bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Risk Factors for Peripheral Neuropathy in Chinese Patients With Gout
Authors: Guo Kaifeng , Liang Nan , Wu Mian , Chen Lihui , Chen Haibing
Published: February 2022

Objective

Peripheral neuropathies (PNs) are a group of disorders that affect the peripheral nervous system. PN in gout has been scarcely described. This study is conducted to determine the prevalence and related risk factors of PN, as assessed by vibration perception threshold (VPT) in patients with gout.

Methods

A total of 442 patients were included in the cross-sectional study. The VPT values were measured by using the Biothesiometer sensory quantitative tester on each patient. The VPT value of either limb higher than 15 V was considered abnormal and is considered to have PN. The univariate and multivariate logistic regression models were used to identify risk factors for PN in patients with gout.

Results

We included 442 patients with gout, 97.5% men, 26.9% tophaceous gout, mean age 45.5 ± 15.2 years, and 7.4 ± 4.6 years of disease duration. The prevalence of PN in patients with gout was 11.1%. Patients in the abnormal VPT group were older, had a longer gout duration, and had significantly higher levels of waist circumference, waist-to-hip ratio, systolic blood pressure (SBP), and erythrocyte sedimentation rate (ESR), as compared to patients in the normal vibration group (P < 0.05). The univariate logistic regression analysis demonstrated that there was a significant association between abnormal VPT and age, duration of gout, SBP, C-reactive protein, ESR, presence of tophi, and estimated glomerular filtration rate (eGFR) in all the subjects (P < 0.05). The multivariate logistic regression analysis indicated that age (odds ratio, 1.094) and presence of tophi (odds ratio, 1.048) were independent risk factors for PN in patients with gout.

Conclusion

The abnormal VPT was significantly correlated with age and presence of tophi in patients with gout and the VPT level may be useful as a screening tool for assessment of PN in gout.
Clot Meniscus Sign Is Associated With Thrombus Permeability and Choice of Mechanical Thrombectomy Technique in Acute Middle Cerebral Artery Occlusion
Authors: Nie Chuang , Kang Zhiming , Tu Mengqi , Wu Xiangbo , Sun Dong , Mei Bin
Published: February 2022

Background and Purpose

The method of mechanical thrombectomy (MT) is related to vascular anatomy and stroke etiology. Meniscus sign and thrombus permeability as imaging markers may be instructive for the selection of MT. This study aims to clarify the relationship among meniscus sign, thrombus permeability, and choice of MT in patients with acute middle cerebral artery occlusion.

Materials and Methods

A total of 111 patients with acute middle cerebral artery occlusion (MCAO) who underwent MT were retrospectively analyzed. Clot meniscus sign was defined as the appearance of meniscoid/edge-like or single- or double-wall contrast channels besides or around insular blood clots. The radiographic, clinical, and surgical data of patients with MCAO with or without meniscus sign were compared.

Results

The meniscus sign positive group (n = 26) has higher thrombus permeability (HUs) (26.92 ± 9.69 vs. 22.84 ± 7.88, p = 0.031) than those without it. Shorter puncture-to-recanalization (P2R) time (65.5 vs. 88, p = 0.012), higher complete recanalization rate (85.71 vs. 33.33%, p < 0.01), and better clinical outcome (p < 0.01) were obtained by selecting contact aspiration (CA) over stent retriever (SR) in patients with positive meniscus sign. In patients with negative meniscus sign, there was no significant difference in clinical outcome after receiving CA or SR.

Conclusion

Patients with MCAO with positive meniscus sign have higher thrombus permeability and are more suitable for CA to acquire better clinical outcomes.
LaminaRGeneVis: A Tool to Visualize Gene Expression Across the Laminar Architecture of the Human Neocortex
Authors: Kim Ethan H. , Howard Derek , Chen Yuxiao , Tripathy Shreejoy J. , French Leon
Published: February 2022

The application of RNA sequencing has enabled the characterization of genome-wide gene expression in the human brain, including distinct layers of the neocortex. Neuroanatomically, the molecular patterns that underlie the laminar organization of the neocortex can help link structure to circuitry and function. To advance our understanding of cortical architecture, we created LaminaRGeneVis, a web application that displays across-layer cortical gene expression from multiple datasets. These datasets were collected using bulk, single-nucleus, and spatial RNA sequencing methodologies and were normalized to facilitate comparisons between datasets. The online resource performs single- and multi-gene analyses to provide figures and statistics for user-friendly assessment of laminar gene expression patterns in the adult human neocortex. The web application is available at https://ethanhkim.shinyapps.io/laminargenevis/.
Novel Hybrid Brain-Computer Interface for Virtual Reality Applications Using Steady-State Visual-Evoked Potential-Based Brain–Computer Interface and Electrooculogram-Based Eye Tracking for Increased Information Transfer Rate
Authors: Ha Jisoo , Park Seonghun , Im Chang-Hwan
Published: February 2022

Brain–computer interfaces (BCIs) based on electroencephalogram (EEG) have recently attracted increasing attention in virtual reality (VR) applications as a promising tool for controlling virtual objects or generating commands in a “hands-free” manner. Video-oculography (VOG) has been frequently used as a tool to improve BCI performance by identifying the gaze location on the screen, however, current VOG devices are generally too expensive to be embedded in practical low-cost VR head-mounted display (HMD) systems. In this study, we proposed a novel calibration-free hybrid BCI system combining steady-state visual-evoked potential (SSVEP)-based BCI and electrooculogram (EOG)-based eye tracking to increase the information transfer rate (ITR) of a nine-target SSVEP-based BCI in VR environment. Experiments were repeated on three different frequency configurations of pattern-reversal checkerboard stimuli arranged in a 3 × 3 matrix. When a user was staring at one of the nine visual stimuli, the column containing the target stimulus was first identified based on the user’s horizontal eye movement direction (left, middle, or right) classified using horizontal EOG recorded from a pair of electrodes that can be readily incorporated with any existing VR-HMD systems. Note that the EOG can be recorded using the same amplifier for recording SSVEP, unlike the VOG system. Then, the target visual stimulus was identified among the three visual stimuli vertically arranged in the selected column using the extension of multivariate synchronization index (EMSI) algorithm, one of the widely used SSVEP detection algorithms. In our experiments with 20 participants wearing a commercial VR-HMD system, it was shown that both the accuracy and ITR of the proposed hybrid BCI were significantly increased compared to those of the traditional SSVEP-based BCI in VR environment.
Differentiation of Neoplastic and Non-neoplastic Intracranial Enhancement Lesions Using Three-Dimensional Pseudo-Continuous Arterial Spin Labeling
Authors: Hu Wen-zhong , Guo Fan , Xu Yong-qiang , Xi Yi-bin , He Bei , Yin Hong , Kang Xiao-wei
Published: February 2022

Background and Purpose

It is sometimes difficult to effectively distinguish non-neoplastic from neoplastic intracranial enhancement lesions using conventional magnetic resonance imaging (MRI). This study aimed to evaluate the diagnostic performance of three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) to differentiate non-neoplastic from neoplastic enhancement lesions intracranially.

Materials and Methods

This prospective study included thirty-five patients with high-grade gliomas (HGG), twelve patients with brain metastasis, and fifteen non-neoplastic patients who underwent conventional, contrast enhancement and 3D-pCASL imaging at 3.0-T MR; all lesions were significantly enhanced. Quantitative parameters including cerebral blood flow (CBF) and relative cerebral blood flow (rCBF) were compared between neoplastic and non-neoplastic using Student’st-test. In addition, the area under the receiver operating characteristic (ROC) curve (AUC) was measured to assess the differentiation diagnostic performance of each parameter.

Results

The non-neoplastic group demonstrated significantly lower rCBF values of lesions and perilesional edema compared with the neoplastic group. For the ROC analysis, both relative cerebral blood flow of lesion (rCBF-L) and relative cerebral blood flow of perilesional edema (rCBF-PE) had good diagnostic performance for discriminating non-neoplastic from neoplastic lesions, with an AUC of 0.994 and 0.846, respectively.

Conclusion

3D-pCASL may contribute to differentiation of non-neoplastic from neoplastic lesions.
Increasing Severity of Spinal Cord Injury Results in Microglia/Macrophages With Annular-Shaped Morphology and No Change in Expression of CD40 and Tumor Growth Factor-β During the Chronic Post-injury Stage
Authors: Akhmetzyanova Elvira Ruslanovna , Timofeeva Anna Viktorovna , Sabirov Davran Khudaishukurovich , Kostennikov Alexander Alexandrovich , Rogozhin Alexander Alexandrovich , James Victoria , Arkhipova S. S. , Rizvanov Albert Anatolevich , Mukhamedshina Yana Olegovna
Published: February 2022

Determination of the quantitative composition of phenotypically and morphologically different populations of resident microglia and infiltrating macrophages in spinal cord injury (SCI) of various degrees of severity could lead to much needed novel therapeutic interventions in neurotrauma. In this regard, we investigated the CD40 and TGF-β expressing populations of microglia/macrophages and their morphological states in a rat model of SCI of varying severity. We are the first to describe the annular-shaped microglia/macrophages, the morphology of which was formed due to the spatial orientation of the processes that form round or oval micro-territories, which include disintegrating myelin fibers. This type of cell morphology was found only in the injured spinal cord and mainly in the white matter. At the same time, an assessment of the number of annular-shaped microglia/macrophages and the diameter of micro-territories formed by their processes showed an elevation in these indicators as the severity of SCI increased. While we did not find significant quantitative changes in the populations of Iba1+/CD40+ and Iba1+/TGF-β+ microglia/macrophages with increased severity of SCI in the chronic period (60 dpi), we did determine changes in the expression of cytokines and mRNAs of genes-encoding microglial marker proteins, finding the greatest changes on days 7 and 14 after SCI between experimental groups with varying severity.
Sex and Species Differences in the Development of Diet-Induced Obesity and Metabolic Disturbances in Rodents
Authors: Maric Ivana , Krieger Jean-Philippe , van der Velden Pauline , Börchers Stina , Asker Mohammed , Vujicic Milica , Wernstedt Asterholm Ingrid , Skibicka Karolina P.
Published: February 2022

Prevalence and health consequences of obesity differ between men and women. Yet, most preclinical studies investigating the etiology of obesity have, to date, been conducted in male rodents. Notably, diet is a major determinant of obesity, but sex differences in rodent models of diet-induced obesity, and the mechanisms that underlie such differences, are still understudied. Here, we aim to determine whether time course and characteristics of diet-induced obesity differ between sexes in rats and mice, and to investigate the potential causes of the observed divergence. To achieve this, we offered the most commonly tested rodents of both sexes, SD rats and C57BL/6 mice, a free choice of 60 % high-fat diet (HFD) and regular chow; body weight, food intake, fat mass, brown adipose responses, locomotor activity and glucose tolerance were assessed in a similar manner in both species. Our results indicate that overall diet-induced hyperphagia is greater in males but that females display a higher preference for the HFD, irrespective of species. Female rats, compared to males, showed a delay in diet-induced weight gain and less metabolic complications. Although male rats increased brown adipose tissue thermogenesis in response to the HFD challenge, this was not sufficient to counteract increased adiposity. In contrast to rats, female and male mice presented with a dramatic adiposity and impaired glucose tolerance, and a decreased energy expenditure. Female mice showed a 5-fold increase in visceral fat, compared to 2-fold increase seen in male mice. Overall, we found that male and female rodents responded very differently to HFD challenge, and engaged different compensatory energy expenditure mechanisms. In addition, these sex differences are divergent in rats and mice. We conclude that SD rats have a better face validity for the lower prevalence of overweight in women, while C57BL/6 mice may better model the increased prevalence of morbid obesity in women.
Effect of Lactic Fermentation and Cooking on Nutrient and Mineral Digestibility of Peas
Authors: Skalickova Sylvie , Ridoskova Andrea , Slama Petr , Skladanka Jiri , Skarpa Petr , Smykalova Iva , Horacek Jiri , Dostalova Radmila , Horky Pavel
Published: February 2022

Peas are prospectively beneficial legumes in the human diet, and especially in a vegan and vegetarian diet, due to their high content of proteins and starch. Their frequent lack of appeal in human nutrition can be caused by their bloating effect and the content of some antinutritional compounds inhibiting the absorption of important nutrients. This study brings a comprehensive comparison of the nutrient content of pea flour after cooking and lactic fermentation before and after digestion in vitro. As a control sample, raw pea flour was used (sample 1). Raw pea flour was cooked for 10 min (sample 2) and 120 min (sample 3) at 100°C or it was fermented by Lactobacillus plantarum (sample 4) and cooked for 10 min at 100°C (sample 5). The samples were analyzed for protein and amino acids content, maltose, glucose, raffinose, total polyphenols, phytic acid, phytase, and mineral composition (P, Mg, Mn, Fe, Cu, Zn) before and after in vitro digestion. The results showed a significant (p < 0.05) increase in the protein digestibility of samples 3, 4 and 5. In the fermented samples were observed a higher concentration of Cys, Met, and Gln when compared to non-fermented samples. The fermentation of pea flour resulted in a significant (p < 0.05) decrease in glucose, maltose, and raffinose content. Cooking of pea flour for 10 and 120 min, but not fermenting, significantly (p < 0.05) decreased the polyphenols content. Cooking and fermentation together did not affect phytic acid concentration and phytase activity. Mg, Mn, Fe, Cu and, Zn concentration in pea flour was significantly (p < 0.05) decreased by cooking. On the other hand, fermentation significantly (p<0.05) improved the bioaccessibility of Mn and Fe. These findings suggest that lactic fermentation of pea flour is a promising culinary preparation that can improve the digestibility of peas.
Diagnostic Accuracy of Artificial Intelligence Based on Imaging Data for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Authors: Zhang Jian , Huang Shenglan , Xu Yongkang , Wu Jianbing
Published: February 2022

Background

The presence of microvascular invasion (MVI) is considered an independent prognostic factor associated with early recurrence and poor survival in hepatocellular carcinoma (HCC) patients after resection. Artificial intelligence (AI), mainly consisting of non-deep learning algorithms (NDLAs) and deep learning algorithms (DLAs), has been widely used for MVI prediction in medical imaging.

Aim

To assess the diagnostic accuracy of AI algorithms for non-invasive, preoperative prediction of MVI based on imaging data.

Methods

Original studies reporting AI algorithms for non-invasive, preoperative prediction of MVI based on quantitative imaging data were identified in the databases PubMed, Embase, and Web of Science. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) scale. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model with 95% CIs. A summary receiver operating characteristic curve and the area under the curve (AUC) were generated to assess the diagnostic accuracy of the deep learning and non-deep learning models. In the non-deep learning group, we further performed meta-regression and subgroup analyses to identify the source of heterogeneity.

Results

Data from 16 included studies with 4,759 cases were available for meta-analysis. Four studies on deep learning models, 12 studies on non-deep learning models, and two studies compared the efficiency of the two types. For predictive performance of deep learning models, the pooled sensitivity, specificity, PLR, NLR, and AUC values were 0.84 [0.75–0.90], 0.84 [0.77–0.89], 5.14 [3.53–7.48], 0.2 [0.12–0.31], and 0.90 [0.87–0.93]; and for non-deep learning models, they were 0.77 [0.71–0.82], 0.77 [0.73–0.80], 3.30 [2.83–3.84], 0.30 [0.24–0.38], and 0.82 [0.79–0.85], respectively. Subgroup analyses showed a significant difference between the single tumor subgroup and the multiple tumor subgroup in the pooled sensitivity, NLR, and AUC.

Conclusion

This meta-analysis demonstrates the high diagnostic accuracy of non-deep learning and deep learning methods for MVI status prediction and their promising potential for clinical decision-making. Deep learning models perform better than non-deep learning models in terms of the accuracy of MVI prediction, methodology, and cost-effectiveness.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID=260891, ID:CRD42021260891.
The Potential Roles of Exosomal Non-Coding RNAs in Hepatocellular Carcinoma
Authors: Wang Wei , Hao Li-Ping , Song Haizhu , Chu Xiao-Yuan , Wang Rui
Published: February 2022

Hepatocellular carcinoma (HCC) is the sixth highest-incidence cancer and the 4th most deadly cancer all over the world, with a high fatality and low diagnostic rate. Nowadays, Excessive alcohol consumption, type-2 diabetes, smoking and obesity have become some primary risk factors of HCC. As intercellular messenger transporting information cargoes between cells, exosomes are a type of extracellular vesicles (EVs) released by most types of cells including tumor cells and non-tumor cells and play a pivotal role in establishing an HCC microenvironment. Exosomes, and more generally EVs, contain different molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids and transcription factors. The three main ncRNAs in exosomes are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs). NcRNAs, identified as essential components, are selectively sorted into exosomes and exosomal ncRNAs show great potential in regulating tumor development, including proliferation, invasion, angiogenesis, metastasis, immune escape and drug resistance. Here, we chiefly review the formation and uptake of exosomes, classification of exosomal ncRNAs and current research on the roles of exosomal ncRNAs in HCC progression. We also explored their clinical applications as new diagnostic biomarkers and therapeutic avenues in HCC.
Emerging Trends on the Correlation Between Neurotransmitters and Tumor Progression in the Last 20 Years: A Bibliometric Analysis via CiteSpace
Authors: Shi Yumiao , Luo Jiamei , Wang Xiaoqiang , Zhang Yiqi , Zhu Hui , Su Diansan , Yu Weifeng , Tian Jie
Published: February 2022

Background

Bibliometric analysis is used to gain a systematic understanding of developments in the correlation between neurotransmitters and tumor progression in research hotspots over the past 20 years.

Methods

Relevant publications from the Web of Science Core Collection (WoSCC) were downloaded on August 1, 2021. Acquired data were then analyzed using the Online Analysis Platform of Literature Metrology (http://biblimetric.com) and the CiteSpace software to analyze and predict trends and hot spots in this field.

Results

A total of 1310 publications on neurotransmitters and tumor progression were identified, and 1285 qualified records were included in the final analysis. The country leading the research was the United States of America. The University of Buenos Aires featured the highest number of publications among all institutions. Co-citation cluster labels revealed the characteristics of 10 main clusters: beta-adrenergic receptors (β-AR), glutamate, neurotransmitters, serotonin, drd2, histamine, glycine, interleukin-2, neurokinin receptor-1, and nicotinic acetylcholine receptors (AchRs). Keywords and references burst detection indicated that apart from β-AR, dopamine receptor and cancer types like gastric cancer and glioblastoma are the newly emerging research hotspots.

Conclusions

This study analyzed 1285 publications and 39677 references covering the topic of neurotransmitters and tumor progression and showed that while β-AR has always been a hot topic in this field, dopamine receptor is an emerging target for this research field, and gastric cancer and glioblastoma are the top two tumors that have garnered increasing attention and have become the focal point of recent studies.
Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study
Authors: Li Qi , Cao Mengran , Yuan Guosheng , Cheng Xiao , Zang Mengya , Chen Ming , Hu Xiaoyun , Huang Jing , Li Rong , Guo Yabing , Ruan Jian , Chen Jinzhang
Published: February 2022

Background

Combining an antiangiogenic agent with an anti-PD-1 agent is a promising strategy for unresectable hepatocellular carcinoma (HCC).

Aims

To explore the effectiveness and tolerability of lenvatinib plus camrelizumab vs. lenvatinib monotherapy as a first-line treatment for unresectable HCC.

Methods

This multicenter, retrospective cohort study included patients with unresectable HCC treated with oral lenvatinib 8 mg daily and intravenous camrelizumab 200 mg every 3 weeks (L+C group) or lenvatinib 12 mg or 8 mg daily (L group) in four Chinese centers between September 2018 and February 2020. Tumor response was evaluated according to RECIST 1.1 and mRECIST. The outcomes included objective response rate (ORR), overall survival (OS), 1-year OS rate, progression-free survival (PFS), and safety.

Results

By March 31, 2021, 92 patients were finally included, with 48 and 44 in the L+C and L groups, respectively. ORR was significantly higher in the L+C group than in the L group (RECIST 1.1: 37.5% vs. 13.6%, P=0.009; mRECIST: 41.7% vs. 20.5%, P=0.029). Median OS and 95% confidence interval (CI) was 13.9 (13.3-18.3) months in the L group and not reached in the L+C group (P=0.015). The 1-year survival rate was 79.2% and 56.8% in the L+C and L groups, respectively. Median PFS was 10.3 (6.6-14.0) months and 7.5 (5.7-9.3) months in the L+C and L groups, respectively (P=0.0098). Combined therapy vs. monotherapy was independently associated with a prolonged OS (hazard ratio=0.380, 95% CI=: 0.196-0.739, P=0.004) and a prolonged PFS (hazard ratio=0.454, 95%CI=0.282-0.731, P=0.001). The safety profile was comparable between the two groups. The most common adverse event in the L+C and L groups was loss of appetite (41.7% vs. 40.9%, P=0.941). Three patients in the L+C group and two in the L group terminated treatment owing to adverse events.

Conclusion

First-line lenvatinib plus camrelizumab showed better effectiveness than lenvatinib alone in patients with unresectable HCC.
Head-to-Head Comparison of 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 PET/CT in Patients With Tumor-Induced Osteomalacia: A Prospective Study
Authors: Hou Guozhu , Zhang Yuwei , Liu Yu , Wang Peipei , Xia Weibo , Xing Xiaoping , Huo Li , Li Fang , Jing Hongli
Published: February 2022

Background

The purpose of this study is to compare the sensitivity of 68Ga-DOTA-JR11 and 68Ga-DOTA-TATE PET/CT for detecting the responsible tumor of tumor-induced osteomalacia (TIO) and investigate if 68Ga-DOTA-JR11 PET/CT can identify the culprit tumor of TIO in multiple suspicious lesions in 68Ga-DOTA-TATE PET/CT.

Methods

A total of 19 patients with suspected TIO were prospectively recruited in this study. Each patient underwent whole-body PET/CT scan 40–60 min postinjection using 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 on the same PET/CT, respectively in sequence, and on consecutive days. The diagnosis of TIO was confirmed by the combination of the postsurgical pathological results of the tumor and clinical information.

Results

Among the 19 patients with TIO who were included in this study, culprit tumors from all patients were confirmed pathologically. 68Ga-DOTA-TATE PET/CT positively identified the causative tumor in 18/19 patients, whereas 68Ga-DOTA-JR11 PET/CT was positive in 11/19 patients (94.7% vs. 57.9%, respectively; p < 0.05). 68Ga-DOTA-TATE PET/CT demonstrated more than one increased focal activity in 7 patients for a total of 16 lesions (3 lesions each in 2 patients and 2 lesions each in the rest 5 patients). However, seven of these 16 lesions showed concordant results on 68Ga-DOTA-JR11 PET/CT by demonstrating increased activity (one lesion in each of the 7 patients). The surgical specimens of the lesions in these 7 patients confirmed the phosphaturic mesenchymal tumor. A total of 11 culprit tumors were positive in both 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 PET/CT. The SUVmax of 11 culprit tumors was significantly higher on 68Ga-DOTA-TATE PET/CT compared with that on 68Ga-DOTA-JR11 PET/CT (17.8 ± 12.5 vs. 6.8 ± 6.2; p < 0.05).

Conclusions

68Ga-DOTA-TATE PET/CT is more sensitive to 68Ga-DOTA-JR11 PET/CT in the detection of the culprit tumor of TIO. However, 68Ga-DOTA-JR11 PET/CT might be helpful to identify the tumor in multiple suspicious lesions in 68Ga-DOTA-TATE PET/CT.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT 04689893.
Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy
Authors: Yang Wentao , Zou Jianling , Li Ye , Liu Rujiao , Yan Zhengqing , Chen Shiqing , Zhao Xiaoying , Guo Weijian , Huang Mingzhu , Li Wenhua , Zhu Xiaodong , Chen Zhiyu
Published: February 2022

Background

Metastatic colorectal cancer (mCRC) is a heterogenous disease with limited precision medicine and targeted therapy options. Monoclonal antibodies against epidermal growth factor receptor (EGFR) have been a crucial treatment option for mCRC. However, proper biomarkers for predicting therapeutic response remain unknown. As a non-invasive test, circulating tumor DNA (ctDNA) is appropriately positioned to reveal tumor heterogeneity and evolution, as it can be used in real-time genomic profiling. To evaluate the significance of ctDNA in monitoring the dynamic therapeutic response and prognosis of mCRC, we detected the baseline and dynamic changes of ctDNA in mCRC patients receiving anti-EGFR therapies.

Methods

A single-center study was conducted retrospectively. Plasma samples from mCRC patients who received anti-EGFR therapies were collected at baseline and continuous treatment points. The ctDNA was extracted and sequenced with a target panel of tumor-related genes via next-generation sequencing (NGS). Clinical information was also collected and analyzed.

Results

We conducted dynamic sampling of 22 mCRC patients, analyzed 130 plasma samples, obtained a baseline genomic mutation profile of the patients. In total, 54 variations were detected in 22 plasma samples, with a positive rate of 77.3% (17/22). TP53 was the most mutated gene (59.1%, 13/22), followed by APC (18.2%, 4/22). There was a high concordance rate of genomic characteristics between the tumor tissue test by polymerase chain reaction and ctDNA test by NGS. The mutation discrepancy increased with an extended course of treatment. During remission TP53 and APC were the most frequently decreased clonal mutations and KRAS, NRAS, ERBB2 and PIK3CA were the most decreased subclonal mutations. Both mutation types were increased during progression. The ctDNA decreased earlier than did the responses of computed tomography and traditional tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen [CEA]). Lactate dehydrogenase level (P = 0.041), CEA level (P = 0.038), and primary lesion site (P = 0.038) were independent risk factors that influenced overall survival. Moreover, patients with RAS mutations tended to have a worse prognosis (P = 0.072).

Conclusions

This study demonstrates that ctDNA is a promising biomarker for monitoring the dynamic response to treatment and determining the prognosis of mCRC.
Tumor-Educated Platelets Facilitate Thrombus Formation Through Migration
Authors: Liu Zheming , Wang Jing , Liao Fuben , Song Qibin , Yao Yi
Published: February 2022

Platelets are small anucleate cells that circulate in the blood and form thrombi. Tumor-educated platelets are the platelets derived from cancer patients. Although many have reported that tumor-educated platelets are associated with cancer-associated thrombosis, their function in this process is poorly understood. Here we first collect the clinical data from 100 different cancer patients, showing that cancer patients are in a hypercoagulable state. Our experiment shows that tumor-educated platelets from melanoma-burdened mouse models can migrate faster and longer, forming more clots (thrombus). However, the plasma from tumor mice can inhibit platelet migration. The RNA sequence profile of tumor-educated platelets shows that many genes associated with cell migration and cell skeleton expressed significantly higher. Our research offers a new insight into the tumor-educated platelets to better understand the thrombus formation.
Acute Lymphoblastic Leukaemia in the Youngest: Haematopoietic Stem Cell Transplantation and Beyond
Authors: Balduzzi Adriana , Buechner Jochen , Ifversen Marianne , Dalle Jean-Hugues , Colita Anca M. , Bierings Marc
Published: February 2022

The ALL SCTped 2012 FORUM (For Omitting Radiation Under Majority age) trial compared outcomes for children ≥4 years of age transplanted for acute lymphoblastic leukaemia (ALL) who were randomised to myeloablation with a total body irradiation (TBI)-based or chemotherapy-based conditioning regimen. The TBI-based preparation was associated with a lower rate of relapse compared with chemoconditioning. Nevertheless, the age considered suitable for TBI was progressively raised over time to spare the most fragile youngest patients from irradiation-related complications. The best approach to use for children <4 years of age remains unclear. Children diagnosed with ALL in their first year of life, defined as infants, have a remarkably poorer prognosis compared with older children. This is largely explained by the biology of their ALL, with infants often carrying a KMT2A gene rearrangement, as well as by their fragility. In contrast, the clinical presentations and biological features of ALL in children >1 year but <4 years often resemble those presented by older children. In this review, we explore the state of the art regarding haematopoietic stem cell transplantation (HSCT) in children <4 years, the preparative regimens available, and new developments in the field that may influence treatment decisions.
Characterizing Neurocognitive Impairment in Juvenile Fibromyalgia Syndrome: Subjective and Objective Measures of Dyscognition
Authors: Gmuca Sabrina , Sonagra Maitry , Xiao Rui , Mendoza Elizabeth , Miller Kimberly S. , Thomas Nina H. , Young Jami F. , Weiss Pamela F. , Sherry David D. , Gerber Jeffrey S.
Published: February 2022

Objectives

Our understanding of brain fog, or dyscognition, among youth with juvenile fibromyalgia syndrome is limited. We aimed to determine the prevalence of subjective (self-reported) and objective dyscognition, as well as factors associated with subjective dyscognition in juvenile fibromyalgia syndrome.

Methods

A cross-sectional cohort study of patients (n = 31) 12-17 years old diagnosed with primary juvenile fibromyalgia syndrome and one of their parents from 2017 to 2019. Subjects completed a series of survey measures and patients completed a brief neurocognitive battery. Subjective dyscognition was determined based on scores on the Pediatric Quality of Life Inventory (PedsQL) Cognitive Functioning Scale and Behavior Rating Inventory of Executive Function (BRIEF-2) global executive composite (GEC). Objective dyscognition was defined as impairment of more than two standard deviations in any of the neurocognitive domains. We used Fisher's exact test or Wilcoxon rank-sum test, as appropriate, to compare clinical patients based on the presence of dyscognition. Multivariable logistic regression modeling was performed to determine factors associated with subjective dyscognition.

Results

Of the 31 subjects, 65% reported subjective dyscognition and 39% had objective dyscognition, primarily in the domains of psychomotor speed (23%), executive function (23%), and attention (3%). Subjective dyscognition was not indicative of objective dyscognition. Subjective dyscognition was independently associated with functional disability (OR: 1.19 [95% CI: 1.02-1.40]) and anxiety (OR: 1.12 [95% CI: 1.02-1.24]).

Discussion

Adolescents with fibromyalgia predominantly experience subjective dyscognition but more than 1/3 also experience objective dyscognition. Future research should explore the impact of interdisciplinary rehabilitation programs on the treatment of dyscognition in youth with JFMS.
Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study
Authors: Huang Anxiong , Luo Xun , Xu Zihui , Huang Lingli , Wang Xu , Xie Shuyu , Pan Yuanhu , Fang Shiwei , Liu Zhenli , Yuan Zonghui , Hao Haihong
Published: February 2022

Clostridium perfringens causes significant morbidity and mortality in swine worldwide. Avilamycin showed no cross resistance and good activity for treatment of C. perfringens. The aim of this study was to formulate optimal regimens of avilamycin treatment for C. perfringens infection based on the clinical breakpoint (CBP). The wild-type cutoff value (COWT) was defined as 0.25 μg/ml, which was developed based on the minimum inhibitory concentration (MIC) distributions of 120 C. perfringens isolates and calculated using ECOFFinder. Pharmacokinetics–pharmacodynamics (PK-PD) of avilamycin in ileal content were analyzed based on the high-performance liquid chromatography method and WinNonlin software to set up the target of PK/PD index (AUC0–24h/MIC)ex based on sigmoid Emax modeling. The PK parameters of AUC0–24h, Cmax, and Tmax in the intestinal tract were 428.62 ± 14.23 h μg/mL, 146.30 ± 13.41 μg/ml,, and 4 h, respectively. The target of (AUC0–24h/MIC)ex for bactericidal activity in intestinal content was 36.15 h. The PK-PD cutoff value (COPD) was defined as 8 μg/ml and calculated by Monte Carlo simulation. The dose regimen designed from the PK-PD study was 5.2 mg/kg mixed feeding and administrated for the treatment of C. perfringens infection. Five respective strains with different MICs were selected as the infection pathogens, and the clinical cutoff value was defined as 0.125 μg/ml based on the relationship between MIC and the possibility of cure (POC) following nonlinear regression analysis, CART, and “Window” approach. The CBP was set to be 0.25 μg/ml and selected by the integrated decision tree recommended by the Clinical Laboratory of Standard Institute. The formulation of the optimal regimens and CBP is good for clinical treatment and to control drug resistance.
Mechanisms and Efficacy of Traditional Chinese Medicine in Heart Failure
Authors: Wang Anzhu , Zhao Wei , Yan Kaituo , Huang Pingping , Zhang Hongwei , Zhang Zhibo , Zhang Dawu , Ma Xiaochang
Published: February 2022

Heart failure (HF) is one of the main public health problems at present. Although some breakthroughs have been made in the treatment of HF, the mortality rate remains very high. However, we should also pay attention to improving the quality of life of patients with HF. Traditional Chinese medicine (TCM) has a long history of being used to treat HF. To demonstrate the clinical effects and mechanisms of TCM, we searched published clinical trial studies and basic studies. The search results showed that adjuvant therapy with TCM might benefit patients with HF, and its mechanism may be related to microvascular circulation, myocardial energy metabolism, oxidative stress, and inflammation.
Dapagliflozin Reduces Apoptosis of Diabetic Retina and Human Retinal Microvascular Endothelial Cells Through ERK1/2/cPLA2/AA/ROS Pathway Independent of Hypoglycemic
Authors: Hu Yuxin , Xu Qian , Li Hongxue , Meng Ziyu , Hao Ming , Ma Xuefei , Lin Wenjian , Kuang Hongyu
Published: February 2022

Introduction: It is known that the metabolic disorder caused by high glucose is one of pathogenesis in diabetic retinopathy (DR), the leading cause of blindness, due to the main pathological change of apoptosis of endothelial cells (ECs). In previous studies, the potential impact of sodium glucose cotransporter-2 (SGLT-2), whose inhibitors slow the progression of DR, has not been elucidated. The purpose of the presented study was to explore the effect of SGLT-2 inhibitors dapagliflozin (DAPA) on apoptosis of diabetic mice retina and human retinal microvascular endothelial cells (HRMECs), examine the effects of dapagliflozin on HRMECs metabolism, and explore the molecular processes that affect DR.

Methods and Results: The eyeballs of male streptozotocin (STZ)-induced diabetic C57BL/6N mice were evaluated. C57BL/6N mice were divided into control group (CON), diabetic untreated group (DM), diabetic dapagliflozin treatment group (DM + DAPA) and diabetic insulin treatment group (DM + INS). Hematoxylin-Eosin (HE) staining was performed to observe the pathological structure of the mice retina, and TUNEL staining to detect apoptosis of mice retinal cells. In vitro, DCFH-DA and western blot (WB) were used to evaluate ROS, Bcl-2, BAX, cleaved-caspase 3 in HRMECs and metabolomics detected the effect of dapagliflozin on the metabolism of HRMECs. And then, we performed correlation analysis and verification functions for significantly different metabolites. In vivo, dapagliflozin reduced the apoptosis of diabetic mice retina independently of hypoglycemic. In vitro, SGLT-2 protein was expressed on HRMECs. Dapagliflozin reduced the level of ROS caused by high glucose, decreased the expression of cleaved-caspase3 and the ratio of BAX/Bcl-2. Metabolomics results showed that dapagliflozin did not affect the intracellular glucose level. Compared with the high glucose group, dapagliflozin reduced the production of arachidonic acid (AA) and inhibited the phosphorylation of ERK1/2, therefore, reducing the phosphorylation of cPLA2, which is a key enzyme for arachidonic acid release.

Conclusion: Collectively, results unearthed for the first time that dapagliflozin reduced apoptosis of retina induced by DM whether in vivo or in vitro. Dapagliflozin did not affect the glucose uptake while mitigated intracellular arachidonic acid in HRMECs. Dapagliflozin alleviated HRMECs apoptosis induced by high glucose through ERK/1/2/cPLA2/AA/ROS pathway.
Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases
Authors: Miao Mengqiu , Wu Mengqiu , Li Yuting , Zhang Lingge , Jin Qianqian , Fan Jiaojiao , Xu Xinyue , Gu Ran , Hao Haiping , Zhang Aihua , Jia Zhanjun
Published: February 2022

Hypoxia inducible factors (HIFs) and their regulatory hydroxylases the prolyl hydroxylase domain enzymes (PHDs) are the key mediators of the cellular response to hypoxia. HIFs are normally hydroxylated by PHDs and degraded, while under hypoxia, PHDs are suppressed, allowing HIF-α to accumulate and transactivate multiple target genes, including erythropoiesis, and genes participate in angiogenesis, iron metabolism, glycolysis, glucose transport, cell proliferation, survival, and so on. Aiming at stimulating HIFs, a group of small molecules antagonizing HIF-PHDs have been developed. Of these HIF-PHDs inhibitors (HIF-PHIs), roxadustat (FG-4592), daprodustat (GSK-1278863), vadadustat (AKB-6548), molidustat (BAY 85-3934) and enarodustat (JTZ-951) are approved for clinical usage or have progressed into clinical trials for chronic kidney disease (CKD) anemia treatment, based on their activation effect on erythropoiesis and iron metabolism. Since HIFs are involved in many physiological and pathological conditions, efforts have been made to extend the potential usage of HIF-PHIs beyond anemia. This paper reviewed the progress of preclinical and clinical research on clinically available HIF-PHIs in pathological conditions other than CKD anemia.
The Role of Neuromuscular Control of Postural and Core Stability in Functional Movement and Athlete Performance
Authors: Zemková Erika , Zapletalová Ludmila
Published: February 2022

Balance and core stabilization exercises have often been associated with improved athlete performance and/or decreased incidence of injuries. While these exercises seem to be efficient in the prevention of injuries, there is insufficient evidence regarding their role in sport-specific performance and related functional movements. The aim of this scoping review is (1) to map the literature that investigates whether currently available variables of postural and core stability are functionally related to athlete performance in sports with high demands on body balance and spinal posture and (2) to identify gaps in the literature and suggest further research on this topic. The literature search conducted on MEDLINE, Scopus, Web of Science, PubMed, and Cochrane Library databases was completed by Google Scholar, SpringerLink, and Elsevier. Altogether 21 articles met the inclusion criteria. Findings revealed that postural stability plays an important role in performance in archery, biathlon, gymnastics, shooting, and team sports (e.g., basketball, hockey, soccer, tennis). Also core stability and strength represent an integral part of athlete performance in sports based on lifting tasks and trunk rotations. Variables of these abilities are associated with performance-related skills in cricket, cycling, running, and team sports (e.g., baseball, football, hockey, netball, soccer, tennis). Better neuromuscular control of postural and core stability contribute to more efficient functional movements specific to particular sports. Training programs incorporating general and sport-specific exercises that involve the use of postural and core muscles showed an improvement of body balance, back muscle strength, and endurance. However, there is controversy about whether the improvement in these abilities is translated into athletic performance. There is still a lack of research investigating the relationship of body balance and stability of the core with sport-specific performance. In particular, corresponding variables should be better specified in relation to functional movements in sports with high demands on postural and core stability. Identifying the relationship of passive, active, and neural mechanisms underlying balance control and spinal posture with athlete performance would provide a basis for a multifaced approach in designing training and testing tools addressing postural and core stability in athletes under sport-specific conditions.
YOLO-VOLO-LS: A Novel Method for Variety Identification of Early Lettuce Seedlings
Authors: Zhang Pan , Li Daoliang
Published: February 2022

Accurate identification of crop varieties is an important aspect of smart agriculture, which is not only essential for the management of later crop differences, but also has a significant effect on unmanned operations in planting scenarios such as facility greenhouses. In this study, five kinds of lettuce under the cultivation conditions of greenhouses were used as the research object, and a classification model of lettuce varieties with multiple growth stages was established. First of all, we used the-state-of-the-art method VOLO-D1 to establish a variety classification model for the 7 growth stages of the entire growth process. The results found that the performance of the lettuce variety classification model in the SP stage needs to be improved, but the classification effect of the model at other stages is close to 100%; Secondly, based on the challenges of the SP stage dataset, we combined the advantages of the target detection mechanism and the target classification mechanism, innovatively proposed a new method of variety identification for the SP stage, called YOLO-VOLO-LS. Finally, we used this method to model and analyze the classification of lettuce varieties in the SP stage. The result shows that the method can achieve excellent results of 95.961, 93.452, 96.059, 96.014, 96.039 in Val-acc, Test-acc, Recall, Precision, F1-score, respectively. Therefore, the method proposed in this study has a certain reference value for the accurate identification of varieties in the early growth stage of crops.
Leaf Stoichiometry of Potentilla fruticosa Across Elevations in China’s Qilian Mountains
Authors: Qin Yanyan , Liu Wei , Zhang Xiaofang , Adamowski Jan F. , Biswas Asim
Published: February 2022

As an individual plant species can develop its own leaf stoichiometry to adapt to environmental changes, this stoichiometry can provide critical information about a plant species’ growth and its potential management in the ecosystem housing it. However, leaf stoichiometry is largely undocumented in regions with large environmental changes arising from differences in elevation. The leaf stoichiometry ofPotentilla fruticosaL., a major alpine shrub playing an important role in supporting ecosystem functions and services in China’s Qilian Mountains (Northeast Qinghai–Tibetan Plateau), was investigated at different elevations (2,400, 2,600, 2,800, 3,000, 3,200, 3,500, and 3,800 m). At each elevation, leaf elemental (C, N, and P) concentrations were measured inP. fruticosaleaves sampled from three plots (10 × 10 m), and edaphic properties were assessed in nine quadrats (1 × 1 m, three quadrats per plot). Temperature and precipitation were calculated using an empirical formula. Maximum and minimum leaf carbon (C) concentrations ([C]leaf) of 524 ± 5.88 and 403 ± 3.01 g kg–1were measured at 2,600 and 3,500 m, respectively. Leaf nitrogen (N) concentration ([N]leaf) showed a generally increasing trend with elevation and peaked at 3,500 m (27.33 ± 0.26 g kg–1). Leaf phosphorus (P) concentration ([P]leaf) varied slightly from 2,400 to 3,200 m and then dropped to a minimum (0.60 ± 0.10 g kg–1) at 3800 m. The [C]leaf:[N]leaf, [C]leaf:[P]leaf, and [N]leaf:[P]leafvaried little from 2,400 to 3,000 m but fluctuated somewhat at higher elevations. The main factors affectingP. fruticosaleaf stoichiometry were soil organic C, pH, and soil total P, and the main limiting element for the growth ofP. fruticosain the study area was P. In conclusion, changes in elevation affected leaf stoichiometry ofP. fruticosamainly due to altered soil properties, and addressing phosphorus limitation, especially at higher elevations mainly due to losses caused by high precipitation and sparse vegetation, is a key measure to promoteP. fruticosagrowth in this region.