bluuebunny/crossref_metadata_2025 huggingface dataset:
Begonia—A Two-Photon Imaging Analysis Pipeline for Astrocytic Ca2+ Signals
Authors: Bjørnstad Daniel M. , Åbjørsbråten Knut S. , Hennestad Eivind , Cunen Céline , Hermansen Gudmund Horn , Bojarskaite Laura , Pettersen Klas H. , Vervaeke Koen , Enger Rune
Published: May 2021

Imaging the intact brain of awake behaving mice without the dampening effects of anesthesia, has revealed an exceedingly rich repertoire of astrocytic Ca2+ signals. Analyzing and interpreting such complex signals pose many challenges. Traditional analyses of fluorescent changes typically rely on manually outlined static region-of-interests, but such analyses fail to capture the intricate spatiotemporal patterns of astrocytic Ca2+ dynamics. Moreover, all astrocytic Ca2+ imaging data obtained from awake behaving mice need to be interpreted in light of the complex behavioral patterns of the animal. Hence processing multimodal data, including animal behavior metrics, stimulation timings, and electrophysiological signals is needed to interpret astrocytic Ca2+ signals. Managing and incorporating these data types into a coherent analysis pipeline is challenging and time-consuming, especially if research protocols change or new data types are added. Here, we introduce Begonia, a MATLAB-based data management and analysis toolbox tailored for the analyses of astrocytic Ca2+ signals in conjunction with behavioral data. The analysis suite includes an automatic, event-based algorithm with few input parameters that can capture a high level of spatiotemporal complexity of astrocytic Ca2+ signals. The toolbox enables the experimentalist to quantify astrocytic Ca2+ signals in a precise and unbiased way and combine them with other types of time series data.
Readmission Trends Related to Unruptured Intracranial Aneurysm Treatment
Authors: Mehta Tapan , Desai Ninad , Patel Smit , Male Shailesh , Khan Adam , Grande Andrew Walker , Tummala Ramachandra Prasad , Jagadeesan Bharathi Dasan
Published: May 2021

Background and Purpose: Aneurysmal subarachnoid hemorrhage (SAH) is associated with high mortality. Prophylactic treatment of the unruptured intracranial aneurysm (UIA) is considered in a select group of patients thought to be at high for aneurysmal rupture. Hospital readmission rates can serve as a surrogate marker for the safety and cost-effectiveness of treatment options for UIAs; we present an analysis of the 30-day rehospitalization rates and predictors of readmission following UIA treatment with surgical and endovascular approaches.

Methods: We retrospectively analyzed data from the National Readmission Database (NRD) derived from the Healthcare Cost and Utilization Project for the year 2014. The cohort included patients with a primary discharge diagnosis of a treated unruptured aneurysm. The primary outcome variable was the 30-day readmission rate in open surgical vs. endovascularly treated groups. The secondary outcomes included predictors of readmissions, and causes of 30-day readmissions in these two groups.

Results: The 30-day readmission rate for the surgical group was 8.37% compared to 4.87% for the endovascular group. The index hospitalization duration was longer in the surgical group. A larger proportion of the patients readmitted following surgical treatment were hypertensive (76.35, vs. 63.43%), but the prevalence of other medical comorbidities was comparable in the two treatment groups.

Conclusions: There is a higher likelihood for 30-day readmission, longer duration of initial hospitalization and a lower likelihood of discharge home following surgical treatment of UIAs when compared to endovascular treatment. These findings, however, do not demonstrate long-term superiority of one specific treatment modality.
Trends in Prevalence and Severity of Pre/Perinatal Cerebral Palsy Among Children Born Preterm From 2004 to 2010: A SCPE Collaboration Study
Authors: Arnaud Catherine , Ehlinger Virginie , Delobel-Ayoub Malika , Klapouszczak Dana , Perra Oliver , Hensey Owen , Neubauer David , Hollódy Katalin , Virella Daniel , Rackauskaite Gija , Greitane Andra , Himmelmann Kate , Ortibus Els , Dakovic Ivana , Andersen Guro L. , Papavasiliou Antigone , Sellier Elodie , Platt Mary Jane , Krägeloh-Mann Inge
Published: May 2021

Aim: To report on prevalence of cerebral palsy (CP), severity rates, and types of brain lesions in children born preterm 2004 to 2010 by gestational age groups.

Methods: Data from 12 population-based registries of the Surveillance of Cerebral Palsy in Europe network were used. Children with CP were eligible if they were born preterm (<37 weeks of gestational age) between 2004 and 2010, and were at least 4 years at time of registration. Severity was assessed using the impairment index. The findings of postnatal brain imaging were classified according to the predominant pathogenic pattern. Prevalences were estimated per 1,000 live births with exact 95% confidence intervals within each stratum of gestational age: ≤27, 28–31, 32–36 weeks. Time trends of both overall prevalence and prevalence of severe CP were investigated using multilevel negative binomial regression models.

Results: The sample comprised 2,273 children. 25.8% were born from multiple pregnancies. About 2-thirds had a bilateral spastic CP. 43.5% of children born ≤27 weeks had a high impairment index compared to 37.0 and 38.5% in the two other groups. Overall prevalence significantly decreased (incidence rate ratio per year: 0.96 [0.92–1.00[) in children born 32–36 weeks. We showed a decrease until 2009 for children born 28–31 weeks but an increase in 2010 again, and a steady prevalence (incidence rate ratio per year = 0.97 [0.92–1.02] for those born ≤27 weeks. The prevalence of the most severely affected children with CP revealed a similar but not significant trend to the overall prevalence in the corresponding GA groups. Predominant white matter injuries were more frequent in children born <32 weeks: 81.5% (≤27 weeks) and 86.4% (28–31 weeks), compared to 63.6% for children born 32–36 weeks.

Conclusion: Prevalence of CP in preterm born children continues to decrease in Europe excepting the extremely immature children, with the most severely affected children showing a similar trend.
Diagnostic Accuracy of PET for Differentiating True Glioma Progression From Post Treatment-Related Changes: A Systematic Review and Meta-Analysis
Authors: Cui Meng , Zorrilla-Veloz Rocío Isabel , Hu Jian , Guan Bing , Ma Xiaodong
Published: May 2021

Purpose: To evaluate the diagnostic accuracy of PET with different radiotracers and parameters in differentiating between true glioma progression (TPR) and post treatment-related change (PTRC).

Methods: Studies on using PET to differentiate between TPR and PTRC were screened from the PubMed and Embase databases. By following the PRISMA checklist, the quality assessment of included studies was performed, the true positive and negative values (TP and TN), false positive and negative values (FP and FN), and general characteristics of all the included studies were extracted. Results of PET consistent with reference standard were defined as TP or TN. The pooled sensitivity (Sen), specificity (Spe), and hierarchical summary receiver operating characteristic curves (HSROC) were generated to evaluate the diagnostic accuracy.

Results: The 33 included studies had 1,734 patients with 1,811 lesions suspected of glioma recurrence. Fifteen studies tested the accuracy of 18F-FET PET, 12 tested 18F-FDG PET, seven tested 11C-MET PET, and three tested 18F-DOPA PET. 18F-FET PET showed a pooled Sen and Spe of 0.88 (95% CI: 0.80, 0.93) and 0.78 (0.69, 0.85), respectively. In the subgroup analysis of FET-PET, diagnostic accuracy of high-grade gliomas (HGGs) was higher than that of mixed-grade gliomas (Pinteraction = 0.04). 18F-FDG PET showed a pooled Sen and Spe of 0.78 (95% CI: 0.71, 0.83) and 0.87 (0.80, 0.92), the Spe of the HGGs group was lower than that of the low-grade gliomas group (0.82 vs. 0.90, P = 0.02). 11C-MET PET had a pooled Sen and Spe of 0.92 (95% CI: 0.83, 0.96) and 0.78 (0.69, 0.86). 18F-DOPA PET had a pooled Sen and Spe of 0.85 (95% CI: 0.80, 0.89) and 0.70 (0.60, 0.79). FET-PET combined with MRI had a pooled Sen and Spe of 0.88 (95% CI: 0.78, 0.94) and 0.76 (0.57, 0.88). Multi-parameters analysis of FET-PET had pooled Sen and Spe values of 0.88 (95% CI: 0.81, 0.92) and 0.79 (0.63, 0.89).

Conclusion: PET has a moderate diagnostic accuracy in differentiating between TPR and PTRC. The high Sen of amino acid PET and high Spe of FDG-PET suggest that the combination of commonly used FET-PET and FDG-PET may be more accurate and promising, especially for low-grade glioma.
The Clinical, Radiologic, and Prognostic Differences Between Pediatric and Adult Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Encephalomyelitis
Authors: Xu Jie , Liu Lingjuan , Xiong Jie , Zhang Lu , Huang Peng , Tang Li , Xiao Yangyang , Li Xingfang , Li Jian , Luo Yingying , Li Huiling , Mao Dingan , Liu Liqun
Published: May 2021

Purpose: To evaluate the clinical differences between pediatric and adult patients with myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM).

Methods: We retrospectively reviewed the clinical features of pediatric and adult patients with MOG-EM in our center between November 2015 and October 2020.

Results: Twenty-eight pediatric patients and 25 adults were admitted to our study. Bilateral optic neuritis (BON) was the most common initial phenotype in the pediatric group but less common in the adult group (28.57 vs. 0%, p = 0.0119). Almost half of the adult patients presented with neuromyelitis optica spectrum disease (NMOSD), which was less prevalent among the pediatrics (48 vs. 21.43%, p = 0.0414). Visual impairment was the most common symptom in both groups during the initial attack (pediatric group, 39.29%; adult group, 64%) and throughout the full course (pediatric group, 57.14%; adult group, 72%). More pediatric patients suffered from fever than adult patients at onset (pediatric group, 28.57%; adult group, 4%; p = 0.0442) and throughout the full course (pediatric group, 39.29%; adult group, 12%; p = 0.0245). Multiple patchy lesions in subcortical white matter (pediatric group, 40.74%; adult group, 45%), periventricular (pediatric group, 25.93%; adult group, 35%), infratentorial (pediatric group, 18.52%; adult group, 30%) and deep gray matter (pediatric group, 25.93%; adult group, 20%) were frequent in all cases, no significant difference was found between the two groups, while bilateral optic nerve involvement was more frequent in pediatric group (61.54 vs. 14.29%, p = 0.0042) and unilateral optic nerve involvement was higher in adult group (64.29 vs. 15.38%, p = 0.0052). At the last follow-up, adult patients had a higher average EDSS score (median 1.0, range 0–3) than pediatrics (median 0.0, range 0–3), though not significant (p = 0.0752). Patients aged 0–9 years (61.54%) and 10–18 years (70%), and patients presenting with encephalitis/meningoencephalitis (100%) and ADEM (75%) were more likely to recover fully.

Conclusions: Visual impairment was the dominant symptom in both pediatric and adult patients, while fever was more frequent in pediatric patients. Data suggested that BON and bilateral optic nerve involvement were more common in pediatric cases whereas NMOSD and unilateral optic nerve involvement were more prevalent in adults. The younger patients and patients presenting with encephalitis/meningoencephalitis and ADEM tended to recover better.
Clinical Validation of the Champagne Algorithm for Epilepsy Spike Localization
Authors: Cai Chang , Chen Jessie , Findlay Anne M. , Mizuiri Danielle , Sekihara Kensuke , Kirsch Heidi E. , Nagarajan Srikantan S.
Published: May 2021

Magnetoencephalography (MEG) is increasingly used for presurgical planning in people with medically refractory focal epilepsy. Localization of interictal epileptiform activity, a surrogate for the seizure onset zone whose removal may prevent seizures, is challenging and depends on the use of multiple complementary techniques. Accurate and reliable localization of epileptiform activity from spontaneous MEG data has been an elusive goal. One approach toward this goal is to use a novel Bayesian inference algorithm—the Champagne algorithm with noise learning—which has shown tremendous success in source reconstruction, especially for focal brain sources. In this study, we localized sources of manually identified MEG spikes using the Champagne algorithm in a cohort of 16 patients with medically refractory epilepsy collected in two consecutive series. To evaluate the reliability of this approach, we compared the performance to equivalent current dipole (ECD) modeling, a conventional source localization technique that is commonly used in clinical practice. Results suggest that Champagne may be a robust, automated, alternative to manual parametric dipole fitting methods for localization of interictal MEG spikes, in addition to its previously described clinical and research applications.
A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease
Authors: Kyrtata Natalia , Emsley Hedley C. A. , Sparasci Oli , Parkes Laura M. , Dickie Ben R.
Published: May 2021

Introduction: Alzheimer's disease (AD) is characterized by cerebral glucose hypometabolism. Hypometabolism may be partly due to reduced glucose transport at the blood-brain barrier (BBB) and across astrocytic and neuronal cell membranes. Glucose transporters (GLUTs) are integral membrane proteins responsible for moving glucose from the bloodstream to parenchymal cells where it is metabolized, and evidence indicates vascular and non-vascular GLUTs are altered in AD brains, a process which could starve the brain of glucose and accelerate cognitive decline. Here we review the literature on glucose transport alterations in AD from human and rodent studies.

Methods: Literature published between 1st January 1946 and 1st November 2020 within EMBASE and MEDLINE databases was searched for the terms “glucose transporters” AND “Alzheimer's disease”. Human and rodent studies were included while reviews, letters, and in-vitro studies were excluded.

Results: Forty-three studies fitting the inclusion criteria were identified, covering human (23 studies) and rodent (20 studies). Post-mortem studies showed consistent reductions in GLUT1 and GLUT3 in the hippocampus and cortex of AD brains, areas of the brain closely associated with AD pathology. Tracer studies in rodent models of AD and human AD also exhibit reduced uptake of glucose and glucose-analogs into the brain, supporting these findings. Longitudinal rodent studies clearly indicate that changes in GLUT1 and GLUT3 only occur after amyloid-β pathology is present, and several studies indicate amyloid-β itself may be responsible for GLUT changes. Furthermore, evidence from human and rodent studies suggest GLUT depletion has severe effects on brain function. A small number of studies show GLUT2 and GLUT12 are increased in AD. Anti-diabetic medications improved glucose transport capacity in AD subjects.

Conclusions: GLUT1 and GLUT3 are reduced in hippocampal and cortical regions in patients and rodent models of AD, and may be caused by high levels of amyloid-β in these regions. GLUT3 reductions appear to precede the onset of clinical symptoms. GLUT2 and GLUT12 appear to increase and may have a compensatory role. Repurposing anti-diabetic drugs to modify glucose transport shows promising results in human studies of AD.
Plasma Circulating Tumor DNA Sequencing Predicts Minimal Residual Disease in Resectable Esophageal Squamous Cell Carcinoma
Authors: Liu Tao , Yao Qianqian , Jin Hai
Published: May 2021

Esophageal squamous cell carcinoma (ESCC) is lethal as tumors are rarely detected at an early stage and have a high recurrence rate. There are no particularly useful biomarkers for the prognostic prediction of ESCC. Circulating tumor DNA (ctDNA) is becoming an important biomarker for non-invasive diagnosis and monitoring tumor prognosis. Here, we aimed to analyze variations in plasma cell-free DNA (cfDNA) amount to search for minimal residual disease (MRD). Plasma and white blood cells (WBCs) of 60 patients were collected before tumor resection and a week after surgery. Tumor specimens were also collected as formalin-fixed paraffin-embedded (FFPE) samples. All samples were extracted to analyze the genetic alterations of 61 genes using capture-based next-generation sequencing (NGS). Tumor variants were detected in 38 patients with ESCC, and the two driver genes with the highest mutation frequency were TP53 and PIK3CA. Of the pre-surgical plasma cfDNA samples, 73.7% of identified variants matched the tissue. In patients who did not receive adjuvant therapy after surgery, postoperative cfDNA-positive patients had shorter overall survival (hazard ratios (HR), 25.8; 95% CI, 2.7–242.6; P = 0.004) and were more likely to relapse than postoperative cfDNA-negative patients (HR, 184.6; 95% CI, 3.6–9576.9; P = 0.01). Detection of ctDNA after surgical tumor excision is associated with tumor relapse and disease-specific survival, and can be used as a prognostic biomarker for MRD detection in ESCC.
Methylation Regulation of TLR3 on Immune Parameters in Lung Adenocarcinoma
Authors: Li Ang , Wu Hongjiao , Tian Qinqin , Zhang Yi , Zhang Zhi , Zhang Xuemei
Published: May 2021

This study aims to analyze the methylation regulation of TLR3 in lung adenocarcinoma (LUAD) and to explore the association of TLR3 expression with immune microenvironment. TLR3 has a decreased expression in LUAD tissues and low expression of TLR3 is not only associated with poor prognosis in patients with LUAD, but also can be used as a diagnostic marker. Bisulfite sequencing PCR (BSP) results showed that the methylation level in the promoter of TLR3 was negatively correlated with the level of TLR3 mRNA in LUAD tissues. TIMER analysis showed that TLR3 was negatively correlated with the tumor purity of LUAD and positively with immune cell infiltration to some extent. ESTIMATE analysis also suggested that TLR3 expression and its methylation had significant correlation with immune score. The lower immune scores were associated with the late stage of LUAD and poor prognosis. The high expression of TLR3 might inhibit the development of LUAD by activating apoptosis pathway. The proteins interacted with TLR3 were mainly involved in the apoptosis pathway and positively correlated with the key genes (MYD88, Caspase 8, BIRC3, PIK3R1) in this pathway. Therefore, TLR3 as a key biomarker for prognosis and diagnosis in LUAD, might be considered as a potential epigenetic and immunotherapeutic target.
Up-Regulation of LINC00665 Facilitates the Malignant Progression of Prostate Cancer by Epigenetically Silencing KLF2 Through EZH2 and LSD1
Authors: Xue Peng , Yan Miao , Wang Kunpeng , Gu Jinbao , Zhong Bing , Tu Chuanquan
Published: May 2021

This study aimed to explore the function of LINC00665 on the proliferation and metastasis of prostate cancer (PCa), and the potential regulatory mechanisms were also investigated. The expression level of LINC00665 in 50 pairs of PCa tissues and adjacent ones was studied by qRT-PCR, and the associations between LINC00665 and clinicopathological characteristics of PCa patients were analyzed. Control group (sh-NC) and LINC00665 knock-down group (sh-LINC00665) were set in 22RV1 and DU145 cells, respectively. The biological functions of LINC00665 in PCa cell lines were assessed by CCK-8, EdU, Transwell assays, and the nude mouse xenograft model was used to evaluate the tumorigenicity in vivo. In addition, qRT-PCR, Western Blot, RIP and ChIP assays were also used to determine the regulation mechanism of LINC00665 in PCa cell lines. In this study, our results showed that LINC00665 expression level in PCa cancer tissues was significantly up-regulated, compared with that in adjacent ones. Besides, similar results were found in PCa cell lines. Knock-down of LINC00665 significantly attenuated the proliferation and migration ability in 22RV1 and DU145 cells, compared to sh-NC. Mechanically, LINC00665 could interact with EZH2 and LSD1, recruiting them to KLF2 promoter region to inhibit its transcription. Moreover, the tumor-suppressive effects mediated by sh-LINC00665 were significantly reversed through the down-regulation of KLF2. Also, the suppression of LINC00665 impaired tumor growth of PCa in vivo. In summary, LINC00665 exerted the oncogenic functions in PCa cell lines by epigenetically silencing KLF2 expression by binding to EZH2 and LSD1, illuminating a novel mechanism of LINC00665 in the malignant progression of PCa and furnishing a prospective therapeutic biomarker to combat PCa.
ITGA3 Is Associated With Immune Cell Infiltration and Serves as a Favorable Prognostic Biomarker for Breast Cancer
Authors: Li Yue , Li Fan , Bai Xiaoyu , Li Yanlei , Ni Chunsheng , Zhao Xiulan , Zhang Danfang
Published: May 2021

Background

ITGA3 is a member of the integrin family, a cell surface adhesion molecule that can interact with extracellular matrix (ECM) proteins. The purpose of this study was to explore the significance of ITGA3 expression in the prognosis and clinical diagnosis of breast cancer patients.

Methods

Oncomine, the Human Protein Atlas (HPA) and UALCAN were used to analyze the expression of ITGA3 in various cancers. PrognoScan, GEPIA, Kaplan–Meier plotter and Easysurv were utilized to analyze the prognosis of ITGA3 in certain cancers. Based on TCGA data, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of ITGA3 expression. cBio-Portal and MethSurv were used to evaluate the genomic mechanism. LinkedOmics, NetworkAnalyst and Metascape were used to build the signaling network. TIMER is a web server for comprehensive analysis of tumor infiltrating immune cells and tumor infiltrating lymphocytes (TILs).

Results

The expression of ITGA3 in normal breast tissues was greater than that in breast cancer tissues at both the mRNA and protein levels. High expression of ITGA3 was associated with better prognosis of breast cancer patients. ROC analysis indicated that ITGA3 had significant diagnostic value. Genomic analysis revealed that promoter methylation of ITGA3 leads to transcriptional silencing, which may be one of the mechanisms underlying ITGA3 downregulation in BRCA. Immune infiltration analysis showed that ITGA3 may be involved in the recruitment of immune cells.

Conclusions

This study identified ITGA3 as a novel biomarker to estimate the diagnosis and prognosis of breast cancer. In addition, ITGA3 is involved in ECM regulation and immune cell infiltration.
The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer
Authors: Carlos-Escalante José A. , de Jesús-Sánchez Marcela , Rivas-Castro Alejandro , Pichardo-Rojas Pavel S. , Arce Claudia , Wegman-Ostrosky Talia
Published: May 2021

Cancer is a complex group of diseases that constitute the second largest cause of mortality worldwide. The development of new drugs for treating this disease is a long and costly process, from the discovery of the molecule through testing in phase III clinical trials, a process during which most candidate molecules fail. The use of drugs currently employed for the management of other diseases (drug repurposing) represents an alternative for developing new medical treatments. Repurposing existing drugs is, in principle, cheaper and faster than developing new drugs. Antihypertensive drugs, primarily belonging to the pharmacological categories of angiotensin-converting enzyme inhibitors, angiotensin II receptors, direct aldosterone antagonists, β-blockers and calcium channel blockers, are commonly prescribed and have well-known safety profiles. Additionally, some of these drugs have exhibited pharmacological properties useful for the treatment of cancer, rendering them candidates for drug repurposing. In this review, we examine the preclinical and clinical evidence for utilizing antihypertensive agents in the treatment of cancer.
Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy
Authors: Raskov Hans , Orhan Adile , Gaggar Shruti , Gögenur Ismail
Published: May 2021

Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell communication within the TME plays a pivotal role in the evolution and progression of cancer. Cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) are major cell populations in the stroma of all solid tumors and often exert protumorigenic functions; however, the origin and precise functions of CAF and TAM are still incompletely understood. CAF and TAM hold significant potential as therapeutic targets to improve outcomes in oncology when combined with existing therapies. The regulation of CAF/TAM communication and/or their differentiation could be of high impact for improving the future targeted treatment strategies. Nevertheless, there is much scope for research and innovation in this field with regards to the development of novel drugs. In this review, we elaborate on the current knowledge on CAF and TAM in cancer and cancer immunotherapy. Additionally, by focusing on their heterogenous functions in different stages and types of cancer, we explore their role as potential therapeutic targets and highlight certain aspects of their functions that need further research.
Advances in Biological Function and Clinical Application of Small Extracellular Vesicle Membrane Proteins
Authors: Huang Defa , Chen Jie , Hu Die , Xie Fangfang , Yang Tong , Li Zhengzhe , Wang Xiaoxing , Xiao Yongwei , Zhong Jianing , Jiang Yu , Zhang Xiaokang , Zhong Tianyu
Published: May 2021

Small extracellular vesicles are membrane-bound vesicles secreted into extracellular spaces by virtually all types of cells. These carry a large number of membrane proteins on their surface that are incorporated during their biogenesis in cells. The composition of the membrane proteins hence bears the signature of the cells from which they originate. Recent studies have suggested that the proteins on these small extracellular vesicles can serve as biomarkers and target proteins for the diagnosis and treatment of diseases. This article classifies small extracellular vesicle membrane proteins and summarizes their pathophysiological functions in the diagnosis and treatment of diseases.
Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia
Authors: Liu Fu-Jia , Cheng Wen-Yan , Lin Xiao-Jing , Wang Shi-Yang , Jiang Tian-Yi , Ma Ting-Ting , Zhu Yong-Mei , Shen Yang
Published: May 2021

The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two cycles of consolidation (n = 421). The latter time point was proved as a superior indicator with independent prognostic significance for both relapse-free survival (RFS, HR = 3.635, 95% CI: 2.433–5.431, P <0.001) and overall survival (OS: HR = 3.511, 95% CI: 2.191–5.626, P <0.001). Furthermore, several representative molecular MRD markers were compared with the MFC MRD. Both approaches can establish prognostic value in patients with NPM1 mutations, and FLT3, C-KIT, or N-RAS mutations involved in kinase-related signaling pathways, while the combination of both techniques further refined the risk stratification. The detection of RUNX1–RUNX1T1 fusion transcripts achieved a considerable net reclassification improvement in predicting the prognosis. Conversely, for patients with biallelic CEBPA or DNMT3A mutations, only the MFC method was recommended due to the poor prognostic discriminability in tracking mutant transcripts. In conclusion, this study demonstrated that the MFC MRD after two consolidation cycles independently predicted clinical outcomes, and the integration of MFC and molecular MRD should depend on different types of AML-related genetic lesions.
PSA Density Help to Identify Patients With Elevated PSA Due to Prostate Cancer Rather Than Intraprostatic Inflammation: A Prospective Single Center Study
Authors: Bruno Salvatore M. , Falagario Ugo G. , d’Altilia Nicola , Recchia Marco , Mancini Vito , Selvaggio Oscar , Sanguedolce Francesca , Del Giudice Francesco , Maggi Martina , Ferro Matteo , Porreca Angelo , Sciarra Alessandro , De Berardinis Ettore , Bettocchi Carlo , Busetto Gian Maria , Cormio Luigi , Carrieri Giuseppe
Published: May 2021

The association between PSA density, prostate cancer (PCa) and BPH is well established. The aim of the present study was to establish whether PSA density can be used as a reliable parameter to predict csPCa and to determine its optimal cutoff to exclude increased PSA levels due to intraprostatic inflammation. This is a large prospective single-center, observational study evaluating the role of PSA density in the discrimination between intraprostatic inflammation and clinically significant PCa (csPCa). Patients with PSA ≥ 4 ng/ml and/or positive digito-rectal examination (DRE) and scheduled for prostate biopsy were enrolled. Prostatic inflammation (PI) was assessed and graded using the Irani Scores. Multivariable binary logistic regression analysis was used to assess if PSA density was associated with clinically significant PCa (csPCa) rather than prostatic inflammation. A total of 1988 patients met the inclusion criteria. Any PCa and csPCa rates were 47% and 24% respectively. In the group without csPCa, patients with prostatic inflammation had a higher PSA (6.0 vs 5.0 ng/ml; p=0.0003), higher prostate volume (58 vs 52 cc; p<0.0001), were more likely to have a previous negative biopsy (29% vs 21%; p=0.0005) and a negative DRE (70% vs 65%; p=0.023) but no difference in PSA density (0.1 vs 0.11; p=0.2). Conversely in the group with csPCa, patients with prostatic inflammation had a higher prostate volume (43 vs 40 cc; p=0.007) but no difference in the other clinical parameters. At multivariable analysis adjusting for age, biopsy history, DRE and prostate volume, PSA density emerged as a strong predictor of csPCA but was not associated with prostatic inflammation. The optimal cutoffs of PSA density to diagnose csPCa and rule out the presence of prostatic inflammation in patients with an elevated PSA (>4 ng/ml) were 0.10 ng/ml2 in biopsy naïve patients and 0.15 ng/ml2 in patients with a previous negative biopsy. PSA density rather than PSA, should be used to evaluate patients at risk of prostate cancer who may need additional testing or prostate biopsy. This readily available parameter can potentially identify men who do not have PCa but have an elevated PSA secondary to benign conditions.
Maprotiline Suppresses Cholesterol Biosynthesis and Hepatocellular Carcinoma Progression Through Direct Targeting of CRABP1
Authors: Zheng Cancan , Zhu Yidong , Liu Qinwen , Luo Tingting , Xu Wenwen
Published: May 2021

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death and has a poor prognosis worldwide, thus, more effective drugs are urgently needed. In this article, a small molecule drug library composed of 1,056 approved medicines from the FDA was used to screen for anticancer drugs. The tetracyclic compound maprotiline, a highly selective noradrenergic reuptake blocker, has strong antidepressant efficacy. However, the anticancer effect of maprotiline remains unclear. Here, we investigated the anticancer potential of maprotiline in the HCC cell lines Huh7 and HepG2. We found that maprotiline not only significantly restrained cell proliferation, colony formation and metastasis in vitro but also exerted antitumor effects in vivo. In addition to the antitumor effect alone, maprotiline could also enhance the sensitivity of HCC cells to sorafenib. The depth studies revealed that maprotiline substantially decreased the phosphorylation of sterol regulatory element-binding protein 2 (SREBP2) through the ERK signaling pathway, which resulted in decreased cholesterol biosynthesis and eventually impeded HCC cell growth. Furthermore, we identified cellular retinoic acid binding protein 1 (CRABP1) as a direct target of maprotiline. In conclusion, our study provided the first evidence showing that maprotiline could attenuate cholesterol biosynthesis to inhibit the proliferation and metastasis of HCC cells through the ERK-SREBP2 signaling pathway by directly binding to CRABP1, which supports the strategy of repurposing maprotiline in the treatment of HCC.
Tunable Magnetic Fano Resonances on Au Nanosphere Dimer–Dielectric–Gold Film Sandwiched Structure
Authors: Gong Tianxun , Guan Fang , Wei Zhenjiang , Huang Wen , Zhang Xiaosheng
Published: May 2021

The Fano resonance demonstrates excellent performance due to its narrow asymmetrical spectral line shape, and its sensitivity to structure and material parameter changes. Compared to conventional Fano resonances, the Fano resonance generated by the magnetic dipole is more advantageous because of its high absorption and low loss. In this study, we propose an Au nanosphere dimer–dielectric–gold film sandwiched structure that supports the magnetic Fano resonance mode. And the Fano resonance can be efficiently tuned from visible to near-infrared wavelength by changing the size of the gold nanospheres and the thickness of the dielectric layer. Different from the single gold nanosphere–dielectric–film structure, the results suggest that the proposed structure is sensitive to the polarization direction of the excitation light. Considering the above characteristics, the proposed structure can be applied in multi-band sensing, surface-enhanced Raman spectroscopy, and dynamically adjustable optical switches.
Soybean Inoculated With One Bradyrhizobium Strain Isolated at Elevated [CO2] Show an Impaired C and N Metabolism When Grown at Ambient [CO2]
Authors: Soba David , Aranjuelo Iker , Gakière Bertrand , Gilard Françoise , Pérez-López Usue , Mena-Petite Amaia , Muñoz-Rueda Alberto , Lacuesta Maite , Sanz-Saez Alvaro
Published: May 2021

Soybean (Glycine max L.) future response to elevated [CO2] has been shown to differ when inoculated with B. japonicum strains isolated at ambient or elevated [CO2]. Plants, inoculated with three Bradyrhizobium strains isolated at different [CO2], were grown in chambers at current and elevated [CO2] (400 vs. 700 ppm). Together with nodule and leaf metabolomic profile, characterization of nodule N-fixation and exchange between organs were tested through 15N2-labeling analysis. Soybeans inoculated with SFJ14-36 strain (isolated at elevated [CO2]) showed a strong metabolic imbalance, at nodule and leaf levels when grown at ambient [CO2], probably due to an insufficient supply of N by nodules, as shown by 15N2-labeling. In nodules, due to shortage of photoassimilate, C may be diverted to aspartic acid instead of malate in order to improve the efficiency of the C source sustaining N2-fixation. In leaves, photorespiration and respiration were boosted at ambient [CO2] in plants inoculated with this strain. Additionally, free phytol, antioxidants, and fatty acid content could be indicate induced senescence due to oxidative stress and lack of nitrogen. Therefore, plants inoculated with Bradyrhizobium strain isolated at elevated [CO2] may have lost their capacity to form effective symbiosis at ambient [CO2] and that was translated at whole plant level through metabolic impairment.
SlTPL1 Silencing Induces Facultative Parthenocarpy in Tomato
Authors: He Mi , Song Shiwei , Zhu Xiaoyang , Lin Yuxiang , Pan Zanlin , Chen Lin , Chen Da , Hu Guojian , Huang Baowen , Chen Mengyi , Wu Caiyu , Chen Riyuan , Bouzayen Mondher , Zouine Mohammed , Hao Yanwei
Published: May 2021

Facultative parthenocarpy is of great practical value. However, the molecular mechanism underlying facultative parthenocarpy remains elusive. Transcriptional co-repressors (TPL) act as a central regulatory hub controlling all nine phytohormone pathways. Previously, we proved that SlTPLs participate in the auxin signaling pathway by interacting with auxin/indole acetic acid (Aux/IAAs) in tomato; however, their function in fruit development has not been studied. In addition to their high expression levels during flower development, the interaction between SlTPL1 and SlIAA9 stimulated the investigation of its functional significance via RNA interference (RNAi) technology, whereby the translation of a protein is prevented by selective degradation of its encoded mRNA. Down-regulation of SlTPL1 resulted in facultative parthenocarpy. Plants of SlTPL1-RNAi transgenic lines produced similar fruits which did not show any pleiotropic effects under normal conditions. However, they produced seedless fruits upon emasculation and under heat stress conditions. Furthermore, SlTPL1-RNAi flower buds contained higher levels of cytokinins and lower levels of abscisic acid. To reveal how SlTPL1 regulates facultative parthenocarpy, RNA-seq was performed to identify genes regulated by SlTPL1 in ovaries before and after fruit set. The results showed that down-regulation of SlTPL1 resulted in reduced expression levels of cytokinin metabolism-related genes, and all transcription factors such as MYB, CDF, and ERFs. Conversely, down-regulation of SlTPL1 induced the expression of genes related to cell wall and cytoskeleton organization. These data provide novel insights into the molecular mechanism of facultative tomato parthenocarpy and identify SlTPL1 as a key factor regulating these processes.
Temperament and School Readiness – A Literature Review
Authors: Potmesilova Petra , Potmesil Milon
Published: May 2021

This review study was conducted to describe how temperament is related to school readiness. The basic research question was whether there is any relationship between later school success and temperament in children and, if so, what characterizes it. A systematic search of databases and journals identified 27 papers that met the two criteria: temperament and school readiness. The analytical strategy followed the PRISMA method. The research confirmed the direct relationship between temperament and school readiness. There is a statistically significant relationship between temperament and school readiness. Both positive and negative emotionality influence behavior (especially concentration), which is reflected in the approach to learning and school success.
Regulatory Focus, Motivation, and Their Relationship With Creativity Among Adolescents
Authors: Wang Ling , Cui Yue , Wang Xinjing , Wang Jin , Du Kaiye , Luo Zheng
Published: May 2021

Due to the close relationship among intrinsic/extrinsic motivation, regulatory focus, and creativity revealed by previous literature, intrinsic/extrinsic motivation may play a mediating role between regulatory focus and creativity. Therefore, the present study aimed to investigate the relationship between regulatory focus and creativity by combining intrinsic/extrinsic motivation. In this study, senior high school students (n = 418) completed the Regulatory Focus Questionnaire, the Working Preference Inventory, the Williams Creativity Assessment Packet, and the Kirton Adaption–Innovation Inventory. The correlation analysis showed that both promotion and prevention focus positively correlated with intrinsic motivation; intrinsic motivation and promotion focus positively correlated with creativity personality and innovative-adaptive cognitive style; and extrinsic motivation and prevention focus negatively correlated with innovative–adaptive cognitive style. Furthermore, a path model showed that promotion focus positively predicted creativity through the mediation of intrinsic motivation. In general, our study suggests that intrinsic motivation plays a mediating role between promotion focus and creativity. Our results complement those of previous studies and serve as inspiration for the cultivation of creativity in classroom or enterprise settings.
Mental Health and Psychosocial Support During COVID-19: A Review of Health Guidelines in Sub-Saharan Africa
Authors: Molebatsi Keneilwe , Musindo Otsetswe , Ntlantsana Vuyokazi , Wambua Grace Nduku
Published: May 2021

The COVID-19 pandemic brought in its wake an unforeseen mental health crisis. The World Health Organization published a guideline as a way of supporting mental health and psychosocial well-being of different groups during this pandemic. The impact of the pandemic has pushed governments to put measures in place to curb not only the physical health of individuals but their mental health and psychosocial well-being as well. The aim of our paper was to review mental health guidelines of some Sub Saharan African (SSA) countries: (i) to assess their appropriateness for the immediate mental health needs at this time, (ii) to form as a basis for ongoing reflection as the current pandemic evolves. Guidelines were retrieved openly from internet search and some were requested from mental health practitioners in various SSA countries. The authors designed a semi structured questionnaire, as a self-interview guide to gain insight on the experience of COVID-19 from experts in the mental health sector in the various countries. While we used a document analysis approach to analyze the data, we made use of the Mental Health Preparedness and Action Framework to discuss our findings. We received health or mental health guidelines from 10 SSA countries. Cameroon, Kenya, South Africa, Tanzania, and Uganda all had mental health guidelines or mental health component in their health guidelines. Our experts highlight that the mental health needs of the people are of concern during this pandemic but have not been given priority. They go further to suggest that the mental health needs are slightly different during this time and requiring a different approach especially considering the measures taken to curb the spread of disease. We conclude that despite the provision of Mental Health and Psychosocial Support guidelines, gaps still exist making them inadequate to meet the mental health needs of their communities.
The Evaluation of Therapeutic Residential Care for Adolescents and Young Adults in France: A Systematic Review
Authors: Hirot France , Huas Caroline , Durand Damien , Godart Nathalie
Published: May 2021

Early psychosocial rehabilitation of young people presenting mental disorders is a major challenge. In France, the therapeutic residential care called “soins-études,” combining care and educational provision, in theFondation Santé des Etudiants de France(FSEF) can have a role in this rehabilitation. After recalling the history and the concept underpinningsoins-étudesin psychiatry, we performed a systematic review of the literature based on the PRISMA statementviaa search for quantitative studies onsoins-étudesfacilities. Eleven quantitative studies on 10 different samples of young people hospitalised in psychiatry in FSEF were identified between the opening of the first unit in 1956 and 2016. The young people involved were mostly aged 16–20 years, which reflects the curricula covered in the FSEF establishments. These young people generally presented severe chronic psychiatric disorders. Their previous care trajectory had lasted for more than 3 years and 24–55% of them had attempted suicide at least once. Their stays lasted more than 6 months. Depending on the severity of the disorders, 44–63% of the young people were considered to have improved at discharge. The contribution ofsoins-étudesappears valuable for these young people, since there was a clinical improvement for 54–74% of them 1–15 years after their hospitalisation, with resumption of schooling, professional training or entry into employment in 60–75% of the cases. These results are compared with data in the international literature concerning therapeutic residential care, and lines for future research are identified.
Relationship of Internalized Transnegativity and Protective Factors With Depression, Anxiety, Non-suicidal Self-Injury and Suicidal Tendency in Trans Populations: A Systematic Review
Authors: Inderbinen Marc , Schaefer Kristin , Schneeberger Andres , Gaab Jens , Garcia Nuñez David
Published: May 2021

Discrimination heavily impacts the lives of trans populations and causes adverse mental health outcomes. As stated by the Gender Minority Stress Model self-stigmatization could play an important role in this process. The aim of this systematic review is to investigate whether there is a positive association between self-stigmatization and mental health and to identify mediation factors. Studies which quantitatively investigated the association between internalized transnegativity and selected mental health outcomes (depression, anxiety, non-suicidal self-injury, suicidal tendency) in self-identified trans populations were included. Comprehensive search of 5 large databases in June 2020 and the following screening and selection procedure, performed by two researchers separately, identified 14 studies which met criteria. The relationship to be studied was reported with correlation and/or mediation analysis of cross-sectional data. IT was directly positively associated with depression, anxiety and suicidal tendency in most of the reviewed studies. Data indicates links between self-stigmatization and other general mental health stressors such as rumination and thwarted belongingness. Community connectedness showed to be the strongest protective factor for mental health impairments. These results should be considered in transition counseling. More research is needed to better understand the underlying mechanisms of the GMSM and to address unsolved operationalization and measurement issues.
Assessment of the Safety Signal for the Abuse Potential of Pregabalin and Gabapentin Using the FAERS Database and Big Data Search Analytics
Authors: Papazisis Georgios , Spachos Dimitrios , Siafis Spyridon , Pandria Niki , Deligianni Eleni , Tsakiridis Ioannis , Goulas Antonios
Published: May 2021

Introduction: The latest decade, an emerging issue has been the abuse potential of the gabapentinoids pregabalin and gabapentin. The aim of our study was to assess this safety signal combining two different methods of surveillance: search analytics big data and the FDA spontaneous reporting system database.

Methods: Analysis of big data and the FAERS was used to detect pregabalin's and gabapentin's abuse potential in comparison with two controls, clonazepam and levetiracetam, and further, the correlation between these domains was investigated. Data from the United States between 2007 and 2020Q2 were analyzed.

Results: The FAERS analysis revealed the following pattern of signals: clonazepam > pregabalin ≥ gabapentin > levetiracetam, for both the primary term “drug abuse and dependence” and the secondary terms (withdrawal, tolerance, overdose). The Google domain pattern was slightly different: clonazepam ≥ gabapentin ≥ pregabalin≥ levetiracetam. A monotonic correlation was found between FAERS and Google searches for gabapentin (r = 0.558; p < 0.001), pregabalin (r = 0.587; p < 0.001), and clonazepam (r = 0.295; p = 0.030).

Conclusion: Our results revealed that there is preliminary evidence of a safety signal for the abuse potential of pregabalin and gabapentin. Analysis of the FAERS database, supplemented by big data search analytics, suggests that there is potential of using these methods as a supplementary tool to detect drug abuse-related safety signals in pharmacovigilance.