AIM： To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal （UGI） bleeding under today＇s therapeutic regimen. METHODS： From 1998 to 2001, 121 patients with the diagnosis ...AIM： To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal （UGI） bleeding under today＇s therapeutic regimen. METHODS： From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients＇ data, a retrospective multivariate data analysis with initially more than 270 single factors was performed. Subsequently, the following potential risk factors underwent a logistic regression analysis： age, gender, initial hemoglobin, coumarines, liver cirrhosis, prothrombin time （PT）, gastric ulcer （small curvature）, duodenal ulcer （bulbus back wall）, Forrest classification, vascular stump, variceal bleeding, MalloryWeiss syndrome, RBC substitution, recurrent bleeding, conservative and surgical therapy. RESULTS： Seventy male （58%） and 51 female （42%） patients with a median age of 70 （range： 21-96） years were treated. Their in-hospital mortality was 14%. While 12% （11/91） of the patients died after conservative therapy, 20% （6/30） died after undergoing surgical therapy. UGI bleeding occurred due to duodenal ulcer （n = 36; 30%）, gastric ulcer （n = 35; 29%）, esophageal varicosis （n = 12; 10%）, Mallory-Weiss syndrome （n = 8, 7%）, erosive lesions of the mucosa （n = 20; 17%）, cancer （n = 5; 4%）, coagulopathy （n = 4; 3%）, lymphoma （n = 2; 2%）, benign tumor （n = 2; 2%） and unknown reason （n = 1, 1%）. A logistic regression analysis of all aforementioned factors revealed that liver cirrhosis and duodenal ulcer （bulbus back wall） were associated risk factors for a fatal course after UGI bleeding. Prior to endoscopy, only liver cirrhosis was an assessable risk factor. Thereafter, liver cirrhosis, the location of a bleeding ulcer （bulbus back wall） andpatients＇ gender （male） were of prognostic importance for the clinical outcome （mortality） of patients with a bleeding ulcer.CONCLUSION： Most prognostic parameters used in clinical routine today展开更多
Anthocyanins are flavonoid pigments that accumulate in the large central vacuole of most plants. Inside the vacuole, anthocyanins can be found uniformly distributed or as part of sub-vacuolar pigment bodies, the Antho...Anthocyanins are flavonoid pigments that accumulate in the large central vacuole of most plants. Inside the vacuole, anthocyanins can be found uniformly distributed or as part of sub-vacuolar pigment bodies, the Anthocyanic Vacuolar Inclusions （AVIs）. Using Arabidopsis seedlings grown under anthocyanin-inductive conditions as a model to un- derstand how AVIs are formed, we show here that the accumulation of AVIs strongly correlates with the formation of cyanidin 3-glucoside （C3G） and derivatives. Arabidopsis mutants that fail to glycosylate anthocyanidins at the 5-0 position （Sgt mutant） accumulate AVIs in almost every epidermal cell of the cotyledons, as compared to wild-type seedlings, where only a small fraction of the cells show AVIs. A similar phenomenon is observed when seedlings are treated with vanadate. Highlighting a role for autophagy in the formation of the AVIs, we show that various mutants that interfere with the autophagic process （atg mutants） display lower numbers of AVIs, in addition to a reduced accumulation of anthocyanins. Interestingly, vanadate increases the numbers of AVIs in the atg mutants, suggesting that several pathways might participate in AVl formation. Taken together, our results suggest novel mechanisms for the formation of sub-vacuolar compartments capable of accumulating anthocyanin pigments.展开更多
Blockade of the interaction of anaphylatoxin C5a with its receptor C5aR1 has been actively studied as a potential treatment for many inflammatory diseases;but current C5a antagonists exhibit inadequate potency and poo...Blockade of the interaction of anaphylatoxin C5a with its receptor C5aR1 has been actively studied as a potential treatment for many inflammatory diseases;but current C5a antagonists exhibit inadequate potency and poor species cross-reactivity, and novel biochemical tools are needed to investigate whether the core region of C5a contains important interaction epitopes that can explain these limitations. Herein, we report the development of chimeric protein C5a probes containing both the complete core region of rat or human C5a, and the small-molecule antagonist PMX53-1. These probes were chemically synthesized through hydrazide-based native chemical ligation of a linear peptide hydrazide with the requisite cyclopeptidic antagonist, both of which were made by solid-phase synthesis. Quasi-racemic X-ray crystallography established that attachment of PMX53-1 did not affect the structure of the core region of C5a. Subsequent C5aR1 activity assays demonstrated the probes can provide valuable insights into the development of C5a antagonists;for example, they exhibited significantly better binding affinity and much improved species cross-reactivity than PMX53-1, supporting the notion that the effect of some epitopes outside the C-terminus of C5a should be taken into consideration when designing better C5a antagonists. Surprisingly, the core region of C5a was found to partially agonize C5aR1, suggesting the presence of more than one agonistic interaction in the binding of C5a to C5aR1. This study exemplifies the value of chemical protein synthesis in developing novel receptor probes for drug discovery research.展开更多
3D geo spatial data have become the normal.However,to view the data,usually expert software is required,which have up to now hindered the wide spread use of 3D scenes for the display of geological data.The internet re...3D geo spatial data have become the normal.However,to view the data,usually expert software is required,which have up to now hindered the wide spread use of 3D scenes for the display of geological data.The internet real time 3D rendering framework X3D is assessed regarding its suitability for building a geological GIS on the internet.Especially important for geological data,3D rendering enhances the intuitive grasp of the data and enables the user to interactively explore it.It is often necessary to find a solution to distribute this data to a wide range of interested parties,experts and non-experts alike.According to the nature of 3D data,the best technique to display geo-data,the modeling of objects and unresolved issues have to be taken into consideration.The internet is the apparent tool for the public distribution and visualization of 3D data and it was found that through the open ISO-standardized format X3D it offers a multitude of possibilities.A 3D geological interactive map was created with these prerequisites to identify challenges and possibilities through this process.It was found that the use of lead to satisfactory results,that could probably not have been achieved with another technology.展开更多
The starting point of this paper is the idea that a comprehensive understanding of the earth and its systems calls for consideration of bygone views of the world.Creating facsimiles of antique globes in the form of di...The starting point of this paper is the idea that a comprehensive understanding of the earth and its systems calls for consideration of bygone views of the world.Creating facsimiles of antique globes in the form of digital globes provides a new opportunity to make such bygone world views accessible to a wide scientific audience.However,up to now,little practical experience in applying digital technology on globes has been made.Considering these attempts by thorough synopsis,this article deduces a comprehensive approach on virtual representations of antique globes that can be described by the superordinate concept of virtual representation.This concept comprises facilities of data acquisition of the original globe,ways of visualising the digitised globe and its final cartographic preparation.Applications that arise from this procedure are exemplified through both virtual hyperglobes and tactile hyperglobes.New findings on a 16th century earth globe are encouraging results of the presented virtual representation approach,which may offer a sustainable visualisation platform of interdisciplinary research.展开更多
The human striatum is essential for both lowand high-level functions and has been implicated in the pathophysiology of various prevalent disorders,including Parkinson's disease(PD)and schizophrenia(SCZ).It is know...The human striatum is essential for both lowand high-level functions and has been implicated in the pathophysiology of various prevalent disorders,including Parkinson's disease(PD)and schizophrenia(SCZ).It is known to consist of structurally and functionally divergent subdivisions.However,previous parcellations are based on a single neuroimaging modality,leaving the extent of the multi-modal organization of the striatum unknown.Here,we investigated the organization of the striatum across three modalities—resting-state functional connectivity,probabilistic diffusion tractography,and structural covariance—to provide a holistic convergent view of its structure and function.We found convergent clusters in the dorsal,dorsolateral,rostral,ventral,and caudal striatum.Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions,while the caudal striatum was related to action execution.Interestingly,significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ,but atrophy in the dorsolateral striatum was specifically attributable to PD.Our study revealed a cross-modal convergent organization of the striatum,representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.展开更多
Objectives: To examine the role of sequential dermoscopy imaging in detecting incipient melanoma and to elucidate the impact of length of follow-up on the relevance of observed changes. Design: Baseline and follow-up ...Objectives: To examine the role of sequential dermoscopy imaging in detecting incipient melanoma and to elucidate the impact of length of follow-up on the relevance of observed changes. Design: Baseline and follow-up images of melanomas and melanocytic nevi excised only because of changes across time were inspected on a computer screen and assessed according to prospectively defined criteria. Lesions were strati-fied into 3 groups according to the length of follow-up. Setting: Three hospital-based referral centers in Europe and Australia. Patients: Four hundred sixty-one patients selected for digital dermoscopy monitoring. Main Outcome Measures: Description and comparison of dermoscopy features and changes in melanomas and melanocytic nevi at baseline and after follow-up. Results: We inspected baseline and follow-up images of 499 melanocytic skin lesions from 461 patients. The histopathologic diagnosis was melanoma in 91 cases and melanocytic nevus in 408. Most melanomas (58.2%; n=53) were in situ, and the median thickness of invasive melanomas was 0.38 mm. Dermoscopy features of melanomas and nevi did not differ significantly at baseline. After follow-up of 1.5 to 4.5 months, 61.8%of the melanomas showed no specific dermoscopy features for melanoma. This value declined to 45.0%after follow-up of 4.5 to 8.0 months and to 35.1%after more than 8.0 months. We could not differentiate melanomas and changing nevi by means of observed changes or dermoscopy features when follow-up was shorter than 4.5 months. With longer follow-up, melanomas tended to enlarge asymmetrically with architectural and color changes, and nevi tended to enlarge symmetrically without architectural and color changes. Conclusions: Sequential dermoscopy imaging detects incipient melanomas when they are still featureless. Interpretation of changes observed during follow-up depends on the length of follow-up.展开更多
AIM:To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS:We used a digital library of HD i-scan still ...AIM:To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS:We used a digital library of HD i-scan still images, comprising twin pictures (surface enhancement and tone enhancement), collected at our university hospital. We defined endoscopic features of adenomatous and non-adenomatous polyps, according to the following parameters:color, surface pattern and vascular pattern. We familiarized the participating endoscopists on optical diagnosis of colorectal polyps using a 20-min didactic training session. All endoscopists were asked to evaluate an image set of 50 colorectal polyps with regard to polyp histology. We classified the diagnoses into high confidence (i.e., cases in which the endoscopist could assign a diagnosis with certainty) and low confidence diagnoses (i.e., cases in which the endoscopist preferred to send the polyp for formal histology). Mean sensitivity, specificity and accuracy per endoscopist/image were computed and differences between groups tested using independent-samples t tests. High vs low confidence diagnoses were compared using the pairedsamples t test. RESULTS:Eleven endoscopists without previous experience on optical diagnosis evaluated a total of 550 images (396 adenomatous, 154 non-adenomatous). Mean sensitivity, specificity and accuracy for diagnosing adenomas were 79.3%, 85.7% and 81.1%, respectively. No significant differences were found between gastroenterologists and trainees regarding performances of optical diagnosis (mean accuracy 78.0%vs 82.9%,P = 0.098). Diminutive lesions were predicted with a lower mean accuracy as compared to non-diminutive lesions (74.2% vs 93.1%, P = 0.008). A total of 446 (81.1%) diagnoses were made with high confidence. High confidence diagnoses corresponded to a significantly higher mean accuracy than low confidence diagnoses (84.0% vs 64.3%, P = 0.008). A total of 319 (58.0%) images were evaluated as having excellent quality. Considering ex展开更多
文摘AIM： To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal （UGI） bleeding under today＇s therapeutic regimen. METHODS： From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients＇ data, a retrospective multivariate data analysis with initially more than 270 single factors was performed. Subsequently, the following potential risk factors underwent a logistic regression analysis： age, gender, initial hemoglobin, coumarines, liver cirrhosis, prothrombin time （PT）, gastric ulcer （small curvature）, duodenal ulcer （bulbus back wall）, Forrest classification, vascular stump, variceal bleeding, MalloryWeiss syndrome, RBC substitution, recurrent bleeding, conservative and surgical therapy. RESULTS： Seventy male （58%） and 51 female （42%） patients with a median age of 70 （range： 21-96） years were treated. Their in-hospital mortality was 14%. While 12% （11/91） of the patients died after conservative therapy, 20% （6/30） died after undergoing surgical therapy. UGI bleeding occurred due to duodenal ulcer （n = 36; 30%）, gastric ulcer （n = 35; 29%）, esophageal varicosis （n = 12; 10%）, Mallory-Weiss syndrome （n = 8, 7%）, erosive lesions of the mucosa （n = 20; 17%）, cancer （n = 5; 4%）, coagulopathy （n = 4; 3%）, lymphoma （n = 2; 2%）, benign tumor （n = 2; 2%） and unknown reason （n = 1, 1%）. A logistic regression analysis of all aforementioned factors revealed that liver cirrhosis and duodenal ulcer （bulbus back wall） were associated risk factors for a fatal course after UGI bleeding. Prior to endoscopy, only liver cirrhosis was an assessable risk factor. Thereafter, liver cirrhosis, the location of a bleeding ulcer （bulbus back wall） andpatients＇ gender （male） were of prognostic importance for the clinical outcome （mortality） of patients with a bleeding ulcer.CONCLUSION： Most prognostic parameters used in clinical routine today
文摘Anthocyanins are flavonoid pigments that accumulate in the large central vacuole of most plants. Inside the vacuole, anthocyanins can be found uniformly distributed or as part of sub-vacuolar pigment bodies, the Anthocyanic Vacuolar Inclusions （AVIs）. Using Arabidopsis seedlings grown under anthocyanin-inductive conditions as a model to un- derstand how AVIs are formed, we show here that the accumulation of AVIs strongly correlates with the formation of cyanidin 3-glucoside （C3G） and derivatives. Arabidopsis mutants that fail to glycosylate anthocyanidins at the 5-0 position （Sgt mutant） accumulate AVIs in almost every epidermal cell of the cotyledons, as compared to wild-type seedlings, where only a small fraction of the cells show AVIs. A similar phenomenon is observed when seedlings are treated with vanadate. Highlighting a role for autophagy in the formation of the AVIs, we show that various mutants that interfere with the autophagic process （atg mutants） display lower numbers of AVIs, in addition to a reduced accumulation of anthocyanins. Interestingly, vanadate increases the numbers of AVIs in the atg mutants, suggesting that several pathways might participate in AVl formation. Taken together, our results suggest novel mechanisms for the formation of sub-vacuolar compartments capable of accumulating anthocyanin pigments.
基金supported by the National Key R&D Program of China (2017YFA0505200)the National Natural Science Foundation of China (21532004, 91753205, 81621002, 21621003)
文摘Blockade of the interaction of anaphylatoxin C5a with its receptor C5aR1 has been actively studied as a potential treatment for many inflammatory diseases;but current C5a antagonists exhibit inadequate potency and poor species cross-reactivity, and novel biochemical tools are needed to investigate whether the core region of C5a contains important interaction epitopes that can explain these limitations. Herein, we report the development of chimeric protein C5a probes containing both the complete core region of rat or human C5a, and the small-molecule antagonist PMX53-1. These probes were chemically synthesized through hydrazide-based native chemical ligation of a linear peptide hydrazide with the requisite cyclopeptidic antagonist, both of which were made by solid-phase synthesis. Quasi-racemic X-ray crystallography established that attachment of PMX53-1 did not affect the structure of the core region of C5a. Subsequent C5aR1 activity assays demonstrated the probes can provide valuable insights into the development of C5a antagonists;for example, they exhibited significantly better binding affinity and much improved species cross-reactivity than PMX53-1, supporting the notion that the effect of some epitopes outside the C-terminus of C5a should be taken into consideration when designing better C5a antagonists. Surprisingly, the core region of C5a was found to partially agonize C5aR1, suggesting the presence of more than one agonistic interaction in the binding of C5a to C5aR1. This study exemplifies the value of chemical protein synthesis in developing novel receptor probes for drug discovery research.
文摘3D geo spatial data have become the normal.However,to view the data,usually expert software is required,which have up to now hindered the wide spread use of 3D scenes for the display of geological data.The internet real time 3D rendering framework X3D is assessed regarding its suitability for building a geological GIS on the internet.Especially important for geological data,3D rendering enhances the intuitive grasp of the data and enables the user to interactively explore it.It is often necessary to find a solution to distribute this data to a wide range of interested parties,experts and non-experts alike.According to the nature of 3D data,the best technique to display geo-data,the modeling of objects and unresolved issues have to be taken into consideration.The internet is the apparent tool for the public distribution and visualization of 3D data and it was found that through the open ISO-standardized format X3D it offers a multitude of possibilities.A 3D geological interactive map was created with these prerequisites to identify challenges and possibilities through this process.It was found that the use of lead to satisfactory results,that could probably not have been achieved with another technology.
文摘The starting point of this paper is the idea that a comprehensive understanding of the earth and its systems calls for consideration of bygone views of the world.Creating facsimiles of antique globes in the form of digital globes provides a new opportunity to make such bygone world views accessible to a wide scientific audience.However,up to now,little practical experience in applying digital technology on globes has been made.Considering these attempts by thorough synopsis,this article deduces a comprehensive approach on virtual representations of antique globes that can be described by the superordinate concept of virtual representation.This concept comprises facilities of data acquisition of the original globe,ways of visualising the digitised globe and its final cartographic preparation.Applications that arise from this procedure are exemplified through both virtual hyperglobes and tactile hyperglobes.New findings on a 16th century earth globe are encouraging results of the presented virtual representation approach,which may offer a sustainable visualisation platform of interdisciplinary research.
基金This work was supported by the Deutsche Forschungsgemeinschaft(GE 2835/1-1,El 816/4-1)the Helmholtz Portfolio Theme 4 Supercomputing and Modelling for the Human Brain'and the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No.785907(HBP SGA2)We gratefully acknowledge financial support from the China Scholarship Council(201606750003).
文摘The human striatum is essential for both lowand high-level functions and has been implicated in the pathophysiology of various prevalent disorders,including Parkinson's disease(PD)and schizophrenia(SCZ).It is known to consist of structurally and functionally divergent subdivisions.However,previous parcellations are based on a single neuroimaging modality,leaving the extent of the multi-modal organization of the striatum unknown.Here,we investigated the organization of the striatum across three modalities—resting-state functional connectivity,probabilistic diffusion tractography,and structural covariance—to provide a holistic convergent view of its structure and function.We found convergent clusters in the dorsal,dorsolateral,rostral,ventral,and caudal striatum.Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions,while the caudal striatum was related to action execution.Interestingly,significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ,but atrophy in the dorsolateral striatum was specifically attributable to PD.Our study revealed a cross-modal convergent organization of the striatum,representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.
文摘Objectives: To examine the role of sequential dermoscopy imaging in detecting incipient melanoma and to elucidate the impact of length of follow-up on the relevance of observed changes. Design: Baseline and follow-up images of melanomas and melanocytic nevi excised only because of changes across time were inspected on a computer screen and assessed according to prospectively defined criteria. Lesions were strati-fied into 3 groups according to the length of follow-up. Setting: Three hospital-based referral centers in Europe and Australia. Patients: Four hundred sixty-one patients selected for digital dermoscopy monitoring. Main Outcome Measures: Description and comparison of dermoscopy features and changes in melanomas and melanocytic nevi at baseline and after follow-up. Results: We inspected baseline and follow-up images of 499 melanocytic skin lesions from 461 patients. The histopathologic diagnosis was melanoma in 91 cases and melanocytic nevus in 408. Most melanomas (58.2%; n=53) were in situ, and the median thickness of invasive melanomas was 0.38 mm. Dermoscopy features of melanomas and nevi did not differ significantly at baseline. After follow-up of 1.5 to 4.5 months, 61.8%of the melanomas showed no specific dermoscopy features for melanoma. This value declined to 45.0%after follow-up of 4.5 to 8.0 months and to 35.1%after more than 8.0 months. We could not differentiate melanomas and changing nevi by means of observed changes or dermoscopy features when follow-up was shorter than 4.5 months. With longer follow-up, melanomas tended to enlarge asymmetrically with architectural and color changes, and nevi tended to enlarge symmetrically without architectural and color changes. Conclusions: Sequential dermoscopy imaging detects incipient melanomas when they are still featureless. Interpretation of changes observed during follow-up depends on the length of follow-up.
文摘AIM:To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS:We used a digital library of HD i-scan still images, comprising twin pictures (surface enhancement and tone enhancement), collected at our university hospital. We defined endoscopic features of adenomatous and non-adenomatous polyps, according to the following parameters:color, surface pattern and vascular pattern. We familiarized the participating endoscopists on optical diagnosis of colorectal polyps using a 20-min didactic training session. All endoscopists were asked to evaluate an image set of 50 colorectal polyps with regard to polyp histology. We classified the diagnoses into high confidence (i.e., cases in which the endoscopist could assign a diagnosis with certainty) and low confidence diagnoses (i.e., cases in which the endoscopist preferred to send the polyp for formal histology). Mean sensitivity, specificity and accuracy per endoscopist/image were computed and differences between groups tested using independent-samples t tests. High vs low confidence diagnoses were compared using the pairedsamples t test. RESULTS:Eleven endoscopists without previous experience on optical diagnosis evaluated a total of 550 images (396 adenomatous, 154 non-adenomatous). Mean sensitivity, specificity and accuracy for diagnosing adenomas were 79.3%, 85.7% and 81.1%, respectively. No significant differences were found between gastroenterologists and trainees regarding performances of optical diagnosis (mean accuracy 78.0%vs 82.9%,P = 0.098). Diminutive lesions were predicted with a lower mean accuracy as compared to non-diminutive lesions (74.2% vs 93.1%, P = 0.008). A total of 446 (81.1%) diagnoses were made with high confidence. High confidence diagnoses corresponded to a significantly higher mean accuracy than low confidence diagnoses (84.0% vs 64.3%, P = 0.008). A total of 319 (58.0%) images were evaluated as having excellent quality. Considering ex
