Miracle-dz/UniFAR-FTUs huggingface dataset:
University of Southern Denmark Associations of Cytomegalovirus Infection With All-Cause and Cardiovascular Mortality in Multiple Observational Cohort Studies of Older Adults

Citation for pulished version (APA): Chen, S. , Pawelec, G. , Trompet, S. , Goldeck, D. , Mortensen, L. H. , Slagboom, P. E. , Christensen, K. , Gussekloo, J., Kearney, P., Buckley, B. M. , Ford, I. , Jukema, J. W. , Westendorp, R. G. J., & Maier, A. B. (2021). Associations of Cytomegalovirus Infection With All-Cause and Cardiovascular Mortality in Multiple Observational Cohort Studies of Older Adults. The Journal of Infectious Diseases, 223(2), 238-246. https://doi.org/10.1093/infdis/jiaa480
Reward Devaluation in Autistic Children and Adolescents with Complex Needs: A Feasibility Study

Rewards act as a motivator for positive behavior and learning. Although compounding evidence indicates that reward processing operates differently in autistic individuals who do not have co‐occurring learning disabilities, little is known about individuals who have such difficulties or other complex needs. This study aimed first to assess the feasibility of using an adapted reward devaluation paradigm to examine basic reward processes in this underrepresented population, and second to investigate whether autistic children and adolescents with complex needs would show dynamic behavioral changes in response to changes in the motivational value of a reward. Twenty‐seven autistic children and adolescents with complex needs and 20 typically developing 5‐year‐old children took part in the study. Participants were presented with two visual cues on a touchscreen laptop, which triggered the delivery of a video, music, or physical reward. One of the rewards was then presented in abundance to decrease its motivational value. Participants showed decreased interest in the video and music rewards after devaluation. The experimental setup was found to be suitable to test individuals with complex needs, although recommendations are made for the use of physical rewards. The results suggest that autistic participants with complex needs demonstrate goal‐directed behavior and that it is feasible to develop experimental paradigms that can shed important light on learning processes that are fundamental to many education and intervention strategies for this population. Autism Res 2020, 13: 1915‐1928. © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.
Flavonoid induction of cytochrome P450 (CYP) in human esophageal carcinoma cells: implications for chemotherapy

Esophageal cancer ranks as the second most common cancer among black males in South Africa and patients often seek medical attention when the cancer has already reached advanced stages. Thus, there is a lot of work investigating factors associated with increased risk, biomarkers for early diagnosis as well as a search for suitable drugs to treat esophageal cancer. In this project, flavonoids were used on esophageal cancer cell lines to identify enzymes that are differentially expressed as well as to evaluate the flavonoids’ direct toxic effects on the cancer cells using ß-Naphthoflavone (BNF) on human esophageal cancer cell lines, WHCO1 and WHCO6. Differential expression of drug metabolising enzymes, CYP1A1, CYP1A2 and CYP1B1 was also investigated. BNF showed a moderate antiproliferative activity in WHCO6 cells (IC50~ 10μM) and a weak activity in WHCO1 cells (IC50~25 μM). Thus, suggesting that esophageal cancer cells may be responsive to the treatment with BNF. BNF resulted in the differential expression of CYP1A1, CYP1A2, and CYP1B1. These results, implicate CYP1 enzymes as potential therapeutic targets for esophageal cancer prevention.
University learning with anti-plagiarism systems

ABSTRACT We have designed an anti-plagiarism software to detect plagiarism in students’ assignments, especially written assignments, homework, and research reports, which will hereinafter be collectively referred to as student work. We used our university network to gather student work to detect plagiarism. To collect data, we used a domain name system to store the student work data based on the respective location, time, and the subject on which each student was assigned work. Once the student work data were collected, they were sent to an extraction module to remove unwanted data. The remaining data were then fed to a similarity index module, which produced similarity values based on comparisons between the collected data and the student work. This module uses mathematical equations that are built using semantic and syntactic similarity reports. Furthermore, in this study, we recommended procedures that can be applied to avoid plagiarism using the programming approach. This approach can raise awareness of plagiarism among students and encourage them to generate innovative ideas instead of plagiarizing. To attract faculty members to use the software, promotional materials can be customized based on the actual control factors that directly affect their adoption of the software. For example, the campaign should provide information highlighting the ease of implementation of the software for senior faculty members.
Detection of Indoor High-Density Crowds via Wi-Fi Tracking Data

Accurate detection of locations of indoor high-density crowds is crucial for early warning and emergency rescue during indoor safety accidents. The spatial structure of indoor environments is more complicated than outdoor environments. The locations of indoor high-density crowds are more likely to be the sites of security accidents. Existing detection methods for high-density crowd locations mostly focus on outdoor environments, and relatively few detection methods exist for indoor environments. This study proposes a novel detection framework for high-density indoor crowd locations termed IndoorSRC (Simplification–Reconstruction–Cluster). In this paper, a novel indoor spatiotemporal clustering algorithm called Indoor-STAGNES is proposed to detect the indoor trajectory stay points to simplify indoor movement trajectory. Then, we propose use of a Kalman filter algorithm to reconstruct the indoor trajectory and properly align and resample the data. Finally, an indoor spatiotemporal density clustering algorithm called Indoor-STOPTICS is proposed to detect the locations of high-density crowds in the indoor environment from the reconstructed trajectory. Extensive experiments were conducted using indoor Wi-Fi positioning datasets collected from a shopping mall. The results show that the IndoorSRC framework evidently outperforms the existing baseline method in terms of detection performance.
Clinical Significance of a MicroRNA Signature for the Identification and Predicting Prognosis in Colorectal Cancers with Mucinous Differentiation.

Accumulating evidence supports the fact that mere presence of mucinous differentiation in colorectal cancer (CRC), rather than its proportion, is a more accurate representative of a particular CRC subtype with distinct clinical and molecular features. In addition, the prognostic significance of mucinous carcinoma (MC) subtype remains poorly understood and biomarkers have been barely explored in this disease. Herein we have performed a systematic and comprehensive analysis in MCs and non-MCs and identified a panel of miRNAs that are differentially expressed between these two subtypes of CRC. Next, we interrogated their clinical significance and demonstrated their robust diagnostic and prognostic clinical ability in CRCs with mucinous differentiation. Finally, we established an integrative risk-assessment model by combining the miRNA-based risk scores together with TNM staging, which was a superior predictor of prognosis in mucinous CRC patients. Collectively, we report a novel miRNA biomarker panel for the identification and predicting survival in CRC patients with mucinous differentiation.
Potentiating the antitumor effects of chemotherapy with the selective PI3K inhibitor XL147

C199 Aberrant activity of the PI3K pathway is observed with high frequency in a variety of tumor types. PI3K signaling through its downstream effectors AKT and mTOR is known to promote tumor cell survival, proliferation and growth. Notably, dysregulation of PI3K signaling is thought to contribute to resistance to a variety of anti-cancer therapies, including receptor tyrosine kinase inhibitors and genotoxic agents. XL147 is a potent and orally bioavailable inhibitor that targets Class I PI3Ks. In cellular assays, treatment with XL147 reduces the levels of phosphatidylinositol-3,4,5-tris-phosphate (PIP3) and decreases phosphorylation of AKT and ribosomal S6 protein, two downstream effectors of PI3K signaling. In addition, XL147 demonstrates potent anti-angiogenic effects in a vascular endothelial growth factor-driven tubule formation assay and potent inhibition of hepatocyte growth factor-stimulated cell migration. Oral administration of XL147 results in significant inhibition of tumor growth in mice bearing xenografts in which PI3K signaling is activated, such as the PTEN-deficient PC-3 prostate adenocarcinoma and MDA-MB-468 breast adenocarcinoma models, or the K-Ras activated Calu-6 non-small cell lung carcinoma model. These effects on pathway signaling correlate with inhibition of tumor cell proliferation, inhibition of tumor angiogenesis, and induction of apoptosis as determined by immunohistochemical analysis. Moreover, combining XL147 in these models with other therapies, such as the mTOR/Raptor inhibitor rapamycin, the chemotherapeutic agents paclitaxel and carboplatin, or an epidermal growth factor receptor (EGFR) inhibitor, results in enhanced anti-tumor efficacy associated with a substantial increase in apoptosis when compared to the individual agents alone. Thus, XL147 may have broad utility in potentiating the effects of a wide range of other therapies in addition to its activity as a single agent in tumors where the PI3K pathway is dysregulated. A phase I clinical trial with XL147 has been initiated in patients with solid tumors.
The Association between Social Integration and Utilization of Essential Public Health Services among Internal Migrants in China: A Multilevel Logistic Analysis

This study investigated the association between social integration and utilization of essential public health services among internal migrants. Data were from the 2017 China Migrants Dynamic Survey. Social integration was measured through four dimensions: economic integration, structural integration, sociocultural adaptation, and self-identity. Multilevel logistic regressions were used taking into account heterogeneity in the level of regional development. The utilization of health records and health education was less than 40% and varied widely across regions. Social integration was related to a higher likelihood of utilization of health records and health education. Moreover, sociocultural adaptation had a stronger effect on the utilization of health records in developed regions than in developing regions, and structural integration was strongly and positively related to the utilization of health education in developed regions. Hence, it appears that the relationship of some dimensions of social integration and utilization of essential public health services is moderated by the level of economic development. Promoting structural integration and sociocultural adaptation could strongly improve utilization of essential public health services in developed regions.
Examining social determinants in use of assistive technology for race/ethnic groups of older adults

Abstract Objective Assistive technologies (AT) can compensate for activity limitations and loss of physical functioning. Little is known regarding how minority older adults differ in AT use as they age. This study examined race and ethnic differences in AT use among a nationally representative sample of older adults in the United States. Design Weighted logistic regression analyses were conducted using the 2012 Behavioural Risk Factor Surveillance System (BRFSS), collected annually by the Centres for Disease Control and Prevention (CDC). The study sample included 282,825 non-Hispanic White, African American, Asian and non-White Hispanic older adults. Activity limitation, health care access, overall health status and sociodemographic characteristics were included as variables in the analysis. Interaction analyses were conducted to examine the moderating effect of race/ethnicity on social determinants with AT use. Results Results indicated that 13.5% of older adults reported the use of an AT. African American older adults had the highest percentage of AT use (21.0%), and Asian older adults had the lowest (5.1%). Those who were 85 years and older, reported an activity limitation, were unmarried and in poor health were most likely to use an AT. Having health insurance was significantly associated with higher AT use for non-Hispanic Whites (OR = 1.66, p < 0.001) and non-White Hispanics (OR = 1.98, p < 0.01), but not African Americans and Asians. Conclusion Health professionals can promote access and address barriers in AT use, particularly in regard to accessibility and acceptability among minority older adults. Implications for rehabilitation African-Americans older adults were most likely to use ATs, and Asian older adults the least Older adults who were 85 years and older, reported an activity limitation, were unmarried and in poor health were most likely to use an AT Different social determinants to AT use were found among race/ethnic groups, highlighting the need to promote access and address barriers to health care utilization
Mouse models for abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) rupture is estimated to cause 200,000 deaths each year. Currently, the only treatment for AAA is surgical repair; however, this is only indicated for large asymptomatic, symptomatic or ruptured aneurysms, is not always durable, and is associated with a risk of serious perioperative complications. As a result, patients with small asymptomatic aneurysms or who are otherwise unfit for surgery are treated conservatively, but up to 70% of small aneurysms continue to grow, increasing the risk of rupture. There is thus an urgent need to develop drug therapies effective at slowing AAA growth. This review describes the commonly used mouse models for AAA. Recent research in these models highlights key roles for pathways involved in inflammation and cell turnover in AAA pathogenesis. There is also evidence for long non‐coding RNAs and thrombosis in aneurysm pathology. Further well‐designed research in clinically relevant models is expected to be translated into effective AAA drugs.
ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones

AAA+ (ATPases associated with diverse cellular activities) chaperones are involved in a plethora of cellular activities to ensure protein homeostasis. The function of AAA+ chaperones is mostly modulated by their hexameric/dodecameric quaternary structures. Here we report the structural and biochemical characterizations of a tetradecameric AAA+ chaperone, ClpL from Streptococcus pneumoniae. ClpL exists as a tetradecamer in solution in the presence of ATP. The cryo‐EM structure of ClpL at 4.5 Å resolution reveals a striking tetradecameric arrangement. Solution structures of ClpL derived from small‐angle X‐ray scattering data suggest that the tetradecameric ClpL could assume a spiral conformation found in active hexameric/dodecameric AAA+ chaperone structures. Vertical positioning of the middle domain accounts for the head‐to‐head arrangement of two heptameric rings. Biochemical activity assays with site‐directed mutagenesis confirmed the critical roles of residues both in the integrity of the tetradecameric arrangement and activities of ClpL. Non‐conserved Q321 and R670 are crucial in the heptameric ring assembly of ClpL. These results establish that ClpL is a functionally active tetradecamer, clearly distinct from hexameric/dodecameric AAA+ chaperones.
Records of RNA locations in living yeast revealed through covalent marks

Significance RNAs move within cells and often reside at specific locations. The need to detect those movements and locales across the transcriptome is pressing. We report an approach in living cells that provides a record of localization across the entire collection of RNAs a cell contains. It relies on covalently marking the RNA when it directly encounters a specific site. Using this approach, we identify a conserved battery of RNAs that are identified at more than one location in yeast and human cells, noncanonical modes of localization, and RNAs undergoing processing or surveillance at discrete subcellular locations. Our findings provide an entrée to the histories of individual RNA molecules through covalent marks. RNA movements and localization pervade biology, from embryonic development to disease. To identify RNAs at specific locations, we developed a strategy in which a uridine-adding enzyme is anchored to subcellular sites, where it directly marks RNAs with 3′ terminal uridines. This localized RNA recording approach yields a record of RNA locations, and is validated through identification of RNAs localized selectively to the endoplasmic reticulum (ER) or mitochondria. We identify a broad dual localization pattern conserved from yeast to human cells, in which the same battery of mRNAs encounter both ER and mitochondria in both species, and include an mRNA encoding a key stress sensor. Subunits of many multiprotein complexes localize to both the ER and mitochondria, suggesting coordinated assembly. Noncoding RNAs in the course of RNA surveillance and processing encounter both organelles. By providing a record of RNA locations over time, the approach complements those that capture snapshots of instantaneous positions.
Geographic variation in larval survival and growth of five Scirpophaga incertulas (Lepidoptera: Pyralidae) strains on different rice hosts

Survival and growth was measured for five geographically distinct strains of Scirpophaga incertulas (Walker) (the yellow stem borer) reared on three wild species of rice ( Oryza nivara, O. barthii , and O. officinalis ), three traditional cultivars of O. sativa rice (‘C018’, ‘W1253’, and ‘Rexoro’), and three modern, high yielding rice ( O. sativa ) cultivars (‘IR56’, ‘IR40’, and ‘IR62’). All yellow stem borer strains showed differential survival and weight gain across the nine rice hosts. There were significant differences in mean survival of the five stem borer strains on all of the rice hosts except two wild rices, O. nivara and O. officinalis , where all five strains had similar survival. Statistically significant host-by-strain interaction in both survival and weight indicates that differences among populations of the S. incertulas were host-dependent and were most likely the result of genetic differentiation. There was some indication of similarity between geographically related stem borer strains, but this was not consistent. The importance of these findings to the development of strategies for deploying rice varieties with resistance to S. incertulas is discussed.
Industrial Hemp (Cannabis sativa subsp. sativa) as an Emerging Source for Value-Added Functional Food Ingredients and Nutraceuticals

Industrial hemp (Cannabis sativa L., Cannabaceae) is an ancient cultivated plant originating from Central Asia and historically has been a multi-use crop valued for its fiber, food, and medicinal uses. Various oriental and Asian cultures kept records of its production and numerous uses. Due to the similarities between industrial hemp (fiber and grain) and the narcotic/medical type of Cannabis, the production of industrial hemp was prohibited in most countries, wiping out centuries of learning and genetic resources. In the past two decades, most countries have legalized industrial hemp production, prompting a significant amount of research on the health benefits of hemp and hemp products. Current research is yet to verify the various health claims of the numerous commercially available hemp products. Hence, this review aims to compile recent advances in the science of industrial hemp, with respect to its use as value-added functional food ingredients/nutraceuticals and health benefits, while also highlighting gaps in our current knowledge and avenues of future research on this high-value multi-use plant for the global food chain.
Efficiency of Different Treatment Regimens Combining Anti-tumor and Anti-inflammatory Liposomes for Metastatic Breast Cancer

Nanomedicines such as liposomes have been widely exploited in the treatment of tumors, and are also involved in combination therapies to enhance anti-tumor efficacy and reduce side effects. However, few studies have systematically discussed the significance and optimized regimens for nanomedicine-based combination therapy. In this study, we used anti-inflammatory and anti-tumor liposomes for co-administration, and compared three regimens: intermittent, metronomic, or sequential administration (IA, MA, and SA). The anti-inflammatory liposome HA/TN-CCLP was constructed in our previous research, which co-loaded curcumin (CUR) and celecoxib (CXB), modified with TAT-NBD peptide (TN) and finally coated with hyaluronic acid (HA), thereby inhibiting NF-κB and STAT3 pathways in the treatment of metastatic breast cancer. Furthermore, doxorubicin liposomes with and without TN modification (namely TN-DOXLP and DOXLP) were constructed and administrated with HA/TN-CCLP. The anti-tumor and anti-metastasis efficacy of different regimens was investigated. Results showed that in vitro cytotoxicity of DOXLP and TN-DOXLP was significantly enhanced when combined with HA/TN-CCLP. In vivo experiments also revealed the superiority of three combination therapies in inhibiting tumor growth, prolonging the survival of tumor-bearing mice, inducing apoptosis, and reducing lung metastases. In particular, the combination therapy could reduce MDSCs (Gr-1+/CD11b+) and CSCs (CD44+/CD24+) infiltration, which are two important factors in tumor metastasis and recurrence. Among three regimens, sequential administration (SA) showed the best therapeutic outcome and was especially effective for the inhibition of CSCs. In general, the results demonstrated that combination therapy, particularly the sequential administration of anti-inflammatory and anti-tumor liposome, was superior to monotherapy in inhibiting the development and metastasis of inflammation-related tumors.
Eosinophils and Neutrophils—Molecular Differences Revealed by Spontaneous Raman, CARS and Fluorescence Microscopy

Leukocytes are a part of the immune system that plays an important role in the host’s defense against viral, bacterial, and fungal infections. Among the human leukocytes, two granulocytes, neutrophils (Ne) and eosinophils (EOS) play an important role in the innate immune system. For that purpose, eosinophils and neutrophils contain specific granules containing protoporphyrin-type proteins such as eosinophil peroxidase (EPO) and myeloperoxidase (MPO), respectively, which contribute directly to their anti-infection activity. Since both proteins are structurally and functionally different, they could potentially be a marker of both cells’ types. To prove this hypothesis, UV−Vis absorption spectroscopy and Raman imaging were applied to analyze EPO and MPO and their content in leukocytes isolated from the whole blood. Moreover, leukocytes can contain lipidic structures, called lipid bodies (LBs), which are linked to the regulation of immune responses and are considered to be a marker of cell inflammation. In this work, we showed how to determine the number of LBs in two types of granulocytes, EOS and Ne, using fluorescence and coherent anti-Stokes Raman scattering (CARS) microscopy. Spectroscopic differences of EPO and MPO can be used to identify these cells in blood samples, while the detection of LBs can indicate the cell inflammation process.