bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and Functional Trajectories of Middle Temporal Gyrus Sub-Regions During Life Span: A Potential Biomarker of Brain Development and Aging
Authors: Xu Jinping , Zhang Jinhuan , Li Jiaying , Wang Haoyu , Chen Jianxiang , Lyu Hanqing , Hu Qingmao
Published: April 2022

Although previous studies identified a similar topography pattern of structural and functional delineations in human middle temporal gyrus (MTG) using healthy adults, trajectories of MTG sub-regions across lifespan remain largely unknown. Herein, we examined gray matter volume (GMV) and resting-state functional connectivity (RSFC) using datasets from the Nathan Kline Institute (NKI), and aimed to (1) investigate structural and functional trajectories of MTG sub-regions across the lifespan; and (2) assess whether these features can be used as biomarkers to predict individual’s chronological age. As a result, GMV of all MTG sub-regions followed U-shaped trajectories with extreme age around the sixth decade. The RSFC between MTG sub-regions and many cortical brain regions showed inversed U-shaped trajectories, whereas RSFC between MTG sub-regions and sub-cortical regions/cerebellum showed U-shaped way, with extreme age about 20 years earlier than those of GMV. Moreover, GMV and RSFC of MTG sub-regions could be served as useful features to predict individual age with high estimation accuracy. Together, these results not only provided novel insights into the dynamic process of structural and functional roles of MTG sub-regions across the lifespan, but also served as useful biomarkers to age prediction.
Case Report: Advantages of High-Resolution MRI in Evaluating the Efficacy of Drug Therapy for Intracranial Atherosclerotic Plaques
Authors: Zheng Tao , Liu Lei , Li Li , Gao Yang , Guo Runcai , Zhou Zhi , Liu Zunjing , Liu Kunpeng
Published: April 2022

Intracranial atherosclerotic stenosis is one of the main causes of ischemic stroke and transient ischemic attack. High-resolution magnetic resonance imaging allows us to directly observe the intracranial artery wall, accurately assess the condition of the vascular wall, and quantitatively analyze the vascular wall and intracranial atherosclerotic plaque load. We report a case of acute cerebral infarction with left middle cerebral artery stenosis. During the first 3 weeks, the patient was treated with aspirin 100 mg and clopidogrel 75 mg daily. Afterwards, the patient continued to be given aspirin, and cilostazol 100 mg twice daily was given instead of clopidogrel. After 24 months of follow-up, we observed a significant reversal of intracranial atherosclerotic plaque using high-resolution MRI (HR-MRI) and discussed the advantages of HR-MRI in evaluating drug therapy for intracranial atherosclerotic plaque.
Toward Precise Localization of Abnormal Brain Activity: 1D CNN on Single Voxel fMRI Time-Series
Authors: Wu Yun-Ying , Hu Yun-Song , Wang Jue , Zang Yu-Feng , Zhang Yu
Published: April 2022

Functional magnetic resonance imaging (fMRI) is one of the best techniques for precise localization of abnormal brain activity non-invasively. Machine-learning approaches have been widely used in neuroimaging studies; however, few studies have investigated the single-voxel modeling of fMRI data under cognitive tasks. We proposed a hybrid one-dimensional (1D) convolutional neural network (1D-CNN) based on the temporal dynamics of single-voxel fMRI time-series and successfully differentiated two continuous task states, namely, self-initiated (SI) and visually guided (VG) motor tasks. First, 25 activation peaks were identified from the contrast maps of SI and VG tasks in a blocked design. Then, the fMRI time-series of each peak voxel was transformed into a temporal-frequency domain by using continuous wavelet transform across a broader frequency range (0.003–0.313 Hz, with a step of 0.01 Hz). The transformed time-series was inputted into a 1D-CNN model for the binary classification of SI and VG continuous tasks. Compared with the univariate analysis, e.g., amplitude of low-frequency fluctuation (ALFF) at each frequency band, including, wavelet-ALFF, the 1D-CNN model highly outperformed wavelet-ALFF, with more efficient decoding models [46% of 800 models showing area under the curve (AUC) > 0.61] and higher decoding accuracies (94% of the efficient models), especially on the high-frequency bands (>0.1 Hz). Moreover, our results also demonstrated the advantages of wavelet decompositions over the original fMRI series by showing higher decoding performance on all peak voxels. Overall, this study suggests a great potential of single-voxel analysis using 1D-CNN and wavelet transformation of fMRI series with continuous, naturalistic, steady-state task design or resting-state design. It opens new avenues to precise localization of abnormal brain activity and fMRI-guided precision brain stimulation therapy.
Enhanced Performance by Interpretable Low-Frequency Electroencephalogram Oscillations in the Machine Learning-Based Diagnosis of Post-traumatic Stress Disorder
Authors: Shim Miseon , Im Chang-Hwan , Lee Seung-Hwan , Hwang Han-Jeong
Published: April 2022

Electroencephalography (EEG)-based diagnosis of psychiatric diseases using machine-learning approaches has made possible the objective diagnosis of various psychiatric diseases. The objective of this study was to improve the performance of a resting-state EEG-based computer-aided diagnosis (CAD) system to diagnose post-traumatic stress disorder (PTSD), by optimizing the frequency bands used to extract EEG features. We used eyes-closed resting-state EEG data recorded from 77 PTSD patients and 58 healthy controls (HC). Source-level power spectrum densities (PSDs) of the resting-state EEG data were extracted from 6 frequency bands (delta, theta, alpha, low-beta, high-beta, and gamma), and the PSD features of each frequency band and their combinations were independently used to discriminate PTSD and HC. The classification performance was evaluated using support vector machine with leave-one-out cross validation. The PSD features extracted from slower-frequency bands (delta and theta) showed significantly higher classification performance than those of relatively higher-frequency bands. The best classification performance was achieved when using delta PSD features (86.61%), which was significantly higher than that reported in a recent study by about 13%. The PSD features selected to obtain better classification performances could be explained from a neurophysiological point of view, demonstrating the promising potential to develop a clinically reliable EEG-based CAD system for PTSD diagnosis.
The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia
Authors: Ma Lin-Hui , Yan Jing , Jiao Xin-Hao , Zhou Cheng-Hua , Wu Yu-Qing
Published: April 2022

It has been widely demonstrated by numerous preclinical studies and clinical trials that the neonates receiving repeated or long-time general anesthesia (GA) could develop prolonged cognitive dysfunction. However, the definite mechanism remains largely unknown. Epigenetics, which is defined as heritable alterations in gene expression that are not a result of alteration of DNA sequence, includes DNA methylation, histone post-translational modifications, non-coding RNAs (ncRNAs), and RNA methylation. In recent years, the role of epigenetic modifications in neonatal GA-induced neurotoxicity has been widely explored and reported. In this review, we discuss and conclude the epigenetic mechanisms involving in the process of neonatal anesthesia-induced cognitive dysfunction. Also, we analyze the wide prospects of epigenetics in this field and its possibility to work as treatment target.
METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker
Authors: Zhou Yubin , Guo Songhe , Li Yiqiu , Chen Fangfang , Wu Yaxian , Xiao Yi , An Jun
Published: April 2022

Methyltransferase-like 3 (METTL3) is an RNA methyltransferase mediating N6 methyladenosine (m6A) modification. Its role in cancer pathogenesis and progression has attracted increasing attention. However, the immunological role, possible immune mechanism, and clinical significance of METTL3 in esophageal squamous cell carcinoma (ESCC) remain to be confirmed. The Tumor Genome Atlas (TCGA) provided clinical and transcriptome sequencing data for this study (162 tumor tissue samples and 11 normal tissue samples), while the Immunology Database and Analysis Portal (immport, https://www.immport.org/home) provided 2483 immune-related genes. METTL3 was substantially expressed in ESCC and linked to poor prognosis in ESCC, according to the findings. Functional analysis revealed that METTL3 is mainly involved in chromosomal homologous recombination and DNA mismatch repair processes, which could be potential mechanisms for tumor disease development and progression. Analysis on the TISIDB website shows that effector memory CD8 T cells, NK cells, neutrophils and other cells are highly correlated with METTL3 expression. We screened immune genes associated with METTL3 by Spearman’s analysis and performed functional analysis. These immune genes were mostly linked with immune processes, such as cytokine receptors, the MAPK signaling pathway, and natural killer cell-mediated cytotoxicity, indicating that METTL3 is a key molecule in the immune regulation of esophageal cancer. In addition, based on METTL3-related immune genes, we separated the patients into several subgroups and constructed a prognostic prediction model consisting of six immune genes. As an independent prognostic indicator for ESCC, the risk score of this model can be employed. A nomogram was also developed to accurately evaluate individual prognoses based on clinical indicators and risk scores. In summary, this study suggests that METTL3 is not only a potential pathogenic molecule for esophageal carcinogenesis and progression but also a potential biological marker for forecasting ESCC patient prognosis and could serve as a basis for clinical decision making.
Expression of CD274 mRNA Measured by qRT-PCR Correlates With PD-L1 Immunohistochemistry in Gastric and Urothelial Carcinoma
Authors: Kang So Young , Heo You Jeong , Kwon Ghee Young , Kim Kyoung-Mee
Published: April 2022

Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is widely used to predict the clinical responses to immune checkpoint inhibitors (ICIs). However, PD-L1 IHC suffers from the complexity of multiple testing platforms and different cutoff values caused by the current one drug-one diagnostic test co-development approach for ICIs. We aimed to test whether PD-L1 (CD274) mRNA expression levels measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) can represent PD-L1 IHC and predict responses to ICI. The FDA-approved PD-L1 IHC results with 22C3 pharmDx (gastric cancer) and SP142 (urothelial carcinoma) were compared with CD274 mRNA expression levels via qRT-PCR using the same formalin-fixed, paraffin-embedded tissue blocks from 59 gastric cancer and 41 urothelial carcinoma samples. CD274 mRNA expression was identified using three independent sets of primers and TaqMan® probes targeting exon 1–2, exon 3–4, and exon 5–6. CD274 mRNA levels in spanning exon 1–2, exon 3–4, and exon 5–6 junctions of CD274 correlated well with PD-L1 expression (r2=0.81, 0.65, and 0.59, respectively). The area under the curve of exon 1–2 was the highest (0.783), followed by exon 3–4 (0.701), and exon 5–6 (0.671) of the CD274 gene against the PD-L1 combined positive score cutoff of 10. When CD274 mRNA expression was matched for response to immunotherapy, the overall response rate was higher in patients with high CD274 mRNA levels with a cutoff of 0.0722 (gastric cancer) and 0.0480 (urothelial carcinoma) than in those with low CD274 mRNA expression (P < 0.001 and P = 0.018, respectively). These results show that CD274 mRNA levels predicted ICI responses in patients with gastric or urothelial carcinomas and could be used as alternatives for PD-L1 IHC.
Dual-Targeted Therapy Circumvents Non-Genetic Drug Resistance to Targeted Therapy
Authors: Wang Wei , Sun Yue , Liu Xiaobo , Kumar Shaji K. , Jin Fengyan , Dai Yun
Published: April 2022

The introduction of various targeted agents into the armamentarium of cancer treatment has revolutionized the standard care of patients with cancer. However, like conventional chemotherapy, drug resistance, either preexisting (primary or intrinsic resistance) or developed following treatment (secondary or acquired resistance), remains the Achilles heel of all targeted agents with no exception, via either genetic or non-genetic mechanisms. In the latter, emerging evidence supports the notion that intracellular signaling pathways for tumor cell survival act as a mutually interdependent network via extensive cross-talks and feedback loops. Thus, dysregulations of multiple signaling pathways usually join forces to drive oncogenesis, tumor progression, invasion, metastasis, and drug resistance, thereby providing a basis for so-called “bypass” mechanisms underlying non-genetic resistance in response to targeted agents. In this context, simultaneous interruption of two or more related targets or pathways (an approach called dual-targeted therapy, DTT), via either linear or parallel inhibition, is required to deal with such a form of drug resistance to targeted agents that specifically inhibit a single oncoprotein or oncogenic pathway. Together, while most types of tumor cells are often addicted to two or more targets or pathways or can switch their dependency between them, DTT targeting either intrinsically activated or drug-induced compensatory targets/pathways would efficiently overcome drug resistance caused by non-genetic events, with a great opportunity that those resistant cells might be particularly more vulnerable. In this review article, we discuss, with our experience, diverse mechanisms for non-genetic resistance to targeted agents and the rationales to circumvent them in the treatment of cancer, emphasizing hematologic malignancies.
A New SteatoScore in the Evaluation of Non-Alcoholic Liver Disease in Oncologic Patients
Authors: Cioni Dania , Gabelloni Michela , Sanguinetti Andrea , De Rosa Laura , Aringhieri Giacomo , Tintori Rachele , Candita Gianvito , Febi Maria , Faita Francesco , Lencioni Riccardo , Neri Emanuele
Published: April 2022

Purpose

The aims of this study were to evaluate the reproducibility of a new multi-parametric steatoscore (new SteatoScore) in oncologic patients with non-alcoholic fatty liver disease (NAFLD) and to compare it with computed tomography (CT).

Materials and Methods

Fifty-one (31 men, 20 women) oncologic patients, with a mean age and weight of 63.9 years and 78.33 kg, respectively, were retrospectively enrolled in the study. Patients underwent ultrasound (US) and computed tomography (CT) examinations as part of their oncologic follow-up protocol. US examinations were performed by using a 3.5-MHz convex probe. During the US examination, three standardized clips were obtained in each patient. Two operators performed all measurements, one of whom repeated the processing twice in 1 year. Hepatic/renal ratio (HR), attenuation rate (AR), diaphragm visualization (DV), hepatic/portal vein ratio (HPV), and portal vein wall visualization (PVW) were acquired and calculated by using Matlab and inserted in a multi-parametric algorithm called new SteatoScore. On unenhanced CT scan, hepatic attenuation (HA), liver-spleen difference (L-S), and liver/spleen ratio (L/S) were measured by placement of a region of interest (ROI) within liver and spleen parenchyma, avoiding areas with vessels and biliary ducts.

Results

The intra-observer variability was greater than the inter-observer one, with intraclass correlation coefficient (ICC) values of 0.94 and 0.97, respectively. Correlation between single US and CT parameters provided an agreement in no case exceeding 50%. New SteatoScore showed high reproducibility, and high coefficient of correlation with L-S (R = −0.64; p < 0.0001) and L/S (R = −0.62; p < 0.0001) at CT.

Conclusion

New SteatoScore has a high reproducibility and shows a good correlation with unenhanced CT in evaluation of oncologic patients with NAFLD.
Modeling Human Prostate Cancer Metastasis in Mice via Resection of Subcutaneous Allografts
Authors: Peiffer Lauren B. , Hicks Jessica , Sosa Rebecca Y. , De Marzo Angelo M. , Sfanos Karen S. , Maynard Janielle P.
Published: April 2022

The 5-year survival rate for patients diagnosed with distant metastatic prostate cancer in the United States is 30.6%. Therefore, there is a great need to develop in vivo model systems to study prostate cancer metastasis and to test potential therapeutics. Most murine prostate cancer metastatic models involve intracardiac or intraosseous implantation of cancer cells, which bypass the early stages of tumor cell migration and invasion. Herein we provide a detailed protocol for a novel method of resecting subcutaneous prostate cancer allografts in immunocompetent mice to produce spontaneous metastases and describe a pilot study using this method of tumor resection. Intact male FVB/NCrl mice (n = 9) were inoculated subcutaneously with Myc-CaP cells. Tumors were surgically resected, and mice were monitored for tumor recurrence. Animals were euthanized or died, and a full set of tissues was collected for histopathologic examination. Tumors took an average of 44 days (range 23–61) to reach 1.7 cm in any direction. All tumors were resectable, and resection of the tumors increased the study length by 70 days (range 30–121). One mouse was euthanized early of an unrelated cause, and of eight remaining mice, four developed tumor recurrence at the site of resection. One mouse developed bone metastases, one mouse developed metastases to the abdominal cavity, and two mice showed signs of local invasion. This study demonstrates that resection of subcutaneous Myc-CaP cell allografts in mice results in local tumor recurrence and the development of distant metastases, providing a new model system to study prostate cancer metastasis in vivo.
Battery Ingestion in Children, an Ongoing Challenge: Recent Experience of a Tertiary Center
Authors: Lorenzo Cristina , Azevedo Sara , Lopes João , Fernandes Ana , Loreto Helena , Mourato Paula , Lopes Ana Isabel
Published: April 2022

Introduction

Morbidity related to childhood battery ingestions (BI) has increased recently due to the expanding use of larger lithium cells. A prompt endoscopic removal is vital to prevent severe complications in cases of esophageal batteries (EB).

Materials and Methods

A retrospective, descriptive study of admissions for BI requiring endoscopic removal in a tertiary hospital's pediatric emergency department (Jan. 2011/Dec. 2020).

Results

We had 35 cases, with an increasing incidence in the last 6 years; median age, 26 m (8 m-10 years), witnessed ingestion in 86%. On the X-ray: 14 (40%) had an EB, 21 (60%), a gastric battery (GB). Symptoms were present in 57% (100% EB/24% GB), and vomiting was the most frequent (50%). Endoscopy revealed: EB, 13 (37%); GB, 17 (49%); duodenal battery, 1 (3%); no battery, 4 (11%). Median time to removal: EB, 7 h (2 h-21days); GB, 12 h (2 h-3 days). All the patients with EB on the X-ray (14) had severe mucosal injury (Zargar classification): Grade IIIa, 7 (50%); IIIb, 5 (36%); IV, 2 (14%). CT-scan showed perforation in 2 patients (total, 4; 29% of EB). In patients with GB (21), 14 (67%) had mucosal damage; 13 (93%), mild (< Grade III, two esophageal erosions); 1 (7%) IIIa (esophageal ulceration). A statistically significant association between exposure time, younger age or battery size and severity of endoscopic lesions was found in EB location. There were no mortality cases. Acute complications occurred in 57% of EB: infection, 50%; perforation, 29%; pneumomediastinum/stridor, 14%; pneumothorax/subglottic stenosis/hemodynamic instability, 7 vs. 0% GB. Stenosis subsequently developed in 6 (43%) of EB: mild, 4 cases (29%); severe, 2 cases (14%, one resolved after endoscopic dilation; one needed a gastrostomy and esophagocoloplasty).

Conclusion

We verified recent increase in admissions due to battery ingestions and associated complications, despite the availability of an emergency pediatric endoscopy team. The patients with EB had more severe mucosal injury and poorer short/long-term outcomes. Children with GB had milder lesions, although the presence of a GB did not exclude esophageal injury. The availability of actual data from national referral centers will support advocacy efforts among stakeholders, including industry representatives and policy makers, in preventing worldwide button battery injury.
NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells
Authors: Cyranka Malgorzata , Monfeuga Thomas , Vedovato Natascia , Larabee Chelsea M , Chandran Anandhakumar , Toledo Enrique M , de Wet Heidi
Published: April 2022

Type 2 diabetes mellitus (T2DM) remains one of the most pressing health issues facing modern society. Several antidiabetic drugs are currently in clinical use to treat hyperglycaemia, but there is a need for new treatments that effectively restore pancreatic islet function in patients. Recent studies reported that both murine and human pancreatic islets exhibit enhanced insulin release and β-cell viability in response to N-methyl-D-aspartate (NMDA) receptor antagonists. Furthermore, oral administration of dextromethorphan, an over-the-counter NMDA receptor antagonist, to diabetic patients in a small clinical trial showed improved glucose tolerance and increased insulin release. However, the effects of NMDA receptor antagonists on the secretion of the incretin hormone GLP-1 was not tested, and nothing is known regarding how NMDA receptor antagonists may alter the secretion of gut hormones. This study demonstrates for the first time that, similar to β-cells, the NMDA receptor antagonist MK-801 increases the release of GLP-1 from a murine L-cell enteroendocrine model cell line, GLUTag cells. Furthermore, we report the 3′ mRNA expression profiling of GLUTag cells, with a specific focus on glutamate-activated receptors. We conclude that if NMDA receptor antagonists are to be pursued as an alternative, orally administered treatment for T2DM, it is essential that the effects of these drugs on the release of gut hormones, and specifically the incretin hormones, are fully investigated.
Metabolomic Differential Compounds Reflecting the Clinical Efficacy of Polyethylene Glycol Recombinant Human Growth Hormone in the Treatment of Childhood Growth Hormone Deficiency
Authors: Li Ji , Pan Weiwei , Qian Jianqin , Ni Yan , Fu Junfen , Ni Shaoqing
Published: April 2022

Understanding metabolite profiles may aid in providing a reference for individualized treatment using PEG-rhGH. Therefore, this study aimed to evaluate the clinical efficacy of PEG-rhGH in treating GHD patients by using a metabolomic approach. Fifty-seven pediatric participants treated with PEG-rhGH were enrolled (28 GHD patients with high clinical efficacy and 29 GHD patients with lower clinical efficacy). Serum samples from all patients were first collected at baseline for biochemical detection; then metabolite levels were measured using gas chromatography time-of-flight mass spectrometry. The candidates included heptadecanoic acid, stearic acid, 2-hydroxybutyric acid, myristic acid, palmitoleic acid, D-galactose, dodecanoic acid, and oleic acid. The related metabolic pathways involved fatty acid metabolism and energy metabolism. This study suggested that growth gains of PEG-rhGH treatment might be differentiated by altered serum levels of fatty acid. Collectively, the metabolomic study provides unique insights into the use of PEG-rhGH as a therapeutic strategy for individualized treatment.
The Histone Deacetylase Inhibitor I1 Induces Differentiation of Acute Leukemia Cells With MLL Gene Rearrangements via Epigenetic Modification
Authors: Yao Jingfang , Li Gentao , Cui Zihui , Chen Peilei , Wang Jinhong , Hu Zhenbo , Zhang Lei , Wei Liuya
Published: April 2022

Acute leukemia (AL) is characterized by excessive proliferation and impaired differentiation of leukemic cells. AL includes acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Previous studies have demonstrated that about 10% of AML and 22% of ALL are mixed lineage leukemia gene rearrangements (MLLr) leukemia. The prognosis of MLLr leukemia is poor and new therapeutics are urgently needed. Differentiation therapy with all-trans-retinoic acid (ATRA) has prolonged the 5-years disease-free survival rate in acute promyelocytic leukemia (APL), a subtype of AML. However, the differentiation therapy has not been effective in other acute leukemia. Here, we aim to explore the cell differentiation effect of the potent HDACs inhibitor, I1, and the possible mechanism on the MLLr-AML and MLLr-ALL cells (MOLM-13, THP-1, MV4-11 and SEM). It is shown that I1 can significantly inhibit the proliferation and the colony-forming ability of MOLM-13, THP-1, MV4-11 and SEM cells by promoting cell differentiation coupled with cell cycle block at G0/G1 phase. We show that the anti-proliferative effect of I1 attributed to cell differentiation is most likely associated with the HDAC inhibition activity, as assessed by the acetylation of histone H3 and H4, which may dictates the activation of hematopoietic cell lineage pathway in both MOLM-13 and THP-1 cell lines. Moreover, the activity of HDAC inhibition of I1 is stronger than that of SAHA in MOLM-13 and THP-1 cells. Our findings suggest that I1, as a chromatin-remodeling agent, could be a potent epigenetic drug to overcome differentiation block in MLLr-AL patients and would be promising for the treatment of AL.
Psychotropic Medication Use Before and During COVID-19: A Population-Wide Study
Authors: Leong Christine , Kowalec Kaarina , Eltonsy Sherif , Bolton James M. , Enns Murray W. , Tan Qier , Yogendran Marina , Chateau Dan , Delaney Joseph A. , Sareen Jitender , Falk Jamison , Spiwak Rae , Logsetty Sarvesh , Alessi-Severini Silvia
Published: April 2022

Background: The coronavirus disease 2019 (COVID-19) pandemic and public health measures that took place have led to concerns regarding mental health and receipt of psychotropic medications. We aimed to study the changes in psychotropic medication dispensation rates before and during the COVID-19 pandemic in the general population.

Methods: Administrative health data from the Canadian province of Manitoba was used to describe the quarterly incidence and prevalence of antipsychotics, antidepressants, and anxiolytic/sedative-hypnotics from January 1, 2015 to December 31, 2020. Individuals who received at least one prescription within each quarter were considered exposed to the medication. The denominator was the total population within each quarter. Incidence was defined as no receipt of medication in the 3 years prior to the quarter of interest. Autoregression models for time series data plus indicator variables were used to compare each quarter of 2020 after public health measures were implemented in March 2020 in relation to the expected trend. Analyses were stratified by age and sex.

Results: There were 1,394,885 individuals in the first quarter of 2020, with a mean (SD) age of 38.9 (23.4) years, 50.3% were female, and 36.1% had a psychiatric diagnosis in the previous 5 years. A significant decrease was observed for incident antidepressant use (p < 0.05 for both sexes and all age groups except for those 65 years and older) and anxiolytic use (p < 0.05 for both sexes and all age groups except 80 years and older) in the second quarter (April-June) of 2020 compared to the expected trend. Females and those aged 40 years and older had a significantly higher incidence of antidepressant and antipsychotic use in the final quarter of 2020 compared to the expected trend (p < 0.05).

Conclusion: Our findings indicate a decrease in new prescriptions for antidepressants and anxiolytics in the 3 months after COVID-19 in-person restrictions were first implemented. We then observed an increase in the new use of antidepressants and antipsychotics at the end of 2020, in females and people aged 40 years and older, with the highest rates of use in the population 80 years and older.
PET/CT Based EGFR Mutation Status Classification of NSCLC Using Deep Learning Features and Radiomics Features
Authors: Huang Weicheng , Wang Jingyi , Wang Haolin , Zhang Yuxiang , Zhao Fengjun , Li Kang , Su Linzhi , Kang Fei , Cao Xin
Published: April 2022

Purpose: This study aimed to compare the performance of radiomics and deep learning in predicting EGFR mutation status in patients with lung cancer based on PET/CT images, and tried to explore a model with excellent prediction performance to accurately predict EGFR mutation status in patients with non-small cell lung cancer (NSCLC).

Method: PET/CT images of 194 NSCLC patients from Xijing Hospital were collected and divided into a training set and a validation set according to the ratio of 7:3. Statistics were made on patients’ clinical characteristics, and a large number of features were extracted based on their PET/CT images (4306 radiomics features and 2048 deep learning features per person) with the pyradiomics toolkit and 3D convolutional neural network. Then a radiomics model (RM), a deep learning model (DLM), and a hybrid model (HM) were established. The performance of the three models was compared by receiver operating characteristic (ROC) curves, sensitivity, specificity, accuracy, calibration curves, and decision curves. In addition, a nomogram based on a deep learning score (DS) and the most significant clinical characteristic was plotted.

Result: In the training set composed of 138 patients (64 with EGFR mutation and 74 without EGFR mutation), the area under the ROC curve (AUC) of HM (0.91, 95% CI: 0.86–0.96) was higher than that of RM (0.82, 95% CI: 0.75–0.89) and DLM (0.90, 95% CI: 0.85–0.95). In the validation set composed of 57 patients (32 with EGFR mutation and 25 without EGFR mutation), the AUC of HM (0.85, 95% CI: 0.77–0.93) was also higher than that of RM (0.68, 95% CI: 0.52–0.84) and DLM (0.79, 95% CI: 0.67–0.91). In all, HM achieved better diagnostic performance in predicting EGFR mutation status in NSCLC patients than two other models.

Conclusion: Our study showed that the deep learning model based on PET/CT images had better performance than radiomics model in diagnosing EGFR mutation status of NSCLC patients based on PET/CT images. Combined with the most statistically significant clinical characteristic (smoking) and deep learning features, our hybrid model had better performance in predicting EGFR mutation types of patients than two other models, which could enable NSCLC patients to choose more personalized treatment schemes.
A Numerical Investigation of Thermal-Induced Explosive Spalling Behavior of a Concrete Material Using Cohesive Interface Model
Authors: Zhang Jiuchang , Chen Jiamin , Zhang Rongwei , Guo Rongxin
Published: April 2022

Thermal-induced spalling is a typical failure behavior of concrete materials exposed to high temperatures. This study uses Abaqus to establish a numerical model of concrete material comprising aggregates and mortar matrix. Cohesive elements considering heat conduction are embedded into this numerical model to simulate the thermal-induced explosive spalling failure process of the concrete material. Simulation results show that the heat gradually transfers from the outer boundaries to the inner areas with increasing temperature. Thermal stresses concentrate in the aggregates-mortar interfaces, where thermal-induced cracks initiate and propagate. The occurrence of thermal-induced cracks reduces the heat conductivity of mortar, reduces thermal stresses and leads to severe spalling failure in the concrete material. This research provides a practical scheme for the numerical simulation of the thermal-induced spalling behavior of concrete materials.
Nanoscale Structure and Dynamics of Model Membrane Lipid Raft Systems, Studied by Neutron Scattering Methods
Authors: Ahmadi Delaram , Thompson Katherine C. , García Sakai Victoria , Schweins Ralf , Moulin Martine , Haertlein Michael , Strohmeier Gernot A. , Pichler Harald , Forsyth V. Trevor , Barlow David J. , Lawrence M. Jayne , Foglia Fabrizia
Published: April 2022

Quasi-elastic neutron scattering (QENS) and small angle neutron scattering (SANS), in combination with isotopic contrast variation, have been used to determine the structure and dynamics of three-component lipid membranes, in the form of vesicles, comprising an unsaturated [palmitoyl-oleoyl-phosphatidylcholine (POPC) or dioleoyl-phosphatidylcholine (DOPC)], a saturated phospholipid (dipalmitoyl-phosphatidylcholine (DPPC)), and cholesterol, as a function temperature and composition. SANS studies showed vesicle membranes composed of a 1:1:1 molar ratio of DPPC:DOPC:cholesterol and a 2:2:1 molar ratio of DPPC:POPC:cholesterol phase separated, forming lipid rafts of ∼18 and ∼7 nm diameter respectively, when decreasing temperature from 308 to 297 K. Phase separation was reversible upon increasing temperature. The larger rafts observed in systems containing DOPC are attributed to the greater mis-match in lipid alkyl chains between DOPC and DPPC, than for POPC and DPPC. QENS studies, over the temperature range 283–323K, showed that the resulting data were best modelled by two Lorentzian functions: a narrow component, describing the “in-plane” lipid diffusion, and a broader component, describing the lipid alkyl chain segmental relaxation. The overall “in-plane” diffusion was found to show a significant reduction upon increasing temperature due to the vesicle membranes transitioning from one containing rafts to one where the component lipids are homogeneously mixed. The use of different isotopic combinations allowed the measured overall reduction of in-plane diffusion to be understood in terms of an increase in diffusion of the saturated DPPC lipid and a corresponding decrease in diffusion of the unsaturated DOPC/POPC lipid. As the rafts are considered to be composed principally of saturated lipid and cholesterol, the breakdown of rafts decreases the exposure of the DPPC to cholesterol whilst increasing the exposure of cholesterol to unsaturated lipid. These results show the sensitivity of lipid diffusion to local cholesterol concentration, and the importance of considering the local, rather that the global composition of a membrane when understanding the diffusion processes of lipids within the membrane. The novel combination of SANS and QENS allows a non-intrusive approach to characterize the structure and dynamics occurring in phase-separated model membranes which are designed to mimic the lateral heterogeneity of lipids seen in cellular membranes–a heterogeneity that can have pathological consequences.
Anomaly Detection Based on Convex Analysis: A Survey
Authors: Wang Tong , Cai Mengsi , Ouyang Xiao , Cao Ziqiang , Cai Tie , Tan Xu , Lu Xin
Published: April 2022

As a crucial technique for identifying irregular samples or outlier patterns, anomaly detection has broad applications in many fields. Convex analysis (CA) is one of the fundamental methods used in anomaly detection, which contributes to the robust approximation of algebra and geometry, efficient computation to a unique global solution, and mathematical optimization for modeling. Despite the essential role and evergrowing research in CA-based anomaly detection algorithms, little work has realized a comprehensive survey of it. To fill this gap, we summarize the CA techniques used in anomaly detection and classify them into four categories of density estimation methods, matrix factorization methods, machine learning methods, and the others. The theoretical background, sub-categories of methods, typical applications as well as strengths and limitations for each category are introduced. This paper sheds light on a succinct and structured framework and provides researchers with new insights into both anomaly detection and CA. With the remarkable progress made in the techniques of big data and machine learning, CA-based anomaly detection holds great promise for more expeditious, accurate and intelligent detection capacities.
Using Curved Fluid Boundaries to Confine Active Nematic Flows
Authors: Khaladj Dimitrius A. , Hirst Linda S.
Published: April 2022

Actively driven, bundled microtubule networks, powered by molecular motors have become a useful framework in which to study the dynamics of energy-driven defects, but achieving control of defect motions is still a challenging problem. In this paper, we present a method to confine active nematic fluid using wetting to curve a layer of oil over circular pillars. This geometry, in which submersed pillars impinge on an oil-water interface, creates a two-tier continuous active layer in which the material is confined above, and surrounds the pillars. Active flows above the pillars are influenced by the circular geometry and exhibit dynamics similar to those observed for active material confined by hard boundaries, e.g., inside circular wells. The thin oil layer beneath the active material is even thinner in the region above the pillars than outside their boundary, consequently producing an area of higher effective friction. Within the pillar region, active length scales and velocities are decreased, while defect densities increase relative to outside the pillar boundary. This new way to confine active flows opens further opportunities to control and organize topological defects and study their behavior in active systems.
What Can We Learn from Single Sarcomere and Myofibril Preparations?
Authors: Herzog Walter
Published: April 2022

Sarcomeres are the smallest functional contractile unit of muscle, and myofibrils are striated muscle organelles that are comprised of sarcomeres that are strictly aligned in series. Furthermore, passive forces in sarcomeres and myofibrils are almost exclusively produced by the structural protein titin, and all contractile, regulatory, and structural proteins are in their natural configuration. For these mechanical and structural reasons single sarcomere and myofibril preparations are arguably the most powerful to answer questions on the mechanisms of striated muscle contraction. We developed and optimized single myofibril research over the past 20 years and were the first to mechanically isolate and test single sarcomeres. The results from this research led to the uncovering of the crucial role of titin in muscle contraction, first molecular explanations for the origins of the passive and the residual force enhancement properties of skeletal and cardiac muscles, the discovery of sarcomere length stability on the descending limb of the force-length relationship, and culminating in the formulation of the three-filament theory of muscle contraction that, aside from actin and myosin, proposes a crucial role of titin in active force production. Aside from all the advantages and possibilities that single sarcomere and myofibril preparations offer, there are also disadvantages. These include the fragility of the preparation, the time-consuming training to master these preparations, the limited spatial resolution for length and force measurements, and the unavailability of commercial systems for single sarcomere/myofibril research. Ignoring the mechanics that govern serially linked systems, not considering the spatial resolution and associated accuracies of myofibril systems, and neglecting the fragility of myofibril preparations, has led to erroneous interpretations of results and misleading conclusions. Here, we will attempt to describe the methods and possible applications of single sarcomere/myofibril research and discuss the advantages and disadvantages by focusing on specific applications. It is hoped that this discussion may contribute to identifying the enormous potential of single sarcomere/myofibril research in discovering the secrets of muscle contraction.
Autonomic Neural Circuit and Intervention for Comorbidity Anxiety and Cardiovascular Disease
Authors: Chen Xuanzhao , Xu Li , Li Zeyan
Published: April 2022

Anxiety disorder is a prevalent psychiatric disease and imposes a significant influence on cardiovascular disease (CVD). Numerous evidence support that anxiety contributes to the onset and progression of various CVDs through different physiological and behavioral mechanisms. However, the exact role of nuclei and the association between the neural circuit and anxiety disorder in CVD remains unknown. Several anxiety-related nuclei, including that of the amygdala, hippocampus, bed nucleus of stria terminalis, and medial prefrontal cortex, along with the relevant neural circuit are crucial in CVD. A strong connection between these nuclei and the autonomic nervous system has been proven. Therefore, anxiety may influence CVD through these autonomic neural circuits consisting of anxiety-related nuclei and the autonomic nervous system. Neuromodulation, which can offer targeted intervention on these nuclei, may promote the development of treatment for comorbidities of CVD and anxiety disorders. The present review focuses on the association between anxiety-relevant nuclei and CVD, as well as discusses several non-invasive neuromodulations which may treat anxiety and CVD.
The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review
Authors: Lei Zhiqiang , Hu Xiang , Wu Yaoqi , Fu Longsheng , Lai Songqing , Lin Jing , Li Xiaobing , Lv Yanni
Published: April 2022

Vascular endothelial cells, forming the inner wall of the blood vessels, participate in the body’s pathological and physiological processes of immunity, tumors, and infection. In response to an external stimulus or internal pathological changes, vascular endothelial cells can reshape their microenvironment, forming a “niche”. Current research on the vascular endothelial niche is a rapidly growing field in vascular biology. Endothelial niches not only respond to stimulation by external information but are also decisive factors that act on neighboring tissues and circulating cells. Intervention through the vascular niche is meaningful for improving the treatment of several diseases. This review aimed to summarize reported diseases affected by endothelial niches and signal molecular alterations or release within endothelial niches. We look forward to contributing knowledge to increase the understanding the signaling and mechanisms of the vascular endothelial niche in multiple diseases.
Juvenile Hormone Membrane Signaling Enhances its Intracellular Signaling Through Phosphorylation of Met and Hsp83
Authors: Gao Yue , Chen Nan , Zhang Xiangle , Li Emma Y. , Luo Wei , Zhang Jie , Zhang Wenqiang , Li Sheng , Wang Jian , Liu Suning
Published: April 2022

Juvenile hormone (JH) regulates insect development and reproduction through both intracellular and membrane signaling, and the two pathways might crosstalk with each other. Recent studies have reported that JH membrane signaling induces phosphorylation of the JH intracellular receptor Met, thus enhancing its transcriptional activity. To gain more insights into JH-induced Met phosphorylation, we here performed phosphoproteomics to identify potential phosphorylation sites of Met and its paralog Germ-cell expressed (Gce) in Drosophila Kc cells. In vitro experiments demonstrate that JH-induced phosphorylation sites in the basic helix-loop-helix (bHLH) domain, but not in the Per-Arnt-Sim-B (PAS-B) domain, are required for maximization of Met transcriptional activity. Moreover, phosphoproteomics analysis reveale that JH also induces the phosphorylation of Hsp83, a chaperone protein involved in JH-activated Met nuclear import. The JH-induced Hsp83 phosphorylation at S219 facilitates Hsp83-Met binding, thus promoting Met nuclear import and its transcription. By using proteomics, subcellular distribution, and co-immunoprecipitation approaches, we further characterized 14-3-3 proteins as negative regulators of Met nuclear import through physical interaction with Hsp83. These results show that JH membrane signaling induces phosphorylation of the key components in JH intracellular signaling, such as Met and Hsp83, and consequently facilitating JH intracellular signaling.
Understanding the Role of Propulsion in the Prediction of Front-Crawl Swimming Velocity and in the Relationship Between Stroke Frequency and Stroke Length
Authors: Morais Jorge E. , Barbosa Tiago M. , Nevill Alan M. , Cobley Stephen , Marinho Daniel A.
Published: April 2022

Introduction: This study aimed to: 1) determine swimming velocity based on a set of anthropometric, kinematic, and kinetic variables, and; 2) understand the stroke frequency (SF)–stroke length (SL) combinations associated with swimming velocity and propulsion in young sprint swimmers.

Methods: 38 swimmers (22 males: 15.92 ± 0.75 years; 16 females: 14.99 ± 1.06 years) participated and underwent anthropometric, kinematic, and kinetic variables assessment. Exploratory associations between SL and SF on swimming velocity were explored using two two-way ANOVA (independent for males and females). Swimming velocity was determined using multilevel modeling.

Results: The prediction of swimming velocity revealed a significant sex effect. Height, underwater stroke time, and mean propulsion of the dominant limb were predictors of swimming velocity. For both sexes, swimming velocity suggested that SL presented a significant variation (males: F = 8.20, p < 0.001, η2 = 0.40; females: F = 18.23, p < 0.001, η2 = 0.39), as well as SF (males: F = 38.20, p < 0.001, η2 = 0.47; females: F = 83.04, p < 0.001, η2 = 0.51). The interaction between SL and SF was significant for females (F = 8.00, p = 0.001, η2 = 0.05), but not for males (F = 1.60, p = 0.172, η2 = 0.04). The optimal SF–SL combination suggested a SF of 0.80 Hz and a SL of 2.20 m (swimming velocity: 1.75 m s−1), and a SF of 0.80 Hz and a SL of 1.90 m (swimming velocity: 1.56 m s−1) for males and females, respectively. The propulsion in both sexes showed the same trend in SL, but not in SF (i.e., non-significant variation). Also, a non-significant interaction between SL and SF was observed (males: F = 0.77, p = 0.601, η2 = 0.05; females: F = 1.48, p = 0.242, η2 = 0.05).

Conclusion: Swimming velocity was predicted by an interaction of anthropometrics, kinematics, and kinetics. Faster velocities in young sprinters of both sexes were achieved by an optimal combination of SF–SL. The same trend was shown by the propulsion data. The highest propulsion was not necessarily associated with higher velocity achievement.