Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics of patients with advanced lung cancer referred to a rapid-access supportive care clinic

Abstract Objective: There is a limited number of pragmatic studies to evaluate the criteria for referral to outpatient palliative care. The aim of our study was to compare the characteristics, symptoms, and survival of patients with advanced non-small-cell lung cancer (NSCLC) referred (RF) versus not referred (NRF) to a novel embedded same-day rapid-access supportive care clinic (RASCC) and to compare the subgroups among referred patients. Method: We reviewed the medical records of all patients who received treatment at the thoracic oncology clinic for advanced non-small-cell lung cancer between August 1, 2012, and June 30, 2013, who were referred to the RASCC and those who were not referred. An oncology-estimated prognosis of ≤6 months and/or severe symptom distress was employed as criteria for referral to the RASCC. Results: Of 410 eligible patients, 155 (37.8%) were referred to the RASCC. RF patients had significantly higher patient-reported scores for pain, fatigue, lack of appetite, and symptom distress, as well as worse performance status and shorter survival than NRF patients. Among the RF patients, those who were referred early (≤3 months) had significantly worse symptom distress and shorter overall survival than patients who were referred later on. The patients treated by thoracic oncologists who referred a smaller proportion of their patients to the RASCC had significantly worse anxiety, well-being, spiritual pain, and symptom distress than patients treated by those who referred a larger proportion of their patients to the RASCC. Significance of Results: We found that patients who were referred to the RASCC had higher reported symptom distress and worse survival ratings. Further studies are needed to evaluate the optimal criteria for timely integration of palliative care and oncology care.
The Role of MicroRNA Signature as Diagnostic Biomarkers in Different Clinical Stages of Colorectal Cancer

Objective Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related death worldwide. The early diagnosis of colorectal tumors is one of the most important challenges in cancer management. MicroRNAs (miRNAs) have provided new insight into CRC development and have been suggested as reliable and stable biomarkers for diagnosis and prognosis. The aim of this study was to analyze the differential expression of miRNAs at different stages of CRC searching for possible correlation with clinicopathological features to examine their potential value as diagnostic biomarkers. Materials and Methods In this case-control study, plasma and matched tissue samples were collected from 74 CRC patients at stage II-IV as well as blood samples from 32 healthy controls. After exhaustive study of the current literature, eight miRNAs including miR-200c, 20a, 21, 31,135b, 133b,145 and let-7g were selected. The expression level of the miRNAs was assayed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Statistical analysis, including t test , Mann-Whitney U, Kruskall-Wallis tests and receiver operating characteristic (ROC) curve was applied, where needed. Results Significantly elevated levels of miR-21, miR-31, miR-20a, miR-135b, and decreased levels of miR- 200c, miR-145 and let-7 g were detected in both plasma and matched tissue samples compared to the healthy group (P<0.05). However, no significant differences were observed in the expression level of plasma and tissue miR-133b (P>0.05). ROC for tissue miRNAs showed an area under the ROC curve (AUC) of 0.98 and P<0.001 for miR-21, 0.91 and P<0.001 for miR-135b, 0.91 and P<0.001 for miR-31, and 0.92 and P<0.001 for miR-20a. Conclusion Our results indicate that the expression levels of microRNAs are systematically altered in CRC tissue and plasma. In conclusion, detection of miR-21, miR-135b, miR-31 and miR-20a levels in the tissue might be helpful to illuminate the molecular mechanisms underlying CRC carcinogenesis and serve as tumor-associated biomarkers for diagnosis.
Flicr, a long noncoding RNA, modulates Foxp3 expression and autoimmunity

Significance Regulatory T cells (Tregs) are an essential population of immunoregulatory cells that play a central role in immune tolerance and the control of autoimmune disease, infections, and cancer. The transcription factor FoxP3 is the central orchestrator of Treg differentiation, stability, and function. Here we report the discovery of the noncoding RNA, Flicr, and its fine-tuning of FoxP3 expression through modification of chromatin accessibility, with marked consequences on the progression of autoimmune diabetes. Our findings add an important piece to the puzzle of Treg differentiation and stability, and how their function adapts to physiological circumstances. A combination of transcription factors, enhancers, and epigenetic marks determines the expression of the key transcription factor FoxP3 in regulatory T cells (Tregs). Adding an additional layer of complexity, the long noncoding RNA (lncRNA) Flicr (Foxp3 long intergenic noncoding RNA) is a negative regulator that tunes Foxp3 expression, resulting in a subset of Tregs with twofold- to fivefold-lower levels of FoxP3 protein. The impact of Flicr is particularly marked in conditions of IL-2 deficiency, and, conversely, IL-2 represses Flicr expression. Flicr neighbors Foxp3 in mouse and human genomes, is specifically expressed in mature Tregs, and acts only in cis. It does not affect DNA methylation, but modifies chromatin accessibility in the conserved noncoding sequence 3 (CNS3)/Accessible region 5 (AR5) region of Foxp3. Like many lncRNAs, Flicr’s molecular effects are subtle, but by curtailing Treg activity, Flicr markedly promotes autoimmune diabetes and, conversely, restrains antiviral responses. This mechanism of FoxP3 control may allow escape from dominant Treg control during infection or cancer, at the cost of heightened autoimmunity.
Hybrid Deformable Models for Medical Segmentation and Registration

Deformable models have had great successes over the past 20 years in medical applications. We have recently developed new classes of deformable models which we term hybrid deformable models to automate the model initialization process and make improvements in segmentation and registration. In this paper we present several hybrid deformable methods we have been developing for segmentation and registration. These methods include metamorphs, a novel shape and texture integration deformable model framework and the integration of deformable models with graphical models and learning methods. We first present a framework for the robust segmentation and tracking of the heart from tagged MRI images and second applications involving brain tumor segmentation as well as brain and cardiac shape registration
Associations of White Matter Microstructure with Clinical and Demographic Characteristics in Heavy Drinkers

Damage to the brain’s white matter is a signature injury of alcohol use disorders (AUDs), yet understanding of risks associated with clinical and demographic characteristics is incomplete. This study investigated alcohol problem severity, recent drinking behavior, and demographic factors in relation to white matter microstructure in heavy drinkers. Magnetic resonance imaging (MRI) scans, including diffusion tensor imaging (DTI), were collected from 324 participants (mean age = 30.9 ± 9.1 years; 30% female) who reported five or more heavy drinking episodes in the past 30 days. Drinking history and alcohol problem severity were assessed. A common white matter factor was created from fractional anisotropy (FA) values of five white matter tracts: body of corpus callosum, fornix, external capsule, superior longitudinal fasciculus, and cingulate gyrus. Previous research has implicated these tracts in heavy drinking. Structural equation modeling (SEM) analyses tested the hypothesis that, after controlling for duration of alcohol exposure, clinical and behavioral measures of alcohol use severity would be associated with lower white matter factor scores. Potential interactions with smoking status, gender, age, treatment-seeking status, and depression or anxiety symptoms also were tested. Controlling for number of years drinking, greater alcohol problem severity and recent drinking frequency were significantly associated with lower white matter factor scores. The effect of drinking frequency differed significantly for men and women, such that higher drinking frequency was linked to lower white matter factor scores in women but not in men. In conclusion, alcohol problem severity was a significant predictor of lower white matter FA in heavy drinkers, after controlling for duration of alcohol exposure. In addition, more frequent drinking contributed to lower FA in women but not men, suggesting gender-specific vulnerability to alcohol neurotoxicity.
Tanezumab: Therapy targeting nerve growth factor in pain pathogenesis

In recent years, nerve growth factor (NGF) and the NGF receptor have become potential therapeutic targets in the treatment of acute and chronic pain states. NGF is a neurotrophin involved in regulating the function of sensory and sympathetic neurons during development. Numerous pain states have been linked to elevated levels of NGF and its role in increasing the perception of pain. Tanezumab, a recombinant humanized monoclonal antibody (IgG), was developed to target NGF, binding both circulating and local tissue NGF preventing interaction with the tropomyosin-related kinase-A and p75 receptors. Recent clinical studies with tanezumab in different patient populations to date, including osteoarthritis, low back pain, and diabetic peripheral neuropathy, demonstrate efficacy with few side effects, including transient arthralgias, paresthesias, hypoesthesia, and rarely, osteonecrosis. Anti-NGF antibodies are a novel therapy in pain management and have shown promise in the treatment of certain pain conditions, which at present are poorly treated. Tanezumab offers an exciting new class of analgesics that has the potential to change the treatment of pain.
Vascular dysfunction across the stages of the menopausal transition is associated with menopausal symptoms and quality of life

Objective: The menopausal transition is associated with somatic symptoms and increased rates of depression, which can impair quality of life (QOL) and increase cardiovascular disease (CVD) risk. This period is also associated with accelerated vascular aging (arterial stiffening and endothelial dysfunction), an antecedent to CVD. This secondary analysis sought to explore associations between depression, menopausal symptoms and QOL, and vascular aging across menopause stages. Methods: Arterial stiffness (carotid artery compliance), endothelial function (brachial artery flow-mediated dilation [FMD]), menopausal symptoms (Menopausal Symptom List [MSL]), depression (Center for Epidemiologic Studies Depression Scale [CES-D]), and QOL (Utian QOL Scale [UQOL]) were measured in 138 women (19-70 years) classified as premenopausal (n = 41, 34 ± 8 years; mean ± SD), early (n = 25, 49 ± 3 years), or late perimenopausal (n = 26, 50 ± 4 years), or early (n = 22, 55 ± 4 years) or late postmenopausal (n = 24, 61 ± 5 years). Differences across menopause stages were determined using one-way analysis of variance; associations between vascular measures and MSL, CES-D, and UQOL were tested using Pearson's correlation analyses. Results: Menopausal symptoms, depression, and QOL worsened across menopause stages, particularly in late perimenopausal women. Vasosomatic symptom frequency, and general somatic symptom frequency and severity were inversely correlated with carotid artery compliance and FMD (r = −0.27 to −0.18, all P < 0.05). Only correlations with general somatic symptoms were significant after adjusting for multiple comparisons. Total QOL was positively correlated with carotid artery compliance (r = 0.23, P = 0.01). CES-D scores were not correlated with carotid artery compliance or FMD (r = −0.08, −0.03, P = 0.35). Conclusions: Vascular dysfunction across the stages of menopause was associated with greater frequency and severity of menopausal symptoms, and lower QOL, but not depression. Mechanisms underlying these associations (eg, inflammation, oxidative stress) should be explored.
Notice of RetractionArtificial neural network potential energy surface for silver nanoparticles

A potential energy surface (PES) for describing the interactions among the atoms in Ag nanoparticles was derived using the feedforward artificial neural network (ANN) method. Based on the preliminary success of constructing ANN PESs using a small number of data sets for Pt, Au, and Ag clusters/nanoparticles, we studied here the accuracy of the ANN method to build the PES for Ag nanoparticles to be employed in molecular dynamics (MD) simulations by including more data sets obtained from density functional theory (DFT) calculations. In this work, more neurons were used to improve the fitting accuracy. The results demonstrated that the new fitting provides a more balanced result in terms of accuracy in training and testing with respect to the previously fitting, however, more asymptotic DFT data sets are required to construct a global ANN PES suitable for MD simulations on the formation of Ag nanoparticles.
Multiple optimality criteria support Ornithoscelida

A recent study of early dinosaur evolution using equal-weights parsimony recovered a scheme of dinosaur interrelationships and classification that differed from historical consensus in a single, but significant, respect; Ornithischia and Saurischia were not recovered as monophyletic sister-taxa, but rather Ornithischia and Theropoda formed a novel clade named Ornithoscelida. However, these analyses only used maximum parsimony, and numerous recent simulation studies have questioned the accuracy of parsimony under equal weights. Here, we provide additional support for this alternative hypothesis using Bayesian implementation of the Mkv model, as well as through number of additional parsimony analyses, including implied weighting. Using Bayesian inference and implied weighting, we recover the same fundamental topology for Dinosauria as the original study, with a monophyletic Ornithoscelida, demonstrating that the main suite of methods used in morphological phylogenetics recover this novel hypothesis. This result was further scrutinized through the systematic exclusion of different character sets. Novel characters from the original study (those not taken or adapted from previous phylogenetic studies) were found to be more important for resolving the relationships within Dinosauromorpha than the relationships within Dinosauria. Reanalysis of a modified version of the character matrix that supports the Ornithischia–Saurischia dichotomy under maximum parsimony also supports this hypothesis under implied weighting, but not under the Mkv model, with both Theropoda and Sauropodomorpha becoming paraphyletic with respect to Ornithischia.
Poecilia picta, a Close Relative to the Guppy, Exhibits Red Male Coloration Polymorphism: A System for Phylogenetic Comparisons

Studies on the evolution of female preference and male color polymorphism frequently focus on single species since traits and preferences are thought to co-evolve. The guppy, Poecilia reticulata, has long been a premier model for such studies because female preferences and orange coloration are well known to covary, especially in upstream/downstream pairs of populations. However, focused single species studies lack the explanatory power of the comparative method, which requires detailed knowledge of multiple species with known evolutionary relationships. Here we describe a red color polymorphism in Poecilia picta, a close relative to guppies. We show that this polymorphism is restricted to males and is maintained in natural populations of mainland South America. Using tests of female preference we show female P. picta are not more attracted to red males, despite preferences for red/orange in closely related species, such as P. reticulata and P. parae. Male color patterns in these closely related species are different from P. picta in that they occur in discrete patches and are frequently Y chromosome-linked. P. reticulata have an almost infinite number of male patterns, while P. parae males occur in discrete morphs. We show the red male polymorphism in P. picta extends continuously throughout the body and is not a Y-linked trait despite the theoretical prediction that sexually-selected characters should often be linked to the heterogametic sex chromosome. The presence/absence of red male coloration of P. picta described here makes this an ideal system for phylogenetic comparisons that could reveal the evolutionary forces maintaining mate choice and color polymorphisms in this speciose group.
Use of Research Interfaces for Psychophysical Studies With Cochlear-Implant Users

A growing number of laboratories are using research interfaces to conduct experiments with cochlear-implant (CI) users. Because these interfaces bypass a subject’s clinical sound processor, several concerns exist regarding safety and stimulation levels. Here we suggest best-practice approaches for how to safely and ethically perform this type of research and highlight areas of limited knowledge where further research is needed to help clarify safety limits. The article is designed to provide an introductory level of technical detail about the devices and the effects of electrical stimulation on perception and neurophysiology. From this, we summarize what should be the best practices in the field, based on the literature and our experience. Findings from the review of the literature suggest that there are three main safety concerns: (a) to prevent biological or neural damage, (b) to avoid presentation of uncomfortably loud sounds, and (c) to ensure that subjects have control over stimulus presentation. Researchers must pay close attention to the software–hardware interface to ensure that the three main safety concerns are closely monitored. An important area for future research will be the determination of the amount of biological damage that can occur from electrical stimulation from a CI placed in the cochlea, not in direct contact with neural tissue. As technology used in research with CIs evolve, some of these approaches may change. However, the three main safety principles outlined here are not anticipated to undergo change with technological advances.
Maternal, Infant Characteristics, Breastfeeding Techniques, and Initiation: Structural Equation Modeling Approaches

Objectives The aim of this study was to examine the relationships among maternal and infant characteristics, breastfeeding techniques, and exclusive breastfeeding initiation in different modes of birth using structural equation modeling approaches. Methods We examined a hypothetical model based on integrating concepts of a breastfeeding decision-making model, a breastfeeding initiation model, and a social cognitive theory among 952 mother-infant dyads. The LATCH breastfeeding assessment tool was used to evaluate breastfeeding techniques and two infant feeding categories were used (exclusive and non-exclusive breastfeeding). Results Structural equation models (SEM) showed that multiparity was significantly positively associated with breastfeeding techniques and the jaundice of an infant was significantly negatively related to exclusive breastfeeding initiation. A multigroup analysis in the SEM showed no difference between the caesarean section and vaginal delivery groups estimates of breastfeeding techniques on exclusive breastfeeding initiation. Breastfeeding techniques were significantly positively associated with exclusive breastfeeding initiation in the entire sample and in the vaginal deliveries group. However, breastfeeding techniques were not significantly associated with exclusive breastfeeding initiation in the cesarean section group. Maternal age, maternal race, gestations, birth weight of infant, and postnatal complications had no significant impacts on breastfeeding techniques or exclusive breastfeeding initiation in our study. Overall, the models fitted the data satisfactorily (GFI = 0.979–0.987; AGFI = 0.951–0.962; IFI = 0.958–0.962; CFI = 0.955–0.960, and RMSEA = 0.029–0.034). Conclusions Multiparity and jaundice of an infant were found to affect breastfeeding technique and exclusive breastfeeding initiation respectively. Breastfeeding technique was related to exclusive breastfeeding initiation according to the mode of birth. This relationship implies the importance of early effective interventions among first-time mothers with jaundice infants in improving breastfeeding techniques and promoting exclusive breastfeeding initiation.
Distributed Quickest Detection in Sensor Networks via Two-Layer Large Deviation Analysis

We propose a distributed Bayesian quickest detection algorithm for sensor networks, based on a random gossip inter-sensor communication structure. Without a control or fusion center, each sensor executes its local change detection procedure in a parallel and distributed fashion, interacting with its neighboring sensors via random inter-sensor communications to propagate information. By modeling the information propagation dynamics in the network as a Markov process, a two-layer large deviation analysis is presented to analyze the performance of the proposed algorithm. The first-layer analysis shows that the relation between the probability of false alarm and the conditional averaged detection delay satisfies the large deviation principle, where the distributed Kullback–Leibler information number is established as a crucial factor. The second-layer analysis studies the probability that not all observations are available at one sensor. It shows that this probability decays exponentially fast to zero as the averaged rounds of communication increases. The large deviation upper and lower bounds for the converge rate are then derived. Finally, we show that the performance of the distributed algorithm converges exponentially fast to that of the centralized optimal one.
A Mixed-Method Application of the Program Sustainability Assessment Tool to Evaluate the Sustainability of 4 Pediatric Asthma Care Coordination Programs

Introduction As part of a cross-site evaluation of the implementation of an evidence-based intervention for pediatric asthma care coordination into low-income communities, we sought to understand the factors that influenced the programs’ expected sustainability of the programs after external funding ended. Methods We administered the Center for Public Health Systems Science’s Program Sustainability Assessment Tool, a 40-item instrument assessing 8 domains of sustainability capacity, to 12 key informants across 4 program sites. We developed open-ended probes for each domain. We examined patterns in site-specific and overall domain scores, and coded qualitative data to identify challenges and strategies in each domain. Results Across sites, the domains of program evaluation (cross-site mean, 5.4 on a scale of 1–7) and program adaptation (mean, 5.2) had the highest ratings (indicating a strong finding during program evaluation) and funding stability had the lowest rating (mean, 2.7). Scores varied most across sites in the domains of strategic planning (SD, 0.9) and funding stability (SD, 0.9). Qualitative data revealed key challenges, including how implementation difficulties and externally led implementation can impede planning for sustainability. Program leaders discussed multiple strategies for enhancing capacity within each domain, including capitalizing on the interconnectedness of all domains, such as using evaluation and communication strategies to bolster internal political support throughout the implementation process. Conclusion Findings indicating weak and strong domains were consistent with previous findings of studies that used the Program Sustainability Assessment Tool. The addition of qualitative probes yielded detailed data describing capacity strengths, weaknesses, and strategies to increase the likelihood that programs are sustained.