Miracle-dz/UniFAR-FTUs huggingface dataset:
Entorhinal cortex tau, amyloid-&bgr;, cortical thickness and memory performance in non-demented subjects

As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.
Efficacy and Safety of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent: The EVOLVE II Randomized Trial

Background—Drug eluting stents with durable polymers may be associated with hypersensitivity, delayed healing, and incomplete endothelialization, which may contribute to late/very late stent thrombosis and the need for prolonged dual antiplatelet therapy. Bioabsorbable polymers may facilitate stent healing, thus enhancing clinical safety. The SYNERGY stent is a thin-strut, platinum chromium metal alloy platform with an ultrathin bioabsorbable Poly(D,L-lactide-co-glycolide) abluminal everolimus-eluting polymer. We performed a multicenter, randomized controlled trial for regulatory approval to determine noninferiority of the SYNERGY stent to the durable polymer PROMUS Element Plus everolimus-eluting stent. Methods and Results—Patients (n=1684) scheduled to undergo percutaneous coronary intervention for non–ST-segment–elevation acute coronary syndrome or stable coronary artery disease were randomized to receive either the SYNERGY stent or the PROMUS Element Plus stent. The primary end point of 12-month target lesion failure was observed in 6.7% of SYNERGY and 6.5% PROMUS Element Plus treated subjects by intention-to-treat (P=0.83 for difference; P=0.0005 for noninferiority), and 6.4% in both the groups by per-protocol analysis (P=0.0003 for noninferiority). Clinically indicated revascularization of the target lesion or definite/probable stent thrombosis were observed in 2.6% versus 1.7% (P=0.21) and 0.4% versus 0.6% (P=0.50) of SYNERGY versus PROMUS Element Plus–treated subjects, respectively. Conclusions—In this randomized trial, the SYNERGY bioabsorbable polymer everolimus-eluting stent was noninferior to the PROMUS Element Plus everolimus-eluting stent with respect to 1-year target lesion failure. These data support the relative safety and efficacy of SYNERGY in a broad range of patients undergoing percutaneous coronary intervention. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT01665053.
How is Endodontics taught? A survey to evaluate undergraduate endodontic teaching in dental schools within the United Kingdom.

AIM To evaluate the delivery of undergraduate endodontic education in UK dental schools using an online survey and to compare the results with those of a previous paper-based survey (Qualtrough & Dummer 1997, Int Endod J, 30, 234). Aspects of delivery were also evaluated in comparison with the Undergraduate Curriculum Guidelines of the European Society of Endodontology (de Moor et al. 2013, Int Endod J, 46, 1105). METHODOLOGY An online version of an earlier paper-based survey on undergraduate Endodontic education (Qualtrough & Dummer 1997, Int Endod J, 30, 234) was created. Invitations to take part were sent via email to the undergraduate endodontic programme leads in the 16 UK dental schools. RESULTS The response rate was 94%. The current survey revealed greater convergence amongst dental schools than previously (Qualtrough & Dummer 1997, Int Endod J, 30, 234) on methods of canal preparation, disinfection and filling. Improvements were also noted in staff: student ratios, the involvement of teachers with advanced endodontic training and a greater diversity of teaching methods; developments which align with the recommendations of ESE Undergraduate Curriculum Guidelines (de Moor et al. 2013, Int Endod J, 46, 1105). The majority of schools appeared to be teaching contemporary instrumentation methods and were recommending the application of calcium silicate cements. The exposure of students to advanced topics included in the ESE Undergraduate Curriculum Guidelines (de Moor et al. 2013, Int Endod J, 46, 1105) such as surgical endodontic treatment, root canal re-treatment and the management of complex cases was mixed. CONCLUSION Undergraduate endodontic training in the UK has advanced in the last 20 years with more consistency between schools and more contemporary methods adopted.
Jellyfish-Associated Microbiome in the Marine Environment: Exploring Its Biotechnological Potential

Despite accumulating evidence of the importance of the jellyfish-associated microbiome to jellyfish, its potential relevance to blue biotechnology has only recently been recognized. In this review, we emphasize the biotechnological potential of host–microorganism systems and focus on gelatinous zooplankton as a host for the microbiome with biotechnological potential. The basic characteristics of jellyfish-associated microbial communities, the mechanisms underlying the jellyfish-microbe relationship, and the role/function of the jellyfish-associated microbiome and its biotechnological potential are reviewed. It appears that the jellyfish-associated microbiome is discrete from the microbial community in the ambient seawater, exhibiting a certain degree of specialization with some preferences for specific jellyfish taxa and for specific jellyfish populations, life stages, and body parts. In addition, different sampling approaches and methodologies to study the phylogenetic diversity of the jellyfish-associated microbiome are described and discussed. Finally, some general conclusions are drawn from the existing literature and future research directions are highlighted on the jellyfish-associated microbiome.
Rapid automated microscopy for microbiological surveillance of ventilator-associated pneumonia.

RATIONALE Diagnosis of ventilator-associated pneumonia (VAP) is imprecise. OBJECTIVES To (1) determine whether alternate-day surveillance mini-bronchoalveolar lavage (mini-BAL) in ventilated adults could reduce time to initiation of targeted treatment and (2) evaluate the potential for automated microscopy to reduce analysis time. METHODS Adult intensive care unit patients who were anticipated to require ventilation for at least a further 48 hours were included. Mini-BALs were processed for identification, quantitation, and antibiotic susceptibility, using (1) clinical culture (50 ± 7 h) and (2) automated microscopy (∼5 h plus offline analysis). MEASUREMENTS AND MAIN RESULTS Seventy-seven mini-BALs were performed in 33 patients. One patient (3%) was clinically diagnosed with VAP. Of 73 paired samples, culture identified 7 containing pneumonia panel bacteria (>10(4) colony-forming units/ml) from five patients (15%) (4 Staphylococcus aureus [3 methicillin-resistant S. aureus], 2 Stenotrophomonas maltophilia, 1 Klebsiella pneumoniae) and resulted in antimicrobial changes/additions to two of five (40%) of those patients. Microscopy identified 7 of 7 microbiologically positive organisms and 64 of 66 negative samples compared with culture. Antimicrobial responses were concordant in four of five comparisons. Antimicrobial changes/additions would have occurred in three of seven microscopy-positive patients (43%) had those results been clinically available in 5 hours, including one patient diagnosed later with VAP despite negative mini-BAL cultures. CONCLUSIONS Microbiological surveillance detected infection in patients at risk for VAP independent of clinical signs, resulting in changes to antimicrobial therapy. Automated microscopy was 100% sensitive and 97% specific for high-risk pneumonia organisms compared with clinical culturing. Rapid microscopy-based surveillance may be informative for treatment and antimicrobial stewardship in patients at risk for VAP.
Extracting the Energy-Dependent Neutrino-Nucleon Cross Section above 10 TeV Using IceCube Showers.

Neutrinos are key to probing the deep structure of matter and the high-energy Universe. Yet, until recently, their interactions had only been measured at laboratory energies up to about 350 GeV. An opportunity to measure their interactions at higher energies opened up with the detection of high-energy neutrinos in IceCube, partially of astrophysical origin. Scattering off matter inside Earth affects the distribution of their arrival directions-from this, we extract the neutrino-nucleon cross section at energies from 18 TeV to 2 PeV, in four energy bins, in spite of uncertainties in the neutrino flux. Using six years of public IceCube High-Energy Starting Events, we explicitly show for the first time that the energy dependence of the cross section above 18 TeV agrees with the predicted softer-than-linear dependence, and reaffirm the absence of new physics that would make the cross section rise sharply, up to a center-of-mass energy sqrt[s]≈1 TeV.
Loss-of-function but not dominant-negative intragenic IKZF1 deletions are associated with an adverse prognosis in adult BCR-ABL-negative acute lymphoblastic leukemia

Genetic alterations of the transcription factor IKZF1 (“IKAROS”) are detected in around 15–30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic leukemia. Different types of intragenic deletions have been observed, resulting in a functionally inactivated allele (“loss-of-function”) or in “dominant-negative” isoforms. The prognostic impact of these alterations especially in adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well-characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic leukemia uniformly treated in the framework of the GMALL studies and detected IKZF1 alterations in 128 cases (27%). In 20%, the IKZF1 alteration was present in a large fraction of leukemic cells (“high deletion load”) while in 7% it was detected only in small subclones (“low deletion load”). Some patients showed more than one IKZF1 alteration (8%). Patients exhibiting a loss-of-function isoform with high deletion load had a shorter overall survival (OS at 5 years 28% vs. 59%; P<0.0001), also significant in a subgroup analysis of standard risk patients according to GMALL classification (OS at 5 years 37% vs. 68%; P=0.0002). Low deletion load or dominant-negative IKZF1 alterations had no prognostic impact. The results thus suggest that there is a clear distinction between loss-of-function and dominant-negative IKZF1 deletions. Affected patients should thus be monitored for minimal residual disease carefully to detect incipient relapses at an early stage and they are potential candidates for alternative or intensified treatment regimes. (clinicaltrials.gov identifiers: 00199056 and 00198991).
Clinical and radiological outcomes of image guided posterior C1-C2 fixation for atlantoaxial osteoarthritis (AAOA).

Background Atlantoaxial (C1-C2) osteoarthritis (AAOA) causes severe suboccipital pain exacerbated by lateral rotation. The pain is usually progressive and resistant to conservative therapy. Posterior fusion surgery is performed to stabilise the C1-C2 segment. This is the first Australian study reporting the outcome of posterior atlantoaxial fixation including hybrid fixations performed for AAOA. Methods All patients who underwent posterior atlantoaxial fixation surgery for AAOA from 2005 to 2015 at our institutions were enrolled (N=23). Patient demographics and surgical technique were recorded. These techniques included transarticular screw (TAS) fixation using image guidance with iliac crest bone graft and supplemental posterior Sonntag wiring, or C1-C2 lateral mass fixation (Harms technique). Some patients required a combination of fixation due to anatomical variation. Primary outcome measures including patient satisfaction, pain, disability scores and range of motion were recorded for all patients pre- and post-operatively. Post-operative assessment was supplemented with CT and X-ray imaging. Results Twenty-three patients (19 women, 4 males, mean age 71.8±6.3 years) underwent surgical fixation. Eight underwent TAS fixation, 8 had Harms fixation, and 7 had a hybrid fixation. All patients reported statistically significant improvement in pain scores [Visual Analogue Scale (VAS) 9.4 pre-op compared to 2.9 post-op, P<0.005]. Disability scores [Neck Disability Index (NDI)] were statistically significantly reduced from 72.2±12.9 pre-operatively to 18.9±11.9 post-operatively, P<0.005. Mean follow-up was 55.3±36.1 months. Results did not vary according to the construct type. Ninety-five point five percent of patients showed radiographic evidence of fusion. Ninety-one percent of patients said they would undergo the surgery again. Conclusions Posterior atlantoaxial fixation with TAS and Harms constructs are highly effective for the surgical treatment of intractable neck pain secondary to atlantoaxial lateral mass osteoarthritis (AAOA). Surgery offers a high rate of symptom relief. If anatomical variability exists, both transarticular and pedicle screw fixation could be safely used in the same patient.
Body fat percentage is more strongly associated with biomarkers of low-grade inflammation than traditional cardiometabolic risk factors in healthy young adults – the Lifestyle, Biomarkers, and Atherosclerosis study

Abstract The primary aim was to appraise the relationship between body fat percentage and the inflammatory markers C-reactive protein (CRP) and orosomucoid in a population of young, non-smoking, healthy, Swedish adults, without any chronic diseases. A secondary aim was to compare whether these associations differed between the women using estrogen contraceptives and those who did not. We assessed the association in linear regression models between body fat percentage based on a bio-impedance measurement and plasma concentrations of CRP and orosomucoid in men and women aged 18–26 years, n = 834. Statistically significant associations were found between body fat percentage and both biomarkers of inflammation, with β coefficients of 0.30 (95% CI 0.24–0.37) and 0.28 (0.22–0.35) for CRP and orosomucoid, respectively (p < .001). Adjustment for established risk factors marginally lowered the effects sizes (partial betas, 0.28 and 0.20, respectively), while the strong statistically significant associations remained. In the female cohort, estrogen and non-estrogen using subpopulations did not significantly differ in the correlations between body fat percentage and the inflammatory biomarkers, even adjusted for established cardiometabolic risk factors. In conclusion, in healthy young adults, higher levels of body fat percentage are associated with elevations in plasma biomarkers of inflammation, suggesting that a systemic inflammatory process, promoting atherosclerosis, may commence already at this early stage in life. CRP and orosomucoid plasma concentrations differed between users and non-users of estrogen contraceptives, but both subgroups showed similar correlations between increasing body fat percentage and increasing plasma concentrations of the biomarkers of inflammation.
Retinoic Acid Treatment Enhances Lipid Oxidation and Inhibits Lipid Biosynthesis Capacities in the Liver of Mice

Vitamin A, mainly as retinoic acid (RA), is known to affect the development and function of adipose tissues. Treatment with RA reduces body weight and adiposity independent of changes in food intake in mice. Lipid metabolism in liver can have a major impact on whole body adiposity. The aim of this work was to investigate the effects of an in vivo treatment with RA on hepatic lipid metabolism in mice. Adult, standard diet-fed mice were treated with different doses of all-trans RA or vehicle (subcutaneous injection) for 4 days before sacrifice. Food intake and body weight changes during treatment were determined, as well as adiposity, liver composition, levels of circulating metabolites and lipoproteins and expression levels of key mRNA species in liver following sacrifice. RA treatment resulted in reduced body weight and adiposity, as expected. In the liver, RA treatment triggered an increase in the mRNA expression levels of peroxisome proliferator-activated receptor alpha, retinoid X receptor alpha, uncoupling protein 2, liver-type carnitine palmitoyltransferase 1, and carnitine/acylcarnitine carrier, and a reduction in the mRNA expression levels of sterol regulatory element binding protein 1c and fatty acid synthase. Consistent with the changes in gene expression, hepatic triacylglycerol content and circulating VLDL fraction were reduced and levels of circulating ketone bodies increased after RA treatment. These results point to a capacity of active vitamin A forms to shift liver lipid metabolism in vivo towards increased catabolism and reduced lipogenesis. These effects might contribute to the reduction of adiposity brought about by RA treatment.
Risk Factors Associated With Multidrug-Resistant Pneumonia in Nonhospitalized Patients.

Successful treatment of pneumonia depends on timely diagnosis and administration of antibiotics. Multidrug-resistant organisms (MDROs) complicate antibiotic therapies by rendering some antibiotic agents ineffective. Inappropriate initial therapy has been associated with a more than 2-fold increase in the risk of mortality. Because culture results are not available immediately, clinicians prescribe antibiotics empirically and must rely on guidelines and knowledge of risk factors associated with MDRO infection to make these selections. Treatment guidelines exist for hospitalacquired and ventilator-associated pneumonia (HAP/VAP) and community-acquired pneumonia (CAP) to assist with empiric antibiotic selection. For HAP/VAP, 2 to 3 antibiotics with a broad-spectrum of activity are used due to increased prevalence of MDROs in hospitals, whereas treatment of CAP involves more narrow coverage because bacteria that cause this infection typically have fewer antibiotic resistances. The HAP/VAP guidelines stratify the risk of pneumonia due to the presence of a MDRO acquired during a hospitalization. However, neither the CAP nor HAP/VAP guidelines offer risk-stratification guidance for nonhospitalized patients who develop pneumonia but who may have become colonized with a MDRO during a previous hospitalization or from another exposure to a health care facility. Health care-associated pneumonia (HCAP) was first described in the 2005 American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA) nosocomial pneumonia guidelines and was associated with criteria intended to aid clinician identification of nonhospitalized patients at risk for MDRO pneumonia, which warranted empiric broad-spectrum antibiotic therapy. According to these guidelines, patients were classified as having HCAP if they had been hospitalized for at least 48 hours in the past 90 days, admitted from a nursing home, received recent intravenous antibiotics, had hemodialysis in the past 30 days, had a history of home infusion therapy or wound care, received intravenous chemotherapy, or had a family member with MDRO colonization. Since publication of the 2005 guidelines, HCAP has been criticized as being a poor predictor of MDRO infection. A 2014 metaanalysis of 24 studies investigated the discriminating ability of HCAP and reported that the specificity and sensitivity for MDRO infections was 71.2% and 53.7%, respectively. In 2016, the ATS/IDSA guidelines were updated to remove HCAP due to the risk of antibiotic overprescribing.
An open access database for the evaluation of respiratory sound classification algorithms

Objective: Over the last few decades, there has been significant interest in the automatic analysis of respiratory sounds. However, currently there are no publicly available large databases with which new algorithms can be evaluated and compared. Further developments in the field are dependent on the creation of such databases. Approach: This paper describes a public respiratory sound database, which was compiled for an international competition, the first scientific challenge of the IFMBE’s International Conference on Biomedical and Health Informatics. The database includes 920 recordings acquired from 126 participants and two sets of annotations. One set contains 6898 annotated respiratory cycles, some including crackles, wheezes, or a combination of both, and some with no adventitious respiratory sounds. In the other set, precise locations of 10 775 events of crackles and wheezes were annotated. Main results: The best system that participated in the challenge achieved an average score of 52.5% with the respiratory cycle annotations and an average score of 91.2% with the event annotations. Significance: The creation and public release of this database will be useful to the research community and could bring attention to the respiratory sound classification problem.
Analyses of the Erosive Potential of Various Soft Drinks and Packaged Fruit Juices on Teeth.

AIM This study aimed to evaluate the erosive potential of twenty beverages (8 carbonated drinks and 12 packaged fruit juices). MATERIALS AND METHODS Twenty-one sound permanent freshly extracted teeth were segmented into small enamel slices and stored in normal saline. The titratable acidity of each experimental drink was measured as the amount of 0.1 N sodium hydroxide (NaOH) required to raise pH to 5.5 and 7. The enamel specimens were incubated in freshly collected human saliva for 3 hours. One enamel slice was immersed in each beverage and percentage weight loss in the enamel slice was calculated after 6 and 24 hours intervals. RESULTS The titratable acidity values of the experimental drinks ranged from 0.2 to 5.6. The mean titratable acidity values of the packaged fruit juices were higher than carbonated drinks. A significant difference (p < 0.0 5) was found in the percentage weight loss of enamel specimens after 6 and 24 hours immersion in the carbonated drinks than packaged fruit juices. Apple juice followed by thumps up were found to be the most erosive drinks with the least effects of Miranda and Guava juice. CONCLUSION Most of the beverages tested in this study showed erosive potential. The carbonated drinks caused significant dental erosion. CLINICAL SIGNIFICANCE Individuals at risk for beverages-associated erosion, particularly those with high intakes or decreased salivary flow, should be provided preventive guidance regarding habits of beverages intake. Specific dietary recommendations for the prevention of dental erosion may now be developed based on the patient's history of beverage consumption.