Miracle-dz/UniFAR-FTUs huggingface dataset:
Spectroscopic Analysis of Rare-Earth Silicide Structures on the Si(111) Surface

Two-dimensional rare-earth silicide layers deposited on silicon substrates have been intensively investigated in the last decade, as they can be exploited both as Ohmic contacts or as photodetectors, depending on the substrate doping. In this study, we characterize rare-earth silicide layers on the Si(111) surface by a spectroscopic analysis. In detail, we combine Raman and reflectance anisotropy spectroscopy (RAS) with first-principles calculations in the framework of the density functional theory. RAS suggests a weakly isotropic surface, and Raman spectroscopy reveals the presence of surface localized phonons. Atomistic calculations allow to assign the detected Raman peaks to phonon modes localized at the silicide layer. The good agreement between the calculations and the measurements provides a strong argument for the employed structural model.
A Model Incorporating Serum Alkaline Phosphatase for Prediction of Liver Fibrosis in Adults with Obesity and Nonalcoholic Fatty Liver Disease

We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy was performed, and liver histology was evaluated by a pathologist blinded to the patients’ data. The endpoint was significant fibrosis defined as fibrosis stage ≥ 2. Independent predictors of fibrosis were identified by logistic regression. Two hundred ten patients were recruited. Liver histology revealed steatosis in 87.1%, steatohepatitis in 21.9%, and significant fibrosis in 10%. Independent predictors of significant fibrosis were ALP (Odds Ratio (OR) 1.03; 95% Confidence interval (CI), 1.01–1.05), alanine aminotransferase (OR 1.02; 95% CI, 1.01–1.03), HbA1c (OR 1.58; 95% CI, 1.20–2.09), and body mass index (OR 1.06; 95% CI, 1.00–1.13). A tree-based model was developed to predict significant fibrosis, with a receiver operating characteristic (ROC) area of 0.845, sensitivity of 0.857, specificity of 0.836, and accuracy of 0.931. The applicability of serum ALP as an independent biomarker of liver fibrosis should be considered in obesity surgery patients, and in the broader context of obese patients with nonalcoholic fatty liver disease.
Dental Applications of Carbon Nanotubes

Glass ionomer cements and resin-based composites are promising materials in restorative dentistry. However, their limited mechanical properties and the risk of bulk/marginal fracture compromise their lifespan. Intensive research has been conducted to understand and develop new materials that can mimic the functional behavior of the oral cavity. Nanotechnological approaches have emerged to treat oral infections and become a part of scaffolds for tissue regeneration. Carbon nanotubes are promising materials to create multifunctional platforms for dental applications. This review provides a comprehensive survey of and information on the status of this state-of-the-art technology and describes the development of glass ionomers reinforced with carbon nanotubes possessing improved mechanical properties. The applications of carbon nanotubes in drug delivery and tissue engineering for healing infections and lesions of the oral cavity are also described. The review concludes with a summary of the current status and presents a vision of future applications of carbon nanotubes in the practice of dentistry.
Effect of Hydrated Ionic Liquid on Photocycle and Dynamics of Photoactive Yellow Protein

The mechanism by which proteins are solvated in hydrated ionic liquids remains an open question. Herein, the photoexcitation dynamics of photoactive yellow protein dissolved in hydrated choline dihydrogen phosphate (Hy[ch][dhp]) were studied by transient absorption and transient grating spectroscopy. The photocyclic reaction of the protein in Hy[ch][dhp] was similar to that observed in the buffer solution, as confirmed by transient absorption spectroscopy. However, the structural change of the protein during the photocycle in Hy[ch][dhp] was found to be different from that observed in the buffer solution. The known change in the diffusion coefficient of the protein was apparently suppressed in high concentrations of [ch][dhp], plausibly due to stabilization of the secondary structure.
Evidence for Protein–Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143

Protein-protein interactions between G protein-coupled receptors (GPCRs) can augment their functionality and increase the repertoire of signaling pathways they regulate. New therapeutics designed to modulate such interactions may allow for targeting of a specific GPCR activity, thus reducing potential for side effects. Dopamine receptor (DR) heteromers are promising candidates for targeted therapy of neurological conditions such as Parkinson’s disease since current treatments can have severe side effects. To facilitate development of such therapies, it is necessary to identify the various DR binding partners. We report here a new interaction partner for DRD2 and DRD3, the orphan receptor G protein-coupled receptor 143 (GPR143), an atypical GPCR that plays multiple roles in pigment cells and is expressed in several regions of the brain. We previously demonstrated that the DRD2/ DRD3 antagonist pimozide also modulates GPR143 activity. Using confocal microscopy and two FRET methods, we observed that the DRs and GPR143 colocalize and interact at intracellular membranes. Furthermore, co-expression of wildtype GPR143 resulted in a 57% and 67% decrease in DRD2 and DRD3 activity, respectively, as determined by β-Arrestin recruitment assay. GPR143-DR dimerization may negatively modulate DR activity by changing affinity for dopamine or delaying delivery of the DRs to the plasma membrane.
Astrocytic NMDA Receptors in the Basolateral Amygdala Contribute to Facilitation of Fear Extinction

Abstract Background Enhancement of N-methyl-D-aspartate (NMDA) receptor function using glycine-site agonist D-cycloserine is known to facilitate fear extinction, providing a means to augment cognitive behavioral therapy in anxiety disorders. A novel class of glycine-site agonists has recently been identified, and we have found that the prototype, AICP, is more effective than D-cycloserine in modulating neuronal function. Methods Using novel glycine-site agonist AICP, local infusion studies, and genetic models, we elucidated the role of GluN2C-containing receptors in fear extinction. Results We tested the effect of intracerebroventricular injection of AICP on fear extinction and found a robust facilitation of fear extinction. This effect was dependent on GluN2C subunit, consistent with superagonist action of AICP at GluN2C-containing receptors. Local infusion studies in wild-type and GluN2C knockout mice suggested that AICP produces its effect via GluN2C-containing receptors in the basolateral amygdala (BLA). Furthermore, consistent with astrocytic expression of GluN2C subunit in the amygdala, we found that AICP did not facilitate fear extinction in mice with conditional deletion of obligatory GluN1 subunit from astrocytes. Importantly, chemogenetic activation of astrocytes in the basolateral amygdala facilitated fear extinction. Acutely, AICP was found to facilitate excitatory neurotransmission in the BLA via presynaptic GluN2C-dependent mechanism. Immunohistochemical studies suggest that AICP-mediated facilitation of fear extinction involves synaptic insertion of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor GluA1 subunit. Conclusion These results identify a unique role of astrocytic NMDA receptors composed of GluN2C subunit in extinction of conditioned fear memory and demonstrate that further development of recently identified superagonists of GluN2C-containing receptors may have utility for anxiety disorders.
Development of a Bispecific Antibody-Based Platform for Retargeting of Capsid Modified AAV Vectors

A major limiting factor for systemically delivered gene therapies is the lack of novel tissue specific AAV (Adeno-associated virus) derived vectors. Bispecific antibodies can be used to redirect AAVs to specific target receptors. Here, we demonstrate that the insertion of a short linear epitope “2E3” derived from human proprotein-convertase subtilisin/kexin type 9 (PCSK9) into different surface loops of the VP capsid proteins can be used for AAV de-targeting from its natural receptor(s), combined with a bispecific antibody-mediated retargeting. We chose to target a set of distinct disease relevant membrane proteins—fibroblast activation protein (FAP), which is upregulated on activated fibroblasts within the tumor stroma and in fibrotic tissues, as well as programmed death-ligand 1 (PD-L1), which is strongly upregulated in many cancers. Upon incubation with a bispecific antibody recognizing the 2E3 epitope and FAP or PD-L1, the bispecific antibody/rAAV complex was able to selectively transduce receptor positive cells. In summary, we developed a novel, rationally designed vector retargeting platform that can target AAVs to a new set of cellular receptors in a modular fashion. This versatile platform may serve as a valuable tool to investigate the role of disease relevant cell types and basis for novel gene therapy approaches.
Smart Materials: Cementitious Mortars and PCM Mechanical and Thermal Characterization

Climate change (CC) is predominantly connected to greenhouse gas (GHG) emissions from the construction sector. It is clear how it is necessary to rethink construction materials in order to reduce GHG emissions. Among the various strategies proposed, recent research has investigated the potential of smart materials. This study in particular aims to develop an innovative building component that combines high energy performance with reduced thickness and weight. For this reason, the potential of Phase Change Materials (PCM) in cement-based mixes is investigated, comparing the performance of a traditional mix with two innovative mixes made with the addition of 3% and 7% PCM. This work characterizes the new material, analyzing its mechanical and thermal performance, highlighting how the mix strength decreases as the PCM ratio increases; however, both mixes may be considered suitable for masonry structures and may be classified as M5 and M15. Furthermore, from the analysis of the thermal performance, it emerges that the mix presents good behavior in terms of insulating properties.
A machine-learning algorithm for the reliable identification of oral lichen planus.

BACKGROUND Oral lichen planus is a relatively common oral disorder which shares clinical and histopathological features with other lichenoid lesions, leading to considerable inter-observer disagreement. This negatively impacts understanding of the pathogenesis and malignant transformation potential of this condition. METHODS Artificial intelligence was employed to create a machine-learning artificial neural network to identify and quantify mononuclear cells and granulocytes within the inflammatory infiltrates in digitized hematoxylin and eosin microscopic slides. Twenty-four regions of interest were extracted from oral lichen planus cases for learning purposes and validated on a retrospective cohort of 130 cases. All cases were related to patients with confirmed diagnoses of oral lichen planus, oral lichenoid lesions, or oral epithelial dysplasia with lichenoid host response. RESULTS The number of inflammatory cells was statistically significantly higher in oral lichen planus compared to oral lichenoid lesions or oral epithelial dysplasia with lichenoid host response (p <.0005). The proposed machine-learning method was reliably capable of detecting oral lichen planus cases based on the number of inflammatory cells and the number of mononuclear cells with an area under the curve of 0.982 and 0.988, respectively. Identifying a cut-off point between oral lichen planus and other lichenoid conditions based on the number of mononuclear cells showed a sensitivity of 100% and an accuracy of 94.62%. CONCLUSION Artificial intelligence has shown promising outcomes and provides a robust approach to enhance the accuracy of anatomical pathologists in accurately diagnosing oral lichen planus using features of disease pathogenesis.
Interactive Effects of HRV and P-QRS-T on the Power Density Spectra of ECG Signals

Different from the traditional methods of assessing the cardiac activities through heart rhythm statistics or P-QRS-T complexes separately, this study demonstrates their interactive effects on the power density spectrum (PDS) of ECG signal with applications for the diagnosis of ST-segment elevation myocardial infarction (STEMI) diseases. Firstly, a mathematical model of the PDS of ECG signal with a random pacing pulse train (PPT) mimicking S-A node firings was derived. Secondly, an experimental PDS analysis was performed on clinical ECG signals from 49 STEMI patients and 42 healthy subjects in PTB Diagnostic Database. It was found that besides the interactive effects which are consistent between theoretical and experimental results, the ECG PDSs of STEMI patients exhibited consistently significant power shift towards lower frequency range in ST-elevated leads in comparison with those of reference leads and leads of health subjects with the highest median frequency shift ratios at 51.39 ± 12.94% found in anterior MI. Thirdly, the results of ECG simulation with systematic changes in PPT firing statistics over various lengths of ECG data ranging from 10 s to 60 mins revealed that the mean and median frequency parameters were less affected by the heart rhythm statistics and the data length but more depended on the alterations of P-QRS-T complexes, which were further confirmed on 33 more STEMI patients in European ST-T Database, demonstrating that the frequency indexes could be potentially used as alternative indicators for STEMI diagnosis even with ultra-short-term ECG recordings suitable for wearable and mobile health applications in living-free environments.
Executive-function tasks in patients with mild cognitive impairment and Alzheimer's Disease: Effects of decline and gender

Abstract It is exceedingly rare to find studies that analyze the effect of gender differences in executive-function tasks in normal cognitive aging, Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). The objective of the present study was to analyze the mean differences in performance in four executive-function tasks, the Clock Drawing Test verbal-command, Clock Drawing Test-copy, Phonetic Fluency Test and Trail Making Test-A, according to the gender and impairment group variables. A total of 90 participants (30 patients with Alzheimer's Disease, 30 patients with Mild Cognitive Impairment, and 30 healthy elderly participants; 50% men and 50% women in each group) took part in the study. As expected, the results showed a main effect of the group in most tasks, with a progressively worse performance according to cognitive impairment. Regarding the effect of gender, there were no significant differences in the Mild Cognitive Impairment and healthy elderly groups, but a significantly higher performance of women compared to men was found in the Alzheimer's group. The clinical and theoretical implications of these results are discussed. In particular, the abnormal performance of women with Alzheimer's in the sample may be related to a possible cognitive reserve due to social and educational background in their sociocultural and generational context.
Connexin43 in Germ Cells Seems to Be Dispensable for Murine Spermatogenesis

Testicular Connexin43 (Cx43) connects adjacent Sertoli cells (SC) and SC to germ cells (GC) in the seminiferous epithelium and plays a crucial role in spermatogenesis. However, the distinction whether this results from impaired inter-SC communication or between GC and SC is not possible, so far. Thus, the question arises, whether a GC-specific Cx43 KO has similar effects on spermatogenesis as it is general or SC-specific KO. Using the Cre/loxP recombinase system, two conditional KO mouse lines lacking Cx43 in premeiotic (pGCCx43KO) or meiotic GC (mGCCx43KO) were generated. It was demonstrated by qRT-PCR that Cx43 mRNA was significantly decreased in adult pGCCx43KO mice, while it was also reduced in mGCCx43KO mice, yet not statistically significant. Body and testis weights, testicular histology, tubular diameter, numbers of intratubular cells and Cx43 protein synthesis and localization did not show any significant differences in semi-quantitative Western blot analysis and immunohistochemistry comparing adult male KO and WT mice of both mouse lines. Male KO mice were fertile. These results indicate that Cx43 in spermatogonia/spermatids does not seem to be essential for successful termination of spermatogenesis and fertility as it is known for Cx43 in somatic SC, but SC-GC communication might rather occur via heterotypic GJ channels.
Sphingolipid metabolism during Toll‐like receptor 4 (TLR4)‐mediated macrophage activation

Macrophage activation in response to stimulation of Toll‐like receptor 4 (TLR4) provides a paradigm for investigating energy metabolism that regulates the inflammatory response. TLR4‐mediated pro‐inflammatory macrophage activation is characterized by increased glycolysis and altered mitochondrial metabolism, supported by selective amino acid uptake and/or usage. Fatty acid metabolism remains as a highly complex rewiring that accompanies classical macrophage activation. TLR4 activation leads to de novo synthesis of fatty acids, which flux into sphingolipids, complex lipids that form the building blocks of eukaryotic cell membranes and regulate cell function. Here, we review the importance of TLR4‐mediated de novo synthesis of membrane sphingolipids in macrophages. We first highlight fatty acid metabolism during TLR4‐driven macrophage immunometabolism. We then focus on the temporal dynamics of sphingolipid biosynthesis and emphasize the modulatory role of some sphingolipid species (i.e. sphingomyelins, ceramides and glycosphingolipids) on the pro‐inflammatory and pro‐resolution phases of LPS/TLR4 activation in macrophages.
Prospective Evaluation of Resection Margins Using Standardized Specimen Protocol Analysis among Patients with Distal Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma

Purpose: Using a standardized specimen protocol analysis, this study aimed to evaluate the resection margin status of patients who underwent resection for either distal cholangiocarcinoma (DC) or pancreatic ductal adenocarcinoma (PDAC). This allowed a precise millimetric analysis of each inked margin. Methods: From 2010 to 2018, 355 consecutively inked specimens from patients with PDAC (n = 288) or DC (n = 67) were prospectively assessed. We assessed relationships between the tumor and the following margins: transection of the pancreatic neck, bile duct, posterior surface, margin toward superior mesenteric artery, and the surface of superior mesenteric vein/portal vein groove. Resection margins were evaluated using a predefined cut-off value of 1 mm; however, clearances of 0 and 1.5 mm were also evaluated. Results: Patients with DC were mostly men (64% vs. 49%, p = 0.028), of older age (68 yo vs. 65, p = 0.033), required biliary stenting more frequently (93% vs. 77%, p < 0.01), and received less neoadjuvant treatment (p < 0.001) than patients with PDAC. The venous resection rate was higher among patients with PDAC (p = 0.028). Postoperative and 90-day mortality rates were comparable. Patients with PDAC had greater tumor size (28.6 vs. 24 mm, p = 0.01) than those with DC. The R1 resection rate was comparable between the two groups, regardless of the clearance margin. Among the three types of resection margins, a venous groove was the most frequent in both entities. In multivariate analysis, the R1 resection margin did not influence patient survival in either PDAC or DC. Conclusion: Our standardized specimen protocol analysis showed that the R1 resection rate was comparable in PDAC and DC.
Exercise Pills for Drug Addiction: Forced Moderate Endurance Exercise Inhibits Methamphetamine-Induced Hyperactivity through the Striatal Glutamatergic Signaling Pathway in Male Sprague Dawley Rats

Physical exercise reduces the extent, duration, and frequency of drug use in drug addicts during the drug initiation phase, as well as during prolonged addiction, withdrawal, and recurrence. However, information about exercise-induced neurobiological changes is limited. This study aimed to investigate the effects of forced moderate endurance exercise training on methamphetamine (METH)-induced behavior and the associated neurobiological changes. Male Sprague Dawley rats were subjected to the administration of METH (1 mg/kg/day, i.p.) and/or forced moderate endurance exercise (treadmill running, 21 m/min, 60 min/day) for 2 weeks. Over the two weeks, endurance exercise training significantly reduced METH-induced hyperactivity. METH and/or exercise treatment increased striatal dopamine (DA) levels, decreased p(Thr308)-Akt expression, and increased p(Tyr216)-GSK-3β expression. However, the phosphorylation levels of Ser9-GSK-3β were significantly increased in the exercise group. METH administration significantly increased the expression of NMDAr1, CaMKK2, MAPKs, and PP1 in the striatum, and exercise treatment significantly decreased the expression of these molecules. Therefore, it is apparent that endurance exercise inhibited the METH-induced hyperactivity due to the decrease in GSK-3β activation by the regulation of the striatal glutamate signaling pathway.
Lutetium-177 Labelled PSMA Targeted Therapy in Advanced Prostate Cancer: Current Status and Future Perspectives

Simple Summary For patients with advanced prostate cancer, many different treatment options are available. One option is the radioligand therapy with 177Lutetium labelled prostate-specific membrane antigen (Lu-PSMA). This treatment showed good results in previous studies with only some non-severe side effects. This review offers a short overview about the application, current standings and the future perspective of the radioligand therapy with Lu-PSMA. An approval of this therapy is awaited within 2021. Abstract Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option 177Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited adverse events. However, to this point, it still remains unclear which patients benefit the most from 177Lu-PSMA therapy, and how to improve the treatment regimen to achieve best outcome while minimizing potential adverse events. The efficacy for mCRPC patients is a given fact, and with the newly published results of the VISION trial its approval is only a matter of time. Recently, investigators started to focus on treating prostate cancer patients in earlier disease stages and in combination with other compounds. This review gives a brief overview of the current state and the future perspectives of 177Lu labelled PSMA radioligand therapy.