Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage

Objective: To characterize the cognitive and neuropsychiatric symptoms of patients with behavioral variant frontotemporal dementia (bvFTD) over the natural course of the disease. Methods: We examined the initial and subsequent neuropsychological test performance and neuropsychiatric symptoms in a large cohort of patients with bvFTD (n = 204) across progressive stages of disease as measured by the Clinical Dementia Rating (CDR). We also compared cognitive and neuropsychiatric impairments of patients with bvFTD to those of an age-matched cohort with Alzheimer disease (AD) dementia (n = 674). Results: At the earliest stage (CDR = 0.5), patients with bvFTD had profound neuropsychiatric disturbances, insensitivity to errors, slower response times, and poor naming, with intact attention span, memory, and facial affect naming. Tests continuing to show progressive, statistically significant stepwise declines after the CDR = 1 stage included free recall, visuoconstruction, set-shifting, error insensitivity, semantic fluency, design fluency, emotion naming, calculations, confrontation naming, syntax comprehension, and verbal agility. At CDR = 0.5, patients with bvFTD significantly outperformed patients with AD in episodic memory and were faster in set-shifting, while scoring quantitatively worse in lexical fluency, emotion naming, and error sensitivity. The overall rate of disease progression in bvFTD was more rapid than in AD. Conclusion: There are distinct patterns of cognitive deficits differentiating the earlier and later disease stages in bvFTD, with the pattern of cognitive decline revealing in greater detail the natural history of the disease. These cognitive symptoms are readily apparent clinical markers of dysfunction in the principal brain networks known to undergo molecular and anatomical changes in bvFTD, thus are important indicators of the evolving pathology in individual patients.
Tuning BRCA1 and BARD1 activity to investigate RING ubiquitin ligase mechanisms

The tumor‐suppressor protein BRCA1 works with BARD1 to catalyze the transfer of ubiquitin onto protein substrates. The N‐terminal regions of BRCA1 and BARD1 that contain their RING domains are responsible for dimerization and ubiquitin ligase activity. This activity is a common feature among hundreds of human RING domain‐containing proteins. RING domains bind and activate E2 ubiquitin‐conjugating enzymes to promote ubiquitin transfer to substrates. We show that the identity of residues at specific positions in the RING domain can tune activity levels up or down. We report substitutions that create a structurally intact BRCA1/BARD1 heterodimer that is inactive in vitro with all E2 enzymes. Other substitutions in BRCA1 or BARD1 RING domains result in hyperactivity, revealing that both proteins have evolved attenuated activity. Loss of attenuation results in decreased product specificity, providing a rationale for why nature has tuned BRCA1 activity. The ability to tune BRCA1 provides powerful tools for understanding its biological functions and provides a basis to assess mechanisms for rescuing the activity of cancer‐associated variations. Beyond the applicability to BRCA1, we show the identity of residues at tuning positions that can be used to predict and modulate the activity of an unrelated RING E3 ligase. These findings provide valuable insights into understanding the mechanism and function of RING E3 ligases like BRCA1.
A Novel Clustering Method Combining Heuristics and Information Theorem

Many data mining tasks require the unsupervised partitioning of a data set into clusters. However, in many case we do not really know any prior knowledge about the clusters, for example, the density or the shape. This paper addresses two major issues associated with conventional competitive learning, namely, sensitivity to initialization and difficulty in determining the number of clusters. Many methods exist for such clustering, but most of then have assumed hyper-ellipsoidal clusters. Many heuristically proposed competitive learning methods and its variants, are somewhat ad hoc without any theoretical support. Under above considerations, we propose an algorithm named as Entropy guided Splitting Competitive Learning (ESCL) in the information theorem framework. Simulations show that minimization of partition entropy can be used to guide the competitive learning process, so to estimate the number and structure of probable data generators.
Dynamic Approximate All-Pairs Shortest Paths: Breaking the O(mn) Barrier and Derandomization

We study dynamic (1 + ϵ)-approximation algorithms for the all-pairs shortest paths problem in unweighted undirected n-node m-edge graphs under edge deletions. The fastest algorithm for this problem is a randomized algorithm with a total update time of Ȏ(mn) and constant query time by Roditty and Zwick (FOCS 2004). The fastest deterministic algorithm is from a 1981 paper by Even and Shiloach (JACM 1981); it has a total update time of O(mn2) and constant query time. We improve these results as follows: (1) We present an algorithm with a total update time of Ȏ(n5/2) and constant query time that has an additive error of two in addition to the 1 + ϵ multiplicative error. This beats the previous Ȏ(mn) time when m = Ω(n3/2). Note that the additive error is unavoidable since, even in the static case, an O(n3-δ)-time (a so-called truly sub cubic) combinatorial algorithm with 1 + ϵ multiplicative error cannot have an additive error less than 2 - ϵ, unless we make a major breakthrough for Boolean matrix multiplication (Dor, Halperin and Zwick FOCS 1996) and many other long-standing problems (Vassilevska Williams and Williams FOCS 2010). The algorithm can also be turned into a (2 + ϵ)-approximation algorithm (without an additive error) with the same time guarantees, improving the recent (3 + ϵ)-approximation algorithm with Ȏ(n5/2+O(1√(log n))) running time of Bernstein and Roditty (SODA 2011) in terms of both approximation and time guarantees. (2) We present a deterministic algorithm with a total update time of Ȏ(mn) and a query time of O(log log n). The algorithm has a multiplicative error of 1 + ϵ and gives the first improved deterministic algorithm since 1981. It also answers an open question raised by Bernstein in his STOC 2013 paper. In order to achieve our results, we introduce two new techniques: (1) A lazy Even-Shiloach tree algorithm which maintains a bounded-distance shortest-paths tree on a certain type of emulator called locally persevering emulator. (2) A derandomization technique based on moving Even-Shiloach trees as a way to derandomize the standard random set argument. These techniques might be of independent interest.
Apolipoprotein L Expression Correlates with Neutrophil Cell Death in Critically Ill Patients

ABSTRACT Delayed neutrophil apoptosis has been demonstrated in sepsis and may contribute to organ damage. It has recently been proposed that apolipoprotein L (ApoL) may be involved in programmed cell death, but the expression and functions of ApoLs in leukocytes (especially neutrophils) during sepsis and other inflammatory conditions are currently unknown. In this prospective observational study in a 36-bed university hospital medicosurgical intensive care unit (ICU), we included 78 adult ICU patients with (n = 41) or without (n = 37) sepsis and 47 healthy volunteers. We analyzed ApoL mRNA expression using quantitative polymerase chain reaction in whole blood leukocytes and protein expression in CD15+ isolated neutrophils using Western blotting. Neutrophil apoptosis was assessed using the APO-BRDU method. Apolipoprotein L mRNA was downregulated in whole blood leukocytes and neutrophils in ICU patients compared with in healthy volunteers, and this effect translated at the protein level as indicated by Western blot analysis of neutrophils. There was a negative correlation between ApoL expression in neutrophils and C-reactive protein levels and a positive correlation between the number of apoptotic neutrophils and mRNA levels of ApoL1 and ApoL2. The degree of neutrophil apoptosis in critically ill patients is therefore correlated with modified expression profiles of ApoLs.
Stress-specific differences in assembly and composition of stress granules and related foci

ABSTRACT Cells have developed different mechanisms to respond to stress, including the formation of cytoplasmic foci known as stress granules (SGs). SGs are dynamic and formed as a result of stress-induced inhibition of translation. Despite enormous interest in SGs due to their contribution to the pathogenesis of several human diseases, many aspects of SG formation are poorly understood. SGs induced by different stresses are generally assumed to be uniform, although some studies suggest that different SG subtypes and SG-like cytoplasmic foci exist. Here, we investigated the molecular mechanisms of SG assembly and characterized their composition when induced by various stresses. Our data revealed stress-specific differences in composition, assembly and dynamics of SGs and SG-like cytoplasmic foci. Using a set of genetically modified haploid human cells, we determined the molecular circuitry of stress-specific translation inhibition upstream of SG formation and its relation to cell survival. Finally, our studies characterize cytoplasmic stress-induced foci related to, but distinct from, canonical SGs, and also introduce haploid cells as a valuable resource to study RNA granules and translation control mechanisms. Highlighted Article: Haploid cells were used to study stress-specific differences in the dynamics and composition of stress granule-like foci, the translation-related mechanisms of their assembly and their connection to cell survival.
PCA-based missing information imputation for real-time crash likelihood prediction under imbalanced data

ABSTRACT As an important research topic, real-time crash likelihood prediction has been studied for many years. However, few research focuses on the missing data imputation in real-time crash likelihood prediction, although missing values are commonly observed due to breakdown of sensors or external interference. Besides, classifying imbalanced data is also a critical issue in real-time crash likelihood prediction, since the number of crash-prone cases is much smaller than that of non-crash cases. In this paper, three principal component analysis (PCA) based approaches are established for imputing missing values, while two kinds of solutions are developed to tackle the issue of imbalanced data. The results show that the proposed methods can help the classifiers achieve better predictive performance under situations with missing data. The two solutions, i.e. cost-sensitive learning, and synthetic minority oversampling technique (SMOTE), can help improve the sensitivity by adjusting the classifiers to pay more attention to the minority class.
Production of truncated MBD4 protein by frameshift mutation in DNA mismatch repair-deficient cells enhances 5-fluorouracil sensitivity that is independent of hMLH1 status

ABSTRACT Methyl-CpG binding domain protein 4 (MBD4) is a DNA glycosylase that can remove 5-fluorodeoxyuracil from DNA as well as repair T:G or U:G mismatches. MBD4 is a target for frameshift mutation with DNA mismatch repair (MMR) deficiency, creating a truncated MBD4 protein (TruMBD4) that lacks its glycosylase domain. Here we show that TruMBD4 plays an important role for enhancing 5-fluorouracil (5FU) sensitivity in MMR-deficient colorectal cancer cells. We found biochemically that TruMBD4 binds to 5FU incorporated into DNA with higher affinity than MBD4. TruMBD4 reduced the 5FU affinity of the MMR recognition complexes that determined 5FU sensitivity by previous reports, suggesting other mechanisms might be operative to trigger cytotoxicity. To analyze overall 5FU sensitivity with TruMBD4, we established TruMBD4 overexpression in hMLH1-proficient or -deficient colorectal cancer cells followed by treatment with 5FU. 5FU-treated TruMBD4 cells demonstrated diminished growth characteristics compared to controls, independently of hMLH1 status. Flow cytometry revealed more 5FU-treated TruMBD4 cells in S phase than controls. We conclude that patients with MMR-deficient cancers, which show characteristic resistance to 5FU therapy, may be increased for 5FU sensitivity via secondary frameshift mutation of the base excision repair gene MBD4.
Effects of high environmental temperatures on cecal coccidiosis.

Maintenance of broiler or White Leghorn cockerels in a high temperature (32 C.), high humidity (90%) environment for six days following artificial infection with Eimeria tenella significantly reduced coccidiosis severity as compared to birds similarly infected and maintained in an ambient environment averaging 24.5 C. , and 62% humidity. Disease severity was determined by lesion scores, fecal scores, and hematocrit readings. The heavier broiler stock maintained body temperatures of 0.7-1.6 C. higher than those birds kept at ambient temperatures for the entire six days. Body temperatures of heat-treated Leghorn cockerels were 0.9 C. higher during the first 48 hours post-inoculation (P.I.), but similar to ambient temperature controls for the last four days. Elevated body temperatures during the first two days following inoculation impaired the survival and development of some parasites while shorter periods (24 hours) of heat treatment did not affect parasite survival.
The Utility of Inflammatory and Endothelial Markers to Identify Infection in Emergency Department Patients

ABSTRACT Background: Identifying infection in emergency department (ED) patients can be challenging. This study assesses the value that inflammatory and endothelial biomarkers add to clinical data when predicting infectious etiologies of abnormal vital signs (AVSs) in ED patients. Methods: This study was a prospective, observational cohort study of ED patients with AVSs at an urban, academic tertiary-care hospital, identified from March 1, 2013, to April 15, 2013. Collected blood samples were assayed for soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule 1, vascular cell adhesion molecule 1, plasminogen activator inhibitor 1, interleukin 6, sFlt-1, and procalcitonin. History and physical examination were abstracted from the ED documentation. The primary outcome, infectious etiology, was adjudicated by review of the hospital documentation. Three multivariate logistic regression models predicting infection were created using clinical data, biomarkers, and combined clinical data and biomarker assessments. Integrated discrimination improvement tested the discriminate value of the biomarker and combined models compared with the clinical data model. Results: We enrolled 115 patients: 49 determined to have an infection (43%) and 66 without (57%). All biomarkers were significantly associated with infection in univariate analysis. The best clinical model (area under the curve [AUC] = 0.76) included initial temperature (odds ratio [OR], 1.6; confidence interval [CI], 1.1–2.2) and history of fever (OR, 5.0; CI, 1.4–14). The best biomarker model (AUC, 0.82) predicting infection included sE-selectin (OR, 11.0; 95% CI, 1.6–74) and interleukin 6 (OR, 5.1; CI, 2.3–11.6). The combined clinical and biomarker model had an AUC of 0.88, with integrated discrimination improvement = 0.21, compared with the clinical model alone. Conclusion: Inflammatory and endothelial markers can improve the clinical identification of infection in ED patients with AVSs.
The effect of melatonin administration on circulating plasma luteinizing hormone concentration in castrated White Leghorn roosters.

Melatonin (MLT) has a significant role in mammalian reproduction, with little or no effect in birds. In the present study we studied the role of MLT in regulation of luteinizing hormone (LH) secretion in castrated White Leghorn (WL) roosters. In Experiment 1, castrated WL roosters (n = 30) were divided into three groups, and each group (n = 10) was subdivided into two subgroups (n = 5). Birds in one subgroup received an injection of MLT at 5 mg (MLT-5), 20 mg (MLT-20), or 80 mg (MLT-80)/kg BW. Birds in the second subgroup were vehicle-injected and served as controls. Each dose of MLT was administered on a separate day at 1100 h. Blood was sampled 30 min before and 10, 30, 60, and 120 min after MLT or vehicle administration. Ten minutes after MLT administration, a significant reduction in plasma LH was observed in the MLT-20 and -80 groups, i.e., 70.3 +/- 8.3% and 62.2 +/- 4.1% of control values, respectively. In the MLT-80 group, plasma LH further declined to 42.1 +/- 9.7% of control values 60 min after injection. In Experiment 2, 18 castrated WL roosters were divided into three groups of six birds each. Two groups were injected with 80 mg MLT/kg BW at the beginning of the experiment; the second group received an additional dose of 80 mg MLT/ kg BW 140 min after the first injection. The third group was injected twice (as in second group) with vehicle and served as control. Blood was sampled 30 min before and 30, 60, 120, 170, 200, and 240 min after injection. Repeated MLT injection maintained low levels of plasma LH level until the end of the experiment. In Experiment 3, 10 castrated WL roosters were divided into two groups (n = 5). The first group was injected daily, for 10 d, with 80 mg MLT/kg BW, the second group was vehicle-treated and served as a control. At Day 3, there was a significant reduction in plasma LH level in the MLT-treated group, which continued for 7 d. This study demonstrates that, in birds, MLT suppresses LH secretion in a dose- and a time-related manner.
Forecasting Transplanted Rice Yield at the Farm Scale Using Moderate-Resolution Satellite Imagery and the AquaCrop Model: A Case Study of a Rice Seed Production Community in Thailand

Thailand has recently introduced agricultural policies to promote large-scale rice farming through supporting and integrating small-scale farmers. However, achieving these policies requires agricultural tools that can assist farmers in rice farming planning and management. Crop models, along with remote sensing technologies, can be useful for farmers and field managers in this regard. In this study, we used the AquaCrop model along with moderate-resolution satellite images (30 m) to simulate the rice yield for small-scale farmers. We conducted field surveys on rice characteristics in order to calibrate the crop model parameters. Data on rice crop, leaf area index (LAI), canopy cover (CC) and agricultural practices were used to calibrate the model. In addition, the optimal rice constant value for conversion of CC was investigated. HJ-1A/B satellite images were used to calculate the CC value, which was then used to simulate yield. The validated results were applied to 126 sample pixels within transplanted rice fields, which were extracted from satellite imagery of activated rice plots using equivalent transplanting methods to the study area. The rice yield simulated using the AquaCrop model and assimilated with the results of HJ-1A/B, produced a satisfactory outcome when implemented into the validated rice plots, with RMSE = 0.18 t ha−1 and R2 = 0.88. These results suggest that integration of moderate-resolution satellite imagery and this crop model are useful tools for assisting rice farmers and field managers in their planning and management.
Influence of Titanium Dioxide Nanoparticles on the Sulfate Attack upon Ordinary Portland Cement and Slag-Blended Mortars

In this study, the effects of titanium dioxide (TiO2) nanoparticles on the sulfate attack resistance of ordinary Portland cement (OPC) and slag-blended mortars were investigated. OPC and slag-blended mortars (OPC:Slag = 50:50) were made with water to binder ratio of 0.4 and a binder to sand ratio of 1:3. TiO2 was added as an admixture as 0%, 3%, 6%, 9% and 12% of the binder weight. Mortar specimens were exposed to an accelerated sulfate attack environment. Expansion, changes in mass and surface microhardness were measured. Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-ray Diffraction (XRD), Thermogravimetry Analysis (TGA) and Differential Scanning Calorimetry (DSC) tests were conducted. The formation of ettringite and gypsum crystals after the sulfate attack were detected. Both these products had caused crystallization pressure in the microstructure of mortars and deteriorated the mortars. Our results show that the addition of nano-TiO2 accelerated expansion, variation in mass, loss of surface microhardness and widened cracks in OPC and slag-blended mortars. Nano-TiO2 containing slag-blended mortars were more resistant to sulfate attack than nano-TiO2 containing OPC mortars. Because nano-TiO2 reduced the size of coarse pores, so it increased crystallization pressure due to the formation of ettringite and gypsum thus led to more damage under sulfate attack.
MetaDiff-a Model Comparison Framework

The increasing importance of models in software development raises a number of new concerns and challenges. This paper has concentrated on the issue of model comparison in the context of model driven development. The goal of the paper is to describe the requirements for, design, and implementation of a model comparison framework called MetaDiff. The framework is based on available implementations of Meta Object Facility (MOF) standard. The authors intend this framework to be useful to the following experimental research in the area of model management and when implementing specific model comparison and merge tools and algorithms.
Characterization of Inpatient Cystic Fibrosis Pulmonary Exacerbations

BACKGROUND AND OBJECTIVES: Pulmonary exacerbations lead to significant morbidity and mortality in patients with cystic fibrosis (CF). National consensus guidelines exist, but few studies report current practice in the treatment and monitoring of pulmonary exacerbations. The goal of this study was to characterize consistency and variability in the inpatient management of CF-related pulmonary exacerbations. We focused on the use of guideline-recommended maintenance therapies, antibiotic selection and treatment regimens, use of systemic corticosteroids, and frequency of lung function testing. We hypothesized that significant variability in these treatment practices exists nationally. METHODS: This trial was a retrospective cross-sectional study. It included patients with CF aged ≤18 years hospitalized for pulmonary exacerbations between July 1, 2010, and June 30, 2015, at hospitals within the US Pediatric Health Information System database that are also Cystic Fibrosis Foundation–accredited care centers. One exacerbation per patient was randomly selected over the 5-year study period. RESULTS: From 38 hospitals, 4827 individual pulmonary exacerbations were examined. Median length of stay was 10.0 days (interquartile range, 6–14.0 days). Significant variation was seen among centers in the use of hypertonic saline (11%–100%), azithromycin (5%–83%), and systemic corticosteroids (3%–61%) and in the frequency of lung function testing. Four different admission antibiotic regimens were used >10% of the time, and the most commonly used admission antibiotic regimen comprised 2 intravenous antibiotics with no additional oral or inhaled antibiotics (29%). CONCLUSIONS: Significant variation exists in the treatment and monitoring of pulmonary exacerbations across Pediatric Health Information System–participating, Cystic Fibrosis Foundation–accredited care centers. Results from this study can inform future research working toward standardized inpatient pulmonary exacerbation management to improve CF care for children and adolescents.