Miracle-dz/UniFAR-FTUs huggingface dataset:
End-of-life transitions among nursing home residents with cognitive issues.

BACKGROUND Health care transitions in the last months of life can be burdensome and potentially of limited clinical benefit for patients with advanced cognitive and functional impairment. METHODS To examine health care transitions among Medicare decedents with advanced cognitive and functional impairment who were nursing home residents 120 days before death, we linked nationwide data from the Medicare Minimum Data Set and claims files from 2000 through 2007. We defined patterns of transition as burdensome if they occurred in the last 3 days of life, if there was a lack of continuity in nursing homes after hospitalization in the last 90 days of life, or if there were multiple hospitalizations in the last 90 days of life. We also considered various factors explaining variation in these rates of burdensome transition. We examined whether there was an association between regional rates of burdensome transition and the likelihood of feeding-tube insertion, hospitalization in an intensive care unit (ICU) in the last month of life, the presence of a stage IV decubitus ulcer, and hospice enrollment in the last 3 days of life. RESULTS Among 474,829 nursing home decedents, 19.0% had at least one burdensome transition (range, 2.1% in Alaska to 37.5% in Louisiana). In adjusted analyses, blacks, Hispanics, and those without an advance directive were at increased risk. Nursing home residents in regions in the highest quintile of burdensome transitions (as compared with those in the lowest quintile) were significantly more likely to have a feeding tube (adjusted risk ratio, 3.38), have spent time in an ICU in the last month of life (adjusted risk ratio, 2.10), have a stage IV decubitus ulcer (adjusted risk ratio, 2.28), or have had a late enrollment in hospice (adjusted risk ratio, 1.17). CONCLUSIONS Burdensome transitions are common, vary according to state, and are associated with markers of poor quality in end-of-life care.
Generation of Transplantable Beta Cells for Patient-Specific Cell Therapy

Islet cell transplantation offers a potential cure for type 1 diabetes, but it is challenged by insufficient donor tissue and side effects of current immunosuppressive drugs. Therefore, alternative sources of insulin-producing cells and isletfriendly immunosuppression are required to increase the efficiency and safety of this procedure. Beta cells can be transdifferentiated from precursors or another heterologous (non-beta-cell) source. Recent advances in beta cell regeneration from somatic cells such as fibroblasts could circumvent the usage of immunosuppressive drugs. Therefore, generation of patient-specific beta cells provides the potential of an evolutionary treatment for patients with diabetes.
Separability-based multiscale basis selection and feature extraction for signal and image classification

Algorithms for multiscale basis selection and feature extraction for pattern classification problems are presented. The basis selection algorithm is based on class separability measures rather than energy or entropy. At each level the "accumulated" tree-structured class separabilities obtained from the tree which includes a parent node and the one which includes its children are compared. The decomposition of the node (or subband) is performed (creating the children), if it provides larger combined separability. The suggested feature extraction algorithm focuses on dimensionality reduction of a multiscale feature space subject to maximum preservation of information useful for classification. At each level of decomposition, an optimal linear transform that preserves class separabilities and results in a reduced dimensional feature space is obtained. Classification and feature extraction is then performed at each scale and resulting "soft decisions" obtained for each area are integrated across scales. The suggested algorithms have been tested for classification and segmentation of one-dimensional (1-D) radar signals and two-dimensional (2-D) texture and document images. The same idea can be used for other tree structured local basis, e.g., local trigonometric basis functions, and even for nonorthogonal, redundant and composite basis dictionaries.
Strategies for Training Large Vocabulary Neural Language Models

Training neural network language models over large vocabularies is still computationally very costly compared to count-based models such as Kneser-Ney. At the same time, neural language models are gaining popularity for many applications such as speech recognition and machine translation whose success depends on scalability. We present a systematic comparison of strategies to represent and train large vocabularies, including softmax, hierarchical softmax, target sampling, noise contrastive estimation and self normalization. We further extend self normalization to be a proper estimator of likelihood and introduce an efficient variant of softmax. We evaluate each method on three popular benchmarks, examining performance on rare words, the speed/accuracy trade-off and complementarity to Kneser-Ney.
Polygonum multiflorum root extract as a potential candidate for treatment of early graying hair

Despite Polygonum multiflorum (PM) has been experiencely used as a drug to treat early graying hair phenomenon in Asian countries for a long time, there is limited study examined the real biological effects of PM on hair graying in vitro and in vivo. In this study, we investigated the effects of PM root extract (PM-RE) on melanin synthesis in human melanoma SKMEL-28 cells and embryos/larvae of wild-type strain AB zebrafish. We also preliminary revealed the molecular mechanism of early hair graying phenomenon in both in vitro and in vivo models. Our results showed that PM-RE significantly induced melanin synthesis in melanin-producing SKMEL-28 melanoma cells and also in zebrafish embryos/larvae at 4-day postfertilization through activation of MC1R/MITF/tyrosinase-signaling pathway. We also investigated the differences in genotype between graying hair follicle and black hair follicle of young peoples and found that early hair graying phenomenon may be related to downregulation of MC1R/MITF/tyrosinase pathway. Taken together, we suggested that PM-RE at safe doses could be used as a potential agent for the treatment of early hair graying and other loss pigmentation-related diseases.
Clinical Perspectives for the Use of Melatonin as a Chronobiotic and Cytoprotective Agent

The circadian time system involves periodic gene expression at the cellular level, synchronized by a hierarchically superior structure located in the hypothalamic suprachiasmatic nuclei. Treatment of circadian rhythm disorders has led to the development of a new type of agent called “chronobiotics” among which melatonin is the prototype. In elderly insomniacs, melatonin treatment decreased sleep latency and increased sleep efficiency, particularly slow‐wave sleep. The effect of melatonin on sleep is the consequence of increasing sleep propensity (by augmenting the amplitude of circadian clock oscillation via MT1 receptors) and of synchronizing the circadian clock via MT2 receptors. Daily melatonin production decreases with age and in several pathologies, attaining its lowest values in Alzheimer's disease (AD) patients. About 45% of AD patients have disruptions in their sleep and “sundowning” agitation. Generally, melatonin treatment decreases sundowning in AD patients and reduced variability of sleep onset time. Both open and controlled studies have indicated a significant decrease of cognitive deterioration in AD patients treated with melatonin. The mechanisms accounting for the possible therapeutic effect of melatonin in AD patients may be manifold. On one hand, melatonin treatment promotes slow‐wave sleep in the elderly and could be beneficial by augmenting the restorative phases of sleep. On the other hand, melatonin protects neurons against β‐amyloid toxicity. By its combined chronobiotic and cytoprotective properties melatonin provides an innovative neuroprotective strategy to reduce the cost of lifetime treatment of some neuropsychiatric disorders.
NEW CONSTRUCTIONS OF SELF-COMPLEMENTARY CAYLEY GRAPHS

Abstract Vertex-primitive self-complementary graphs were proved to be affine or in product action by Guralnick et al. [‘On orbital partitions and exceptionality of primitive permutation groups’, Trans. Amer. Math. Soc. 356 (2004), 4857–4872]. The product action type is known in some sense. In this paper, we provide a generic construction for the affine case and several families of new self-complementary Cayley graphs are constructed.
Phylogeny of Shiga Toxin-Producing Escherichia coli O157 Isolated from Cattle and Clinically Ill Humans

Cattle are a major reservoir for Shiga toxin-producing Escherichia coli O157 (STEC O157) and harbor multiple genetic subtypes that do not all associate with human disease. STEC O157 evolved from an E. coli O55:H7 progenitor; however, a lack of genome sequence has hindered investigations on the divergence of human- and/or cattle-associated subtypes. Our goals were to 1) identify nucleotide polymorphisms for STEC O157 genetic subtype detection, 2) determine the phylogeny of STEC O157 genetic subtypes using polymorphism-derived genotypes and a phage insertion typing system, and 3) compare polymorphism-derived genotypes identified in this study with pulsed field gel electrophoresis (PFGE), the current gold standard for evaluating STEC O157 diversity. Using 762 nucleotide polymorphisms that were originally identified through whole-genome sequencing of 189 STEC O157 human- and cattle-isolated strains, we genotyped a collection of 426 STEC O157 strains. Concatenated polymorphism alleles defined 175 genotypes that were tagged by a minimal set of 138 polymorphisms. Eight major lineages of STEC O157 were identified, of which cattle are a reservoir for seven. Two lineages regularly harbored by cattle accounted for the majority of human disease in this study, whereas another was rarely represented in humans and may have evolved toward reduced human virulence. Notably, cattle are not a known reservoir for E. coli O55:H7 or STEC O157:H− (the first lineage to diverge within the STEC O157 serogroup), which both cause human disease. This result calls into question how cattle may have originally acquired STEC O157. The polymorphism-derived genotypes identified in this study did not surpass PFGE diversity assessed by BlnI and XbaI digestions in a subset of 93 strains. However, our results show that they are highly effective in assessing the evolutionary relatedness of epidemiologically unrelated STEC O157 genetic subtypes, including those associated with the cattle reservoir and human disease.
Synthesis of biologically realistic human motion using joint torque actuation

Using joint actuators to drive the skeletal movements is a common practice in character animation, but the resultant torque patterns are often unnatural or infeasible for real humans to achieve. On the other hand, physiologically-based models explicitly simulate muscles and tendons and thus produce more human-like movements and torque patterns. This paper introduces a technique to transform an optimal control problem formulated in the muscle-actuation space to an equivalent problem in the joint-actuation space, such that the solutions to both problems have the same optimal value. By solving the equivalent problem in the joint-actuation space, we can generate human-like motions comparable to those generated by musculotendon models, while retaining the benefit of simple modeling and fast computation offered by joint-actuation models. Our method transforms constant bounds on muscle activations to nonlinear, state-dependent torque limits in the joint-actuation space. In addition, the metabolic energy function on muscle activations is transformed to a nonlinear function of joint torques, joint configuration and joint velocity. Our technique can also benefit policy optimization using deep reinforcement learning approach, by providing a more anatomically realistic action space for the agent to explore during the learning process. We take the advantage of the physiologically-based simulator, OpenSim, to provide training data for learning the torque limits and the metabolic energy function. Once trained, the same torque limits and the energy function can be applied to drastically different motor tasks formulated as either trajectory optimization or policy learning.
Sequence of the rat factor VIII cDNA

Summary FactorVIII acts as an essential compound of the tenase complex of the coagulation system. Herein we report the cDNA of the rat factor VIII. The rat cDNA comprises 6777 nucleotides and encodes a protein of 2258 amino acids, 61 amino acids less than mouse and 92 amino acids less than human factor VIII. The overall identity compared to human cDNA is 61% on the cDNA and 51% on the amino acid level. In cDNA, highest levels of sequence identity can be observed in the A and C domains (ranging between 68% and 73%), whereas B domain and the small acidic regions are more divergent (34%-49%). Compared to mouse and human most sites for posttranslational modifications such as sulfatation and glycosylation as well as thrombin and protein C cleavage sites are conserved in rat. Alternative transcripts lacking exon 17 and/or comprising additional 26 bp due to alternative splicing of exon 20 were found. Furthermore, 13 polymorphisms (seven in exon 14, one in exon 20, 23, 24, and 25, two in the 3’UTR) three of which lead to an amino acid exchange could be detected. Our findings might provide new insights into the structure-function analysis of the factor VIII protein and might prove useful for future animal models addressing the function of factor VIII.
A Multiobjective Genetic Algorithm to Find Communities in Complex Networks

A multiobjective genetic algorithm to uncover community structure in complex network is proposed. The algorithm optimizes two objective functions able to identify densely connected groups of nodes having sparse inter-connections. The method generates a set of network divisions at different hierarchical levels in which solutions at deeper levels, consisting of a higher number of modules, are contained in solutions having a lower number of communities. The number of modules is automatically determined by the better tradeoff values of the objective functions. Experiments on synthetic and real life networks show that the algorithm successfully detects the network structure and it is competitive with state-of-the-art approaches.
A gray box manifesto for evolutionary combinatorial optimization

It is almost an article of faith that most evolutionary algorithms utilize random mutation and random recombination operators. Often the mutation is uniform random and sometimes the recombination operator is also a type of "Uniform Crossover. " However when solving classic combinatorial optimization problems, random mutation and recombination operators are often both unnecessary and unproductive.
Kudzu (pueraria lobata) vine isoflavone, puerarin, improves weight gain, glucose metabolism and osteoporosis and their biokinetics in ovariectomized mouse

Aged people, especially postmenopausal women are at increased risk of metabolic disorders such as obesity, which in turn raises the risk of developing further serious conditions, including diabetes [1,2], cancers, neurological disorders, hypertension, and other cardiovascular diseases [3]. Postmenopausal diabetes is induced by estrogen deficiency, which exacerbates insulin resistance [4,5]. The number of postmenopausal patients with diabetes has increased recently due to population aging; therefore, dietary strategies to reduce the risk of diabetes are expected to be necessary in order to improve postmenopausal health. OVX animals are used as a model of postmenopausal diabetes [68]. OVX mice show glucose intolerance, insulin resistance, and increased body weight [7,8]. This mini review aims to summarize recent findings in the area of weight and fat mass control by kudzu (Pueraria lobata) vine isoflavones and their biokinetics in OVX mice.
On the Information Rate of Multiantenna Systems With Isotropic Unitary Input Signals in the Presence of Channel Estimation Errors

This correspondence focuses on the evaluation of the information rate conveyed by block-faded pilot-based multiple-input multiple-output (MIMO) systems when the input signals are isotropic-unitary (IU)-distributed and imperfect (e.g., error-affected) channel estimates are available at receiver and transmitter. Main contributions may be so summarized. First, we develop closed-form analytical formulas for the computation of the ergodic information rate conveyed by the considered MIMO systems equipped with a large number of transmit antennas. Second, we point out that no rate gain may be accomplished by shaping the transmitted streams on the basis of (possibly partial) channel state information (CSI) so that the feedback link becomes, indeed, useless when the system is block faded and fed by IU-distributed input signals. Third, we compare the obtained information rate with those supported by the corresponding MIMO systems fed by Gaussian-distributed input signals for various values of the mean-squared error (MSE) impairing the available MIMO channel estimates. So doing, we gain some insight about the operating conditions where actual implementation of a feedback link may be justified by the resulting improvement in the rate conveyed by the overall system
Polyphenic trait promotes liver cancer in a model of epigenetic instability in mice

Hepatocellular carcinoma (HCC) represents the fifth‐most common form of cancer worldwide and carries a high mortality rate attributed to lack of effective treatment. Males are 8 times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28hep–/– mice display sex‐specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males. We now demonstrate that obesity and aging precipitate alterations of TRIM28‐dependent transcriptional dynamics, leading to a metabolic infection state responsible for highly penetrant male‐restricted hepatic carcinogenesis. Molecular analyses implicate aberrant androgen receptor stimulation, biliary acid disturbances, and altered responses to gut microbiota in the pathogenesis of Trim28hep–/–‐associated HCC. Correspondingly, androgen deprivation markedly attenuates the frequency and severity of tumors, and raising animals under axenic conditions completely abrogates their abnormal phenotype, even upon high‐fat diet challenge. Conclusion: This work underpins how discrete polyphenic traits in epigenetically metastable conditions can contribute to a cancer‐prone state and more broadly provides new evidence linking hormonal imbalances, metabolic disturbances, gut microbiota, and cancer. (Hepatology 2017;66:235–251).
Association of a Functional Polymorphism in the Serotonin Transporter Gene with Personality Traits in Females in a Polish Population

The aim of our study was to determine whether the 5-HTTLPR polymorphism is related to temperamental traits measured using the Formal Characteristics of Behavior – Temperament Inventory (FCB-TI) and personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI) questionnaire. The sample comprised 200 unrelated females, aged 18–29 years. DNA of the subjects was isolated from buccal epithelial cells, and 5-HTTLPR polymorphism was genotyped using PCR. The subjects were divided into SS, SL and LL groups according to their genotype. The differences in results on the endurance scale (F = 11.29, p = 0.001), measured using FCB-TI and neuroticism measured using NEO-FFI (F = 15.32, p = 0.000) between the S group (short-form allele; genotypes SS and SL) and the L group (long-form allele; genotype LL) were statistically significant. Additionally, statistically significant differences between the LL and SS groups, and between the SL and SS groups with respect to ‘activity’ (FCB-TI) were found (F = 4.5, p = 0.012). These findings support a role of the 5-HTTLPR polymorphism in the modulation of personality and temperamental traits.
Neuroblastoma in Iran: an experience of 32 years at a referral childrens hospital.

BACKGROUND This survey aim was to evaluate the epidemiology and outcomes of neuroblastoma patients in one the most important children referral hospitals in Iran as a model from developing countries. MATERIALS AND METHODS This retrospective, non-randomized analytic study was conducted on 219 newly diagnosed neuroblastoma cases. RESULTS The age of patients ranged from 1-156 months with the average of 40.5±2.44, with a male/female ratio of 1.9/1. Of the total, 172 (78.5%) were children and 47 (21.5%) were infants The adrenals were the most common primary site (60%). Stage 4 at diagnosis accounted for about 54% of all enrolled patients. Infants had significantly better cumulative survival (85±8%) than children (33±7%) during the follow up period and the survival rate improved from 33±7% in 1974-1994 to 58±9% in 1995-2005. CONCLUSIONS This study indicates that our patient population with neuroblastomas tends to have more advanced disease, perhaps with poor biologic markers, but our analysis shows that the outcomes have improved over 32 years although the overall survival of Iranian neuroblastoma patients is still lower than developed countries. Late diagnosis, inability to determine risk group during the years of study and using single protocol for all enrolled patients can be the reasons of lower survival rate.
Longterm mortality outcome in patients with rheumatoid arthritis: early presenters continue to do well.

OBJECTIVE Patients with rheumatoid arthritis (RA) have reduced life expectancy; however, there are few data on the changing pattern of causes of death with longterm followup, or on the longterm effect of early presentation. The objectives of this study were (1) to examine the effect of early presentation on subsequent mortality; (2) to compare the causes of death early and late in the followup period; and (3) to compare survival of the cohort with that of the general population (adjusted for age and sex) over a followup period of up to 27 years. METHODS A cohort of 448 patients with RA (inpatients and outpatients), assembled 1968-74, were followed to December 31, 1990. Death certificates were obtained for all who had died and coded using the International Classification of Diseases. Kaplan-Meier survival curves were constructed. RESULTS By the end of the study, 266 patients (59%) had died. The standardized mortality ratio (SMR) was 2.7 (95% CI 2.4-3.1). Patients who presented early continued to do well. Most excess deaths were due to cardiovascular disease. SMR due to infection, renal failure, and non-Hodgkin's lymphoma rose with disease duration. CONCLUSION Patients with RA should be referred early, and those with chronic disease should be closely monitored for evidence of infection and renal impairment.
Ovulation Induction in In-Vitro Fertilization

Reproductive endocrinology, a relatively new subspecialty of obstetrics and Gynecology, came of age during the 1980s. The discipline has benefited greatly from substantial recent advances in reproductive biology and allied fields and technologic improvements in computers, ultrasonography, and surgical instrumentation. All of these developments have been applied to clinical practice at an unprecedented rate.