Miracle-dz/UniFAR-FTUs huggingface dataset:
Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone

Background The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array. Results At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.
Highly Efficient Synthesis of Rare Sugars from Glycerol in Endotoxin-Free ClearColi by Fermentation

Rare sugars possess potential applications as low-calorie sweeteners, especially for anti-obesity and anti-diabetes. In this study, a fermentation biosystem based on the “DHAP-dependent aldolases strategy” was established for D-allulose and D-sorbose production from glycerol in endotoxin-free ClearColi BL21 (DE3). Several engineering strategies were adopted to enhance rare sugar production. Firstly, the combination of different plasmids for aldO, rhaD, and yqaB expression was optimized. Then, the artificially constructed ribosomal binding site (RBS) libraries of aldO, rhaD, and yqaB genes were assembled individually and combinatorially. In addition, a peroxidase was overexpressed to eliminate the damage or toxicity from hydrogen peroxide generated by alditol oxidase (AldO). Finally, stepwise improvements in rare sugar synthesis were elevated to 15.01 g/L with a high yield of 0.75 g/g glycerol in a 3 L fermenter. This research enables the effective production of rare sugars from raw glycerol in high yields.
Dielectric Spectroscopy Shows a Permittivity Contrast between Meningioma Tissue and Brain White and Gray Matter—A Potential Physical Biomarker for Meningioma Discrimination

Simple Summary Meningiomas are the most common primary central nervous system tumors, and surgery is their primary treatment of choice. The surgical intervention aims for the maximum extent of tumor resection whilst preserving the brain’s neurological functions. The effectiveness of such intervention thus depends on the capability to intraoperatively discriminate between the meningioma tissue and the surrounding brain white matter and gray matter. This study investigated dielectric contrast as a potential physical biomarker for meningioma discrimination. Dielectric contrast is based on the difference in complex permittivity, a physical property of tissues, measurable by dielectric spectroscopy. This study shows that the dielectric contrast is relevant as a potential physical biomarker to discriminate the meningioma tissue from the surrounding brain tissues. Such a biomarker has a meaningful potential to make a positive impact on the management of neurooncological patients in terms of intraoperative tumor discrimination, as well as future diagnostic or therapeutic applications. Abstract The effectiveness of surgical resection of meningioma, the most common primary CNS tumor, depends on the capability to intraoperatively discriminate between the meningioma tissue and the surrounding brain white and gray matter tissues. Aiming to find a potential biomarker based on tissue permittivity, dielectric spectroscopy of meningioma, white matter, and gray matter ex vivo tissues was performed using the open-ended coaxial probe method in the microwave frequency range from 0.5 to 18 GHz. The averages and the 95% confidence intervals of the measured permittivity for each tissue were compared. The results showed the absence of overlap between the 95% confidence intervals for meningioma tissue and for brain white and gray matter, indicating a significant difference in average permittivity (p ≤ 0.05) throughout almost the entire measured frequency range, with the most pronounced contrast found between 2 GHz and 5 GHz. The discovered contrast is relevant as a potential physical biomarker to discriminate meningioma tissue from the surrounding brain tissues by means of permittivity measurement, e.g., for intraoperative meningioma margin assessment. The permittivity models for each tissue, developed in this study as its byproducts, will allow more accurate electromagnetic modeling of brain tumor and healthy tissues, facilitating the development of new microwave-based medical devices and tools.
Social activities and long-term depressive-symptoms trajectories among middle-aged and older adults in China: a population-based cohort study

Background The association between social activities and depressive symptoms remains unclear. This study aimed to explore the relationship between social activities at baseline and the long-term depressive-symptoms trajectories among a cohort of middle-aged and older adults in China. Methods This study included 13,258 participants aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms across four waves from 2011 to 2018 were evaluated using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Four types of social activities were assessed at baseline by self-report: (1) interacting with friends; (2) playing Mahjong, chess, and cards or attending a community club; (3) providing help to family, friends, or neighbors; and (4) attending a sporting or social event or club. Group-based trajectory modeling (GBTM) was used to map depressive-symptoms trajectories during the follow-up period. Results Not interacting with friends at baseline was associated with an increased risk of increasing (adjusted odds ratio [aOR]: 1.21, 95% confidence interval [CI]: 1.03, 1.41) and severe-stable (aOR: 1.35, 95% CI: 1.10, 1.65) depressive-symptoms trajectories. Participants who did not play Mahjong, cards, or chess and did not attend a sporting or social event or club at baseline were more likely to have mild-stable, decreasing, increasing, and severe-stable depressive-symptoms trajectories. Conclusion Social activities play an important role in long-term depressive-symptoms trajectories in middle-aged and older Chinese adults. Interacting with friends, attending sports, or social clubs may prevent depressive symptoms.
Parents’ attachment anxiety and preoccupation with their child’s social functioning: The moderating role of social rejection and acceptance

In three studies, we examined the contribution of parents’ attachment anxiety to preoccupation with their child’s social functioning and the moderating role of social rejection and acceptance. In Study 1 (N = 191), we assessed parents’ attachment anxiety, retrospective accounts of peer rejection at school, and obsession regarding their child’s social competence. In Study 2 (N = 186), we asked parents to listen and reflect on a podcast about social rejection or acceptance and examined the effects of these manipulations (vs. a control condition) on parents’ worry about their child’s flaws in the social domain. In Study 3 (N = 226), we examined the effects of the above manipulations on parents’ tendency to expect and overreact to their child’s peer rejection. Across the three studies, parents’ attachment anxiety was associated with more preoccupation with their child’s social functioning. This association was amplified among parents who reported more frequent episodes of peer rejection at school and among those who listened to a podcast about social rejection. In contrast, a podcast about social acceptance buffered the link between parents’ attachment anxiety and preoccupation with their child’s social functioning.
Effects of Digestion, Cell Culture Media, and Mucous on the Physical Properties, Cellular Effects, and Translocation of Polystyrene and Polymethacrylate Nanoparticles

The discovery of plastic and metal nanoparticles in organisms, foods, and beverages has generated numerous studies on the effects of these particles on the barrier cells and their subsequent absorption into the body. Following ingestion, nanoparticles travel down the gastrointestinal tract (GIT), and their physicochemical characteristics change in response to the change in proteins and pH during their digestion. We measured the translocation of digested nanoparticles across a co-culture monolayer of Caco-2 and various combinations (1:9, 5:5, and 9:1) of HT29-MTX-E12. The in vitro model of the intestine was used to determine the translocation of digested 20 nm polymethacrylate (PMA) particles and the accompanying monolayer barrier effects after a 72 h exposure. The in vitro digestion increased the agglomeration and hydrodynamic diameters and decreased the surface charge of the nanoparticles. For NH2-functionalized polymethacrylate nanoparticles (PMA-NH2), the diameters increased from 57 nm (water) to 3800 nm (media), or 2660 nm (chyme). These nanoparticles compromised the integrity of the monolayer (trans-epithelial electrical resistance, Lucifer yellow translocation) and translocated across all the cell ratio configurations. Digestion can have a large effect on nanoparticle agglomeration and surface charge. Excess mucous was not seen as a barrier to the translocation of PMA-NH2.
Assessment of the proarrhythmic effects of repurposed antimalarials for COVID-19 treatment using a comprehensive in vitro proarrhythmia assay (CiPA)

Due to the outbreak of the SARS-CoV-2 virus, drug repurposing and Emergency Use Authorization have been proposed to treat the coronavirus disease 2019 (COVID-19) during the pandemic. While the efficiency of the drugs has been discussed, it was identified that certain compounds, such as chloroquine and hydroxychloroquine, cause QT interval prolongation and potential cardiotoxic effects. Drug-induced cardiotoxicity and QT prolongation may lead to life-threatening arrhythmias such as torsades de pointes (TdP), a potentially fatal arrhythmic symptom. Here, we evaluated the risk of repurposed pyronaridine or artesunate-mediated cardiac arrhythmias alone and in combination for COVID-19 treatment through in vitro and in silico investigations using the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. The potential effects of each drug or in combinations on cardiac action potential (AP) and ion channels were explored using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and Chinese hamster ovary (CHO) cells transiently expressing cardiac ion channels (Nav1.5, Cav1.2, and hERG). We also performed in silico computer simulation using the optimized O’Hara-Rudy human ventricular myocyte model (ORd model) to classify TdP risk. Artesunate and dihydroartemisinin (DHA), the active metabolite of artesunate, are classified as a low risk of inducing TdP based on the torsade metric score (TMS). Moreover, artesunate does not significantly affect the cardiac APs of hiPSC-CMs even at concentrations up to 100 times the maximum serum concentration (Cmax). DHA modestly prolonged at APD90 (10.16%) at 100 times the Cmax. When considering Cmax, pyronaridine, and the combination of both drugs (pyronaridine and artesunate) are classified as having an intermediate risk of inducing TdP. However, when considering the unbound concentration (the free fraction not bound to carrier proteins or other tissues inducing pharmacological activity), both drugs are classified as having a low risk of inducing TdP. In summary, pyronaridine, artesunate, and a combination of both drugs have been confirmed to pose a low proarrhythmogenic risk at therapeutic and supratherapeutic (up to 4 times) free Cmax. Additionally, the CiPA initiative may be suitable for regulatory use and provide novel insights for evaluating drug-induced cardiotoxicity.
Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic UTI patients aged ≥ 60 years and correlated them with detected levels of the immune response biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β). The objective was to identify the microbial densities associated with significant elevation of these biomarkers in order to determine an optimal threshold for diagnosing symptomatic UTIs. Biobanked midstream voided urine samples were analyzed for microbial identification and quantification using standard urine culture (SUC) and multiplex-polymerase chain reaction (M-PCR) testing, while NGAL, IL-8, and IL-1β levels were measured via enzyme-linked immunosorbent assay (ELISA). NGAL, IL-8, and IL-1β levels were all significantly elevated at microbial densities ≥ 10,000 cells/mL when measured via M-PCR (p < 0.0069) or equivalent colony-forming units (CFUs)/mL via SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable than 100,000 CFU/mL for diagnosing UTIs.
Clonal diversity and population genetic structure of the grain aphid Sitobion avenae(F.) in central Europe

The grain aphid, Sitobion avenae (F.), displays a number of different life-cycles. These range from complete asexual viviparous and frost-sensitive lineages (anholocyclic) to those including a single sexual generation and which produce frost resistant eggs (holocyclic). In addition, combinations of both life cycles can occur. The spread of life-cycles in a population is known to be dependent on winter climate and earlier studies have used highly polymorphic DNA-markers (microsatellites) to elucidate the influence of seasonal factors on life-cycle variation. However, to date, no such field studies have been performed in geographic areas were mild and cold winters vary between years. Therefore, the central aim of this project was to analyse populations of S. avenae from four diverse geographic regions, viz. northern Germany, two regions from central Germany and one from southern Hungary in three consecutive years. Changes of clonal diversity and population genetic structure were compared within and between years at 32 locations from central and northern Germany differing in the complexity of their landscape structure. The results revealed that seven asexual clones (= multilocus microsatellite genotypes) of S. avenae were common on wheat (Triticum aestivum) and widespread over locations and regions in Germany, including a single clone that was also present in Hungary over two consecutive years. Furthermore, genotypic diversity was dependent on winter climate in Hungary and central Germany, although the two parameters were apparently not correlated in northern Germany. Beside climate effects, genotypic diversity showed a significant positive relationship to simple structured landscapes in central and northern Germany in 2001, but this effect was outweighed in central Germany by successive colder winters in 2002 and 2003. Analysis of the within-season dynamics of clones revealed contrary development in time and space in a yearly repeating pattern. The change in clonal communities was probably dependent on regional insecticide management, clonal variation in host-plant shifts and a restriction of short distance migration by natural geographic barriers. However, long distance migration was high enough to prevent the genetic isolation of populations from northern Germany to Hungary. Overall, the present results confirmed the homogenising effects of migration at a scale of 100km. This project was part of the project BIOPLEX ( Biodiversitat und raumliche Komplexitat in Agrarlandschaften unter Global Change , Project ID: 01LC0020), financed by the Federal Ministry of Education and Research.
Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence?

Despite significant improvements in survival following preterm birth in recent years, the neurodevelopmental burden of prematurity, with its long-term cognitive and behavioral consequences, remains a significant challenge in neonatology. Neuroprotective treatment options to improve neurodevelopmental outcomes in preterm infants are therefore urgently needed. Alleviating inflammatory and oxidative stress (OS), melatonin might modify important triggers of preterm brain injury, a complex combination of destructive and developmental abnormalities termed encephalopathy of prematurity (EoP). Preliminary data also suggests that melatonin has a direct neurotrophic impact, emphasizing its therapeutic potential with a favorable safety profile in the preterm setting. The current review outlines the most important pathomechanisms underlying preterm brain injury and correlates them with melatonin’s neuroprotective potential, while underlining significant pharmacokinetic/pharmacodynamic uncertainties that need to be addressed in future studies.
Numerical modelling of infragravity waves in coastal regions

Infragravity waves are a common feature in the nearshore wave field and have a significant impact on numerous coastal processes. It is therefore important to accurately predict infragravity wave conditions at a given location. However, analytical relations do not exist with which to make such predictions and one has to rely on numerical models. In this study infragravity waves are simulated with a linear 1D surf beat model (IDSB) and a non-hydrostatic model (SWASH). The aim of this study is to perform a detailed numerical investigation into the nearshore behaviour of infragravity waves. Specific attention is paid to the generation, propagation and reflection of IG-waves.
Impulse Control Disorders in the Polish Population of Patients with Parkinson’s Disease

Background and Objectives: Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the world. It is characterized by the presence of not only typical motor symptoms but also several less known and aware non-motor symptoms (NMS). The group of disorders included in the NMS is Impulse Control Disorders (ICDs). ICDs are a group of disorders in which patients are unable to resist temptations and feel a strong, pressing desire for specific activities such as gambling, hypersexuality, binge eating, and compulsive buying. The occurrence of ICDs is believed to be associated primarily with dopaminergic treatment, with the use of dopamine agonists (DA), and to a lesser extent with high doses of L-dopa. The aim of our study was to develop a profile of Polish ICDs patients and assess the frequency of occurrence of ICDs, as well as determine the risk factors associated with these disorders against the background of the PD population from other countries. Materials and Methods: Our prospective study included 135 patients with idiopathic PD who were hospitalized between 2020 and 2022 at the Neurological Department of University Central Hospital in Katowice. In the assessment of ICDs, we used the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP). Other scales with which we assessed patients with PD were as follows: MDS-UPDRS part III and modified Hoehn–Yahr staging. Clinical data on age, gender, disease duration and onset, motor complications, and medications were collected from electronic records. Results: ICDs were detected in 27.41% of PD patients (binge eating in 12.59%, hypersexuality in 11.11%, compulsive buying in 10.37%, and pathological gambling occurred in only 5.19% of patients. In total, 8.89% had two or more ICDs). The major finding was that ICDs were more common in patients taking DA than in those who did not use medication from this group (83.78% vs. 54.07%, respectively; p = 0.0015). Patients with ICDs had longer disease duration, the presence of motor complications, and sleep disorders. An important finding was also a very low detection of ICDs in a routine medical examination; only 13.51% of all patients with ICDs had a positive medical history of this disorder. Conclusions: ICDs are relatively common in the population of Polish PD patients. The risk factors for developing ICDs include longer duration of the disease, presence of motor complications, sleep disorders, and use of DA and L-dopa. Due to the low detectability of ICDs in routine medical history, it is essential for physicians to pay more attention to the possibility of the occurrence of these symptoms, especially in patients with several risk factors. Further prospective studies on a larger group of PD patients are needed to establish a full profile of Polish PD patients with ICDs.
The Use of Ultrasound-Assisted Maceration for the Extraction of Carnosic Acid and Carnosol from Sage (Salvia officinalis L.) Directly into Fish Oil

The aim of the study was to examine the effect of ultrasonic maceration (U) on the extraction of carnosic acid (CA) and its derivative—carnosol (C)—directly from sage into fish oil, compared to homogenization-assisted maceration (H). It was shown that the ultrasonic maceration process (U) allowed for obtaining a macerate enriched in carnosic acid (CA) and carnosol (C), also containing rosmarinic acid (RA), total polyphenols, and plant pigments, and showing antioxidant properties (DPPH test). There was no unequivocal difference in the efficiency of extracting ingredients from sage into the oil macerate between U and H, with the use of ultrasound in most cases resulting in a greater extraction of C and less extraction of pigments from sage into the macerate than in H. The highest simultaneous contents of CA (147.5 mg/100 g) and C (42.7 mg/100 g) in the macerate were obtained after 60 min of maceration U when using a higher power (320 W). The amount of determined compounds also depended on the concentration of methanol (methanol; 70% methanol) used for the analysis. The maceration U is a simple, safe, “green method” of obtaining active substances, with a reduced number of steps, enabling an interesting application form of CA and C, e.g., for food or cosmetics.