Miracle-dz/UniFAR-FTUs huggingface dataset:
Patients' priorities for treatment decision making during periods of incapacity: quantitative survey

Abstract Objective: Clinical practice aims to respect patient autonomy by basing treatment decisions for incapacitated patients on their own preferences. Yet many patients do not complete an advance directive, and those who do frequently just designate a family member to make decisions for them. This finding raises the concern that clinical practice may be based on a mistaken understanding of patient priorities. The present study aimed to collect systematic data on how patients prioritize the goals of treatment decision making. Method: We employed a self-administered, quantitative survey of patients in a tertiary care center. Results: Some 80% or more of the 1169 respondents (response rate = 59.8%) ranked six of eight listed goals for treatment decision making as important. When asked which goal was most important, 38.8% identified obtaining desired or avoiding unwanted treatments, 20.0% identified minimizing stress or financial burden on their family, and 14.6% identified having their family help to make treatment decisions. No single goal was designated as most important by 25.0% of participants. Significance of Results: Patients endorsed three primary goals with respect to decision making during periods of incapacity: being treated consistent with their own preferences; minimizing the burden on their family; and involving their family in the decision-making process. However, no single goal was prioritized by a clear majority of patients. These findings suggest that advance care planning should not be limited to documenting patients' treatment preferences. Clinicians should also discuss and document patients' priorities for how decisions are to be made. Moreover, future research should evaluate ways to modify current practice to promote all three of patients primary goals for treatment decision making.
YKL-40 as a Potential Biomarker and a Possible Target in Therapeutic Strategies of Alzheimer’s Disease

Background: Growing body of evidence suggests that the pathogenesis of Alzheimer’s disease (AD), a progressing neurodegenerative condition, is not limited to the neuronal compartment, but also involves various immunological mechanisms. Insoluble Aβ aggregates in the brain can induce the activation of microglia, resulting in the synthesis of proinflammatory mediators, which further can stimulate astrocytic expression of YKL-40. Therefore, the aim of the current review is to present up-to-date data about the role of YKL-40 as a biomarker of AD as well as the possibility of therapeutic strategies targeting neuroinflammation. Objective/Methods: We searched PubMed articles for the terms “YKL-40”, “neurodegeneration”, “neuroinflammation” and “Alzheimer’s disease”, and included papers focusing on this review’s scope. Results: Recent studies indicate that CSF concentrations of YKL-40 were significantly higher in AD patients than in cognitively normal individuals and correlated with dementia biomarkers, such as tau proteins and amyloid beta. Determination of YKL-40 CSF concentration may be also helpful in differentiation between types of dementia and in the distinction of patients in the stable phase of MCI from those who progressed to dementia. Moreover, significantly increased levels of YKL-40 mRNA were found in AD brains in comparison with non-demented controls. Additionally, it was suggested that anti-inflammatory treatment might relief the symptoms of AD and slow its progression. Conclusion: Based on the recent knowledge, YKL-40 might be useful as a possible biomarker in the diagnosis and prognosis of AD. Modulation of risk factors and targeting of immune mechanisms, including systemic inflammation could lead to future preventive or therapeutic strategies for AD.
Measurement of urine indolylacroylglycine is not useful in the diagnosis or dietary management of autism

To measure urine indolylacroylglycine (IAG) excretion using the IAG:creatinine ratio in children with autism spectrum disorder (ASD) compared with two groups of age matched controls, one with special needs but without ASD (SEN) and one typically developing (TD) and in subgroups with/without current gastrointestinal problems and ASD with and without regression. IAG:creatinine ratio was measured in the urine of 279 children aged 10–14 years: 129 children with ASD (28 with and 101 without regression), 62 SEN controls and 88 TD controls. The prevalence of gastro‐intestinal symptoms (GIS) was recorded. No differences were found in the urine IAG:creatinine ratio among groups ASD, TD and SEN; nor in the ASD groups with/without regression, nor in those with/without GIS. This study finds no evidence of increased urine IAG excretion in children with ASD, with or without GIS or with or without regression. Urinary IAG measurements in children with ASD offer no support for increased presence of neuroactive peptides proposed to result from increased gut permeability. We found measurement of urinary IAG to have no value in the diagnosis of autism or in the dietary management of children with ASD. Autism Res 2017, 10: 408–413. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Identity, politics, and public policy

ABSTRACT Although much has been written about ‘identity politics’ in the narrow sense of the term, students of politics and public policy can take a more systematic look at the connection between identity and politics, as related to public policy. This essay shows that, by putting identity at the center of their analysis of politics and public policy, scholars can gain powerful insight about both explanation and policy prescription. In other words, how actors understand themselves and are seen by others are key aspects of political and policy analysis and they each deserve a systematic and interdisciplinary treatment. The essay suggests this by drawing on recent social science literature, such as identity economics, to explore the relevance of the connection between identity and politics for policy research across different policy areas and regions of the world. Because several of these literatures are seldom discussed together, this essay offers a particularly broad and multi-faceted identity perspective for the analysis of politics and public policy.
Multiple Criteria Portfolio Choice with Variance Decomposition onto Half Spaces

In this paper we propose a multiple criteria framework (MCF) for generalizing the traditional two-moment CAPM. It includes the Sharpe-Lintner CAPM as a special case. The model decomposes effective portfolio variance into two parts, an undesirable total variance part and a desirable positive variability part. Minimization is taken with respect not to total variance as in the Sharpe-Lintner CAPM, but to the total variance less the positive variability. Positive covariability reduces risk premium, and has a similar effect compared to positive skewness or upper partial moment. The empirical results in our MCF model indicate good performance of the model. Most importantly, the model produces computable portfolio showing analytical tradeoffs between the MCF skewness and idiosyncratic volatility that could explain the negative premium of the latter in the literature.
PTRF suppresses the progression of colorectal cancers

As a key component of caveolae structure on the plasma membrane, accumulated evidence has suggested that Polymerase I and Transcript Release Factor (PTRF) plays a pivotal role in suppressing the progression of human malignances. However, the function of PTRF in the development of colorectal cancers is still unclear. Here we report that the expression of PTRF is significantly reduced in tumor tissues derived from human patients with colorectal cancers, and that the downregulation of PTRF correlates to the advanced stage of the disease. In addition, we found that the expression of PTRF negatively regulates the tumorigenic activities of colorectal cell lines (Colo320, HT29 and CaCo2). Furthermore, ectopic PTRF expression caused significant suppression of cellular proliferation, and anchorage-independent colony growth of Colo320 cells, which have the lowest expression level of PTRF in the three studied cell lines. Meanwhile, shRNA mediated knockdown of PTRF in CaCo2 cells significantly promoted cellular proliferation and anchorage-independent colony growth. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic PTRF expression as compared to untreated Colo320 cells, but was markedly enhanced in PTRF knockdown CaCo2 cells. Biochemical studies revealed that overexpression of PTRF led to the suppression of the AKT/mTOR pathway, as evidenced by reduced phosphorylation of AKT, mTOR, and downstream MMP-9. Thus, these findings, for the first time, demonstrated that PTRF inhibits the tumorigenesis of colorectal cancers and that it might serve as a potential therapeutic target for human colon cancer patients.
LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION

Purpose: To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Methods: Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Results: Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow–white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Conclusion: Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.
Some Notes about a Responsive Phenomenology. A Response to John Schlapobersky: ‘On Making a Home Amongst Strangers’

Dear John, dear colleagues, I am grateful for the honour of being invited to respond to such a thoughtful and stimulating Foulkes Lecture. ‘Making a home amongst strangers’—this paradox, which is characteristic for the group psychotherapeutic process, was the focus of your presentation (Schlapobersky, 2015). In my response I want to take a look at this paradox from an opposite and perhaps complementary direction: It starts not with the strangers who try to build in the group a home for themselves, but with the home in which the stranger and the alien will be and remain present. Dear John, from our conversation and email-exchange I know that we share among other things an interest, which is for me rather important: we both studied philosophy as part of our academic education and are curious to explore the more or less implicit philosophical premises of the group analytic project. This common interest shall serve me in the following remarks as a point of view from which I want to elucidate the paradox of the stranger’s presence in my own home or of the alien in the own.
A Single Bout of High-Intensity Interval Training Improves Motor Skill Retention in Individuals With Stroke

Background. One bout of high-intensity cardiovascular exercise performed immediately after practicing a motor skill promotes changes in the neuroplasticity of the motor cortex and facilitates motor learning in nondisabled individuals. Objective. To determine if a bout of exercise performed at high intensity is sufficient to induce neuroplastic changes and improve motor skill retention in patients with chronic stroke. Methods. Twenty-two patients with different levels of motor impairment were recruited. On the first session, the effects of a maximal graded exercise test on corticospinal and intracortical excitability were assessed from the affected and unaffected primary motor cortex representational area of a hand muscle with transcranial magnetic stimulation. On the second session, participants were randomly assigned to an exercise or a nonexercise control group. Immediately after practicing a motor task, the exercise group performed 15 minutes of high-intensity interval training while the control group rested. Twenty-four hours after motor practice all participants completed a test of the motor task to assess skill retention. Results. The graded exercise test reduced interhemispheric imbalances in GABAA-mediated short-interval intracortical inhibition but changes in other markers of excitability were not statistically significant. The group that performed high-intensity interval training showed a better retention of the motor skill. Conclusions. The performance of a maximal graded exercise test triggers only modest neuroplastic changes in patients with chronic stroke. However, a single bout of high-intensity interval training performed immediately after motor practice improves skill retention, which could potentially accelerate motor recovery in these individuals.
Model-Based Reasoning in Humans Becomes Automatic with Training

Model-based and model-free reinforcement learning (RL) have been suggested as algorithmic realizations of goal-directed and habitual action strategies. Model-based RL is more flexible than model-free but requires sophisticated calculations using a learnt model of the world. This has led model-based RL to be identified with slow, deliberative processing, and model-free RL with fast, automatic processing. In support of this distinction, it has recently been shown that model-based reasoning is impaired by placing subjects under cognitive load—a hallmark of non-automaticity. Here, using the same task, we show that cognitive load does not impair model-based reasoning if subjects receive prior training on the task. This finding is replicated across two studies and a variety of analysis methods. Thus, task familiarity permits use of model-based reasoning in parallel with other cognitive demands. The ability to deploy model-based reasoning in an automatic, parallelizable fashion has widespread theoretical implications, particularly for the learning and execution of complex behaviors. It also suggests a range of important failure modes in psychiatric disorders.
Insufficient levels of the nrdAB‐encoded ribonucleotide reductase underlie the severe growth defect of the Δhda E. coli strain

The ATP‐bound form of the Escherichia coli DnaA replication initiator protein remodels the chromosomal origin of replication, oriC, to load the replicative helicase. The primary mechanism for regulating the activity of DnaA involves the Hda and β clamp proteins, which act together to dramatically stimulate the intrinsic DNA‐dependent ATPase activity of DnaA via a process termed Regulatory Inactivation of DnaA. In addition to hyperinitiation, strains lacking hda function also exhibit cold sensitive growth at 30°C. Strains impaired for the other regulators of initiation (i.e., ΔseqA or ΔdatA) fail to exhibit cold sensitivity. The goal of this study was to gain insight into why loss of hda function impedes growth. We used a genetic approach to isolate 9 suppressors of Δhda cold sensitivity, and characterized the mechanistic basis by which these suppressors alleviated Δhda cold sensitivity. Taken together, our results provide strong support for the view that the fundamental defect associated with Δhda is diminished levels of DNA precursors, particularly dGTP and dATP. We discuss possible mechanisms by which the suppressors identified here may regulate dNTP pool size, as well as similarities in phenotypes between the Δhda strain and hda+ strains exposed to the ribonucleotide reductase inhibitor hydroxyurea.
Association of cerebrospinal fluid β-amyloid 1-42, T-tau, P-tau181, and α-synuclein levels with clinical features of drug-naive patients with early Parkinson disease.

IMPORTANCE We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. OBJECTIVE To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. MAIN OUTCOMES AND MEASURES The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. RESULTS Slightly, but significantly, lower levels of Aβ1-42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181. CONCLUSIONS AND RELEVANCE In this first report of CSF biomarkers in PPMI study subjects,we found that measures of CSF Aβ1-42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression
Critical Success Factors of E-Government: A Proposed Model for E-Government Implementation

This paper draws on the extant literature on e-government policy formulation, implementation and execution. The purpose of the synthesis of this literature is to advance our understanding of the factors leading to success and failure and to elaborate on the underlying enabling and inhibiting conditions. This exercise is significant with respect to research and practice to avoid the pitfalls of imposing universal approaches to research and policy practices. Rather, it draws a distinction between generic (general) and specific (context-contingent) factors. With this fundamental understanding, we can suggest the kind of factors that have strategic importance and which are irrelevant in terms of e-government policy formulations. The paper, further, provides a model for successful e-government implementation
Satisfaction With College

Satisfaction with college is an important component of various theories of college student retention and academic performance but empirical support for the relationship of satisfaction with college with these two criteria has been mixed. Using data from two large datasets (N = 34,047 and N = 35,503) from 300 institutions we examine whether satisfaction with college exhibits stronger relationships with retention intentions and academic performance when assessed using an inventory that acknowledges the likely multi-faceted structure of satisfaction with college. Results indicate that satisfaction with college is multi-faceted, exhibits a hierarchical structure, exhibits moderate to strong relationships with retention intentions, and relatively weak relationships with academic performance.
Role of weak ties in link prediction of complex networks

Plenty of algorithms for link prediction have been proposed and were applied to various real networks. Among these works, the weights of links are rarely taken into account. In this paper, we use local similarity indices to estimate the likelihood of the existence of links in weighted networks, including Common Neighbor, Adamic-Adar Index, Resource Allocation Index, and their weighted versions. In both the unweighted and weighted cases, the resource allocation index performs the best. To our surprise, the weighted indices perform worse, which reminds us of the well-known Weak Tie Theory. Further experimental study shows that the weak ties play a significant role in the link prediction problem, and to emphasize the contribution of weak ties can remarkably enhance the predicting accuracy.
Telomerase Is Involved in IL-7-Mediated Differential Survival of Naive and Memory CD4+ T Cells1

IL-7 plays an essential role in T cell maintenance and survival. The survival effect of IL-7 is thought to be mediated through regulation of Bcl2 family proteins. After a comparative analysis of IL-7-induced growth and cell death of human naive and memory CD4+ T cells, we observed that more memory CD4+ T cells underwent cell division and proceeded to apoptosis than naive cells in response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2, Bcl-xL, Bax, and Bad) were similar between naive and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in naive cells than in memory cells, and the levels of IL-7-induced telomerase activity had a significant inverse correlation with cell death in CD4+ T cells. Furthermore, we showed that reducing expression of telomerase reverse transcriptase and telomerase activity significantly increased cell death of IL-7-cultured CD4+ T cells. Together, these findings demonstrate that telomerase is involved in IL-7-mediated differential survival of naive and memory CD4+ T cells.