bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomes form tunneling nanotubes (TUNTs) in the blood-brain barrier: a nano-anatomical perspective of barrier genesis
Authors: Mentor Shireen , Fisher David
Published: September 2022

The blood-brain barrier (BBB) is a robust interface between the blood and the central nervous system. Barrier type endothelium is able to limit paracellular (PC) movement, relegating molecular flux to the transendothelial pathways of brain endothelial cells (BECs). It is, therefore, apparent that any leakage via the PC shunts would effectively nullify the regulation of molecular flux across the transcellular pathways. The application of higher-resolution scanning electron microscopy (HR-SEM) illuminates the heterogenous, morphological profile that exists on the surface of BEC membranes and the relationship between these ultrastructures during the molecular construction of the PC space between adjacent BECs. In this study developing BEC monolayers were grown on mixed, cellulose esters insert membranes in a bicameral system. BEC monolayers were fixed in 2.5% glutaraldehyde, hydrated, critically dried, and sputter-coated, for imaging utilizing HR-SEM. This study, for the first time, showed membrane-bound exosomes were attached to the plasma membrane surfaces of the BECs. The exosomes were characterized as small membrane-bound, nano-sized exosomes (30–300 nm). Based on their membrane morphology and anatomical structure, exosomes appear to possess two distinct functions, namely: paracrine secretion and nanotube construction between adjacent BECs, during in vitro barrier genesis. The HR-SEM micrographs in conjunction with the Tipifarnib inhibition of exosome formation, suggests that brain capillary endothelial exosomes play a prominent role in the bilateral signaling, which contribute to the regulation of the permeability of the BBB. Given that blood-brain barrier permeability has been implicated in the progression of many neurodegenerative pathologies, the role of these exosomes and TUNTs posits the capacity of these structures to exacerbate neuropathologies that implicate BBB permeability. These findings could lead to the development of novel treatment interventions and moreover, the characterization of BBB exosomes may be a reliable target for identifying therapeutic biomarkers in neurodegenerative disease. Conversely, the presence of BBB exosomes raises a critical enterprise to target the exosome-induced nanotubes as a vehicle for transferring therapeutic treatments across the BBB.
Development of a time-resolved fluorescence microsphere Eu lateral flow test strip based on a molecularly imprinted electrospun nanofiber membrane for determination of fenvalerate in vegetables
Authors: Zhang Le , Zheng Yiliu , Shao Hua , Xiao Ming , Sun Jianchun , Jin Maojun , Jin Fen , Wang Jing , Abd El-Aty A. M. , She Yongxin
Published: September 2022

Fenvalerate residues in fruits and vegetables may result in biological immune system disorders. Current sensor detection methods are harsh due to the shortcomings of antibody preparation and preservation conditions. Therefore, developing a recognition material with strong specificity, good stability, and low cost is of practical significance in designing a sensitive, simple, and rapid method. This study used precipitation polymerization to synthesize molecularly imprinted polymers (MIPs). The MIP was prepared into a fiber membrane using the electrostatic spinning method. After that, the fenvalerate hapten-mouse IgG-Eu fluorescent probe was synthesized, and the side flow chromatography strip was constructed to determine fenvalerate in vegetables using the immunocompetition method. The results showed that the adsorption capacity of MIP to fenvalerate was 3.65, and the adsorption capacity on MIPFM (an electrospinning membrane containing the fenvalerate MIPs) was five times that of free MIP. The test strip showed good linearity with R2 = 0.9761 within the range of 50 μg/L-1,000 μg/L. In conclusion, substituting fenvalerate monoclonal antibodies with a molecularly imprinted electrospinning membrane is ideal for rapid onsite detection of pyrethroids.
Effect of wheat bran dietary fiber on structural properties and hydrolysis behavior of gluten after synergistic fermentation of Lactobacillus plantarum and Saccharomyces cerevisiae
Authors: Wang Zhen , Ma Sen , Li Li , Huang Jihong
Published: September 2022

The effect of synergistic fermentation of Lactobacillus plantarum and Saccharomyces cerevisiae on the structural properties and aggregation behavior of gluten containing different wheat bran dietary fiber (WBDF) levels (0, 3, 6, 9, and 12%) was investigated. The results showed that WBDF addition affected the aggregation behavior of gluten at the molecular level, while WBDF significantly induced depolymerization behaviors in large aggregated gluten proteins (Molecular weight > 130 kDa) under reducing conditions (p < 0.05). In terms of secondary structure, WBDF significantly reduced glutamine side chain levels and reduced antiparallel β-sheet structures from 28.57 to 24.53% (p < 0.05). In addition, WBDF thermal properties and its water holding capacity were the main factors causing changes in thermal properties in the overall gluten system. This study provides new data for the improved production of sourdough whole grain and/or high fiber flour products.
Real-world efficacy and safety of mobocertinib in EGFR exon 20 insertion-mutated lung cancer
Authors: Kian Waleed , Christopoulos Petros , Remilah Areen A. , Levison Esther , Dudnik Elizabeth , Shalata Walid , Krayim Bilal , Marei Ranin , Yakobson Alexander , Faehling Martin , Kahala Dolev , Sara Granot Inbal , Levitas Dina , Peled Nir , Roisman Laila C.
Published: September 2022

Background

Non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions (EGFRex20ins) is relatively resistant to the existing EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is a novel TKI that selectively targets EGFRex20ins and has demonstrated therapeutic efficacy in pretreated patients with tumors harboring these mutations.

Methods

This is a retrospective, non-interventional, multicenter real-world study aimed at assessing the efficacy and safety of mobocertinib in patients with EGFRexon20ins who received 160 mg QD monotherapy as part of expanded access. Data collection was based on patients’ records. PET-CT or CT scans were used to measure systemic response, while brain MRIs were used to examine intracranial response as part of the follow-up.

Results

16 patients were included in this report. Mobocertinib was administered to 31.3% (5) of patients as first-line, 50% (8) as second-line, and 18.7% (3) as a later-line therapy. The median age was 65 years (range, 38-83), 75% (12/16) were female, and 50% (8/16) had brain metastases at baseline before mobocertinib treatment. The objective response rate (ORR) to mobocertinib was 25% (4/16) (1/5 for first line and 3/11 for other lines), disease control rate (DCR) was 75% (12/16) with a follow-up period of 11 months. The median duration of treatment (mDoT) was 5.6 months across all patients, and 8.6 months in responders. Based on the presence or absence of brain metastasis, the mDoT was 14.8 and 5.4 months (p=0.01), respectively. Mobocertinib Grade ≥3 treatment-related adverse events (TRAEs) included diarrhea (19%), nausea (6%) and renal failure (6%). Dose reduction was reported in 25% of cases to 80 mg.

Conclusion

Mobocertinib in compassionate use exhibited an ORR of 25%, which is very similar to that of the phase 2 EXCLAIM study and clearly better than historical data of monochemotherapy or conventional EGFR inhibitors. The greatest benefit was noted in patients without brain metastases, who showed durable effects with mDoT 14.8 months, while intracranial activity was limited. These findings may assist therapeutic considerations, inasmuch as results from the EXCLAIM cohort-3 dedicated to brain lesions are not available yet.
Malignant granular cell tumor in the thoracic wall: A case report
Authors: Gao Shengnan , Xing Bin , Lichao Sun , Luo Jie , Tang Jiao , Wang Ye , Zhang Xiaoyan
Published: September 2022

Granulosa cell tumor (GCT) is a rare tumor that originates from neural/Schwann cells. GCTs can occur at any age and at any site in the body. The most common site is the tongue, followed by the mammary gland, upper respiratory tract ( throat and bronchus), and gastrointestinal tract (esophagus, large intestine and perianal area, stomach, small intestine, and bile duct). Malignant GCTs account for less than 1%–2% of all GCTs. Fewer than five GCTs in the thoracic wall have been reported, almost all of these benign. Here, we report a new case of malignant GCT of the thoracic wall, with rib invasion and pleural metastasis, in an Asian male. Microscopic examination revealed round, granular cells with eosinophilic cytoplasm and without prominent atypia. Despite these findings the disease showed rapid clinical progression. In summary, the tumor, although histologically ‘benign’, was clinically ‘malignant’.
Evaluation of colorectal cancer liver metastases based on liquid biopsy combined with folate receptor– Positive circulating tumor cells and HSP90
Authors: Huang Maosen , Cheng Linyao , Mo SiSi , Ru Haiming , Mo Xianwei , Yan Linhai
Published: September 2022

Objective

Liver metastasis of colorectal cancer (LMCRC) is a major cause of cancer-related deaths worldwide. We can reduce the mortality rate by discerning the risk of liver metastases in patients with colorectal cancer at an early stage. Hence, we combined the use of folate receptor (FR)–labeled circulating tumor cells (FR+CTCs) and the metastasis-related marker, heat shock protein 90 (HSP90), to screen patients with colorectal cancer and explore the prognostic factors of patients with high expression of FR+CTC and HSP90.

Patients and methods

A retrospective study of 356 patients with measurable colorectal cancer was performed. Negative enrichment and FR-targeted fluorescence quantitative PCR was utilized to detect FR+CTC. An ELISA kit was used to detect HSP90 expression. A timely follow-up study of patients with colorectal cancer was made.

Results

Colorectal patients with liver metastases showed high expression of FR+CTCs and HSP90. The diagnostic ability of the combined receiver operating characteristic curve of FR+CTC and HSP90 (area under the curve [AUC]=0.79, sensitivity 70.55%, specificity 92.66%) was significantly greater than that of a single index. The results of timely follow-up of patients showed that the high expression of FR+CTC significantly shortened the median disease-free survival (mDFS) of 36.5 months (95% confidence interval [CI]: 14.13–58.87, Logrank p < 0.0001) compared with the low expression cohort. The mDFS of the HSP90 high-expression cohort was significantly higher than that of the low-expression cohort (Logrank p = 0.0002), mDFS=58.47 months (95% CI: 37.12–79.81, Logrank p < 0.0001). We performed univariate and multivariate analyses to show that FR+CTC and HSP90 were risk factors for the progression of metastatic colorectal cancer (MCRC) disease. We then constructed a high- and low-risk score model of risk factors to evaluate MCRC. The diagnostic sensitivity of the risk model for MCRC was significantly improved (AUC=0.89, sensitivity 85.29%, specificity 81.33%), and the mDFS of patients in a high-risk group increased to 33.28 months (95% CI: 27.24–39.31, Logrank p < 0.0001). The establishment of the model improves the early screening of patients with MCRC.

Conclusion

Patients with colorectal cancer and high expression of FR+CTC and HSP90 are at risk of liver metastasis and this suggests a poor prognosis. Combining the two markers can improve the early screening and diagnosis of LMCRC patients. In addition, combining a multivariate risk model can further assist patients in appropriate stratification and the design of tailored treatment regimens. However, further validation these markers is needed before their routine clinical application.
Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials
Authors: Xu Yi-Fang , Chen Yun-Ru , Bu Fan-Long , Huang Yu-Bei , Sun Yu-Xin , Li Cheng-Yin , Sellick Jodi , Liu Jian-Ping , Qin Dan-Mei , Liu Zhao-Lan
Published: September 2022

Background

Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE.

Methods

Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/).

Results

A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%).

Conclusions

Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence.

Systematic review registration

PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.
Electrochemotherapy for the treatment of cutaneous squamous cell carcinoma: The INSPECT experience (2008-2020)
Authors: Bertino Giulia , Groselj Ales , Campana Luca G. , Kunte Christian , Schepler Hadrian , Gehl Julie , Muir Tobian , Clover James A. P. , Quaglino Pietro , Kis Erika , Mascherini Matteo , Bisase Brian , Pecorari Giancarlo , Bechara Falk , Matteucci Paolo , Odili Joy , Russano Francesco , Orlando Antonio , Pritchard-Jones Rowan , Moir Graeme , Mowatt David , Silvestri Barbara , Seccia Veronica , Saxinger Werner , de Terlizzi Francesca , Sersa Gregor
Published: September 2022

Introduction

Cutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC.

Materials and methods

Patients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures.

Results

The analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p<0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%).

Conclusion

In the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (<3 cm) using intravenous bleomycin administration.
Diagnostic performance of elastosonography in the differential diagnosis of benign and malignant salivary gland tumors: A meta-analysis
Authors: Wu Jiangfeng , Zhou Zhijuan , Wang Xiaoyun , Jin Yun , Wang Zhengping , Jin Guilong
Published: September 2022

Purpose

The clinical practice of elastosonography for the detection of salivary gland tumors is still a controversial issue. The objective of this meta-analysis was to evaluate the effect of elastosonography for the diagnosis of salivary gland tumors and to compare the diagnostic value of elastosonography and conventional ultrasound in the diagnosis of salivary gland tumors.

Methods

A comprehensive literature search through PubMed, EMBASE, and Cochrane Library was carried out from inception to November 2021. Two researchers independently extracted the data from the enrolled papers using a standard data extraction form. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the diagnostic performance of elastosonography. The Quality Assessment of Diagnostic Accuracy Studies—2 (QUADAS-2) tool was utilized to evaluate the quality of each included study. Meta-DiSc version 1.4, Review Manager 5.3, and StataSE 15 were used.

Results

Sixteen studies with a total of 1105 patients with 1146 lesions were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of elastosonography for the differentiation between benign and malignant salivary gland tumors were 0.73 (95%CI, 0.66–0.78), 0.64 (95%CI, 0.61–0.67), 2.83 (95%CI, 1.97–4.07), 0.45 (95%CI, 0.32–0.62), and 9.86 (95%CI, 4.49–21.62), respectively, with an AUC of 0.82. Four studies provided data regarding the conventional ultrasound for the differentiation between benign and malignant salivary gland tumors. The pooled sensitivity, specificity, and DOR were 0.62 (95%CI, 0.50–0.73), 0.93 (95%CI, 0.90–0.96), and 25.07 (95%CI, 4.28–146.65), respectively. The meta-regression and subgroup analyses found that assessment methods were associated with significant heterogeneity, and quantitative or semiquantitative elastosonography performed better than the qualitative one.

Conclusions

Elastosonography showed a limited value for diagnosing malignant salivary gland tumors; it could be considered as a supplementary diagnostic technology to conventional ultrasound, and quantitative or semiquantitative elastosonography was superior to the qualitative one.
Development and validation of a screening model for lung cancer using machine learning: A large-scale, multi-center study of biomarkers in breath
Authors: Li Jing , Zhang Yuwei , Chen Qing , Pan Zhenhua , Chen Jun , Sun Meixiu , Wang Junfeng , Li Yingxin , Ye Qing
Published: September 2022

Objectives

Lung cancer (LC) is the largest single cause of death from cancer worldwide, and the lack of effective screening methods for early detection currently results in unsatisfactory curative treatments. We herein aimed to use breath analysis, a noninvasive and very simple method, to identify and validate biomarkers in breath for the screening of lung cancer.

Materials and methods

We enrolled a total of 2308 participants from two centers for online breath analyses using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS). The derivation cohort included 1007 patients with primary LC and 1036 healthy controls, and the external validation cohort included 158 LC patients and 107 healthy controls. We used eXtreme Gradient Boosting (XGBoost) to create a panel of predictive features and derived a prediction model to identify LC. The optimal number of features was determined by the greatest area under the receiver‐operating characteristic (ROC) curve (AUC).

Results

Six features were defined as a breath-biomarkers panel for the detection of LC. In the training dataset, the model had an AUC of 0.963 (95% CI, 0.941–0.982), and a sensitivity of 87.1% and specificity of 93.5% at a positivity threshold of 0.5. Our model was tested on the independent validation dataset and achieved an AUC of 0.771 (0.718–0.823), and sensitivity of 67.7% and specificity of 73.0%.

Conclusion

Our results suggested that breath analysis may serve as a valid method in screening lung cancer in a borderline population prior to hospital visits. Although our breath-biomarker panel is noninvasive, quick, and simple to use, it will require further calibration and validation in a prospective study within a primary care setting.
Diagnostic value of radiomics model based on gray-scale and contrast-enhanced ultrasound for inflammatory mass stage periductal mastitis/duct ectasia
Authors: Zheng Yan , Bai Lu , Sun Jie , Zhu Lin , Huang Renjun , Duan Shaofeng , Dong Fenglin , Tang Zaixiang , Li Yonggang
Published: September 2022

Objective

The present study aimed to investigate the clinical application value of the radiomics model based on gray-scale ultrasound (GSUS) and contrast-enhanced ultrasound (CEUS) images in the differentiation of inflammatory mass stage periductal mastitis/duct ectasia (IMSPDM/DE) and invasive ductal carcinoma (IDC).

Methods

In this retrospective study, 254 patients (IMSPDM/DE: 129; IDC:125) were enrolled between January 2018 and December 2020 as a training cohort to develop the classification models. The radiomics features were extracted from the GSUS and CEUS images. The least absolute shrinkage and selection operator (LASSO) regression model was employed to select the corresponding features. Based on these selected features, logistic regression analysis was used to aid the construction of these three radiomics signatures (GSUS, CEUS and GSCEUS radiomics signature). In addition, 80 patients (IMSPDM/DE:40; IDC:40) were recruited between January 2021 and November 2021 and were used as the validation cohort. The best radiomics signature was selected. Based on the clinical parameters and the radiomics signature, a classification model was built. Finally, the classification model was assessed using nomogram and decision curve analyses.

Results

Three radiomics signatures were able to differentiate IMSPDM/DE from IDC. The GSCEUS radiomics signature outperformed the other two radiomics signatures and the AUC, sensitivity, specificity, and accuracy were estimated to be 0.876, 0.756, 0.804, and 0.798 in the training cohort and 0.796, 0.675, 0.838 and 0.763 in the validation cohort, respectively. The lower patient age (p<0.001), higher neutrophil count (p<0.001), lack of pausimenia (p=0.023) and GSCEUS radiomics features (p<0.001) were independent risk factors of IMSPDM/DE. The classification model that included the clinical factors and the GSCEUS radiomics signature outperformed the GSCEUS radiomics signature alone (the AUC values of the training and validation cohorts were 0.962 and 0.891, respectively). The nomogram was applied to the validation cohort, reaching optimal discrimination, with an AUC value of 0.891, a sensitivity of 0.888, and a specificity of 0.750.

Conclusions

The present study combined the clinical parameters with the GSCEUS radiomics signature and developed a nomogram. This GSCEUS radiomics-based classification model could be used to differentiate IMSPDM/DE from IDC in a non-invasive manner.
Predicting non-small cell lung cancer-related genes by a new network-based machine learning method
Authors: Cai Yong , Wu Qiongya , Chen Yun , Liu Yu , Wang Jiying
Published: September 2022

Lung cancer is the leading cause of cancer death globally, killing 1.8 million people yearly. Over 85% of lung cancer cases are non-small cell lung cancer (NSCLC). Lung cancer running in families has shown that some genes are linked to lung cancer. Genes associated with NSCLC have been found by next-generation sequencing (NGS) and genome-wide association studies (GWAS). Many papers, however, neglected the complex information about interactions between gene pairs. Along with its high cost, GWAS analysis has an obvious drawback of false-positive results. Based on the above problem, computational techniques are used to offer researchers alternative and complementary low-cost disease–gene association findings. To help find NSCLC-related genes, we proposed a new network-based machine learning method, named deepRW, to predict genes linked to NSCLC. We first constructed a gene interaction network consisting of genes that are related and irrelevant to NSCLC disease and used deep walk and graph convolutional network (GCN) method to learn gene–disease interactions. Finally, deep neural network (DNN) was utilized as the prediction module to decide which genes are related to NSCLC. To evaluate the performance of deepRW, we ran tests with 10-fold cross-validation. The experimental results showed that our method greatly exceeded the existing methods. In addition, the effectiveness of each module in deepRW was demonstrated in comparative experiments.
Impact of examined lymph node number on lymph node status and prognosis in FIGO stage IB-IIA cervical squamous cell carcinoma: A population-based study
Authors: Yong Jiahui , Ding Baicheng , Dong Yaqin , Yang Mingwei
Published: September 2022

Objective

We aimed to investigate the association of examined lymph node (ELN) number with lymph node status and long-term survival in FIGO stage IB-IIA cervical squamous cell carcinoma(CSCC) and to determine the minimum number of ELN associated with survival improvement.

Method

Data from the Surveillance, Epidemiology, and End Results Program (SEER) database of FIGO stage IB-IIA CSCC patients undergoing hysterectomy and pelvic lymphadenectomy in 2004-2016 were analyzed to explore the relationship between ELN number and lymph node status and overall survival (OS) by using the multivariable approach. The estimated probability of falsely identifying a patient as node-negative and the hazard ratios (HRs) for each ELN was fitted with a LOWESS smoother, and the structural breakpoints were determined. X-tile software was used to determine the optimal cutoff value for ELNs.

Results

A total of 2627 patients were analyzed. The optimal cutoff value of the ELN number was identified as 7 based on the results of X-tile software. The structural breakpoints according to the associations between the number of ELNs and the estimated risk of false-negative lymph node dissection and HRs for overall survival were 9 and 8, respectively. The multivariate analysis indicated that ELN number was an independent prognostic factor for OS, both as a continuous or categorical variable. To further explore the effect of more ELNs on survival, another cutoff value of 17 was chosen to compare the survival curves of patients. The multivariate-adjusted COX model showed that patients with ELN<8 had a significantly higher risk of death than those with ELN8-17 (HR=1.447, 95% CI =1.075-1.947, p=0.015), but there was no significant difference in overall survival between patients with ELN>17 and patients with ELN8-17 (HR=0.822, 95%CI =0.665-1.016, p=0.070).

Conclusion

A sufficient number of ELNs was associated with better long-term survival in FIGO stage IB-IIA CSCC. At least 8 ELNs need to be examined for prognostic stratification. Excessive lymph node dissection (ELN>17) may not confer additional survival benefits.
Effect of cochlear implantation on vestibular function in children: A scoping review
Authors: Gerdsen Max , Jorissen Cathérine , Pustjens Daphne Catharina Francisca , Hof Janke Roelofke , Van Rompaey Vincent , Van De Berg Raymond , Widdershoven Josine Christine Colette
Published: September 2022

Objective

To provide a scoping review of the available literature for determining objectively the effect of cochlear implantation on vestibular function in children.

Methods

A literature search was performed and the following criteria were applied: vestibular tests that were performed on subjects within the range of 0–18 years old before and after cochlear implantation. The papers conducted at least one of the following tests: (video) head impulse test, caloric test, cervical and ocular vestibular evoked myogenic potentials or rotatory chair test. Included papers underwent quality assessment and this was graded by risk of bias and directness of evidence.

Results

Fourteen articles met the selection criteria. The included studies showed that cochlear implantation leads to a decrease in vestibular function in a proportion of the patient population. This loss of vestibular function can be permanent, but (partial) restoration over the course of months to years is possible. The pooling of data determined that the articles varied on multiple factors, such as time of testing pre- and post-operatively, age of implantation, etiologies of hearing loss, used surgical techniques, type of implants and the applied protocols to determine altered responses within vestibular tests. The overall quality of the included literature was deemed as high risk of bias and medium to low level of directness of evidence. Therefore, the data was considered not feasible for systematic analysis.

Conclusion

This review implicates that vestibular function is either unaffected or shows short-term or permanent deterioration after cochlear implantation in children. However, the heterogeneity of the available literature indicates the importance of standardized testing to improve our knowledge of the effect of cochlear implantation on the vestibular function and subsequent developmental consequences for the concerned children.
Thresholds for blood transfusion in extremely preterm infants: A review of the latest evidence from two large clinical trials
Authors: Meyer Michael P. , O'Connor Kristin L. , Meyer Jill H.
Published: September 2022

There are two recently completed large randomized clinical trials of blood transfusions in the preterm infants most at risk of requiring them. Liberal and restrictive strategies were compared with composite primary outcome measures of death and neurodevelopmental impairment. Infants managed under restrictive guidelines fared no worse in regard to mortality and neurodevelopment in early life. The studies had remarkably similar demographics and used similar transfusion guidelines. In both, there were fewer transfusions in the restrictive arm. Nevertheless, there were large differences between the studies in regard to transfusion exposure with almost 3 times the number of transfusions per participant in the transfusion of prematures (TOP) study. Associated with this, there were differences between the studies in various outcomes. For example, the combined primary outcome of death or neurodevelopmental impairment was more likely to occur in the TOP study and the mortality rate itself was considerably higher. Whilst the reasons for these differences are likely multifactorial, it does raise the question as to whether they could be related to the transfusions themselves? Clearly, every effort should be made to reduce exposure to transfusions and this was more successful in the Effects of Transfusion Thresholds on Neurocognitive Outcomes (ETTNO) study. In this review, we look at factors which may explain these transfusion differences and the differences in outcomes, in particular neurodevelopment at age 2 years. In choosing which guidelines to follow, centers using liberal guidelines should be encouraged to adopt more restrictive ones. However, should centers with more restrictive guidelines change to ones similar to those in the studies? The evidence for this is less compelling, particularly given the wide range of transfusion exposure between studies. Individual centers already using restrictive guidelines should assess the validity of the findings in light of their own transfusion experience. In addition, it should be remembered that the study guidelines were pragmatic and acceptable to a large number of centers. The major focus in these guidelines was on hemoglobin levels which do not necessarily reflect tissue oxygenation. Other factors such as the level of erythropoiesis should also be taken into account before deciding whether to transfuse.
Assessment of brain two-dimensional metrics in infants born preterm at term equivalent age: Correlation of ultrasound scans with magnetic resonance imaging
Authors: Vo Van Philippe , Beck Jonathan , Meunier Hélène , Venot Perrine , Mac Caby Gratiella , Bednarek Nathalie , Loron Gauthier
Published: September 2022

Context

Developing brain imaging is a critical subject for infants born preterm. Impaired brain growth is correlated with poor neurological outcomes, regardless of overt brain lesions, such as hemorrhage or leukomalacia. As magnetic resonance imaging (MRI) remains a research tool for assessing regional brain volumes, two-dimensional metrics (2D metrics) provide a reliable estimation of brain structures. In neonatal intensive care, cerebral ultrasound (cUS) is routinely performed to assess brain integrity. This prospective work has compared US and MRI accuracy for the measurement of 2D brain metrics and identification of overt injuries.

Methods

MRI and cUS were performed at term equivalent age (TEA) in infants born before 32 weeks of gestation (GW). Demographical data and results of serial cUS (Neonatal Intensive Care Unit [NICU]-US) performed during hospitalization were gathered from medical charts. Blinded, experienced senior doctors reviewed the scans for both standard analysis and standardized, 2D measurements. The correlation of 2D metrics and inter-/intraobserver agreements were evaluated using Pearson’s coefficient, Bland-Altman plots, and intraclass coefficient (ICC), respectively.

Results

In total, 102 infants born preterm were included. The performance of “TEA-cUS and NICU-cUS” when compared to “TEA-MRI and NICU-cUS” was identical for the detection of high-grade hemorrhages and close for low-grade ones. However, TEA-MRI only detected nodular lesions of the white matter (WM). No infant presented a cerebellar infarct on imaging. Intra- and inter-observer agreements were excellent for all 2D metrics except for the corpus callosum width (CCW) and anteroposterior vermis diameter. MRI and cUS showed good to excellent correlation for brain and bones biparietal diameters, corpus callosum length (CCL), transcerebellar diameters (TCDs), and lateral ventricle diameters. Measures of CCW and vermis dimensions were poorly correlated.

Conclusion and perspective

The cUS is a reliable tool to assess selected 2D measurements in the developing brain. Repetition of these metrics by serial cUS during NICU stay would allow the completion of growth charts for several brain structures. Further studies will assess whether these charts are relevant markers of neurological outcome.
Edible bird’s nest, an Asian health food supplement, possesses anti-inflammatory responses in restoring the symptoms of atopic dermatitis: An analysis of signaling cascades
Authors: Lai Queenie Wing Sze , Fan Qunyan , Zheng Brody Zhongyu , Chen Yanxian , Dong Tina Tingxia , Tsim Karl Wah Keung
Published: September 2022

Edible bird’s nest (EBN) is a Chinese delicacy possessing skin rejuvenating functions. To verify skin anti-inflammatory function of EBN, water extract and enzymatic digest of EBN, as well as the major sialic acid, N-acetyl neuraminic acid (NANA), were probed in TNF-α-treated HaCaT keratinocytes. The mRNA expressions of pro-inflammatory cytokines, e.g., IL-1β, IL-6, TNF-α, and an enzyme responsible for inflammatory response, i.e., Cox-2, as well as filaggrin and filaggrin-2, were markedly altered after treating with different preparations of EBN. The EBN-mediated responses could be accounted by its robust reduction of reactive oxygen species (ROS), NF-κB signaling and phosphorylation of p38 MAPK and JNK, as triggered by TNF-α-induced inflammation. The anti-inflammatory response of EBN was further supported in animal model. In 2,4-dinitrochlorobenzene (DNCB)-induced dermatitic mice, the effects on skin thickness, severity level of damage and scratching behavior, exerted by DNCB, were reversed after EBN treatments, in dose-dependent manners. In parallel, the levels of immune cells and pro-inflammatory cytokines in dermatitic skin were markedly reduced by treatment of EBN preparations. In general, NANA and enzymatic digest of EBN showed better anti-inflammatory responses in both models ofin vitroandin vivo. These lines of evidence therefore suggest the possible application of EBN in treating atopic dermatitis.
Bioinformatics and network-based screening and discovery of potential molecular targets and small molecular drugs for breast cancer
Authors: Alam Md Shahin , Sultana Adiba , Sun Hongyang , Wu Jin , Guo Fanfan , Li Qing , Ren Haigang , Hao Zongbing , Zhang Yi , Wang Guanghui
Published: September 2022

Accurate identification of molecular targets of disease plays an important role in diagnosis, prognosis, and therapies. Breast cancer (BC) is one of the most common malignant cancers in women worldwide. Thus, the objective of this study was to accurately identify a set of molecular targets and small molecular drugs that might be effective for BC diagnosis, prognosis, and therapies, by using existing bioinformatics and network-based approaches. Nine gene expression profiles (GSE54002, GSE29431, GSE124646, GSE42568, GSE45827, GSE10810, GSE65216, GSE36295, and GSE109169) collected from the Gene Expression Omnibus (GEO) database were used for bioinformatics analysis in this study. Two packages, LIMMA and clusterProfiler, in R were used to identify overlapping differential expressed genes (oDEGs) and significant GO and KEGG enrichment terms. We constructed a PPI (protein–protein interaction) network through the STRING database and identified eight key genes (KGs) EGFR, FN1, EZH2, MET, CDK1, AURKA, TOP2A, and BIRC5 by using six topological measures, betweenness, closeness, eccentricity, degree, MCC, and MNC, in the Analyze Network tool in Cytoscape. Three online databases GSCALite, Network Analyst, and GEPIA were used to analyze drug enrichment, regulatory interaction networks, and gene expression levels of KGs. We checked the prognostic power of KGs through the prediction model using the popular machine learning algorithm support vector machine (SVM). We suggested four TFs (TP63, MYC, SOX2, and KDM5B) and four miRNAs (hsa-mir-16-5p, hsa-mir-34a-5p, hsa-mir-1-3p, and hsa-mir-23b-3p) as key transcriptional and posttranscriptional regulators of KGs. Finally, we proposed 16 candidate repurposing drugs YM201636, masitinib, SB590885, GSK1070916, GSK2126458, ZSTK474, dasatinib, fedratinib, dabrafenib, methotrexate, trametinib, tubastatin A, BIX02189, CP466722, afatinib, and belinostat for BC through molecular docking analysis. Using BC cell lines, we validated that masitinib inhibits the mTOR signaling pathway and induces apoptotic cell death. Therefore, the proposed results might play an effective role in the treatment of BC patients.
RSK2 promotes melanoma cell proliferation and vemurafenib resistance via upregulating cyclin D1
Authors: Wu Hai-Zhou , Li Lan-Ya , Jiang Shi-Long , Li Yi-Zhi , Shi Xiao-Mei , Sun Xin-Yuan , Li Zhuo , Cheng Yan
Published: September 2022

BRAF inhibitors are commonly used in targeted therapies for melanoma patients harboring BRAFV600E mutant. Despite the benefit of vemurafenib therapy, acquired resistance during or after treatment remains a major obstacle in BRAFV600E mutant melanoma. Here we found that RSK2 is overexpressed in melanoma cells and the high expression of RSK2 indicates poor overall survival (OS) in melanoma patients. Overexpression of RSK2 leads to vemurafenib resistance, and the deletion of RSK2 inhibits cell proliferation and sensitizes melanoma cells to vemurafenib. Mechanistically, RSK2 enhances the phosphorylation of FOXO1 by interacting with FOXO1 and promoting its subsequent degradation, leading to upregulation of cyclin D1 in melanoma cells. These results not only reveal the presence of a RSK2-FOXO1-cyclin D1 signaling pathway in melanoma, but also provide a potential therapeutic strategy to enhance the efficacy of vemurafenib against cancer.
Esketamine prevents propofol-induced injection pain: Randomized controlled trial
Authors: Xu Chaozhi , Wei Xiaotang , Zhang Cuiwen , Huang Xiaofang , Lan Hongmeng , Xu Yanping , Wu Xiaoyan , Li Fuping , Guan Xuehai
Published: September 2022

Background: Propofol is widely used during anesthesia. However, propofol-induced injection pain (PIP) is considered an unpleasant perioperative outcome. This study aimed to investigate the efficacy of a mixture of esketamine and propofol in preventing propofol injection pain in patients undergoing general anesthesia.

Methods: This was a prospective, double-blind, multicenter, and randomized controlled trial. We included 252 adult patients with the American Society of Anesthesiologists physical status I to II who underwent surgery under general anesthesia. Patients were randomly allocated in a 1:1:1:1 ratio to four groups (n = 63 per group). Group NS received a mixture of 1% propofol (20 ml) and 0.9% normal saline (1 ml), group ESK-4 received a mixture of 1% propofol (20 ml) and esketamine 4 mg (diluted with 0.9% normal saline, 1 ml), group ESK-12 received a mixture of 1% propofol (20 ml) and esketamine 12 mg (diluted with 0.9% normal saline, 1 ml), and group ESK-20 received a mixture of 1% propofol (20 ml) and esketamine 20 mg (diluted with 0.9% normal saline, 1 ml) as sedative drugs during anesthesia. The primary outcome was the incidence and distribution of different degrees of PIP. The secondary outcomes were vital signs, characteristics of surgery and anesthesia, and adverse events.

Results: The incidence of PIP in group ESK-20 (33.3%) was significantly lower than that in groups NS, ESK-4, and ESK-12 (63.3%, 62.2%, and 49.1%, respectively; p < 0.01). The incidence of moderate PIP in group NS (33.3%) and group ESK-4 (22.6%) was higher than that in groups ESK-12 (7.5%) and ESK-20 (6.7%). The incidence of severe PIP in group NS (6.7%) and group ESK-4 (9.4%) was higher than that in groups ESK-12 (1.9%) and ESK-20 (0%). There were no differences in the vital signs, characteristics of surgery and anesthesia, or adverse events between the groups.

Conclusion: Our results indicated that the esketamine–propofol admixture reduced the incidence of PIP in patients undergoing general anesthesia without severe side effects.
E. coli strain-dependent lipid alterations in cocultures with endothelial cells and neutrophils modeling sepsis
Authors: Amunugama Kaushalya , Pike Daniel P. , Ford David A.
Published: September 2022

Dysregulated lipid metabolism is common in infection and inflammation and is a part of the complex milieu underlying the pathophysiological sequelae of disease. Sepsis is a major cause of mortality and morbidity in the world and is characterized by an exaggerated host response to an infection. Metabolic changes, including alterations in lipid metabolism, likely are important in sepsis pathophysiology. Here, we designed an in vitro cell culture model using endothelial cells, E. coli, and neutrophils to mimic sepsis in a simplified cell model. Lipid alterations were studied in the presence of the pathogenic E. coli strain CFT073 and non-pathogenic E. coli strain JM109. We employed untargeted lipidomics to first identify lipid changes and then targeted lipidomics to confirm changes. Both unique and shared lipid signatures were identified in cocultures with these E. coli strains. In the absence of neutrophils, the CFT073 strain elicited alterations in lysophosphatidylcholine and diglyceride molecular species during coculture while both strains led to increases in phosphatidylglycerols. Lipid alterations in these cocultures changed with the addition of neutrophils. In the presence of neutrophils with E. coli and endothelial cells, triglyceride increases were a unique response to the CFT073 strain while phosphatidylglycerol and diglyceride increases occurred in response to both strains. Phosphatidylethanolamine also increased in neutrophils, E. coli and endothelial cells cocultures, and this response was greater in the presence of the CFT073 strain. We further evaluated changes in phosphatidylethanolamine in a rat model of sepsis, which showed multiple plasma phosphatidylethanolamine molecular species were elevated shortly after the induction of sepsis. Collectively, these findings demonstrate unique lipid responses by co-cultures of E. coli with endothelial cells which are dependent on the E. coli strain as well as the presence of neutrophils. Furthermore, increases in phosphatidylethanolamine levels in CFT073 urosepsis E. coli, endothelial cell, neutrophil cocultures were similarly observed in the plasma of septic rats.
Plant-soil-enzyme C-N-P stoichiometry and microbial nutrient limitation responses to plant-soil feedbacks during community succession: A 3-year pot experiment in China
Authors: Xu Hongwei , Qu Qing , Wang Zhanhui , Xue Sha , Xu Zhenfeng
Published: September 2022

Studying plant-soil feedback (PSF) can improve the understanding of the plant community composition and structure; however, changes in plant-soil-enzyme stoichiometry in response to PSF are unclear. The present study aimed to analyze the changes in plant-soil-enzyme stoichiometry and microbial nutrient limitation to PSF, and identify the roles of nutrient limitation in PSF. Setaria viridis, Stipa bungeana, and Bothriochloa ischaemum were selected as representative grass species in early-, mid-, and late-succession; furthermore, three soil types were collected from grass species communities in early-, mid-, and late-succession to treat the three successional species. A 3-year (represents three growth periods) PSF experiment was performed with the three grasses in the soil in the three succession stages. We analyzed plant biomass and plant-soil-enzyme C-N-P stoichiometry for each plant growth period. The plant growth period mainly affected the plant C:N in the early- and late- species but showed a less pronounced effect on the soil C:N. During the three growth periods, the plants changed from N-limited to P-limited; the three successional species soils were mainly limited by N, whereas the microbes were limited by both C and N. The plant-soil-enzyme stoichiometry and plant biomass were not significantly correlated. In conclusion, during PSF, the plant growth period significantly influences the plant–soil–microbial nutrient limitations. Plant-soil-enzyme stoichiometry and microbial nutrient limitation cannot effectively explain PSF during succession on the Loess Plateau.