Miracle-dz/UniFAR-FTUs huggingface dataset:
Ozone-primed neutrophils promote early steps of tumour cell metastasis to lungs by enhancing their NET production

Background Air pollution, including particulates and gazes such as ozone (O3), is detrimental for patient’s health and has repeatedly been correlated to increased morbidity and mortality in industrialised countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O3 exposure and metastatic dissemination to lungs. Objectives To outline the mechanisms through which pulmonary O3 exposure modulates metastasis kinetics in an experimental mouse model of O3 exposure. Methods Metastatic responses to pulmonary O3 exposure were assessed using a reliable experimental mouse model of concomitant pulmonary O3 exposure and tumour cell injection. Roles of neutrophils in O3-induced lung metastasis were highlighted using blocking anti-Ly6G antibodies; moreover, the implication of neutrophil extracellular traps (NETs) in metastatic processes was evaluated using MRP8cre-Pad4lox/lox mice or by treating mice with DNase I. Results Pulmonary O3 exposure strongly facilitates the establishment of lung metastasis by (1) Inducing a pulmonary injury and neutrophilic inflammation, (2) Influencing very early steps of metastasis, (3) Priming neutrophils’ phenotype to release NETs that favour tumour cell colonisation in lungs. The ability of O3-primed neutrophils to enhance lung colonisation by tumour cells was proven after their adoptive transfer in Balb/c mice unexposed to O3. Conclusions Pulmonary neutrophils induced by O3 promote metastatic dissemination to lungs by producing NETs. These findings open new perspectives to improve treatment and prevention strategies in patients affected by metastatic diseases.
iTRAQ-Based Quantitative Analysis of Responsive Proteins Under PEG-Induced Drought Stress in Wheat Leaves

Drought is an important abiotic stress that seriously restricts crop productivity. An understanding of drought tolerance mechanisms offers guidance for cultivar improvement. In order to understand how a well-known wheat genotype Jinmai 47 responds to drought, we adopted the iTRAQ and LC/MS approaches and conducted proteomics analysis of leaves after exposure to 20% of polyethylene glycol-6000 (PEG)-induced stress for 4 days. The study identified 176 differentially expressed proteins (DEPs), with 65 (36.5%) of them being up-regulated, and 111 (63.5%) down-regulated. DEPs, located in cellular membranes and cytosol mainly, were involved in stress and redox regulation (51), carbohydrate and energy metabolism (36), amino acid metabolism (24), and biosynthesis of other secondary metabolites (20) primarily. Under drought stress, TCA cycle related proteins were up-regulated. Antioxidant system, signaling system, and nucleic acid metabolism etc. were relatively weakened. In comparison, the metabolism pathways that function in plasma dehydration protection and protein structure protection were strongly enhanced, as indicated by the improved biosynthesis of 2 osmolytes, sucrose and Proline, and strongly up-regulated protective proteins, LEA proteins and chaperones. SUS4, P5CSs, OAT, Rab protein, and Lea14-A were considered to be important candidate proteins, which deserve to be further investigated.
Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients

Abstract Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome (HHS) are life threatening complications that occur in patients with diabetes. In addition to timely identification of the precipitating cause, the first step in acute management of these disorders includes aggressive administration of intravenous fluids with appropriate replacement of electrolytes (primarily potassium). In patients with diabetic ketoacidosis, this is always followed by administration of insulin, usually via an intravenous insulin infusion that is continued until resolution of ketonemia, but potentially via the subcutaneous route in mild cases. Careful monitoring by experienced physicians is needed during treatment for diabetic ketoacidosis and HHS. Common pitfalls in management include premature termination of intravenous insulin therapy and insufficient timing or dosing of subcutaneous insulin before discontinuation of intravenous insulin. This review covers recommendations for acute management of diabetic ketoacidosis and HHS, the complications associated with these disorders, and methods for preventing recurrence. It also discusses why many patients who present with these disorders are at high risk for hospital readmissions, early morbidity, and mortality well beyond the acute presentation.
A Systematic review and meta-analysis

Background: To perform a systematic review and meta-analysis evaluating the perioperative, functional, and oncological outcomes and cost of robot-assisted radical prostatectomy (RARP), or laparoscopic radical prostatectomy (LRP) comparing with open radical prostatectomy (ORP) in men with clinically localized prostate cancer through all prospective comparative studies. Methods:A comprehensive literature search was performed in August 2018 using the Pubmed, Medline, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) and prospective studies including patients with clinically localized prostate cancer were eligible for study inclusion. Cumulative analysis was conducted using Review Manager v. 5.3 software. Results: Two RCTs and 9 prospective studies were included in this systematic review. There were no significant differences between RARP/LRP and ORP in overall complication rate, major complication rate, overall positive surgical margin (PSM) rate, pT2 tumor PSM rate, ≥pT3 tumor PSM rate. Moreover, RARP/LRP and ORP showed similarity in biochemical recurrence (BCR) rate at 3, 12, 24 months postoperatively. Urinary continence and erectile function at 12 months postoperatively between RARP and ORP are also comparable. RARP/LRP were associated with significantly lower estimated blood loss [mean difference (MD) 749.67, 95% CI 1038.52 to 460.82, P= . 001], lower transfusion rate (OR 0.17, 95% CI 0.10 to 0.30, P< .001) and less hospitalization duration (MD 1.18, 95% CI 2.18 to 0.19, P= .02). And RARP/LRP required more operative time (MD 50.02, 95% CI 6.50 to 93.55, P= .02) and cost. Conclusion: RARP/LRP is associated with lower blood loss, transfusion rate and less hospitalization duration. The available data were insufficient to prove the superiority of any surgical approach in terms of postoperative complications, functional and oncologic outcomes. Abbreviations: BCR = biochemical recurrence, BMI = body mass index, IIEF-5 = international index of erectile function, LRP = laparoscopic radical prostatectomy, ORP = open radical prostatectomy, PSA = prostate-specific antigen, PSM = positive surgical margin, RARP = robotic-assisted radical prostatectomy, RCT = randomized controlled trial, RP = radical prostatectomy.
Molecular Classification of Epithelial Ovarian Cancer Based on Methylation Profiling: Evidence for Survival Heterogeneity

Purpose: Ovarian cancer is a heterogeneous disease that can be divided into multiple subtypes with variable etiology, pathogenesis, and prognosis. We analyzed DNA methylation profiling data to identify biologic subgroups of ovarian cancer and study their relationship with histologic subtypes, copy number variation, RNA expression data, and outcomes. Experimental Design: A total of 162 paraffin-embedded ovarian epithelial tumor tissues, including the five major epithelial ovarian tumor subtypes (high- and low-grade serous, endometrioid, mucinous, and clear cell) and tumors of low malignant potential were selected from two different sources: The Polish Ovarian Cancer study, and the Surveillance, Epidemiology, and End Results Residual Tissue Repository (SEER RTR). Analyses were restricted to Caucasian women. Methylation profiling was conducted using the Illumina 450K methylation array. For 45 tumors array copy number data were available. NanoString gene expression data for 39 genes were available for 61 high-grade serous carcinomas (HGSC). Results: Consensus nonnegative matrix factorization clustering of the 1,000 most variable CpG sites showed four major clusters among all epithelial ovarian cancers. We observed statistically significant differences in survival (log-rank test, P = 9.1 × 10−7) and genomic instability across these clusters. Within HGSC, clustering showed three subgroups with survival differences (log-rank test, P = 0.002). Comparing models with and without methylation subgroups in addition to previously identified gene expression subtypes suggested that the methylation subgroups added significant survival information (P = 0.007). Conclusions: DNA methylation profiling of ovarian cancer identified novel molecular subgroups that had significant survival difference and provided insights into the molecular underpinnings of ovarian cancer. See related commentary by Ishak et al., p. 5729
The potential therapeutic actions of melatonin in colorectal cancer

Abstract Colorectal cancer (CRC) is the third most common cancer and lethal disease worldwide. Melatonin, an indoleamine produced in pineal gland, shows anticancer effects on a variety of cancers, especially CRC. After clarifying the pathophysiology of CRC, the association of circadian rhythm with CRC, and the relationship between shift work and the incidence of CRC is reviewed. Next, we review the role of melatonin receptors in CRC and the relationship between inflammation and CRC. Also included is a discussion of the mechanism of gene regulation, control of cell proliferation, apoptosis, autophagy, antiangiogenesis and immunomodulation in CRC by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as comprehensive reference for the various mechanisms of action of melatonin against CRC, and as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for CRC.
Pattern of caries and gingivitis in a selected population of schoolchildren aged 9 to 11 years

The objectives of this study were to determine the prevalence of caries and gingivitis in a selected population of schoolchildren and to examine the relationship between prevalence of the diseases with their oral health behaviours. A total of 39 subjects, aged nine to 11 years, from 147 schoolchildren of a private school in Selangor, Malaysia were examined by two calibrated examiners trained in their own field. The subjects were interviewed using structured questionnaires. Erupted first permanent molars and permanent anterior teeth were examined. Dental caries, Plaque Score and Gingival Index were recorded. Descriptive statistics using frequency distribution were used to analyse the data. Forty-one percent of the subjects presented with more than 75 of total plaque accumulation. Prevalence of caries and gingivitis for the subject population was 18.0 and 31.0, respectively. Caries was found on both the smooth (buccal/lingual/palatal) and occlusal surfaces. Gingivitis, diagnosed around 31.6 of teeth, was found more on the incisors (16.9) than molars (14.7). A relatively higher distribution of gingivitis was found on labial aspect of the incisors (5.5) and palatal/lingual aspect of the molars (4.7). The prevalence of caries and gingivitis in this selected population was low. Certain dentition sites were more susceptible to dental caries and gingivitis. Good toothbrushing habits and regular visits to the dentists do not guarantee the efficacy of plaque removal.
Performance of triage systems in emergency care: a systematic review and meta-analysis

Objective To assess and compare the performance of triage systems for identifying high and low-urgency patients in the emergency department (ED). Design Systematic review and meta-analysis. Data sources EMBASE, Medline OvidSP, Cochrane central, Web of science and CINAHL databases from 1980 to 2016 with the final update in December 2018. Eligibility criteria Studies that evaluated an emergency medical triage system, assessed validity using any reference standard as proxy for true patient urgency and were written in English. Studies conducted in low(er) income countries, based on case scenarios or involving less than 100 patients were excluded. Review methods Reviewers identified studies, extracted data and assessed the quality of the evidence independently and in duplicate. The Quality Assessment of studies of Diagnostic Accuracy included in Systematic Reviews -2 checklist was used to assess risk of bias. Raw data were extracted to create 2×2 tables and calculate sensitivity and specificity. ED patient volume and casemix severity of illness were investigated as determinants of triage systems’ performance. Results Sixty-six eligible studies evaluated 33 different triage systems. Comparisons were restricted to the three triage systems that had at least multiple evaluations using the same reference standard (Canadian Triage and Acuity Scale, Emergency Severity Index and Manchester Triage System). Overall, validity of each triage system to identify high and low-urgency patients was moderate to good, but performance was highly variable. In a subgroup analysis, no clear association was found between ED patient volume or casemix severity of illness and triage systems’ performance. Conclusions Established triage systems show a reasonable validity for the triage of patients at the ED, but performance varies considerably. Important research questions that remain are what determinants influence triage systems’ performance and how the performance of existing triage systems can be improved.
Anesthetic Technique in a Patient With Multiple Sclerosis Scheduled for Laparoscopic Nephrectomy for a Renal Tumor: A Case Report

Perioperative stress and anesthesia are risk factors for exacerbation of Multiple Sclerosis (MS) attacks. Infection, emotional labiality and hyperpyrexia are also known to increase the risk of postoperative MS attacks. Appropriate preoperative evaluation, administration of a good premedication, control of fever, selection of the anesthetic agents and effective postoperative pain control can prevent problems after prolonged major surgery in patients with MS diagnosed. This report presents the anesthetic technique in a patient who was a known case of MS for past nine years and presented with renal tumor to undergo laparoscopic nephrectomy under general anesthesia.
Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer's disease

Arterial spin labeling (ASL) is an emerging MRI technique for noninvasive measurement of cerebral blood flow (CBF) that has been used to show hemodynamic changes in the brains of people with Alzheimer's disease (AD). CBF changes have been measured using positron emission tomography (PET) across the AD spectrum, but ASL showed limited success in measuring CBF variations in the preclinical phase of AD, where amyloid β (Aβ) plaques accumulate in the decades prior to symptom onset.
A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts

Purpose: To screen for mutations of connexin50 (Cx50)/GJA8 in a panel of patients with inherited cataract and to determine the cellular and functional consequences of the identified mutation. Methods: All patients in the study underwent a full clinical examination and leucocyte DNA was extracted from venous blood. The GJA8 gene was sequenced directly. Connexin function and cellular trafficking were examined by expression in Xenopus oocytes and HeLa cells. Results: Screening of the GJA8 gene identified a 139 G to A transition that resulted in the replacement of aspartic acid by asparagine (D47N) in the coding region of Cx50. This change co-segregated with cataract among affected members of a family with autosomal dominant nuclear pulverulent cataracts. While pairs of Xenopus oocytes injected with wild type Cx50 RNA formed functional gap junction channels, pairs of oocytes injected with Cx50D47N showed no detectable intercellular conductance. Co-expression of Cx50D47N did not inhibit gap junctional conductance of wild type Cx50. In transiently transfected HeLa cells, wild type Cx50 localised to appositional membranes and within the perinuclear region, but Cx50D47N showed no immunostaining at appositional membranes with immunoreactivity confined to the cytoplasm. Incubation of HeLa cells transfected with Cx50D47N at 27°C resulted in formation of gap junctional plaques. Conclusions: The pulverulent cataracts present in members of this family are associated with a novel GJA8 mutation, Cx50D47N, that acts as a loss-of-function mutation. The consequent decrease in lens intercellular communication and changes associated with intracellular retention of the mutant connexin may contribute to cataract formation.
Encapsulation of Thermo-Sensitive Lauric Acid in Silica Shell: A Green Derivate for Chemo-Thermal Therapy in Breast Cancer Cell

Lauric acid is a green derivate that is abundant in some seeds such as coconut oil where it represents the most relevant fatty acid. Some studies have emphasized its anticancer effect due to apoptosis induction. In addition, the lauric acid is a Phase Change Material having a melting temperature of about 43.2 °C: this property makes it a powerful tool in cancer treatment by hyperthermal stress, generally induced at 43 °C. However, the direct use of lauric acid can have some controversial effects, and it can undergo degradation phenomena in the extracellular environment. For this reason, we have encapsulated lauric acid in a silica shell with a one-step and reproducible synthetic route in order to obtain a monodispersed SiO2@LA NPs with a good encapsulation efficiency. We have used these NPs to expose breast cancer cell lines (MCF-7) at different concentrations in combination with hyperthermal treatment. Uptake, viability, oxidative stress induction, caspases levels, and morphometric parameters were analyzed. These nanovectors showed double action in anticancer treatments thanks to the synergic effect of temperature and lauric acid activity.
High-Intensity Single-Leg Cycling Improves Cardiovascular Disease Risk Factor Profile.

INTRODUCTION Regular exercise can reduce the risk of developing cardiovascular disease through risk factor modification, with high intensity exercise and more recently small muscle mass training providing alternatives to moderate intensity exercise. METHODS This study randomly assigned 53 healthy middle-aged adults (age: 62 ± 6 y) to complete 24 sessions (8 wk; 3 d.wk) of exercise training, using either high intensity double-leg cycling (n=17; HITDL), high intensity single-leg cycling (n=18; HITSL) or moderate intensity double-leg cycling (n=18; MCTDL). Biomarkers of cardiovascular risk (total cholesterol, triglycerides, HDL-c, LDL-c, apo-B48, glucose), anthropometry measures (body mass, body mass index, waist circumference, waist-to-hip ratio), resting blood pressure and aerobic capacity were assessed pre- and post-intervention. RESULTS Total work completed was greater (p<0.01) in MCTDL (5938 ± 1462 kJ) compared with the HITDL (3462 ± 1063 kJ) and HITSL (4423 ± 1875 kJ). Pre- to post-training differences were observed for waist-to-hip ratio (0.84 ± 0.09 vs 0.83 ± 0.09; p<0.01), resting systolic blood pressure (129 ± 11 mmHg vs 124 ± 12 mmHg; p<0.01), total cholesterol (5.87 ± 1.17 mmol·L vs 5.55 ± 0.98 mmol·L; p<0.01) and LDL-c (3.70 ± 1.04 mmol·L vs 3.44 ± 0.84 mmol·L; p<0.01), with no differences between conditions. Additionally, aerobic capacity increased following training (22.3 ± 6.4 mL·kg·min vs 24.9 ± 7.6 mL·kg·min; p<0.01), with no differences between conditions. CONCLUSION These findings suggest that all three modes of exercise can be prescribed to achieve cardiovascular risk reduction in an ageing population.
An updated meta-analysis of randomized controlled trials

Background: To assess the effectiveness of acupuncture in patients with post-stroke depression (PSD). Methods: The Cochrane Library, CINAHL, EMBASE, PubMed, SCOPUS, Web of Science, and 4 Chinese databases were electronically searched for articles published between January 1, 2010 and May 31, 2018. Randomized controlled trials (RCTs) investigating the effects of acupuncture on PSD were included. The quality of all included trials was assessed according to guidelines published by the Cochrane Collaboration. Results: Seven trials compared the effectiveness of acupuncture therapy with that of control in alleviating the symptoms of PSD. Pooled analysis demonstrated that patients in the acupuncture intervention group experienced a significantly higher treatment effect than controls (RR 1.16 [95% CI 1.08–1.24]; P< .0001), with low study heterogeneity (I=4%). Based on intervention methods, further analysis revealed a statistically significant difference in effectiveness between the acupuncture alone andmedicine groups (RR 1.25 [95% CI 1.11 1.41]; Z=3.78; P= .0002). There was no statistically significant difference in efficacy between the acupuncture combined with medicine and medicine groups (RR 1.07 [95% CI 0.98–1.17]; P= .11). Conclusions: This meta-analysis provides evidence supporting the viewpoint that acupuncture is an effective and safe treatment for PSD. Subgroup analyses further revealed that acupuncture alone resulted in better outcomes than drug therapy in improving depressive symptoms. Further high-quality RCTs are needed to systematically evaluate the effectiveness of acupuncture for PSD and develop standardized acupuncture protocols. Abbreviations: BDNF= brain-derived neurotrophic factor, CI= confidence interval, Hamilton HRSD= rating scale for depression, PSD = post-stroke depression, RCTs = randomized controlled trials, RR = risk ratio.
Diet of Paranthropus boisei in the early Pleistocene of East Africa

The East African hominin Paranthropus boisei was characterized by a suite of craniodental features that have been widely interpreted as adaptations to a diet that consisted of hard objects that required powerful peak masticatory loads. These morphological adaptations represent the culmination of an evolutionary trend that began in earlier taxa such as Australopithecus afarensis, and presumably facilitated utilization of open habitats in the Plio-Pleistocene. Here, we use stable isotopes to show that P. boisei had a diet that was dominated by C4 biomass such as grasses or sedges. Its diet included more C4 biomass than any other hominin studied to date, including its congener Paranthropus robustus from South Africa. These results, coupled with recent evidence from dental microwear, may indicate that the remarkable craniodental morphology of this taxon represents an adaptation for processing large quantities of low-quality vegetation rather than hard objects.