Miracle-dz/UniFAR-FTUs huggingface dataset:
Prolongation of Tick-Borne Encephalitis Cycles in Warmer Climatic Conditions

Tick-borne encephalitis exhibits profound inter-annual fluctuations in incidence. Previous studies showed that three-fifths of the variation can be explained in terms of four superimposed oscillations: a quasi-biennial, triennial, pentennial, and a decadal cycle. This study was conducted to determine how these cycles could be influenced by climate change. Epidemiological data, spanning from the 1970s to the present, and originating from six regions/countries bridging Scandinavia and the Mediterranean, represented a temporal/latitudinal gradient. Spectral analysis of time series was used to determine variation in the cycles’ length/amplitude with respect to these gradients. The analysis showed that—whereas the lengths of the shorter cycles do not vary substantially—cycles in the decadal band tend to be longer southwards. When comparing the disease’s oscillations before- and after the mid-1990s, a shift towards longer oscillations was detected in the pentennial–decadal band, but not in the biennial– triennial band. Simultaneously, oscillations in the latter band increased in intensity whereas the decadal oscillations weakened. In summary, the rhythm of the cycles has been altered by climate change. Lengthened cycles may be explained by prolonged survival of some animal hosts, and consequently greater inertia in herd immunity changes, slowing down a feedback loop between the herd immunity and amount of virus circulating in nature.
THE ARGUMENT FOR EARLY INTERVENTION, ADVANCED LIPOPROTEIN TESTING, AND COMBINATION THERAPY

Vol. 2, No. 13 ■September 2002 Dr Maciejko: The Heart Protection Study (HPS) data indicate that in both the placebo and treatment arms, the incidence of coronary heart disease (CHD) events increased with time. Although the treatment group experienced a lesser increase, Dr Robertson points out that the incidence never actually reached a plateau or waned. Dr Robertson, what do you believe to be the significance behind this finding? Dr Robertson: Obviously, cumulative incidence can never truly plateau, as some events will always occur, but the rate of decline appeared constant over time for treatment versus placebo. This study did not appear to indicate an accumulating benefit, suggesting a steeper event rate reduction for the first year or 2, then a lesser event rate reduction as the disease process stabilized. Dr Maciejko: Another possible explanation for the incidence of coronary events not reaching a plateau in the lipid-lowering arm of the HPS is the likelihood that the majority of the participants designated as being free of clinically evident CHD at baseline had asymptomatic, undiagnosed coronary atherosclerosis. The lipid-lowering treatment in this study actually reduced the rate of coronary events, which would be defined here as progression of coronary atherosclerosis to coronary artery disease. If this is the case, in order to observe either a plateau or a decrease of coronary events in a treated group compared with a control group, a study population free of coronary atherosclerosis at baseline is necessary. With a cohort completely free of coronary atherosclerosis, those receiving lipid reduction would develop coronary atherosclerosis at a reduced rate compared with the control group. Fewer participants in the treated group would have the potential to develop a coronary event compared to the control group. This would translate to a plateau in the coronary event curve in the treated group relative to the control group. The recent data from The Cleveland Clinic would lead one to believe that many of the participants of the HPS designated as being free of coronary artery disease actually had coronary atherosclerosis. Of approximately 260 heart transplant recipients, virtually all of the donor hearts had coronary atherosclerosis, which was determined by intravascular ultrasound performed following coronary angiography about 30 days after transplantation. Even the hearts from donors ages 13 to 19 were affected, with approximately 20% showing ROUNDTABLE DISCUSSION
Early Protection against Pertussis Induced by Live Attenuated Bordetella pertussis BPZE1 Depends on TLR4

Key Points Live pertussis vaccine BPZE1 protects against B. pertussis infection within days. Early protection induced by BPZE1 does not depend on adaptive immune responses. Early protection induced by BPZE1 depends on TLR4-mediated innate immune responses. Pertussis is a severe respiratory disease mainly caused by Bordetella pertussis. Despite wide global vaccination coverage with efficacious pertussis vaccines, it remains one of the least well-controlled vaccine-preventable diseases, illustrating the shortcomings of the current vaccines. We have developed the live attenuated nasal pertussis vaccine BPZE1, currently undergoing clinical evaluation in human phase 2 trials. We have previously shown that in mice, BPZE1 provides strong and long-lasting protection against B. pertussis challenge by inducing potent Ab and T cell responses as well as secretory IgA and IL-17–producing resident memory T lymphocytes in the nasal cavity. In this study, we show that BPZE1 induces protection in mice against B. pertussis within days after vaccination, at a time when Ab and T cell responses were not detectable. Early protection was independent of T and B cell responses, as demonstrated by the use of SCID mice. Instead, it was due to TLR4-dependent signaling through the MyD88-dependent pathway of the innate immune response, as demonstrated in experiments with TLR4-deficient and MyD88-knockout mice. TLR2-dependent signaling did not play a major role in early protection. In addition, this study also shows that even at high doses, BPZE1 is safe in the severely immunocompromised MyD88-deficient mice, whereas virulent B. pertussis caused a severe pathological condition and death in these mice, even at a low dose. Finally, coadministration of virulent B. pertussis with BPZE1 did not cause exacerbated outgrowth of the virulent strain, thereby adding to the safety profile of this live vaccine candidate.
The Quality, Quantity, and Intraindividual Variability of Sleep Among Students and Student-Athletes

Background: Student-athletes are subject to significant demands due to their concurrent sporting and academic commitments, which may affect their sleep. This study aimed to compare the self-reported sleep quality, quantity, and intraindividual variability (IIV) of students and student-athletes through an online survey. Hypothesis: Student-athletes will have a poorer sleep quality and quantity and experience more IIV. Study Design: Case-control study. Level of Evidence: Level 4. Methods: Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while sleep quantity and IIV were assessed using the Consensus Sleep Diary. Initially, the PSQI and additional questions regarding sport participation habits were completed by 138 participants (65 students, 73 student-athletes). From within this sample, 44 participants were recruited to complete the sleep diary for a period of 14 days. Results: The mean PSQI score was 6.89 ± 3.03, with 65% of the sample identified as poor sleepers, but no difference was observed between students and student-athletes. Analysis of sleep patterns showed only possibly to likely small differences in sleep schedule, sleep onset latency, and subjective sleep quality between groups. IIV analysis showed likely moderate to possibly small differences between groups, suggesting more variable sleep patterns among student-athletes. Conclusion: This study highlights that sleep issues are prevalent within the university student population and that student-athletes may be at greater risk due to more variable sleep patterns. Clinical Relevance: University coaches should consider these results to optimize sleep habits of their student-athletes.
DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts

Abstract DIANA-LncBase v3.0 (www.microrna.gr/LncBase) is a reference repository with experimentally supported miRNA targets on non-coding transcripts. Its third version provides approximately half a million entries, corresponding to ∼240 000 unique tissue and cell type specific miRNA–lncRNA pairs. This compilation of interactions is derived from the manual curation of publications and the analysis of >300 high-throughput datasets. miRNA targets are supported by 14 experimental methodologies, applied to 243 distinct cell types and tissues in human and mouse. The largest part of the database is highly confident, AGO-CLIP-derived miRNA-binding events. LncBase v3.0 is the first relevant database to employ a robust CLIP-Seq-guided algorithm, microCLIP framework, to analyze 236 AGO-CLIP-Seq libraries and catalogue ∼370 000 miRNA binding events. The database was redesigned from the ground up, providing new functionalities. Known short variant information, on >67,000 experimentally supported target sites and lncRNA expression profiles in different cellular compartments are catered to users. Interactive visualization plots, portraying correlations of miRNA–lncRNA pairs, as well as lncRNA expression profiles in a wide range of cell types and tissues, are presented for the first time through a dedicated page. LncBase v3.0 constitutes a valuable asset for ncRNA research, providing new insights to the understanding of the still widely unexplored lncRNA functions.
Wnt Glycation Inhibits Canonical Signaling

Glycation occurs as a non-enzymatic reaction between amino and thiol groups of proteins, lipids, and nucleotides with reducing sugars or α-dicarbonyl metabolites. The chemical reaction underlying is the Maillard reaction leading to the formation of a heterogeneous group of compounds named advanced glycation end products (AGEs). Deleterious effects have been observed to accompany glycation such as alterations of protein structure and function resulting in crosslinking and accumulation of insoluble protein aggregates. A substantial body of evidence associates glycation with aging. Wnt signaling plays a fundamental role in stem cell biology as well as in regeneration and repair mechanisms. Emerging evidence implicates that changes in Wnt/β-catenin pathway activity contribute to the aging process. Here, we investigated the effect of glycation of Wnt3a on its signaling activity. Methods: Glycation was induced by treatment of Wnt3a-conditioned medium (CM) with glyoxal (GO). Effects on Wnt3a signaling activity were analyzed by Topflash/Fopflash reporter gene assay, co-immunoprecipitation, and quantitative RT-PCR. Results: Our data show that GO-treatment results in glycation of Wnt3a. Glycated Wnt3a suppresses β-catenin transcriptional activity in reporter gene assays, reduced binding of β-catenin to T-cell factor 4 (TCF-4) and extenuated transcription of Wnt/β-catenin target genes. Conclusions: GO-induced glycation impairs Wnt3a signaling function.
Intraoperative graft flow profiles in coronary artery bypass surgery: A meta‐analysis

Conduits used in coronary artery bypass artery grafting (CABG) have different properties and flow profiles. We compared intraoperative mean graft flow (MGF) between arterial and venous conduits, off‐pump CABG (OPCABG) and on‐pump CABG (ONCABG) procedures, skeletonized and pedicled internal mammary artery (IMA) grafts, and pulsatility index (PI) between OPCABG and ONCABG, in pairwise meta‐analyses.
Contemporary rehabilitation at cancer centres

Aim. Cancer rehabilitation is an important, but often underutilized treatment in the comprehensive care of the cancer patient. The lack of appropriate referral by physicians unfamiliar with the concept of rehabilitation was identified as primary barriers to optimal delivery of rehabilitation care. Therefore, the aim of this paper is to describe the current situation in the world of science of cancer rehabilitation and to describe availability of professional resources in the selected countries in the world. Material and methods. This paper is a review article to describe rehabilitation models in cancer services for patients in selected cases in the world. Results. Rehabilitation should be applied in various settings, depending on the level of disability, extent of disease, medical acuity level of the patient, and available services. However, the rehabilitation systems in the world differ depending on the various social security and health-care systems, but they are largely based on a similar, multidimensional and multidisciplinary understanding of cancer rehabilitation. Conclusions. On the basis of description of the bio-psycho-social models, it can be seen that rehabilitation must be an integral and continuous part of all cancer care. There is strong evidence that rehabilitation is a well-tolerated and safe adjunct therapy that can mitigate several common treatment-related side effects among cancer patients.
Structural and Functional Dynamics of Soil Microbes following Spruce Beetle Infestation

Belowground impacts of bark beetle infestation have not been explored as thoroughly as their aboveground counterparts. In order to accurately model impacts of bark beetle-induced tree mortality on carbon and nutrient cycling and forest regeneration, the intricacies of soil microbial communities must be examined. In this study, we investigated the structure and function of soil bacterial and fungal communities following bark beetle infestation. Our results show bark beetle infestation to impact soil conditions, as well as soil microbial community structure and function. ABSTRACT As the range of bark beetles expands into new forests and woodlands, the need to understand their effects on multiple trophic levels becomes increasingly important. To date, much attention has been paid to the aboveground processes affected by bark beetle infestation, with a focus on photoautotrophs and ecosystem level processes. However, indirect effects of bark beetle on belowground processes, especially the structure and function of soil microbiota remains largely a black box. Our study examined the impacts of bark beetle-induced tree mortality on soil microbial community structure and function using high-throughput sequencing of the soil bacterial and fungal communities and measurements of extracellular enzyme activities. The results suggest bark beetle infestation affected edaphic conditions through increased soil water content, pH, electrical conductivity, and carbon/nitrogen ratio and altered bulk and rhizosphere soil microbial community structure and function. Finally, increased enzymatic activity suggests heightened microbial decomposition following bark beetle infestation. With this increase in enzymatic activity, nutrients trapped in organic substrates may become accessible to seedlings and potentially alter the trajectory of forest regeneration. Our results indicate the need for incorporation of microbial processes into ecosystem level models. IMPORTANCE Belowground impacts of bark beetle infestation have not been explored as thoroughly as their aboveground counterparts. In order to accurately model impacts of bark beetle-induced tree mortality on carbon and nutrient cycling and forest regeneration, the intricacies of soil microbial communities must be examined. In this study, we investigated the structure and function of soil bacterial and fungal communities following bark beetle infestation. Our results show bark beetle infestation to impact soil conditions, as well as soil microbial community structure and function.
Antimicrobial, Antioxidant, and Immunomodulatory Properties of Essential Oils: A Systematic Review

Essential oils (EOs) are a mixture of natural, volatile, and aromatic compounds obtained from plants. In recent years, several studies have shown that some of their benefits can be attributed to their antimicrobial, antioxidant, anti-inflammatory, and also immunomodulatory properties. Therefore, EOs have been proposed as a natural alternative to antibiotics or for use in combination with antibiotics against multidrug-resistant bacteria in animal feed and food preservation. Most of the results come from in vitro and in vivo studies; however, very little is known about their use in clinical studies. A systematic and comprehensive literature search was conducted in PubMed, Embase®, and Scopus from December 2014 to April 2019 using different combinations of the following keywords: essential oils, volatile oils, antimicrobial, antioxidant, immunomodulation, and microbiota. Some EOs have demonstrated their efficacy against several foodborne pathogens in vitro and model food systems; namely, the inhibition of S. aureus, V. cholerae, and C. albicans has been observed. EOs have shown remarkable antioxidant activities when used at a dose range of 0.01 to 10 mg/mL in cell models, which can be attributed to their richness in phenolic compounds. Moreover, selected EOs exhibit immunomodulatory activities that have been mainly attributed to their ability to modify the secretion of cytokines.
Short-Term Microgravity Influences Cell Adhesion in Human Breast Cancer Cells

With the commercialization of spaceflight and the exploration of space, it is important to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We examined the influence of r-µg, simulated microgravity (s-µg, incubator random positioning machine (iRPM)), hypergravity (hyper-g), and vibration (VIB) on triple-negative breast cancer (TNBC) cells (MDA-MB-231 cell line) with the aim to study early changes in the gene expression of factors associated with cell adhesion, apoptosis, nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. We had the opportunity to attend a parabolic flight (PF) mission and to study changes in RNA transcription in the MDA-MB cells exposed to PF maneuvers (29th Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). PF maneuvers induced an early up-regulation of ICAM1, CD44 and ERK1 mRNAs after the first parabola (P1) and a delayed upregulation of NFKB1, NFKBIA, NFKBIB, and FAK1 after the last parabola (P31). ICAM-1, VCAM-1 and CD44 protein levels were elevated, whereas the NF-κB subunit p-65 and annexin-A2 protein levels were reduced after the 31st parabola (P31). The PRKCA, RAF1, BAX mRNA were not changed and cleaved caspase-3 was not detectable in MDA-MB-231 cells exposed to PF maneuvers. Hyper-g-exposure of the cells elevated the expression of CD44 and NFKBIA mRNAs, iRPM-exposure downregulated ANXA2 and BAX, whereas VIB did not affect the TNBC cells. The early changes in ICAM-1 and VCAM-1 and the rapid decrease in the NF-κB subunit p-65 might be considered as fast-reacting, gravity-regulated and cell-protective mechanisms of TNBC cells exposed to altered gravity conditions. This data suggest a key role for the detected gravity-signaling elements in three-dimensional growth and metastasis.
Cholest-4,6-Dien-3-One Promote Epithelial-To-Mesenchymal Transition (EMT) in Biliary Tree Stem/Progenitor Cell Cultures In Vitro

Human biliary tree stem/progenitor cells (hBTSCs), reside in peribiliary glands, are mainly stimulated by primary sclerosing cholangitis (PSC) and cholangiocarcinoma. In these pathologies, hBTSCs displayed epithelial-to-mesenchymal transition (EMT), senescence characteristics, and impaired differentiation. Here, we investigated the effects of cholest-4,6-dien-3-one, an oxysterol involved in cholangiopathies, on hBTSCs biology. hBTSCs were isolated from donor organs, cultured in self-renewal control conditions, differentiated in mature cholangiocytes by specifically tailored medium, or exposed for 10 days to concentration of cholest-4,6-dien-3-one (0.14 mM). Viability, proliferation, senescence, EMT genes expression, telomerase activity, interleukin 6 (IL6) secretion, differentiation capacity, and HDAC6 gene expression were analyzed. Although the effect of cholest-4,6-dien-3-one was not detected on hBTSCs viability, we found a significant increase in cell proliferation, senescence, and IL6 secretion. Interestingly, cholest-4.6-dien-3-one impaired differentiation in mature cholangiocytes and, simultaneously, induced the EMT markers, significantly reduced the telomerase activity, and induced HDAC6 gene expression. Moreover, cholest-4,6-dien-3-one enhanced bone morphogenic protein 4 (Bmp-4) and sonic hedgehog (Shh) pathways in hBTSCs. The same pathways activated by human recombinant proteins induced the expression of EMT markers in hBTSCs. In conclusion, we demonstrated that chronic exposition of cholest-4,6-dien-3-one induced cell proliferation, EMT markers, and senescence in hBTSC, and also impaired the differentiation in mature cholangiocytes.
Identifying Faculty and Peer Interaction Patterns of First-Year Biology Doctoral Students: A Latent Class Analysis

Faculty and peer interactions play a key role in shaping graduate student socialization. Yet, within the literature on graduate student socialization, researchers have primarily focused on understanding the nature and impact of faculty alone, and much less is known about how peer interactions also contribute to graduate student outcomes. Using a national sample of first-year biology doctoral students, this study reveals distinct categories that classify patterns of faculty and peer interaction. Further, we document inequities such that certain groups (e.g., underrepresented minority students) report constrained types of interactions with faculty and peers. Finally, we connect faculty and peer interaction patterns to student outcomes. Our findings reveal that, while the classification of faculty and peer interactions predicted affective and experiential outcomes (e.g., sense of belonging, satisfaction with academic development), it was not a consistent predictor of more central outcomes of the doctoral socialization process (e.g., research skills, commitment to degree). These and other findings are discussed, focusing on implications for future research, theory, and practice related to graduate training.
Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) was classified by the Centers for Disease Control and Prevention in 2014 as the 3rd leading cause of death in the United States (US). The main cause of COPD is exposure to tobacco smoke and air pollutants. Problems associated with COPD include under-diagnosis of the disease and an increase in the number of smokers worldwide. The goal of our study is to identify disease variability in the gene expression profiles of COPD subjects compared to controls, by reanalyzing pre-existing, publicly available microarray expression datasets. Our inclusion criteria for microarray datasets selected for smoking status, age and sex of blood donors reported. Our datasets used Affymetrix, Agilent microarray platforms (7 datasets, 1,262 samples). We re-analyzed the curated raw microarray expression data using R packages, and used Box-Cox power transformations to normalize datasets. To identify significant differentially expressed genes we used generalized least squares models with disease state, age, sex, smoking status and study as effects that also included binary interactions, followed by likelihood ratio tests (LRT). We found 3,315 statistically significant (Storey-adjusted q-value <0.05) differentially expressed genes with respect to disease state (COPD or control). We further filtered these genes for biological effect using results from LRT q-value <0.05 and model estimates’ 10% two-tailed quantiles of mean differences between COPD and control), to identify 679 genes. Through analysis of disease, sex, age, and also smoking status and disease interactions we identified differentially expressed genes involved in a variety of immune responses and cell processes in COPD. We also trained a logistic regression model using the common array genes as features, which enabled prediction of disease status with 81.7% accuracy. Our results give potential for improving the diagnosis of COPD through blood and highlight novel gene expression disease signatures.