Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the Predictive Potential of 18F-FDG PET and DWI Data Sets for Relevant Prognostic Parameters of Primary Soft-Tissue Sarcomas

Simple Summary In this study, we assessed the potential of simultaneously acquired 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and magnetic resonance imaging-derived quantitative imaging parameters to predict the tumor grade, metastatic status, and response to neoadjuvant therapy of primary soft-tissue sarcomas of the extremities. Based on the results of the present study, quantifications of the 18F-FDG PET uptake provide useful prognostic data for the evaluation of histopathological response to neoadjuvant treatment as well as the aggressiveness of high-risk sarcomas, whereas no correlation between the different outcome variables and the results for tumor size and diffusion-weighted imaging-derived apparent diffusion coefficient values was found. Accordingly, measurements of the metabolic activity of primary and untreated soft-tissue sarcomas could non-invasively deliver relevant information, that may be used for treatment planning and risk-stratification of sarcoma patients in a pretherapeutic setting. Abstract Background: To evaluate the potential of simultaneously acquired 18F-FDG PET- and MR-derived quantitative imaging data sets of primary soft-tissue sarcomas for the prediction of neoadjuvant treatment response, the metastatic status and tumor grade. Methods: A total of 52 patients with a high-risk soft-tissue sarcoma underwent a 18F-FDG PET/MR examination within one week before the start of neoadjuvant treatment. For each patient, the maximum tumor size, metabolic activity (SUVs), and diffusion-restriction (ADC values) of the tumor manifestations were determined. A Mann–Whitney-U test was used, and ROC analysis was performed to evaluate the potential to predict histopathological treatment response, the metastatic status or tumor grade. The results from the histopathological analysis served as reference standard. Results: Soft-tissue sarcomas with a histopathological treatment response revealed a significantly higher metabolic activity than tumors in the non-responder group. In addition, grade 3 tumors showed a significant higher 18F-FDG uptake than grade 2 tumors. Furthermore, no significant correlation between the different outcome variables and tumor size or calculated ADC-values could be identified. Conclusion: Measurements of the metabolic activity of primary and untreated soft-tissue sarcomas could non-invasively deliver relevant information that may be used for treatment planning and risk-stratification of high-risk sarcoma patients in a pretherapeutic setting.
Immunotherapeutic Approaches in Malignant Pleural Mesothelioma

Simple Summary Immune checkpoint inhibitors (ICIs) have emerged as a very promising therapeutic option for the treatment of many difficult-to-treat cancers and a number of clinical trials have explored their efficacy in malignant pleural mesothelioma patients. ICIs were initially evaluated in the salvage setting, resulting in a modest activity, not superior to chemotherapy. However, in the last year the combination of nivolumab and ipilimumab as first line treatment has proved a superior efficacy compared to chemotherapy especially in the non-epithelioid subtype, obtaining the FDA approval in October 2020. Encouraging results are also emerging from other immunological approaches that take advantage of tumor-specific antigens, such as advanced cell-based therapies with the CAR-T cells and tumor vaccines. Abstract Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerging immunotherapy treatments for MPM (ICIs, engineered T cells to express chimeric antigen receptors (CARs), dendritic cells (DCs) vaccines), focusing on the biological and immunological features of this tumor as well as on the issues surrounding clinical trial design.
Noncompaction Cardiomyopathy—History and Current Knowledge for Clinical Practice

Noncompaction cardiomyopathy (NCCM) has gained increasing attention over the past twenty years, but in daily clinical practice NCCM is still rarely considered. So far, there are no generally accepted diagnostic criteria and some groups even refuse to acknowledge it as a distinct cardiomyopathy, and grade it as a variant of dilated cardiomyopathy or a morphological trait of different conditions. A wide range of morphological variants have been observed even in healthy persons, suggesting that pathologic remodeling and physiologic adaptation have to be differentiated in cases where this spongy myocardial pattern is encountered. Recent studies have uncovered numerous new pathogenetic and pathophysiologic aspects of this elusive cardiomyopathy, but a current summary and evaluation of clinical patient management are still lacking, especially to avoid mis- and overdiagnosis. Addressing this issue, this article provides an up to date overview of the current knowledge in classification, pathogenesis, pathophysiology, epidemiology, clinical manifestations and diagnostic evaluation, including genetic testing, treatment and prognosis of NCCM.
Theoretical Study of the Aliphatic-Chain Length’s Electronic Effect on the Corrosion Inhibition Activity of Methylimidazole-Based Ionic Liquids

Density Functional Theory based studies about the inhibition of corrosion affecting the cathode hematite surface by coverage with an methylimidazole-based ionic liquid, IL, were performed. Inhibition performance is tuned through the length of aliphatic chains Cn attached to the imidazolium aromatic ring, where n = 1, . , 20. Frontier molecular orbitals and energy gaps for single ILs and a pristine (112) hematite surface, the energy difference between ILs and hematite-surface, Fukui indices for the ILs, and adsorption energies and charge transfers for ILs/hematite surface systems were calculated. Results show that adsorption activity is due to the donation/back-donation bonding among the imidazolium aromatic ring of the ILs and the exposed iron atoms of the hematite surface. Dispersive long-range interactions from the ILs alkyl tails allow a closer bonding of the corrosion inhibitor molecules to the hematite surface; the charge transfer between the IL and the hematite is in C18. The optimal alkyl chain s.
An Interactive Haptic Guidance System for Intuitive Programming CNC Machine Tool

The human-machine interfaces in modern CNC machine tools are not very intuitive and still based on archaic input systems, i.e., switches, handwheels, and buttons. This type of solution has two major drawbacks. The pushed button activates the movement only in one direction and is insensitive to the amount of the force exerted by the operator, which makes it difficult to move the machine axes at variable speeds. The paper proposes a novel and intuitive system of manual programming of a CNC machine tool based on a control lever with strain-gauge sensors. The presented idea of manual programming is aimed at eliminating the need to create a machining program and at making it possible to move the machine intuitively, eliminating mistakes in selecting directions and speeds. The article describes the concept of the system and the principle of operation of the control levers with force sensors. The final part of the work presents the experimental validation of the proposed system and a functionality comparison with the traditional CNC control.
Carbonized Cotton Fabric-Based Flexible Capacitive Pressure Sensor Using a Porous Dielectric Layer with Tilted Air Gaps

Flexible and wearable pressure sensors have attracted significant attention owing to their roles in healthcare monitoring and human–machine interfaces. In this study, we introduce a wide-range, highly sensitive, stable, reversible, and biocompatible pressure sensor based on a porous Ecoflex with tilted air-gap-structured and carbonized cotton fabric (CCF) electrodes. The knitted structure of electrodes demonstrated the effectiveness of the proposed sensor in enhancing the pressure-sensing performance in comparison to a woven structure due to the inherent properties of naturally generated space. In addition, the presence of tilted air gaps in the porous elastomer provided high deformability, thereby significantly improving the sensor sensitivity compared to other dielectric structures that have no or vertical air gaps. The combination of knitted CCF electrodes and the porous dielectric with tilted air gaps achieved a sensitivity of 24.5 × 10−3 kPa−1 at 100 kPa, along with a wide detection range (1 MPa). It is also noteworthy that this novel method is low-cost, facile, scalable, and ecofriendly. Finally, the proposed sensor integrated into a smart glove detected human motions of grasping water cups, thus demonstrating its potential applications in wearable electronics.
Nurses and Pharmaceutical Care: Interprofessional, Evidence-Based Working to Improve Patient Care and Outcomes

Pharmaceutical care necessitates significant efforts from patients, informal caregivers, the interprofessional team of health care professionals and health care system administrators. Collaboration, mutual respect and agreement amongst all stakeholders regarding responsibilities throughout the complex process of pharmaceutical care is needed before patients can take full advantage of modern medicine. Based on the literature and policy documents, in this position paper, we reflect on opportunities for integrated evidence-based pharmaceutical care to improve care quality and patient outcomes from a nursing perspective. Despite the consensus that interprofessional collaboration is essential, in clinical practice, research, education and policy-making challenges are often not addressed interprofessionally. This paper concludes with specific advises to move towards the implementation of more interprofessional, evidence-based pharmaceutical care.
Analysis of Relationships between Immune Checkpoint and Methylase Gene Polymorphisms and Outcomes after Unrelated Bone Marrow Transplantation

Simple Summary Hematopoietic stem-cell transplantation (HSCT) is a curative therapy for blood disorders. Unrelated bone marrow transplantation (uBMT) is a type of allogeneic HSCT that uses the bone marrow of an unrelated donor. While HLA mismatch is a risk factor for poor outcomes in HSCT, such as graft-versus-host disease (GVHD), the importance of non-HLA single-nucleotide polymorphisms (SNPs) remains unclear. The clinical application of immune checkpoint and chromatin methylation inhibitors to cancer has been attracting attention. In the present study, we retrospectively genotyped five SNPs in four immune checkpoint genes, BTLA, PD-1, LAG3, and CTLA4, and two SNPs in methylase genes, DNMT1 and EZH2, in 999 uBMT pairs. Although no correlations were observed between these SNPs and post-uBMT outcomes, recipient EZH2 SNP exhibited a low p-value in the analysis of grade 2–4 acute GVHD (p = 0.010). This SNP may be useful for outcome predictions and needs to be confirmed in a larger-scale study. Abstract Unrelated bone marrow transplantation (uBMT) is performed to treat blood disorders, and it uses bone marrow from an unrelated donor as the transplant source. Although the importance of HLA matching in uBMT has been established, that of other genetic factors, such as single-nucleotide polymorphisms (SNPs), remains unclear. The application of immunoinhibitory receptors as anticancer drugs has recently been attracting attention. This prompted us to examine the importance of immunoinhibitory receptor SNPs in uBMT. We retrospectively genotyped five single-nucleotide polymorphisms (SNPs) in the immune checkpoint genes, BTLA, PD-1, LAG3, and CTLA4, and two SNPs in the methylase genes, DNMT1 and EZH2, in 999 uBMT donor–recipient pairs coordinated through the Japan Marrow Donor Program matched at least at HLA-A, -B, and -DRB1. No correlations were observed between these SNPs and post-uBMT outcomes (p > 0.005). This result questions the usefulness of these immune checkpoint gene polymorphisms for predicting post-BMT outcomes. However, the recipient EZH2 histone methyltransferase gene SNP, which encodes the D185H substitution, exhibited a low p-value in regression analysis of grade 2–4 acute graft-versus-host disease (p = 0.010). Due to a low minor allele frequency, this SNP warrants further investigation in a larger-scale study.
Proximate Composition, Antioxidant Properties, and Hepatoprotective Activity of Three Species of Shellfish of the Pacific Coast of Russia

The objective of the present study was to investigate the proximate composition, antiradical properties and hepatoprotective activity of three species of shellfish, Corbicula japonica, Spisula sachalinensis, and Anadara broughtonii, from the coastal areas of Far East Russia. Biologically active peptides such as taurine (3.74 g/100 g protein) and ornithine (2.12 g/100 g protein) have been found in the tissues of A. broughtonii. C. japonica contains a high amount of ornithine (5.57 g/100 g protein) and taurine (0.85 g/100 g protein). The maximum DPPH and ABTS radical scavenging activity (36.0 µg ascorbic acid/g protein and 0.68 µmol/Trolox equiv/g protein, respectively) was determined for the tissue of C. japonica. The protein and peptide molecular weight distribution of the shellfish tissue water extracts was investigated using HPLC. It was found that the amount of low molecular weight proteins and peptides were significantly and positively correlated with radical scavenging activity (Pearson’s correlation coefficient = 0.96), while the amount of high molecular weight proteins negatively correlated with radical scavenging activity (Pearson’s correlation coefficient = −0.86). Hepatoprotective activity, measured by the survival rate of HepG2 hepatocytes after cotreatment with t-BHP, was detected for C. japonica. The highest protection (95.3 ± 2.4%) was achieved by the cold water extract of C. japonica at the concentration of 200 mg/mL. Moreover, oral administration of hot water extract of C. japonica to rats before the treatment with CCl4 exhibited a markedly protective effect by lowering serum levels of ALT and AST, inhibiting the changes in biochemical parameters of functional state of rat liver, including MDA, SOD, GSH and GST.
Elucidating the Aromatic Properties of Covalent Organic Frameworks Surface for Enhanced Polar Solvent Adsorption

Covalent organic frameworks (COFs) have a distinguished surface as they are mostly made by boron, carbon, nitrogen and oxygen. Many applications of COFs rely on polarity, size, charge, stability and hydrophobicity/hydrophilicity of their surface. In this study, two frequently used COFs sheets, COF-1 and covalent triazine-based frameworks (CTF-1), are studied. In addition, a theoretical porous graphene (TPG) was included for comparison purposes. The three solid sheets were investigated for aromaticity and stability using quantum mechanics calculations and their ability for water and ethanol adsorption using molecular dynamics simulations. COF-1 demonstrated the poorest aromatic character due to the highest energy delocalization interaction between B–O bonding orbital of sigma type and unfilled valence-shell nonbonding of boron. CTF-1 was identified as the least kinetically stable and the most chemically reactive. Both COF-1 and CTF-1 showed good surface properties for selective adsorption of water via hydrogen bonding and electrostatic interactions. Among the three sheets, TPG’s surface was mostly affected by aromatic currents and localized π electrons on the phenyl rings which in turn made it the best platform for selective adsorption of ethanol via van der Waals interactions. These results can serve as guidelines for future studies on solvent adsorption for COFs materials.
Effects of Preoperative Telerehabilitation on Muscle Strength, Range of Motion, and Functional Outcomes in Candidates for Total Knee Arthroplasty: A Single-Blind Randomized Controlled Trial

This study aims to investigate the effect of a preoperative telerehabilitation (PT) program on muscle strength, knee range of motion (ROM), and functional outcomes in candidates for total knee arthroplasty (TKA). Sixty patients (all women, mean age 70.53 ± 2.7 years) scheduled for bilateral TKA participated in this study. The PT and preoperative patient education (PE) groups participated in a 3-week intensive exercise program (30 min/session, 2 times/day, 5 days/week), whereas the control group received the usual care before TKA. Quadriceps muscle strength, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), ROM of knee flexion, pain, and time up-and-go (TUG) test time were evaluated at 4 weeks preoperatively, post-interventionally, and 6 weeks after TKA. Significant differences were found in the time-by-group interaction for 60°/s extension peak torque [F(4, 100) = 2.499, p = 0.047, η2p = 0.91], 180°/s extension peak torque [F(4, 100) = 3.583, p = 0.009, η2p = 0.125], ROM [F(4, 100) = 4.689, p = 0.002, η2p = 0.158], TUG time [F(4, 100) = 7.252, p < 0.001, η2p = 0.225], WOMAC pain [F(4, 100) = 9.113, p < 0.001, η2p = 0.267], WOMAC functional outcome [F(4, 100) = 6.579, p < 0.001, η2p = 0.208], and WOMAC total score [F(4, 100) = 10.410, p < 0.001, η2p = 0.294]. The results of this study demonstrate the early benefits of a PT program in elderly female patients with end-stage osteoarthritis. The PT program improved muscle strength, ROM, and functional outcomes before TKA, which contributed to better functional recovery after TKA.
Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease and related diseases, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease.
Switching Ticagrelor to 600 mg or 300 mg Clopidogrel Loading Bridge in Patients with Unstable Angina

Ticagrelor is believed to be a more potent and faster antiplatelet agent compared with clopidogrel and may result in lower ischemic outcomes in patients with acute coronary syndrome. However, the best strategy of switching from ticagrelor to clopidogrel is unclear. Current guidelines advocate clopidogrel bridging with a 600 mg loading dose (LD). This study aimed to compare the safety and feasibility of switching protocols from ticagrelor to clopidogrel 600 mg or 300 mg LD in patients with unstable angina pectoris (USAP). One hundred and eighty patients with USAP undergoing adhoc percutaneous coronary intervention (PCI) received preprocedural ticagrelor 180 mg/daily. The decision to switch antiplatelet therapy to clopidogrel with either 300 mg LD or 600 mg LD at 12 h was left to the discretion of the treating physician. The primary outcome was a composite of an efficacy endpoint major adverse cardiac and cerebrovascular events (MACCEs) and a safety endpoint Bleeding Academic Research Consortium scale (BARC) (≥1). There were no differences in our composite clinical endpoint of MACCE between the two strategies, with one event occurring in each group. One patient in each group had myocardial infarction due to stent thrombosis, and the patient in the 300 mg switching group died due to stent thrombosis. No difference between the two arms was observed in terms of BARC bleeding criteria. This study showed that among USAP patients undergoing PCI, switching to clopidogrel with 300 mg LD showed no significant difference compared to 600 mg clopidogrel LD. Ticagrelor LD in ad hoc PCI and de-escalation to clopidogrel with 300 mg LD could translate to lower costs for patients with USAP without compromising safety and efficacy.
3′ Tth Endonuclease Cleavage Polymerase Chain Reaction (3TEC-PCR) Technology for Single-Base-Specific Multiplex Pathogen Detection using a Two-Oligonucleotide System

Polymerase chain reaction (PCR) is the standard in nucleic acid amplification technology for infectious disease pathogen detection and has been the primary diagnostic tool employed during the global COVID-19 pandemic. Various PCR technology adaptations, typically using two-oligonucleotide dye-binding methods or three-oligonucleotide hydrolysis probe systems, enable real-time multiplex target detection or single-base specificity for the identification of single-nucleotide polymorphisms (SNPs). A small number of two-oligonucleotide PCR systems facilitating both multiplex detection and SNP identification have been reported; however, these methods often have limitations in terms of target specificity, production of variable or false-positive results, and the requirement for extensive optimisation or post-amplification analysis. This study introduces 3′ Tth endonuclease cleavage PCR (3TEC-PCR), a two-oligonucleotide PCR system incorporating a modified primer/probe and a thermostable cleavage enzyme, Tth endonuclease IV, for real-time multiplex detection and SNP identification. Complete analytical specificity, low limits of detection, single-base specificity, and simultaneous multiple target detection have been demonstrated in this study using 3TEC-PCR to identify bacterial meningitis associated pathogens. This is the first report of a two-oligonucleotide, real-time multiplex PCR technology with single-base specificity using Tth endonuclease IV.