Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified as a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of lncRNA-miRNA/mRNA network might yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there was different expression of 34 transcripts (two lncRNAs, XIST and MIR222HG, 29 mRNA, and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of the lncRNA XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA–miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells and negative correlations in the infiltration of Th1 CD4+ T cells.

Fatty acid desaturase 2 (Fads2) is the key enzyme of long chain polyunsaturated fatty acid (LC-PUFA) biosynthesis. Endogenous production of these biomolecules in vertebrates, if present, is insufficient to meet demand. Hence, LC-PUFA are considered as conditionally-essential. At present however, LC-PUFA are globally-limited nutrients due to anthropogenic factors. Attention of research is given therefore to find ways to maximize endogenous LC-PUFA production especially in production species, whereby deeper knowledge on molecular mechanisms of enzymatic steps involved is being generated. This review first briefly informs about the milestones in the history of LC-PUFA essentiality exploration before it focuses on the main aim – to highlight the fascinating Fads2 potential to play roles fundamental to adaptation to novel environmental conditions. Investigations are summarized, which elucidate the evolutionary history of fish Fads2 providing an explanation for the remarkable plasticity of this enzyme in fish. Further, structural implications of Fads2 substrate specificity are discussed and some relevant studies performed on organisms other than fish are mentioned in cases when such studies have so far not been conducted on fish models. The importance of Fads2 in the context of growing aquaculture demand and dwindling LC-PUFA supply is depicted and a few remedies in the form of genetic engineering to improve endogenous production of these biomolecules are outlined.

Data is present in the data sources like Files and Data bases, Retrieval of information from that data sources is one of the important issue nowadays. So for retrieval information from the data sources clustering is used. In the present market different types of clustering algorithms were available. But opting of the clustering is based on user requirements. This paper focuses on the study of hierarchical clustering approach on different conditions or measures or with customer choices like clustering process number of clusters generated at each level, number of levels, attributes range for performing the clustering on the given data set. In brief overview we discuss the hierarchical approach for clustering algorithm with the user opting choices.

This article attempts to identify factors impacting on the quantity of municipal waste in Polish 2478 communes (LAU-2), taking into account the variability of particular determinants influence depending on their regional diversification. The analysis covers the years 2005-2018. The dependent variable is the volume of municipal waste in kg per capita, whereas the group of determinants include: economic and human development, uncontrolled dumping sites, population density, population at the working age, migration, tourism, urbanization, dwellings and housing, retail sales, entities, education and investments in waste management; The geographically weighted regression with spatial error term (GWR-SEM) was employed in this study. The model enabled not only the specification of the waste production determinants, but also the analysis of the variability in the strength and direction of dependencies occurring between the examined variables in individual communes. The results proved that the higher the level of education the less waste is generated (in the north-central Poland); the business entities and working-age population are crucial for the waste quantity in communes of eastern Poland; the factors most considerably as to regional range affecting the waste quantity are urban and business development; as to strength–higher education and the share of working age individuals;

The neurologic effects of long-COVID are a therapeutic challenge. This article discusses the immunologic manifestations of long-COVID and proposes a non-androgenic, synthetic analog of dehydroepiandrosterone (DHEA), bromo-epi-androsterone (BEA), as a candidate for clinical trials for this exigent collection of neurologic conditions. Moreover, because there is an association between long-COVID and Alzheimer’s disease, the evaluation of BEA in long-COVID may serve as a proxy for its effect on neuroinflammatory biomarkers of Alzheimer’s disease that are shared with long-COVID.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Since the outbreak of COVID-19, social media platforms, such as Twitter, have experienced a tremendous increase in conversations related to Long COVID. The term “Long COVID” describes the persistence of symptoms of COVID-19 for several weeks or even months following the initial infection. Recent works in this field have focused on sentiment analysis of Tweets related to COVID-19 to unveil the multifaceted spectrum of emotions, viewpoints, and perspectives held by the Twitter community. However, most of these works did not focus on Long COVID, and the few works that focused on Long COVID have limitations. Furthermore, no prior work in this field has investigated Tweets where individuals self-reported experiencing Long COVID on Twitter. The work presented in this paper aims to address these research challenges by presenting multiple novel findings from a comprehensive analysis of a dataset comprising 1,244,051 Tweets about Long COVID, posted on Twitter between May 25, 2020, and January 31, 2023. First, the analysis shows that the average number of Tweets per month where individuals self-reported Long COVID on Twitter, has been considerably high in 2022 as compared to the average number of Tweets per month in 2021. Second, findings of sentiment analysis using VADER show that the percentage of Tweets with positive, negative, and neutral sentiment were 43.12%, 42.65%, and 14.22%, respectively. Third, the analysis of sentiments associated with these Tweets also shows that the emotion of sadness was expressed in most of these Tweets. It was followed by the emotions of fear, neutral, surprise, anger, joy, and disgust, respectively.

Long coronavirus disease 2019 (COVID-19) may occur after experiencing acute COVID-19 infec-tion with many effects on patients´ kidneys. This study aimed to evaluate the clinical and labora-tory aspects of kidney function in individuals with long COVID in the Amazon region of Brazil. This cross-sectional study selected participants from a ‘long COVID’ clinical care program. Clini-cal data and baseline demographics were obtained, and blood samples were collected to quantify kidney-related markers. Patients were evaluated after COVID-19 infection at several time points as follows: 0–3 months, 3–6 months, 6–12 months, and 12 months. Altogether, 246 patients were selected for this study, and only 79 were hospitalised (9 in the intensive care unit because of COVID-19. Of the patients, 38 were diagnosed with hypertension after COVID-19, 52 cases had to have their medications adjusted, and 83 patients presented with kidney function decline. The older age group and individuals with glycaemic alterations presented with a higher risk of devel-oping kidney dysfunction. Therefore, health professionals should monitor long-term kidney mark-ers in long COVID.

In this study, a structural profiling of equid alphaherpesvirus 1 (EHV-1) transcriptome was carried out using next-generation (Illumina) and third-generation (Oxford Nanopore Technologies) sequencing platforms. We annotated the canonical mRNA molecules and their isoforms, including transcript start and end site isoforms, and splice variants. Additionally, a number of putative 5′-truncated mRNAs containing shorter in-frame ORFs were detected. We also demonstrated that EHV-1 produces a high number of non-coding transcripts, including antisense and intergenic RNAs. One of the most remarkable features of the EHV-1 is the generation of abundant fusion transcripts some of which encoding chimeric polypeptides. We observed a higher number of splicing and transcriptional overlaps than in related viruses. Additionally, we found that many upstream genes of tandem gene clusters have their own transcript end sites (TESs) besides the co-terminal TESs, which is rare in other alphaherpesviruses. We show here that the replication origins (OriS and OriL) of the virus are co-localized with promoter sequences and overlap with specific RNA molecules. Furthermore, we discovered a novel non-coding RNA (designated as NOIR) that overlaps the 5′-ends of the longer transcript variants encoded by the two main transactivator genes ORF64 and 65 bracketing the OriL. These all suggest the existence of a central regulatory system which controls the genome-wide transcription and the replication through a mechanism based on the interference between the machineries carrying out the synthesis of DNA and RNA.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19.There is good reason to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID-19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background.

PTB7-Th is an important donor copolymer used in construction of many organic devices and other industrial applications. In this work, we investigate the structure and energetics of PTB7-Th. We employ density functional theory (DFT) (B3LYP), dispersion corrected DFT (B3LYP-D3) and long-range corrected DFT (CAM-B3LYP, LC-BLYP, and ωB97xD) to analyze the conformational structures and their corresponding energies to determine the lowest energy state of PTB7-Th. The role of the alkane side chains is carefully investigated. Our findings indicate that, when branched ethylhexyl side chains are present, the lowest energy structure of PTB7-Th has fluorine in the same plane and the same side as the double bonded oxygen in the TT-CF part of the monomer and S-C-C-S dihedral angles along the chain backbone are cis-like having values in the range of 20-30 degrees in most cases. Without these side chains the polymer, not unexpectedly, has many near conformational degeneracies.

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

Lung cancer is a common malignant tumor of the lung and the leading cause of cancer mortality worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80%–85% of lung cancer, 40% of NSCLCs will have spread beyond the lungs by the time it is diagnosed. Long non-coding RNA (LncRNA) prostate androgen-regulated transcript 1 (PART-1) was reported that promote the development of several cancers. In the current study, we conducted experiments to investigate the role of PART-1 in the proliferation, invasion, and migration of NSCLC. The expression level of the PART-1 gene increased significantly in the NSCLC cell lines, including A549, H1229, H1650, H1975, and PC9. Knocking down of PART-1 inhibited the proliferation, invasion, and migration of A549 cells, moreover, decreased the tumor proliferation in nude mice. We confirmed that PART-1 targeted miR-204-3p directly, and miR-204-3p targeted the insulin-like growth factor binding protein 2 (IGFBP-2) directly. Furthermore, we discovered that PART-1 involved the NSCLC progression by regulating the miR-204-3p-targeted IGFBP-2 pathway. LncRNA PART-1 might be a target for treating NSCLC, and a warning sign of diagnosis of early lung cancer.

Among the components of a healthy life, sexuality is an essential part, contributing not only to psychophysical well-being, but also to the social well-being of women and, consequently to their quality of life. A poorly investigated standpoint is the acceptability of a contraceptive method, not only in terms of tolerability and metabolic neutrality, but also concerning the impact that it can have on sexual life. In this context, we will provide an overview of the different methods of contraception and their effects on female sexuality from the biological changes, to organic, social, and psychological factors, which can all shape sexuality.A MEDLINE/PUBMED review of the literature between 2010 and 2021 was conducted using the following key words/phrases: hormonal contraception, contraceptives, female sexual function, libido, sexual arousal and desire, and sexual pain. Recent studies have supported the effects of contraceptives on women’s sexuality, describing a variety of positive and negative events on several domains of the sexual function (desire, arous-al, orgasm, pain, enjoyment). However, satisfaction with sexual activity depends on factors that extend beyond sexual functioning alone. A more holistic approach is needed to better under-stand the multitude of factors linked to women’s sexuality and contraception. Contraceptive counselling must necessarily consider these important elements since they are closely related to good compliance.

We outline and test a new methodology for genuine simulation of stochastic processes with any dependence and any marginal distribution. We reproduce time dependence with a generalized, time symmetric or asymmetric, moving-average scheme. This implements linear filtering of non-Gaussian white noise, with the weights of the filter determined by analytical equations in terms of the autocovariance of the process. We approximate the marginal distribution of the process, irrespective of its type, using a number of its cumulants, which in turn determine the cumulants of white noise in a manner that can readily support the generation of random numbers from that approximation, so that it be applicable for stochastic simulation. The simulation method is genuine as it uses the process of interest directly without any transformation (e.g. normalization). We illustrate the method in a number of synthetic and real-world applications with either persistence or antipersistence, and with non-Gaussian marginal distributions that are bounded, thus making the problem more demanding. These include distributions bounded from both sides, such as uniform, and bounded form below, such as exponential and Pareto, possibly having a discontinuity at the origin (intermittence). All examples studied show the satisfactory performance of the method.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

Non-coding RNA regions have long been considered the "dark matter" of the genome, with their significance in gene regulation remaining enigmatic. However, recent advances in genomics and molecular biology have illuminated the pivotal role that non-coding RNA regions play in the fine-tuned orchestration of hemoglobin expression. Hemoglobin, the oxygen-carrying protein vital for life, is tightly regulated, and any disruption in its production can lead to severe medical conditions, such as hemoglobinopathies. This review delves into the intricate world of non-coding RNA regions, exploring how they act as master conductors in controlling hemoglobin gene expression. We will discuss various classes of non-coding RNAs, including long non-coding RNAs, microRNAs, and circular RNAs, and their specific mechanisms in fine-tuning hemoglobin levels. Additionally, we will highlight emerging therapeutic approaches that target non-coding RNA regions to ameliorate hemoglobin-related disorders. Understanding the critical role of non-coding RNA regions in hemoglobin regulation opens new avenues for precision medicine and gene therapies, offering hope for those affected by hemoglobinopathies and related conditions. This comprehensive review sheds light on the significance of these non-coding RNA regions, demonstrating that the "silent" players in the genome are, in fact, the conductors of harmony in the symphony of hemoglobin regulation.

RNA polymerase II (RNAPII) frequently transcribes non-protein coding DNA sequences in eukaryotic genomes into long non-coding RNA (lncRNA). Here, we focus on the impact of the act of lncRNA transcription on nearby functional DNA units. Distinct molecular mechanisms linked to the position of lncRNA relative to the coding gene illustrate how non-coding transcription controls gene expression. We review the biological significance of the act of lncRNA transcription on DNA processing, highlighting common themes, such as mediating cellular responses to environmental changes. This review presents the background in chromatin signaling to appreciate examples in different organisms where we can interpret functions of non-coding DNA through the act of RNAPII transcription.

Microalgae are abundant components of biosphere rich in low molecular weight carbohy-drate-containing natural products (glycoconjugates). Glycoconjugates take a part in processes of photosynthesis, provide producers with important biological properties, influence other organ-isms and known by biological activities. Some of them, for example glycosylated toxins and ar-senicals, are detrimental and can be transferring via food chains into higher organisms including humans. So far, the studies on a series of particular groups of microalgal glycoconjugates were not comprehensively discussed in special reviews. In this review, a special focus was made on the isolation, structure determination, properties and approaches to the search for new bioactive metabolites. Analysis of literature data concerning structures, functions and biological activities of ribosylated arsenicals, galactosylated and sulfoquinovosylated lipids, phosphoglycolipids, gly-coside derivatives of toxins, and other groups of glycoconjugates was carried out and discussed. The discovery of a great variety of new carbohydrate-containing metabolites, important biological roles some of them, participation in regulation of microalgal blooms via viral infections as well as the detection of potent immunomodulatory activity, shown by these type metabolites could be attributed to the most interesting recent achievements. Structures, properties and biological roles of glycoconjugates from microalgae attract a great attention growing year to year.

This paper presents an overview of EREMI, a two-year project funded under ERASMUS+ KA203, and its results. The project team's main objective was to develop and validate an advanced interdisciplinary higher education curriculum, which includes lifelong learning components. The curriculum focuses on enhancing resource efficiency in manufacturing industries and optimizing poorly or non-digitized industrial physical infrastructure systems. The paper also discusses the results of the project, highlighting the successful achievement of its goals. EREMI effectively supports the transition to Industry 5.0 by preparing a common European pool of future experts. Through comprehensive research and collaboration, the project team has designed curriculum that equips students with the necessary skills and knowledge to thrive in the evolving manufacturing landscape. Furthermore, the paper explores the significance of EREMI's contributions to the field, emphasizing the importance of resource efficiency and system optimization in industrial settings. By addressing the challenges posed by under-digitized infrastructure, the project aims to drive sustainable and innovative practices in manufacturing. All five project partner organisations have been actively engaged in offering relevant educational content and framework for decentralised sustainable economic development in regional and national contexts through capacity building at local level. A crucial element of the added value is the new channel for feedback from students. The survey results, which are outlined in the paper, offer valuable insights gathered from students, contributing to the continuous improvement of the project.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

The official recommendations to manage COVID-19 in the outpatient setting focus on high-cost drugs (remdesivir, nirmatrelvir-ritonavir, molnupiravir), suffering from many problems. Therefore, one may consider also other treatments meeting these criteria: • promising effectiveness, based on favorable randomized controlled trials (RCTs) of sufficient validity. Even without definitive evidence, physicians and informed patients can consider them if they are also: • safe, to the state of knowledge • with a very favorable opportunity cost • biologically plausible/not implausible • accessible • without major commercial sponsors in the trials promoting them, and with researchers without major conflicts of interests. The main focus is on a limited group of functional foods and some their active ingredients, with further mention of other substances of different origin, yet fully meeting all the aforementioned criteria. The functional foods and substances described and discussed certainly do not cover all the known effective therapies for COVID-19 (in one case also for Long-COVID), but the only therapies proposed in this paper currently satisfy all the above criteria. The supporting scientific evidence will favor meta-analyses of RCTs that include the most definitive outcome: all-cause mortality, i.e. the outcome that most fully informed people tend to prioritize. Furthermore, the reported evidence favors clinical studies of the most valid design, i.e. RCTs.

Background: The scaffold protein tyrosine kinase substrate 4 (TKS4) undergoes tyrosine phos-phorylation by the epidermal growth factor receptor (EGFR) pathway via Src kinase. The TKS4 deficiency in humans is responsible for the manifestation of a genetic disorder known as Frank-Ter Haar syndrome (FTHS). Based on our earlier investigation, the absence of TKS4 triggers migration, invasion, and epithelial-mesenchymal transition (EMT)-like phenomena while concurrently suppressing cell proliferation in HCT116 colorectal carcinoma cells. This indicates that TKS4 may play a unique role in the progression of cancer. In this study, we demonstrated that the enhancer of zeste homolog 2 (EZH2) and the histone methyltransferase of polycomb repressive complex 2 (PRC2) are involved in the migration, invasion, and EMT-like changes in TKS4-deficient cells (KO). EZH2 is responsible for the maintenance of the trimethylated lysine 27 on histone H3 (H3K27me3). Methods: We performed the transcriptome sequencing, chromatin immunoprecipitation, protein and RNA quantitative studies, cell mobility, invasion, and proliferation studies combined with/without EZH2 activity inhibitor 3-deazanoplanocine (DZNep) Results: We detected an elevation of global H3K27me3 levels in the TKS4 KO cells, which could be reduced with treatment with DZNep, an EZH2 inhibitor. Inhibition of EZH2 activity reversed the phenotypic effects of the knockout of TKS4, reducing the migration speed and wound healing capacity of the cells as well as decreasing the invasion capacity, while the decrease in cell prolif-eration became stronger. In addition, inhibition of EZH2 activity also reversed most epithelial and mesenchymal markers. We investigated the wider impact of TKS4 deletion on the gene expression profile of colorectal cancer cells using transcriptome sequencing of wild-type and TKS4 knockout cells, particularly before and after treatment with DZNep. Additionally, we observed changes in the expression of several protein-coding genes and long non-coding RNAs that showed a recovery in expression levels following EZH2 inhibition. Conclusions: Our results indicate that the removal of TKS4 causes a notable disruption in the gene expression pattern, leading to the disruption of several signal transduction pathways. Inhibiting the activity of EZH2 can restore most of these transcriptomics and phenotypic effects.

In our recent publications, based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. In this paper, we make an attempt to understand and estimate the maximum binding energy associated with any mass number. It can be expressed as, for A > 4, $\left(BE\right)_A\cong \left[A-0.000935A^2-A^{1/3}-A^{-1/2}\right]$ MeV. We are working on refining the 4^th term with even-odd corrections, shell corrections and other microscopic corrections. Proceeding further, stable mass numbers and super heavy mass numbers can be understood with a relation of the form, $\left[\textrm{RoundOff}\left(\left(Z+2.9464\right)^{1.2}-1.7165\right)\right]\pm\left[0,1\right]\pm\left(2n\right)$ where $n \cong 0,1,2$. It needs a review with respect to even-odd proton numbers and other microscopic corrections.Very interesting point to be noted is that based on the concept of “binding energy per nucleon”, the most complicated Avogadro number and Unified atomic mass unit can be estimated in a unified approach.

Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD) patients using neuropsychological testing. The study involved 71 post-COVID patients, with matched control groups: recovered COVID-19 individuals without complications (n=18) and individuals without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, a comparison group (noPCD, n=46) included participants with neurological COVID-19 complications, excluding clinical depression. The PCD patients showed significantly less scores in the MoCA test, decreased immediate memory recall in the Word Memory Test, decreased processing speed and higher accuracy in the Trail Making Test, and near to significant worse executive control and processing speed in the Stroop task compared to controls and the noPCD patients. The number of post-COVID symptoms negatively correlated with immediate word memory recall and processing speed among all post-COVID patients. In PCD patients, negative correlations between number of post-COVID symptoms and delayed recall, between time after recovery and immediate recall, and positive correlation between the number of acute symptoms and processing speed in the incongruent condition of the Stroop task were found. No differences between groups in Sniffin’s stick olfactory test was found. Overall, our study revealed cognitive impairment in PCD patients similar to those in major depressive disorder.

In the face of the upcoming 30th anniversary of econophysics, we review our contributions and other related works on the modeling of the long–range memory phenomenon in physical, economic, and other social complex systems. Our group has shown that the long–range memory phenomenon can be reproduced using various Markov processes, such as point processes, stochastic differential equations and agent–based models. Reproduced well enough to match other statistical properties of the financial markets, such as return and trading activity distributions and first–passage time distributions. Research has lead us to question whether the observed long–range memory is a result of actual long–range memory process or just a consequence of non–linearity of Markov processes. As our most recent result we discuss the long–range memory of the order flow data in the financial markets and other social systems from the perspective of the fractional Lèvy stable motion. We test widely used long-range memory estimators on discrete fractional Lèvy stable motion represented by the ARFIMA sample series. Our newly obtained results seem indicate that new estimators of self–similarity and long–range memory for analyzing systems with non–Gaussian distributions have to be developed.

Long-range interactions are relevant for a large variety of quantum systems in quantum optics and condensed matter physics. In particular, the control of quantum-optical platforms promises to gain deep insights in quantum-critical properties induced by the long-range nature of interactions. From a theoretical perspective, long-range interactions are notoriously complicated to treat. Here, we give an overview of recent advancements to investigate quantum magnets with long-range interactions focusing on two techniques based on Monte Carlo integration. First, the method of perturbative continuous unitary transformations where classical Monte Carlo integration is applied within the embedding scheme of white graphs. This linked-cluster expansion allows to extract high-order series expansions of energies and observables in the thermodynamic limit. Second, stochastic series expansion quantum Monte Carlo which enables calculations on large finite systems. Finite-size scaling can then be used to determine physical properties of the infinite system. In recent years, both techniques have been applied successfully to one- and two-dimensional quantum magnets involving long-range Ising, XY, and Heisenberg interactions on various bipartite and non-bipartite lattices. Here, we summarise the obtained quantum-critical properties including critical exponents for all these systems in a coherent way. Further, we review how long-range interactions are used to study quantum phase transitions above the upper critical dimension and the scaling techniques to extract these quantum critical properties from the numerical calculations.

This literature review provides a comprehensive analysis of the functional morphology and paleoecology of Pteranodon, a prominent genus of Pterosaur from the Late Cretaceous period. By synthesizing recent research findings with classic studies, this paper elucidates the aerodynamic and ecological adaptations of Pteranodon, which was one of the largest pterosaurs to ever soar the skies. The review examines the distinctive cranial features, including its elongated cranial crest and its implications for sexual dimorphism and species identification. Detailed analysis of wing morphology and limb proportions reveals insights into its flight mechanics, suggesting that Pteranodon was adapted for dynamic soaring, leveraging its expansive wingspan for efficient long-distance travel. Additionally, the paper explores Pteranodon's feeding habits and dietary preferences based on dental and jaw structure, indicating a diet primarily consisting of fish and other aquatic prey. The review also integrates fossil evidence with ecological models to reconstruct the paleoenvironment of the Late Cretaceous, highlighting the role of Pteranodon in its ecosystem as both a predator and a competitor. This synthesis not only enhances our understanding of Pteranodon’s physiological and ecological roles but also contributes to broader discussions on pterosaur evolution and behavior.

The morphology of virgin reactor powder (RP) of high-density polyethylene HDPE with MW = 160,000 g/mol was investigated with the help of DSC, SEM, SAXS and WAXS methods. The morphological SEM analysis showed, that the main morphological units of RP are macro- and micro-shish kebab structures with significantly different geometric dimensions, as well as individual lamellae of folded chain crystals. Quantitative analysis of an asymmetric SAXS reflection made it possible to reveal the presence of several periodic morphoses in the RP with long periods from 20 nm to 60 nm and to correlate them with the observed powder morphology. According to the DSC crystallinity data, the thickness of the lamellae in each long period was estimated. Their surface energy was calculated in the framework of the Gibbs-Thompson theory. The presence of regular and irregular folds on the surface of the different shish-kebab lamellae is discussed. The percentage of identified morphoses in the RP was calculated. It has been suggested that the specific structure of HDPE RP is due to the peculiarity of polymer crystallization during suspension synthesis in a quasi-stationary regime, in which local overheating and inhomogeneous distribution of shear stresses in a chemical reactor are possible.

We delve into the axion-dilaton model within the supergravity framework, with a specific focus on the intricacies of domain wall construction and stability. Employing holographic vitrification, we unravel the dynamics of domain wall formation in gauge theories featuring periodic vacuum structures. Our model, incorporating a QCD-like axion term and a stabilizing dilaton, undergoes scrutiny for conductivity variations under weak disorder. The investigation reveals the model's resilience, manifesting near-perfect conductivity under mild disorder conditions. However, the rigorous mathematical motivation for the holographic setup demands further elucidation. The scattered nature of our results prompts the necessity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model's behavior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

Abstract:Shown is the derivation of Lorentz-Einstein k-factor in SRT as an amplitude-term of oscillation-differential equations of second order.This case is shown for classical Lorentz-factor as solution of an equation for undamped oscillation as well as the developed theorem as a second solution for advanced SRT of fourth order with an equation for damped oscillation-states.This advanced term allows a calculation for any velocities by real rest mass

We introduce the linear subgroup of volume-preserving diffeomorphism as the underlying symmetry to construct an action within the effective field theory framework and the Schwinger-Keldish formalism. The formulated action is posited to effectively incorporate dissipative effects into the Navier-Stokes equations.