Miracle-dz/UniFAR-FTUs huggingface dataset:
Design, Synthesis and Bioactivity Evaluation of Novel Chalcone Derivatives Possessing Tryptophan Moiety with Dual Activities of Anti-cancer and Partially Restoring the Proliferation of Normal Kidney Cells Pre-treated with Cisplatin.

BACKGROUND Chalcone is a broad-spectrum natural product with anti-cancer and anti-inflammatory activities. However, low potency, low selectivity, and serious side effects limit its druggability. L-Tryptophan is an essential precursor molecule of an anti-cancer active substance. Also, the indole moiety inhibits the proliferation of tumor cells by binding to colchicine sites. A decrease in kidney cell activity caused by kidney inflammation is the primary side effect of cancer therapy. OBJECTIVE The purpose of this work was to design, synthesize, and perform bioactivity evaluation of novel chalcone derivatives possessing tryptophan moiety with dual activities of anti-cancer and partially restoring the proliferation of normal kidney cells pre-treated with cisplatin. METHODS A series of novel chalcone derivatives possessing tryptophan moiety (5a-5g, 6a-6o) were designed, synthesized, and evaluated for anti-cancer activity against four cancer cell lines (gastric (HGC-27), colon (HCT-116), prostate (PC-3), and lung (A549)), and a human normal cell line (gastric mucosal epithelial (GES-1)). The activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin was evaluated by MTT assay. Cell cycle, apoptosis, and apoptosis proteins (Bax and Bcl-2) were used to evaluate the anti-cancer mechanism of the most potent compound. Moreover, a docking study was performed to explain the high anti-cancer activity of 6n. The expressions of TNF-α, IL-6, and MCP-1 were detected by ELISA. RESULTS Most of the compounds exhibited high anti-cancer activity against the HGC-27 cell line and exhibited low toxicity against the normal cell line. Based on three rounds of a structure optimization, 6n was discovered as the most potent compound against HGC-27 cells with an IC50 value of 2.02 μM and an SI value of 28.47. Further studies demonstrated that 6n could induce cell cycle arrest at the G2/M phase and the apoptosis of the HGC-27 cell line by reducing the expression of Bcl-2 and improving the expression level of Bax. Molecular docking result displayed 6n bound to the colchicine site. At the same time, 6n also exhibited moderate activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin by reducing the expression of inflammatory substances. CONCLUSION Our findings collectively suggested that 6n should be further studied as a potential anti-cancer agent that could partially restore the proliferation of normal kidney cells pre-treated with cisplatin in gastric cancer patients by an anti-inflammatory pathway.
Oak Species Quercus robur L. and Quercus petraea Liebl. Identification Based on UHPLC-HRMS/MS Molecular Networks

Two species of oak are dominant in French forests: pedunculate oak (Quercus robur L.) and sessile oak (Quercus petraea Liebl.). Their differentiation is not straightforward but is essential to better understand their respective molecular content in order to better valorize them. Thus, to improve oak species identification, an untargeted UHPLC-HRMS/MS method associated with a two-step data treatment was developed to analyze a wide range of specialized metabolites enabling the comparison of both species of oak extracts. Pooled extracts from sessile and pedunculate oaks, composed of extracts from several trees of pure species from various origins, were compared using first the Venn diagram, as a quick way to get an initial idea of how close the extracts are, and then using a molecular network to visualize, on the one hand, the ions shared between the two species and, on the other hand, the compounds specific to one species. The molecular network showed that the two species shared common clusters mainly representative of tannins derivatives and that each species has specific molecules with similar fragmentation patterns, associated in specific clusters. This methodology was then applied to compare these two pooled extracts to unknown individuals in order to determine the species. The Venn diagram allowed for the quick presumption of the species of the individual and then the species could be assigned more precisely with the molecular network, at the level of specific clusters. This method, developed for the first time, has several interests. First, it makes it possible to discriminate the species and to correctly assign the species of unknown samples. Moreover, it gave an overview of the metabolite composition of each sample to better target oak tree utilization and valorization.
Health Profile of Preterm Males With Duchenne Muscular Dystrophy

In this retrospective cohort study, we characterize the health profile of preterm males with Duchenne muscular dystrophy. Major clinical milestones (ambulation cessation, assisted ventilation use, and onset of left ventricular dysfunction) and corticosteroids use in males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using Kaplan-Meier survival curves and Cox proportional hazards modeling. The adjusted risk of receiving any respiratory intervention among preterm males with Duchenne muscular dystrophy was 87% higher than among the corresponding full-term males with Duchenne muscular dystrophy. The adjusted risks for ambulation cessation and left ventricular dysfunction were modestly elevated among preterm compared to full-term males, but the 95% confidence intervals contained the null. No difference in the start of corticosteroid use between preterm and full-term Duchenne muscular dystrophy males was observed. Overall, the disease course seems to be similar between preterm and full-term males with Duchenne muscular dystrophy; however, pulmonary function seems to be affected earlier among preterm males with Duchenne muscular dystrophy.
Flexible Krylov Methods for Edge Enhancement in Imaging

Many successful variational regularization methods employed to solve linear inverse problems in imaging applications (such as image deblurring, image inpainting, and computed tomography) aim at enhancing edges in the solution, and often involve non-smooth regularization terms (e.g., total variation). Such regularization methods can be treated as iteratively reweighted least squares problems (IRLS), which are usually solved by the repeated application of a Krylov projection method. This approach gives rise to an inner–outer iterative scheme where the outer iterations update the weights and the inner iterations solve a least squares problem with fixed weights. Recently, flexible or generalized Krylov solvers, which avoid inner–outer iterations by incorporating iteration-dependent weights within a single approximation subspace for the solution, have been devised to efficiently handle IRLS problems. Indeed, substantial computational savings are generally possible by avoiding the repeated application of a traditional Krylov solver. This paper aims to extend the available flexible Krylov algorithms in order to handle a variety of edge-enhancing regularization terms, with computationally convenient adaptive regularization parameter choice. In order to tackle both square and rectangular linear systems, flexible Krylov methods based on the so-called flexible Golub–Kahan decomposition are considered. Some theoretical results are presented (including a convergence proof) and numerical comparisons with other edge-enhancing solvers show that the new methods compute solutions of similar or better quality, with increased speedup.
Toxicometabolomics: Small Molecules to Answer Big Toxicological Questions

Given the high biological impact of classical and emerging toxicants, a sensitive and comprehensive assessment of the hazards and risks of these substances to organisms is urgently needed. In this sense, toxicometabolomics emerged as a new and growing field in life sciences, which use metabolomics to provide new sets of susceptibility, exposure, and/or effects biomarkers; and to characterize in detail the metabolic responses and altered biological pathways that various stressful stimuli cause in many organisms. The present review focuses on the analytical platforms and the typical workflow employed in toxicometabolomic studies, and gives an overview of recent exploratory research that applied metabolomics in various areas of toxicology.
Preventive health care information and social media: Consumer preferences

Abstract The dissemination of preventive health care information (PHCI) can create social and economic value. Enhanced communication of health information depends upon the identification of effective channels and user preferences. Recognizing consumers find the internet and, increasingly, social media sites (Facebook and YouTube) to be important sources of PHCI, this research analyzed questionnaire responses from U.S. adults to identify the social media sites (SMSs), communication preferences, and sources consumers prefer when obtaining PHCI via social media.
Impact of Periprocedural Myocardial Injury and Infarction Definitions on Long-Term Mortality After Chronic Total Occlusion Percutaneous Coronary Intervention

Supplemental Digital Content is available in the text. Background: The prognostic implications of biomarker elevation following percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) lesions remain controversial. This study assessed the association of periprocedural myocardial injury and clinically relevant definition of periprocedural myocardial infarction with subsequent outcomes after CTO-PCI. Methods: We enrolled consecutive patients between January 2010 and December 2013 who underwent CTO-PCI at a large-volume center with serial CK-MB (creatine kinase–myocardial band) or cTnI (cardiac troponin I) measurements. The primary outcome was 5-year cardiovascular death. Results: A total of 2616 patients (2691 CTOs) with postprocedural CK-MB or cTnI undergoing PCI recanalization were included, per-lesion technical success rate was 74.4%. Postprocedural CK-MB and cTnI elevation occurred in 5.6% and 65.5% patients, respectively. For 2485 patients with serial CK-MB measurements, only postprocedural peak CK-MB ≥5× upper reference limit was associated with increased 5-year cardiovascular death (adjusted hazard ratio, 9.88 [95% CI, 3.06–31.9]). In contrast, for 1233 patients with serial cTnI measurements, no such association was present in any threshold. The Society for Cardiovascular Angiography and Interventions definition of periprocedural myocardial infarction was associated with 5-year cardiovascular death (adjusted hazard ratio, 8.45 [95% CI, 3.58–20.0]), whereas the ARC-2 (Academic Research Consortium-2) and fourth UDMI (Universal Definition of Myocardial Infarction) were not. Conclusions: In a large cohort of CTO-PCI, moderate to high levels of peak postprocedural CK-MB were prognostically significant, whereas such association was not observed in postprocedural cTnI. The Society for Cardiovascular Angiography and Intervention criteria (but not ARC-2 and fourth UDMI) were identified as clinically relevant periprocedural myocardial infarction definition following CTO-PCI.
Advances in Magnetic Nanoparticles Engineering for Biomedical Applications—A Review

Magnetic iron oxide nanoparticles (MNPs) have been developed and applied for a broad range of biomedical applications, such as diagnostic imaging, magnetic fluid hyperthermia, targeted drug delivery, gene therapy and tissue repair. As one key element, reproducible synthesis routes of MNPs are capable of controlling and adjusting structure, size, shape and magnetic properties are mandatory. In this review, we discuss advanced methods for engineering and utilizing MNPs, such as continuous synthesis approaches using microtechnologies and the biosynthesis of magnetosomes, biotechnological synthesized iron oxide nanoparticles from bacteria. We compare the technologies and resulting MNPs with conventional synthetic routes. Prominent biomedical applications of the MNPs such as diagnostic imaging, magnetic fluid hyperthermia, targeted drug delivery and magnetic actuation in micro/nanorobots will be presented.
Intelligent type 2 diabetes risk prediction from administrative claim data

ABSTRACT Type 2 diabetes is a chronic, costly disease and is a serious global population health problem. Yet, the disease is well manageable and preventable if there is an early warning. This study aims to apply supervised machine learning algorithms for developing predictive models for type 2 diabetes using administrative claim data. Following guidelines from the Elixhauser Comorbidity Index, 31 variables were considered. Five supervised machine learning algorithms were used for developing type 2 diabetes prediction models. Principal component analysis was applied to rank variables’ importance in predictive models. Random forest (RF) showed the highest accuracy (85.06%) among the algorithms, closely followed by the k-nearest neighbor (84.48%). The analysis further revealed RF as a high performing algorithm irrespective of data imbalance. As revealed by the principal component analysis, patient age is the most important predictor for type 2 diabetes, followed by a comorbid condition (i.e., solid tumor without metastasis). This study’s finding of RF as the best performing classifier is consistent with the promise of tree-based algorithms for public data in other works. Thus, the outcome can guide in designing automated surveillance of patients at risk of forming diabetes from administrative claim information and will be useful to health regulators and insurers.
Efficient Photocatalytic Degradation of Organic Pollutant in Wastewater by Electrospun Functionally Modified Polyacrylonitrile Nanofibers Membrane Anchoring TiO2 Nanostructured

In this study, polyacrylonitrile (PAN_P) nanofibers (NFs) were fabricated by electrospinning. The PAN_P NFs membrane was functionalized with diethylenetriamine to prepare a functionalized polyacrylonitrile (PAN_F) NFs membrane. TiO2 nanoparticles (NPs) synthesized in the laboratory were anchored to the surface of the PAN_F NFs membrane by electrospray to prepare a TiO2 NPs coated NFs membrane (PAN_Coa). A second TiO2/PAN_P composite membrane (PAN_Co) was prepared by embedding TiO2 NPs into the PAN_P NFs by electrospinning. The membranes were characterized by microscopic, spectroscopic and X-ray techniques. Scanning electron micrographs (SEM) revealed smooth morphologies for PAN_P and PAN_F NFs membranes and a dense cloud of TiO2 NPs on the surface of PAN_Coa NFs membrane. The attenuated total reflectance in the infrared (ATR-IR) proved the addition of the new amine functionality to the chemical structure of PAN. Transmission electron microscope images (TEM) revealed spherical TiO2 NPs with sizes between 18 and 32 nm. X-ray powder diffraction (XRD) patterns and energy dispersive X-ray spectroscopy (EDX) confirmed the existence of the anatase phase of TiO2. Surface profilometry da-ta showed increased surface roughness for the PAN_F and PAN_Coa NFs membranes. The adsorption-desorption isotherms and hysteresis loops for all NFs membranes followed the IV -isotherm and the H3 -hysteresis loop, corresponding to mesoporous and slit pores, respectively. The photocatalytic activities of PAN_Coa and PAN_Co NFs membranes against methyl orange dye degradation were evaluated and compared with those of bare TiO2 NPs.The higher photocatalytic activity of PAN_Coa membrane (92%, 20 ppm) compared to (PAN_Co) NFs membrane (41.64%, 20 ppm) and bare TiO2 (49.60%, 20 ppm) was attributed to the synergy between adsorption, lower band gap, high surface roughness and surface area.
Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2

Failed or altered gliogenesis is a major characteristic of diffuse white matter injury in survivors of premature birth. The developmentally regulated long noncoding RNA (lncRNA) H19 inhibits S-adenosylhomocysteine hydrolase (SAHH) and contributes to methylation of diverse cellular components, such as DNA, RNA, proteins, lipids, and neurotransmitters. We showed that the pregnancy-derived synthetic PreImplantation Factor (sPIF) induces expression of the nuclear receptor corepressor 2 (NCOR2) via H19/SAHH-mediated DNA demethylation. In turn, NCOR2 affects oligodendrocyte differentiation markers. Accordingly, after hypoxic-ischemic brain injury in rodents, myelin protection and oligodendrocytes’ fate are in part modulated by sPIF and H19. Our results revealed an unexpected mechanism of the H19/SAHH axis underlying myelin preservation during brain recovery and its use in treating neurodegenerative diseases can be envisioned.
Early-life formula feeding is associated with infant gut microbiota alterations and an increased antibiotic resistance load

ABSTRACT Background Infants are at a high risk of acquiring fatal infections, and their treatment relies on functioning antibiotics. Antibiotic resistance genes (ARGs) are present in high numbers in antibiotic-naive infants’ gut microbiomes, and infant mortality caused by resistant infections is high. The role of antibiotics in shaping the infant resistome has been studied, but there is limited knowledge on other factors that affect the antibiotic resistance burden of the infant gut. Objectives Our objectives were to determine the impact of early exposure to formula on the ARG load in neonates and infants born either preterm or full term. Our hypotheses were that diet causes a selective pressure that influences the microbial community of the infant gut, and formula exposure would increase the abundance of taxa that carry ARGs. Methods Cross-sectionally sampled gut metagenomes of 46 neonates were used to build a generalized linear model to determine the impact of diet on ARG loads in neonates. The model was cross-validated using neonate metagenomes gathered from public databases using our custom statistical pipeline for cross-validation. Results Formula-fed neonates had higher relative abundances of opportunistic pathogens such as Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Klebsiella oxytoca, and Clostridioides difficile. The relative abundance of ARGs carried by gut bacteria was 69% higher in the formula-receiving group (fold change, 1.69; 95% CI: 1.12–2.55; P = 0.013; n = 180) compared to exclusively human milk–fed infants. The formula-fed infants also had significantly less typical infant bacteria, such as Bifidobacteria, that have potential health benefits. Conclusions The novel finding that formula exposure is correlated with a higher neonatal ARG burden lays the foundation that clinicians should consider feeding mode in addition to antibiotic use during the first months of life to minimize the proliferation of antibiotic-resistant gut bacteria in infants.
Safety of Oral P2Y12 Inhibitors in Interventional Neuroradiology: Current Status and Perspectives

SUMMARY: In the field of interventional neuroradiology, antiplatelet agents are commonly used to prepare patients before the implantation of permanent endovascular materials. Among the available drugs, clopidogrel is the most frequently used one, but resistance phenomena are considered to be relatively common. Prasugrel and ticagrelor were recently added to the pharmacologic arsenal, but the safety of these agents in patients undergoing neurointerventional procedures is still a subject of discussion. The cumulative experience with both drugs is less extensive than that with clopidogrel, and the experience with patients in the neurology field is less extensive than in the cardiology domain. In the present article, we provide a narrative review of studies that investigated safety issues of oral P2Y12 inhibitors in interventional neuroradiology and discuss potential routes for future research.
MIF versus SIF Motoneurons, What Are Their Respective Contribution in the Oculomotor Medial Rectus Pool?

Multiply-innervated muscle fibers (MIFs) are peculiar to the extraocular muscles as they are non-twitch but produce a slow build up in tension on repetitive stimulation. The motoneurons innervating MIFs establish en grappe terminals along the entire length of the fiber, instead of the typical en plaque terminals that singly-innervated muscle fibers (SIFs) motoneurons establish around the muscle belly. MIF motoneurons have been proposed to participate only in gaze holding and slow eye movements. We aimed to discern the function of MIF motoneurons by recording medial rectus motoneurons of the oculomotor nucleus. Single-unit recordings in awake cats demonstrated that electrophysiologically-identified medial rectus MIF motoneurons participated in different types of eye movements, including fixations, rapid eye movements or saccades, convergences, and the slow and fast phases of the vestibulo-ocular nystagmus, the same as SIF motoneurons did. However, MIF medial rectus motoneurons presented lower firing frequencies, were recruited earlier and showed lower eye position (EP) and eye velocity (EV) sensitivities than SIF motoneurons. MIF medial rectus motoneurons were also smaller, had longer antidromic latencies and a lower synaptic coverage than SIF motoneurons. Peristimulus time histograms (PSTHs) revealed that electrical stimulation to the myotendinous junction, where palisade endings are located, did not recurrently affect the firing probability of medial rectus motoneurons. Therefore, we conclude there is no division of labor between MIF and SIF motoneurons based on the type of eye movement they subserve. SIGNIFICANCE STATEMENT In addition to the common singly-innervated muscle fiber (SIF), extraocular muscles also contain multiply-innervated muscle fibers (MIFs), which are non-twitch and slow in contraction. MIF motoneurons have been proposed to participate only in gaze holding and slow eye movements. In the present work, by single-unit extracellular recordings in awake cats, we demonstrate, however, that both SIF and MIF motoneurons, electrophysiologically-identified, participate in the different types of eye movements. However, MIF motoneurons showed lower firing rates (FRs), recruitment thresholds, and eye-related sensitivities, and could thus contribute to the fine adjustment of eye movements. Electrical stimulation of the myotendinous junction activates antidromically MIF motoneurons but neither MIF nor SIF motoneurons receive a synaptic reafferentation that modifies their discharge probability.