Miracle-dz/UniFAR-FTUs huggingface dataset:
VelA and LaeA are Key Regulators of Epichloë festucae Transcriptomic Response during Symbiosis with Perennial Ryegrass

VelA (or VeA) is a key global regulator in fungal secondary metabolism and development which we previously showed is required during the symbiotic interaction of Epichloë festucae with perennial ryegrass. In this study, comparative transcriptomic analyses of ∆velA mutant compared to wild-type E. festucae, under three different conditions (in culture, infected seedlings, and infected mature plants), were performed to investigate the impact of VelA on E. festucae transcriptome. These comparative transcriptomic studies showed that VelA regulates the expression of genes encoding proteins involved in membrane transport, fungal cell wall biosynthesis, host cell wall degradation, and secondary metabolism, along with a number of small secreted proteins and a large number of proteins with no predictable functions. In addition, these results were compared with previous transcriptomic experiments that studied the impact of LaeA, another key global regulator of secondary metabolism and development that we have shown is important for E. festucae–perennial ryegrass interaction. The results showed that although VelA and LaeA regulate a subset of E. festucae genes in a similar manner, they also regulated many other genes independently of each other suggesting specialised roles.
Self-Imaging Effect in Liquid-Filled Hollow-Core Capillary Waveguide for Sensing Applications

A high sensitivity fiber-optic sensor based on self-imaging effect in a hollow-core capillary waveguide (HCCW) is presented for sensing applications. The sensor is composed of a section of HCCW fusion spliced between single mode fibers (SMFs). The self-imaging effect in the HCCW is investigated with different fiber lengths and arc-fusion parameters. By infiltrating the hollow core with index matching liquids, the peak wavelength of the proposed device shifts towards longer wavelengths. The temperature and refractive index (RI) responses of the sensor are studied systematically. When temperature is increased from 25 °C to 75 °C, the temperature sensitivity of the device can be improved significantly with the infiltrated structure, and reaches −0.49 nm/°C, compared with that of the un-filled device, which is 9.8 pm/°C. For the RI response, the liquid-filled structure achieves sensitivity of 12,005 nm/RIU in the range between 1.448 and 1.450, slightly higher than the 11,920 nm/RIU achieved by the un-filled one. The proposed sensor exhibits the advantages of simple structure, high sensitivity and low cost, which may find potential applications in physical and chemical sensing.
Seasonal variations of digestive enzymes in sea cucumbers (Holothuria tubulosa, G. 1788) under culture conditions.

Sea cucumber, Holothuria tubulosa (Gmelin, 1788), is an economically valuable species due to its rich nutrients content that being exported in Turkey. However, culture of this species is difficult due to a lack of knowledge. The main objective of this study is to investigate seasonal activities of main digestive enzymes (protease, lipase, and amylase) for nutritional requirements. In this sense, sea cucumbers were stocked in the glass aquarium and sediment was 10 cm. It was replaced monthly and enriched (1% of the living individual weight) by dried Sargassum sp. Total protease and amylase enzymes have shown higher activity compared to lipase. All three enzyme activities were maximum in the summer and minimum in the winter. In summer, the highest measured total protease, amylase, and lipase activity values were 6.45 ± 0.66, 6.77 ± 0.72, and 2.78 ± 0.32 U/mg per protein, respectively. In winter, the lowest total protease, amylase, and lipase activity values were measured as 2.03 ± 0.16, 1.14 ± 0.14, and 0.12 ± 0.01 U/mg per protein, respectively. As a conclusion of the study, seasonal expression of the main digestive enzymes was strictly dependent on water temperatures and food abundance and also it was ideal to feed this species with food containing high protein and carbohydrate under appropriate temperatures for commercial culture.
Ruxolitinib and interferon-α2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study

We report the final 2-year end-of-study results from the first clinical trial investigating combination treatment with ruxolitinib and low-dose pegylated interferon-α2 (PEG-IFNα2). The study included 32 patients with polycythemia vera and 18 with primary or secondary myelofibrosis; 46 patients were previously intolerant of or refractory to PEGIFNα2. The primary outcome was efficacy, based on hematologic parameters, quality of life measurements, and JAK2 V617F allele burden. We used the 2013 European LeukemiaNet and International Working Group- Myeloproliferative Neoplasms Research and Treatment response criteria, including response in symptoms, splenomegaly, peripheral blood counts, and bone marrow. Of 32 patients with polycythemia vera, ten (31%) achieved a remission which was a complete remission in three (9%) cases. Of 18 patients with myelofibrosis, eight (44%) achieved a remission; five (28%) were complete remissions. The cumulative incidence of peripheral blood count remission was 0.85 and 0.75 for patients with polycythemia vera and myelofibrosis, respectively. The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score decreased from 22 [95% confidence interval (95% CI):, 16-29] at baseline to 15 (95% CI: 10-22) after 2 years. The median JAK2 V617F allele burden decreased from 47% (95% CI: 33-61%) to 12% (95% CI: 6-22%), and 41% of patients achieved a molecular response. The drop-out rate was 6% among patients with polycythemia vera and 32% among those with myelofibrosis. Of 36 patients previously intolerant of PEG-IFNα2, 31 (86%) completed the study, and 24 (67%) of these received PEG-IFNα2 throughout the study. In conclusion, combination treatment improved cell counts, reduced bone marrow cellularity and fibrosis, decreased JAK2 V617F burden, and reduced symptom burden with acceptable toxicity in several patients with polycythemia vera or myelofibrosis. #EudraCT2013-003295-12.
miR-10a-5p and miR-29b-3p as Extracellular Vesicle-Associated Prostate Cancer Detection Markers

Extracellular vesicles (EVs) are shed by many different cell types. Their nucleic acids content offers new opportunities for biomarker research in different solid tumors. The role of EV RNA in prostate cancer (PCa) is still largely unknown. EVs were isolated from different benign and malignant prostate cell lines and blood plasma from patients with PCa (n = 18) and controls with benign prostatic hyperplasia (BPH) (n = 7). Nanoparticle tracking analysis (NTA), Western blot, electron microscopy, and flow cytometry analysis were used for the characterization of EVs. Non-coding RNA expression profiling of PC3 metastatic PCa cells and their EVs was performed by next generation sequencing (NGS). miRNAs differentially expressed in PC3 EVs were validated with qRT-PCR in EVs derived from additional cell lines and patient plasma and from matched tissue samples. 92 miRNAs were enriched and 48 miRNAs were depleted in PC3 EVs compared to PC3 cells, which could be confirmed by qRT-PCR. miR-99b-5p was significantly higher expressed in malignant compared to benign EVs. Furthermore, expression profiling showed miR-10a-5p (p = 0.018) and miR-29b-3p (p = 0.002), but not miR-99b-5p, to be overexpressed in plasma-derived EVs from patients with PCa compared with controls. In the corresponding tissue samples, no significant differences in the miRNA expression could be observed. We thus propose that EV-associated miR-10a-5p and miR-29b-3p could serve as potential new PCa detection markers.
Leptin, Ghrelin, and Leptin/Ghrelin Ratio in Critically Ill Patients

The objective of this study was to evaluate leptin, ghrelin, and leptin/ghrelin ratio in critically ill patients and association of leptin/ghrelin ratio with outcomes. This is a sub-study of the PermiT trial (ISRCTN68144998). A subset of 72 patients who were expected to stay >14 days in the Intensive care unit were enrolled. Blood samples were collected on days 1, 3, 5, 7, and 14. Samples were analyzed for leptin and active ghrelin in addition to other hormones. Baseline leptin/ghrelin ratio was calculated, and patients were stratified into low and high leptin/ghrelin ratio based on the median value of 236. There was a considerable variation in baseline leptin level: Median 5.22 ng/mL (Q1, Q3: 1.26, 17.60). Ghrelin level was generally low: 10.61 pg/mL (Q1, Q3: 8.62, 25.36). Patients with high leptin/ghrelin ratio compared to patients with low leptin/ghrelin ratio were older, had higher body mass index and more likely to be diabetic. There were no differences in leptin/ghrelin ratio between patients who received permissive underfeeding and standard feeding. Multivariable logistic regression analysis showed that age and body mass index were significant independent predictors of high leptin–ghrelin ratio. Leptin–ghrelin ratio was not associated with 90-day mortality or other outcomes. Age and body mass index are predictors of high leptin/ghrelin ratio. Leptin/ghrelin ratio is not affected by permissive underfeeding and is not associated with mortality.
Combination antibiotic delivery in PMMA provides sustained broad-spectrum antimicrobial activity and allows for post-implantation refilling.

Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, but also as implantable antimicrobial "beads". However, this strategy is of limited value in high risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also when only one drug is incorporated and applied toward poly-microbial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance. To combat these limitations, we developed a combination-antibiotic PMMA composite system comprised of rifampicin-filled β-cyclodextrin (β-CD) microparticles added into PMMA filled with a second drug. Different formulations were evaluated through Zone-of-Inhibition, drug activity, antibiotic release and re-filling, as well as mechanical studies. Our combination-antibiotic PMMA composite system achieved up to an eight-fold increase in duration of antimicrobial activity in comparison to clinically used antibiotic-filled PMMA. Inclusion of CD microparticles also allowed for refilling of additional antibiotics after simulated implantation, resulting in additional windows of therapeutic efficacy. Mechanical testing showed that our tested formulations did have a small, but significant decrease in mechanical properties when compared to unmodified controls. While further studies are needed to determine whether the tested formulations are still suitable for load-bearing applications (e.g. bone cement), our composites are certainly amenable for a variety of non-load bearing applications (e.g. antimicrobial "beads" and temporary spacer in two-stage arthroscopic revisions).
Choice-induced inter-trial inhibition is modulated by idiosyncratic choice-consistency

Humans constantly decide among multiple action plans. Carrying out one action usually implies that other plans are suppressed. Here we make use of inter-trial effects to determine whether suppression of non-chosen action plans is due to proactively preparing for upcoming decisions or due to retroactive influences from previous decisions. Participants received rewards for timely and accurate saccades to targets appearing left or right from fixation. Each block interleaved trials with one (single-trial) or two targets (choice-trial). Whereas single-trial rewards were always identical, rewards for the two targets in choice-trials could either be identical (unbiased) or differ (biased) within one block. We analyzed single-trial latencies as a function of idiosyncratic choice-consistency or reward-bias, the previous trial type and whether the same or the other target was selected in the preceding trial. After choice-trials, single-trial responses to the previously non-chosen target were delayed. For biased choices, inter-trial effects were strongest when choices were followed by a single-trial to the non-chosen target. In the unbiased condition, inter-trial effects increased with increasing individual consistency of choice behavior. These findings suggest that the suppression of alternative action plans is not coupled to target selection and motor execution but instead depends on top-down signals like the overall preference of one target over another.
The South African 24-Hour Movement Guidelines for Birth to 5 Years: Results From the Stakeholder Consultation.

BACKGROUND In 2018, South Africa developed 24-hour movement behavior guidelines for children from birth to 5 years. This study reports on the stakeholder consultation as part of this development process. METHODS An online survey was completed by 197 participants; 9 focus groups (with parents/caregivers, early childhood development practitioners, and community health workers, total n = 70) were conducted, and a meeting with stakeholders from government and nongovernment organizations (n = 15) was held. RESULTS In the online survey, stakeholders overwhelmingly agreed with the guidelines (97.0%) and recognized the benefit of putting the guidelines into practice (88.8%). Most online survey respondents (88.3%) reported that the guidelines would benefit all South African children equally. Responses to open-ended questions in the online survey and focus group discussions revealed issues including safety and nutrition of children, perceived parental barriers to using the guidelines, and education. Training and provision of educational materials were identified from all stakeholders as key in the dissemination and implementation of the guidelines. CONCLUSIONS The findings informed the development of the South African 24-hour movement behavior guidelines and revealed several important factors to address in the dissemination and implementation of the guidelines to ensure that they are applicable and equitable in South Africa.
Accelerated Osteogenic Differentiation of MC3T3-E1 Cells by Lactoferrin-Conjugated Nanodiamonds through Enhanced Anti-Oxidant and Anti-Inflammatory Effects

The purpose of this study was to investigate the effects of lactoferrin (LF)-conjugated nanodiamonds (NDs) in vitro on both anti-oxidant and anti-inflammation activity as well as osteogenic promotion. The application of LF-NDs resulted in sustained release of LF for up to 7 days. In vitro anti-oxidant analyses performed using Dichlorofluorescin diacetate (DCF-DA) assay and cell proliferation studies showed that LF (50 μg)-NDs effectively scavenged the reactive oxygen species (ROS) in MC3T3-E1 cells (osteoblast-like cells) after H2O2 treatment and increased proliferation of cells after H2O2 treatment. Treatment of lipopolysaccharide (LPS)-induced MC3T3-E1 cells with LF-NDs suppressed levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, LF-NDs were associated with outstanding enhancement of osteogenic activity of MC3T3-E1 cells due to increased alkaline phosphatase (ALP) and calcium deposition. Our findings suggest that LF-NDs are an important substrate for alleviating ROS effects and inflammation, as well as promoting osteogenic differentiation of cells.
RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

Collecting duct carcinoma (CDC) is a rare renal cell carcinoma subtype with a very poor prognosis. There have been only a few studies on gene expression analysis in CDCs. We compared the gene expression profiles of two CDC cases with those of eight normal tissues of renal cell carcinoma patients. At a threshold of |log2fold-change| ≥1, 3349 genes were upregulated and 1947 genes were downregulated in CDCs compared to the normal samples. Pathway analysis of the deregulated genes revealed that cancer pathways and cell cycle pathways were most prominent in CDCs. The most upregulated gene was keratin 17, and the most downregulated gene was cubilin. Among the most downregulated genes were four solute carrier genes (SLC3A1, SLC9A3, SLC26A7, and SLC47A1). The strongest negative correlations between miRNAs and mRNAs were found between the downregulated miR-374b-5p and its upregulated target genes HIST1H3B, HK2, and SLC7A11 and between upregulated miR-26b-5p and its downregulated target genes PPARGC1A, ALDH6A1, and MARC2. An upregulation of HK2 and a downregulation of PPARGC1A, ALDH6A1, and MARC2 were observed at the protein level. Survival analysis of the cancer genome atlas (TCGA) dataset showed for the first time that low gene expression of MARC2, cubilin, and SLC47A1 and high gene expression of KRT17 are associated with poor overall survival in clear cell renal cell carcinoma patients. Altogether, we identified dysregulated protein-coding genes, potential miRNA-target interactions, and prognostic markers that could be associated with CDC.
The Effectiveness and Value of Esketamine for the Management of Treatment-Resistant Depression

DISCLOSURES Funding for this summary was contributed by the Laura and John Arnold Foundation, National Institute for Health Care Management, California Health Care Foundation, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Healthcare, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, AstraZeneca, Allergan, Alnylam, Biogen, Blue Shield of California, Cambia Health Services, CVS Caremark, Editas, Express Scripts, Genentech, GlaxoSmithKline, Harvard Pilgrim Health Care, Health Care Service Corporation, HealthPartners, HealthFirst, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinkrodt Pharmaceuticals, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fazioli, and Pearson are employed by ICER. Touchette reports grants from ICER during the course of this work and personal fees from Monument Analytics, unrelated to this work. Atlas has nothing to disclose.
The Influence of Quadruplex Structure in Proximity to P53 Target Sequences on the Transactivation Potential of P53 Alpha Isoforms

p53 is one of the most studied tumor suppressor proteins that plays an important role in basic biological processes including cell cycle, DNA damage response, apoptosis, and senescence. The human TP53 gene contains alternative promoters that produce N-terminally truncated proteins and can produce several isoforms due to alternative splicing. p53 function is realized by binding to a specific DNA response element (RE), resulting in the transactivation of target genes. Here, we evaluated the influence of quadruplex DNA structure on the transactivation potential of full-length and N-terminal truncated p53α isoforms in a panel of S. cerevisiae luciferase reporter strains. Our results show that a G-quadruplex prone sequence is not sufficient for transcription activation by p53α isoforms, but the presence of this feature in proximity to a p53 RE leads to a significant reduction of transcriptional activity and changes the dynamics between co-expressed p53α isoforms.
Inhibition of Drug Resistance of Staphylococcus aureus by Efflux Pump Inhibitor and Autolysis Inducer to Strengthen the Antibacterial Activity of β-lactam Drugs

Abstract This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). In vitro, the combination treatment of TZ and MCZ significantly reduced 4096-fold (Σ (FIC) = 0.1 – 1.25) the MIC value of CXN against S. aureus. In vivo, the combination therapy significantly relieved breast redness and swelling in mice infected with either clinical or standard strains of S. aureus. Meanwhile, the number of bacteria isolated from the MRSA135-infected mice decreased significantly (p = 0.0427 < 0.05) after the combination therapy when compared to monotherapy. Moreover, the number of bacteria isolated from the mice infected with a reference S. aureus strain also decreased significantly (p = 0.0191 < 0.05) after the combination therapy when compared to monotherapy. The pathological changes were more significant in the CXN-treated group when compared to mice treated with a combination of three drugs. In addition, we found that combination therapy reduced the release of the bacteria-stimulated cytokines such as IL-6, IFN-γ, and TNF-α. Cytokine assays in serum revealed that CXN alone induced IL-6, IFN-γ, and TNF-α in the mouse groups infected with ATCC 29213 or MRSA135, and the combination of these three drugs significantly reduced IL-6, IFN-γ, and TNF-α concentrations. Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.
Effect of Exergame Training and Detraining on Lower-Body Strength, Agility, and Cardiorespiratory Fitness in Women with Fibromyalgia: Single-Blinded Randomized Controlled Trial

The aim of this study was to analyze the effects of a 24 week exergame intervention and 24 weeks of detraining on lower-limb strength, agility, and cardiorespiratory fitness in women with fibromyalgia (FM). It was performed as a single-blinded randomized controlled trial of 55 women with FM. University facilities were used. The 24 week exergame intervention was focused on mobility, postural control, upper- and lower-limb coordination, aerobic fitness, and strength. Participants performed 120 min of exergaming per week, which was divided into two sessions. Twenty-four weeks after the end of the intervention, participants were re-evaluated. A chair–stand test, 10 step stair test, and six-minute walk test were conducted to assess lower-body strength, agility, and cardiorespiratory fitness, respectively. The exergame intervention significantly improved lower-limb strength and cardiorespiratory fitness. However, no significant effects on agility were observed. After the detraining period, lower-limb strength and agility returned to their baseline level, but improvements in cardiorespiratory fitness were sustained over time. Exergaming was therefore shown to be beneficial for physical fitness in people with FM. However, exergames had to be played regularly to maintain the benefits. This long-term intervention (24 weeks) may have changed the lifestyle of women with FM, which could explain why cardiorespiratory fitness improvements remained after the detraining period. Future research should focus on lifestyle changes after long-term interventions.