bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream
Authors: Cepparulo Pasquale , Cuomo Ornella , Vinciguerra Antonio , Torelli Monica , Annunziato Lucio , Pignataro Giuseppe
Published: October 2021

To date, the only effective pharmacological treatment for ischemic stroke is limited to the clinical use of recombinant tissue plasminogen activator (rtPA), although endovascular therapy has also emerged as an effective treatment for acute ischemic stroke. Unfortunately, the benefit of this treatment is limited to a 4.5-h time window. Most importantly, the use of rtPA is contraindicated in the case of hemorrhagic stroke. Therefore, the identification of a reliable biomarker to distinguish hemorrhagic from ischemic stroke could provide several advantages, including an earlier diagnosis, a better treatment, and a faster decision on ruling out hemorrhage so that tPA may be administered earlier. microRNAs (miRNAs) are stable non-coding RNAs crucially involved in the downregulation of gene expression via mRNA cleavage or translational repression. In the present paper, taking advantage of three preclinical animal models of stroke, we compared the miRNA blood levels of animals subjected to permanent or transient middle cerebral artery occlusion (MCAO) or to collagenase-induced hemorrhagic stroke. Preliminarily, we examined the rat miRNome in the brain tissue of ischemic and sham-operated rats; then, we selected those miRNAs whose expression was significantly modulated after stroke to create a list of miRNAs potentially involved in stroke damage. These selected miRNAs were then evaluated at different time intervals in the blood of rats subjected to permanent or transient focal ischemia or to hemorrhagic stroke. We found that four miRNAs—miR-16-5p, miR-101a-3p, miR-218-5p, and miR-27b-3p—were significantly upregulated in the plasma of rats 3 h after permanent MCAO, whereas four other different miRNAs—miR-150-5p, let-7b-5p, let-7c-5p, and miR-181b-5p—were selectively upregulated by collagenase-induced hemorrhagic stroke. Collectively, our study identified some selective miRNAs expressed in the plasma of hemorrhagic rats and pointed out the importance of a precise time point measurement to render more reliable the use of miRNAs as stroke biomarkers.
Neurorights in History: A Contemporary Review of José M. R. Delgado’s “Physical Control of the Mind” (1969) and Elliot S. Valenstein’s “Brain Control” (1973)
Authors: Schleim Stephan
Published: October 2021

Scholars from various disciplines discuss the ethical, legal, and social implications of neurotechnology. Some have proposed four concrete “neurorights”. This review presents the research of two pioneers in brain stimulation from the 1950s to 1970s, José M. R. Delgado and Elliot S. Valenstein, who also reflected upon the ethical, legal, and social aspects of their and other scientists’ related research. Delgado even formulated the vision “toward a psychocivilized society” where brain stimulation is used to control, in particular, citizens’ aggressive and violent behavior. Valenstein, by contrast, believed that the brain is not organized in such a way to allow the control or even removal of only negative processes without at the same time diminishing desirable ones. The paper also describes how animal and human experimentation on brain stimulation was carried out in that time period. It concludes with a contemporary perspective on the relevance of neurotechnology for neuroethics, neurolaw, and neurorights, including two recent examples for brain-computer interfaces.
New Methods, Old Brains—A Systematic Review on the Effects of tDCS on the Cognition of Elderly People
Authors: Siegert Anna , Diedrich Lukas , Antal Andrea
Published: October 2021

The world's population is aging. With this comes an increase in the prevalence of age-associated diseases, which amplifies the need for novel treatments to counteract cognitive decline in the elderly. One of the recently discussed non-pharmacological approaches is transcranial direct current stimulation (tDCS). TDCS delivers weak electric currents to the brain, thereby modulating cortical excitability and activity. Recent evidence suggests that tDCS, mainly with anodal currents, can be a powerful means to non-invasively enhance cognitive functions in elderly people with age-related cognitive decline. Here, we screened a recently developed tDCS database (http://tdcsdatabase.com) that is an open access source of published tDCS papers and reviewed 16 studies that applied tDCS to healthy older subjects or patients suffering from Alzheimer's Disease or pre-stages. Evaluating potential changes in cognitive abilities we focus on declarative and working memory. Aiming for more standardized protocols, repeated tDCS applications (2 mA, 30 min) over the left dorso-lateral prefrontal cortex (LDLPFC) of elderly people seem to be one of the most efficient non-invasive brain stimulation (NIBS) approaches to slow progressive cognitive deterioration. However, inter-subject variability and brain state differences in health and disease restrict the possibility to generalize stimulation methodology and increase the necessity of personalized protocol adjustment by means of improved neuroimaging techniques and electrical field modeling.
Evaluation of the Relationship Between Preferential Looking Testing and Visual Evoked Potentials as a Biomarker of Cerebral Visual Impairment
Authors: Raja Sruti , Emadi Batool Sahar , Gaier Eric D. , Gise Ryan A. , Fulton Anne B. , Heidary Gena
Published: October 2021

Cerebral visual impairment (CVI) is a leading cause of visual impairment in children in developed countries, but diagnostic tools to detect CVI are limited. We sought to analyze the visual acuity of children with CVI as assessed by visual evoked potentials (VEPs) and preferential looking test (PLT) to determine whether the relationship between the visual outcomes on these two testing methods may serve as a biomarker of CVI. We performed a retrospective chart review of patients with a confirmed diagnosis of CVI and at least one ophthalmological assessment with visual acuity measured by VEP and PLT. Of the 218 patients included in the study, the most common condition associated with CVI was an underlying genetic disorder (36%, 79/218). Treatment for seizures occurred in the majority of the entire cohort of patients (80%, 175/218). Ophthalmic comorbidities included retinal disease in 23 patients, optic nerve disease in 68 patients, nystagmus in 78 patients, and strabismus in 176 patients. When assessed by either VEP or PLT, visual acuity in children with CVI fell below expected norms. At initial and final presentations, VEP acuity exceeded PLT acuity by one or more octaves, and this difference was greater than expected compared with normal visual development. We propose utilizing this quantifiable disparity between VEP and PLT as a biomarker of CVI.
Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Executive Function and Its Neural Mechanism: An Event-Related Potential Study
Authors: Liu Sishi , Wang Xianglong , Ma Junqin , Wang Kangling , Wang Zhengtao , Li Jie , Chen Jiali , Zhan Hongrui , Wu Wen
Published: October 2021

Objective: Executive function refers to the conscious control of thinking and behavior in psychological process. Executive dysfunction widely exists in a variety of neuropsychiatric diseases, and is closely related to the decline of daily living ability and function. This study intends to explore the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on executive function and its neural mechanism by using event-related potential (ERP), so as to provide basis for further study on the relationship between cerebral cortex and executive function.

Methods: Task switching paradigm was used to study the cognitive flexibility in executive function. Thirty-one healthy subjects were randomly assigned to receive rTMS stimulations (1 Hz rTMS or sham rTMS) to the left dorsolateral prefrontal cortex (DLPFC) twice. The switching task and the electroencephalography EEG recordings were performed before (pre-rTMS/pre-sham rTMS) and immediately after the end of the rTMS application (post-rTMS/post-sham rTMS).

Results: The analysis of RTs showed that the main effects of switching and time were statistically significant. Further analysis revealed that the RT of rTMS stimulation was longer than sham rTMS at post-stimulation. ERP analysis showed that there was a significant switching effect in frontal and central scalp location, and the P2 amplitude in switch trials was greater than that in non-switch trials. At post-stimulation, the N2 amplitude of rTMS is more negative than that of sham rTMS at non-switch trials, whereas no such difference was found at switch trials. The P3 amplitude and LPC amplitude are significantly reduced by rTMS at post-stimulation.

Conclusion: Low-frequency rTMS of the left DLPFC can cause decline of cognitive flexibility in executive function, resulting in the change of N2 amplitude and the decrease of P3 and LPC components during task switching, which is of positive significance for the evaluation and treatment of executive function.
Case Report: Disruption of Resting-State Networks and Cognitive Deficits After Whole Brain Irradiation for Singular Brain Metastasis
Authors: Kocher Martin , Jockwitz Christiane , Lerche Christoph , Sabel Michael , Lohmann Philipp , Stoffels Gabriele , Filss Christian , Mottaghy Felix M. , Ruge Maximilian I. , Fink Gereon R. , Shah Nadim J. , Galldiks Norbert , Caspers Svenja , Langen Karl-Josef
Published: October 2021

Introduction: Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited. Therefore, we here report a rare case with a singular brain metastasis treated by resection and WBRT that survived for more than 10 years where we investigated the integrity of brain networks using resting-state functional MRI.

Methods: A female patient with a left frontal non-small cell lung cancer (NSCLC) brain metastasis had resection and postoperative WBRT (30.0 in 3.0 Gy fractions) and stayed free from brain metastasis recurrence for a follow-up period of 11 years. Structural magnetic resonance imaging (MRI) and amino acid [O-(2-[18F]fluoroethyl)-L-tyrosine] positron emission tomography (FET PET) were repeatedly acquired. At the last follow up, neurocognitive functions and resting-state functional connectivity (RSFC) using resting-state fMRI were assessed. Within-network and inter-network connectivity of seven resting-state networks were computed from a connectivity matrix. All measures were compared to a matched group of 10 female healthy subjects.

Results: At the 11-year follow-up, T2/FLAIR MR images of the patient showed extended regions of hyper-intensities covering mainly the white mater of the bilateral dorsal frontal and parietal lobes while sparing most of the temporal lobes. Compared to the healthy subjects, the patient performed significantly worse in all cognitive domains that included executive functions, attention and processing speed, while verbal working memory, verbal episodic memory, and visual working memory were left mostly unaffected. The connectivity matrix showed a heavily disturbed pattern with a widely distributed, scattered loss of RSFC. The within-network RSFC revealed a significant loss of connectivity within all seven networks where the dorsal attention and fronto-parietal control networks were affected most severely. The inter-network RSFC was significantly reduced for the visual, somato-motor, and dorsal and ventral attention networks.

Conclusion: As demonstrated here in a patient with a metastatic NSCLC and long-term survival, WBRT may lead to extended white matter damage and cause severe disruption of the RSFC in multiple resting state networks. In consequence, executive functioning which is assumed to depend on the interaction of several networks may be severely impaired following WBRT apart from the well-recognized deficits in memory function.
Representation of Body Orientation in Vestibular-Defective Patients Before and After Unilateral Vestibular Loss
Authors: Borel Liliane , Honoré Jacques , Bachelard-Serra Mathilde , Lavieille Jean-Pierre , Saj Arnaud
Published: October 2021

Introduction: The unilateral vestibular syndrome results in postural, oculomotor, perceptive, and cognitive symptoms. This study was designed to investigate the role of vestibular signals in body orientation representation, which remains poorly considered in vestibular patients.

Methods: The subjective straight ahead (SSA) was investigated using a method disentangling translation and rotation components of error. Participants were required to align a rod with their body midline in the horizontal plane. Patients with right vestibular neurotomy (RVN; n =8) or left vestibular neurotomy (LVN; n = 13) or vestibular schwannoma resection were compared with 12 healthy controls. Patients were tested the day before surgery and during the recovery period, 7 days and 2 months after the surgery.

Results: Before and after unilateral vestibular neurotomy, i.e., in the chronic phases, patients showed a rightward translation bias of their SSA, without rotation bias, whatever the side of the vestibular loss. However, the data show that the lower the translation error before neurotomy, the greater its increase 2 months after a total unilateral vestibular loss, therefore leading to a rightward translation of similar amplitude in the two groups of patients. In the early phase after surgery, SSA moved toward the operated side both in translation and in rotation, as typically found for biases occurring after unilateral vestibular loss, such as the subjective visual vertical (SVV) bias.

Discussion and Conclusion: This study gives the first description of the immediate consequences and of the recovery time course of body orientation representation after a complete unilateral vestibular loss. The overall evolution differed according to the side of the lesion with more extensive changes over time before and after left vestibular loss. It is noteworthy that representational disturbances of self-orientation were highly unusual in the chronic stage after vestibular loss and similar to those reported after hemispheric lesions causing spatial neglect, while classical ipsilesional biases were reported in the acute stage. This study strongly supports the notion that the vestibular system plays a major role in body representation processes and more broadly in spatial cognition. From a clinical point of view, SSA appeared to be a reliable indicator for the presence of a vestibular disorder.
The Histogram Analysis of Intravoxel Incoherent Motion-Kurtosis Model in the Diagnosis and Grading of Prostate Cancer—A Preliminary Study
Authors: Li Chunmei , Yu Lu , Jiang Yuwei , Cui Yadong , Liu Ying , Shi Kaining , Hou Huimin , Liu Ming , Zhang Wei , Zhang Jintao , Zhang Chen , Chen Min
Published: October 2021

Objectives

This study was conducted in order to explore the value of histogram analysis of the intravoxel incoherent motion-kurtosis (IVIM-kurtosis) model in the diagnosis and grading of prostate cancer (PCa), compared with monoexponential model (MEM).

Materials and Methods

Thirty patients were included in this study. Single-shot echo-planar imaging (SS-EPI) diffusion-weighted images (b-values of 0, 20, 50, 100, 200, 500, 1,000, 1,500, 2,000 s/mm2) were acquired. The pathologies were confirmed by in-bore MR-guided biopsy. The postprocessing and measurements were processed using the software tool Matlab R2015b for the IVIM-kurtosis model and MEM. Regions of interest (ROIs) were drawn manually. Mean values of D, D*, f, K, ADC, and their histogram parameters were acquired. The values of these parameters in PCa and benign prostatic hyperplasia (BPH)/prostatitis were compared. Receiver operating characteristic (ROC) curves were used to investigate the diagnostic efficiency. The Spearman test was used to evaluate the correlation of these parameters and Gleason scores (GS) of PCa.

Results

For the IVIM-kurtosis model, D (mean, 10th, 25th, 50th, 75th, 90th), D* (90th), and f (10th) were significantly lower in PCa than in BPH/prostatitis, while D (skewness), D* (kurtosis), and K (mean, 75th, 90th) were significantly higher in PCa than in BPH/prostatitis. For MEM, ADC (mean, 10th, 25th, 50th, 75th, 90th) was significantly lower in PCa than in BPH/prostatitis. The area under the ROC curve (AUC) of the IVIM-kurtosis model was higher than MEM, without significant differences (z = 1.761, P = 0.0783). D (mean, 50th, 75th, 90th), D* (mean, 10th, 25th, 50th, 75th), and f (skewness, kurtosis) correlated negatively with GS, while D (kurtosis), D* (skewness, kurtosis), f (mean, 75th, 90th), and K (mean, 75th, 90th) correlated positively with GS. The histogram parameters of ADC did not show correlations with GS.

Conclusion

The IVIM-kurtosis model has potential value in the differential diagnosis of PCa and BPH/prostatitis. IVIM-kurtosis histogram analysis may provide more information in the grading of PCa than MEM.
miR-17-5p and miR-4443 Promote Esophageal Squamous Cell Carcinoma Development by Targeting TIMP2
Authors: Wang Xiaojun , Han Jiayi , Liu Yatian , Hu Jingwen , Li Ming , Chen Xi , Xu Lin
Published: October 2021

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most frequently diagnosed cancers in the world with a high mortality rate. The mechanism about ESCC development and whether miRNAs play a critical role remains unclear and needs carefully elucidated.

Materials and Methods

High-throughput miRNA sequencing was used to identify the different expression miRNAs between the ESCC tissues and paired adjacent normal tissues. Next, both CCK-8, Transwell and apotosis assay were used to evaluate the role of miRNA in ESCCcells. In addition, we used bioinformatic tools to predict the potential target of the miRNAs and verified by Western Blot. The function of miRNA-target network was further identified in xenograft mice model.

Results

In ESCC, we identified two miRNAs, miR-17-5p and miR-4443, were significantly upregulated in ESCC tissues than adjacent normal tissues. TIMP2 was proved to be the direct target of both two miRNAs. The miR-17-5p/4443- TIMP2 axis was shown to promote the tumor progression in vitro and in vivo experiments.

Conclusions

This study highlights two oncomiRs, miR-17-5p and miR-4443, and its potential role in ESCC progression by regulating TIMP2 expression, suggesting miR-17-5p and miR-4443 may serve as a novel molecular target for ESCC treatment.
Tumor-Infiltrating CD8+ T Cells Driven by the Immune Checkpoint-Associated Gene IDO1 Are Associated With Cervical Cancer Prognosis
Authors: Zhang Shun , Wan Junhui , Chen Minjie , Cai Desheng , Xu Junlan , Chen Qi
Published: October 2021

Tumor-infiltrating immune cells, associated with tumor progression, are promising prognostic biomarkers. However, the relationship between levels of gene expression and that of immune cell infiltration in cervical cancer prognosis is unknown. In this study, three cervical cancer gene expression microarrays (GSE6791, GSE63678 and GSE55940) were obtained from the GEO database. The IDO1 gene was identified by differentially expressed gene screening. The gene expression profiles of TCGA and GTEx databases along with comprehensive bioinformatics analysis identified that the IDO1 gene was upregulated in cervical cancer with significant difference in expression at different N stages. In addition, it was also upregulated in HPV16 positive sample. The pan-cancer analysis identified that IDO1 was highly expressed in most cancers. TIMER analysis revealed that the expression of IDO1 in CESC shows positive correlation with CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells. IDO1 expression showed remarkable positive correlation with all immune cell markers except M1 macrophages. CD8+ T cell infiltration GSEA results showed that IDO1 was mainly associated with tumor immune-related signaling pathways.
Knockdown of Oligosaccharyltransferase Subunit Ribophorin 1 Induces Endoplasmic-Reticulum-Stress-Dependent Cell Apoptosis in Breast Cancer
Authors: Ding Jiajun , Xu Jiahui , Deng Qiaodan , Ma Wei , Zhang Rui , He Xueyan , Liu Suling , Zhang Lixing
Published: October 2021

Ribophorin 1 (RPN1) is a major part of Oligosaccharyltransferase (OST) complex, which is vital for the N-linked glycosylation. Though it has been verified that the abnormal glycosylation is closely related to the development of breast cancer, the detail role of RPN1 in breast cancer remains unknown. In this study, we explored the public databases to investigate the relationship between the expression levels of OST subunits and the prognosis of breast cancer. Then, we focused on the function of RPN1 in breast cancer and its potential mechanisms. Our study showed that the expression of several OST subunits including RPN1, RPN2, STT3A STT3B, and DDOST were upregulated in breast cancer samples. The protein expression level of RPN1 was also upregulated in breast cancer. Higher expression of RPN1 was correlated with worse clinical features and poorer prognosis. Furthermore, knockdown of RPN1 suppressed the proliferation and invasion of breast cancer cells in vitro and induced cell apoptosis triggered by endoplasmic reticulum stress. Our results identified the oncogenic function of RPN1 in breast cancer, implying that RPN1 might be a potential biomarker and therapeutic target for breast cancer.
Knowledge of and Compliance With Guidelines in the Management of Non-Muscle-Invasive Bladder Cancer: A Survey of Chinese Urologists
Authors: Wang Dan-Qi , Huang Qiao , Huang Xing , Jin Ying-Hui , Wang Yun-Yun , Shi Yue-Xian , Yan Si-Yu , Yang Lu , Li Bing-Hui , Liu Tong-Zu , Zeng Xian-Tao
Published: October 2021

Background

Non-muscle-invasive bladder cancer (NMIBC) still poses a heavy load for resulting in many new cases which contribute significantly to medical costs. Although many NMIBC guidelines have been developed, their implementation remains deficient.

Objective

This study was conducted in order to analyze the knowledge of and compliance with the guidelines for NMIBC of Chinese urologists and to identify associated factors.

Methods

We conducted an online survey between August 2019 and January 2021. Respondents who were more than 65 years old or did not give informed consent were excluded. Linear/logistic regressions were performed to identify factors associated with the knowledge of and compliance with the guidelines of urologists, respectively. McNemar’s tests were used to explore the divergence between knowledge and compliance.

Results

A total of 814 responses were received, and 98.77% of urologists acknowledged the positive effects of high-quality guidelines. The average knowledge score was 6.10 ± 1.28 (out of a full score of 9), and it was positively associated with educational level and the number of guidelines consulted. Only 1.61% and 39.36% of the respondents realized that the guidelines did not recommend further chemotherapy or BCG infusion for low-risk patients. There were 38.87% and 51.84% respondents “often” or more frequently utilizing BCG therapy for intermediate- and high-risk NMIBC patients, respectively. Divergence between knowledge and compliance in performing a second TURBT after incomplete initial resection reached statistical significance (p < 0.001).

Conclusions

Although the vast majority of urologists acknowledged the positive effects of guidelines, knowledge of and compliance with some recommendations of NMIBC guidelines are still inadequate. Factors associated with guidelines, individual professionals, patients, organizations, and the environment jointly contributed to the non-compliance.
Pilocytic Astrocytoma-Derived Cells in Peripheral Blood: A Case Report
Authors: Volpentesta Giorgio , Donato Giuseppe , Ferraro Elisabetta , Mignogna Chiara , Radaelli Riccardo , Sabatini Umberto , La Torre Domenico , Malara Natalia
Published: October 2021

Imaging limitations, invasive tissue biopsies and poor information over the course of treatment to evaluate ‘real-time’ tumor dynamics justify the emerging use of liquid biopsies in the field of brain tumors. Circulating tumor cells (CTCs) from high-grade astrocytomas might reach the circulation by crossing the blood–brain barrier. Here, for the first time, CTCs cytology in a case of pylocitic astrocytoma is described. An obstructive hydrocephalous due to a lateral mesencephalic tectum mass occluding the Silvio Aqueduct was diagnosed in a young, 18 years old, male. Considering the location of the tumor and the rapid deterioration of the neurological status, it has been decided to urgency treat the patient with ventriculoperitoneal shunting. Magnetic resonance imaging showed a nodular shaped lesion localized within the left lateral mesencephalic tectum. Stereotactic biopsy was not approachable due significant risk of neurological consequences. The diagnosis was performed by blood sampling, a non-invasive procedure for the patient, in order to provide tumor information. Cytopathological features on detected circulating atypical GFAP positive cells led to pilocytic diagnosis confirmed by the patient’s 68 months outcome.
Integrin Alpha-2 as a Potential Prognostic and Predictive Biomarker for Patients With Lower-Grade Glioma
Authors: Lin Li , Huang Kai , Tu Zewei , Zhu Xingen , Li Jingying , Lei Kunjian , Luo Min , Wang Peng , Gong Chuandong , Long Xiaoyan , Wu Lei
Published: October 2021

Diffuse gliomas are the most common malignant brain tumors with the highest mortality and recurrence rate in adults. Integrin alpha-2 (ITGA2) is involved in a series of biological processes, including cell adhesion, stemness regulation, angiogenesis, and immune/blood cell functions. The role of ITGA2 in lower-grade gliomas (LGGs) is not well defined. Firstly, we downloaded RNA sequencing and relevant clinical information from The Cancer Genome Atlas cohort, the Chinese Glioma Genome Atlas cohort, and related immune cohorts. Next, prognosis analysis, difference analysis, clinical model construction, enrichment analysis, and immune infiltration analysis are performed for this study. These analyses indicated that ITGA2 may have clinical application value and research value in LGG immunotherapy. We also detected the mRNA and protein expression of ITGA2 in three LGG cell lines and normal glial cells using quantitative real-time polymerase chain reaction assay and western blot assay. Our study not only offers a novel target for LGG immunotherapy but also can better comprehend the mechanism of the development and progression of patients with LGG. This study revealed that ITGA2 may be a potential prognostic and predictive biomarker for LGG, which can bring new insights into targeted immunotherapy.
HMGB1 Promotes Resistance to Doxorubicin in Human Hepatocellular Carcinoma Cells by Inducing Autophagy via the AMPK/mTOR Signaling Pathway
Authors: Li Junhua , Zhou Wei , Mao Qiang , Gao Dandan , Xiong Lin , Hu Xinyao , Zheng Yongfa , Xu Ximing
Published: October 2021

Chemoresistance remains as a major hindrance in the treatment of hepatocellular carcinoma (HCC). High mobility group box protein 1 (HMGB1) enhances autophagic flux and protects tumor cells from apoptosis, which results in acquired drug resistance. However, the exact mechanisms underlying HMGB1-modulated autophagy in HCC chemoresistance remain to be defined. In the present study, we found that administration of doxorubicin (DOX) significantly promoted HMGB1 expression and induced HMGB1 cytoplasmic translocation in human HCC cell lines BEL7402 and SMMC7721, which enhanced autophagy that contributes to protecting HCC cells from apoptosis and increasing drug resistance. Moreover, we observed HMGB1 translocation and elevation of autophagy in DOX-resistant BEL7402 and SMMC7721 cells. Additionally, inhibition of HMGB1 and autophagy increased the sensitivities of BEL-7402 and SMMC-7721 cells to DOX and re-sensitized their DOX-resistant cells. Subsequently, we confirmed with HMGB1 regulated autophagy by activating the 5ʹ adenosine monophosphate-activated protein kinase (AMPK)/mTOR pathway. In summary, our results indicate that HMGB1 promotes acquired DOX resistance in DOX-treated BEL7402 and SMMC7721 cells by enhancing autophagy through the AMPK/mTOR signaling pathway. These findings provide the proof-of-concept that HMGB1 inhibitors might be an important targeted treatment strategy for HCC.
A Novel Nomogram for Predicting the Risk of Short-Term Recurrence After Surgery in Glioma Patients
Authors: Wang Tianwei , Zhu Chihao , Zheng Shuyu , Liao Zhijun , Chen Binghong , Liao Keman , Yang Xi , Zhou Zhiyi , Bai Yongrui , Wang Zhenwei , Hou Yanli , Qiu Yongming , Huang Renhua
Published: October 2021

Objective

The aim of this study was to establish a nomogram model for predicting the risk of short-term recurrence in glioma patients.

Methods

The clinical data of recurrent glioma patients were summarized and analyzed in this study. Univariate and multivariate logistic regression analyses were performed to analyze the correlation between clinical data and the risk of short-term recurrence after operation. A nomogram was established based on the multivariate logistic regression model results.

Results

A total of 175 patients with recurrent glioma were enrolled, with 53 patients in the short-term recurrence (STR) group (recurrent time ≤6 months) and 122 patients in the long-term recurrence (LTR) group (recurrent time ≥36 months). Univariate analysis revealed that age at diagnosis, Karnofsky performance scores (KPSs), tumor location, glioma grade, glioma type, extent of resection (EOR), adjuvant chemotherapy (ad-CT), concurrent chemotherapy (co-CT), and isocitrate dehydrogenase (IDH) status were significantly associated with the short-term glioma recurrence. Multivariate analyses revealed that age at diagnosis, KPS, glioma grade, EOR, and IDH were independent risk factors for short-term glioma recurrence. A risk nomogram for the short-term recurrence of glioma was established, with the concordance index (C-index) of 0.971. The findings of calibration and receiver operating characteristic (ROC) curves showed that our nomogram model had good performance and discrimination to estimate short-term recurrence probability.

Conclusion

This nomogram model provides reliable information about the risk of short-term glioma recurrence for oncologists and neurosurgeons. This model can predict the short-term recurrence probability and give assistance to decide the interval of follow-up or formulate individualized treatment strategies based on the predicted results. A free online prediction risk tool for this nomogram is provided: https://rj2021.shinyapps.io/Nomogram_ recurrence-risk/.
The Intratumor Microbiota Signatures Associate With Subtype, Tumor Stage, and Survival Status of Esophageal Carcinoma
Authors: Wang Yangyang , Guo Hua , Gao Xiaoguang , Wang Jihan
Published: October 2021

Altered human microbiome characteristic has been linked with esophageal carcinoma (ESCA), analysis of microbial profiling directly derived from ESCA tumor tissue is beneficial for studying the microbial functions in tumorigenesis and development of ESCA. In this study, we identified the intratumor microbiome signature and investigated the correlation between microbes and clinical characteristics of patients with ESCA, on the basis of data and information obtained from The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA) databases. A total of 82 samples were analyzed for microbial composition at various taxonomic levels, including 40 tumor samples of esophageal squamous cell carcinoma (ESCC), 20 tumor samples of esophageal adenocarcinoma (EAD), and 22 adjacent normal samples. The results showed that the relative abundance of several microbes changed in tumors compared to their paired normal tissues, such as Firmicutes increased significantly while Proteobacteria decreased in tumor samples. We also identified a microbial signature composed of ten microbes that may help in the classification of ESCC and EAD, the two subtypes of ESCA. Correlation analysis demonstrated that compositions of microbes Fusobacteria/Fusobacteriia/Fusobacteriales, Lactobacillales/Lactobacillaceae/Lactobacillus, Clostridia/Clostridiales, Proteobacteria, and Negativicutes were correlated with the clinical characteristics of ESCA patients. In summary, this study supports the feasibility of detecting intratumor microbial composition derived from tumor sequencing data, and it provides novel insights into the roles of microbiota in tumors. Ultimately, as the second genome of human body, microbiome signature analysis may help to add more information to the blueprint of human biology.
The Value of MRI Findings Combined With Texture Analysis in the Differential Diagnosis of Primary Ovarian Granulosa Cell Tumors and Ovarian Thecoma–Fibrothecoma
Authors: Li Nai-yu , Shi Bin , Chen Yu-lan , Wang Pei-pei , Wang Chuan-bin , Chen Yao , Ge Ya-qiong , Dong Jiang-ning , Wei Chao
Published: October 2021

Objective

This study aims to explore the value of magnetic resonance imaging (MRI) and texture analysis (TA) in the differential diagnosis of ovarian granulosa cell tumors (OGCTs) and thecoma-fibrothecoma (OTCA–FTCA).

Methods

The preoperative MRI data of 32 patients with OTCA–FTCA and 14 patients with OGCTs, confirmed by pathological examination between June 2013 and August 2020, were retrospectively analyzed. The texture data of three-dimensional MRI scans based on T2-weighted imaging and clinical and conventional MRI features were analyzed and compared between tumor types. The Mann–Whitney U-test, χ2 test/Fisher exact test, and multivariate logistic regression analysis were used to identify differences between the OTCA–FTCA and OGCTs groups. A regression model was established by using binary logistic regression analysis, and receiver operating characteristic curve analysis was carried out to evaluate diagnostic efficiency.

Results

A multivariate analysis of the imaging-based features combined with TA revealed that intratumoral hemorrhage (OR = 0.037), log-sigma-20mm-3D_glszm_SmallAreaEmphasis (OR = 4.40), and log-sigma-2-0mm-3D_glszm_SmallAreaHighGrayLevelEmphasis (OR = 1.034) were independent features for discriminating between OGCTs and OTCA–FTCA (P < 0.05). An imaging-based diagnosis model, TA-based model, and combination model were established. The areas under the curve of the three models in predicting OGCTs and OTCA–FTCA were 0.935, 0.944, and 0.969, respectively; the sensitivities were 93.75, 93.75, and 96.87%, respectively; and the specificities were 85.71, 92.86, and 92.86%, respectively. The DeLong test indicated that the combination model had the highest predictive efficiency (P < 0.05), with no significant difference among the three models in differentiating between OGCTs and OTCA–FTCA (P > 0.05).

Conclusions

Compared with OTCA–FTCA, intratumoral hemorrhage may be characteristic MR imaging features with OGCTs. Texture features can reflect the microheterogeneity of OGCTs and OTCA–FTCA. MRI signs and texture features can help differentiate between OGCTs and OTCA–FTCA and provide a more comprehensive and accurate basis for clinical treatment.
Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis
Authors: Sakai Kazuko , Sakurai Toshiharu , De Velasco Marco A. , Nagai Tomoyuki , Chikugo Takaaki , Ueshima Kazuomi , Kura Yurie , Takahama Takayuki , Hayashi Hidetoshi , Nakagawa Kazuhiko , Kudo Masatoshi , Nishio Kazuto
Published: October 2021

Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis.
Syndecans and Their Synstatins: Targeting an Organizer of Receptor Tyrosine Kinase Signaling at the Cell-Matrix Interface
Authors: Rapraeger Alan C.
Published: October 2021

Receptor tyrosine kinases (RTKs) and integrin matrix receptors have well-established roles in tumor cell proliferation, invasion and survival, often functioning in a coordinated fashion at sites of cell-matrix adhesion. Central to this coordination are syndecans, another class of matrix receptor, that organize RTKs and integrins into functional units, relying on docking motifs in the syndecan extracellular domains to capture and localize RTKs (e.g., EGFR, IGF-1R, VEGFR2, HER2) and integrins (e.g., αvβ3, αvβ5, α4β1, α3β1, α6β4) to sites of adhesion. Peptide mimetics of the docking motifs in the syndecans, called “synstatins”, prevent assembly of these receptor complexes, block their signaling activities and are highly effective against tumor cell invasion and survival and angiogenesis. This review describes our current understanding of these four syndecan-coupled mechanisms and their inhibitory synstatins (SSTNIGF1R, SSTNVEGFR2, SSTNVLA-4, SSTNEGFRand SSTNHER2).
COVID-19 Pneumomediastinum: Possible Role of Transesophageal Echo in Bedside Percutaneous Bicaval Double-Lumen ECMO Cannulation in Children. A Case Report
Authors: Moscatelli Andrea , Pezzato Stefano , Buratti Silvia , Lampugnani Elisabetta , Di Mascio Alberto , Damasio Maria Beatrice , Caorsi Roberta , Gattorno Marco , Castagnola Elio
Published: October 2021

COVID-19 is generally uneventful in children. Only 8% of severe acute respiratory distress syndrome corona virus 2 pediatric patients require intensive care; of these, 1% may need extracorporeal membrane oxygenation. Preexisting medical conditions are an independent risk factor for pediatric intensive care unit admission. We describe the case of an 11-year-old girl with adenosine deaminase 2 deficiency who presented severe COVID-19 acute respiratory distress syndrome, complicated by a massive air leak syndrome. The respiratory failure, refractory to conventional support, required veno-venous extracorporeal membrane oxygenation. To prevent viral diffusion, bicaval double-lumen cannulation was performed percutaneously at the bedside under exclusive echo guidance. Because of pneumomediastinum, pneumothorax, and subcutaneous emphysema, ultrasound visualization of the heart was possible only with transesophageal echo. To our knowledge, this is the first description of a transesophageal echo guided bedside percutaneous bicaval double-lumen extracorporeal membrane oxygenation cannulation in a pediatric patient. Pitfalls of the technique are highlighted.
Medium-Term Pulmonary Function Test After Thoracoscopic Lobectomy and Segmentectomy for Congenital Lung Malformation: A Comparative Study With Normal Control
Authors: Huang Jin-Xi , Hong Song-Ming , Hong Jun-Jie , Chen Qiang , Cao Hua
Published: October 2021

Purpose: This study aimed to compare the outcomes and pulmonary function test (PFT) of thoracoscopic segmentectomy and lobectomy in infants with congenital lung malformation and study the result of PFT on a medium-term basis.

Methods: The clinical data of 19 infants with congenital lung malformation who underwent thoracoscopic surgery in our hospital from January 2018 to March 2019 were retrospectively studied; these infants were paired with another 19 infants who underwent thoracoscopic lobectomy during the same period using propensity score matching. Age-matched healthy individuals with similar body sizes were recruited for PFT as the control group. Patient characteristics, postoperative PFT, and outcomes were extracted for statistical analysis.

Results: The average length of hospital stay did not significantly differ between segmentectomy and lobectomy groups. The segmentectomy group had more chest tube drainage than the lobectomy group. PFT 1 month after the operation showed that the tidal volume of the lobectomy group was lower than that of the segmentectomy group. Time to peak expiratory flow/time of expiration and peak flow/terminal airway velocity (V25%) indicated small airway dysfunction in the lobectomy group, and no obvious abnormalities were found in “time of inspiratory/time of expiration” in either group. Reexamination of pulmonary function 2 years after the operation showed that the small airway function of the segmentectomy group returned to normal, and no significant difference in pulmonary function was noted among the three groups.

Conclusion: The short-term pulmonary function recovery was better after segmentectomy than after lobectomy. Patients who underwent thoracoscopic lobectomy and segmentectomy have normal lung function 2 years after the operation.
Hematuria as an Early Sign of Multisystem Inflammatory Syndrome in Children: A Case Report of a Boy With Multiple Comorbidities and Review of Literature
Authors: Generalić Ana , Davidović Maša , Kos Ivanka , Vrljičak Kristina , Lamot Lovro
Published: October 2021

Introduction: While the clinical course of SARS-CoV-2 infection seems to be milder or asymptomatic within the pediatric population, growing attention has been laid to the rare complication elicited by virus, multisystem inflammatory syndrome in children temporarily associated with COVID-19 (MIS-C). Published definition and criteria of MIS-C include persistent fever, multisystem involvement, and elevated markers of inflammation, without obvious microbial inflammation or other plausible diagnosis. However, the aim of this case report is to emphasize the diversity of symptoms of MIS-C, beyond the defined criteria.

Case Presentation: We present a 10-year-old boy with 8p23.1 microdeletion syndrome and multiple comorbidities who initially came to our attention due to hematuria, persistent fever, rash, and elevated markers of inflammation. Within the next 2 days, his condition worsened despite the broad-spectrum antibiotic therapy. Assuming his past history of SARS-CoV-2 exposure, MIS-C was suspected. A high level of clinical suspicion was further supported by significant clinical features (vomiting, abdominal pain, conjunctivitis, arrhythmia, and mild left ventricular systolic dysfunction with pleural effusion) along with laboratory findings (elevated ESR, CRP, proBNP, D-dimers and fibrinogen, positive IgG SARS-CoV-2 antibodies, and negative microbiological cultures). The patient was given intravenous immunoglobulin (IVIG) and began to show instantaneous clinical and laboratory improvement.

Conclusion: Despite numerous reports of MIS-C cases in children, there are still many uncertainties regarding the clinical presentation and laboratory findings, as well as mechanisms beyond this intriguing disorder. In our case, for the first time hematuria is reported as an early symptom of MIS-C. We strongly believe that reporting various manifestations and outcomes in MIS-C patients will lead to improved diagnosis, treatment, and overall understanding of this novel inflammatory condition.
Stercoral Colitis in a Patient With Pediatric-Onset Systemic Lupus Erythematosus: Case Analysis and Review of the Literature
Authors: Gau Chun-Chun , Lin Li-Lun , Wu Chao-Yi , Huang Jing-Long
Published: October 2021

Systemic lupus erythematosus (SLE) is an autoantibody-related disease that affects multiple organs. Stercoral colitis (SC) is a rare type of inflammatory colitis with a high mortality rate. Here, we report the first case of pediatric-onset lupus in a case complicated by stercoral colitis. We also conducted a literature review of patients with SC under 30 years old to provide useful clues for rapid diagnosis at a young age. A 28-year-old female with a history of lupus and neuropsychiatric SLE was admitted with severe abdominal pain. She was found to have stercoral colitis during surgery. Two years later, the patient underwent Hartman's operation due to ischemia of the colon. In addition, 10 patients younger than 30 years old with a diagnosis of SC were analyzed based on clinical presentation, physical examination, laboratory exam, imaging and treatment. All cases had a favorable outcome without mortality. Stercoral colitis is a rare but lethal complication, emphasizing the importance of a multidisciplinary approach. Differential diagnosis should include stercoral colitis for patients with SLE developing unexplained sharp abdominal pain.
Phytopharmacological Evaluation of Different Solvent Extract/Fractions From Sphaeranthus indicus L. Flowers: From Traditional Therapies to Bioactive Compounds
Authors: Ahmad Hafiz Ibtesam , Nadeem Muhammad Faisal , Shoaib Khan Haji Muhammad , Sarfraz Muhammad , Saleem Hammad , Khurshid Umair , Locatelli Marcello , Ashraf Muhammad , Akhtar Naveed , Zainal Abidin Syafiq Asnawi , Alghamdi Adel
Published: October 2021

Sphaeranthus indicus L. is a medicinal herb having widespread traditional uses for treating common ailments. The present research work aims to explore the in-depth phytochemical composition and in vitro reactivity of six different polarity solvents (methanol, n-hexane, benzene, chloroform, ethyl acetate, and n-butanol) extracts/fractions of S. indicus flowers. The phytochemical composition was accomplished by determining total bioactive contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolomics. The reactivity of the phenolic compounds was tested through the following biochemical assays: antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation) and enzyme inhibition (AChE, BChE, α-glucosidase, α-amylase, urease, and tyrosinase) assays were performed. The methanol extract showed the highest values for phenolic (94.07 mg GAE/g extract) and flavonoid (78.7 mg QE/g extract) contents and was also the most active for α-glucosidase inhibition as well as radical scavenging and reducing power potential. HPLC-PDA analysis quantified rutin, naringenin, chlorogenic acid, 3-hydroxybenzoic acid, gallic acid, and epicatechin in a significant amount. UHPLC-MS analysis of methanol and ethyl acetate extracts revealed the presence of well-known phytocompounds; most of these were phenolic, flavonoid, and glycoside derivatives. The ethyl acetate fraction exhibited the highest inhibition against tyrosinase and urease, while the n-hexane fraction was most active for α-amylase. Moreover, principal component analysis highlighted the positive correlation between bioactive compounds and the tested extracts. Overall, S. indicus flower extracts were found to contain important phytochemicals, hence could be further explored to discover novel bioactive compounds that could be a valid starting point for future pharmaceutical and nutraceuticals applications.