Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicenter Registry Analysis of Center Characteristics Associated with Technique Failure in Patients on Incident Peritoneal Dialysis.

BACKGROUND AND OBJECTIVES Technique failure is a major limitation of peritoneal dialysis. Our study aimed to identify center- and patient-level predictors of peritoneal dialysis technique failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All patients on incident peritoneal dialysis in Australia from 2004 to 2014 were included in the study using data from the Australia and New Zealand Dialysis and Transplant Registry. Center- and patient-level characteristics associated with technique failure were evaluated using Cox shared frailty models. Death-censored technique failure and cause-specific technique failure were analyzed as secondary outcomes. RESULTS The study included 9362 patients from 51 centers in Australia. The technique failure rate was 0.35 (95% confidence interval, 0.34 to 0.36) episodes per patient-year, with a sevenfold variation across centers that was mainly associated with center-level characteristics. Technique failure was significantly less likely in centers with larger proportions of patients treated with peritoneal dialysis (>29%; adjusted hazard ratio, 0.83; 95% confidence interval, 0.73 to 0.94) and more likely in smaller centers (<16 new patients per year; adjusted hazard ratio, 1.10; 95% confidence interval, 1.00 to 1.21) and centers with lower proportions of patients achieving target baseline serum phosphate levels (<40%; adjusted hazard ratio, 1.15; 95% confidence interval, 1.03 to 1.29). Similar results were observed for death-censored technique failure, except that center target phosphate achievement was not significantly associated. Technique failure due to infection, social reasons, mechanical causes, or death was variably associated with center size, proportion of patients on peritoneal dialysis, and/or target phosphate achievement, automated peritoneal dialysis exposure, icodextrin use, and antifungal use. The variation of hazards of technique failure across centers was reduced by 28% after adjusting for patient-specific factors and an additional 53% after adding center-specific factors. CONCLUSIONS Technique failure varies widely across centers in Australia. A significant proportion of this variation is related to potentially modifiable center characteristics, including peritoneal dialysis center size, proportion of patients on peritoneal dialysis, and proportion of patients on peritoneal dialysis achieving target phosphate level.
Correlations between computed tomography perfusion enhancement parameters and lymph node metastasis in non-small cell lung cancer

This study aims to study the values of computed tomography (CT) perfusion enhancement parameters (CT-PEPs) in predicting lymph node metastasis (LNM) of lung cancer. A total of 80 patients with non-small cell lung cancer (NSCLC) underwent CT perfusion scanning. CT-PEPs were calculated according to the time-density curve (TDC) in the first-pass phase, and microvessel density (MVD) was determined to analyze the diagnostic efficacies of MVD and CT-PEPs in evaluating LNM of lung cancer. MVD in the LNM group was higher than that in the non-LNM group [(59.66±6.82) vs. (49.81±7.76)/0.74 mm2, P < 0.05), and the blood volume (BV) of the tumor mass in the LNM group was higher than that in the non-LNM group [(9.00±3.12) vs. (5.97±2.76) ml·100 g-1, t = -4.529, P < 0.05)]. MVD ≥ 54/0.74 mm2 or BV ≥ 7 ml·100 g-1 had high sensitivity and specificity (83% and 83%; 78% and 83%, respectively) for strongly suggesting the possibility of LNM of lung cancer. Among CT-PEPs, BV could be an important parameter for the preoperative judgment of LNM of lung cancer.
FEBRE: A Fast and Efficient Bit-Flipping Reduction Technique to Extend PCM lifetime

Minimizing flipped bits per write is an effective method to extend the lifetime of Phase Change Memory (PCM). However, there still remains the challenge of reaching the minimal flips without significantly compromising the speed of read/write operation. Toward this end, we propose a differential-write technique FEBRE: a Fast and Efficient Bit-flipping Reduction technique to Extend PCM lifetime. Its basic idea is to generate multiple encoded vectors from one writing data vector, so the vector with the minimal number of flips can be selected for writing. Specifically, we design a new scheme to rapidly generate multiple highly random encoded vectors from one writing data, and propose an innovative pipelined encoding algorithm to further accelerate this procedure. Compared to the current state-of-the-art technique Pseudo-Random Encoding Scheme (PRES), the FEBRE technique proposed in the present study can improve the encoding speed by at least 229%, reduce decoding operations by at least 45%, and reduce bit flips by at most 5.13%.
Regulation of Trafficking of Activated TrkA Is Critical for NGF‐Mediated Functions

Upon activation by nerve growth factor (NGF), TrkA is internalized, trafficked and sorted through different endosomal compartments. Proper TrkA trafficking and sorting are crucial events as alteration of these processes hinders NGF‐mediated functions. However, it is not fully known which proteins are involved in the trafficking and sorting of TrkA. Here we report that Nedd4‐2 regulates the trafficking of TrkA and NGF functions in sensory neurons. Depletion of Nedd4‐2 disrupts the correct sorting of activated TrkA at the early and late endosome stages, resulting in an accumulation of TrkA in these compartments and, as a result of the reduced trafficking to the degradative pathway, TrkA is either reverted to the cell surface through the recycling pathway or retrogradely transported to the cell body. In addition, Nedd4‐2 depletion enhances TrkA signaling and the survival of NGF‐dependent dorsal root ganglion neurons, but not those of brain‐derived neurotrophic factor‐dependent neurons. Furthermore, neurons from a knock‐in mouse expressing a TrkA mutant that does not bind Nedd4‐2 protein exhibit increased NGF‐mediated signaling and cell survival. Our data indicate that TrkA trafficking and sorting are regulated by Nedd4‐2 protein.
The mid-childhood and adolescent antecedents of women's external locus of control orientation.

Background: External locus of control orientation (ELOC) is a powerful predictor of adverse consequences in regard to health, educational attainment, inter-personal relationships and well-being. Although many cross-sectional studies have been carried out, relatively little is known about antecedent factors influencing the development of ELOC. Methods: Over 12,000 pregnant women who enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) in south-west England, had completed a brief version of the Adult Nowicki-Strickland Internal-External LOC scale, together with detailed questions concerning their own parents and childhood. A series of hypothesis-free structured backwards stepwise logistic regression analyses used an exposome approach with ELOC as the outcome. Results: Significant positive associations were found with smoking of the parents of the surveyed women, including prenatal exposure, and their own onset of regular smoking in mid-childhood (6-11 years). Increased odds of ELOC were also found with the absence of their fathers in early childhood, presence of older siblings, and with being born and brought up in the same area as they resided in at the time surveyed. Protective influences in the surveyed women included positive rating of their mother's care, having a relatively educated mother, attending boarding school, their own age (the older they were, the less likely were they to have an external orientation), having a mentally ill parent, a sibling hospitalized or a relative die. Conclusions: There are two conclusions: (i) that not all stressful events contribute to the development of ELOC and it would be essential for models of antecedents of ELOC to take note of this complexity, and (ii) there are consistent (albeit unexpected) findings that highlight associations with cigarette smoke exposure of the woman from fetal life through to when starting to smoke regularly herself in mid-childhood. It is important that these findings are tested in other populations.
Finnish university student activists’ resources in student union activities: A Positive Youth Development (PYD) perspective

Active citizenship is an important political goal in the Finnish society. In this study, the challenges faced in student activism were studied through twelve student activists’ narratives. The activists interviewed in this study were the chairpersons of the Finnish student unions at universities. The study leaned on the Positive Youth Development (PYD) theory. Challenges the interviewees mentioned were categorized into social, functional, emotion, and cognitive challenges and related resources. The positive coping with these challenges was analyzed through the elements of PYD. An especially relevant finding was that the student activists showed the development of active citizenship, which was contrasted as the sixth “C” of PYD, contributions to self, others, and society.
Are Incidence Rates of Adult Leukemia in the United States Significantly Associated with Birth Cohort?

Background: Leukemia is a common cancer among U.S. adults but there are few established risk factors. If leukemia risks are substantially influenced by exposures that vary in prevalence across generations, then population incidence rates should vary significantly by birth cohort. However, prior studies have not examined leukemia birth cohort effects using contemporary data and methods. Methods: We used incidence data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program from 1992 through 2009 for adults 25–84 years old and age period cohort models to estimate incidence rate ratios according to birth cohort for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphoid leukemia (CLL). Results: Leukemia incidence varied significantly between birth cohorts for each major leukemia type in men and women except female AMLs; changes on the order of 1% per birth year or 20% per generation were observed. The most significant birth cohort signatures were observed for CLLs and AMLs in men, which were decreasing and increasing, respectively, in cohorts born since 1946. Conclusions: Our results support the hypothesis that adult leukemia risks are significantly modulated by environmental and lifestyle exposures. Impact: A number of well-established (smoking, certain chemicals, radiation) and newly recognized (obesity) leukemia risk factors are modifiable; ultimately, efforts to promote healthy lifestyles might also help reduce incidence rates of adult leukemia. Cancer Epidemiol Biomarkers Prev; 21(12); 2159–66. ©2012 AACR.
Abnormal baseline brain activity in patients with cancer-induced bone pain : a resting-state functional magnetic resonance imaging study

Objective: To investigate the alternations of brain activities in patients with cancer-induced bone pain at resting state. Methods: The present study uses resting-state functional magnetic resonance imaging (fMRI) to explore functional brain activities in 12 lung cancer patients with cancer-induced bone pain, 12 lung cancer patients without cancer-induced bone pain, and 12 healthy controls. All of the lung cancer patients were in stage M1 at beginning of the study. The amplitude of low-frequency fluctuations (ALFF) was analyzed on the whole brain in all subjects. Results: There was significantly ALFF in the anterior cingulated cortex (ACC) and the medial prefrontal cortex (mPFC) in patients with cancer-induced bone pain in comparison with patients without cancer-induced bone pain. In addition, when compared with healthy controls, the patients with cancer-induced bone pain and patients without cancer-induced bone pain both showed altered activities, mainly in the posterior cingulate cortex (PCC). There was a significantly positive correlation between the visual analogue scale (VAS) and ALFF in the mPFC in patients with cancer-induced bone pain. Conclusion: Patients with cancer-induced bone pain displayed abnormal variations in baseline brain activity in some brain regions related to prefrontal-limbic network based on ALFF. All abnormalities in the brain regions may be viewed as a key marker and meanwhile could add insight into the judgment of the therapeutic effect of pain in patients with cancer-induced bone pain in future.
Assessment of PAXgene Fixation on Preservation of Morphology and Nucleic Acids in Microdissected Retina Tissue

ABSTRACT Aim: To compare the effect of the two fixatives on tissue morphology and utility to obtain good quality nucleic acids for molecular analysis from micro-dissected retinal samples. Methods: Enucleated specimens from New Zealand white rabbits were fixed in formalin or PAXgene fixative according to standard protocols, and then processed and embedded in paraffin for sectioning. Sections were stained with hematoxylin and eosin to assess the structural integrity of retina. Retinal tissue on slides was micro-dissected. DNA/RNA were extracted and assessed for preservation of the quality and quantity of the retinal tissue. Results: The retinal morphology was well preserved with both PAXgene and formalin fixation. The RNA yield obtained using both fixation methods was similar, but RNA from PAXgene fixed paraffin embedded (PFPE) samples had better purity than that from formalin fixed paraffin embedded (FFPE) samples. There was a twofold greater yield of DNA in PFPE compared to FFPE samples but with similar purity. Quantitative reverse transcription PCR analyses showed that the mean cycle threshold values for beta-actin, beta-microglobin, Opsin 1-sw, Rhodopsin, and 18S RNA of the PFPE group were significantly lower than those of the FFPE group (p < 0.01). Greater than 10-fold greater levels of gene expression were detected in PFPE relative to FFPE for the above genes. Conclusion: PAXgene fixed tissue retinal morphology is comparable to FFPE tissue. PAXgene may be a good alternative to formalin, providing good tissue morphology and ability to isolate high quality nucleic acids from micro-dissected paraffin embedded retinal samples.
Genetics of Primary Intraocular Tumors

Primary intraocular neoplasms are tumors that originate within the eye. The most common malignant primary intraocular tumor in adults is uveal melanoma and the second is primary intraocular lymphoma or vitreoretinal (intraocular) lymphoma. The most common malignant intraocular tumor in children is retinoblastoma. Genetics plays a vital role in the diagnosis and detection of ocular tumors. In uveal melanoma, monosomy 3 is the most common genetic alteration and somatic mutations of BAP1, a tumor suppressor gene, have been reported in nearly 50% of primary uveal melanomas. The retinoblastoma gene RB1 is the prototype tumor suppressor gene—mutations in RB1 alleles lead to inactivated RB protein and the development of retinoblastoma. Immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement is observed in B-cell or T-cell primary vitreoretinal lymphoma, respectively. Other factors related to the genetics of these three common malignancies in the eye are discussed and reviewed.
A Comparative Genomics, Network-Based Approach to Understanding Virulence in Vibrio cholerae

ABSTRACT Our views of the genes that drive phenotypes have generally been built up one locus or operon at a time. However, a given phenotype, such as virulence, is a multilocus phenomenon. To gain a more comprehensive view of the genes and interactions underlying a phenotype, we propose an approach that incorporates information from comparative genomics and network biology and illustrate it by examining the virulence phenotype of Vibrio cholerae O1 El Tor N16961. We assessed the associations among the virulence-associated proteins from Vibrio cholerae and all the other proteins from this bacterium using a functional-association network map. In the context of this map, we were able to identify 262 proteins that are functionally linked to the virulence-associated genes more closely than is typical of the proteins in this strain and 240 proteins that are functionally linked to the virulence-associated proteins with a confidence score greater than 0.9. The roles of these genes were investigated using functional information from online data sources, comparative genomics, and the relationships shown by the protein association map. We also incorporated core proteome data from the family Vibrionaceae; 35% of the virulence-associated proteins have orthologs among the 1,822 orthologous groups of proteins in the core proteome, indicating that they may be dual-role virulence genes or encode functions that have value outside the human host. This approach is a valuable tool in searching for novel functional associations and in investigating the relationship between genotype and phenotype.
Regulation of Alternative Splicing by Histone Modifications

Histones and Alternative Splicing Alternative splicing—the inclusion of different combinations of gene exons within a messenger RNA transcript—occurs in the majority of human genes and is regulated by basal and tissue-specific splicing factors, by transcription kinetics, and by chromatin structure. Luco et al. (p. 996, published online 4 February) analyzed the alternative splicing of the human fibroblast growth factor receptor 2 gene in tissue culture cells and found that inclusion of exon IIIb or IIIc was modulated by the levels of histone H3 lysine 36 trimethylation (H3-K36me3) and H3-K4me3. Histone H3-K36me3 enrichment correlated with binding of the chromatin protein, MRG15. The MRG15 protein in turn recruited the polypyrimidine tract–binding protein (PTB) splicing factor, which acts to repress alternative exon inclusion, thus establishing a direct link between histone modifications and the splicing machinery. Histone modifications regulate alternative splicing through physical cross talk with the splicing machinery. Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. We demonstrated a direct role for histone modifications in alternative splicing. We found distinctive histone modification signatures that correlate with the splicing outcome in a set of human genes, and modulation of histone modifications causes splice site switching. Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery.
Induction of p53 suppresses chronic myeloid leukemia

Abstract Chronic myeloid leukemia (CML) is characterized by the chromosomal translocation 9;22, known as the Philadelphia chromosome (Ph), which produces the BCR-ABL fusion tyrosine kinase. Although well-managed by BCR-ABL tyrosine kinase inhibitors (TKIs), treatment fails to eliminate Ph + primitive progenitors, and cessation of therapy frequently results in relapse. The p53 protein is an important regulator of cell cycle and apoptosis. The small molecules MI-219 target the interaction between p53 and its negative regulator HDM2, leading to its stabilization and activation. We show that treatment with MI-219 reduced the number of CML cells in both in vitro and in vivo settings but not that of normal primitive progenitors, and activated different gene signatures in CML potentially explaining the differential impact of this agent on each population. Our data suggest that a p53-activating agent may be an effective approach in the management and potential operational cure of CML.
Recurrent Lumbar Disc Herniation: Results of Revision Surgery and Assessment of Factors that May Affect the Outcome. A Non-Concurrent Prospective Study

Study Design Non-concurrent prospective study. Purpose To determine the functional outcome after open 'fragment' discectomy for recurrent lumbar disc herniation, and to analyze the factors that may affect the outcome. Overview of Literature Literature search revealed only four studies where the factors affecting the outcome of a revision surgery for recurrent disc herniation have been evaluated. None of these studies analyzed for diabetes, disc degeneration and facet arthropathy. We have analyzed these features, in addition to the demographic and clinical factors. Methods Thirty-four patients who underwent the procedure were followed up for an average period of 27.1 months. The Japanese Orthopaedic Association (JOA) score and Oswestry disability index (ODI) were used to assess the functional outcome. Age, gender, smoking, diabetic status, duration of recurrent symptoms, the side of leg pain, level and type of disc herniation, degree of disc degeneration on magnetic resonance imaging, and facet joint arthritis before first and second surgeries, were analyzed as factors affecting the outcome. Results The average Hirabayashi improvement in JOA was 56.4%. The mean preoperative ODI was 74.5% and the mean ODI at final follow-up was 32.2%, the difference being statistically significant (p<0.01). Patients with diabetes, all of whom had poor long term glycemic control, were found to have a poor outcome in terms of ODI improvement (p=0.03). Conclusions Open fragment discectomy is a safe and effective surgical technique for the treatment of recurrent disc herniation. However, patients with uncontrolled diabetes may have a less favorable outcome.
OPRM1 gene variants modulate amphetamine‐induced euphoria in humans

The μ‐opioid receptor is involved in the rewarding effects of not only opioids like morphine but also psychostimulants like amphetamine. This study aimed to investigate associations between subjective response to amphetamine and genetic polymorphisms and haplotypes in the μ‐opioid receptor including the exonic variant rs1799971 (Asp40Asn). One hundred and sixty‐two Caucasian volunteers participated in three sessions receiving either placebo or d‐amphetamine (10 and 20 mg). Associations between levels of self‐reported Euphoria, Energy and Stimulation [Addiction Research Center Inventory 49‐item questionnaire (ARCI‐49)] after d‐amphetamine ingestion and polymorphisms in OPRM1 were investigated. The intronic single nucleotide polymorphisms (SNPs) rs510769 and rs2281617 were associated with significantly higher ratings of Euphoria, Energy and Stimulation after 10 mg amphetamine. Feelings of Euphoria, Energy and Stimulation were also found to be associated with a two‐SNP haplotype formed with rs1799971 and rs510769 and a three‐SNP haplotype formed with rs1918760, rs2281617 and rs1998220. These results support the hypothesis that genetic variability in the μ‐opioid receptor gene influences the subjective effects of amphetamine and may suggest new strategies for prevention and treatment of psychostimulant abuse.