Miracle-dz/UniFAR-FTUs huggingface dataset:
Pancreatic cancer serum biomarker PC-594: Diagnostic performance and comparison to CA19-9.

AIM To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer (PaC) patients, and to compare its performance to CA19-9. METHODS Using tandem mass spectrometry, we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects. We determined CA19-9 levels by ELISA. Significance between PaC patients and controls, and association with clinical variables was determined by analysis of variance and t-tests. Diagnostic performance was evaluated by receiver-operator characteristic (ROC) curve analysis, and PC-594 correlation with age and CA19-9 determined by regression analysis. RESULTS Mean PC-594 levels were 3.7 times lower in PaC patients compared to controls (P < 0.0001). The mean level in PaC patient serum was 0.76 ± 0.07 μmol/L, and the mean level in control subjects was 2.79 ± 0.15 μmol/L. There was no correlation between PC-594 and age, disease stage or gender (P > 0.05). Using 1.25 μmol/L as a PC-594 threshold produced a relative risk (RR) of 9.4 (P < 0.0001, 95%CI: 5.0-17.7). The area under the receiver-operator characteristic curve (ROC-AUC) was 0.93 (95%CI: 0.91-0.95) for PC-594 and 0.85 (95%CI: 0.82-0.88) for CA19-9. Sensitivity at 90% specificity was 87% for PC-594 and 71% for CA19-9. Six PaC patients with CA19-9 above 35 U/mL showed normal PC-594 levels, while 24 PaC patients with normal CA19-9 showed low PC-594 levels. Eighty-five of the 99 control subjects (86%) showed normal levels of both markers. CONCLUSION PC-594 biomarker levels are significantly reduced in North American PaC patients, and showed superior diagnostic performance compared to CA19-9.
Winter ecology of the sea ice biota in Weddell Sea pack ice

During winter 1988, we examined the ice community in the ice edge region of the Wed-dell and Scotia Seas. We measured chemical and physical characteristics of the ice habitat, chlorophyll a (chl a), particulate organic carbon and nitrogen (POC and PON) and ATP. We also analyzed the composition and biomass of the ice biota by microscopy. Air temperature during the study ranged from above freezing to as low as-18°C. Large fluctuations over a few days were common. Temperature at the ice surface generally followed air temperature, but with a short lag period. As a result of low temperatures at the ice surface, in situ s a h i t y in the upper layer of ice floes reached > 100%. Samples were taken from newly forming, young, first-year and older sea ice. Ice floes had variable amounts of snow cover. Floes were primarily comprised of congelabon ice (56 %) but also contained significant amounts of frazil ice (41 %). Chl a ranged from <0.01 to >29.0 mg chl a m-2. Total integrated chlorophyll as well as chlorophyll concentrations and integrated POC, PON and ATP generally increased with increasing ice age or thickness. High C:chl a, C:N and C:ATP ratios characterized all ice types and suggested substantial detritus in the ice. The ice biota was comprised of bacteria, algae, protozoans and some meta-zoa. Microscopically estimated biomass in floes ranged from <50 to > 1000 mg C m-', with the highest values from older ice floes. Estimates of carbon calculated from ATP showed good agreement with estimates derived from rnicroscopy. The high concentrations of living orgamsms and detritus in sea ice suggest the potential importance of the ice community to the pelagic system particularly during the winter. The source of unexpectedly high concentrations of detritus, at least in young sea ice, is uncertain. The winter ice assemblage did not U f e r markedly from the assemblages found during other seasons, and overall the seasonal biomass variation within the pack ice community appears to be low. Resting stages such as archaeomonads and dinoflagellate cysts were common in the ice, and cyst formation for the dinoflagellates appears to take place during the winter as well as in the late summer. Although earlier studies have emphasized the importance of harvesting and concentration of organisms from the water during episodes of frazil ice formation, we did not see evidence for this from our analysis of …
Mitosis Counting in Breast Cancer: Object-Level Interobserver Agreement and Comparison to an Automatic Method

Background Tumor proliferation speed, most commonly assessed by counting of mitotic figures in histological slide preparations, is an important biomarker for breast cancer. Although mitosis counting is routinely performed by pathologists, it is a tedious and subjective task with poor reproducibility, particularly among non-experts. Inter- and intraobserver reproducibility of mitosis counting can be improved when a strict protocol is defined and followed. Previous studies have examined only the agreement in terms of the mitotic count or the mitotic activity score. Studies of the observer agreement at the level of individual objects, which can provide more insight into the procedure, have not been performed thus far. Methods The development of automatic mitosis detection methods has received large interest in recent years. Automatic image analysis is viewed as a solution for the problem of subjectivity of mitosis counting by pathologists. In this paper we describe the results from an interobserver agreement study between three human observers and an automatic method, and make two unique contributions. For the first time, we present an analysis of the object-level interobserver agreement on mitosis counting. Furthermore, we train an automatic mitosis detection method that is robust with respect to staining appearance variability and compare it with the performance of expert observers on an “external” dataset, i.e. on histopathology images that originate from pathology labs other than the pathology lab that provided the training data for the automatic method. Results The object-level interobserver study revealed that pathologists often do not agree on individual objects, even if this is not reflected in the mitotic count. The disagreement is larger for objects from smaller size, which suggests that adding a size constraint in the mitosis counting protocol can improve reproducibility. The automatic mitosis detection method can perform mitosis counting in an unbiased way, with substantial agreement with human experts.
Whole-Genome Sequencing of a Canine Family Trio Reveals a FAM83G Variant Associated with Hereditary Footpad Hyperkeratosis

Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10–20 cases and 10–20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted resequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-of-concept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrländer dogs. To our knowledge, this is the first time this family trio WGS-approach has been used successfully to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrländer dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences, and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G > C (p.R52P) was found to be concordant in eight additional cases, and 16 healthy Kromfohrländer dogs.
Comparative study of fuzzy methods in breast cancer diagnosis

This paper describes a comparison of results in breast cancer diagnosis, using two fuzzy logic methods; the first case uses fuzzy clustering with the fuzzy c-means (FCM) algorithm, which tries to find similarities between different variables; the second method is an implementation of a fuzzy inference system (FIS) with a genetic algorithm (GA) for creating and activating the optimal rules.
The severity of retinal degeneration in Rp1h gene-targeted mice is dependent on genetic background.

PURPOSE The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1h(tm1Eap)) on several different genetic backgrounds and analyzed their retinal phenotypes. METHODS The Rp1h(tm1Eap) allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretinographic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy. RESULTS Analysis of the retinal phenotype of incipient congenic (N6) B6.129S-Rp1h(+/tm1Eap), DBA.129S(B6)-Rp1h(+/tm1Eap), and A.129S(B6)-Rp1h(+/tm1Eap) mice at 1 year of age showed retinal degeneration only in the A.129S(B6)-Rp1h(+/tm1Eap) mice. Further analyses revealed that the photoreceptors of the fully congenic A.129S(B6)-Rp1h(+/tm1Eap) mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6.129S-Rp1h(+/tm1Eap) mice remain healthy up to 18 months. CONCLUSIONS The severity of the retinal degeneration caused by the Rp1h(tm1Eap) allele is notably dependent on genetic background. The development and characterization of the B6.129S-Rp1h(+/tm1Eap) and A.129S(B6)-Rp1h(+/tm1Eap) congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease.
Theory of mind and paranoia in schizophrenia: A game theoretical investigation framework

Introduction. Ample evidence already shows that theory of mind (ToM) is impaired in people with schizophrenia. Our aim was to critically review this literature. Method. We completed a selected review of the research literature on ToM in schizophrenia. Results. Gaps in ToM research were identified. A specific relationship between impaired ToM and paranoid delusions, although intuitively reasonable from a theoretical basis, has only been demonstrated in a few studies. Psychometric properties of ToM tasks employed in these studies may be a confounding factor in drawing conclusions about the relationship. Because most ToM measures have focused on the third-person perspective, participants are not actively interacting. The tasks fail to capture the cognitive demands faced by individuals in real-life situations, and, in effect, are not a direct measure of ToM. Conclusions. Potential research areas are discussed. Since game theoretical paradigms require the direct involvement of the first person and situate the participant's interpersonal reasoning within an interactive context, they provide more ecologically valid experimental platforms than conventional questionnaire measures to assess ToM in schizophrenia research.
Chinese Herbal Medicine in Treating Primary Sjögren's Syndrome: A Systematic Review of Randomized Trials

Background. There is no curative treatment for primary Sjögren's syndrome (PSS). Chinese herbal medicine (CHM) is widely used in the treatment of PSS in China. Objective. To evaluate the effectiveness and safety of CHM for PSS. Methods. PubMed, Cochrane Library, China Knowledge Resource Integrated Database, Chinese Biomedical Database, Wanfang Data, and the Database for Chinese Technical Periodicals were searched for randomized controlled trials (RCTs) of CHM or CHM plus conventional medicine for PSS compared with placebo or conventional medicine. RevMan 5.0. 17 was employed to conduct data analyses and assess homogeneity. Statistical models were chosen according to heterogeneity. Results. A total of 52 RCTs were included. The overall methodological quality of included trials was low. 49 trials reported response rates, of which 32 found significant improvements favoring CHM treatment against controls; 20 trials reported lacrimal function by Schirmer test scores, of which 16 trials reported a significant difference favoring CHM treatment. 21 trials reported salivary function by salivary flow rate, of which 10 reported significant favorable effects of CHM treatment. Other trials found no difference. The reported adverse effects of CHM included nausea, diarrhea, and other minor digestive symptoms, but more frequent adverse effects occurred in conventional medicine groups. Conclusions. Preliminary evidence from RCTs suggests the effect of CHM is promising for relieving symptoms, improving lacrimal and salivary function in PSS. However, the poor methodological quality of the included trials means that further well-designed, multicentered, larger trials are needed.
Neural Decoding of Visual Imagery During Sleep

Reading Dreams How specific visual dream contents are represented by brain activity is unclear. Machine-learning–based analyses can decode the stimulus- and task-induced brain activity patterns that represent specific visual contents. Horikawa et al. (p. 639, published online 4 April) examined patterns of brain activity during dreaming and compared these to waking responses to visual stimuli. The findings suggest that the visual content of dreams is represented by the same neural substrate as observed during awake perception. Machine-learning models can predict specific visual dream contents from brain activity measurement alone. Visual imagery during sleep has long been a topic of persistent speculation, but its private nature has hampered objective analysis. Here we present a neural decoding approach in which machine-learning models predict the contents of visual imagery during the sleep-onset period, given measured brain activity, by discovering links between human functional magnetic resonance imaging patterns and verbal reports with the assistance of lexical and image databases. Decoding models trained on stimulus-induced brain activity in visual cortical areas showed accurate classification, detection, and identification of contents. Our findings demonstrate that specific visual experience during sleep is represented by brain activity patterns shared by stimulus perception, providing a means to uncover subjective contents of dreaming using objective neural measurement.
Cariporide (HOE-642) improves cardiac allograft preservation in a porcine model of orthotopic heart transplantation

Background. Acute graft dysfunction caused by ischemia-reperfusion injury is recognized as a major source of morbidity and mortality following adult heart transplantation. The aim of this study was to determine whether treating the donor and recipient with cariporide, an inhibitor of the sodium-hydrogen exchanger, could reduce ischemia-reperfusion injury. Methods. A porcine model of donor brain death, hypothermic ischemic preservation, and orthotopic cardiac transplantation was used. Allografts in both the control group (CON, n=6) and treatment group (CAR, n=6) were arrested and stored for 4 hours in the extracellular crystalloid cardioplegia currently used in the clinical transplantation program at our institution. In addition, both the donor and recipient animals in the CAR group received a single intravenous dose of cariporide (2 mg/kg) 15 minutes before harvesting and reperfusion, respectively. Results. The initial rate of troponin I release was significantly lower in recipients of CAR hearts than in recipients of CON hearts (P =0.020). All hearts were weaned successfully from bypass. More CAR hearts were weaned successfully at the first attempt, at 1 hour post-reperfusion, than CON hearts (6 of 6 vs 3 of 6), but this did not achieve statistical significance. Left ventricular contractility (preload recruitable stroke-work relationship) and left ventricular compliance (end-diastolic pressure-volume relationship) were significantly better preserved in CAR hearts than CON hearts (both P <0.0001). Conclusions. Myocardial injury was reduced, and contractile function was better preserved in allografts that received cariporide, compared with allografts that received conventional preservation alone.
Sensitivity Analyses Comparing Outcomes Only Existing in a Subset Selected Post‐Randomization, Conditional on Covariates, with Application to HIV Vaccine Trials

Summary In many experiments, researchers would like to compare between treatments and outcome that only exists in a subset of participants selected after randomization. For example, in preventive HIV vaccine efficacy trials it is of interest to determine whether randomization to vaccine causes lower HIV viral load, a quantity that only exists in participants who acquire HIV. To make a causal comparison and account for potential selection bias we propose a sensitivity analysis following the principal stratification framework set forth by Frangakis and Rubin (2002, Biometrics58, 21–29). Our goal is to assess the average causal effect of treatment assignment on viral load at a given baseline covariate level in the always infected principal stratum (those who would have been infected whether they had been assigned to vaccine or placebo). We assume stable unit treatment values (SUTVA), randomization, and that subjects randomized to the vaccine arm who became infected would also have become infected if randomized to the placebo arm (monotonicity). It is not known which of those subjects infected in the placebo arm are in the always infected principal stratum, but this can be modeled conditional on covariates, the observed viral load, and a specified sensitivity parameter. Under parametric regression models for viral load, we obtain maximum likelihood estimates of the average causal effect conditional on covariates and the sensitivity parameter. We apply our methods to the world's first phase III HIV vaccine trial.
The Conserved Arginine Cluster in the Insert of the Third Cytoplasmic Loop of the Long Form of the D2 Dopamine Receptor (D2L-R) Acts as an Intracellular Retention Signal

This study examined whether the conserved arginine cluster present within the 29-amino acid insert of the long form of the D2 dopamine receptor (D2L-R) confers its predominant intracellular localization. We hypothesized that the conserved arginine cluster (RRR) located within the insert could act as an RXR-type endoplasmic reticulum (ER) retention signal. Arginine residues (R) within the cluster at positions 267, 268, and 269 were charge-reserved to glutamic acids (E), either individually or in clusters, thus generating single, double, and triple D2L-R mutants. Through analyses of cellular localization by confocal microscopy and enzyme-linked immunosorbent assay (ELISA), radioligand binding assay, bioluminescence resonance energy transfer (BRET2) β-arrestin 2 (βarr2) recruitment assay, and cAMP signaling, it was revealed that charge reversal of the R residues at all three positions within the motif impaired their colocalization with ER marker calnexin and led to significantly improved cell surface expression. Additionally, these data demonstrate that an R to glutamic acid (E) substitution at position 2 within the RXR motif is not functionally permissible. Furthermore, all generated D2L-R mutants preserved their functional integrity regarding ligand binding, agonist-induced βarr2 recruitment and Gαi-mediated signaling. In summary, our results show that the conserved arginine cluster within the 29-amino acid insert of third cytoplasmic loop (IC3) of the D2L-R appears to be the ER retention signal.
Estimation of the Meridional Heat and Mass Transport in the South Atlantic by Using the Joint Atmosphere and Ocean Circulation Model with Data Assimilation and Visualization Facilities

The joint ocean-Earth-atmosphere model of the Max Planck Institute for Meteorology with application of original data assimilation methods are used to estimate the meridional heat and mass flows. The CTD-sections of temperature and salinity across the Atlantic Ocean for 1991—1995 obtained in the course of the WOCE (The World Ocean Circulation Experiment) international experiment are used as observation data. The sections contain about 650 stations; each of them provides from 100 to 3000 measurements from the sea surface to the bottom. In our study both the control estimates for the velocities of currents and those with assimilation of the data of these experiments are obtained. Using visualization facilities, we have shown how data assimilation changes the model characteristics, including velocities of currents and temperature fields at different sea levels. The graphs demonstrate the influence of the change in the initial field after data assimilation on the results of the model calculations after 6 and 11 months of integration for both the observed model characteristics and those which are not observed directly. The Generalized Kalman Filter (GKF) method which coincides in a particular case with the classical Ensemble Kalman Filter (EnKF) is used as the data assimilation method. The results of calculations of the heat and mass flows are analyzed and compared with those of control calculations with no data assimilation. The calculations were performed on the supercomputers ―Mistral‖ in DKRZ (Deutsches Klimarechenzentrum, Hamburg, Germany) and ―Lomonosov-2‖ in the Lomonosov Moscow State University. This work was supported by the Russian Science Foundation, project no. 14-11-00434.
Numerical quadrature and nonlinear sequence transformations; unified rules for efficient computation of integrals with algebraic and logarithmic endpoint singularities

Some nonlinear transformations for accelerating the convergence of infinite sequences due to Levin are reviewed, and new results of practical importance in applications are given. Using these results, the transformations of Levin are modified and used to obtain new numerical integration formulas for weight functions with algebraic and logarithmic endpoint singularities, which are simpler to compute and practically as efficient as the corresponding Gaussian formulas. They also have the additional advantage that different weight functions of a certain type can have the same set of abscissas associated with them. It is shown that the formulas obtained are of interpolatory type. Furthermore, for some cases it is proved that the abscissas are in the interval of integration, although numerical results indicate that this is so in all cases and that the weights are all positive. Several numerical examples that illustrate the high accuracy and convenience of the new formulas are appended.
Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease involving chronic arthritis. The clinical course is characterized by a fluctuating pattern of active and inactive disease. We have described in detail the clinical course in different JIA subtypes during the first 2 years after diagnosis and studied its relationship to disease activity in the following years.