bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning-Based Model for Predicting Incidence and Severity of Acute Ischemic Stroke in Anterior Circulation Large Vessel Occlusion
Authors: Cui Junzhao , Yang Jingyi , Zhang Kun , Xu Guodong , Zhao Ruijie , Li Xipeng , Liu Luji , Zhu Yipu , Zhou Lixia , Yu Ping , Xu Lei , Li Tong , Tian Jing , Zhao Pandi , Yuan Si , Wang Qisong , Guo Li , Liu Xiaoyun
Published: December 2021

Objectives: Patients with anterior circulation large vessel occlusion are at high risk of acute ischemic stroke, which could be disabling or fatal. In this study, we applied machine learning to develop and validate two prediction models for acute ischemic stroke (Model 1) and severity of neurological impairment (Model 2), both caused by anterior circulation large vessel occlusion (AC-LVO), based on medical history and neuroimaging data of patients on admission.

Methods: A total of 1,100 patients with AC- LVO from the Second Hospital of Hebei Medical University in North China were enrolled, of which 713 patients presented with acute ischemic stroke (AIS) related to AC- LVO and 387 presented with the non-acute ischemic cerebrovascular event. Among patients with the non-acute ischemic cerebrovascular events, 173 with prior stroke or TIA were excluded. Finally, 927 patients with AC-LVO were entered into the derivation cohort. In the external validation cohort, 150 patients with AC-LVO from the Hebei Province People's Hospital, including 99 patients with AIS related to AC- LVO and 51 asymptomatic AC-LVO patients, were retrospectively reviewed. We developed four machine learning models [logistic regression (LR), regularized LR (RLR), support vector machine (SVM), and random forest (RF)], whose performance was internally validated using 5-fold cross-validation. The performance of each machine learning model for the area under the receiver operating characteristic curve (ROC-AUC) was compared and the variables of each algorithm were ranked.

Results: In model 1, among the included patients with AC-LVO, 713 (76.9%) and 99 (66%) suffered an acute ischemic stroke in the derivation and external validation cohorts, respectively. The ROC-AUC of LR, RLR and SVM were significantly higher than that of the RF in the external validation cohorts [0.66 (95% CI 0.57–0.74) for LR, 0.66 (95% CI 0.57–0.74) for RLR, 0.55 (95% CI 0.45–0.64) for RF and 0.67 (95% CI 0.58–0.76) for SVM]. In model 2, 254 (53.9%) and 31 (37.8%) patients suffered disabling ischemic stroke in the derivation and external validation cohorts, respectively. There was no difference in AUC among the four machine learning algorithms in the external validation cohorts.

Conclusions: Machine learning methods with multiple clinical variables have the ability to predict acute ischemic stroke and the severity of neurological impairment in patients with AC-LVO.
Sevoflurane Promotes Neurodegeneration Through Inflammasome Formation in APP/PS1 Mice
Authors: Li Guohua , Wang Yu , Cao Fang , Wang Dawei , Zhou Limin , Jin Yanwu
Published: December 2021

Sevoflurane (SEVO) is a highly fluorinated methyl isopropyl ether used as an inhalational anesthetic for general anesthesia. Previous studies have shown that SEVO may induce impaired memory and recognition ability and may be associated with neurodegenerative disease, e.g., Alzheimer’s disease (AD). However, the underlying mechanism remains unknown. Here, we used a mouse AD model, APP/PS1, to study the effects of SEVO on neurodegeneration occurring in AD. We found that SEVO exposure significantly impaired the spatial reference memory, sensorimotor, and cognitive function of the mice. Mechanistically, we found that SEVO induced formation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and its downstream caspase 1-mediated production of IL-1β and IL-18, which subsequently deactivated brain-derived neurotrophic factor (BDNF) to promote neurodegeneration. Together, these data suggest that NLRP3 inflammasome is essential for SEVO-induced AD.
Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs
Authors: Bhat Umer Saleem , Shahi Navneet , Surendran Siju , Babu Kavita
Published: December 2021

One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.
Classification of MR-Detected Additional Lesions in Patients With Breast Cancer Using a Combination of Radiomics Analysis and Machine Learning
Authors: Lee Hyo-jae , Nguyen Anh-Tien , Ki So Yeon , Lee Jong Eun , Do Luu-Ngoc , Park Min Ho , Lee Ji Shin , Kim Hye Jung , Park Ilwoo , Lim Hyo Soon
Published: December 2021

Objective

This study was conducted in order to investigate the feasibility of using radiomics analysis (RA) with machine learning algorithms based on breast magnetic resonance (MR) images for discriminating malignant from benign MR-detected additional lesions in patients with primary breast cancer.

Materials and Methods

One hundred seventy-four MR-detected additional lesions (benign, n = 86; malignancy, n = 88) from 158 patients with ipsilateral primary breast cancer from a tertiary medical center were included in this retrospective study. The entire data were randomly split to training (80%) and independent test sets (20%). In addition, 25 patients (benign, n = 21; malignancy, n = 15) from another tertiary medical center were included for the external test. Radiomics features that were extracted from three regions-of-interest (ROIs; intratumor, peritumor, combined) using fat-saturated T1-weighted images obtained by subtracting pre- from postcontrast images (SUB) and T2-weighted image (T2) were utilized to train the support vector machine for the binary classification. A decision tree method was utilized to build a classifier model using clinical imaging interpretation (CII) features assessed by radiologists. Area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, and specificity were used to compare the diagnostic performance.

Results

The RA models trained using radiomics features from the intratumor-ROI showed comparable performance to the CII model (accuracy, AUROC: 73.3%, 69.6% for the SUB RA model; 70.0%, 75.1% for the T2 RA model; 73.3%, 72.0% for the CII model). The diagnostic performance increased when the radiomics and CII features were combined to build a fusion model. The fusion model that combines the CII features and radiomics features from multiparametric MRI data demonstrated the highest performance with an accuracy of 86.7% and an AUROC of 91.1%. The external test showed a similar pattern where the fusion models demonstrated higher levels of performance compared with the RA- or CII-only models. The accuracy and AUROC of the SUB+T2 RA+CII model in the external test were 80.6% and 91.4%, respectively.

Conclusion

Our study demonstrated the feasibility of using RA with machine learning approach based on multiparametric MRI for quantitatively characterizing MR-detected additional lesions. The fusion model demonstrated an improved diagnostic performance over the models trained with either RA or CII alone.
Why Single-Cell Sequencing Has Promise in MDS
Authors: Zhang Xuan , Grimes H. Leighton
Published: December 2021

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis. The risk of MDS is associated with aging and the accumulation of somatic mutations in hematopoietic stem cells and progenitors (HSPC). While advances in DNA sequencing in the past decade unveiled clonal selection driven by mutations in MDS, it is unclear at which stage the HSPCs are trapped or what prevents mature cells output. Single-cell-sequencing techniques in recent years have revolutionized our understanding of normal hematopoiesis by identifying the transitional cell states between classical hematopoietic hierarchy stages, and most importantly the biological activities behind cell differentiation and lineage commitment. Emerging studies have adapted these powerful tools to investigate normal hematopoiesis as well as the clonal heterogeneity in myeloid malignancies and provide a progressive description of disease pathogenesis. This review summarizes the potential of growing single-cell-sequencing techniques, the evolving efforts to elucidate hematopoiesis in physiological conditions and MDS at single-cell resolution, and discuss how they may fill the gaps in our current understanding of MDS biology.
High-Dose-Rate Brachytherapy as Monotherapy for Low- and Intermediate-Risk Prostate Cancer. Oncological Outcomes After a Median 15-Year Follow-Up
Authors: Behmueller Manuel , Tselis Nikolaos , Zamboglou Nikolaos , Zoga Eleni , Baltas Dimos , Rödel Claus , Chatzikonstantinou Georgios
Published: December 2021

Introduction

To evaluate the oncological outcome of high dose rate (HDR) brachytherapy (BRT) as monotherapy for clinically localised prostate cancer (PCA).

Material and Methods

Between January 2002 and February 2004, 141 consecutive patients with clinically localised PCA were treated with HDR-BRT monotherapy. The cohort comprised 103 (73%) low-, 32 (22.7%) intermediate- and 6 (4.3%) high risk patients according to D’Amico classification or 104 (73.8%) low-, 24 (17.0%) intermediate favourable-, 12 (8.5%) intermediate unfavourable- and one (0.7%) very high risk patient according to National Comprehensive Cancer Network (NCCN) one. Patients received four fractions of 9.5 Gy delivered within a single implant up to a total physical dose of 38 Gy. Catheter-implantation was transrectal ultrasound-based whereas treatment planning CT-based. Thirty-three patients (23.4%) received ADT neoadjuvantly and continued concurrently with BRT. Biochemical relapse-free survival (BRFS) was defined according to the Phoenix Consensus Criteria and genitourinary (GU)/gastrointestinal (GI) toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 5.0.

Results

Median age at treatment and median follow-up time was 67.2 and 15.2 years, respectively. Twenty-three (16.3%) patients experienced a biochemical relapse and 5 (3.5%) developed distant metastases, with only one patient dying of PCA. The BRFS was 85.1% at 15 years and 78.7% at 18 years. The corresponding overall survival, metastases-free survival, and prostate cancer specific mortality at 15- and 18-years was 73.9%/59.1%, 98.3%/90.6%, and 100%/98.5% respectively. Late grade 3 GI and GU toxicity was 4.2% and 5.6% respectively. Erectile dysfunction grade 3 was reported by 27 (19%) patients. From the prognostic factors evaluated, tumor stage (≤T2b compared to ≥T2c) along with the risk group (low-intermediate vs. high) when using the D’Amico classification but not when the NCCN one was taken into account, correlated significantly with BRFS.

Conclusion

Our long-term results confirm HDR-BRT to be a safe and effective monotherapeutic treatment modality for low- and intermediate risk PCA.
Individualized Cerebral Artery Protection Strategies for the Surgical Treatment of Parasellar Meningiomas on the Basis of Preoperative Imaging
Authors: Li Yang , Zhang XingShu , Su Jun , Qin Chaoying , Wang Xiangyu , Xiao Kai , Liu Qing
Published: December 2021

Objective

Parasellar meningiomas (PMs) represent a cohort of skull base tumors that are localized in the parasellar region. PMs tend to compress, encase, or even invade the cerebral arteries and their perforating branches. The surgical resection of PMs without damaging neurovascular structures is challenging. This study aimed to analyze functional outcomes in a series of patients who underwent surgery with individualized cerebral artery protection strategies based on preoperative imaging.

Methods

A retrospective review was performed on a single surgeon’s experience of the microsurgical removal of PMs in 163 patients between January 2012 and March 2020. Individualized approaches with a bidirectional dissection strategy were used. Cerebral artery invasion classification, neurological outcomes, MRC Scale for muscle strength, and Karnofsky performance scale were used to assess tumor vascular invasion, functional outcome, and patient quality-of-life outcomes, respectively.

Results

Total resection (Simpson grade I or II) was achieved in 114 patients (69.9%) in our study. A total of 44.7% of patients had improved vision at consecutive follow-ups, 51.1% were stable, and 3.8% deteriorated. Improvements in cranial nerves III, IV, and VI were observed in 41.1%, 36.2%, and 44.8% of patients, respectively. The mean follow-up time was (38.8 ± 27.9) months, and the KPS at the last follow-up was 89.6 ± 8.5. Recurrence was observed in eight patients (13.8%) with cavernous sinus meningiomas, and the recurrence rates in anterior clinoid meningiomas and medial sphenoid wing meningiomas were 3.8% and 2.8%, respectively.

Conclusions

Preoperative imaging is important in the selection of surgical approaches. Maximum tumor resection and cerebral artery protection can be achieved concurrently by utilizing the bidirectional dissection technique. Individualized cerebral artery protection strategies provide great utility in improving a patient’s quality of life.
Health-Related Quality of Life for Patients Receiving Tumor Treating Fields for Glioblastoma
Authors: Palmer Joshua D. , Chavez Gordon , Furnback Wesley , Chuang Po-Ya , Wang Bruce , Proescholdt Christina , Tang Chao-Hsiun
Published: December 2021

Background

To date, there has been no large-scale, real-world study of the health-related quality of life outcomes for patients using tumor treating fields (TTFields) therapy for glioblastoma (GBM) treatment.

Methods

A survey was mailed to 2,815 patients actively using TTFields for treatment of GBM in the USA (n = 2,182) and Europe (n = 633). The survey included patient-reported demographic and clinical information, as well as EuroQol’s EQ-5D-5L and visual analogue scale (EQ-VAS) overall health score.

Results

A total of 1,106 applicable patients responded to the survey (USA = 782 and Europe = 324), with a mean age of 58.6 years (SD = 12.3). The average time since diagnosis and time using TTFields were 21.5 months (SD = 25.1) and 13.5 months (SD = 13.2), respectively. Over 61% of patients had been diagnosed at least 1 year prior and 28.4% at least 2 years prior; 45 patients (4.2%) had been diagnosed at least 5 years prior. Progressed disease was reported in 307 patients, while 690 reported non-progressed disease. Regression analyses showed that GBM disease progression and older age had predictable negative associations (p < 0.001) with most EQ-5D-5L dimensions and the EQ-VAS. However, longer time since diagnosis was associated with improved self-care (p < 0.05), usual activities (p < 0.01), and EQ-VAS (p < 0.05) overall and in patients with progressed disease (p < 0.01,p < 0.05, andp < 0.01, respectively). Additionally, longer time using TTFields was associated with improved mobility (p < 0.05), self-care (p < 0.001), usual activities (p < 0.01), and EQ-VAS (p < 0.01) overall; with improved EQ-VAS in progression-free patients (p < 0.05); and with improved mobility (p < 0.05), self-care (p < 0.01), usual activities (p < 0.05), and EQ-VAS (p < 0.05) in patients with progressed disease.

Conclusion

This is the largest real-world study of patient-reported quality of life in GBM and TTFields treatment to date. It shows unsurprising negative associations between quality of life and disease progression and older age, as well as more novel, positive associations between quality of life and longer time since diagnosis and time using TTFields therapy.
Postoperative Adjuvant Radiotherapy in Atypical Meningioma Patients: A Meta-Analysis Study
Authors: Song Dengpan , Xu Dingkang , Han Hongjie , Gao Qiang , Zhang Mingchu , Wang Fang , Wang Guoqing , Guo Fuyou
Published: December 2021

Background and Purpose

Consensus regarding the need for adjuvant radiotherapy (RT) in patients with atypical meningiomas (AMs) is lacking. We compared the effects of adjuvant RT after surgery, gross total resection (GTR), and subtotal resection (STR) on progression-free survival (PFS) and overall survival (OS) in patients with AMs, respectively.

Methods

We performed a systematic review and meta-analysis of the literature published in PubMed, Embase, and the Cochrane Library from inception to February 1, 2021, to identify articles comparing the PFS and OS of patients receiving postoperative RT after surgery, GTR and STR.

Results

We identified 2307 unique studies; 24 articles including 3078 patients met the inclusion criteria. The sensitivity analysis results showed that for patients undergoing undifferentiated surgical resection, adjuvant RT reduced tumor recurrence (HR=0.70, p<0.0001) with no significant effect on survival (HR=0.89, p=0.49). Postoperative RT significantly increased PFS (HR=0.69, p=0.01) and OS (HR=0.55, p=0.007) in patients undergoing GTR. The same improvement was observed in patients undergoing STR plus RT (PFS: HR=0.41, p<0.00001; OS: HR=0.47, p=0.01). A subgroup analysis of RT in patients undergoing GTR showed no change in PFS in patients undergoing Simpson grade I and II resection (HR=1.82, p=0.22) but significant improvement in patients undergoing Simpson grade III resection (HR=0.64, p=0.02).

Conclusion

Regardless of whether GTR or STR was performed, postoperative RT improved PFS and OS to varying degrees. Especially for patients undergoing Simpson grade III or IV resection, postoperative RT confers the benefits for recurrence and survival.
Mechanisms Underlying Lumbopelvic Pain During Pregnancy: A Proposed Model
Authors: Daneau Catherine , Abboud Jacques , Marchand Andrée-Anne , Houle Mariève , Pasquier Mégane , Ruchat Stephanie-May , Descarreaux Martin
Published: December 2021

Up to 86% of pregnant women will have lumbopelvic pain during the 3rd trimester of pregnancy and women with lumbopelvic pain experience lower health-related quality of life during pregnancy than women without lumbopelvic pain. Several risk factors for pregnancy-related lumbopelvic pain have been identified and include history of low back pain, previous trauma to the back or pelvis and previous pregnancy-related pelvic girdle pain. During pregnancy, women go through several hormonal and biomechanical changes as well as neuromuscular adaptations which could explain the development of lumbopelvic pain, but this remains unclear. The aim of this article is to review the potential pregnancy-related changes and adaptations (hormonal, biomechanical and neuromuscular) that may play a role in the development of lumbopelvic pain during pregnancy. This narrative review presents different mechanisms that may explain the development of lumbopelvic pain in pregnant women. A hypotheses-driven model on how these various physiological changes potentially interact in the development of lumbopelvic pain in pregnant women is also presented. Pregnancy-related hormonal changes, characterized by an increase in relaxin, estrogen and progesterone levels, are potentially linked to ligament hyperlaxity and joint instability, thus contributing to lumbopelvic pain. In addition, biomechanical changes induced by the growing fetus, can modify posture, load sharing and mechanical stress in the lumbar and pelvic structures. Finally, neuromuscular adaptations during pregnancy include an increase in the activation of lumbopelvic muscles and a decrease in endurance of the pelvic floor muscles. Whether or not a causal link between these changes and lumbopelvic pain exists remains to be determined. This model provides a better understanding of the mechanisms behind the development of lumbopelvic pain during pregnancy to guide future research. It should allow clinicians and researchers to consider the multifactorial nature of lumbopelvic pain while taking into account the various changes and adaptations during pregnancy.
Screen Time and Bone Status in Children and Adolescents: A Systematic Review
Authors: de Lamas Carmela , Sánchez-Pintos Paula , José de Castro María , Sáenz de Pipaon Miguel , Couce María Luz
Published: December 2021

Introduction: Technological advances over the last 2 decades have led to an increase in the time spent by children and youth engaged in screen-based activities, and growing recognition of deleterious effects on health. In this systematic review of cohort and cross-sectional studies, we assess current data on the relationship between screen time and bone status in children and teenagers.

Methods: We searched PUBMED and SCOPUS databases for studies of children and adolescents that assessed screen time and bone status, determined by measuring bone mineral content or density, bone stiffness index, bone speed of sound, bone broadband ultrasound attenuation, or frame index. Searches were limited to studies published between 1900 and 2020, and performed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The studies included were evaluated using the Newcastle-Ottawa quality assessment scale.

Results: Ten cohort and cross-sectional studies including pediatric population were selected. The combined study population was 20,420 children/adolescents, of whom 18,444 participated in cross-sectional studies. Four studies assessed the effects of total screen time, seven the consequences of TV viewing time, and six the effects of recreational computer use on bone health. Our findings indicate an inverse association between total and weekly screen time and bone health in children and adolescents. In 57% of the studies included also a negative correlation between television viewing time and bone status was observed, while recreational computer time did not have a significant impact on bone health. According to the only four studies that included dietetic factors, no relevant differences were found between calcium intake and screen time or bone broadband ultrasound attenuation and bone speed of sound.

Conclusions: Review of the literature of the past three decades provides strong support for comprehensive education of screen time on bone status. The findings of this systematic review support a negative association between screen time and bone status in children and adolescents, with a different impact when considering the different technological devices. As peak bone mass in adolescents is the strongest predictor of osteoporosis risk, strategies aimed at improving bone health should incorporate conscious use of digital technology.
Arrhythmogenic Right Ventricular Cardiomyopathy in Pediatric Patients: An Important but Underrecognized Clinical Entity
Authors: te Riele Anneline S. J. M. , James Cynthia A. , Calkins Hugh , Tsatsopoulou Adalena
Published: December 2021

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by fibrofatty infiltration of predominantly the right ventricular (RV) myocardium. Affected patients typically present as young adults with hemodynamically stable ventricular tachycardia, although pediatric cases are increasingly recognized. These young subjects often have a more severe phenotype with a high risk of sudden cardiac death (SCD) and progression toward heart failure. Diagnosis of ARVC is made by combining multiple sources of information as prescribed by the consensus-based Task Force Criteria. The description of Naxos disease, a fully penetrant autosomal recessive disorder that is associated with ARVC and a cutaneous phenotype of palmoplantar keratoderma and wooly hair facilitated the identification of the genetic cause of ARVC. At present, approximately 60% of patients are found to carry a pathogenic variant in one of five genes associated with the cardiac desmosome. The incomplete penetrance and variable expressivity of these variants however implies an important role for environmental factors, of which participation in endurance exercise is a strong risk factor. Since there currently is no definite cure for ARVC, disease management is directed toward symptom reduction, delay of disease progression, and prevention of SCD. This clinically focused review describes the spectrum of ARVC among children and adolescents, the genetic architecture underlying this disease, the cardio-cutaneous syndromes that led to its identification, and current diagnostic and therapeutic strategies in pediatric ARVC subjects.
Risk Factors for Fetal Death and Maternal AP Severity in Acute Pancreatitis in Pregnancy
Authors: Shi Xiaolei , Hu Yuepeng , Pu Na , Zhang Guofu , Zhang Jingzhu , Zhou Jing , Ye Bo , Li Gang , Ke Lu , Liu Yuxiu , Yang Qi , Tong Zhihui , Li Weiqin
Published: December 2021

Background: Acute pancreatitis in pregnancy is a rare but highly life-threatening gestational and perinatal disease.

Objective: This study aimed to identify the risk factors for fetal death and acute pancreatitis severity.

Methods: This retrospective cohort study enrolled patients with acute pancreatitis in pregnancy in our center from January 1, 2012, to August 1, 2020, and classified them according to two clinical endpoints, fetal outcome and disease severity. The groups were examined and compared according to gestational week, etiology, gravidity and parity, complications in pre- and post-delivery, and medical history. Logistic regression analysis was performed to identify the independent risk factors for fetal death and acute pancreatitis severity.

Results: Of the 90 enrolled patients, 28 (31.1%) had fetal death and 43 (47.8%) had severe acute pancreatitis. Logistic regression analysis showed that pre-delivery acute respiratory distress syndrome (OR, 5.8; 95% CI, 1.5–22.4; p = 0.010) and gestational week (OR, 0.9; 95% CI, 0.8–1.0; p = 0.011) were risk factors for fetal death. Gestation week (OR, 1.2; 95% CI, 1.1–1.3; p = 0.003) and fetal intrauterine death (OR, 5.9; 95% CI, 1.8–19.4; p = 0.003) were risk factors for severe acute pancreatitis.

Conclusions: Pre-delivery acute respiratory distress syndrome and gestational week were independent risk factors for fetal death. Fetal intrauterine death and gestational week were independent risk factors for severe acute pancreatitis.
Dauricine Attenuates Vascular Endothelial Inflammation Through Inhibiting NF-κB Pathway
Authors: Hu Ji , Chen Ru , An Jie , Wang Yilong , Liang Minglu , Huang Kai
Published: December 2021

Endothelial cells are the fundamental components of blood vessels that regulate several physiological processes including immune responses, angiogenesis, and vascular tone. Endothelial dysfunction contributes to the development of various diseases such as acute lung injury, and endothelial inflammation is a vital part of endothelial dysfunction. Dauricine is an extract isolated from Menispermum dauricum DC, a traditional Chinese medical plant that can be used for pharyngitis. In this work, we found that IL-1β-induced overexpression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was inhibited by dauricine in primary human umbilical vein endothelial cells (HUVECs). Correspondingly, adhesion of human acute monocytic leukemia cell line (THP-1) to HUVECs was decreased by dauricine. Further studies showed that dauricine inhibited the activation of nuclear factor-κB (NF-κB) pathway in HUVECs stimulated with IL-1β. In vivo, dauricine protected mice from lipopolysaccharide (LPS)-induced acute lung injury. In lung tissues, the activation of NF-κB pathway and the expression of its downstream genes (ICAM-1, VCAM-1, and E-selectin) were decreased by dauricine, consistent with what was found in vitro. In summary, we concluded that dauricine could alleviate endothelial inflammation by suppressing NF-κB pathway, which might serve as an effective candidate for diseases related with endothelial inflammation.
Predicting the Prognosis of Esophageal Adenocarcinoma by a Pyroptosis-Related Gene Signature
Authors: Zeng Ruijie , Huang Shujie , Qiu Xinqi , Zhuo Zewei , Wu Huihuan , Jiang Lei , Sha Weihong , Chen Hao
Published: December 2021

Esophageal adenocarcinoma (EAC) is a highly malignant type of digestive tract cancers with a poor prognosis despite therapeutic advances. Pyroptosis is an inflammatory form of programmed cell death, whereas the role of pyroptosis in EAC remains largely unknown. Herein, we identified a pyroptosis-related five-gene signature that was significantly correlated with the survival of EAC patients in The Cancer Genome Atlas (TCGA) cohort and an independent validation dataset. In addition, a nomogram based on the signature was constructed with novel prognostic values. Moreover, the downregulation of GSDMB within the signature is notably correlated with enhanced DNA methylation. The pyroptosis-related signature might be related to the immune response and regulation of the tumor microenvironment. Several inhibitors including GDC-0879 and PD-0325901 are promising in reversing the altered differentially expressed genes in high-risk patients. Our findings provide insights into the involvement of pyroptosis in EAC progression and are promising in the risk assessment as well as the prognosis for EAC patients in clinical practice.
Air-Fluidized Aggregates of Black Soldier fly Larvae
Authors: Ko Hungtang , Cassidy Grace J. , Shishkov Olga , Aydin Enes , Hu David L. , Goldman Daniel I.
Published: December 2021

Black soldier fly larvae are a sustainable protein source and play a vital role in the emerging food-waste recycling industry. One of the challenges of raising larvae in dense aggregations is their rise in temperature during feeding, which, if not mitigated, can become lethal to the larvae. We propose applying air-fluidization to circumvent such overheating. However, the behavior of such a system involves complex air-larva interactions and is poorly understood. In this combined experimental and numerical study, we show that the larval activity changes the behavior of the ensemble when compared to passive particles such as dead larvae. Over a cycle of increasing and then decreasing airflow, the states (pressure and height) of the live larva aggregates are single-value functions of the flow speed. In contrast, dead larva aggregates exhibit hysteresis characteristic of traditional fluidized beds, becoming more porous during the ramp down of airflow. This history-dependence for passive particles is supported by simulations that couple agent-based dynamics and computational fluid dynamics. We show that the hysteresis in height and pressure of the aggregates decreases as the activity of simulated larvae increases. To test if air fluidization can increase larval food intake, we performed feeding trials in a fluidization chamber and visualized the food consumption via x-ray imaging. Although the food mixes more rapidly in faster airflow, the consumption rate decreases. Our findings suggest that providing moderate airflow to larval aggregations may alleviate overheating of larval aggregations and evenly distribute the food without reducing feeding rates.
The Evolution of Blood Flow Restricted Exercise
Authors: Freitas Eduardo D. S. , Karabulut Murat , Bemben Michael G.
Published: December 2021

The use of blood flow restricted (BFR) exercise has become an accepted alternative approach to improve skeletal muscle mass and function and improve cardiovascular function in individuals that are not able to or do not wish to use traditional exercise protocols that rely on heavy loads and high training volumes. BFR exercise involves the reduction of blood flow to working skeletal muscle by applying a flexible cuff to the most proximal portions of a person’s arms or legs that results in decreased arterial flow to the exercising muscle and occluded venous return back to the central circulation. Safety concerns, especially related to the cardiovascular system, have not been consistently reported with a few exceptions; however, most researchers agree that BFR exercise can be a relatively safe technique for most people that are free from serious cardiovascular disease, as well as those with coronary artery disease, and also for people suffering from chronic conditions, such as multiple sclerosis, Parkinson’s, and osteoarthritis. Potential mechanisms to explain the benefits of BFR exercise are still mostly speculative and may require more invasive studies or the use of animal models to fully explore mechanisms of adaptation. The setting of absolute resistive pressures has evolved, from being based on an individual’s systolic blood pressure to a relative measure that is based on various percentages of the pressures needed to totally occlude blood flow in the exercising limb. However, since several other issues remain unresolved, such as the actual external loads used in combination with BFR, the type of cuff used to induce the blood flow restriction, and whether the restriction is continuous or intermittent, this paper will attempt to address these additional concerns.
Elder Mice Exhibit More Severe Degeneration and Milder Regeneration in Temporomandibular Joints Subjected to Bilateral Anterior Crossbite
Authors: Zhang Yuejiao , Xu Xiaojie , Zhou Peng , Liu Qian , Zhang Mian , Yang Hongxu , Yu Shibin , Zhang Jing , Huo Wanqiu , Zhao Yali , Wang Meiqing
Published: December 2021

Temporomandibular joints (TMJs) have a biomechanical relationship with dental occlusion. Aberrant occlusion initiates degenerative remodeling responses in TMJ condyles. Aging is a promoting factor of osteoarthritis (OA) development. The aim of this study was to assess the effect of aging on degenerative remodeling in TMJ condyles in response to occlusal biomechanical stimulation caused by the installation of aberrant prostheses and observe rehabilitation after their removal. The experiments involved 84 female C57BL/6J mice (42 at 6 weeks old and 42 at 28 weeks old). A bilateral anterior crossbite (BAC) model was developed, and the TMJs were sampled at 3, 7, and 11 weeks. BAC was removed at 7 weeks in a subset of mice, which accepted BAC treatment at 6 week of age, and maintained for another 4 weeks after BAC removal. TMJ changes were assessed with micro-CT, histomorphology, immunohistochemistry (IHC), and immunofluorescence staining assays. The results showed that BAC induced typical OA-like TMJ lesions that were more severe in the elder groups as evaluated by the acellular zones, clustered chondrocytes, fissures between cartilage and subchondral bone, reductions in matrix amount and the cartilage thickness as revealed by histomorphological measurements, and subchondral bone loss as detected on micro-CT images. IHC indicated significant increases in cleaved caspase-3-expressing cells and decreases in ki67-positive cells in the BAC groups. There were obvious age-dependent changes in the numbers of superficial zone cells and CD90-expressing cells. Supportively, cleaved caspase-3-expressing cells obviously increased, while ki67-expressing cells significantly decreased with aging. In the elder BAC groups, the superficial zone cells such as CD90-expressing cells were greatly reduced. At 11 weeks, the superficial zone cells were almost non-existent, and there were clear serrated injuries on the cartilage surface. BAC removal attenuated the degenerative changes in the condylar cartilage and subchondral bone. Notably, the rescue effect was more pronounced in the younger animals. Our findings demonstrate the impacts of aging on both TMJ degenerative changes in response to BAC and regenerative changes following BAC removal. The reduced number of chondro-progenitor cells in aged TMJ cartilage provides an explanation for this age-related decline in TMJ rehabilitative behaviors.
Mechanosensitive Piezo1 in Periodontal Ligament Cells Promotes Alveolar Bone Remodeling During Orthodontic Tooth Movement
Authors: Jiang Yukun , Guan Yuzhe , Lan Yuanchen , Chen Shuo , Li Tiancheng , Zou Shujuan , Hu Zhiai , Ye Qingsong
Published: December 2021

Orthodontic tooth movement (OTM) is a process depending on the remodeling of periodontal tissues surrounding the roots. Orthodontic forces trigger the conversion of mechanical stimuli into intercellular chemical signals within periodontal ligament (PDL) cells, activating alveolar bone remodeling, and thereby, initiating OTM. Recently, the mechanosensitive ion channel Piezo1 has been found to play pivotal roles in the different types of human cells by transforming external physical stimuli into intercellular chemical signals. However, the function of Piezo1 during the mechanotransduction process of PDL cells has rarely been reported. Herein, we established a rat OTM model to study the potential role of Piezo1 during the mechanotransduction process of PDL cells and investigate its effects on the tension side of alveolar bone remodeling. A total of 60 male Sprague-Dawley rats were randomly assigned into three groups: the OTM + inhibitor (INH) group, the OTM group, and the control (CON) group. Nickel-titanium orthodontic springs were applied to trigger tooth movement. Mice were sacrificed on days 0, 3, 7, and 14 after orthodontic movement for the radiographic, histological, immunohistochemical, and molecular biological analyses. Our results revealed that the Piezo1 channel was activated by orthodontic force and mainly expressed in the PDL cells during the whole tooth movement period. The activation of the Piezo1 channel was essential for maintaining the rate of orthodontic tooth movement and facilitation of new alveolar bone formation on the tension side. Reduced osteogenesis-associated transcription factors such as Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio were examined when the function of Piezo1 was inhibited. In summary, Piezo1 plays a critical role in mediating both the osteogenesis and osteoclastic activities on the tension side during OTM.
Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia
Authors: Medina Yollyseth , Acosta Lucas , Reppetti Julieta , Corominas Ana , Bustamante Juanita , Szpilbarg Natalia , Damiano Alicia E.
Published: December 2021

Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in lactate transfer across the human placenta. Explants from normal term placentas were cultured in low glucose medium with or without L-lactic acid and in the presence and absence of AQP9 blockers (0.3 mM HgCl2 or 0.5 mM Phloretin). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and Terminal Deoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9 expression was detected by Western blot. We found that apoptosis was induced when placental explants were cultured in low glucose medium while the addition of L-lactic acid prevented cell death. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmed the presence of two mitochondrial subpopulations which exhibit different morphologic and metabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrial subpopulation. This is the first report that shows that AQP9 is expressed in the heavy/large mitochondrial subpopulation of trophoblasts. Thus, AQP9 may mediate not only the lactic acid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionality in preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affecting the survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.
Advances in the Regulation of Epidermal Cell Development by C2H2 Zinc Finger Proteins in Plants
Authors: Han Guoliang , Li Yuxia , Qiao Ziqi , Wang Chengfeng , Zhao Yang , Guo Jianrong , Chen Min , Wang Baoshan
Published: December 2021

Plant epidermal cells, such as trichomes, root hairs, salt glands, and stomata, play pivotal roles in the growth, development, and environmental adaptation of terrestrial plants. Cell fate determination, differentiation, and the formation of epidermal structures represent basic developmental processes in multicellular organisms. Increasing evidence indicates that C2H2 zinc finger proteins play important roles in regulating the development of epidermal structures in plants and plant adaptation to unfavorable environments. Here, we systematically summarize the molecular mechanism underlying the roles of C2H2 zinc finger proteins in controlling epidermal cell formation in plants, with an emphasis on trichomes, root hairs, and salt glands and their roles in plant adaptation to environmental stress. In addition, we discuss the possible roles of homologous C2H2 zinc finger proteins in trichome development in non-halophytes and salt gland development in halophytes based on bioinformatic analysis. This review provides a foundation for further study of epidermal cell development and abiotic stress responses in plants.
Regulation of MYB Transcription Factors of Anthocyanin Synthesis in Lily Flowers
Authors: Yin Xiaojuan , Zhang Yibing , Zhang Li , Wang Baohua , Zhao Yidi , Irfan Muhammad , Chen Lijing , Feng Yulong
Published: December 2021

Flower color is the decisive factor that affects the commercial value of ornamental flowers. Therefore, it is important to study the regulation of flower color formation in lily to discover the positive and negative factors that regulate this important trait. In this study, MYB transcription factors (TFs) were characterized to understand the regulatory mechanism of anthocyanin biosynthesis in lily. Two R2R3-MYB TFs, LvMYB5, and LvMYB1, were found to regulate anthocyanin biosynthesis in lily flowers. LvMYB5, which has an activation motif, belongs to the SG6 MYB protein subgroup of Arabidopsis thaliana. Transient expression of LvMYB5 indicated that LvMYB5 can promote coloration in Nicotiana benthamiana leaves, and that expression of LvMYB5 increases the expression levels of NbCHS, NbDFR, and NbANS. VIGS experiments in lily petals showed that the accumulation of anthocyanins was reduced when LvMYB5 was silenced. Luciferase assays showed that LvMYB5 can promote anthocyanin synthesis by activating the ANS gene promoter. Therefore, LvMYB5 plays an important role in flower coloration in lily. In addition, the transient expression experiment provided preliminary evidence that LvMYB1 (an R2R3-MYB TF) inhibits anthocyanin synthesis in lily flowers. The discovery of activating and inhibitory factors related to anthocyanin biosynthesis in lily provides a theoretical basis for improving flower color through genetic engineering. The results of our study provide a new direction for the further study of the mechanisms of flower color formation in lilies.
Relationships of Sources of Meaning and Resilience With Meaningfulness and Satisfaction With Life: A Population-Based Study of Norwegians in Late Adulthood
Authors: Sørensen Torgeir , Hestad Knut , Grov Ellen Karine
Published: December 2021

Health-promoting initiatives incorporating meaning-making to enhance the well-being of people in late adulthood are important, particularly as the number of older people is increasing. Resilience and sources of meaning may be related to individuals’ experience of meaningfulness and satisfaction with life. However, few studies have investigated these relations among people in late adulthood. In the present exploratory study, we asked the following questions: What are the differences regarding scores on sources of meaning, resilience, meaningfulness, and satisfaction between people in late adulthood (≥65) and other adults (18–64)? What is the association between sources of meaning and meaningfulness, and between resilience and meaningfulness? What is the association between sources of meaning and satisfaction with life, and between resilience and satisfaction with life? A cross-sectional design was used. A population-based sample of 925 participants (aged 18–91 years) was recruited from the National Population Register in Norway. Of these, 219 participants were 65 years old and older (mean age 73 years). Additionally, sub-analyses for the age-group ≥ 75 (N = 71) were performed. Independent-samples t-tests, chi-square tests, one-way ANOVA, and linear regressions adjusted for demographics, anxiety, and depression were performed utilizing standardized questionnaires. It was found that people in late adulthood (≥65 years) scored significantly higher on meaningfulness compared to younger adults (18–64). Of the sources of meaning, vertical self-transcendence, including explicit religiosity and spirituality, had the strongest relation to meaningfulness for people in late adulthood, after adjusting for demographics, anxiety, and depression. For the same group, accomplishment, including generativity and unselfish engagement with the surroundings and future generations, also stood out as a prominent source of meaning when related to meaningfulness. No sources of meaning were associated with satisfaction with life in the older group. No associations between resilience and meaningfulness, nor between resilience and satisfaction with life, were found among people in late adulthood. However, positive associations were found between resilience and meaningfulness, as well as between resilience and satisfaction with life, in the 18–64 age group. Longitudinal research and interventional studies are needed to confirm whether the designated sources contribute to meaningfulness in a Norwegian context. The implications of the findings are discussed.
Application of the Multidimensional Fatigue Inventory to Ethiopian Cancer Patients
Authors: Wondie Yemataw , Hinz Andreas
Published: December 2021

Objectives: Fatigue is a frequent debilitating symptom associated with cancer. However, scientific data on cancer-related fatigue is scarce in developing nations. This work examines psychometric properties of the multidimensional fatigue inventory (MFI-20) and analyzes the level of fatigue among Ethiopian patients with cancer in comparison with data from Germany.

Methods: A sample of 256 patients with cancer drawn from a hospital in Ethiopia was examined with the MFI-20 and the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30). A comparative sample of 780 German patients with cancer served as the control.

Results: The MFI-20 scales and total score showed acceptable reliability (α = 0.60–0.93) with a considerable convergent validity between MFI-20 and the EORTC QLQ-C30 fatigue scale (r = 0.67–0.75). The Ethiopian patients with cancer reported higher levels of fatigue than the German patients. Analyses of variance showed that Ethiopian patients with cancer who were illiterate, having advanced cancer, and those who did not receive either surgery or chemotherapy reported especially high levels of fatigue.

Conclusion: The MFI-20 is a fairly reliable and valid instrument to be used with Amharic speaking patients with cancer. The high level of fatigue in these patients implies that appropriate cancer care is needed in developing countries.