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| 1 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 2 | Artificial intelligence applications in inflammatory bowel disease:Emerging technologies and future directions显示文摘Inflammatory bowel disease(IBD)is a complex and multifaceted disorder of the gastrointestinal tract that is increasing in incidence worldwide and associated with significant morbidity.The rapid accumulation of large datasets from electronic health records,high-definition multi-omics(including genomics,proteomics,transcriptomics,and metagenomics),and imaging modalities(endoscopy and endomicroscopy)have provided powerful tools to unravel novel mechanistic insights and help address unmet clinical needs in IBD.Although the application of artificial intelligence(AI)methods has facilitated the analysis,integration,and interpretation of large datasets in IBD,significant heterogeneity in AI methods,datasets,and clinical outcomes and the need for unbiased prospective validations studies are current barriers to incorporation of AI into clinical practice.The purpose of this review is to summarize the most recent advances in the application of AI and machine learning technologies in the diagnosis and risk prediction,assessment of disease severity,and prediction of clinical outcomes in patients with IBD. | John Gubatan Steven Levitte Akshar Patel Tatiana Balabanis Mike T Wei Sidhartha R Sinha | 2021 | World Journal of Gastroenterology2021，27，17： | 2 |
| 3 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 4 | Apparent digestibility of gross nutrients from feedstuffs in extruded feeds for rainbow trout (Oncorhynchus mykiss ) 显示文摘 | GAYLORD T G BARROWS F T STEVEN D R | 2008 | Journal of the World Aquaculture Society2008，39，6： | 1 |
| 5 | Atrazine:Mechanisms of hormonal imbalance in female SD rats显示文摘 | Chapin R E Stevens J T Hughes C L | 1996 | Funda Appl Toxicol1996，29，： | 1 |
| 6 | Finding drug targets in microbial genomes 显示文摘 | Timothy D R Steven R G Herve T | 2001 | Res Focus2001，6，17： | 1 |
| 7 | Atrazine: Mechanisms of hormonal imbalance in female SD rats 显示文摘 | Chapin R E Stevens J T Hughes C L | 1996 | Funda Appl Toxicol1996，29，： | 1 |
| 8 | Development of a statewide col- laborative to decrease NICU central line-associated bloodstream infec- tions 显示文摘 | Schulman J Stricof R Stevens T | 2009 | J Perinatol2009，29，： | 1 |
| 9 | The proto- toxin lynxl acts on nicotinic acetylcholine receptors to balance neuronal activity and survival in vivo显示文摘 | Miwa J M Stevens T R King S L | 2006 | Neu- ron2006，51，5： | 1 |
| 10 | Economic analy- sis of the treatment of posterior epistaxis 显示文摘 | Miller T R Stevens E S Orlandi R R | 2005 | Am J Rhi- nol2005，19，1： | 1 |
| 11 | Controlled multidose pharrnacwkinetic evaluation of two extended release carbamazepine formulations carbatro and tegreto 显示文摘 | STEVENS R E LIMSAKUN T EVANS G | 1998 | J Pharm Sci1998，87，12： | 1 |
| 12 | Does a latitudinal gradient in seedling survival favour larger seeds in the tropics显示文摘 | Moles A T Warton D I Stevens R D | 2004 | Ecology Letters2004，7，： | 1 |
| 13 | Provenance of silt and claywithin sandy deposits of the Lithuanian coastal zone(BalticSea)显示文摘 | Milda K Stevens R L Egidijus T | 2005 | Marine Geology2005，218，1： | 1 |
| 14 | Visibility and aerosol composition in Houston,Texas显示文摘 | Dzubay T G Stevens R K Lewis C W | 1982 | Environ Sci Technol1982，16，8： | 1 |
| 15 | Presence and severity of intensive care unit-acquired paresis at time of awakening are associated with increased intensive care unit and hospital mortality 显示文摘 | SHARSHAR T BASTUJI-GARIN S STEVEN R D | 2009 | Crit Care Med2009，37，12： | 1 |
| 16 | Converting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria显示文摘 | KANG T S WANG L STEVENS R C | 2010 | Mol Genet Metab2010，99，1： | 1 |
| 17 | Comparison of contingent valuation and conjoint analysis in ecosystem management显示文摘 | Stevens T Belkner R Dennis D | 2000 | Ecological Economics2000，32，1： | 1 |
| 18 | Economic analysis of the treatment of posterior epistaxis显示文摘 | MILLER T R STEVENS E S ORLANDI R R | 2005 | Am J Rhinol2005，19，： | 1 |
| 19 | Measuring the existence value of wildlife:What do CVM estimates really show?显示文摘 | Echeverria J Glass R J | 1991 | Land Economies1991，67，4： | 1 |
| 20 | Anomalous functional organi- zation of barrel cortex in GAP43 deficient mice 显示文摘 | Dubroff J G Stevens R T Hitt J | 2006 | Neuroimage2006，29，4： | 1 |
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