The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve...The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.展开更多
A high-entropy metal disilicide,(Mo_(0.2)Nb_(0.2)Ta_(0.2)Ti_(0.2)W_(0.2))Si_(2),has been successfully synthesized.X-ray diffraction(XRD),energy dispersive X-ray spectroscopy(EDX),and electron backscatter diffraction(E...A high-entropy metal disilicide,(Mo_(0.2)Nb_(0.2)Ta_(0.2)Ti_(0.2)W_(0.2))Si_(2),has been successfully synthesized.X-ray diffraction(XRD),energy dispersive X-ray spectroscopy(EDX),and electron backscatter diffraction(EBSD)collectively show the formation of a single high-entropy silicide phase.This high-entropy(Mo_(0.2)Nb_(0.2)Ta_(0.2)Ti_(0.2)W_(0.2))Si_(2) possesses a hexagonal C40 crystal structure with ABC stacking sequence and a space group of P6222.This discovery expands the known families of high-entropy materials from metals,oxides,borides,carbides,and nitrides to a silicide,for the first time to our knowledge,as well as demonstrating that a new,non-cubic,crystal structure(with lower symmetry)can be made into highentropy phase.This(Mo_(0.2)Nb_(0.2)Ta_(0.2)Ti_(0.2)W_(0.2))Si_(2) exhibits high nanohardness of 16.7±1.9 GPa and Vickers hardness of 11.6±0.5 GPa.Moreover,it has a low thermal conductivity of 6.9±1.1Wm^(-1) K^(-1),which is approximately one order of magnitude lower than that of the widely-used tetragonal MoSi_(2) and ~1/3 of those reported values for the hexagonal NbSi_(2) and TaSi_(2) with the same crystal structure.展开更多
Worldwide trends in mobile electrification,largely driven by the popularity of electric vehicles(EVs)will skyrocket demands for lithium-ion battery(LIB)production.As such,up to four million metric tons of LIB waste fr...Worldwide trends in mobile electrification,largely driven by the popularity of electric vehicles(EVs)will skyrocket demands for lithium-ion battery(LIB)production.As such,up to four million metric tons of LIB waste from EV battery packs could be generated from 2015 to 2040.LIB recycling directly addresses concerns over longterm economic strains due to the uneven geographic distribution of resources(especially for Co and Li)and environmental issues associated with both landfilling and raw material extraction.However,LIB recycling infrastructure has not been widely adopted,and current facilities are mostly focused on Co recovery for economic gains.This incentive will decline due to shifting market trends from LiCoO2 toward cobalt-deficient and mixed-metal cathodes(eg,LiNi1/3Mn1/3Co1/3O2).Thus,this review covers recycling strategies to recover metals in mixed-metal LIB cathodes and comingled scrap comprising different chemistries.As such,hydrometallurgical processes can meet this criterion,while also requiring a low environmental footprint and energy consumption compared to pyrometallurgy.Following pretreatment to separate the cathode from other battery components,the active material is dissolved entirely by reductive acid leaching.A complex leachate is generated,comprising cathode metals(Li+,Ni2+,Mn2+,and Co2+)and impurities(Fe3+,Al3+,and Cu2+)from the current collectors and battery casing,which can be separated and purified using a series of selective precipitation and/or solvent extraction steps.Alternatively,the cathode can be resynthesized directly from the leachate.展开更多
microRNAs （miRNAs） are an abundant class of-22 nucleotide （nt） regulatory RNAs that are pervasive in higher eukaryotic genomes. In order to fully understand their prominence in genomes, it is necessary to elucidat...microRNAs （miRNAs） are an abundant class of-22 nucleotide （nt） regulatory RNAs that are pervasive in higher eukaryotic genomes. In order to fully understand their prominence in genomes, it is necessary to elucidate the molecular mechanisms that can diversify miRNA activities. In this review, we describe some of the many strategies that allow novel miRNA functions to emerge, with particular emphasis on how miRNA genes evolve in animals. These mechanisms include changes in their sequence, processing, or expression pattern; acquisition of miRNA^＊ functionality or antisense processing; and de novo gene birth. The facility and versatility of miRNAs to evolve and change likely underlies how they have become dominant constituents of higher genomes.展开更多
micro RNAs(mi RNAs or mi Rs) are small non-coding RNAs that are involved in posttranscriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that mi RNAs are critical ...micro RNAs(mi RNAs or mi Rs) are small non-coding RNAs that are involved in posttranscriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that mi RNAs are critical regulators of lipid synthesis, fatty acid oxidation and lipoprotein formation and secretion. Dysregulation of mi RNAs disrupts gene regulatory network, leading to metabolic syndrome and its related diseases. In this review, we introduced epigenetic and transcriptional regulation of mi RNAs expression. We emphasized on several representative mi RNAs that are functionally involved into lipid metabolism, including mi R-33/33 n, mi R122, mi R27a/b, mi R378/378 n, mi R-34 a and mi R-21.Understanding the function of mi RNAs in lipid homeostasis may provide potential therapeutic strategies for fatty liver disease.展开更多
Artificial intelligence(AI) enables machines to provide unparalleled value in a myriad of industries and applications. In recent years, researchers have harnessed artificial intelligence to analyze large-volume, unstr...Artificial intelligence(AI) enables machines to provide unparalleled value in a myriad of industries and applications. In recent years, researchers have harnessed artificial intelligence to analyze large-volume, unstructured medical data and perform clinical tasks, such as the identification of diabetic retinopathy or the diagnosis of cutaneous malignancies. Applications of artificial intelligence techniques, specifically machine learning and more recently deep learning, are beginning to emerge in gastrointestinal endoscopy. The most promising of these efforts have been in computeraided detection and computer-aided diagnosis of colorectal polyps, with recent systems demonstrating high sensitivity and accuracy even when compared to expert human endoscopists. AI has also been utilized to identify gastrointestinal bleeding, to detect areas of inflammation, and even to diagnose certain gastrointestinal infections. Future work in the field should concentrate on creating seamless integration of AI systems with current endoscopy platforms and electronic medical records, developing training modules to teach clinicians how to use AI tools, and determining the best means for regulation and approval of new AI technology.展开更多
Endoscopic submucosal dissection(ESD) is a wellestablished, minimally invasive treatment for superficial neoplasms of the gastrointestinal tract. The universal adoption of ESD has been limited by its slow learning cur...Endoscopic submucosal dissection(ESD) is a wellestablished, minimally invasive treatment for superficial neoplasms of the gastrointestinal tract. The universal adoption of ESD has been limited by its slow learning curve, long procedure times, and high risk of complications. One technical challenge is the lack of a second hand that can provide traction, as in conventional surgery. Reliable tissue retraction that exposes the submucosal plane of dissection would allow for safer and more efficient dissection. Magnetic anchor guided endoscopic submucosal dissection(MAGESD) has potential benefits compared to other current traction methods. MAG-ESD offers dynamic tissue retraction independent of the endoscope mimicking a surgeon's "second hand". Two types of magnets can be used: electromagnets and permanent magnets. In this article we review the MAG-ESD technology, published work and studies of magnets in ESD. We also review the use of magnetic anchor guidance systems in natural orifice transluminal endoscopic surgery and the idea of magnetic non-contact retraction using surface ferromagentization. We discuss the current limitations, the future potential of MAG-ESD and the developments needed for adoption of this technology.展开更多
AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and spec...AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.展开更多
Although high-entropy materials are attracting considerable interest due to a combination of useful properties and promising applications,predicting their formation remains a hindrance for rational discovery of new sy...Although high-entropy materials are attracting considerable interest due to a combination of useful properties and promising applications,predicting their formation remains a hindrance for rational discovery of new systems.Experimental approaches are based on physical intuition and/or expensive trial and error strategies.Most computational methods rely on the availability of sufficient experimental data and computational power.Machine learning(ML)applied to materials science can accelerate development and reduce costs.In this study,we propose an ML method,leveraging thermodynamic and compositional attributes of a given material for predicting the synthesizability(i.e.,entropy-forming ability)of disordered metal carbides.展开更多
Puccinia striiformis f.sp.tritici(Pst),a biotrophic plant pathogen,secretes numerous effectors to modulate host defense systems.Understanding the molecular mechanisms by which Pst effectors regulate wheat immunity is ...Puccinia striiformis f.sp.tritici(Pst),a biotrophic plant pathogen,secretes numerous effectors to modulate host defense systems.Understanding the molecular mechanisms by which Pst effectors regulate wheat immunity is of great importance for the development of novel strategies for durable control of stripe rust.In this study,we identified a glycine-serine-rich effector gene,PstGSRE1,which is highly induced dur-ing early infection.Transgenic expression of PstGSRE1 RNAi constructs in wheat significantly reduced virulence of Pst and increased H2O2 accumulation in wheat.PstGSRE1 was shown to target the reactive ox-ygen species(ROS)-associated transcription factor TaLOL2,a positive regulator of wheat immunity.PstGSRE1 disrupted nuclear localization of TaLOL2 and suppressed ROS-mediated cell death induced by TaLOL2,thus compromising host immunity.This work reveals a previously unrecognized strategy whereby rust fungi exploit the PstGSRE1 effector to defeat ROS-associated plant defense by modulating the subcellular compartment of a host immune regulator and facilitate pathogen infection.展开更多
AIM To identify the effect of hydrogen-rich water(HRW) and electrolyzed-alkaline water(EAW) on high-fat-induced non-alcoholic fatty acid disease in mice.METHODS Mice were divided into four groups:(1) Regular diet(RD)/...AIM To identify the effect of hydrogen-rich water(HRW) and electrolyzed-alkaline water(EAW) on high-fat-induced non-alcoholic fatty acid disease in mice.METHODS Mice were divided into four groups:(1) Regular diet(RD)/regular water(RW);(2) high-fat diet(HFD)/RW;(3) RD/EAW; and(4) HFD/EAW. Weight and body composition were measured. After twelve weeks, animals were sacrificed, and livers were processed for histology and reverse-transcriptase polymerase chain reaction. A similar experiment was performed using HRW to determine the influence and importance of molecular hydrogen(H2) in EAW. Finally, we compared the response of hepatocytes isolated from mice drinking HRW or RW to palmitate overload.RESULTS EAW had several properties important to the study:(1) pH = 11;(2) oxidation-reduction potential of-495 mV; and(3) H2 = 0.2 mg/L. However, in contrast to other studies, there were no differences between the groups drinking EAW or RW in either the RD or HFD groups. We hypothesized that the null result was due to low H2 concentrations. Therefore, we evaluated the effects of RW and low and high HRW concentrations(L-HRW = 0.3 mg H2/L and H-HRW = 0.8 mg H2/L, respectively) in mice fed an HFD. Compared to RW and L-HRW, H-HRW resulted in a lower increase in fat mass(46% vs 61%), an increase in lean body mass(42% vs 28%), and a decrease in hepatic lipid accumulation(P < 0.01). Lastly, exposure of hepatocytes isolated from mice drinking H-HRW to palmitate overload demonstrated a protective effect from H2 by reducing hepatocyte lipid accumulation in comparison to mice drinking regular water.CONCLUSION H2 is the therapeutic agent in electrolyzed-alkaline water and attenuates HFD-induced nonalcoholic fatty liver disease in mice.展开更多
BACKGROUND Li-Fraumeni syndrome(LFS)is a rare autosomal dominant cancer-predisposing syndrome,which can manifest as a polymorphic spectrum of malignancies.LFS is associated with an early onset in life,with the majorit...BACKGROUND Li-Fraumeni syndrome(LFS)is a rare autosomal dominant cancer-predisposing syndrome,which can manifest as a polymorphic spectrum of malignancies.LFS is associated with an early onset in life,with the majority of cases occurring prior to the age of 46.Notwithstanding the infrequency of primary cardiac tumors,it behooves clinicians to remain vigilant in considering the differential diagnosis of such tumors in LFS patients who present with a cardiac mass.This is due to the markedly elevated risk for malignancy in this particular population,far surpassing that of the general populace.CASE SUMMARY Herein,we present a case of a 30-year-old female with LFS who was found to have a tricuspid valve leaflet mass.CONCLUSION This case exemplifies valuable learning points in the diagnostic approach for this exceptionally rare patient population.展开更多
High power dissipating artificial intelligence (AI) chips require significant cooling to operate at maximum performance. Current trends regarding the integration of AI, as well as the power/cooling demands of high-per...High power dissipating artificial intelligence (AI) chips require significant cooling to operate at maximum performance. Current trends regarding the integration of AI, as well as the power/cooling demands of high-performing server systems pose an immense thermal challenge for cooling. The use of refrigerants as a direct-to-chip cooling method is investigated as a potential cooling solution for cooling AI chips. Using a vapor compression refrigeration system (VCRS), the coolant temperature will be sub-ambient thereby increasing the total cooling capacity. Coupled with the implementation of a direct-to-chip boiler, using refrigerants to cool AI server systems can materialize as a potential solution for current AI server cooling demands. In this study, a comparison of 8 different refrigerants: R-134a, R-153a, R-717, R-508B, R-22, R-12, R-410a, and R-1234yf is analyzed for optimal performance. A control theoretical VCRS model is created to assess variable refrigerants under the same operational conditions. From this model, the coefficient of performance (COP), required mass flow rate of refrigerant, work required by the compressor, and overall heat transfer coefficient is determined for all 8 refrigerants. Lastly, a comprehensive analysis is provided to determine the most optimal refrigerants for cooling applications. R-717, commonly known as Ammonia, was found to have the highest COP value thus proving to be the optimal refrigerant for cooling AI chips and high-performing server applications.展开更多
Objective: Fetal Alcohol Spectrum Disorders (FASDs) are common, often undiagnosed, lifelong developmental disorders that result from prenatal alcohol exposure. FASD is present at birth and typically identified around ...Objective: Fetal Alcohol Spectrum Disorders (FASDs) are common, often undiagnosed, lifelong developmental disorders that result from prenatal alcohol exposure. FASD is present at birth and typically identified around seven years of age. The most severe outcome in cases of FASD is mortality. The purpose of this scoping review is to 1) use a systematic review to provide an estimated mortality proportion for children with FASD, and 2) update a study published in 2014 by reviewing published reports of mortality in individuals diagnosed with FASD. Method: A search of PubMed, CINAHL, and Google Scholar for reports published between 2013 and 2023 on mortality in individuals with FASD. Results: Three population-based studies have reported on all-cause mortality rates, finding a combined mortality rate of 10.9%, a 2.63 fold (95% CI: 2.61 to 2.65) increase in mortality risk over the general population. Since 2016, this review identified only eight new cases meeting the study inclusion criteria. The reported causes of death were five cases of pneumonia, and one case each of failure to thrive and dehydration, intestinal dilatation and asphyxiation caused by overeating due to pica, and acute gastric volvulus. Discussion: While current research suggests a diagnosis of FASD is associated with a 2.6-fold increase in mortality risk, this is likely an underestimation, as most cases of FASD-related mortality go unreported. Globally, about 1 new case is reported every 15 months. However, in the United States alone, between 1752 to 4400 FASD related deaths occur annually. Our review suggests that FASD is rarely identified as a causal or contributing factor in deaths of children and adolescents, resulting in a substantial undercount of FASD-related deaths. Increased attention to the role of FASD in infant and child mortality case reviews, child death review committee reports, and mortality reviews is needed.展开更多
Background: Fetal Alcohol Spectrum Disorders (FASDs) are a global public health concern with lifelong consequences for affected individuals. Recent prevalence studies suggest FASD prevalence rates range from 1-5% amon...Background: Fetal Alcohol Spectrum Disorders (FASDs) are a global public health concern with lifelong consequences for affected individuals. Recent prevalence studies suggest FASD prevalence rates range from 1-5% among school age children. Most people with FASD are not correctly diagnosed and inadequate screening to identify patients with increased risk may contribute to under-diagnosis. This study developed a 10-item screening tool for FASD and examined its feasibility. Methods: The sample consisted of 355 children who had been evaluated at an FASD clinic. Data from the 33-item Alcohol Related Neurodevelopmental Disorder Behavioral Checklist was used to develop a brief FASD screen by comparing the changes in Cronbach’s alpha for different combinations of items. The validity of the brief scale was then further examined using receiving operating characteristic analyses. Results: The 10-item screen demonstrated acceptable sensitivity, specificity, and accuracy to identify children at high risk for FASD. The percentage correctly classified was 91.3 and the area under the receiving operating characteristic curve was 0.971. Conclusions: This feasibility study demonstrated that a screen for FASD consisting of 10 items with yes or no responses can be completed in 3 - 4 minutes. The tool is brief, with a low administration burden and has acceptable epidemiologic performance characteristics including accuracy. Future research should examine the performance of this tool when used in larger, community-based populations where screening for FASD would be appropriate.展开更多
文摘The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.
基金the partial financial support from an Office of Naval Research MURI program(grant no.N00014-15-1-2863,Program Mangers:Dr.Kenny Lipkowitz and Dr.Eric Wuchina)funding from the National Science Foundation,Grant No.CBET-1706388supported by the Deparment of Defense(DoD)through the National Defense Science and Engineering Graduate Fellowship(NDSEG)program as well as the ARCS foundation.
文摘A high-entropy metal disilicide,(Mo_(0.2)Nb_(0.2)Ta_(0.2)Ti_(0.2)W_(0.2))Si_(2),has been successfully synthesized.X-ray diffraction(XRD),energy dispersive X-ray spectroscopy(EDX),and electron backscatter diffraction(EBSD)collectively show the formation of a single high-entropy silicide phase.This high-entropy(Mo_(0.2)Nb_(0.2)Ta_(0.2)Ti_(0.2)W_(0.2))Si_(2) possesses a hexagonal C40 crystal structure with ABC stacking sequence and a space group of P6222.This discovery expands the known families of high-entropy materials from metals,oxides,borides,carbides,and nitrides to a silicide,for the first time to our knowledge,as well as demonstrating that a new,non-cubic,crystal structure(with lower symmetry)can be made into highentropy phase.This(Mo_(0.2)Nb_(0.2)Ta_(0.2)Ti_(0.2)W_(0.2))Si_(2) exhibits high nanohardness of 16.7±1.9 GPa and Vickers hardness of 11.6±0.5 GPa.Moreover,it has a low thermal conductivity of 6.9±1.1Wm^(-1) K^(-1),which is approximately one order of magnitude lower than that of the widely-used tetragonal MoSi_(2) and ~1/3 of those reported values for the hexagonal NbSi_(2) and TaSi_(2) with the same crystal structure.
基金The authors gratefully acknowledge the financial support from the Natural Sciences and Engineering Research Council of Canada(NSERC)and the University of Waterloo.This work was financially supported by the 111 Project(no.D17007).Karthikeyan Kaliyappan acknowledges the financial support from Henan Normal University,China for this work.Tyler Or was supported through the NSERC Canada Graduate Scholarships—Master’s Program.
文摘Worldwide trends in mobile electrification,largely driven by the popularity of electric vehicles(EVs)will skyrocket demands for lithium-ion battery(LIB)production.As such,up to four million metric tons of LIB waste from EV battery packs could be generated from 2015 to 2040.LIB recycling directly addresses concerns over longterm economic strains due to the uneven geographic distribution of resources(especially for Co and Li)and environmental issues associated with both landfilling and raw material extraction.However,LIB recycling infrastructure has not been widely adopted,and current facilities are mostly focused on Co recovery for economic gains.This incentive will decline due to shifting market trends from LiCoO2 toward cobalt-deficient and mixed-metal cathodes(eg,LiNi1/3Mn1/3Co1/3O2).Thus,this review covers recycling strategies to recover metals in mixed-metal LIB cathodes and comingled scrap comprising different chemistries.As such,hydrometallurgical processes can meet this criterion,while also requiring a low environmental footprint and energy consumption compared to pyrometallurgy.Following pretreatment to separate the cathode from other battery components,the active material is dissolved entirely by reductive acid leaching.A complex leachate is generated,comprising cathode metals(Li+,Ni2+,Mn2+,and Co2+)and impurities(Fe3+,Al3+,and Cu2+)from the current collectors and battery casing,which can be separated and purified using a series of selective precipitation and/or solvent extraction steps.Alternatively,the cathode can be resynthesized directly from the leachate.
文摘microRNAs （miRNAs） are an abundant class of-22 nucleotide （nt） regulatory RNAs that are pervasive in higher eukaryotic genomes. In order to fully understand their prominence in genomes, it is necessary to elucidate the molecular mechanisms that can diversify miRNA activities. In this review, we describe some of the many strategies that allow novel miRNA functions to emerge, with particular emphasis on how miRNA genes evolve in animals. These mechanisms include changes in their sequence, processing, or expression pattern; acquisition of miRNA^＊ functionality or antisense processing; and de novo gene birth. The facility and versatility of miRNAs to evolve and change likely underlies how they have become dominant constituents of higher genomes.
基金supported by National Institutes of Health (Nos.R01 DK080440 and AHA 13GRNT14700043)VA Merit Award 1I01BX002634 to Li Wang
文摘micro RNAs(mi RNAs or mi Rs) are small non-coding RNAs that are involved in posttranscriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that mi RNAs are critical regulators of lipid synthesis, fatty acid oxidation and lipoprotein formation and secretion. Dysregulation of mi RNAs disrupts gene regulatory network, leading to metabolic syndrome and its related diseases. In this review, we introduced epigenetic and transcriptional regulation of mi RNAs expression. We emphasized on several representative mi RNAs that are functionally involved into lipid metabolism, including mi R-33/33 n, mi R122, mi R27a/b, mi R378/378 n, mi R-34 a and mi R-21.Understanding the function of mi RNAs in lipid homeostasis may provide potential therapeutic strategies for fatty liver disease.
文摘Artificial intelligence(AI) enables machines to provide unparalleled value in a myriad of industries and applications. In recent years, researchers have harnessed artificial intelligence to analyze large-volume, unstructured medical data and perform clinical tasks, such as the identification of diabetic retinopathy or the diagnosis of cutaneous malignancies. Applications of artificial intelligence techniques, specifically machine learning and more recently deep learning, are beginning to emerge in gastrointestinal endoscopy. The most promising of these efforts have been in computeraided detection and computer-aided diagnosis of colorectal polyps, with recent systems demonstrating high sensitivity and accuracy even when compared to expert human endoscopists. AI has also been utilized to identify gastrointestinal bleeding, to detect areas of inflammation, and even to diagnose certain gastrointestinal infections. Future work in the field should concentrate on creating seamless integration of AI systems with current endoscopy platforms and electronic medical records, developing training modules to teach clinicians how to use AI tools, and determining the best means for regulation and approval of new AI technology.
文摘Endoscopic submucosal dissection(ESD) is a wellestablished, minimally invasive treatment for superficial neoplasms of the gastrointestinal tract. The universal adoption of ESD has been limited by its slow learning curve, long procedure times, and high risk of complications. One technical challenge is the lack of a second hand that can provide traction, as in conventional surgery. Reliable tissue retraction that exposes the submucosal plane of dissection would allow for safer and more efficient dissection. Magnetic anchor guided endoscopic submucosal dissection(MAGESD) has potential benefits compared to other current traction methods. MAG-ESD offers dynamic tissue retraction independent of the endoscope mimicking a surgeon's "second hand". Two types of magnets can be used: electromagnets and permanent magnets. In this article we review the MAG-ESD technology, published work and studies of magnets in ESD. We also review the use of magnetic anchor guidance systems in natural orifice transluminal endoscopic surgery and the idea of magnetic non-contact retraction using surface ferromagentization. We discuss the current limitations, the future potential of MAG-ESD and the developments needed for adoption of this technology.
文摘AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.
基金We acknowledge support through the Office of Naval Research ONR-MURI(grant number N00014-15-1-2863)K.K.acknowledges support by the Department of Defense(DoD)through the National Defense Science and Engineering Graduate Fellowship(NDSEG)Program+1 种基金K.K.also acknowledges the financial support of the ARCS Foundation,San Diego ChapterK.S.V.acknowledges the financial generosity of the Oerlikon Group in support of his research group.
文摘Although high-entropy materials are attracting considerable interest due to a combination of useful properties and promising applications,predicting their formation remains a hindrance for rational discovery of new systems.Experimental approaches are based on physical intuition and/or expensive trial and error strategies.Most computational methods rely on the availability of sufficient experimental data and computational power.Machine learning(ML)applied to materials science can accelerate development and reduce costs.In this study,we propose an ML method,leveraging thermodynamic and compositional attributes of a given material for predicting the synthesizability(i.e.,entropy-forming ability)of disordered metal carbides.
基金This study was financially supported by the National Natural Science Foundation of China(31972224,31430069,and 31620103913)the National Key R&D Program of China(2018YFD0200402)the 111 Project from the Ministry of Education of China(no.B07049).
文摘Puccinia striiformis f.sp.tritici(Pst),a biotrophic plant pathogen,secretes numerous effectors to modulate host defense systems.Understanding the molecular mechanisms by which Pst effectors regulate wheat immunity is of great importance for the development of novel strategies for durable control of stripe rust.In this study,we identified a glycine-serine-rich effector gene,PstGSRE1,which is highly induced dur-ing early infection.Transgenic expression of PstGSRE1 RNAi constructs in wheat significantly reduced virulence of Pst and increased H2O2 accumulation in wheat.PstGSRE1 was shown to target the reactive ox-ygen species(ROS)-associated transcription factor TaLOL2,a positive regulator of wheat immunity.PstGSRE1 disrupted nuclear localization of TaLOL2 and suppressed ROS-mediated cell death induced by TaLOL2,thus compromising host immunity.This work reveals a previously unrecognized strategy whereby rust fungi exploit the PstGSRE1 effector to defeat ROS-associated plant defense by modulating the subcellular compartment of a host immune regulator and facilitate pathogen infection.
基金Tel Hai College Research funding Grant,No.25-2-14-114
文摘AIM To identify the effect of hydrogen-rich water(HRW) and electrolyzed-alkaline water(EAW) on high-fat-induced non-alcoholic fatty acid disease in mice.METHODS Mice were divided into four groups:(1) Regular diet(RD)/regular water(RW);(2) high-fat diet(HFD)/RW;(3) RD/EAW; and(4) HFD/EAW. Weight and body composition were measured. After twelve weeks, animals were sacrificed, and livers were processed for histology and reverse-transcriptase polymerase chain reaction. A similar experiment was performed using HRW to determine the influence and importance of molecular hydrogen(H2) in EAW. Finally, we compared the response of hepatocytes isolated from mice drinking HRW or RW to palmitate overload.RESULTS EAW had several properties important to the study:(1) pH = 11;(2) oxidation-reduction potential of-495 mV; and(3) H2 = 0.2 mg/L. However, in contrast to other studies, there were no differences between the groups drinking EAW or RW in either the RD or HFD groups. We hypothesized that the null result was due to low H2 concentrations. Therefore, we evaluated the effects of RW and low and high HRW concentrations(L-HRW = 0.3 mg H2/L and H-HRW = 0.8 mg H2/L, respectively) in mice fed an HFD. Compared to RW and L-HRW, H-HRW resulted in a lower increase in fat mass(46% vs 61%), an increase in lean body mass(42% vs 28%), and a decrease in hepatic lipid accumulation(P < 0.01). Lastly, exposure of hepatocytes isolated from mice drinking H-HRW to palmitate overload demonstrated a protective effect from H2 by reducing hepatocyte lipid accumulation in comparison to mice drinking regular water.CONCLUSION H2 is the therapeutic agent in electrolyzed-alkaline water and attenuates HFD-induced nonalcoholic fatty liver disease in mice.
文摘BACKGROUND Li-Fraumeni syndrome(LFS)is a rare autosomal dominant cancer-predisposing syndrome,which can manifest as a polymorphic spectrum of malignancies.LFS is associated with an early onset in life,with the majority of cases occurring prior to the age of 46.Notwithstanding the infrequency of primary cardiac tumors,it behooves clinicians to remain vigilant in considering the differential diagnosis of such tumors in LFS patients who present with a cardiac mass.This is due to the markedly elevated risk for malignancy in this particular population,far surpassing that of the general populace.CASE SUMMARY Herein,we present a case of a 30-year-old female with LFS who was found to have a tricuspid valve leaflet mass.CONCLUSION This case exemplifies valuable learning points in the diagnostic approach for this exceptionally rare patient population.
文摘High power dissipating artificial intelligence (AI) chips require significant cooling to operate at maximum performance. Current trends regarding the integration of AI, as well as the power/cooling demands of high-performing server systems pose an immense thermal challenge for cooling. The use of refrigerants as a direct-to-chip cooling method is investigated as a potential cooling solution for cooling AI chips. Using a vapor compression refrigeration system (VCRS), the coolant temperature will be sub-ambient thereby increasing the total cooling capacity. Coupled with the implementation of a direct-to-chip boiler, using refrigerants to cool AI server systems can materialize as a potential solution for current AI server cooling demands. In this study, a comparison of 8 different refrigerants: R-134a, R-153a, R-717, R-508B, R-22, R-12, R-410a, and R-1234yf is analyzed for optimal performance. A control theoretical VCRS model is created to assess variable refrigerants under the same operational conditions. From this model, the coefficient of performance (COP), required mass flow rate of refrigerant, work required by the compressor, and overall heat transfer coefficient is determined for all 8 refrigerants. Lastly, a comprehensive analysis is provided to determine the most optimal refrigerants for cooling applications. R-717, commonly known as Ammonia, was found to have the highest COP value thus proving to be the optimal refrigerant for cooling AI chips and high-performing server applications.
文摘Objective: Fetal Alcohol Spectrum Disorders (FASDs) are common, often undiagnosed, lifelong developmental disorders that result from prenatal alcohol exposure. FASD is present at birth and typically identified around seven years of age. The most severe outcome in cases of FASD is mortality. The purpose of this scoping review is to 1) use a systematic review to provide an estimated mortality proportion for children with FASD, and 2) update a study published in 2014 by reviewing published reports of mortality in individuals diagnosed with FASD. Method: A search of PubMed, CINAHL, and Google Scholar for reports published between 2013 and 2023 on mortality in individuals with FASD. Results: Three population-based studies have reported on all-cause mortality rates, finding a combined mortality rate of 10.9%, a 2.63 fold (95% CI: 2.61 to 2.65) increase in mortality risk over the general population. Since 2016, this review identified only eight new cases meeting the study inclusion criteria. The reported causes of death were five cases of pneumonia, and one case each of failure to thrive and dehydration, intestinal dilatation and asphyxiation caused by overeating due to pica, and acute gastric volvulus. Discussion: While current research suggests a diagnosis of FASD is associated with a 2.6-fold increase in mortality risk, this is likely an underestimation, as most cases of FASD-related mortality go unreported. Globally, about 1 new case is reported every 15 months. However, in the United States alone, between 1752 to 4400 FASD related deaths occur annually. Our review suggests that FASD is rarely identified as a causal or contributing factor in deaths of children and adolescents, resulting in a substantial undercount of FASD-related deaths. Increased attention to the role of FASD in infant and child mortality case reviews, child death review committee reports, and mortality reviews is needed.
文摘Background: Fetal Alcohol Spectrum Disorders (FASDs) are a global public health concern with lifelong consequences for affected individuals. Recent prevalence studies suggest FASD prevalence rates range from 1-5% among school age children. Most people with FASD are not correctly diagnosed and inadequate screening to identify patients with increased risk may contribute to under-diagnosis. This study developed a 10-item screening tool for FASD and examined its feasibility. Methods: The sample consisted of 355 children who had been evaluated at an FASD clinic. Data from the 33-item Alcohol Related Neurodevelopmental Disorder Behavioral Checklist was used to develop a brief FASD screen by comparing the changes in Cronbach’s alpha for different combinations of items. The validity of the brief scale was then further examined using receiving operating characteristic analyses. Results: The 10-item screen demonstrated acceptable sensitivity, specificity, and accuracy to identify children at high risk for FASD. The percentage correctly classified was 91.3 and the area under the receiving operating characteristic curve was 0.971. Conclusions: This feasibility study demonstrated that a screen for FASD consisting of 10 items with yes or no responses can be completed in 3 - 4 minutes. The tool is brief, with a low administration burden and has acceptable epidemiologic performance characteristics including accuracy. Future research should examine the performance of this tool when used in larger, community-based populations where screening for FASD would be appropriate.
