Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient-Derived Non-Muscular Invasive Bladder Cancer Xenografts of Main Molecular Subtypes of the Tumor for Anti-Pd-l1 Treatment Assessment

Background: Establishment of heterotopic patient-derived xenografts of primary and relapsed non-muscular invasive bladder cancer (NMIBC) to explore the biological property of PD-L1 signaling that may impact bladder tumor growth in humanized animals. Methods: Tumor cells of luminal, basal, and p53 subtypes of primary and relapsed NMIBC were engrafted to irradiated (3.5 Gy) NOG/SCID female mice along with intraperitoneal transplantation of human lymphocytes (5 × 107 cells/mouse); a role of PD-L1 signaling pathway inhibition for bladder cancer growth was assessed in humanized animals that carried PD-L1-expressing main molecular subtypes of bladder carcinoma patient-derived xenografts (PDX) and provided with selective anti-PD-L1 treatment. We used two-tailed Student’s t test to explore differences between main and control subgroups. Significance of intergroup comparison was measured with one-way ANOVA followed by the Tukey’s or Newman–Keul’s criterion. Survival curves were analyzed with the Gehan’s criterion with the Yate’s correction. The Spearman’s correlation was used to assess the link between CD8+ expression and sPD-L1 serum level. Differences were considered statistically significant at p < 0.05. Results: Heterotopic primary and relapsed luminal, basal, and p53 subtypes of NMIBC PDXs were established. More than 25% of counted tumor cells of all PDX specimens expressed PD-L1, so the tumors were ranged as PD-L1 positive. Anti-PD-L1 intervention increased survival of the animals that carried both primary and relapsed luminal noninvasive, muscular invasive, and relapsed luminal bladder cancer xenografts. There was significant retardation of tumor volume duplication time in aforementioned subgroups correlated with PD-L1 expression. Bad response of p53 mutant subtypes of NMIBC on specific anti-PD-L1 treatment may be associated with low CD8+ cells representation into the tumors tissue. Conclusions: Established PD-L1-positive NMIBC PDXs differently replied on anti-PD-L1 treatment due to both NMIBC molecular subtype and tumor T-suppressors population. The results may have major implications for further clinical investigations.
Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation

T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. ABSTRACT T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. Reducing the splicing efficiency at 4 to 6 h poststimulation significantly impaired murine T cell activation, which was dependent on the expression dynamics of the Egr1–Nab2–interleukin-2 (IL-2) pathway. This time window overlaps the time of peak IL-2 de novo transcription, which, we suggest, represents a permissive time window in which decreased splicing (or transcription) efficiency reduces mature IL-2 production, thereby hampering murine T cell activation. Notably, the distinct expression kinetics of the Egr1–Nab2–IL-2 pathway between mouse and human render human T cells refractory to this vulnerability. We propose that the rational temporal modulation of splicing or transcription during peak de novo expression of key effectors can be used to fine-tune stimulation-dependent biological outcomes. Our data also show that critical consideration is required when extrapolating mouse data to the human system in basic and translational research.
Clustering Big Data streams: recent challenges and contributions

Abstract Traditional clustering algorithms merely considered static data. Today's various applications and research issues in big data mining have however to deal with continuous, possibly infinite streams of data, arriving at high velocity. Web traffic data, surveillance data, sensor measurements and stock trading are only some examples of these daily-increasing applications. Since the growth of data volumes is accompanied by a similar raise in their dimensionalities, clusters cannot be expected to completely appear when considering all attributes together. Subspace clustering is a general approach that solved that issue by automatically finding the hidden clusters within different subsets of the attributes rather than considering all attributes together. In this article, novel methods for an efficient subspace clustering of high-dimensional big data streams are presented. Approaches that efficiently combine the anytime clustering concept with the stream subspace clustering paradigm are discussed. Additionally, efficient and adaptive density-based clustering algorithms are presented for high-dimensional data streams. Novel open-source assessment framework and evaluation measures are additionally presented for subspace stream clustering.
Acute peripheral metabolic effects of intraarterial ghrelin infusion in healthy young men.

CONTEXT Ghrelin is the endogenous agonist for the growth hormone secretagogue receptor (GHS-R). Intravenous administration of ghrelin induces insulin resistance and hyperglycemia and increases the levels of free fatty acids (FFA). OBJECTIVE To investigate whether these effects are mediated directly by ghrelin in skeletal muscle tissue. DESIGN This study was single blinded, randomized, and placebo controlled. Eight healthy men (25.5 ± 3.1 years) received 240 min of intraarterial ghrelin infusion (4.2 ng × kg(-1) × min(-1)) into one femoral artery and intraarterial placebo infusion into the contralateral artery. Simultaneous blood samples were drawn from both femoral veins and muscle biopsies were obtained from both legs during both a basal period and during a hyperinsulinemic and euglycemic clamp period. RESULTS Ghrelin significantly elevated venous FFA levels and venous dilution of palmitate, suggestive of increased lipolysis. Glucose metabolism was unchanged, and there were no direct effects on pertinent enzymes in the insulin signaling cascade. The metabolic clearance rate of acyl ghrelin was 12.5 ± 3.3 ml × kg(-1) × min(-1). Acyl and desacyl ghrelin levels both increased. CONCLUSIONS The results of this study suggest that ghrelin may stimulate lipolysis directly in skeletal muscle.
Pigs Ferment Enzymatically Digestible Starch when it Is Substituted for Resistant Starch

ABSTRACT Background Feeding behavior is controlled by satiety mechanisms, which are affected by the extent of starch digestion, and thus resistant starch (RS) intake. Alterations in feeding behavior to changes in RS intake may depend on the adaptation of processes involved when shifting from starch digestion to fermentation or vice versa. Objectives The aim of this study was to investigate how growing pigs adapt their feeding behavior in response to increasing and decreasing dietary RS concentrations. Methods Thirty-six groups of 6 pigs (25.4 ± 2.8 kg; Hypor Libra × Hypor Maxter; male:female, 1:1) were fed diets containing 50% high-amylose maize starch (high RS; HRS) or waxy maize starch (low RS; LRS). Over 28 d, diets were exchanged following a 5-step titration (25% per step) that was executed in the upward (LH) or downward direction (HL). Twelve groups received a control diet to correct for changes over time. Individual feeding behavior and total tract starch digestion and fermentation were evaluated. The response in each parameter to increasing dietary HRS inclusion was estimated through the use of linear regression procedures, and tested for titration direction and sex effects. Results Complete substitution of LRS with HRS increased the proportion of starch fermented, which was greater in LH pigs than in HL pigs (17.6% compared with 8.18%; P < 0.001), and decreased the feed intake (106 g/d; P = 0.021) and meal size (12.6 g; P < 0.001) of LH pigs, but not of HL pigs. In LH pigs, the size of the starch fermentation response positively correlated with the size of the feed intake response (r = 0.90, P < 0.001). Conclusions The attenuated response in starch fermentation in HL pigs indicates that pigs adapt more slowly to dietary supply of digestible starch than to RS, consequently resulting in fermentation of enzymatically digestible starch. Feed intake and feeding behavior only changed in pigs poorly adapting to RS, indicating that adequacy of adaptation, rather than RS itself, drives feed intake. These findings stress the importance of diet history for nutrient digestion and feeding behavior.
Using Fidelity Measurement to Assess Quality of Early Psychosis Intervention Services in Ontario.

OBJECTIVES The First Episode Psychosis Services Fidelity Scale (FEPS-FS) is a validated measure of program delivery in relation to international standards. This study assessed fidelity in Ontario programs and the utility of the FEPS-FS for program improvement. METHODS Assessments were conducted in a volunteer sample of nine early psychosis intervention (EPI) programs. Thirty components of care were each rated on a 5-point scale; a rating of 4 indicates satisfactory performance. Trained assessor teams conducted site visits, and ratings were made by consensus. RESULTS Program mean fidelity ratings ranged from 3.1 to 4.4 and exceeded 4 in five programs. Across the programs, item mean fidelity ratings ranged from 2.1 to 5 and exceeded 4 for 14 of 30 items. CONCLUSIONS The FEPS-FS captured variation in program implementation and provided a baseline for measuring change. Additions to the scale are planned to address components of the Ontario EPI standards not covered by the FEPS-FS.
Analysis of ontology development methodology based on OTK and CMMI level 4

OTK methodology which is one of the most frequently used modeling method for ontology development nowadays but for effectiveness of development, it requires quality management of development itself. To provide quality management, CMMI reference model for process improvement suggests effective way of quality management by quantitative way. Especially level 4 process areas of CMMI provide practical approach to manage quality of projects which face quality problems of their projects. The main topic of the paper is to describe relations between 5 steps of OTK development process and process areas belong to CMMI level 4 and provide collaboration details how to adopt CMMI level 4 process areas to OTK methodology for quality management of ontology development.
Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis

The PI3K/Akt pathway plays a crucial role in the survival, proliferation, and migration of macrophages, which may impact the development of atherosclerosis. Changes in Akt isoforms or modulation of the Akt activity levels in macrophages significantly affect their polarization phenotype and consequently atherosclerosis in mice. Moreover, the activity levels of Akt signaling determine the viability of monocytes/macrophages and their resistance to pro-apoptotic stimuli in atherosclerotic lesions. Therefore, elimination of pro-apoptotic factors as well as factors that antagonize or suppress Akt signaling in macrophages increases cell viability, protecting them from apoptosis, and this markedly accelerates atherosclerosis in mice. In contrast, inhibition of Akt signaling by the ablation of Rictor in myeloid cells, which disrupts mTORC2 assembly, significantly decreases the viability and proliferation of blood monocytes and macrophages with the suppression of atherosclerosis. In addition, monocytes and macrophages exhibit a threshold effect for Akt protein levels in their ability to survive. Ablation of two Akt isoforms, preserving only a single Akt isoform in myeloid cells, markedly compromises monocyte and macrophage viability, inducing monocytopenia and diminishing early atherosclerosis. These recent advances in our understanding of Akt signaling in macrophages in atherosclerosis may have significant relevance in the burgeoning field of cardio-oncology, where PI3K/Akt inhibitors being tested in cancer patients can have significant cardiovascular and metabolic ramifications.
Soil Quality: A Concept, Definition, and Framework for Evaluation (A Guest Editorial)

This essay summarizes deliberation by the Soil Science Society of America (SSSA) Ad Hoc Committee on Soil Quality (S-581) and was written to spur discussion among SSSA members. Varying perceptions of soil quality have emerged since the concept was suggested in the early 1990s, and dialogue among members is important ecause, unlike air and water quality, legislative standards for soil quality have not been and perhaps should not be defined. In simplest terms, soil quality is the capacity (of soil) to function. This definition, based on function, reflects the living and dynamic nature of soil. Soil quality can be conceptualized as a three-legged stool, the function and balance of which requires an integration of three major components - sustained biological productivity, environmental quality, and plant and animal health. The concept attempts to balance multiple soil uses (e.g., for agricultural production, remediation of wastes, urban development, forest, range, or recreation) with goals for environmental quality. Assessing soil quality will require collaboration among all disciplines of science to examine and interpret their results in the context of land management strategies, interactions, and trade-offs. Society is demanding solutions from science. Simply measuring and reporting the response of an individual soil parmeter to a given perturbation or management practice is no longer sufficient. The soil resource must be recognized as a dynamic living system that emerges through a unique balance and interaction of its biological, chemical, and physical components. We encourage SSSA members to consider the concept of soil quality (perhaps as a marketing tool) and to debate how it might enable us to more effectively meet the diverse natural resource needs and conerns of our rural, urban, and suburban clientele of today and tomorrow.
Monitoring nitric oxide: here to stay for bench and bedside

This editorial accompanies the publication, on April 15, 2005, of a joint American Thoracic Society (ATS) and European Respiratory Society (ERS) statement, which focuses on the measurement of exhaled and nasal nitric oxide (NO) 1. This statement is an excellent example of collaboration between the two societies to produce a document of great relevance to researchers and clinicians alike. For the societies, the publication of recommendations in specific areas of practice is perhaps the best example of how these organisations lead to practical outcomes. NO is an essential biological mediator of both physiological and pathological processes 2. Its pivotal role in central and peripheral neurotransmission and smooth muscle relaxation is well established, while NO is also a mediator of inflammation and a player in oxidative stress pathways. Its net effect is probably a balance between its physiological and pathological roles, while, for our purposes, it serves as a marker for these processes. Groups of researchers from many countries produced separate guidelines for the measurement of exhaled and nasal NO, which appeared in the European Respiratory Journal in 1997 3, and the American Journal of Respiratory and Critical Care Medicine in 1999 4. The current document consolidates and builds upon these efforts. A separate ATS/ERS statement …
Use of the BESTest and the Mini-BESTest for Fall Risk Prediction in Community-Dwelling Older Adults Between 60 and 102 Years of Age

Background and Purpose: Reference values for the Balance Evaluation Systems Test (BESTest) and the Mini-Balance Evaluation Systems Test (Mini-BESTest) need to be established to predict falls in older adults during every stage of aging. The purpose of this study was to determine the cutoff scores for the BESTest and the Mini-BESTest for community-dwelling older adults in order to predict fall risk. Methods: A total of 264 older adults, of both sexes, between the ages of 60 and 102 years, were divided into 4 groups according to age range. After evaluation, participants received telephone follow-up for 6 months to record the number of fall episodes. To define the reference values of the tests in relation to fall risk prediction, a receiver operating characteristic curve was drawn to identify the area under the curve and the sensitivity and specificity of the tests. Statistical analyses were done using SPSS (Version 16.0—SPSS Inc) with a significance level of 5% (P ≤ .05). Results: The cutoff scores to identify older adults with fall risk according to the BESTest and the Mini-BESTest in the different age groups were 99 and 25 points, respectively, for people 60 to 69 years of age, 92 and 23 points for the age group of 70 to 79 years, 85 and 22 points for people 80 to 89 years of age, and 74 and 17 points for people 90 years of age or older. Conclusion: The BESTest and the Mini-BESTest are good tools for predicting fall risk in the 6 months following an initial evaluation in community-dwelling Brazilian older adults. The study also determined that cutoff values vary for different age groups.
The Relationships between Process Parameters and Polymeric Nanofibers Fabricated Using a Modified Coaxial Electrospinning

The concrete relationship between the process parameters and nanoproduct properties is an important challenge for applying nanotechnology to produce functional nanomaterials. In this study, the relationships between series of process parameters and the medicated nanofibers’ diameter were investigated. With an electrospinnable solution of hydroxypropyl methylcellulose (HPMC) and ketoprofen as the core fluid, four kinds of nanofibers were prepared with ethanol as a sheath fluid and under the variable applied voltages. Based on these nanofibers, a series of relationships between the process parameters and the nanofibers’ diameters (D) were disclosed, such as with the height of the Taylor cone (H, D = 125 + 363H), with the angle of the Taylor cone (α, D = 1576 − 19α), with the length of the straight fluid jet (L, D = 285 + 209L), and with the spreading angle of the instable region (θ, D = 2342 − 43θ). In vitro dissolution tests verified that the smaller the diameters, the faster ketoprofen (KET) was released from the HPMC nanofibers. These concrete process-property relationships should provide a way to achieve new knowledge about the electrostatic energy-fluid interactions, and to meanwhile improve researchers’ capability to optimize the coaxial process conditions to achieve the desired nanoproducts.
Towards Patient-centered Diagnosis of Pediatric Obstructive Sleep Apnea—A Review of Biomedical Engineering Strategies

ABSTRACT Introduction: Obstructive sleep apnea in children has a prevalence of 5%. Polysomnography is considered to be the gold standard for diagnosis and stratification of the condition. However, it is resource-intensive, expensive and uncomfortable for children and their families. Areas covered: We focus this review on technical developments in sensor technology, materials and predictive analytics for translation to (i) patient comfort and compliance in the laboratory and (ii) validation of home sleep apnea testing in children. Key developments in adult polysomnography that could be considered for adoption in children are also highlighted. This review is organized by Sleep, Cardiovascular, Oximetry, Position, Effort, and Respiratory (SCOPER) parameters of interest. Expert opinion: In the past decade, improvements in respiratory sensors and signal processing strategies have transitioned sleep apnea testing in adults from the laboratory to home, thus reducing costs and improving access. Unfortunately, such benefits have not been observed for children principally due to the lack of high-quality studies. The increasing cost of diagnosis of sleep apnea in children needs urgent attention. Recent technical developments as described in this review have the potential to support further evaluation of home sleep apnea testing while improving the current circumstances of in-lab polysomnography for children.
Encoding and retrieval biases for health-related scenes in patients with severe health anxiety*

ABSTRACT Severe health anxiety is a disorder characterised by excessive worries about harbouring or having a serious illness. The present study examines cognitive biases in evaluation and memory for health-related scenes in severe health anxiety in order to provide insights into the effect of these biases and the formation of illness intrusions in severe health anxiety. Twenty patients with severe health anxiety and 20 healthy participants completed a computerised task consisting of encoding, involuntary retrieval, voluntary retrieval and recognition of health-related, negative and neutral scenes. The results demonstrated that patients with severe health anxiety reported more negative emotional valence and greater physiological arousal to health-related scenes, both during encoding (ps < .031, > .09) and retrieval (ps < .044, ds > 0.18). Furthermore, in contrast to the comparison group, patients with severe health anxiety did not show shorter retrieval time for health-related scenes during involuntary compared with voluntary retrieval (p = .789, d = 0.08), possibly due to greater demands on emotion regulation during involuntary retrieval. The results suggest an important role for negative emotional valence and physiological arousal to health-related stimuli in severe health anxiety, and highlight how cognitive biases in evaluation and memory might be at play in this disorder.
The Consumption of Breakfast, Fish and/or Caffeine does not Predict Study Progress in Adult Distance Education.

Consumption of breakfast, fish, or caffeine are each separately often investigated in relation to learning performance in traditional education, but not in distance education (DE). The objective of this study was to investigate whether the relations between the consumption of breakfast, fish, and/or caffeine on the one hand and learning performance on the other are also found in DE students. This population is different from traditional students and characterized by a different profile in terms of age, personal and work responsibilities as well as other demographics. In an observational longitudinal study, the consumption of breakfast, fish, and caffeine of 1157 DE students (18-76 years old, mean 35.8 ± 11.1 years) was used to predict learning performance using multiple regression analysis. In an online digital survey, university students provided information about their consumption of these nutritional measures and on important covariates. Learning performance, measured as study progress (i.e., the number of successfully completed modules), was evaluated objectively after 14 months. Results showed that adding the consumption of breakfast, fish, and caffeine to the covariate model did not fit the data better, χ2 (3, N = 1155) = 3.287, p = 0.35. This means that neither the consumption of breakfast nor fish nor caffeine predicted study progress in adults participating in DE. This study is important as it is the first to report on these relations in this specific age group and educational setting, which is increasingly important due to the increased preference for this type of education.