Miracle-dz/UniFAR-FTUs huggingface dataset:
A survey of ABCA1 sequence variation confirms association with dementia

We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1,567 Swedish dementia cases (including 1,275 with Alzheimer disease) and 2,203 controls, providing evidence of association with maximum significance at marker rs2230805 (odds ratio [OR]=1.39; 95% confidence interval [CI] 1.23–1.57, p=7.7×10−8). Haplotype‐based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of β‐amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease. Hum Mutat 30:1–7, 2009. © 2009 Wiley‐Liss, Inc.
Single‐Dose Gene‐Replacement Therapy for Spinal Muscular Atrophy

Background Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve motor milestones and in death or the need for mechanical ventilation by 2 years of age. We studied functional replacement of the mutated gene encoding survival motor neuron 1 (SMN1) in this disease. Methods Fifteen patients with SMA1 received a single dose of intravenous adeno‐associated virus serotype 9 carrying SMN complementary DNA encoding the missing SMN protein. Three of the patients received a low dose (6.7×1013 vg per kilogram of body weight), and 12 received a high dose (2.0×1014 vg per kilogram). The primary outcome was safety. The secondary outcome was the time until death or the need for permanent ventilatory assistance. In exploratory analyses, we compared scores on the CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) scale of motor function (ranging from 0 to 64, with higher scores indicating better function) in the two cohorts and motor milestones in the high‐dose cohort with scores in studies of the natural history of the disease (historical cohorts). Results As of the data cutoff on August 7, 2017, all 15 patients were alive and event‐free at 20 months of age, as compared with a rate of survival of 8% in a historical cohort. A rapid increase from baseline in the score on the CHOP INTEND scale followed gene delivery, with an increase of 9.8 points at 1 month and 15.4 points at 3 months, as compared with a decline in this score in a historical cohort. Of the 12 patients who had received the high dose, 11 sat unassisted, 9 rolled over, 11 fed orally and could speak, and 2 walked independently. Elevated serum aminotransferase levels occurred in 4 patients and were attenuated by prednisolone. Conclusions In patients with SMA1, a single intravenous infusion of adenoviral vector containing DNA coding for SMN resulted in longer survival, superior achievement of motor milestones, and better motor function than in historical cohorts. Further studies are necessary to confirm the safety and efficacy of this gene therapy. (Funded by AveXis and others; ClinicalTrials.gov number, NCT02122952.)
Proton Magnetic Resonance Spectroscopy–Detected Changes of Marrow Fat Content in a Rabbit Model of Osteoporosis Treated With Epigallocatechin-3-Gallate

Objective The aim of this study was to longitudinally evaluate the changes in marrow fat content of ovariectomized (OVX) rabbits treated with epigallocatechin-3-gallate (EGCG) using proton magnetic resonance spectroscopy (1H-MRS). Methods Thirty-six female New Zealand rabbits were equally divided into sham operation, OVX controls, and OVX treated with EGCG (intraperitoneally, 1.8 mg/kg) for 5 months. Marrow fat fraction by 1H-MRS and bone density by peripheral quantitative computed tomography were determined at 0, 3, and 5 months. Serum biomarkers and marrow adipocytes were determined at the end of experiment. Results Estrogen deficiency increased marrow fat content in a time-dependent manner, with a variation of marrow fat fraction (FF) (+25.3%) at month 3 from baseline, and it was maintained until month 5 (+66.6%, all P < 0.001). In comparison with the sham-operated controls, adipocytes density, size, and percentage of adipocytes area in the OVX controls increased by 62.9%, 44.4%, and 178%, respectively (all P < 0.05). These OVX-induced pathological changes were partly reversed by EGCG treatment. In addition, EGCG treatment reduced bone turnover and increased bone density of OVX rabbits. Conclusions Epigallocatechin-3-gallate exhibits an anabolic effect on osteoporotic bone by concomitantly rescuing bone mass and mitigating marrow adiposity. 1H-MRS appears to be a useful tool for monitoring osteoporosis-related treatments.
Antidepressants and heart-rate variability in older adults: a population-based study

Background Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study. Method In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991–2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs. Results We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes. Conclusion TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.
Scalable Thin-Film Manufacturing Technologies for Organic Electronics

Over the last years, research in the field of organic electronics has primarily targeted the development of more efficient and stable materials along with the optimization of parameters within common techniques, with the aim of achieving more competitive device performance. The development of novel processing technologies required for enabling industrial-scale, large-area and high-throughput manufacturing were consequently given less attention among researchers. In this thesis a generalized framework for the development of innovative processing technologies suitable for scalable manufacturing of solution-processable organic thin-film electronics is introduced. Three promising technologies, nanoimprint lithography, transfer printing, and spray deposition are in focus, rendering the core of this thesis. Their evaluation is performed within the context of application to polymer and carbon nanotube thin-film technologies.
Replacement correction factors for cylindrical ion chambers in electron beams.

PURPOSE In the TG-21 dosimetry protocol, for cylindrical chambers in electron beams the replacement correction factorPrepl (or the product pdispcav in the IAEA's notation), was conceptually separated into two components: the gradient correction (Pgr) accounting for the effective point of measurement and the fluence correction (Pfl) dealing with the change in the electron fluence spectrum. At the depth of maximum dose (dmax), Pgr is taken as 1. There are experimental data available at dmax for the values of Pfl (or Prepl). In the TG-51 dosimetry protocol, the calibration is at the reference depth dref=0.6R50-0.1(cm) where Pgr is required for cylindrical chambers and Pfl is unknown and so the measured values at dmax are used with the corresponding mean electron energy at dref. Monte Carlo simulations are employed in this study to investigate the replacement correction factors for cylindrical chambers in electron beams. METHODS Using previously established Monte Carlo calculation methods, the values ofPrepl and Pfl are calculated with high statistical precision (<0.1%) for cylindrical cavities of a variety of diameters and lengths in a water phantom irradiated by various electron beams. The values of Pgr as defined in the TG-51 dosimetry protocol are also calculated. RESULTS The calculated values of the fluence correction factorsPfl are in good agreement with the measured values when the wall correction factors are taken into account for the plane-parallel chambers used in the measurements. An empirical formula for Pfl for cylindrical chambers at dref in electron beams is derived as a function of the chamber radius and the beam quality specifier R50. CONCLUSIONS The mean electron energy at depth is a good beam quality specifier forPfl. Thus TG-51's adoption of Pfl at dmax with the same mean electron energy for use at dref is proven to be accurate. The values of Pgr for a Farmer-type chamber as defined in the TG-51 dosimetry protocol may be wrong by 0.3% for high-energy electron beams and by more than 1% for low-energy electron beams.
Exercise Capacity, Physical Activity, and Obesity in Adults With Repaired Aortic Coarctation

Background:Patients with aortic coarctation (COA) have a reduced exercise capacity and seem to be more prone to adopt a sedentary lifestyle. During clinical practice, we often observe that patients seem to be overweight. However, data on physical activity and weight status in this population are currently not available. Objective:This study aimed to describe weight status, self-reported physical activity levels, and self-perceived health status in adults with repaired COA in comparison with healthy counterparts and to investigate the relationships among exercise capacity, physical activity, weight status, and perceived health status. Methods:We studied 103 COA patients who underwent cardiopulmonary exercise testing and who completed the Flemish Physical Activity Computerized Questionnaire and the short-form 36 health survey questionnaire. Results:Patients with COA show a significantly lower exercise tolerance than what would be expected in healthy persons (P < .0001). Weight status was similar to the overall Belgian population, but a tendency toward higher body mass index was present. Patients with COA report a lower level of habitual physical activity (P < .05) as well as reductions in perceived vitality, general health, and mental health (P < .05). Parameters of habitual physical activity are related to exercise capacity (total energy expenditure: r = 0.278, P = .0015). The more active COA patients report higher scores of perceived physical functioning, general health, and mental health. Overweight patients did not perform significantly different than patients with a healthy weight did. Conclusions:Adults with repaired COA have a reduced exercise tolerance, which is related to low physical activity levels. Up to one-third of the COA patients we studied are overweight. As a poor exercise capacity identifies patients at risk for hospitalization and death and obesity might adversely influence the development of cardiovascular disease, it is important to improve the exercise capacity in these patients. Guiding patients toward more physical activity in daily life might therefore be the number 1 preventive measure to be taken in this patient group.
The chemical composition of mineral trioxide aggregate

Mineral trioxide aggregate (MTA) is composed of Portland cement, with 4:1 addition of bismuth oxide added so that the material can be detected on a radiograph. The cement is made up of calcium, silicon and aluminium. The main constituent phases are tricalcium and dicalcium silicate and tricalcium aluminate. There are two commercial forms of MTA, namely the grey and the white. The difference between the grey and the white materials is the presence of iron in the grey material, which makes up the phase tetracalcium alumino-ferrite. This phase is absent in white MTA. Hydration of MTA occurs in two stages. The initial reaction between tricalcium aluminate and water in the presence of calcium sulphate results in the production of ettringite. Tricalcium and dicalcium silicate react with water to produce calcium silicate hydrate and calcium hydroxide, which is leached out of the cement with time.
Assessment of Metabolic Stability Using the Rainbow Trout (Oncorhynchus mykiss) Liver S9 Fraction

Standard protocols are given for assessing metabolic stability in rainbow trout using the liver S9 fraction. These protocols describe the isolation of S9 fractions from trout livers, evaluation of metabolic stability using a substrate depletion approach, and expression of the result as in vivo intrinsic clearance. Additional guidance is provided on the care and handling of test animals, design and interpretation of preliminary studies, and development of analytical methods. Although initially developed to predict metabolism impacts on chemical accumulation by fish, these procedures can be used to support a broad range of scientific and risk assessment activities including evaluation of emerging chemical contaminants and improved interpretation of toxicity testing results. These protocols have been designed for rainbow trout and can be adapted to other species as long as species‐specific considerations are modified accordingly (e.g., fish maintenance and incubation mixture temperature). Rainbow trout is a cold‐water species. Protocols for other species (e.g., carp, a warm‐water species) can be developed based on these procedures as long as the specific considerations are taken into account. Curr. Protoc. Toxicol. 53:14.10. 1‐14.10. 28. © 2012 by John Wiley & Sons, Inc.
A low-delay MAC solution for MIMO ad hoc networks

Beamforming is regarded as a key element for multiantenna ad hoc networks. However, it cannot simultaneously provide the omnidirectional and long-range coverage required by broadcast transmissions, a problem known as the Asymmetry in Gain. We propose a scheme for control packet exchange over an extended radio coverage based on a Space Time Code technique. This solution is shown to solve the Asymmetry in Gain issue, and is proposed as part of a MAC protocol for MIMO ad hoc networks, whose performance benefits include increased throughput and reduced delay and energy consumption.
Crystalline and correlated phases in two-dimensional transition metal dichalcogenides

This thesis is dedicated to the study of various aspects of the electronic structure of twodimensional transition metal dichalcogenides (TMDs) of chemical composition MX2 (where M is a transition metal atom and X= S, Se, Te), using a combination of ab inito density-functional methods. We first address the relative stability of the 1T and 1H phases of two-dimensional TMDs as a function of the column of the transition metal atom in the periodic table. Using a Wannierfunction approach, we calculate crystal field and ligand field parameters for a broad range of members of this family of materials. Taking TaS2 as an example, we show how the splitting of the d electron states arises from an interplay of electrostatic effects and hybridization with the ligands’ s, p and d states. We show that the ligand field alone cannot explain the stabilization of the 1H polymorph for d 1 and d 2 TMDs, and that band structure effects are dominant. We present trends of the calculated parameters across the periodic table, and argue that these allow developing simple chemical intuition. Secondly, we study the occurrence of charge density wave phases and periodic lattice distortion in metallic 1T transition metal dichalcogenides. The phonon dispersion and fermiology of representative examples with different d electron counts are studied as a function of doping. Two qualitatively different behaviours are found as a function of the filling of the t2g subshell. We argue that away from half-filling, weak-coupling nesting arguments are a useful starting point for understanding, whereas closer to half-filling a strong-coupling real-space picture is more correct. Using Wannier functions, it is shown that strong metal-metal bonds are formed and that simple bond-counting arguments apply. Thirdly, the recently synthesized 1T phase of NbSe2, in monolayer form, is investigated from first principles. We find that 1T -NbSe2 is unstable towards the formation of an incommensurate charge density wave phase, whose periodicity can be understood from the Fermi surface topology. We investigate different scenarios for the experimentally observed superlattice and insulating behaviour, and conclude that the star-of-David phase is the most stable commensurate charge density wave phase. We study the electronic properties of the star-of-David phase at various levels of theory and confirm its Mott insulating character, as speculated and in analogy with TaS2. The Heisenberg exchange couplings are found to be ferromagnetic, which suggests a parallel with the so-called flat-band ferromagnetism in certain multiband Hubbard models. Finally, we address the possibility of the occurrence of the excitonic insulator phase in singlelayer TiSe2. The relative role of electron-electron and electron-phonon interactions in driving the charge density wave in layered and two-dimensional TiSe2 has been disputed and is still
Robotic-assisted intracorporeal anastomosis versus extracorporeal anastomosis in laparoscopic right hemicolectomy for cancer: a case control study.

INTRODUCTION Extracorporeal ileocolic anastomosis in laparoscopic right hemicolectomy for cancer has a significant risk of complications. The aim of this study is to evaluate the operative and postoperative results of hybrid right hemicolectomy with intracorporeal robotic-assisted anastomosis for adenocarcinoma of the ascending colon compared with the standard extracorporeal anastomosis in a case control study. PATIENTS AND METHODS Forty-eight right hemicolectomies for cancer (2009-2012) with laparoscopic medial to lateral dissection, vascular ligation, bowel transection, and robotic-assisted intracorporeal anastomosis with specimen extraction through a Pfannestiel incision (robotic group [RG]) were compared with 48 laparoscopic hemicolectomies (2009-2011) with extracorporeal anastomosis (laparoscopic group [LG]). RESULTS The two groups were comparable with respect to age, gender, stage of cancer, and body mass index. Surgery time was significantly longer in RG patients (RG, 266±41 minutes; LG, 223±51 minutes; P<.05). Operative results were similar in the two groups. Recovery of bowel function (day of first bowel movement: RG, 3.0±1.0 days; LG, 4.0±1.2 days; P<.05) and hospital stay (RG, 7.5±2.0 days; LG, 9.0±3.2 days; P<.05) were quicker and shorter, respectively, in RG. There were four anastomotic complications and four incisional hernias in LG and none in RG (P<.05). CONCLUSIONS There are fewer anastomotic and wound complications in RG patients. Intracorporeal robotic-assisted ileocolic anastomosis allows a faster recovery compared with extracorporeal anastomosis.
Ribavirin dose reduction during telaprevir/ribavirin/peg‐interferon therapy overcomes the effect of the ITPA gene polymorphism

Treatment success of chronic hepatitis C virus genotype 1 infection has improved with the advent of telaprevir plus peg‐interferon/ribavirin triple combination therapy. However, the effect of inosine triphosphatase (ITPA) polymorphism on dose reduction during triple therapy, especially during the postmarketing phase, has not been sufficiently evaluated. We analysed 273 patients with genotype 1 infection who were treated with triple therapy and assessed the effect of the ITPA polymorphism on dose reduction. ITPA and IFNL4 SNP genotypes were determined by the Invader assay. A stepwise multivariate regression analysis was performed to identify factors associated with outcome of the therapy. The overall sustained viral response (SVR) rate 12 weeks after the end of therapy was 80.2% (219/273). Decline of haemoglobin was significantly faster, and ribavirin was more extensively reduced in patients with ITPA SNP rs1127354 genotype CC than CA/AA. Extensive reduction of ribavirin resulted in mild reduction of telaprevir and peg‐interferon, but no significant increase in viral breakthrough. Although the amount of telaprevir given was slightly higher in CA/AA patients, the total dose of peg‐interferon and the SVR rate did not differ between the two groups. Multivariate analysis showed that IFNL4 but not ITPA SNP genotype, platelet count and peg‐interferon adherence were significantly associated with outcome of therapy. Postmarketing‐phase triple therapy resulted in a high SVR rate in spite of extensive ribavirin dose reduction in a diverse patient population, indicating the importance of treatment continuation and appropriate management of adverse events.
The Eutos long‐term survival score accurately predicts the risk of death in chronic myeloid leukaemia patients treated outside of clinical trials

gle center study with a small sample of pediatric patients receiving MSDT. Second, MFC based MRD detection does not have a uniform sensitivity across all cases. In summary, our results indicate that for pre-MRD positive cases, haplo-SCT should be chosen, and prophylaxis donor lymphocyte infusion (DLI) should be performed if MSDT is used. Our results, together with the available literature, suggest that monitoring MRD during the peri-transplantation period, in combination with MRD-directed prophylaxis or preemptive therapies, could reduce the incidence of morphologic relapse and improve survival.
Round-robin Arbiter Design and Generation

In this paper, we introduce a Round-robin Arbiter Generator (RAG) tool. The RAG tool can generate a design for a Bus Arbiter (BA). The BA is able to handle the exact number of bus masters for both on-chip and off-chip buses. RAG can also generate a distributed and parallel hierarchical Switch Arbiter (SA). The first contribution of this paper is the automated generation of a round-robin token passing BA to reduce time spent on arbiter design. The generated arbiter is fair, fast, and has a low and predictable worst-case wait time. The second contribution of this paper is the design and integration of a distributed fast arbiter, e.g., for a terabit switch, based on 2/spl times/2 and 4/spl times/4 switch arbiters (SAs). Using a . 25/spl mu/ TSMC standard cell library from LEDA Systems [10, 14], we show the arbitration time of a 256/spl times/256 SA for a terabit switch and demonstrate that the SA generated by RAG meets the time constraint to achieve approximately six terabits of throughput in a typical network switch design. Furthermore, our generated SA performs better than the Ping-Pong Arbiter and Programmable Priority Encoder by a factor of 1.9/spl times/ and 2.4/spl times/, respectively.