bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe Acute Respiratory Syndrome Coronavirus 2 Diagnostic Tests for Border Screening During the Very Early Phase of Coronavirus Disease 2019 Pandemic: A Systematic Review and Meta-Analysis
Authors: Chua Pearleen Ee Yong , Gwee Sylvia Xiao Wei , Wang Min Xian , Gui Hao , Pang Junxiong
Published: February 2022

Diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during border screening among returning residents and prioritized travelers during the early phase of a pandemic can reduce the risk of importation and transmission in the community. This study aimed to compare the accuracy of various SARS-CoV-2 diagnostics and assess their potential utility as border screening for infection and immunity. Systematic literature searches were conducted in six electronic databases for studies reporting SARS-CoV-2 diagnostics (up to April 30, 2020). Meta-analysis and methodological assessment were conducted for all included studies. The performance of the diagnostic tests was evaluated with pooled sensitivity, specificity, and their respective 95% confidence intervals. A total of 5,416 unique studies were identified and 95 studies (at least 29,785 patients/samples) were included. Nucleic acid amplification tests (NAAT) consistently outperformed all other diagnostic methods regardless of the selected viral genes with a pooled sensitivity of 98% and a pooled specificity of 99%. Point-of-care (POC) serology tests had moderately high pooled sensitivity (69%), albeit lower than laboratory-based serology tests (89%), but both had high pooled specificity (96–98%). Serology tests were more sensitive for sampling collected at ≥ 7 days than ≤ 7 days from the disease symptoms onset. POC NAAT and POC serology tests are suitable for detecting infection and immunity against the virus, respectively as border screening. Independent validation in each country is highly encouraged with the preferred choice of diagnostic tool/s.
One-year Observation of Safety of Implantable Collamer Lens V4c Implantation Without Using an Ophthalmic Viscosurgical Device
Authors: Chen Zhuoyi , Niu Lingling , Zhao Jing , Yao Peijun , Wang Xiaoying , Zhou Xingtao
Published: February 2022

Purpose

To investigate the feasibility and safety of the implantable collamer lens V4c (ICL V4c) implantation without using an ophthalmic viscosurgical device (OVD-free technique).

Methods

This prospective consecutive case study enrolled 118 eyes of 60 patients (15 eyes were of male patients, 103 eyes were of female patients, age 26.19 ± 5.03 years, spherical equivalent −10.05 ± 2.73 D). Eyes were considered for OVD-free or OVD-using ICL V4c implantation based on the maintenance of the anterior segment during the surgery. The follow-up lasted for 12 months. The main measurements were visual acuity and changes in endothelial cell density (ECD) at 12 months.

Results

A total of 75 eyes were included in the OVD-free group and 43 in the OVD group. No infection or other complications were observed in any eye. In the OVD-free group, the safety and efficacy indices were 1.19 ± 0.15 and 1.05 ± 0.20, respectively. 74.5% of the eyes gained one or two lines of corrected distance visual acuity (CDVA), and 25.5% were stable. In the OVD group, the safety and efficacy indices were 1.17 ± 0.17 and 1.03 ± 0.15, respectively; 65.7% of the eyes gained one or two lines of CDVA, and 34.3% were stable. The mean change of ECD was 65.34 cell/ mm2 compared to the baseline in the OVD-free group and 25.94 cell/ mm2 compared to baseline in the OVD group (P = 0.038).

Conclusions

The ICL V4c implantation with an OVD-free technique is a safe and feasible method in eyes with good maintenance of the anterior segment.
A Cell-Based Screen Identifies HDAC Inhibitors as Activators of RIG-I Signaling
Authors: Fraile-Bethencourt Eugenia , Foss Marie H. , Nelson Dylan , Malhotra Sanjay V. , Anand Sudarshan
Published: February 2022

Enhancing the immune microenvironment in cancer by targeting the nucleic acid sensors is becoming a potent therapeutic strategy. Among the nucleic acid sensors, activation of the RNA sensor Retinoic Acid-inducible Gene (RIG-I) using small hairpin RNAs has been shown to elicit powerful innate and adaptive immune responses. Given the challenges inherent in pharmacokinetics and delivery of RNA based agonists, we set out to discover small molecule agonists of RIG-I using a cell-based assay. To this end, we established and validated a robust high throughput screening assay based on a commercially available HEK293 reporter cell line with a luciferase reporter downstream of tandem interferon stimulated gene 54 (ISG54) promoter elements. We first confirmed that the luminescence in this cell line is dependent on RIG-I and the interferon receptor using a hairpin RNA RIG-I agonist. We established a 96-well and a 384-well format HTS based on this cell line and performed a proof-of-concept screen using an FDA approved drug library of 1,200 compounds. Surprisingly, we found two HDAC inhibitors Entinostat, Mocetinostat and the PLK1 inhibitor Volasertib significantly enhanced ISG-luciferase activity. This luminescence was substantially diminished in the null reporter cell line indicating the increase in signaling was dependent on RIG-I expression. Combination treatment of tumor cell lines with Entinostat increased RIG-I induced cell death in a mammary carcinoma cell line that is resistant to either Entinostat or RIG-I agonist alone. Taken together, our data indicates an unexpected role for HDAC1,-3 inhibitors in enhancing RIG-I signaling and highlight potential opportunities for therapeutic combinations.
Keeping Track of the Genealogy of Heterozygotes Using Epigenetic Reference Codes and Breeding Tables
Authors: Liberati Anna Sara , Calcaprina Barbara , Adriani Walter
Published: February 2022

Studying neurobehavioral consequences of the hypofunctional dopamine transporter (DAT) across several generations entails the need to monitor allelic transmission to offspring, taking into account both maternal and paternal inheritance. Since each type of heterozygote expresses differential phenotypes, based on lineage of inheritance for wild and mutated alleles (from male or female ancestors), it is important to track transgenerational epigenetic effects. We deemed it essential to assign specific abbreviations identifying their characteristics. Therefore, we devised a Mendelian-inspired table to keep track of these. Starting from two progenitors (WT and KO) we named resulting heterozygous progenies MAT and PAT to differentiate them based on inheritance of the wild allele (from the mother or father). Tracing subsequent generations, similar logic has been followed: if coupling HET dams with KO males, initials “M” [(grand)maternal] and “P” [(grand)paternal] are kept, but “AT” is turned into “IX” (MIX and PIX), while if breeding HETs with WTs, “M” is changed to “W” resembling an upside down “M” and “P” to “S” for “sperm” (WAT and SOT). To underline the development within “hyperdopaminergic-uterus” a central letter “U” is added (MUX, PUX, and QULL), while a Greek initial (μAT, μIX, and νIX) underlines the uterine-worsened origin of the allele. In HET × HET breeding (GIX and DIX), the mutated allele can be inherited from both sides of the genealogical line. However, when the mother is MAT, wild and mutated alleles encounter for the first time, causing putative anomalies in the progeny. Replacing dam with a second-generation female (MIX and MUX) may mitigate epigenetic effects on third-generation offspring; therefore suffixes (“-f,” “-fu,” “-ϕ,” and “-ϕu”) emphasize that subsequent-generation dams imply that the alleles already encountered in HET (rather than WT) grand-dams.
Effect of Flaxseed Supplementation in Diet of Dairy Cow on the Volatile Organic Compounds of Raw Milk by HS-GC–IMS
Authors: Huang Guoxin , Li Ning , Liu Kaizhen , Yang Jiyong , Zhao Shengguo , Zheng Nan , Zhou Jinhui , Zhang Yangdong , Wang Jiaqi
Published: February 2022

Flaxseed supplementation in diet of dairy cow can effectively enhance the production of ω-3 polyunsaturated fatty acids (n-3 PUFA) in raw milk, which further give rise to the changes of volatile organic compounds (VOCs). In this study, we used headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) to investigate the VOCs in milk from cows fed three different diets (CK: supplemented with 0 g/d flaxseed; WF: 1,500 g/d whole flaxseed and GF: 1,500 g/d ground flaxseed). A total of 40 VOCs including three acids, six esters, 11 aldehydes, seven alcohols, 13 ketones were identified in all the raw milk samples. Compared with GF supplementation, suppling with WF could influence more compounds in raw milk (GF: five compounds; WF: 22 compounds). Supplementation with WF could increase the concentration of nonanal, heptanal, hexanal, which could cause the occurrence of off-flavors, and reduce the concentration of hexanoic acid (monomer; M), 2-hexanol, ethanol (M), 2-heptanone (dimer; D), 2-pentanone (M), 2-pentanone (D), acetoin (M) in raw milk. GF supplementation in diet could reduce the 2-pentanone (M), 2-pentanone (D). In addition, principal component analysis (PCA) based on the signal intensity of identified VOCs indicated that it is possible to distinguish between the CK and WF milk. However, GF milk could not be distinguished from CK milk. The results demonstrate that compared with GF milk, WF supplementation in diet of dairy cows could increase fishy (heptanal) cardboard-like (pentanal) flavor in milk and decrease sweet (hexanoic acid, 2-heptanone), fruity (ethyl butanoate, ethyl hexanoate, 2-heptanone) flavor which may lead the milk less acceptable. In conclusion, compared with WF, GF supplementation in diet of dairy cow showed higher increase in n-3 PUFA in raw milk, and less influence in VOCs of raw milk and this study might provide theoretical supports for the production of milk rich in n-3 PUFA.
The Risk of Hippocampal Metastasis and the Associated High-Risk Factors in 411 Patients With Brain Metastases
Authors: Xie Peng , Qiao Hui , Hu Huiling , Xin Wenlong , Zhang Huanyu , Lan Ning , Chen Xiaohua , Ma Yan
Published: February 2022

Background and Aims

To retrospectively analyze the incidence of hippocampal metastasis and the associated high-risk factors in patients with brain metastases and evaluate the safety of hippocampal avoidance whole-brain radiation therapy (HA-WBRT).

Methods

We retrospectively analyzed the data of patients with brain metastases diagnosed by contrast-enhanced cranial Magnetic resonance imaging (MRI) at the First Hospital of Lanzhou University from 2017 to 2020. The boundaries of the hippocampus, hippocampus + 5 mm area, hippocampus + 10 mm area, and hippocampus + 20 mm area were delineated, and the distances from the brain metastases to the hippocampus were measured. Univariate and multivariate logistic regressions were adopted to analyze the high-risk factors of hippocampal metastasis.

Results

A total of 3,375 brain metastases in 411 patients were included in the analysis. The metastasis rates in the hippocampus and surrounding areas of the entire group were as follows: 7.3% (30/411) in the hippocampus, 16.5% (68/411) in the hippocampus + 5 mm area, 23.8% (98/411) in the hippocampus + 10 mm area, and 36.5% (150/411) in the hippocampus + 20 mm area. Univariate logistic regression showed that the pathological type, the number of metastases, the maximum diameter of metastases, and the volume of brain metastases were all correlated with hippocampal metastasis. Multivariate logistic regression showed that the pathological type, the number of metastases, and the total volume of metastases were correlated with hippocampal metastasis.

Conclusion

The pathological type, the number of metastases, and the total volume of metastases are the high-risk factors associated with hippocampal metastasis. Small cell lung cancer (SCLC) has a significantly higher rate of hippocampal metastasis than other tumor types. The greater the number and total volume of metastases, the more likely the hippocampal metastasis. For patients with SCLC or a greater number and total volume of brain metastases, the implementation of HA-WBRT may bring a higher risk of tumor recurrence.
DLC1 Is a Prognosis-Related Biomarker Correlated With Tumor Microenvironment Remodeling in Endometrial Carcinoma
Authors: Wu Yalan , Zheng Li-e , Chen Shumin , Lv Chengyu , Huang Yuxiu
Published: February 2022

Background and Aim

Deleted in liver cancer 1 (DLC1) is confirmed as a metastasis suppressor gene in endometrial carcinoma (EC). However, its functional mechanisms remain unclear. This study aimed to explore the relationship between DLC1 expression and EC.

Methods

The Cancer Genome Atlas database was used for evaluating the expression of DLC1 in pan-cancer. CIBERSORT was used to assess the relationship between DLC1 and tumor immune infiltration. We applied real-time quantitative polymerase chain reaction to determine the expression of DLC1 in EC and adjacent normal tissue samples. The targeting endogenous protein levels were assessed using the dataset from the cBioPortal database.

Results

DLC1 expression negatively correlated with the clinical characteristics (clinical stage, histologic grade) and positively correlated with the survival of patients with uterine corpus EC (UCEC). The gene set enrichment analysis displayed that the low-expression DLC1 group was enriched in metabolic pathways. Concomitantly, the high-expression DLC1 group was enriched in tumor immune-related activities. The CIBERSORT analysis showed that the number of resting memory CD4 T cells and resting mast cells positively correlated with DLC1 expression, while the number of macrophages M2 had a negative correlation, indicating that DLC1 played a key role in mediating immune cell infiltration. The target gene validation confirmed that DLC1 expression was downregulated in tumor samples. The target protein level was consistently downregulated in tumor samples.

Conclusions

DLC1 levels might be useful in predicting the prognosis of patients with UCEC and especially governing the status of tumor microenvironment transition from immune-dominant to metabolic-dominant. The findings shed a different light on the immune therapeutics of UCEC.
Perioperative Respiratory Adverse Events Among Pediatric Surgical Patients in University Hospitals in Northwest Ethiopia; A Prospective Observational Study
Authors: Wudineh Desalegn Muche , Berhe Yophtahe Woldegerima , Chekol Wubie Birlie , Adane Habtu , Workie Misganaw Mengie
Published: February 2022

Introduction

Perioperative respiratory adverse events (PRAEs) are frequent among pediatrics surgical patients and are accountable for 3/4th of perioperative critical incidents and 1/3rd of cardiac arrests.

Objective

Assess the prevalence and factors associated with PRAEs among pediatric surgical patients in University Hospitals in Northwest Ethiopia, 2020.

Methodology

After ethical approval obtained prospective observational study was conducted among 210 pediatric surgical patients. Perioperative respiratory adverse events were defined as the occurrence of any episode of single/combination of coughing, breath holding, hypoxemia, laryngospasm and bronchospasm. Bivariate and multivariate binary logistic regression analyses were performed and variables with p < 0.05 at 95% confidence interval were considered as statistically significant.

Results

The prevalence of PRAEs was 26.2% (CI: 20.5–30.9%). A total of 129 episodes of PRAEs were occurred and of them, 89 (69.0%) were occurred in the postoperative period. Desaturation was the predominant adverse event which was observed 61 (47.3%) times. Age <1 year (AOR: 3.6, CI: 1.3–10.0), ASA ≥ 3 (AOR: 5.2, CI: 1.9–22.9), upper respiratory tract infections (URTIs) (AOR: 7.6, CI: 1.9–30.2), secretions in the upper airway (AOR: 4.8, CI: 1.4–15.9) and airway related surgery (AOR: 6.0, CI: 1.5–24.1) were significantly associated with PRAEs.

Conclusions

Prevalence of PRAEs was high among pediatric surgical patients; the postoperative period was the most critical time for the occurrence of PRAEs and desaturation was the commonest PRAE. Age <1 year, URTIs (recent or active), secretions in the upper airways, ASA ≥ 3 and airway related surgery were significantly associated with PRAEs. Clinicians should perform effective risk assessment, preoperative optimization and preparation for the management of PRAEs.
The Impact of Urban Culture on Street Vending: A Path Model Analysis of the General Public's Perspective
Authors: Al-Jundi Salem A. , Al-Janabi Haitham A. , Salam Mohammad Asif , Bajaba Saleh , Ullah Shakir
Published: February 2022

This study examined the relationship between urban culture and street vending. Prior research on this topic is limited and inconclusive. Therefore, we have proposed an integrated model to test the positive effect of urban culture on street vending using multiple mediations of consumption patterns, resistance, and microfinance. We tested a sample of 425 responses that reflect the public opinion in Baghdad, Iraq. These responses were collected between September and November 2018. A partial least squares–based structural equation modeling is employed to test the validity of measurement models and the significance of the entire structural model, predictive power, and mediation analysis. We found that resistance mediates the effect of urban culture on street vending; low-income consumption and resistance sequentially mediate the effect of urban culture on street vending, while resistance mediates the effect of a lack of microfinance on street vending. The direct impact of culture on street vending is not significant, and a lack of microfinance positively influences the pervasiveness of trading on streets. This study contributes to the extant literature as it proposed and tested a novel and comprehensive model to analyze the relationship between urban culture and street vending, simultaneously examining the effects of culture, consumption, resistance, and microfinance on street vending.
Is Consciousness First in Virtual Reality?
Authors: Slater Mel , Sanchez-Vives Maria V.
Published: February 2022

The prevailing scientific paradigm is that matter is primary and everything, including consciousness can be derived from the laws governing matter. Although the scientific explanation of consciousness on these lines has not been realized, in this view it is only a matter of time before consciousness will be explained through neurobiological activity in the brain, and nothing else. There is an alternative view that holds that it is fundamentally impossible to explain how subjectivity can arise solely out of material processes—“the hard problem of consciousness”—and instead consciousness should be regarded in itself as a primary force in nature. This view attempts to derive, for example, the laws of physics from models of consciousness, instead of the other way around. While as scientists we can understand and have an intuition for the first paradigm, it is very difficult to understand what “consciousness is primary” might mean since it has no intuitive scientific grounding. Here we show that worlds experienced through virtual reality (VR) are such that consciousness is a first order phenomenon. We discuss the Interface Theory of Perception which claims that in physical reality perceptions are not veridical and that we do not see the “truth” but that perception is based on evolutionary payoffs. We show that this theory may provide an accurate description of perception and consciousness within VR, and we put forward an experimental study that could throw light on this. We conclude that VR does offer an experimental frame that provides intuition with respect to the idea that “consciousness is first” and what this might mean regarding the perceived world. However, we do not draw any conclusions about the veracity of this notion with respect to physical reality or question the emergence of consciousness from brain function.
Optimal Guidance Laws for a Hypersonic Multiplayer Pursuit-Evasion Game Based on a Differential Game Strategy
Authors: Liang Haizhao , Li Zhi , Wu Jinze , Zheng Yu , Chu Hongyu , Wang Jianying
Published: February 2022

The guidance problem of a confrontation between an interceptor, a hypersonic vehicle, and an active defender is investigated in this paper. As a hypersonic multiplayer pursuit-evasion game, the optimal guidance scheme for each adversary in the engagement is proposed on the basis of linear-quadratic differential game strategy. In this setting, the angle of attack is designed as the output of guidance laws, in order to match up with the nonlinear dynamics of adversaries. Analytical expressions of the guidance laws are obtained by solving the Riccati differential equation derived by the closed-loop system. Furthermore, the satisfaction of the saddle-point condition of the proposed guidance laws is proven mathematically according to the minimax principle. Finally, nonlinear numerical examples based on 3-DOF dynamics of hypersonic vehicles are presented, to validate the analytical analysis in this study. By comparing different guidance schemes, the effectiveness of the proposed guidance strategies is demonstrated. Players in the engagement could improve their performance in confrontation by employing the proposed optimal guidance approaches with appropriate weight parameters.
Prenatal Fine Particulate Matter, Maternal Micronutrient Antioxidant Intake, and Early Childhood Repeated Wheeze: Effect Modification by Race/Ethnicity and Sex
Authors: Chiu Yueh-Hsiu Mathilda , Carroll Kecia N. , Coull Brent A. , Kannan Srimathi , Wilson Ander , Wright Rosalind J.
Published: February 2022

Fine particulate matter (PM2.5) potentiates in utero oxidative stress influencing fetal development while antioxidants have potential protective effects. We examined associations among prenatal PM2.5, maternal antioxidant intake, and childhood wheeze in an urban pregnancy cohort (n = 530). Daily PM2.5 exposure over gestation was estimated using a satellite-based spatiotemporally resolved model. Mothers completed the modified Block98 food frequency questionnaire. Average energy-adjusted percentile intake of β-carotene, vitamins (A, C, E), and trace minerals (zinc, magnesium, selenium) constituted an antioxidant index (AI). Maternal-reported child wheeze was ascertained up to 4.1 ± 2.8 years. Bayesian distributed lag interaction models (BDLIMs) were used to examine time-varying associations between prenatal PM2.5 and repeated wheeze (≥2 episodes) and effect modification by AI, race/ethnicity, and child sex. Covariates included maternal age, education, asthma, and temperature. Women were 39% Black and 33% Hispanic, 36% with ≤high school education; 21% of children had repeated wheeze. Higher AI was associated with decreased wheeze in Blacks (OR = 0.37 (0.19–0.73), per IQR increase). BDLIMs identified a sensitive window for PM2.5 effects on wheeze among boys born to Black mothers with low AI (at 33–40 weeks gestation; OR = 1.74 (1.19–2.54), per µg/m3 increase in PM2.5). Relationships among prenatal PM2.5, antioxidant intake, and child wheeze were modified by race/ethnicity and sex.
Mouthwash Formulation Co-Delivering Quercetin and Mint Oil in Liposomes Improved with Glycol and Ethanol and Tailored for Protecting and Tackling Oral Cavity
Authors: Castangia Ines , Manconi Maria , Allaw Mohamad , Perra Matteo , Orrù Germano , Fais Sara , Scano Alessandra , Escribano-Ferrer Elvira , Ghavam Mansureh , Rezvani Maryam , Manca Maria Letizia
Published: February 2022

The aim of this work was the simultaneous loading of quercetin and mint essential oil (mint oil) in phospholipid vesicles specifically tailored to obtain an antibacterial and antioxidant mouthwash. The vesicles were prepared using soy lecithin and Tween 80 as bilayer components, and a mixture of phosphate buffer solution (33%), propylene glycol (33%) and ethanol (33%) as dispersing phase. The formation of regularly shaped, spherical and unilamellar vesicles was confirmed by cryogenic transmission electron microscopy analyses. Similarly, light scattering results disclosed that the size of the vesicles increased by increasing the concentration of mint oil, but at the same time the high amount of mint oil ensured high stability, as the size of these vesicles remained unchanged during 12 months of storage. All tested formulations were highly biocompatible towards epithelial cells and capable of counteracting oxidative cell damages caused by hydrogen peroxide. Moreover, the vesicles prepared with the highest concentration of mint oil inhibited the proliferation of the cariogenic Streptococcus mutans (S. mutans) and Lactobacillus acidophilus (L. acidophilus).
Finding Biomarkers in Antioxidant Molecular Mechanisms for Ensuring Food Safety of Bivalves Threatened by Marine Pollution
Authors: López-Pedrouso María , Lorenzo José M. , Varela Zulema , Fernández J. Ángel , Franco Daniel
Published: February 2022

Aquaculture production as an important source of protein for our diet is sure to continue in the coming years. However, marine pollution will also likely give rise to serious problems for the food safety of molluscs. Seafood is widely recognized for its high nutritional value in our diet, leading to major health benefits. However, the threat of marine pollution including heavy metals, persistent organic pollutants and other emerging pollutants is of ever-growing importance and seafood safety may not be guaranteed. New approaches for the search of biomarkers would help us to monitor pollutants and move towards a more global point of view; protocols for the aquaculture industry would also be improved. Rapid and accurate detection of food safety problems in bivalves could be carried out easily by protein biomarkers. Hence, proteomic technologies could be considered as a useful tool for the discovery of protein biomarkers as a first step to improve the protocols of seafood safety. It has been demonstrated that marine pollutants are altering the bivalve proteome, affecting many biological processes and molecular functions. The main response mechanism of bivalves in a polluted marine environment is based on the antioxidant defense system against oxidative stress. All these proteomic data provided from the literature suggest that alterations in oxidative stress due to marine pollution are closely linked to robust and confident biomarkers for seafood safety.
Research Progress on Cordycepin Synthesis and Methods for Enhancement of Cordycepin Production in Cordyceps militaris
Authors: Wang Li , Yan Huanhuan , Zeng Bin , Hu Zhihong
Published: February 2022

C. militaris is an insect-born fungus that belongs to Ascomycota and Cordyceps. It has a variety of biological activities that can be applied in medicine, health-care products, cosmeceuticals and other fields. Cordycepin (COR) is one of the major bioactive components identified from C. militaris. Thus, C. militaris and COR have attracted extensive attention. In this study, chemical synthetic methods and the biosynthesis pathway of COR were reviewed. As commercially COR was mainly isolated from C. militaris fermentation, the optimizations for liquid and solid fermentation and genetic modifications of C. militaris to increase COR content were also summarized. Moreover, the research progress of genetic modifications of C. militaris and methods for separation and purification COR were introduced. Finally, the existing problems and future research direction of C. militaris were discussed. This study provides a reference for the production of COR in the future.
Cell-Based Double-Screening Method to Identify a Reliable Candidate for Osteogenesis-Targeting Compounds
Authors: Fukuyasu Sho , Kayashima Hiroki , Moribayashi Akihito , Matsuoka Shu , Nagasaki Atsuhiro , Okawa Hiroko , Yatani Hirofumi , Saeki Makio , Egusa Hiroshi
Published: February 2022

Small-molecule compounds strongly affecting osteogenesis can form the basis of effective therapeutic strategies in bone regenerative medicine. A cell-based high-throughput screening system might be a powerful tool for identifying osteoblast-targeting candidates; however, this approach is generally limited with using only one molecule as a cell-based sensor that does not always reflect the activation of the osteogenic phenotype. In the present study, we used the MC3T3-E1 cell line stably transfected with the green fluorescent protein (GFP) reporter gene driven by a fragment of type I collagen promoter (Col-1a1GFP-MC3T3-E1) to evaluate a double-screening system to identify osteogenic inducible compounds using a combination of a cell-based reporter assay and detection of alkaline phosphatase (ALP) activity. Col-1a1GFP-MC3T3-E1 cells were cultured in an osteogenic induction medium after library screening of 1280 pharmacologically active compounds (Lopack1280). After 7 days, GFP fluorescence was measured using a microplate reader. After 14 days of osteogenic induction, the cells were stained with ALP. Library screening using the Col-1a1/GFP reporter and ALP staining assay detected three candidates with significant osteogenic induction ability. Furthermore, leflunomide, one of the three detected candidates, significantly promoted new bone formation in vivo. Therefore, this double-screening method could identify candidates for osteogenesis-targeting compounds more reliably than conventional methods.
Transcriptomic Analysis Identifies Differentially Expressed Genes Associated with Vascular Cuffing and Chronic Inflammation Mediating Early Thrombosis in Arteriovenous Fistula
Authors: Rai Vikrant , Agrawal Devendra K.
Published: February 2022

Arteriovenous fistula (AVF) is vascular access created for hemodialysis in end-stage renal disease patients. AVF creation causes increased blood flow in the outflow vein with increased pressure. Increased blood flow, blood volume, and shear stress causes outward remodeling so that the outflow vein can withstand the increased pressure. Outward remodeling of the vein involved in AVF is necessary for AVF maturation, however, inward remodeling due to excessive neointimal hyperplasia (NIH) and chronic inflammation may end up with vessel thrombosis and AVF maturation failure. Early thrombosis of the vessel may be due to the luminal factors including NIH and chronic inflammation or due to chronic inflammation of the adventitial due to perivascular cuffing. Inflammation may either be due to an immune response to the vascular injury during AVF creation or injury to the surrounding muscles and fascia. Several studies have discussed the role of inflammation in vascular thrombosis due to intimal injury during AVF creation, but there is limited information on the role of inflammation due to surrounding factors like a muscle injury. The concept of perivascular cuffing has been reported in the nervous system, but there is no study of perivascular cuffing in AVF early thrombosis. We performed the bulk RNA sequencing of the femoral arterial tissue and contralateral arteries as we found thrombosed arteries after AVF creation. RNA sequencing revealed several significantly differentially expressed genes (DEGs) related to chronic inflammation and perivascular cuffing, including tripartite motif-containing protein 55 (TRIM55). Additionally, DEGs like myoblast determination protein 1 (MYOD1) increased after muscle injury and relates to skeletal muscle differentiation, and network analysis revealed regulation of various genes regulating inflammation via MYOD1. The findings of this study revealed multiple genes with increased expression in the AVF femoral artery and may provide potential therapeutic targets or biomarkers of early thrombosis in AVF maturation failure. Thus, not only the luminal factors but also the surrounding factors mediating vascular cuffing contribute to vessel thrombosis and AVF failure via early thrombosis, and targeting the key regulatory factors may have therapeutic potential.
The Spectrum of Acute Cerebrovascular Disease in Patients with COVID-19
Authors: Triay Rachel , Buchhanolla Prabandh , Gaudet Alexas , Winter Victoria , Gaudet Alexandra , Faraji Mehdi , Gonzalez-Toledo Eduardo , Siddaiah Harish , Cuellar-Saenz Hugo H. , Bailey Steven , Javalkar Vijayakumar , Riel-Romero Rosario Maria S. , Kelley Roger E. , Gavins Felicity N. E. , Ansari Junaid
Published: February 2022

(1) Background: COVID-19 infection is responsible for the ongoing pandemic and acute cerebrovascular disease (CVD) has been observed in COVID-19 patients. (2) Methods: We conducted a retrospective, observational study of hospitalized adult patients admitted to our hospital with SARS-CoV-2 and acute cerebrovascular disease. All clinical data were reviewed including epidemiology, clinical features, laboratory data, neuroradiological findings, hospital management and course from 32 patients hospitalized for COVID-19 management with acute cerebrovascular disease. (3) Results: Acute CVD with COVID-19 was associated with higher NIH stroke scale on discharge compared to non-COVID-19 CVDs. Seizures complicated the hospital course in 16% of COVID-19 patients with CVD. The majority of the acute CVDs were ischemic (81%) in nature followed by hemorrhagic (22%). Acute CVD with COVID-19 resulted in average hospital stays greater than twice that of the control group (13 days in COVID-19, 5 days in control). Acute CVD with COVID-19 patients had worse clinical outcomes with 31% patient deaths and 6% discharged to hospice. In the control group, 6% of patients died. (4) Conclusions: Acute CVD associated with COVID-19 tends to be more complicated with unique and adverse clinical phenotype, longer hospital admissions, and worse clinical outcomes.
Cryptocaryone Promotes ROS-Dependent Antiproliferation and Apoptosis in Ovarian Cancer Cells
Authors: Chen Yu-Chieh , Yang Che-Wei , Chan Te-Fu , Farooqi Ammad Ahmad , Chang Hsun-Shuo , Yen Chia-Hung , Huang Ming-Yii , Chang Hsueh-Wei
Published: February 2022

Cryptocaryone (CPC) is a bioactive dihydrochalcone derived from Cryptocarya plants, and its antiproliferation was rarely reported, especially for ovarian cancer (OVCA). This study aimed to examine the regulation ability and mechanism of CPC on three histotypes of OVCA cells (SKOV3, TOV-21G, and TOV-112D). In a 24 h MTS assay, CPC showed antiproliferation effects to OVCA cells, i.e., IC50 values 1.5, 3, and 9.5 μM for TOV-21G, SKOV3, and TOV-112D cells. TOV-21G and SKOV3 cells showed hypersensitivity to CPC when applied for exposure time and concentration experiments. For biological processes, CPC stimulated the generation of reactive oxygen species and mitochondrial superoxide and promoted mitochondrial membrane potential dysfunction in TOV-21G and SKOV3 cells. Apoptosis was detected in OVCA cells through subG1 accumulation and annexin V staining. Apoptosis signaling such as caspase 3/7 activities, cleaved poly (ADP-ribose) polymerase, and caspase 3 expressions were upregulated by CPC. Specifically, the intrinsic and extrinsic apoptotic caspase 9 and caspase 8 were overexpressed in OVCA cells following CPC treatment. Moreover, CPC also stimulated DNA damages in terms of γH2AX expression and increased γH2AX foci. CPC also induced 8-hydroxy-2′-deoxyguanosine DNA damages. These CPC-associated principal biological processes were validated to be oxidative stress-dependent by N-acetylcysteine. In conclusion, CPC is a potential anti-OVCA natural product showing oxidative stress-dependent antiproliferation, apoptosis, and DNA damaging functions.
Communication and Social Relations: A Qualitative Study of Families’ Experience with Their Outpatient Pediatric Diabetes Visits
Authors: Jespersen Louise Norman , Svensson Jannet , Pilgaard Kasper Ascanius , Grabowski Dan
Published: February 2022

Clinical outpatient visits comprise a relatively small part of the lives of children with diabetes and their families, but there is evidence that these visits have a strong impact on the long-term management of diabetes. Because children with diabetes are looking at frequent hospital visits for the rest of their lives, it is important to explore their experiences to ensure visits meet their needs. This study aimed to investigate families’ experiences with outpatient visits at a pediatric diabetes clinic. Thirteen semi-structured family interviews were conducted. Systematic text condensation was used to analyze the data. With an analytical focus on communication and social relations, nine themes were identified: 1. Discrepancies in perception of diabetes tasks, 2. Talking about adult things, but the children listen, 3. The importance of spoken and written words, 4. Confusion about division of responsibilities, 5. Relief when someone eases the burden, 6. Courtesy when visiting the clinic, 7. Understanding of the family context, 8. Importance of continuous personal relations, and 9. Need for a facilitated peer network. The findings encourage reflection on how to improve communication and underline the importance of establishing a continuous and personal relation between families and health care professionals to improve families’ experience with pediatric outpatient visits.
COVID-19 Pandemic Experiences and Maternal Stress in Neonatal Intensive Care Units
Authors: Erdei Carmina , Feldman Natalie , Koire Amanda , Mittal Leena , Liu Cindy
Published: February 2022

COVID-19 compounds the already high levels of psychological distress experienced by NICU mothers. We aimed to describe the rates of NICU-related maternal stress during the COVID-19 pandemic and to determine how COVID-19 experiences correlate with high levels of stress experienced by NICU mothers. We conducted a cross-sectional analysis based on responses to a nationwide online survey to understand the relationship between COVID-19-related experiences and the stress experienced by mothers of infants admitted to U.S. NICUs (n = 108) during the pandemic. Results indicate that 61.9% of surveyed mothers reported experiencing high levels of stress on the Parental Stressor Scale: NICU. COVID-19-related grief was significantly associated with higher levels of maternal stress, as it related to seeing the baby’s appearance and behavior in the NICU and exposure to sights and sounds within the NICU environment. No significant associations were noted between parental stress and COVID-19-related health worries or worries about resources. Of note, our recruitment relied on convenience sampling, limiting the generalizability of study results. In conclusion, mothers who experience COVID-19-related grief appear to be more vulnerable to NICU-related stress. Prioritizing parent involvement and enhancing psychosocial support are essential strategies to mitigate the long-term consequences of heightened stress for NICU families.
Accuracy and Precision in Electronic Structure Computation: Wien2k and FPLO
Authors: Richter Manuel , Kim Seo-Jin , Koepernik Klaus , Rosner Helge , Möbius Arnulf
Published: February 2022

Electronic structure calculations in the framework of density functional theory are based on complex numerical codes which are used in a multitude of applications. Frequently, existing experimental information is used as a gauge for the reliability of such codes. However, their results depend both on the chosen exchange-correlation energy functional and on the specific numerical implementation of the Kohn-Sham equations. The only way to disentangle these two items is a direct comparison of two or more electronic structure codes. Here, we address the achievable numerical accuracy and numerical precision in the total energy computation of the two all-electron density-functional codes Wien2k and FPLO. Both codes are based on almost independent numerical implementations and largely differ in the representation of the Bloch wave function. Thus, it is a highly encouraging result that the total energy data obtained with both codes agree within less than 10−6. We here relate the term numerical accuracy to the value of the total energy E, while the term numerical precision is related to the numerical noise of E as observed in total energy derivatives. We find that Wien2k achieves a slightly higher accuracy than FPLO at the price of a larger numerical effort. Further, we demonstrate that the FPLO code shows somewhat higher precision, i.e., less numerical noise in E than Wien2k, which is useful for the evaluation of physical properties based on derivatives of E.
Antimicrobial Activity of Zymomonas mobilis Is Related to Its Aerobic Catabolism and Acid Resistance
Authors: Rutkis Reinis , Ļaša Zane , Rubina Marta , Ščerbaka Rita , Kalniņš Gints , Bogans Jānis , Kalnenieks Uldis
Published: February 2022

Zymomonas mobilis is an ethanologenic, facultatively anaerobic alpha-proteobacterium, known for its inhibitory effect on the growth of a wide variety of microorganisms. This property might be interesting for the design of novel antimicrobials, yet it has negative implications for biotechnology, as it hinders the use of Z. mobilis as a producer microorganism in cocultivation. So far, the chemical nature of its inhibitory compound(s) has not been established. In the present study, we demonstrate that the putative inhibitor is a low-molecular-weight (below 3 kDa), thermostable compound, resistant to protease treatment, which is synthesized under aerobic conditions in Z. mobilis strains via the active respiratory chain. It is also synthesized by aerated nongrowing, glucose-consuming cells in the presence of chloramphenicol, thus ruling out its bacteriocin-like peptide nature. The inhibitory activity is pH-dependent and strongly correlated with the accumulation of propionate and acetate in the culture medium. Although, in Z. mobilis, the synthesis pathways of these acids still need to be identified, the acid production depends on respiration, and is much less pronounced in the non-respiring mutant strain, which shows low inhibitory activity. We conclude that propionate and acetate play a central role in the antimicrobial effects of Z. mobilis, which itself is known to bear high resistance to organic acids.
Reduced Numerical Modeling of Turbulent Flow with Fully Resolved Time Advancement. Part 1. Theory and Physical Interpretation
Authors: Kerstein Alan R.
Published: February 2022

A multiscale modeling concept for numerical simulation of multiphysics turbulent flow utilizing map-based advection is described. The approach is outlined with emphasis on its theoretical foundations and physical interpretations in order to establish the context for subsequent presentation of the associated numerical algorithms and the results of validation studies. The model formulation is a synthesis of existing methods, modified and extended in order to obtain a qualitatively new capability. The salient feature of the approach is that time advancement of the flow is fully resolved both spatially and temporally, albeit with modeled advancement processes restricted to one spatial dimension. This one-dimensional advancement is the basis of a bottom-up modeling approach in which three-dimensional space is discretized into under-resolved mesh cells, each of which contains an instantiation of the modeled one-dimensional advancement. Filtering is performed only to provide inputs to a pressure correction that enforces continuity and to obtain mesh-scale-filtered outputs if desired. The one-dimensional advancement, the pressure correction, and coupling of one-dimensional instantiations using a Lagrangian implementation of mesh-resolved volume fluxes is sufficient to advance the three-dimensional flow without time advancing coarse-grained equations, a feature that motivates the designation of the approach as autonomous microscale evolution (AME). In this sense, the one-dimensional treatment is not a closure because there are no unclosed terms to evaluate. However, the approach is additionally suitable for use as a subgrid-scale closure of existing large-eddy-simulation methods. The potential capabilities and limitations of both of these implementations of the approach are assessed conceptually and with reference to demonstrated capabilities of related methods.
Polysaccharides from Spores of Cordyceps cicadae Protect against Cyclophosphamide-Induced Immunosuppression and Oxidative Stress in Mice
Authors: Zheng Yi , Li Shiying , Li Chuang , Shao Ying , Chen Anhui
Published: February 2022

This study investigated the purification, preliminary structure and in vivo immunomodulatory activities of polysaccharides from the spores of Cordyceps cicadae (CCSP). The crude CCSP was purified by diethylaminoethyl (DEAE)-cellulose and Sephadex G-100 chromatography, affording CCSP-1, CCSP-2 and CCSP-3 with molecular weights of 1.79 × 106, 5.74 × 104 and 7.93 × 103 Da, respectively. CCSP-2 consisted of mannose and glucose, while CCSP-1 and CCSP-3 are composed of three and four monosaccharides with different molar ratios, respectively. CCSP-2 exhibited its ameliorative effects in cyclophosphamide-induced immunosuppressed mice through significantly increasing spleen and thymus indices, enhancing macrophage phagocytic activity, stimulating splenocyte proliferation, improving natural killer (NK) cytotoxicity, improving bone marrow suppression, regulating the secretion of cytokines and immunoglobulins, and modulating antioxidant enzyme system. These results indicate that CCSP-2 might be exploited as a promising natural immunomodulator.
Effect of Combination of Time and Temperature on Quality Characteristics of Sous Vide Chicken Breast
Authors: Hasani Endrit , Csehi Barbara , Darnay Lívia , Ladányi Márta , Dalmadi István , Kenesei György
Published: February 2022

The use of minimal thermal processing techniques such as sous vide technology to improve the quality of meat-based foods has gained a special focus in recent years. A proper combination of temperature and time parameters in sous vide processing plays an important role in the water-holding capacity, texture properties, and juiciness of the meat. The present study aimed to assess the impact of the one-step and two-step sous vide processing on different quality properties of chicken breast with special emphasis on the cooking loss, color, texture properties, protein solubility, and lipid oxidation. According to the results, chicken breast treated with a two-step temperature (50 and 60 °C) showed improved texture parameters (shear force, hardness, chewiness, and gumminess), lower cooking loss, acceptable redness values, and decreased lipid oxidation levels than the chicken breast treated with the one-step temperature of 60 °C. Moreover, the two-step sous vide technique revealed significantly higher total protein solubility of the chicken breast than the one-step sous vide. Based on pasteurization values, the two-step sous vide technique was equally safe as the one-step sous vide technique for vegetative cells’ inactivation for the main pathogens of interest (C. perfringens and L. monocytogenes).
Antibacterial Properties of TMA against Escherichia coli and Effect of Temperature and Storage Duration on TMA Content, Lysozyme Activity and Content in Eggs
Authors: Shi Xuefeng , Li Xingzheng , Li Xianyu , He Zhaoxiang , Chen Xia , Song Jianlou , Zeng Lingsen , Liang Qianni , Li Junying , Xu Guiyun , Zheng Jiangxia
Published: February 2022

Studies on trimethylamine (TMA) in egg yolk have focused on how it impacts the flavor of eggs, but there has been little focus on its other functions. We designed an in vitro antibacterial test of TMA according to TMA concentrations that covered the TMA contents typically found in egg yolk. The change in TMA content in yolk was analyzed at different storage temperatures and for different storage durations. The known antibacterial components of eggs, including the cuticle quality of the eggshell and the lysozyme activity and content in egg white, were also assessed. The total bacterial count (TBC) of different parts of eggs were detected. The results showed that the inhibitory effect of TMA on Escherichia coli (E. coli) growth increased with increasing TMA concentration, and the yolk TMA content significantly increased with storage duration (p < 0.05). The cuticle quality and lysozyme content and activity significantly decreased with storage time and increasing temperature, accompanied by a significant increase in the TBC on the eggshell surface and in the egg white (p < 0.05). This work reveals a new role for trace TMA in yolks because it reduces the risk of bacterial colonization, especially when the antibacterial function of eggs is gradually weakened during storage.