Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer stem cells in relation to treatment

The classical cancer therapies, including chemotherapy and radiation therapy, can initially show good results and tumor shrinkage; however, for most cancer patients disease recurrence is a common event. This tumor regrowth following therapy is now thought to depend on a small population of cancer stem cells (CSCs), which, similar to other stem cells, have the capacity for self-renewal and multipotent differentiation. Cancer stem cells have been identified based on cell surface protein expression in many tumor types, and for all diseases studied, this specific cell population is required for serial transplantation in animal models. However, a specific signature of cell surface proteins that can identify cancer stem cells has not been developed for many solid tumors. In this review, we summarize a new technique for identifying and quantifying cancer stem cells in situ, which could be a valuable technique for evaluating the effects of therapies on this cell population. Finally, we conclude by discussing several preclinical treatment strategies that either reprogram cancer stem cells or cause them to be specifically attacked by immune cells. In summary, therapeutic and diagnostic methodologies that can attack and quantify cancer stem cells, respectively, will be valuable tools for eradicating cancer.
Using Membrane Partitioning Simulations To Predict Permeability of Forty-Nine Drug-Like Molecules

A simple descriptor calculated from molecular dynamics simulations of the membrane partitioning event is found to correlate well with experimental measurements of passive membrane permeation from the high-throughput MDCK-LE assay using a data set of 49 drug-like molecules. This descriptor approximates the energy cost of translocation across the hydrophobic membrane core (flip-flop), which for many molecules limits permeability. Performance is found to be superior in comparison to calculated properties such as clogP, clogD, or polar surface area. Furthermore, the atomistic simulations provide a structural understanding of the partitioned drug-membrane complex, facilitating medicinal chemistry optimization of membrane permeability.
Influenza Virus Infection Enhances Antibody-Mediated NK Cell Functions via Type I Interferon-Dependent Pathways

Protection from severe influenza may be assisted by antibodies that engage NK cells to kill infected cells through ADCC. Studies have primarily focused on antibodies that have ADCC activity, rather than the capacity of NK cells to become activated and mediate ADCC during an influenza virus infection. We found that type I interferon released in response to influenza virus infection primes NK cells to become highly reactive to anti-influenza virus ADCC antibodies. Enhancing the capacity of NK cells to mediate ADCC could assist in controlling influenza virus infections. ABSTRACT Natural killer (NK) cells are an important component in the control of influenza virus infection, acting to both clear virus-infected cells and release antiviral cytokines. Engagement of CD16 on NK cells by antibody-coated influenza virus-infected cells results in antibody-dependent cellular cytotoxicity (ADCC). Increasing the potency of antibody-mediated NK cell activity could ultimately lead to improved control of influenza virus infection. To understand if NK cells can be functionally enhanced following exposure to influenza virus-infected cells, we cocultured human peripheral blood mononuclear cells (PBMCs) with influenza virus-infected human alveolar epithelial (A549) cells and evaluated the capacity of NK cells to mediate antibody-dependent functions. Preincubation of PBMCs with influenza virus-infected cells markedly enhanced the ability of NK cells to respond to immune complexes containing hemagglutinin (HA) and anti-HA antibodies or transformed allogeneic cells in the presence or absence of a therapeutic monoclonal antibody. Cytokine multiplex, RNA sequencing, supernatant transfer, Transwell, and cytokine-blocking/cytokine supplementation experiments showed that type I interferons released from PBMCs were primarily responsible for the influenza virus-induced enhancement of antibody-mediated NK cell functions. Importantly, the influenza virus-mediated increase in antibody-dependent NK cell functionality was mimicked by the type I interferon agonist poly(I·C). We conclude that the type I interferon secretion induced by influenza virus infection enhances the capacity of NK cells to mediate ADCC and that this pathway could be manipulated to alter the potency of anti-influenza virus therapies and vaccines. IMPORTANCE Protection from severe influenza may be assisted by antibodies that engage NK cells to kill infected cells through ADCC. Studies have primarily focused on antibodies that have ADCC activity, rather than the capacity of NK cells to become activated and mediate ADCC during an influenza virus infection. We found that type I interferon released in response to influenza virus infection primes NK cells to become highly reactive to anti-influenza virus ADCC antibodies. Enhancing the capacity of NK cells to mediate ADCC could assist in controlling influenza virus infections.
Effect of the application of high-frequency mechanical vibration on tooth length concurrent with orthodontic treatment using clear aligners: A retrospective study

OBJECTIVES: To evaluate the possible change in teeth lengths as an indicator of orthodontically induced tooth root resorption (OITRR) after high-frequency mechanical vibration (HFV) treatment concurrent with Invisalign Smart Track® aligners as evaluated by cone beam computed tomography (CBCT). MATERIALS AND METHODS: The sample, composed of 30 patients with an average age of 26 ± 11 years and Class I malocclusion with an initial anterior crowding ranging from 3 to 5 mm, was divided equally into two groups; Group I received adjunctive high-frequency mechanical vibration (HFV); Group II, the control, did not receive adjunctive mechanical treatment. The maxillary incisor's teeth lengths were measured using Mimics software before (T1) and after (T2) treatment. All data were analyzed using Student's t-test. Reliability testing was completed by randomly selecting 10 patients' CBCTs, and their teeth lengths were measured twice by the same investigator over a 15-day interval and compared confirming intra-operator accuracy. RESULTS: The control group showed a statistically significant decrease in tooth lengths compared to the HFV group which showed nonstatistically significant change of tooth lengths. CONCLUSION: Patients treated with HFV showed minimum tooth length changes after treatment, which may indicate that HFV can reduce OITRR with treatment using clear aligners.
The Hidden Curriculum of ICT and the Social Behavior of Young Children

ICT can have unintended impacts on the social behavior of children, but knowledge about the mechanisms by which they unfold is limited. To fill this gap, this paper examines the social behavioral impacts of ICT on young children (under seven-year-olds) who are in a critical developmental period for learning their basics of social behavior. This paper focuses on the ways in which ICT encourage them to modify their turn taking, the fundamental mechanism for conducting social behavior. Analyzing qualitative video data from real life child-computer interactions and parental interviews, these modifications are summarized as the hidden curriculum of ICT. Two dynamics unique to ICT interaction, the reprehension-free breaching of social expectations and the unlimited repetition of interactions, facilitate young children internalizing these modifications, with dual impacts on their social behavior. The negative impacts stem from the hidden curriculum of ICT desensitizing young children to the situational expectations of their social surroundings. The positives emerge from it promoting resilience sustaining social behavior in general. These results implicate that harnessing the hidden curriculum of ICT is important, especially when designing ICT for young children, because the conducts of social behavior internalized before the age of seven can persist for life.
A Taxonomy of Recurring Data Analysis Problems in Maintenance Analytics

Modern maintenance strategies increasingly focus on vast amounts of diverse data and multifaceted analytical approaches in order to make efficient use of given resources and unveil hidden potentials. While there is often no universal solution approach to a specific case at hand, it is still possible to observe recurring problem classes for which generic solution templates can be applied and thus the establishment of a reusable knowledge base appears beneficial. To this end, we apply a taxonomy development approach to identify and systematize dimensions and characteristics of recurring data analysis problems in data-driven maintenance scenarios. Our research method integrates findings from a systematic literature review and expert interviews with data scientists from industry. Thus, we add descriptive theory to the field of maintenance analytics and propose a taxonomy that distinguishes be-tween analytical maintenance objectives, data characteristics and analytical techniques.
How to Choose between Robotic Process Automation and Back-end System Automation?

Recent literature has identified two main types of IT-enabled innovation and labelled them as lightweight IT and heavyweight IT. In this study, we look into robotic process automation (RPA) as lightweight IT and traditional back-end system automation as heavyweight IT and study how a case company Telco makes the choice between these two alternative ways of implementing automation. Drawing on an empirical study conducted at Telco examining two automation projects, we find support for earlier studies addressing specifically the choice problem of RPA. Our main contribution lies in uncovering the role of the two-dimensional feature stability on the choice. While heavyweight IT is preferred when system architecture is stable, lightweight IT, operating on the presentation layer, holds a prerequisite of stable system interfaces.
The Interaction of Bluetongue Virus VP6 and Genomic RNA Is Essential for Genome Packaging

Genome packaging is a critical stage during virus replication. For viruses with segmented genomes, the genome segments need to be correctly packaged into a newly formed capsid. However, the detailed mechanism of this packaging is unclear. Here we focus on VP6, a minor viral protein of bluetongue virus, which is critical for genome packaging. We used multiple approaches, including a robust RNA-protein fingerprinting assay, to map the ssRNA binding sites of recombinant VP6 and the genomic dsRNA binding sites of capsid-associated VP6. By these means, together with virological and biochemical methods, we identify the viral RNA-packaging motif of a segmented dsRNA virus for the first time. ABSTRACT The genomes of the Reoviridae, including the animal pathogen bluetongue virus (BTV), are multisegmented double-stranded RNA (dsRNA). During replication, single-stranded (ss) positive-sense RNA segments are packaged into the assembling virus capsid, triggering genomic dsRNA synthesis. However, exactly how this packaging event occurs is not clear. A minor capsid protein, VP6, unique for the orbiviruses, has been proposed to be involved in the RNA-packaging process. In this study, we sought to characterize the RNA binding activity of VP6 and its functional relevance. A novel proteomic approach was utilized to map the ssRNA/dsRNA binding sites of a purified recombinant protein and the genomic dsRNA binding sites of the capsid-associated VP6. The data revealed that each VP6 protein has multiple distinct RNA-binding regions and that only one region is shared between recombinant and capsid-associated VP6. A combination of targeted mutagenesis and reverse genetics identified the RNA-binding region that is essential for virus replication. Using an in vitro RNA-binding competition assay, a unique cell-free assembly assay, and an in vivo single-cycle replication assay, it was possible to identify a motif within the shared binding region that binds BTV ssRNA preferentially in a manner consistent with specific RNA recruitment during capsid assembly. These data highlight the critical roles that this unique protein plays in orbivirus genome packaging and replication. IMPORTANCE Genome packaging is a critical stage during virus replication. For viruses with segmented genomes, the genome segments need to be correctly packaged into a newly formed capsid. However, the detailed mechanism of this packaging is unclear. Here we focus on VP6, a minor viral protein of bluetongue virus, which is critical for genome packaging. We used multiple approaches, including a robust RNA-protein fingerprinting assay, to map the ssRNA binding sites of recombinant VP6 and the genomic dsRNA binding sites of capsid-associated VP6. By these means, together with virological and biochemical methods, we identify the viral RNA-packaging motif of a segmented dsRNA virus for the first time.
A Brainstem Neural Substrate for Stopping Locomotion

Locomotion occurs sporadically and needs to be started, maintained, and stopped. The neural substrate underlying the activation of locomotion is partly known, but little is known about mechanisms involved in termination of locomotion. Recently, reticulospinal neurons (stop cells) were found to play a crucial role in stopping locomotion in the lamprey: their activation halts ongoing locomotion and their inactivation slows down the termination process. Intracellular recordings of these cells revealed a distinct activity pattern, with a burst of action potentials at the beginning of a locomotor bout and one at the end (termination burst). The termination burst was shown to be time linked to the end of locomotion, but the mechanisms by which it is triggered have remained unknown. We studied this in larval sea lampreys (Petromyzon marinus; the sex of the animals was not taken into account). We found that the mesencephalic locomotor region (MLR), which is known to initiate and control locomotion, stops ongoing locomotion by providing synaptic inputs that trigger the termination burst in stop cells. When locomotion is elicited by MLR stimulation, a second MLR stimulation stops the locomotor bout if it is of lower intensity than the initial stimulation. This occurs for MLR-induced, sensory-evoked, and spontaneous locomotion. Furthermore, we show that glutamatergic and, most likely, monosynaptic projections from the MLR activate stop cells during locomotion. Therefore, activation of the MLR not only initiates locomotion, but can also control the end of a locomotor bout. These results provide new insights onto the neural mechanisms responsible for stopping locomotion. SIGNIFICANCE STATEMENT The mesencephalic locomotor region (MLR) is a brainstem region well known to initiate and control locomotion. Since its discovery in cats in the 1960s, the MLR has been identified in all vertebrate species tested from lampreys to humans. We now demonstrate that stimulation of the MLR not only activates locomotion, but can also stop it. This is achieved through a descending glutamatergic signal, most likely monosynaptic, from the MLR to the reticular formation that activates reticulospinal stop cells. Together, our findings have uncovered a neural mechanism for stopping locomotion and bring new insights into the function of the MLR.
Designing for Business Model Comprehension - Principles for an Extended Business Model Tool

Business modelling is recognized as an important concept to make company strategies more explicit and to compare alternatives combined with their translation to the operational layer. Typically, business modelling is performed by a group of experts building on established frameworks like the Business Model Canvas. In a subsequent step, different stakeholders in a company should build upon and work with the defined business models, thus, comprehension is critical. However, this is challenging from a practical point of view and existing research has not addressed the issue of business model comprehension. In order to close this research gap and to increase users’ business model comprehension, we propose an advanced business model tool and an experimental design in this research-inprogress paper. Following the design science approach, we derive a first set of meta-requirements and design principles and present an advanced business model tool instantiation. The presented tool should contribute to an increased business model comprehension by providing semantic relationships and extended business performance indicators. Finally, we present a set of testable hypotheses and the research design for an experimental tool evaluation. With this research we intend to provide a solution to the problem of business model comprehension and contribute to the design knowledge base of business model tools.
Evaluation of neck circumference as an easy and reliable predictor for non-alcoholic fatty liver disease.

BACKGROUND/AIMS The aim of the present study was to investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and neck circumference (NC) and to compare the NC predictive value with other anthropometric indices in the prediction of NAFLD and metabolic syndrome (MetS) as well as to find the NC cut-off point for the prediction of NAFLD and MetS in an Iranian population. MATERIALS AND METHODS A total of 590 individuals who fulfilled our criteria were enrolled in the study. Anthropometric measurements, physical examinations, and abdominal ultrasonography were performed by trained staff. Blood samples for biochemical tests were also obtained after fasting for 12 h. RESULTS Neck circumference was associated with NAFLD and MetS in both genders (p<0.0001) and remained significant even after adjustment for possible confounding factors. It was also significantly associated with other anthropometric indices, such as fatty liver severity, aspartate aminotransferase, alanine aminotransferase, fasting blood sugar, triglycerides, low-density lipoprotein, systolic and diastolic blood pressure, and family history of diabetes in both sexes (p<0.05). There was a significant negative correlation between high-density lipoprotein levels and NC in both sexes (p<0.001). CONCLUSION Neck circumference was significantly correlated with NAFLD and MetS. In addition, it had the highest predictive value for NAFLD and MetS among other common anthropometric indices. Therefore, it can be used as a simple and feasible tool for screening NAFLD in a large population.
Use of plasma-enriched demineralized freeze-dried bone matrix in postsurgical jaw defects

Aim and Objectives: The aim is to know the augmented new bone formation in postsurgical bony defects in the maxillofacial region when filled with plasma-enriched demineralized freeze-dried bone allograft (DFDBA). Materials and Methods: The study group included 45 patients, selected randomly, and divided in three equated groups. In Group I (control) patients, the wound was closed primarily without incorporating any graft in the bony defect. In Group II, the defect was filled with DFDBA alone and in Group III with DFDBA enriched with platelet-rich plasma (PRP). The said graft material was procured from the (to be discarded) femur head, treated to get rid of its antigenicity, made suitable to be incorporated as a graft material, sterilized by gamma irradiation and then implanted into the jaw defects. Results: The results were evaluated and interpreted both clinically and radiographically by studying the changes post 1 week, 1 month, 3 months, and 6 months, respectively. Bone density was evaluated using computed tomography scan in addition to standard conventional radiographs. Evidence of trabecular formation and calcification were noted down. Measurements were recorded by taking note of Hounsfield units. Statistically, one-way ANOVA test followed by least significant difference post hoc test was done. Final results showed that the patients in the Group III had more bone density at the grafted site when compared to the Group II and I patients. These findings were significant. Conclusion: PRP-enriched DFDBA is a superior grafting material in terms of other grafting materials available. It possesses both osteoconductive and osteoinductive properties and elicits the least immunological response, thereby making it one of the best effective combinations of grafting material to be used in oral and maxillofacial reconstructive purposes.
Designing for Knowledge Based Cyber-Security - Episode 1: What Should We Teach?

Cybercrime proliferates and cyber-security seems evermore challenging. Literature offers large support that cyber-security is rather of behavioral than of pure technical matter. While prior research has focused on explaining organizational and individual (mis)behavior and agreed on the crucial role of cyber-security education programs, less is known on the question of what to teach in order to change behavior. With an exhaustive literature review, this article helps to build a foundation for developing training based interventions, grounded on strong behavioral models, taking a knowledge management view to foster behavioral change by supplying relevant knowledge entities. Embedded in a stream of design science research (DSR) activities this article reports on DSR’s first two phases, problem description and definition of solution objectives. This article ends with a set of design requirements to a cybersecurity training environment in terms of content and learning approach grounded on the results of the literature review.
Efficacy of several biological therapies for treating moderate to severe psoriasis: A network meta-analysis

The aim of the present meta-analysis was to systematically assess the efficacy of the various treatments available for moderate to severe psoriasis. PubMed and Embase databases were systematically searched to select relevant studies up to February 2015. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect estimates. In addition, the Psoriasis Area and Severity Index (PASI) 50, PASI 75 and PASI 90 responses for the therapies were systematically assessed. A total of 33 randomized controlled trials were included in the present study. For the PASI 75 response rate, infliximab (5 mg) may be the most effective option for the treatment of moderate to severe psoriasis. Furthermore, the pooled results of the PASI 50 response rate demonstrated that infliximab (5 mg) and ustekinumab (90 mg) may be superior to other drugs for treating moderate to severe psoriasis. For the PASI 90 response rate, infliximab (5 mg), ustekinumab (90 mg) and briakinumab (weeks 0 and 4, 200 mg; week 8, 100 mg) exhibited improved results compared with other treatments. In conclusion, infliximab (5 mg) may be a superior option to treat moderate to severe psoriasis due to the relatively high PASI scores. However, despite the high PASI 90 responses, further studies are required to identify the efficacy of ustekinumab (90 mg) and briakinumab.