Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic performance of serum pepsinogen assay for the prediction of atrophic gastritis and gastric neoplasms

Background: Serum pepsinogen assay (sPGA) combining concentration of pepsinogen I (PG I), and the ratio of PG I/II is the noninvasive biomarker for predicting chronic atrophic gastritis (CAG) and neoplasms reflecting mucosal secretory status. Although various cut-off values have been suggested, PG I ⩽70 ng/mL and PG I/II ⩽3 have been widely accepted. However, previous studies for diagnostic test accuracy presented only pooled outcomes, which cannot discriminate the diagnostic validity of sPGA with cut-off of PG I ⩽70 ng/mL and PG I/II ⩽3. Methods: We will search the core databases [MEDLINE (through PubMed), the Cochrane Library, and Embase] from their inception to December 2018 by 2 independent evaluators. The P.I. C.O. is as follows; Patients: who have histologically proven CAG or gastric neoplasms, Intervention: sPGA with cut-off of PG I ⩽70 ng/mL and/or PG I/II ⩽3, Comparison: none, Outcome: diagnostic performance indices of sPGA for CAG and gastric neoplasms (sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios) (if, true/false positive, true/false negative values are presented, diagnostic performance indices will be calculated). All types of study design with full text will be sought and included. The risk of bias will be assessed using the QUADAS-2 tool. Descriptive data synthesis is planned and quantitative synthesis (bivariate and HSROC model) will be used if the included studies are sufficiently homogenous. Publication bias will be assessed. Results: The results will provide clinical evidence for diagnostic validity of sPGA. Conclusion: This study will provide evidence of sPGA for predicting CAG and gastric neoplasms.
Functional polymorphisms on chromosome 5p15.33 disturb telomere biology and confer the risk of non‐small cell lung cancer in Chinese population

The chromosome 5p15.33 has been reported as a susceptibility locus for lung cancer. However, causal variants in this region have not been fully uncovered. In this study, we intended to identify functional polymorphisms associated with non‐small cell lung cancer (NSCLC) susceptibility in Chinese population. A targeted sequencing on 5p15.33 region was conducted in 400 NSCLC cases. We selected candidate variants by comparing genotypic frequency with data from 1000 Genomes Project, and their associations with NSCLC were validated in 985 cases and 970 controls. The relationships between risk variants and telomere length were evaluated in 774 healthy subjects. Luciferase assays and electrophoretic mobility shift assays (EMSA) were performed to explore potential functions and reveal carcinogenic mechanisms. As a result, we identified 1478 variants through targeted sequencing and selected 17 candidates. Four polymorphisms exhibited prominent associations with lung cancer risk, including rs7726159 (OR = 1.34, 95%CI: 1.18‐1.52, P = 7.78 × 10−6), rs10054203 (OR = 1.29, 95%CI: 1.13‐1.46, P = 1.37 × 10−4), rs2736107 (OR = 1.28, 95%CI: 1.11‐1.47, P = 5.14 × 10−4), and rs2853677 (OR = 1.23, 95%CI: 1.08‐1.39, P = 0.002). The minor allele of rs7726159 and rs10053203 were associated with long telomeres (P = 0.008 and 0.036, respectively). Mechanistically, the rs7726159‐A increased TERT transcription through mediating allele‐specific MYC binding. In conclusion, the functional variant rs7726159 confers lung cancer susceptibility might by affecting MYC binding and inducing telomere lengthening, which provides a new insight into the crucial role of telomere biology in tumorigenesis.
Twentieth Century Harmony Creative Aspects And Practice

Thank you for reading twentieth century harmony creative aspects and practice. Maybe you have knowledge that, people have look hundreds times for their chosen novels like this twentieth century harmony creative aspects and practice, but end up in malicious downloads. Rather than reading a good book with a cup of tea in the afternoon, instead they are facing with some infectious virus inside their laptop.
Identifying coupled clusters of allostery participants through chemical shift perturbations

Significance Allostery is a common strategy used by nature to transmit information in proteins, including membrane signaling systems, wherein binding of one ligand affects avidity for binding another ligand in a distal site. Methods are needed for elucidation of functional groups that are critical for coupling between the binding sites, which we call allosteric participants. Identifying and characterizing allosteric participants is important for understanding the allosteric mechanism and crucial for developing new drugs. We develop an NMR method to detect allosteric participants that relies on their multistate nature, and we apply this method to a membrane protein, the potassium channel KcsA. We confirm the importance of specific amino acid side chains for allostery through analysis of binding affinities. Allosteric couplings underlie many cellular signaling processes and provide an exciting avenue for development of new diagnostics and therapeutics. A general method for identifying important residues in allosteric mechanisms would be very useful, but remains elusive due to the complexity of long-range phenomena. Here, we introduce an NMR method to identify residues involved in allosteric coupling between two ligand-binding sites in a protein, which we call chemical shift detection of allostery participants (CAP). Networks of functional groups responding to each ligand are defined through correlated NMR perturbations. In this process, we also identify allostery participants, groups that respond to both binding events and likely play a role in the coupling between the binding sites. Such residues exhibit multiple functional states with distinct NMR chemical shifts, depending on binding status at both binding sites. Such a strategy was applied to the prototypical ion channel KcsA. We had previously shown that the potassium affinity at the extracellular selectivity filter is strongly dependent on proton binding at the intracellular pH sensor. Here, we analyzed proton and potassium binding networks and identified groups that depend on both proton and potassium binding (allostery participants). These groups are viewed as candidates for transmitting information between functional units. The vital role of one such identified amino acid was validated through site-specific mutagenesis, electrophysiology functional studies, and NMR-detected thermodynamic analysis of allosteric coupling. This strategy for identifying allostery participants is likely to have applications for many other systems.
The future of nanomedicine in optimising the treatment of inflammatory bowel disease

Abstract There have been major advancements in the treatment of inflammatory bowel disease (IBD) over the past three decades. However despite significant progress, the best available treatments continue to demonstrate variable efficacy in patients and are associated with adverse effects. Therefore there remains an unmet clinical need for ongoing therapeutic advances for IBD. In recent years nanomedicines have emerged as promising diagnostic and therapeutic tools. Nanoparticles in particular show promise to facilitate targeted oral drug delivery in IBD. Here we discuss the pitfalls of current therapies and explore the potential for nanoparticles to improve the treatment of IBD. This review examines the range of conventional and novel therapies which have benefited from nanoparticle-mediated delivery and highlights the proven therapeutic efficacy of this approach in preclinical models. These strategies under development represent a novel and innovative treatment for IBD.
The Intonation and Pragmatics of Greek wh-Questions

We experimentally tested three hypotheses regarding the pragmatics of two tunes (one high-ending, one flat-ending) used with Greek wh-questions: (a) the high-ending tune is associated with information-seeking questions, while the flat-ending tune is also appropriate when wh-questions are not information-seeking, in which case their function can instead be akin to that of a statement; (b) the high-ending tune is more polite, and (c) more appropriate for contexts leading to information-seeking questions. The wh-questions used as experimental stimuli were elicited from four speakers in contexts likely to lead to either information-seeking or non-information-seeking uses. The speakers produced distinct tunes in response to the contexts; acoustic analysis indicates these are best analysed as L*+H L-! H% (rising), and L+H* L-L% (flat). In a perception experiment where participants heard the questions out of context, they chose answers providing information significantly more frequently after high-ending than flat-ending questions, confirming hypothesis (a). In a second experiment testing hypotheses (b) and (c), participants evaluated wh-questions for appropriateness and politeness in information- and non-information-seeking contexts. High-ending questions were rated more appropriate in information-seeking contexts, and more polite independently of context relative to their flat-ending counterparts. Finally, two follow-up experiments showed that the interpretation of the two tunes was not affected by voice characteristics of individual speakers, and confirmed a participant preference for the high-ending tune. Overall, the results support our hypotheses and lead to a compositional analysis of the meaning of the two tunes, while also showing that intonational meaning is determined by both tune and pragmatic context.
Motor context dominates output from purkinje cell functional regions during reflexive visuomotor behaviours

The cerebellum integrates sensory stimuli and motor actions to enable smooth coordination and motor learning. Here we harness the innate behavioral repertoire of the larval zebrafish to characterize the spatiotemporal dynamics of feature coding across the entire Purkinje cell population during visual stimuli and the reflexive behaviors that they elicit. Population imaging reveals three spatially-clustered regions of Purkinje cell activity along the rostrocaudal axis. Complementary single-cell electrophysiological recordings assign these Purkinje cells to one of three functional phenotypes that encode a specific visual, and not motor, signal via complex spikes. In contrast, simple spike output of most Purkinje cells is strongly driven by motor-related tail and eye signals. Interactions between complex and simple spikes show heterogeneous modulation patterns across different Purkinje cells, which become temporally restricted during swimming episodes. Our findings reveal how sensorimotor information is encoded by individual Purkinje cells and organized into behavioral modules across the entire cerebellum.
Correlates of light physical activity among cancer survivors

Emerging evidence demonstrates the positive health benefits of light physical activity (LPA) for cancer survivors. Yet, little research has explored modifiable factors that facilitate or hinder LPA behavior in this population. Correlates of LPA among cancer survivors were examined, and stratified by moderate‐to‐vigorous physical activity (MVPA) status.
Robust Adaptive Control Scheme for Teleoperation Systems With Delay and Uncertainties

This paper proposes a robust adaptive algorithm that effectively copes with time-varying delay and uncertainties in Internet-based teleoperation systems. Time-delay induced by the communication network, as a major problem in teleoperation systems, along with uncertainties in modeling of robotic manipulators and remote environment warn the stability and performance of the system. A robust adaptive control algorithm is developed to deal with the system uncertainties and to provide a smooth estimation of delayed reference signals. The proposed control algorithm generates chattering-free torques which is one of the practical considerations for robotic applications. In addition, the achieved input-to-state stability gains do not necessarily require high gain control torques to retain the system’s stability. Experimental simulation studies validate the effectiveness of the proposed control strategy on a teleoperation system consisting of a Phantom Omni Haptic device and SimMechanics model of the industrial manipulator UR10. The validation of the proposed control methodology was executed through a real-time Internet-based communication established over 4G mobile networks between Australia and Scotland.
Modelling pancreatic β-cell inflammation in zebrafish identifies the natural product wedelolactone for human islet protection

ABSTRACT Islet inflammation and cytokine production are implicated in pancreatic β-cell dysfunction and diabetes pathogenesis. However, we lack therapeutics to protect the insulin-producing β-cells from inflammatory damage. Closing this clinical gap requires the establishment of new disease models of islet inflammation to facilitate screening efforts aimed at identifying new protective agents. Here, we have developed a genetic model of Interleukin-1β (Il-1β)-driven islet inflammation in zebrafish, a vertebrate that allows for non-invasive imaging of β-cells and in vivo drug discovery. Live imaging of immune cells and β-cells in our model revealed dynamic migration, increased visitation and prolonged macrophage retention in the islet, together with robust activation of NF-κB signalling in β-cells. We find that Il-1β-mediated inflammation does not cause β-cell destruction but, rather, it impairs β-cell function and identity. In vivo, β-cells exhibit impaired glucose-stimulated calcium influx and reduced expression of genes involved in function and maturity. These defects are accompanied by α-cell expansion, glucose intolerance and hyperglycemia following a glucose challenge. Notably, we show that a medicinal plant derivative (wedelolactone) is capable of reducing the immune-cell infiltration while also ameliorating the hyperglycemic phenotype of our model. Importantly, these anti-diabetic properties in zebrafish are predictive of wedelolactone's efficacy in protecting rodent and human islets from cytokine-induced apoptosis. In summary, this new zebrafish model of diabetes opens a window to study the interactions between immune and β-cells in vivo, while also allowing the identification of therapeutic agents for protecting β-cells from inflammation. Summary: A model of islet inflammation in zebrafish exhibits functional β-cell silencing and a lack of glucose responsiveness. A natural compound that rescues the glucose defect in zebrafish can protect human islets from inflammation.
Emerging Functional Imaging Biomarkers of Tumour Responses to Radiotherapy

Tumour responses to radiotherapy are currently primarily assessed by changes in size. Imaging permits non-invasive, whole-body assessment of tumour burden and guides treatment options for most tumours. However, in most tumours, changes in size are slow to manifest and can sometimes be difficult to interpret or misleading, potentially leading to prolonged durations of ineffective treatment and delays in changing therapy. Functional imaging techniques that monitor biological processes have the potential to detect tumour responses to treatment earlier and refine treatment options based on tumour biology rather than solely on size and staging. By considering the biological effects of radiotherapy, this review focusses on emerging functional imaging techniques with the potential to augment morphological imaging and serve as biomarkers of early response to radiotherapy.
Evaluation of SUMO1 and POU2AF1 in whole blood from rheumatoid arthritis patients and at risk relatives

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic and symmetrical inflammation of synovial tissue with subsequent joint destruction. SUMO1 is an important regulator of apoptosis through non‐canonical mechanism in synovial fibroblasts, and POU2AF1 is a known B‐cell transcriptional co‐activator. The specific objective of this study was to measure the expression of SUMO1 and POU2AF1 on first‐degree relatives of patients with RA and also in the preclinical and clinical stages of RA and describe their possible role in RA physiopathology. Blood samples were collected from ACPA+, ACPA‐, early and established RA subjects recruited. ACPAs and CarP autoantibodies were determined by ELISA Eurodiagnostica CCplus kit according to previously described protocols. RNA was isolated from blood samples; the purity as integrity was determined. Gene expression analysis was made by RT‐qPCR using specific primers for SUMO1 and POU2AF1 mRNAs; relative expression was determined according to the 2‐ΔΔct method procedure. Significant differences in the expression of both, SUMO1 and POU2AF1 were identified when comparing arthritis versus healthy or ACPA+ individuals, suggesting that the down regulation of such genes starts after the onset of symptoms in RA patients. Also, a significant correlation was identified for POU2AF1 and disease progression whit a downward trend for those with established RA. The implications of such gene down regulation are discussed in the context of RA physiopathology.
Differential Cytotoxicity of Different Sizes of Graphene Oxide Nanoparticles in Leydig (TM3) and Sertoli (TM4) Cells

Graphene oxide (GO) is an common nanomaterial and has attracted unlimited interest in academia and industry due to its physical, chemical, and biological properties, as well as for its tremendous potential in applications in various fields, including nanomedicine. Whereas studies have evaluated the size-dependent cytotoxicity of GO in cancer cells, there have been no studies on the biological behavior of ultra-small graphene nanosheets in germ cells. To investigate, for the first time, the cyto- and geno- toxic effects of different sizes of GO in two different cell types, Leydig (TM3) and Sertoli (TM4) cells, we synthesized different sized GO nanosheets with an average size of 100 and 20 nm by a modification of Hummers’ method, and characterized them by various analytical techniques. Cell viability and proliferation assays showed significant size- and dose-dependent toxicity with GO-20 and GO-100. Interestingly, GO-20 induced significant loss of cell viability and cell proliferation, higher levels of leakage of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) generation compared to GO-100. Both GO-100 and GO-20 induced significant loss of mitochondrial membrane potential (MMP) in TM3 and TM4 cells, which is a critical factor for ROS generation. Furthermore, GO-100 and GO-20 caused oxidative damage to DNA by increasing the levels of 8-oxo-dG, which is formed by direct attack of ROS on DNA; GO-100 and GO-20 upregulate various genes responsible for DNA damage and apoptosis. We found that phosphorylation levels of EGFR/AKT signaling molecules, which are related to cell survival and apoptosis, were significantly altered after GO-100 and GO-20 exposure. Our results showed that GO-20 has more potent toxic effects than GO-100, and that the loss of MMP and apoptosis are the main toxicity responses to GO-100 and GO-20 treatments, which likely occur due to EGFR/AKT pathway regulation. Collectively, our results suggest that both GO-100 and GO-20 exhibit size-dependent germ cell toxicity in male somatic cells, particularly TM3 cells, which seem to be more sensitive compared to TM4, which strongly suggests that applications of GO in commercial products must be carefully evaluated.
Association of the glycaemic index and the glycaemic load with colorectal cancer in the population of Córdoba (Argentina): results of a case-control study using a multilevel modelling approach.

The glycaemic index (GI) and glycaemic load (GL) are involved in the aetiology of different diseases, and they could be related to the development of colorectal cancer (CRC). The aim of this study was to evaluate the association between the quality and quantity indicators of carbohydrates consumed by the population of Córdoba (Argentina) and the odds of developing CRC in 2008–2016 period. A case–control study was conducted with 492 participants (161/331 cases/controls), interviewed through a validated FFQ. Multilevel logistic regression models were used to assess the effect of GI, GL and the quantity or weekly intake of high-GI foods on CRC occurrence, following adjustment for individual/first-level covariates, and using level of urbanisation as the contextual variable. The models were stratified by sex. Participants in the highest v. lowest tertile of dietary GL and weekly intake of high-GI foods had increased odds of CRC presence in the entire sample (OR 1·64, 95 % CI 1·16, 2·34 and OR 1·11, 95 % CI 1·09, 1·14, respectively) and in women (OR 1·98, 95 % CI 1·24, 3·18 and OR 1·41, 95 % CI 1·09, 1·83, respectively). In men, the second tertile of GL and weekly intake of high-GI foods were associated with CRC (OR 1·44, 95 % CI 1·04, 1·99 and OR 1·48, 95 % CI 1·32, 1·65, respectively). Also, GI was associated with CRC in women (highest v. lowest tertile OR 2·12, 95 % CI 1·38, 3·27). In addition to the quantity and quality of carbohydrates intake, it is important to consider the frequency of consumption of high-GI foods in CRC prevention.
Cell type-specific structural plasticity of the ciliary transition zone in C. elegans

Background information The current consensus on cilia development posits that the ciliary transition zone (TZ) is formed via extension of nine centrosomal microtubules. In this model, TZ structure remains unchanged in microtubule number throughout the cilium life cycle. This model does not however explain structural variations of TZ structure seen in nature, and could also lend itself to the misinterpretation that deviations from nine-doublet microtubule ultrastructure represent an abnormal phenotype. Thus, a better understanding of events that occur at the TZ in vivo during metazoan development is required. Results To address this issue, we characterized ultrastructure of two types of sensory cilia in developing Caenorhabditis elegans. We discovered that, in cephalic male (CEM) and inner labial quadrant (IL2Q) sensory neurons, ciliary TZs are structurally plastic and remodel from one structure to another during animal larval development. The number of microtubules doublets forming the TZ can be increased or decreased over time, depending on cilia type. Both cases result in structural TZ intermediates different from TZ in adult cilia. In CEM cilia, axonemal extension and maturation occurs concurrently with TZ structural maturation. Conclusions and Significance Our work extends the current model to include the structural plasticity of metazoan transition zone, which can be structurally delayed, maintained or remodeled in cell type-specific manner.
Heterogeneity in Response to Treatment of Adolescents with Severe Obesity: The Need for Precision Obesity Medicine

Treating pediatric severe obesity is challenging because of the complex biological, behavioral, and environmental factors that underpin the disease. The multifactorial etiology of obesity combined with the physiologic complexity of the energy regulatory system contributes to treatment variability. The goal of this secondary analysis of pooled data was to describe the degree of individual variation in response to various interventions among adolescents with severe obesity.