Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep Learning Based Prediction of Gas Chromatographic Retention Indices for a Wide Variety of Polar and Mid-Polar Liquid Stationary Phases

Prediction of gas chromatographic retention indices based on compound structure is an important task for analytical chemistry. The predicted retention indices can be used as a reference in a mass spectrometry library search despite the fact that their accuracy is worse in comparison with the experimental reference ones. In the last few years, deep learning was applied for this task. The use of deep learning drastically improved the accuracy of retention index prediction for non-polar stationary phases. In this work, we demonstrate for the first time the use of deep learning for retention index prediction on polar (e.g., polyethylene glycol, DB-WAX) and mid-polar (e.g., DB-624, DB-210, DB-1701, OV-17) stationary phases. The achieved accuracy lies in the range of 16–50 in terms of the mean absolute error for several stationary phases and test data sets. We also demonstrate that our approach can be directly applied to the prediction of the second dimension retention times (GC × GC) if a large enough data set is available. The achieved accuracy is considerably better compared with the previous results obtained using linear quantitative structure-retention relationships and ACD ChromGenius software. The source code and pre-trained models are available online.
Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells

Up-regulated expression of programmed death-ligand 1 (PD-L1) by interferon-gamma (IFN-γ) has been associated with promotion of cancer cell survival and tumor cell escape from anti-tumor immunity. Therefore, a blockade of PD-L1 expression can potentially be used as a molecular target for cancer therapy. The aim of this study was to investigate whether suppression of IFN-γ induced PD-L1 expression in two oral cancer cell lines, HN6 and HN15, by hesperidin effectively decreased cell proliferation and migration. Further, our objective was to elucidate the involvement of the signal transducer and activator of transcription 1 (STAT1) and STAT3 in the inhibition of induced PD-L1 expression by hesperidin. Our findings indicate that IFN-γ induced expression of PD-L1 protein in HN6 and HN15 via phosphorylation of STAT1 and STAT3 and that hesperidin significantly reduced that induction through suppression of phosphorylated STAT1 and STAT3 in both cell lines. Moreover, hesperidin also significantly decreased the viability, proliferation, migration, and invasion of both cell lines. In conclusion, hesperidin exerted anticancer effects against oral cancer cells through the suppression of PD-L1 expression via inactivation of the STAT1 and STAT3 signaling molecules. The findings of this study support the use of hesperidin as a potential adjunctive treatment for oral cancer.
Longitudinal assessment of quality assurance measurements in a 1.5T MR‐linac: Part I—Linear accelerator

Abstract Purpose To describe and report longitudinal quality assurance (QA) measurements for the mechanical and dosimetric performance of an Elekta Unity MR‐linac during the first year of clinical use in our institution. Materials and methods The mechanical and dosimetric performance of the MR‐linac was evaluated with daily, weekly, monthly, and annual QA testing. The measurements monitor the size of the radiation isocenter, the MR‐to‐MV isocenter concordance, MLC and jaw position, the accuracy and reproducibility of step‐and‐shoot delivery, radiation output and beam profile constancy, and patient‐specific QA for the first 50 treatments in our institution. Results from end‐to‐end QA using anthropomorphic phantoms are also included as a reference for baseline comparisons. Measurements were performed in water or water‐equivalent plastic using ion chambers of various sizes, an ion chamber array, MR‐compatible 2D/3D diode array, portal imager, MRI, and radiochromic film. Results The diameter of the radiation isocenter and the distance between the MR/MV isocenters was (μ ± σ) 0.39 ± 0.01 mm and 0.89 ± 0.05 mm, respectively. Trend analysis shows both measurements to be well within the tolerance of 1.0 mm. MLC and jaw positional accuracy was within 1.0 mm while the dosimetric performance of step‐and‐shoot delivery was within 2.0%, irrespective of gantry angle. Radiation output and beam profile constancy were within 2.0% and 1.0%, respectively. End‐to‐end testing performed with ion‐chamber and radiochromic film showed excellent agreement with treatment plan. Patient‐specific QA using a 3D diode array identified gantry angles with low‐pass rates allowing for improvements in plan quality after necessary adjustments. Conclusion The MR‐linac operates within the guidelines of current recommendations for linear accelerator performance, stability, and safety. The analysis of the data supports the recently published guidance in establishing clinically acceptable tolerance levels for relative and absolute measurements.
Thermal and Dielectric Properties of Cyanate Ester Cured Main Chain Rigid-Rod Epoxy Resin

Thermal and dielectric properties of rigid-rod bifunctional epoxy resin 4,4-bis(2,3-epoxypropoxy) biphenyl epoxy (BP) and commercial epoxy resin diglycidyl ether of bisphenol A (DGEBA) were studied using differential scanning calorimeter (DSC), thermogravimetric analyzer (TGA), dynamic mechanical analyzer (DMA), thermal mechanical analyzer (TMA) and dielectric analyzer (DEA). These two epoxies were cured with cyanate ester hardener 2,2’-bis(4-cyanatophenyl) propane (AroCy B10). The BP/B10 system consisting of a rigid-rod structure exhibited better thermal properties than the DGEBA/B10 system with a flexible structure. Anisotropic BP/B10 (2:1) had the highest 5% weight loss temperature, the highest amount of residue and a smaller thermal expansion coefficient than the commercial DGEBA/B10 system. The BP/B10 system, which cured at the LC phase temperature, had higher Tg than the commercial DGEBA/B10 system, as found from dynamic mechanical analysis. The BP/B10 system also demonstrated better dielectric properties than the commercial DGEBA/B10 system when enough curing agent was provided.
Exploring the Binding Mechanism of PF-07321332 SARS-CoV-2 Protease Inhibitor through Molecular Dynamics and Binding Free Energy Simulations

The novel coronavirus disease, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), rapidly spreading around the world, poses a major threat to the global public health. Herein, we demonstrated the binding mechanism of PF-07321332, α-ketoamide, lopinavir, and ritonavir to the coronavirus 3-chymotrypsin-like-protease (3CLpro) by means of docking and molecular dynamic (MD) simulations. The analysis of MD trajectories of 3CLpro with PF-07321332, α-ketoamide, lopinavir, and ritonavir revealed that 3CLpro–PF-07321332 and 3CLpro–α-ketoamide complexes remained stable compared with 3CLpro–ritonavir and 3CLpro–lopinavir. Investigating the dynamic behavior of ligand–protein interaction, ligands PF-07321332 and α-ketoamide showed stronger bonding via making interactions with catalytic dyad residues His41–Cys145 of 3CLpro. Lopinavir and ritonavir were unable to disrupt the catalytic dyad, as illustrated by increased bond length during the MD simulation. To decipher the ligand binding mode and affinity, ligand interactions with SARS-CoV-2 proteases and binding energy were calculated. The binding energy of the bespoke antiviral PF-07321332 clinical candidate was two times higher than that of α-ketoamide and three times than that of lopinavir and ritonavir. Our study elucidated in detail the binding mechanism of the potent PF-07321332 to 3CLpro along with the low potency of lopinavir and ritonavir due to weak binding affinity demonstrated by the binding energy data. This study will be helpful for the development and optimization of more specific compounds to combat coronavirus disease.
Quality of Life and Physical Activity of Persons with Spinal Cord Injury

The higher quality of life of people with spinal cord injury is closely related with their reintegration into the social environment. Social reintegration is a demanding and complex process, requiring individuals to become active again and acquire age-, gender-, and culture-appropriate roles and social status. It also involves independence and productive behavior as part of multiple interpersonal relationships with family, friends, and others. In order to establish whether individuals with spinal cord injury who are physically active subjectively rate their quality of life to be higher compared to those who are not, sixty-two respondents from Slovenia with spinal cord injury were interviewed. Thirty-one of them were physically active, and 31 were not. The level of injury of the responders was from Th6–Th12. The participants gave the highest assessments to their interpersonal relationships, and the lowest to their satisfaction with material prosperity. Data comparison showed that subjective estimates in all areas of quality of life are higher in respondents who were involved in physical activity after their injury. The results may encourage persons with spinal cord injury to participate more often in sports programs, and also encourage others to do so.
Altered Volcanic Tuffs from Los Frailes Caldera. A Study of Their Pozzolanic Properties

This work presents the results of the study of the physical, chemical, mineralogical and pozzolanic properties of the altered volcanic tuffs (AVT) that lie in the Los Frailes caldera, south of the Iberian Peninsula, and demonstrates their qualities as pozzolans for the manufacturing of mortars and pozzolanic cements of high mechanical strength. The main objective of this research is to show to what extent the AVTs can replace portland cement (PC) in mortars, with standardised proportions of 75:25% and 70:30% (PC-AVT). To achieve these objectives, three AVT samples were studied by a petrographic analysis of thin section (PATS), DRX, FRX and MEB. The pozzolanic properties were determined by three methods: electrical conductivity (ECT), chemical pozzolanicity tests (CPT) at 8 and 15 days and mechanical strength tests (MS) of the specimens at 2, 7, 28 and 90 days. Studies of a PATS, DRX, FRX and MEB showed that the AVT samples’ constitutions are complex where smectite (montmorillonite), mordenite, quartz, halloysite, illite, kaolinite, volcanic glass and lithic fragments coexist. The results of the ECT and CPT tests confirmed the pozzolanic properties of the samples analysed and proved an increase in mechanical strength from 2 to 90 days of testing.
Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

Simple Summary Accumulation of excess fluid in the abdomen typically indicates abnormal function or disease, such as cancer, in the underlying tissues. This accumulation of fluid, or ascites, occurs more frequently in patients with advanced-stage ovarian cancer than any other type of cancer. The presence of ascites indicates the poorest outcomes for patients with advanced stage ovarian cancer, but little is known about the reasons for these dismal outcomes. This review discusses the current understanding of ascites, starting with an overview of ovarian cancer and ascites, followed by a description of the tools used to analyze the components of ascites and how these components modulate ovarian cancer biology. A perspective on the mechanical effects of ascites and the impact of mechanical stress on treatment resistance is provided. Lastly, treatment options for ascites and opportunities to develop new therapeutic strategies to improve outcomes are discussed. Abstract Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.
Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte Ratios, and Systemic Immune-Inflammation Index as Potential Biomarkers of Chronic Inflammation in Patients with Newly Diagnosed Acromegaly: A Single-Centre Study

Acromegaly is a rare disease caused by overproduction of growth hormone (GH) by a pituitary adenoma, and consequently increased insulin-like growth factor 1 (IGF-1) concentration. The GH/IGF-1 axis and immune cells interactions are hypothesized to be involved in subclinical inflammation. This retrospective study aimed to investigate the differences in neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) ratios, and systemic immune-inflammation index (SII) in GH-secreting adenomas compared with non-functioning pituitary adenomas (NFPAs) concerning clinical and radiological findings. After evaluation of 665 patients with pituitary tumors, 62 individuals with newly diagnosed acromegaly and 134 with NFPAs were enrolled in the analysis. The control group consisted of 120 healthy individuals. Fifty-eight patients with acromegaly were re-evaluated after medical or surgical therapies. NLR, PLR, SII values, and neutrophil count were significantly higher (p ≤ 0.001), whereas lymphocyte count was lower in acromegaly than in NFPAs (p = 0.001). No significant differences between NFPAs and controls were observed in analyzed ratios. Higher preoperative NLR, PLR, SII values were found in patients who failed to achieve a cure with surgery (p < 0.05). Although NLR, PLR, and SII values were significantly higher in acromegaly, these indices cannot be used to discriminate GH-secreting pituitary tumors from NFPAs. Treatment of acromegaly decreased the value of NLR and SII, but it requires further studies to consolidate the real clinical role of these inflammation-related ratios.
Olympic coaching excellence: A quantitative study of Olympic swimmers’ perceptions of their coaches

ABSTRACT Although coaching is a co-created process, researchers investigating the psychological aspects of Olympic coaching have tended to overlook the perceptions of athletes and whether these distinguish between performance-related outcomes. The objective of this research was to examine whether athletes’ perceptions of their coaches discriminate between world-leading (i.e., Olympic gold medal winning) and world-class (i.e., Olympic non-gold medal winning) coaches. Observer-reported psychometric questionnaires were completed by 38 Olympic swimmers who had collectively won 59 Olympic medals, of which 31 were gold. The questionnaires assessed perceptions of 12 variables within the Big Five personality traits, the dark triad, and emotional intelligence, and the data was analyzed using three one-way multivariate analysis of variance and follow-up univariate F-tests. The results showed that world-leading coaches were perceived to be significantly higher on conscientiousness, openness to experience, perception of emotion, and management of others emotion, and lower on narcissism, than world-class coaches. This suggests that athletes’ perceptions of their coaches may discriminate between world-leading and world-class coaches. The implications for coaches’ psychological development are discussed and compared with previously reported Olympic coaches’ perceptions of themselves.
Interstitial Lung Disease at High Resolution CT after SARS-CoV-2-Related Acute Respiratory Distress Syndrome According to Pulmonary Segmental Anatomy

Background: The purpose of this study was to evaluate High-Resolution CT (HRCT) findings in SARS-CoV-2-related ARDS survivors treated with prolonged low-dose methylprednisolone after hospital discharge. Methods: A total of 44 consecutive patients (M: 32, F: 12, average age: 64), hospitalised in our department from April to September 2020 for SARS-CoV-2-related ARDS, who had a postdischarge CT scan, were enrolled into this retrospective study. We reviewed the electronic medical charts to collect laboratory, clinical, and demographic data. The CT findings were evaluated and classified according to lung segmental distribution. The imaging findings were correlated with spirometry results and included ground glass opacities (GGOs), consolidations, reticulations, bronchiectasis/bronchiolectasis, linear bands, and loss of pulmonary volume. Results: Alterations in the pulmonary parenchyma were observed in 97.7% of patients at HRCT (median time lapse between ARDS diagnosis and HRCT: 2.8 months, range 0.9 to 6.7). The most common findings were linear bands (84%), followed by GGOs (75%), reticulations (34%), bronchiolectasis (32%), consolidations (30%), bronchiectasis (30%) and volume loss (25%). They had a symmetric distribution, and both lower lobes were the most affected areas. Conclusions: A reticular pattern with a posterior distribution was observed 3 months after discharge from severe COVID-19 pneumonia, and this differs from previously described postCOVID-19 fibrotic-like changes. We hypothesized that the systematic use of prolonged low-dose of corticosteroid could be the main reason of this different CT scan appearance.
MYC Rules: Leading Glutamine Metabolism toward a Distinct Cancer Cell Phenotype

Simple Summary In the last decade, metabolic reprogramming has emerged as a driving characteristic of cancer cells. The MYC oncogene, a transcription factor, has become of growing interest as a fundamental driver of differential cancer cell metabolism. Furthermore, the non-essential amino acid glutamine is deemed to be an important nutrient for cancer cells. In fact, glutamine can integrate into a wide variety of metabolic pathways, from energy metabolism to nucleotide synthesis. This review offers a comprehensive and specific overview of recent discoveries in the regulation of MYC oncogene activation on glutamine metabolism in cancer cells. Abstract Metabolic reprogramming and deregulated cellular energetics are hallmarks of cancer. The aberrant metabolism of cancer cells is thought to be the product of differential oncogene activation and tumor suppressor gene inactivation. MYC is one of the most important oncogenic drivers, its activation being reported in a variety of cancer types and sub-types, among which are the most prevalent and aggressive of all malignancies. This review aims to offer a comprehensive overview and highlight the importance of the c-Myc transcription factor on the regulation of metabolic pathways, in particular that of glutamine and glutaminolysis. Glutamine can be extensively metabolized into a variety of substrates and be integrated in a complex metabolic network inside the cell, from energy metabolism to nucleotide and non-essential amino acid synthesis. Together, understanding metabolic reprogramming and its underlying genetic makeup, such as MYC activation, allows for a better understanding of the cancer cell phenotype and thus of the potential vulnerabilities of cancers from a metabolic standpoint.
Therapeutic Effects of Aripiprazole in the 5xFAD Alzheimer’s Disease Mouse Model

Global aging has led to growing health concerns posed by Alzheimer’s disease (AD), the most common type of dementia. Aripiprazole is an atypical FDA-approved anti-psychotic drug with potential against AD. To investigate its therapeutic effects on AD pathology, we administered aripiprazole to 5xFAD AD model mice and examined beta-amyloid (βA)-induced AD-like phenotypes, including βA production, neuroinflammation, and cerebral glucose metabolism. Aripiprazole administration significantly decreased βA accumulation in the brains of 5xFAD AD mice. Aripiprazole significantly modified amyloid precursor protein processing, including carboxyl-terminal fragment β and βA, a disintegrin and metalloproteinase domain-containing protein 10, and beta-site APP cleaving enzyme 1, as determined by Western blotting. Neuroinflammation, as evidenced by ionized calcium binding adapter molecule 1 and glial fibrillary acidic protein upregulation was dramatically inhibited, and the neuron cell layer of the hippocampal CA1 region was preserved following aripiprazole administration. In 18F-fluorodeoxyglucose positron emission tomography, after receiving aripiprazole, 5xFAD mice showed a significant increase in glucose uptake in the striatum, thalamus, and hippocampus compared to vehicle-treated AD mice. Thus, aripiprazole effectively alleviated βA lesions and prevented the decline of cerebral glucose metabolism in 5xFAD AD mice, suggesting its potential for βA metabolic modification and highlighting its therapeutic effect over AD progression.
Brain Plasticity in Humans and Model Systems: Advances, Challenges, and Future Directions

Plasticity, and in particular, neurogenesis, is a promising target to treat and prevent a wide variety of diseases (e.g., epilepsy, stroke, dementia). There are different types of plasticity, which vary with age, brain region, and species. These observations stress the importance of defining plasticity along temporal and spatial dimensions. We review recent studies focused on brain plasticity across the lifespan and in different species. One main theme to emerge from this work is that plasticity declines with age but that we have yet to map these different forms of plasticity across species. As part of this effort, we discuss our recent progress aimed to identify corresponding ages across species, and how this information can be used to map temporal variation in plasticity from model systems to humans.
Early Bone Healing on Hydroxyapatite-Coated and Chemically-Modified Hydrophilic Implant Surfaces in an Ovine Model

Implant topography affects early peri-implant bone healing by changing the osteoconduction rate in the surrounding biological environment. Implant surfaces have been designed to promote faster and stronger bone formation for rapid and stable prosthesis loading. Early peri-implant bone healing has been observed with a sandblasted, acid-etched implant that was chemically modified to be hydrophilic (cmSLA). The present study investigates whether early peri-implant bone healing extends to a rough surface implant with a high crystalline hydroxyapatite surface (TSV MP-1 HA). Three implants were randomly placed in porous trabecular bone within both medial femoral condyles of 10 sheep. Early peri-implant bone stability was measured at 3- and 6-weeks healing time following implant insertion. Results indicated a similar implant stability quotient between the implants at insertion and over time. The significant increase over time of reverse torque values with respect to insertion torque (p < 0.001) did not differ between the implants. However, the bone-to-implant contact of TSV MP-1 HA was significantly higher than that of cmSLA implants at 6 weeks (p < 0.01). These data validate previous findings of a hydrophilic implant surface and extend the observation of early osseointegration to a rough surface implant in porous trabecular bone.