Miracle-dz/UniFAR-FTUs huggingface dataset:
Foxp3 Post-translational Modifications and Treg Suppressive Activity

Regulatory T cells (Tregs) are engaged in maintaining immune homeostasis and preventing autoimmunity. Treg cells include thymic Treg cells and peripheral Treg cells, both of which can suppress the immune response via multiple distinct mechanisms. The differentiation, proliferation, suppressive function and survival of Treg cells are affected by distinct energy metabolic programs. Tissue-resident Treg cells hold unique features in comparison with the lymphoid organ Treg cells. Foxp3 transcription factor is a lineage master regulator for Treg cell development and suppressive activity. Accumulating evidence indicates that the activity of Foxp3 protein is modulated by various post-translational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation. These modifications affect multiple aspects of Foxp3 function. In this review, we define features of Treg cells and roles of Foxp3 in Treg biology, and summarize current research in PTMs of Foxp3 protein involved in modulating Treg function. This review also attempts to define Foxp3 dimer modifications relevant to mediating Foxp3 activity and Treg suppression. Understanding Foxp3 protein features and modulation mechanisms may help in the design of rational therapies for immune diseases and cancer.
The Rise of NK Cell Checkpoints as Promising Therapeutic Targets in Cancer Immunotherapy

Checkpoint immunotherapy that targets inhibitory receptors of T cells, thereby reversing the functional exhaustion of T cells, marks a breakthrough in anticancer therapy. The success of T cell-directed checkpoint inhibitors of CTLA-4 and PD-1/PD-L1 has opened a new approach for cancer immunotherapy and resulted in extensive research on immune checkpoints. However, it is only in recent years that research on NK cell exhaustion and potential checkpoints impacting NK cells has become popular. NK cells, as the major player in innate immunity, are critical for immune surveillance, particularly the control of metastasis and hematological cancers. The balance between activating and inhibitory signals fine tunes the activation and effector functions of NK cells, and transformed cells modulate NK cells by upregulating negative signaling that “exhausts” NK cells. Exhausted NK cells with excessive expression of inhibitory receptors (checkpoint molecules) are impaired in the recognition of tumor cells as well as antitumor cytotoxicity and cytokine secretion. Therefore, an understanding of the potential checkpoint molecules involved in NK cell exhaustion is particularly important in terms of NK cell-targeted cancer immunotherapy. In this review, we summarize recent advances in NK cell checkpoint inhibitors and their progress in clinical trials. Moreover, we highlight some of the latest findings in fundamental NK cell receptor biology and propose potential NK cell checkpoint molecules for future immunotherapeutic applications.
Genomic Profiling of Driver Gene Mutations in Chinese Patients With Non-Small Cell Lung Cancer

Worldwide, especially in China, lung cancer accounts to a major cause of mortality related to cancer. Treatment decisions mainly depend on oncogenic driver mutations, which offer novel therapeutic targets for anticancer therapy. However, studies of genomic profiling of driver gene mutations in mainland China are rare. Hence, this is an extensive study of these mutations in Non-small-cell lung cancer (NSCLC) Chinese patients. Comparison of driver gene mutations of lung adenocarcinoma with other races showed that the mutational frequencies were similar within the different East Asian populations, while there were differences between East Asian and non-Asian populations. Further, four promising candidates for druggable mutations of epidermal growth factor receptor (EGFR) were revealed that open up avenues to develop and design personal therapeutic approaches for patients harboring mutations. These results will help to develop personalized therapy targeting NSCLC.
Effects of Non-invasive Brain Stimulation on Stimulant Craving in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-Analysis

Dopamine system plays a pivotal role in specific kinds of substance use disorders (SUD, i. e., cocaine and methamphetamine use disorders). Many studies addressed whether dopamine-involved craving could be alleviated by non-invasive brain stimulation (NIBS) techniques. Nevertheless, the outcomes were highly inconsistent and the stimulating parameters were highly variable. In the current study, we ran a meta-analysis to identify an overall effect size of NIBS and try to find stimulating parameters of special note. We primarily find 2,530 unduplicated studies in PubMed, Psychology and Behavioral Sciences Collection, PsycARTICLES, PsycINFO, and Google Scholar database involving “Cocaine”/“Amphetamine”/“Methamphetamine” binded with “TMS”/“tDCS”/“non-invasive stimulation” in either field. After visual screening, 26 studies remained. While 16 studies were further excluded due to the lack of data, invalid craving scoring or the absence of sham condition. At last, 16 units of analysis in 12 eligible studies were coded and forwarded to a random-effect analysis. The results showed a large positive main effect of stimulation (Hedge's g = 1.116, CI = [0.597, 1.634]). Further subgroup analysis found that only high-frequency repetitive transcranial magnetic stimulation (rTMS) could elicit a significant decrease in craving, while the outcome of low-frequency stimulation was relatively controversial. Moreover, univariate meta regression revealed that the number of pulses per session could impose negative moderation toward the intervention. No significant moderation effect was found in types of abuse, overall days of stimulation and other variables of stimulating protocol. In conclusion, this meta-analysis offered a persuasive evidence for the feasibility of using NIBS to remit substance addictive behavior directly based on dopamine system. We also give clear methodological guidance that researchers are expected to use high-frequency, sufficiently segmented rTMS to improve the efficacy in future treatments.
Patients Aged ≥55 Years With Stage T1-2N1M1 Differentiated Thyroid Cancer Should Be Downstaged in the Eighth Edition AJCC/TNM Cancer Staging System

Objectives: Since the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC/TNM) cancer staging system introduced some significant changes, we investigated whether patients with stage T1-2N1M1 differentiated thyroid cancer (DTC) should be placed in stage IVB, with the goal of providing suggestions for improved survival prediction. Materials and Methods: We divided 30,234 DTC patients aged ≥55 years enrolled from the Surveillance, Epidemiology, and End Results (SEER) database into different stage groups based on the new stage system but in a more thorough manner. Univariate and multivariate Cox regression analyses were conducted to explore the clinicopathological factors associated with cancer-specific survival. Survival of different stage groups was assessed by mortality rates per 1,000 person-years, Cox proportional hazards regression analyses, and Kaplan-Meier analyses with log-rank tests and the propensity score matching method. Results: Univariate and multivariate analyses demonstrated that age at diagnosis, T stage, lymph node metastasis, distant metastasis, histological types, extrathyroidal extension, and radiation therapy were associated with cancer-specific survival. Patients with stage T1-2N1M1 had a lower cancer-specific mortality rate per 1,000 person-years (28.081, 95% confidence interval [CI]: 12.616–62.505) and all-cause mortality rate per 1,000 person-years (70.203, 95% CI: 42.323–116.448) than those with low-level stages such as stage T4aN1M0, stage IVA, and stage T1-2N0M1. Cox proportional hazards regression analyses suggested that patients with stage T4bN1M0 belonging to stage IVA (hazard ratio: 2.529, 95% CI: 1.018–6.278, p = 0.046) had a significantly higher risk of cancer-specific mortality than those with stage T1-2N1M1. Kaplan-Meier analyses with log-rank tests suggested that the cancer-specific survival curve of patients with stage T1-2N1M1 had a more modest decline than that of stage T4bN1M0 (p = 0.0125), and the cancer-specific survival curve and all-cause survival curve of patients with stage T1-2N1M1 were not different from those of stage T3N1M0, stage T4aN0M0, stage T4aN1M0, stage T4bN0M0, and stage T1-2N0M1 (all, p > 0.05). The analysis yielded similar results after propensity score matching for other clinicopathological characteristics. Conclusion: Patients aged ≥55 years with stage T1-2N1M1 DTC according to the eighth edition AJCC/TNM cancer staging system should be downstaged and those with stage T4bN1M0 upstaged accordingly.
Heidelberg Risk Sport-Specific Stress Test: A Paradigm to Investigate the Risk Sport-Specific Psycho-Physiological Arousal

In risk sports with medium to high risks of injury (e.g., surfing, free solo climbing, wingsuit flying), athletes frequently find themselves in unexpected and threatening situations. Elevated psycho-physiological stress responses to these situations might have tremendous consequences for their performance as well as for their long-term health. To gain a better understanding of the psycho-physiological response to such events, innovative, externally valid and standardized stress induction protocols are needed. Therefore, the aim of this paper is to introduce and evaluate a risk sport-specific stress protocol, i.e., the Heidelberg Risk Sport-Specific Stress Test (HRSST), which utilizes fear of falling as the stressful event. Climbing novices were asked to climb up a 12 m high wall. Then, participants were requested to “jump into the rope”, leading to a secured fall of about 3 m. This imposed physical danger assumed to elicit psycho-physiological responses. Self-reported state anxiety, salivary cortisol, and heart rate/heart rate variability were measured before, during, and after the HRSST. Results of four independent studies that investigated the psycho-physiological response to the HRSST in 214 participants were analyzed, leading to conclusions about the stressor’s effectiveness. Results showed that self-reported state anxiety consistently increased after the HRSST in all four experiments (moderate to large effects). The results of the physiological indicators were inconclusive. Salivary cortisol significantly increased after the HRSST in one of four experiments (small effect sizes). Although heart rate significantly increased during the “jump in the rope” in experiment 1, heart rate variability significantly decreased after the HRSST in only one of three experiments (small effect sizes). Findings suggest that the HRSST is a valid method to induce risk sport-specific emotional stress, but effects on physiological stress markers were rather minor. To sum up, in case of appropriate sports climbing facilities, the HRSST appears to be a cost-efficient and promising stress induction protocol: It offers the possibility to investigate risk sport-specific stress responses and their underlying mechanisms in climbing novices. These findings may also find application in professions in which individuals are exposed to risky situations, such as police officers, medical first responders, firefighters and military personnel.
The Impact of Type VI Secretion System, Bacteriocins and Antibiotics on Bacterial Competition of Pectobacterium carotovorum subsp. brasiliense and the Regulation of Carbapenem Biosynthesis by Iron and the Ferric-Uptake Regulator

The complexity of plant microbial communities provides a rich model for investigating biochemical and regulatory strategies involved in interbacterial competition. Within these niches, the soft rot Enterobacteriaceae (SRE) represents an emerging group of plant–pathogens causing soft rot/blackleg diseases resulting in economic losses worldwide in a variety of crops. A preliminary screening using next-generation sequencing of 16S rRNA comparatively analyzing healthy and diseased potato tubers, identified several taxa from Proteobacteria to Firmicutes as potential potato endophytes/plant pathogens. Subsequent to this, a range of molecular and computational techniques were used to determine the contribution of antimicrobial factors such as bacteriocins, carbapenem and type VI secretion system (T6SS), found in an aggressive SRE (Pectobacterium carotovorum subsp. brasiliense strain PBR1692 – Pcb1692) against these endophytes/plant pathogens. The results showed growth inhibition of several Proteobacteria by Pcb1692 depends either on carbapenem or pyocin production. Whereas for targeted Firmicutes, only the Pcb1692 pyocin seems to play a role in growth inhibition. Furthermore, production of carbapenem by Pcb1692 was observably dependent on the presence of environmental iron and oxygen. Additionally, upon deletion of fur, slyA and expI regulators, carbapenem production ceased, implying a complex regulatory mechanism involving these three genes. Finally, the results demonstrated that although T6SS confers no relevant advantage during in vitro competition, a significant attenuation in competition by the mutant strain lacking a functional T6SS was observed in planta. IMPORTANCE Soft rot Enterobacteriaceae (SRE) represents important phytopathogens causing soft rot/blackleg diseases in a variety of crops leading to huge economic losses worldwide. These pathogens have been isolated alongside other bacteria from different environments such as potato tubers, stems, roots and from the soil. In these environments, SREs coexist with other bacteria where they have to compete for scarce nutrients and other resources. In this report, we show that Pectobacterium carotovorum subsp. brasiliense strain PBR1692 – Pcb1692, which represents one of the SREs, inhibits growth of several different bacteria by producing different antimicrobial compounds. These antimicrobial compounds can be secreted inside or outside the plant host, allowing Pcb1692 to effectively colonize different types of ecological niches. By analyzing the genome sequences of several SREs, we show that other SREs likely deploy similar antimicrobials to target other bacteria.
Sub-Sequence-Based Dynamic Time Warping

In time series classification the most commonly used approach is k Nearest Neighbor classification, where k = 1, coupled with Dynamic Time Warping (DTW) similarity checking. A challenge is that the DTW process is computationally expensive. This paper presents a new approach for speeding-up the DTW process, Sub-Sequence-Based DTW, which offers the additional benefit of improving accuracy. This paper also presents an analysis of the impact of the Sub-Sequence-Based method in terms of efficiency and effectiveness in comparison with standard DTW and the Sakoe-Chiba Band technique.
Hämophilie-A-Therapie bei Erwachsenen

Summary In a retrospective study from a single treatment centre (Centre for Haemostaseology Muenster) the current treatment conditions of patients with severe haemophilia A (FVIII:C <1%) at the age of ≥ 16 years are described. Data were extracted from paper based diaries of patients in home treatment (n = 70). Results: A progressive preference towards prophylactic treatment compared to on demand therapy is observed. On average 2.4 injections per week (mean: 1750 IU FVIII per injection) are used in the prophylactic regimen. The consumption of FVIII concentrates is approximately fivefold increased compared to on demand therapy (average 0.5 injections per week). Meanwhile, recombinant FVIII concentrates have become widely accepted in all age groups, they show a proportion of 60% in the clinical practice of the study population.
Social Service Delivery Preferences Among African American Women Who Use Crack Cocaine

Abstract African American women involved in high-risk, substance use-related behaviors are affected by extremely high rates of HIV infection. While research has demonstrated that HIV is preventable, in order for prevention efforts to be successful in reducing disparities, perceptions of African American women who use crack cocaine need to be taken into account. This qualitative study presents results of eleven focus groups with eighty-nine African American women respondents presenting their perceptions of service needs and preferences for service delivery. The results indicate two important findings for social service providers: the respondents' lack of a perceived need for HIV prevention services as a spontaneously identified need, and respondents' desires for more basic services such as childcare, safe shelter, basic necessities, and especially substance abuse treatment before they could be approached about HIV prevention services. The findings are relevant for developing gender-and culture-specific prevention strategies to reduce the spread of HIV.
Flaws Validation of Maze Mobility Model using Spatial-temporal Synthetic Mobility Metrics

Mobility modeling represents a critical task in mobile wireless networks to improve the overall throughput. This paper evaluates relevant spatial-temporal stochastic properties of the most frequently used synthetic mobility models compared to a new efficient mobility model named Maze Mobility Model (Maze MM). It imitates a real-life movement according to diverse mobility features, as spatial and temporal dependencies with also geographic restrictions. To demonstrate the efficiency of this new model, various metrics were validated such as; the speed decay problem, the density wave phenomenon, the spatial node distribution, the average neighbor percentage, and mobile neighbors range. Each mobility pattern may bear from diverse mobility flaws, as shown by network simulations. So, numerous metrics are employed to describe mobility features. The current research aims to deeply understand mobility features of Maze MM with the aim to deduce a definite judgment of each mobility metric, given that further this fact affects the whole network performances. The validation results are discussed to remark the effectiveness and robustness of Maze MM according to the validated mobility metrics.
Fuzzy-rough Fuzzification in General FL Classifiers

In this paper, a three-dimensional version of fuzzy-rough fuzzification is examined for classification tasks. Similar approach based on interval fuzzy-rough fuzzification has been demonstrated to classify with three decision labels of confidence, one of which were uncertain. The method proposed here relies on the use of fuzzification of inputs with a triangular membership function describing the nature of imprecision in data. As a result, we implement in fuzzy classifiers three dimensional membership functions using the calculus of general type-2 fuzzy sets. The approach is justified when more confidence labels are expected from the decision system, especially when the classifier is embedded in a recurrent hierarchical decision system working on easily available economic, extended, and advanced expensive real data.
Influence of Emotions on Software Developer Productivity

The Software developer productivity is an important indicator that has attracted the attention of the industry over the years. It has been established that improving software productivity enhances the performance of organizations. Despite its importance, a full understanding of contextual factors and how they influence productivity is not attained. One such important factor is the developer’s emotions. In this paper, we conduct an experiment on 11 participants where they attempt to solve 10 ACM-style problems as we monitor their emotions and behaviour in the background. The experiments performed achieve an accuracy of 55.4% on the test set using a random forest classifier. There is room for multiple improvements such as increasing dataset size, performing class balancing, and utilizing different aggregation methods for the data. This paper opens a different track for experimentation relating to the relationship between emotions and software productivity. Achieving a better understanding of this relationship can aid further research that would utilize it to build context aware and pervasive systems that can automatically react to developers’ emotions when going through a low productivity phase and orient them towards emotions that are correlated with positive productivity.
CATI: An Active Learning System for Event Detection on Mibroblogs' Large Datasets

Today, there are plenty of tools and techniques to perform text- or image-based classification of large datasets, targeting different levels of user expertise and abstraction. Specialists usually collaborate in projects by creating ground truth datasets and do not always have deep knowledge in Information Retrieval. This article presents a full platform for assisted binary classification of very large textual and text and image composed documents. Our goal is to enable human users to classify collections of several hundred thousand documents in an assisted way, within a humanly acceptable number of clicks. We propose a graphical user interface, based on several classification assistants: text- and image-based event detection, Active Learning (AL), search engine and rich visual metaphors to visualize the results. We also propose a novel query strategy in the context of Active Learning, considering the top unlabeled bi-grams and duplicated (e.g. re-tweeted) content in the target corpus to classify. These contributions are supported not only by a tool whose code is freely accessible but also by an evaluation of the impact of using the aforementioned methods on the number of clicks needed to reach a stable level of accuracy.
Human-cobot Teams: Exploring Design Principles and Behaviour Models to Facilitate the Understanding of Non-verbal Communication from Cobots

Now that collaborative robots are becoming more widespread in industry, the question arises how we can make them better co-workers and team members. Team members cooperate and collaborate to attain common goals. Consequently they provide and receive information, often non-linguistic, necessary to accomplish the work at hand and coordinate their activities. The cooperative behaviour needed to function as a team also entails that team members have to develop a certain level of trust towards each other. In this paper we argue that for cobots to become trusted, successful co-workers in an industrial setting we need to develop design principles for cobot behaviour to provide legible, that is understandable, information and to generate trust. Furthermore, we are of the opinion that modelling such non-verbal cobot behaviour after animal co-workers may provide useful opportunities, even though additional communication may be needed for optimal collaboration. Marijke Bergman, Elsbeth de Joode, +1 author Janienke Sturm Published in CHIRA 2019 Computer Science
Effective Remote Drone Control using Augmented Virtuality

Since the remote drones control is mentally very demanding, supporting the pilot with both, first person view (FPV) and third person view (TPV) of the drone may help the pilot with orientation capability during the mission. Therefore, we present a system that is based on augmented virtuality technology, where real data from the drone are integrated into the virtual 3D environment model (video-stream, 3D structures, location information). In our system, the pilot is mostly piloting the drone using FPV, but can whenever switch to TPV in order to freely look around the situation of poor orientation. The proposed system also enables efficient mission planning, where the pilot can define 3D areas with different potential security risks or set navigation waypoints, which will be used during the mission to navigate in defined zones and visualize the overall situation in the virtual scene augmented by online real data.