Miracle-dz/UniFAR-FTUs huggingface dataset:
Amelioration of amyloid β‐FcγRIIb neurotoxicity and tau pathologies by targeting LYN

SRC‐family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid β (Aβ)‐triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fcγ receptor IIb2 (FcγRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to Aβ 1–42 (Aβ1–42). Knockdown of LYN expression inhibited Aβ1–42‐induced neuronal cell death. Of note, LYN interacted with FcγRIIb2 upon exposure to Aβ1–42 and phosphorylated FcγRIIb2 at Tyr273 within immunoreceptor tyrosine‐based inhibitory motif in neuronal cells. With the use of the structure‐based drug design, we isolated KICG2576, an ATP‐competitive inhibitor of LYN. Determination of cocrystal structure illustrated that KICG2576 bound to the cleft in the LYN kinase domain and inhibited LYN with a half‐maximal inhibitory concentration value of 0.15 µM. KICG2576 inhibited Aβ‐ or FcγRIIb2‐induced cell death, and this effect was better than pyrazolopyrimidine 1, a widely used inhibitor of SFK. Upon exposure to Aβ, KICG2576 blocked the phosphorylation of FcγRIIb2 and translocation of phosphatidylinositol 3,4,5‐trisphosphate 5‐phosphatase 2, a binding protein to the phosphorylated FcγRIIb2, to the plasma membrane, resulting in the inhibition of tau hyperphosphorylation, the downstream event of Aβ1–42‐FcγRIIb2 binding. Furthermore, intracerebroventricular injection of KICG2576 into mice ameliorated Aβ‐induced memory impairment. These results suggest that LYN plays a crucial role in Aβ1–42‐mediated neurotoxicity and tau pathology, providing a therapeutic potential of LYN in AD. —Gwon, Y. , Kim, S. ‐H. , Kim, H. T. , Kam, T. ‐I. , Park, J., Lim, B. , Cha, H. , Chang, H. ‐J., Hong, Y. R. , Jung, Y. ‐K. Amelioration of amyloid β‐FcγRIIb neurotoxicity and tau pathologies by targeting LYN. FASEB J. 33, 4300–4313 (2019). www.fasebj. org
Decision Making in Emergency Management: The Role of Social Media

Researchers and practitioners alike recognise the importance of emergency management (EM) in limiting the adverse impacts of crisis events, as well as the promise of social media to support these efforts. Decision making, which is crucial to ensure the effective management of immediate, emerging, and sustained crises, is one facet of EM potentially affected by social media. While much research has investigated social media in a crisis context more generally, little is known thus far about what it means for EM decision making. In this paper, we investigate the current knowledge base of this phenomenon and infer from it factors that are crucial for its understanding. To this end, we propose an analytical framework of EM decision making based on previous work on complex problem solving and social media networks. We then systematically review and rethink existing research from a decisioncentred point of view to identify and synthesise key findings that are relevant to the role of social media in the EM decision-making process. Finally, we outline the research gaps that need to be closed to arrive at a more comprehensive understanding of social media for EM decision support and to begin moving towards theoretically grounded explanations of the phenomenon.
Towards a Framework for Digital Transfor-Mation Success in manufacturing

Digital Transformation (DT) affects whole enterprises and is expected to drive a disruptive change in the way people work. Digital technologies leverage changes from simple tasks to the enterprise-wide strategy. Enterprises expect major benefits from investments in DT. However, digital transformation is a complex process and hence difficult to understand. Many different use scenarios exist so that decisions about the adoption of technologies are challenging. Therefore, it is critical to understand which benefits might be achieved with DT. With our research, we contribute to the understanding of digital transformation success. We develop and evaluate a framework that covers the main dimensions of digital transformation success. Literature from IS success and DT research is used to identify these dimensions. To evaluate this framework, we use data gained in a qualitative approach. We combine findings from a literature research with qualitative results to offer deeper insights into peoples' understanding of what shapes the success. The framework is useful to classify benefits achieved by DT and to point out new possibilities of gaining success with DT.
The Collaboration of Crowd Workers

Crowdsourcing is used for problem solving in different domains. A promising key to optimal solutions is collaboration among crowd workers. However, due to the distributed and asynchronous nature of crowd work, often with a large number of heterogeneous, anonymous and varying workers, crowd collaboration support is challenging. Thus, platform providers and crowdsourcers still struggle with or refrain from making full use of the potential of collaboration. The current state of research on this field explores this topic mostly for a specific domain, such as idea contests. This paper widens this scope and aims to validate a general process design framework for collaboration in crowdsourcing across various domains in an ongoing design science research project. To achieve this, we analyze current projects on crowdsourcing platforms with a conceptual process structure and a corresponding set of criteria for effective crowd collaboration support. We conduct a content analysis of ten real world projects to gain insights on their collaboration support features and collaborative interactions of crowd workers. This paper contributes to crowdsourcing research and practice by deriving recommendations for advancing the collaboration process design framework as well as for improving the conclusiveness of collaboration support on crowdsourcing platforms.
Accessibility of substituted cysteines in TM2 and TM10 transmembrane segments in the Plasmodium falciparum equilibrative nucleoside transporter PfENT1

Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophic. They import purines via an equilibrative nucleoside transporter (ENT). In P. falciparum, the most virulent species, the equilibrative nucleoside transporter 1 (PfENT1) represents the primary purine uptake pathway. This transporter is a potential target for the development of antimalarial drugs. In the absence of a high-resolution structure for either PfENT1 or a homologous ENT, we used the substituted cysteine accessibility method (SCAM) to investigate the membrane-spanning domain structure of PfENT1 to identify potential inhibitor-binding sites. We previously used SCAM to identify water-accessible residues that line the permeation pathway in transmembrane segment 11 (TM11). TM2 and TM10 lie adjacent to TM11 in an ab initio model of a homologous Leishmania donovani nucleoside transporter. To identify TM2 and TM10 residues in PfENT1 that are at least transiently on the water-accessible transporter surface, we assayed the reactivity of single cysteine-substitution mutants with three methanethiosulfonate (MTS) derivatives. Cysteines substituted for 12 of 14 TM2 segment residues reacted with MTS-ethyl-ammonium-biotin (MTSEA-biotin). At eight positions, MTSEA-biotin inhibited transport, and at four positions substrate transport was potentiated. On an α helical wheel projection of TM2, the four positions where potentiation occurred were located in a cluster on one side of the helix. In contrast, although MTSEA-biotin inhibited 9 of 10 TM10 cysteine-substituted mutants, the reactive residues did not form a pattern consistent with either an α helix or β sheet. These results may help identify the binding site(s) of PfENT1 inhibitors.
Poor Oral Health and Blood Pressure Control Among US Hypertensive Adults: Results From the National Health and Nutrition Examination Survey 2009 to 2014

Periodontal disease is a chronic inflammatory disorder of the tissues surrounding the teeth, with evidence of systemic effects. Some studies showed the benefit of periodontal therapy on blood pressure (BP), but the impact of periodontitis on BP control is unknown. We retrospectively analyzed cross-sectional, nationally representative data from treated hypertensive adults aged ≥30 years with and without periodontitis. BP was examined as both continuous (mm Hg) and categorical (treatment goal achievement status according to guidelines: at goal and above goal) variable according to the presence or absence of periodontitis and its clinical parameters (probing depth, clinical attachment loss, and disease severity [mild, moderate, and severe]). Systolic BP means and odds ratios for uncontrolled BP according to the presence and severity of periodontitis were calculated using progressively adjusted models. Among treated hypertensive adults, mean systolic BP was about 2.3 to 3 mm Hg higher in the presence of periodontitis (P<0.0001). Periodontitis was associated with unsuccessful antihypertensive treatment after multiple adjustments, with higher odds by disease severity. A good periodontal health is associated with better systolic BP profile during antihypertensive therapy by about 2.3 to 3 mm Hg and with lower odds of antihypertensive treatment failure. Dedicated studies are needed to test the impact of periodontal therapy on BP and the long-term effects on cardiovascular outcomes of this complementary approach to systemic health.
User Attitudes and Support in Health Information Systems Implementation - the Case of the Danish Sundhedsplatformen

The implementation of Health Information Systems (HIS) has been heralded as bringing numerous benefits to the healthcare sector. When implementing a HIS, the attitudes of the various users (nurses, doctors, admin people) towards the HIS can be influenced by a number of different factors. User support has proved to be one of the most important ones. Most recently, Sundhedsplatformen, one of the largest public HIS in Denmark, is being implemented in 18 hospitals across Zealand. In this context, we conducted 21 interviews at one of the major hospitals, Rigshospitalet, and qualitatively coded them. This allowed us to explore three archetypical groups of user attitudes toward Sundhedsplatformen: ‘Dedicated’, ‘Frustrated’ and ‘Despondent’. Further, we identified manifestations of insufficient user support on different levels. We clustered these elements into three levels of support: ‘Individual’, ‘Technological’ and ‘Organisational’. Reflecting on the manifestations of insufficient user support enables us to achieve a nuanced and holistic understanding of user support as an important adoption factor and further how user attitudes can be addressed when implementing HIS.
Exposure to N‐chlorotaurine induces oxidative stress responses in Aspergillus fumigatus

Purpose. The neutrophil‐derived oxidant N‐chlorotaurine (NCT) displays remarkable in vivo tolerability and efficacy against a range of pathogens. The aim of this study was to characterize the response of the pulmonary pathogen Aspergillus fumigatus to NCT. Methodology. The effect of NCT on the growth and viability of A. fumigatus was characterized. NCT‐induced alteration of amino acids and gliotoxin from A. fumigatus mycelium was assessed. Label‐free shotgun quantitative proteomic analysis was performed on A. fumigatus exposed to NCT for 24 h. Results. Incubation of A. fumigatus with NCT at concentrations ranging from 6.8 to 55 mM decreased conidial growth and viability, and mycelium biomass relative to the controls. Exposure to NCT (13.77 mM) resulted in increased amino acids and gliotoxin levels from A. fumigatus mycelium. Exposure of A. fumigatus mycelium to NCT (6.8 mM) revealed an enrichment in proteins associated with the ribosome, transcription and translation and non‐ribosomal peptide biosynthesis (e.g. Pes1, Pes3), which play an essential role in oxidative stress resistance in A. fumigatus. A decrease in the abundance of proteins associated with fumagillin and pseurotin biosynthesis highlighted the anti‐virulence activity of NCT. Conclusion. These results indicate that NCT induces an oxidative stress response in A. fumigatus as evidenced by alterations in the proteome and inhibits conidial and mycelial growth. Clinical investigations of topical application of NCT to treat Aspergillus infections are encouraged.
Ketogenic diet for weight loss.

Is the ketogenic diet effective for weight loss? Ketogenic diets can help patients lose about 2 kg more than low-fat diets do at 1 year, but higher-quality studies show no difference. Weight loss peaks at about 5 months but is often not sustained. Individual weight change can vary from losing 30
Sleepmore in Seattle: Later school start times are associated with more sleep and better performance in high school students

After a 55-min delay in high school start times, students increased their sleep significantly and improved attendance and grades. Most teenagers are chronically sleep deprived. One strategy proposed to lengthen adolescent sleep is to delay secondary school start times. This would allow students to wake up later without shifting their bedtime, which is biologically determined by the circadian clock, resulting in a net increase in sleep. So far, there is no objective quantitative data showing that a single intervention such as delaying the school start time significantly increases daily sleep. The Seattle School District delayed the secondary school start time by nearly an hour. We carried out a pre-/post-research study and show that there was an increase in the daily median sleep duration of 34 min, associated with a 4.5% increase in the median grades of the students and an improvement in attendance.
Observational Study Examining the Association of Baseline Frailty and Postcardiac Surgery Delirium and Cognitive Change.

BACKGROUND Frailty is a geriatric syndrome thought to identify the most vulnerable older adults, and morbidity and mortality has been reported to be higher for frail patients after cardiac surgery compared to nonfrail patients. However, the cognitive consequences of frailty after cardiac surgery have not been well described. In this study, we examined the hypothesis that baseline frailty would be associated with postoperative delirium and cognitive change at 1 and 12 months after cardiac surgery. METHODS This study was nested in 2 trials, each of which was conducted by the same research team with identical measurement of exposures and outcomes. Before surgery, patients were assessed with the validated "Fried" frailty scale, which evaluates 5 domains (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed) and classifies patients as nonfrail, prefrail, and frail. The primary outcome was postoperative delirium during hospitalization, which was assessed using the Confusion Assessment Method, Confusion Assessment Method for the Intensive Care Unit, and validated chart review. Neuropsychological testing was a secondary outcome and was generally performed within 2 weeks of surgery and then 4-6 weeks and 1 year after surgery, and the outcome of interest was change in composite Z-score of the test battery. Associations were analyzed using logistic and linear regression models, with adjustment for variables considered a priori (age, gender, race, education, and logistic European System for Cardiac Operative Risk Evaluation). Multiple imputation was used to account for missing data at the 12-month follow-up. RESULTS Data were available from 133 patients with baseline frailty assessments. Compared to nonfrail patients (13% delirium incidence), the incidence of delirium was higher in prefrail (48% delirium incidence; risk difference, 35%; 95% CI, 10%-51%) and frail patients (48% delirium incidence; risk difference, 35%; 95% CI, 7%-53%). In both univariable and multivariable models, the odds of delirium were significantly higher for prefrail (adjusted odds ratio, 6.43; 95% CI, 1.31-31.64; P = .02) and frail patients (adjusted odds ratio, 6.31; 95% CI, 1.18-33.74; P = .03) compared to nonfrail patients. The adjusted decline in composite cognitive Z-score was greater from baseline to 1 month only in frail patients compared to nonfrail patients. By 1 year after surgery, there were no differences in the association of baseline frailty with change in cognition. CONCLUSIONS Compared to nonfrail patients, both prefrail and frail patients were at higher risk for the primary outcome of delirium after cardiac surgery. Frail patients were also at higher risk for the secondary outcome of greater decline in cognition from baseline to 1 month, but not baseline to 1 year, after surgery.
Recommendations in Augmented Reality Applications - the effect of Customer Reviews and Seller Recommendations on Purchase Intention and Product Selection

Not only since the launch of Pokémon Go in July 2016, augmented reality (AR) has received a big boost in awareness and popularity. AR-based start-ups have entered the market, and established companies start to offer AR functionalities in their smartphone applications. A new distribution channel in form of augmented commerce has been emerging, although only little is known about optimized design of AR environments due to the limited number of user studies researching the effects of AR usage. This paper’s research objective is to tackle this gap by analysing AR technology in combination with online recommendations, a well-established, ubiquitous design element in today’s e-commerce. We conducted a controlled online experiment with 208 subjects to examine the effects of customer recommendations (CR) and increasingly emerging seller recommendations (SR) in AR applications. Our results demonstrate that CRs in AR applications positively influence the intention to purchase and the selection of products by decreasing a customer’s product fit uncertainty, whereas SRs displayed no significant influence. These insights are the first steps to further understand how AR and online recommendations can be used and have to be implemented to provide customers with novel and accepted sources of value.
Business Process Model Quality - Results from a Structured literature Review

Business process models are, among other things, used for documentation, reorganization and standardization purposes. However, no agreement on the quality dimensions relevant for business process models could be reached so far. In this paper, we try to contribute to the terminological discussion about business process model quality and aim to identify basic quality properties. For this reason, we examine how quality can be assessed depending on the intended purpose of the business process model. The resulting list of application scenarios is based on a structured literature review of 128 publications. The investigation shows that understandability and semantic quality are most frequently mentioned for several intended purposes of business process models. Our results can be considered as useful for research, since ‘business process model quality’ is linked to the intended purpose of business process models for the first time. In addition, the state of the art of the connections between quality dimensions of business process models is depicted.
Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs

Abstract Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. In vivo study confirms the regulation effects of ALKBH3 on growth of tumor xenograft. The m1A demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs) around the anticodon regions. tDRs are conserved among species, which strengthen the ribosome assembly and prevent apoptosis triggered by cytochrome c (Cyt c). Our discovery opens a potential and novel paradigm of tRNA demethylase, which regulates biological functions via generation of tDRs.
In situ hybridization detection and subtyping of rotaviruses in swine samples

Rotavirus groups A, B, and C (RVA, RVB, and RVC, respectively) have been the most prevalent and pathogenic in pigs. To date, immunohistochemistry is only available for RVA because of the lack of commercial antibodies for RVB and RVC. We developed a novel in situ hybridization RNA-based chromogenic technique (ISH-RNA) to detect and subtype RVA, RVB, and RVC. We evaluated 33 samples that were reverse-transcription PCR positive for RVA, RVB, and/or RVC. ISH-RNA was able to detect as few as 103 RV RNA copies/mL. The new ISH-RNA test can be useful for routine investigation of rotavirus enteritis in order to guide strategies for control of the infection in pigs, but a full validation study needs to be completed. Pathogenesis studies may be conducted using ISH-RNA based on the identification of replicating virus.
An Approach for Generation of SPARQL Query from SQL Algebra based Transformation Rules of RDB to Ontology

: Semantic web is a web of linked RDF data that can exchange and reuse data allowing for more use of traditional web documents. However, the huge amount of data on the web are still formed and stored in relational databases (RDBs), such data cannot be used directly via the Semantic Web. Consequently, construction of ontology (Semantic Web -side) from relational schema and data (RDBs - side) and querying of constructed ontology semantically are fundamental challenges for the development and integration of the Semantic Web from the data source (i.e. database). This paper proposes an approach for providing a formulated operation rules to express semantic queries against structured graph ontology in the relational query language SQL. This approach applied by rewriting SPARQL queries over generated ontology (i.e. RDF triples) corresponding to advantages of SQL relational algebra operation queries in RDBs and performed by two phases. The first phase focused on proposing and improving rules of extracting ontology directly from the important concepts in the relational database with considering database containing null-values to avoid data losses during the transformation process. The generated ontology represented in the form of OWL-RDFS/RDF triples to ensure its availability at Semantic Web, thus help semantic query engines to answer more queries. Furthermore, the first phase providing additional rules to generate the Internationalized Resource Identifiers (IRIs) for RDB schema and data. In the second phase, we proposed a set of rules inspired by fundamental operations of relational algebra (SQL algebra) for rewriting a relational algebra for SPARQL over RDBs that represented in RDF triples. In other words, translating SQL relational algebra operation queries into equivalent graph semantic queries (SPARQL). The proposed approach is demonstrated with examples, validated, implemented and compared with existing approach methods. The effectiveness of the proposed approach is evaluated by experimental results.