Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between vaginal microecological changes and oncogene E6/E7 and high-risk human papillomavirus infection

Abstract High-risk (HR)-human papillomavirus (HPV) is the leading cause of precancerous cervical lesions in patients with chronic untreated infection. We investigated the relationships among several vaginal microbiological alterations, oncogene E6/E7 expression, and HR-HPV. A total of 1327 women who underwent HPV screening, vaginal microecology determination, and fluid-based thin-layer cytological test were enrolled and classified into the HPV-negative group, the low-risk (LR)-HPV-positive group, and the HR-HPV-positive group. The status of cervical HPV infection, vaginal microecology, and E6/E7 mRNA expression were examined sequentially. The effect of HR-HPV infection on cervical cancer (CC) was meticulously assessed, and associations between HR-HPV infection and vaginal microecology and E6/E7 mRNA were identified. In total 548/1327 patients were HPV positive, including LR-HPV infection (N = 132) and HR-HPV infection (N = 416). Patients in the HR-HPV positive group revealed higher detection rates of bacterial vaginosis (BV), trichomonal vaginitis (TV), and vulvovaginal candidiasis (VVC) relative to the HPV negative group. A higher E6/E7 mRNA expression was identified in HR-HPV patients compared to LR-HPV patients. BV and E6/E7 mRNA were classified as independent risk factors for HR-HPV infection. Patients with HR-HPV infection were more susceptible to CC development. Overall, BV and E6/E7 mRNA expression were identified as independent risk factors for HR-HPV infection. IMPACT STATEMENT What is already known on this subject? Through literature review, we found that vaginal ecological changes increase the risk of HPV infection, and HPV persistent infection is an important risk factor for cervical precancerous lesions and cervical cancer. In addition, HPV gene E6/E7 is expressed in HPV-positive cervical cancer cells, which is related to cell malignant transformation and even tumorigenesis. What do the results of this study add? This study further revealed that bacterial vaginosis (BV) and E6/E7 mRNA were independently correlated with HR-HPV infection, and HR-HPV infection increased the risk of cervical cancer. What are the implications of these findings for clinical practice and/or further research? E6/E7 mRNA detection may be used as a new auxiliary diagnostic index for HR-HPV infection. In addition, this study provides a reference for whether the restoration of vaginal microecological balance in patients with BV undergoing clinical treatment is conducive to HR-HPV regression, and provides theoretical support for the prevention and control of cervical cancer microecological approach and the occurrence and development of cervical cancer.
Potential plasma microRNAs signature miR-190b-5p, miR-215-5p and miR-527 as non-invasive biomarkers for prostate cancer

Abstract Background Prostate cancer (PCa) is the most prevalent (20%) pathological cancer among males globally. MicroRNAs (miRNAs) are short (19–22 nucleotide), conserved, noncoding molecules that regulate post-transcriptional processes either by repressing or degrading mRNA or by translation inhibition binding to complementary sites on mRNA. The goal of this study was to find out whether differentially expressed microRNA (DEM) could be used as a potential marker in the prognosis and diagnosis of PCa. Methodology The miRNAs profiling was done both from plasma and tissue samples of the same PCa patient (n = 3) by real-time quantitative PCR (qRT-PCR) and compared with BPH (benign prostatic hyperplasia) patients (n = 3) as controls and further validation of selected miRNAs. Results We found 55 significant overexpressed DEMs, 44 significant underexpressed DEMs in plasma and 6 significant overexpressed DEMs, 27 significant underexpressed DEMs in tissue compared between PCa and BPH. Furthermore, there were eight miRNAs namely miR-190b, miR-215, miR-300, miR-329, miR-504, miR-525-3p, miR-527, miR-548a-3p found to be significantly differentially expressed in plasma and tissue samples via profiling, however only three showed concordant expression. After validation, miR-190b-5p were shown to be significantly downexpressed with fold changes of 0.4177 (p value – 0.0072) and 0.7264 (p value – 0.0143) in plasma and tissue samples, respectively. The expression of miR-215-5p was shown to be significantly overexpressed with fold change of 1.820 (p – 0.0016) and 1.476 (p – 0.0407) in plasma and tissue samples, respectively. Furthermore, miR-527 was shown to be significantly downexpressed with fold changes of 0.6018 (p – 0.0095) and 0.6917 (p – 0.0155) in plasma and tissue samples, respectively. Conclusion According to our findings, plasma miR-190b-5p, miR-215-5p, miR-527 levels alteration is consistently linked with PCa tissue. For establishing significant miRNAs as biomarkers, additional research of a larger population is needed.
Investigation of IL-35 and IL-39, New Members of the IL-12 Family, in Different Clinical Presentations of Brucellosis

ABSTRACT Brucellosis is significantly influenced by the interactions between the causative Brucella bacteria and host immunity. Recently identified cytokines have been described for their immunomodulatory effects in numerous inflammatory, autoimmune and infectious diseases. Some of them are new members of cytokine superfamilies, including several members of the IL-12 superfamily (IL-35, IL-39). The major purpose of the present study was to investigate the role of these new immunomodulatory cytokines in Brucella infections. The levels of IL-35 and IL-39 in the serum of 40 acute and 40 chronic brucellosis patients and 40 healthy controls were measured by ELISA. The mRNA levels of IL-35 and IL-39 in PBMCs were detected by RT-qPCR. Both IL-35 and IL-39 serum concentrations were significantly higher in healthy control subjects than in brucellosis patients, and IL-35 and IL-39 serum levels of chronic brucellosis patients were higher than those of acute cases. It was also found that the expression of Ebi3/IL-12A (IL-35 genes) and Ebi3/IL-23A (IL-39 genes) was upregulated in chronic brucellosis patients compared to healthy controls. Moreover, the expression of the Ebi3/IL-12A and Ebi3/IL-23A genes was lower in patients with acute brucellosis than in patients with chronic brucellosis. Overall, this study showed that IL-35 and IL-39 are positively correlated in brucellosis and significantly decreased during the disease. Significantly lower levels of IL-35 and IL-39 in acute brucellosis than in chronic brucellosis and healthy controls suggest that these cytokines may play a key role in suppressing the immune response to brucellosis and its progression to chronicity. HIGHLIGHTS IL-35 and IL-39, new members of the IL-12 cytokine family, are immunomodulatory cytokines characterized as anti-inflammatory and pro-inflammatory, respectively. In acute and chronic brucellosis, serum IL-35 and IL-39 are significantly decreased. In acute brucellosis, serum IL-35 are significantly lower than in chronic brucellosis, suggesting that this cytokine may play a role in chronification. A positive correlation was found between IL-35 and IL-39 in acute and chronic brucellosis, suggesting that the common protein subunit Ebi may be suppressed. According to the results of this study, IL-35 and IL-39 may play a role in the pathogenesis of brucellosis.
Study of the permeation-promoting effect and mechanism of solid microneedles on different properties of drugs

Abstract In transdermal drug delivery systems, the physicochemical properties of the drug affect its percutaneous permeability. However, whether the physicochemical properties of drugs change their transdermal permeability in the presence of pores in the presence of solid microneedles (MNs) has been less studied in this area. In this project, cinnamaldehyde, curcumin, ferulic acid and geniposide were selected as model drugs for the study of their transdermal permeability under the action of MNs, and a combination of classical experiments and visualization means such as scanning electron microscopy and laser confocal was used to investigate the permeation-promoting mechanism of MNs. The results showed that the MNs had significant permeation-promoting effects on different properties of drugs, with the permeation-promoting effects on cinnamaldehyde, curcumin, ferulic acid and geniposide being 6.36, 17.43, 29.54 and 8.91 times, respectively, and the permeation-promoting effects were more pronounced for lipid-soluble and amphiphilic drugs. Using scanning electron microscopy, transmission electron microscopy and other means to confirm that MNs can promote the penetration by acting on the skin to produce pores, and their effect on skin structure is greater than that of drugs. In addition, the existence of pores increases the amount of drug transdermal, which may enhance the diffusion of drug on the skin, and has no effect on lipid exchange and transdermal route. Through the research, it has been found that MNs is equivalent to direct peeling of the stratum corneum (SC), but it is simpler and safer for the patient.
Wave–wave interactions, microseisms, and infrasonic ambient noise in the ocean

Underwater ambient noise is known to be wind dependent. Several mechanisms have been proposed to explain the nature of the transfer of energy from the wind to the acoustic noise field. Examples include wind and wave turbulence and nonlinear interactions between surface waves. This study examines these wind‐related mechanisms at the low end of the acoustic spectrum. Data from a long‐term investigation of ocean waves and the associated microseism response recorded ashore have provided evidence helpful in identifying the active processes. It is concluded that the noise field below 5 Hz is controlled by nonlinear wave–wave interactions and that existing theories account adequately for the effects observed.
Analytical and Numerical Modeling of Solute Intrusion, Recovery, and Rebound in Fractured Bedrock

Contaminated groundwater in fractured bedrock can expose ecosystems to undesired levels of risk for extended periods due to prolonged back‐diffusion from rock matrix to permeable fractures. Therefore, it is key to characterize the diffusive mass loading (intrusion) of contaminants into the rock matrix for successful management of contaminated bedrock sites. Even the most detailed site characterization techniques often fail to delineate contamination in rock matrix. This study presents a set of analytical solutions to estimate diffusive mass intrusion into matrix blocks, it is recovered by pumping and concentration rebound when pumping ceases. The analytical models were validated by comparing the results with (1) numerical model results using the same model parameters and (2) observed chloride mass recovery, rebound concentration, and concentration in pumped groundwater at a highly fractured bedrock site in Alberta, Canada. It is also demonstrated that the analytical solutions can be used to estimate the total mass stored in the fractured bedrock prior to any remediation thereby providing insights into site contamination history. The predictive results of the analytical models clearly show that successful remediation by pumping depends largely on diffusive intrusion period. The results of initial mass from the analytical model was used to successfully calibrate a three‐dimensional discrete fracture network numerical model further highlighting the utility of the simple analytical solutions in supplementing the more detailed site numerical modeling. Overall, the study shows the utility of simple analytical methods to support long‐term management of a contaminated fractured bedrock site including site investigations and complex numerical modeling.
Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors

Abstract Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research’s primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex’s stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate. Communicated by Ramaswamy H. Sarma
Collective excitations in semiconductor superlattices

Abstract Collective excitations in semiconductor superlattices are studied beyond tbe random-phase approximation (RPA). The Singwi, Tosi, Land and Sjolander (STLS) theory, which accounts for exchange and short-range correlations effects through an effective potential depending on the structurc factor, is generalized to the layered electron system described by the model of Visscher and Falicov. The exact numerical solution of the STLS self-consistent equations provides information about intraplane and interplane correlations. The plasmon dispersion curves are evaluated for some typical values of the coupling constant rs of the electron system and the distance between the planes for GaAs/AlGaAs semiconductor superlattices. For comparison, the RPA and the Hubbard approximation are also considered.
Detecting level shifts in ARMA-GARCH (1,1) Models

The purpose of this article is to present a new method to detect level shifts in the context of conditional heteroscedastic models. First, we define precisely what type of outlier we are referring to, a concept that has been scarcely touched in the field of GARCH (1,1) models, and then we go on to present our methodology based on the nature of the Lagrange multiplier tests. The validity and efficiency of the proposed procedure are demonstrated through different simulation experiments. To conclude, we present a practical application of the method to the time series of returns of US short-term interest rates.
Re-envisioning the design of nanomedicines: harnessing automation and artificial intelligence

ABSTRACT Introduction Interest in nanomedicines has surged in recent years due to the critical role they have played in the COVID-19 pandemic. Nanoformulations can turn promising therapeutic cargo into viable products through improvements in drug safety and efficacy profiles. However, the developmental pathway for such formulations is non-trivial and largely reliant on trial-and-error. Beyond the costly demands on time and resources, this traditional approach may stunt innovation. The emergence of automation, artificial intelligence (AI) and machine learning (ML) tools, which are currently underutilized in pharmaceutical formulation development, offers a promising direction for an improved path in the design of nanomedicines. Areas covered the potential of harnessing experimental automation and AI/ML to drive innovation in nanomedicine development. The discussion centers on the current challenges in drug formulation research and development, and the major advantages afforded through the application of data-driven methods. Expert opinion The development of integrated workflows based on automated experimentation and AI/ML may accelerate nanomedicine development. A crucial step in achieving this is the generation of high-quality, accessible datasets. Future efforts to make full use of these tools can ultimately contribute to the development of more innovative nanomedicines and improved clinical translation of formulations that rely on advanced drug delivery systems.
SEH: Size Estimate Hedging Scheduling of Queues

For a single server system, Shortest Remaining Processing Time (SRPT) is an optimal size-based policy. In this article, we discuss scheduling a single-server system when exact information about the jobs’ processing times is not available. When the SRPT policy uses estimated processing times, the underestimation of large jobs can significantly degrade performance. We propose an index-based policy with a single parameter, Size Estimate Hedging (SEH), that only uses estimated processing times for scheduling decisions. A job’s priority is increased dynamically according to an SRPT rule until it is determined that it is underestimated, at which time the priority is frozen. Numerical results suggest that SEH has desirable performance for estimation error variance that is consistent with what is seen in practice.
DDIFN: A Dual-discriminator Multi-modal Medical Image Fusion Network

Multi-modal medical image fusion is a long-standing important research topic that can obtain informative medical images and assist doctors diagnose and treat diseases more efficiently. However, most fusion methods extract and fuse features by subjectively defining constraints, which easily distorts the unique information of source images. In this work, we present a novel end-to-end unsupervised network to fuse multi-modal medical images. It is composed of a generator and two symmetrical discriminators. The former aims to generate a ”real-like” fused image based on a specifically designed content and structure loss, while the latter are devoted to distinguishing the differences between the fused image and the source ones. They are trained alternately until discriminators cannot distinguish the fused image from the source ones. In addition, the symmetrical discriminator scheme is conducive to maintaining the feature consistency among different modalities. More importantly, to enhance the retention degree of texture details, U-Net is adopted as the generator heuristically, where the up-sampling method is modified to bilinear interpolation for avoiding checkerboard artifacts. As for the optimization, we define the content loss function, which preserves the gradient information and pixel activity of source images. Both visual analysis and quantitative evaluation of experimental results show the superiority of our method as compared to the cutting-edge baselines.
E-government Service Adoption by Citizens: A Literature Review and a High-level Model of Influential Factors

E-government services refer to services offered by governments using information technology (IT). Many governments around the globe are investing heavily in IT to enhance service delivery to their citizens. However, citizens do not always use these services so that they often forgo their potential benefits because of key interconnected considerations that are perceived to transpire from their use. Over the years several studies examined IT adoption in e-government services contexts, building a rich albeit fragmented body of knowledge in the process. Indeed, the diversity found in these studies and the fast and continuous change that characterizes IT in general, make the identification and the synthesis of the main factors influencing citizens’ adoption of E-government services a relevant and timely endeavor. For this reason, this study builds on the findings of a systematic literature review to provide a high-level framework that conceptually structures the state of knowledge on the topic, and that informs both researchers and practitioners on the main factors influencing e-government services adoption by citizens.
Formalizing UML State Machines for Automated Verification – A Survey

The Unified Modeling Language (UML) is a standard for modeling dynamic systems. UML behavioral state machines are used for modeling the dynamic behavior of object-oriented designs. The UML specification, maintained by the Object Management Group (OMG), is documented in natural language (in contrast to formal language). The inherent ambiguity of natural languages may introduce inconsistencies in the resulting state machine model. Formalizing UML state machine specification aims at solving the ambiguity problem and at providing a uniform view to software designers and developers. Such a formalization also aims at providing a foundation for automatic verification of UML state machine models, which can help to find software design vulnerabilities at an early stage and reduce the development cost. We provide here a comprehensive survey of existing work from 1997 to 2021 related to formalizing UML state machine semantics for the purpose of conducting model checking at the design stage.
Conductance of molecular wires: coherent and incoherent transport (Invited Paper)

The emerging field of molecular electronics has brought together physicists, chemists, engineers and biologists. Large efforts on both, the experimental techniques and the theoretical methodologies, have led to fascinating developments in this field. It has been shown that the charge transport mechanisms at the molecular scale can considerably differ from those well-known in bulk solids. Phase coherent, ballistic transport as well as fully incoherent, hopping-like motion of the charge carriers may compete in determining the transport through a molecule. We review in this article basic facts related to charge transport and some of the theoretical approaches that have been developed to deal with this problem. We further show, in the special case of a DNA molecular wire, how the presence of a dissipative environment can appreciably modify the electronic spectrum of the system and thus lead to a change in its low-energy transport properties.
Printable electronics: flexibility for the future

Printed electronics is an emerging technology with huge potential. Market studies predict a multi‐billion dollar market size within less than 5 years. Due to its compatibility with flexible substrates and low‐cost fabrication, printed electronics is able to bring electronic functionality to markets unfit for rigid and expensive silicon electronics. Key to its success are innovative printing technologies and high‐quality material systems, engineered for specific device applications. Printed electronics is a complex multidisciplinary research area, with still a number of fundamental problems to be solved before the technology can grow to its full potential. Evonik Industries is involved in the development of printed electronics through its unique science‐to‐business concept. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Complete Genome Sequence of the Microbacterium Bacteriophage Chako

We characterized the complete genome sequence of Chako, an obligate lytic bacteriophage with siphovirus morphology from subcluster EA1 that infects Microbacterium foliorum NRRL B-24224. Its 41.6-kb genome contains 62 putative protein-coding genes and is highly similar to that of bacteriophage HanSolo (99.26% nucleotide identity). ABSTRACT We characterized the complete genome sequence of Chako, an obligate lytic bacteriophage with siphovirus morphology from subcluster EA1 that infects Microbacterium foliorum NRRL B-24224. Its 41.6-kb genome contains 62 putative protein-coding genes and is highly similar to that of bacteriophage HanSolo (99.26% nucleotide identity).