Effect of real-time computer-aided polyp detection system (ENDO-AID) on adenoma detection in endoscopists-in-training: a randomized trial

Background The effect of computer-aided polyp detection (CADe) on adenoma detection rate (ADR) among endoscopists-in-training remains unknown. Methods We performed a single-blind, parallel-group, randomized controlled trial in Hong Kong between April 2021 and July 2022 (NCT04838951). Eligible subjects undergoing screening/surveillance/diagnostic colonoscopies were randomized 1:1 to receive colonoscopies with CADe (ENDO-AID(OIP-1), Olympus Co., Japan) or not (control) during withdrawal. Procedures were performed by endoscopists-in-training with <500 procedures and <3 years’ experience. Randomization was stratified by patient age, sex, and endoscopist experience (beginner vs intermediate-level, <200 vs 200-500 procedures). Image enhancement and distal attachment devices were disallowed. Subjects with incomplete colonoscopies or inadequate bowel preparation were excluded. Treatment allocation was blinded to outcome assessors. The primary outcome was ADR. Secondary outcomes were ADR for different adenoma sizes and locations, mean number of adenomas, and non-neoplastic resection rate. Results 386 and 380 subjects were randomized to CADe and control groups, respectively. The overall ADR was significantly higher in CADe than control group (57.5% vs 44.5%, adjusted relative risk 1.41, 95%CI 1.17-1.72, p<0.001). The ADRs for <5mm (40.4% vs 25.0%) and 5-10mm adenomas (36.8% vs 29.2%) were higher in CADe group. The ADRs were higher in CADe group in both right (42.0% vs 30.8%) and left colon (34.5% vs 27.6%), but there was no significant difference in advanced ADR. The ADRs were higher in CADe group among beginners (60.0% vs 41.9%) and intermediate-level endoscopists (56.5% vs 45.5%). Mean number of adenomas (1.48 vs 0.86) and non-neoplastic resection rate were higher in CADe group (52.1% vs 35.0%). Conclusions Among endoscopists-in-training, the use of CADe during colonoscopies was associated with increased overall ADR. (ClinicalTrials.gov: NCT04838951

Inhibition of Hedgehog Signaling Decreases Proliferation and Clonogenicity of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology

Meeting the cultural and service needs of Arabic international students by using QFD

Quality has become an important factor in global competition for many reasons. Intensive global competition and the demand for better quality by customers has led organizations to realize the benefits of providing quality products and services in order to successfully compete and survive. Higher education institutions are one example of these organisations. Higher education institutions work in an intensive competitive environment worldwide driven by increasing demands for learning by local and international students. As a result, the managers of these sectors have realized that improving the quality of services is important for achieving customer satisfaction which can help survival in an internationally competitive market. To do this, it is necessary for organizations to know their customers and identify their requirements. To this end, many higher education institutions have adopted principles of total quality management (TQM) to improve their education quality which leads to better performance through involvement of every department to achieve excellence in business. This chapter considers the importance of measuring quality in order to assist universities to proactively manage the design and improvement of the social and academic experiences of postgraduate international students, and plan management decision-making processes to deliver high-quality services in a globalized business of provision of higher education. Higher education institutions must operate effectively and efficiently and be able to deliver quality programs, by seeking to better understand the needs of their customers to be competitive in this market space

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases

Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence

BACKGROUND: Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. OBJECTIVE: To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. METHODS: 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). FINDINGS AND CONCLUSIONS: In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955) polymorphism in the promoter

Constraints on sub-GeV dark-matter-electron scattering from the DarkSide-50 experiment

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOWe present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matterelectron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c(2).1211117FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2016/09084-0Agências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

DarkSide-50 532-day dark matter search with low-radioactivity argon

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe DarkSide-50 direct-detection dark matter experiment is a dual-phase argon time projection chamber operating at Laboratori Nazionali del Gran Sasso. This paper reports on the blind analysis of a (16 660 +/- 270) kg d exposure using a target of low-radioactivity argon extracted from underground sources. We find no events in the dark matter selection box and set a 90% C. L. upper limit on the dark matter-nucleon spin-independent cross section of 1.14 x 10(-44) cm(2) (3.78 x 10(-44) cm(2), 3.43 x 10(-43) cm(2)) for a WIMP mass of 100 GeV/c(2) (1 TeV/c(2), 10 TeV/c(2)).9810117FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2016/09084-0Agências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Search for dark matter annual modulation with DarkSide-50

Dark matter induced event rate in an Earth-based detector is predicted to show an annual modulation as a result of the Earth's orbital motion around the Sun. We searched for this modulation signature using the ionization signal of the DarkSide-50 liquid argon time projection chamber. No significant signature compatible with dark matter is observed in the electron recoil equivalent energy range above $40~{\rm eV_{ee}}$, the lowest threshold ever achieved in such a search.Comment: 8 pages, 4 figure

Search for dark matter-nucleon interactions via Migdal effect with DarkSide-50

Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c$^2$ mass dark matter. We present new constraints for sub-GeV/c$^2$ dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12306 $\pm$ 184) kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40 MeV/c$^2$. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below $3.6$ GeV/c$^2$.Comment: 7 pages, 3 figure