BACKGROUND Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy(UGE)to perform gastric juice analysis and real-time detection of Helicobacter pylori(H.pylori).AIM To assess...BACKGROUND Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy(UGE)to perform gastric juice analysis and real-time detection of Helicobacter pylori(H.pylori).AIM To assess the diagnostic performance of this technology and its impact on the management of H.pylori in the real-life clinical setting.METHODS Patients undergoing routine UGE were prospectively recruited.Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test(RUT).Gastric juice sampling and analysis was performed using the Endofaster,and the diagnosis of H.pylori was based on real-time ammonium measurements.Histological detection of H.pylori served as the diagnostic gold standard for comparing Endofaster-based H.pylori diagnosis with RUT-based H.pylori detection.RESULTS A total of 198 patients were prospectively enrolled in an H.pylori diagnostic study by Endofasterbased gastric juice analysis(EGJA)during the UGE.Biopsies for RUT and histological assessment were performed on 161 patients(82 men and 79 women,mean age 54.8±19.2 years).H.pylori infection was detected by histology in 47(29.2%)patients.Overall,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value(NPV)for H.pylori diagnosis by EGJA were 91.5%,93.0%,92.6%,84.3%,and 96.4%,respectively.In patients on treatment with proton pump inhibitors,diagnostic sensitivity was reduced by 27.3%,while specificity and NPV were unaffected.EGJA and RUT were comparable in diagnostic performance and highly concordant in H.pylori detection(κ-value=0.85).CONCLUSION Endofaster allows for rapid and highly accurate detection of H.pylori during gastroscopy.This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.展开更多
BACKGROUND Biliary microlithiasis/sludge is detected in approximately 30%of patients with idiopathic acute pancreatitis(IAP).As recurrent biliary pancreatitis can be prevented,the underlying aetiology of IAP should be...BACKGROUND Biliary microlithiasis/sludge is detected in approximately 30%of patients with idiopathic acute pancreatitis(IAP).As recurrent biliary pancreatitis can be prevented,the underlying aetiology of IAP should be established.AIM To develop a machine learning(ML)based decision tool for the use of endosonography(EUS)in pancreatitis patients to detect sludge and microlithiasis.METHODS We retrospectively used routinely recorded clinical and laboratory parameters of 218 consecutive patients with confirmed AP admitted to our tertiary care hospital between 2015 and 2020.Patients who did not receive EUS as part of the diagnostic work-up and whose pancreatitis episode could be adequately explained by other causes than biliary sludge and microlithiasis were excluded.We trained supervised ML classifiers using H_(2)O.ai automatically selecting the best suitable predictor model to predict microlithiasis/sludge.The predictor model was further validated in two independent retrospective cohorts from two tertiary care centers(117 patients).RESULTS Twenty-eight categorized patients’variables recorded at admission were identified to compute the predictor model with an accuracy of 0.84[95%confidence interval(CI):0.791-0.9185],positive predictive value of 0.84,and negative predictive value of 0.80 in the identification cohort(218 patients).In the validation cohort,the robustness of the prediction model was confirmed with an accuracy of 0.76(95%CI:0.673-0.8347),positive predictive value of 0.76,and negative predictive value of 0.78(117 patients).CONCLUSION We present a robust and validated ML-based predictor model consisting of routinely recorded parameters at admission that can predict biliary sludge and microlithiasis as the cause of AP.展开更多
Background:Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer(NSCLC),pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group pe...Background:Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer(NSCLC),pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status(ECOG PS)0-1 and a median age of 65 years or younger.We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy.Methods:This trial was a phase 3,open-label,randomised controlled study conducted at 91 sites in 23 countries across Asia,Europe,North America,and South America.Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3,or alternatively,being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy.Patients were randomised 2:1 by permuted-block randomisation(block size of six)to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy(vinorelbine[oral or intravenous]or gemcitabine[intravenous];dosing per local label)at 3-weekly or 4-weekly cycles.The primary endpoint was overall survival assessed in the intention-to-treat population.Safety analyses were conducted in the safety-evaluable population,which included all randomised patients who received any amount of atezolizumab or chemotherapy.This trial is registered with ClinicalTrials.gov,NCT03191786.展开更多
Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and spec...Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed byultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single "all-in-one" biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on micro RNA.展开更多
Despite the simple structure of male conifer cones, there is an enormous variability in cone properties observed upon more careful examination. The diversity ranges from simple cones to compound cones. Moreover, cones...Despite the simple structure of male conifer cones, there is an enormous variability in cone properties observed upon more careful examination. The diversity ranges from simple cones to compound cones. Moreover, cones can be distinguished according to different spatial distributions on the tree. Simple cones are distributed either as solitary cones or as fascicular or clustered aggregations, while compound cones only exhibit fascicular or clustered aggregations. Here, we demonstrate that these different spatial distribution patterns correlate with distinct leaf types and variable branching frequencies. Furthermore, we provide new insights into the evolution of the sporangiophore, particularly in Taxaceae. Two notably important and fast-evolving characters of conifers are the number of sporangia per sporangiophore and the number of sporangiophores per cone. We demonstrate, across many species and types of cones, how these characters are able to adjust according to the optimal amount of pollen.展开更多
作为锂离子电池的潜在替代品,钠离子电池由于成本、安全性等方面的优势吸引了广泛关注.但如何进一步提高其正极材料的能量密度仍是挑战,而通过激活阴离子氧化还原提供额外容量是一种可行的策略.本文报告了一种高性能锰基氧化物正极材料,...作为锂离子电池的潜在替代品,钠离子电池由于成本、安全性等方面的优势吸引了广泛关注.但如何进一步提高其正极材料的能量密度仍是挑战,而通过激活阴离子氧化还原提供额外容量是一种可行的策略.本文报告了一种高性能锰基氧化物正极材料,Na_(0.67)Mg_(0.1)Zn_(0.1)Mn_(0.8)O_(2)(NMZMO).通过共掺杂策略协同激活阴离子氧化还原,此材料首圈可以放出~233 mAh g^(-1)的超高容量,明显高于Mg或Zn单掺杂的同类材料.综合多种光谱技术,作者证明了更高的容量源于更强的阴离子氧化还原活性.结合中子全散射以及共振非弹性X射线散射发现,Mg与Zn在高电压下会向面外迁移至四面体位点,诱导面内重排形成空位团簇,将氧阴离子以分子O_(2)的形式困于其中.Mg/Zn共存时,刺激了彼此更多的向面外迁移,为形成更多晶内分子O_(2)提供先决条件.本文提出了关于阴离子氧化还原的新见解,并为高容量钠电正极材料的开发提供了理论依据.展开更多
基金Supported by the Deutsches Zentrum für Infektionsforschung,Partner Site Munich,Germany,No.TTU 06.715_00the Bavarian Ministry of Science and the Arts within the framework of the Bavarian Research Network“New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking–bayresq.net”.
文摘BACKGROUND Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy(UGE)to perform gastric juice analysis and real-time detection of Helicobacter pylori(H.pylori).AIM To assess the diagnostic performance of this technology and its impact on the management of H.pylori in the real-life clinical setting.METHODS Patients undergoing routine UGE were prospectively recruited.Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test(RUT).Gastric juice sampling and analysis was performed using the Endofaster,and the diagnosis of H.pylori was based on real-time ammonium measurements.Histological detection of H.pylori served as the diagnostic gold standard for comparing Endofaster-based H.pylori diagnosis with RUT-based H.pylori detection.RESULTS A total of 198 patients were prospectively enrolled in an H.pylori diagnostic study by Endofasterbased gastric juice analysis(EGJA)during the UGE.Biopsies for RUT and histological assessment were performed on 161 patients(82 men and 79 women,mean age 54.8±19.2 years).H.pylori infection was detected by histology in 47(29.2%)patients.Overall,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value(NPV)for H.pylori diagnosis by EGJA were 91.5%,93.0%,92.6%,84.3%,and 96.4%,respectively.In patients on treatment with proton pump inhibitors,diagnostic sensitivity was reduced by 27.3%,while specificity and NPV were unaffected.EGJA and RUT were comparable in diagnostic performance and highly concordant in H.pylori detection(κ-value=0.85).CONCLUSION Endofaster allows for rapid and highly accurate detection of H.pylori during gastroscopy.This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.
基金the Deutsche Forschungsgemeinschaft(German Research Foundation),No.413635475 to Sirtl Sthe LMU Munich Clinician Scientist ProgramŻorniak M is supported by the United European Gastroenterology Research Fellowship.
文摘BACKGROUND Biliary microlithiasis/sludge is detected in approximately 30%of patients with idiopathic acute pancreatitis(IAP).As recurrent biliary pancreatitis can be prevented,the underlying aetiology of IAP should be established.AIM To develop a machine learning(ML)based decision tool for the use of endosonography(EUS)in pancreatitis patients to detect sludge and microlithiasis.METHODS We retrospectively used routinely recorded clinical and laboratory parameters of 218 consecutive patients with confirmed AP admitted to our tertiary care hospital between 2015 and 2020.Patients who did not receive EUS as part of the diagnostic work-up and whose pancreatitis episode could be adequately explained by other causes than biliary sludge and microlithiasis were excluded.We trained supervised ML classifiers using H_(2)O.ai automatically selecting the best suitable predictor model to predict microlithiasis/sludge.The predictor model was further validated in two independent retrospective cohorts from two tertiary care centers(117 patients).RESULTS Twenty-eight categorized patients’variables recorded at admission were identified to compute the predictor model with an accuracy of 0.84[95%confidence interval(CI):0.791-0.9185],positive predictive value of 0.84,and negative predictive value of 0.80 in the identification cohort(218 patients).In the validation cohort,the robustness of the prediction model was confirmed with an accuracy of 0.76(95%CI:0.673-0.8347),positive predictive value of 0.76,and negative predictive value of 0.78(117 patients).CONCLUSION We present a robust and validated ML-based predictor model consisting of routinely recorded parameters at admission that can predict biliary sludge and microlithiasis as the cause of AP.
文摘Background:Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer(NSCLC),pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status(ECOG PS)0-1 and a median age of 65 years or younger.We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy.Methods:This trial was a phase 3,open-label,randomised controlled study conducted at 91 sites in 23 countries across Asia,Europe,North America,and South America.Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3,or alternatively,being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy.Patients were randomised 2:1 by permuted-block randomisation(block size of six)to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy(vinorelbine[oral or intravenous]or gemcitabine[intravenous];dosing per local label)at 3-weekly or 4-weekly cycles.The primary endpoint was overall survival assessed in the intention-to-treat population.Safety analyses were conducted in the safety-evaluable population,which included all randomised patients who received any amount of atezolizumab or chemotherapy.This trial is registered with ClinicalTrials.gov,NCT03191786.
文摘Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed byultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single "all-in-one" biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on micro RNA.
文摘Despite the simple structure of male conifer cones, there is an enormous variability in cone properties observed upon more careful examination. The diversity ranges from simple cones to compound cones. Moreover, cones can be distinguished according to different spatial distributions on the tree. Simple cones are distributed either as solitary cones or as fascicular or clustered aggregations, while compound cones only exhibit fascicular or clustered aggregations. Here, we demonstrate that these different spatial distribution patterns correlate with distinct leaf types and variable branching frequencies. Furthermore, we provide new insights into the evolution of the sporangiophore, particularly in Taxaceae. Two notably important and fast-evolving characters of conifers are the number of sporangia per sporangiophore and the number of sporangiophores per cone. We demonstrate, across many species and types of cones, how these characters are able to adjust according to the optimal amount of pollen.
基金supported by the National Key R&D Program of China(2020YFA0406203)Shenzhen Fundamental Research Program(GXWD20201231165807007-20200807125314001)the National Natural Science Foundation of China(U2032167 and 52072008)。
文摘作为锂离子电池的潜在替代品,钠离子电池由于成本、安全性等方面的优势吸引了广泛关注.但如何进一步提高其正极材料的能量密度仍是挑战,而通过激活阴离子氧化还原提供额外容量是一种可行的策略.本文报告了一种高性能锰基氧化物正极材料,Na_(0.67)Mg_(0.1)Zn_(0.1)Mn_(0.8)O_(2)(NMZMO).通过共掺杂策略协同激活阴离子氧化还原,此材料首圈可以放出~233 mAh g^(-1)的超高容量,明显高于Mg或Zn单掺杂的同类材料.综合多种光谱技术,作者证明了更高的容量源于更强的阴离子氧化还原活性.结合中子全散射以及共振非弹性X射线散射发现,Mg与Zn在高电压下会向面外迁移至四面体位点,诱导面内重排形成空位团簇,将氧阴离子以分子O_(2)的形式困于其中.Mg/Zn共存时,刺激了彼此更多的向面外迁移,为形成更多晶内分子O_(2)提供先决条件.本文提出了关于阴离子氧化还原的新见解,并为高容量钠电正极材料的开发提供了理论依据.