Miracle-dz/UniFAR-FTUs huggingface dataset:
microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome

Objective To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation. Methods miRNA and mRNA expression were measured by OpenArray and RNA-sequencing in pDCs of SLE, SLE + APS (APS secondary to SLE) and primary APS (PAPS) patients. The miRNA profile of patients was compared with the miRNA pattern of TLR7-activated pDCs. Results Among 131 miRNAs detected in pDCs, 35, 17 and 21 had a significantly lower level of expression in SLE, SLE + APS and PAPS patients, respectively, as compared with healthy controls (HC). Notably, the miRNA profile did not significantly differ between SLE and APS, but was driven by the presence or absence of an IFN signature. TLR7 stimulation induced a general downregulation of miRNAs, similar to the pattern observed in SLE and APS patients. miR-361-5p, miR-128-3p and miR-181a-2-3p expression was lower in patients with a high IFN signature (false discovery rate <0.05) as compared with patients with a low IFN signature and HCs. Pathway enrichment on the overlap of miRNA targets and upregulated genes from the RNAseq indicated that these miRNAs are involved in pDC activation and apoptosis. Conclusion Lower miRNA expression in pDCs is shared between SLE, SLE + APS and PAPS and is related to the IFN signature. As pDCs are the alleged source of the IFN signature in these patients, a better understanding of the molecular mechanisms/pathways leading to pDC dysregulation in SLE and APS might open novel pathways for therapeutic intervention.
Computational modeling of methionine cycle-based metabolism and DNA methylation and the implications for anti-cancer drug response prediction

The relationship between metabolism and methylation is considered to be an important aspect of cancer development and drug efficacy. However, it remains poorly defined how to apply this aspect to improve preclinical disease characterization and clinical treatment outcome. Using available molecular information from Kyoto Encyclopedia of Genes and Genomes (KEGG) and literature, we constructed a large-scale knowledge-based metabolic in silico model. For the purpose of model validation, we applied data from the Cancer Cell Line Encyclopedia (CCLE) to investigate computationally the impact of metabolism on chemotherapy efficacy. In our model, different metabolic components such as MAT2A, ATP6V0E1, NNMT involved in methionine cycle correlate with biologically measured chemotherapy outcome (IC50) that are in agreement with findings of independent studies. These proteins are potentially also involved in cellular methylation processes. In addition, several components such as 3,4-dihydoxymandelate, PAPSS2, UPP1 from metabolic pathways involved in the production of purine and pyrimidine correlate with IC50. This study clearly demonstrates that complex computational approaches can reflect findings of biological experiments. This demonstrates their high potential to grasp complex issues within systems medicine such as response prediction, biomarker identification using available data resources.
An investigation into the Omp85 protein BamK in hypervirulent Klebsiella pneumoniae, and its role in outer membrane biogenesis

Members of the Omp85 protein superfamily have important roles in Gram‐negative bacteria, with the archetypal protein BamA being ubiquitous given its essential function in the assembly of outer membrane proteins. In some bacterial lineages, additional members of the family exist and, in most of these cases, the function of the protein is unknown. We detected one of these Omp85 proteins in the pathogen Klebsiella pneumoniae B5055, and refer to the protein as BamK. Here, we show that bamK is a conserved element in the core genome of Klebsiella, and its expression rescues a loss‐of‐function ∆bamA mutant. We developed an E. coli model system to measure and compare the specific activity of BamA and BamK in the assembly reaction for the critical substrate LptD, and find that BamK is as efficient as BamA in assembling the native LptDE complex. Comparative structural analysis revealed that the major distinction between BamK and BamA is in the external facing surface of the protein, and we discuss how such changes may contribute to a mechanism for resistance against infection by bacteriophage.
Immunomodulation by adoptive regulatory T‐cell transfer improves Coxsackievirus B3‐induced myocarditis

Regulatory T (Treg) cells offer new therapeutic options for controlling undesired systemic and local immune responses. The aim of the current study was to determine the impact of therapeutic Treg administration on systemic and cardiac inflammation and remodeling in coxsackievirus B3 (CVB3) ‐induced myocarditis. Therefore, syngeneic Treg cells were applied intravenously in CVB3‐infected mice 3 d after infection. Compared with CVB3 + PBS mice, CVB3 + Treg mice exhibited lower left ventricle (LV) chemokine expression, accompanied by reduced cardiac presence of proinflammatory Ly6ChighCCR2highCx3Cr1low monocytes and higher retention of proin flammatory Ly6CmidCCR2highCx3Cr1low monocytes in the spleen. In addition, splenic myelopoiesis was reduced in CVB3 + Treg compared with CVB3 + PBS mice. Coculture of Treg cells with splenocytes isolated from mice 3 d post‐ CVB3 infection further demonstrated the ability of Treg cells to modulate monocyte differentiation in favor of the anti‐inflammatory Ly6ClowCCR2lowCx3Cr1high subset. Treg‐mediated immunomodulation was paralleled by lower collagen 1 protein expression and decreased levels of soluble and insoluble collagen in LV of CVB3 + Treg compared with CVB3 + PBS mice. In agreement with these findings, LV systolic and diastolic function was improved in CVB3 + Treg mice compared with CVB3 + PBS mice. In summary, adoptive Treg transfer in the inflammatory phase of viral‐induced myocarditis protects the heart against inflammatory damage and fibrosis via modulation of monocyte subsets. —Pappritz, K. , Savvatis, K. , Miteva, K. , Kerim, B. , Dong, F. , Fechner, H. , Müller, I. , Brandt, C. , Lopez, B. , González, A. , Ravassa, S. , Klingel, K. , Diez, J., Reinke, P., Volk, H. ‐D. , Van Linthout, S. , Tschöpe, C. Immunomod ulation by adoptive regulatory T‐cell transfer improves Coxsackievirus B3‐induced myocarditis. FASEB J. 32, 6066–6078 (2018). www.fasebj. org
The Persistent Homology Mathematical Framework Provides Enhanced Genotype-to-Phenotype Associations for Plant Morphology1[OPEN]

Persistent homology offers a mathematical framework to quantify diverse plant morphologies and significantly increases the ability to capture phenotypic variation caused by genetic introgressions. Efforts to understand the genetic and environmental conditioning of plant morphology are hindered by the lack of flexible and effective tools for quantifying morphology. Here, we demonstrate that persistent-homology-based topological methods can improve measurement of variation in leaf shape, serrations, and root architecture. We apply these methods to 2D images of leaves and root systems in field-grown plants of a domesticated introgression line population of tomato (Solanum pennellii). We find that compared with some commonly used conventional traits, (1) persistent-homology-based methods can more comprehensively capture morphological variation; (2) these techniques discriminate between genotypes with a larger normalized effect size and detect a greater number of unique quantitative trait loci (QTLs); (3) multivariate traits, whether statistically derived from univariate or persistent-homology-based traits, improve our ability to understand the genetic basis of phenotype; and (4) persistent-homology-based techniques detect unique QTLs compared to conventional traits or their multivariate derivatives, indicating that previously unmeasured aspects of morphology are now detectable. The QTL results further imply that genetic contributions to morphology can affect both the shoot and root, revealing a pleiotropic basis to natural variation in tomato. Persistent homology is a versatile framework to quantify plant morphology and developmental processes that complements and extends existing methods.
Associations of blood mitochondrial DNA copy number with social-demographics and cancer risk: results from the Mano-A-Mano Mexican American Cohort

The relationship between blood mitochondrial DNA (mtDNA) copy number and subsequent cancer risk has been investigated previously. However, such association has never been examined in Mexican Americans. In the current study, we examined association between social-demographic factors and blood mtDNA copy number, as well as longitudinal relationship between cancer and mtDNA copy number, among 10,802 Mexican Americans in the Mano-A-Mano Mexican American Cohort. Overall, mtDNA copy number was statistically significantly higher among participants who developed cancer during the study period than among cancer-free controls (0.17 vs 0.13, P = 0.007). Among cancer-free control participants, mtDNA copy number significantly differed by social-demographic characteristics. However, there was a large degree of heterogeneity in these effects across the mtDNA copy number distribution. In the longitudinal analysis, we observed that higher mtDNA copy number was positively associated with increased risk of all cancer types (adjusted hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.09–1.17). Participants with mtDNA copy number in the fourth (highest) quartile had a higher risk of all cancer (adjusted HR, 2.12; 95% CI, 1.65–2.73) than did participants in the first (lowest) quartile. In summary, our results in Mexican Americans support an association between increased mtDNA copy number and cancer risk. Our results also suggest that mtDNA copy number may be influenced by social and demographic factors.
Impact of a Bilingual Pharmacy Diabetes Service in a Federally Qualified Health Center

Background: Diabetes and its complications disproportionately affect Hispanic patients, many of whom receive care at federally qualified health centers (FQHCs) and prefer to receive care in a language other than English. There is little published data on clinical pharmacy diabetes services in this setting. Objective: This study aims to measure the impact of a Collaborative Drug Therapy Management–driven bilingual clinical pharmacy service on diabetes outcomes in an FQHC that primarily serves Hispanic patients, many of whom prefer to receive their care in Spanish. Methods: Patients were included if they had a diagnosis of diabetes and initial pharmacy visit between July 1, 2015, and March 31, 2016. Individual charts were analyzed for changes in hemoglobin A1C (A1C), changes in blood pressure (BP), number of visits, ethnicity, and primary language preference. Data for these patients were collected through September 30, 2016. Results: The median preintervention A1C was 10.5%; the median postintervention A1C was 9.1% (n = 211; P < 0.0001). Statistically significant BP reductions were also found in patients with uncontrolled hypertension at baseline. There were no statistically significant differences in A1C improvement based on ethnicity or language preference. Conclusion and Relevance: Patients with diabetes managed by Spanish-speaking clinical pharmacists had significant improvement in their A1C. Hispanic and non-Hispanic patients, as well as patients who preferred their care in Spanish, had similar improvements in A1C. Clinical pharmacists who speak Spanish may help reduce diabetes-related health disparities in this population. This collaborative care model could be replicated at other institutions to help underserved patients.
Learning Kolmogorov Models for Binary Random Variables

We consider a set of binary random variables and address the open problems of inferring provable logical relations among these random variables, and prediction. We propose to solve these two problems by learning a Kolmogorov model (KM) for these random variables. Our proposed framework allows us to derive provable logical relations, i.e., mathematical relations among the outcomes of the random variables in the training set, and thus, extract valuable relations from that set. The proposed method to discover the logical relations is established using implication in mathematical logic, thereby offering a provable analytical basis for asserting these relations, unlike similar factorization methods. We also propose an efficient algorithm for learning the KM model and show its first-order optimality, despite the combinatorial nature of the learning problem. We illustrate our general framework by applying to recommendation systems and gene expression data. In recommendation systems, the proposed logical relations identify groups of items for which a user liking an item logically implies that he/she likes all items in that group. Our work is a significant step toward interpretable machine learning.
Translating Hispanic Genomic Factors in Lung Cancer Into Clinical Practice: EGFR Testing for Improved Outcomes

1Department of Health Outcomes and Behavior, H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States 2Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States 3Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States 4Department of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, United States 5Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States
Visibility of Work: How Digitalization Changes the Workplace

Digitalization is rapidly reshaping our workplaces, as digital technologies often change individual’s work and collective work practices in significant but unpredictable ways. In this paper, we look at how digitalization changes the nature of work regarding work visibility, and examine this in the context of business-to-business (B2B) sales work. We report on a single case study using a practice approach to examine B2B sales work in a small SaaS company. Our findings show how the visibility of B2B sales work changes due to digitalization, increasing the visibility of work in relation to co-workers while decreasing it in relation to customers. Based on these findings, we discuss the complex tradeoffs in making work visible to different audiences and the gradual and constructed nature of work visibility.
Scientific Knowledge of the Human Side of Information Security as a Basis for Sustainable Trainings in Organizational Practices

Comprehensive digitization leads to new challenges because of cybercrime and related security countermeasures. There is no doubt that this will fundamentally affect our lives and is leading to an increase in the importance of information security (IS). However, technology solutions alone are not sufficient to ensure IS countermeasures. The human side of security is important to protect organizational assets like user information and systems. The paper illustrates these relationships in terms of information security awareness (ISA), examining its goals and the factors influencing it through the systematic analysis and review of scientific literature and the transfer of scientific knowledge for practical purposes. We reviewed the publications of leading academic journals in the field of IS over the
Legitimate Peripheral Participation in Hybrid FOSS Community Innovation

FOSS communities are increasingly employing a hybrid model where free, open source software development is combined with commercial customer support to ensure community sustainability. This makes it difficult for peripheral users, who are not part of the core administrative or sponsoring organization to participate meaningfully. The paper presents a study of modes of Legitimate Peripheral Participation by users who attempt to introduce product feature innovations to hybrid FOSS communities. We identify eight modes of virtual peripheral participation by users, exploring the technology and social/community affordances, and the performativity and participation effects that these engender to move peripheral users towards core membership.
Taimikonhoitotarpeen arviointi valtakunnan metsien inventoinnin metsävarakartan pohjalta

Valtakunnan metsien inventoinnin (VMI) tulokset osoittavat taimikoissa ja nuorissa metsissa olevan runsaasti hoitorasteja. Hoitotoiden edistamiseksi tarvitaan tarkasti paikannettua tietoa hoitokohteiden sijainnista. Tutkimuksessa selvitettiin satelliittikuvien kayttoon perustuvan metsaninventointiaineiston kayttokelpoisuutta hoitoa tarvitsevien kuvioiden paikantamisessa. Landsat TM -satelliittikuvien avulla tuotetusta VMI:n metsavarakartasta tuotettiin teemakartta taimikonhoitotarpeesta. Puuston pituusja lehtipuuosuustietojen perusteella tuotettu kartta ilmaisee taimikonhoidon ja nuoren metsan hoitotarpeen ja hoidon kiireellisyyden ajankohdan neljana luokkana. Maastotyona tehdyin tarkastusmittauksin selvitettiin karttatason luotettavuutta. Tulokset koottiin virhematriiseihin, joissa vertailtiin VMI-karttatason kiireellisyysluokitusta maastotarkastuksen pohjalta arvioituun kiireellisyysluokitukseen. Tutkimustulokset osoittivat, etta satelliittikuvatulkinnalla saadaan kayttokelpoista tietoa hoitokohteiden paikantamiseksi. Kankailla kiireellisyysluokituksen onnistuminen oli huomattavasti parempi kuin soilla. Kun hoitotarpeet voidaan paikantaa tarkasti, hoitotoita pystytaan kohdistamaan ja markkinoimaan paremmin maanomistajille ja taimikonhoitomaarat saadaan paremmin vastaamaan todellista tarvetta.
Variations in physiotherapy practices across reablement settings

ABSTRACT Background: Reablement aims to improve the self-dependence of people with or at risk of functional decline. Physiotherapists (PTs) are responsible for assessments, developing interventions and supervising home trainers (HTs), who mostly conduct the reablement training. The content of reablement practice is not clearly described. This study explores how physiotherapy practice is performed in reablement settings and the content of the service provided to reablement users. Methods: Fieldwork was performed in seven Norwegian reablement teams. We conducted observations of seven triads, including PTs, HTs, and reablement users, followed by interviews with the PTs and HTs. We then conducted a systematic content analysis. Results: Three themes emerged from the analysis: 1) division of labor; 2) assessment; and 3) intervention. Different practices within these three characteristics of practice revealed two typologies of reablement teams. Teams with a fixed division of labor provided limited assessments and a nonspecific approach. Teams with a flexible division of labor were characterized by interdisciplinary collaboration, thorough assessments, and user-tailored interventions. Discussion: Values emphasizing responsivity enable a flexible and individually tailored reablement approach, in contrast to values emphasizing efficiency, which facilitate a nonspecific approach.
Moderate patchiness optimizes heterogeneity, stability, and beta diversity in mesic grassland

Abstract Heterogeneous disturbance patterns are fundamental to rangeland conservation and management because heterogeneity creates patchy vegetation, broadens niche availability, increases compositional dissimilarity, and enhances temporal stability of aboveground biomass production. Pyrodiversity is a popular concept for how variability in fire as an ecological disturbance can enhance heterogeneity, but mechanistic understanding of factors that drive heterogeneity is lacking. Mesic grasslands are examples of ecosystems in which pyrodiversity is linked strongly to broad ecological processes such as trophic interactions because grazers are attracted to recently burned areas, creating a unique ecological disturbance referred to as the fire–grazing interaction, or pyric herbivory. But several questions about the application of pyric herbivory remain: What proportion of a grazed landscape must burn, or how many patches are required, to create sufficient spatial heterogeneity and reduce temporal variability? How frequently should patches burn? Does season of fire matter? To bring theory into applied practice, we studied a gradient of grazed tallgrass prairie landscapes created by different sizes, seasons, and frequencies of fire, and used analyses sensitive to nonlinear trends. The greatest spatial heterogeneity and lowest temporal variability in aboveground plant biomass, and greatest plant functional group beta diversity, occurred in landscapes with three to four patches (25%–33% of area burned) and three‐ to four‐year fire return intervals. Beta diversity had a positive association with spatial heterogeneity and negative relationship with temporal variability. Rather than prescribing that these results constitute best management practices, we emphasize the flexibility offered by interactions between patch number and fire frequency for matching rangeland productivity and offtake to specific management goals. As we observed no differences across season of fire, we recommend future research focus on fire frequency within a moderate proportion of the landscape burned, and consider a wider seasonal burn window.
Carcass fabrication yields of beef steers supplemented zilpaterol hydrochloride and offered ad libitum or maintenance energy intake1

Abstract An experiment was conducted to evaluate the fabrication yields of carcasses from beef steers supplemented zilpaterol hydrochloride (ZH) and fed at maintenance (MA) or ad libitum (AB) intake levels. Beef steers (n = 56) from a common sire were blocked (n = 28 per block) by terminal growth implant and sorted into pairs by BW. Four pairs (n = 8) were harvested on day 0; the remaining 24 pairs (n = 48) were assigned to a dietary intake level (MA or AB) and days on feed (28 or 56 d). Within pairs of MA or AB intakes, steers harvested on day 56 were randomly assigned to supplementation of ZH (90 mg·d−1 per steer) for 20 d followed by a withdrawal period of 4 d or control (C). Steers (BW = 603.5 ± 48.1 kg) were harvested at a commercial processing facility. After a 24-h chill period, standard USDA grading procedures were used to derive a calculated yield grade and quality grade. Following grading, left carcass sides were transported to the West Texas A&M University Meat Laboratory for fabrication. Each side was fabricated into subprimals to determine individual red meat yield (RMY), trimmable fat yield (TFY), and bone yield (BY). A mixed model was used for analysis; fixed effects included treatment combinations and random effects included block and pairs. Single df contrasts tested day 0 vs. 28, day 0 vs. 56, day 28 vs. 56, MA vs. AB, and C vs. ZH. Yield of chuck eye roll differed (P = 0.05) by days on feed (0 d = 4.14, 28 d = 4.11, 56 d = 4.55%). Similarly, eye of round yield was impacted (P = 0.02) by days on feed (0 d = 1.51, 28 d = 1.37, 56 d = 1.36%). Additionally, brisket yield was altered (P < 0.01) by days on feed (0 d = 4.08, 28 d = 3.56, 56 d = 3.48%) and treatment (C = 3.34, ZH = 3.61%). For remaining subprimals, no differences (P ≥ 0.15) were detected. Furthermore, results indicated that RMY tended (P = 0.07) to differ by treatment (C = 61.35, ZH = 63.67%). Comparatively, TFY was impacted (P = 0.04) by intake (MA = 20.44, AB = 23.33%). Results from this study indicate that a MA intake level during the last 56 d of the finishing period concurrent with ZH supplementation impacts subprimal yields as well as carcass RMY and TFY of beef steers.