Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting Human Papillomavirus-Associated Cancer by Oncoprotein-Specific Recombinant Antibodies

In recent decades, recombinant antibodies against specific antigens have shown great promise for the therapy of infectious diseases and cancer. Human papillomaviruses (HPVs) are involved in the development of around 5% of all human cancers and HPV16 is the high-risk genotype with the highest prevalence worldwide, playing a dominant role in all HPV-associated cancers. Here, we describe the main biological activities of the HPV16 E6, E7, and E5 oncoproteins, which are involved in the subversion of important regulatory pathways directly associated with all known hallmarks of cancer. We then review the state of art of the recombinant antibodies targeted to HPV oncoproteins developed so far in different formats, and outline their mechanisms of action. We describe the advantages of a possible antibody-based therapy against the HPV-associated lesions and discuss the critical issue of delivery to tumour cells, which must be addressed in order to achieve the desired translation of the antibodies from the laboratory to the clinic.
A Small Area Estimation Method for Investigating the Relationship between Public Perception of Drug Problems with Neighborhood Prognostics: Trends in London between 2012 and 2019

The correlation of the public’s perception of drug problems with neighborhood characteristics has rarely been studied. The aim of this study was to investigate factors that correlate with public perceptions in London boroughs using the Mayor’s Office for Policing and Crime (MOPAC) Public Attitude Survey between 2012 and 2019. A subject-specific random effect deploying a Generalized Linear Mixed Model (GLMM) using an Adaptive Gaussian Quadrature method with 10 integration points was applied. To obtain time trends across inner and outer London areas, the GLMM was fitted using a Restricted Marginal Pseudo Likelihood method. The perception of drug problems increased with statistical significance in 17 out of 32 London boroughs between 2012 and 2019. These boroughs were geographically clustered across the north of London. Levels of deprivation, as measured by the English Index of Multiple Deprivation, as well as the percentage of local population who were non-UK-born and recorded vehicle crime rates were shown to be positively associated with the public’s perception of drug problems. Conversely, recorded burglary rate was negatively associated with the public’s perception of drug problems in their area. The public are influenced in their perception of drug problems by neighborhood factors including deprivation and visible manifestations of antisocial behavior.
New Carvone-Based Deep Eutectic Solvents for Siloxanes Capture from Biogas

During biogas combustion, siloxanes form deposits of SiO2 on engine components, thus shortening the lifespan of the installation. Therefore, the development of new methods for the purification of biogas is receiving increasing attention. One of the most effective methods is physical absorption with the use of appropriate solvents. According to the principles of green engineering, solvents should be biodegradable, non-toxic, and have a high absorption capacity. Deep eutectic solvents (DES) possess such characteristics. In the literature, due to the very large number of DES combinations, conductor-like screening models for real solvents (COSMO-RS), based on the comparison of siloxane activity coefficient of 90 DESs of various types, were studied. DESs, which have the highest affinity to siloxanes, were synthesized. The most important physicochemical properties of DESs were carefully studied. In order to explain of the mechanism of DES formation, and the interaction between DES and siloxanes, the theoretical studies based on σ-profiles, and experimental studies including the 1H NMR, 13C NMR, and FT-IR spectra, were applied. The obtained results indicated that the new DESs, which were composed of carvone and carboxylic acids, were characterized by the highest affinity to siloxanes. It was shown that the hydrogen bonds between the active ketone group (=O) and the carboxyl group (-COOH) determined the formation of stable DESs with a melting point much lower than those of the individual components. On the other hand, non-bonded interactions mainly determined the effective capture of siloxanes with DES.
The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study

Herein, we report on the reaction of nitro-substituted azidobenzofuroxans with 1,3-dicarbonyl compounds in basic media. The known reactions of benzofuroxans and azidofuroxans with 1,3-dicarbonyl compounds in the presence of bases are the 1,3-dipolar cycloaddition and the Beirut reaction. In contrast with this, azidonitrobenzofuroxan reacts with 1,3-carbonyl compounds through Regitz diazo transfer, which is the first example of this type of reaction for furoxan derivatives. This difference is seemingly due to the strong electron-withdrawing effect of the superelectrophilic azidonitrobenzofuroxan, which serves as the azido transfer agent rather than 1,3-dipole in this case.
A Multidisciplinary Journey towards Bone Tissue Engineering

Millions of patients suffer yearly from bone fractures and disorders such as osteoporosis or cancer, which constitute the most common causes of severe long-term pain and physical disabilities. The intrinsic capacity of bone to repair the damaged bone allows normal healing of most small bone injuries. However, larger bone defects or more complex diseases require additional stimulation to fully heal. In this context, the traditional routes to address bone disorders present several associated drawbacks concerning their efficacy and cost-effectiveness. Thus, alternative therapies become necessary to overcome these limitations. In recent decades, bone tissue engineering has emerged as a promising interdisciplinary strategy to mimic environments specifically designed to facilitate bone tissue regeneration. Approaches developed to date aim at three essential factors: osteoconductive scaffolds, osteoinduction through growth factors, and cells with osteogenic capability. This review addresses the biological basis of bone and its remodeling process, providing an overview of the bone tissue engineering strategies developed to date and describing the mechanisms that underlie cell–biomaterial interactions.
Balanced Convolutional Neural Networks for Pneumoconiosis Detection

Pneumoconiosis remains one of the most common and harmful occupational diseases in China, leading to huge economic losses to society with its high prevalence and costly treatment. Diagnosis of pneumoconiosis still strongly depends on the experience of radiologists, which affects rapid detection on large populations. Recent research focuses on computer-aided detection based on machine learning. These have achieved high accuracy, among which artificial neural network (ANN) shows excellent performance. However, due to imbalanced samples and lack of interpretability, wide utilization in clinical practice meets difficulty. To address these problems, we first establish a pneumoconiosis radiograph dataset, including both positive and negative samples. Second, deep convolutional diagnosis approaches are compared in pneumoconiosis detection, and a balanced training is adopted to promote recall. Comprehensive experiments conducted on this dataset demonstrate high accuracy (88.6%). Third, we explain diagnosis results by visualizing suspected opacities on pneumoconiosis radiographs, which could provide solid diagnostic reference for surgeons.
Stress-Shot-Peened Leaf Springs Material Analysis through Nano- and Micro-Indentations

Heat-treated and shot-peened lightweight steels with demanding requirements for durability are applied in high-performance automotive leaf springs. Due to their heat-treatment they exhibit degraded properties in the surface-near area compared to the core. This area, which may extend until 300 μm from the surface to the core, experiences the highest bending stresses at operation. The microstructure in the surface and sub-surface layers determines the mechanical performance as well as the wear resistance. The present study refers to the material properties of a stress shot-peened 51CrV4 steel at various depths from the surface. The effect of the manufacturing process has been captured both by Vickers micro-hardness measurements and nanoindentation. The latter combined with a Fine Element Method (FEM)-based algorithm enables the determination of variations in the material’s stress–strain curves over the affected layers, which translate to internal stress changes. The nanoindentation technique has been applied here successfully for the first time ever on leaf springs. The combination of microstructural analysis, microhardness and nanoindentation captures the changes of the treated material, offering insights on the material characteristics, and yielding accurate elastoplastic material properties for local, layered-based analysis of the components’ mechanical performance at operational loading scenarios, i.e., in the framework of stress shot-peening simulation models.
Characterization of Sustainable Asphalt Mixtures Containing High Reclaimed Asphalt and Steel Slag

Policymakers are implementing the transition to a circular model in all economic sectors to drastically mitigate the effects of climate change. In this regard, the producers of paving products should promote the reuse and recycling of solid waste in the design of sustainable asphalt materials. This study evaluated the performance-based properties of three highly recycled mixtures for wearing courses of asphalt pavements containing steel slag and varying amounts (25, 40, and 50%) of fractionated reclaimed asphalt (RA). In addition, the mixtures incorporated a warm mix asphalt (WMA) organic additive to lower production temperatures compared to a reference hot mix asphalt (HMA). Based on the experimental results, the warm recycled asphalt mixtures show equivalent or better performance compared to HMA in terms of moisture susceptibility, stiffness, rutting and fracture resistance, and surface macrotexture. Therefore, the combined incorporation of RA and steel slag with WMA was proven to be an effective option in designing environmentally friendly and high-performance wearing course mixtures.
Lab-In-Syringe with Bead Injection Coupled Online to High-Performance Liquid Chromatography as Versatile Tool for Determination of Nonsteroidal Anti-Inflammatory Drugs in Surface Waters

We report on the hyphenation of the modern flow techniques Lab-In-Syringe and Lab-On-Valve for automated sample preparation coupled online with high-performance liquid chromatography. Adopting the bead injection concept on the Lab-On-Valve platform, the on-demand, renewable, solid-phase extraction of five nonsteroidal anti-inflammatory drugs, namely ketoprofen, naproxen, flurbiprofen, diclofenac, and ibuprofen, was carried out as a proof-of-concept. In-syringe mixing of the sample with buffer and standards allowed straightforward pre-load sample modification for the preconcentration of large sample volumes. Packing of ca. 4.4 mg microSPE columns from Oasis HLB® sorbent slurry was performed for each sample analysis using a simple microcolumn adapted to the Lab-On-Valve manifold to achieve low backpressure during loading. Eluted analytes were injected into online coupled HPLC with subsequent separation on a Symmetry C18 column in isocratic mode. The optimized method was highly reproducible, with RSD values of 3.2% to 7.6% on 20 µg L−1 level. Linearity was confirmed up to 200 µg L−1 and LOD values were between 0.06 and 1.98 µg L−1. Recovery factors between 91 and 109% were obtained in the analysis of spiked surface water samples.
On the Origins of Some Spectroscopic Properties of “Purple Iron” (the Tetraoxoferrate(VI) Ion) and Its Pourbaix Safe-Space

In this work, the authors attempt to interpret the visible, infrared and Raman spectra of ferrate(VI) by means of theoretical physical-inorganic chemistry and historical highlights in this field of interest. In addition, the sacrificial decomposition of ferrate(VI) during water treatment will also be discussed together with a brief mention of how Rayleigh scattering caused by the decomposition of FeVIO42− may render absorbance readings erroneous. This work is not a compendium of all the instrumental methods of analysis which have been deployed to identify ferrate(VI) or to study its plethora of reactions, but mention will be made of the relevant techniques (e.g., Mössbauer Spectroscopy amongst others) which support and advance this overall discourse at appropriate junctures, without undue elaboration on the foundational physics of these techniques.
Perceived Risk in the Population Living near the Turin Incinerator: Comparison between before and at Three Years of Operation

When the Turin incinerator went into operation in 2013, it was accompanied by surveillance of health effects that included a human biomonitoring survey of 394 residents. They responded to items investigating their awareness of environmental and health issues and perception of environmental health risks. In this study, we compared the questionnaire responses before plant startup and at 3 years of operation. To accomplish this, we investigated changes in perceived risk and evaluated the efficacy of communication strategies. A total of 344 participants equally distributed in an exposed and an unexposed group responded to the follow-up questionnaire. Survey items investigated the perception of a relationship between illness and exposure to environmental pollution, feeling at risk of developing an illness, and concern about natural and anthropogenic hazards. The proportion of ‘certain’ and ‘very probable’ responses was compared to the total using the difference-in-differences method. Analyses showed an overall decrease in the differences between the two groups, which suggests that the communication actions undertaken for the exposed group were effective. Future communication plans should also include initiatives targeting the unexposed group.
Ruthenium Olefin Metathesis Catalysts Featuring N-Heterocyclic Carbene Ligands Tagged with Isonicotinic and 4-(Dimethylamino)benzoic Acid Rests: Evaluation of a Modular Synthetic Strategy

A modular and flexible strategy towards the synthesis of N-heterocyclic carbene (NHC) ligands bearing Brønsted base tags has been proposed and then adopted in the preparation of two tagged NHC ligands bearing rests of isonicotinic and 4-(dimethylamino)benzoic acids. Such tagged NHC ligands represent an attractive starting point for the synthesis of olefin metathesis ruthenium catalysts tagged in non-dissociating ligands. The influence of the Brønsted basic tags on the activity of such obtained olefin metathesis catalysts has been studied.
Additive Manufacturing of Plastics Used for Protection against COVID19—The Influence of Chemical Disinfection by Alcohol on the Properties of ABS and PETG Polymers

In this paper, the influence of disinfection on structural and mechanical properties of additive manufactured (AM) parts was analyzed. All AM parts used for a fight against COVID19 were disinfected using available methods—including usage of alcohols, high temperature, ozonation, etc.—which influence on AM parts properties has not been sufficiently analyzed. During this research, three types of materials dedicated for were tested in four different disinfection times and two disinfection liquid concentrations. It has been registered that disinfection liquid penetrated void into material’s volume, which caused an almost 20% decrease in tensile properties in parts manufactured using a glycol-modified version of polyethylene terephthalate (PETG).
Medical Students’ Personalities: A Critical Factor for Doctor-Patient Communication

The aim of this study was to assess the level of creativity and personality traits and their mutual influence on medical students using the DECAS and BWAS. We performed a prospective descriptive study on 119 medical students from Târgu Mureș, Romania between November 2020 and July 2021, who answered questions relating to the BWAS and DECAS scales to evaluate their creativity and personality traits. Our findings pointed out a reverse correlation between age and both the original and revised BWAS (r = −0.2037, p = 0.0263; r = −0.1931, p = 0.0354). In terms of extraversion, we found a significant positive correlation for both openness (r = 0.3032, p = 0.0008) and emotional stability (r = 0.2868, p = 0.0016) and a negative correlation between extraversion and agreeability (r = −0.2394, p = 0.0087). Regarding creativity, we found positive correlations between emotional stability and both the original and revised BWAS (r = 0.20, p = 0.0279; r = 0.20, p = 0.0245). Medical students’ creativity might be positively influenced by emotional stability and seems to decrease with age. Higher extraversion scores could be related to increased openness and emotional stability as well as decreased agreeability.
Constructing of Bacillus subtilis-Based Lux-Biosensors with the Use of Stress-Inducible Promoters

Here, we present a new lux-biosensor based on Bacillus subtilis for detecting of DNA-tropic and oxidative stress-causing agents. Hybrid plasmids pNK-DinC, pNK-AlkA, and pNK-MrgA have been constructed, in which the Photorhabdus luminescens reporter genes luxABCDE are transcribed from the stress-inducible promoters of B. subtilis: the SOS promoter PdinC, the methylation-specific response promoter PalkA, and the oxidative stress promoter PmrgA. The luminescence of B. subtilis-based biosensors specifically increases in response to the appearance in the environment of such common toxicants as mitomycin C, methyl methanesulfonate, and H2O2. Comparison with Escherichia coli-based lux-biosensors, where the promoters PdinI, PalkA, and Pdps were used, showed generally similar characteristics. However, for B. subtilis PdinC, a higher response amplitude was observed, and for B. subtilis PalkA, on the contrary, both the amplitude and the range of detectable toxicant concentrations were decreased. B. subtilis PdinC and B. subtilis PmrgA showed increased sensitivity to the genotoxic effects of the 2,2′-bis(bicyclo [2.2.1] heptane) compound, which is a promising propellant, compared to E. coli-based lux-biosensors. The obtained biosensors are applicable for detection of toxicants introduced into soil. Such bacillary biosensors can be used to study the differences in the mechanisms of toxicity against Gram-positive and Gram-negative bacteria.
Nitrogen-doped hierarchical porous carbon derived from a chitosan/polyethylene glycol blend for high performance supercapacitors

Nitrogen-doped hierarchical porous carbon (NHPC) materials were synthesized by using a chitosan/polyethylene glycol (PEG) blend as raw material through a facile carbonization–activation process. In this method, chitosan was used as a nitrogen-containing carbon precursor, low cost and large-scale commercial PEG was employed as a porogen. The physical and electrochemical properties of the resultant NHPC were affected by the ratio of chitosan and PEG. The sample obtained by the ratio of 3 : 2 exhibits a high specific surface area (2269 m2 g−1), moderate nitrogen doping (3.22 at%) and optimized pore structure. It exhibits a high specific capacitance of 356 F g−1 in 1 M H2SO4 and 271 F g−1 in 2 M KOH at a current density of 1 A g−1, and over 230 F g−1 can be still retained at a high current density of 20 A g−1 in both electrolytes. Additionally, the assembled symmetric supercapacitors show an excellent cycling stability with 94% (in 1 M H2SO4) and 97% (in 2 M KOH) retention after 10 000 cycles at 1 A g−1. These results indicate that the chitosan/PEG blend can act as a novel and appropriate precursor to prepare low-cost NHPC materials for high-performance supercapacitors.
Positive Charges in the Brace Region Facilitate the Membrane Disruption of MLKL-NTR in Necroptosis

Necroptosis is a type of programmed cell death executed through the plasma membrane disruption by mixed lineage kinase domain-like protein (MLKL). Previous studies have revealed that an N-terminal four-helix bundle domain (NBD) of MLKL is the executioner domain for the membrane permeabilization, which is auto-inhibited by the first brace helix (H6). After necroptosis initiation, this inhibitory brace helix detaches and the NBD can integrate into the membrane, and hence leads to necroptotic cell death. However, how the NBD is released and induces membrane rupture is poorly understood. Here, we reconstituted MLKL2–154 into membrane mimetic bicelles and observed the structure disruption and membrane release of the first brace helix that is regulated by negatively charged phospholipids in a dose-dependent manner. Using molecular dynamics simulation we found that the brace region in an isolated, auto-inhibited MLKL2–154 becomes intrinsically disordered in solution after 7 ns dynamic motion. Further investigations demonstrated that a cluster of arginines in the C-terminus of MLKL2–154 is important for the molecular conformational switch. Functional mutagenesis showed that mutating these arginines to glutamates hindered the membrane disruption of full-length MLKL and thus inhibited the necroptotic cell death. These findings suggest that the brace helix also plays an active role in MLKL regulation, rather than an auto-inhibitory domain.
Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity

Cell adhesion to stromal support and the associated intracellular signaling are central to drug resistance, therefore blocking both has been effective in increasing drug sensitization in leukemia. The stromal Ser/Thr protein kinase C (PKC) has been found to be important for conferring protection to leukemic cells. We aimed at elucidating the intracellular signals connected to cell adhesion and to stromal PKC. We found that NF-κB and Akt were up-regulated in mesenchymal stem cells (MSC) after binding of B-cell acute lymphoblastic leukemia (B-ALL) cells. Nevertheless, Akt inhibition did not induce B-ALL cell detachment. In spite of a clear activation of the NF-κB signaling pathway after B-ALL cell binding (up-regulation NF-κB1/2, and down-regulation of the IKBε and IKBα inhibitors) and an important reduction in cell adhesion after NF-κB inhibition, sensitization to the drug treatment was not observed. This was opposite to the PKC inhibitors Enzastaurin and HKPS, a novel chimeric peptide inhibitor, that were able to increase sensitization to dexamethasone, methotrexate, and vincristine. PLCγ1, Erk1/2, and CREB appear to be related to PKC signaling and PKC effect on drug sensitization since they were contra-regulated by HKPS when compared to dexamethasone-treated cells. Additionally, PKC inhibition by HKPS, but not by Enzastaurin, in MSC reduced the activity of three ABC transporters in leukemic cells treated with dexamethasone, a new indirect mechanism to increase sensitization to drug treatment in B-ALL cells. Our results show the validity of targeting the functional characteristic acquired and modulated during cell-to-cell interactions occurring in the leukemic niche.