Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of 2-Aminoquinazolin-4-(3H)-one Derivatives as Potent Inhibitors of SARS-CoV-2: Improved Synthesis and Pharmacokinetic Properties

We previously reported the potent antiviral effect of the 2-aminoquinazolin-4-(3H)-one 1, which shows significant activity (IC50 = 0.23 μM) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with no cytotoxicity. However, it is necessary to improve the in vivo pharmacokinetics of compound 1 because its area under the curve (AUC) and maximum plasma concentration are low. Here, we designed and synthesized N-substituted quinazolinone derivatives that had good pharmacokinetics and that retained their inhibitory activity against SARS-CoV-2. These compounds were conveniently prepared on a large scale through a one-pot reaction using Dimroth rearrangement as a key step. The synthesized compounds showed potent inhibitory activity, low binding to hERG channels, and good microsomal stability. In vivo pharmacokinetic studies showed that compound 2b had the highest exposure (AUC24h = 41.57 μg∙h/mL) of the synthesized compounds. An in vivo single-dose toxicity evaluation of compound 2b at 250 and 500 mg/kg in rats resulted in no deaths and an approximate lethal dose greater than 500 mg/kg. This study shows that N-acetyl 2-aminoquinazolin-4-(3H)-one 2b is a promising lead compound for developing anti-SARS-CoV-2 agents.
Experimental Study on the Potential of nLDMOSFETs with Partial Drain Slit Structure

It is well-known that a drain multi-finger STI nLDMOSFET structure in which an STI section and a silicon surface section in the drift region are repeated in the channel width direction can improve the specific on-resistance (Rsp) versus the off-state breakdown voltage (BVoff) trade-off. However, an nLDMOSFET to which this structure is applied is not suitable for high BVoff (> 50 V) because it is difficult to relax the electric field at both sides of the drain silicon slit and at the channel side edge of the silicon slit. To overcome the first drawback, it is proposed to incorporate an STI section without silicon slits into the drain side region (partial drain slit structure) in this paper. The gate polysilicon cutout structure on an accumulation region is also proposed to overcome the second drawback.
When Does CSR Fail to Incentive Employees’ Affective Organizational Commitment? Exploring the Moderating Effects Based on the C-S-R Concerns Model

Corporate social responsibility (CSR) is a strategy employed to engage stakeholders. Prior studies explored the different mechanisms by which employees, as one of an organization’s biggest stakeholder groups, positively respond to organizational CSR behavior. However, limited attention has been paid to the conditional boundaries when employees’ positive responses are stronger or weaker, overlooking the possibility that sometimes CSR fails to obtain employees’ support. The study employed the “C-S-R concerns” model to systematically investigate how caring-based (i.e., moral identity), self-based (i.e., corporate ability), and relational-based (i.e., importance of CSR) factors moderate the relationship between perceived CSR (PCSR) and affective organizational commitment (AOC). Using data collected from 326 employees in the Chinese high-tech industry, we found that the positive effects of employees’ PCSR on their AOC becomes negative when employees have higher levels of moral identity, when their organizations are perceived as having greater ability, and when CSR is perceived as more important to the success of their organization. The findings advance our understanding of the inconclusive impacts of CSR on firm performance by providing micro-level evidence from employees. This also provides practical implications for managers about how to select employees, set CSR strategies and cultivate organizational cultures.
Exploratory examination of environmental protection behaviors in a hospital setting using the theory of planned behavior and ethical leadership

Most research focused on understanding the general environmental awareness or attitudes around the world, targeting residents, students, or undergraduates. There were limited attempts to understand the environmental protection behaviors in Taiwan healthcare sector. A questionnaire survey was designed with current healthcare personnel in Taiwan as target population. From the theory of planned behavior and ethical leadership, structural equation modelling allowed a better explanation of the social-psychological indicators affecting environmental protection behaviors in the healthcare sector. Attitude, subjective norms and perceived behavioral control are positively impacted by ethical leadership. Environmental protection behavior is significantly influenced by environmental protection intention, while environmental protection intention is strongly affected by perceived behavioral control which is the strongest predictor, followed by attitude. However, there is insignificant correlation of subjective norms to environmental protection intention, due to the weaken social connection among healthcare personals, especially with the heavily burdened workload and restrictive measure during the COVID-19 crisis in a hospital environment.
Docetaxel remodels prostate cancer immune microenvironment and enhances checkpoint inhibitor-based immunotherapy

Background: Prostate cancer is usually considered as immune “cold” tumor with poor immunogenic response and low density of tumor-infiltrating immune cells, highlighting the need to explore clinically actionable strategies to sensitize prostate cancer to immunotherapy. In this study, we investigated whether docetaxel-based chemohormonal therapy induces immunologic changes and potentiates checkpoint blockade immunotherapy in prostate cancer. Methods: We performed transcriptome and histopathology analysis to characterize the changes of prostate cancer immune microenvironment before and after docetaxel-based chemohormonal therapy. Furthermore, we investigated the therapeutic benefits and underlying mechanisms of chemohormonal therapy combined with anti-PD1 blockade using cellular experiments and xenograft prostate cancer models. Finally, we performed a retrospective cohort analysis to evaluate the antitumor efficacy of anti-PD1 blockade alone or in combination with docetaxel-based chemotherapy. Results: Histopathology assessments on patient samples confirmed the enrichment of tumor-infiltrating T cells after chemohormonal therapy. Moreover, we found that docetaxel activated the cGAS/STING pathway in prostate cancer, subsequently induced IFN signaling, resulting in lymphocytes infiltration. In a xenograft mouse model, docetaxel-based chemohormonal therapy prompted the intratumoral infiltration of T cells and upregulated the abundance of PD1 and PD-L1, thereby sensitizing mouse tumors to the anti-PD1 blockade. To determine the clinical significance of these results, we retrospectively analyzed a cohort of 30 metastatic castration-resistant prostate cancer patients and found that docetaxel combined with anti-PD1 blockade resulted in better prostate-specific antigen progression-free survival when compared with anti-PD1 blockade alone. Conclusions: Our study demonstrates that docetaxel activates the antitumoral immune response and facilitates T cell infiltration in a cGAS/STING-dependent manner, providing a combination immunotherapy strategy that would improve the clinical benefits of immunotherapy.
Front to Back Ratio Improvement using Higher Order Mode in Substrate Integrated Coaxial Line (SICL) Based Cavity Backed Slot Antenna

This paper presents step by step novel technique to improve the Front to Back Ratio (FTBR) of Substrate Integrated Coaxial Line (SICL) based cavity backed slot antenna (CBSA). The design consists of three linear 45° inclined slot etched on the bottom plate of cavity. The proposed slot configuration excites ${\text{TE}}_{110(odd)}^z$ mode which helps the proposed three λg/4 slots to radiate in a unique way such that a higher order mode $\operatorname{TE} _{110(odd)}^z$ is excited and the surface current is disturbed by the proposed slot configuration which results in electromagnetic radiations. The novelty of the work lies in exciting the slot antenna with new higher order cavity mode to get better FTBR. The proposed antenna exhibits measured FTBR of 25 dB and gain of 4.2 dBi with co-pol to cross-pol ratio of 17 dB. This novel method is the simplest known low profile technique that efficiently utilizes SICL cavity modes to improve FTBR while maintaining compactness of the antenna design.
Complementing preregistered confirmatory analyses with rigorous, reproducible exploration using machine learning

The Many-Analysts Religion Project illustrates how researcher degrees of freedom cause one research question to be analyzed in many di ﬀ erent ways (Hoogeveen et al., 2022). Each submission showcases a di ﬀ erent perspective on “ best practices. ” My submission (Team #067, https://osf.io/ n4jcf/) illustrates two practices I consider important: First, how the Work ﬂ ow for Open Reproducible Code in Science can be used to create a fully reproducible paper and an unambiguous prere-gistration (WORCS, Van Lissa et al., 2021). Second, how rigorous exploration can complement con ﬁ rmatory (hypothesis-testing) research, even in a preregistered study. WORCS is a conceptual work ﬂ ow based on three principles: (1) writing papers as dynamic documents that combine prose and analysis code and can be reproduced with a single click; (2) using version control to track every change to the project since its inception; and (3) managing dependencies, which means documenting all software required to reproduce the project. These principles
THE LEGAL IMPACT OF COVID-19 ON SMALL AND MEDIUM-SIZED ENTERPRISES (SMEs) IN MALAYSIA

The COVID-19 pandemic has impulsively posed new challenges to many businesses and companies around the globe due to travel and business restrictions. COVID-19 which has been declared a pandemic by the World Health Organization (WHO) on the 11th of March 2020, which originated from Wuhan City, the People’s Republic of China has consequently crashed the downtime of the economy in Malaysia and caused a significant impact on the Small-to-Medium Enterprises (SMEs) business operation. The present study employs a mixed methodology, which includes an analysis of primary and secondary legal sources, and a questionnaires survey. The aim of this research is to identify the legal impacts on SMEs due to the COVID-19 pandemic influences on a business operation which will further assist policymakers to develop actionable policies and support the growth of SMEs in Malaysia. The government should be transparent in disseminating the post-COVID-19 data because it can be a thrust for the SMEs in planning their future agenda to “bounce back” the economic sectors effectively.
1-Dimensional Convolutional Neural Network Based Blood Pressure Estimation with Photo plethysmography Signals and Semi-Classical Signal Analysis

In this paper, we propose a 1-Dimensional Convolutional Neural Network (1D-CNN) based Blood Pressure (BP) estimation using Photo plethysmography (PPG) signals and their features obtained through Semi-classical Signal Analysis (SCSA). The procedure of the proposed BP estimation technique is as follows. First, PPG signals are divided into each beat. Then, 9 features are obtained through SCSA for the divided beats. In addition, 5 biometric data are used. The Biometrics data include Heart Rate (HR), age, sex, height, and weight. The total 14 features are used for training and validating the 1D-CNN BP estimation model. After testing three types of 1D-CNNs, the model with the most optimal performance is selected. The selected model structure consists of three convolutional layers and one fully connected layer. The performance is measured by Mean Error (ME) ± Standard Deviation (STD) following the Association for the Advancement of Medical Instrumentation (AAMI) standard. According to the results of the test, Systolic Blood Pressure (SBP) is -2.99±14.48 mmHg and Diastolic Blood Pressure (DBP) is 1.16±9.30 mmHg. Using the proposed technique, blood pressure can be easily predicted using PPG obtained with a non-invasive and cuff-less wearable sensor.
An Ultra-broadband and Low Noise distributed Drain Mixer with Filtering Structure

This paper presents a 6 to 64 GHz passive distributed drain mixer implemented by using a standard 0.13 um CMOS process. To improve the bandwidth, low conversion loss and low noise figure, filtering structures is utilized for wideband matching. Both Chebyshev and Butterworth filters are used instead of the classical constant-k sections of the conventional DA in order to form respectively the gate and drain transmission lines. This mixer consumes zero dc power and exhibits a conversion loss of 4.9-7.9 dB and noise figure (DSB) of 6.8-8.1 dB from 6 to 64 GHz.
Thermal Spray Technology Growth in Gas Turbine Coatings

For many years coatings have been successfully applied to aerospace engine components to improve life and performance. The key success areas have been in thermal barrier coatings, clearance control, oxidation/hot corrosion and wear coatings. Today, design engineers in the industrial gas turbine sector have leveraged the “aerospace” technology into the power generation industry. This paper gives a general overview of key coatings used in the compressor and turbine sections. Design requirements will be reviewed and compared between aerospace and power generation coatings. Application process improvement areas will also be discussed as a method of reducing component cost. Therefore, the total solution will be more reproducible, cost effective coatings that add value. This will result in engineered components that operate at higher temperatures and/or last for longer periods of time.
Comparison of Endodontic Failures between Nonsurgical Retreatment and Endodontic Surgery: Systematic Review and Meta-Analysis with Trial Sequential Analysis

Background and Objectives: In the presence of a persistent endodontic lesion or endodontic failure, the alternative for the recovery of the dental element is endodontic retreatment or endodontic surgery, which consists in the surgical removal of the root apices with retrograde closure of the endodontium. The objective of this systematic review and meta-analysis was to provide an updated value of the Risk Ratio between the two types of treatment in order to offer to clinicians who propose a non-surgical endodontic retreatment or an endodontic surgery a direct comparison. Materials and Methods: The revision was performed according to PRISMA indications: three databases (PubMed, Scopus and Cochrane register) were consulted through the use of keywords relevant to the revision topic: surgical endodontic retreatment, endodontic retreatment, apicoectomy. This search produced 7568 records which, after eliminating duplicates and applying the inclusion and exclusion criteria, resulted in a total of seven included articles. The meta-analyses were conducted by applying fixed-effects models, given the low percentage of heterogeneity. In addition, trial sequency analysis (TSA) was performed for the analysis of the statistical power of the results and GRADE for the quality of the evidence. Results: The results of the meta-analyses’ data report an aggregate risk ratio (RR) between non-surgical endodontic retreatment and surgical endodontic retreatment of: 1.05 [0.74, 1.47] at one year of follow-up; RR 2.22 [1.45, 3.41] at two years of follow-up; an RR 1.08 [0.73 1.62] for a follow-up period of 3–4 years; and an RR 0.92 [0.53, 1.61] for a follow-up period of 8–10 years. Conclusions: The results of the present meta-analysis show that in the long term, the risk of failure is identical for the two groups, and there is only a slightly higher risk of failure for non-surgical endodontic retreatments, when only two years of follow-up are considered.
Extracellular vesicles as bioactive nanotherapeutics: An emerging paradigm for regenerative medicine

In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis and tissue repair, have emerged as one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review of the latest progress of EVs for regenerative applications. Firstly, we will briefly introduce the biogenesis, function and isolation technology of EVs. Then, the underlying therapeutic mechanisms of the native unmodified EVs and engineering strategies of the modified EVs as regenerative entities will be discussed. Subsequently, the main focus will be placed on the tissue repair and regeneration applications of EVs on various organs including brain, heart, bone and cartilage, liver and kidney, as well as skin. More importantly, current clinical trials of EVs for regenerative medicine will also be briefly highlighted. Finally, the future challenges and insightful perspectives of the currently developed EV-based nanotherapeutics in biomedicine will be discussed. In short, the bioactive EV-based nanotherapeutics have opened new horizons for biologists, chemists, nanoscientists, pharmacists, as well as clinicians, making possible powerful tools and therapies for regenerative medicine.
Evolution of the ADHD concept and its relation to the hyperkinetic disorders: Narrative review

Porucha pozornosti s hyperaktivitou (ADHD) je unikátní poruchou. Většinou se rozvine v raném dětství a v 50 % případů přerůstá v celoživotní poruchu, což přináší významné výzvy pro výzkumníky i odborníky v praxi. Nová kritéria vytvořená Světovou zdravotnickou organizací spojila kategorie hyperkinetických poruch a ADHD. Cílem této narativní přehledové studie bylo prozkoumat a usnadnit osvojení konceptu ADHD odborníky a výzkumníky, kteří byli zvyklí pracovat s hyperkinetickými poruchami. 1) Byla analyzována evoluce konceptu ADHD od jeho ustanovení ve 3. edici Diagnostického a statistického manuálu duševních poruch (DSM-III) až po DSM-5;2) byly porovnány současné koncepty ADHD v DSM-5 a hyperkinetické poruchy v Mezinárodní statistické klasifikaci nemocí a přidružených zdravotních problémů (MKN-10);a 3) byly popsány některé nové výzvy, kterým může koncept ADHD čelit v budoucnosti. Prozkoumány byly dimenze a struktura konceptu včetně potenciálních nových symptomů, jako jsou například emocionální dysregulace a tzv. mind wandering. Před- staveny byly také dospělé prezentace symptomů hyperaktivity, impulzivity a nepozornosti. Autoři se dotkli také nedávných výzev spojených s globální pandemií covid-19. Závěrem lze konstatovat, že koncept ADHD se od svého vzniku významně zlepšil. Ve vědeckém výzkumu zabývajícím se ADHD by však měla být více zohledněna psycho-bio-sociální perspektiva.Alternate :Attention Deficit Hyperactivity Disorder (ADHD) is a unique disorder. It usually develops in early childhood and, in 50% of cases, continues to be a lifelong disorder, which poses significant challenges for researchers and cians. The criteria set by the World Health Organization merged the category of Hyperkinetic Disorders and the ADHD category. This narrative review aims to explore and ease the adoption of the ADHD concept for clinicians and researchers who were used to working with Hyperkinetic Disorders by (1) analyzing the evolution of the ADHD concept from its establishment in the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition (DSM-III) until DSM-5;(2) comparing the contemporary concepts of ADHD in DSM-5 and Hyperkinetic Disorders in International Statistical Classification of Diseases and Related Health Problems (ICD-10);and (3) describing some new challenges the ADHD concept will face in the future. The structure and the dimensions of the concept are explored, including some possible new core symptoms such as emotional dysregulation and mind wandering. Adult presentations of symptoms of hyperactivity, impulsivity, and inattention are presented. The recent challenges of the global pandemic of covid-19 are also addressed. In conclusion, the concept of ADHD has been dramatically improved since its establishment. However, the bio-psycho-social perspective needs to be better balanced in ADHD-related science.
Emerging Optoelectronic Devices Based on Microscale LEDs and Their Use as Implantable Biomedical Applications

Thin-film microscale light-emitting diodes (LEDs) are efficient light sources and their integrated applications offer robust capabilities and potential strategies in biomedical science. By leveraging innovations in the design of optoelectronic semiconductor structures, advanced fabrication techniques, biocompatible encapsulation, remote control circuits, wireless power supply strategies, etc., these emerging applications provide implantable probes that differ from conventional tethering techniques such as optical fibers. This review introduces the recent advancements of thin-film microscale LEDs for biomedical applications, covering the device lift-off and transfer printing fabrication processes and the representative biomedical applications for light stimulation, therapy, and photometric biosensing. Wireless power delivery systems have been outlined and discussed to facilitate the operation of implantable probes. With such wireless, battery-free, and minimally invasive implantable light-source probes, these biomedical applications offer excellent opportunities and instruments for both biomedical sciences research and clinical diagnosis and therapy.
UBR5 promotes tumor immune evasion through enhancing IFN-γ-induced PDL1 transcription in triple negative breast cancer

Background: The up-regulation of PD-L1 is recognized as an adaption of cancer cells to evade immune surveillance and attack. However, the intrinsic mechanisms of the induction of PD-L1 by interferon-γ (IFN-γ) in tumor microenvironment remain incompletely characterized. Ubiquitin ligase E3 component N-recognition protein 5 (UBR5) has a critical role in tumorigenesis of triple negative breast cancer (TNBC) by triggering specific immune responses to the tumor. Dual targeting of UBR5 and PD-L1 exhibited superior therapeutic benefits in a preclinical TNBC model in short term. Methods: The regulation of UBR5 to PD-L1 upon IFN-γ stimulation was evaluated through in UBR5 deficiency, reconstitution or overexpression cell line models by quantitative PCR, immunohistochemistry and RNA-seq. The effects of PD-L1 regulation by UBR5 and double blockade of both genes were evaluated in mouse TNBC model. Luciferase reporter assay, chromatin immunoprecipitation-qPCR and bioinformatics analysis were performed to explore the transcription factors involved in the regulation of UBR5 to PD-L1. Results: E3 ubiquitin ligase UBR5 plays a key role in IFN-γ-induced PDL1 transcription in TNBC in an E3 ubiquitination activity-independent manner. RNA-seq-based transcriptomic analyses reveal that UBR5 globally affects the genes in the IFN-γ-induced signaling pathway. Through its poly adenylate binding (PABC) domain, UBR5 enhances the transactivation of PDL1 by upregulating protein kinase RNA-activated (PKR), and PKR's downstream factors including signal transducers and activators of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF1). Restoration of PD-L1 expression in UBR5-deficient tumor cells recoups their malignancy in vivo, whereas CRISPR/Cas9-mediated simultaneous abrogation of UBR5 and PD-L1 expression yields synergistic therapeutic benefits than either blockade alone, with a strong impact on the tumor microenvironment. Conclusions: This study identifies a novel regulator of PDL1 transcription, elucidates the underlying molecular mechanisms and provides a strong rationale for combination cancer immunotherapies targeting UBR5 and PD-L1.