Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian rhythm of erythropoietin in human serum

Summary. When a sensitive radioimmunoassay for erythropoietin in serum (S‐Epo), using labelled recombinant hEpo and antiserum to urinary hEpo, was evaluated for clinical use, a large intra‐individual variation was observed during a 24 h period. The possibility of a circadian rhythm with a variation during day time which has to be considered for clinical evaluation of the S‐Epo level was investigated in 27 hospitalized adult patients. They had various illnesses, but all had a level of S‐Epo at 08.00 or 12.00 hours within the reference range of healthy individuals and normal cortisol levels during the 24 h. A well‐marked circadian rhythm of S‐Epo was found with the lowest mean level at 08.00 hours, a 42% increase at 16.00 hours and a 60% increase to the highest at 20.00 hours. Twelve (44%) of the 27 patients, with S‐Epo levels within the reference range (3.3–13.5 IU/l) at 08.00 or 12.00 hours, had levels above this range at 16.00 hours. For clinical evaluation of the S‐Epo level, the time of day for collection of the blood specimen has to be taken into consideration. It is recommended that blood specimens are taken in the morning between 07.30 and 12.00 hours. The mechanisms behind the observed circadian rhythm of S‐Epo are unknown.
Detection of adverse drug events through data mining techniques

Adverse Drug Reaction (ADR) is a major problem faced by medical practitioners with respect to drug safety. A number of Pre-marketing trials have fail to detect adverse drug reactions, instead, they are only observed after long term post-marketing surveillance of drug usage. The detection of Adverse Drug Reactions should be done as early as possible for the progress and safety of pharmaceutical industry. The increase in the number of adverse events and development of mining technology have motivated development of statistical and data mining methods for ADRs detection. These methods are inconvenient and tedious for users and exploration processes are time consuming. There are particular health units which provide access to electronic records of patients Aggregating and integrating electronic health records from multiple sources is rather challenging. The manual addition of data about drugs, adverse drug reactions, disease reported in scientific literature has been used to create tables as data collection technique In this work, Proportional Reporting Ratio (PRR) have been used, in combination with an estimator of the precision of point estimate such as the Chi-square test, to mine the different associations between drugs and adverse reactions. This work proposes a system for the detection of ADRs allowing an interactive discovery of associations between drugs and symptoms, called a drug-ADR association which has been further developed using other factors of interest to the user, such as demographic information, the current analysis has been done on 5000 records.
Strong artificial selection in the wild results in predicted small evolutionary change

Estimates of genetic variation and selection allow for quantitative predictions of evolutionary change, at least in controlled laboratory experiments. Natural populations are, however, different in many ways, and natural selection on heritable traits does not always result in phenotypic change. To test whether we were able to predict the evolutionary dynamics of a complex trait measured in a natural, heterogeneous environment, we performed, over an 8‐year period, a two‐way selection experiment on clutch size in a subdivided island population of great tits (Parus major). Despite strong artificial selection, there was no clear evidence for evolutionary change at the phenotypic level. Environmentally induced differences in clutch size among years are, however, large and can mask evolutionary changes. Indeed, genetic changes in clutch size, inferred from a statistical model, did not deviate systematically from those predicted. Although this shows that estimates of genetic variation and selection can indeed provide quantitative predictions of evolutionary change, also in the wild, it also emphasizes that demonstrating evolution in wild populations is difficult, and that the interpretation of phenotypic trends requires great care.
A population-based study of the epidemiology and clinical features of methicillin-resistant Staphylococcus aureus infection in Pennsylvania, 2001–2010

SUMMARY No U.S. general population-based study has characterized the epidemiology and risk factors, including skin and soft tissue infection (SSTI), for healthcare-associated (HA) and community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA). We estimated the incidence of HA- and CA-MRSA and SSTI over a 9-year period using electronic health record data from the Geisinger Clinic in Pennsylvania. MRSA cases were frequency-matched to SSTI cases and controls in a nested case-control analysis. Logistic regression was used to assess risk factors, while accounting for antibiotic administration. We identified 1713 incident CA- and 1506 HA-MRSA cases and 78 216 SSTI cases. On average, from 2005 to 2009, the annual incidence of CA-MRSA increased by 34%, HA-MRSA by 7%, and SSTI by 4%. Age, season, community socioeconomic deprivation, obesity, smoking, previous SSTI, and antibiotic administration were identified as independent risk factors for CA-MRSA.
Characterization of the human myeloid leukemia‐derived cell line GF‐D8 by multiplex fluorescence in situ hybridization, subtelomeric probes, and comparative genomic hybridization

The human myeloid leukemia cell line GF‐D8 was established from the peripheral blood blasts of a patient with acute myeloid leukemia FAB subtype M1 (AML‐M1). The karyotype, which has not changed significantly over several years of culture, was described initially as 44,XY,‐5,del(7q),inv(7q),add(8q),add(11q),del(12p),‐15,‐17,+mar. With the advent of multicolor fluorescence in situ hybridization (FISH) techniques, the prospect of accurately characterizing this complex karyotype became feasible. In the present study, we applied 24‐color whole‐chromosome painting and analyzed the results using a filter‐based detection system and proprietary software for multiplex FISH (M‐FISH). This resulted in the refinement of the karyotype and the identification of hitherto unsuspected chromosome rearrangements. M‐FISH identified the origin of the add(8q) and add(11q) as well as the small marker chromosome. Both the del(7q) and del(12p) were redefined as unbalanced translocations and an apparently normal chromosome 11 was shown to be t(11;17). Importantly, the del(12p) was shown to be a der(12)t(7;12). Single‐color whole‐chromosome painting studies confirmed these findings, but also identified a cryptic t(Y;12) not seen in the original M‐FISH analysis. We then carried out a FISH screening assay using a complete set of chromosome‐specific subtelomeric probes. This allowed the identification of p and q subtelomeric regions involved in the translocations and indicated amplification of the 8q subtelomeric region. Comparative genomic hybridization (CGH) revealed a highly unbalanced karyotype, as deletions accompanied the majority of translocations, and identified the regions of amplification as 8q22.3‐qter and 11q21‐qter. Finally, conventional FISH with centromeric and unique sequence probes was necessary to elucidate all of the rearrangements. Genes Chromosomes Cancer 24:213–221, 1999. © 1999 Wiley‐Liss, Inc.
Quantum-Enhanced Reinforcement Learning for Finite-Episode Games with Discrete State Spaces

Quantum annealing algorithms belong to the class of metaheuristic tools, applicable for solving binary optimization problems. Hardware implementations of quantum annealing, such as the quantum annealing machines produced by D-Wave Systems, have been subject to multiple analyses in research, with the aim of characterizing the technology's usefulness for optimization and sampling tasks. Here, we present a way to partially embed both Monte Carlo policy iteration for finding an optimal policy on random observations, as well as how to embed (n) sub-optimal state-value functions for approximating an improved state-value function given a policy for finite horizon games with discrete state spaces on a D-Wave 2000Q quantum processing unit (QPU). We explain how both problems can be expressed as a quadratic unconstrained binary optimization (QUBO) problem, and show that quantum-enhanced Monte Carlo policy evaluation allows for finding equivalent or better state-value functions for a given policy with the same number episodes compared to a purely classical Monte Carlo algorithm. Additionally, we describe a quantum-classical policy learning algorithm. Our first and foremost aim is to explain how to represent and solve parts of these problems with the help of the QPU, and not to prove supremacy over every existing classical policy evaluation algorithm.
N-Glycolylneuraminic Acid Deficiency in Mice: Implications for Human Biology and Evolution

ABSTRACT Humans and chimpanzees share >99% identity in most proteins. One rare difference is a human-specific inactivating deletion in the CMAH gene, which determines biosynthesis of the sialic acid N-glycolylneuraminic acid (Neu5Gc). Since Neu5Gc is prominent on most chimpanzee cell surfaces, this mutation could have affected multiple systems. However, Neu5Gc is found in human cancers and fetuses and in trace amounts in normal human tissues, suggesting an alternate biosynthetic pathway. We inactivated the mouse Cmah gene and studied the in vivo consequences. There was no evidence for an alternate pathway in normal, fetal, or malignant tissue. Rather, null fetuses accumulated Neu5Gc from heterozygous mothers and dietary Neu5Gc was incorporated into oncogene-induced tumors. As with humans, there were accumulation of the precursor N-acetylneuraminic acid and increases in sialic acid O acetylation. Null mice showed other abnormalities reminiscent of the human condition. Adult mice showed a diminished acoustic startle response and required higher acoustic stimuli to increase responses above the baseline level. In this regard, histological abnormalities of the inner ear occurred in older mice, which had impaired hearing. Adult animals also showed delayed skin wound healing. Loss of Neu5Gc in hominid ancestors ∼2 to 3 million years ago likely had immediate and long-term consequences for human biology.
Mapping Power Law Distributions in Digital Health Social Networks: Methods, Interpretations, and Practical Implications

Background Social networks are common in digital health. A new stream of research is beginning to investigate the mechanisms of digital health social networks (DHSNs), how they are structured, how they function, and how their growth can be nurtured and managed. DHSNs increase in value when additional content is added, and the structure of networks may resemble the characteristics of power laws. Power laws are contrary to traditional Gaussian averages in that they demonstrate correlated phenomena. Objectives The objective of this study is to investigate whether the distribution frequency in four DHSNs can be characterized as following a power law. A second objective is to describe the method used to determine the comparison. Methods Data from four DHSNs—Alcohol Help Center (AHC), Depression Center (DC), Panic Center (PC), and Stop Smoking Center (SSC)—were compared to power law distributions. To assist future researchers and managers, the 5-step methodology used to analyze and compare datasets is described. Results All four DHSNs were found to have right-skewed distributions, indicating the data were not normally distributed. When power trend lines were added to each frequency distribution, R 2 values indicated that, to a very high degree, the variance in post frequencies can be explained by actor rank (AHC .962, DC .975, PC .969, SSC .95). Spearman correlations provided further indication of the strength and statistical significance of the relationship (AHC .987. DC .967, PC .983, SSC .993, P<.001). Conclusions This is the first study to investigate power distributions across multiple DHSNs, each addressing a unique condition. Results indicate that despite vast differences in theme, content, and length of existence, DHSNs follow properties of power laws. The structure of DHSNs is important as it gives insight to researchers and managers into the nature and mechanisms of network functionality. The 5-step process undertaken to compare actor contribution patterns can be replicated in networks that are managed by other organizations, and we conjecture that patterns observed in this study could be found in other DHSNs. Future research should analyze network growth over time and examine the characteristics and survival rates of superusers.
Systematic Analysis of Enhancer and Critical cis-Acting RNA Elements in the Protein-Encoding Region of the Hepatitis C Virus Genome

ABSTRACT Hepatitis C virus (HCV) causes chronic hepatitis, cirrhosis, and liver cancer. cis-acting RNA elements of the HCV genome are critical for translation initiation and replication of the viral genome. We hypothesized that the coding regions of nonstructural proteins harbor enhancer and essential cis-acting replication elements (CRE). In order to experimentally identify new cis RNA elements, we utilized an unbiased approach to introduce synonymous substitutions. The HCV genome coding for nonstructural proteins (nucleotide positions 3872 to 9097) was divided into 17 contiguous segments. The wobble nucleotide positions of each codon were replaced, resulting in 33% to 41% nucleotide changes. The HCV genome containing one of each of 17 mutant segments (S1 to S17) was tested for genome replication and infectivity. We observed that silent mutations in segment 13 (S13) (nucleotides [nt] 7457 to 7786), S14 (nt 7787 to 8113), S15 (nt 8114 to 8440), S16 (nt 8441 to 8767), and S17 (nt 8768 to 9097) resulted in impaired genome replication, suggesting CRE structures are enriched in the NS5B region. Subsequent high-resolution mutational analysis of NS5B (nt 7787 to 9289) using approximately 51-nucleotide contiguous subsegment mutant viruses having synonymous mutations revealed that subsegments SS8195-8245, SS8654-8704, and SS9011-9061 were required for efficient viral growth, suggesting that these regions act as enhancer elements. Covariant nucleotide substitution analysis of a stem-loop, JFH-SL9098, revealed the formation of an extended stem structure, which we designated JFH-SL9074. We have identified new enhancer RNA elements and an extended stem-loop in the NS5B coding region. Genetic modification of enhancer RNA elements can be utilized for designing attenuated HCV vaccine candidates.
Matrix metalloproteinase-1 and -3 gene promoter polymorphisms in Japanese patients with periodontitis.

BACKGROUND/AIMS Matrix metalloproteinase (MMP)-1 and MMP-3 have important roles in the connective tissue remodelling and destruction processes in periodontitis. MMP-1 1G/2G (-1607) and MMP-3 5A/6A (-1171) polymorphisms have been identified and appear to influence the transcription of the genes. The aim of this study was to investigate whether these gene promoter polymorphisms were associated with the susceptibility to periodontitis. MATERIAL AND METHODS Genomic DNA was obtained from 37 generalised aggressive, 205 slight-to-severe generalised chronic-periodontitis patients and 142 healthy subjects. All subjects were non-smoking Japanese. We genotyped by using TaqMan PCR assay. The statistics were analysed by chi2-test. RESULTS We found no significant differences in genotype distributions, allele frequencies, carriage rates and haplotype frequencies in the MMP-1 and the MMP-3 gene promoter polymorphisms among all groups. The distributions of MMP-1 and MMP-3 genotypes in our study were different from those of previously reported in Caucasians or Brazilians, but consistent with previously reported in Japanese. CONCLUSION Our data did not support the hypothesis that MMP-1 and/or MMP-3 gene promoter polymorphisms influenced the susceptibility to periodontitis in Japanese patients, indicating MMP-1 and MMP-3 expressions were regulated by complex processes such as cytokine network in periodontal disease rather than gene polymorphisms.
Community monopolization: local adaptation enhances priority effects in an evolving metacommunity

The diversity and composition of biological communities might often depend on colonization history because early colonists can exclude future colonists through a priority effect. These priority effects, which have been observed across a wide variety of ecosystems, often arise because early colonists have sufficient time to use available resources efficiently and subsequently withhold them from invaders. Here, we explore the extent to which rapid local adaptive evolution contributes to the pervasiveness of these priority effects. Using an individual-based simulation, we show that early colonization allows the descendants of colonists to adapt to novel conditions and reduce the establishment success of an initially ecologically equivalent competing species. Our model predicts that slight differences in colonization timing and adaptive capacity between species can substantially alter the dynamics and diversity of communities. We also show that priority effects and gene flow can generate a novel mechanism for the expansion and retraction of species distributions in a metacommunity. Our results suggest that local adaptation combined with stochastic colonization events can obscure direct relationships between species distributions and environmental gradients. Given the increasing recognition of rapid, microgeographic evolution in natural populations, we expect that evolutionary priority effects could affect the structure and dynamics of many natural metacommunities.
A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar ATPase through its homeodomain

LASS2/TMSG1 was a novel tumor metastasis suppressor gene, which was first cloned by our laboratory from non‐metastatic and metastatic cancer cell variants of human prostate carcinoma PC‐3M using mRNA differential display in 1999. LASS2/TMSG1 could interact with the C subunit of vacuolar ATPase (V‐ATPase, ATP6V0C) and regulate V‐ATPase activity. In an attempt to provide molecular mechanism of the interaction between LASS2/TMSG1 and V‐ATPase, we constructed four variant transfectants containing different functional domain of LASS2/TMSG1 and stably transfected the variants to human prostate cancer cell line PC‐3M‐1E8 cell with high metastatic potential. Results showed that there were no obvious differences of V‐ATPase expression among different transfected cells and the control. However, V‐ATPase activity and intracellular pH was significantly higher in the variant transfectants with Homeodomain of LASS2/TMSG1 than that in the control using the pH‐dependent fluorescence probe BECEF/AM. Immunoprecipitation, immunofluorescence and immuno‐electron microscope alone or in combination demonstrated the direct interaction of Homeodomain of LASS2/TMSG1 and ATP6V0C. Loss of Homeodomain markedly enhanced the proliferation ability but weakened the apoptotic effect of LASS2/TMSG1 in PC‐3M‐1E8 cells. These lines of results for the first time contribute to the conclusion that LASS2/TMSG1 could regulate V‐ATPase activity and intracellular pH through the direct interaction of its Homeodomain and the C subunit of V‐ATPase. Their interaction could play important roles in the apoptosis of tumor cells. J. Cell. Biochem. 114: 570–583, 2013. © 2012 Wiley Periodicals, Inc.
Psychosocial work conditions, social capital, and daily smoking: a population based study

Objective: To investigate the associations between psychosocial conditions at work, social capital/social participation, and daily smoking. Design/setting/participants/measurements: The 2000 public health survey in Scania is a cross sectional postal questionnaire study with a 59% participation rate. A total of 5180 persons aged 18–64 years that belonged to the work force and the unemployed were included in this study. Logistic regression models were used to investigate the associations between psychosocial factors at work/unemployment, social participation, and daily smoking. Psychosocial conditions at work were defined according to the Karasek-Theorell demand–control/decision latitudes into relaxed, active, passive, and jobstrain categories. The multivariate analyses included age, country of origin, education and economic stress. Results: 17.2% proportion of all men and 21.9% of all women were daily smokers. The jobstrain (high demands/low control) and unemployed categories had significantly higher odds ratios of daily smoking among both men and women compared to the relaxed (low demands/high control) reference category. The passive (low demands/low control), jobstrain, and unemployed categories were also significantly associated with low social participation. Low social participation was significantly and positively associated with daily smoking within each of the psychosocial work conditions and unemployed categories. Conclusions: The positive association between low social capital/low social participation and daily smoking is well known. However, both social participation and daily smoking are associated with psychosocial work conditions and unemployment. Psychosocial work conditions and unemployment may affect daily smoking both directly and through a pathway including social participation.
Error Performance of Sparse Code Multiple Access Networks with Joint ML Detection

This paper investigates error performance of sparse code multiple access (SCMA) networks with multiple access channels (MAC) and broadcast channels (BC). We give the closed-form expression for the pairwise error probability (PEP) of joint maximum likelihood (ML) detection for multiuser signals over additive white Gaussian noise (AWGN) and Rayleigh fading channels with an arbitrary number of users and multidimensional codebooks. An upper bound for the average symbol error rate (SER) is calculated. The bound is tight in both AWGN channel and Rayleigh fading channels for high SNR regions. The analytical bounds are compared with simulations, and the results confirm the effectiveness of the analysis for both AWGN and Rayleigh fading channels.
Genome-Wide Identiﬁcation and Analysis of the MYB Transcription Factor Superfamily in Solanum lycopersicum

MYB proteins constitute one of the largest transcription factor families in the plant kingdom, members of which perform a variety of functions in plant biological processes. However, there are only very limited reports on the characterization of MYB transcription factors in tomato ( Solanum lycopersicum ). In our study, a total of 127 MYB genes have been identiﬁed in the tomato genome. A complete overview of these MYB genes is presented, including the phylogeny, gene structures, protein motifs, chromosome locations and expression patterns. The 127 SlMYB proteins could be classiﬁed into 18 subgroups based on domain similarity and phylogenetic topology. Phylogenetic analysis of SlMYBs along with MYBs from Arabidopsis ( Arabidopsis thaliana ) and rice ( Oryza sativa ) indicated 14 subfamilies. Conserved motifs outside the MYB domain may reﬂect their functional conservation. The identiﬁed tomato MYB genes were distributed on 12 chromosomes at various densities but mainly in chromosomes 6 and 10 (12.6% and 11.8%, respectively). Genome-wide segmental and tandem duplications were also found, which may contribute to the expansion of SlMYB genes. RNA-sequencing and microarray data revealed tissue-speciﬁc and stress-responsive expression patterns of SlMYB genes. The expression proﬁles of SlMYB genes in response to salicylic acid (SA) and jasmonic acid methyl ester (MeJA) were also investigated by real-time PCR. Moreover, ethylene-responsive element-binding factor-associated amphiphilic repression (EAR) motifs were found in 24 SlMYB proteins. Collectively, our comprehensive analysis of SlMYB genes will facilitate future functional studies of the tomato MYB gene family and probably other Solanaceae plants.