Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by cognitive decline and neuronal loss, representing a most challenging health issue. We present a computational analysis of transcriptomic data of AD tissues vs. healthy controls, focused on elucidation of functional roles played by long non-coding RNAs (lncRNAs) throughout the AD progression. We first assembled our own lncRNA transcripts from the raw RNA-Seq data generated from 527 samples of dorsolateral prefrontal cortex, resulting in the identification of 31,574 novel lncRNA genes. Based on co-expression analyses between mRNAs and lncRNAs, a co-expression network is constructed. Maximal subnetworks with dense connections are identified as functional clusters. Pathway enrichment analyses are conducted over mRNAs and lncRNAs in each cluster, which serve as the basis for the inference of functional roles played by lncRNAs involved in each of the key steps in an AD development model that we have previously build based on transcriptomic data of protein-encoding genes. Detailed information is presented about the functional roles by lncRNAs in activities related to stress response, reprogrammed metabolism, cell-polarity, and development. Our analyses have also revealed that lncRNAs have discerning power in distinguishing between AD samples of each stage and healthy controls. This study represents the first of its kind.

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs. Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

The aim of this study was to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in the endometrium of individuals with and without EMS during the proliferative (P) and secretory (S) phases of the menstrual cycle. Tissues were obtained from 18 control (CT; P-phase [pCT], n=8; S-phase [sCT], n=13) and 23 EMS patients (P-phase [pEMS], n=13; S-phase [sEMS], n=12). DElncRNAs and DEmRNAs were analyzed using total RNA-sequencing. In P-phase, expression of NONHSAG019742.2 and NONHSAT120701.2 was significantly higher in EMS than control patients, that of while NONHSAG048398.2 and NONHSAG016560.2 was lower in EMS patients. In S-phase, expression of NONHSAT000959.2, NONHSAT203423.1, and NONHSAG053769.2 was significantly increased in EMS patients, while that of NONHSAG012105.2 and NONHSAG020839.2 was lower. In addition, the expression of HSD11B2, THBS1, GPX3, and SHISA6 was similar to that of neighboring lncRNAs in both P- and S-phases. In contrast, ELP3 and NR4A1, respectively, were up- or downregulated in pEMS tissues. In sEMS, expression of LAMB3 and HIF1A was increased, while expression of PAM was reduced. Our findings on lncRNAs and mRNAs encourage not only to explore the potential clinical applications of lncRNAs and mRNAs as prognostic or diagnostic biomarkers for EMS but also to gain valuable insights into its pathogenesis.

Long non-coding RNAs (lncRNAs) have been found to be involved in many biological processes, including the regulation of cell differentiation, but a complete characterization of lncRNA is still lacking. Additionally, there is evidence that lncRNAs interact with ribosomes, raising questions about their functions in cells. Here, we used a developmentally staged protocol to induce cardiogenic commitment of hESCs and then investigated the differential association of lncRNAs with polysomes. Our results identified lncRNAs in both the ribosome-free and polysome-bound fractions during cardiogenesis and showed a very well-defined temporal lncRNA association with polysomes. Clustering of lncRNAs was performed according to the gene expression patterns during the five timepoints analyzed. In addition, differential lncRNA recruitment to polysomes was observed when comparing the differentially expressed lncRNAs in the ribosome-free and polysome-bound fractions or when calculating the polysome-bound vs ribosome-free ratio. The association of lncRNAs with polysomes could represent an additional cytoplasmic role of lncRNAs, e.g., in translational regulation of mRNA expression.

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.

Mucosal melanomas (MM) are rare aggressive cancers in humans and one of the most common forms of oral cancers in dogs. Similar biological and histological features are shared between MM in both species making dogs a powerful model for comparative oncology studies of melanomas. Although exome sequencing recently identified recurrent coding mutations in canine MM, little is known about changes in non-coding gene expression and more particularly in canine long non-coding RNAs (lncRNAs), which are commonly dysregulated in human cancers. Here, we sampled a large cohort (n= 52) of canine normal/tumor oral MM from three predisposed breeds (poodles, Labrador retrievers and golden retrievers) and used deep transcriptome sequencing to identify more than 400 differentially expressed (DE) lncRNAs. We further prioritized candidate lncRNAs by comparative genomic analysis to pinpoint 26 dog-human conserved DE lncRNAs, including SOX21-AS, ZEB2-AS and CASC15 lncRNAs. Using unsupervised co-expression networks analysis with coding genes, we inferred potential functions of DE lncRNAs suggesting associations with cancer-related genes, cell cycle and carbohydrate metabolism GO terms. Finally, we exploited our multi-breed design to identify DE lncRNAs per breed. This study provides a unique transcriptomic resource for studying oral melanoma in dogs and highlights lncRNAs that may potentially be diagnostic or therapeutic targets for human and veterinary medicine.

Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development have not been studied. Here, we conducted a scRNA-seq survey of cells from sheep from the oocyte to the blastocyst developmental stages. We then carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS). We founded that between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.

Formalin-Fixed Paraffin Embedded (FFPE) tissues are a valuable resource in studying different markers and mechanistic molecules (protein, DNA and RNA) in order to understand the etiology of different cancers as well as many other diseases. Degradation and modification of RNA is the major challenge in utilizing FFPE tissue samples in medical research. Recently, non-protein coding transcripts long non-coding RNAs (lncRNAs), have gained significant attention due to their important biological actions and potential involvement in cancer. There is no validated method except qRTPCR or RNAseq to evaluate and study lncRNA expression. We have standardized and are reporting a sensitive Z probe based in situ hybridization method to identify, localize and quantitate lncRNA in FFPE tissues. This assay is sensitive to single transcript and localizes lncRNA in individual cells within tumor. We have characterized a tumor suppressor lncRNA-NRON (non coding repressor of NFAT), which is scarcely expressed, a moderately expressed oncogeneic lncRNA UCA1 (urothelial cancer associated 1), and a highly studied and expressed lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript1) in different cancers. High MALAT1 staining was found in colorectal, breast and pancreatic cancer. MALAT1 expression increased with the progression of the stage in colorectal cancer and invasiveness in breast cancer.

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.

A small phylogenetically conserved sequence of 11,231 bp termed FAM247 is repeated in human chromosome 22 by segmental duplications. This sequence forms part of diverse genes that span evolutionary time, the protein genes being the earliest as they are present in zebrafish and/or mice genomes, the long non-coding RNA genes and pseudogenes the most recent as they appear to be present only in the human genome. We propose that the conserved sequence provides a nucleation site for new gene development at evolutionary conserved chromosomal loci where the FAM247 sequences reside. The FAM247 sequence also carries information in its open reading frames that provides protein exon amino acid sequences; one exon plays an integral role in immune system regulation, specifically, the function of ubiquitin specific protease (USP18) in the regulation of interferon. An analysis of this multifaceted sequence and the genesis of genes that contain it are presented.

It is generally accepted that atherosclerosis is a chronic inflammatory disease. The link between atherosclerosis and other inflammatory diseases such as psoriasis, type 2 diabetes mellitus (T2DM), and rheumatoid arthritis (RA) via metabolic, inflammatory, and immunoregulatory pathways is well established. The aim of our review was to summarize the associations between selected microRNAs (miRs) and long non-coding RNAs (lncRNAs) and atherosclerosis, psoriasis, T2DM, and RA. MicroRNAs are short noncoding RNA molecules involved in cell signaling, intracellular communication, and gene expression. We reviewed the role of miR-146a, miR-210, miR-143, miR-223, miR-126, miR-21, miR-155, miR-145, miR-200, miR-133, miR-135, miR-221, miR-424, and let-7 in atherosclerosis, psoriasis, T2DM, and RA. LncRNAs are RNA transcripts longer than 200 nucleotides that are involved in cellular processes such as apoptosis, metabolism, inflammation, cell differentiation, and proliferation. We evaluated the role of lncRNA-H19, lncRNA-MEG3, lncRNA-UCA1, and lncRNA-XIST in atherosclerosis and psoriasis, T2DM, and RA. Extracellular vesicles (EVs) are a method of intracellular signal transduction. Their function depends on surface expression, cargo, and the cell from which they originate.

Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of the heterogeneity of programmed cell death. The purpose of this work is to investigate and develop a cuproptosis-associated lncRNA-based LUAD prediction marker. We firstly performed bioinformatic analysis of the Cuprotosis database and The Cancer Genome Atlas (TCGA) database to obtain 19 cuprotosis-related gene datasets and transcriptional data for LUAD. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were utilized to construct cuproptosis-associated lncRNA modes. LUAD patients were thus classified into high-risk and low-risk categories based on prognostic risk values, with a median of It acted as a boundary. Risk models were evaluated and validated using Kaplan-Meier analysis, principal component analysis (PCA), gene set enrichment analysis (GSEA) and nomograms. Utilizing the TCGA-LUAD dataset, we identified seven predicted cuproptosis-associated lncRNAs in tumor microenvironment to create the risk model. 95.54% (214/224) of high-risk category tumor samples included cuproptosis-associated gene alterations, compared to 85.65% (203/237) of low-risk category tumor samples, with TP53 accounting for the bulk of occurrences. According to these findings, risk value was superior to other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival (OS). The predictive validity of the cuproptosis-associated lncRNA-based risk model for LUAD is high, and this may have implications for how lung cancer patients are treated individually.

This study aimed to characterize the long non-coding RNA (lncRNA) expression in the bovine mammary gland and to infer their functions in dietary response to 5% linseed oil (LSO) or 5% safflower oil (SFO). Twelve cows (six per treatment) in mid lactation were fed a control diet for 28 days followed by a treatment period (control diet supplemented with 5% LSO or 5% SFO) of 28 days. Mammary gland biopsies were collected from each animal on day-14 (D-14, control period), D+7 (early treatment period) and D+28 (late treatment period) and were subjected to RNA-Sequencing and subsequent bioinformatics analyses. Functional enrichment of lncRNA was performed via potential cis regulated target genes located within 50 Kb flanking regions of lncRNAs and having expression correlation of >0.7 with mRNAs. A total of 4955 lncRNAs (325 known and 4630 novel) were identified which potentially cis targeted 59 and 494 genes in LSO and SFO treatments, respectively. Enrichments of cis target genes of lncRNAs indicated potential roles of lncRNAs in immune function, nucleic acid metabolism and cell membrane organization processes as well as involvement in Notch, cAMP and TGF-β signaling pathways. Thirty-two and 21 lncRNAs were differentially expressed (DE) in LSO and SFO treatments, respectively. Six genes (KCNF1, STARD13, BCL6, NXPE2, HHIPL2 and MMD) were identified as potential cis target genes of six DE lncRNAs. In conclusion, this study indicated potential roles for lncRNAs in mammary gland immune functions and development and provided potential candidate genes and pathways via which lncRNAs can function in diet responses.

In this review, we will cover a general overview of the current panorama on lncRNAs with an actual or potential role as biological markers in cancer. We will discuss examples of multi-omics approaches that integrates information on somatic aberrations, gene expression and epigenomics, with the scope of providing a more comprehensive view of the functional impact of lncRNA profiles and how these paradigm can be exploited for the discovery and selection of lncRNAs with a functional role and their use as variables informing on progression and prognostic and help guiding the selection of therapeutic strategies for cancers. Finally, we propose a perspective for future evolution of the study of lncRNAs and the discovery of their functional and harnessing their potential to assist in clinical management of malignancies.

Evidence indicates that the long noncoding RNAs are involved in the metformin-mediated anti-cancer processes. However, the potential effects of the long noncoding RNAs in metformin-mediated anti-tumor processes in esophageal squamous cell carcinomas (ESCC) are still elusive. This study uncovered that metformin decreases the level of long noncoding RNAs CCAT1 and SPRY4-IT1 thereby contributing to the down-regulation of c-Myc and vimentin. Also, the RNA level test of human ESCC tissue confirmed the positive correlation between CCAT1 and c-Myc. These findings demonstrated that metformin facilitated anti-cancer effects by targeting the 2 long noncoding RNAs (CCAT1 and SPRY4-IT1) and their consequential targets c-Myc and vimentin. Therefore, the CCAT1 and SPRY4-IT1 might act as novel molecular targets that mediate the anti-tumor effects in esophageal squamous cell carcinoma. This helps in predicting the treatment response of metformin in patients diagnosed with esophageal squamous cell carcinoma.

Long noncoding RNAs (lncRNAs) of virus origin accumulate in cells infected by many positive strand (+) RNA viruses to bolster viral infectivity. Their biogenesis mostly utilizes exoribonucleases of host cells that degrade viral genomic or subgenomic RNAs in the 5’-to-3’ direction until being stalled by well-defined RNA structures. Here we report a viral lncRNA that is produced by a novel replication-dependent mechanism. This lncRNA corresponds to the last 283 nucleotides of the turnip crinkle virus (TCV) genome, hence is designated tiny TCV subgenomic RNA (ttsgR). ttsgR accumulated to high levels in TCV-infected Nicotiana benthamiana cells when the TCV-encoded RNA-dependent RNA polymerase (RdRp), also known as p88, was overexpressed. Both (+) and (-) strand forms of ttsgR were produced in these cells in a manner dependent on the RdRp functionality. Strikingly, templates as short as ttsgR itself were sufficient to program ttsgR amplification, as long as the TCV-encoded replication proteins, p28 and p88, were provided in trans. Consistent with its replicational origin, ttsgR accumulation required a 5’ terminal G₃(A/U)₄ motif shown by others to be crucial for the replication of a TCV satellite RNA. More importantly, introducing a new G₃(A/U)₄ motif elsewhere in the TCV genome was alone sufficient to cause the emergence of another lncRNA. Collectively our results unveil a replication-dependent mechanism for the biogenesis of viral lncRNAs, thus suggesting that multiple mechanisms, individually or in combination, may be responsible for viral lncRNA production.

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.

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

Exponential increase in mobile video delivery will continue with the demand for higher resolution, multi-view and large-scale multicast video services. Novel fifth generation (5G) 3GPP New Radio (NR) standard will bring a number of new opportunities for optimizing video delivery across both 5G core and radio access network. One of the promising approaches for video quality adaptation, throughput enhancement and erasure protection is the use of packet-level random linear network coding (RLNC). In this work, we discuss the integration of RLNC into the 5G NR standard, building upon the ideas and opportunities identified in 4G LTE. We explicitly identify and discuss in detail novel 5G NR features that provide support for RLNC-based video delivery in 5G, thus pointing out to the promising avenues for future research.

Hepatocellular carcinoma (HCC) is a liver cancer that originates from hepatocytes. It is a primary health issue and one of the most common malignant tumors. The US FDA approved Sorafenib as the first-line anti-cancer drug for advanced HCC patients. A few patients with advanced HCC may benefit from Sorafenib treatment, but most of the patients eventually develop resistance to Sorafenib, which leads to its poor prognosis. Long-noncoding RNAs (lncRNA) have been found to play a critical role in tumorigenesis and the development of HCC, as well as various cancers. It also plays a vital role in tumor drug resistance, while the mechanisms of LncRNAs in HCC sorafenib resistance have not been characterized yet. In this review article, we summarized the molecular mechanisms, such as the involvement of transporters, receptors, cell death regulation, and other factors impacting sorafenib resistance in HCC.

Background/Objectives: To develop a novel method for isolating proteins associated with Long Non-coding RNAs (LncRNAs) using high-throughput Liquid Chromatography Mass Spectrometry (LC-MS) and proteomics approaches for identifying cancer-associated proteins involved in post-translational modifications (PTMs) such as glycosylation, phosphorylation, citrullination, methylation, and acetylation. Additionally, the focus is on identifying and quantifying differentially modulated or regulated proteins associated with LncRNAs to discover novel molecular signatures or biomarkers. Methods: Identification, quantification, and characterization of LncRNAs associated pro-teins by using Label free Quantification (LFQ) of proteins by Nono LC-Mass Spectrometry (LC-MS)., use Employ bioinformatics, biostatistics analysis for find out the differentially expressed, exclusive protein or modulated., find outInvestigate the mechanisms and pathways involving these unique or specific proteins analysis of unique/specific proteins and Validation of these unique/specific proteins by Immunohistochemistry (IHC) and western blotting/ enzyme-linked immunosorbent assay (ELISA) for to achieve better out-come. Conclusions: Identified and validated novel proteins associated with LncRNAs could be early detective molecular biomarkers of cancer and it could be useful in clinical practice for diagnosis, prognosis of liver, colorectal and other several types of cancer types.

Children account for a significant proportion of the world's population and are a particularly vulnerable subpopulation regarding environmental factors. In a scoping review of a total of 3130 articles compiled from relevant medical literature, including 107 publications, we provide an empirical overview of the literature on masks in connection with children, particularly with regard to its' expected effects on viruses during the pandemic 2020-2023 versus scientific reality and evidence, including the side effects. While masks lack ecological validity from a strictly empirical point of view (transferability of experimental results from laboratories and modelling to the real world, e.g. to situations or environments typical of everyday life) and high-quality studies are showing little evidence of their effectiveness in real-world scenarios, whereas the side effects appear to be clear. An individual risk-benefit analysis is necessary and also a consideration of the situations, in which the use of masks in children could be justified. This review including the literature found and analysed will be able to help when making decisions in this regard.

Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

Non-pharmaceutical interventions (NPIs), including social distancing, wearing personal protective equipment, and lockdown measures, have been at the forefront of outbreak control in nursing homes. We used a mixed methodology to assess which NPIs nursing homes in the canton of Geneva, Switzerland, followed for their staff and residents during the first wave of the pandemic, between March 1, 2020 and June 1, 2020. For the qualitative component, we interviewed the attending physicians and/or director of each nursing home. Based on in-vivo codes, NPIs for nursing home workers and residents in each nursing home were thematically classified as: maximally restrictive, moderately restrictive, and minimally restrictive. In the quantitative component, we calculated incident rate ratios (IRR) for infection between the three levels of COVID-19-related measures taken in these nursing homes. We found an equal distribution of maximally (n=4), moderately (n=4), and minimally (n=4) restrictive NPIs. The extent of restriction did not show to be significantly associated with the cumulative incidence of COVID-19 cases among residents (maximally restrictive IRR = 3.90, 95%CI 0.82-45.54, p = 0.184; moderately restrictive IRR = 3.55, 95%CI 0.75-41.42, p = 0.212 ; minimally restrictive IRR = reference). Variabilities in NPIs adopted by nursing homes, and the number of COVID-19 cases appear to be randomly affected.

We dive 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 featur- ing 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 neces- sity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model’s be- havior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

Recently, several reports have emerged describing the long-term consequences of COVID-19 that may affect multiple systems, suggesting its chronicity. As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients discharged from the TCH, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p<0·00001). Women were more prone than men to develop long-term symptoms and invasive mechanical ventilation also increased the frequency of symptoms at 30-days post-discharge. Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.

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.

The present study examines the long-term care service awareness, needs, and usage intention of elderly male homosexuals in Taiwan and their ideal long-term care service model. This study of five elderly male homosexual subjects aged 66 to 73 years was intended as a preliminary exploration. Interviews were used to collect data. The study determined that the five subjects had high awareness of long-term care services, as they had actual experience of long-term care services or even participated in care service staff training to obtain certificates. Some even had experience in applying for home care services and experienced problems during use. The subjects perceived that they were very likely to require long-term care services in the future and tended to use home care services if they required long-term care services. Due to their personal experiences, the subjects had negative awareness of long-term care services and worried that long-term care service staff had poor attitudes toward homosexuals. The subjects considered the most important aspects of long-term care to be basic medical care and lifestyle care. However, they worried that long-term care staff would delay or refuse to provide such services due to the subjects’ sexual orientation or stereotypes, and they were concerned above all about the “friendly attitude” of long-term care staff. They hoped that long-term care staff were friendly toward homosexuals and did not discriminate against them, and they felt that it would be more appropriate for homosexual long-term care staff to provide assistance. In terms of vision, while preferring organizations with homosexual employees, the subjects worried that they would be stigmatized and discriminated against . With regard to ideal long-term care services, while considering institutions with homosexual staff to be ideal, the subjects also worried that these would be labeled as institutions that were dedicated to homosexuals, potentially resulting in discrimination. Therefore, they hoped that the sexuality sensitivity of long-term care staff could be improved and that they would undergo professional continuing education to learn about homosexuals, the situation and care needs of homosexuals, and care techniques for homosexuals.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection. This phenomenon, termed Post-Acute Sequelae of SARS-CoV-2 (PASC) or Long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of auto-antibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include degree of host response (inflammation, NETinjury), residual viral antigen (persistent antigen) and exogenous factors (microbial translocation). Determinants of PASC may be amplified by co-morbidities, age, and sex. Keywords: long COVID, PASC, long haulers, NETosis, T cell, NK cell, DC, neutrophil,

Abstract: Epigenetic approaches in direct correlation with assessment of critical genetic mutations in non-small cell lung cancer (NSCLC) are currently very intensive, as the epigenetic components in NSCLC development and progression have attained high recognition. In this level of research, established human NSCLC cell lines as well as experimental animals are widely used to detect novel biomarkers and pharmacological targets to treat NSCLC. The epigenetic background of NSCLC is highly complex and requires precise definition as these phenomena are variable between NSCLC subtypes and systems origin. We engaged an in-depth characterization of non-coding (nc)RNAs prevalent in human KRAS-mutant NSCLC cell lines A549 and H460 and mouse KRAS-mutant NSCLC tissue by Next Generation Sequencing (NGS) and quantitative Real Time PCRs (qPCRs). Also, the effect of transcription factor (TF) LRF, a known epigenetic silencer, was examined on the epigenome modulation. Finally, interacting networks underlying epigenetic variations in NSCLC subtypes were created. Data derived from our study highlights the divergent epigenetic profiles of NSCLC of human and mouse origin, as well as the significant contribution of 12qf1: 109,709,060-109,747,960 mouse chromosomal region to micro-RNA upregulated species. Fur-thermore, the novel epigenetic miR-148b-3p/PVT1/ZBTB7A axis was identified, which differentiates lung adenocarcinoma from large cell lung carcinoma, two characteristic NSCLC subtypes. The detailed recording of epigenetic events in NSCLC and combinational studies including networking between ncRNAs and TFs validate the identification of significant epigenetic features, prevailing in NSCLC subtypes and among experimental models. Our results enrich knowledge in the field and empower research on the epigenetic prognostic biomarkers of the disease and patient-tailored treatments.

Dinoflagellates are one of the largest groups of marine microalgae and exhibit diverse trophic strategies. Within these niches, dinoflagellates can produce secondary metabolites that are known to be toxic, which can lead to ecologically harmful blooms. Amphidinium carterae is one species of dinoflagellate that produces toxic compounds and is used as a model for dinoflagellate studies. The extent to which the microbiome surrounding A. carterae affects its growth and secondary metabolite synthesis is still being assessed, as well as the impact of bacterial data on sequencing and assembly. An antibiotic cocktail was previously shown to eliminate 16S amplification from the dinoflagellate culture. Even with drastically reduced bacterial numbers, bacterial populations are likely to be present. In this experiment we used novel Nanopore long-read sequencing techniques on A. carterae cultures to assemble 15 full bacterial genomes ranging from 2.9-6.0 Mb and found that the use of antibiotics decreased the percentage of reads mapping back to bacteria. We also identified shifts in the microbiome composition and identified a potentially deleterious bacterial species arising in the absence of the antibiotic-treatment. Multiple antibiotic-resistance genes were identified, as well as evidence that the bacterial population do not contribute to toxic secondary metabolite synthesis.

Objective: To summarize the prevalence of PASC/Long COVID symptoms among the general population reported in published articles. This narrative review examined 21 PASC symptoms. Methods: A PubMed/manual search returned 114 articles on general PASC/Long COVID symptoms. Manuscripts were excluded if they were not research studies, didn’t report symptom prevalence, or used a pediatric population. Ninety-eight studies were selected for review and 59 met criteria for inclusion. Risk of bias was assessed with the Hoy critical appraisal tool. Results: After excluding studies with high risk of bias, meta-analysis of prevalence for 21 symptom categories ranged from 2.6-28.7% in studies based on surveys to 0.3%-7.1% in studies based on EHR data. Conclusions: PASC symptom studies are limited by variability in study design and representation of the general population. Further research is needed to effectively cluster symptoms in meaningful ways that enable focused treatment.

Background: To analyze long-term outcomes in patients undergoing thoracic endovascular aortic repair (TEVAR). Methods: All consecutive 97 patients undergoing TEVAR between September 2014 and September 2022 were included in the study. Primary outcome was long-term incidence of overall death and major adverse cardiovascular and cerebrovascular events (MACCE). Results: Mean age was 70.4 years, and 22(23.2%) had cerebrovascular disease (CBVD). A total of 49(51.6%) of patients had prior cardiac surgery intervention and 8(8.5%) had prior aortic valve replacement. Twenty-eight patients(28.8%) presented with aortic dissection, 60(61.8%) had aortic aneurysm, 4(4.1%) had intramural hematoma, and 5(5.1%) had other presentations. An emergent procedure was performed in 6(6.2%) patients, an urgent procedure in 37(38.1%) patients and 54(55.7%) patients had an elective procedure. Intraoperatively, 78.3% had percutaneous TEVAR, 5.1% had ministernotomy TEVAR, while 10.3% had concomitant full sternotomy TEVAR repair. Hospital mortality was 7 patients(7.2%). At 8-years follow-up, 76% were alive, 25.8% had MACCE, 21.6% were diagnosed with endoleaks(13 patients type II and 2 patients type 1) while 10.3% un-derwent repeat intervention. Conclusions: This single center experience in patients undergoing TEVAR evidenced good short and long-term survival and MACCE. Nonetheless, almost half of the patients underwent an ur-gent/emergent procedure, clinical results were favourable for TEVAR.

There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. Often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub functions level. Therefore, we first aim to summarize current level of evidence supporting a negative impact of COVID-19 infection on cognitive functions. 27 studies have been included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3,786 healthy controls). We then performed a meta-analysis summarizing the results of 5 studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in Standardized Mean Differences, is -0.56 [95%CI -0.79 ; -0.34]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and to avoid long-term complication.

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state of the art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states which interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological sates, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented adding an exponential cutoff to the interaction term of PPP model. In this way, an adjusted cutoff distance λ = 2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond Hubbard model but not completely unscreened as is the case for the PPP model.

Long Covid is a debilitating condition that has been well-documented over the past 4 years and shares many similarities with other post-viral chronic illnesses. Despite this, clinicians are not confident in recognising the signs of Long Covid, or effectively managing the symptoms of their patients. This paper presents a single patient case report from a biomedical researcher who has had Long Covid for 2 years; it is written in relatively plain language to be accessible to both patients and clinicians across multiple specialities. The author has had the ability and expertise to keep up with the Long Covid research literature, and from that has cobbled together a management strategy that has alleviated her own symptoms, and those of other people with whom she has shared her protocol. The author’s experience of developing and managing her Long Covid is presented here, in the hopes that it may be of assistance to clinicians in identifying and managing Long Covid in their own patients.

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

Long COVID affects a significant number of people after acute coronavirus disease 2019 (COVID-19), and haematological changes can persist in the COVID-19 phase. This study aimed to evaluate these haematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a ‘long COVID’ clinical care programme in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected for quantification of erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalised in the acute phase had higher mean red/white cell, platelet, and plateletcrit levels and red cell distribution width. In addition, haematimetric parameters were higher in shorter periods of long COVID. Patients presenting with more than six concomitant long COVID symptoms had a higher white blood cell count, shorter prothrombin time (PT), and increased PT activity. Within up to 985 days of long COVID, our results suggest a probable benign compensation for erythrogram-related markers. Increased levels of leukogram-related markers and increased coagulation activity were observed in the worse long COVID groups, also indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.

Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..

We study the possibility of determining the octant of the neutrino mixing angle 23, that is, whether 23 > 45 or 23 < 45, in long baseline neutrino experiments. Here we numerically derived the sensitivity limits within which these experiments can determine, by measuring the probability of the  ! e transitions, the octant of 23 with a 5 certainty. The interference of the CP violation angle  with these limits, as well as the effects of the baseline length and the run-time ratio of neutrino and antineutrino modes of the beam have been analyzed.

(1)Background: Evidence on the association between air pollution and the risk of exacerbations of chronic obstructive pulmonary disease (COPD) is scarce and inconsistent. We aimed to analyze the association between long-term exposure to particulate matter with a diameter of less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) and exacerbation of COPD (COPD-E) in Bogotá, Colombia; (2) Methods: Retrospective cohort study of 722 COPD patients in the AIREPOC program of the Colombian Pneumological Foundation between 2018 and 2021. Exposure to PM2.5 and NO2 was estimated for residential locations using the inverse squared distance weighted regression (IDWR) method. Hazard Ratios (HR) were calculated for the first COPD-E during follow-up using Cox models, adjusted for meteorological, demographic, and clinical variables; (3) Results: COPD-E was associated with long-term exposure to PM2.5 (HR:1.03, 95%CI: 1.02-1.05) and NO2 (HR:1.05, 95%CI: 1.03-1.07) controlling for the effect of quality of life, history of COPD-E, Forced Expiratory Volume in One Second (FEV1) pre-bronchodilator and exposure to solar radiation. An association was found between COPD-E and concentrations ≥ 25µg/m3 of NO2 (HR:1.49, 95%CI: 1.12-1.98) but not with concentrations ≥15 µg/m3 of PM2.5; (4) Conclusions: This study suggests that people with COPD exposed to higher concentrations of PM2.5 and NO2 had an increased risk of COPD-E. Solar radiation was also associated with an increased risk of COPD-E. The results highlight the importance of continuing efforts to reduce air pollution.

Mortality due to suicide is amongst the largest public health concerns across the world today and in Bharat (India). There have been concerns that the COVID-19 pandemic has contributed to worsening mental health outcomes across the world, and in Bharat. Furthermore, long COVID has been proposed to be a major consequence of COVID-19, which can also worsen mental health outcomes. Therefore, our objective in this study was to analyse trends in suicide mortality across Bharat, and to compare these trends to changes prior to the COVID-19 pandemic; as well, we aimed to analyse if long COVID had any role in these changes. It was found that, at a national level, the average annual increase of the suicide rate between 2019 and 2022 was 0.7 per 100,000 people (6.41% increase)., There was also an average annual rise in suicide rates across 27 states/union territories (out of the 33 that were analysed). States/UTs with the highest annual increases since the start of the COVID-19, despite a decrease from 2018 to 2019, were Tamil Nadu (increase by 2.7; 15.17% increase), and Telangana (increase by 1.9; 9.22% increase), Multi-linear regression had shown that the annual suicide rate changes were not associated with COVID-19 deaths per 10,000 people (standardized beta coefficient = 0.077; p = 0.605) but were associated with COVID cases per 100 people (standardized beta coefficient = 0.578; p<0.001). It has been shown that suicide mortality has worsened, and long COVID may have a potential role in this in Bharat.

Background/Objectives: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection se-verity. However, this topic has not been studied in detail. We therefore investigated mortality risk post-acute COVID-19 in the CRIT-COV-U cohort. Methods: We could retrieve survival data from 651 patients and also assess the association between urinary peptides and future death. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched non-infected controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomics datasets. Results: Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than non-infected controls, particularly evident in younger individuals (&lt;65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease, but also beyond, for a period of about one year. In our study we were further able to identify 201 Urinary peptides linked to mortality, and integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death. Conclusions: Our findings underscore the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. Our data also suggest that mortality should be considered as one possible symptom or conse-quence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.

Background: Donor shortage limits the utilization of heart transplantation making it available for only a fraction of the patients on the transplant wait list. Continuous flow left ventricular assist devices have therefore risen in importance as a standard of care for end-stage heart failure. Short, mid and long-term survival rates as well as quality of life are now being studied with newer and more sophisticated machines. This study attempts to assess the impact of several commonly associated risk factors on long-term survival of LVAD recipients. Methods The TriNetX dataset comprises de-identified patient information across healthcare organizations. The study assesses the impact of demographics, infections, comorbidities, types of cardiomyopathies, arrhythmias, and end-organ dysfunction on long-term LVAD survival. The Log-rank test was used to assess post-implant survival effects, while Cox regression was used in univariate analysis to obtain Hazard Ratio (HR). Patients with unknown lab results were removed before the univariate analysis and K-M survival curves were generated. Samples with missing values or data errors (e.g., implantation is after recorded death) were excluded. All analyses were conducted using the Python programming language and the lifelines library. This study is IRB-exempt Results This study identified common risk factors that significantly impact survival such as CMV, hepatitis A exposure, atrial fibrillation, paroxysmal ventricular tachycardia, ischemic cardiomyopathy, renal dysfunction, diabetes, COPD, mitral valve disease, and hypertension. Conclusions This is the first report of a detailed long-term survival assessment of several risk factors that impact the LVAD population.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

We conducted a hybrid-design study on a historical cohort of 359 adult recipients of a liver graft who received transplants between 1996 and 2002. The study aimed to identify predictors of survival and investigate the prevalence of co-morbidities among long-term survivors. The actuarial (95% CI) patient survival of the overall study cohort was 96% (94.6%-98.3%), 69% (64.2%-73.6%), 55% (49.8%-59.9%), 42.8% (37.6%-47.8%), and 34% (29.2%-38.9%) at 1, 5, 10, 15, and 20 years, respectively. The actuarial (95% CI) graft survival was 93.8% (91.6%-97.2%), 67.6% (62.2%-71.5%), 54.3% (49.6%-59.3%), 42.1% (37.3%-47.4%), and 33.8% (29.0%-38.4%) at 1, 5, 10, 15, and 20 years, respectively. The leading cause of death was hepatitis C virus recurrence (24.6%), followed by extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The Cox proportional hazards analysis revealed that several independent factors were associated with the survival probability. These factors include younger donor and recipient ages (p=0.001 and 0.004, respectively), female recipient sex (p<0.001), absence of HCV (p<0.01), absence of HCC (p=0.001), and absence of diabetes mellitus at one year (p<0.01). At the latest follow-up, the leading comorbidities in the long-term survivors were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. The Kaplan-Meier probability (95% CI) of complication-free survival was 65.4% (60.2%-70.3%), 38.4% (33.4%-43.7%), 17.8% (14.1%-22.2%), 7.2% (4.8%-10.5%), and 1.94% (0.85%-4.15%) at 1, 5, 10, 15, and 20 years, respectively. Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

The collective considerations presented here lead to a crucial question: What truly constitutes the primary public health challenge posed by SARSCoV-2 infection and its variants?The findings of Bowen et al.(1) and Noé et al.(4) have offered us new insights into the actual repercussions of SARSCoV-2 virus infections on public health. They unmistakably point to the late sequelae and complications arising as secondary effects of the viral infection, causing severe and long-term damage to global public health. Rather than the acute infection which has a very low mortality rate in the general population, as initially and commonly believed.

Background: There are ongoing workforce challenges with the delivery of long-term care (LTC), such as staffing decisions based on arbitrary standards. The Synergy tool, a resident-centered approach to staffing, pro-vides objective, real-time acuity and dependency scores (Synergy scores) for residents. The purpose of this study was to implement and evaluate the impact of the Synergy tool on LTC delivery. Methods: A longitudinal mixed methods study took place within two publicly-funded LTC homes in British Columbia, Canada. Quantitative data included weekly Synergy scores for residents (24 weeks), monthly aggregated resident falls data (18 months) and a six-month economic evaluation. Qualitative data were gathered from family caregivers and thematically analyzed. Results: Quantitative findings from Synergy scores revealed considerable variability for resident acuity/dependency needs within and across units; and falls decreased during implementation. The six-month economic evaluation demonstrated some cost savings by comparing Synergy tool training and implementation costs with savings from resident fall rates reductions. Qualitative analyses yielded three positive impacts themes (improved care delivery, better communication, and improved resident-family-staff relationships), and two negative structural themes (language barrier and staff shortages). Conclusions: The Synergy tool provides useful data for enhancing a ‘fit’ between resident needs and available staff.

Conclusive evidence that specic long-term memory formation relies on den- dritic growth and structural synaptic changes has proven elusive. Connec- tionist models of memory based on this hypothesis are confronted with the so-called plasticity stability dilemma or catastrophic interference. Other fun- damental limitations of these models are the feature binding problem, the speed of learning, the capacity of the memory, the localisation in time of an event and the problem of spatio-temporal pattern generation. This paper suggests that the generalisation and long-term memory mechanisms are not correlated. Only the development and the improvement of the feature ex- tractors in the cortex involves structural synaptic changes. We suggest the long-term memory has a separate mechanism which involves protein synthe- sis to encode the information into the structure of these proteins. A model of memory should be capable of explaining the dierence between memorisation and learning. Learning has in our approach two dierent mechanisms. The generalisation in the brain is handled by the proper development of the links between neurons via synapses. The Hebbian learning rule could be applied only for this part of learning. Storing an internal ring pattern involves, in our approach, a new mechanism which puts the information regarding this ring pattern into the structure of special proteins in such a way that it can be retrieved later. The hypotheses introduced in this article includes a physiological assumption which has not been yet verified because it is not currently experimentally accessible. Keywords: Waves, Protein Synthesis, Resonance, Long Term Memory Preprint submitted to Neural Networks

The increasing number of people living with Long COVID requires the development of more personalized care, as for now limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratifying people with Long COVID. Individual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified 3 patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean=2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and a poor sleep and respiratory quality of life. Cluster-Severe was characterized by a higher proportion of women and smokers as in the other clusters, with a higher number of Long COVID symptoms, in particular of vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified in 3 sub-categories in terms of severity. If replicated in other populations, this simple classification will help clinicians to personalize the care of people with Long COVID.

The rainfall study in the long term is essential for climatic change understanding and socioeconomic development. The main goal of this study is to explore the spatial and temporal variations of precipitation in different time scales (seasonal and annual) in Cameroon. The Mann–Kendall and Pettitt tests were applied to analyze the precipitation variability. On temporal plan, the different regions of Cameroon have recorded significant drops in annual rainfall that Pet-titt's test generally situates around the 1970s. The decreases observed for the northern part of Cameroon regions are between –5.4% (Adamawa) and –7.4% (Far North). Those of west-ern part regions oscillate between –7.5% (South-West) and –12.5% (West). The southern part of Cameroon regions recorded decreases varying between –4.3% (East) and –5.9% (Center). On spatial plan, the divisions of the northern, western and southern parts of Cameroon respectively recorded after the 1970s (a pivotal period in the evolution of precipitation on temporal plan), a precipitation decrease towards the South, the South-West and the West. This study's findings could be helpful for planning and managing water resources in Cameroon.

This paper deals with the analysis of trends in road accidents on major highways in Brazil. Using updated time series techniques, our results indicate that a low degree of long memory was detected in the series with shocks having transitory effects over time. We further find that the number of accidents taking place in Brazil has been reducing over time, though in the presence of negative shocks, the recovery is not going to be immediate due to the long memory nature of the data. Despite the absence of relevant investment relating to infrastructure expansion, it is worth mentioning the consolidation of a nationwide tolled road system in Brazil involving concessions to private administrators, alongside more severe traffic laws that can impose limitations on driving licences.

Background Recently, a surge of COVID 19 was observed globally, regionally and nationally. With increasing numbers of cases, the frequency of long COVID is on the rise. Management and control of long COVID depend on changes in respect of human behaviors and requires an understanding of knowledge, attitudes, and practices (KAP) regarding health threats. MethodsA descriptive cross sectional study using online survey to gather data on the socio-economic background, knowledge, attitudes and practices on long-term complications of COVID. Results: Out of 201 respondents, 89.2% participants have heard about long-term complications of COVID 19. Only 35.9% have demonstrated adequate knowledge in the questions relating to co-morbidities and risk factors of COVID-19. A total of 92.2% believe that they should adhere to preventive measures following vaccination. Less than 60 % were following the advice on avoiding unnecessary travel and crowded places. Further, less than 50% were following COVID preventive measures. ConclusionAlthough the majority of participants have heard about long-term complications and common symptoms, the knowledge regarding co-morbidities that can lead to severe disease and long COVID was not satisfactory. The attitudes of the participants indicated increasing concern about long COVID. Practices indicate lack of adherence to key measures such as avoiding crowded places. These findings highlight the need for further increasing of awareness.

The whole genome sequencing (WGS) has become a crucial tool to understand genome structure and genetic variation. The MinION sequencing of Oxford Nanopore Technologies (ONT) is an excellent approach for performing WGS and has advantages in comparison with other Next-Generation Sequencing (NGS): It is relatively inexpensive, portable, has simple library preparation, can be monitored in real-time, and has no theoretical limits on read length. Sorghum bicolor (L.) Moench is diploid (2n = 2x = 20) with a genome size of about 730 Mb, and its genome sequence information is released in the Phytozome database. Therefore, sorghum can be be used as a good reference. However, plant species have complex and large genomes compared to animals or microorganisms. As a result, complete genome sequencing is difficult for plant species. MinION sequencing that produces long-reads can be an excellent tool to overcome the weak assembly of short-reads generated from NGS by minimizing the generation of gaps or covering the repetitive sequence that appears on the plant genome. Here, we conducted the genome sequencing for S. bicolor cv. BTx623 using the MinION platform and obtained 895,678 reads and 17.9 gigabytes(Gb) (ca. 25X coverage of reference) from long-read sequence data. Through a de novo assembly using two different tools and mapped assembled contigs against the sorghum reference genome, a total of 6,124 contigs (covering 45.9%) were generated from Canu, and a total of 2,661 contigs (covering 50%) were generated from Minimap and Miniasm with a Racon pipeline. Our results provide a pipeline of long-read sequencing analysis for plant species using the MinION platform and a clue to determine the total sequencing scale for optimal coverage based on various genome sizes.

Here, we have discovered a X-ray excited long afterglow phosphor β-NaYF₄: Tb³⁺. After the irradiation of X-ray, the green emission can persist for more than 240 h. After 36 h, the afterglow intensity arrived at 0.69 mcd•m^-2, which can clearly be observed by naked eyes. Even after 84 h, the afterglow emission brightness still reached 0.087 mcd•m^-2. Also, combined with the results of thermoluminescence and photoluminescence, the super long afterglow emission of β-NaYF₄: Tb³⁺ can be ascribed to the tunneling model associated with F centers. More importantly, the super long green afterglow emission of β-NaYF₄: Tb³⁺ has been successfully used as in vivo light source to activate g-C₃N₄ for photodynamic therapy（PDT）and bacteria destruction. Furthermore, super long persistent luminescence of β-NaYF₄: Tb³⁺ could be repeatedly charged by X-ray for many circulations, which indicates that the phosphors have high photo stability under repeated cycles of alternating X-ray irradiation.

In this study, 6 residents of a long-term care facility were asked to try on Virtual Reality glasses and report their first experiences with Virtual Reality. The results show that Virtual Reality is of great interest to elderly residents of in-patient long-term care facilities. The wearing period was longer than expected and no symptoms of cyber sickness occurred. For the residents it was exciting to explore the virtual environments. Austrian destinations, nature scenes in the mountains and forests but also trips to the zoo, the museum, in churches or even densely populated areas like shopping streets or train stations would be places for the residents, they would like to explore virtually. Far-off destinations such as Rio de Janeiro or the Caribbean are more of an exception. Biographically relevant places such as the parental home or the location of their wedding were not named. Concerning the usability, an adjustment of the VR glasses is necessary for a longer-term use in any case.

Muscarinic acetylcholine receptors are well-known for their crucial involvement in hippocampus-dependent learning and memory, but the exact roles of the various receptor subtypes (M1-M5) are still not fully understood. Here, we studied how M1 and M3 receptors affect plasticity at the mossy fiber (MF)-CA3 pyramidal cell synapse. In hippocampal slices from M1/M3 receptor double knockout (M1/M3-dKO) mice, the signature short-term plasticity of the MF-CA3 synapse was not significantly affected. However, the rather unique, NMDA receptor-independent and presynaptic form of long-term potentiation (LTP) of this synapse was much larger in M1/M3-deficient slices compared to wild type slices, in both field potential and whole-cell recordings. Consistent with its presynaptic origin, induction of MF-LTP strongly enhanced the excitatory drive onto single CA3 pyramidal cells, with the effect being more pronounced in M1/M3-dKO cells. In an earlier study [1], we found that deletion of M2 receptors in mice disinhibits MF-LTP in a similar fashion, suggesting that endogenous acetylcholine employs both M1/M3 and M2 receptors to constrain MF-LTP. Importantly, such synergism was not observed for MF long-term depression (LTD). Low-frequency stimulation, which reliably induced LTD of MF synapses in control slices, failed to do so in M1/M3-dKO slices and gave rise to LTP instead. In striking contrast, loss of M2 augmented LTD when compared to control slices. Taken together, our data demonstrate convergence of M1/M3 and M2 receptors on MF-LTP, but functional divergence on MF-LTD, the net effect being well-balanced bidirectional plasticity of the MF-CA3 pyramidal cell synapse.

Inside hippocampal circuits, neuroplasticity events that individual cells may undergo during synaptic transmissions occur in the form of Long Term Potentiation (LTP) and Long Term Depression (LTD). The high density of NMDA receptors expressed on the surface of the dendritic CA1 spines confers to hippocampal CA3-CA1 synapses, the ability to easily undergo NMDA-mediated LTP and LTD, that is essential for some forms of explicit learning in mammals. Providing a comprehensive kinetic model that can be used for running computer simulations of the synaptic transmission process is currently a major challenge. Here, we propose a compartmentalized kinetic model for CA3-CA1 synaptic transmission. Our major goal was to tune our model in order to predict the functional impact caused by disease associated variants of NMDA receptors related to severe cognitive impairment. Indeed, for variants Glu413Gly and Cys461Phe, our model predicts negative shifts in the glutamate affinity and changes in the kinetic behavior, consistent with experimental data. These results pinpoint to the predictive power of this multiscale viewpoint, which aims to integrate the quantitative kinetic description of large interaction networks typical of system biology approaches with a focus on the quality of few, key, molecular interactions typical of structural biology ones.

Stock price prediction has long been a critical area of research in financial modeling. The inherent complexity of financial markets, characterized by both short-term fluctuations and long-term trends, poses significant challenges in accurately capturing underlying patterns. While Long Short-Term Memory (LSTM) networks have shown strong performance in short-term stock price prediction, they struggle with effectively modeling long-term dependencies. In this paper, we propose an advanced stock price prediction model based on the Extended Long Short-Term Memory (xLSTM) algorithm, designed to enhance predictive accuracy over both short and long-term periods. We conduct extensive experiments by building and evaluating models based on xLSTM and LSTM architectures for multiple stocks. Our results demonstrate that the xLSTM model consistently outperforms the LSTM model across all stocks and time horizons, with the performance gap widening as the prediction period extends. The observations underscore the superior capability of the xLSTM-based model to capture long-term patterns in financial data, offering a promising approach for more accurate and reliable stock price predictions.

The extensions of Boltzmann-Gibbs classical entropic form are presented. The focus is on the thermodynamical entropies which do not obey classical definition of additivity and extensity with main motivation coming from the gravitational systems admitting long-range interactions both in astrophysics (black holes) and in cosmology. Horizon entropies are the main concern. In the paper, the plethora of non-Boltzmann-Gibbs entropies are studied and the comparative analysis of their properties with respect to additivity and extensivity is presented.

Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question as to whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known ‘risk factors’ for AF, and in particular exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots are cytotoxic by inducing hypoxia/reperfusion and other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.

Introduction: Congenital heart defects (CHD) are the most frequent group of major congenital anomalies, accounting for almost 1% of all births. They comprise a very heterogeneous group of birth defects in terms of their severity, clinical management, epidemiology and embryologic origins. Taking this heterogeneity into account is an important imperative to provide reliable prognostic information to patients and their caregivers, as well as to compare results between centers or to assess alternative diagnostic and treatment strategies. The Anatomic and Clinical Classification of CHD (ACC-CHD) aims to facilitate both the CHD coding process and data analysis in clinical and epidemiological studies. Objectives: 1) To describe the long-term childhood survival of newborns with CHD and 2) To develop and validate predictive models of infant mortality based on the ACC-CHD. Materials and Methods: This study is based on data from a population-based, prospective cohort study: Epidemiological Study of Children with Congenital Heart Defects (EPICARD). The final study population comprised 1881 newborns with CHD after excluding cases that were associated with chromosomal and other anomalies. Statistical analysis included non-parametric survival analysis and flexible parametric survival models. The predictive performance of models was assessed by Harrell’s C index and the Royston-Sauerbrei R2 with internal validation by bootstrap. Results: The overall 8-year survival rate for newborns with isolated CHD was 0.96 [0.93- 0.95]. There was a substantial difference between the survival rate of the categories of ACC-CHD. The highest and lowest 8-year survival rates were 0.995 [0.989-0.997] and 0.34 [0.21-0.50] for “interatrial communication abnormalities and ventricular septal defects” and "functionally univentricular heart", respectively. Model discrimination as measured by Harrell’s C was 87% and 89% for the model with ACC-CHD alone and the full model, which included other known predictors of infant mortality, respectively. The predictive performance as measured by R2 was 45% and 50%, for the ACC-CHD alone and the full model. These measures were essentially the same after internal validation by bootstrap. Conclusion: The ACC-CHD classification provided the basis of a highly discriminant survival model with good predictive ability for the 8-year survival of newborns with CHD. Prediction of individual outcomes remains an important clinical and statistical challenge.

Permeable asphalt pavement refers to an asphalt mixture layer with an air void content of more than 18% and internal water permeability and drainage capabilities, which can quickly drain away water on the road surface, improve rainy day travel safety and ride comfort. This paper aims to explore the optimal asphalt mixture mix design for long longitudinal slope roads. By using CT scanning technology to analyze the air void content of different rotated and compacted asphalt mixture specimens, and extensively testing and evaluating the performance of permeable pavement mixtures, the following conclusions are drawn: Based on the research philosophy of functional integration, a new asphalt mixture gradation suitable for long longitudinal slope roads is proposed, with the optimal key factor composition being: 0.075mm passing rate of 7%, 2.36mm passing rate of 20%, 9.5mm passing rate of 55%, and oil-stone ratio of 4.8%. The FAM mixture was divided into three parts for air void analysis, with the upper part having a slightly higher air void content than the lower part. The air void distribution diagram of the FAM mixture is concave, with higher air void rate curves on both sides and a lower middle curve. Compared with laboratory dry measurement method, CT scanning test showed slightly higher air void content in specimens. Through dynamic modulus testing, the strength requirement for road asphalt mixture in pavement structure design was evaluated. It was found that at high temperature conditions (50℃), the minimum dynamic modulus value of the FAM mixture was 323 MPa, with a peak value of 22746MPa at a temperature of -10℃ and a frequency of 25HZ. The dynamic modulus value at high temperature conditions is lower than at low temperature conditions, while the dynamic modulus value at high frequency conditions is higher than at low frequency conditions. This study provides useful information and experimental data for the design of new asphalt mixtures for long longitudinal slope roads, and has conducted in-depth research on the air void distribution and performance of the mixture, providing strong support for related research fields and practical applications.

Landsat and Sentinel-2 data archives provide ever-increasing amounts of satellite data for studying land cover and land use change (LCLUC) over the past four decades. However, the availability of cloud-, shadow-, and snow-free observations varies spatially and temporally due to climate and satellite data acquisition schemes. Spatio-temporal heterogeneity poses a major issue for some time-series analysis approaches, but can be addressed with pixel-based compositing that generates temporally equidistant cloud-free or near-cloud free synthetic images. Although much consideration is given to methods identifying the ‘best’ pixel value for each composite, determining the aggregation period receives less attention and is often done arbitrary, or based on expert intuition. Here, we evaluated data compositing windows ranging from five days to one year for 1984-2021 Landsat and 2015-2021 Sentinel‑2 time series across Europe. We considered separate and joint use of both data archives and analyzed spatio-temporal availability of composites during each calendar year and pixel-specific growing season. We reported mean annual composites’ availability investigating differences among biogeographical regions, checked feasibility of pan‑European analyses for three LCLUC applications based on annual, monthly and 10-day composites, and analyzed the shortest feasible compositing window ensuring ≥50% temporal data availability and interpolation of the remaining composites for individual years and across a variety of medium- and long‑term time windows. Our results highlighted low data coverage in the 1980s, 1990s, and in 2012, as well as spatial variability in data availability driven by climate and orbit overlaps, which altogether impact spatio-temporal consistency of medium- and long-term time series, limiting feasibility of some LCLUC analyses. We demonstrated that prior to 2011 monthly composites ensured overall 50-62% data coverage for each calendar year, and ~75% afterwards, with further increase to ~82% when Landsat and Sentinel-2 were combined. Temporal consistency of monthly composites was overall low and temporal interpolation augmenting up to 50% missing data each year and across a time window of interest, ensured feasibility of analyses. Applications based on shorter than monthly composites were challenging without joining Landsat and Sentinel‑2 archives after 2015, and beyond the Mediterranean biogeographical region. Using pixel-specific growing season data typically boosted data availability in most geographies and diminished most of the latitudinal differences, but feasibility of complete time series with sub-monthly compositing windows was still restricted to the most recent years, and required data interpolation. Overall, our analyses provided a detailed assessment of Landsat and Sentinel-2 data availability over Europe, and based on selected application examples, highlighted often lacking spatio-temporal consistency of time series with sub-monthly compositing windows and long-time periods, which might hinder feasibility of some LCLUC applications.

Asian dust (AD) events and total suspended particle (TSP) was observed at Kanazawa University Wajima Air Monitoring Station (KUWAMS), a Japanese background site, during the East Asian winter monsoon periods (from November to May of the following year) from 2010 to 2021. Nine kinds of polycyclic aromatic hydrocarbons (PAHs) were determined in each TSP sample. In this study, a total of 54 AD events were observed. According to the different pathways of long-range transportation, AD events were divided into AD-high (transported at higher altitude, around 4000 m) and AD-low (transported at lower altitude, around 2500 m). The TSP concentrations in-creased sharply in the AD and was higher in AD-high (39.8 ± 19.5 μg/m³) than that in AD-low (23.5 ± 10.5 μg/m³). While AD didn’t have significant effect on ΣPAHs characteristic variation, as ΣPAHs concentration in non-AD periods, AD-high, AD-low were 543 ± 374, 404 ± 221, 436 ± 265 pg/m³, respectively. PAHs compositions were also consistent. As a result, TSP concentration was affected by the input air mass transported at higher altitude from the desert region while PAHs concentration was under the impact of air mass at lower altitude which carried the PAHs emitted from fossil fuels and biomass combustion in northeastern China. Moreover, the health risks of PAHs were calculated by inhalation lifetime cancer risk which ranged from 10−6 to 10−5 ng/m3, in-dicating a potential carcinogenic risk at KUWAMS during the East Asian winter monsoon period.

To solve the problem that the common long-tailed classification method does not use the semantic features of the original label text of the image, and the difference between the classification accuracy of most classes and minority classes is large, the long-tailed image classification method based on enhanced contrast visual language trains the head class and tail class samples separately, uses text image to pre-train the information, and uses enhanced momentum contrast loss function and RandAugment enhancement to improve the learning of tail class samples. On the ImageNet-LT long-tailed dataset, the enhanced contrastive visual-language based long-tailed image classification method has improved all class accuracy, tail class accuracy, middle class accuracy, and F1 values by 3.4%, 7.6%, 3.5%, and 11.2%, respectively, compared to the BALLAD method. The difference in accuracy between the head class and tail class is reduced by 1.6% compared to the BALLAD method. The results of three comparative experiments indicate that the long-tailed image classification method based on enhanced contrastive visual-language has improved the performance of tail classes and reduced the accuracy difference between majority and minority classes.

Background: Chronic neurologic diseases are common sequelae of COVID. They severely impact the quality of life and increase the burden on healthcare systems. The long COVID neurological symptoms are due to the robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to neuroinvasion and inflammation of the central nerve system (CNS). Currently used medications and vaccines do not inhibit the robust SARS-CoV-2 replication in the nasal epithelial cells. EGCG-palmitate (EC16), a multifunctional compound, has the potential to become a novel intranasal-delivered drug for minimizing post-COVID neurologic symptoms. Method: EC16-containing formulations were developed and tested in vitro against human β coronavirus OC43 (CoV-OC43) using a TCID50 assay following three test protocols differing in exposure sequence. Results: EC16 formulations in normal saline, phosphate buffered saline, and cell culture medium were found to effectively inhibit human β-coronavirus infection (&gt;99.99%) after a 30-min contact. A single 10-min application to cells after infection (i.e., without direct contact with the virus) resulted in &gt;99% inhibition of viral replication. Conclusion: With its antiviral, antioxidant, anti-inflammatory, and neuroprotective properties, EC16 in nasal formulations could be further developed for clinical applications to COVID-19 patients for minimizing long COVID neurological symptoms.

Background: The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long Covid is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long Covid, living in communities recognised as more deprived. Methods: The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual ‘clinic’ was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual’s participation and their completion of the intervention. Results: Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long Covid difficulties. Conclusions: This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long Covid.

Memory is probably one of the most complex cognitive functions of the human, and in many years, thousands of studies have helped us to better recognize this brain function. One of the reference textbooks in neuroscience, which has also elaborated on the memory function, is written by Prof. Kandel and his colleagues. In this book, I encountered a number of ambiguities when it was explaining the memory system. Here, I am sharing those points, either to find an answer for them, or to let them be a suggestion for our future works. Prof. Kandel has spent most of his meritorious lifetime on studying the memory system; however, the brain is extremely complex, and as a result, we still have many years to comprehensively understand the neural mechanisms of brain functions.

The Eastern Mediterranean is a highly populated area with air quality problems as well where climate change already is noticed by higher temperatures and changing precipitation pattern. The anthropogenic aerosol affects health and changing concentra-tions and properties of the atmospheric aerosol affect radiation balance and clouds. Continuous long-term observations are essential in assessing the influence of anthro-pogenic aerosols on climate and health. We present 6 years of observations from Navarino Environmental Observatory (NEO), a new station located at the south west tip of Pelo-ponnese, Greece. The two sites at NEO, were evaluated to show the influence of the local meteorology but also to assess the general background aerosol possible. It was found that the background aerosol was originated from aged European aerosols and was strongly influenced by biomass burning, fossil fuel combustion, and industry. When subsiding into the boundary layer, local sources contributed in the air masses moving south. Mesoscale meteorology determined the diurnal variation of aerosol properties such as mass and number by means of typical sea breeze circulation, giving rise to pronounced morning and evening peaks in pollutant levels. While synoptic scale meteorology, mainly large-scale air mass transport and precipitation, strongly influenced the season-ality of the aerosol properties.

Abstract: Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), an lncRNA, is located adjacent to MYC, linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis, however, its role and regulation machinery remain uncertain. We examined PVT1/MYC expression through real time PCR in plasma cells purified from 59 MGUS and 140 MM patients. MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, a MYC superenhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p &lt; 0.0001), and showed positive correlation with disease progression (r = 0.394, p &lt; 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, synchronous downregulation of MYC and PVT1 by JQ1, and no effect of MYC inhibitor on PVT1 expression suggest that the expression of these two genes is coregulated by a superenhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.

Great Britain’s stocks of coal, natural gas, and petroleum have seen major changes to the levels of stored energy over the years 2005 to 2019, a reduction of 200 TWh (35%) from 570 TWh to 370 TWh. The transformation of its electrical system over this timeframe saw a reduction in coal generation, leading to a corresponding reduction of the levels of stockpiled coal of 85 TWh (68%), partially offset by an increase in the stocks of biomass for electrical generation. The reduction in natural gas storage of 24 TWh (44%) was primarily due to the closure of Britain’s only long-term seasonal natural gas storage facility in January 2018. This was partially offset by the construction of medium-term natural gas storage facilities and the use of LNG storage in the years preceding its closure. For stocks of crude oil and oil products the reduction was 35 TWh (21%), linked to the overall reduction in demand.

Background: Glioblastomas (GBM) is generally burdened, to date, by a dismal prognosis, although Long Term Survivors have a relatively significant incidence. Our specific aim was to determine the exact impact of many surgery-, patient- and tumor-related variable on Survival parameters. Methods: The surgical, radiological and clinical outcomes of patients have been retrospectively reviewed for the present study. All the patients have been operated on in our Institution and classified according their Overall Survival in LTS (Long Term Survivors) and STS (Short Term Survivors). A thorough Review of our surgical series was conducted to compare the oncologic results of the patients in regards to 1. Surgical , 2. Molecular, and 3.Treatment related features. Results: A total of 177 patients were included in the final cohort. Extensive statistical analysis by means of univariate, multivariate and survival analyses disclosed a survival advantage for patients presenting a younger age, a smaller lesion and a better functional status at presentation. From the Histochemical point of view, Ki67(%) was the strongest predictor of better oncologic outcomes. A stepwise analysis of variance outlines the existence of 8 prognostic subgroups according to the molecular patterns of Ki67 overexpression and EGFR, p53 and IDH mutations. Conclusions: On the ground of our statistical analyses we can affirm that the following factors were significant predictors of survival advantage: KPS, Age, Volume of the lesion, Motor disorder at presentation, a Ki67 overexpression. A fine molecular profiling is feasible to precisely stratify the prognosis of GBM patients.

Long memory plays an important role in many fields by determining the behaviour and predictability of systems; for instance, climate, hydrology, finance, networks and DNA sequencing. In particular, it is important to test if a process is exhibiting long memory since that impacts the accuracy and confidence with which one may predict future events on the basis of a small amount of historical data. A major force in the development and study of long memory was the late Benoit B. Mandelbrot. Here we discuss the original motivation of the development of long memory and Mandelbrot's influence on this fascinating field. We will also elucidate the sometimes contrasting approaches to long memory in different scientific communities

The purposes of this study were to identify clinician’s characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the information sources influencing medical decision-making about treatment of schizophrenia. We surveyed 202 psychiatrists during 6 regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic and information sources about their clinical decisions were collected. Most of psychiatrists used second-generation antipsychotic (SGA), and preferentially an oral formulation, in the treatment of schizophrenia. SGA LAI was prescribed to 30.4% of schizophrenic patients. The duration and the type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with the higher use of LAI antipsychotics and the lower use of oral SGA. Personal experience, government regulatory approval and guidelines for the treatment of schizophrenia were the 3 main contributing factors guiding the clinical decision-making of clinicians about treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotic. The development of specialised programmes with top specialists should lead to better use of LAI in the treatment of schizophrenia.

The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. As a result, to monitor the health of individuals affected by these conditions, they must maintain up-to-date health records using digital health informatics apps for surveillance. In this review, we provide an overview of the existing literature on identifying long COVID manifestations through hierarchical classification and the characterization of long COVID by different hierarchical groups based on the Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) in artificial intelligence (AI) to identify long COVID. Knowledge exploration, using the concept map for the clinical pathways of long COVID presented in this paper, provides an overview of the data needed to explore tackling the long-term effect of COVID-19 by integrating innovative cohesive frameworks and designing health informatics-based applications. To the best of our knowledge, this is the first paper to explore the potential incorporation of long COVID as a variable risk factor within a digital health informatics application.

This study investigated whether positive self-talk (ST) over 4 weeks would improve standing long jump (SLJ) performance in men and women in their 20s. The participants of this study were 36 men and 28 women, selected through interviews with male and female students. The test subjects’ performance was measured 10 times over a 4-week period, 2-3 sessions per week. In the experimental group, participants performed SLJ while reciting positive ST; the control group performed SLJ without any specific conditions. A pre-and post-intervention survey was conducted using the Rosenberg Self-Esteem Scale (RSE). The results revealed a significant difference in the performance of experimental group (p < 0.05), while no significant difference was observed in the control group. RSE survey results also showed a significant difference only in the experimental group (p < 0.05). These findings indicate that self-affirmation yields positive effects on SLJ performance.

Long COVID is a phenomenon in which individuals experience persistent symptoms after recovering from COVID-19. The symptoms are discovered to be unique for every individual and can affect multiple organs systems in the body. This study aims to identify effective natural remedies for long COVID by analyzing hub genes associated with the symptoms of the condition and evaluating the repurposed drugs catered and used for treating the symptoms of long COVID. The most common and prevalent symptoms of long COVID were identified; Fatigue, Shortness of Breath, Loss of Smell, Headache, Brain Fog, Chest Pain, Insomnia, Heart Palpitations, Dizziness, Joint Pain, Depression, Anxiety, Tinnitus, Loss of Appetite. Hub genes for each of the symptoms provided an insight on the key biological pathways of the symptom. Repurposed drugs identified, provided the template to identify the natural compounds with similar structure as a potential therapeutic drug. The natural compounds were retrieved using fingerprint search of the repurposed drugs from the NPASS Database. The findings of this study suggest several natural remedies for each symptom based on the molecular docking of the hub gene and natural compound using iGEMDOCK. The identified natural remedies may hold promise in treating long COVID, but further research is required to explore the efficacy and effectiveness of the proposed natural compounds. The results of the study pose important implications for the development of effective treatments for long COVID.

Long COVID (Post-Acute Sequelae of COVID-19, PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of Long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that longterm dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

The key to the practical application of organometal–halide–crystals perovskite solar cells (PSCs) is to achieve thermal stability through robust encapsulation. This paper presents a method to significantly extend the thermal stability lifetime of perovskite solar cells to over 5,000 h at 85 °C by demonstrating an optimal combination of encapsulation methods and perovskite composition for carbon–based multiporous–layered–electrode (MPLE)–PSCs. We fabricated the four types of MPLE-PSCs using two encapsulation structures (over– and side–sealing with thermoplastic resin films) and two perovskite compositions ((5–AVA)x(methylammonium (MA))1–xPbI3 and (formamidinium (FA))0.9Cs0.1PbI3), and analyzed the 85 ºC thermal stability followed by ISOS–D–2 protocol. Without encapsulation, FA0.9Cs0.1PbI3 exhibited higher thermal stability than (5–AVA)x(MA)1–xPbI3. However, encapsulation reversed the phenomenon (that of (5–AVA)x(MA)1–xPbI3 became stronger). The combination of (5–AVA)x(MA)1–xPbI3 perovskite absorber and over–sealing encapsulation effectively suppressed the thermal degradation, resulting in the PCE value at 91.2% of the initial value after 5,072 h. On the other hand, another combination (side–sealing on (5–AVA)x(MA)1–xPbI3, over– and side–sealing on FA0.9Cs0.1PbI3) resulted in decreased stability. The FA–based perovskite was decomposed for these degradation mechanisms by the condensation reaction between FA and carbon. For side–sealing, the space between the cell and the encapsulant was estimated to contain approximately 1,260,000 times more H2O than in over–sealing, which catalyzed the degradation of the perovskite crystal. Our results demonstrate that MA–based PSCs, which are generally considered to be thermally sensitive, can significantly extend their thermal stability after the proper encapsulation. Therefore, we emphasize that finding the appropriate combination of encapsulation technique and perovskite composition is quite important to achieve further device stability.

In the plot under study, rice is grown under anaerobic conditions by means of flood irrigation that maintains a constant water depth during most of the crop cycle. Thus, water requirements reach a very high volume of about 12,000 m3/ha. At the outlet there is a drainage channel where there are no measuring devices. Its control will allow us to establish practices to reduce the high water consumption. We have designed a long-throated flume that can cover the entire range of flow rates to measure, between 0.02 and 0.05 m3/s in this case. Since the drainage channel has a trapezoidal cross section and is built on land, the throat of the flume will also be trapezoidal to ease the transition between the two sections and reduce head losses. A new procedure has been developed that allows to directly design the dimensions of the narrowed section, side slope and bottom width, by previ-ously choosing the modular limit, the sill height and the length of the throat more in accordance with the characteristics of the channel where the flume is to be installed. The analysis of the obtained results demonstrates the accuracy and feasibility of the presented procedure.

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

Background: Severe eosinophilic asthma (SEA) represents a substantial global health burden. Benralizumab has been shown to restore good control of asthma. Robust data on benralizumab effectiveness over periods longer than 2 years are still scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Clinical outcomes were evaluated at 6, 12, 24 and 36 months. Partial and complete clinical remission (CR) were also assessed. Data were analysed either with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: Benralizumab induced a persistent reduction in exacerbation rates (p

(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: Recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.

THz radiation has assumed a great importance thanks to the efforts in the development of technological tools used in this versatile band of the electromagnetic spectrum. Here we propose a reflecting bi-mirror axicon-like device with wavelength-independent long focusing performances in the THz band, by exploiting the high thermo-mechanical deformation of the elastomer polydimethylsiloxane (PDMS). This deformation permits to achieve significant optical path modulations in the THz band and effective focusing. The surface of a PDMS layer is covered with a gold thin film, acting as heater thanks to its absorption for wavelengths below ~500 nm . An invariance property of the Fresnel integral has been exploited to verify experimentally the THz performances of the device with an ordinary visible laser source, finding excellent agreement with the theoretical predictions at 1 and 3 THz. The same property allowed also to verify experimentally that the axicon focus has a longitudinal extension much greater than that one exhibited by a benchmark cylindrical mirror with the same optical power. The axicon is thermo-mechanically stable up to a heating power of 270 mW, although it might be potentially exploited at higher powers with a minor degradation of the optical performances.

SARS-CoV-2, the virus that causes theCOVID-19 disease, has been demonstrated to cause immune suppression in certain individuals. This can manifest as a reduced ability for the host's immune system to effectively control the infection. Studies have reported that patients with COVID-19 can exhibit a decline in white blood cell counts, including natural killer cells and T cells, which are integral components of the immune system's response to viral pathogens. These cells play critical roles in the immune response to viral infections, and their depletion can make it harder for the body to mount an effective defense against the virus. Additionally, the virus can also directly infect immune cells, further compromising their ability to function. Some individuals with severe COVID-19 pneumonia may develop a "cytokine storm," an overactive immune response that may result in tissue damage and organ malfunction. The underlying mechanisms of immune suppression in SARS-CoV-2 are not entirely comprehended at this time, and ongoing research is being conducted to gain a more comprehensive understanding. Research has shown that severe SARS-CoV-2 infection promotes the synthesis of IgG4 antibodies. In this work, we propose the hypothesis that the IgG4 antibody produced by B cells in response to infection by SARS-CoV2 generates immunological tolerance that prevents its elimination, and leads to persistence and chronic infection. In sum, we believe that this constitutes another immune evasion mechanism that bears striking similarities to that developed by cancer cells to evade immune surveillance.

The atmospheric concentrations of sodium, aluminum, silicon, sulphur, chlorine, potassium, calcium, titanium, vanadium, chromium, manganese, iron, nickel, copper, zinc, bromine and lead were measured in air filters at the Finnish Meteorological Institute station, in Helsinki, Finland, during a period of 44 years (1962-2005). The mean annual concentrations were calculated and are presented from the lowest values to the highest ones Cr&lt;Ni&lt;Ti&lt;Br&lt;V&lt;Mn&lt;Cu&lt;Zn&lt;Cl&lt;Al&lt;Fe&lt;K&lt;Ca&lt;Na&lt;Pb&lt;Si&lt;S. Most of the elements (Fe, Si, Ti, K, Ca, Zn, Br, Pb, V, Ni, S, Cr, Na, Al, Cl) present higher values during spring and winter season while in summer the elements (Ti, Ca, S, Na) are found in higher concentrations. There is a strong correlation between the elements (V-Ni, Si-Pb, Fe-Ca, V-Cr, Si-K, K-Ca, Fe-Ti, K-Na, Si-Ca, V-S), indicating their common source. The identification of the sources of trace elements was performed based on positive matrix factorization analysis, using SoFi software. Four PM sources were identified: road dust (due to usage of leaded fuel), heavy oil combustion/secondary sulfates, traffic emissions and natural dust (soil). For the total of 44 years studied, significant decreases in concentrations were observed for all trace elements, most of which were over 50%: Na (-74%), Al (-86%), Si (-88%), S (-82%), K (-82%), Ca (-89%), Ti (-80%), V (-89%), Cr (-82%), Mn (-77%), Fe (-77%), Ni (-61%), Zn (-72%), Pb (-95%). The current data are consistent with previous air studies covering the whole territory of Finland. Finally, a significant decline has been observed in the majority of the elemental concentrations since the end of 70s, underlying the effectiveness of different environmental policies that have been applied during the last decades.

Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), later renamed Coronavirus Disease 2019 (COVID-19) was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province on December 31, 2019. This would subsequently result in a global pandemic with over 76 million confirmed cases of COVID-19 and 6.9 million deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We look at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study comprehensively assesses of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of June 2023, this paper contains the most recent data made accessible.

In the wake of the Covid-19 crisis, a need has arisen to prevent and treat two related conditions, Covid vaccine injury and long Covid, both of which have a significant vascular component. Therefore, the management of these conditions require the development of strategies to prevent or dissolve blood clots and restore circulatory health. This review summarizes the evidence on strategies that can be applied to treat both long and vaccine injuries based on similar mechanisms of action.

Bovine herpesvirus (BoHV)-5 is a worldwide distributed pathogen usually associated with a lethal neurological disease (meningoencephalitis) in dairy and beef cattle resulting in important economic losses due to the cattle industry. Using recombinant glycoprotein D of BoHV-5 (rgD5), we evaluated the long-duration humoral immunity of the recombinant vaccines in a cattle model. Here we report that two doses of intramuscular immunization, particularly with the rgD5ISA vaccine, are superior to iBoHV-5ISA immunization in the induction of long-lasting antibody responses. Recombinant gD5 antigen elicited tightly mRNA transcription of the Bcl6 and the chemokine receptor CXCR5 which mediate memory B cells and long-lived plasma cells in germinal centers (GCs). In addition, using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) we observed higher and earlier responses of rgD5-specific IgG antibody and the upregulation of mRNA transcription of IL2, IL4, IL10, IL15 and IFN-γ cytokines in rgD5 vaccinated cattle, indicating a mixed immune response. We further show that rgD5 immunization provides protection against both BoHV -1 and -5. Our findings indicate that the rgD5-based vaccine represents an effective vaccine strategy to induce an efficient control of alpha-herpesviruses.

Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.

Introduction Early prediction of long term outcomes in patients resuscitated after cardiac arrest (CA) is still challenging. Guidelines suggested a multimodal approach combining multiple predictors. We evaluated whether the combination of the electroencephalography (EEG) reactivity, somatosensory evoked potentials (SSEPs) cortical complex and Gray to White matter ratio (GWR) on brain computed tomography (CT) at different temperatures could predict survival and good outcome at hospital discharge and after six months. Methods We performed a retrospective cohort study including consecutive adult, non-traumatic patients resuscitated from out-of-hospital CA who remained comatose on admission to our intensive care unit from 2013 to 2017. We acquired SSEPs and EEGs during the treatment at 36°C and after rewarming at 37°C, Gray to white matter ratio (GWR) was calculated on the brain computed tomography scan performed within six hours of the hospital admission. We primarily hypothesized that SSEP was associated with favorable functional outcome at distance and secondarily that SSEP provides independent information from EEG and CT. Outcomes were evaluated using the Cerebral Performance Category (CPC) scale at six months from discharge. Results Of 171 resuscitated patients, 75 were excluded due to missing of data or uninterpretable neurophysiological findings. EEG reactivity at 37 °C has been shown the best single predictor of good outcome (AUC 0.803) while N20P25 was the best single predictor for survival at each time point. (AUC 0.775 at discharge and AUC 0.747 at six months follow up) Predictive value of a model including EEG reactivity, average GWR, and SSEP N20P25 amplitude was superior (AUC 0.841 for survival and 0.920 for good outcome) to any combination of two tests or any single test. Conclusion Our study, in which life-sustaining treatments were never suspended, suggests SSEP cortical complex N20P25, after normothermia ad off sedation, is a reliable predictor for survival at any time. When SSEP cortical complex N20P25 is added into a model with GWR average and EEG reactivity, the predictivity for good outcome and survival at distance is superior than each single test alone.

Objectives: A wealth of literature has established risk factors for social isolation among older people, however much of this research has focused on community-dwelling populations. Relatively little is known about how risk of social isolation is experienced among those living in long-term care (LTC) homes. We conducted a scoping review to identify possible risk factors for social isolation among older adults living in LTC homes. Methods: A systematic search of five online databases retrieved 1535 unique articles. Eight studies met the inclusion criteria. Results: Thematic analyses revealed that possible risk factors exist at three levels: individual (e.g., communication barriers), systems (e.g., location of LTC facility), and structural factors (e.g., discrimination). Discussion: Our review identified several risk factors for social isolation that have been previously documented in literature, in addition to several risks that may be unique to those living in LTC homes. Results highlight several scholarly and practical implications.

In higher eukaryotes, enhancers determine the activation of developmental gene transcription in specific cell types and stages of embryogenesis. Enhancers transform the signals produced by various transcription factors within a given cell, activating the transcription of the targeted genes. Often, developmental genes can be associated with dozens of enhancers, some of which are located at large distances from the promoters that they regulate. Currently, the mechanisms that underly the specific distance interactions between enhancers and promoters remain unknown. This review describes the properties and activities of enhancers and discusses the mechanisms of distance interactions and potential proteins involved in this process.

Refractive surgery is an increasingly popular procedure to decrease spectacle or contact lens dependency. The two most commonly used surgical techniques to correct myopia is Photorefractive keratectomy (PRK) and Femtosecond- Lasik (FS-LASIK)There are few publications that gathers such a long term follow up of both surgical techniques (2) Methods It has been performed a retrospective non-randomized study 509 PRK eyes and 310 FS-LASIK surgeries were followed for 10 years for the treatment of myopia and compound myopic astigmatism. Patients were followed up three months, one year, 2 years, 5 and 10 years. The safety index of both procedures was defined as a quotient between the postoperative BCVA (Best Corrected Visual Acuity) and the preoperative BCVA. The predictability is calculated as difference between the expected spherical equivalent and the achieved spherical equivalent. The efficacy index was calculated as a quotient between postoperative UCVA divided by the preoperative BCVA (3) Results. The results were: a safety index higher than 100% (109%) and an efficacy index of 82.4% after 10 years of PRK surgery in both groups. FS-LASIK was the safest surgery after 10 years and the most efficacy technique although in this case there were no statistically significant differences (4) Conclusions. All these data demonstrated better indexes for FS-LASIK

This paper studies long economic series to assess the long-lasting effects of pandemics. We analyze if periods of time that cover pandemics have a change in trend and persistence in growth, and in level and persistence in unemployment. We find that there is an upward trend in the persistence level of growth across the centuries. In particular, shocks originated by pandemics in recent times seem to have permanent effect in growth. Moreover, our results show that the unemployment rate increases and it becomes more persistent after a pandemic. In this regard, our findings support the design and implementation of counter-cyclical policies to soften the shock of the pandemic.

Research background: Relationship between inflation rate, unemployment rate, interest rate and real gross domestic product per capita in Nigeria. However, there seems to be a short-run or long-run relationship among the macroeconomic variables.Purpose: This study investigated the impact of the inflation rate, unemployment rate and interest rate on real gross domestic product per capita (RGDPPC) (proxy for economic growth) and proffered recommendations towards enhancing economic growth and to reduce the distasteful effects of inflation rate, unemployment rate and interest rate in Nigeria in this present time economic challenges.Research methodology: This study applied a linear dynamic model Autoregressive Distributed Lag (ARDL) modeling technique to analyze the short-run dynamics and long-run relationship of the economic growth in Nigeria over the sample period between 1984 and 2017 using annual secondary data extracted from World Bank Development Indicators Report (last updated January 2019).Results: The empirical results showed that there was long-run relationship between inflation rate, unemployment rate and interest rate on real gross domestic product per capita (proxy for economic growth) in Nigeria. The result further revealed that only unemployment rate had a significant positive impact on real gross domestic product per capita in the long-run and inflation rate had a significant negative impact on real gross domestic product per capita in the short-run.Novelty: Therefore, the study concluded that unemployment rate and inflation rate proved to have significant impacts on economic growth in the long-run and short-run respectively. Formulation of policies to reduce unemployment through the adoption of labour concentrated technique of production, entrepreneurship development and policy to keep the inflation rate at single digit.