Miracle-dz/UniFAR-FTUs huggingface dataset:
Pulmonary hypertension in chronic heart failure: definitions, advances, and unanswered issues

Pulmonary hypertension (PH) is a common and severe complication of heart failure (HF). Consequently, HF is the leading cause of PH. For many years, specialists have attempted to better understand the pathophysiology of PH in HF, to define its prevalence and its impact on prognosis in order to improve the therapeutic management of these patients. Nowadays, despite the recent guidelines published on the subject, several points remain unclear or debated, and until now, no study has demonstrated the efficacy of any treatment. The aim of this review is to report the evolution of the concepts on post‐capillary PH (diagnosis, prevalence, prognosis, and therapeutics). The main issues are raised, focusing especially on the link between structural alterations and haemodynamic abnormalities, to discuss the possible reasons for treatment failures and future potential targets.
Higher event rate in patients with high-risk Duke Treadmill Score despite normal exercise-gated myocardial perfusion imaging

This prospective study was carried out to find the negative predictive value of various Duke Treadmill Scores (DTSs) in patients with normal myocardial perfusion imaging (MPI). This study was conducted from August 2012 to July 2015, and 603 patients having normal exercise MPIs were included. Patients were followed for 2 years for fatal myocardial infarction (FMI) and nonfatal myocardial infarction (NFMI). Follow-up was not available in 23 patients, leaving a cohort of 583 participants. DTS was low risk (≥5) in 286, intermediate risk (between 4 and − 10) in 211, and high risk (≤−11) in 86 patients. Patients with high- and intermediate-risk DTS were significantly elder than low-risk DTS cohort. Patients with high-risk DTS had significantly higher body mass index with male preponderance compared to other groups. No significant difference was found among three groups regarding modifiable or nonmodifiable risk factors and left ventricular ejection fraction. On follow-up, single FMI was observed in high-risk DTS group (log-rank test value = 5.779, P = 0.056). Five NFMI events were observed in high-risk DTS (94.2% survival; log-rank test value = 19.398, P = 0.0001; significant) as compared to two events each in low- and intermediate-risk DTS (nonsignificant). We conclude that patients with normal exercise MPI and low-to-intermediate risk DTS have significantly low NFMI. High-risk DTS despite normal exercise MPI had high NFMI. Further, validation studies to find the predictive value of symptomatic and asymptomatic ST deviation resulting in high-risk DTS in patients with normal exercise MPI are warranted.
Enhancement of Antibacterial Activity of Orange Oil in Pectin Thin Film by Microemulsion

The purpose of this study was to prepare orange oil microemulsion (ME) and to investigate the antimicrobial activity of film containing orange oil ME. First, surfactants and co-surfactants were screened on their efficiency to form ME using pseudo-ternary phase diagrams. The influences of surfactant and co-surfactant mass ratios were studied and optimized ME-loaded-films were prepared. Then, films containing orange oil ME were characterized by SEM and texture analyzer, and then evaluated for antimicrobial activity against Staphylococcus aureus and Propionibacterium acnes using an agar disc diffusion method. The results showed that Tween 80 as surfactant and propylene glycol as co-surfactant at a 1:1 ratio possessed the maximum ME area. Three ME formulations of ME 20, ME 25, and ME 30, which consisted of 20, 25, and 30% w/v of orange oil were prepared, respectively. All ME formulations showed particle sizes of about 60.26⁻80.00 nm, with broad a polydispersity index of 0.42. The orange oil ME films exhibited higher elastic values than the control. The diameters of inhibition zones for FME 20, FME 25, and FME 30 against P. acnes were 13.64, 15.18, and 16.10 mm, respectively. Only the FME 30 had an antimicrobial activity against S. aureus with 8.32 mm of inhibition zone. Contrarily, the control film had no antimicrobial activity against both bacteria. In conclusion, the present study found that the antibacterial activity of orange oil in pectin thin film could be enhanced by preparing orange oil as an ME before loading into pectin thin film.
Lactobacillus plantarum LRCC 5273 isolated from Kimchi ameliorates diet-induced hypercholesterolemia in C57BL/6 mice

ABSTRACT This study was designed to select potent cholesterol-lowering probiotic strains on HepG2 cell and investigate the effect of selected strain, Lactobacillus plantarum LRCC 5273 and LRCC 5279 in hypercholesterolemic mice. In the results, LP5273 group showed significantly reduced total and LDL cholesterol compared to HCD group. In addition to significantly up-regulated hepatic mRNA expression of LXR-α and CYP7A1, intestinal LXR-α and ABCG5 were significantly up-regulated in LP5273 group. With activation of hepatic and intestinal LXR-α and its target genes, fecal cholesterol and bile acid excretion were increased in LP5273 fed mice. These results suggest that LP5273 ameliorates hypercholesterolemia in mice through the activation of hepatic and intestinal LXR-α, resulting in enhancement of fecal cholesterol and bile acids excretion in the small intestine. The results of present study suggest mechanistic evidences for hypocholesterolemic effects of L. plantarum spp. , and may contribute to future researches for prevention of hypercholesterolemia and cardiovascular disease. Graphical Abstract LP5273 ameliorates hypercholesterolemia through the activation of hepatic and intestinal LXR-alpha, resulting in enhancement of fecal cholesterol and bile acids excretion.
Does the level of forage neutral detergent fiber affect the ruminal fermentation, digestibility and feeding behavior of goats fed cactus pear?

This study aimed to evaluate the effects of forage neutral detergent fiber (fNDF) levels on the voluntary feed intake, digestibility, ruminal fermentation and feeding behavior of goats fed diets with cactus pear. Five non-lactating ruminally cannulated goats fed ad libitum were randomly assigned to a 5 × 5 Latin square design. Treatments consisted of levels of fNDF at 0, 109, 222, 339 and 463 g/kg of dry matter (DM) in cactus pear-based diets. The intakes of DM and NDF were quadratically affected (p ≦ .045) by fNDF levels. Voluntary water intake (VWI) increased linearly as the fNDF levels increased in the diet. The digestibility coefficients of organic matter, NDF and ether extract and total digestible nutrients concentration were quadratically affected (p ≦ .048) by fNDF levels. The ruminal pH linearly increased (p = .001) with fNDF levels, ranging from 5.44 to 5.81 for diets containing 0 and 463 g fNDF/kg DM, respectively. The fNDF levels promoted a linear increase (p = .006) in chewing time, linearly decreased (p = .007) resting time and quadratically affected (p = .033) rumination time. The inclusion of fNDF in the diets provided favorable conditions for ruminal function, digestibility and feeding behavior in goats fed diets containing cactus pear.
Isolation of improved free fatty acid overproducing strains of Escherichia coli via nile red based high‐throughput screening

Biological production of hydrocarbons is an attractive strategy to produce drop‐in replacement transportation fuels. Several methods for converting microbially produced fatty acids into reduced compounds compatible with petrodiesel have been reported. For these processes to become economically viable, microorganisms must be engineered to approach the theoretical yield of fatty acid products from renewable feedstocks such as glucose. Strains with increased titers can be obtained through both rational and random approaches. While powerful, random approaches require a genetic selection or facile screen that is amenable to high throughput platforms. Here, we present the use of a high throughput screen for fatty acids based on the hydrophobic dye Nile red. The method was applied to screening a transposon library of a free fatty acid overproducing strain of Escherichia coli in search of high producing mutants. Ten gene targets were identified via primary and secondary screening. A strain comprising a clean knockout of one of the identified genes led to a 20% increase in titer over the baseline strain. A selection strategy that combines these findings and can act in an iterative fashion has been developed and can be used for future strain optimization in hydrocarbon producing strains. © 2011 American Institute of Chemical Engineers Environ Prog, 2012
Positive antenatal Edinburgh Depression Scale: examining behavioral and pharmacological therapy on maternal and neonatal outcomes

Abstract Objective: We hypothesized that women with a positive antenatal Edinburgh Depression Screen (EPDS) (≥10), undergoing behavioral or pharmacologic therapy have improved maternal and neonatal outcomes. Study design: This is a retrospective study of singleton pregnancies at UC, San Diego from 2010 to 2014. Patients with an antenatal EPDS were subdivided based on their intervention: negative score, positive score no treatment, behavioral therapy only, and pharmacologic therapy. The primary outcome was rate of preterm birth with secondary outcomes of maternal and neonatal outcomes. Results: Patients with a positive EPDS had a higher rate of preterm delivery, small-for-gestational age, NICU admission and Apgar score <7. Rates of adverse outcomes were highest among women receiving pharmacologic therapy. Rates of adverse outcomes women were not increased in the behavioral therapy group compared to the negative EPDS group. When adjusting for confounding variables, patient with a positive EPDS were more likely deliver preterm with an adjusted odds ratio of 1.71. Among varying treatment modalities, the odds ratio for preterm delivery was not statistically significant. Conclusion: Adverse pregnancy outcomes were highest among those requiring pharmacotherapy. Behavioral therapy had a positive effect on outcomes. Intervention to reduce these adverse outcomes in these patients needs further study.
Does tDCS over prefrontal cortex improve episodic memory retrieval? Potential importance of time of day

ABSTRACT We report 4 experiments aiming to replicate and extend the finding that anodal transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex after encoding and just prior to retrieval improves accuracy on an episodic recollection task. Our first 3 experiments failed to replicate the tDCS effect in planned analyses, but post-hoc analyses uncovered tDCS effects on recollection accuracy during morning sessions. To further investigate, Experiment 4 randomly assigned participants to morning or afternoon sessions. As predicted, tDCS (compared to sham stimulation) improved recollection accuracy in the morning. We hypothesize that tDCS effects are easier to detect during nonoptimal cognitive processing times (e.g., mornings for younger adults). Importantly, we found both significant and null tDCS results across our experiments, indicating that more research is needed to determine the extent that anodal tDCS to left prefrontal cortex reliably improves recollection accuracy at different stimulation times.
Clinical Impact of the Immune Microenvironment in Spinal Chordoma: Immunoscore as an Independent Favorable Prognostic Factor.

BACKGROUND Currently, clinical implications of immune system cells in chordoma remain to be elucidated. OBJECTIVE To characterize in situ immune cell infiltrates, the Immunoscore, and investigate their correlation with clinicopathologic data of spinal chordoma patients and outcome. METHODS Tumor-infiltrating lymphocytes (TILs) subtypes were assessed in 54 tumor specimens using immunohistochemistry for CD3, CD4, CD8, CD20, Foxp3, PD-1, and PD-L1. RESULTS Overall, immune cell infiltrates were present in all samples and there was low or moderate correlation among several TILs subsets. PD-1+ TILs density, CD3+, and CD8+ TILs densities in the tumor interior (TI) subarea were associated with surrounding muscle invasion by tumor, whereas PD-L1+ TILs showed inverse association with tumor pathological grade and stage. The density of PD-1+ TILs, PD-L1+ TILs, CD4+ TILs, and CD3+ TILs both in the TI and combined tumor regions (TI and invasion margin) were significantly associated with local recurrence-free survival and overall survival (OS). However, Foxp3+ TILs (P = .024) and CD8+ TILs evaluated in the TI (P < .001) only correlated with OS. The Immunoscore predicted less aggressive clinical features and favorable outcomes. Patients with an Immunoscore of 4 had a median OS of 128 mo, while I0 (Immunoscore of 0) patients survived only 27 mo. Multivariate analysis demonstrated that the Immunoscore was an independent favorable prognostic factor of both local recurrence-free survival (P = .026) and OS (P = .046). CONCLUSION Our data suggest a clinically relevant role of the immune microenvironment in spinal chordoma and identify the Immunoscore as promising prognostic marker.
Detection of exosome miRNAs using molecular beacons for diagnosing prostate cancer

Abstract Prostate cancer is the fifth leading cause of cancer-related deaths among males worldwide. However, the biomarker for diagnosing prostate cancer that is used currently has limitations that must be overcome. Recently, several studies have demonstrated that the cancer liquid biopsy can be implemented by using exosome miRNAs. However, the current methods for the detection of exosome miRNAs are time-consuming, expensive, and laborious. Thus, we investigated a novel method for diagnosing prostate cancer that involves the use of molecular beacons for the in situ detection of miRNAs in exosomes from prostate cancer cells. We chose miRNA-375 and miRNA-574-3p as the target miRNAs for prostate cancer, and these markers in exosomes produced by prostate cancer cells including DU145 and PC-3 were successfully detected using molecular beacons. High fluorescent signals were obtained from MB and miRNA hybridization in exosomes in a concentration-dependent manner. In addition, exosome miRNAs can be detected even in the presence of human urine, so this method can be applied directly using human urine to perform liquid biopsies for prostate cancer. Overall, the in situ detection of exosome miRNAs using molecular beacons can be developed as a simple, cost effective, and non-invasive liquid biopsy for diagnosing prostate cancer.
The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

Abstract Background: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. Methods: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel–Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. Results: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). Conclusion: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.
Short and long-term effects of a synbiotic on clinical signs, the fecal microbiome, and metabolomic profiles in healthy research cats receiving clindamycin: a randomized, controlled trial

Background Antibiotic-associated gastrointestinal signs (AAGS) occur commonly in cats. Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. The purpose of this double-blinded randomized-controlled trial was to compare AAGS and the fecal microbiome and metabolome between healthy cats that received clindamycin with a placebo or synbiotic. Methods 16 healthy domestic shorthair cats from a research colony were randomized to receive 150 mg clindamycin with either a placebo (eight cats) or commercially-available synbiotic (eight cats) once daily for 21 days with reevaluation 603 days thereafter. All cats ate the same diet. Food consumption, vomiting, and fecal score were recorded. Fecal samples were collected daily on the last three days of baseline (days 5–7), treatment (26–28), and recovery (631–633). Sequencing of 16S rRNA genes and gas chromatography time-of-flight mass spectrometry was performed. Clinical signs, alpha and beta diversity metrics, dysbiosis indices, proportions of bacteria groups, and metabolite profiles were compared between treatment groups using repeated measures ANOVAs. Fecal metabolite pathway analysis was performed. P < 0.05 was considered significant. The Benjamini & Hochberg’s False Discovery Rate was used to adjust for multiple comparisons. Results Median age was six and five years, respectively, for cats in the placebo and synbiotic groups. Hyporexia, vomiting, diarrhea, or some combination therein were induced in all cats. Though vomiting was less in cats receiving a synbiotic, the difference was not statistically significant. Bacterial diversity decreased significantly on days 26–28 in both treatment groups. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with incomplete normalization by days 631–633. Derangements in short-chain fatty acid, bile acid, indole, sphingolipid, benzoic acid, cinnaminic acid, and polyamine profiles also occurred, some of which persisted through the terminal sampling timepoint and differed between treatment groups. Discussion Cats administered clindamycin commonly develop AAGS, as well as short- and long-term dysbiosis and alterations in fecal metabolites. Despite a lack of differences in clinical signs between treatment groups, significant differences in their fecal metabolomic profiles were identified. Further investigation is warranted to determine whether antibiotic-induced dysbiosis is associated with an increased risk of future AAGS or metabolic diseases in cats and whether synbiotic administration ameliorates this risk.
Reduction of Driveline Infections through Doubled Driveline Tunneling of Left Ventricular Assist Devices—Five-Year Follow-up

Background Driveline infection (DLI) is one of the leading causes for unplanned re-admissions of patients undergoing therapy with left ventricular assist devices (LVAD). In previous studies our group was able to show that a double tunneling implantation technique could significantly reduce infection rates one year after implantation. We now report the results of the five-year-follow up of patients receiving the double tunneling technique. Methods We retrospectively analyzed patients receiving LVAD therapy with the HeartWare ventricular assist device (HVAD) (Medtronic, Minnesota, MN, USA) LVAD. For 36 patients (group 1) the driveline was tunneled via a conventional technique. In the remaining 33 patients (group 2) the drivelines were implanted by means of a double tunneling technique. The double tunnel driveline technique involved placement of the driveline in the sheath of the rectus muscle in the umbilical direction and then subcutaneously to the left (alternatively right) upper quadrant. We retrospectively compared both groups. Primary outcome parameters were infection rate and mortality. Results Five years after LVAD implantation the DLI rate of patients operated by a double tunneling technique was significantly lower than in the conventional technique group [61% (n=22) group 1 vs. 30% (n=10) group 2, P=0.004]. The 5-year mortality was lower in group 2 [42% (n=15) group 1 vs. 27% (n=9) group 2] but did not achieve statistical significance (P=0.10). The days of LVAD support between the two groups were comparable (1,275.56±885.89 group 1 vs. 1,321.94±711.37 group 2). The tunnel technique itself showed to be strongly associated with the occurrence of DLI. Other elevated variables are liver disease and dilated cardiomyopathy as primary disease. Conclusions Double tunneling technique for driveline implantation leads to significantly lowered infection rates after 5 years of LVAD therapy and it is associated with a lower mortality.
Biocompatibility of mineral trioxide aggregate flow and biodentine

AIM To evaluate the influence of powder-to-gel ratio (0.19 g powder to 50 μL of gel, thick MTA Flow, and 0.06 g powder to 50 μL of gel, fluid MTA Flow) on biocompatibility of MTA Flow (Ultradent Products Inc., South Jordan, UT, USA, lot: 2015122901) and compare it with Biodentine (Septodont Inc., Saint-Maur-des-Fossés, France, lot: B18542A). METHODOLOGY The materials were manipulated and inserted into polyethylene tubes for implantation in twenty rats. After 7, 15, 30 and 60 days, the specimens were removed and embedded in paraffin. Haematoxylin and eosin sections were used to count the number of inflammatory cells (IC) and fibroblasts mm-2 (Fb). In the Masson's trichrome-stained sections, the fibrous capsule thickness was measured; picrosirius red-stained sections were used for birefringent collagen quantification. The data were submitted to two-way ANOVA and Tukey test (P ≤ 0.05). RESULTS A significantly lower number of IC and consequently higher number of Fb were observed in the capsules adjacent to thick MTA Flow at all periods, in comparison with other materials (P ≤ 0.05). At 60 days, the quantity of birefringent collagen was significantly greater in the tissue in contact with thick MTA Flow, when compared with fluid MTA Flow and Biodentine. CONCLUSIONS Although thick MTA Flow induced a less intense inflammatory response, all evaluated materials are biocompatible because they allowed regression of this process after 60 days.