bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Diagnosis of Microduplication of Fetal Chromosome 17 Following Noninvasive Prenatal Testing
Authors: Shi Ye , Zheng Fang-xiu , Wang Jing , Zhou Qin , Chen Ying-ping , Zhang Bin
Published: June 2021

Background

Chromosome 17q12 duplication syndrome is a disease caused by the complete or partial duplication of q12 in the long arm of chromosome 17, there were no cases reported about the prenatal diagnosis of the syndrome. Most of the fetal phenotype of the syndrome may not be evident during the pregnancy, which means the syndrome was only be discovered accidentally or missed during the prenatal examination.
Objective

Noninvasive prenatal testing (NIPT) is widely used in the screening of common fetal chromosome aneuploidy. However, reports on chromosomal microduplication and microdeletion are rare. The aim of the study was to investigate the application value of NIPT for the detection of chromosomal microduplication.
Case presentations:

We found two cases of microduplication in the long arm of chromosome 17(17q12), they were first detected by NIPT and then were further diagnosed by copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). The CMA results of prenatal diagnosis showed that the microduplications in 17q12 (one was 1.5Mb, the other was 1.9Mb) were consistent with the NIPT results. The amniotic fluid karyotype analysis showed no abnormalities. Finally, because it was pathogenic copy number variant, both of the parents chose to terminate the pregnancy.
Conclusion

In the study, two cases of microduplication fragment in the long arm of chromosome 17 were detected by NIPT and were confirmed by CMA. To our knowledge, this is the first report of prenatal diagnosis of chromosome 17q12 duplication syndrome following NIPT. This suggests that NIPT is an effective method to screen chromosome microduplications in prenatal diagnosis, especially for the chromosome 17q12 duplication syndrome.
Function Analysis of Drought Resistance Related Gene TaGAPCs and TaWRKYs in Wheat
Authors: Wang Qiuzhu , Zhang Lin , Yang Shushen
Published: June 2021

Backgrounds: Wheat (Triticum aestivum L.) is one of the most important food crops in the world. It faces various abiotic stresses during its growth. Drought is one of the main factors limiting the growth and development of wheat. Severe drought stress will Lead to a decline in wheat production. Cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GAPC) is an important member of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) family, which is widely present in plant cytoplasm. Plants play an important role in the process of primary metabolism and stress resistance.Result: In this study, a comparative transcriptomic analysis of the TaGAPCs-RNAi strain of Changwu 134 and the wild-type wheat seedlings of Changwu 134 under natural drought conditions was carried out. A total of 30067 differentially expressed genes were screened in RNAi strains and wild-type strains, of which 19,959 genes were up-regulated in RNAi strains and 10,108 genes were down-regulated in transcription. GO analysis shows that differential genes are mainly enriched in biological regulation, cellular processes, metabolic processes, and responses to stimuli. KEGG analysis showed that the differential genes were mainly concentrated in the biosynthesis of phenylpropane, plant hormone signal transduction and flavonoid biosynthesis pathways. By analyzing the expression levels of differential transcription factors, the significantly down-regulated transcription factor WRKY family member TaWRKY2 / 22/28/29/33/40/47/52 in wheat was screened out. The TaWRKY28/33/40/47 gene silencing line was successfully obtained using the barley stripe mosaic virus (BSMV-VIGS) technology. The plants with TaWRKY28/33/40/47 gene silenced were subjected to natural drought treatment, and physiological and biochemical index tests were carried out. The results showed that the growth status of gene-silenced plants was worse than that of wild-type plants, and the relative water content and chlorophyll content decreased. The content of MDA, H2O2 and superoxide anion increases, the activity of antioxidant enzymes (SOD, POD, CAT) decreases, and the content of proline decreases. Conclusion: The results showed that TaGAPCs regulates the expression of some TaWRKYs transcription factors, activates antioxidant pathways, enhances tolerance of wheat to drought stress.
mTORC2 is the Primary Target for Simvastatin-Associated Toxicity in C2C12 Cells and in Mouse Skeletal Muscle
Authors: Sanvee Gerda M , Hitzfeld Leonie , Bouitbir Jamal , Krahenbuhl Stephan
Published: June 2021

Statins decrease the serum LDL-cholesterol concentration and reduce the risk for cardiovascular diseases but can cause myopathy, which may be related to mTORC inhibition. In the current study, we investigated which mTORC is inhibited by simvastatin and by which mechanisms. In C2C12 myoblasts and myotubes and mouse gastrocnemius, simvastatin was cytotoxic and inhibited S6rp and Akt Ser473 phosphorylation, indicating inhibition of mTORC1 and mTORC2, respectively. In contrast to simvastatin, the mTORC1 inhibitor rapamycin did not inhibit mTORC2 and was not cytotoxic. Like simvastatin, knock-down of Rictor, an essential component of mTORC2, impaired Akt Ser473 and S6rp phosphorylation and was cytotoxic for C2C12 myoblasts, suggesting that mTORC2 inhibition is an important myotoxic mechanism. The investigation of the mechanism of mTORC2 inhibition showed that simvastatin impaired Ras farnesylation, which was prevented by farnesol but without restoring mTORC2 activity. In comparison, Rap1 knock-down reduced mTORC2 activity and was cytotoxic for C2C12 myoblasts. Simvastatin impaired Rap1 prenylation and function, which was prevented by geranylgeraniol. In addition, simvastatin and the complex III inhibitor antimycin A caused mitochondrial superoxide accumulation and decreased the activity of mTORC2, which could partially be prevented by the antioxidant MitoTEMPO. In conclusion, mTORC2 inhibition is an important mechanism of simvastatin-induced myotoxicity. Simvastatin inhibits mTORC2 by impairing geranylgeranylation of Rap1 and by inducing mitochondrial dysfunction.
Separation of DC Electrical Method Anomaly By Using Multifractal Modelling
Authors: Jing Cao , Linhua Sun , Cancan Wu
Published: June 2021

A more accurate method of DC processing data to distinguish the anomalous body is important for the prediction and detection of potential risk such as goaf and water inrush. In this paper, we have performed a DC data processing process, which relies on the theory of aggregation-area(C-A). We investigate the apparent resistant and apparent resistant isograms cumulative area as a function to search the threshold as the boundary value. Comparisons of the conventional data processing method to physical simulation that the C-A identified the higher resistance anomalous body better than the lower resistance because its sensitivity. Scoped the higher resistance area almost identical with the physical model, while the lower approach the nearest boundary. The results are in good agreement with the physical model, validating C-A multifractal theory as an effective way for DC accurate interpretation.
The Impact of Environmental Information Disclosure on the Cost of Debt: Evidence From China
Authors: Yang Yongliang , Wen Jing , Li Yi
Published: June 2021

With the growing attention the public has paid to environmental issues, environmental disclosure is not only a vital means for firms to convey social responsibility but also an important information source for lending institutions to assess the credit risk of firms. Based on the data of listed companies in China from 2007 - 2016, this paper applies a two-way fixed effects model to determine the impact of environmental information disclosure on the cost of debt. It reveals that environmental information disclosure could decrease companies’ cost of debt and that CEO duality and ownership concentration play vital roles in this relationship to some extent. After considering endogenous problems and testing the robustness, the conclusions still prove to be valid.
Fast Response PANI/MMT-rGO Polymer Nanocomposite Material for Sensing HCN Gas
Authors: Dipak Pukhrambam , Singh Aparna , Iqbal Asif , Samadhiya Anuradha , Dwivedi Shailendra Kumar , Tiwari Dinesh Chandra , Tiwari Rajendra Kumar , Pandey Kailash Nath
Published: June 2021

In the present work, we have developed a polymer based gas sensor. The polymer nanocomposites are synthesized by the chemical oxidative polymerization of aniline with ammonium persulfate and sulfuric acid. The fabricated sensor is able to achieve a sensing response of 4.56% for PANI/MMT-rGO at 2 ppm of hydrogen cyanide (HCN) gas. The sensitivity of the sensors PANI/MMT and PANI/MMT-rGO are 0.89 ppm-1 and 1.12 ppm-1 respectively. The increase in the sensitivity of the sensor may be due to an increase in the surface area provided by MMT and rGO which provided more binding sites for the HCN gas. The sensing response of the sensor increases as the concentration of the gas exposed increases but saturates after 10 ppm. The sensor recovers automatically. The sensor is stable and can work for 8 months.
Reversible Splenial Lesion Syndrome with Mental Disorders as Only Manifestation
Authors: Xu Ziyun , Zhou Zhaoguang , Jang Wentao , Tian Jianhong , Hou Gangqiang
Published: June 2021

Background

Reversible splenial lesion syndrome (RESLES) was reported to be associated with variable entities. However, much less is known about the cases in which the mental disorders act as the only manifestation.
Method:

Total ten patients of RESLES were obtained in this retrospective study from Shenzhen Kangning Hospital. T1-fluid attenuated inversion recovery (T1-FLAIR), T2-weighted images, T2-FLAIR, diffusion-weighted images and apparent diffusion coefficient map were performed on all the patients. Clinical manifestations, laboratory examination results, magnetic resonance imaging (MRI) findings, treatments and outcomes were analyzed.
Result

All patients showed different mental disorders as the only manifestation. There were two cases of alcohol abuse, one of Asperger’s syndrome with malnutrition, one of infection and one of invasive pituitary adenoma. The other cases were diagnosis as major depressive disorder, dissociative and conversion disorders, undifferentiated somatoform disorder, unspecified psychosis and bipolar disorder, respectively. Three patients were completely recovered while the clinical symptoms of rest seven patients partially recovered at the follow-up three months later. Oval-shaped lesion centered on the splenial of corpus callosum (SCC) was observed in all patients using MRI. The lesions of SCC of all patients were completely resolved within five weeks.
Conclusion

MRI is an essential tool to identify the RESLES. For the patients with acute mental disorders, clinicians should be alert to the possibility of RESLES. Excluding other possible etiologies, we suggest that different mental disorders might be precipitating factors of RESLES.
Elderly Breast Cancer Patients Benefit from Surgery According to Guidelines
Authors: Mejdahl Mathias Kvist , Christensen Mette Haulund , Nielsen Birgitte Paaschburg , Tvedskov Tove Holst Filtenborg
Published: June 2021

Purpose

To investigate among women ≥ 70 years with early stage invasive breast cancer, whether primary endocrine therapy and omission of surgery resulted in an inferior relative survival, whether the omission of preoperative imaging resulted in an inferior local control, and whether the omission of axillary staging resulted in an inferior regional control and inferior relative survival.
Methods

A single center retrospective cohort study at Herlev Hospital, Denmark. Relative survival was expressed as standardized mortality ratios (SMR) and differences were estimated using Poisson regression and evaluated by rate ratios (RR). Differences in local and in regional recurrence were estimated by a Cause Specific Hazard Model and evaluated by hazard ratios (HR). Models were adjusted for age, comorbidity, and tumor size.
Results

We identified 1,142 women. Patients who received only endocrine therapy had a higher SMR than patients treated with primary surgery (RR = 2.57;95%CI:2.01–3.30). Patients treated with primary breast conserving surgery (BCS) did not have a lower risk of local recurrence if they received preoperative imaging (HR = 0.88;95%CI:0.27–2.81). Finally, patients who received an axillary staging had a lower risk of regional recurrence compared to patients who did not receive axillary surgery (HR = 0.25;95%CI:0.08–0.84), but not a statistically significant superior relative survival (RR = 0.78;95%CI:0.60-1.00).
Conclusion

Elderly women with early stage breast cancer treated with only endocrine therapy had an inferior relative survival, omission of axillary staging resulted in a higher risk of regional recurrence and a tendency to an inferior relative survival, and omission of preoperative imaging before BCS did not result in a higher risk of local recurrence.
Duration of Acute Kidney Injury and in-hospital Mortality in Elder Patients With Severe COVID-19: a Retrospective Cohort Study
Authors: Cai Yue , Li Qinglin , Guo Shanshan , Chen Yanyan , Wang Fang , Li Yangping , Lei Yan , Tao Ling , Li Fei
Published: June 2021

Background Patients with severe coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) in the intensive care unit (ICU) have extremely high rates of mortality. This study evaluated the prognostic impact of AKI duration on in-hospital mortality in elder patients.Methods We performed a retrospective study of 126 patients with confirmed COVID-19 with severe or critical disease who treated in the ICU from February 4, 2020, to April 16, 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes serum creatinine (Scr) criteria. AKI patients were divided into transient AKI and persistent AKI groups based on whether Scr level returned to baseline within 48 h post-AKI.Results In total, 107 patients were included in the final analysis. The mean age was 70 (64–78) years, and 69 (64.5%) patients were men. AKI occurred in 48 (44.9%) during their ICU stay. Of these, 11 (22.9%) had transient AKI, 37 (77.9%) had persistent AKI. In-hospital mortality was 18.6% (n =11) for patients without AKI, 72.7% (n=8) for patients with transient AKI, and 86.5% (n=32) for patients with persistent AKI (P<0.001). Kaplan–Meier curve analysis revealed that patients with both transient AKI and persistent AKI had significantly higher death rates than those without AKI (log-rank P<0.001). Multivariate Cox regression analysis revealed that transient and persistent AKI were an important risk factor for in-hospital mortality in older patients with severe COVID-19 even after adjustment for variables (hazard ratio [HR]=2.582; 95% CI: 1.025–6.505; P=0.044; and HR=6.974; 95% CI: 3.334–14.588; P<0.001).Conclusions AKI duration is a useful parameter to predict of worse clinical outcomes in elder patients with COVID-19 in the ICU. Among AKI patients, those persistent AKI have a lower in-hospital survival rate than those transient AKI, emphasizing the importance of identifying an appropriate treatment window for early intervention.
Thigmomorphogenic Responses of Epiphytic Bromeliads to Mechanical Perturbation
Authors: Tay Jessica Y. L , Zotz Gerhard , Einzmann Helena J. R.
Published: June 2021

Vascular epiphytes represent almost 10% of all terrestrial plant diversity. Despite their growing sites exposed to frequent extensive storms, nothing is known about how external mechanical perturbations by wind affects epiphytes’ growth and development. Therefore, this study investigated the effect of such mechanical stress on the growth rate and morphology of epiphytes. Juvenile plants of two species of bromeliads, grown in the greenhouse, were subjected to varying degrees of mechanical stress – Permanent displacement, tilting and mechanical flexing. ANOVAs were used to test possible treatment effects on growth, root-shoot ratio, root diameter, and leeward-windward root area ratio. Contrary to previous studies on herbaceous plants, these bromeliads showed little to no change in root and shoot properties in either species. Although the root-shoot ratio increased in disturbed Guzmania lingulata plants (Tukey HSD, p < 0.001), it was not observed in Vriesea sp. Treatment effects on growth were inconsistent: stress effect on growth was significant only in the first three months of the experiment (padj < 0.05) in G. lingulata, while none of the stress treatments resulted in negative growth in Vriesea sp. All disturbed plants showed some degree of curvature on their stems and leaves against the area of stress to obtain an upright position. This was probably related to the maintenance of a functional tank. This study provided quantitative and qualitative data to understand thigmomorphogenic responses of bromeliads to mechanical stress. Future studies could include field surveys to quantify on-site wind stress and the corresponding morphological changes in vascular epiphytes.
Nomogram for Benign Anastomotic Stricture After Surgery for Colorectal Cancer
Authors: Hu Xuhua , Guo Peiyuan , Zhang Ning , Guo Ganlin , Li Baokun , Liu Youqiang , Niu Jian , Wang Guiying
Published: June 2021

Background

Benign anastomotic stricture remains among the most prevalent complications following surgery for colorectal cancer, albeit its incidence is very low.
Objective

This study is aimed at identifying risk factors of anastomotic stricture as well as generating an effective nomogram for the stricture.
Design:
This is a retrospective study.
Setting:

This study was conducted from January, 2015 to December, 2019 in a single tertiary center with colorectal cancer.
Patients:

A total of 117 colorectal patients after surgery without recurrence including 39 with anastomotic stricture (the distance between anastomotic site and anal margin < = 20 cm) and 78 without the stricture were enrolled in this study.
Main outcome measures:

Their clinical and pathological data were collected. Multiple logistic regression analysis was conducted for identifying risk factors for anastomotic stricture, and the nomogram prediction model was generated.
Results

Multivariate analysis of the primary cohort led to identification of LCA (left colon artery) preservation (OR, 0.074; P = 0.0015), protective stoma (OR, 5.353; P = 0.012), anastomotic leakage (OR, 12.027; P = 0.005), and anastomotic distance (OR, 7.578; P = 0.012) as independent risk factors for anastomotic stricture. The following predictive model was derived: Logit (anastomotic stricture) = 0.074* LCA + 5.353* Protective stoma + 12.027* Anastomotic leakage + 7.578* Anastomotic distance. Assessment of the predictive model revealed that the area under curve (AUC) was 0.871, while the cutoff value was 15.444, with a sensitivity of 64.1% and a specificity of 94.8%.
Limitations:

A retrospective and case-controlled design with a small sample size from one single center is the main Limitation.
Conclusions

LCA preservation, protective stoma, anastomotic leakage, and anastomotic distance may affect the occurrence of anastomotic stricture following surgery for colorectal cancer. The nomogram model generated in the present study can be valuable in prediction of anastomotic stricture. Registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR 2100043775).
Multi-omics Prediction of Oat Agronomic and Seed Nutritional Traits Across Environments and in Distantly Related Populations
Authors: Hu Haixiao , Campbell Malachy , Yeats Trevor Howard , Zheng Xuying , Runcie Daniel , Covarrubias-Pazaran Giovanny , Broeckling Corey , Yao Linxing , Caffe-Treml Melanie , Gutiérrez Lucı́a , Smith Kevin , Tanaka James , Hoekenga Owen , Sorrells Mark , Gore Michael , Jannink Jean-Luc
Published: June 2021

Key message Integration of multi-omics data improved prediction accuracies of oat agronomic and seed nutritional traits in multi-environment trials and distantly-related populations in addition to the single-environment prediction.Multi-omics prediction has been shown to be superior to genomic prediction with genome-wide DNA-based genetic markers (G) for predicting phenotypes. However, most of the existing studies were based on historical datasets from one environment; therefore, they were unable to evaluate the efficiency of multi-omics prediction in multi-environment trials and distantly-related populations. To fill those gaps, we designed a systematic experiment to collect omics data and evaluate 17 traits in two oat breeding populations planted in single and multiple environments. In the single-environment trial, transcriptomic BLUP (T), metabolomic BLUP (M), G + T, G + M and G + T + M models showed greater prediction accuracy than GBLUP for 5, 10, 11, 17 and 17 traits, respectively, and metabolites generally performed better than transcripts when combined with SNPs. In the multi-environment trial, multi-trait models with omics data outperformed both counterpart multi-trait GBLUP models and single-environment omics models, and the highest prediction accuracy was achieved when modeling genetic covariance as an unstructured covariance model. We also demonstrated that omics data can be used to prioritize loci from one population with omics data to improve genomic prediction in a distantly-related population using a two-kernel linear model that accommodated both likely casual loci with large-effect and loci that explain little or no phenotypic variance. We propose that the two-kernel linear model is superior to most genomic prediction models that assume each variant is equally likely to affect the trait and can be used to improve prediction accuracy for any trait with prior knowledge of genetic architecture.
“Evaluation of Anti-Inflammatory Effects of Allopurinol in Diabetic Patients with Chronic Kidney Disease (DM-CKD): A Clinical Study”
Authors: Daniyali Mahya , Mahmoudieh Leila , Afzal Golnaz , Hematian Farzaneh , Moradi Omid , ziaie Shadi
Published: June 2021

Background: Diabetic nephropathy is the most prevalent cause of end-stage kidney disease (ESRD). Besides, factors such as; pro-fibrotic, cytokines, vascular endothelial growth factor, inflammatory factor, and uric acid may play a role in creating and progressing diabetic nephropathy. Decreasing the serum level of inflammatory factors can be useful in the treatment of diabetic nephropathy. Therefore, this study aimed to evaluate allopurinol's anti-inflammatory effects in diabetic patients with chronic kidney disease.Methods: In this clinical trial, 60 diabetic patients with chronic kidney disease and normal uric acid level were enrolled into the study with certain inclusion and exclusion criteria. Patients received allopurinol at a dose of 100 mg daily. Demographic parameters, laboratory results in blood urea nitrogen (BUN), serum creatinine (sCr), glomerular filtration rate (GFR), 24-hour urine protein (PrUrine24h), uric acid, serum albumin (Alb), systolic blood pressure (SBP), diastolic blood pressure (DBP), glycosylated hemoglobin (HbA1C) and high sensitivity C reactive protein (HSCRP), as well as adverse reactions, were recorded at baseline, ones and three months after.Results: The results showed that patients were not different in point of demographic parameters at baseline. Laboratory results such as; BUN, sCr, GFR, PrUrine24h, Alb, SBP, DBP, and HbA1C did not change significantly over study duration (P>0.05), except uric acid and HSCRP, which were significantly decreased in patients (P=0.024 and P=0.016, respectively). There was not any notable adverse reaction among patients.Conclusion: Low dose Allopurinol (100 mg/day) reduced uric acid and inflammatory biomarker (HSCRP) after three administration months. According to the present study results, Allopurinol can be considered an auxiliary, inexpensive, and low side-effect therapy in diabetic patients with chronic kidney disease.
Magnetic Field Compensation Coil Design for Magnetoencephalography
Authors: Sonntag Hermann , Doeller Christian F. , Haueisen Jens , Maess Burkhard
Published: June 2021

While optically pumped magnetometers (OPMs) can be attached to the head of a person and allow for highly sensitive recordings of the human magnetoencephalogram (MEG), they are mostly limited to an operational range of approximately ±5 nT. Consequently, even inside a magnetically shielded room (MSR), movements in the remnant magnetic field disable the OPMs. Active suppression of the remnant field utilizing compensation coils is therefore essential. We propose 8 compensation coils on 5 sides of a cube with a side length of approximately 2 m which were optimized for operation inside an MSR. Compared to previously built bi-planar compensation coils, the coils proposed in this report are more complex in geometry and achieved 10 times smaller errors for simulated compensation fields. The proposed coils will allow for larger head movements or smaller movement artifacts in future MEG experiments compared to existing coils.
Cardiopulmonary Exercise Testing and Impedance Cardiography in The Assessment of Exercise Capacity of Patients with Coronary Artery Disease
Authors: Kurpaska Małgorzata , Krzesiński Paweł , Prof Grzegorz Gielerak , Gołębiewska Karina , Piotrowicz Katarzyna
Published: June 2021

Background

Patients with coronary artery disease (CAD) are characterized by different levels of physical capacity, which depends not only on the anatomical advancement of atherosclerosis, but also on the individual cardiovascular hemodynamic response to exercise. The aim of this study was to evaluate the relationship between parameters of exercise capacity assessed via cardiopulmonary exercise testing (CPET) and impedance cardiography (ICG) hemodynamics in patients with CAD.
Methods

Exercise capacity was assessed in 54 patients with CAD (41 men, aged 59.5 ± 8.6 years) within 6 weeks after revascularization by means of oxygen uptake (VO2), assessed via CPET, and hemodynamic parameters (heart rate (HR), stroke volume (SV), cardiac output (CO), left cardiac work index (LCWi)), measured by ICG. Correlations between these parameters at anaerobic threshold (AT) and at the peak of exercise as well as their changes (Δpeak–rest, Δpeak–AT) were evaluated.
Results

A large proportion of patients exhibited reduced exercise capacity, with 63% not reaching 80% of predicted peak VO2. Clinically relevant correlations were noted between the absolute peak values of VO2 vs. HR, VO2 vs. CO, and VO2 vs. LCWi (R = 0.45, p = 0.0005; R = 0.33, p = 0.015; and R = 0.40, p = 0.003, respectively). There was no correlation between AT VO2 and hemodynamic parameters at the AT time point. Furthermore ΔVO2(peak–AT) correlated with ΔHR(peak–AT), ΔCO(peak–AT) and ΔLCWi(peak–AT) (R = 0.52, p < 0.0001, R = 0.49, p = 0.0001; and R = 0.49, p = 0.0001, respectively). ΔVO2(peak–rest) correlated with ΔHR(peak–rest), ΔCO(peak–rest), and ΔLCWi(peak–rest) (R = 0.47, p < 0.0001; R = 0.41, p = 0.002; and R = 0.43, p = 0.001, respectively).
Conclusion

ICG is a reliable method of assessing the cardiovascular response to exercise in patients with CAD. Some ICG parameters show definite correlations with parameters of cardiovascular capacity of proven clinical utility, such as peak VO2.
Flavonoid-modifying capabilities of the gut microbiome – an in silico study
Authors: Goris Tobias , Cuadrat Rafael , Braune Annett
Published: June 2021

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of human gut metagenome data and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes is now feasible. With sequences from characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and quantification of putative flavonoid-modifying enzymes was carried out. The results revealed that flavonoid-modifying enzymes are often highly abundant in bacteria hitherto not considered as flavonoid-modifying gut bacteria. The enzymes for the physiologically important daidzein to equol conversion, well studied in Slackia isoflavoniconvertens, were encoded only to a low extent in Slackia MAGs, but more abundant in Adlercreutzia equolifaciens and an uncharacterizedEggerthellaceae species. In addition, a high abundance of genes with a similarity of only about 35% in uncultivated Collinsella species suggest a hitherto uncharacterized Daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase (all three most abundant in Flavonifractor plautii) and O-demethylase (Intestinibacter bartlettii) homologs were of intermediate prevalence (several hundreds of MAGs). This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as key organisms in flavonoid modification by the human gut microbiota. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications which rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.
Synthesis of Finely Controllable Sizes of Au Nanoparticles on a Silica Template and Their Nanozyme Properties
Authors: Seong Bomi , Kim Jaehi , Kim Wooyeon , Lee Sang Hun , Pham Xuan-Hung , Jun Bong-Hyun
Published: June 2021

The precise synthesis of fine-sized nanoparticles is critical for realizing the advantages of nanoparticles for various applications. We developed a technique for preparing finely controllable sizes of gold nanoparticles (Au NPs) on a silica template using the seed-mediated growth and interval dropping methods. These Au NPs, embedded on silica nanospheres (SiO2@Au NPs), possess peroxidase-like activity as nanozymes and have several advantages over other nanoparticle-based nanozymes. We confirmed their peroxidase activity; in addition, factors affecting the activity were investigated by varying the reaction conditions such as concentrations of tetramethyl benzidine and H2O2, pH, particle amount, reaction time, and termination time. We found that SiO2@Au NPs are highly stable under long-term storage and reusable for five cycles. Our study, therefore, provides a novel method for controlling the properties of nanoparticles and for developing nanoparticle-based nanozymes.
Case Series: Four Cases of Anorexia Nervosa Concomitant with Central Adrenal Insufficiency
Authors: Matsubayashi Sunao , Tanaka Madoka , Hara Takeshi
Published: June 2021

Objective: Widespread attention has been paid to the misdiagnosis of life-threatening Addison's disease as anorexia nervosa. However, there are no reports on the possible comorbidity of Addison's disease and other adrenal insufficiencies with anorexia nervosa.Methods: A case-series presentation of anorexia nervosa concomitant with central adrenal insufficiency.Results: Four anorexia nervosa patients (21-35 years old, all females) complained of severe fatigue during their treatment. After a thorough examination of the hypothalamus-pituitary-adrenal axis using stimulation with a rapid adenocorticotropic hormone test of 250-µg Cortrosyn®, a corticotropin-releasing hormone test, and an insulin tolerance test, central adrenal insufficiency was diagnosed. Two of the four patients had a history of exogenous steroids for their history of comorbidity. One of the residual two patient had Rathke’s cleft cyst. After the initiation of hydrocortisone replacement the patient's fatigue symptoms improved and they　were able to return to school and their workplace. In some cases, their weight obsession was reduced after the initiation of hydrocortisone replacement.Conclusion: Anorexia nervosa may be concomitant with central adrenal insufficiency partly in relation to exogenous steroids used for their history of comorbidity, which needs to be kept in mind when treating such patients.Level of EvidenceLevel V, descriptive study.
Virus-Like Particles With FLAG-Tagged Envelope Protein as A Tetravalent Dengue Vaccine Candidate
Authors: Imagawa Toshifumi , Ito Masahiko , Matsuda Mami , Nakashima Kenji , Tokunaga Yuhei , Ohta Isao , Li Tian-Cheng , Suzuki Ryosuke , Suzuki Tetsuro
Published: June 2021

The global incidence of dengue, which is caused by dengue virus (DENV) infection, has grown dramatically in recent decades and secondary infection with heterologous serotype of the virus may cause severe symptoms. Efficacious dengue vaccines should be able to provide long-lasting immunity against all four DENV serotypes simultaneously. In this study, we constructed a novel vaccine platform based on tetravalent dengue virus-like particles (DENV-LPs) in which envelope (E) protein carried a FLAG tag sequence at the position located not only in the exterior loop on the protruding domain but outside of dimerization interface of the protein. We demonstrated an effective strategy to produce the DENV-LPs by transient transfection with expression plasmids for pre-membrane and E proteins of DENV-1 to DENV-4 in mammalian cells and to concentrate and purify them with one-step affinity chromatography. Characteristic features of VLPs such as particle size, shape and density were comparable to flavivirus-like particles reported. The neutralizing activity against all four DENV serotypes was successfully induced by immunization with the purified tetravalent VLPs in mice. Simple, one-step purification systems for VLP vaccine platforms using epitope-tagging strategy should be advantageous for vaccine development not only for dengue but for emerging pandemics in the future.
Antimicrobial Susceptibility, Multilocus Sequence Typing, and Virulence of Listeria Isolated From A Slaughterhouse
Authors: Wu Liting , Bao Hongduo , Yang Zhengquan , He Tao , Tian Yuan , Zhou Yan , Pang Maoda , Wang Ran , Zhang Hui
Published: June 2021

Background: Listeria monocytogenes is one of the deadliest foodborne pathogens, and the bacterium can tolerate severe environments through biofilm formation and antimicrobial resistance. The objective of this study was to investigate the antimicrobial susceptibility, resistance genes,virulence and molecular epidemiology about Listeria from meat processing environments. Methods: This study evaluated the antibiotic resistance and virulence of Listeria isolates from slaughtering and processing plants. All isolates were subjected to antimicrobial susceptibility testing by using a standard microbroth dilution method. The carrying of resistant genes were identified by Polymerase Chain Reaction (PCR). The multilocus sequence typing (MLST) was determined subtyping of the isolates and to characterize possible routes of contamination from meat processing environments. The virulence of different STs of L. monocytogenes isolates were evaluated by Caco-2 cells invasion assay. Results: A total of 59 Listeria isolates were identified from 320 samples, including 37 L. monocytogenes (62.71%). This study evaluated the virulence of L. monocytogenes and antibiotic resistance of Listeria isolates from slaughtering and processing plants. The susceptibility of these 59 isolates against eight antibiotics was analyzed, and the resistance levels to ceftazidime, ciprofloxacin, and lincomycin were as high as 98.31% (L. m 37; L. innocua 7; L. welshimeri 14), 96.61% (L. m 36; L. innocua 7; L. welshimeri 14), and 93.22% (L. m 35; L. innocua 7; L. welshimeri 13) respectively. Over 90% of the isolates were resistant to 3-6 antibiotics, indicating that Listeria isolated from meat processing environments has high antimicrobial resistance. Up to 60% of the isolates carried the tetracycline-resistance genes tetA and tetM. The frequencies of ermA, ermB, ermC, and aac(6’)-Ib were 16.95%, 13.56%, 15.25%, and 6.78%, respectively. Notably, the resistant phenotype and genotype did not match exactly, suggesting that the mechanisms of antibiotic resistance of these isolates were likely related to the processing environment. Multilocus sequence typing (MLST) revealed that 59 Listeria isolates were grouped into 10 sequence types (STs). The dominant L. monocytogenes STs were ST5, ST9, and ST121 in the slaughtering and processing plant of Jiangsu province. Moreover, ST5 subtypes exhibited high invasion in Caco-2 cells compared with ST9 and ST121. Conclusions: The results of this study predict a prevalence of Listeria contamination in the slaughtering and processing plant , and resistance of the ST5 subtypes isolates to the antimicrobials may cause potential public health risks.
ZFX expression is connected with improved survival in patients with breast cancer
Authors: Carney Gideon , Bush Duncan , Sellers Scarlet , Carpenter Roan , Hewitt Maira , Molloy Alistair , K James
Published: June 2021

We analyzed published tumor transcriptome data in conjunction with linked survival data to identify genes linked with breast cancer survival outcomes (1, 2). When comparing tumor transcriptomes based on 24-month survival, we discovered that the zinc-finger protein X-linked ZFX (3, 4) was among the most differentially expressed genes in both original and metastatic tumor tissues. ZFX expression was considerably enhanced in metastatic tumors of patients who survived more than 24 months, indicating that enhanced ZFX expression offers a survival advantage for patients with stage IV metastatic breast cancer.
The Resistance of Peanut to Soil-Borne Pathogens Improved by Rhizosphere Probiotics Under Calcium Treatment
Authors: Zhang Wei , Zhang Bo-wen , Li Lin , Yi Tu-yong , Hong Yan-yun
Published: June 2021

Background: Peanut (Arachis hypogaea L.) is an important oil and economic crop. Calcium can regulate plant autoimmunity, respond to biotic and abiotic stresses, and improve plant resistance to pathogens. The enrichment of beneficial microorganisms in the rhizosphere is related to plant disease resistance and soil development. The purpose was to analyze the differences of peanut rhizosphere microbial community structure between calcium treatment and control during two growth stages, and the reason that calcium application could improve peanut’s resistance to soil-borne pathogens.. Results: The 16S amplicon sequencing of rhizosphere microbiome showed that calcium application significantly enriched Serratia marcescens and other three dominant strains at the seedling stage. At the pod filling stage, ten dominant stains such as Sphingomonas changbaiensis and Novosphingobium panipatense were enriched by calcium. Serratia marcescens aseptic fermentation filtrate was mixed with PDA medium and inoculated with soil-borne pathogens, which could inhibit the growth of Fusarium solani and Aspergillus flavus at the seedling stage. The fermentation filtrate of Novosphingobium panipatense was mixed with PDA medium and inoculated with main pathogens, which could inhibit the growth of Sclerotium rolfsii and Leptosphaerulina arachidicola.Conclusions: Calcium application enhanced the ability of peanuts to resist pathogens by enriching specific dominant bacteria.
Sensing single molecule under micromanipulation to quantify nucleic acids
Authors: Zeng Qiang , Zhou Xiaoyan , Yang Yuting , Wang Jingan , Zhai Chunhui , Yu Hui
Published: June 2021

Rapid molecular diagnosis using nucleic acid biomarkers is important for timely identification of acute pathogenic infections. We introduce an active kinetic approach called sensing single molecule under micromanipulation (SSM3) to quantify nucleic acids, which circumvents hydrodynamic limits of reaction rate, sensitivity and specificity. We demonstrate the 15-minute assay to detect synthetic miRNAs with subfemtomolar limit of detection and high-confidence discrimination of single-base-pair mismatch.
Comparison of COVID-19 vaccine prioritization strategies
Authors: Chapman Lloyd , Shukla Poojan , Rodriguez-Barraquer Isabel , Shete Priya , Leon Tomas , Bibbins-Domingo Kirsten , Rutherford George , Schechter Robert , Lo Nathan
Published: June 2021

Background: For countries that have only recently started COVID-19 vaccinations, there remains a key public health question of who should be prioritized for early vaccination. Most vaccine prioritization analyses have only considered variation in risk of infection and death by age. We provide a more granular analysis with stratification by demographics, risk factors, and location. Methods: We used a simulation model to compare the impact of different prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout. We calibrated the model to demographic and location data on 28,175 COVID-19 deaths in California up to December 30, 2020, and incorporated variation in risk by occupation and comorbidity status using published estimates. We estimated the proportion of clinical cases, deaths and DALYs averted relative to a scenario of no vaccination for strategies prioritizing vaccination by a single risk factor (special population status (e.g. incarcerated individual), age, essential worker status, comorbidity status) or multiple risk factors (e.g. age and location). Results: We found that age-based targeting averted the most deaths (65% for 5 million individuals vaccinated) and DALYs (40%) of strategies targeting by a single risk factor and targeting essential workers averted the least deaths (33%) and DALYs (25%) over the first 6 months of vaccine rollout. However, targeting by two or more risk factors simultaneously averted up to 40% more DALYs. Conclusions: Our findings highlight the potential value of multiple-risk-factor targeting of COVID-19 vaccination. Where vaccine supply is limited and logistical challenges in vaccine delivery persist, age-based targeting offers a means of ensuring that vaccines reach those most at risk of poor health outcomes. If operational challenges can be overcome, more granular vaccination strategies that overlap age with other risk factors can be adopted.
Efficacy of Abdomen-Rubbing Gigong Exercise for Chronic Insomnia: Study Protocol for a Randomized Controlled Trial
Authors: Guan Chong , Cheng Ziji , Xie Fangfang , Wang Ruiping , Zhang Jing , Yao Fei , Fang Min
Published: June 2021

BackgroundInsomnia is a common sleeping disorder which affects the quality of life which can bring harms to physical and mental health of human beings and even economic development. Traditional Chinese medicine (TCM) plays an outstanding role in treating chronic diseases and alleviating their symptoms. Therefore, the purpose of this study is to assess the treatment efficacy in patients with insomnia treated with abdomen-rubbing qigong exercise (ARQE). In addition, the brain function changes of patients will be explored by resting state functional magnetic resonance imaging(rs-fMRI).Method/designThis trial is a randomized, single-blind, controlled study planned to transpire between July 1, 2020, and July 31, 2021. A sample size of 114 participants (57 per group) with chronic insomnia will be randomly assigned to receive ARQE or CBTI for 8 weeks. The study duration will be 13 weeks, including a 1-week screening period, 8 weeks of intervention, and another 4 weeks of follow-up. The primary outcome is the Pittsburgh sleep quality index scores. Secondary outcomes include insomnia severity index, gastrointestinal symptom rating scale, the Hamilton depression scale, and rs-fMRI scan. The adverse events will be in control. DiscussionThe results of this study will help to clarify the efficacy of ARQE in the treatment of insomnia, and try to use rs-fMRI technology to explore the brain function changes of ARQE in improving sleep quality in patients with insomnia disorder. If the results are as expected, this study will provide high-quality evidence for the treatment of insomnia with ARQE. Trial registrationChina Clinical Registration Agency (registration number: ChiCTR1900028009). Registered on 19 December 2019. http://www.chictr.org.cn/showproj.aspx?proj=46679
Investigating the Factors Affecting Myopia in Retinopathy of Prematurity after Laser Treatment
Authors: Asano Shotaro , Inoue Tatsuya , Kure Kana , Kitano Marie , Fujita Asahi , Nagahara Miyuki , Asaoka Ryo , Obata Ryo
Published: June 2021

To elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes, we investigated the effect of the number of laser shots applied on the myopic variables. A total of 33 eyes of 17 infants with laser-treated ROP were included. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age- and axial length (AL)-matched control group without ROP was prepared to compare ocular structural parameters. Although there was no statistical difference in AL between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p < 0.001). SE was associated with AL, corneal refraction (CR), and crystalline lens power (CLP) in the ROP group. Of these three factors (AL, CR, and CLP), only CLP was significantly correlated with the number of laser shots applied (p = 0.003); no correlations were observed between the number of laser shots and AL or CR (p = 0.15 and 0.10, respectively). Very similar tendency was observed in the analysis of the difference between right and left eyes in each child.
Identifies Oncogene PDRG1 as a Potential Prognostic Biomarker in Hepatocellular Carcinoma: A Study Based on Bioinformatics Analysis
Authors: Lin Jianyang , Ding Xin , Chen Zhihong , Pan Huiwen , Wu Yinyan , Zhao Kun
Published: June 2021

Background: Hepatocellular carcinoma (HCC) is globally recognized as one of the most frequently occurring primary malignant liver tumor, making the identification of HCC biomarkers critically important. Methods: The gene expression and clinicopathology analysis, GO enrichment analysis (GSEA) and immune infiltration analysis are based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. The statistical analysis was conducted in R. The protein-protein interaction (PPI) networks was constructed and the module analysis was performed using STRING and Cytoscape. Construction and evaluation of prognostic model based on PDRG1 and tumor status used nomogram and calibration.Results: The expression of PDRG1 was significantly higher in HCC tumor tissues. High expression of PDRG1 in HCC patients was significantly correlated with poor Overall Survival and adverse clinicopathological features including advanced T stage, residual tumor, histologic grade, vascular invasion, TP53 status and AFP level. GO, GSEA revealed that PDRG1 was closely correlated with DNA repair, DNA replication and cell cycle. Spearman correlation showed high expression of PDRG1 was significantly correlated with Th2 cells level in HCC patients. Nomograms based on PDRG1 and tumor stage had good predictive performance on overall survival rates of HCC patients.Conclusions: Our study demonstrated the potential significance of PDRG1 expression in the diagnosis and prognosis of HCC and further explored the function in HCC. Further study is still needed to confirm these results. The underlying mechanism revealed by these results provides a basis for PDRG1 as a new molecular target for the prevention and treatment of HCC.