Miracle-dz/UniFAR-FTUs huggingface dataset:
Two-Year Follow-Up after Endovenous Closure with Short-Chain Cyanoacrylate versus Laser Ablation in Venous Insufficiency

Background: The current treatment of venous disease is focused on the minimally invasive exclusion of the affected vein. Besides widely used thermal ablation, chemical ablation with cyanoacrylate, reported as safe and highly effective, has been gaining increasing interest. Patients and methods: In the current report, we present data from a two-year observation in 89 patients (61 female/28 male, mean age 44.3 ± 13.5) suffering from venous insufficiency (C2–C4), treated either using short-chain cyanoacrylate, the VenaBlock system (n = 43) or laser thermoablation with ELVeS 1470 (n = 46). The assessment comprised the occurrence of venous disease-related symptoms and the ultrasound examination of the leg venous system. Results: The frequency of recanalization after 2 years from the VenaBlock procedure was significantly higher than after laser treatment (37.2 vs. 8.7%). Apart from recanalization, in some individuals from both groups, the symptoms of recurrence and/or disease progression, including the development of insufficiency in other veins of treated or contralateral legs (9.3 vs. 15.2% and 9.3 vs. 17.4%, respectively), were observed. Unexpectedly, the general prevalence of the disease progression did not differ significantly between the VenaBlock and ELVeS groups (44.2 vs. 34.8%, respectively). Conclusions: Despite the higher recanalization rate of VenaBlock compared to ELVeS, the overall effectiveness of cyanoacrylate and laser thermoablation after two years was similar. Therefore, both methods similarly failed to prevent recurrence and disease progression, which seem to be method-independent.
Control and Optimization of a Three Phase Industrial Hydrogenation Reactor

Three phase catalytic reactors are very important industrial reactors with complex steady state and dynamic behavior. In fact, the interaction among the gas, solid and liquid phases with the kinetic, mass and heat transfer mechanisms lead the system to have a challenging behavior. That is the case for the o-cresol hydrogenation to obtain 2-methyl-cyclohexanol, which is carried out in a three phase catalyst slurry reactor. A determinist mathematical model was developed using the mass and energy conservation equations for each phase, so that a system of differential equations is generated. In order to identify some suitable control structures an extensive dynamic behavior analysis was carried out. The controller implemented was a multivariable predictive controller based on the philosophy of Dynamic Matrix Control (DMC). The problem of optimization was solved through non-linear programming making use of the Successive Quadratic Programming (SQP) algorithm.
Malignant potential of colorectal neoplasms in Lynch syndrome: an analysis of 325 lesions endoscopically treated at a single institute.

BACKGROUND Patients with Lynch syndrome are at an increased risk of developing colorectal cancer, and the adenoma-carcinoma sequence is accelerated in these patients. However, the clinicopathological characteristics of colorectal neoplasms in Lynch syndrome patients are not well-known. METHODS A total of 325 consecutive colorectal neoplasms were endoscopically removed from 68 patients with Lynch syndrome between June 2005 and May 2018 and retrospectively reviewed. RESULTS Of the 325 lesions, 94 (29%), 220 (68%) and 11 (3%) were from patients with MLH1, MSH2 and MSH6 mutations, respectively. The median lesion size was 5 mm (range 2-40 mm), with 229 (71%) lesions having a non-polypoid morphology. The frequencies of advanced neoplasms, including high-grade adenomas, intramucosal carcinomas and submucosal invasive carcinomas were 14, 34, 97 and 93% for lesions with diameters of <5, ≥5 and <10, ≥10 and <20, and ≥20 mm, respectively. The frequencies of advanced neoplasms in the proximal colon, distal colon and rectum did not significantly differ (36, 35 and 41%, respectively). CONCLUSIONS Our results suggest that the malignant transformation interval from low-grade adenomas to advanced neoplasms is similar in all parts of the colon. Furthermore, since one-third of neoplastic lesions with diameters of ≥5 and <10 mm and most of those ≥10 mm were advanced neoplasms, we recommend that in Lynch syndrome patients, careful colonoscopic surveillance should be performed throughout the colon, and all neoplastic lesions, regardless of the size, should be subjected to detailed endoscopic examination, complete resection and detailed pathological examination.
Defective phagocyte association during infection of Galleria mellonella with Yersinia pseudotuberculosis is detrimental to both insect host and microbe

ABSTRACT Adhesins facilitate bacterial colonization and invasion of host tissues and are considered virulence factors, but their impact on immune-mediated damage as a driver of pathogenesis remains unclear. Yersinia pseudotuberculosis encodes for a multivalent adhesion molecule (MAM), a mammalian cell entry (MCE) family protein and adhesin. MAMs are widespread in Gram-negative bacteria and enable enteric bacteria to colonize epithelial tissues. Their role in bacterial interactions with the host innate immune system and contribution to pathogenicity remains unclear. Here, we investigated howY. pseudotuberculosis MAM contributes to pathogenesis during infection of the Galleria mellonella insect model. We show that Y. pseudotuberculosis MAM is required for efficient bacterial binding and uptake by hemocytes, the host phagocytes. Y. pseudotuberculosis interactions with insect and mammalian phagocytes are determined by bacterial and host factors. Loss of MAM, and deficient microbe–phagocyte interaction, increased pathogenesis in G. mellonella. Diminished phagocyte association also led to increased bacterial clearance. Furthermore, Y. pseudotuberculosis that failed to engage phagocytes hyperactivated humoral immune responses, most notably melanin production. Despite clearing the pathogen, excessive melanization also increased phagocyte death and host mortality. Our findings provide a basis for further studies investigating how microbe- and host-factors integrate to drive pathogenesis in a tractable experimental system.
Impact of the B.1.1.7 variant on neutralizing monoclonal antibodies recognizing diverse epitopes on SARS-CoV-2 Spike

The interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the ACE2 receptor on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, the N-terminal domain (NTD) and S2 subunits of Spike. To fully understand how these mutations affect the antigenicity of Spike, we have isolated and characterized neutralizing antibodies targeting epitopes beyond the already identified RBD epitopes. Using recombinant Spike as a sorting bait, we isolated >100 Spike-reactive monoclonal antibodies from SARS-CoV-2 infected individuals. ~45% showed neutralizing activity of which ~20% were NTD-specific. None of the S2-specific antibodies showed neutralizing activity. Competition ELISA revealed that NTD-specific mAbs formed two distinct groups: the first group was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Importantly, mutations present in B.1. 1.7 Spike frequently conferred resistance to neutralization by the NTD-specific neutralizing antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes need to be considered when investigating antigenic drift in emerging variants.
Resveratrol Promotes Hypertrophy in Wildtype Skeletal Muscle and Reduces Muscle Necrosis and Gene Expression of Inflammatory Markers in Mdx Mice

Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. Resveratrol is a nutraceutical with anti-inflammatory properties. Previous studies have shown high doses (100–400 mg/kg bodyweight/day) benefit mdx mice. We treated 4-week-old mdx and wildtype mice with a lower dose of resveratrol (5 mg/kg bodyweight/day) for 15 weeks. Voluntary exercise was used to test if a lower dosage than previously tested could reduce exercise-induced damage where a greater inflammatory infiltrate is present. We found resveratrol promoted skeletal muscle hypertrophy in wildtype mice. In dystrophic muscle, resveratrol reduced exercise-induced muscle necrosis. Gene expression of immune cell markers, CD86 and CD163 were reduced; however, signalling targets associated with resveratrol’s mechanism of action including Sirt1 and NF-κB were unchanged. In conclusion, a lower dose of resveratrol compared to the dosage used by other studies reduced necrosis and gene expression of inflammatory cell markers in dystrophic muscle suggesting it as a therapeutic candidate for treating DMD.
Effect of Pore Connectivity on the Behavior of Fluids Confined in Sub-Nanometer Pores: Ethane and CO2 Confined in ZSM-22

The behavior of fluids under nano-confinement varies from that in bulk due to an interplay of several factors including pore connectivity. In this work, we use molecular dynamics simulations to study the behavior of two fluids—ethane and CO2 confined in ZSM-22, a zeolite with channel-like pores of diameter 0.55 nm isolated from each other. By comparing the behavior of the two fluids in ZSM-22 with that reported earlier in ZSM-5, a zeolite with pores of similar shape and size connected to each other via sinusoidal pores running perpendicular to them, we reveal the important role of pore connectivity. Further, by artificially imposing pore connectivity in ZSM-22 via inserting a 2-dimensional slab-like inter-crystalline space of thickness 0.5 nm, we also studied the effect of the dimensionality and geometry of pore connectivity. While the translational motion of both ethane and CO2 in ZSM-22 is suppressed as a result of connecting the pores by perpendicular quasi-one-dimensional pores of similar dimensions, the effect of connecting the pores by inserting the inter-crystalline space is different on the translational motion of the two fluids. For ethane, pores connected via inter-crystalline space facilitate translational motion but suppress rotational motion, whereas in the case of CO2, both types of motion are suppressed by pore connection due to the strong interaction of CO2 with the surface of the substrate.
Mutational Landscape of Virus- and UV-Associated Merkel Cell Carcinoma Cell Lines Is Comparable to Tumor Tissue

Simple Summary Merkel cell carcinoma (MCC) is an aggressive, rare skin cancer which is caused either by a virus or chronic UV exposure. For both forms, distinct genetic alterations have been described; however, these observations were mostly made in tumor tissue. Since cancer cell lines are frequently used as preclinical models to investigate biological function, we considered it necessary to establish the genomic landscape of MCC cell lines by whole-exome sequencing. We confirmed the presence of UV-induced DNA damage, a high number of mutations and several coding mutations in virus-negative cell lines which were absent in virus-positive cell lines; these, however, harbored characteristic copy number variations, suggesting some virally caused genetic instability. Knowing the genomic features of MCC cell lines validates previous, and facilitates upcoming, experimental studies to discover their biological and translational relevance. Abstract Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy that is either associated with the integration of the Merkel cell polyomavirus or chronic UV exposure. These two types of carcinogenesis are reflected in characteristic mutational features present in MCC tumor lesions. However, the genomic characteristics of MCC cell lines used as preclinical models are not well established. Thus, we analyzed the exomes of three virus-negative and six virus-positive MCC cell lines, all showing a classical neuroendocrine growth pattern. Virus-negative cell lines are characterized by a high tumor mutational burden (TMB), UV-light-induced DNA damage, functionally relevant coding mutations, e.g., in RB1 and TP53, and large amounts of copy number variations (CNVs). In contrast, virus-positive cell lines have a low TMB with few coding mutations and lack prominent mutational signatures, but harbor characteristic CNVs. One of the virus-negative cell lines has a local MYC amplification associated with high MYC mRNA expression. In conclusion, virus-positive and -negative MCC cell lines with a neuroendocrine growth pattern resemble mutational features observed in MCC tissue samples, which strengthens their utility for functional studies.
Hierarchical Porous, N-Containing Carbon Supports for High Loading Sulfur Cathodes

The lithium-polysulfide (LiPS) dissolution from the cathode to the organic electrolyte is the main challenge for high-energy-density lithium-sulfur batteries (LSBs). Herein, we present a multi-functional porous carbon, melamine cyanurate (MCA)-glucose-derived carbon (MGC), with superior porosity, electrical conductivity, and polysulfide affinity as an efficient sulfur support to mitigate the shuttle effect. MGC is prepared via a reactive templating approach, wherein the organic MCA crystals are utilized as the pore-/micro-structure-directing agent and nitrogen source. The homogeneous coating of spherical MCA crystal particles with glucose followed by carbonization at 600 °C leads to the formation of hierarchical porous hollow carbon spheres with abundant pyridinic N-functional groups without losing their microstructural ordering. Moreover, MGC enables facile penetration and intensive anchoring of LiPS, especially under high loading sulfur conditions. Consequently, the MGC cathode exhibited a high areal capacity of 5.79 mAh cm−2 at 1 mA cm−2 and high loading sulfur of 6.0 mg cm−2 with a minor capacity decay rate of 0.18% per cycle for 100 cycles.
ΔMST and the Regulation of Cardiac CSE and OTR Expression in Trauma and Hemorrhage

Genetic deletion of 3-mercaptopyruvate sulfurtransferase (MST) is known to result in hypertension and cardiac hypertrophy in older mice, and is associated with increased anxiety-like behaviors. Endogenous hydrogen sulfide (H2S) produced by MST in the mitochondria is also known to be involved in physiological and cellular bioenergetics, and its dysfunction associated with depressive behavior and increased cardiovascular morbidity. Interestingly, early life stress has been shown to lead to a significant loss of cystathionine-γ-lyase (CSE) and oxytocin receptor (OTR) expression in the heart. Thus, we were interested in testing the hypothesis of whether genetic MST mutation (ΔMST) would affect cardiac CSE and OTR expression and affect the mitochondrial respiration in a clinically relevant, resuscitated, mouse model of trauma and hemorrhagic shock. In ΔMST mice, we found a reduction of CSE and OTR in both the naive as well as injured state, in contrast to the wild type (wt) controls. Interestingly, the ΔMST showed a different complex IV response to injury than the wt controls, although our claims are based on the non-demonstrated assumption that naive wt and naive ΔMST mice have comparable complex IV activity. Finally, hemorrhagic shock led to a reduction of CSE and OTR, confirming previous results in the injured mouse heart. To date, the exact mechanisms of the cardiac interaction between H2S and OT are not clear, but they point the way to potential cardioprotective therapies.
Redox reactions of organoselenium compounds: Implication in their biological activity

Abstract Antioxidant activity of organoselenium compounds belonging to different classes i.e. functionalized aliphatic, aromatic and cyclic selenoethers, are compared on the basis of their ability to scavenge reactive oxygen species like hydroxyl and peroxyl radicals and to exhibit glutathione peroxidase (GPx) like catalytic activity. The comparative analysis has revealed that the antioxidant activity of the organoselenium compounds show direct correlation with the energy of the highest occupied molecular orbital (HOMO) and neighboring group participation that stabilizes the reaction intermediate. Finally, structural features responsible for improving the rate of reaction of organoselenium compounds with free radical/molecular oxidants have been discussed on the basis of the compounds screened at our institute.
Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma.

BACKGROUND Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor treating fields, the median survival of Glioblastoma (GBM) patients is less than 15 months. Protein Arginine Methyltransferase 5 (PRMT5) catalyzes the symmetric di-methylation of arginine residues and is overexpressed in GBM. Inhibition of PRMT5 causes senescence in stem-like GBM tumor cells. LB100, a first-in-class small molecular inhibitor of Protein Phosphatase 2A (PP2A) can sensitize therapy-resistant tumor cells. Here, we tested the anti-GBM effect of concurrent PRMT5 and PP2A inhibition. METHODS Patient-derived primary GBM neurospheres (GBMNS), transfected with PRMT5 target-specific siRNA were treated with LB100 and subjected to in vitro assays including PP2A activity and western blot. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination treatment. RESULTS We found that PRMT5-depletion increased PP2A activity in GBMNS. LB100 treatment significantly reduced the viability of PRMT5-depleted GBMNS compared to PRMT5 intact GBMNS. LB100 enhanced G1 cell cycle arrest induced by PRMT5-depletion. Combination therapy also increased the expression of phospho-MLKL. Necrostatin-1 rescued PRMT5-depleted cells from the cytotoxic effects of LB100, indicating that necroptosis caused the enhanced cytotoxicity of combination therapy. In the in vivo mouse tumor xenograft model, LB100 treatment combined with transient depletion of PRMT5 significantly decreased tumor size and prolonged survival, while LB100 treatment alone had no survival benefit. CONCLUSION Overall, combined PRMT5 and PP2A inhibition had significantly greater antitumor effects than PRMT5 inhibition alone.
Structuring in liquid alkanes between solid surfaces: Force measurements and mean‐field theory

Measurements have been made of the solvation forces between mica surfaces in the even‐numbered n‐alkanes from hexane to hexadecane. In all cases the force law is qualitatively very similar, characterized by a decaying oscillatory function of distance, as occurs for simple isotropic liquids. The spacing between successive minima in the force does not increase with carbon number, and is comparable to the width of a linear alkane molecule rather than its length or any average diameter. This suggests that the alkanes have some tendency towards a parallel orientation near the mica surfaces. The measurements give no indication of any strong repulsive component expected from mean‐field theories of higher alkanes or polymers. The results of one such theory are presented, and the reasons for its failure to match the experimental data are discussed.
Effects of COVID-19 pandemic on breastfeeding rates in a neonatal intensive care unit

Abstract Objectives To find out if the expressed breast milk delivery rate to neonatal intensive care unit (NICU) for babies who were hospitalized for any reason other than COVID-19, and exclusive breastfeeding (EB) rates between discharge date and 30th day of life of those babies were affected by COVID-19 pandemic. Methods Babies who were hospitalized before the date first coronavirus case was detected in our country were included as control group (CG). The study group was divided into two groups; study group 1 (SG1): the mothers whose babies were hospitalized in the period when mother were asked not to bring breast milk to NICU, study group 2 (SG2): the mothers whose babies were hospitalized after the date we started to use the informed consent form for feeding options. The breast milk delivery rates to NICU during hospitalization and EB rates between discharge and 30th day of life were compared between groups. Results Among 154 mother-baby dyads (CG, n=50; SG1, n=46; SG2, n=58), the percentage of breast milk delivery to NICU was 100%, 79% for CG, SG2, respectively (p<0.001). The EB rate between discharge and 30th day of life did not change between groups (CG:90%, SG1:89%, SG2:75.9; p=0.075). Conclusions If the mothers are informed about the importance of breast milk, the EB rates are not affected by the COVID-19 pandemic in short term, even if the mothers are obligatorily separated from their babies. The breast milk intake rate of the babies was lowest while our NICU protocol was uncertain, and after we prepared a protocol this rate increased.
Green Synthesis of Silver Nanoparticles Using Annona muricata Extract as an Inducer of Apoptosis in Cancer Cells and Inhibitor for NLRP3 Inflammasome via Enhanced Autophagy

Annona muricata is one of the most important traditional medicinal plants which contains numerous chemicals that exhibit various pharmacological properties. In this study, silver nanoparticles were prepared using A. muricata peel extract as a reducing agent and the effect was enhanced through A. muricata like pharmaceutical activity. AgNPs formation was confirmed by color changes, UV-visible spectroscopy, SEM, DLS, and XRD. The anti-proliferative activity of AgNPs against THP-1, AMJ-13, and HBL cell lines was studied. Apoptotic markers were tested using AO/EtBr staining assay, cell cycle phases using flowcytometry, and the expression of P53. Autophagy takes an essential part in controlling inflammasome activation by primary bone marrow-derived macrophages (BMDMs). We report novel functions for AgNPs-affected autophagy, represented by the control of the release of IL-1β, caspase-1, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and NLRP3 in BMDMs following treatment with LPS+ATP. The current study revealed that the AgNPs inhibited THP-1 and AMJ-13 cell proliferation. Meanwhile, the AgNPs significantly increased autophagy and reduced IL-1b and NLRP3 levels in both in vivo and in vitro models. The secretion of IL-1β was reduced whereas the degradation of NLRP3 inflammasome was enhanced. These findings propose that AgNPs apply an anti-proliferative activity against THP-1 and AMJ-13 cells through the stimulation of apoptosis via mitochondrial damage and induction of p53 protein pathway. In addition, AgNP-induced autophagy reduced the levels of IL-1β and NLRP3 inflammasome activation. This indicated that the AgNPs augment autophagy controlled by the IL-1β pathway via two different novel mechanisms. The first one is regulating activation of the IL-1 β, caspase-1, and ASC, while the second is NLRP3 targeting for lysosomal degradation. Overall, this study suggests that AgNPs could be a potent therapy for various types of cancer and an alternative treatment for preventing inflammation via enhancing autophagy.