Miracle-dz/UniFAR-FTUs huggingface dataset:
Classification of Aortic Stenosis Using Time–Frequency Features From Chest Cardio-Mechanical Signals

Objectives: This paper introduces a novel method for the detection and classification of aortic stenosis (AS) using the time-frequency features of chest cardio-mechanical signals collected from wearable sensors, namely seismo-cardiogram (SCG) and gyro-cardiogram (GCG) signals. Such a method could potentially monitor high-risk patients out of the clinic. Methods: Experimental measurements were collected from twenty patients with AS and twenty healthy subjects. Firstly, a digital signal processing framework is proposed to extract time-frequency features. The features are then selected via the analysis of variance test. Different combinations of features are evaluated using the decision tree, random forest, and artificial neural network methods. Two classification tasks are conducted. The first task is a binary classification between normal subjects and AS patients. The second task is a multi-class classification of AS patients with co-existing valvular heart diseases. Results: In the binary classification task, the average accuracies achieved are 96.25% from decision tree, 97.43% from random forest, and 95.56% from neural network. The best performance is from combined SCG and GCG features with random forest classifier. In the multi-class classification, the best performance is 92.99% using the random forest classifier and SCG features. Conclusion: The results suggest that the solution could be a feasible method for classifying aortic stenosis, both in the binary and multi-class tasks. It also indicates that most of the important time-frequency features are below 11 Hz.Significance: The proposed method shows great potential to provide continuous monitoring of valvular heart diseases to prevent patients from sudden critical cardiac situations.
Preliminary safety assessment of oridonin in zebrafish

Abstract Context: Oridonin, isolated from the leaves of Isodon rubescens (Hemsl.) H.Hara (Lamiaceae), has good antitumor activity. However, its safety in vivo is still unclear. Objective: To investigate the preliminary safety of oridonin in zebrafish. Materials and methods: Embryo, larvae and adult zebrafish (n = 40) were used. Low, medium and high oridonin concentrations (100, 200 and 400 mg/L for embryo; 150, 300 and 600 mg/L for larvae; 200, 400 and 800 mg/L for adult zebrafish) and blank samples were administered. At specific stages of zebrafish development, spontaneous movement, heartbeat, hatching rate, etc., were recorded to assess the developmental effects of oridonin. VEGFA, VEGFR2 and VEGFR3 gene expression were also examined. Results: Low-dose oridonin increased spontaneous movement and hatching rate with median effective doses (ED50) of 115.17 mg/L at 24 h post-fertilization (hpf) and 188.59 mg/L at 54 hpf, but these values decreased at high doses with half maximal inhibitory concentrations (IC50) of 209.11 and 607.84 mg/L. Oridonin decreased heartbeat with IC50 of 285.76 mg/L at 48 hpf, and induced malformation at 120 hpf with half maximal effective concentration (EC50) of 411.94 mg/L. Oridonin also decreased body length with IC50 of 324.78 mg/L at 144 hpf, and increased swimming speed with ED50 of 190.98 mg/L at 120 hpf. The effects of oridonin on zebrafish embryo development may be attributed to the downregulation of VEGFR3 gene expression. Discussions and conclusions: Oridonin showed adverse effects at early stages of zebrafish development. We will perform additional studies on mechanism of oridonin based on VEGFR3.
Force of infection of Middle East respiratory syndrome in dromedary camels in Kenya

Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease transmitted from dromedary camels to people, which can result in outbreaks with human-to-human transmission. Because it is a subclinical infection in camels, epidemiological measures other than prevalence are challenging to assess. This study estimated the force of infection (FOI) of MERS-CoV in camel populations from age-stratified serological data. A cross-sectional study of MERS-CoV was conducted in Kenya from July 2016 to July 2017. Seroprevalence was stratified into four age groups: <1, 1–2, 2–3 and >3 years old. Age-independent and age-dependent linear and quadratic generalised linear models were used to estimate FOI in pastoral and ranching camel herds. Models were compared based on computed AIC values. Among pastoral herds, the age-dependent quadratic FOI was the best fit model, while the age-independent FOI was the best fit for the ranching herd data. FOI provides an indirect estimate of infection risk, which is especially valuable where direct estimates of incidence and other measures of infection are challenging to obtain. The FOIs estimated in this study provide important insight about MERS-CoV dynamics in the reservoir species, and contribute to our understanding of the zoonotic risks of this important public health threat.
Colicin U from Shigella boydii Forms Voltage-Dependent Pores

Currently, a dramatic increase in antibiotic resistance is driving researchers to find new antimicrobial agents. The large group of toxins called bacteriocins appears to be very promising from this point of view, especially because their narrow killing spectrum allows specific targeting against selected bacterial strains. Colicins are a subgroup of bacteriocins that act on Gram-negative bacteria. To date, some colicins are commercially used for the treatment of animals (1) and tested as a component of engineered species-specific antimicrobial peptides, which are studied for the potential treatment of humans (2). Here, we present a thorough single-molecule study of colicin U which leads to a better understanding of its mode of action. It extends the range of characterized colicins available for possible future medical applications. ABSTRACT Colicin U is a protein produced by the bacterium Shigella boydii (serovars 1 and 8). It exerts antibacterial activity against strains of the enterobacterial genera Shigella and Escherichia. Here, we report that colicin U forms voltage-dependent pores in planar lipid membranes; its single-pore conductance was found to be about 22 pS in 1 M KCl at pH 6 under 80 mV in asolectin bilayers. In agreement with the high degree of homology between their C-terminal domains, colicin U shares some pore characteristics with the related colicins A and B. Colicin U pores are strongly pH dependent, and as we deduced from the activity of colicin U in planar membranes at different protein concentrations, they have a monomeric pore structure. However, in contrast to related colicins, we observed a very low cationic selectivity of colicin U pores (1.5/1 of K+/Cl− at pH 6) along with their atypical voltage gating. Finally, using nonelectrolytes, we determined the inner diameter of the pores to be in the range of 0.7 to 1 nm, which is similar to colicin Ia, but with a considerably different inner profile. IMPORTANCE Currently, a dramatic increase in antibiotic resistance is driving researchers to find new antimicrobial agents. The large group of toxins called bacteriocins appears to be very promising from this point of view, especially because their narrow killing spectrum allows specific targeting against selected bacterial strains. Colicins are a subgroup of bacteriocins that act on Gram-negative bacteria. To date, some colicins are commercially used for the treatment of animals (1) and tested as a component of engineered species-specific antimicrobial peptides, which are studied for the potential treatment of humans (2). Here, we present a thorough single-molecule study of colicin U which leads to a better understanding of its mode of action. It extends the range of characterized colicins available for possible future medical applications.
A fast‐moving target: achieving marine conservation goals under shifting climate and policies

Abstract In the Anthropocene, marine ecosystems are rapidly shifting to new ecological states. Achieving effective conservation of marine biodiversity has become a fast‐moving target because of both global climate change and continuous shifts in marine policies. How prepared are we to deal with this crisis? We examined EU Member States Programs of Measures designed for the implementation of EU marine environmental policies, as well as recent European Marine Spatial Plans, and discovered that climate change is rarely considered operationally. Further, our analysis revealed that monitoring programs in marine protected areas are often insufficient to clearly distinguish between impacts of local and global stressors. Finally, we suggest that while the novel global Blue Growth approach may jeopardize previous marine conservation efforts, it can also provide new conservation opportunities. Adaptive management is the way forward (e.g., preserving ecosystem functions in climate change hotspots, and identifying and targeting climate refugia areas for protection) using Marine Spatial Planning as a framework for action, especially given the push for Blue Growth.
Graphene-Based Catalysts for Ozone Processes to Decontaminate Water

The use of graphene-based materials as catalysts in both ozone and ozone/radiation processes is creating interest among researchers devoted to the study of advanced oxidation processes (AOPs) for the degradation of organic pollutants in water. In this review, detailed explanations of catalytic and photocatalytic ozonation processes mediated by graphene-based materials are presented, focusing on aspects related to the preparation and characterization of catalysts, the nature of the water pollutants treated, the type of reactors and radiation sources applied, the influence of the main operating variables, catalyst activity and stability, and kinetics and mechanisms.
GC-072, a Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat Pathogens

Burkholderia pseudomallei, the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care; in the case of septicemia, left untreated, it can range from 50% to 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for 2 weeks or longer, followed by oral eradication-phase treatment lasting several months. ABSTRACT Burkholderia pseudomallei, the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care; in the case of septicemia, left untreated, it can range from 50% to 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for 2 weeks or longer, followed by oral eradication-phase treatment lasting several months. An effective oral therapeutic for outpatient treatment of acute-phase melioidosis is needed. GC-072 is a potent, 4-oxoquinolizine antibiotic with selective inhibitory activity against bacterial topoisomerases. GC-072 has demonstrated in vitro potency against susceptible and drug-resistant strains of B. pseudomallei and is also active against Burkholderia mallei, Bacillus anthracis, Yersinia pestis, and Francisella tularensis. GC-072 is bactericidal both extra- and intracellularly, with rapid killing noted within a few hours and reduced development of resistance compared to that for ceftazidime. GC-072, delivered intragastrically to mimic oral administration, promoted dose-dependent survival in mice using lethal inhalational models of B. pseudomallei infection following exposure to a 24- or 339-LD50 (50% lethal dose) challenge with B. pseudomallei strain 1026b. Overall, GC-072 appears to be a strong candidate for first-line oral treatment of melioidosis.
Face-to-Face and Digital Multidomain Lifestyle Interventions to Enhance Cognitive Reserve and Reduce Risk of Alzheimer’s Disease and Related Dementias: A Review of Completed and Prospective Studies

Background: Currently, there is no pharmaceutical intervention to treat or delay pathological cognitive decline or Alzheimer’s disease and related dementias (ADRD). Multidomain lifestyle interventions are increasingly being studied as a non-pharmacological solution to enhance cognitive reserve, maintain cognition, and reduce the risk of or delay ADRD. Review of completed and prospective face-to-face (FTF) and digital multidomain interventions provides an opportunity to compare studies and informs future interventions and study design. Methods: Electronic databases (PubMed, PsycINFO, clinicaltrials.gov and NIH RePORTER) were searched for multidomain lifestyle programs. Studies were included if the program (1) included a control group, (2) included at least 3 interventions, (3) were at least 6 months in duration, and (4) included measurement of cognitive performance as an outcome. Results: In total, 17 multidomain lifestyle programs aimed at enhancing cognitive reserve and reducing risk of ADRD were found. Thirteen programs are FTF in intervention delivery, with 3 FTF programs replicating the FINGER protocol as part of the World Wide Fingers Consortium. Four programs are delivered digitally (website, Web application, or mobile app). Program characteristics (e.g., target population, duration, frequency, outcomes, and availability) and results of completed and prospective studies are reviewed and discussed. Conclusion: This review updates and discusses completed and current multidomain lifestyle interventions aimed at enhancing cognitive reserve and reducing risk of ADRD. A growing number of international studies are investigating the efficacy and utility of these programs in both FTF and digital contexts. While a diversity of study designs and interventions exist, FTF and digital programs that build upon the foundational work of the FINGER protocol have significant potential to enhance cognitive reserve and reduce risk of ADRD.
Relating Ettringite Formation and Rheological Changes during the Initial Cement Hydration: A Comparative Study Applying XRD Analysis, Rheological Measurements and Modeling

In order to gain a deeper understanding of the rheological development of hydrating ordinary Portland cement (OPC) pastes at initial state, and to better understand their underlying processes, quantitative X-ray diffraction (XRD) analysis and rheological measurements were conducted and their results combined. The time-dependent relation between phase development and flow behavior of cement paste was investigated at two different temperatures (20 and 30 °C), over a period of two hours. Regarding the phase development during hydration, ettringite precipitation was identified as the dominant reaction in the first two hours. For both temperatures, the increasing ettringite content turned out to correlate very well with the loss of workability of the reacting cement paste. An exponential relationship between ettringite growth and flow behavior was observed that could be explained by applying the Krieger-Dougherty equation, which describes the influence of solid fraction on the viscosity of a suspension.
The FBXW2–MSX2–SOX2 axis regulates stem cell property and drug resistance of cancer cells

Significance SOX2, one of the pluripotency-associated stem cell factors, is aberrantly amplified in many types of human cancer and could be an attractive target for cancer therapy. We report here that MLN4924, a small-molecule inhibitor of neddylation, down-regulates SOX2 expression via inactivating FBXW2 E3 ligase to cause accumulation of MSX2, a transcription repressor known to repress SOX2 expression. We therefore established an FBXW2–MSX2–SOX2 axis and found it regulates cancer stem cell property and drug resistance. Specifically, FBXW2 or SOX2 promotes tumor sphere formation and tamoxifen resistance, which is blocked by MSX2. Our study revealed an anticancer mechanism of MLN4924 by which MLN4924 inactivates the FBXW2–MSX2–SOX2 axis to suppress stem cell property and sensitize cancer cells to chemotherapy. SOX2 is a key transcription factor that plays critical roles in maintaining stem cell property and conferring drug resistance. However, the underlying mechanisms by which SOX2 level is precisely regulated remain elusive. Here we report that MLN4924, also known as pevonedistat, a small-molecule inhibitor of neddylation currently in phase II clinical trials, down-regulates SOX2 expression via causing accumulation of MSX2, a known transcription repressor of SOX2 expression. Mechanistic characterization revealed that MSX2 is a substrate of FBXW2 E3 ligase. FBXW2 binds to MSX2 and promotes MSX2 ubiquitylation and degradation. Likewise, FBXW2 overexpression shortens the protein half-life of MSX2, whereas FBXW2 knockdown extends it. We further identified hypoxia as a stress condition that induces VRK2 kinase to facilitate MSX2–FBXW2 binding and FBXW2-mediated MSX2 ubiquitylation and degradation, leading to SOX2 induction via derepression. Biologically, expression of FBXW2 or SOX2 promotes tumor sphere formation, which is blocked by MSX2 expression. By down-regulating SOX2 through inactivation of FBXW2 E3 ligase, MLN4924 sensitizes breast cancer cells to tamoxifen in both in vitro and in vivo cancer cell models. Thus, a negative cascade of the FBXW2–MSX2–SOX2 axis was established, which regulates stem cell property and drug resistance. Finally, an inverse correlation of expression was found between FBXW2 and MSX2 in lung and breast cancer tissues. Collectively, our study revealed an anticancer mechanism of MLN4924. By inactivating FBXW2, MLN4924 caused MSX2 accumulation to repress SOX2 expression, leading to suppression of stem cell property and sensitization of breast cancer cells to tamoxifen.
Survey of Deep-Learning Approaches for Remote Sensing Observation Enhancement

Deep Learning, and Deep Neural Networks in particular, have established themselves as the new norm in signal and data processing, achieving state-of-the-art performance in image, audio, and natural language understanding. In remote sensing, a large body of research has been devoted to the application of deep learning for typical supervised learning tasks such as classification. Less yet equally important effort has also been allocated to addressing the challenges associated with the enhancement of low-quality observations from remote sensing platforms. Addressing such channels is of paramount importance, both in itself, since high-altitude imaging, environmental conditions, and imaging systems trade-offs lead to low-quality observation, as well as to facilitate subsequent analysis, such as classification and detection. In this paper, we provide a comprehensive review of deep-learning methods for the enhancement of remote sensing observations, focusing on critical tasks including single and multi-band super-resolution, denoising, restoration, pan-sharpening, and fusion, among others. In addition to the detailed analysis and comparison of recently presented approaches, different research avenues which could be explored in the future are also discussed.
Biochemical characterization of phospho enol pyruvate carboxykinases from Arabidopsis thaliana.

ATP-dependent phospho enol pyruvate carboxykinases (PEPCKs, EC 4.1.1.49) from C4 and CAM plants have been widely studied due to their crucial role in photosynthetic CO2 fixation. However, our knowledge on the structural, kinetic and regulatory properties of the enzymes from C3 species is still limited. In this work, we report the recombinant production and biochemical characterization of two PEPCKs identified in Arabidopsis thaliana : Ath PEPCK1 and Ath PEPCK2. We found that both enzymes exhibited high affinity for oxaloacetate and ATP, reinforcing their role as decarboxylases. We employed a high-throughput screening for putative allosteric regulators using differential scanning fluorometry and confirmed their effect on enzyme activity by performing enzyme kinetics. Ath PEPCK1 and Ath PEPCK2 are allosterically modulated by key intermediates of plant metabolism, namely succinate, fumarate, citrate and α-ketoglutarate. Interestingly, malate activated and glucose 6-phosphate inhibited Ath PEPCK1 but had no effect on Ath PEPCK2. Overall, our results demonstrate that the enzymes involved in the critical metabolic node constituted by phospho enol pyruvate are targets of fine allosteric regulation.
Commercial Screen-Printed Electrodes Based on Carbon Nanomaterials for a Fast and Cost-Effective Voltammetric Determination of Paracetamol, Ibuprofen and Caffeine in Water Samples

Carbon screen-printed electrode (SPCE), multi-walled carbon nanotubes modified screen-printed electrode (SPCNTE), carbon nanofibers modified screen-printed electrode (SPCNFE), and graphene modified screen-printed electrode (SPGPHE) were in a pioneer way tested as sensors for the simultaneous determination of the two most consumed pain-killers, paracetamol (PA) and ibuprofen (IB), and the stimulant caffeine (CF) in water by differential pulse voltammetry (DPV). Their analytical performances were compared, and the resulting sensitivities (2.50, 0.074, and 0.24 μA V mg−1 L for PA, IB, and CF, respectively), detection limits (0.03, 0.6, and 0.05 mg L−1 for PA, IB, and CF, respectively) and quantification limits (0.09, 2.2, and 0.2 mg L−1 for PA, IB, and CF, respectively) suggested that the SPCNFE was the most suitable carbon-based electrode for the voltammetric determination of the selected analytes in water at trace levels. The methodology was validated using both spiked tap water and hospital wastewater samples. The results were compared to those achieved by liquid chromatography–tandem mass spectrometry (LC-MS/MS), the technique of choice for the determination of the target analytes.
Control and Monitoring of Milk Renneting Using FT-NIR Spectroscopy as a Process Analytical Technology Tool

Failures in milk coagulation during cheese manufacturing can lead to decreased yield, anomalous behaviour of cheese during storage, significant impact on cheese quality and process wastes. This study proposes a Process Analytical Technology approach based on FT-NIR spectroscopy for milk renneting control during cheese manufacturing. Multivariate Curve Resolution optimized by Alternating Least Squares (MCR-ALS) was used for data analysis and development of Multivariate Statistical Process Control (MSPC) charts. Fifteen renneting batches were set up varying temperature (30, 35, 40 °C), milk pH (6.3, 6.5, 6.7), and fat content (0.1, 2.55, 5 g/100 mL). Three failure batches were also considered. The MCR-ALS models well described the coagulation processes (explained variance ≥99.93%; lack of fit <0.63%; standard deviation of the residuals <0.0067). The three identified MCR-ALS profiles described the main renneting phases. Different shapes and timing of concentration profiles were related to changes in temperature, milk pH, and fat content. The innovative implementation of MSPC charts based on T2 and Q statistics allowed the detection of coagulation failures from the initial phases of the process.