bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive phylogeographic and phylodynamic analyses of global Senecavirus A
Authors: Gao Han , Chen Yong-jie , Xu Xiu-qiong , Xu Zhi-ying , Xu Si-jia , Xing Jia-bao , Liu Jing , Zha Yun-feng , Sun Yan-kuo , Zhang Gui-hong
Published: September 2022

Senecavirus A (SVA) is a member of the genus Senecavirus in the family Picornaviridae that infects pigs and shows symptoms similar to foot and mouth diseases and other vesicular diseases. It is difficult to prevent, thus, causing tremendous economic loss to the pig industry. However, the global transmission routes of SVA and its natural origins remain unclear. In this study, we processed representative SVA sequences from the GenBank database along with 10 newly isolated SVA strains from the field samples collected from our lab to explore the origins, population characteristics, and transmission patterns of SVA. The SVA strains were firstly systematically divided into eight clades including Clade I–VII and Clade Ancestor based on the maximum likelihood phylogenetic inference. Phylogeographic and phylodynamics analysis within the Bayesian statistical framework revealed that SVA originated in the United States in the 1980s and afterward spread to different countries and regions. Our analysis of viral transmission routes also revealed its historical spread from the United States and the risk of the global virus prevalence. Overall, our study provided a comprehensive assessment of the phylogenetic characteristics, origins, history, and geographical evolution of SVA on a global scale, unlocking insights into developing efficient disease management strategies.
Biosynthesis of silver nanoparticles from Syzygium cumini leaves and their potential effects on odontogenic pathogens and biofilms
Authors: Bernardo Wagner Luis de Carvalho , Boriollo Marcelo Fabiano Gomes , Tonon Caroline Coradi , da Silva Jeferson Júnior , Oliveira Mateus Cardoso , de Moraes Fernando Cruz , Spolidorio Denise Madalena Palomari
Published: September 2022

This study analyzed the antimicrobial and antibiofilm action and cytotoxicity of extract (HEScL) and silver nanoparticles (AgNPs-HEScL) from Syzygium cumini leaves. GC–MS, UV–Vis, EDX, FEG/SEM, DLS and zeta potential assays were used to characterize the extract or nanoparticles. Antimicrobial, antibiofilm and cytotoxicity analyses were carried out by in vitro methods: agar diffusion, microdilution and normal oral keratinocytes spontaneously immortalized (NOK-SI) cell culture. MICs of planktonic cells ranged from 31.2–250 (AgNPs-HEScL) to 1,296.8–10,375 μg/ml (HEScL) for Actinomyces naeslundii, Fusobacterium nucleatum, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Streptococcus oralis, Veillonella dispar, and Candida albicans. AgNPs-HEScL showed antibiofilm effects (125–8,000 μg/ml) toward Candida albicans, Streptococcus mutans and Streptococcus oralis, and Staphylococcus aureus and Staphylococcus epidermidis. The NOK-SI exhibited no cytotoxicity when treated with 32.8 and 680.3 μg/ml of AgNPs-HEScL and HEScL, respectively, for 5 min. The data suggest potential antimicrobial and antibiofilm action of HEScL, and more specifically, AgNPs-HEScL, involving pathogens of medical and dental interest (dose-, time- and species-dependent). The cytotoxicity of HEScL and AgNPs-HEScL detected in NOK-SI was dose- and time-dependent. This study presents toxicological information about the lyophilized ethanolic extract of S. cumini leaves, including their metallic nanoparticles, and adds scientific values to incipient studies found in the literature.
Identification of the hub and prognostic genes in liver hepatocellular carcinoma via bioinformatics analysis
Authors: Gao Qiannan , Fan Luyun , Chen Yutong , Cai Jun
Published: September 2022

Hepatocellular carcinoma (HCC) is a common malignancy. However, the molecular mechanisms of the progression and prognosis of HCC remain unclear. In the current study, we merged three Gene Expression Omnibus (GEO) datasets and combined them with The Cancer Genome Atlas (TCGA) dataset to screen differentially expressed genes. Furthermore, protein‒protein interaction (PPI) and weighted gene coexpression network analysis (WGCNA) were used to identify key gene modules in the progression of HCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that the terms were associated with the cell cycle and DNA replication. Then, four hub genes were identified (AURKA, CCNB1, DLGAP5, and NCAPG) and validated via the expression of proteins and transcripts using online databases. In addition, we established a prognostic model using univariate Cox proportional hazards regression and least absolute shrinkage and selection operator (LASSO) regression. Eight genes were identified as prognostic genes, and four genes (FLVCR1, HMMR, NEB, and UBE2S) were detrimental gens. The areas under the curves (AUCs) at 1, 3 and 5 years were 0.622, 0.69, and 0.684 in the test dataset, respectively. The effective of prognostic model was also validated using International Cancer Genome Consortium (ICGC) dataset. Moreover, we performed multivariate independent prognostic analysis using multivariate Cox proportional hazards regression. The results showed that the risk score was an independent risk factor. Finally, we found that all prognostic genes had a strong positive correlation with immune infiltration. In conclusion, this study identified the key hub genes in the development and progression of HCC and prognostic genes in the prognosis of HCC, which was significant for the future diagnosis and prognosis of HCC.
Insights from DOCK2 in cell function and pathophysiology
Authors: Ji Lulin , Xu Shuquan , Luo Haiqing , Zeng Fanwei
Published: September 2022

Dedicator of cytokinesis 2 (DOCK2) can activate the downstream small G protein Rac and regulate cytoskeletal reorganization. DOCK2 is essential for critical physiological processes such as migration, activation, proliferation, and effects of immune cells, including lymphocytes, neutrophils, macrophages, and dendritic cells. For example, DOCK2 is involved in the development and activation of T and B lymphocytes by affecting synapse formation and inhibiting the development of the Th2 lineage by downregulating IL-4Rα surface expression. Not only that, DOCK2 may be a molecular target for controlling cardiac transplant rejection and Alzheimer’s disease (AD). Patients with defects in the DOCK2 gene also exhibit a variety of impaired cellular functions, such as chemotactic responses of lymphocytes and reactive oxygen species (ROS) production by neutrophils. To date, DOCK2 has been shown to be involved in the development of various diseases, including AD, pneumonia, myocarditis, colitis, tumors, etc. DOCK2 plays different roles in these diseases and the degree of inflammatory response has a different impact on the progression of disease. In this paper, we present a review of recent advances in the function of DOCK2 in various immune cells and its role in various diseases.
Behavioral effects in disorders of consciousness following transcranial direct current stimulation: A systematic review and individual patient data meta-analysis of randomized clinical trials
Authors: Xu Zeyu , Zheng Ruizhe , Xia Tiantong , Qi Zengxin , Zang Di , Wang Zhe , Wu Xuehai
Published: September 2022

Background

In patients with Disorders of Consciousness (DoC), recent evidence suggests that transcranial direct current stimulation (tDCS) can be a promising intervention for them. However, there has been little agreement on the treatment effect and the optimal treatment strategy for the tDCS in patients with DoC.

Objective

In this meta-analysis of individual patient data (IPD), we assess whether tDCS could improve DoC patients' behavioral performance. We also determine whether these treatment effects could be modified by patient characteristics or tDCS protocol.

Methods

We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials until 7 April 2022 using the terms “persistent vegetative state,” “minimally conscious state,” “disorder of consciousness,” or “unresponsive wakefulness syndrome,” and “transcranial direct current stimulation” to identify Randomized Controlled Trials (RCTs) in English-language publications. Studies were eligible for inclusion if they reported pre- and post-tDCS Coma Recovery Scale-Revised (CRS-R) scores. From the included studies, patients who had incomplete data were excluded. We performed a meta-analysis to assess the treatment effect of the tDCS compared with sham control. Additionally, various subgroup analyses were performed to determine whether specific patient characteristics could modify the treatment effect and to find out the optimal tDCS protocol.

Results

We identified 145 papers, but eventually eight trials (including 181 patients) were included in the analysis, and one individual data were excluded because of incomplete data. Our meta-analysis demonstrated a mean difference change in the CRS-R score of 0.89 (95% CI, 0.17–1.61) between tDCS and sham-control, favoring tDCS. The subgroup analysis showed that patients who were male or with a minimally conscious state (MCS) diagnosis were associated with a greater improvement in CRS-R score. We also found that patients who underwent five or more sessions of tDCS protocol had a better treatment effect than just one session.

Conclusion

The result shows that tDCS can improve the behavioral performance of DoC patients. The heterogeneity of the treatment effect existed within the patients' baseline conditions and the stimulation protocol. More explorative studies on the optimal tDCS protocol and the most beneficial patient group based on the mechanism of tDCS are required in the future.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42022331241.
Association of fruits, vegetables, and fiber intake with COVID-19 severity and symptoms in hospitalized patients: A cross-sectional study
Authors: Tadbir Vajargah Kiana , Zargarzadeh Nikan , Ebrahimzadeh Armin , Mousavi Seyed Mohammad , Mobasheran Parnia , Mokhtari Pari , Rahban Habib , Găman Mihnea-Alexandru , Akhgarjand Camellia , Taghizadeh Mohsen , Milajerdi Alireza
Published: September 2022

Background and aims

Fruits and vegetables are rich in fiber and a good source of anti-inflammatory and immune-boosting vitamins, minerals, and antioxidants. We investigated the association between fruits, vegetables, and fiber intake and severity of COVID-19 and related symptoms in hospitalized patients.

Methods

A total of 250 COVID-19 hospitalized patients aged 18 to 65 years were recruited for this cross-sectional study in Kashan, Iran, between June and September of 2021. Dietary intakes were assessed using an online validated 168-item food frequency questionnaire (FFQ). COVID-19 severity and symptoms were evaluated using the National Institutes of Health (NIH) COVID-19 Treatment Guidelines. Moreover, we examined COVID-19 symptoms, inflammatory biomarkers, and additional factors.

Results

The mean age of participants was 44.2 ± 12.1 years, and 46% had severe COVID-19. Patients with higher consumption of fruits (OR: 0.28; 95% CI: 0.14-0.58, P-trend <0.001), vegetables (OR: 0.33; 95% CI: 0.16-0.69, P-trend <0.001), and dietary fiber (OR: 0.25; 95% CI: 0.12-0.53, P-trend <0.001) had lower odds of having severe COVID-19. In addition, they had shorter hospitalization and convalescence periods, lower serum C-reactive protein (CRP), and a reduced risk of developing COVID-19 symptoms such as sore throat, nausea and vomiting, dyspnea, myalgia, cough, weakness, fever, and chills.

Conclusion

Higher consumption of fruits, vegetables, and fiber was inversely linked with COVID-19 severity, clinical symptoms, hospitalization and convalescence duration, and CRP concentrations. The results should be interpreted with caution in light of the limitations, and prospective cohort studies are required to further evaluate these findings.
Association between maternal erythrocyte polyunsaturated fatty acid levels during pregnancy and offspring weight status: A birth cohort study
Authors: Wu Shengchi , Zhao Feng , He Yannan , He Tingchao , Duan Sufang , Feng Gang , Chen Yujing , Wang Xin , Szeto Ignatius Man-Yau , Lin Lizi , Cai Li
Published: September 2022

Background

The findings of the association between maternal polyunsaturated fatty acid (PUFA) levels during pregnancy and offspring weight status are controversial. Furthermore, few studies have focused on Asian populations or used erythrocyte membranes as biological markers. We aimed to examine the associations between maternal erythrocyte PUFA and offspring weight status within the first 2 years among the Chinese population.

Materials and methods

A total of 607 mother-child pairs were recruited from a birth cohort. Maternal erythrocyte n-3 and n-6 PUFA during pregnancy were measured by gas chromatography, and the ratio of PUFA was calculated. Weight- and body mass index (BMI)-for-age z (WAZ and BAZ) scores were calculated for offspring at 1, 3, 6, 8, 12, 18, and 24 months of age. The risk of overweight and obesity was defined by the WHO criterion. The Generalized Estimating Equation (GEE) model was carried out for repeated anthropometric data within 2 years of age.

Results

Maternal erythrocyte docosapentaenoic acid (DPA, n-3) was inversely associated with offspring BAZ score [tertile 2 vs. tertile 1, β: −0.18 (−0.29, −0.00)]. Higher maternal erythrocyte arachidonic acid (AA) was inversely associated with lower offspring WAZ and BAZ [tertile 3 vs. tertile 1, β: −0.18 (−0.35, −0.02), −0.22 (−0.38, −0.06), respectively]. Furthermore, higher maternal erythrocyte AA [tertile 3 vs. tertile 1, odds ratio [OR]: 0.52 (0.36, 0.75), ptrend < 0.001] and total n-6 PUFA [tertile 3 vs. tertile 1, OR: 0.56 (0.39, 0.81), ptrend = 0.002] were associated with decreased risk of overweight and obesity in offspring. Maternal erythrocyte n-6/n-3 PUFA and AA/eicosapentaenoic acid (EPA) ratios were not associated with offspring weight status.

Conclusion

Maternal erythrocyte PUFA might influence offspring weight status within 2 years of age in the Chinese population. Further Asian studies are still needed.
The gastrointestinal and microbiome impact of a resistant starch blend from potato, banana, and apple fibers: A randomized clinical trial using smart caps
Authors: Hanes Douglas , Nowinski Brent , Lamb Joseph J. , Larson Ilona A. , McDonald Daniel , Knight Rob , Song Se Jin , Patno Noelle
Published: September 2022

The gastrointestinal (GI) impact of fibers including resistant starch (RS) consumption depends on various types and amounts of fibers, the initial microbiome states, and accurate intake measurements. A randomized clinical trial evaluated the GI impact of varying doses of a novel resistant starch blend (RSB) with smart cap monitoring. RSB contained at least 50% RS and was a proprietary mixture of a potato starch, green banana flour, and apple fiber powder (a source of apple pectin, not resistant starch). The study design randomized participants to one of four arms: 10 g/day of potato starch (0 RSB), 10 g/day of RSB, 10 to 20 to 20 g/day of RSB or 10 to 20 to 30 g/day RSB for two-week intervals over 6 weeks. Results confirmed that while resistant starch of approximately 5 g per day improves GI symptoms at 2, 4, and 6 weeks, it did not demonstrate a detectable effect on short chain fatty acids. Increasing doses of the blend (RSB) led to a decrease in the diarrhea score. Using an estimate of total consumption of RSB based on smart cap recordings of container openings and protocol-specified doses of RSB, a reduction in the sleep disturbance score was associated with higher RSB dose. The exploratory microbiome evaluation demonstrated that among the 16S rRNA gene sequences most associated with the consumption of the novel blend RSB, two belong to taxa of notable interest to human health: Faecalibacterium and Akkermansia.
A case report of adenofibroma arising from the seminal vesicle: A rare giant pelvic mass
Authors: Lu Youyi , Sun Di , Wu Jitao
Published: September 2022

Primary seminal vesicle tumors are extremely rare. Several rare pathological types of primary seminal vesicle tumors have been reported, such as adenocarcinoma, but there is no report on adenofibroma. We report the first case of adenofibroma arising from the seminal vesicle. A 50-year-old man, with no history or clinical evidence of any other tumors, accidentally found a pelvic mass during an ultrasound examination. As the mass grew, the patient developed mild constipation, without genitourinary or other symptoms. All laboratory examinations were normal. MRI of the pelvis revealed a mixed density, measuring 11.7×9.9×8.2cm, well circumscribed mass. The rectum, bladder, prostate and lymph nodes were normal. We successfully performed the open surgery and removed the mass. Histopathological results confirmed that the mass was a primary seminal vesicle adenofibroma. In literature, we found that for biphasic differentiated tumors, it is easy to reduce the accuracy of pathological diagnosis because of insufficient puncture. Therefore, preoperative puncture biopsy for seminal vesicle tumors should be investigated further.
The effects of radiation therapy on the macrophage response in cancer
Authors: Beach Callum , MacLean David , Majorova Dominika , Arnold James N. , Olcina Monica M.
Published: September 2022

The efficacy of radiotherapy, a mainstay of cancer treatment, is strongly influenced by both cellular and non-cellular features of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a heterogeneous population within the TME and their prevalence significantly correlates with patient prognosis in a range of cancers. Macrophages display intrinsic radio-resistance and radiotherapy can influence TAM recruitment and phenotype. However, whether radiotherapy alone can effectively “reprogram” TAMs to display anti-tumor phenotypes appears conflicting. Here, we discuss the effect of radiation on macrophage recruitment and plasticity in cancer, while emphasizing the role of specific TME components which may compromise the tumor response to radiation and influence macrophage function. In particular, this review will focus on soluble factors (cytokines, chemokines and components of the complement system) as well as physical changes to the TME. Since the macrophage response has the potential to influence radiotherapy outcomes this population may represent a drug target for improving treatment. An enhanced understanding of components of the TME impacting radiation-induced TAM recruitment and function may help consider the scope for future therapeutic avenues to target this plastic and pervasive population.
Research progress on microRNA-1258 in the development of human cancer
Authors: Qian Mengjia , Xia Yuke , Zhang Gong , Yu Han , Cui Yiyao
Published: September 2022

microRNAs (miRNAs) are small endogenous RNAs composed of 20-22 nucleotides that do not encode proteins, which regulate the expression of downstream genes by targeting the 3’ untranslated region of mRNA. Plentiful research has demonstrated that miRNAs participate in the initiation and development of diverse diseases and malignant tumors. miR-1258 exerts great influence on tumors, including tumor growth, distant metastasis, migration, invasion, chemosensitivity, cell glycolysis, apoptosis, and stemness. Interestingly, miR-1258 is a miRNA with explicit functions and has been investigated to act as a tumor suppressor in studies on various types of tumors. With accumulating research on miR-1258, it has been found to be used as a biomarker in the early diagnosis and prognosis prediction of tumor patients. In this review, we outline the development of miR-1258 research, describe its regulatory network, and discuss its roles in cancer. Additionally, we generalize the potential clinical applications of miR-1258. This review offers emerging perspectives and orientations for further comprehending the function of miR-1258 as a diagnostic and prognostic biomarker and potent therapeutic target in cancer.
Transplant or dialysis: What’s the better choice for RCC-induced ESRD patients? A 20-year analysis of OPTN/UNOS data
Authors: Hao Xiaowei , Lai Wenhui , Xia Xinze , Xu Junnan , Wu Yangyang , Lv Chao , Lv Kaikai , Huang Shuai , Luo Zhenjun , Meng Qingyang , Yuan Qing , Dong Jun
Published: September 2022

Purpose

The incidence of end-stage renal disease (ESRD) caused by renal cell carcinoma (RCC) is increasing with the high prevalence of RCC as well as those with treatment-related renal function impairment. Worries about tumor recurrence after transplant-related immunosuppression hinder the recommendation of kidney transplantation for RCC-induced ESRD patients. However, no direct analysis has been performed to identify whether kidney transplantation can offer better survival than maintaining dialysis.

Materials and methods

This retrospective population-based cohort study was based on Organ Procurement and Transplantation Network data released in March 2021. Characteristics and outcomes were compared, including the patient and graft survival of candidates and recipients with RCC-induced ESRD etiology as well as other primary diseases.

Results

Patients with RCC-induced ESRD were older; more likely to be male, White, and obese; and more likely to have a history of diabetes and dialysis. They also had higher creatinine levels, more delayed graft function, more primary non-function, and higher Kidney Donor Profile Index score donors, compared with the glomerulonephritis (GN) group. While waiting, RCC candidates suffered the worst outcomes of all groups, a 44% (adjusted hazard ratio [aHR], 1.44 [1.27–1.62]) higher risk of removal than GN patients. After transplantation, RCC recipients demonstrated comparable patient survival and better graft survival (p=0.21 and p=0.13, respectively). Compared with still-waiting RCC patients, the RCC recipients who received kidney transplants had significantly better outcomes (13.6 [9.3–17.8] vs. 61 [52–68.4] %), decreasing the death or deteriorating risk by 84% (aHR, 0.16 [0.13–0.20]).

Conclusions

Patients with RCC-induced ESRD can dramatically benefit from kidney transplantation. Hence, these patients should not be limited to transplantation by strict strategies or a delayed waiting time out of their malignancy history.
SVMMDR: Prediction of miRNAs-drug resistance using support vector machines based on heterogeneous network
Authors: Duan Tao , Kuang Zhufang , Deng Lei
Published: September 2022

In recent years, the miRNA is considered as a potential high-value therapeutic target because of its complex and delicate mechanism of gene regulation. The abnormal expression of miRNA can cause drug resistance, affecting the therapeutic effect of the disease. Revealing the associations between miRNAs-drug resistance can help in the design of effective drugs or possible drug combinations. However, current conventional experiments for identification of miRNAs-drug resistance are time-consuming and high-cost. Therefore, it’s of pretty realistic value to develop an accurate and efficient computational method to predicting miRNAs-drug resistance. In this paper, a method based on the Support Vector Machines (SVM) to predict the association between MiRNA and Drug Resistance (SVMMDR) is proposed. The SVMMDR integrates miRNAs-drug resistance association, miRNAs sequence similarity, drug chemical structure similarity and other similarities, extracts path-based Hetesim features, and obtains inclined diffusion feature through restart random walk. By combining the multiple feature, the prediction score between miRNAs and drug resistance is obtained based on the SVM. The innovation of the SVMMDR is that the inclined diffusion feature is obtained by inclined restart random walk, the node information and path information in heterogeneous network are integrated, and the SVM is used to predict potential miRNAs-drug resistance associations. The average AUC of SVMMDR obtained is 0.978 in 10-fold cross-validation.
Extended endoscopic endonasal approach for resecting anterior intrinsic third ventricular craniopharyngioma
Authors: Zhou Yuefei , Wei Jialiang , Jin Tao , Hei Yue , Jia Pengfei , Lin Jincai , Yang Shuangwu , Jiang Xiaofan , Liu Weiping , Gao Dakuan
Published: September 2022

Background

The surgical treatment of the extended endoscopic endonasal approach (EEEA) is a safe and effective treatment for suprasellar craniopharyngiomas. However, due to damage to the hypothalamus and third ventricle floor (TVF), EEEA is generally regarded as unsuitable in treating intrinsic third ventricle craniopharyngioma (ITVC) that is entirely within the third ventricle. Until now, there have been only a small number of reports using EEEA to treat TVC via a supra-infrachiasmatic approach. Given that the translamina terminalis (TLT) corridor was used in the transcranial subfrontal approach, EEEA via a suprachiasmatic approach may be feasible and practical to treat ITVC. In the current study, we accumulated experience applying the suprachiasmatic translamina terminalis (STLT) corridor for anterior treatment of ITVC.

Methods

From March 2016 to December 2020, 14 patients with ITVC in our center were analyzed retrospectively. All patients underwent surgery by EEEA via an STLT corridor. The multilayer reconstruction technique was adopted to achieve skull base reconstruction. Data concerning the patient’s tumor resection, vision, hypophyseal hormone, and complications were collected.

Results

Gross-total resection was achieved in 13 (92.8%) of14 patients, with achievement of near-total (90%) resection in the remaining 1 patient. Nine cases (64.3%) were papillary craniopharyngiomas, and the other 5 cases were adamantinomatous subtypes. Postoperatively, 3 patients with pituitary insufficiency received hormone replacement therapy. No permanent diabetes insipidus or hypothalamic obesity was found. All pairs showed significant improvement or stability in vision except 1 patient who encountered visual deterioration. No other neurological deficit occurred postoperatively. Observation results for the exudation of nasal tissue and the length of hospitalization were satisfactory. After a mean follow-up period of 26.2 months, tumor recurrence was not observed.

Conclusion

TLT is a minimally invasive corridor used in EEEA for treating anterior ITVC without increasing risks of visual and hormonal deficits. The multilayered reconstruction technique we used is a safe and effective method for achieving watertight closure and avoiding cerebrospinal fluid leaks and infection. The endonasal approach via STLT provides a new, safe and efficacious operative strategy that should be considered a surgical alternative in treating ITVC.
The correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction
Authors: Milivojevic Sasa , Zelenovic Aleksandra , Milin-Lazovic Jelena , Radojicic Ognjen , Laketic Darko , Dasic Ivana , Milic Natasa , Radojicic Zoran
Published: September 2022

Background

The aim of this study was to examine the correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction.

Methods

Between 2014 and 2022, we prospectively evaluated 81 consecutive spina bifida children with neurogenic bowel and bladder dysfunction (35 boys and 46 girls, mean age 9.5 ± 3.4 years). All patients underwent echosonographic measurement of transverse rectal diameter and urodynamic studies.

Results

We found a strong negative correlation between transverse rectal diameter and maximum bladder capacity (r = −0.682, p < 0.001) and compliance (r = −0.690, p < 0.001). There was also a strong positive correlation between transverse rectal diameter and maximal detrusor pressure (r = 0.650, p < 0.001), leak point pressure (r = 0.793, p < 0.001), and PVR (r = 0.762, p < 0.001). In ROC analysis, transverse rectal diameter demonstrated good performance for distinguishing children with upper urinary tract deterioration, with an AUC of 0.857 (95% CI 0.761–0.953). A transverse rectal diameter ≥40 mm was 83.3% sensitive and 100% specific for the diagnosis of unfavorable urodynamic patterns.

Conclusion

There is a correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction. Ultrasonographically assessed transverse rectal diameter of ≥40 mm may be used as a risk factor for upper urinary tract deterioration (unfavorable urodynamic findings). We suggest the transverse rectal diameter echosonographic measurement use as an integral part of the diagnostic approach in children with neurogenic bowel and bladder dysfunction, as it can help decision-making while waiting for urodynamic testing.
TSLP bronchoalveolar lavage levels at baseline are linked to clinical disease severity and reduced lung function in children with asthma
Authors: Chorvinsky Elizabeth , Nino Gustavo , Salka Kyle , Gaviria Susana , Gutierrez Maria J. , Pillai Dinesh K.
Published: September 2022

Rationale

Thymic stromal lymphopoietin (TSLP) is increasingly recognized as a key molecule in asthma pathogenesis and as a promising therapeutic target in adults. In contrast, in asthmatic children the clinical relevance of TSLP secretion in the lower airways has been remarkably understudied. We tested the hypothesis that pulmonary TSLP levels in asthmatic children correlate with clinical severity, airway inflammation and lower airway obstruction.

Methods

Bronchoalveolar lavage (BAL) samples and relevant clinical data were collected from asthmatic children undergoing clinically indicated bronchoscopy at Children's National Hospital in Washington D.C. Protein levels of TSLP, IL-5, IL-1β, and IL-33 were quantified in BAL at baseline and correlated with individual severity and clinical features including spirometry, serum IgE and eosinophils, BAL neutrophil and eosinophil counts.

Results

We enrolled a total of 35 asthmatic children (median age: 9 years). Pediatric subjects with severe asthma had greater TSLP BAL levels at baseline relative to mild or moderate asthmatic subjects (p = 0.016). Asthmatic children with the highest TSLP levels (>75th percentile) had higher IL-5 and IL-1β BAL levels and greater lower airway obstruction (lower FEV1/FVC ratios).

Conclusion

Our study demonstrates for the first time that higher pulmonary TSLP levels obtained at baseline are linked to asthma disease severity in a subset of children. These data indicate that TSLP may play a key role in the pathogenesis of pediatric asthma and thus provide initial support to investigate the potential use of anti-TSLP biologics to treat severe uncontrolled asthmatic children.
Novel compound heterozygous CCDC40 mutations in a familial case of primary ciliary dyskinesia
Authors: Zhao Liqing , Huang Suqiu , Wei Wei , Zhang Bingyao , Shi Wenxiang , Liang Yongzhou , Xu Rang , Wu Yurong
Published: September 2022

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by motile ciliary dysfunction and impaired ultrastructure. Despite numerous studies, the genetic basis for about 30% of PCD cases remains to be elucidated. Here, we present the identification and functional analysis of two novel mutations in the gene encoding coiled-coil domain-containing protein 40 (CCDC40), which are found in a familial case of PCD. These novel CCDC40 mutations, NM_017950.4: c.2236-2delA and c.2042_2046delTCACA, NP_060420.2: p.(Ile681fs), were identified by whole-exome sequencing (WES). Sanger sequencing was then performed to confirm the WES results and determine the CCDC40 gene sequences of the proband’s parents. The c.2042_2046delTCACA mutation disrupts the reading frame of the protein and is therefore predicted to produce a non-functional protein. Using a minigene assay with the pcDNA3.1(+) plasmid, we further investigated the potential pathogenic effects of the c.2236-2delA mutation and found that this mutation leads to formation of a truncated protein via splicing disruption. Thus, in summary, we identified two mutations of the CCDC40 gene that can be considered pathogenic compound heterozygous mutations in a case of familial PCD, thereby expanding the known mutational spectrum of the CCDC40 gene in this disease.
Uncovering the pharmacology of Ginkgo biloba folium in the cell-type-specific targets of Parkinson’s disease
Authors: Yan Yu-Chen , Xu Zhi-Heng , Wang Jian , Yu Wen-Bo
Published: September 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disease with a fast-growing prevalence. Developing disease-modifying therapies for PD remains an enormous challenge. Current drug treatment will lose efficacy and bring about severe side effects as the disease progresses. Extracts from Ginkgo biloba folium (GBE) have been shown neuroprotective in PD models. However, the complex GBE extracts intertwingled with complicated PD targets hinder further drug development. In this study, we have pioneered using single-nuclei RNA sequencing data in network pharmacology analysis. Furthermore, high-throughput screening for potent drug-target interaction (DTI) was conducted with a deep learning algorithm, DeepPurpose. The strongest DTIs between ginkgolides and MAPK14 were further validated by molecular docking. This work should help advance the network pharmacology analysis procedure to tackle the limitation of conventional research. Meanwhile, these results should contribute to a better understanding of the complicated mechanisms of GBE in treating PD and lay the theoretical ground for future drug development in PD.
BNTA alleviates inflammatory osteolysis by the SOD mediated anti-oxidation and anti-inflammation effect on inhibiting osteoclastogenesis
Authors: Wang Huidong , Cao Xiankun , Guo Jiadong , Yang Xiao , Sun Xiaojiang , Fu Zhiyi , Qin An , Wu Yujie , Zhao Jie
Published: September 2022

Abnormal activation and overproliferation of osteoclast in inflammatory bone diseases lead to osteolysis and bone mass loss. Although current pharmacological treatments have made extensive advances, limitations still exist. N-[2-bromo-4-(phenylsulfonyl)-3-thienyl]-2-chlorobenzamide (BNTA) is an artificially synthesized molecule compound that has antioxidant and anti-inflammatory properties. In this study, we presented that BNTA can suppress intracellular ROS levels through increasing ROS scavenging enzymes SOD1 and SOD2, subsequently attenuating the MARK signaling pathway and the transcription of NFATc1, leading to the inhibition of osteoclast formation and osteolytic resorption. Moreover, the results also showed an obvious restrained effect of BNTA on RANKL-stimulated proinflammatory cytokines, which indirectly mediated osteoclastogenesis. In line with the in vitro results, BNTA protected LPS-induced severe bone loss in vivo by enhancing scavenging enzymes, reducing proinflammatory cytokines, and decreasing osteoclast formation. Taken together, all of the results demonstrate that BNTA effectively represses oxidation, regulates inflammatory activity, and inhibits osteolytic bone resorption, and it may be a potential and exploitable drug to prevent inflammatory osteolytic bone diseases.
Kaempferol attenuates nonalcoholic steatohepatitis by regulating serum and liver bile acid metabolism
Authors: Lu Yifei , Shao Mingmei , Zhang Caiyun , Xiang Hongjiao , Wang Junmin , Wu Tao , Ji Guang
Published: September 2022

Objective: Changes in bile acids (BAs) are increasingly recognized as potential targets for non-alcoholic steatohepatitis (NASH). Kaempferol has been proved to be anti-inflammatory and reduce the disorder of lipid metabolism. In order to analyze the BA profile in NASH mice and determine the predictive biomarkers of kaempferol treatment, serum-targeted metabolomics and liver tissue RNA sequencing (RNA-seq) were carried out.

Design: Six normal control mice (NC group), eight HFD-fed mice (HFD group), and eight kaempferol-treated HFD-fed mice (HFD + KP group) were included in the present study. Ultra-performance liquid chromatography coupled to a tandem mass spectrometry system (UPLC-MS/MS) was used to quantify serum and liver BAs, and RNA-seq was used to quantify liver differentially expressed genes related to BA metabolism.

Results: The serum levels of CA, βMCA, UDCA, and 12-DHCA, as well as ωMCA in both the serum and liver, were significantly decreased in the HFD group compared with those in the NC group, and kaempferol can increase the serum levels of βMCA, UDCA, and ωMCA and the liver level of 12-DHCA. The serum levels of TDCA, THDCA, TUDCA, TDCA/CA, and TDCA/DCA were significantly increased in the HFD group compared with those of the NC group, and kaempferol can decrease them. Furthermore, NASH mice had a higher liver level of total CA%, total CDCA%, primary BAs/secondary BAs, 12α-OH BAs/non-12α-OH Bas, and conjugated BAs/unconjugated BAs, and all decreased after kaempferol treatment. According to the RNA-seq results, we found that compared with the NC group, the mRNA expression of cholesterol-7α-hydroxylase (CYP7A1) in the HFD group was significantly increased, and the mRNA expression of sterol 12α‐hydroxylase (CYP8B1) and multidrug resistance-related protein 3 (MRP3) was significantly decreased, while kaempferol significantly promoted the mRNA expression of mitochondrial sterol 27-hydroxylase (CYP27A1) and Na+ -taurocholate cotransporting polypeptide (NTCP).

Conclusion: βMCA, CA, UDCA, 12-DHCA, ωMCA, CDCA, TωMCA, TDCA, THDCA, TCDCA, and TUDCA in the serum, as well as 6,7-diketoLCA, 12-DHCA, and ωMCA in the liver, may be potential biomarkers for kaempferol to improve NASH. HFD-induced NASH may be associated with the increase of CYP7A1 and the decrease of CYP8B1, leading to increased BA synthesis, and the decrease of MRP3 leading to decreased BA synthesis, and kaempferol may alleviate NASH by increasing CYP27A1 and NTCP to enhance BA transport.
Multi-omics analysis reveals the pathogenesis of db/db mice diabetic kidney disease and the treatment mechanisms of multi-bioactive compounds combination from Salvia miltiorrhiza
Authors: Xu Zhuo , Xiang Xiang , Su Shulan , Zhu Yue , Yan Hui , Guo Sheng , Guo Jianming , Shang Er-Xin , Qian Dawei , Duan Jin-ao
Published: September 2022

Diabetic kidney disease (DKD) is a common diabetic complication. Salvia miltiorrhiza has significant therapeutic effects on diabetes complications, although the mechanism remains unclear. Here, biochemical indicators and pathological changes were used to screen out the optimal Salvia miltiorrhiza multi-bioactive compounds combination. Metabolomics, transcriptomics and proteomics were used to explore the pathogenesis of DKD. RT-PCR and parallel reaction monitoring targeted quantitative proteome analysis were utilized to investigate treatment mechanisms of the optimal Salvia miltiorrhiza multi-bioactive compounds combination. The db/db mice showed biochemical abnormalities and renal lesions. The possible metabolic pathways were steroid hormone biosynthesis and sphingolipid metabolism. The 727 differential genes found in transcriptomics were associated with biochemical indicators via gene network to finally screen 11 differential genes, which were mainly key genes of TGF-β/Smad and PI3K/Akt/FoxO signaling pathways. Salvia miltiorrhiza multi-bioactive compounds combination could significantly regulate the Egr1, Pik3r3 and Col1a1 genes. 11 differentially expressed proteins involved in the two pathways were selected, of which 9 were significantly altered in db/db mice compared to db/m mice. Salvia miltiorrhiza multi-bioactive compounds combination could callback Q9DBM2, S4R1W1, Q91Y97, P47738, A8DUK4, and A2ARV4. In summary, Salvia miltiorrhiza multi-bioactive compounds combination may ameliorate kidney injury in diabetes through regulation of TGF-β/Smad and PI3K/Akt/FoxO signaling pathways.
Augmented reduced order models for turbulence
Authors: Kaneko Kento , Fischer Paul
Published: September 2022

The authors introduce an augmented-basis method (ABM) to stabilize reduced-order models (ROMs) of turbulent incompressible flows. The method begins with standard basis functions derived from proper orthogonal decomposition (POD) of snapshot sets taken from a full-order model. These are then augmented with divergence-free projections of a subset of the nonlinear interaction terms that constitute a significant fraction of the time-derivative of the solution. The augmenting bases, which are rich in localized high wavenumber content, are better able to dissipate turbulent kinetic energy than the standard POD bases. Several examples illustrate that the ABM significantly out-performs L2-, H1- and Leray-stabilized POD ROM approaches. The ABM yields accuracy that is comparable to constraint-based stabilization approaches yet is suitable for parametric model-order reduction in which one uses the ROM to evaluate quantities of interests at parameter values that differ from those used to generate the full-order model snapshots. Several numerical experiments point to the importance of localized high wavenumber content in the generation of stable, accurate, and efficient ROMs for turbulent flows.
Effect of facemask use on cognitive function during a maximal running aerobic fitness test
Authors: Slimani Maamer , Paravlic Armin , Abazovic Ensar , Znazen Hela , Bragazzi Nicola Luigi
Published: September 2022

Background: The aim of the present randomized, crossover study was to determine the physiological and cognitive function responses while wearing a facemask during a maximal running aerobic fitness test.

Methods: Fourteen healthy, nonsmoking physical education students (age = 17.5 years, height = 1.72 m, body mass = 70.4 kg) volunteered to participate in this study. They carried out a 20 m multistage fitness test (MSFT) while wearing or not a cloth facemask on two separate occasions performed in random order. The “Rating of Perceived Exertion” (RPE) and the d2 test for visual attention were administered and assessed before and immediately after the MSFT for both conditions (with or without a facemask).

Results: When wearing the facemask, the participants exhibited lower maximal aerobic speed (p = 0.039), VO2max (p = 0.039), distance covered during the MSFT (p = 0.057), and concentration performance (p < 0.001), when compared with the control situation (without facemask). Moreover, they made more errors compared with the control condition (p = 0.021). The use of a cloth facemask during maximal endurance running tests (such as the MSFT) reduced VO2max, and measures of cognitive performance as assessed by the test of focused visual attention (the d2 test). This data suggests avoiding using a cloth facemask during maximal aerobic fitness tests, and before any tasks that require a high level of visual attention.
Extracellular CIRP induces acute kidney injury via endothelial TREM-1
Authors: Siskind Sara , Zhang Fangming , Brenner Max , Wang Ping
Published: September 2022

Introduction: Acute kidney injury is associated with elevated serum levels of extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern released during ischemia/reperfusion injury, hemorrhagic shock, and sepsis. It is unknown if circulating eCIRP and eCIRP-induced activation of receptor triggering receptor expressed on myeloid cells-1 (TREM-1), expressed on endothelial cells, play an important role in the pathogenesis of AKI.

Methods: Male B6 wild-type (WT) and TREM-1−/− mice were subjected to intravenous injection of recombinant murine (rm) CIRP. Serum, urine, and renal tissue were collected 6 h later for analysis. Additionally, primary human renal glomerular endothelial cells (HRGEC) were stimulated in vitro with rmCIRP after pretreatment with M3, a novel inhibitory peptide of TREM-1, or vehicle. Supernatants and cells were collected 20 h after stimulation.

Results: After injection with rmCIRP, WT mice had a significant increase in serum levels of BUN, creatinine, and NGAL compared to control. Additionally, NGAL was significantly increased in the urine of rmCIRP-injected mice, suggesting that circulating eCIRP can directly induce AKI. The levels of TREM-1 mRNA in the kidneys, as well as soluble (s) TREM-1 released into the serum and urine, were significantly increased in rmCIRP-injected mice. TREM-1−/− mice injected with rmCIRP had attenuated AKI, indicated by significantly decreased serum BUN, creatinine, and NGAL, and renal mRNA expression of NGAL and KIM-1 compared to WT mice. TREM-1−/− mice also had attenuated endothelial activation, with decreased mRNA and protein expression of ICAM-1 in renal tissue. HRGEC stimulated with rmCIRP in vitro had significant increases in cytokine production and sTREM-1 release, which was attenuated in cells treated with M3.

Conclusion: Activation of renal TREM-1 with circulating eCIRP is sufficient to cause AKI. Elevated levels of eCIRP may be critical for the development of AKI under conditions such as ischemia/reperfusion injury, hemorrhagic shock, and sepsis. Mice deficient in the TREM-1 receptor have attenuated AKI and reduced endothelial cell activation after injection of rmCIRP. TREM-1 inhibition with M3 attenuates HRGEC activation after eCIRP stimulation. Targeting eCIRP activation of TREM-1 may provide a novel and effective treatment for AKI.
Quadriceps or triceps surae proprioceptive neuromuscular facilitation stretching with post-stretching dynamic activities does not induce acute changes in running economy
Authors: Konrad A. , Tilp M. , Stöcker F. , Mehmeti L. , Mahnič N. , Seiberl W. , Behm D. G. , Paternoster F. K.
Published: September 2022

Previous studies reported that both a more compliant quadriceps tendon and a stiffer Achilles tendon are associated with better running economy. While tendon stiffness can be decreased by a single bout of proprioceptive neuromuscular facilitation (PNF), post-stretching dynamic activities (PSA) can counteract the potential stretch-induced force loss. Thus, the purpose of this study was to investigate if a single, moderate duration, (4 × 15 s), bout of PNF stretching of either the quadriceps or triceps surae muscles followed each by PSA, causes either an improvement or impairment in running economy. Eighteen trained male runners/triathletes visited the laboratory five times. The first two visits were to familiarize the participants and to test for maximal oxygen consumption (VO2max) respectively. The further three appointments were randomly assigned to either 1.) quadriceps PNF stretching + PSA or 2.) triceps surae PNF stretching + PSA or 3.) no stretching + PSA. Following the interventions, participants performed a 15-min run on the treadmill with a speed reflecting a velocity of 70% VO2max to assess oxygen consumption (i.e., running economy) and running biomechanics. Our results showed neither a difference in oxygen consumption (p = 0.15) nor a change in any variable of the running biomechanics (p > 0.33) during the steady-state (i.e., last 5 min) of the 15-min run. Athletes can perform moderate duration PNF stretching of the quadriceps or triceps surae + PSA prior to a running event, without affecting running economy. Future studies should emphasize long-term training effects on tendon stiffness adaptations and running economy.