Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of clofarabine, cyclophosphamide, and etoposide for relapsed or refractory childhood and adolescent acute myeloid leukemia

ABSTRACT Relapsed/refractory acute myeloid leukemia (AML) has an extremely poor prognosis. We describe 17 children and adolescents with relapsed/refractory AML who received clofarabine, cyclophosphamide, and etoposide. Seven patients (41%) responded: 4 with a complete response (CR); 1 with CR with incomplete platelet recovery; and 2 with a partial response. Additionally, 4 developed hypocellular marrow without evidence of leukemia; 5 patients had resistant disease; and 1 suffered early toxic death. After further therapy including transplantation, 4 patients (24%) are alive without evidence of disease at a median of 60 months. This anthracycline-free regimen may be studied for relapsed or refractory AML, but due to the high risk of marrow aplasia reduced doses of clofarabine and cyclophosphamide should be used.
Nuclear and mitochondrial sequences confirm complex colonization patterns and clear species boundaries for flightless weevils in the Galápagos archipelago

Nuclear sequence data were collected from endemic Galápagos species and an introduced close relative, and contrasted with mitochondrial DNA sequences, continuing investigation into the colonization history and modes of diversification in the weevil genus Galapaganus. The current combined phylogeny together with previously published penalized likelihood age estimates builds a complex picture of the archipelago's colonization history. The present reconstruction relies on submerged platforms to explain the early divergence of the young southern Isabela endemics or the Española or San Cristobal populations. Diversity is later built through inter-island divergence starting on older islands and continuing on two simultaneous tracks towards younger islands. The amount of diversity generated through intra-island processes is skewed towards older islands, suggesting that island age significantly influences diversity. Phylogenetic concordance between nuclear and mitochondrial datasets and well-supported monophyletic species in mitochondrial derived topologies appear to reject the possibility of inter-species hybridization. These clear species boundaries might be related to the tight host associations of adult weevils in discrete ecological zones. If shared hosts facilitate hybridization, then host- or habitat-promoted divergences could prevent it, even in the case of species that share islands, since the altitudinal partitioning of habitats minimizes range overlap.
INTRASEXUAL SELECTION CONSTRAINS THE EVOLUTION OF THE DORSAL COLOR PATTERN OF MALE BLACK SWALLOWTAIL BUTTERFLIES, PAPILIO POLYXENES

Males of the eastern black swallowtail (Papilio polyxenes asterius Stoll) with typical coloration were more successful in intrasexual competition for mating territories than were males altered to have female‐like mimetic coloration. Sibling males were matched for wingspan and emergence date and released as pairs, one with its pattern altered and one a control that was marked but with unaltered appearance. Significantly fewer altered males were resighted one or more days after release compared with control males (33% vs. 76%, 1990; 46% vs. 83%, 1993). Altered males were less able to establish and maintain themselves in preferred territories. The inability of released, altered males to establish a territory appears related to significantly longer male‐male encounters. Encounters involving at least one participant with altered appearance averaged 66 s compared with 24 s if neither male was altered. However, altering the coloration of P. polyxenes males that already had established themselves in a territory had little effect. After courtships of similar duration (≈ 40 s), released virgin females were equally likely to mate with either altered or control males. This suggests that male‐male intrasexual selection is of greater importance than female mate choice in maintaining a non‐mimetic dorsal coloration in male P. polyxenes.
Mixed gonococcal infections in a high-risk population, Sydney, Australia 2015: implications for antimicrobial resistance surveillance?

Objectives Previous studies have shown that mixed-strain gonococcal infections can occur. However, it remains unclear whether such infections impact upon the reliability of Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance. In this study, we aimed to resolve this question by intensively sampling isolates from gonorrhoea-positive specimens in a high-risk population in Sydney, Australia. Methods A total of 615 N. gonorrhoeae isolates, originating from 63 clinical samples (31 rectal swabs and 32 throat swabs), were characterized. All isolates were subject to N. gonorrhoeae identification, antimicrobial susceptibility testing and genotyping by SNP-based MLST. Results Only 2 of the 63 (3.2%) samples provided evidence of mixed-strain infections. These comprised two rectal swabs that harboured isolates of different SNP-based MLST genotypes; however, the AMR susceptibility profiles of the different genotypes from these samples were indistinguishable. Within-sample differences in the AMR susceptibility profiles were observed for a further seven samples; however, the differences were not considered significant; MIC values were typically within a 2-fold difference or were close to test breakpoints. Conclusions Results of this study provide further evidence that mixed-strain gonococcal infections do occur, although at low prevalence. Our data indicate that at a population level such infections are unlikely to impact significantly upon N. gonorrhoeae AMR surveillance.
Genome-wide association study of Alcohol Use Disorder Identification Test (AUDIT) scores in 20,328 research participants of European ancestry

Genetic factors contribute to the risk for developing alcohol use disorder (AUD). In collaboration with the genetics company 23andMe, Inc., we performed a genome-wide association (GWAS) study of the Alcohol Use Disorder Identification Test (AUDIT), an instrument designed to screen for alcohol misuse over the past year. Our final sample consisted of 20,328 research participants of European ancestry (55.3% females; mean age = 53.8, SD = 16.1) who reported ever using alcohol. Our results showed that the ‘chip-heritability’ of AUDIT score, when treated as a continuous phenotype, was 12%. No loci reached genome-wide significance. The gene ADH1C, which has been previously implicated in AUD, was among our most significant associations (4.4 × 10−7; rs141973904). We also detected a suggestive association on chromosome 1 (2.1 × 10−7; rs182344113) near the gene KCNJ9, which has been implicated in mouse models of high ethanol drinking. Using LD score regression, we identified positive genetic correlations between AUDIT score and AUD, high alcohol consumption, and cigarette smoking. We also observed an unexpected positive genetic correlation between AUDIT and educational attainment, and additional unexpected negative correlations with BMI/obesity and attention-deficit/hyperactivity disorder (ADHD). We conclude that conducting a genetic study using data from a population unselected for AUD and responding to an online questionnaire may represent a cost-effective strategy for elucidating the etiology of AUD.
Evaluation of a bicycle skills training program for young children: a randomized controlled trial

Objective—To evaluate the effectiveness of a skills training program in improving safe cycling behavior, knowledge, and attitudes in young children. Methods—Grade 4 children from six elementary schools in East York (a borough of Metropolitan Toronto) participated. The intervention—playground based instruction on bicycle handling skills by certified instructors—was randomly allocated to three schools. Altogether 141 children participated: 73 in the intervention group and 68 in the control group, with follow up evaluations available on 117 (83%). The primary outcome was safe cycling behavior (straight line riding, coming to a complete stop, and shoulder checking before a left turn). A self report questionnaire collected data on knowledge and attitudes. Baseline assessments were made in June, with follow up evaluations in September, 1995. Results—The prevalence of safe cycling behaviors at follow up in the intervention and control groups respectively, were: straight line riding (90% v 88%; p=0.782), coming to a complete stop (90% v 76%; p=0.225), and shoulder checking (0% v 2%; p=1.000). Over time (from baseline to follow up) children in both groups were more likely to maintain straight line riding, less likely to ride on the sidewalk, and less likely to consider that a car had more right to the road. Conclusions—This brief skills training program was not effective in improving safe cycling behavior, knowledge, or attitudes among grade 4 children.
Nutritional Status of Patients with Alzheimer's Disease and Their Caregivers.

BACKGROUND Malnutrition is one of the most important conditions that negatively affects the health of elder people, particularly in patients with dementia. OBJECTIVE To provide an assessment of nutritional status of patients affected by Alzheimer's disease (AD) living at home and of their caregivers by means of Mini Nutritional Assessment (MNA), and to explore the influence of different factors on nutrition. METHODS 90 patients affected by AD living at home and 90 age- and sex-matched caregivers were enrolled. Patients and caregivers, coming from an urban-rural fringe of Southern Italy, were assessed using full MNA, Mini-Mental State Examination, Geriatric Depression Scale- short form, Activity of Daily Living, and Instrumental Activities of Daily Living scales. RESULTS Malnutrition was found with high prevalence in patients affected by AD of different severity (more than 95% of patients were malnourished or at risk of malnutrition), and associated with reduced functional status. An altered nutrition was also recognized with high rate in the group of caregivers (23.3% were malnourished and 41.1% at risk of malnutrition) and the worse nutritional condition was correlated with higher age and lower functional and cognitive status and education. A positive correlation between MNA score of AD patients and caregivers was found. CONCLUSION Corrective measures should be taken in order to early identify nutritional deficiencies and risk of malnutrition observed with high rate in both groups of AD patients and their caregivers; in these subjects a nutrition education program and intervention policies are mandatory to restore nutritional status.
Activity recognition of the elderly

The development of context aware services is one proposed way to support independent living for the elderly. Performing test scenarios with the elderly helps when developing the context aware services. However, rigorous testing is not always desirable when working with elderly subjects. Our research proposes to capture the activity data of the subjects to use with a virtual environment and virtual human to test the services. This paper begins a larger set of research by describing a process in which the daily activities of the elderly are captured using accelerometer sensors. The process consists of pre-investigation, data capturing and data postprocessing. Using common activity recognition methods daily activities chosen by two elderly subjects themselves are recognized reasonably well. This allows using the described process in larger experiments to acquire more activity data.
Survivable lightpath provisioning in multi-domain optical networks

This paper proposes a survivable lightpath provisioning scheme that allows traffic splitting in multi-domain optical networks to minimize the cumulative cost of a set of paths. The proposed scheme, called two-phase lightpath provisioning' employs an integer linear programming (ILP) formulation based on hierarchical path computation with full-mesh topology abstraction. There are two phases in the scheme. The first phase solves the ILP problem on an inter-domain topology and then feeds the results as intra-domain requests. The second phase solves the ILP problem in each related domain. Finally, we concatenate all the intra-domain solutions along routing sequences. Three different protection strategies are considered with varying degrees of primary and backup route separation. Furthermore, to support various types of traffic demands, we investigate two cases in terms of the number of requested wavelengths. First, the number of requested wavelengths is less than link wavelength capacity. Second, the number of requested wavelengths is greater than link wavelength capacity. For the latter case, the proposed scheme allows traffic splitting among feasible primary and backup routes. The proposed scheme well supports the implementation of heuristic algorithms for lightpath provisioning since it can provide reference values, including upper and lower bounds, that are useful as benchmarks.
The cost-effectiveness of an extended course (12+12 weeks) of varenicline compared with other available smoking cessation strategies in the United States: an extension and update to the BENESCO model.

OBJECTIVES This study aimed to estimate the cost-effectiveness of an extended (12+12 weeks) course of varenicline using the (Benefits of Smoking Cessation on Outcomes) BENESCO smoking cessation model. METHODS Data on the efficacy of 12+12 weeks varenicline therapy in aiding smoking cessation were analyzed in conjunction with the efficacy data for 12 weeks of varenicline, bupropion, and placebo previously included in the BENESCO model, by using a mixed treatment comparison. This analysis provided updated efficacy estimates for all the interventions, and these were used to update the model to estimate the relative cost-effectiveness of all smoking cessation interventions considered, now including 12+12 weeks of varenicline. RESULTS The updated 1-year abstinence estimates derived from the mixed treatment comparison were, for 12+12 weeks of varenicline, 12 weeks of varenicline, 12 weeks of bupropion, and 12 weeks of placebo, respectively: 27.7%, 22.9%, 15.9%, and 9.3%. The average cost of the course of 12+12 weeks of varenicline was estimated at $603.89, based on a 12-week course followed by a further 12 weeks for successful quitters. Over all subjects' lifetimes, 12+12 weeks of varenicline is less costly and more effective than (dominates) all other strategies compared in the updated BENESCO model, with the exception of 12 weeks of varenicline. In this comparison, 12+12 weeks of varenicline is a very cost-effective alternative to the 12-week course, with an incremental cost of less than $1000 per quality-adjusted life year (QALY) gained. CONCLUSIONS A total of 12 weeks of varenicline followed by a further 12-week course for successful quitters is a highly cost-effective alternative compared with currently available smoking cessation options.
Treatment of Dabigatran-Associated Bleeding

Dabigatran etexilate is a competitive, direct thrombin inhibitor that works in the coagulation cascade to ultimately prevent thrombus formation. It is recommended by the 2012 American College of Chest Physicians evidence-based clinical practice guidelines as first-line therapy over vitamin k antagonists for long-term antithrombotic therapy in patients with paroxysmal or persistent nonrheumatic atrial fibrillation who are at intermediate to high risk of stroke and systemic embolism (grade 2B). However, serious postmarketing events involving life-threatening bleeding are emerging with no antidote for reversal of the anticoagulant effect being available for use. Potential reversal agents are being used in clinical practice with questionable efficacy and safety profiles. We report a case involving an 84-year-old male with acute kidney injury who developed life-threatening gastrointestinal and surgical site bleeding secondary to dabigatran accumulation. Use of the Naranjo probability scale indicated a probable cause between the bleeding event and dabigatran use. After discontinuation of drug therapy, fresh frozen plasma, recombinant coagulation factor VIIa, and cryoprecipitate were administered as potential reversal agents with negligible benefit. However, this patient appeared to slowly benefit with administration of continuous venovenous hemodialysis. Based upon our experience with this patient and literature review, the most effective treatment algorithm for dabigatran-associated bleeding may be to utilize hemodialysis initially.
Accrual of organ damage over time in patients with systemic lupus erythematosus.

OBJECTIVE To determine the pattern of accumulation of damage in an inception cohort of patients with systemic lupus erythematosus (SLE) followed yearly for at least 15 years, and to identify damage items that might be related to corticosteroid therapy. METHODS An inception cohort was identified from among patients with SLE followed prospectively in the University of Toronto Lupus Clinic. Only patients who had at least yearly evaluations and were followed for at least 15 years were included. Using the SLICC/ACR damage index (SDI) accumulated damage was calculated at yearly intervals. Each new organ system involved was designated as either definitely, possibly, or not at all related to corticosteroid therapy. RESULTS Of the 73 patients, 85% were women and 87.7% were Caucasian. Their mean age at diagnosis was 34.9 years. The mean (range) SLEDAI at presentation was 11.9 (0-37). Prednisone was used by 87.7% of the patients (mean maximum dose 37.7 mg/day, mean cumulative dose 36.8 g) for a mean of 117.1 months. Antimalarial drugs were used by 70% of the patients and 50% were taking immunosuppressive agents. The mean SDI for the whole cohort increased over time from 0.33 (0.89) during the first year to 1.90 (1.99) at 15 years. A significant proportion of the damage both early and late could be attributed to corticosteroid therapy, and this damage accumulated over time such that it constituted most of the damage at 15 years. CONCLUSION While the overall accrual of damage is gradual, the specific systems demonstrate varying patterns of damage accrual.
A Unified Architecture of Transcriptional Regulatory Elements

Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However, recent studies have revealed broad similarities between enhancers and promoters, blurring the distinction: active enhancers often initiate transcription, and some gene promoters have the potential of enhancing transcriptional output of other promoters. Here, we propose a model in which promoters and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements, and surrounding sequences, determine local transcriptional output as well as the enhancer and promoter activities of individual elements.
Central connections of the nucleus mesencephalicus nervi trigemini in the mallard (Anas platyrhynchosL.).

In the mallard duck, functionally distinct groups of jaw muscles are each innervated by a different subnucleus of the main trigeminal (mV) or facial (mVII) motor nucleus. The other subnuclei of mV and mVII innervate several head muscles, including lingual muscles. The reticular premotor cells of the trigeminal and facial jaw motor subnuclei occupy different areas in the parvocellular reticular formation (RPc). The cell bodies of jaw muscle spindle afferents are situated in the mesencephalic nucleus (MesV). In the present study, the central connections of MesV with jaw motor subnuclei and their premotor areas are investigated.
The role of parents in the detection of developmental and behavioral problems.

OBJECTIVE The success of early identification of children with developmental and behavioral problems is influenced by the manner in which pediatricians elicit, recognize, and select clinical information and derive appropriate impressions. Parents are ready sources of clinical information, and they can be asked to provide two broad types of data: appraisals, including concerns, estimations, and predictions; and descriptions, including recall and report. The purpose of this article is to help pediatricians make optimal use of clinical information from parents to increase the accuracy of clinical judgment in detecting children with developmental and behavioral problems. DESIGN Review of 78 research articles and tests relying on parent information from pediatric, psychological, and education literature. RESULTS AND CONCLUSION There are several formats for eliciting parental information that are superior in terms of accuracy and ease of evocation. Specifically, parents' concerns and good-quality standardized parent report measures such as the Child Development Inventories capitalize best on parents' observations and insights into their children. In combination, these two types of parental information offer an effective method for the early detection of behavioral and developmental problems in primary-care settings.
Self‐organized criticality and the development of EEG phase reset

Objectives: The purpose of this study was to explore human development of self‐organized criticality as measured by EEG phase reset from infancy to 16 years of age. Methods: The electroencephalogram (EEG) was recorded from 19 scalp locations from 458 subjects ranging in age from 2 months to 16.67 years. Complex demodulation was used to compute instantaneous phase differences between pairs of electrodes and the 1st and 2nd derivatives were used to detect the sudden onset and offset times of a phase shift followed by an extended period of phase locking. Mean phase shift duration and phase locking intervals were computed for two symmetrical electrode arrays in the posterior‐to‐anterior locations and the anterior‐to‐posterior directions in the α frequency band (8–13 Hz). Results: Log–log spectral plots demonstrated 1/f α distributions (α ≈ 1) with longer slopes during periods of phase shifting than during periods of phase locking. The mean duration of phase locking (150–450 msec) and phase shift (45–67 msec) generally increased as a function of age. The mean duration of phase shift declined over age in the local frontal regions but increased in distant electrode pairs. Oscillations and growth spurts from mean age 0.4–16 years were consistently present. Conclusions: The development of increased phase stability in local systems is paralleled by lengthened periods of unstable phase in distant connections. Development of the number and/or density of synaptic connections is a likely order parameter to explain oscillations and growth spurts in self‐organized criticality during human brain maturation. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.