Miracle-dz/UniFAR-FTUs huggingface dataset:
Kidney biopsy in AA amyloidosis: impact of histopathology on prognosis

Abstract In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by clinicians, there is no evidence that the detailed investigation of renal histopathology can be utilized for the prognosis and clinical outcomes. In this study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA amyloidosis might have prognostic and clinical value. This is a retrospective cohort study that included 38 patients who were diagnosed with AA amyloidosis by kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were evaluated and graded for several characteristics of histopathological lesions and their relationship with renal outcomes. Segmental amyloid deposition in the kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of patients. Histopathologically, glomerular enlargement, interstitial fibrosis, tubular atrophy, interstitial inflammation and global amyloid deposition were significantly associated with lower estimated glomerular filtration rate (eGFR) (p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate analysis. In multivariate analysis, tubular atrophy was the only predictor of eGFR (p = .019 B = −20.573). In the follow-up at an average of 27 months, 18 patients developed end-stage renal disease (ESRD). Among them, global amyloid deposition was the only risk factor for the development of ESRD (p = .01, OR = 18.750, %95 CI= 2.021–173.942). This is the first study showing that the histopathological findings in kidney biopsy of AA amyloidosis might have a prognostic and clinical value for renal outcomes.
Low Information Games - Experimental Evidence on Learning in Ultimatum Bargaining

This paper reports experimental evidence on behaviour in an Ultimatum Game where responders have low structural information and feedback so that they have to learn the nature of the game during repeated play. The results lend support to the view that certain learning conditions are less favourable in terms of individual outcomes than others as suggested by the contingent learning approach (Slembeck, 1998). Furthermore, there is evidence that proposers behave "less fair" when responders lack structural information, which contrasts with common notions of fairness or "manners" in ultimatum bargaining (Camerer and Thaler 1995).
The Relationship between Search Efficiency and Crowding

The role of target salience in crowding has remained controversial largely because salience usually escapes objective measurement. Here we address this problem using search efficiency as a measure of target salience. In separate experiments observers determined whether parafoveal arrays of vertical Gabor patterns contained targets having a unique colour, a unique direction of motion, and a unique temporal frequency. We analysed search efficiency in the conventional manner using reaction-time gradients (in seconds per item). We also considered accuracy gradients (in percent-correct per item). Crowding is typically quantified by comparing the acuity for a target within an array to the acuity for a target presented alone. We measured orientation acuity for determining whether a slightly tilted target was clockwise or anticlockwise of vertical. Targets with a unique colour or direction of motion were found to pop out, ie (with one exception) reaction-time and accuracy gradients were insignificantly different from zero. Acuity for these targets was significantly greater than acuity for targets whose neighbours had the same colour and direction of motion. Manipulation of temporal frequency produced a wide range of search efficiencies. For three of four observers we found a linear relationship between acuity and the accuracy gradient, shallow gradients being associated with high acuity. In general, we find that crowding is weakened when observers can find a parafoveally presented target quickly and accurately.
Impairment of the Ubiquitin-Proteasome Pathway Is a Downstream Endoplasmic Reticulum Stress Response Induced by Extracellular Human Islet Amyloid Polypeptide and Contributes to Pancreatic β-Cell Apoptosis

OBJECTIVE—Human islet amyloid polypeptide (hIAPP) aggregation plays a major role in the development of islet amyloidosis in type 2 diabetes. It is known that extracellular hIAPP oligomers are toxic to pancreatic β-cells and associated with apoptosis. We therefore investigated the molecular mechanism by which extracellular hIAPP mediates pancreatic β-cell apoptosis. RESEARCH DESIGN AND METHODS—MIN6 cells and primary cultures of human pancreatic islets were treated with freshly dissolved hIAPP peptide. Morphology of the cultures was evaluated by electron microscopy. Gene expression was analyzed by microarray, RT-PCR, and immunoblot. Calcium levels were measured in fura-2–loaded cells. Apoptosis was quantified by cytometry. RESULTS—Increased expression of several heat shock proteins and activation of the spliced form of XBP-1, a transcription factor for overexpression of chaperones during endoplasmic reticulum (ER) stress, were detected together with morphological evidence of ER dysfunction. Intracellular calcium overload was detected in association with this process. Moreover, reduction in the proteasome activity, which was detected over time, contributed to the intracellular accumulation of ubiquitinated proteins, leading to a functional suppression of the ubiquitin-proteasome pathway. In addition, impairment of the proteasome function contributed to apoptosis, while, despite the presence of hIAPP, cell viability improved when a proteasome activator was overexpressed. The key cytotoxic events induced by extracellular hIAPP were also observed in treated human islets. CONCLUSIONS—Our data suggest that ER stress responses are intracellular signaling mechanisms induced by extracellular hIAPP aggregation and that impairment of the ubiquitin-proteasome pathway is implicated in ER stress–mediated pancreatic β-cell apoptosis.
High Throughput Large Scale Sorting on a CPU-FPGA Heterogeneous Platform

Recently accelerating sorting using FPGA has been of growing interest in both industry and academia. However, the supported size of data set is usually small for FPGA-only sorting designs due to limited on-chip memory. In this paper, we propose a design to speed-up large scale sorting using a CPU-FPGA heterogeneous platform. We first optimize a fully-pipelined merge sort based accelerator and employ several such designs working in parallel on FPGA. The partial results from the FPGA are then merged on the CPU. On the Intel QuickAssist QPI FPGA Platform, for a range of data set size, we improve the throughput by 2.9× and 1.9× compared with CPU-only and FPGA-only baselines, respectively. Compared with the state-of-the-art FPGA implementation for sorting, our design achieves 2.3× throughput improvement.
Integration of Goal- and Stimulus-Related Visual Signals Revealed by Damage to Human Parietal Cortex

Where we look is determined both by our current intentions and by the tendency of visually salient items to “catch our eye. ” After damage to parietal cortex, the normal process of directing attention is often profoundly impaired. Here, we tracked parietal patients' eye movements during visual search to separately map impairments in goal-directed orienting to targets versus stimulus-driven gaze shifts to salient but task-irrelevant probes. Deficits in these two distinct types of attentional selection are shown to be identical in both magnitude and spatial distribution, consistent with damage to a “priority map” that integrates goal- and stimulus-related signals to select visual targets. When goal-relevant and visually salient items compete for attention, the outcome depends on a biased competition in which the priority of contralesional targets is undervalued. On the basis of these findings, we further demonstrate that parietal patients' spatial bias (neglect) in goal-directed visual exploration can be corrected and even reversed by systematically manipulating the spatial distribution of stimulus salience in the visual array.
Motor impairment in sibling pairs concordant and discordant for autism spectrum disorders

Aim: Although motor impairment is frequently observed in children with autism spectrum disorders (ASD), the manner in which these impairments aggregate in families affected by autism is unknown. We used a standardized measure of motor proficiency to objectively examine quantitative variation in motor proficiency in sibling pairs concordant and discordant for ASD. Methods: Motor impairment of sibling pairs from 67 ASD-affected families comprising 29 concordant pairings and 48 discordant pairings were assessed using the Bruininks Oseretsky Test of Motor Proficiency, 2nd Edition, a standardized measure of motor proficiency. Results: Motor skills were substantially impaired among ASD-affected children and highly correlated with autistic severity and IQ, whereas motor skills in unaffected siblings were essentially normal. Total motor composite scores of at least one standard deviation below the general population mean were seen in 83% of the affected group compared with 6% in the unaffected siblings. Interpretation: Findings indicate that motor impairment constitutes a core characteristic of ASD (not necessarily an ASD endophenotype), which has distinct implications for taxonomy, diagnosis, and approaches to intervention.
Heterogeneous Beliefs and Prediction Market Accuracy

We consider a prediction market in which traders have heterogeneous prior beliefs in probabilities. In the two-state case, we derive necessary and sufficient conditions so that the prediction market is accurate in the sense that the equilibrium state price equals the mean probabilities of traders' beliefs. We also provide a necessary and sufficient condition for the well documented favorite-longshot bias. In an extension to many states, we revisit the results of Varian (1985) on the relationship between equilibrium state price and belief heterogeneity.
A core of kinase-regulated interactomes defines the neoplastic MDSC lineage

Myeloid-derived suppressor cells (MDSCs) differentiate from bone marrow precursors, expand in cancer-bearing hosts and accelerate tumor progression. MDSCs have become attractive therapeutic targets, as their elimination strongly enhances anti-neoplastic treatments. Here, immature myeloid dendritic cells (DCs), MDSCs modeling tumor-infiltrating subsets or modeling non-cancerous (NC)-MDSCs were compared by in-depth quantitative proteomics. We found that neoplastic MDSCs differentially expressed a core of kinases which controlled lineage-specific (PI3K-AKT and SRC kinases) and cancer-induced (ERK and PKC kinases) protein interaction networks (interactomes). These kinases contributed to some extent to myeloid differentiation. However, only AKT and ERK specifically drove MDSC differentiation from myeloid precursors. Interfering with AKT and ERK with selective small molecule inhibitors or shRNAs selectively hampered MDSC differentiation and viability. Thus, we provide compelling evidence that MDSCs constitute a distinct myeloid lineage distinguished by a “kinase signature” and well-defined interactomes. Our results define new opportunities for the development of anti-cancer treatments targeting these tumor-promoting immune cells.
Plasmodium vivax Infection in Duffy-Negative People in Africa

The understanding that red blood cells (RBCs) lacking the Duffy receptor are resistant to blood stage infection by Plasmodium vivax has provided the conceptual path for productive investigation into malaria parasite invasion of the human RBC overthelast40years. 1 Followingtheleadthatmalariaparasites co-opt RBC surface proteins to provide orientation to, and enable merozoite manipulationof the RBC surface, has made it possible to identify many proteins involved in RBC invasion. 2 With the availability of the polymerase chain reaction (PCR), increased sensitivity and speci ﬁ city have signi ﬁ cantly improved detection and classi ﬁ cation of malaria parasites. Compatibility of PCR assays with microwell formatting has dramatically increased the capacity and processing speed of large patient sample numbers. a result easily in size from ten-thousands samples. diagnostic many new perspectives have gained malaria ﬁ
Maintaining balance against force perturbations: impaired mechanisms unresponsive to levodopa in Parkinson's disease

We introduce a new method to investigate postural instability in Parkinson's disease (PD) using computer-controlled motors to deliver precise pulls to the shoulders of subjects while standing. It mimics the clinical pull test but uses forces with unpredictable timing, direction, and magnitude. It revealed a number of balance control deficits in PD. Notably, the identified deficits were not significantly altered by levodopa medication, suggesting that disruption to nondopaminergic systems contributes to postural instability in PD.
Elderly patients with an atypical presentation of illness in the emergency department.

BACKGROUND Very little information is available on the prevalence and clinical outcome of elderly patients with atypical presentations of illness in the emergency department. The objective was to determine the prevalence and clinical outcome of elderly patients seen in the emergency department with an atypical presentation. METHODS A monocentric retrospective observational study on 355 elderly patients presenting to the emergency department. Patients of 80 years and older were included. Data were extracted from the electronic medical file. RESULTS A total of 355 patients were included, with a mean age of 86 years; 53% of these elderly patients had an atypical presentation of illness. Mostly this was due to a fall (71%). A total of 15% of the patients with an atypical presentation reported no specific symptoms of the underlying disease. Patients with atypical presentation were more likely to have a longer stay in hospital (p < 0.001), to be discharged to a care institution (p = 0.000), and to have a higher delirium observation score (p < 0.001). There was no significant difference in one-year survival (p = 0.056). CONCLUSION Atypical presentation of illness in elderly patients is highly prevalent in the emergency department. Falling accidents are the most important reason for this. Patients with an atypical presentation have a worse clinical outcome. Accurate training of emergency staff is necessary to recognise this group of patients to ensure proper clinical monitoring and timely treatment.
Elevated CO2 stimulates grassland soil respiration by increasing carbon inputs rather than by enhancing soil moisture

It is not clear whether the consistent positive effect of elevated CO2 on soil respiration (soil carbon flux, SCF) results from increased plant and microbial activity due to (i) greater C availability through CO2‐induced increases in C inputs or (ii) enhanced soil moisture via CO2‐induced declines in stomatal conductance and plant water use. Global changes such as biodiversity loss or nitrogen (N) deposition may also affect these drivers, interacting with CO2 to affect SCF. To determine the effects of these factors on SCF and elucidate the mechanism(s) behind the effect of elevated CO2 on SCF, we measured SCF and soil moisture throughout a growing season in the Biodiversity, CO2, and N (BioCON) experiment. Increasing diversity and N caused small declines in soil moisture. Diversity had inconsistent small effects on SCF through its effects on abiotic conditions, while N had a small positive effect that was unrelated to soil moisture. Elevated CO2 had large consistent effects, increasing soil moisture by 26% and SCF by 45%. However, CO2‐induced changes in soil moisture were weak drivers of SCF: CO2 effects on SCF and soil moisture were uncorrelated, CO2 effect size did not change with soil moisture, within‐day CO2 effects via soil moisture were neutral or weakly negative, and the estimated effect of increased C availability was 14 times larger than that of increased soil moisture. Combined with previous BioCON results indicating elevated CO2 increases C availability to plants and microbes, our results suggest that increased SCF is driven by CO2‐induced increases in substrate availability. Our results provide further support for increased rates of belowground C cycling at elevated CO2 and evidence that, unlike the response of productivity to elevated CO2 in BioCON, the response of SCF is not strongly N limited. Thus, N limited grasslands are unlikely to act as a N sink under elevated CO2.
High Prevalence of Simian Immunodeficiency Virus Infection in a Community of Savanna Chimpanzees

ABSTRACT Simian immunodeficiency virus of chimpanzees (SIVcpz) has a significant negative impact on the health, reproduction, and life span of chimpanzees, yet the prevalence and distribution of this virus in wild-living populations are still only poorly understood. Here, we show that savanna chimpanzees, who live in ecologically marginal habitats at 10- to 50-fold lower population densities than forest chimpanzees, can be infected with SIVcpz at high prevalence rates. Fecal samples were collected from nonhabituated eastern chimpanzees (Pan troglodytes schweinfurthii) in the Issa Valley (n = 375) and Shangwa River (n = 6) areas of the Masito-Ugalla region in western Tanzania, genotyped to determine the number of sampled individuals, and tested for SIVcpz-specific antibodies and nucleic acids. None of 5 Shangwa River apes tested positive for SIVcpz; however, 21 of 67 Issa Valley chimpanzees were SIVcpz infected, indicating a prevalence rate of 31% (95% confidence interval, 21% to 44%). Two individuals became infected during the 14-month observation period, documenting continuing virus spread in this community. To characterize the newly identified SIVcpz strains, partial and full-length viral sequences were amplified from fecal RNA of 10 infected chimpanzees. Phylogenetic analyses showed that the Ugalla viruses formed a monophyletic lineage most closely related to viruses endemic in Gombe National Park, also located in Tanzania, indicating a connection between these now separated communities at some time in the past. These findings document that SIVcpz is more widespread in Tanzania than previously thought and that even very low-density chimpanzee populations can be infected with SIVcpz at high prevalence rates. Determining whether savanna chimpanzees, who face much more extreme environmental conditions than forest chimpanzees, are more susceptible to SIVcpz-associated morbidity and mortality will have important scientific and conservation implications.
High EMT Signature Score of Invasive Non-Small Cell Lung Cancer (NSCLC) Cells Correlates with NFκB Driven Colony-Stimulating Factor 2 (CSF2/GM-CSF) Secretion by Neighboring Stromal Fibroblasts

We established co-cultures of invasive or non-invasive NSCLC cell lines and various types of fibroblasts (FBs) to more precisely characterize the molecular mechanism of tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown to contribute to the onset of the invasive phenotype of Calu-1 with HGF being secreted by FBs. Differential expression analysis of the respective mono- and co-cultures revealed an upregulation of NFκB-related genes exclusively in co-cultures with Calu-1. Cytokine Array- and ELISA-based characterization of the “cytokine fingerprints” identified CSF2 (GM-CSF), CXCL1, CXCL6, VEGF, IL6, RANTES and IL8 as being specifically upregulated in various co-cultures. Whilst CXCL6 exhibited a strictly FB-type-specific induction profile regardless of the invasiveness of the tumor cell line, CSF2 was only induced in co-cultures of invasive cell lines regardless of the partnered FB type. These cultures revealed a clear link between the induction of CSF2 and the EMT signature of the cancer cell line. The canonical NFκB signaling in FBs, but not in tumor cells, was shown to be responsible for the induced and constitutive CSF2 expression. In addition to CSF2, cytokine IL6, IL8 and IL1B, and chemokine CXCL1 and CXCL6 transcripts were also shown to be increased in co-cultured FBs. In contrast, their induction was not strictly dependent on the invasiveness of the co-cultured tumor cell. In a multi-reporter assay, additional signaling pathways (AP-1, HIF1-α, KLF4, SP-1 and ELK-1) were found to be induced in FBs co-cultured with Calu-1. Most importantly, no difference was observed in the level of inducibility of these six signaling pathways with regard to the type of FBs used. Finally, upon tumor fibroblast interaction the massive induction of chemokines such as CXCL1 and CXCL6 in FBs might be responsible for increased recruitment of a monocytic cell line (THP-1) in a transwell assay.
Comparing Springtime Ice-Algal Chlorophyll a and Physical Properties of Multi-Year and First-Year Sea Ice from the Lincoln Sea

With near-complete replacement of Arctic multi-year ice (MYI) by first-year ice (FYI) predicted to occur within this century, it remains uncertain how the loss of MYI will impact the abundance and distribution of sea ice associated algae. In this study we compare the chlorophyll a (chl a) concentrations and physical properties of MYI and FYI from the Lincoln Sea during 3 spring seasons (2010-2012). Cores were analysed for texture, salinity, and chl a. We identified annual growth layers for 7 of 11 MYI cores and found no significant differences in chl a concentration between the bottom first-year-ice portions of MYI, upper old-ice portions of MYI, and FYI cores. Overall, the maximum chl a concentrations were observed at the bottom of young FYI. However, there were no significant differences in chl a concentrations between MYI and FYI. This suggests little or no change in algal biomass with a shift from MYI to FYI and that the spatial extent and regional variability of refrozen leads and younger FYI will likely be key factors governing future changes in Arctic sea ice algal biomass. Bottom-integrated chl a concentrations showed negative logistic relationships with snow depth and bulk (snow plus ice) integrated extinction coefficients; indicating a strong influence of snow cover in controlling bottom ice algal biomass. The maximum bottom MYI chl a concentration was observed in a hummock, representing the thickest ice with lowest snow depth of this study. Hence, in this and other studies MYI chl a biomass may be under-estimated due to an under-representation of thick MYI (e.g., hummocks), which typically have a relatively thin snowpack allowing for increased light transmission. Therefore, we suggest the on-going loss of MYI in the Arctic Ocean may have a larger impact on ice–associated production than generally assumed.