bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan
Authors: Do Phuong Thao , Chen Li-Ying , Chan Lung , Hu Chaur-Jong , Chien Li-Nien
Published: May 2022

Background

The incidence of ischemic stroke has been increasing in the young population over the past 20 years. Poststroke epilepsy (PSE) is a common complication after stroke. However, few population-based studies with sufficient follow-up have investigated factors associated with PSE, especially factors related to comorbidities and unhealthy lifestyles in the modern young population. Accordingly, this study aimed to determine the long-term incidence and these risk factors for PSE young adults.

Methods

This cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) from 2002 to 2018. All patients aged between 19 and 44 years and diagnosed with ischemic stroke from 2002 to 2015 were retrospectively enrolled with a follow-up of at least 3 years. Multivariable Cox regression models were performed to identify predictors of PSE, including patients' demographics, baseline conditions, stroke severity, etiologies, comorbidities, and unhealthy behaviors.

Results

Among 6,512 ischemic stroke patients, 402 cases (6.2%) developed PSE who were with a mean follow-up period of 8.3 years (SD = 4.3 years). During the overall follow-up, stroke severity and manifestations were associated with PSE, including National Institutes of Health Stroke Scale (NIHSS) score ≥10 (aHR, 1.98; 95% CI, 1.50–2.61), seizure at first stroke admission [adjusted hazard ratio (aHR), 57.39; 95% confidence interval (CI), 43.02–76.55], length of hospital stay ≥14 days (aHR, 1.60; 95% CI, 1.26–2.02), recurrent stroke (aHR, 2.32; 95% CI, 1.85–2.90), aphasia (aHR, 1.77; 95% CI, 1.20–2.60), and malignancy (aHR, 2.05; 95% CI, 1.30–3.24). Furthermore, stroke patients with drug abuse were 2.90 times more likely to develop PSE than those without (aHR, 2.90; 95% CI, 1.53–5.50). By contrast, statin use (aHR, 0.62; 95% CI, 0.48–0.80) was associated with a lower risk of PSE. The risk factors at 1-year and 5-year PSE were similar to that of an overall follow-up.

Conclusions

Stroke severity, aphasia, malignancy, and drug abuse were associated increased risk of PSE and statin use may protect against PSE in young adults. Reducing the severity of stroke, statin use and controlling unhealthy behaviors might be able to decrease the development of PSE. Since PSE is associated with poor outcomes, early identification or intervention of PSE based on the risk factors might reduce the harmful effects of PSE.
The Increasing Effect of Interoception on Brain Frontal Responsiveness During a Socially Framed Motor Synchronization Task
Authors: Angioletti Laura , Balconi Michela
Published: May 2022

This research explored the effect of explicit Interoceptive Attentiveness (IA) manipulation on hemodynamic brain correlates during a task involving interpersonal motor coordination framed with a social goal. Participants performed a task requiring interpersonal movement synchrony with and without a social framing in both explicit IA and control conditions. Functional Near-Infrared Spectroscopy (fNIRS) was used to record oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) changes during the tasks. According to the results, the prefrontal cortex (PFC), which is involved in high-order social cognition and interpersonal relations processing, was more responsive when inducing the explicit focus (IA) on the breath during the socially framed motor task requiring synchronization, as indicated by increased O2Hb. In the absence of a broader social frame, this effect was not significant for the motor task. Overall, the present study suggests that when a joint task is performed and the individual focuses on his/her physiological body reactions, the brain hemodynamic correlates are “boosted” in neuroanatomical regions that support sustained attention, reorientation of attention, social responsiveness, and synchronization. Furthermore, the PFC responds significantly more as the person consciously focuses on physiological interoceptive correlates and performs a motor task requiring synchronization, particularly when the task is socially framed.
Brain Function and Upper Limb Deficit in Stroke With Motor Execution and Imagery: A Cross-Sectional Functional Magnetic Resonance Imaging Study
Authors: Ma Zhen-Zhen , Wu Jia-Jia , Hua Xu-Yun , Zheng Mou-Xiong , Xing Xiang-Xin , Ma Jie , Li Si-Si , Shan Chun-Lei , Xu Jian-Guang
Published: May 2022

Background

Motor imagery training might be helpful in stroke rehabilitation. This study explored if a specific modulation of movement-related regions is related to motor imagery (MI) ability.

Methods

Twenty-three patients with subcortical stroke and 21 age-matched controls were recruited. They were subjectively screened using the Kinesthetic and Visual Imagery Questionnaire (KVIQ). They then underwent functional magnetic resonance imaging (fMRI) while performing three repetitions of different motor tasks (motor execution and MI). Two separate runs were acquired [motor execution tasks (ME and rest) and motor imagery (MI and rest)] in a block design. For the different tasks, analyses of cerebral activation and the correlation of motor/imagery task-related activity and KVIQ scores were performed.

Results

During unaffected hand (UH) active grasp movement, we observed decreased activations in the contralateral precentral gyrus (PreCG), contralateral postcentral gyrus (PoCG) [p < 0.05, family wise error (FWE) corrected] and a positive correlation with the ability of FMA-UE (PreCG: r = 0.46, p = 0.028; PoCG: r = 0.44, p = 0.040). During active grasp of the affected hand (AH), decreased activation in the contralateral PoCG was observed (p < 0.05, FWE corrected). MI of the UH induced significant activations of the contralateral superior frontal gyrus, opercular region of the inferior frontal gyrus, and ipsilateral ACC and deactivation in the ipsilateral supplementary motor area (p < 0.05, AlphaSim correction). Ipsilateral anterior cingulate cortex (ACC) activity negatively correlated with MI ability (r = =–0.49, p = 0.022). Moreover, we found significant activation of the contralesional middle frontal gyrus (MFG) during MI of the AH.

Conclusion

Our results proved the dominant effects of MI dysfunction that exist in stroke during the processing of motor execution. In the motor execution task, the enhancement of the contralateral PreCG and PoCG contributed to reversing the motor dysfunction, while in the MI task, inhibition of the contralateral ACC can increase the impaired KVIQ ability. The bimodal balance recovery model can explain our results well. Recognizing neural mechanisms is critical to helping us formulate precise strategies when intervening with electrical or magnetic stimulation.
αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B
Authors: Nath Madhu , Fort Patrice Elie
Published: May 2022

Phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway mediates pro-survival function in neurons. In the retina, PI3K/AKT/mTOR signaling pathway is related to the early pathogenesis of diabetic retinopathy. Signaling molecules in the membrane-initiated signaling pathway exhibiting neuroprotective function interacts with the PI3K/Akt pathway as an important survival pathway. Molecular chaperone α-crystallins are known to potentially interact and/or regulate various pro-survival and pro-apoptotic proteins to regulate cell survival. Among these demonstrated mechanisms, they are well-reported to regulate and inhibit apoptosis by interacting and sequestrating the proapoptotic proteins such as Bax and Bcl-Xs. We studied the importance of metabolic stress-induced enhanced Akt signaling and αA-crystallin interdependence for exhibiting neuroprotection in metabolically challenged retinal neurons. For the first time, this study has revealed that αA-crystallin and activated Akt are significantly neuroprotective in the stressed retinal neurons, independent of each other. Furthermore, the study also highlighted that significant inhibition of the PI3K-Akt pathway does not alter the neuroprotective ability of αA-crystallin in stressed retinal neurons. Interestingly, our study also demonstrated that in the absence of Akt activation, αA-crystallin inhibits the translocation of Bax in the mitochondria during metabolic stress, and this function is regulated by the phosphorylation of αA-crystallin on residue 148.
The Effect of Delayed Oncology Surgery on Survival Outcomes for Patients With Gastric Cancer During the COVID-19 Pandemic: Evidence-Based Strategies
Authors: Ma Jichun , Zhu Chenglou , Li Weidong , Qiu Zhisheng , Yang Jian , Ge Long , Da Mingxu
Published: May 2022

Objective

To evaluate the impact of delay in gastrectomy on gastric cancer patients’ survival outcomes during the COVID-19 pandemic.

Methods

Databases including PubMed, MEDLINE (using the Ovid platform), Embase, the Cochrane Library, COVID-19 Open Research Dataset Challenge, COVID-19 Research Database (WHO), ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform were searched for studies of any design and in any setting that included patients with gastric cancer from their inception to July 31, 2021. Hazard ratio (HR) and 95% confidence intervals (CI) of research endpoints in each study were calculated. Statistical analyses were performed with Stata 12.0.

Results

A total of 8 studies involving 4,052 gastric cancer patients were eligible and included in the present meta-analysis. The result of the meta-analysis was shown that delaying surgery for less than 8 weeks may not decrease OS (HR = 0.91, 95% CI: 0.80~1.04, p = 0.167) and DFS (HR = 0.96, 95% CI: 0.62~1.50, p = 0.872) in gastric cancer. Our meta-analysis also illustrated that delay in surgery for more than 4 weeks (HR = 0.85, 95% CI: 0.56~1.27, p = 0.421), 6 weeks (HR = 0.88, 95% CI: 0.61~1.27, p = 0.490), and 8 weeks (HR = 0.93, 95% CI: 0.80~1.07, p = 0.314) was also not associated with a decreased OS.

Conclusion

A delay in surgery of less than 8 weeks is not associated with worse overall survival for patients with gastric cancer.
Molecular Classification in Patients With Endometrial Cancer After Fertility-Preserving Treatment: Application of ProMisE Classifier and Combination of Prognostic Evidence
Authors: Ran Xuting , Hu Tingwenyi , Li Zhengyu
Published: May 2022

The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) is a molecular classification system that identifies endometrial cancer (EC) into four prognostically distinct subtypes: POLE-mutated, mismatch repair deficiency (MMR-D), p53 wild-type (p53wt), and p53 abnormal (p53abn). However, few reports have applied the ProMisE classifier to EC patients who underwent fertility-preserving treatment (FPT) so far. This study evaluated whether the ProMisE classifier predicted in early-stage EC patients after FPT. We first summarized the three reported outcomes of ProMisE applied to EC patients who received FPT. The hormone-treated patients with EC from 2010 to 2020 in our facility were then analyzed. By sequential immunohistochemistry and Sanger sequencing of POLE according to the ProMisE system, formalin-fixed paraffin-embedded blocks of patients before treatment were collected and classified into POLE-mutated, MMR-D, p53wt, and p53abn subtypes. The primary outcome was a complete response rate after FPT. Thirteen patients were enrolled from our facility, with 3 (3/13) MMR-D, 0 (0/13) POLE, 8 (8/13) p53wt, 1 (1/13) p53abn, and 1 (1/13) failed with DNA amplification. Six (6/8) patients with p53wt, 2 (2/3) patients with MMR-D, and 1 (1/1) patient with p53abn achieved a complete response in 6 months after treatment. The results of our study and the reported outcomes were finally combined. A total of 106 patients who underwent FPT were included. Of these, 23 (21.7%) were classified as MMR-D, 3 (2.8%) as POLE-mutated, 3 (2.8%) as p53abn, and 77 (72.6%) as p53wt. There was no significant difference in the complete response rate (P = 0.152) and recurrence rate (P = 0.174) between MMR-D and p53wt subtypes after FPT. Based on current data, we observed no prognostic significance of the ProMisE classifier in EC patients who underwent FPT. Larger prospective studies are needed to elucidate the precise prognostic meaning of this molecular classifier in these cases.
Advances in Imaging in Evaluating the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer
Authors: Kong Xianshu , Zhang Qian , Wu Xuemei , Zou Tianning , Duan Jiajun , Song Shujie , Nie Jianyun , Tao Chu , Tang Mi , Wang Maohua , Zou Jieya , Xie Yu , Li Zhenhui , Li Zhen
Published: May 2022

Neoadjuvant chemotherapy (NAC) is increasingly widely used in breast cancer treatment, and accurate evaluation of its response provides essential information for treatment and prognosis. Thus, the imaging tools used to quantify the disease response are critical in evaluating and managing patients treated with NAC. We discussed the recent progress, advantages, and disadvantages of common imaging methods in assessing the efficacy of NAC for breast cancer.
The Value of Whole-Tumor Texture Analysis of ADC in Predicting the Early Recurrence of Locally Advanced Cervical Squamous Cell Cancer Treated With Concurrent Chemoradiotherapy
Authors: Zhang Xiaomiao , Zhang Qi , Xie Lizhi , An Jusheng , Wang Sicong , Yu Xiaoduo , Zhao Xinming
Published: May 2022

Objectives

To investigate the value of whole-tumor texture analysis of apparent diffusion coefficient (ADC) map in predicting the early recurrence of patients with locally advanced cervical squamous cell cancer (LACSC) treated with concurrent chemoradiotherapy (CCRT) and establish a combined prediction model including clinical variables and first-order texture features.

Methods

In total, 219 patients (training: n = 153; testing: n = 66) with stage IIB-IVA LACSC treated by CCRT between January 2014 and December 2019 were retrospectively enrolled in this study. Clinical variables and 22 first-order texture features extracted from ADC map were collected. The Mann-Whitney U test or independent sample t test, chi-square test or Fisher’s exact were used to analyze statistically significant parameters, logistic regression analysis was used for multivariate analysis, and receiver operating characteristic analysis was used to compare the diagnostic performance.

Results

In the clinical variables, T stage and lymph node metastasis (LNM) were independent risk factors, and the areas under the curve (AUCs) of the clinical model were 0.697 and 0.667 in the training and testing cohorts, the sensitivity and specificity were 48.8% and 85.5% in the training cohort, and 84.1% and 51.1% in the testing cohort, respectively. In the first-order texture features, mean absolute deviation (MAD) was the independent protective factor, with an AUC of 0.756 in the training cohort and 0.783 in the testing cohort. The sensitivity and specificity were 95.3% and 52.7% in the training cohort and 94.7% and 53.2% in the testing cohort, respectively. The combined model (MAD, T stage, and LNM) was established, it exhibited the highest AUC of 0.804 in the training cohort and 0.821 in the testing cohort, which was significantly higher than the AUC of the clinical prediction model. The sensitivity and specificity were 67.4% and 85.5% in the training cohort and 94.7% and 70.2% in the testing cohort, respectively.

Conclusions

The first-order texture features of the ADC map could be used along with clinical predictive biomarkers to predict early recurrence in patients with LACSC treated by CCRT.
Genomics of Tumor Origin and Characteristics for Adenocarcinoma and Malignant Pleural Mesothelioma: A Case Report
Authors: Usuda Katsuo , Niida Yo , Ishikawa Masahito , Iwai Shun , Yamagata Aika , Iijima Yoshihito , Motono Nozomu , Yamada Sohsuke , Uramoto Hidetaka
Published: May 2022

A female underwent a right middle lobectomy for a pulmonary adenocarcinoma (AD). She eventually died of a right malignant pleural mesothelioma (MPM; sarcomatoid type) 4 years and 7 months after the removal of the AD even though she did not have any history of asbestos exposure, smoking, or radiation exposure. Her chest CT revealed multiple pulmonary nodules and bilateral pleural effusion with a right pleural tumor directly invading into the abdominal cavity. The genomics of tumor origin and characteristics were examined for the AD and the MPM. As a result, 50 somatic variants were detected in the AD, and 29 somatic variants were detected in the MPM. The variants which were common in both the AD and the MPM were not present, which suggested that the AD and the MPM had occurred independently in different origins. The MPM had two driver oncogenes of TP53 and EP300, but the AD did not. Two driver oncogenes of TP53 and EP300 were hypothesized to make the MPM aggressive. The speed at which the MPM progressed without the patient having a history of asbestos exposure, smoking, or radiation exposure was alarming.
Liquid Biopsy Based Circulating Biomarkers in Metastatic Prostate Cancer
Authors: Dathathri Eshwari , Isebia Khrystany T. , Abali Fikri , Lolkema Martijn P. , Martens John W. M. , Terstappen Leon W. M. M. , Bansal Ruchi
Published: May 2022

Prostate cancer is the most dominant male malignancy worldwide. The clinical presentation of prostate cancer ranges from localized indolent to rapidly progressing lethal metastatic disease. Despite a decline in death rate over the past years, with the advent of early diagnosis and new treatment options, challenges remain towards the management of metastatic prostate cancer, particularly metastatic castration sensitive prostate cancer (mCSPC) and castration resistant prostate cancer (mCRPC). Current treatments involve a combination of chemotherapy with androgen deprivation therapy and/or androgen receptor signalling inhibitors. However, treatment outcomes are heterogeneous due to significant tumor heterogeneity indicating a need for better prognostic biomarkers to identify patients with poor outcomes. Liquid biopsy has opened a plethora of opportunities from early diagnosis to (personalized) therapeutic disease interventions. In this review, we first provide recent insights about (metastatic) prostate cancer and its current treatment landscape. We highlight recent studies involving various circulating biomarkers such as circulating tumor cells, genetic markers, circulating nucleic acids, extracellular vesicles, tumor-educated platelets, and the secretome from (circulating) tumor cells and tumor microenvironment in metastatic prostate cancer. The comprehensive array of biomarkers can provide a powerful approach to understanding the spectrum of prostate cancer disease and guide in developing improved and personalized treatments for patients.
Nano Drug Delivery System for Tumor Immunotherapy: Next-Generation Therapeutics
Authors: Zhou Lili , Zou Manshu , Xu Yilin , Lin Peng , Lei Chang , Xia Xinhua
Published: May 2022

Tumor immunotherapy is an artificial stimulation of the immune system to enhance anti-cancer response. It has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing in recent years, and many treatments are in clinical and preclinical stages. Despite this progress, the special tumor heterogeneity and immunosuppressive microenvironment of solid tumors made immunotherapy in the majority of cancer cases difficult. Therefore, understanding how to improve the intratumoral enrichment degree and the response rate of various immunotherapy drugs is key to improve efficacy and control adverse reactions. With the development of materials science and nanotechnology, advanced biomaterials such as nanoparticle and drug delivery systems like T-cell delivery therapy can improve effectiveness of immunotherapy while reducing the toxic side effects on non-target cells, which offers innovative ideas for improving immunity therapeutic effectiveness. In this review, we discuss the mechanism of tumor cell immune escape and focus on current immunotherapy (such as cytokine immunotherapy, therapeutic monoclonal antibody immunotherapy, PD-1/PD-L1 therapy, CAR-T therapy, tumor vaccine, oncolytic virus, and other new types of immunity) and its challenges as well as the latest nanotechnology (such as bionic nanoparticles, self-assembled nanoparticles, deformable nanoparticles, photothermal effect nanoparticles, stimuli-responsive nanoparticles, and other types) applications in cancer immunotherapy.
The Role of 3D-pCASL MRI in the Differential Diagnosis of Glioblastoma and Brain Metastases
Authors: Solozhentseva Kristina , Batalov Artem , Zakharova Natalia , Goryaynov Sergey , Pogosbekyan Eduard , Pronin Igor
Published: May 2022

Purpose

The first aim of this study was to compare the intratumoral and peritumoral blood flow parameters in glioblastomas and brain metastases measured by pseudocontinuous arterial spin labeling MRI (3D pCASL). The second aim of this study was to determine whether pCASL could aid in identifying the source of brain metastases.

Materials and Methods

This study included 173 patients aged 12 to 83 years (median age—61 years), who were observed at the National Medical Research Center for Neurosurgery. All patients underwent preoperative MRI with pCASL perfusion. Thereafter patients were operated on and received histological diagnosis. No patients received preoperative chemo or radiotherapy.

Results

The values of maximum and normalized intratumoral blood flow were significantly higher in the group with gliblastoma than in the group with brain metastases: 168.98 + −91.96 versus 152.1 + −173.32 and 7.6 + −8.4 versus 9.3 + −5.33 respectively (p <0.01). However, ROC analysis showed low AUC specificity and sensitivity (0.64, 70%, 60% for mTBF and 0.66, 77%, 62% for nTBF). Peritumoral blood flow parameters were also higher in the glioblastoma group (29.61 + −22.89 versus 16.58 + −6.46 for mTBF and 1.63 + −1.14 versus 0.88 + −0.38 for nTBF, respectively; p <0.01). ROC analysis showed the following measurements of AUC, specificity, and sensitivity (0.75, 68%, 73% for mTBF and 0.77, 58%, 91% for nTBF). Regarding pCASL and various histological subsets of brain metastases, the study found statistically significant differences between the lung and melanoma metastases and the lung and kidney metastases. ROC analysis gave the following values for lung and melanoma metastases: AUC—0.76, specificity—75%, and sensitivity—73% for mTBF; 0.83, 67%, and 93% respectively, for nTBF. For lung and kidney metastases: AUC—0.74, specificity—70%, and sensitivity—93% for mTBF; 0.75, 70%, and 93% respectively, for nTBF.

Conclusions

pCASL could aid in differential diagnosis between glioblastoma and brain metastases. Measurement of peritumoral blood flow demonstrates higher specificity and sensitivity than with intratumoral blood flow. Moreover, pCASL provides the ability to distinguish lung metastases from kidney and melanoma metastases.
Low-Intensity Focused Ultrasound Technique in Glioblastoma Multiforme Treatment
Authors: Mungur Rajneesh , Zheng Jiesheng , Wang Ben , Chen Xinhua , Zhan Renya , Tong Ying
Published: May 2022

Glioblastoma is one of the central nervous system most aggressive and lethal cancers with poor overall survival rate. Systemic treatment of glioblastoma remains the most challenging aspect due to the low permeability of the blood-brain barrier (BBB) and blood-tumor barrier (BTB), limiting therapeutics extravasation mainly in the core tumor as well as in its surrounding invading areas. It is now possible to overcome these barriers by using low-intensity focused ultrasound (LIFU) together with intravenously administered oscillating microbubbles (MBs). LIFU is a non-invasive technique using converging ultrasound waves which can alter the permeability of BBB/BTB to drug delivery in a specific brain/tumor region. This emerging technique has proven to be both safe and repeatable without causing injury to the brain parenchyma including neurons and other structures. Furthermore, LIFU is also approved by the FDA to treat essential tremors and Parkinson’s disease. It is currently under clinical trial in patients suffering from glioblastoma as a drug delivery strategy and liquid biopsy for glioblastoma biomarkers. The use of LIFU+MBs is a step-up in the world of drug delivery, where onco-therapeutics of different molecular sizes and weights can be delivered directly into the brain/tumor parenchyma. Initially, several potent drugs targeting glioblastoma were limited to cross the BBB/BTB; however, using LIFU+MBs, diverse therapeutics showed significantly higher uptake, improved tumor control, and overall survival among different species. Here, we highlight the therapeutic approach of LIFU+MBs mediated drug-delivery in the treatment of glioblastoma.
Robot-Assisted Laparoscopic IVC Treatment Strategy in Retroperitoneal Tumors
Authors: Liu Lei , Tang Shiying , Liu Zhuo , Liu Cheng , Zhang Hongxian , Tian Xiaojun , Wang Guoliang , Zhang Shudong , Ma Lulin
Published: May 2022

Objectives

To show the practice of robot-assisted laparoscopic inferior vena cava (IVC) treatment strategies in patients with retroperitoneal tumors.

Patients and Methods

From October 2020 to July 2021, 17 patients with retroperitoneal tumors successfully underwent robot-assisted laparoscopic tumor resection with IVC management. The patient details, tumor characteristics, intraoperative data, pathological features and severe complications were assessed. The IVC treatment strategies were divided into 4 ways: ①local resection and primary repair of the IVC; ②IVC ligation; ③ IVC reconstruction by bovine pericardial grafts; and ④ IVC transection and anastomosis.

Results

In terms of IVC management, 5 cases had conventional total occlusion of the IVC and its branches, 3 cases had delayed occlusion of the proximal IVC technique, 2 cases had IVC resection by Satinsky clamp, 5 cases had IVC ligation, 1 case had IVC reconstruction by bovine pericardial grafts and 1 case had IVC transection and anastomosis. The median operation time was 151 min, and blood loss was 500 ml. There was no severe complication perioperatively. The follow-up time of 17 patients was 8 to 17 months (median: 12 months). No local recurrence or overall death was found during follow-up.

Conclusions

These robot-assisted laparoscopic IVC treatment strategies were considered to be safe and feasible in experienced centers, as well as helpful to completely remove the tumor for better oncological prognosis and restore the blood reflux of IVC as much as possible to ensure fewer postoperative complications.
Clinical and Magnetic Resonance Imaging Characteristics of Pediatric Acute Disseminating Encephalomyelitis With and Without Antibodies to Myelin Oligodendrocyte Glycoprotein
Authors: Lei Meifang , Cui Yaqiong , Dong Zhaoying , Zhi Xiufang , Shu Jianbo , Cai Chunquan , Li Dong
Published: May 2022

Background

Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated disorders (MOGADs) have been considered as a new inflammatory disease entity of the central nervous system (CNS) and have heterogeneous clinical and imaging presentations. Acute disseminated encephalomyelitis (ADEM) is one of the most important phenotypes. Our research is aimed to compare the clinical and magnetic resonance imaging (MRI) characteristics of ADEM with or without MOG-IgG in pediatric-acquired demyelinating syndromes (ADSs).

Methods and Results

We retrospectively reviewed the clinical characteristics, MRI features, and outcomes of pediatric patients with ADSs from March 2017 to February 2021 in our center. MOG-IgG was analyzed by transfected cell-based assay (CBA). Among 46 children with ADEM, 21 children (11 girls and 10 boys) were positive for MOG-IgG. Headache, fever, vomiting, vertigo, ataxia, and decreased muscle strength were common in all enrolled children. No significant difference existed in demographic characteristics, symptoms at an initial episode, or laboratory cerebrospinal fluid (CSF) findings between children with MOG-IgG and children without MOG-IgG. For children with MOG-IgG seropositive ADEM, cerebral MRI showed widespread, poorly demarcated bilateral lesions, especially in cortical and subcortical white matter, and spinal MRI often showed lesions spanning more than three segments. The significant difference in MRI features between the two groups was the presence of lesions in the thalamus and cortical area (p < 0.05). Most children in both groups showed clinical improvement 1 week after immunotherapy and achieved recovery during their hospital stay. Three children with MOG-IgG and four children without MOG-IgG had one or more relapsing courses with median interattack intervals of 4 (range: 1–7) months and 10 (range: 1–24) months, respectively. New clinical symptoms and lesions on cerebral and spinal MRI were found during relapsing courses in two groups. No recurrences were recorded 6–51 months after each patient’s last episode.

Conclusions

There was no significant difference in clinical characteristics between ADEM children with MOG-IgG and ADEM children without MOG-IgG. For children with MOG-IgG seropositive ADEM, cerebral MRI showed large, bilateral lesions and spinal MRI often showed lesions spanning more than three segments. Children achieved a favorable outcome regardless of MOG-IgG serostatus.
Clinical and Neurodevelopmental Characteristics of Enterovirus and Parechovirus Meningitis in Neonates
Authors: Bucci Silvia , Coltella Luana , Martini Ludovica , Santisi Alessandra , De Rose Domenico Umberto , Piccioni Livia , Campi Francesca , Ronchetti Maria Paola , Longo Daniela , Lucignani Giulia , Dotta Andrea , Auriti Cinzia
Published: May 2022

Background

Non-polio-enteroviruses (EV) and human parechoviruses (HPeV) are small RNA viruses, which in newborns cause infections with a wide range of severity. Today molecular biology tools allow us to diagnose viral meningitis in neonates, sparing patients from useless antibiotics. Data on neurodevelopmental outcome of children who contract enterovirus meningitis in early childhood are still limited in the literature.

Aims

To evaluate the neurodevelopmental outcome of newborns with documented enterovirus and parechovirus meningitis contracted within the first months of life.

Methods

Enterovirus and parechovirus were detected on cerebrospinal fluid (CSF) and plasma by RT-PCR. The virological typing was done according to WHO recommendations. During the hospitalization each neonate underwent many diagnostic and instrumental examinations, to evaluate any neurological lesions attributable to the infection. After the discharge children entered in an outpatient interdisciplinary assessment process, comprehensive of the administration of Bayley III scales up to 12 months old.

Results

We observed longitudinally 30 children, born at term (mean GA 39.7 ± 0.8 weeks, mean birthweight was 3,457 ± 405 grams), who contracted enterovirus and parechovirus meningitis within the first month of life (mean age at diagnosis was 15.8 ± 7.33 days). We were able to perform the genetic typing only on 15/30 (50.0%) cerebrospinal fluid (CSF) samples from 15 neonates. We found MRI anomalies in 9/26 observed neonates (34.6%): one of them presented brainstem abnormality that are specific of enteroviral central nervous system (CNS) involvement. During the follow up children displayed an overall normal neurodevelopment and no deficit in visual and hearing areas. The mean cognitive (105.19 ± 8.71), speech (100.23 ± 8.22) and motor (97.00 ± 8.98) composite scores, assessed by Bayley III, were normal in 29/30 (96.7%). Despite this, children with pathological brain magnetic resonance imaging (MRI) scored significantly lower (p = 0.01) than children with normal brain MRI on cognitive subscale at 12 months of life.

Conclusions

Early enterovirus infections can be associated to brain MRI abnormalities, more frequently the earlier the infection. Although within a normal range, our children with pathological brain MRI scored significantly lower than those with normal brain MRI on cognitive subscale at 12 months of life.
Does Tranexamic Acid Reduce the Blood Loss in Various Surgeries? An Umbrella Review of State-of-the-Art Meta-Analysis
Authors: Hong Pan , Liu Ruikang , Rai Saroj , Liu JiaJia , Ding Yuhong , Li Jin
Published: May 2022

Background: Tranexamic acid (TXA) has been applied in various types of surgery for hemostasis purposes. The efficacy and safety of TXA are still controversial in different surgeries. Guidelines for clinical application of TXA are needed.

Materials and method: We systematically searched multiple medical databases for meta-analyses examining the efficacy and safety of TXA. Types of surgery included joint replacement surgery, other orthopedic surgeries, cardiac surgery, cerebral surgery, etc. Outcomes were blood loss, blood transfusion, adverse events, re-operation rate, operative time and length of hospital stay, hemoglobin (Hb) level, and coagulation function. Assessing the methodological quality of systematic reviews 2 (AMSTAR 2) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used for quality assessment of the included meta-analyses. Overlapping reviews were evaluated by calculating the corrected covered area (CCA).

Result: In all, we identified 47 meta-analyses, of which 44 of them were of “high” quality. A total of 319 outcomes were evaluated, in which 58 outcomes were assessed as “high” quality. TXA demonstrates significant hemostatic effects in various surgeries, with lower rates of blood transfusion and re-operation, shorter operative time and length of stay, and higher Hb levels. Besides, TXA does not increase the risk of death and vascular adverse events, but it is a risk factor for seizure (a neurological event) in cardiac surgery.

Conclusion: Our study demonstrates that TXA has a general hemostatic effect with very few adverse events, which indicates TXA is the recommended medication to prevent excessive bleeding and reduce the blood transfusion rate. We also recommend different dosages of TXA for different types of adult surgery. However, we could not recommend a unified dosage for different surgeries due to the heterogeneity of the experimental design.

Systematic Review Registration:clinicaltrials.gov/, identifier CRD42021240303
Integrative Pan-Cancer Analysis Confirmed that FCGR3A is a Candidate Biomarker Associated With Tumor Immunity
Authors: Li Lilin , Huang Zijian , Du Kunpeng , Liu Xiang , Li Chunhui , Wang Duanyu , Zhang Yangfeng , Wang Changqian , Li Jiqiang
Published: May 2022

Background:Fc gamma receptor 3A (FCGR3A) encodes a receptor for the Fc portion of immunoglobulin G, which plays a significant role in the immune response. However, the role of FCGR3A in cancers remains unclear. This study aimed to visualize the prognostic landscape of FCGR3A in pan-cancer and investigate the relationship between FCGR3A expression and tumor microenvironment.

Method:Based on the TCGA database, GTEx database, and GDSC database, we analyzed the expression of FCGR3A in pan-cancers and adjacent normal tissues and its relationship with prognosis, immune cells infiltration, immune-related genes, DNA mismatch repair (MMR) genes, DNA methylation, and drugs sensitivity. The gene alteration frequency of FCGR3A was acquired on the cBioportal website. Moreover, we constructed PPI networks, performed GO and KEGG analysis to illustrate the function, and signaling pathways of FCGR3A-related genes, and conducted gene set enrichment analysis (GSEA) of FCGR3A to further explore its potential biological functions.

Result:The differential analysis results of the publicly available databases showed that FCGR3A was generally highly expressed in pan-cancer. Survival analysis revealed that FCGR3A predominated as a risk prognostic factor in most cancers. Additionally, the expression of FCGR3A was confirmed to be associated with several immune cells infiltration, multiple immune checkpoint genes, and DNA mismatch repair genes expression in generalized carcinoma. We also identified a negative correlation between FCGR3A and DNA methylation levels. Through GO/KEGG and GESA, we found that FCGR3A was involved in many pathologic and physiological processes, and was most closely related to tumor immune-related pathways. Drug sensitivity analysis showed that higher FCGR3A expression predicts a low IC50 value for the vast majority of drugs.

Conclusions:FCGR3A may be an immune-oncogenic molecule that correlates with tumor immune infiltration levels and affects drug sensitivity, thus it can be served as a promising biomarker for cancer detection, prognosis, therapeutic design, and follow-up.
TRAF6 Suppresses the Development of Pulmonary Fibrosis by Attenuating the Activation of Fibroblasts
Authors: Min Jiali , Li Qiao , Liu Suosi , Wang Qianrong , Yin Min , Zhang Yan , Yan Jun , Cui Bing , Liu Shanshan
Published: May 2022

Pulmonary fibrosis (PF) has a high mortality rate, and its pathogenesis is unknown. TNF receptor-associated factor 6 (TRAF6), a signal transducer for inflammatory signaling, plays crucial roles in the pathogenesis of immune diseases. However, its function in PF remains unknown. Herein, we demonstrated that lungs from mice with bleomycin (BLM)-induced PF were characterized by decreased expression of TRAF6 in lung fibroblasts. Enhancing TRAF6 expression protected mice from BLM-induced PF coupled with a significant reduction in fibroblast differentiation. Furthermore, we demonstrated that overexpression of TRAF6 reversed the activation of myofibroblasts from PF mice by reducing the expression of Wnt3a and subsequently suppressing Wnt/β-catenin signaling. Additionally, the abundance of Tribbles pseudokinase 3 (TRIB3), a stress sensor, was negatively correlated with the abundance of TRAF6 in lung fibroblasts. TRIB3 overexpression decreased TRAF6 abundance by reducing TRAF6 stability in lung fibroblasts during PF. Mechanistic studies revealed that TRIB3 bound to TRAF6 and accelerated basal TRAF6 ubiquitination and degradation. Collectively, our data indicate that reduced TRAF6 expression in fibroblasts is essential for the progression of PF, and therefore, genetically increasing TRAF6 expression or disrupting the TRIB3-TRAF6 interaction could be potential therapeutic strategies for fibroproliferative lung diseases in clinical settings.
Preservation of a Dust Crystal as it Falls in an Afterglow Plasma
Authors: Chaubey Neeraj , Goree J.
Published: May 2022

In an experiment, the power that sustains a plasma was extinguished, so that microspheres, which had been levitated, fell downward toward a lower electrode. At the beginning of their fall, the microspheres were self-organized with a crystalline structure. This structure was found to be preserved as the microspheres accelerated all the way to the lower electrode. Although microspheres had, in this afterglow plasma, large positive charges of 12,500 e, their interparticle repulsion was unable to significantly alter the crystalline arrangement of the microspheres, as they fell. After their impact on the lower electrode, the microspheres bounced upward, and only then was the crystalline structure lost.
Interaction Between Cecal Metabolites and Liver Lipid Metabolism Pathways During Induced Molting in Laying Hens
Authors: Zhang Jun , Geng Xiaoqing , Zhang Yihui , Zhao Xinlong , Zhang Pengwei , Sun Guirong , Li Wenting , Li Donghua , Han Ruili , Li Guoxi , Tian Yadong , Liu Xiaojun , Kang Xiangtao , Jiang Ruirui
Published: May 2022

Moult is a normal physiological phenomenon in poultry. Induced molting (IM) is the most widely used and economical molting technique. By inducing moult, the laying hens can grow new feathers during the next laying cycle and improve laying performance. However, the lack of energy supply has a huge impact on both the liver and intestines and acts on the intestines and liver through the “gut-liver axis”. More importantly, lipid metabolism in the liver is closely related to the laying performance of laying hens. Therefore, in this study, cecal metabolites and liver transcriptome data during IM of laying hens at the late stage of laying (stop feeding method) were analyzed together to reveal the regulatory mechanism of “gut-liver axis” affecting the laying performance of laying hens from the perspective of lipid metabolism. Transcriptome analysis revealed that 4,796 genes were obtained, among which 2,784 genes had significant differences (p < 0.05). Forty-nine genes were associated with lipid metabolism, and five core genes (AGPAT2, SGPL1, SPTLC1, PISD, and CYP51A1) were identified by WGCNA. Most of these differential genes are enriched in steroid biosynthesis, cholesterol metabolism, drug metabolism—cytochrome P450, synthesis and degradation of ketone bodies, PPAR signaling pathway, and bile secretion. A total of 96 differential metabolites were obtained by correlating them with metabolome data. Induced moult affects laying performance by regulating genes related to lipid metabolism, and the cecal metabolites associated with these genes are likely to regulate the expression of these genes through the “enterohepatic circulation”. This experiment enriched the theoretical basis of induced moult and provided the basis for prolonging the feeding cycle of laying hens.
Central Commands to the Elbow and Shoulder Muscles During Circular Planar Movements of Hand With Simultaneous Generation of Tangential Forces
Authors: Kostyukov Alexander I. , Gorkovenko Andriy V. , Kulyk Yurii A. , Lehedza Oleksii V. , Shushuiev Dmytro I. , Zasada Mariusz , Strafun Serhii S.
Published: May 2022

This study examines some of the non-linear effects of signal transduction in the human motor system, with particular emphasis on muscle hysteresis. The movement tests were analyzed in a group of eight subjects, which were asked to develop tangential force using visual biofeedback while performing slow, externally imposed, circular movements of right hand holding a moving handle operated by a computerized mechatronic system. The positional changes in the averaged EMGs of the elbow and shoulder muscles were compared for all combinations of direction of movement and generated force. Additionally, for one of the subjects, there was carried out MRI identification and 3D printing of the bones of the forelimb, shoulder, scapula and collarbone, which made it possible to reconstruct for him the length and force traces of all the muscles under study. The averaged EMG traces in muscles of both joints show their close correspondence to the related force traces, however, the co-activation patterns of activity in agonists and antagonists were also often encountered. The EMG waves related to the respective force waves were strongly dependent on the predominant direction of the muscle length changes within the correspondent force wave locations: the EMG intensities were higher for the shortening muscle movements (concentric contractions) and lower during muscle lengthening (eccentric contractions). The data obtained allows to suggest that for two-joint movements of the forelimbs, it is sufficient to consider the force and activation synergies (patterns of simultaneous activity in different muscles), ignoring at the first stage the effects associated with kinematic synergy. On the other hand, the data obtained indicate that the movement kinematics has a strong modulating effect on the activation synergy, dividing it into concentric and eccentric subtypes, in accordance with the known non-linear features of the muscle dynamics. It has been shown that the concentric and eccentric differences in the responses of the shoulder muscles are more clearly distinguishable than those in the elbow muscles. The shoulder muscles also have a more pronounced symmetry of the averaged EMG responses with respect to the ascending and descending phases of force waves, while demonstrating a lower degree of antagonist cocontraction. The data obtained suggest that the central commands in two-joint movements are determined mainly by the interdependence of force and activation synergies including both intra- and inter-joint components, while kinematic synergy can be interpreted as a potent modulator of activation synergy.
Membrane Localization of Piezo1 in the Context of Its Role in the Regulation of Red Blood Cell Volume
Authors: Božič Bojan , Svetina Saša
Published: May 2022

Piezo1 is a membrane nonspecific cation channel involved in red blood cells (RBCs) in the regulation of their volume. Recently, it was shown that it is distributed on the RBC membrane in a nonuniform manner. Here it is shown that it is possible to interpret the lateral distribution of Piezo1 molecules on RBC membrane by the curvature dependent Piezo1—bilayer interaction which is the consequence of the mismatch between the intrinsic principal curvatures of the Piezo1 trimer and the principal curvatures of the membrane at Piezo1′s location but without its presence. This result supports the previously proposed model for the role of Piezo1 in the regulation of RBC volume.
A Segmentation-Guided Deep Learning Framework for Leaf Counting
Authors: Fan Xijian , Zhou Rui , Tjahjadi Tardi , Das Choudhury Sruti , Ye Qiaolin
Published: May 2022

Deep learning-based methods have recently provided a means to rapidly and effectively extract various plant traits due to their powerful ability to depict a plant image across a variety of species and growth conditions. In this study, we focus on dealing with two fundamental tasks in plant phenotyping, i.e., plant segmentation and leaf counting, and propose a two-steam deep learning framework for segmenting plants and counting leaves with various size and shape from two-dimensional plant images. In the first stream, a multi-scale segmentation model using spatial pyramid is developed to extract leaves with different size and shape, where the fine-grained details of leaves are captured using deep feature extractor. In the second stream, a regression counting model is proposed to estimate the number of leaves without any pre-detection, where an auxiliary binary mask from segmentation stream is introduced to enhance the counting performance by effectively alleviating the influence of complex background. Extensive pot experiments are conducted CVPPP 2017 Leaf Counting Challenge dataset, which contains images of Arabidopsis and tobacco plants. The experimental results demonstrate that the proposed framework achieves a promising performance both in plant segmentation and leaf counting, providing a reference for the automatic analysis of plant phenotypes.