Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk factors for breast cancer brain metastases: a systematic review

Background: Brain metastasis (BM) is an increasingly common and devastating complication of breast cancer (BC). Methods: A systematic literature search of EMBASE and MEDLINE was conducted to elucidate the current state of knowledge on known and novel prognostic factors associated with 1) the risk for BCBM and 2) the time to brain metastases (TTBM). Results: A total of 96 studies involving institutional records from 28 countries were identified. Of these, 69 studies reported risk factors of BCBM, 46 factors associated with the TTBM and twenty studies examined variables for both outcomes. Young age, estrogen receptor negativity (ER-), overexpression of human epidermal factor (HER2+), and higher presenting stage, histological grade, tumor size, Ki67 labeling index and nodal involvement were consistently found to be independent risk factors of BCBM. Of these, triple-negative BC (TNBC) subtype, ER-, higher presenting histological grade, tumor size, and nodal involvement were also reported to associate with shorter TTBM. In contrast, young age, hormone receptor negative (HR-) status, higher presenting stage, nodal involvement and development of liver metastasis were the most important risk factors for BM in HER2-positive patients. Conclusions: The study provides a comprehensive and individual evaluation of the risk factors that could support the design of screening tools and interventional trials for early detection of BCBM.
miR-584 inhibits cell proliferation, migration and invasion in vitro and enhances the sensitivity to cisplatin in human cervical cancer by negatively targeting GLI1

Cervical cancer is the most lethal malignancy amongst women worldwide. MicroRNAs (miRNAs/miRs) play a critical role in the progression of cervical cancer. Compelling evidence indicates that miR-584 acts as a tumor suppressor in some types of cancers. However, the function of miR-584 in cervical cancer has not been illustrated. In the present study, the effects and mechanism of miR-584 in the process of proliferation, migration and invasion, and drug sensitivity to cisplatin in cervical cancer were determined. miR-584 expression decreased markedly in cervical cancer tissues and cell lines compared with healthy control samples. Dual-luciferase reporter assays confirmed that glioma-associated oncogene 1 (GLI1) is a novel molecular target of miR-584. The overexpression of miR-584 inhibited the expression of GLI1, reduced cell proliferation, migration and invasion, and induced apoptosis in HeLa cells. However, the silencing of miR-584 in CaSki cells produced the opposite effects. In addition, the overexpression of GLI1 in HeLa-cells overexpressing miR-584 markedly reversed the miR-584-induced inhibitory effect. Flow cytometry results showed that miR-584 enhanced cisplatin sensitivity by promoting chemotherapy-induced apoptosis. Therefore, miR-584 acted as a tumor suppressor miRNA and might be a novel target gene for future cervical cancer treatments.
No island-effect on glucocorticoid levels for a rodent from a near-shore archipelago

Island rodents are often larger and live at higher population densities than their mainland counterparts, characteristics that have been referred to as “island syndrome”. Island syndrome has been well studied, but few studies have tested for island-mainland differences in stress physiology. We evaluated island syndrome within the context of stress physiology of white-footed mice (Peromyscus leucopus) captured from 11 islands and five mainland sites in Thousand Islands National Park, Ontario, Canada. Stress physiology was evaluated by quantifying corticosterone (a stress biomarker), the primary glucocorticoid in mice, from hair and its related metabolites from fecal samples. White-footed mice captured in this near-shore archipelago did not display characteristics of island syndrome, nor differences in levels of hair corticosterone or fecal corticosterone metabolites compared with mainland mice. We suggest that island white-footed mice experience similar degrees of stress in the Thousand Islands compared with the mainland. Although we did not find evidence of island syndrome or differences in glucocorticoid levels, we identified relationships between internal (sex, body mass) and external (season) factors and our hormonal indices of stress in white-footed mice.
Prognostic Values of LDH and CRP in Cervical Cancer

Purpose Cervical cancer is one of the deadliest tumors among women in China. C-reactive protein (CRP), an indicator of inflammation, and lactate dehydrogenase (LDH), an enzyme ubiquitously expressed in cells, both play important roles in tumor growth and metastasis. Patients and Methods Based on pre-radiotherapy LDH and CRP median levels, we divided patients into four groups: high LDH and CRP group, high LDH group, high CRP group, and low LDH and CRP group. Then, based on pre-/post-radiotherapy LDH and CRP ratios, we divided patients into four groups: high LDH and CRP ratio group, high LDH ratio group, high CRP ratio group, and low LDH and CRP ratio group. Kaplan–Meier (KM) curves were constructed to show overall survival (OS). A multivariate Cox regression model was employed to identify the independent risk factors. Results High pre-radiotherapy LDH and CRP levels and increased pre-/post-radiotherapy LDH and CRP ratios were correlated with worst OS compared with the other three groups. Conclusion LDH and CRP were correlated with outcomes in patients with locally advanced cervical cancer.
Using Satellite AIS to Analyze Vessel Speeds Off the Coast of Washington State, U.S., as a Risk Analysis for Cetacean-Vessel Collisions

Most species of whales are vulnerable to vessel collisions, and the probability of lethality increases logistically with vessel speed. An Automatic Identification System (AIS) can provide valuable vessel activity data, but terrestrial-based AIS has a limited spatial range. As the need for open ocean monitoring increases, AIS broadcasts relayed over earth-orbiting satellites, satellite AIS (SAIS), provides a method for expanding the range of AIS broadcast reception. We used SAIS data from 2013 and 2014 to calculate vessel density and speed over ground around the coast of Washington state in the northwestern United States. Nearby shipping lanes connecting the Ports of Seattle, Tacoma, Portland, and in Canada, Vancouver, have the greatest density of vessel traffic arriving and departing. Knowledge of shipping activity is important in this area due to the nearby presence of NOAA designated Cetacean Density and Distribution Working Group’s Biologically Important Areas (BIA) for large whale species vulnerable to vessel collisions. We quantified density and speed for each vessel type that transits through BIA’s. We found that cargo and tanker vessels traveled the farthest distance at the greatest speeds. As ship-strike risk assessments have traditionally relied on terrestrial AIS, we explored issues in the application of SAIS data. Temporal gaps in SAIS data led to a resulting systematic underestimation of vessel speed in calculated speed over ground. However, SAIS can be helpful in documenting minimum vessel speeds across large geographic areas and across national boundaries, especially beyond the reach of terrestrial AIS receivers. SAIS data can also be useful in examining vessel density at broad scales and could be used to assess basin-wide open ocean routes. Future use of additional satellite platforms with AIS receivers and technological advances will help rectify this issue and improve data coverage and quality.
Dual-Ligand Functionalized Core-Shell Chitosan-Based Nanocarrier for Hepatocellular Carcinoma-Targeted Drug Delivery

Introduction Hepatocellular carcinoma represents a major health problem with the related death numbers still increasing. Active targeting is considered an attractive choice for the development of selective therapeutics with limited side effects and improved efficiency. In this study, we report the design, development and evaluation of a novel dual-ligand functionalized core-shell chitosan-based nanocarrier for the selective delivery of doxorubicin (DOX) for treatment of hepatocellular carcinoma (HCC). Methods Following factorial design experiments, DOX was initially complexed with negatively charged carboxymethyl chitosan-g-poly(acrylate) and then the complex was coated with a positively charged dual-ligand (lactobionic acid and glycyrrhetinic acid)-conjugated chitosan. The developed active targeting system was then tested in vitro on Hep-G2 cells using flow cytometry and fluorescence imaging. Results The obtained results proved the ability of the dual-ligand system to enhance the intracellular uptake of the drug by 4-fold and 8-fold after 4 hrs and 24 hrs of incubation, respectively. The efficiency of the dual-ligand functionalized nanoparticles was also tested in vivo on Wistar rats with induced liver tumors. Testing of serum biomarkers (albumin, creatinine, urea, alpha fetoprotein, ALT, AST and ALP) in addition to histopathological microscopic examination of liver, kidney and heart tissues confirmed the enhanced safety of the developed targeted nanocarrier system compared to the conventional DOX. Discussion The developed targeted system showed improved intracellular drug delivery and uptake as well as enhanced safety profile. The nanoparticles were formed based on electrostatic interactions providing the flexibility that allows their use as a model for delivery of other drugs and other targets.
Comparison of Pharmacokinetics of a Fixed-Dose Combination of Amlodipine/Losartan/Rosuvastatin with Concomitant Administration of Amlodipine/Losartan and Rosuvastatin in Healthy Volunteers

Background A fixed-dose combination (FDC) tablet formulation of amlodipine/losartan/rosuvastatin 5/100/20 mg was developed to improve medication compliance in patients with both hypertension and dyslipidemia. The comparative pharmacokinetic study was performed to compare the profile of an FDC tablet formulation of amlodipine/losartan/rosuvastatin with that of concomitant administration of a currently marketed FDC tablet of amlodipine/losartan with a rosuvastatin tablet. Subjects and Methods A randomized, open-label, single oral dose, two-way crossover study was conducted in 60 healthy subjects. Subjects were orally administered the FDC tablet of amlodipine/losartan/rosuvastatin and a loose combination (LC) of two tablets comprising an FDC of amlodipine/losartan and rosuvastatin. Blood samples were collected for up to 144 h post dose for pharmacokinetic evaluations. Plasma concentrations of amlodipine, losartan, EXP3174 (an active metabolite of losartan), and rosuvastatin were measured by using liquid chromatography-tandem mass spectrometry. The geometric mean ratio (GMR) and its 90% confidence interval (90% CI) in the FDC treatment to LC treatment for the area under the concentration-time curve from zero to the last quantifiable time point (AUClast) and the maximum plasma concentration (Cmax) were calculated. Safety was monitored throughout the study. Results The GMR (90% CI) values of AUClast and Cmax were 0.9946 (0.9663–1.0238) and 0.9690 (0.9379–1.0011) for amlodipine, 0.9855 (0.9422–1.0308) and 0.9178 (0.8349–1.0089) for losartan, 0.9814 (0.9501–1.0136) and 0.9756 (0.9313–1.0219) for EXP3174, and 0.9448 (0.8995–0.9923) and 0.9609 (0.8799–1.0494) for rosuvastatin, respectively. No clinically significant changes were observed in any of the safety parameters, including clinical laboratory tests, vital signs, electrocardiograms, and physical examinations, between the FDC treatment and the LC treatment. Conclusion We confirmed the pharmacokinetic equivalence of the FDC and LC treatments. This triple combination FDC formulation could be a clinically useful replacement for LC therapy.
Proof of the elusive high-temperature incommensurate phase in CuO by spherical neutron polarimetry

After three decades of research on CuO, the AF3 phase is proven by neutrons, which clears up the mystery of symmetry-broken phases. CuO is the only known binary multiferroic compound, and due to its high transition temperature into the multiferroic state, it has been extensively studied. In comparison to other prototype multiferroics, the nature and even the existence of the high-temperature incommensurate paraelectric phase (AF3) were strongly debated—both experimentally and theoretically—since it is stable for only a few tenths of a kelvin just below the Néel temperature. Until now, there is no proof by neutron diffraction techniques owing to its very small ordered Cu magnetic moment. Here, we demonstrate the potential of spherical neutron polarimetry, first, in detecting magnetic structure changes, which are not or weakly manifest in the peak intensity and, second, in deducing the spin arrangement of the so far hypothetic AF3 phase. Our findings suggest two coexisting spin density waves emerging from an accidental degeneracy of the respective states implying a delicate energy balance in the spin Hamiltonian.
Isolation of a Novel Jumbo Bacteriophage Effective Against Klebsiella aerogenes

Increasing levels of bacterial resistance to many common and last resort antibiotics has increased interest in finding new treatments. The low rate of approval of new antibiotics has led to the search for new and alternative antimicrobial compounds. Bacteriophages (phages) are bacterial viruses found in almost every environment. Phage therapy was historically investigated to control bacterial infections and is still in use in Georgia and as a treatment of last resort. Phage therapy is increasingly recognized as an alternative antimicrobial treatment for antibiotic resistant pathogens. A novel lytic Klebsiella aerogenes phage N1M2 was isolated from maize silage. Klebsiella aerogenes, a member of the ESKAPE bacterial pathogens, is an important target for new antimicrobial therapies. Klebsiella aerogenes can form biofilms on medical devices which aids its environmental persistence and for this reason we tested the effect of phage N1M2 against biofilms. Phage N1M2 successfully removed a pre-formed Klebsiella aerogenes biofilm. Biofilm assays were also carried out with Staphylococcus aureus and Phage K. Phage K successfully removed a preformed Staphylococcus aureus biofilm. Phage N1M2 and Phage K in combination were significantly better at removing a mixed community biofilm of Klebsiella aerogenes and Staphylococcus aureus than either phage alone.
Future Meteorological Droughts in Ecuador: Decreasing Trends and Associated Spatio-Temporal Features Derived From CMIP5 Models

Droughts are one of the most spatially extensive disasters that are faced by societies. Despite the urgency to define mitigation strategies, little research has been done regarding droughts related to climate change. The challenges are due to the complexity of droughts and to future precipitation uncertainty from Global Climate Models (GCMs). It is well-known that climate change will have more impact on developing countries. This is the case for Ecuador, which also has the additional challenges of lacking meteorological drought studies covering its three main regions: Coast, Highlands, and Amazon, and of having an intricate orography. Thus, this study assesses the spatio-temporal characteristics of present and future droughts in Ecuador under Representative Concentrations Pathways (RCP) 4.5 and 8.5. The 10 km dynamically downscaled products (DGCMs) from Coupled Model Intercomparison Project 5 (CMIP5) was used. The Standardized Precipitation Index (SPI) for droughts was calculated pixel-wise for present time 1981–2005 and for future time 2041-2070. The results showed a slightly decreasing trend for future droughts for the whole country, with a larger reduction for moderate droughts, followed by severe and extreme drought events. In the Coast and Highland regions, the intra-annual analysis showed a reduction of moderate and severe future droughts for RCP 4.5 and for RCP 8.5 throughout the year. Extreme droughts showed small and statistically non-significant decreases. In the Amazon region, moderate droughts showed increases from May to October, and decreases for the rest of the year. Additionally, severe drought increases are expected from May to December, and decreases from January to April. Finally, extreme drought increases are expected from January to April, with larger increases in October and November. Thus, in the Amazon, the rainy period showed a decreasing trend of droughts, following the wetter in wet- and drier in dry paradigm. Climate change causes decision-making process and calls for adaptation strategies being more challenging. In this context, our study has contributed to better mapping the space-time evolution of future drought risk in Ecuador, thus providing valuable information for water management and decision making as Ecuador faces climate change.
Violent Behavior Is Associated With Emotion Salience Network Dysconnectivity in Schizophrenia

Background: Despite individuals with schizophrenia being at an elevated risk of violence compared to the general population, limited efforts have been invested in investigating the neurobiological etiology explaining the increase. Among the few studies examining functional disruptions pertaining to violent schizophrenia patients using fMRI, only one study has considered functional connectivity. The current state of knowledge does not allow to infer deficits in functional connectivity specific to distinct cognitive/emotional states that have been associated with the emergence of violence in schizophrenia, such as negative emotion processing. This study sought to identify disrupted connectivity among men with schizophrenia and a history of violence (SCZ+V), compared to men with schizophrenia without a history of violence (SCZ-V) and healthy controls, during negative emotion processing using fMRI. Methods: Twenty SCZ+V, 19 SCZ-V, and 21 healthy men were scanned while viewing negative images. Results: Negative images elicited an increased connectivity between the dorsal anterior cingulate cortex (dACC) and the bilateral rostral prefrontal cortex (rPFC), as well as a decreased functional connectivity between the frontal regions (bilateral rPFC and dACC) and the putamen and hippocampus in SCZ+V men as compared to SCZ-V men and healthy controls. Concurrently, the centrality of the dACC within the network was reduced in SCV+V subjects. Conclusions: These results suggest an inefficient integration of the information by the dACC between frontal and limbic regions in SCZ+V men during negative emotion processing and highlight the importance of the ACC in the neurobiological bases of violent behavior in schizophrenia.
Depressive Symptoms, Sleep Profiles and Serum Melatonin Levels in a Sample of Breast Cancer Patients

Background Chronobiological changes have been detected in various physiological functions of patients with breast cancer, suggesting dysregulation in the pineal gland and melatonin secretion. This study aimed to assess and measure serum melatonin levels pre- and postoperatively in patients who had been diagnosed for the first time with breast cancer. Methods A sample of first-time breast cancer patients, consisting of 45 women aged 25–65 years, was evaluated and psychometric assessment was completed using the Beck Depression Inventory (BDI), Insomnia Severity Index (White, Weinberg et al) and the Epworth Sleepiness Scale (Cardoso, Spence et al). The Morningness-Eveningness questionnaire (MEQ) was used to assess the chronotype. Serum melatonin levels were measured by radioimmunoassay. Results Morning and moderately morning chronotypes were prevalent among the sample (25%, 45.8%, respectively). The finding of a mean BDI score of 13.5±11.2 indicated that depressive symptoms were prevalent among the sample. Despite the finding that a mean of the participants apparently had no symptoms of daytime sleepiness (the mean and standard deviations of the ESS were 7.5±4.4), scores on the ISI (a mean of 16.7±SD 7.3) indicated that insomnia symptoms were prevalent in the sample. Melatonin levels showed an inverse relationship with insomnia severity as measured by the ISI and depression severity, as assessed by the BDI. The postoperative melatonin levels were higher than the preoperative levels. Additionally, the psychometric profile differed among various pathological types of breast cancer according to their hormone receptor profile. Conclusion Serum melatonin levels correlated significantly with self-reported sleep quality and psychometric profiles of depression in the present sample of breast cancer patients. The melatonin assay, which is relatively easy to carry out, provided a convenient, objective measure of an important biological correlate of sleep quality and depression. This assay thus represented a confirmatory alternative to the self-report instruments, which may sometimes be unreliable. Future studies should further evaluate the utility of melatonin measures in psychiatric and sleep complaints of breast cancer patients.
Identification and Characterization of a Non-muscular Myostatin in the Nile Tilapia

The growth and differentiation factor Myostatin (MSTN, also known as GDF8) negatively regulates skeletal muscle development and growth in vertebrates. Most fish genomes contain two or more mstn genes, which are expressed in muscle and other tissues. Yet, in the genome of Nile tilapia (Oreochromis niloticus), which is one of the world's most important aquaculture fish species, only one mstn gene has previously been identified. Here, we identify a second mstn gene in Nile tilapia. We show that it clusters phylogenetically with other piscine mstn2 genes and that it shares chromosomal synteny with the human and zebrafish orthologs. We further show that mstn2 is not expressed in red or white muscles of Nile tilapia, but rather that its main site of expression is the brain. To determine which physiological functions are correlated with mstn expression, adult Nile tilapia were exposed to various environmental conditions and their effect on mstn1 and mstn2 expression in the brain and muscles was measured using real-time PCR. We found that the centrally- and muscle-expressed mstn genes differ in their responsiveness to diverse challenges, suggesting differential gene- and tissue-specific regulation of their expression. Metabolic and stress marker analyses showed that the altered mstn expression is not regulated by classical stress response. Taken together, our findings expand the understanding of the MSTN system in Nile tilapia and provide evolutionary insight into its function.
Oral Probiotics Alleviate Intestinal Dysbacteriosis for People Receiving Bowel Preparation

Background: Bowel preparation is necessary for successful colonoscopy, while it can seriously affect intestinal microbial composition and damage the intestinal mucosal barriers in humans. Methods: To figure out whether probiotics can sustain intestinal homeostasis and guard people's health, the probiotic drug of Bifidobacterium Tetragenous viable Bacteria Tablets (P group, n = 16) or placebo (C group, n = 16) was used for volunteers receiving bowel preparation, and high-throughput sequencing method was applied to monitor their intestinal microbial changes. Results: The present results suggested that bowel preparation obviously reduced the intestinal microbial diversity, while taking probiotics significantly restored it to normal level. In addition, probiotics sharply reduced the abundance of pathogenic Proteobacteria, and obviously lowered the ratio of Firmicutes/Bacteroidetes compared with control group at phylum level (P < 0.05). And probiotics markedly decreased the abundance of pathogenic Acinetobacter and Streptococcus, while greatly enriched the relative abundance of beneficial bacteria Bacteroides, Roseburia, Faecalibacterium, and Parabacteroides at genus level (P < 0.05). Conclusion: Probiotic drugs, e.g., Bifidobacterium Tetragenous viable Bacteria Tablets, can be used to restore intestinal dysbacteriosis caused by bowel preparation, and reduce side effects during colonoscopy.