Miracle-dz/UniFAR-FTUs huggingface dataset:
Dehydroepiandrosterone (DHEA) Sensitizes Irinotecan to Suppress Head and Neck Cancer Stem-Like Cells by Downregulation of WNT Signaling

Purpose Current treatment options for head and neck squamous cell carcinoma (HNSCC) are limited, especially for cases with cancer stem cell-induced chemoresistance and recurrence. The WNT signaling pathway contributes to maintenance of stemness via translocation of β-catenin into the nucleus, and represents a promising druggable target in HNSCC. Dehydroepiandrosterone (DHEA), a steroid hormone, has potential as an anticancer drug. However, the potential anticancer mechanisms of DHEA including inhibition of stemness, and its therapeutic applications in HNSCC remain unclear. Methods Firstly, SRB assay and sphere formation assay were used to examine cellular viability and cancer stem cell-like phenotype, respectively. The expressions of stemness related factors were measured by RT-qPCR and western blotting. The luciferase reporter assay was applied to evaluate transcriptional potential of stemness related pathways. The alternations of WNT signaling pathway were measured by nuclear translocation of β-catenin, RT-qPCR and western blotting. Furthermore, to investigate the effect of drugs in vivo, both HNSCC orthotopic and subcutaneous xenograft mouse models were applied. Results We found that DHEA reduced HNSCC cell viability, suppressed sphere formation, and inhibited the expression of cancer-stemness markers, such as BMI-1 and Nestin. Moreover, DHEA repressed the transcriptional activity of stemness-related pathways. In the WNT pathway, DHEA reduced the nuclear translocation of the active form of β-catenin and reduced the protein expression of the downstream targets, CCND1 and CD44. Furthermore, when combined with the chemotherapeutic drug, irinotecan (IRN), DHEA enhanced the sensitivity of HNSCC cells to IRN as revealed by reduced cell viability, sphere formation, expression of stemness markers, and activation of the WNT pathway. Additionally, this combination reduced in vivo tumor growth in both orthotopic and subcutaneous xenograft mouse models. Conclusion These findings indicate that DHEA has anti-stemness potential in HNSCC and serves as a promising anticancer agent. The combination of DHEA and IRN may provide a potential therapeutic strategy for patients with advanced HNSCC.
A Novel Type I Interferon Primed Dendritic Cell Subpopulation in TREX1 Mutant Chilblain Lupus Patients

Heterozygous TREX1 mutations are associated with monogenic familial chilblain lupus and represent a risk factor for developing systemic lupus erythematosus. These interferonopathies originate from chronic type I interferon stimulation due to sensing of inadequately accumulating nucleic acids. We here analysed the composition of dendritic cell (DC) subsets, central stimulators of immune responses, in patients with TREX1 deficiency. We performed single-cell RNA-sequencing of peripheral blood DCs and monocytes from two patients with familial chilblain lupus and heterozygous mutations in TREX1 and from controls. Type I interferon pathway genes were strongly upregulated in patients. Cell frequencies of the myeloid and plasmacytoid DC and of monocyte populations in patients and controls were similar, but we describe a novel DC subpopulation highly enriched in patients: a myeloid DC CD1C+ subpopulation characterized by the expression of LMNA, EMP1 and a type I interferon- stimulated gene profile. The presence of this defined subpopulation was confirmed in a second cohort of patients and controls by flow cytometry, also revealing that an increased percentage of patient’s cells in the subcluster express costimulatory molecules. We identified a novel type I interferon responsive myeloid DC subpopulation, that might be important for the perpetuation of TREX1-induced chilblain lupus and other type I interferonopathies.
Self-Reported Clinical Practice of Small Animal Cardiopulmonary Resuscitation and Compliance With RECOVER Guidelines Among Veterinarians in Eight Western European Regions

Introduction The objective of this study was to assess whether small animal veterinarians across Western Europe are compliant with the 2012 cardiopulmonary resuscitation (CPR) guidelines by the Reassessment Campaign on Veterinary Resuscitation (RECOVER). Methods A previously published online questionnaire from Switzerland was adapted and translated into 7 languages, corresponding to national languages in Austria, France, Germany, Ireland, Italy, Liechtenstein, Netherlands, Portugal, Spain, and the United Kingdom. The survey was distributed via respective national veterinary organizations and social media outlets. A subset of questions was analyzed to evaluate respondent demographics, RECOVER guideline awareness, and to allocate composite compliance scores for CPR preparedness, basic life support (BLS) and advanced life support (ALS). Percentages of group total (95% confidence interval) were calculated. Multivariable logistic regression was used to evaluate the effects of region of practice, gender, age, specialty training, and guideline awareness on compliance. Odds ratios (95% confidence interval) were generated and significance set at P < 0.05. Results Nine-hundred and thirty respondents were included in analysis. Awareness of and compliance with RECOVER guidelines varied widely across regions. Compliance with all assessed RECOVER guideline recommendations was highest in Germany/Austria [14% (7- 27%)] and lowest in France and Portugal [0% (0–3%)]. CPR preparedness compliance was higher in participants aware of RECOVER guidelines [OR 10.1 (5.2-19.5)], those practicing in Germany/Austria [OR 4.1 (1.9–8.8)] or UK/Ireland [OR 2.2 (1.3–3.7)], and lower in those practicing in Portugal [OR 0.2 (0.1–0.9)]. Specialty training [OR 1.8 (1.1–2.9)], guideline awareness [OR 5.2 (3.2–8.6)], and practice in Germany/Austria [OR 3.1 (1.5–6.5)], UK/Ireland [OR 2.6 (1.7–4.1)], or the Netherlands [OR 5.3 (2.0–14.2)] were associated with increased BLS compliance. ALS compliance was higher in participants with guideline awareness [OR 7.0 (2.9–17.0)], specialty training [OR 6.8 (3.8–12.1)], those practicing in Germany/Austria [OR 3.5 (1.3–9.6)], UK/Ireland [OR 4.0 (1.9–8.3)], or Spain [OR 3.2 (1.2–8.3)] and in younger survey participants [OR 0.9 (0.9–1.0)]. Conclusions Awareness and compliance with RECOVER guidelines varied widely among countries surveyed, however overall compliance scores in all countries were considered low. Further research may highlight factors surrounding poor guideline awareness and compliance so targeted efforts can be made to improve veterinary CPR in Europe.
Nexus Between Financial Events and Emotional Exhaustion: Mediating Roles of Deliberate Thinking and Negative Interpersonal Events

Financial stress and emotional exhaustion have become prevalent elements of modern society, especially after COVID-19. This pandemic has changed people’s lives, particularly in a negative way. Individuals have begun to face the stress and emotional exhaustion associated with particular financial stressor events. However, limited studies have analyzed the relationship between financial stressor events and emotional exhaustion to date. Therefore, the current study aims to explore the relationship between different financial stressor events in an individual’s life and emotional exhaustion based on their well-being. This study also identifies the variables that play a mediating role in assessing the relationship between emotional exhaustion and financial stressor events. To achieve this, the researcher collected data from employees working in large organizations in May 2021 and December 2021. The study employs path analysis to assess the relationship between the identified variables. The study found that both organizations and employees are directly affected by financial stress, leading to emotional exhaustion or a decline in the mental well-being of the individuals. In addition, the study also found that financial stress and emotional exhaustion can directly affect the physical health of individuals. The study further revealed that deliberate thinking, negative interpersonal events, and individual characteristics are some of the identified variables that act as mediators between financial stressor events and emotional exhaustion.
Mapping Genetic Events of SARS-CoV-2 Variants

Genetic mutation and recombination are driving the evolution of SARS-CoV-2, leaving many genetic imprints which could be utilized to track the evolutionary pathway of SARS-CoV-2 and explore the relationships among variants. Here, we constructed a complete genetic map, showing the explicit evolutionary relationship among all SARS-CoV-2 variants including 58 groups and 46 recombination types identified from 3,392,553 sequences, which enables us to keep well informed of the evolution of SARS-CoV-2 and quickly determine the parents of novel variants. We found that the 5′ and 3′ of the spike and nucleoprotein genes have high frequencies to form the recombination junctions and that the RBD region in S gene is always exchanged as a whole. Although these recombinants did not show advantages in community transmission, it is necessary to keep a wary eye on the novel genetic events, in particular, the mutants with mutations on spike and recombinants with exchanged moieties on spike gene.
Pathways to Positive Youth Development in Malaysian Undergraduate Co-curricular Programs: A Moderated Mediation Model of Youth Voice and Psychological Hardiness

Youth voice is gaining more attention globally as a core feature of program quality within positive youth development programs. Few studies have examined the relationship between youth voice and positive youth development in high power-distance cultures, however, where young people often face psychological barriers to exercising decision-making in their work with program adults. Research is needed on the psychological mechanisms that might help youth thrive within settings that are less structurally and psychologically supportive of youth voice. Drawing on bioecological systems and hardiness theories, this quantitative correlational study evaluates the moderating effect of psychological hardiness on the relationship between youth voice, the mediators of program safety and engagement, and the 6 C’s of positive youth development. A moderated mediation model was tested among 436 first-year undergraduate co-curricular program participants from public universities in Malaysia (M = 21.192 years, SD = 1.191 years; 65.6% female). Youth voice positively predicted positive youth development; the relationship was partially mediated by program engagement, but not safety. The mediated pathway through program engagement was more predictive for hardier youth. By combining programmatic and individual psychological factors into the hypothesized model, this research identifies the potential importance of hardiness on the practice of youth voice for young adults in high power distance cultures. The findings highlight the need to identify other individual and programmatic factors that may contribute to the development of positive youth development in diverse cultural settings.
SteE Enhances the Virulence of Salmonella Pullorum in Chickens by Regulating the Inflammation Response

Salmonella enterica serovar Pullorum (S. Pullorum) is a host-specific pathogen, which causes acute gastroenteritis with high mortality in poultry. However, the association between steE, encoded by type III secretion system 2, and Salmonella virulence is not well-understood. To elucidate the functions of steE in S. Pullorum, ΔsteE strain was constructed using the λ-Red recombination technology. Compared to that in the wild-type, the deletion of steE in S. Pullorum reduced bacterial invasion, proliferation, and late apoptosis in the infected HD-11 cells. In addition, we analyzed the mRNA expression levels of effector genes and cytokines by qRT-PCR. SteE was associated with the regulation of various effector genes and inflammatory cytokines in HD-11 cells during S. Pullorum infection. The wild-type effector steE promoted the expression of anti-inflammatory cytokines (IL-4 and IL-10) and reduced that of pro-inflammatory cytokines (IL-1β, IL-6, and IL-12) compared to that in the ΔsteE-infected HD-11 cells and chicken spleens. Results from the chicken infection model showed that the deletion of steE resulted in significantly decreased colonization and long-term survival of the bacteria and alleviated pathological lesions compared to those in the wild-type. Further, steE increased the virulence of S. Pullorum in chickens by regulating the expression of inflammatory cytokines. Our findings provide insights into the persistent infection and autoimmunity associated with steE in S. Pullorum.
Effective Mechanisms for Improving Seed Oil Production in Pennycress (Thlaspi arvense L.) Highlighted by Integration of Comparative Metabolomics and Transcriptomics

Pennycress is a potentially lucrative biofuel crop due to its high content of long-chain unsaturated fatty acids, and because it uses non-conventional pathways to achieve efficient oil production. However, metabolic engineering is required to improve pennycress oilseed content and make it an economically viable source of aviation fuel. Research is warranted to determine if further upregulation of these non-conventional pathways could improve oil production within the species even more, which would indicate these processes serve as promising metabolic engineering targets and could provide the improvement necessary for economic feasibility of this crop. To test this hypothesis, we performed a comparative biomass, metabolomic, and transcriptomic analyses between a high oil accession (HO) and low oil accession (LO) of pennycress to assess potential factors required to optimize oil content. An evident reduction in glycolysis intermediates, improved oxidative pentose phosphate pathway activity, malate accumulation in the tricarboxylic acid cycle, and an anaplerotic pathway upregulation were noted in the HO genotype. Additionally, higher levels of threonine aldolase transcripts imply a pyruvate bypass mechanism for acetyl-CoA production. Nucleotide sugar and ascorbate accumulation also were evident in HO, suggesting differential fate of associated carbon between the two genotypes. An altered transcriptome related to lipid droplet (LD) biosynthesis and stability suggests a contribution to a more tightly-packed LD arrangement in HO cotyledons. In addition to the importance of central carbon metabolism augmentation, alternative routes of carbon entry into fatty acid synthesis and modification, as well as transcriptionally modified changes in LD regulation, are key aspects of metabolism and storage associated with economically favorable phenotypes of the species.
Long Non-Coding RNA LINC01929 Facilitates Cell Proliferation and Metastasis as a Competing Endogenous RNA Against MicroRNA miR-1179 in Non-Small Cell Lung Carcinoma

Introduction: Non-small cell lung carcinoma (NSCLC) constitutes most lung cancers and has a poor prognosis. LncRNAs are a potential repository for the discovery of cancer prognostic markers. This study explored the role of LINC01929 in NSCLC, both the clinical prognostic significance and the mechanism of its influence on cells. Materials and Methods: LINC01929 levels in 143 pairs of NSCLC tissues and non-cancerous tissues were detected by RT-qPCR. Kaplan-Meier curves and multivariate Cox regression assays were generated for evaluating the prognostic values of LINC01929. To evaluate the cellular function, an XTT assay and transwell invasion assays were performed. Results: LINC01929 was up-regulated in NSCLC tissues compared with healthy tissues. A positive correlation was observed between LINC01929 expression level and tumor T (p = 0.002) or N stage (p = 0.010). Patients with higher LINC01929 levels had shorter overall survival (p = 0.009). Compared with other factors, high LINC01929 expression was significantly associated with poor survival in univariate Cox analysis (HR: 2.485, 95%CI: 1.220–5.060, p = 0.012). After multivariate Cox regression assays, LINC01929 was a independent prognostic factor (HR: 3.021, 95%CI: 1.377–6.628, p = 0.006). miR-1179 was a target miRNA of LINC01929. Inhibited expression of LINC01929 significantly reduced the proliferation, migration, and invasion of NSCLC cells by targeting miR-1179. Discussion: This study revealed the upregulation of LINC01929 in NSCLC. This study supports previous studies showing LINC01929 as a potential prognostic factor for NSCLC.
Effect of Experiential Learning on Self-Esteem, Resilience and Tolerance for Disagreement

This paper attempts to explore the role of experiential learning in groups on the participants Self-esteem, Resilience and Tolerance for disagreement. Sample consisted of undergraduate students (N=41) from a seminary located in Nagpur. The Pre-test result showed that over all, initial participant’s responses fell within the normal ranges for self-esteem, resilience and tolerance for disagreement. Paired t test were computed for (N=41) who completed both the pre-test and post-test. These comparisons show a significant increase in means of self esteem, resilience and tolerance for disagreement scores. This increase indicates the importance of team-building workshop having recreation activities, games and exercises.
Introduction to Gaussian processes

Feedforward neural networks such as multilayer perceptrons are popular tools for nonlinear regression and classification problems. From a Bayesian perspective, a choice of a neural network model can be viewed as defining a prior probability distribution over non-linear functions, and the neural network's learning process can be interpreted in terms of the posterior probability distribution over the unknown function. (Some learning algorithms search for the function with maximum posterior probability and other Monte Carlo methods draw samples from this posterior probability). In the limit of large but otherwise standard networks, Neal (1996) has shown that the prior distribution over non-linear functions implied by the Bayesian neural network falls in a class of probability distributions known as Gaussian processes. The hyperparameters of the neural network model determine the characteristic length scales of the Gaussian process. Neal's observation motivates the idea of discarding parameterized networks and working directly with Gaussian processes. Computations in which the parameters of the network are optimized are then replaced by simple matrix operations using the covariance matrix of the Gaussian process. In this chapter I will review work on this idea by Williams and Rasmussen (1996), Neal (1997), Barber and Williams (1997) and Gibbs and MacKay (1997), and will assess whether, for supervised regression and classification tasks, the feedforward network has been superceded.
Image reconstruction and Monte Carlo simulations in the development of proton computed tomography for applications in proton radiation therapy

Proton therapy is a rapidly expanding form of cancer treatment. Because protons have a finite range in matter, this treatment modality allows for a greater degree of conformality than conventional external beam X-ray therapy. To maximize the inherent advantages of proton therapy, the range of protons inside the patient must be able to be predicted with millimetre resolution. In current clinical practice, proton therapy treatment plans are made with pre-treatment X-ray CT scans of the patient. To convert the X-ray CT Hounsfield units to proton relative stopping powers, which are required by the treatment planning software, an empirically derived calibration function is used, which is specific to each X-ray CT machine. However, because of the different dependence on Z and the Z/A ratio of X-ray attenuation and proton energy loss, the relationship between Hounsfield units and relative stopping powers is not unique. This conversion process leads to range uncertainties at treatment time. A preferable scenario is one in which the relative stopping power of each patient is reconstructed directly. This is the goal of proton computed tomography (pCT). Proton CT was first proposed in the 1960s but a clinical system is yet to be realised. Difficulties experienced in previous projects included long acquisition times and substandard spatial resolution relative to X-ray CT. The current pCT development project makes use of advances in high energy physics detector technology and focuses on generating pCT specific image reconstruction algorithms to counteract the aforementioned issues. The work presented in this Doctoral Thesis will focus on two aspects of the pCT development project; image reconstruction and Monte Carlo simulations to aid in the design of the first generation preclinical system. The current image reconstruction approach for our pCT concept is to treat individual proton paths as line integrals through the unknown object. The path of individual protons are predicted with a most likely path (MLP) formalism, which is based on spatial measurements made upstream and downstream of the object. Advances presented in this thesis include a more flexible derivation of the MLP, a more accurate implementation of the MLP in iterative reconstruction algorithms, the use of parallel compatible iterative reconstruction algorithms to speed up the image reconstruction process with parallel processing and the adaptation of other state-of-the-
Integrin LFA-1 Agonistic Antibodies to the I Domain of Antagonistic, Allosteric Antagonistic, and The Binding Sites for Competitive

We explore the binding sites for mAbs to the (cid:1) I domain of the integrin (cid:1) L (cid:2) 2 that can competitively inhibit, allosterically inhibit, or activate binding to the ligand ICAM-1. Ten mAbs, some of them clinically important, were mapped to species-speciﬁc residues. The results are interpreted with independent structures of the (cid:1) L I domain determined in seven different crystal lattices and in solution, and which are present in three conformational states that differ in afﬁnity for ligand. Six mAbs bind to adjacent regions of the (cid:2) 1- (cid:1) 1 and (cid:1) 3- (cid:1) 4 loops, which show only small (mean, 0.8 Å; maximum, 1.8 Å) displacements among the eight I domain structures. Proximity to the ligand binding site and to noncontacting portions of the ICAM-1 molecule explains competitive inhibition by these mAbs. Three mAbs bind to a segment of seven residues in the (cid:2) 5- (cid:1) 6 loop and (cid:1) 6 helix, in similar proximity to the ligand binding site, but on the side opposite from the (cid:2) 1- (cid:1) 1/ (cid:1) 3- (cid:1) 4 epitopes, and far from noncontacting portions of ICAM-1. These residues show large displacements among the eight structures in response to lattice contacts (mean, 3.6 Å; maximum, 9.4 Å), and movement of a buried Phe in the (cid:2) 5- (cid:1) 6 loop is partially correlated with afﬁnity change at the ligand binding site. Together with a lack of proximity to noncontacting portions of ICAM-1, these observations explain variation among this group of mAbs, which can either act as competitive or allosteric antagonists. One agonistic mAb binds distant from the ligand binding site
Validating Analytical Model for Steady-State Can Losses in a Canned Permanent Magnet Motor

ABSTRACT The canned permanent magnet motor (CPMM) is a more effective and safer technology as compared to the conventional motor pump when it comes to handling toxic, dangerous and corrosive liquids. This research work presents an electromagnetic analysis simulation and test validation of the analytical method in a steady-state condition for predicting the behaviour and can losses of these motors. The induced losses are computed in cans that are engaging both stator and rotor. Comparison between analytical method, finite element simulations and measured values are presented. This research contributes in the analysis and design of canned motor's pumps.