bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of high-altitude cerebral edema using multimodal imaging
Authors: Long Changyou , Bao Haihua
Published: January 2023

Objective

To analyze the brain imaging features of high-altitude cerebral edema (HACE) using computed tomography (CT) and multi-sequence magnetic resonance imaging (MRI) and to explore its injury characteristics.

Materials and methods

We selected 30 patients with HACE diagnosed between January 2012 to August 2022 as the experimental group and 60 patients with dizziness on traveling from the plain to the plateau or from lower altitude to higher altitude in a short period of time as the control group. We collected general clinical data from the experimental group and classified it according to clinical symptoms. In both groups, we then performed a head CT and multi-sequence MRI (T1WI, T2WI, FLAIR, and DWI). Among them, nine patients with HACE were also scanned using susceptibility-weighted imaging (SWI). Finally, we analyzed the images.

Results

According to clinical symptoms, we divided the 30 cases of HACE into 12 mild cases and 18 severe cases. There was no significant difference in sex, age, leukocyte, neutrophil, or glucose content between mild and severe HACE. The sensitivity and specificity of the MRI diagnosis were 100 and 100%, respectively, while the sensitivity and specificity of the CT diagnosis were 23.3 and 100%, respectively. The distribution range of deep and juxtacortical white matter edema was significantly larger in severe HACE than in mild HACE (p < 0.001). The corpus callosum edema distribution range in severe HACE was significantly larger than that in mild HACE (p = 0.001). The ADC value of the splenium of the corpus callosum was significantly lower in severe HACE than in mild HACE (p = 0.049). In mild and severe HACE, the signal intensity of the DWI sequence was significantly higher than that of conventional MRI sequences (T1WI, T2WI, FLAIR) (p = 0.008, p = 0.025, respectively). In severe HACE, seven cases showed bilateral corticospinal tract edema at the thalamic level, and SWI showed cerebral microbleeds (CMBs) in five cases, especially in the corpus callosum.

Conclusions

MRI has more advantages than CT in the evaluation of HACE, especially in the DWI sequence. The white matter injury of severe HACE is more severe and extensive, especially in the corpus callosum, and some CMBs and corticospinal tract edema may also appear.
Diagnostic models and predictive drugs associated with cuproptosis hub genes in Alzheimer's disease
Authors: Zhang Erdong , Dai Fengqiu , Chen Tingting , Liu Shanhui , Xiao Chaolun , Shen Xiangchun
Published: January 2023

Alzheimer's disease (AD) is a chronic neurodegenerative disease, and its underlying genes and treatments are unclear. Abnormalities in copper metabolism can prevent the clearance of β-amyloid peptides and promote the progression of AD pathogenesis. Therefore, the present study used a bioinformatics approach to perform an integrated analysis of the hub gene based on cuproptosis that can influence the diagnosis and treatment of AD. The gene expression profiles were obtained from the Gene Expression Omnibus database, including non-demented (ND) and AD samples. A total of 2,977 cuproptosis genes were retrieved from published articles. The seven hub genes associated with cuproptosis and AD were obtained from the differentially expressed genes and WGCNA in brain tissue from GSE33000. The GO analysis demonstrated that these genes were involved in phosphoribosyl pyrophosphate, lipid, and glucose metabolism. By stepwise regression and logistic regression analysis, we screened four of the seven cuproptosis genes to construct a diagnostic model for AD, which was validated by GES15222, GS48350, and GSE5281. In addition, immune cell infiltration of samples was investigated for correlation with these hub genes. We identified six drugs targeting these seven cuproptosis genes in DrugBank. Hence, these cuproptosis gene signatures may be an important prognostic indicator for AD and may offer new insights into treatment options.
Identifying vulnerable plaques: A 3D carotid plaque radiomics model based on HRMRI
Authors: Zhang Xun , Hua Zhaohui , Chen Rui , Jiao Zhouyang , Shan Jintao , Li Chong , Li Zhen
Published: January 2023

Background

Identification of vulnerable carotid plaque is important for the treatment and prevention of stroke. In previous studies, plaque vulnerability was assessed qualitatively. We aimed to develop a 3D carotid plaque radiomics model based on high-resolution magnetic resonance imaging (HRMRI) to quantitatively identify vulnerable plaques.

Methods

Ninety patients with carotid atherosclerosis who underwent HRMRI were randomized into training and test cohorts. Using the radiological characteristics of carotid plaques, a traditional model was constructed. A 3D carotid plaque radiomics model was constructed using the radiomics features of 3D T1-SPACE and its contrast-enhanced sequences. A combined model was constructed using radiological and radiomics characteristics. Nomogram was generated based on the combined models, and ROC curves were utilized to assess the performance of each model.

Results

48 patients (53.33%) were symptomatic and 42 (46.67%) were asymptomatic. The traditional model was constructed using intraplaque hemorrhage, plaque enhancement, wall remodeling pattern, and lumen stenosis, and it provided an area under the curve (AUC) of 0.816 vs. 0.778 in the training and testing sets. In the two cohorts, the 3D carotid plaque radiomics model and the combined model had an AUC of 0.915 vs. 0.835 and 0.957 vs. 0.864, respectively. In the training set, both the radiomics model and the combination model outperformed the traditional model, but there was no significant difference between the radiomics model and the combined model.

Conclusions

HRMRI-based 3D carotid radiomics models can improve the precision of detecting vulnerable carotid plaques, consequently improving risk classification and clinical decision-making in patients with carotid stenosis.
Case report: Subacute combined degeneration of the spinal cord due to nitrous oxide abuse
Authors: Wu Huijuan , Huang Huiqing , Xu Liaoyang , Ji Niu , Zhou Xinyu , Xie Kang
Published: January 2023

Background

Nitrous oxide (N2O) is an increasingly popular recreational drug. N2O irreversibly disturbs the metabolism of vitamin B12, resulting in a functional deficiency. Vitamin B12 is vital for myelin synthesis and its deficiency primarily produces neurological complications. Inhaling N2O is more common and neurological complications are more evident than before.

Case presentation

We report a young man who developed progressive limb numbness and unsteady walking after N2O abuse. The dominant diagnosis was subacute combined degeneration of the spinal cord (SCD). The patient was admitted to the hospital and given adenosylcobalamin treatment, but his symptoms progressed significantly from before and he developed acute cognitive impairment. After methylprednisolone combined with vitamin B12 treatment, symptoms significantly improved.

Conclusion

Clinicians need to understand the presentation and treatment of SCD caused by N2O abuse. When symptoms progress despite conventional vitamin B12 therapy, the combination of methylprednisolone and vitamin B12 may be considered.
Efficient suppression of parkinsonian beta oscillations in a closed-loop model of deep brain stimulation with amplitude modulation
Authors: Bahadori-Jahromi Fatemeh , Salehi Sina , Madadi Asl Mojtaba , Valizadeh Alireza
Published: January 2023

Introduction

Parkinson's disease (PD) is a movement disorder characterized by the pathological beta band (15–30 Hz) neural oscillations within the basal ganglia (BG). It is shown that the suppression of abnormal beta oscillations is correlated with the improvement of PD motor symptoms, which is a goal of standard therapies including deep brain stimulation (DBS). To overcome the stimulation-induced side effects and inefficiencies of conventional DBS (cDBS) and to reduce the administered stimulation current, closed-loop adaptive DBS (aDBS) techniques were developed. In this method, the frequency and/or amplitude of stimulation are modulated based on various disease biomarkers.

Methods

Here, by computational modeling of a cortico-BG-thalamic network in normal and PD conditions, we show that closed-loop aDBS of the subthalamic nucleus (STN) with amplitude modulation leads to a more effective suppression of pathological beta oscillations within the parkinsonian BG.

Results

Our results show that beta band neural oscillations are restored to their normal range and the reliability of the response of the thalamic neurons to motor cortex commands is retained due to aDBS with amplitude modulation. Furthermore, notably less stimulation current is administered during aDBS compared with cDBS due to a closed-loop control of stimulation amplitude based on the STN local field potential (LFP) beta activity.

Discussion

Efficient models of closed-loop stimulation may contribute to the clinical development of optimized aDBS techniques designed to reduce potential stimulation-induced side effects of cDBS in PD patients while leading to a better therapeutic outcome.
The Topo-Speech sensory substitution system as a method of conveying spatial information to the blind and vision impaired
Authors: Maimon Amber , Wald Iddo Yehoshua , Ben Oz Meshi , Codron Sophie , Netzer Ophir , Heimler Benedetta , Amedi Amir
Published: January 2023

Humans, like most animals, integrate sensory input in the brain from different sensory modalities. Yet humans are distinct in their ability to grasp symbolic input, which is interpreted into a cognitive mental representation of the world. This representation merges with external sensory input, providing modality integration of a different sort. This study evaluates the Topo-Speech algorithm in the blind and visually impaired. The system provides spatial information about the external world by applying sensory substitution alongside symbolic representations in a manner that corresponds with the unique way our brains acquire and process information. This is done by conveying spatial information, customarily acquired through vision, through the auditory channel, in a combination of sensory (auditory) features and symbolic language (named/spoken) features. The Topo-Speech sweeps the visual scene or image and represents objects’ identity by employing naming in a spoken word and simultaneously conveying the objects’ location by mapping the x-axis of the visual scene or image to the time it is announced and the y-axis by mapping the location to the pitch of the voice. This proof of concept study primarily explores the practical applicability of this approach in 22 visually impaired and blind individuals. The findings showed that individuals from both populations could effectively interpret and use the algorithm after a single training session. The blind showed an accuracy of 74.45%, while the visually impaired had an average accuracy of 72.74%. These results are comparable to those of the sighted, as shown in previous research, with all participants above chance level. As such, we demonstrate practically how aspects of spatial information can be transmitted through non-visual channels. To complement the findings, we weigh in on debates concerning models of spatial knowledge (the persistent, cumulative, or convergent models) and the capacity for spatial representation in the blind. We suggest the present study’s findings support the convergence model and the scenario that posits the blind are capable of some aspects of spatial representation as depicted by the algorithm comparable to those of the sighted. Finally, we present possible future developments, implementations, and use cases for the system as an aid for the blind and visually impaired.
Methods for the isolation and analysis of Aβ from postmortem brain
Authors: Hong Wei , Liu Wen , Desousa Alexandra O. , Young-Pearse Tracy , Walsh Dominic M.
Published: January 2023

Amyloid β-protein (Aβ) plays an initiating role in Alzheimer’s disease (AD), but only a small number of groups have studied Aβ extracted from human brain. Most prior studies have utilized synthetic Aβ peptides, but the relevance of these test tube experiments to the conditions that prevail in AD is uncertain. Here, we describe three distinct methods for studying Aβ from cortical tissue. Each method allows the analysis of different ranges of species thus enabling the examination of different questions. The first method allows the study of readily diffusible Aβ with a relatively high specific activity. The second enables the analysis of readily solubilized forms of Aβ the majority of which are inactive. The third details the isolation of true Aβ dimers which have disease-related activity. We also describe a bioassay to study the effects of Aβ on the neuritic integrity of iPSC-derived human neurons. The combined use of this bioassay and the described extraction procedures provides a platform to investigate the activity of different forms and mixtures of Aβ species, and offers a tractable system to identify strategies to mitigate Aβ mediated neurotoxicity.
A nomogram based on combining clinical features and contrast enhanced ultrasound is not able to identify Her-2 over-expressing cancer from other breast cancers
Authors: Lin Zi-mei , Wang Ting-ting , Zhu Jun-Yan , Xu Yong-yuan , Chen Fen , Huang Pin-tong
Published: January 2023

Objective

The aim of this study was to evaluate whether a predictive model based on a contrast enhanced ultrasound (CEUS)-based nomogram and clinical features (Clin) could differentiate Her-2-overexpressing breast cancers from other breast cancers.

Methods

A total of 152 pathology-proven breast cancers including 55 Her-2-overexpressing cancers and 97 other cancers from two units that underwent preoperative CEUS examination, were included and divided into training (n = 102) and validation cohorts (n = 50). Multivariate regression analysis was utilized to identify independent indicators for developing predictive nomogram models. The area under the receiver operating characteristic (AUC) curve was also calculated to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared.

Results

In the training cohort, 7 clinical features (menstruation, larger tumor size, higher CA153 level, BMI, diastolic pressure, heart rate and outer upper quarter (OUQ)) + enlargement in CEUS with P < 0.2 according to the univariate analysis were submitted to the multivariate analysis. By incorporating clinical information and enlargement on the CEUS pattern, independently significant indicators for Her-2-overexpression were used for further predictive modeling as follows: Model I, nomogram model based on clinical features (Clin); Model II, nomogram model combining enlargement (Clin + Enlargement); Model III, nomogram model based on typical clinical features combining enlargement (MC + BMI + diastolic pressure (DP) + outer upper quarter (OUQ) + Enlargement). Model II achieved an AUC value of 0.776 at nomogram cutoff score value of 190, which was higher than that of the other models in the training cohort without significant differences (all P>0.05). In the test cohort, the diagnostic efficiency of predictive model was poor (all AUC<0.6). In addition, the sensitivity and specificity were not significantly different between Models I and II (all P>0.05), in either the training or the test cohort. In addition, Clin exhibited an AUC similar to that of model III (P=0.12). Moreover, model III exhibited a higher sensitivity (70.0%) than the other models with similar AUC and specificity, only in the test cohort.

Conclusion

The main finding of the study was that the predictive model based on a CEUS-based nomogram and clinical features could not differentiate Her-2-overexpressing breast cancers from other breast cancers.
Early post-bevacizumab change in rCBV from DSC-MRI identifies pseudoresponse in recurrent glioblastoma: Results from ACRIN 6677/RTOG 0625
Authors: Boxerman Jerrold L. , Snyder Bradley S. , Barboriak Daniel P. , Schmainda Kathleen M.
Published: January 2023

Background

Progressive enhancement predicted poor survival in ACRIN 6677/RTOG 0625, a multi-center trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma, but pseudoresponse likely limited enhancement-based survival prognostication in T1 non-progressors. We aimed to determine whether early change in cerebral blood volume from baseline (ΔCBV) could further stratify the T1 non-progressors according to overall (OS) and progression-free (PFS) survival.

Methods

37/123 enrolled patients had DSC-MRI, including 13, 15, and 8 patients without 2D-T1 progression at 2, 8, and 16 weeks post-treatment initiation, respectively. Mean CBV normalized to white matter (nRCBV) and mean standardized CBV (sRCBV) were extracted from enhancing tumor. ROC curves were derived for ΔCBV using six-month PFS and one-year OS as reference standards. Kaplan-Meier survival estimates and log-rank test compared PFS and OS for both ΔCBV (increase vs. decrease) and T1 response status (stable vs. decreasing enhancement).

Results

PFS and OS were significantly worse for increasing CBV at 2 weeks (p=0.003 and p=0.002 for nRCBV, and p=0.03 and p=0.03 for sRCBV, respectively), but not for 2D-T1 patients with stable vs. decreasing enhancement (p=0.44 and p=0.86, respectively). ΔCBV at week 2 was also a good prognostic marker for OS-1 and PFS-6 using ROC analysis. By contrast, 2D-T1 response status at weeks 2, 8, and 16 was not associated with PFS-6. ΔCBV at 16 weeks (p=0.008 for sRCBV) but not 8 weeks (p=0.74 for nRCBV and p=0.56 for sRCBV) was associated with significant difference in median survival, but no difference in survival was observed for 2D-T1 patients with stable vs. decreasing enhancement at 8 weeks (p=0.69) or 16 weeks (p=0.21). At 16 weeks, OS did not differ significantly between 2D-T1 progressors and 2D-T1 non-progressors with increasing CBV (median survival 3.3 months post week 16 scan vs. 9.2 months, respectively; p=0.13), suggesting that 2D-T1 non-progressors with increasing CBV may have a prognosis like that of 2D-T1 progressors.

Conclusion

After 2 weeks of anti-angiogenic therapy, ΔCBV in 2D-T1 non-progressors significantly prognosticated PFS and OS, whereas 2D-T1 response status did not, identifying a subpopulation that benefits from bevacizumab. Combining 2D-T1 progression and ΔCBV may yield a response assessment paradigm with 3-tiered OS stratification.
Case report: Successful use of mepolizumab for immune checkpoint inhibitors–induced hypereosinophilic syndrome in two patients with solid malignancies
Authors: Lazzari Chiara , Yacoub Mona Rita , Campochiaro Corrado , Bulotta Alessandra , Palumbo Diego , Ogliari Francesca Rita , Dagna Lorenzo , Marchesi Silvia , Ponzoni Maurilio , Gregorc Vanesa
Published: January 2023

Hypereosinophilic syndrome (HES) represents a group of blood disorders characterized by an absolute eosinophil count (AEC) > 1.5 × 103/μl in the peripheral blood, which eventually extravasate and cause organ damage. It can be primary or secondary to infections or tumors. The infiltration of eosinophils in tissue and organs is associated with different disorders and, in some cases, with life-threatening manifestations. Albeit the pathogenesis of HES in patients with solid tumo\rs is not yet clarified; recently, HES has also been described as an immune-related adverse event in patients with solid tumors receiving immune checkpoint inhibitors. Treatment of HES is still debated, especially in patients with concomitant solid tumors, and different drugs including imatinib, hydroxyurea, interferon-ɑ, glucocorticoids, and the monoclonal antibody targeting circulating IL-5 mepolizumab have been proposed according to the underlying cause and the severity of HES. Herein, we describe, for the first time, the successful use of mepolizumab for the treatment of immune checkpoint–induced HES in two patients with metastatic solid tumor.
The efficacy of targeted therapy combined with radiotherapy and temozolomide-based chemotherapy in the treatment of glioma: A systemic review and meta-analysis of phase II/III randomized controlled trials
Authors: Ma Yifan , Wang Yue , Nie Chen , Lin Yongzhong
Published: January 2023

Background

Glioma is the most common intracranial tumor, accounting for about half of the primary intracranial tumors, with the characteristics of hidden onset and high mortality. Even after surgery, radiotherapy and chemotherapy, the prognosis of glioma is not ideal. Targeted therapy has developed rapidly in the treatment of other malignant tumors, which is also an important direction in the research and development of new therapies for glioma. So far, targeting combined with radiotherapy and chemotherapy have been used as the treatment of glioma in many clinical trials, but the role of targeted combined radiotherapy and chemotherapy in the treatment of glioma is still controversial. The purpose of this study was to evaluate the efficacy of targeted therapy combined with radiotherapy and temozolomide (TMZ)-based chemotherapy in the treatment of glioma.

Methods

Phase II or phase III clinical trials involving targeted therapy combined with radiotherapy and chemotherapy and temozolomide-based radiotherapy and chemotherapy for gliomas were searched using PubMed, Embase and Web of Science databases, and a comprehensive meta-analysis was conducted. The primary outcome was overall survival time (OS) and progression-free survival time (PFS), and the secondary outcome was adverse reaction. The time-to-event data is summarized as hazard ratio (HR), and the binary results are summarized as odds ratio (OR). Two researchers conducted literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria. Stata16.0 software was used for analysis, random effect model was used for data merging, and forest map was used for display.

Results

A total of 11 eligible literatures and 12 prospective randomized controlled clinical trials of 1284 cases were included in the meta-analysis. The results showed that compared with radiotherapy and chemotherapy alone, targeted drugs combined with temozolomide-based radiotherapy and chemotherapy could significantly improve OS in phase II trial, but there was no improvement in Phase III trial, and PFS of newly diagnosed glioma patients was improved (HR=0.82(0.71-0.94) 95%CI, p =0.005). The PFS of the third phase of the experiment also improved. Compared with radiotherapy and chemotherapy alone, there was no statistically significant increase in adverse events in targeted combined radiotherapy and chemotherapy group.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42022326012.
A population-based study of synchronous distant metastases and prognosis in patients with PDAC at initial diagnosis
Authors: Zhang Leiming , Jin Rong , Yang Xuanang , Ying Dongjian
Published: January 2023

Objective

Cancer of the pancreas is a life-threatening condition and has a high distant metastasis (DM) rate of over 50% at diagnosis. Therefore, this study aimed to determine whether patterns of distant metastases correlated with prognosis in pancreatic ductal adenocarcinoma (PDAC) with metastatic spread, and build a novel nomogram capable of predicting the 6, 12, 18-month survival rate with high accuracy.

Methods

We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for cases of PDAC with DM. Kaplan-Meier analysis, log-rank tests and Cox-regression proportional hazards model were used to assess the impact of site and number of DM on the cancer-specific survival (CSS) and over survival (OS). A total of 2709 patients with DM were randomly assigned to the training group and validation group in a 7:3 ratio. A nomogram was constructed by the dependent risk factors which were determined by multivariate Cox-regression analysis. An assessment of the discrimination and ability of the prediction model was made by measuring AUC, C-index, calibration curve and decision curve analysis (DCA). In addition, we collected 98 patients with distant metastases at the time of initial diagnosis from Ningbo University Affiliated LiHuili Hospital to verify the efficacy of the prediction model.

Results

There was a highest incidence of liver metastases from pancreatic cancer (2387,74.36%), followed by lung (625,19.47%), bone (190,5.92%), and brain (8,0.25%). The prognosis of liver metastases differed from that of lung metastases, and the presence of multiple organ metastases was associated with poorer prognosis. According to univariate and multivariate Cox-regression analyses, seven factors (i.e., diagnosis age, tumor location, grade of tumor differentiation, T-stage, receipt of surgery, receipt of chemotherapy status, presence of multiple organ metastases) were included in our nomogram model. In internal and external validation, the ROC curves, C-index, calibration curves and DCA were calculated, which confirmed that this nomogram can precisely predict prognosis of PDAC with DM.

Conclusion

Metastatic PDAC patients with liver metastases tended to have a worse prognosis than those with lung metastases. The number of DM had significant effect on the overall survival rate of metastatic PDAC. This study had a high prediction accuracy, which was helpful clinicians to analyze the prognosis of PDAC with DM and implement individualized diagnosis and treatment.
Diagnosis of cervical lymph node metastasis with thyroid carcinoma by deep learning application to CT images
Authors: Wang Tiantian , Yan Ding , Liu Zhaodi , Xiao Lianxiang , Liang Changhu , Xin Haotian , Feng Mengmeng , Zhao Zijian , Wang Yong
Published: January 2023

Introduction

The incidence of thyroid diseases has increased in recent years, and cervical lymph node metastasis (LNM) is considered an important risk factor for locoregional recurrence. This study aims to develop a deep learning-based computer-aided diagnosis (CAD) method to diagnose cervical LNM with thyroid carcinoma on computed tomography (CT) images.

Methods

A new deep learning framework guided by the analysis of CT data for automated detection and classification of LNs on CT images is proposed. The presented CAD system consists of two stages. First, an improved region-based detection network is designed to learn pyramidal features for detecting small nodes at different feature scales. The region proposals are constrained by the prior knowledge of the size and shape distributions of real nodes. Then, a residual network with an attention module is proposed to perform the classification of LNs. The attention module helps to classify LNs in the fine-grained domain, improving the whole classification network performance.

Results

A total of 574 axial CT images (including 676 lymph nodes: 103 benign and 573 malignant lymph nodes) were retrieved from 196 patients who underwent CT for surgical planning. For detection, the data set was randomly subdivided into a training set (70%) and a testing set (30%), where each CT image was expanded to 20 images by rotation, mirror image, changing brightness, and Gaussian noise. The extended data set included 11,480 CT images. The proposed detection method outperformed three other detection architectures (average precision of 80.3%). For classification, ROI of lymph node metastasis labeled by radiologists were used to train the classification network. The 676 lymph nodes were randomly divided into 70% of the training set (73 benign and 401 malignant lymph nodes) and 30% of the test set (30 benign and 172 malignant lymph nodes). The classification method showed superior performance over other state-of-the-art methods with an accuracy of 96%, true positive and negative rates of 98.8 and 80%, respectively. It outperformed radiologists with an area under the curve of 0.894.

Discussion

The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images. The future research can consider adding radiologists' experience and domain knowledge into the deep-learning based CAD method to make it more clinically significant.

Conclusion

The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images.
Advances in the intraoperative delineation of malignant glioma margin
Authors: Jiang Shan , Chai Huihui , Tang Qisheng
Published: January 2023

Surgery plays a critical role in the treatment of malignant glioma. However, due to the infiltrative growth and brain shift, it is difficult for neurosurgeons to distinguish malignant glioma margins with the naked eye and with preoperative examinations. Therefore, several technologies were developed to determine precise tumor margins intraoperatively. Here, we introduced four intraoperative technologies to delineate malignant glioma margin, namely, magnetic resonance imaging, fluorescence-guided surgery, Raman histology, and mass spectrometry. By tracing their detecting principles and developments, we reviewed their advantages and disadvantages respectively and imagined future trends.
Testing the circulation of expanded flaps—prevention of necrosis of expanded flaps (a clinic study)
Authors: Han Tao , Chen Haini , Chen Jianbin , Cui Jie , Shen Weimin
Published: January 2023

Background

Expanded flaps are commonly used in plastic surgery. Although expanded flaps are more resistant to hypoxia than unexpanded flaps, flap necrosis can sometimes occur, particularly with skin incisions of regular proportion. Distal skin necrosis of the expansion flap can be avoided by careful design; however, the utilization rate of the expansion flap decreases. Consequently, successfully avoiding distal skin flap necrosis remains a challenge. In this study, we designed a device for testing the circulation of the expanded flap that can decrease the risk of expanded flap necrosis, thus maximizing the use of an expanded flap.

Methods

A total of 128 patients who underwent surgical repair between 2011 and 2019 and were retrospectively examined with the device for testing the circulation of the expanded flap were included in the study. The procedure included (1) making a device for testing the circulation, (2) implanting a skin expander, (3) injecting normal saline into the skin expander, (4) testing the circulation of the expanded flap, and (5) transferring the expanded flap to repair the defect.

Results

One hundred forty-eight expanded flaps were implanted in 128 patients. The expanded flap that was transferred to repair the defect had no necrosis or infection. None of the expanded flaps with separated blood supply, which could be observed during operations, revealed complications. The survival rates of the expanded flap were increased by testing the circulation of the expanded flap. Expanded flaps designed by this method showed no swelling or paleness and no obvious temperature changes. In addition, the length-to-width ratio could be extended to 3:1.

Conclusions

Our proposed method resulted in an effective surgical procedure for the repair of tissue defects. This approach could effectively change the direction of the blood vessel of the expanded skin flap and prevent necrosis of the expanded flap, thus representing a practical way to increase the use of expanded flaps and the flap survival rate, making the whole expanded flap transfer procedure more convenient.
The molecular mechanism of Gaucher disease caused by compound heterozygous mutations in GBA1 gene
Authors: Liu Qi , Shen Zongrui , Pan Hong , Ma Shunfei , Xiong Fu , He Fei
Published: January 2023

Gaucher disease (GD, ORPHA355) is a rare autosomal recessive genetic disease caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). Here, we report a patient with GD who carried the heterozygous c.1240G > C (p.Val414Leu) mutation and the heterozygous pathogenic c.1342G > C (p.Asp448His) mutation in GBA1. Bioinformatics analysis suggested that the two mutations are pathogenic. Functional studies showed that GBA1 mRNA and GCase protein levels of mutant types were significantly less than the wild-type. In the cell lysates, the two mutations of GBA1 c.1240G > C and c.1342G > C caused a decreased GCase concentration, while the two mutations did not change the distribution in the cell. The pathogenicity of the compound heterozygous mutations was verified. Early diagnosis and treatment can improve the quality of life and prevent unnecessary procedures in patients with GD.
Cytotoxic and pro-apoptotic effects of botanical drugs derived from the indigenous cultivated medicinal plant Paris polyphylla var. yunnanensis
Authors: Yan Xiu-Xiang , Zhao Yan-Qiang , He Yun , Disayathanoowat Terd , Pandith Hataichanok , Inta Angkhana , Yang Li-Xin
Published: January 2023

Background: Cancer is one of the top two leading causes of death worldwide. Ethnobotanical research, it is one of methods, which is able to discover effective anticancer drugs based on “prototype” of indigenous people’s historical experiences and practices. The rhizomes of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. have been used as botanical drugs to treat cancer by Yi, Bai, Dai, and Naxi ethnic groups in Yunnan, China, where this species is widely cultivated in a large scale in Yunnan.

Materials and methods: To identify the substances of anticancer activities based on indigenous medicine knowledge, chromatography was performed to separate saponins from the rhizomes of P. polyphylla var. yunnanensis, followed by spectroscopy to determine the structure of six isolated saponins. The cytotoxicity of five extracts and six pure compounds were evaluated by MTS method. Quantitative determination of total saponins of P. polyphylla var. yunnanensis was analyzed by HPLC. Cell cycle assay, apoptosis assay, and mitochondrial membrane potential were used to evaluate the pro-apoptotic activity in vitro.

Results: Five extracts and six pure saponins showed significant inhibitory cytotoxic activities of three human liver cancer cell lines (SMMC-7721, HepG2, and SK-HEP-1) and one non-small-cell lung cancer cell line (A549). The contents of Paris saponins I, II, and VII were 6.96% in the rhizomes of P. polyphylla var. yunnanensis, much higher than Chinese Pharmacopoeia standards (0.6%). Six saponins induced significant apoptosis and cell cycle arrest in three human cancer cell lines (A549, SMMC-7721, and HepG2), which was associated with the loss of mitochondrial membrane potential.

Conclusion: The result of this study support that cultivated P. polyphylla var. yunnanensis could be a substitute for wild resource as an anticancer medicine based on indigenous medicine knowledge.
Advances in Alzheimer’s disease’s pharmacological treatment
Authors: Conti Filho Carlos Elias , Loss Lairane Bridi , Marcolongo-Pereira Clairton , Rossoni Junior Joamyr Victor , Barcelos Rafael Mazioli , Chiarelli-Neto Orlando , Silva Bruno Spalenza da , Passamani Ambrosio Roberta , Castro Fernanda Cristina de Abreu Quintela , Teixeira Sarah Fernandes , Mezzomo Nathana Jamille
Published: January 2023

Alzheimer’s disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists’ data were discouraging. However, anti-Aβ vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results.
Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
Authors: Zhang Xin , Shu Shibin , Feng Zhenhua , Qiu Yong , Bao Hongda , Zhu Zezhang
Published: January 2023

Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD.
Labetalol and soluble endoglin aggravate bile acid retention in mice with ethinylestradiol-induced cholestasis
Authors: Cristina Igreja Sá Ivone , Tripska Katarina , Alaei Faradonbeh Fatemeh , Hroch Milos , Lastuvkova Hana , Schreiberova Jolana , Kacerovsky Marian , Pericacho Miguel , Nachtigal Petr , Micuda Stanislav
Published: January 2023

Labetalol is used for the therapy of hypertension in preeclampsia. Preeclampsia is characterized by high soluble endoglin (sEng) concentration in plasma and coincides with intrahepatic cholestasis during pregnancy (ICP), which threatens the fetus with the toxicity of cumulating bile acids (BA). Therefore, we hypothesized that both labetalol and increased sEng levels worsen BA cumulation in estrogen-induced cholestasis. C57BL/6J, transgenic mice overexpressing human sEng, and their wild-type littermates were administrated with ethinylestradiol (EE, 10 mg/kg s.c., the mice model of ICP) and labetalol (10 mg/kg s.c.) for 5 days with sample collection and analysis. Plasma was also taken from healthy pregnant women and patients with ICP. Administration of labetalol to mice with EE cholestasis aggravated the increase in BA plasma concentrations by induction of hepatic Mrp4 efflux transporter. Labetalol potentiated the increment of sEng plasma levels induced by estrogen. Increased plasma levels of sEng were also observed in patients with ICP. Moreover, increased plasma levels of human sEng in transgenic mice aggravated estrogen-induced cholestasis in labetalol-treated mice and increased BA concentration in plasma via enhanced reabsorption of BAs in the ileum due to the upregulation of the Asbt transporter. In conclusion, we demonstrated that labetalol increases plasma concentrations of BAs in estrogen-induced cholestasis, and sEng aggravates this retention. Importantly, increased sEng levels in experimental and clinical forms of ICPs might present a novel mechanism explaining the coincidence of ICP with preeclampsia. Our data encourage BA monitoring in the plasma of pregnant women with preeclampsia and labetalol therapy.
Ensemble averaging for categorical variables: Validation study of imputing lost data in 24-h recorded postures of inpatients
Authors: Ogasawara Takayuki , Mukaino Masahiko , Matsuura Hirotaka , Aoshima Yasushi , Suzuki Takuya , Togo Hiroyoshi , Nakashima Hiroshi , Saitoh Eiichi , Yamaguchi Masumi , Otaka Yohei , Tsukada Shingo
Published: January 2023

Acceleration sensors are widely used in consumer wearable devices and smartphones. Postures estimated from recorded accelerations are commonly used as features indicating the activities of patients in medical studies. However, recording for over 24 h is more likely to result in data losses than recording for a few hours, especially when consumer-grade wearable devices are used. Here, to impute postures over a period of 24 h, we propose an imputation method that uses ensemble averaging. This method outputs a time series of postures over 24 h with less lost data by calculating the ratios of postures taken at the same time of day during several measurement-session days. Whereas conventional imputation methods are based on approaches with groups of subjects having multiple variables, the proposed method imputes the lost data variables individually and does not require other variables except posture. We validated the method on 306 measurement data from 99 stroke inpatients in a hospital rehabilitation ward. First, to classify postures from acceleration data measured by a wearable sensor placed on the patient’s trunk, we preliminary estimated possible thresholds for classifying postures as ‘reclining’ and ‘sitting or standing’ by investigating the valleys in the histogram of occurrences of trunk angles during a long-term recording. Next, the imputations of the proposed method were validated. The proposed method significantly reduced the missing data rate from 5.76% to 0.21%, outperforming a conventional method.
Updates in the chronic kidney disease-mineral bone disorder show the role of osteocytic proteins, a potential mechanism of the bone—Vascular paradox, a therapeutic target, and a biomarker
Authors: Williams Matthew J. , White Sarah C. , Joseph Zachary , Hruska Keith A.
Published: January 2023

The chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex multi-component syndrome occurring during kidney disease and its progression. Here, we update progress in the components of the syndrome, and synthesize recent investigations, which suggest a potential mechanism of the bone-vascular paradox. The discovery that calcified arteries in chronic kidney disease inhibit bone remodeling lead to the identification of factors produced by the vasculature that inhibit the skeleton, thus providing a potential explanation for the bone-vascular paradox. Among the factors produced by calcifying arteries, sclerostin secretion is especially enlightening. Sclerostin is a potent inhibitor of bone remodeling and an osteocyte specific protein. Its production by the vasculature in chronic kidney disease identifies the key role of vascular cell osteoblastic/osteocytic transdifferentiation in vascular calcification and renal osteodystrophy. Subsequent studies showing that inhibition of sclerostin activity by a monoclonal antibody improved bone remodeling as expected, but stimulated vascular calcification, demonstrate that vascular sclerostin functions to brake the Wnt stimulation of the calcification milieu. Thus, the target of therapy in the chronic kidney disease-mineral bone disorder is not inhibition of sclerostin function, which would intensify vascular calcification. Rather, decreasing sclerostin production by decreasing the vascular osteoblastic/osteocytic transdifferentiation is the goal. This might decrease vascular calcification, decrease vascular stiffness, decrease cardiac hypertrophy, decrease sclerostin production, reduce serum sclerostin and improve skeletal remodeling. Thus, the therapeutic target of the chronic kidney disease-mineral bone disorder may be vascular osteoblastic transdifferentiation, and sclerostin levels may be a useful biomarker for the diagnosis of the chronic kidney disease-mineral bone disorder and the progress of its therapy.
Deciphering immune responses primed by a bacterial lipopeptide in wheat towards Zymoseptoria tritici
Authors: Platel Rémi , Lucau-Danila Anca , Baltenweck Raymonde , Maia-Grondard Alessandra , Trapet Pauline , Magnin-Robert Maryline , Randoux Béatrice , Duret Morgane , Halama Patrice , Hilbert Jean-Louis , Coutte François , Jacques Philippe , Hugueney Philippe , Reignault Philippe , Siah Ali
Published: January 2023

Plant immunity induction with natural biocontrol compounds is a valuable and promising ecofriendly tool that fits with sustainable agriculture and healthy food. Despite the agroeconomic significance of wheat, the mechanisms underlying its induced defense responses remain obscure. We reveal here, using combined transcriptomic, metabolomic and cytologic approach, that the lipopeptide mycosubtilin from the beneficial bacterium Bacillus subtilis, protects wheat against Zymoseptoria tritici through a dual mode of action (direct and indirect) and that the indirect one relies mainly on the priming rather than on the elicitation of plant defense-related mechanisms. Indeed, the molecule primes the expression of 80 genes associated with sixteen functional groups during the early stages of infection, as well as the accumulation of several flavonoids during the period preceding the fungal switch to the necrotrophic phase. Moreover, genes involved in abscisic acid (ABA) biosynthesis and ABA-associated signaling pathways are regulated, suggesting a role of this phytohormone in the indirect activity of mycosubtilin. The priming-based bioactivity of mycosubtilin against a biotic stress could result from an interaction of the molecule with leaf cell plasma membranes that may mimic an abiotic stress stimulus in wheat leaves. This study provides new insights into induced immunity in wheat and opens new perspectives for the use of mycosubtilin as a biocontrol compound against Z. tritici.
Class-attention-based lesion proposal convolutional neural network for strawberry diseases identification
Authors: Hu Xiaobo , Wang Rujing , Du Jianming , Hu Yimin , Jiao Lin , Xu Taosheng
Published: January 2023

Diseases have a great impact on the quality and yield of strawberries, an accurate and timely field disease identification method is urgently needed. However, identifying diseases of strawberries in field is challenging due to the complex background interference and subtle inter-class differences. A feasible method to address the challenges is to segment strawberry lesions from the background and learn fine-grained features of the lesions. Following this idea, we present a novel Class-Attention-based Lesion Proposal Convolutional Neural Network (CALP-CNN), which utilizes a class response map to locate the main lesion object and propose discriminative lesion details. Specifically, the CALP-CNN firstly locates the main lesion object from the complex background through a class object location module (COLM) and then applies a lesion part proposal module (LPPM) to propose the discriminative lesion details. With a cascade architecture, the CALP-CNN can simultaneously address the interference from the complex background and the misclassification of similar diseases. A series of experiments on a self-built dataset of field strawberry diseases is conducted to testify the effectiveness of the proposed CALP-CNN. The classification results of the CALP-CNN are 92.56%, 92.55%, 91.80% and 91.96% on the metrics of accuracy, precision, recall and F1-score, respectively. Compared with six state-of-the-art attention-based fine-grained image recognition methods, the CALP-CNN achieves 6.52% higher (on F1-score) than the sub-optimal baseline MMAL-Net, suggesting that the proposed methods are effective in identifying strawberry diseases in the field.