Miracle-dz/UniFAR-FTUs huggingface dataset:
The voltage‐gated potassium channel Kv1.3 is required for microglial pro‐inflammatory activation in vivo

Microglia show a rich repertoire of activation patterns regulated by a complex ensemble of surface ion channels, receptors, and transporters. We and others have investigated whether microglia vary their K+ channel expression as a means to achieve functional diversity. However, most of the prior studies were conducted using in vitro models such as BV2 cells, primary microglia, or brain slices in culture, which may not accurately reflect microglia physiology in adult individuals. Here we employed an in vivo mouse model of selective innate immune activation by intracerebroventricular injection of lipopolysaccharides (ICV‐LPS) to determine the role of the voltage‐gated Kv1.3 channel in LPS‐induced M1‐like microglial activation. Using microglia acutely isolated from adult brains, we detected Kv1.3 and Kir2.1 currents, and found that ICV‐LPS increased the current density and RNA expression of Kv1.3 but did not affect those of Kir2.1. Genetic knockout of Kv1.3 abolished LPS‐induced microglial activation exemplified by Iba‐1 immunoreactivity and expression of pro‐inflammatory mediators such as IL‐1β, TNF‐α, IL‐6, and iNOS. Moreover, Kv1.3 knockout mitigated the LPS‐induced impairment of hippocampal long‐term potentiation (hLTP), suggesting that Kv1.3 activity regulates pro‐inflammatory microglial neurotoxicity. Pharmacological intervention using PAP‐1, a small molecule that selectively blocks homotetrameric Kv1.3 channels, achieved anti‐inflammatory and hLTP‐recovery effects similar to Kv1.3 knockout. We conclude that Kv1.3 is required for microglial M1‐like pro‐inflammatory activation in vivo. A significant implication of our in vivo data is that Kv1.3 blockers could be therapeutic candidates for neurological diseases where microglia‐mediated neurotoxicity is implicated in the pathogenesis.
A Parametric Level Set-Based Approach to Difference Imaging in Electrical Impedance Tomography

This paper presents a novel difference imaging approach based on the recently developed parametric level set (PLS) method for estimating the change in a target conductivity from electrical impedance tomography measurements. As in conventional difference imaging, the reconstruction of conductivity change is based on data sets measured from the surface of a body before and after the change. The key feature of the proposed approach is that the conductivity change to be reconstructed is assumed to be piecewise constant, while the geometry of the anomaly is represented by a shape-based PLS function employing Gaussian radial basis functions (GRBFs). The representation of the PLS function by using GRBF provides flexibility in describing a large class of shapes with fewer unknowns. This feature is advantageous, as it may significantly reduce the overall number of unknowns, improve the condition number of the inverse problem, and enhance the computational efficiency of the technique. To evaluate the proposed PLS-based difference imaging approach, results obtained via simulation, phantom study, and in vivo pig data are studied. We find that the proposed approach tolerates more modeling errors and leads to a significant improvement in image quality compared with the conventional linear approach.
Role Based Platform Independent Web Application Modeling

Web application modeling and implementation method are related with middleware platform tightly, and its models usually can’t be reused on different platform. In order to reuse web application models, it is necessary to raise the level of abstraction of models, constructing middleware platform independent models. Roles are meant to capture observable behavioral aspects of objects. Role models describe the set of valid object collaboration tasks. This paper proposes a method for constructing platform independent models for Web applications. It consists of a stepwise process, a template role model and a mapping from role model to class model. The method can improve the reusability of models at different level of abstraction. The paper shows how the method works by a simple example
Impact of the Proposed IEEE 1584 Empirical Model in Comparison to Existing Arc-Flash Hazard Assessment Calculation Methods

The purpose of this paper is to present an analysis of the July 2017 - IEEE Draft Guide for Performing Arc-Flash Hazard Calculations (P1584/D2) mathematical model compared to the existing and active standard IEEE Guide for Performing Arc-Flash Hazard Calculations (IEEE 1584) methods used throughout the rural electric utility industry. The impacts addressed in this paper include calculations of incident energy, arcing current, and boundary ranges using the new IEEE 1584 model at typical distribution utility working conditions. A sensitivity analysis developed to present a comparison between industry standard arc-flash hazard assessment methodologies is also included. The impact analyses are designed to test the laboratory developed empirical models for impacts to rural electric utility personnel during day-to-day electric system operations and maintenance. The analyses will also be summarized for use by distribution electric utility engineers with an appreciation of the industry scope of changes acquired through analytical experience and experimentation, and regulatory changes.
Factors promoting resilience among breast cancer patients: a qualitative study

Objective: The purpose of this study was to investigate resilience factors that helped Chinese breast cancer patients adapt to the trauma in the traditional Chinese cultural context. Method: Checklist-guided in-depth interviews were conducted on 15 Chinese breast cancer patients recruited from two affiliated teaching hospitals. All had adapted to the illness successfully. All interviews were guided by checklist-guided interview guidelines based on the social ecosystem theory. They were recorded digitally and transcribed verbatim. Data analysis was performed using published content analysis approach. Findings: The main themes found to be relevant included hope for rehabilitation, hardiness, confidence in situation, optimistic attitude to the disease, gratitude to supporters, mastery of life. Each level of these individual resource interacted with each other, which was consistent with the micro system of social ecosystem theory. Conclusion: This study showed that individual resource played a significant role in helping the Chinese breast cancer patients deal with the illness. There is a clear need to develop a comprehensive evaluation system to help clinical nurses assess patients’ individual resource and promote better adaption to breast cancer.
European Society of Endocrinology Clinical Practice Guidelines on the Management of Adrenocortical Carcinoma in Adults, in collaboration with the European Network for the Study of Adrenal Tumors.

Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. SELECTED RECOMMENDATIONS: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess, and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en-bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemo-embolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin, and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.
A Semi‐Mechanistic Population Pharmacokinetic Model of Nusinersen: An Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy

A pharmacokinetic (PK) model was developed for nusinersen, an antisense oligonucleotide (ASO) that is the first approved treatment for spinal muscular atrophy (SMA). The model was built with data from 92 nonhuman primates (NHPs) following intrathecal doses (0.3–7 mg) and characterized the PK in cerebrospinal fluid (CSF), plasma, total spinal cord, brain, and pons. The estimated volumes were 13.6, 937, 4.5, 53.8, and 2.11 mL, respectively. Global sensitivity analysis demonstrated that the CSF‐to‐plasma drug distribution rate (0.09 hour−1) is a major determinant of the maximum nusinersen concentration in central nervous system (CNS) tissues. Physiological age‐based and body weight‐based allometric scaling was implemented with exponent values of −0.08 and 1 for the rate constants and the volume of distribution, respectively. Simulations of the scaled model were in agreement with clinical observations from 52 pediatric phase I PK profiles. The developed model can be used to guide the design of clinical trials with ASOs.
Anti-Entropy Bandits for Geo-Replicated Consistency

Eventually consistent systems can be made more consistent by reducing the time until a write is fully replicated, thereby improving global update visibility. While gossip-based anti-entropy methods scale well, random selection of anti-entropy partners is less than efficient. Moreover, while eventual consistency may be consistent enough in a single data center, geographic replication increases visibility latency and leads to externally observable inconsistencies. In this paper, we explore an improvement to pairwise, bilateral anti-entropy; instead of uniform random selection, we introduce reinforcement learning mechanisms to assign selection probabilities to replicas most likely to have information. The result is more efficient replication, faster visibility, and stronger eventual consistency while maintaining high availability and partition tolerance.
Mouse mammary tumour virus-like env nucleotide and p14 signal peptide are present in feline mammary carcinomas, but not in neoplastic or dysplastic canine mammary lesions

Mouse mammary tumour virus-like (MMTV-like) is suspected to be involved in human breast cancer and it has been hypothesized that companion animals might have a role in viral transmission. The aim of our study was to investigate the presence of MMTV-like nucleotide sequences and viral protein in a larger number of feline (FMCs) and canine mammary carcinomas (CMCs) by nested PCR and immunohistochemistry. Results showed that the presence of MMTV-like env sequence in FMCs was 7% (6/86), while all the CMCs and canine dysplastic lesions scored negative. All PCR-positive FMCs scored positive for the MMTV p14 signal peptide of the envelope precursor protein of the virus. In contrast, all PCR-negative FMCs and canine mammary lesions were also negative for immunohistochemistry analysis. Canine and feline normal mammary gland tissues scored negative for both PCR and MMTV-p14 protein. Multiple nucleotide alignment of MMTV-like env gene sequences isolated from cat showed 97% and 99% similarity with HMTV and MMTV, respectively, while the others two presented some polimorphisms. Particularly the sequences of one of these two tumors showed a polymorphism (c.7575 A> G), that causes a previously unreported amino acid substitution (Thr > Ala). In conclusion, the results of our study showed the presence of MMTV-like sequences and viral protein in some FMCs. Further studies are needed to understand whether this virus does play a role in the development of FMCs, if MMTV-like is an exogenous virus as these data suggest and, in such a case, how and from whom this virus was acquired.
GPU-based Commonsense Paradigms Reasoning for Real-Time Query Answering and Multimodal Analysis

We utilize commonsense knowledge bases to address the problem of real- time multimodal analysis. In particular, we focus on the problem of multimodal sentiment analysis, which consists in the simultaneous analysis of different modali- ties, e.g., speech and video, for emotion and polarity detection. Our approach takes advantages of the massively parallel processing power of modern GPUs to enhance the performance of feature extraction from different modalities. In addition, in order to ex- tract important textual features from multimodal sources we generate domain-specific graphs based on commonsense knowledge and apply GPU-based graph traversal for fast feature detection. Then, powerful ELM classifiers are applied to build the senti- ment analysis model based on the extracted features. We conduct our experiments on the YouTube dataset and achieve an accuracy of 78% which outperforms all previous systems. In term of processing speed, our method shows improvements of several orders of magnitude for feature extraction compared to CPU-based counterparts.
Cross-species screening of microsatellite markers for individual identification of snow petrel Pagodroma nivea and Wilson's storm petrel Oceanites oceanicus in Antarctica

Seabirds are important indicators of marine ecosystem health. Species within the order Procellariiformes are the most abundant seabird species group distributed from warm tropical to cold temperate regions including Antarctica. There is a paucity of information on basic biology of the pelagic seabird species nesting on the Antarctic continents, and long-term studies are required to gather data on their population demography, genetics and other ecological parameters. Under the ‘Biology and Environmental Sciences’ component of the Indian Antarctic programme, long-term monitoring of Antarctic biodiversity is being conducted. In this paper, we describe results of cross-species screening of a panel of 12 and 10 microsatellite markers in two relatively little studied seabird species in Antarctica, the snow petrel Pagodroma nivea and the Wilson's storm petrel Oceanites oceanicus, respectively. These loci showed high amplification success and moderate levels of polymorphism in snow petrel (mean no. of alleles 7.08 ± 3.01 and mean observed heterozygosity 0.35 ± 0.23), but low polymorphism in Wilson's storm petrel (mean no. of alleles 3.9 ± 1.3 and mean observed heterozygosity 0.28 ± 0.18). The results demonstrate that these panels can unambiguously identify individuals of both species (cumulative PIDsibs for snow petrel is 3.7 × 10−03 and Wilson's storm petrel is 1.9 × 10−02) from field-collected samples. This work forms a baseline for undertaking long-term genetic research of these Antarctic seabird species and provides critical insights into their population genetics.
Sleep disturbances negatively affect balance and gait function in post-stroke patients.

BACKGROUND Impaired gait function after stroke contributes strongly to overall patient disability. Recently, sleep disturbance was reported to negatively affect functional recovery after stroke. OBJECTIVE The aim of this study was to identify the impact of sleep disturbance on balance and gait function in stroke patients. METHODS We retrospectively reviewed 140 patients with first-ever stroke. The patients were divided into two groups according to the presence of sleep disturbances, and differences in characteristics, such as demographic information, lesion factors, initial balance, and gait function. Lesion volume was measured on magnetic resonance images. Linear regression analyses were performed to examine predictors of balance and gait function after a 1-month rehabilitation program. RESULTS Of the 140 patients, 35 had sleep disturbance (25%). The patients with sleep disturbance were older than those without. Patients who had sleep disturbance had worse balance and gait function. BBS and FAC were also predicted by the initial BBS and sleep disturbance. The 10-m velocity was strongly associated with initial BBS, onset duration, and the presence of sleep disturbance. CONCLUSIONS Our study showed that sleep disturbances negatively affected functional outcomes, especially balance and gait function. Therefore, sleep problems should be controlled to improve outcomes in stroke patients.
Talk, Text, Tag? Understanding Self-Annotation of Smart Home Data from a User’s Perspective

Delivering effortless interactions and appropriate interventions through pervasive systems requires making sense of multiple streams of sensor data. This is particularly challenging when these concern people’s natural behaviours in the real world. This paper takes a multidisciplinary perspective of annotation and draws on an exploratory study of 12 people, who were encouraged to use a multi-modal annotation app while living in a prototype smart home. Analysis of the app usage data and of semi-structured interviews with the participants revealed strengths and limitations regarding self-annotation in a naturalistic context. Handing control of the annotation process to research participants enabled them to reason about their own data, while generating accounts that were appropriate and acceptable to them. Self-annotation provided participants an opportunity to reflect on themselves and their routines, but it was also a means to express themselves freely and sometimes even a backchannel to communicate playfully with the researchers. However, self-annotation may not be an effective way to capture accurate start and finish times for activities, or location associated with activity information. This paper offers new insights and recommendations for the design of self-annotation tools for deployment in the real world.
Investigating ToM in aging with the MASC: from accuracy to error type

ABSTRACT Growing evidence indicates that Theory of Mind (ToM) declines in normal aging. However, the majority of this research has used classic and static verbal tasks that present scenarios, which are very different from real life. The present study was designed to fill this gap by administering the Movie for the Assessment of Social Cognition (MASC) to young and older participants. It allows one to analyze not only the accuracy, but also the typology of error in mental states attribution distinguishing between iper-ToM (over-mentalization), ipo-ToM (insufficient mentalization), and no-ToM (lack of mentalization). We recruited 30 young (20–29 years), 39 young-old (65–74 years), and 31 old-old (75–86 years) participants. Along with the MASC, we administered a classic ToM task, the Strange Stories, and several measures of cognitive functioning. Results showed that older adults were less accurate in mental state attribution than young adults in the MASC, but not in the Strange Stories. In addition, compared to young adults, older adults committed more errors of both ipo- and no-ToM, while young adults committed more often iper-ToM errors. Additionally, older adults, but not young adults, did not show a difference between iper-ToM and ipo-ToM errors, which were equally frequent in this age group. Globally, results indicated that older adults’ failure in classic ToM tasks may be due to both ipo- and iper-ToM and provide needed evidence for the MASC as a suitable measure of ToM in aging.
NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression

Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor with diverse functions. It has been reported that NR4A1, as a transcriptional activator, is implicated in glucose and lipid metabolism. The aim of this study was to investigate the regulatory role of NR4A1 in adipogenesis and explore the underlying mechanisms. Quantitative real‐time PCR and Western blotting were used to analyse the expression of genes involved in synthesis and mobilization of fats in vivo and in vitro. Dual‐luciferase reporter assay was conducted to study the regulatory mechanisms of NR4A1. Our data from in vivo study confirmed that NR4A1 knockout (KO) mice fed with high‐fat diet were more prone to obesity, and gene expression levels of PPARγ and FAS were increased in KO mice compared to controls; our data from in vitro study showed that NR4A1 overexpression in 3T3‐L1 pre‐adipocytes inhibited adipogenesis. Moreover, NR4A1 enhanced GATA binding protein 2 (GATA2) expression, which in turn inhibited peroxisome proliferator‐activated receptor γ (PPARγ); NR4A1 inhibited sterol regulatory element binding transcription factor 1 (SREBP1) and its downstream gene fatty acid synthase (FAS) by up‐regulating p53. NR4A1 inhibits the differentiation and lipid accumulation of adipocytes by enhancing the expression of GATA2 and p53.
Differences in Balance Function Between Cancer Survivors and Healthy Subjects: A Pilot Study

Older adults who have survived cancer experience significantly more falls compared with healthy adults. Adult cancer survivors may also have a lower balance function than healthy adults. We examined muscle strength and balance function among 19 cancer survivors and 14 healthy subjects. The mean age of the cancer survivors was 51.5 ± 11.2 years; 6 men and 13 women. Cancer diagnoses included breast cancer, retroperitoneal sarcoma, acute leukemia, lung cancer, colorectal cancer, thyroid cancer, Ewing’s sarcoma, and tongue cancer. The mean age of healthy subjects was 47.4 ± 14 years; 3 men, 11 women. Muscle strength was assessed using hand grip and knee extensor strength tests. Balance function was evaluated using the Timed Up and Go (TUG) test, and body sway was tested using a force platform. No significant differences were found with respect to right and left grip strength or right and left knee extension strength between the 2 groups. A significantly higher TUG time was observed in cancer survivors than in healthy subjects (P < .05). With eyes open, the area of the center of pressure was significantly larger in cancer survivors than in healthy subjects (P < .05). Similarly, the length per area was significantly lower both with eyes open and closed for cancer survivors than for healthy subjects (P < .05). TUG was significantly correlated with muscle strength in both groups (P < .05). However, no body sway parameters were related to muscle strength in either group. Cancer survivors had lower balance function that might not have been related to muscle strength. Cancer survivors should be evaluated for balance function as there is a potential for impairment. The findings of this study will be relevant for planning the prevention of falls for cancer survivors.