Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) amyloidosis and its relationship with skeletal muscle and soft tissue amyloid

Aims High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR amyloidosis. Methods and results Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A-associated ATTRm (n = 59) amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001). Conclusion 99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.
Review of Hybrid Bayesian Inference and Its Applications

Incorporating both Bayesian and frequentist methods in the same model the hybrid Bayesian statistical inference possesses some advantages over either of the methods used individually. It has been increasingly applied to biomedical research including genomics, viral load modeling, biomedical engineering, and survey. In this article we briefly describe the theoretical framework of hybrid Bayesian inference and review its applications. We also discuss the potential future research topics in this area.
Lactobacillus reuteri DSM 17938 as a Probiotic for Preterm Neonates: A Strain-Specific Systematic Review.

INTRODUCTION Prevention of necrotizing enterocolitis (NEC) while optimizing enteral nutrition (EN) is a priority in preterm neonates. Lactobacillus reuteri DSM 17938 (L reuteri) is known to improve gut motility. Previous systematic reviews have not adequately assessed the effects of L reuteri in improving feed tolerance in preterm neonates. OBJECTIVE To assess the effects of L reuteri in preterm neonates. DESIGN A systematic review of randomized controlled trials (RCTs) and non-RCTs of L reuteri was conducted. We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and CINAHL databases and proceedings of Pediatric Academic Society meetings in December 2014. RESULTS Six RCTs (n = 1778) and 2 non-RCTs (n = 665) were included. Meta-analysis of RCTs estimated that the time to full feeds (mean difference [MD], -1.34 days; 95% confidence interval [CI], -1.81 to -0.86; 2 RCTs), duration of hospitalization (-10.77 days; 95% CI, -13.67 to -7.86; 3 RCTs), and late-onset sepsis (LOS) (relative risk [RR], 0.66; 95% CI, 0.52 to 0.83; 4 RCTs) were reduced in the L reuteri group. Mortality (RR, 0.79; 95% CI, 0.57-1.09; 3 RCTs) and ≥ stage II NEC (RR, 0.69; 95% CI, 0.47-1.01; 3 RCTs) were reduced but statistically not significant. There were no adverse effects of supplementation. Both non-RCT studies showed significant improvement in the incidence of NEC with L reuteri supplementation. CONCLUSIONS Evidence from a limited number of studies suggests that L reuteri supplementation has the potential to reduce the risk of NEC and LOS while facilitating EN in preterm infants. Larger definitive RCTs are needed to confirm these findings.
Understanding Oceanic Migrations with Intrinsic Biogeochemical Markers

Migratory marine vertebrates move annually across remote oceanic water masses crossing international borders. Many anthropogenic threats such as overfishing, bycatch, pollution or global warming put millions of marine migrants at risk especially during their long-distance movements. Therefore, precise knowledge about these migratory movements to understand where and when these animals are more exposed to human impacts is vital for addressing marine conservation issues. Because electronic tracking devices suffer from several constraints, mainly logistical and financial, there is emerging interest in finding appropriate intrinsic markers, such as the chemical composition of inert tissues, to study long-distance migrations and identify wintering sites. Here, using tracked pelagic seabirds and some of their own feathers which were known to be grown at different places and times within the annual cycle, we proved the value of biogeochemical analyses of inert tissue as tracers of marine movements and habitat use. Analyses of feathers grown in summer showed that both stable isotope signatures and element concentrations can signal the origin of breeding birds feeding in distinct water masses. However, only stable isotopes signalled water masses used during winter because elements mainly accumulated during the long breeding period are incorporated into feathers grown in both summer and winter. Our findings shed new light on the simple and effective assignment of marine organisms to distinct oceanic areas, providing new opportunities to study unknown migration patterns of secretive species, including in relation to human-induced mortality on specific populations in the marine environment.
Colorectal Cancer Incidence in Korea Is Not the Highest in the World

Recently, media as well as academic societies have referred to GLOBOCAN 2012 to support the high incidence rate of colorectal cancer in Korea. According to GLOBOCAN 2012, colorectal cancer incidence ranked third for men and fifth for women, and the highest when both sexes were combined among 184 countries (Table 1) [1]. Because GLOBOCAN intended to provide the most recent estimates of cancer incidence, mortality, and prevalence for 28 cancers worldwide, the quality of country estimates varied from high quality national or regional data to no data [1]. Therefore, the accuracy of estimates are dependent on the availability and the accuracy of the data from each country [1]. Korean data is high quality national data with rates projected to 2012. The most recent incidence data used for GLOBOCAN estimates was for the year 2009 [2]. Indeed, the age-standardized incidence of colorectal cancer increased by 5.3% annually between 1999 and 2012 [3]. However, according to the Korea Central Cancer Registry data, the colorectal cancer incidence decreased for men and stabilized for women in 2012 [3]. Since projection used for GLOBOCAN 2012 applied trends until 2009, which was an annual percent change of 6.2% for both sexes [4], the GLOBOCAN estimates overestimated the incidence for the Korean population. Table 1. Estimated incidence of colorectal cancer, GLOBOCAN 2012 [1] We retrieved published incidence data of selected countries from 2008 to 2012 (or nearest year to 2012) (Table 2). In comparison of age-standardized incidence rates, Czech (2011), Slovakia (2008), and Slovenia (2011) showed higher incidence than Korea (2011 or 2012) in men. In women, most countries with recent data showed higher incidence compared to Korea. When both sexes were combined, incidence of Japan (2010), Netherlands (2012), Australia (2012), and New Zealand (2012) was higher than that of Korea. Table 2. Observed age-standardized incidence ratesa) of colorectal cancer from selected cancer registries In conclusion, the aim of GLOBOCAN 2012 is to provide worldwide estimates for cancer burden, and there are substantial differences between GLOBOCAN estimates and observed statistics due to methodology applied. Korea has experienced rapid transition in colorectal cancer epidemiology, therefore predicted estimates using past trends may not appropriately reflect the observed statistics. Although GLOBOCAN is useful for overviewing cancer burden, caution should be used in direct comparison or referring of the estimated incidence or mortality.
Community health workers improve disease control and medication adherence among patients with diabetes and/or hypertension in Chiapas, Mexico: an observational stepped-wedge study

Background Non-communicable diseases (NCDs) contribute greatly to morbidity and mortality in low-income and middle-income countries (LMICs). Community health workers (CHWs) may improve disease control and medication adherence among patients with NCDs in LMICs, but data are lacking. We assessed the impact of a CHW-led intervention on disease control and adherence among patients with diabetes and/or hypertension in Chiapas, Mexico. Methods We conducted a prospective observational study among adult patients with diabetes and/or hypertension, in the context of a stepped-wedge roll-out of a CHW-led intervention. We measured self-reported adherence to medications, blood pressure and haemoglobin A1c at baseline and every 3 months, timed just prior to expansion of the intervention to a new community. We conducted individual-level mixed effects analyses of study data, adjusting for time and clustering by patient and community. Findings We analysed 108 patients. The CHW-led intervention was associated with a twofold increase in the odds of disease control (OR 2.04, 95% CI 1.15 to 3.62). It was also associated with optimal adherence assessed by 30-day recall (OR 1.86; 95% CI 1.15 to 3.02) and a positive self-assessment of adherence behaviour (OR 2.29; 95% CI 1.26 to 4.15), but not by 5-day recall. Interpretation A CHW-led adherence intervention was associated with disease control and adherence among adults with diabetes and/or hypertension. This study supports a role of CHWs in supplementing comprehensive primary care for patients with NCDs in LMICs. Trial registration number NCT02549495.
Perspectives on Communicating Biomarker-Based Assessments of Alzheimer’s Disease to Cognitively Healthy Individuals

In clinical trials which target pathophysiological mechanisms associated with Alzheimer’s disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer’s dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants’ experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer’s disease biomarkers.
Structure -- Magnetic Property Correlations in TiO 2 Nanotube Arrays

TiO 2 nanotube arrays are promising candidates for applications such as photocatalysis and for potential employment in spin-electronic (spintronic) devices. The functionality of TiO 2-based nanotubes is highly dependent on their structure (microstructure and crystallographic symmetry) and magnetic properties. Unified understanding of the influence of these factors on the electronic structure of TiO 2 is of paramount importance towards engineering these materials. This Dissertation aims at investigating the correlations of the crystallinity, crystal structure, electronic structure and magnetic properties of TiO 2 nanotubes, with potential relevance to their functionality. Self-ordered arrays of amorphous TiO 2 nanotubes (pure and Fe-doped with cationic concentration of ~2.1 at%) were synthesized by the electrochemical anodization technique, followed by subjecting them to thermal treatments up to 450 °C to crystallize these nanostructures. A variety of probes – morphological, structural, magnetic and spectroscopic – were used to characterize the properties of these nanostructures as functions of their processing conditions and the dopant content. Structure-functionality relationships in these nanostructures were verified by examining the photodegradation rate of methyl orange (a model water pollutant) in presence of TiO 2 nanotubes under UV-Visible light irradiation.
Adaptivity of averaged stochastic gradient descent to local strong convexity for logistic regression

In this paper, we consider supervised learning problems such as logistic regression and study the stochastic gradient method with averaging, in the usual stochastic approximation setting where observations are used only once. We show that after N iterations, with a constant step-size proportional to 1/R2√N where N is the number of observations and R is the maximum norm of the observations, the convergence rate is always of order O(1/√N), and improves to O(R2/µN) where µ is the lowest eigenvalue of the Hessian at the global optimum (when this eigenvalue is greater than R2/√N. Since µ does not need to be known in advance, this shows that averaged stochastic gradient is adaptive to unknown local strong convexity of the objective function. Our proof relies on the generalized self-concordance properties of the logistic loss and thus extends to all generalized linear models with uniformly bounded features.
The Antibody Response Following a Booster With Either a 10- or 13-valent Pneumococcal Conjugate Vaccine in Toddlers Primed With a 13-valent Pneumococcal Conjugate Vaccine in Early Infancy

Background: Both the 13- and 10-valent pneumococcal conjugate vaccines (PCV-13; PCV-10) are immunogenic and effective against vaccine-type pneumococcal disease when given to young children. However, limited data are available regarding the interchangeability of these 2 vaccines. Methods: UK children (n = 178) who had previously been vaccinated with PCV-13 at 2 and 4 months were randomized to receive either a PCV-13 or a PCV-10 booster at 12 months of age. PCV-13 vaccine-type antipolysaccharide serum immunoglobulin G (IgG) concentrations and opsonophagocytic assay titers were measured before and at 1 and 12 months following vaccination. The primary objective was to assess noninferiority of PCV-10 compared with PCV-13. Results: For 8 of the PCV-10 serotypes at least 97% of participants in both groups had IgG concentrations ≥0.35 µg/mL at 1 month after vaccination; inferior responses were seen for serotypes 5 and 9V following the PCV-10 compared with the PCV-13 booster. Post booster geometric mean IgG concentrations and opsonophagocytic assay titers were significantly superior for most serotypes in PCV-13 compared with PCV-10 recipients, whereas similar or inferior responses were seen for serotypes 4, 18C, and 19F. Although some increase in antibody was seen in PCV-10 recipients against the serotypes 6A and 19A (serotypes that cross-react with 6B and 19F in PCV-10, respectively) at 1-month post booster, these responses were significantly lower than in the PCV-13 group. Conclusions: In PCV-13 primed infants, a PCV-10 booster is generally less immunogenic than a PCV-13 booster. For the 3 serotypes in PCV-10 with higher antigen content and/or conjugation to diphtheria or tetanus toxoid carrier proteins, higher or similar booster responses were seen in PCV-10 recipients. Although these findings suggest that responses are generally better with a PCV-13 booster among PCV-13 primed children, the clinical significance of these differences in immunogenicity is unclear.
Parent and Teacher Perspectives on Emerging Executive Functioning in Preschoolers With Neurofibromatosis Type 1: Comparison to Unaffected Children and Lab‐Based Measures

Objective Children with neurofibromatosis type 1 (NF1) are at risk for executive functioning (EF) challenges, with little research with preschoolers. Methods EF was examined using parent and teacher ratings of preschool‐aged children with NF1 (n = 26) and parent ratings of unaffected children (n = 37) on the Behavior Rating Inventory for Executive Functioning—Preschool Form. Relations to performance on laboratory measures were also examined. Results Based on parent ratings, children with NF1 had more dysfunction than the normative mean on the Working Memory (WM) scale and Emergent Metacognition Index (EMI). Teacher ratings indicated greater dysfunction than the normative mean on the WM and Planning/Organization scales, EMI, and General Executive Composite. Children with NF1 showed more difficulties than unaffected children on the WM scale. Teacher report of WM was significantly correlated with Differential Ability Scales—Second Edition Digits Forward performance. Conclusions WM emerged as an area of difficulty for young children with NF1.
Development and validation of probe drug cocktails for the characterization of CYP450-mediated metabolism by human heart microsomes

Abstract 1. The objective of our study was to develop and validate a cocktail approach to allow the simultaneous characterization of various CYP450-mediated oxidations by human heart microsomes for nine probe drug substrates, namely, 7-ethoxyresorufin, bupropion, repaglinide, tolbutamide, bufuralol, chlorzoxazone, ebastine, midazolam and dodecanoic acid. 2. The first validation step was conducted using recombinant human CYP450 isoenzymes by comparing activity measured for each probe drug as a function of (1) buffer used, (2) selectivity towards specific isoenzymes and (3) drug interactions between probes. Activity was all measured by validated LC-MSMS methods. 3. Two cocktails were then constituted with seven of the nine drugs and subjected to kinetic validation. Finally, all probe drugs were incubated with human heart microsomes prepared from ventricular tissues obtained from 12 patients undergoing cardiac transplantation. 4. Validated cocktail #1 including bupropion, chlorzoxazone, ebastine and midazolam was used to characterize CYP2B6-, 2E1-, 2J2- and 3A5-mediated metabolism in human hearts. 5. Cocktail #2 which includes bufuralol, 7-ethoxyresorufin and repaglinide failed the validation step. Substrates in cocktail #2 as well as tolbutamide and dodecanoic acid had to be incubated separately because of their physico-chemical characteristics (solubility and ionization) or drug interactions. 6. Activity in HHM was the highest towards ebastine, chlorzoxazone and tolbutamide.
“This is Not Who I Want to be:” Experiences of Opioid-Dependent Youth Before, and During, Combined Buprenorphine and Behavioral Treatment

Novel, qualitative data were collected from youth in treatment for opioid dependence (2009–2010) regarding their experiences with opioid dependence and combined behavioral–pharmacological treatment. Urban youth participants were recruited from a larger randomized controlled trial examining the relative efficacy of two tapers of buprenorphine–naloxone, combined with behavioral treatment (ages 13–24 eligible). Twenty-two youth participated in 1- to 1.5-hour semi-structured interviews. A grounded theory approach guided the analysis. The results have the potential to inform the development of efficacious treatments for this growing, yet understudied, group of youth. Study implications and limitations are noted, and future research is prescribed. (NIDA #1R01 DA018297).
Outcomes of HIV-infected versus HIV-non-infected patients treated for drug-resistance tuberculosis: Multicenter cohort study

Background The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance. Methods We retrospectively reported and compared the DR-TB treatment outcomes of HIV-positive and HIV-negative patients treated with an individualized regimen based on WHO guidelines in seven countries: Abkhazia, Armenia, Colombia, Kenya, Kyrgyzstan, Swaziland and Uzbekistan. Results Of the 1,369 patients started DRTB treatment, 809 (59.1%) were multi-drug resistant (MDR-TB) and 418 (30.5%) were HIV-positive. HIV-positive patients were mainly from African countries (90.1%) while HIV-negative originated from Former Soviet Union (FSU) countries. Despite a higher case fatality rate (19.0% vs 9.4%), HIV-positive MDR-TB patients had a 10% higher success rate than HIV-negative patients (64.0% vs 53.2%, p = 0.007). No difference in treatment success was found among polydrug-resistant (PDR-TB) patients. Overall, lost to follow-up rate was much higher among HIV-negative (22.0% vs. 8.4%). Older age and not receiving ART were the only factors associated with unfavorable treatment outcome among HIV-positive patients. Conclusions As already known for HIV-negative patients, success rate of DR-TB HIV-positive patients remains low and requires more effective DR-TB regimen using new drugs also suitable to HIV-infected patients on ART. The study also confirms the need of ART introduction in HIV co-infected patients.