Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonadherence to oral mercaptopurine and risk of relapse in Hispanic and non-Hispanic white children with acute lymphoblastic leukemia: a report from the children's oncology group.

PURPOSE Systemic exposure to mercaptopurine (MP) is critical for durable remissions in children with acute lymphoblastic leukemia (ALL). Nonadherence to oral MP could increase relapse risk and also contribute to inferior outcome in Hispanics. This study identified determinants of adherence and described impact of adherence on relapse, both overall and by ethnicity. PATIENTS AND METHODS A total of 327 children with ALL (169 Hispanic; 158 non-Hispanic white) participated. Medication event-monitoring system caps recorded date and time of MP bottle openings. Adherence rate, calculated monthly, was defined as ratio of days of MP bottle opening to days when MP was prescribed. RESULTS After 53,394 person-days of monitoring, adherence declined from 94.7% (month 1) to 90.2% (month 6; P < .001). Mean adherence over 6 months was significantly lower among Hispanics (88.4% v 94.8%; P < .001), patients age ≥ 12 years (85.8% v 93.1%; P < .001), and patients from single-mother households (80.6% v 93.1%; P = .001). A progressive increase in relapse was observed with decreasing adherence (reference: adherence ≥ 95%; 94.9% to 90%: hazard ratio [HR], 4.1; 95% CI,1.2 to 13.5; P = .02; 89.9% to 85%: HR, 4.0; 95% CI, 1.0 to 15.5; P = .04; < 85%: HR. 5.7; 95% CI, 1.9 to 16.8; P = .002). Cumulative incidence of relapse (± standard deviation) was higher among Hispanics (16.5% ± 4.0% v 6.3% ± 2.2%; P = .02). Association between Hispanic ethnicity and relapse (HR, 2.6; 95% CI, 1.1 to 6.1; P = .02) became nonsignificant (HR, 1.8; 95% CI, 0.6 to 5.2; P = .26) after adjusting for adherence and socioeconomic status. At adherence rates ≥ 90%, Hispanics continued to demonstrate higher relapse, whereas at rates < 90%, relapse risk was comparable to that of non-Hispanic whites. CONCLUSION Lower adherence to oral MP increases relapse risk. Ethnic difference in relapse risk differs by level of adherence-an observation currently under investigation.
Automatic Determination of a Domain Adaptation Method for Word Sense Disambiguation Using Decision Tree Learning

Domain adaptation (DA), which involves adapting a classifier developed from source to target data, has been studied intensively in recent years. However, when DA for word sense disambiguation (WSD) was carried out, the optimal DA method varied according to the properties of the source and target data. This paper describes how the optimal method for DA was determined depending on these properties using decision tree learning, given a triple of the target word type of WSD, the source data, and the target data, and discusses what properties affected the determination of the best method when Japanese WSD was performed.
Electro-acupuncture as a peroperative analgesic method and its effects on implantation rate and neuropeptide Y concentrations in follicular fluid.

BACKGROUND In a previous study on the effect of electro-acupuncture (EA) in combination with a paracervical block (PCB) as an analgesic method during oocyte aspiration in IVF treatment, EA appeared to increase the pregnancy rate. This study was designed to test the hypothesis that EA as an analgesic during oocyte aspiration would result in: (i) a better IVF pregnancy rate than with alfentanil; (ii) peroperative analgesia that was as good as that produced by alfentanil; (iii) less postoperative abdominal pain, nausea and stress; and (iv) a reduction in the use of additional analgesics. Neuropeptide Y (NPY) concentrations in follicular fluid (FF) were analysed when possible. METHODS AND RESULTS In this prospective, randomized, multicentre clinical trial, 286 women undergoing oocyte aspiration were randomly allocated to the EA group (EA plus a PCB) or to the alfentanil group (alfentanil plus a PCB). No significant differences were found between the EA and alfentanil groups in any of the IVF variables. NPY concentrations in FF were significantly higher in the EA group compared with the alfentanil group. No correlation between pregnancy rate and NPY concentrations was found in either analgesic group. Both EA plus a PCB and alfentanil plus a PCB induced adequate peroperative analgesia during oocyte aspiration evaluated using the visual analogue scale. After 2 h, the EA group reported significantly less abdominal pain, other pain, nausea and stress than the alfentanil group. In addition, the EA group received significantly lower amounts of additional alfentanil than the alfentanil group. CONCLUSION EA does not improve pregnancy rate in the present clinical situation. The observation that NPY concentrations in FF were higher in the EA group may be important for human ovarian steroidogenesis. The analgesic effects produced by EA are as good as those produced by conventional analgesics, and the use of opiate analgesics with EA is lower than when conventional analgesics alone are used.
Effectiveness of low vision services in improving patient quality of life at Aravind Eye Hospital

Context: In India, where the heavy burden of visual impairment exists, low vision services are scarce and under-utilized. Aims: Our study was designed to survey the effectiveness of low vision exams and visual aids in improving patient quality of life in southern rural India. Subjects and Methods: The low vision quality of life (LVQOL) questionnaire measures vision-related quality of life through 25 questions on a Likert scale of 0–5 that pertain to (1) mobility, distance vision, and lighting; (2) psychological adjustment; (3) reading and fine work; and (4) activities of daily living. This tool was translated into Tamil and verbally administered to 55 new low vision referral patients before their first visit at the low vision clinic at Aravind Eye Hospital. Low vision aids (LVAs) were prescribed at the discretion of the low vision specialist. 1-month later, the same questionnaire was administered over the phone. Results: About 44 of 55 low vision patients completed baseline and follow-up LVQOL surveys, and 30 normal vision controls matched for age, gender, and education were also surveyed (average 117.34 points). After the low vision clinic visit, the low vision group demonstrated a 4.55-point improvement in quality of life (from 77.77 to 82.33 points, P = 0.001). Adjusting for age, gender, and education, the low vision patients who also received LVAs (n = 24) experienced an even larger increase than those who did not (n = 20) (8.89 points, P < 0.001). Conclusion: Low vision services and visual aids can improve the quality of life in South Indian rural population regardless of age, gender, and education level. Thus, all low vision patients who meet the criteria should be referred for evaluation.
Effect of Signal Peptide on Stability and Folding of Escherichia coli Thioredoxin

The signal peptide plays a key role in targeting and membrane insertion of secretory and membrane proteins in both prokaryotes and eukaryotes. In E. coli, recombinant proteins can be targeted to the periplasmic space by fusing naturally occurring signal sequences to their N-terminus. The model protein thioredoxin was fused at its N-terminus with malE and pelB signal sequences. While WT and the pelB fusion are soluble when expressed, the malE fusion was targeted to inclusion bodies and was refolded in vitro to yield a monomeric product with identical secondary structure to WT thioredoxin. The purified recombinant proteins were studied with respect to their thermodynamic stability, aggregation propensity and activity, and compared with wild type thioredoxin, without a signal sequence. The presence of signal sequences leads to thermodynamic destabilization, reduces the activity and increases the aggregation propensity, with malE having much larger effects than pelB. These studies show that besides acting as address labels, signal sequences can modulate protein stability and aggregation in a sequence dependent manner.
Open access - Invited review THIS PAPER IS PART OF A SPECIAL ISSUE ENTITLED 'MOLECULAR BASIS OF PLANT STRESS' Hydrogen peroxide—a central hub for information flow in plant cells

Background Hydrogen peroxide (H2O2) was initially recognized as a toxic reactive oxygen species, able to cause damage to a variety of cellular structures. However, it became clear in the last decade that H2O2 can also act as a potent signalling molecule, involved in a plethora of physiological functions. Scope In the present review, we offer a brief summary of H2O2 signalling events and focus on the mechanisms of its perception and signal transduction, the factors that act downstream, as well as H2O2 interference with other information transfer mechanisms. Conclusion The significant scientific effort in the last 10 years to determine the position of H2O2 in signal transduction networks in plants demonstrated that it is essential for both the communication with external biotic and abiotic stimuli and the control of developmentally regulated processes. In addition, H2O2 complements, synergizes or antagonizes many cellular regulatory circuits by active interaction with other signals and plant hormones during growth, development and stress responses. Therefore, further understanding of H2O2 signal transduction is not only of fundamental, but also of practical importance, since this knowledge may contribute to improve agricultural practices and reduce stress-induced damage to crops.
A novel approach for assigning levels to monkey and human lumbosacral spinal cord based on ventral horn morphology

Proper identification of spinal cord levels is crucial for clinical-pathological and imaging studies in humans, but can be a challenge given technical limitations. We have previously demonstrated in non-primate models that the contours of the spinal ventral horn are determined by the position of motoneuron pools. These positions are preserved within and among individuals and can be used to identify lumbosacral spinal levels. Here we tested the hypothesis that this approach can be extended to identify monkey and human spinal levels. In 7 rhesus monkeys, we retrogradely labeled motoneuron pools that represent rostral, middle and caudal landmarks of the lumbosacral enlargement. We then aligned the lumbosacral enlargements among animals using absolute length, segmental level or a relative scale based upon rostral and caudal landmarks. Inter-animal matching of labeled motoneurons across the lumbosacral enlargement was most precise when using internal landmarks. We then reconstructed 3 human lumbosacral spinal cords, and aligned these based upon homologous internal landmarks. Changes in shape of the ventral horn were consistent among human subjects using this relative scale, despite marked differences in absolute length or age. These data suggest that the relative position of spinal motoneuron pools is conserved across species, including primates. Therefore, in clinical-pathological or imaging studies in humans, one can assign spinal cord levels to even single sections by matching ventral horn shape to standardized series.
Variable Pricing : A Customer Learning Perspective

Recent works question the benefit of Promotional Pricing (Hi-Lo) formats. In this essay, we characterize a setting in which cost-disadvantaged firms would rationally and profitably opt for the Hi-Lo format. Essentially, cost-disadvantaged retail firms, such as mall outlets and smaller chains lacking the economies of scale of their rivals, charge higher prices than their cost-competitive rivals. These firms will want to and are able to reduce customer sensitivity to price differences by pursuing a variable pricing (Hi-Lo) strategy, whereas a cost-advantaged firm will wish to pursue Every Day Low Price (EDLP). We demonstrate that in experimental settings consumers’ sensitivity to payoff differences declines in observed payoff variability. We then show that in real settings, lower price firms experience reduced market share during high price variability periods.
Evolutionary Conservation of Bacterial Essential Metabolic Genes across All Bacterial Culture Media

One of the basic postulates of molecular evolution is that functionally important genes should evolve slower than genes of lesser significance. Essential genes, whose knockout leads to a lethal phenotype are considered of high functional importance, yet whether they are truly more conserved than nonessential genes has been the topic of much debate, fuelled by a host of contradictory findings. Here we conduct the first large-scale study utilizing genome-scale metabolic modeling and spanning many bacterial species, which aims to answer this question. Using the novel Media Variation Analysis, we examine the range of conservation of essential vs. nonessential metabolic genes in a given species across all possible media. We are thus able to obtain for the first time, exact upper and lower bounds on the levels of differential conservation of essential genes for each of the species studied. The results show that bacteria do exhibit an overall tendency for differential conservation of their essential genes vs. their non-essential ones, yet this tendency is highly variable across species. We show that the model bacterium E. coli K12 may or may not exhibit differential conservation of essential genes depending on its growth medium, shedding light on previous experimental studies showing opposite trends.
Identification of Amino Acid Residues in Angiotensin II Type 1 Receptor Sensing Mechanical Stretch and Function in Cardiomyocyte Hypertrophy

Background/Aims: Angiotensin II (AngII) type 1 receptor (AT<sub>1</sub>R) could be activated by mechanical stress without the involvement of AngII during the development of cardiac hypertrophy. We aimed to identify sensing sites of AT<sub>1</sub>R for activation by mechanical stretch. Methods: We constructed several site-directed mutations of AT<sub>1</sub>R (AT<sub>1</sub>R<sup>K199Q</sup>, AT<sub>1</sub>R<sup>L212F</sup>, AT<sub>1</sub>R<sup>Q257A</sup> and AT<sub>1</sub>R<sup>C289A</sup>), transfected them respectively into COS7 cells or angiotensinogen knockout cardiomyocytes (ATG<sup>−/−</sup>-CMs), and observed cellular events after mechanical stretch. Results: AngII-induced phosphorylation of ERKs and Jak2, and redistribution of Gαq11 in AT<sub>1</sub>R<sup>WT</sup>- COS7 or -ATG<sup>−/−</sup>-CMs were dramatically decreased in AT<sub>1</sub>R<sup>K199Q</sup>- or AT<sub>1</sub>R<sup>Q257A</sup>- COS7 cells or -ATG<sup>−/−</sup>-CMs, while those effects induced by mechanical stretch were greatly suppressed in COS7 cells or ATG<sup>−/−</sup>-CMs expressing AT<sub>1</sub>R<sup>L212F</sup>, AT<sub>1</sub>R<sup>Q257A</sup> or AT<sub>1</sub>R<sup>C289A</sup> compared with these cells expressing AT<sub>1</sub>R<sup>WT</sup>. AngII-induced hypertrophic responses (the increase in hypertrophic genes expression and cross-sectional area) in AT<sub>1</sub>R<sup>WT</sup>- ATG<sup>−/−</sup>-CMs were partly abolished in AT<sub>1</sub>R<sup>K199Q</sup>-ATG<sup>−/−</sup>-CMs or AT<sub>1</sub>R<sup>Q257A</sup>-ATG<sup>−/−</sup>-CMs, while these responses induced by mechanical stretch were greatly inhibited in ATG<sup>−/−</sup>-CMs overexpressing AT<sub>1</sub>R<sup>L212F</sup>, AT<sub>1</sub>R<sup>Q257A</sup> or AT<sub>1</sub>R<sup>C289A</sup>. Conclusion: These results indicated that Leu212, Gln257 and Cys289 in AT<sub>1</sub>R are not only sensing sites for mechanical stretch but also functional amino residues for activation of the receptor and cardiomyocytes hypertrophy induced by mechanical stretch.
Multiple objective optimization in recommender systems

We address the problem of optimizing recommender systems for multiple relevance objectives that are not necessarily aligned. Specifically, given a recommender system that optimizes for one aspect of relevance, semantic matching (as defined by any notion of similarity between source and target of recommendation; usually trained on CTR), we want to enhance the system with additional relevance signals that will increase the utility of the recommender system, but that may simultaneously sacrifice the quality of the semantic match. The issue is that semantic matching is only one relevance aspect of the utility function that drives the recommender system, albeit a significant aspect. In talent recommendation systems, job posters want candidates who are a good match to the job posted, but also prefer those candidates to be open to new opportunities. Recommender systems that recommend discussion groups must ensure that the groups are relevant to the users' interests, but also need to favor active groups over inactive ones. We refer to these additional relevance signals (job-seeking intent and group activity) as extraneous features, and they account for aspects of the utility function that are not captured by the semantic match (i.e. post-CTR down-stream utilities that reflect engagement: time spent reading, sharing, commenting, etc). We want to include these extraneous features into the recommendations, but we want to do so while satisfying the following requirements: 1) we do not want to drastically sacrifice the quality of the semantic match, and 2) we want to quantify exactly how the semantic match would be affected as we control the different aspects of the utility function. In this paper, we present an approach that satisfies these requirements. We frame our approach as a general constrained optimization problem and suggest ways in which it can be solved efficiently by drawing from recent research on optimizing non-smooth rank metrics for information retrieval. Our approach features the following characteristics: 1) it is model and feature agnostic, 2) it does not require additional labeled training data to be collected, and 3) it can be easily incorporated into an existing model as an additional stage in the computation pipeline. We validate our approach in a revenue-generating recommender system that ranks billions of candidate recommendations on a daily basis and show that a significant improvement in the utility of the recommender system can be achieved with an acceptable and predictable degradation in the semantic match quality of the recommendations.
The residential continuum from home to nursing home: size, characteristics and unmet needs of older adults.

OBJECTIVES Older adults with care needs live in a variety of settings-from traditional community housing to nursing homes. This analysis provides new estimates of the size and characteristics of the older population across settings and examines unmet needs for assistance. METHOD Data are from the 2011 National Health and Aging Trends Study (N = 8,077). Multinomial logistic regressions focus on people in settings other than nursing homes who are at risk for unmet needs, defined as receiving help or having difficulty with household, self-care, or mobility activities (N = 4,023). RESULTS Of 38.1 million Medicare beneficiaries ages 65 and older, 5.5 million (15%) live in settings other than traditional housing: 2.5 million in retirement or senior housing communities, nearly 1 million in independent- and 1 million in assisted-living settings, and 1.1 million in nursing homes. The prevalence of assistance is higher and physical and cognitive capacity lower in each successive setting. Unmet needs are common in traditional community housing (31%), but most prevalent in retirement or senior housing (37%) and assisted living settings (42%). After controlling for differences in resident characteristics across settings, those in retirement or senior housing communities have a higher likelihood of unmet needs than those in traditional community housing, while those in independent or assisted living settings have a lower relative likelihood. DISCUSSION Substantial numbers of older adults, many with care needs, live in a continuum of settings other than traditional community housing. Unmet needs are prevalent among older adults with limitations across all settings and warrant further investigation and monitoring.
In Vivo Labeling of Parvalbumin-Positive Interneurons and Analysis of Electrical Coupling in Identified Neurons

GABAergic interneurons can pace the activity of principal cells and are thus critically involved in the generation of oscillatory and synchronous network activity. The specific role of various GABAergic subpopulations, however, has remained elusive. This is in part attributable to the scarcity of certain GABAergic neurons and the difficulty of identifying them in slices obtained from brain regions in which anatomical structures are not readily recognizable in the live preparation. To facilitate the functional analysis of GABAergic interneurons, we generated transgenic mice in which the enhanced green fluorescent protein (EGFP) was specifically expressed in parvalbumin-positive neurons. The high fidelity of expression obtained using bacterial artificial chromosome transgenes resulted in EGFP-labeled neurons in nearly all brain regions known to contain parvalbumin-expressing neurons. Immunocytochemical analysis showed that EGFP expression was primarily restricted to parvalbumin-positive cells. In addition to cell body labeling, EGFP expression was high enough in many neurons to enable the visualization of dendritic structures. With the help of these mice, we investigated the presence of electrical coupling between parvalbumin-positive cells in brain slices obtained from young and adult animals. In dentate gyrus basket cells, electrical coupling was found in slices from young [postnatal day 14 (P14)] and adult (P28 and P42) animals, but both strength and incidence of coupling decreased during development. However, electrical coupling between parvalbumin-positive multipolar cells in layer II/III of the neocortex remains unaltered during development. Yet another developmental profile of electrical coupling was found between layer II/III parvalbumin-positive cells and excitatory principal cells. Between these neurons, electrical coupling was found at P14 but not at P28. The results indicate that the presence and strength of electrical coupling is developmentally regulated with respect to brain area and cell type.
Prospective blinded study of BRAFV600E mutation detection in cell-free DNA of patients with systemic histiocytic disorders.

UNLABELLED Patients with Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) have a high frequency of BRAF(V600E) mutations and respond to RAF inhibitors. However, detection of mutations in tissue biopsies is particularly challenging in histiocytoses due to low tumor content and stromal contamination. We applied a droplet-digital PCR assay for quantitative detection of the BRAF(V600E) mutation in plasma and urine cell-free (cf) DNA and performed a prospective, blinded study in 30 patients with ECD/LCH. There was 100% concordance between tissue and urinary cfDNA genotype in treatment-naïve samples. cfDNA analysis facilitated identification of previously undescribed KRAS(G12S)-mutant ECD and dynamically tracked disease burden in patients treated with a variety of therapies. These results indicate that cfDNA BRAF(V600E) mutational analysis in plasma and urine provides a convenient and reliable method of detecting mutational status and can serve as a noninvasive biomarker to monitor response to therapy in LCH and ECD. SIGNIFICANCE Patients with BRAF(V600E)-mutant histiocytic disorders have remarkable responses to RAF inhibition, but mutation detection in tissue in these disorders is challenging. Here, we identify that analysis of plasma and urinary cfDNA provides a reliable method to detect the BRAF(V600E) mutation and monitor response to therapy in these disorders.