Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Characterization of Adrenocortical Masses in Nononcologic Patients Using 68Ga-Pentixafor

Visual Abstract We aimed to investigate the diagnostic and prognostic value of 68Ga-pentixafor PET/CT imaging in noncancer patients with suspected adrenal masses. Methods: Sixty-four patients who had benign adrenal masses on CT were retrospectively included in our study. All patients underwent 68Ga-pentixafor PET/CT, and 56 of these patients subsequently underwent adrenalectomy. The subtypes of 81 adrenal tumors, including 14 nonfunctioning adrenal nodules, 4 cortisol-producing adenomas, 41 aldosterone-producing adenomas, 5 cases of suspected unilateral adrenal hyperplasia, 15 cases of idiopathic aldosterone hyperplasia, and 2 pheochromocytomas, were determined by histology or follow-up evaluations. The diagnostic efficiency of functional lateralization was calculated by visual analysis. Semiquantitative parameters of these lesions, including SUVmax, the ratio of lesional SUVmax to normal liver SUVmean (LLR), and the ratio of lesional SUVmax to contralateral adrenal tissue SUVmean (LCR), were also calculated. Dynamic analysis was also performed on 15 patients. In addition, clinical outcomes were assessed and compared in patients who underwent adrenalectomy. Results: The sensitivity and specificity of 68Ga-pentixafor PET for functional lateralization in patients with adrenocortical lesions were 97.8% (45/46) and 87.5% (14/16), respectively. The 2 pheochromocytoma lesions had lower pentixafor uptake than the normal adrenal glands. Functioning (active) adrenocortical adenomas showed an elevated SUVmax of 16.3 ± 7.9, in comparison to 4.4 ± 1.7 in nonfunctioning (inactive) adenomas and 5.5 ± 2.7 in hyperplasia lesions (P < 0.0001). To identify active adrenocortical adenomas, a cutoff of 7.1 for SUVmax showed a sensitivity of 90.9% and a specificity of 85.3% (area under receiver-operating-characteristic curve, 0.96; P < 0.0001); a cutoff of 2.5 for LLR showed a sensitivity of 95.5% and a specificity of 88.2% (area under receiver-operating-characteristic curve, 0.97; P < 0.0001); and a cutoff of 2.4 for LCR showed a sensitivity of 88.6% and a specificity of 91.8% (area under receiver-operating-characteristic curve, 0.95; P < 0.0001). The graphical influx rate constant of active adrenocortical adenomas was significantly higher than that of inactive adenomas. Uptake values for 68Ga-pentixafor were significantly higher in patients with preferable outcomes (cured/improved) (SUVmax, 15.5 ± 8.0; LLR, 6.5 ± 4.3; LCR, 6.2 ± 5.0) than in patients with nonpreferable outcomes (no improvement) (SUVmax, 4.2 ± 0.5; LLR, 1.3 ± 0.2; LCR, 1.5 ± 0.6; all P < 0.0001). Conclusion: 68Ga-pentixafor PET/CT imaging exhibits great potential for noninvasive functional lateralization and characterization in patients with adrenocortical masses.
Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models

Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including genetic predispositions to AF development. Genome-wide association studies have identified a number of genetic variants in association with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research is insufficient for understanding the functional impacts of PITX2 variants on AF. Linking PITX2 properties to ion channels, cells, tissues, atriums and the whole heart, computational models provide a supplementary tool for achieving a quantitative understanding of the functional role of PITX2 in remodelling atrial structure and function to predispose to AF. It is hoped that computational approaches incorporating all we know about PITX2-related structural and electrical remodelling would provide better understanding into its proarrhythmic effects leading to development of improved anti-AF therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives.
Green Composite of Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Reinforced with Porous Cellulose

In this study, a green composite from bacterial polyester, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH), and cellulose was developed. Cellulose gel was prepared from a Ca(SCN)2 aqueous solution, and subsequent washing by ethanol gave regenerated porous cellulose without shrinkage. The PHBH/cellulose composite was fabricated by immersion of porous cellulose in a polymer solution. The cellulose content of the composite was controlled by changing the cellulose concentration of the Ca(SCN)2 aqueous solution. The resulting composites showed a relatively good transparency with improvements in mechanical properties such as tensile strength, toughness, and brittleness. Furthermore, the thermal stability of the composites was improved by the introduction of cellulose. These composites from renewable resources are expected to contribute to the development of biobased materials in composite science.
SiO2 Coating on Stainless Steel Sheets from CH3Si(OC2H5)3

The sol-gel coating process of stainless steel sheets with SiO2 films has been studied using CH3Si(OC2H5)3 as a starting material. The obtained SiO2 films had improved extensibility over that obtained from Si(OC2H5)4. Results of DTA-TG and infrared spectra showed that CH3 groups remained in the films even after the heat-treatment at 400°C for 1min. Thus, extensibility of these SiO2 films was ascribed to the flexible structure resulting from the remaining CH3 groups.
Depth Completion and Super-Resolution with Arbitrary Scale Factors for Indoor Scenes †

Depth sensing has improved rapidly in recent years, which allows for structural information to be utilized in various applications, such as virtual reality, scene and object recognition, view synthesis, and 3D reconstruction. Due to the limitations of the current generation of depth sensors, the resolution of depth maps is often still much lower than the resolution of color images. This hinders applications, such as view synthesis or 3D reconstruction, from providing high-quality results. Therefore, super-resolution, which allows for the upscaling of depth maps while still retaining sharpness, has recently drawn much attention in the deep learning community. However, state-of-the-art deep learning methods are typically designed and trained to handle a fixed set of integer-scale factors. Moreover, the raw depth map collected by the depth sensor usually has many depth data missing or misestimated values along the edges and corners of observed objects. In this work, we propose a novel deep learning network for both depth completion and depth super-resolution with arbitrary scale factors. The experimental results on the Middlebury stereo, NYUv2, and Matterport3D datasets demonstrate that the proposed method can outperform state-of-the-art methods.
Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors

The α7-type nicotinic acetylcholine receptor is one of the most unique and interesting of all the members of the cys-loop superfamily of ligand-gated ion channels. Since it was first identified initially as a binding site for α-bungarotoxin in mammalian brain and later as a functional homomeric receptor with relatively high calcium permeability, it has been pursued as a potential therapeutic target for numerous indications, from Alzheimer disease to asthma. In this review, we discuss the history and state of the art for targeting α7 receptors, beginning with subtype-selective agonists and the basic pharmacophore for the selective activation of α7 receptors. A key feature of α7 receptors is their rapid desensitization by standard “orthosteric” agonist, and we discuss insights into the conformational landscape of α7 receptors that has been gained by the development of ligands binding to allosteric sites. Some of these sites are targeted by positive allosteric modulators that have a wide range of effects on the activation profile of the receptors. Other sites are targeted by direct allosteric agonist or antagonists. We include a perspective on the potential importance of α7 receptors for metabotropic as well as ionotropic signaling. We outline the challenges that exist for future development of drugs to target this important receptor and approaches that may be considered to address those challenges. Significance Statement The α7-type nicotinic acetylcholine receptor (nAChR) is acknowledged as a potentially important therapeutic target with functional properties associated with both ionotropic and metabotropic signaling. The functional properties of α7 nAChR can be regulated in diverse ways with the variety of orthosteric and allosteric ligands described in this review.
Removal of peptidoglycan and inhibition of active cellular processes leads to daptomycin tolerance in Enterococcus faecalis

Daptomycin is a cyclic lipopeptide antibiotic used in the clinic for treatment of severe enterococcal infections. Recent reports indicate that daptomycin targets active cellular processes, specifically, peptidoglycan biosynthesis. Within, we examined the efficacy of daptomycin against Enterococcus faecalis under a range of environmental growth conditions including inhibitors that target active cellular processes. Daptomycin was far less effective against cells in late stationary phase compared to cells in exponential phase, and this was independent of cellular ATP levels. Further, the addition of either the de novo protein synthesis inhibitor chloramphenicol or the fatty acid biosynthesis inhibitor cerulenin induced survival against daptomycin far better than controls. Alterations in metabolites associated with peptidoglycan synthesis correlated with protection against daptomycin. This was further supported as removal of peptidoglycan induced physiological daptomycin tolerance, a synergistic relation between daptomycin and fosfomycin, an inhibitor of the fist committed step peptidoglycan synthesis, was observed, as well as an additive effect when daptomycin was combined with ampicillin, which targets crosslinking of peptidoglycan strands. Removal of the peptidoglycan of Enterococcus faecium, Staphylococcus aureus, and Bacillus subtilis also resulted in significant protection against daptomycin in comparison to whole cells with intact cell walls. Based on these observations, we conclude that bacterial growth phase and metabolic activity, as well as the presence/absence of peptidoglycan are major contributors to the efficacy of daptomycin.
Diffusion in nanoporous materials: fundamental principles, insights and challenges

Following a brief review of Fick's laws and the theory of diffusion in a homogeneous medium, we consider the application of the Fickian model to diffusion in nanoporous materials. If the pore system is statistically uniform the simple Fickian model is directly applicable. Inhomogeneities such as surface or internal barriers require some adjustments to the model but Fick's equations still provide a valid approach. Hierarchical pore systems present a more serious challenge. When there is rapid exchange between the different regions such systems conform to the simple Fickian model, with a diffusivity corresponding to the mean of the diffusivities in the different regions. In contrast, when the condition of rapid exchange is not fulfilled the simple Fickian model is not applicable and the situation becomes more complicated. Simple hierarchical pore structures such as the micropore/macropore system typically found in commercial adsorbents and catalysts can still be described by a dual resistance Fickian model but for more complex hierarchical pore structures Monte Carlo or MD simulations offer the only realistic approach. The measurement of self-diffusion by PFG NMR and by microimaging (notably by interference microscopy) is also reviewed and selected examples are presented to show the detailed information that can be extracted from such measurements, especially when accompanied by molecular simulations. Examples highlighting the relevance of a detailed knowledge of the various steps of mass transfer for a transport-optimized technological application of nanoporous materials, notably for molecular separations and mass conversions, are provided.
Mental and Physical Health Problems as Conditions of Ex-Prisoner Re-Entry

The article focuses on a less-discussed issue of social marginalization of people leaving penitentiaries, which is the prevalence of multifaceted health problems experienced by people in this category. It includes poor health status, resulting from, among others, poor housing conditions, harmful or risky lifestyle, and lack of access to medical services. Data from the District Inspectorate of the Prison Service in Lodz, Poland on the health conditions of inmates was accessed. These data were supplemented by qualitative research conducted in 21 juvenile detention centers and 8 prisons across the country, conducting direct observations and In-Depth Interviews (IDI). A total of 198 IDIs were conducted with incarcerated (72) and released (30) juvenile offenders, and incarcerated (68) and released (28) adult offenders. These were complemented by IDIs with experts (50) and Focus Group Interviews (FGIs; 8) with male and female inmates in 4 Polish prisons. The study revealed that mental and physical health is a serious obstacle to social reintegration of ex-prisoners. It is rarely addressed by state institutions. There are strong associations between neglect of health issues in the prison population and increasing social exclusion after leaving prison. As Poland has a restrictive penal policy, former prisoners remain a group with social stigma and little support.
Comprehensive Assessment and Potential Ecological Risk of Trace Element Pollution (As, Ni, Co and Cr) in Aquatic Environmental Samples from an Industrialized Area

A global assessment of arsenic (As), nickel (Ni), cobalt (Co) and chromium (Cr) was performed in environmental samples from an important industrial bay. Different fractions of water, sediments and tissues from four species of fish were analysed. Samples were collected from selected sampling sites during four consecutive samplings in spring and autumn seasons, in order to evaluate concentrations and their possible correlations among the aquatic compartments. While a higher availability of Cr and Ni was found in water, Co and As were the most available elements in sediments. In fish, the liver was the tissue with the highest proportion of As and Co, and gills showed the highest concentrations of Ni and Cr. Significance differences were observed among sites showing the pollution sources. In sediments, high correlations were found between total Co content and the most available fractions. Total Ni content highly correlated with the oxidisable fraction, while Cr total content tightly correlated with the least available fractions. Quality guideline values for sediments were frequently exceeded. In sediments and biota, concentrations were slightly higher than in other ecosystems, indicating that maritime, industrial and urban activities are affecting this type of ecosystem with great anthropogenic influence.
Support Vector Machine as a Supervised Learning for the Prioritization of Novel Potential SARS-CoV-2 Main Protease Inhibitors

In the last year, the COVID-19 pandemic has highly affected the lifestyle of the world population, encouraging the scientific community towards a great effort on studying the infection molecular mechanisms. Several vaccine formulations are nowadays available and helping to reach immunity. Nevertheless, there is a growing interest towards the development of novel anti-covid drugs. In this scenario, the main protease (Mpro) represents an appealing target, being the enzyme responsible for the cleavage of polypeptides during the viral genome transcription. With the aim of sharing new insights for the design of novel Mpro inhibitors, our research group developed a machine learning approach using the support vector machine (SVM) classification. Starting from a dataset of two million commercially available compounds, the model was able to classify two hundred novel chemo-types as potentially active against the viral protease. The compounds labelled as actives by SVM were next evaluated through consensus docking studies on two PDB structures and their binding mode was compared to well-known protease inhibitors. The best five compounds selected by consensus docking were then submitted to molecular dynamics to deepen binding interactions stability. Of note, the compounds selected via SVM retrieved all the most important interactions known in the literature.
Combined Exposure to Diazinon and Nicotine Exerts a Synergistic Adverse Effect In Vitro and Disrupts Brain Development and Behaviors In Vivo

A real-life environment during pregnancy involves multiple and simultaneous exposures to toxic chemicals. Perinatal exposures to toxic chemicals have been reported to exert an inhibitory effect on mouse neural development and behaviors. However, the effect of combined exposures of organophosphate and nicotine has not been previously reported. In this study, we investigated whether a combined exposure of diazinon and nicotine can have a synergistic effect. The effects of the combined chemical exposure on cell viability and neuronal differentiation were examined using mouse Sox1-GFP cells. Additionally, mice were maternally administered 0.18 mg/kg diazinon, a no adverse effect level (NOAEL) dose, combined with 0.4, 1, and 2 mg/kg nicotine. Mice offspring underwent behavior tests to assess locomotor, depressive, cognitive, and social behaviors. Morphological change in the brain was investigated with immunolocalization. We revealed that the combined exposure to diazinon and nicotine can have a synergistic adverse effect in vitro. In addition, the chemical-treated mouse offspring showed abnormalities in motor learning, compulsive-like behaviors, spatial learning, and social interaction patterns. Moreover, 0.18 mg/kg diazinon and 2 mg/kg nicotine co-exposure resulted in an increase in tyrosine hydroxylase (TH)-positive dopaminergic neurons. Thus, the findings suggest that perinatal co-exposure to nicotine and diazinon can result in abnormal neurodevelopment and behavior, even at low-level administration.
Comparison Study of the Histomorphometric Results after Socket Preservation with PRF and Allograft Used for Socket Preservation—Randomized Controlled Trials

The aim of the present clinical study was to assess and compare the histomorphometric results and efficacy of freeze-dried bone allograft (FDBA) in combination with platelet-rich fibrin (PRF), and PRF as a sole grafting material for socket preservation. Ninety patients in need of tooth extraction and implant restoration were included in this study. The participants were randomly divided into three groups based on post-extraction clinical protocol: socket preservation procedure with allograft in combination with a PRF membrane (PRFm), PRF as a sole grafting material, and a control group. A total of 90 implants were placed four months post-extraction. During the surgical re-entry a bone biopsy was harvested with a trephine drill. Histological samples were prepared and analyzed for percentage vital bone and connective tissue. One-way ANOVA with Bonferroni post-hoc analysis were used to assess the results. Both test groups revealed a significantly higher percentage of vital bone formation compared to the control group. No statistically significant differences regarding vital bone formation and connective tissue quantity between the tested groups were observed (FDBA + PRFm: 3.29 ± 13.03%; and PRF: 60.79 ± 9.72%). From a clinical and histological point of view, both materials in the test groups are suitable for the filling of post-extraction sockets without bone defects. Both of the tested groups revealed a significantly higher percentage of vital bone formation compared to the control group.
Internalization of Neutrophil-Derived Microvesicles Modulates TNFα-Stimulated Proinflammatory Cytokine Production in Human Fibroblast-Like Synoviocytes

Neutrophil-derived microvesicles (NDMVs) have the potential to exert anti-inflammatory effects. Our study aimed to explore the effects of NDMVs on proinflammatory cytokines expressed by tumor necrosis factor α (TNFα)-stimulated fibroblast-like synoviocytes (FLS). FLS were isolated from the synovium of knee osteoarthritis (OA) patients undergoing surgery. NDMVs, isolated from TNFα-stimulated healthy neutrophils, were characterized by electron microscopy and nanoparticle tracking analysis. MTT and scratch wound healing assays were used to measure FLS viability and migration after treatment with NDMVs, while internalization of fluorescently labeled NDMVs was appraised by flow cytometry and confocal microscopy. Levels of proinflammatory cytokines in supernatants were quantified by the Bio-Plex system. Incubation of FLS with NDMVs at a vesicle/cell ratio of 100 resulted in a time-dependent uptake, with 35% of synoviocytes containing microvesicles over a 6–24 h time period, with no significant change in cell viability. TNFα stimulated the cytokine expression in FLS, and NDMVs down-regulated TNFα-induced expression of IL-5, IL-6, IL-8, MCP-1, IFNγ and MIP-1β. However, this down-regulation was selective, as NDMVs had no significant effects on TNFα-stimulated expression of IL-2 or IL-4. NDMVs were internalized by FLS to inhibit TNFα-stimulated broad-spectrum proinflammatory cytokine secretion. NDMVs, therefore, may exhibit an anti-inflammatory role in the regulation of the FLS function.
Cysteine Proteome Reveals Response to Endogenous Oxidative Stress in Bacillus cereus

At the end of exponential growth, aerobic bacteria have to cope with the accumulation of endogenous reactive oxygen species (ROS). One of the main targets of these ROS is cysteine residues in proteins. This study uses liquid chromatography coupled to high-resolution tandem mass spectrometry to detect significant changes in protein abundance and thiol status for cysteine-containing proteins from Bacillus cereus during aerobic exponential growth. The proteomic profiles of cultures at early-, middle-, and late-exponential growth phases reveals that (i) enrichment in proteins dedicated to fighting ROS as growth progressed, (ii) a decrease in both overall proteome cysteine content and thiol proteome redox status, and (iii) changes to the reduced thiol status of some key proteins, such as the transition state transcriptional regulator AbrB. Taken together, our data indicate that growth under oxic conditions requires increased allocation of protein resources to attenuate the negative effects of ROS. Our data also provide a strong basis to understand the response mechanisms used by B. cereus to deal with endogenous oxidative stress.