Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes.Miniaturized endoscopic probes are necessary for imaging small luminal or delicate or...Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes.Miniaturized endoscopic probes are necessary for imaging small luminal or delicate organs without causing trauma to tissue.However,current fabrication methods limit the imaging performance of highly miniaturized probes,restricting their widespread application.To overcome this limitation,we developed a novel ultrathin probe fabrication technique that utilizes 3D microprinting to reliably create side-facing freeform micro-optics(<130μm diameter)on single-mode fibers.Using this technique,we built a fully functional ultrathin aberration-corrected optical coherence tomography probe.This is the smallest freeform 3D imaging probe yet reported,with a diameter of 0.457 mm,including the catheter sheath.We demonstrated image quality and mechanical flexibility by imaging atherosclerotic human and mouse arteries.The ability to provide microstructural information with the smallest optical coherence tomography catheter opens a gateway for novel minimally invasive applications in disease.展开更多
BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the dia...BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.展开更多
Automatic segmentation of key microstructural features in atomic-scale electron microscope images is critical to improved understanding of structure–property relationships in many important materials and chemical sys...Automatic segmentation of key microstructural features in atomic-scale electron microscope images is critical to improved understanding of structure–property relationships in many important materials and chemical systems.However,the present paradigm involves time-intensive manual analysis that is inherently biased,error-prone,and unable to accommodate the large volumes of data produced by modern instrumentation.While more automated approaches have been proposed,many are not robust to a high variety of data,and do not generalize well to diverse microstructural features and material systems.Here,we present a flexible,semi-supervised few-shot machine learning approach for segmentation of scanning transmission electron microscopy images of three oxide material systems:(1)epitaxial heterostructures of SrTiO_(3)/Ge,(2)La_(0.8)Sr_(0.2)FeO_(3) thin films,and(3)MoO_(3) nanoparticles.We demonstrate that the few-shot learning method is more robust against noise,more reconfigurable,and requires less data than conventional image analysis methods.This approach can enable rapid image classification and microstructural feature mapping needed for emerging high-throughput characterization and autonomous microscope platforms.展开更多
Forecasting models are a central part of many control systems,where high-consequence decisions must be made on long latency control variables.These models are particularly relevant for emerging artificial intelligence...Forecasting models are a central part of many control systems,where high-consequence decisions must be made on long latency control variables.These models are particularly relevant for emerging artificial intelligence(AI)-guided instrumentation,in which prescriptive knowledge is needed to guide autonomous decision-making.Here we describe the implementation of a long short-term memory model(LSTM)for forecasting in situ electron energy loss spectroscopy(EELS)data,one of the richest analytical probes of materials and chemical systems.We describe key considerations for data collection,preprocessing,training,validation,and benchmarking,showing how this approach can yield powerful predictive insight into order-disorder phase transitions.Finally,we comment on how such a model may integrate with emerging AI-guided instrumentation for powerful high-speed experimentation.展开更多
Machine learning(ML)has become critical for post-acquisition data analysis in(scanning)transmission electron microscopy,(S)TEM,imaging and spectroscopy.An emerging trend is the transition to real-time analysis and clo...Machine learning(ML)has become critical for post-acquisition data analysis in(scanning)transmission electron microscopy,(S)TEM,imaging and spectroscopy.An emerging trend is the transition to real-time analysis and closed-loop microscope operation.The effective use of ML in electron microscopy now requires the development of strategies for microscopy-centric experiment workflow design and optimization.Here,we discuss the associated challenges with the transition to active ML,including sequential data analysis and out-of-distribution drift effects,the requirements for edge operation,local and cloud data storage,and theory in the loop operations.Specifically,we discuss the relative contributions of human scientists and ML agents in the ideation,orchestration,and execution of experimental workflows,as well as the need to develop universal hyper languages that can apply across multiple platforms.These considerations will collectively inform the operationalization of ML in next-generation experimentation.展开更多
The year 1963 was pivotal for broadcast news. Walter Cronkite forever changed how the American people receive their news when he anchored the first 30 minute nightly news. During the 60s, television news had two stron...The year 1963 was pivotal for broadcast news. Walter Cronkite forever changed how the American people receive their news when he anchored the first 30 minute nightly news. During the 60s, television news had two strong rivals： the newspaper and the radio. The target audience for nightly newscasts was to a generation of people that were used to getting news elsewhere. Since people were familiar with getting the news from radio, news stations relayed the news the same way as it was done on the radio： as talking heads. In other words, the news stations used a trusted face to read the news to people without any improvements on presentation. This all changed when CBS and NBC saw a robust and lucrative future for the nightly news. This paper will outline the steps taken by the two networks to make an extended half hour evening news a reality.展开更多
In anticipation of the massive burden of neurodegenerative disease within super-aged societies, great efforts have been made to utilize neural stem and progenitor cells for regenerative medicine. The capacity of intri...In anticipation of the massive burden of neurodegenerative disease within super-aged societies, great efforts have been made to utilize neural stem and progenitor cells for regenerative medicine. The capacity of intrinsic neural stem and progenitor cells to regenerate damaged brain tissue remains unclear, due in part to the lack of knowledge about how these newly born neurons integrate into functional circuitry. As sizable integration of adult-born neurons naturally occurs in the dentate gyrus region of the hippocampus, clarifying the mechanisms of this process could provide insights for applying neural stem and progenitor cells in clinical settings. There is convincing evidence of functional correlations between adult-born neurons and memory consolidation and sleep; therefore, we describe some new advances that were left untouched in our recent review.展开更多
Growth hormone (GH) and estrogen are essential stimulators of mammary cell proliferation and mammary development as mammals near puberty. Mammary ductal growth requires modifications of the extracellular matrix (ECM) ...Growth hormone (GH) and estrogen are essential stimulators of mammary cell proliferation and mammary development as mammals near puberty. Mammary ductal growth requires modifications of the extracellular matrix (ECM) for this tissue expansion to occur. Our purpose was to evaluate the effects of exogenous GH and ovariectomy (known to impact estrogen production) on gene expression of selected ECM proteins in the mammary parenchyma (PAR) and mammary fat pad (MFP) of prepubertal calves. Our hypothesis was that both GH and ovariectomy would alter the mRNA expression of multiple mammary ECM proteins. However, treatment with GH significantly reduced the expression of only fibronectin in PAR. However, the mRNA expression of all of the ECM proteins tested was numerically lower in PAR from GH treated calves. In contrast, staged ovariectomy decreased expression of fibronectin and heat shock protein 90 but increased expression of epimorphin in mammary PAR. In the MFP expression of Rac-1 and fascin were increased. These findings suggest that effects of exogenous GH on mammary gland composition are only marginally dependent on alterations in ECM proteins but the more pronounced effects of ovariectomy (reduced PAR mass and altered myoepithelial ontogeny) are more likely linked to changes in expression of ECM proteins.展开更多
Individuals successful at weight loss maintenance (WTLM) utilize similar behaviors but in varying amounts and combinations. Research identifying characteristics which predict WTLM success could be used to develop effe...Individuals successful at weight loss maintenance (WTLM) utilize similar behaviors but in varying amounts and combinations. Research identifying characteristics which predict WTLM success could be used to develop effective WTLM treatment programs. The purpose of this retrospective analysis was to determine behavioral (e.g., self monitoring of dietary intake) and biological factors (e.g., sex) which may influence WTLM success. Methods: In a previously conducted 12-month WTLM study, weight-reduced middle-aged and older men and women (n = 39) were assigned behavioral goals and asked to daily self-monitor body weight, fruit and vegetable intake, water consumption, and physical activity. This investigation utilized a crisp set qualitative comparative analysis (QCA) to characterize individuals’ weight changes and behaviors. Sex difference in clinically significant weight loss (WL) (≥5% WL) at 12 months was investigated, and growth curve models estimated interaction effects between sex and WTLM predictors. Results: QCA findings suggest patterns of weight change during the initial three months of WTLM treatment may dictate 12-month weight outcomes. No sex difference was found in clinically significant WL or in the interaction of sex and behaviors on weight change. Conclusions: WTLM treatments should provide more intensive support during transition from WL to WTLM, particularly during the first three months.展开更多
Introduction: For persons with diabetes, cardiovascular disease is the major cause of morbidity and mortality that is reflected in a two-to- four times greater risk for both heart disease and stroke when compared to a...Introduction: For persons with diabetes, cardiovascular disease is the major cause of morbidity and mortality that is reflected in a two-to- four times greater risk for both heart disease and stroke when compared to adults without diabetes. Although not without controversy, diabetes and cardiovascular disease (CVD) management guidelines in the US recommend the use of once-daily aspirin. This epidemiological study was undertaken to fill the knowledge gap regarding the prevalence of daily or near daily aspirin use for US age-appropriate adults with diabetes. Methods: Using bivariate and multivariate techniques, a cross-sectional analysis of an amalgamated database using 2005, 2007, and 2009 Behavioral Risk Factor Surveillance Survey data was performed. The dependent variable for this analysis was daily or near daily aspirin use. The population of interest was US adults, men >= 45 - 79 and women >= 55 - 79 years of age. Results: Overall the prevalence of daily or near daily aspirin use by age-appropriate US adults with diabetes was 62.5%;it was 41.0% for similar non-diabetic adults. Logistic regression analysis yielded that age-appropriate adults, of both genders, with diabetes taking daily or near daily aspirin were more likely to be: physically active, male, live in rural locales, not have a health care provider, have deferred medical care because of cost, have an elevated BMI, a smoker, and have hypertension. Conclusion: It was determined that the age-appropriate use of aspirin in the US adult population with diabetes is underutilized. The role of the pharmacist through- out the continuum of care is one way to improve appropriate aspirin use in patients with diabetes.展开更多
基金funded by the Australian Research Council(CE140100003)a Premier’s Research and Industry Fund grant provided by the South Australian Government Department for Industry and Skills+5 种基金BMBF PRINTOPTICS(13N14096,13N14097),Baden-Wurttemberg(BW)Stiftung OPTERIAL,European Research Council Advanced Grant COMPLEXPLAS,European Research Council Proof of Concept 3DPrintedOptics,and German Research Foundation(DFG)Integrated quantum science and technology(IQST)the National Health and Medical Research Council(NHMRC,Principle Research Fellowship 1111630)the National Heart Foundation(Lin Huddleston Senior Fellowship,and Postdoctoral Fellowship 102093)the University of Adelaide(Faculty of Health and Medical Sciences Emerging Leadership Program grant and Research Travel Award)Australia-Germany Joint Research Co-operation Scheme(UA-DAAD).
文摘Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes.Miniaturized endoscopic probes are necessary for imaging small luminal or delicate organs without causing trauma to tissue.However,current fabrication methods limit the imaging performance of highly miniaturized probes,restricting their widespread application.To overcome this limitation,we developed a novel ultrathin probe fabrication technique that utilizes 3D microprinting to reliably create side-facing freeform micro-optics(<130μm diameter)on single-mode fibers.Using this technique,we built a fully functional ultrathin aberration-corrected optical coherence tomography probe.This is the smallest freeform 3D imaging probe yet reported,with a diameter of 0.457 mm,including the catheter sheath.We demonstrated image quality and mechanical flexibility by imaging atherosclerotic human and mouse arteries.The ability to provide microstructural information with the smallest optical coherence tomography catheter opens a gateway for novel minimally invasive applications in disease.
文摘BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.
基金The authors would like to thank Drs.Jan Irvahn,Jenna Pope,and Bryan Stanfill for useful discussions.This research was supported by a Chemical Dynamics Initiative(CDi)Laboratory Directed Research and Development(LDRD)project at Pacific Northwest National Laboratory(PNNL).PNNL is a multiprogram national laboratory operated for the U.S.Department of Energy(DOE)by Battelle Memorial Institute under Contract No.DEAC05-76RL0-1830Initial code development was performed on Nuclear Processing Science Initiative(NPSI)and I3T Commercialization Program LDRD projects.The growth and STEM data collection of the STO/Ge was supported by the U.S.Department of Energy(DOE),Office of Basic Energy Sciences,Division of Materials Science and Engineering under award no.10122.A portion of the STEM imaging shown was performed in the Radiological Microscopy Suite(RMS),located in the Radiochemical Processing Laboratory(RPL)at PNNL.Thin film synthesis and additional characterization was performed using the Environmental Molecular Sciences Laboratory(EMSL),a national scientific user facility sponsored by the Department of Energy’s Office of Biological and Environmental Research and located at PNNL.
文摘Automatic segmentation of key microstructural features in atomic-scale electron microscope images is critical to improved understanding of structure–property relationships in many important materials and chemical systems.However,the present paradigm involves time-intensive manual analysis that is inherently biased,error-prone,and unable to accommodate the large volumes of data produced by modern instrumentation.While more automated approaches have been proposed,many are not robust to a high variety of data,and do not generalize well to diverse microstructural features and material systems.Here,we present a flexible,semi-supervised few-shot machine learning approach for segmentation of scanning transmission electron microscopy images of three oxide material systems:(1)epitaxial heterostructures of SrTiO_(3)/Ge,(2)La_(0.8)Sr_(0.2)FeO_(3) thin films,and(3)MoO_(3) nanoparticles.We demonstrate that the few-shot learning method is more robust against noise,more reconfigurable,and requires less data than conventional image analysis methods.This approach can enable rapid image classification and microstructural feature mapping needed for emerging high-throughput characterization and autonomous microscope platforms.
基金C.D.,B.E.M.,S.A.,and S.R.S.were supported by the Chemical Dynamics Initiative/Investment,under the Laboratory Directed Research and Development(LDRD)Program at Pacific Northwest National Laboratory(PNNL)PNNL is a multi-program national laboratory operated for the U.S.Department of Energy(DOE)by Battelle Memorial Institute under Contract No.DE-AC05-76RL01830+1 种基金N.L.,Y.J.,X.T.,and V.S.were supported by the Data Intensive Research Enabling Clean Technology(DI-RECT)National Science Foundation(NSF)National Research Traineeship(DGE-1633216)the State of Washington through the University of Washington(UW)Clean Energy Institute and the UW eScience Institute.
文摘Forecasting models are a central part of many control systems,where high-consequence decisions must be made on long latency control variables.These models are particularly relevant for emerging artificial intelligence(AI)-guided instrumentation,in which prescriptive knowledge is needed to guide autonomous decision-making.Here we describe the implementation of a long short-term memory model(LSTM)for forecasting in situ electron energy loss spectroscopy(EELS)data,one of the richest analytical probes of materials and chemical systems.We describe key considerations for data collection,preprocessing,training,validation,and benchmarking,showing how this approach can yield powerful predictive insight into order-disorder phase transitions.Finally,we comment on how such a model may integrate with emerging AI-guided instrumentation for powerful high-speed experimentation.
文摘Machine learning(ML)has become critical for post-acquisition data analysis in(scanning)transmission electron microscopy,(S)TEM,imaging and spectroscopy.An emerging trend is the transition to real-time analysis and closed-loop microscope operation.The effective use of ML in electron microscopy now requires the development of strategies for microscopy-centric experiment workflow design and optimization.Here,we discuss the associated challenges with the transition to active ML,including sequential data analysis and out-of-distribution drift effects,the requirements for edge operation,local and cloud data storage,and theory in the loop operations.Specifically,we discuss the relative contributions of human scientists and ML agents in the ideation,orchestration,and execution of experimental workflows,as well as the need to develop universal hyper languages that can apply across multiple platforms.These considerations will collectively inform the operationalization of ML in next-generation experimentation.
文摘The year 1963 was pivotal for broadcast news. Walter Cronkite forever changed how the American people receive their news when he anchored the first 30 minute nightly news. During the 60s, television news had two strong rivals： the newspaper and the radio. The target audience for nightly newscasts was to a generation of people that were used to getting news elsewhere. Since people were familiar with getting the news from radio, news stations relayed the news the same way as it was done on the radio： as talking heads. In other words, the news stations used a trusted face to read the news to people without any improvements on presentation. This all changed when CBS and NBC saw a robust and lucrative future for the nightly news. This paper will outline the steps taken by the two networks to make an extended half hour evening news a reality.
基金partially supported by the MEXT World Premier International Research Center Initiative,CREST JST,MEXT KAKENHI for Scientific Research on Innovative Areas "Microendophenotype"(25116530)and "Memory Dynamism"(26115502)JSPS KAKENHI Grants(16K18359,15F15408)+12 种基金Research Foundation for Opto-Science and TechnologyKato Memorial Bioscience FoundationJapan Foundation for Applied EnzymologyUehara Memorial Foundation2016 Inamori Research Grants ProgramIchiro Kanehara Foundation for the Promotion of Medical Sciences and Medical CareLife Science Foundation of JapanKowa Life Science Foundation Research GrantGSK Japan Research GrantKANAE Foundation for the Promotion of Medical ScienceShimadzu Foundation for the Promotion of Science and TechnologyTakeda Science Foundation to MSThe Tokyo Biochemical Research Foundation to SS
文摘In anticipation of the massive burden of neurodegenerative disease within super-aged societies, great efforts have been made to utilize neural stem and progenitor cells for regenerative medicine. The capacity of intrinsic neural stem and progenitor cells to regenerate damaged brain tissue remains unclear, due in part to the lack of knowledge about how these newly born neurons integrate into functional circuitry. As sizable integration of adult-born neurons naturally occurs in the dentate gyrus region of the hippocampus, clarifying the mechanisms of this process could provide insights for applying neural stem and progenitor cells in clinical settings. There is convincing evidence of functional correlations between adult-born neurons and memory consolidation and sleep; therefore, we describe some new advances that were left untouched in our recent review.
文摘Growth hormone (GH) and estrogen are essential stimulators of mammary cell proliferation and mammary development as mammals near puberty. Mammary ductal growth requires modifications of the extracellular matrix (ECM) for this tissue expansion to occur. Our purpose was to evaluate the effects of exogenous GH and ovariectomy (known to impact estrogen production) on gene expression of selected ECM proteins in the mammary parenchyma (PAR) and mammary fat pad (MFP) of prepubertal calves. Our hypothesis was that both GH and ovariectomy would alter the mRNA expression of multiple mammary ECM proteins. However, treatment with GH significantly reduced the expression of only fibronectin in PAR. However, the mRNA expression of all of the ECM proteins tested was numerically lower in PAR from GH treated calves. In contrast, staged ovariectomy decreased expression of fibronectin and heat shock protein 90 but increased expression of epimorphin in mammary PAR. In the MFP expression of Rac-1 and fascin were increased. These findings suggest that effects of exogenous GH on mammary gland composition are only marginally dependent on alterations in ECM proteins but the more pronounced effects of ovariectomy (reduced PAR mass and altered myoepithelial ontogeny) are more likely linked to changes in expression of ECM proteins.
文摘Individuals successful at weight loss maintenance (WTLM) utilize similar behaviors but in varying amounts and combinations. Research identifying characteristics which predict WTLM success could be used to develop effective WTLM treatment programs. The purpose of this retrospective analysis was to determine behavioral (e.g., self monitoring of dietary intake) and biological factors (e.g., sex) which may influence WTLM success. Methods: In a previously conducted 12-month WTLM study, weight-reduced middle-aged and older men and women (n = 39) were assigned behavioral goals and asked to daily self-monitor body weight, fruit and vegetable intake, water consumption, and physical activity. This investigation utilized a crisp set qualitative comparative analysis (QCA) to characterize individuals’ weight changes and behaviors. Sex difference in clinically significant weight loss (WL) (≥5% WL) at 12 months was investigated, and growth curve models estimated interaction effects between sex and WTLM predictors. Results: QCA findings suggest patterns of weight change during the initial three months of WTLM treatment may dictate 12-month weight outcomes. No sex difference was found in clinically significant WL or in the interaction of sex and behaviors on weight change. Conclusions: WTLM treatments should provide more intensive support during transition from WL to WTLM, particularly during the first three months.
文摘Introduction: For persons with diabetes, cardiovascular disease is the major cause of morbidity and mortality that is reflected in a two-to- four times greater risk for both heart disease and stroke when compared to adults without diabetes. Although not without controversy, diabetes and cardiovascular disease (CVD) management guidelines in the US recommend the use of once-daily aspirin. This epidemiological study was undertaken to fill the knowledge gap regarding the prevalence of daily or near daily aspirin use for US age-appropriate adults with diabetes. Methods: Using bivariate and multivariate techniques, a cross-sectional analysis of an amalgamated database using 2005, 2007, and 2009 Behavioral Risk Factor Surveillance Survey data was performed. The dependent variable for this analysis was daily or near daily aspirin use. The population of interest was US adults, men >= 45 - 79 and women >= 55 - 79 years of age. Results: Overall the prevalence of daily or near daily aspirin use by age-appropriate US adults with diabetes was 62.5%;it was 41.0% for similar non-diabetic adults. Logistic regression analysis yielded that age-appropriate adults, of both genders, with diabetes taking daily or near daily aspirin were more likely to be: physically active, male, live in rural locales, not have a health care provider, have deferred medical care because of cost, have an elevated BMI, a smoker, and have hypertension. Conclusion: It was determined that the age-appropriate use of aspirin in the US adult population with diabetes is underutilized. The role of the pharmacist through- out the continuum of care is one way to improve appropriate aspirin use in patients with diabetes.
