafiltration. Among them, 14 and 10 compounds from Arnebiae Radix showed affinity with estrogen receptor α and estrogen receptor β, respectively. All of those ligands could have a good affinity for the multiple amino acid residues of the estrogen receptor based on molecular docking. In addition, six compounds display the great affinity by SPR. The method established in the study could be used to rapidly screen estrogen receptor ligands in Traditional Chinese medicine. The results demonstrated that the affinity ultrafiltration–UHPLC-Q-Exactive Orbitrap mass spectrometry method not only aids in the interpretation of the potential bioactive components and possible mechanisms of action of Arnebiae Radix but also provides a further effective basis for the quality control of this valuable herb medicine.