Miracle-dz/UniFAR-FTUs huggingface dataset:
CARLo‐7—A plausible biomarker for bladder cancer

Cancer is defined as undifferentiated and unchecked growth of cells damaging the surrounding tissue. Cancers manifest altered gene expression. Gene expression is regulated by a diverse array of non‐protein‐coding RNA. Aberrant expression of long non‐coding RNAs (lncRNAs) has been recently found to have functional consequences in cancers. In the current study, we report CARLo‐7 as the only bladder cancer–specific lncRNA from the CARLos cluster. The expression of this lncRNA correlates with bladder cancer grade. We propose that CARLo‐7 has an oncogenic potential and might be regulator of cell proliferation. Furthermore, by comparison the expression of proto‐oncogene MYC, which is the only well‐annotated gene close to the cancer ‐ associated linkage disequilibrium blocks of this region, does not show a pronounced change in expression between the low‐ and high‐grade tumours. Our results indicate that CARlo‐7 can act as a prognostic marker for bladder cancer.
A different suite: The assemblage of distinct fungal communities in water-damaged units of a poorly-maintained public housing building

Water-damaged housing has been associated with a number of negative health outcomes, principally respiratory disease and asthma. Much of what we know about fungi associated with water-damaged buildings has come from culture-based and immunochemical methods. Few studies have used high-throughput sequencing technologies to assess the impact of water-damage on microbial communities in residential buildings. In this study we used amplicon sequencing and quantitative-PCR to evaluate fungal communities on surfaces and in airborne dust in multiple units of a condemned public housing project located in the San Francisco Bay Area. We recruited 21 households to participate in this study and characterized their apartments as either a unit with visible mold or no visible mold. We sampled airborne fungi from dust settled over a month-long time period from the outdoors, in units with no visible mold, and units with visible mold. In units with visible mold we additionally sampled the visible fungal colonies from bathrooms, kitchens, bedrooms, and living rooms. We found that fungal biomass in settled dust was greater outdoors compared to indoors, but there was no significant difference of fungal biomass in units with visible mold and no visible mold. Interestingly, we found that fungal diversity was reduced in units with visible mold compared to units with no visible mold and the outdoors. Units with visible mold harbored fungal communities distinct from units with no visible mold and the outdoors. Units with visible mold had a greater abundance of taxa within the classes Eurotiomycetes, Saccharomycetes, and Wallemiomycetes. Colonies of fungi collected from units with visible mold were dominated by two Cladosporium species, C. sphaerospermum and C halotolerans. This study demonstrates that high-throughput sequencing of fungi indoors can be a useful strategy for distinguishing distinct microbial exposures in water-damaged homes with visible and nonvisible mold growth, and may provide a microbial means for identifying water damaged housing.
Interleukin-2/antibody complex expanding Foxp3+ regulatory T cells exacerbates Th2-mediated allergic airway inflammation

Foxp3+ regulatory CD4+ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation.
Ab initio derivation of the FRET equations resolves old puzzles and suggests measurement strategies

Quantitative FRET-based imaging methods rely on the determination of an apparent FRET efficiency (Eapp) as well as donor and acceptor concentrations, in order to uncover the identity and relative abundance of the oligomeric (or quaternary) structures of associating macromolecules. Theoretical work has provided “upwards” relationships between the experimentally determined Eapp distributions and the quaternary structure models that underlie them. By contrast, the body of work that predicates the “downwards” dependence of Eapp on directly measurable quantities (i.e., fluorescence emission of donors and acceptors) relies largely on plausibility arguments, one of which is the seemingly obvious assumption that the fraction of fluorescent molecules in the ground state pretty nearly equals the total concentration of molecules. In this work, we use the kinetic models of fluorescence in the presence and absence of FRET to rigorously derive useful relationships between Eapp and measurable fluorescence signals. Analysis of these relationships reveals a few anticipated surprises and some unexpected explanations for known experimental FRET puzzles, and it provides theoretical foundations for optimizing measurement strategies.
Abscisic Acid Receptors and Coreceptors Modulate Plant Water Use Efficiency and Water Productivity1[OPEN]

Abscisic acid signaling can be exploited for generating plants with improved water use efficiency, resilient to water availability and light intensity but sensitive to heat. Improving the water use efficiency (WUE) of crop plants without trade-offs in growth and yield is considered a utopic goal. However, recent studies on model plants show that partial restriction of transpiration can occur without a reduction in CO2 uptake and photosynthesis. In this study, we analyzed the potentials and constraints of improving WUE in Arabidopsis (Arabidopsis thaliana) and in wheat (Triticum aestivum). We show that the analyzed Arabidopsis wild-type plants consume more water than is required for unrestricted growth. WUE was enhanced without a growth penalty by modulating abscisic acid (ABA) responses either by using overexpression of specific ABA receptors or deficiency of ABA coreceptors. Hence, the plants showed higher water productivity compared with the wild-type plants; that is, equal growth with less water. The high WUE trait was resilient to changes in light intensity and water availability, but it was sensitive to the ambient temperature. ABA application to plants generated a partial phenocopy of the water-productivity trait. ABA application, however, was never as effective as genetic modification in enhancing water productivity, probably because ABA indiscriminately targets all ABA receptors. ABA agonists selective for individual ABA receptors might offer an approach to phenocopy the water-productivity trait of the high WUE lines. ABA application to wheat grown under near-field conditions improved WUE without detectable growth trade-offs. Wheat yields are heavily impacted by water deficit, and our identification of this crop as a promising target for WUE improvement may help contribute to greater food security.
Cannabinoids Stimulate the TRP Channel-Dependent Release of Both Serotonin and Dopamine to Modulate Behavior in C. elegans

Cannabis sativa alters sensory perception and exhibits potential medicinal benefits. In mammals, cannabinoids activate two canonical receptors, CB1/CB2, as well additional receptors/ion channels whose overall contributions to cannabinoid signaling have yet to be fully assessed. In Caenorhabditis elegans, the endogenous cannabinoid receptor agonist, 2-arachidonoylglycerol (2-AG) activates a CB1 ortholog, NPR-19, to modulate behavior (Oakes et al., 2017). In addition, 2-AG stimulates the NPR-19 independent release of both serotonin (5-HT) and dopamine (DA) from subsets of monoaminergic neurons to modulate locomotory behaviors through a complex monoaminergic signaling pathway involving multiple serotonin and dopamine receptors. 2-AG also inhibits locomotion in remodeled monoamine receptor mutant animals designed to measure the acute release of either 5-HT or DA, confirming the direct effects of 2-AG on monoamine release. 2-AG-dependent locomotory inhibition requires the expression of transient receptor potential vanilloid 1 (TRPV1) and TRPN-like channels in the serotonergic or dopaminergic neurons, respectively, and the acute pharmacological inhibition of the TRPV1-like channel abolishes both 2-AG-dependent 5-HT release and locomotory inhibition, suggesting the 2-AG may activate the channel directly. This study highlights the advantages of identifying and assessing both CB1/CB2-dependent and independent cannabinoid signaling pathways in a genetically tractable, mammalian predictive model, where cannabinoid signaling at the molecular/neuronal levels can be correlated directly with changes in behavior. SIGNIFICANCE STATEMENT This study is focused on assessing CB1/CB2-independent cannabinoid signaling in a genetically tractable, whole-animal model where cannabinoid signaling at the molecular/neuronal levels can be correlated with behavioral change. Caenorhabditis elegans contains a cannabinoid signaling system mediated by a canonical cannabinoid receptor, NPR-19, with orthology to human CB1/CB2 (Oakes et al., 2017). The present study has characterized an NPR-19-independent signaling pathway that involves the cannabinoid-dependent release of both serotonin and dopamine and the expression of distinct TRP-like channels on the monoaminergic neurons. Our work should be of interest to those studying the complexities of CB1/CB2-independent cannabinoid signaling, the role of TRP channels in the modulation of monoaminergic signaling, and the cannabinoid-dependent modulation of behavior.
Allergy to food additives

Purpose of review To provide an update of the studies concerning the diagnosis and management of food additives allergy. Recent findings Additives improve specific characteristics of food products, but they may induce allergic even life-threatening reactions. Physical examination and medical history are basic to assess specific in-vivo and in-vitro tests. The only treatment for allergic patients consists in avoiding the food containing culprit additives. High-risk patients should be able to recognize severe reactions and self-manage them. Summary The prevalence of adverse reactions to food additives is low, and it may depend on comorbidities, like asthma or chronic idiopathic urticaria. Food labels may help the correct identification of ingredients. Natural additives like spices should cause immediate reactions because of a pollen-sensitization or panallargen proteins presence. Additive-free diets may help the patient care, but the authors suggest assessing an oral food challenge with the culprit substance if there are no contraindications.
Water Quality Disturbances on Phytoplankton Species Composition and Abundance in Mini-Ndai Creek, Niger Delta, Nigeria

This study was carried out in collaboration between both authors. The design of the study and the field as well as the laboratory work was carried out jointly by the two authors. While author UF wrote the first draft of the manuscript, author OAFW handled the statistical analysis. Both authors read and approved the final manuscript. ABSTRACT An investigation into the this study influenced the species composition, distribution and abundance of the phytoplankton community of Mini-Ndai Creek.
Aerosolized agents for airway clearance in cystic fibrosis

The outlook for people with cystic fibrosis (CF) has improved considerably as a result of conventional therapies including aerosolized agents for airway clearance. These will continue to play a significant role in maintaining well‐being and improving survival, even as newer agents emerge that correct the underlying CF defect. In this review, we explore the evidence supporting the use of dornase alfa, hypertonic saline, and mannitol in improving mucus clearance in patients with CF from different age groups with differing disease severity. We also discuss the clinical use of these agents in the context of available international guidelines as well as practical considerations in the clinic, highlighting the importance of a multidisciplinary approach and shared decision‐making. Unanswered questions regarding the optimal use of these agents are highlighted.
A Multi-screening Evaluation of the Nutritional and Nutraceutical Potential of the Mediterranean Jellyfish Pelagia noctiluca

The phylum Cnidaria is one of the most important contributors in providing abundance of bio- and chemodiversity. In this study, a comprehensive chemical investigation on the nutritional and nutraceutical properties of Mediterranean jellyfish Pelagia noctiluca was carried out. Also, compositional differences between male and female organisms, as well as between their main anatomical parts, namely bell and oral arms, were explored in an attempt to select the best potential sources of nutrients and/or nutraceuticals from jellyfish. With the exception of higher energy densities and total phenolic contents observed in females than males, no statistically significant differences related to the specimen’s sex were highlighted for the other compound classes. Rather, the distribution of the investigated chemical classes varied depending on the jellyfish’s body parts. In fact, crude proteins were more abundant in oral arms than bells; saturated fatty acids were more concentrated in bells than oral arms, whereas polyunsaturated fatty acids were distributed in the exact opposite way. On the other hand, major elements and trace elements demonstrated an opposite behavior, being the latter most accumulated in oral arms than bells. Additionally, important nutraceuticals, such as eicosapentaenoic and docosahexaenoic acids, and antioxidant minerals, were determined. Overall, obtained data suggest the potential employment of the Mediterranean P. noctiluca for the development of natural aquafeed and food supplements.
Trends in pesticide suicide in South Korea, 1983–2014

Abstract Aims Self-poisoning using pesticides is among the major methods of suicide worldwide, and accounts for one-fifth of suicides in 2006–2010 in South Korea. We investigated long-term trends in pesticide suicide rates in South Korea and factors related to these trends. Methods We calculated age-standardised rates of pesticide suicide in South Korea (1983–2014) using registered death data. We used graphical approach and joinpoint regression analysis to examine secular trends in pesticide suicide by sex, age and area, and a time-series analysis to investigate association of pesticide suicide rate with socioeconomic and agriculture-related factors. Age, period and cohort effects were examined using the intrinsic estimator method. Results Age-standardised rate of pesticide suicide fluctuated between 1983 and 2000 before it markedly increased in 2000–2003 (annual percent change 29.7%), followed by a gradual fall (annual percent change −6.3%) in 2003–2011. Following the paraquat ban (2011–2012), there was a marked reduction (annual percent change −28.2%) in 2011–2014. Trend in pesticide suicide was associated with divorce rate but not with other factors studied. Declines in pesticide suicide in 2003–2011 were most noticeable in younger groups and metropolises; by contrast, elderly adults aged 70+ living in rural areas showed an upward trend until after the 2011–2012 paraquat ban, when it turned downward. In the age–period–cohort modelling, having been born between 1938 and 1947 was associated with higher pesticide suicide rates. Conclusions Pesticide suicide trend changed substantially in South Korea over the last three decades. Effective prevention should include close monitoring of trends and strong regulations of toxic pesticides.
Breathlessness and incidence of COPD, cardiac events and all-cause mortality: A 44-year follow-up from middle age throughout life

Background Breathlessness is prevalent in the general population and may be associated with adverse health outcomes. This study aimed to evaluate the association of breathlessness with Chronic Obstructive Pulmonary Disease (COPD) events, cardiac events and all-cause mortality from middle-age throughout life. Methods Breathlessness was measured in 699, 55-year old men residing in Malmö, Sweden using modified Medical Research Council (mMRC). COPD events (hospitalisation, death or diagnosis) cardiac events and all-cause mortality was assessed using The Swedish Causes of Death Register and Hospital Discharge Register. Data was analyzed using Cox- and competing risks (Fine-Gray) regression analysis. Results 695 (99%) of 699 participants died and four emigrated during follow up. Eighty-seven (12%) had mMRC = 1 and 19 (3%) had mMRC≥2. Breathlessness was associated with COPD events; adjusted Sub-Hazard Ratio 2.1 (95% CI, 1.2–3.6) for mMRC = 1 and 7.5 (2.6–21.7) for mMRC ≥ 2 but not associated with cardiac events when adjusting for competing events and confounding. Breathlessness was associated increased all- cause mortality (Hazard Ratios of 1.4 (1.1–1.7) (mMRC = 1) and 3.4 (2.1–5.6) (mMRC ≥ 2)). Conclusion Breathlessness is associated with increased risk of COPD events and increase in all-cause mortality from age 55 until death.
A novel berberine‐metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats

In this study, we investigated the biological activities of a novel berberine‐metformin hybrid compound (BMH473) as an anti‐diabetic agent. BMH473 exhibited significant anti‐hyperglycaemic and anti‐hyperlipidaemic effects on T2DM rats. In white adipose tissue, BMH473 reduced the perirenal and epididymal adipose tissue mass and modulated the lesions in perirenal adipose tissue, by inhibiting the protein expressions of PPAR‐Ɣ, C/EBP‐α and SREBP‐1c as well as the mRNA expressions of lipogenic genes. Moreover, BMH473 downregulated the levels of pro‐inflammatory cytokines in perirenal adipose tissue through the suppression of p‐NF‐κB. In liver, BMH473 reduced liver ectopic fat accumulation, by regulating the protein expression levels of SREBP‐1c and PPAR‐α as well as the mRNA expression levels of lipogenic genes. In addition, BMH473 inhibited hepatic gluconeogenesis by promoting the phosphorylation levels of AMPK α and ACC, and down‐regulating the mRNA expression levels of FBPase, G6Pase and PEPCK. Furthermore, BMH473 exhibited significant inhibitory effects on lipogenesis and lipid accumulation in 3T3‐L1 adipocytes by modulating the protein expression levels of PPAR‐Ɣ, C/EBP‐α and SREBP‐1 c as well as the mRNA expression levels of lipogenic genes. In conclusion, our results suggest that the newly synthesized BMH473 is beneficial for maintaining glucose and lipid homeostasis in type 2 diabetic rats, and exhibits better anti‐hyperlipidaemic effects compared to metformin and berberine.
Increased expression of neurotensin in high grade serous ovarian carcinoma with evidence of serous tubal intraepithelial carcinoma

High grade serous ovarian carcinoma (HGSC) without identifiable serous tubal intraepithelial carcinoma (STIC) within the fallopian tube (FT) occurs in approximately 50% of patients. The objective of this study was to use a multisite tumor sampling approach to study HGSC with and without STIC. RNAseq analysis of HGSC samples collected from multiple sites e.g. ovary, FT and peritoneum, revealed moderate levels of intrapatient heterogeneity in gene expression that could influence molecular profiles. Mixed‐model ANOVA analysis of gene expression in tumor samples from patients with multiple tumor sites (n = 13) and patients with a single site tumor sample (n = 11) to compare HGSC‐STIC to HGSC‐NOSTIC identified neurotensin (NTS) as significantly higher (> two‐fold change, False Discovery Rate (FDR) < 0.10) in HGSC‐STIC. This data was validated using publicly available RNA‐Seq datasets. Concordance between higher NTS gene expression and NTS peptide levels in HGSC‐STIC samples was demonstrated by immunohistochemistry. To determine the role of NTS in HGSC, five ovarian cancer (OvCa) cell lines were screened for expression of NTS and its receptors, NTSR1 and NTSR3. Increased expression of NTS and NSTR1 was observed in several of the OvCa cells, whereas the NTSR3 receptor was lower in all OvCa cells, compared to immortalized FT epithelial cells. Treatment with NTSR1 inhibitor (SR48692) decreased cell proliferation, but increased cell migration in OvCa cells. The effects of SR48692 were receptor mediated, since transient RNAi knockdown of NTSR1 mimicked the migratory effects and knockdown of NTSR3 mimicked the anti‐proliferative effects. Further, knockdown of NTSR1 or NTSR3 was associated with acquisition of distinct morphological phenotypes, epithelial or mesenchymal, respectively. Taken together, our results reveal a difference in a biologically active pathway between HGSC with and without STIC. Furthermore, we identify neurotensin signaling as an important pathway involved in cell proliferation and epithelial–mesenchymal transition in HGSC‐STIC which warrants further study as a potential therapeutic target. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Significance People may suffer large losses of mandibular (jaw) bone due to cancer, infection, trauma, congenital disease, or other disorders. The resulting bony defects are both aesthetically disfiguring and functionally disabling. We have designed a strategy to use biomaterials and 3D printing to leverage the body’s own innate healing capacity to generate customized engineered tissues that fit the patient’s defect. Using a large animal (sheep) model, we 3D printed bioreactors, filled them with biomaterial scaffold materials, and implanted them against the ribs to grow customized bony tissues. These tissues were then successfully surgically transplanted to repair a large defect in the sheep mandible. This approach results in tissue flaps with custom geometry and reduced risk of rejection. Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.