Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Vitamin D Insufficiency and Seasonal Decrease on Cognition

Background: Vitamin D3 (cholecalciferol) deficiency has been associated with dementia and cognitive decline. Which cognitive domains are most associated with D3 levels and how seasonal fluctuations in levels relate to cognition is unclear. We addressed these questions using a prospective observational study examining associations between D3 levels and cognition among individuals living in northern latitudes (54°N) in summer and winter. Methods: Healthy adult participants underwent testing in summer and winter of D3 levels and cognition, using the Symbol digit Modalities test, phonemic fluency, digit Span and CANTAB® battery. Results: Of 32 participants tested in the summer, 46% were D3 insufficient (<75 nmol/L) and performed worse on digit Span Backward (DS-B) (μ=5.8, SD=2) than those who were sufficient (μ=7.9, SD=2), p=0.018. In multivariate analyses, sufficiency status was an independent predictor of dS-B, (b=0.41, p=0.02). The majority (63%) of 19 participants tested in winter were D3 insufficient, with levels declining by a median of 15 nmol/L overall. Those with insufficient levels performed worse (i.e., higher scores) on the CANTAB® Spatial Working Memory (SWM) task (μ=36.1, SD=6 versus μ=29.3, SD=8), p=0.05). Those with larger drops in levels (≥15 nmol/L) showed decline/less improvement on the CANTAB® one touch Stockings of Cambridge (OTS) task, (μ=0.50, SD=1.9 versus μ=-2.11, SD=2.6, p=0.01), a test of working memory/executive functioning. Conclusions: Vitamin D3 insufficiency and seasonal declines ≥15 nmol/L were associated with inferior working memory/executive functioning. While our findings require confirmation, they suggest that sufficient D3 levels should be maintained year-round, likely necessitating supplementation, at least during winter at higher latitudes.
Estimating reassortment rates in co-circulating Eurasian swine influenza viruses

Swine have often been considered as a mixing vessel for different influenza strains. In order to assess their role in more detail, we undertook a retrospective sequencing study to detect and characterize the reassortants present in European swine and to estimate the rate of reassortment between H1N1, H1N2 and H3N2 subtypes with Eurasian (avian-like) internal protein-coding segments. We analysed 69 newly obtained whole genome sequences of subtypes H1N1–H3N2 from swine influenza viruses sampled between 1982 and 2008, using Illumina and 454 platforms. Analyses of these genomes, together with previously published genomes, revealed a large monophyletic clade of Eurasian swine-lineage polymerase segments containing H1N1, H1N2 and H3N2 subtypes. We subsequently examined reassortments between the haemagglutinin and neuraminidase segments and estimated the reassortment rates between lineages using a recently developed evolutionary analysis method. High rates of reassortment between H1N2 and H1N1 Eurasian swine lineages were detected in European strains, with an average of one reassortment every 2–3 years. This rapid reassortment results from co-circulating lineages in swine, and in consequence we should expect further reassortments between currently circulating swine strains and the recent swine-origin H1N1v pandemic strain.
Lack of publicly available scientific evidence on the safety and effectiveness of implanted medical devices.

IMPORTANCE Under the 510(k) process, the US Food and Drug Administration (FDA) clears about 400 implanted medical devices that are considered moderate to high risk for market each year without requiring clinical testing. Instead, the FDA requires the applicant to provide scientific evidence that the new device is "substantially equivalent" to a device or devices already on the market (predicate devices). Companies are legally required to submit the evidence to the FDA and to make publicly available at least a summary of the evidence. OBJECTIVE To assess the types of scientific evidence used to determine substantial equivalence, safety, or effectiveness for a representative sample of implanted medical devices; the number of predicates for each implant; and whether this evidence was publicly available. DESIGN Using FDA databases, we determined the device categories of the first 5 implanted medical devices cleared through the 510(k) process in 2008: cardiovascular, dental, general and plastic surgery, neurological, and orthopedic. We then identified the first 2 implanted medical devices approved in each of the 5 categories for each year from 2008 through 2012. The sample of 50 devices included, for example, total hip implants, vascular embolization devices, and surgical mesh. We also identified the 1105 predicates the manufacturers listed for these devices. MAIN OUTCOMES AND MEASURES For each implanted medical device and its predicates, we determined whether clinical or nonclinical scientific evidence was provided to the FDA to support the claim of substantial equivalence and whether this evidence was publicly available. We also determined if safety or effectiveness data were provided. RESULTS Scientific data to support the claim of substantial equivalence were publicly available for 8 of the 50 newly cleared implants (16%) and 31 of their 1105 listed predicates (3%). Most of the evidence was nonclinical data; some of the data also evaluated safety or effectiveness. CONCLUSIONS AND RELEVANCE Despite the legal requirement that scientific evidence of substantial equivalence be publicly available for medical devices cleared by the FDA through the 501(k) process, such information is lacking for most implanted medical devices cleared between 2008 and 2012, as well as for their predicates.
PSP-SOI: A Surface Potential Based Compact Model of Partially Depleted SOI MOSFETs

This paper reports recent progress on partially depleted (PD) SOI modeling using a surface potential based approach. The new model, called PSP-SOI, is formulated within the framework of the latest industry standard bulk MOSFET model PSP. In addition to its physics-based formulation and scalability inherited from PSP, PSP-SOI captures SOI specific effects by including a floating body simulation capability, a parasitic bipolar model, and self-heating. A nonlinear body resistance is included for modeling body-contacted SOI devices. The PSP-SOI model has been extensively tested on several PD/SOI technologies.
Pathogen evolution: slow and steady spreads the best

The theory of life history evolution provides a powerful framework to understand the evolutionary dynamics of pathogens in both epidemic and endemic situations. This framework, however, relies on the assumption that pathogen populations are very large and that one can neglect the effects of demographic stochasticity. Here we expand the theory of life history evolution to account for the effects of finite population size on the evolution of pathogen virulence. We show that demographic stochasticity introduces additional evolutionary forces that can qualitatively affect the dynamics and the evolutionary outcome. We discuss the importance of the shape of pathogen fitness landscape and host heterogeneity on the balance between mutation, selection and genetic drift. In particular, we discuss scenarios where finite population size can dramatically affect classical predictions of deterministic models. This analysis reconciles Adaptive Dynamics with population genetics in finite populations and thus provides a new theoretical toolbox to study life-history evolution in realistic ecological scenarios.
Resynchronization therapy in an adolescent with pacemaker-related ventricular dysfunction

A 15-year-old female patient was admitted to our ward with exhaustion, weakness, fatigue, and edema. She had a prosthetic aortic valve replacement 9 years ago. She developed atrioventricular (AV) block in the postoperative period and a single chamber pacemaker was implanted then. On admission, she had NYHA class 2–3 symptoms; chest X-ray showed cardiomegaly [Figure 1a], and electrocardiogram (ECG) had pacemaker rhythm and complete left-bundle block. Transthoracic echocardiography showed dilatation of left ventricle and left atrium, normally functioning prosthetic aortic valve, and LV systolic dysfunction. Left ventricular end diastolic
Biochemical Analysis of Hypermutation by the Deoxycytidine Deaminase APOBEC3A*

Background: The ssDNA cytosine deaminase activity of the HIV restriction factor APOBEC3A was analyzed. Results: APOBEC3A does not deaminate ssDNA with high processivity. Conclusion: Deamination motif and not processivity appears more important for mutational inactivation of HIV. APOBEC3A may deaminate genomic DNA during transcription. Significance: Genomic DNA may undergo enzymatic deoxycytidine deamination as a cost for a deamination-based viral restriction mechanism. APOBEC3A belongs to a family of single-stranded DNA (ssDNA) DNA cytosine deaminases that are known for restriction of HIV through deamination-induced mutational inactivation, e.g. APOBEC3G, or initiation of somatic hypermutation and class switch recombination (activation-induced cytidine deaminase). APOBEC3A, which is localized to both the cytoplasm and nucleus, not only restricts HIV but can also initiate catabolism of cellular DNA. Despite being ascribed these roles, there is a paucity of data available on the biochemical mechanism by which APOBEC3A deaminates ssDNA. Here we assessed APOBEC3A deamination activity on ssDNA and in dynamic systems modeling HIV replication (cytoplasmic event) and DNA transcription (nuclear event). We find that APOBEC3A, unlike the highly processive APOBEC3G, exhibits low or no processivity when deaminating synthetic ssDNA substrates with two cytosines located 5–63 nucleotides apart, likely because of an apparent Kd in the micromolar range (9.1 μm). APOBEC3A was able to deaminate nascently synthesized (−)DNA in an in vitro model HIV replication assay but induced fewer mutations overall in comparison to APOBEC3G. However, the data indicate that the target deamination motif (5′-TC for APOBEC3A and 5′-CC for APOBEC3G) and not the number of mutations best predicted the ability to mutationally inactivate HIV. We further assessed APOBEC3A for the ability to deaminate dsDNA undergoing transcription, which could allow for collateral deaminations to occur in genomic DNA similar to the action of activation-induced cytidine deaminase. That APOBEC3A was able to deaminate dsDNA undergoing transcription suggests a genomic cost of a deamination-based retroviral restriction system.
GABAA Receptor Subtype‐Selective Efficacy: TPA023, an α2/α3 Selective Non‐sedating Anxiolytic and α5IA, an α5 Selective Cognition Enhancer

TPA023 and α5IA are structurally related compounds that selectively modulate certain GABAA receptor subtypes. Hence, TPA023 has weak partial agonist efficacy at the α2 and α3 subtypes whereas α5IA has inverse agonist efficacy at the α5 subtype. These efficacy characteristics translate into novel pharmacological profiles in preclinical species with TPA023 being a nonsedating anxiolytic in rats and primates whereas α5IA enhanced cognition in rats but was devoid of the proconvulsant or kindling liabilities associated with nonselective inverse agonists. In vitro and in vivo metabolic studies showed that TPA023 was metabolized via CYP3A4‐mediated t‐butyl hydroxylation and N‐deethylation whereas α5IA was metabolized to produce the hydroxymethyl isoxazole, the latter of which was highly insoluble and caused renal toxicity in preclinical species. In humans, TPA023 had a half‐life in the region of 6–7 h whereas the half‐life of α5IA was 2–2.5 h. TPA023 was clearly differentiated from the nonselective agonist lorazepam in terms of saccadic eye movement and unlike lorazepam, it did not impair either postural stability, as judged by body sway, or cognition. The occurrence of the hydroxymethyl isoxazole metabolite of α5IA in human urine precluded the use of α5IA in prolonged dosing studies. Nevertheless, α5IA was evaluated in an alcohol‐induced cognitive impairment model in healthy normal volunteers and was found to reverse the memory‐impairing effects of alcohol. To date, however, no efficacy data for either TPA023 or α5IA in patient populations has been reported, although at the very least, the preclinical and limited clinical data with TPA023 and α5IA validate the approach of targeting specific GABAA receptors through subtype‐selective efficacy.
Smoking habits and benign prostatic hyperplasia

AbstractPrevious studies have warned against the promoting effects of cigarette smoking on benign prostatic hyperplasia (BPH). In contrast, some have argued that smoking confers a protective effect regarding BPH, while others have observed an aggravated effect. Thus, we performed this meta-analysis to determine whether cigarette use is associated with BPH risk.To identify articles from observational studies of relevance, a search was performed concurrent to March 21, 2016, on PubMed, Web of Science, Cochrane, EBSCO, and EMBASE databases. Random-effect model, according to the heterogeneity, was calculated to reveal the relative risks (RRs) and corresponding 95% confidence intervals (CIs). Eight articles were included in this meta-analysis, representing data for 44,100 subjects, of which 5221 (11.8%) had BPH as defined according to the criteria. Seven reports are concerned with analysis between nonsmokers and ex-smokers, in which no significant difference was observed (RR = 0.99, 95% CI 0.94–1.05). Another meta-analysis of 7 studies indicated an observable trend, but without significant difference between groups of nonsmokers and current smokers (RR = 1.17, 95% CI 0.98–1.41). Between groups of heavy (6 articles; RR = 1.02, 95% CI 0.84–1.24) and light smokers (5 articles; RR = 0.90, 95% CI 0.71–1.15), again no significant difference appears. Finally, we combined individuals as never-smokers and ever-smokers and still found no significant difference between the 2 groups of patients (RR = 1.03, 95% CI 0.92–1.15). Sensitivity analysis was displayed and confirmed the stability of the present results.Combined evidence from observational studies shows no significant association between cigarette smoking and BPH risk, either for ex-smokers or for current smokers. The trend of elevated BPH risk from smoking was observed only in current smokers compared with nonsmokers, while marginal significance was observed in comparing ever-smokers with never-smokers in operative patients with BPH.
The Do Not Disturb Challenge: A Day Without Notifications

We asked 12 people to disable notification alerts for 24 hours on all computing devices. We collected data through open post-hoc interviews and analyzed the qualitative data using Open Coding. The participants showed very strong and polarized opinions towards notification alerts. During work, some participants felt less stressed and more productive thanks to not being interrupted, however outside of the work context, some became stressed and anxious because they were afraid of missing important information and violating expectations of others. This is the first holistic approach to notifications studying their effect across services, devises and work and private life. In contrast to previous studies, some participants acted upon the positive experiences and turned notifications of some applications off.
Allocation and scheduling algorithms for IEEE 802.14 and MCNS in hybrid fiber coaxial networks

IEEE 802.14 and MCNS (multimedia cable network system) are two standards developed for the hybrid fiber coaxial (HFC) CATV networks. Both standards model an upstream channel as a stream of minislots. But their philosophies on resolving collisions in the shared upstream channel are rather different, where IEEE 802.14 adopts the priority+FIFO first-transmission rule and the n-ary tree retransmission rule, and MCNS adopts the binary exponential backoff algorithm with adjustable window sizes. Both provide reservation access, while IEEE 802.14 and MCNS also support isochronous access and immediate access, respectively. In this paper, we try to prepare a suggestion list for vendors on how to allocate minislots for reservation access and immediate access and how to schedule the reserved bandwidth, which greatly affect the performance of a cable network and are left open by the standards.
New Reference Curves for Head Circumference at Birth, by Gestational Age

BACKGROUND: The measurement of head circumference (HC) at birth reflects intrauterine brain development. HC charts currently used in Canada are either dated, mixed-gender, nonrepresentative of lower gestational ages (GAs), or reflective of other populations. METHODS: To create both birth weight and HC curves, we combined weight and HC data from the Canadian Neonatal Network (CNN) database (admissions in NICUs across Canada) with McGill’s Obstetrical Neonatal Database (MOND; all births at a tertiary hospital in Montreal, Canada). We included CNN data for GAs of 23 to 34 weeks (2003–2007) and MOND data for GAs of 35 to 41 weeks (1995–2006). Nonsingletons, congenital anomalies, and measurements greater than ±4 SD from the mean were excluded. Distributions of birth weight and HC at each GA were statistically (penalized spline regression) smoothed. Birth weight curves were compared with recent Canadian reference curves and HC curves with historical and/or frequently used curves. RESULTS: We included 39 896 births (3121 births at <30 weeks’ GA) to generate the curves. Current weight curves were similar to Canadian reference charts for both genders. Weight and HC measurements in boys were higher than in girls. When classified according to recent international references, the proportion of CNN-MOND infants at ≥32 weeks’ GA with HCs <10th percentile was significantly underestimated. When classified according to historical reference curves, a significant number of CNN-MOND infants of all GAs with HCs <10th and >90th percentiles were misclassified. CONCLUSIONS: We developed recent gender-specific reference curves for HC at birth for singletons at 23 to 41 completed weeks’ GA, which included a large number of very premature infants, reflecting the current geotemporal Canadian population.
Scoring schemes of palindrome clusters for more sensitive prediction of replication origins in herpesviruses

Many empirical studies show that there are unusual clusters of palindromes, closely spaced direct and inverted repeats around the replication origins of herpesviruses. In this paper, we introduce two new scoring schemes to quantify the spatial abundance of palindromes in a genomic sequence. Based on these scoring schemes, a computational method to predict the locations of replication origins is developed. When our predictions are compared with 39 known or annotated replication origins in 19 herpesviruses, close to 80% of the replication origins are located within 2% of the genome length. A list of predicted locations of replication origins in all the known herpesviruses with complete genome sequences is reported.
Combining structure and dynamics: non-denaturing high-pressure effect on lysozyme in solution

Small-angle X-ray scattering (SAXS) and elastic and quasi-elastic neutron scattering techniques were used to investigate the high-pressure-induced changes on interactions, the low-resolution structure and the dynamics of lysozyme in solution. SAXS data, analysed using a global-fit procedure based on a new approach for hydrated protein form factor description, indicate that lysozyme completely maintains its globular structure up to 1500 bar, but significant modifications in the protein–protein interaction potential occur at approximately 600–1000 bar. Moreover, the mass density of the protein hydration water shows a clear discontinuity within this pressure range. Neutron scattering experiments indicate that the global and the local lysozyme dynamics change at a similar threshold pressure. A clear evolution of the internal protein dynamics from diffusing to more localized motions has also been probed. Protein structure and dynamics results have then been discussed in the context of protein–water interface and hydration water dynamics. According to SAXS results, the new configuration of water in the first hydration layer induced by pressure is suggested to be at the origin of the observed local mobility changes.
The population‐based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US

There have been no large population‐based studies of the prevalence of achondroplasia and thanatophroic dysplasia in the United States. This study compared data from seven population‐based birth defects monitoring programs in the United States. We also present data on the association between older paternal age and these birth defects, which has been described in earlier studies. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths (1/27,780–1/16,670 livebirths). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 livebirths (1/33,330–1/47,620 livebirths). In Texas, fathers that were 25–29, 30–34, 35–39, and ≥40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers. The adjusted prevalence odds ratios were 2.8 (95% CI; 1.2, 6.7), 2.8 (95% CI; 1.0, 7.6), 4.9 (95% CI; 1.7, 14.3), and 5.0 (95% CI; 1.5, 16.1), respectively. Using the same age categories, the crude prevalence odds ratios for de novo cases of thanatophoric dysplasia in Texas were 5.8 (95% CI; 1.7, 9.8), 3.9 (95% CI; 1.1, 6.7), 6.1 (95% CI; 1.6, 10.6), and 10.2 (95% CI; 2.6, 17.8), respectively. These data suggest that thanatophoric dysplasia is one‐third to one‐half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. Birth defects monitoring programs may be a good source of ascertainment for population‐based studies of achondroplasia and thanatophoric dysplasia, provided that diagnoses are confirmed by review of medical records. © 2008 Wiley‐Liss, Inc.
Factor Analysis of Clustered Cardiovascular Risks in Adolescence: Obesity Is the Predominant Correlate of Risk Among Youth

Background—Clustering of cardiovascular (CV) risks begins in childhood, yet studies of the factor structure underlying this clustering have focused on adults. The increasing rates of obesity and type 2 diabetes and the growing importance of metabolic syndrome among adolescents make assessment of CV risk clustering even more urgent in this age group. Methods and Results—Exploratory factor analysis (principal components analysis) was performed with data from 1578 healthy seventh to 12th graders from the Princeton School District Study, a school-based study in Cincinnati, Ohio. Measured CV risks included cholesterol, triglycerides, fasting insulin and glucose, body mass index (BMI), waist circumference, fibrinogen, and blood pressure. Factor analysis yielded 4 uncorrelated factors (adiposity [BMI, waist, fibrinogen, insulin], cholesterol [LDL and total cholesterol], carbohydrate-metabolic [glucose, insulin, HDL cholesterol, triglycerides], and blood pressure [systolic and diastolic blood pressure]). These factors explained approximately 67% of the total variance. A summary cumulative risk scale was derived from factor scores, and high risk was defined as scoring in the top 5%. Although insulin loaded onto both the adiposity and carbohydrate-metabolic factors, obesity was a much stronger correlate of high cumulative risk (odds ratio=19.2; 95% CI, 7.6 to 48.5) than hyperinsulinemia (odds ratio=3.5; 95% CI, 1.8 to 6.8). A sizable proportion (18.5%; n=12) of those who were at high cumulative risk were not at high risk for any of the individual factors. Conclusions—The patterning of CV risk clustering seen among adults is present in healthy adolescents. Among youth, obesity is the predominant correlate of cumulative risk.