Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical Mechanisms behind the Field‐Cycling Behavior of HfO2‐Based Ferroelectric Capacitors

Novel hafnium oxide (HfO2)‐based ferroelectrics reveal full scalability and complementary metal oxide semiconductor integratability compared to perovskite‐based ferroelectrics that are currently used in nonvolatile ferroelectric random access memories (FeRAMs). Within the lifetime of the device, two main regimes of wake‐up and fatigue can be identified. Up to now, the mechanisms behind these two device stages have not been revealed. Thus, the main scope of this study is an identification of the root cause for the increase of the remnant polarization during the wake‐up phase and subsequent polarization degradation with further cycling. Combining the comprehensive ferroelectric switching current experiments, Preisach density analysis, and transmission electron microscopy (TEM) study with compact and Technology Computer Aided Design (TCAD) modeling, it has been found out that during the wake‐up of the device no new defects are generated but the existing defects redistribute within the device. Furthermore, vacancy diffusion has been identified as the main cause for the phase transformation and consequent increase of the remnant polarization. Utilizing trap density spectroscopy for examining defect evolution with cycling of the device together with modeling of the degradation results in an understanding of the main mechanisms behind the evolution of the ferroelectric response.
Safety of Memantine in Combination with Potentially Interactive Drugs in the Real World: A Pharmacovigilance Study Using the Japanese Adverse Drug Event Report (JADER) Database

Background: Memantine, an NMDA receptor antagonist, is used for the treatment of Alzheimer’s disease. There is a caution to refrain from administrating memantine in combination with some specific drugs such as amantadine or dextromethorphan due to potential interactions that might augment the adverse effects of memantine. Objective: This notification has not been validated in real-world data, which we aim to address using a large self-reporting database from Japan. Methods: We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database reported between April 2004 and March 2019 for detecting the neuropsychiatric adverse event (AE) signals associated with memantine and other potentially interactive drugs including amantadine, dextromethorphan, cimetidine, ranitidine, procainamide, quinidine, acetazolamide, citrate, and bicarbonate. Drug-drug interactions between memantine and these drugs were assessed using multiplicative and additive models. Results: There was no statistically robust evidence to support multiplicative or additive interactions between memantine and the aforementioned drugs to increase the reporting of any included neuropsychiatric AEs or AE categories. Conclusion: The real-world JADER data did not raise the concern about the interactive increase in the neuropsychiatric AEs in patients with dementia taking memantine in combination with amantadine or dextromethorphan, suggesting there may be no urgent need to prohibit the co-administration of these drugs presently.
Exosomes released from mesenchymal stem cells overexpressing microRNA-30e ameliorate heart failure in rats with myocardial infarction.

AIM Bone marrow-derived mesenchymal stem cells (BMMSCs) exert cardioprotective effects on myocardial infarction (MI). In this investigation, we elucidated the protective effects of BMMSCs-exosomes (Exo) expressing microRNA-30e (miR-30e) against heart failure (HF) in MI rats. METHODS First, the differentially expressed miRNAs were analyzed using a miRNA-based microarray of MI. Subsequently, we overexpressed miR-30e in rat BMMSCs to isolate exosomes. A rat model with MI was developed and treated with Exo. Next, we examined the cardiac function of the rats, followed by the myocardial tissue extraction. HE, TUNEL and Masson's staining were used to assess the protective effects of exosomes against HF in rats. Subsequently, H9C2 cells exposed to OGD were further co-cultured with Exo. We used bioinformatics to predict the target mRNA of miR-30e and verified the binding relationship. Finally, we tested the expression and role of NF-κB p65/Caspase-9 signaling in myocardial tissues and cells. RESULTS miR-30e was poorly expressed in myocardial tissues of MI rats. Moreover, treatment of rats with Exo overexpressing miR-30e ameliorated pathological damage, cardiomyocyte apoptosis, and fibrosis in rat myocardial tissues. Furthermore, miR-30e negatively regulated LOX1 expression, which was overexpressed in the MI rats, but further Exo treatment inhibited LOX1 expression. Moreover, Exo overexpressing miR-30e impaired the NF-κB p65/Caspase-9 signaling in myocardial tissues of MI rats. The NF-κB p65/Caspase-9 signaling inhibitor repressed the apoptosis and fibrosis of cardiomyocytes as well. CONCLUSION Exosomal miR-30e from rat BMMSCs markedly inhibited LOX1 expression, thereby downregulating the activity of the NF-κB p65/Caspase-9 signaling and ameliorating HF after MI in rats.
Identification of 3D motifs based on sequences and structures for binding to CFI‐400945, and deep screening‐based design of new lead molecules for PLK‐4

PLK‐4 kinase plays an essential role in the cell cycle from regulating centriole duplication till cytokinesis and is therefore an attractive drug target in cancers such as breast, lung, and central nervous system tumors. CFI‐400945 is an efficient PLK‐4 inhibitor and inhibits other non‐PLK family proteins at nanomolar concentrations. We have compared PLK‐4 with other kinases to understand its similarity based on multiple sequence alignments from protein sequences of primary structures, outer and buried residues, and compact active site conservation based on three‐dimensional motifs. These in‐depth studies provide information on known interface targets and design of more selective inhibitors to PLK‐4. Further, pharmacophore features based on CFI‐400945 bound to PLK‐4 were used for searching library of compounds that were screened using deep learning methods to bind PLK‐4. The shortlisted molecules were docked into PLK‐4 active site and were validated using molecular docking and molecular dynamics simulations studies. MM‐PBSA calculations revealed the stability of hit molecules and PLK‐4 complexes in comparison with CFI‐400945 and the contribution to binding from key active site residues.
Taurolidine lock in the treatment of colonization and infection of totally implanted venous access devices in cancer patients

Background: Taurolidine lock is known to be effective in preventing catheter-related infections in a variety of venous access devices, including long term venous access devices for chemotherapy. Though, literature about the use of taurolidine for treating catheter colonization or catheter-related blood stream infection is scarce. Method: We have retrospectively reviewed the safety and efficacy of 2% taurolidine lock for treatment of catheter-colonization and of catheter-related bloodstream infection in cancer patients with totally implanted venous access devices. Diagnosis of colonization or catheter-related infection was based on paired peripheral and central blood cultures, according to the method of Delayed Time to Positivity. Results: We recorded 24 cases of catheter-related infection and two cases of colonization. Taurolidine lock—associated with systemic antibiotic therapy—was successful in treating all cases of catheter-related infection, with disappearance of clinical symptoms, normalization of laboratory values, and eventually negative blood cultures. Taurolidine lock was also safe and effective in treating device colonization. No adverse effect was reported. Conclusion: In our retrospective analysis, 2% taurolidine lock was completely safe and highly effective in the treatment of both catheter-colonization and catheter-related bloodstream infection in cancer patients with totally implanted venous access devices.
LncRNA BCAR4 expression predicts the clinical response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

BACKGROUND: Neoadjuvant chemotherapy (NAC) is an important treatment for locally advanced breast cancer (LABC). However, there are no effective biomarkers to predict the efficacy. Therefore, there is an urgent need for new biomarkers to predict the response of LABC to NAC. LncRNA BCAR4 has been detected in a variety of malignant tumor tissues and used as a new biomarker for diagnosis and prognosis. However, LncRNA BCAR4 predicts the response of LABC to NAC is unclear. OBJECTIVE: Explore the predictive effect of LncRNA BCAR4 on the efficacy of NAC for LABC in three different evaluation systems. METHODS: First, the TCGA database was used to analyze the expression of LncRNA BCAR4 in 33 kinds of malignant tumors, and further explore its expression in breast cancer and its impact on the survival and prognosis of breast cancer. Furthermore, quantitative methods were used to measure the expression level of LncRNA BCAR4 in cancer tissues of 48 LABC patients, and the correlation between LncRNA BCAR4 and clinicopathological status and response to NAC under the evaluation system of 3, RECIST1.1, Miller-Payne (MP) score and whether it reaches pCR,was analyzed. RESULTS: TCGA data analysis found that LncRNA is highly expressed in a variety of malignant tumor tissues, including breast cancer. And relatively low expression, the shorter the overall survival time of high expression patients. The high expression of LncRNA BCAR4 is related to the size of the tumor, and there are differences in expression between stage I and other stages, but there is no obvious correlation with the positive lymph node and hormone receptor status. Among the three evaluation systems, only in the RECIST 1.1 evaluation system LncRNA BCAR4 has a predictive effect on NAC for LABC. The expression of LncRNA BCAR4 has no significant correlation with clinical stage, Ki-67% and hormone receptor status, and has no significant correlation with whether patients with locally advanced breast cancer obtain pCR during neoadjuvant chemotherapy. CONCLUSION: LncRNA BCAR4 is highly expressed in LABC tissues and may be an effective marker for predicting the efficacy of NAC for LABC.
Investigation of the Effect of COVID-19 Perceived Risk on Death Anxiety, Satisfaction With Life, and Psychological Well-Being

This study aims to examine the effect of COVID-19 perceived risk on death anxiety, satisfaction with life, and psychological well-being. The application part of the research was conducted on staff working in a public hospital. A convenience sample of staff working in a public hospital was used and data were obtained from 573 individuals. The result of the analysis determined that the COVID-19 perceived risk explains 13.5% of the total variance on death anxiety. The regression models identified that the increase in COVID-19 risk perceptions of the participants statistically increased their death anxiety and decreased their satisfaction with life and psychological well-being.
Work-Related Risk Factors for Rotator Cuff Syndrome in a Prospective Study of Manufacturing and Healthcare Workers

Objective This prospective study assessed the risk of developing rotator cuff syndrome (RCS) with separate or specific combinations of biomechanical exposures measures, controlling for individual confounders. Background Compared with other musculoskeletal disorders, rates of work-related shoulder musculoskeletal disorders have been declining more slowly. Method We conducted up to 2 years of individual, annual assessments of covariates, exposures, and health outcomes for 393 U.S. manufacturing and healthcare workers without RCS at baseline. Task-level biomechanical exposures assessed exposure to forceful exertions (level, exertion rates, duty cycles), vibration, and upper arm postures (flexion, abduction). Hazard ratios (HRs) were calculated with Cox proportional hazard models. Results We observed 39 incident RCS cases in 694 person-years (incidence rate = 5.62 per 100 person-years). Adjusting for confounders, we found increased risk of incident RCS associated with forceful hand exertions per minute for three upper arm posture tertiles: flexion ≥45° (≥28.2% time, HR = 1.11, CI [1.01, 1.22]), abduction ≥30° (11.9–21.2%-time, HR = 1.18, CI [1.04, 1.34]), and abduction >60° (≥4.8% time, HR = 1.16, CI [1.04, 1.29]). We failed to observe statistically significant effects for other interactions or any separate measures of biomechanical exposure. Conclusion This study highlights the importance of assessing combinations of exposure to forceful repetition and upper arm elevation when developing interventions for preventing RCS. Application Based on these results, interventions that reduce exposure to forceful repetition (i.e., lower force levels and/or slower exertion rates) may reduce the risk of RCS, especially when upper arm elevation cannot be avoided.
Screening and bioinformatics analysis of cellular proteins interacting with chicken bromodomain-containing protein 2 in DF-1 cells

ABSTRACT 1. Bromodomain-containing protein 2 (BRD2) is an important member of the BET protein family, which can specifically bind histone acetylated lysine to participate in gene transcriptional regulation, chromatin remodelling, cell proliferation and apoptosis. The following investigation of cellular proteins interacting with chBRD2 will be helpful in understanding the new functions of chBRD2 and the mechanism of NDV replication. 2. The recombinant eukaryotic expression vector pEGFP-chBRD2 and empty vector pEGFP-C1 were transfected into DF-1 cells to overexpress GFP-chBRD2 and GFP, respectively. GO annotation, KEGG pathway, and protein-protein interaction network were used to analyse the cellular proteins interacting with chBRD2. In addition, one targeted protein was selected to verify its interaction with chBRD2 using fluorescent co-localisation and Co-IP. 3. A total of 225 cellular proteins were identified that potentially interact with chBRD2. GO analysis showed that these play key roles in gene transcriptional regulation, cell cycle and development, immunity and viral infection. Further KEGG pathway analysis showed that these proteins were mainly involved in genetic information processing, immune system, cellular processes and translation. In addition, one targeted cellular protein chicken matrin 3 (chMATR3) was also identified as chBRD2 complex using both fluorescence co-localisation and Co-IP analysis. 4. This study presents the interactome data of chBRD2 protein in DF-1 cells, which provides new information to understand the functions of chBRD2 and new targets for further investigating the replication and pathogenesis of NDV.
Novel variants of engineered water soluble mu opioid receptors with extensive mutations and removal of cysteines

We have shown that water‐soluble variants of the human mu opioid receptor (wsMOR) containing a reduced number of hydrophobic residues at the lipid‐facing residues of the transmembrane (TM) helices can be expressed in E. coli. In this study, we tested the consequences of increasing the number of mutations on the surface of the transmembrane domain on the receptor's aqueous solubility and ligand binding properties, along with mutation of 11 cysteine residues regardless of their solvent exposure value and location in the protein. We computationally engineered 10 different variants of MOR, and tested four of them for expression in E. coli. We found that all four variants were successfully expressed and could be purified in high quantities. The variants have alpha helical structural content similar to that of the native MOR, and they also display binding affinities for the MOR antagonist (naltrexone) similar to the wsMOR variants we engineered previously that contained many fewer mutations. Furthermore, for these full‐length variants, the helical content remains unchanged over a wide range of pH values (pH 6 ~ 9). This study demonstrates the flexibility and robustness of the water‐soluble MOR variants with respect to additional designed mutations in the TM domain and changes in pH, whereupon the protein's structural integrity and its ligand binding affinity are maintained. These variants of the full‐length MOR with less hydrophobic surface residues and less cysteines can be obtained in large amounts from expression in E. coli and can serve as novel tools to investigate structure‐function relationships of the receptor.
Diagnostic salivary biomarkers in oral cancer and oral potentially malignant disorders and their relationships to risk factors – A systematic review

ABSTRACT Introduction Oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) are a significant health burden globally. Smoking, alcohol, and betel quid are the main risk factors. Lack of screening methods has been highlighted as a significant challenge in management. Salivary biomarkers are proposed as noninvasive diagnostic tools. The aim of this systematic review was to study salivary biomarkers reported in OSCC and OPMD. Specific objectives were to select a salivary biomarker panel suitable for early detection of OSCC and OPMD and to assess relationships between salivary biomarkers and risk factors. Methods Electronic literature search was conducted in academic databases (Scopus, Medline, Embase and Web of Science) without any restrictions. Following calibration, two blinded reviewers screened the studies and extracted data. A risk of bias assessment was conducted using Newcastle Ottawa scale. 295 studies were included with descriptive data analysis. Expert opinion A salivary biomarker panel including Interleukin (IL) 1β, IL6, and IL8 was selected for OSCC and OPMD. Reported relationships between salivary biomarkers and risk factors are discussed and research gaps are highlighted. Future research should be directed to assess potential salivary biomarkers and their relationships to risk factors in order to understand the biomarker’s role in disease initiation.
Structural variability and dynamics in the ectodomain of an ancestral-type classical cadherin revealed by AFM imaging

ABSTRACT Type III cadherin represents the ancestral form of classical cadherin in bilaterian metazoans. Drosophila possesses type III and type IVa cadherins, known as DN- and DE-cadherins, respectively. Mature DN- and DE-cadherins have 15 and 7 extracellular cadherin domain (EC) repeats, respectively, with DN-cadherin EC6–EC11 homologous to DE-cadherin EC1–EC6. These EC repeats contain predicted complete or partial Ca2+-free inter-EC linkers that potentially contribute to adhesion. Comparative structure–function studies of DN- and DE-cadherins may help us understand the ancestral and derived states of classical cadherin-mediated adhesion mechanisms. Here, using bead aggregation assays, we found that DN-cadherin EC1–EC11 and DE-cadherin EC1–EC6 exhibit Ca2+-dependent adhesive properties. Using high-speed atomic force microscopy (HS-AFM) imaging in solution, we show that both DN- and DE-cadherin ectodomains share a common morphological framework consisting of a strand-like and a globule-like portion. Furthermore, the DN-cadherin EC repeats are highly variable, flexible in morphology and have at least three bendable sites, one of which is located in EC6–EC11 and can act as a flexible hinge. Our findings provide insights into diversification of classical cadherin-mediated adhesion mechanisms. This article has an associated First Person interview with the first author of the paper.
Past Levels of Mental Health Intervention and Current Nondisclosure of Suicide Risk Among Men Older Than Age 50

Suicide risk screening depends heavily on accurate patient self-report. However, past negative experiences with mental health care may contribute to intentional nondisclosure of suicide risk during screening. This study investigated among 282 men older than age 50 whether likelihood for current explicit risk nondisclosure was associated with previous highest level of mental health care received. This sample was selected post hoc out of a larger sample of participants from higher risk and lower help-seeking populations (i.e., military service members and veterans, men older than age 50, and lesbian gay bisexual, transgender, and queer young adults), however, the other groups were underpowered for analysis. Among these men, history of psychiatric hospitalization was significantly associated with likelihood for explicit nondisclosure of current suicide risk, while history of receiving only outpatient therapy for suicidal thoughts or behaviors was significantly associated with likelihood for full reporting of suicide risk. Severity of suicidal ideation and internalized stigma against mental illness were significant indirect contributors to the effect. Although causality could not be determined, results suggest that a potential cost to consider for psychiatric hospitalization may be future nondisclosure of suicide risk. Conversely, outpatient interventions that appropriately manage suicidal thoughts or behaviors may encourage future full reporting of suicide risk and improve screening detection.
Clinical and neuroimaging findings in MOGAD–MRI and OCT

Myelin oligodendrocyte glycoprotein antibody‐associated disorders (MOGAD) are rare in both children and adults, and have been recently suggested to be an autoimmune neuroinflammatory group of disorders that are different from aquaporin‐4 autoantibody‐associated neuromyelitis optica spectrum disorder and from classic multiple sclerosis. In‐vivo imaging of the MOGAD patient central nervous system has shown some distinguishing features when evaluating magnetic resonance imaging of the brain, spinal cord and optic nerves, as well as retinal imaging using optical coherence tomography. In this review, we discuss key clinical and neuroimaging characteristics of paediatric and adult MOGAD. We describe how these imaging techniques may be used to study this group of disorders and discuss how image analysis methods have led to recent insights for consideration in future studies.
Application value of UPLC-MS/MS in detecting serum concentration of anti-schizophrenic drugs in patients with mental illnes.

OBJECTIVE This study was designed to demonstrate the accuracy of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in detecting serum concentration of anti-schizophrenic drugs in patients with mental illness. METHODS The study participants were 186 schizophrenia patients treated in our hospital. Serum concentrations of anti-schizophrenic drugs in Chinese patients with mental illness were evaluated according to the reference intervals of drug therapy recommended in the guidelines. RESULTS Five drugs, namely Aripiprazole (ARI), Amisulpride (AMI), Olanzapine (OLA), Paliperidone (PAL) and Ziprasidone (ZIP) all showed good linearity within the linear range. The within-day precision of the above five drugs was all between 1.3%-8.9% and the inter-day precision was between 1.8%-7.6%, with within-day and inter-day relative standard deviations (RSDs) less than 15.00% and accuracy ranging from 87.00% to 106.73%. However, AMI had a mean blood concentration of 436.31±241.05 ng/mL (median concentration: 379.34 ng/mL), which was significantly higher than the reference range (100-320 ng/mL) recommended in the guidelines. Good recovery rates (86.21%-99.77%) were obtained after the samples were stored at room temperature for 24 h, at 4°C for 48h and at -20°C for half a year. CONCLUSIONS Given that UPLC-MS/MS renders more accurate results in detecting the concentration of psychotropic drugs, it can be applied clinically to detect the concentration of therapeutic drugs in patients with mental illness.