Dear Editor,We report a case of multiple evanescent white dot syndrome(MEWDS)relapse following mRNA corona virus disease 2019(COVID-19)vaccination.MEWDS is a choroidal inflammatory disease belonging to the group of“w...Dear Editor,We report a case of multiple evanescent white dot syndrome(MEWDS)relapse following mRNA corona virus disease 2019(COVID-19)vaccination.MEWDS is a choroidal inflammatory disease belonging to the group of“white dot syndromes”group,with an excellent prognosis[1].MEWDS is usually idiopathic,but there have been reports of MEWDS following viral infection or vaccination[1-2].展开更多
Dear Editor,Herein,we report a case of a patient who presented with refractory ocular hypertension(OHT)after a dexamethasone implant(DEX-I)injection.Intraocular pressure(IOP)was finally managed after Preserflo Micro S...Dear Editor,Herein,we report a case of a patient who presented with refractory ocular hypertension(OHT)after a dexamethasone implant(DEX-I)injection.Intraocular pressure(IOP)was finally managed after Preserflo Micro Shunt implantation,allowing the continued use of dexamethasone implant.展开更多
Gastric cancer associated peritoneal carcinomatosis(GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase...Gastric cancer associated peritoneal carcinomatosis(GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery( CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in longterm survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.展开更多
Prostate multi-parametric magnetic resonance imaging(mpMRI)has shown excellent sensitivity for Gleason7 cancers,especially when their volume is0.5 mL.As a result,performing an mpMRI before prostate biopsy could impr...Prostate multi-parametric magnetic resonance imaging(mpMRI)has shown excellent sensitivity for Gleason7 cancers,especially when their volume is0.5 mL.As a result,performing an mpMRI before prostate biopsy could improve the detection of clinically significant prostate cancer(csPCa)by adding targeted biopsies to systematic biopsies.Currently,there is a consensus that targeted biopsies improve the detection of csPCa in the repeat biopsy setting and at confirmatory biopsy in patients considering active surveillance.Several prospective multicentric controlled trials recently showed that targeted biopsy also improved csPCa detection in biopsy-naǐve patients.The role of mpMRI and targeted biopsy during the follow-up of active surveillance remains unclear.Whether systematic biopsy could be omitted in case of negative mpMRI is also a matter of controversy.mpMRI did show excellent negative predictive values(NPV)in the literature,however,since NPV depends on the prevalence of the disease,negative mpMRI findings should be interpreted in the light of a priori risk for csPCa of the patient.Nomograms combining mpMRI findings and classical risk predictors(age,prostatespecific antigen density,digital rectal examination,etc.)will probably be developed in the future to decide whether a prostate biopsy should be obtained.mpMRI has a good specificity for detecting T3 stage cancers,but its sensitivity is low.It should therefore not be used routinely for staging purposes in low-risk patients.Nomograms combining mpMRI findings and other clinical and biochemical data will also probably be used in the future to better assess the risk of T3 stage disease.展开更多
Pancreatic ductal adenocarcinoma(PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately...Pancreatic ductal adenocarcinoma(PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment(TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy-most commonly using a local high single dose-are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.展开更多
Background:In Mediterranean mountain socio-ecosystems,both grazing by livestock and the dry season may influence tree regeneration.However,the relative contributions of these drivers are poorly known,even though prese...Background:In Mediterranean mountain socio-ecosystems,both grazing by livestock and the dry season may influence tree regeneration.However,the relative contributions of these drivers are poorly known,even though present and future canopy composition might result from past and present variations in climate and herbivore density.This study aims to test how semi-feral cattle presence and season affect tree regeneration.Methods:The study was conducted using permanent plots inside and outside a cattle exclosure in an old-growth Mediterranean forest.Saplings and seedlings were counted five times per year(winter,early spring,middle spring,summer,fall)and monitored over 7 yrs.Results:Semi-feral cattle exclusion increased Acer,Fagus,Ilex,Pinus,Prunus and Quercus sapling densities and increased Acer,Fraxinus,Ilex,Quercus and Sorbus seedling densities.Interestingly,the dry season did not exert any noticeable effects on the sapling or seedling densities of any of the studied taxa.Discussion:Semi-feral cattle presence may limit tree regeneration through taxon-dependent effects,which suggests that the current decrease in grazing livestock across the Mediterranean basin will modify recruitment processes and,likely,future forest composition.Conclusions:Semi-feral cattle presence acts as a selective driver of tree community composition.展开更多
Aims.Return to work(RTW)after breast cancer is a complex process that questions the individual trajectories of patients and stakeholders.Program planning in this context requires relying on appropriate methods like In...Aims.Return to work(RTW)after breast cancer is a complex process that questions the individual trajectories of patients and stakeholders.Program planning in this context requires relying on appropriate methods like Intervention Mapping(IM)which encompasses such complexity.The aim of the methodological study is to describe an application of IM for both the design and production of a patient guide supporting RTW after breast cancer.Procedure.According to IM,the guide was co-constructed with a Community Advisory Board(CAB)of stakeholders(patients/associations,health professionals,companies,institutions)after considering other options(interactive website,mobile application).The design was done with empirical and theoretical anchoring,guided here by an Ecosystem Process of Change model.A communication agency was chosen to produce the document.Pre-tests were conducted with a representative panel of the target audience to assess the different prototypes elaborated,using questionnaires and a focus group.Results.The final structure of the guide is presented with comments in order to concretely illustrate the management of IM steps 3 and 4.The final structure of the guide is presented,along with a description of its components that target women(according to Prochaska et Di Clemente’s stages of change)and their environment(by use of levers they may activate).The results of the pre-test led to the simplification of the guide and its structure.Conclusion.IM allows a rich integration of experiential knowledge in the planning of complex health and public health programs.The development of the guide has attempted to integrate its aspects,in particular to promote both its implementation and its effects.Reflections are brought about the realistic evaluation of such complex interventions.展开更多
Light emission of europium(Eu^(3+))ions placed in the vicinity of optically resonant nanoantennas is usually controlled by tailoring the local density of photon states(LDOS).We show that the polarization and shape of ...Light emission of europium(Eu^(3+))ions placed in the vicinity of optically resonant nanoantennas is usually controlled by tailoring the local density of photon states(LDOS).We show that the polarization and shape of the excitation beam can also be used to manipulate light emission,as azimuthally or radially polarized cylindrical vector beam offers to spatially shape the electric and magnetic fields,in addition to the effect of silicon nanorings(Si-NRs)used as nanoantennas.The photoluminescence(PL)mappings of the Eu^(3+)transitions and the Si phonon mappings are strongly dependent of both the excitation beam and the Si-NR dimensions.The experimental results of Raman scattering and photoluminescence are confirmed by numerical simulations of the near-field intensity in the Si nanoantenna and in the Eu^(3+)-doped film,respectively.The branching ratios obtained from the experimental PL maps also reveal a redistribution of the electric and magnetic emission channels.Our results show that it could be possible to spatially control both electric and magnetic dipolar emission of Eu^(3+)ions by switching the laser beam polarization,hence the near field at the excitation wavelength,and the electric and magnetic LDOS at the emission wavelength.This paves the way for optimized geometries taking advantage of both excitation and emission processes.展开更多
Importance:Combination therapies of anti-PD-1 and anti-angiogenesis regimens are emerging rapidly and exhibit more promising anti-tumor efficacy for advanced hepatocellular carcinoma(HCC),and consistently it is the ho...Importance:Combination therapies of anti-PD-1 and anti-angiogenesis regimens are emerging rapidly and exhibit more promising anti-tumor efficacy for advanced hepatocellular carcinoma(HCC),and consistently it is the hotspot in clinical studies.Objective:To elaborate several issues which are warranted further consideration as more regimens are being investigated in combination therapies.Evidence Review:We searched PubMed,MEDLINE,Cochrane Library and Google Scholar by 2021 February for publications on combination therapies for HCC.Findings:Several clinical issues are worth reconsidering,such as the evaluation on appropriate primary endpoints in phase III clinical trials as for different practical problems,the translation of surrogate endpoint objective response rate(ORR)benefits into overall survival(OS)benefits,and whether conversion surgery contributes to initial expectations of long-term survival or not.New concepts in novel immunotherapy and targeted therapy in combination with loco-regional therapies may improve overall survival for HCC.Conclusions and Relevance for Reviews:Comprehensive understanding of the mechanism of immunotherapy and targeted therapy contributes to better prognosis of advanced HCC and more explorative combination therapies are needed.展开更多
By means of an ultrafast optical technique,we track focused gigahertz coherent phonon pulses in objects down to sub-micron in size.Infrared light pulses illuminating the surface of a single metal-coated silica fibre g...By means of an ultrafast optical technique,we track focused gigahertz coherent phonon pulses in objects down to sub-micron in size.Infrared light pulses illuminating the surface of a single metal-coated silica fibre generate longitudinal-phonon wave packets.Reflection of visible probe light pulses from the fibre surface allows the vibrational modes of the fibre to be detected,and Brillouin optical scattering of partially transmitted light pulses allows the acoustic wavefronts inside the transparent fibre to be continuously monitored.We thereby probe acoustic focusing in the time domain resulting from generation at the curved fibre surface.An analytical model,supported by three-dimensional simulations,suggests that we have followed the focusing of the acoustic beam down to a~150-nm diameter waist inside the fibre.This work significantly narrows the lateral resolution for focusing of picosecond acoustic pulses,normally limited by the diffraction limit of focused optical pulses to~1μm,and thereby opens up a new range of possibilities including nanoscale acoustic microscopy and nanoscale computed tomography.展开更多
The bioaccumulation of PAHs and metal elements in the indigenous lichens Xanthoria parietina was monitored during two years at a quarterly frequency,in 3 sites of contrasted anthropic influence.The impact of the meteo...The bioaccumulation of PAHs and metal elements in the indigenous lichens Xanthoria parietina was monitored during two years at a quarterly frequency,in 3 sites of contrasted anthropic influence.The impact of the meteorological factors(temperature,relative humidity,rainfall,wind speed)was first estimated through principal component analysis,and then by stepwise multilinear regressions to include wind directions.The pollutants levels reflected the proximity of atmospheric emissions,in particular from a large industrial harbor.High humidity and mild temperatures,and in a lower extent low wind speed and rainfall,also favored higher concentration levels.The contributions of these meteorological aspects became minor when including wind direction,especially when approaching major emission sources.The bioaccumulation integration time towards meteorological variations was on a seasonal basis(1–2 months)but the wind direction and thus local emissions also relied on a longer time scale(12 months).This showed that the contribution of meteorological conditions may be prevalent in remote places,while secondary in polluted areas,and should be definitely taken into account regarding long-term lichen biomonitoring and inter-annual comparisons.In the same time,a quadruple sampling in each site revealed a high homogeneity among supporting tree species and topography.The resulting uncertainty,including sampling,preparation and analysis was below 30%when comfortable analytical conditions were achieved.Finally,the occurrence of unexpected events such as a major forest fire,permitted to evaluate that this type of short,although intense,events did not have a strong influence on PAH and metals bioaccumulation by lichen.展开更多
Carbon catabolite repression(CCR)plays a key role in many physiological and adaptive responses in a broad range of microorganisms that are commonly associated with eukaryotic hosts.When a mixture of different carbon s...Carbon catabolite repression(CCR)plays a key role in many physiological and adaptive responses in a broad range of microorganisms that are commonly associated with eukaryotic hosts.When a mixture of different carbon sources is available,CCR,a global regulatory mechanism,inhibits the expression and activity of cellular processes associated with utilization of secondary carbon sources in the presence of the preferred carbon source.CCR is known to be executed by completely different mechanisms in different bacteria,yeast,and fungi.In addition to regulating catabolic genes,CCR also appears to play a key role in the expression of genes involved in plant–microbe interactions.Here,we present a detailed overview of CCR mechanisms in various bacteria.We highlight the role of CCR in beneficial as well as deleterious plant–microbe interactions based on the available literature.In addition,we explore the global distribution of known regulatory mechanisms within bacterial genomes retrieved from public repositories and within metatranscriptomes obtained from different plant rhizospheres.By integrating the available literature and performing targeted meta-analyses,we argue that CCR-regulated substrate use preferences of microorganisms should be considered an important trait involved in prevailing plant–microbe interactions.展开更多
A hallmark of low-temperature plasticity in body-centered cubic(BCC)metals is its departure from Schmid’s law.One aspect is that non-glide stresses,which do not produce any driving force on the dislocations,may affec...A hallmark of low-temperature plasticity in body-centered cubic(BCC)metals is its departure from Schmid’s law.One aspect is that non-glide stresses,which do not produce any driving force on the dislocations,may affect the yield stress.We show here that this effect is due to a variation of the relaxation volume of the 1/2<111>screw dislocations during glide.We predict quantitatively nonglide effects by modeling the dislocation core as an Eshelby inclusion,which couples elastically to the applied stress.This model explains the physical origin of the generalized yield criterion classically used to include non-Schmid effects in constitutive models of BCC plasticity.We use first-principles calculations to properly account for dislocation cores and use tungsten as a reference BCC metal.However,the methodology developed here applies to other BCC metals,other energy models and other solids showing nonglide effects.展开更多
Dear Editor,The proto-oncogene MYC has a well-documented role in driving androgen receptor(AR)oncogenic functions in prostate cancer(PCa cells)[1]and was recently reported as a key activator in the regulation of AR tr...Dear Editor,The proto-oncogene MYC has a well-documented role in driving androgen receptor(AR)oncogenic functions in prostate cancer(PCa cells)[1]and was recently reported as a key activator in the regulation of AR transcription[2].Dissecting the mechanisms underlying MYC-mediated AR regulation may be crucial for better understanding PCa development and improving its management.We recently demonstrated that menin,encoded by the MEN1 gene,plays an oncosuppressive role in the generation of ARlow/CD44+microinvasive prostate adenocarcinoma in mice but exerts oncogenic effects specifically in ARdependent human PCa cells,both likely by modulating AR transcription and AR targets[3].We herein wondered whether this oncogenic function of menin would occur through its interaction with other factors known to play a crucial role forAR transcription in PCa,in particular,MYC.展开更多
文摘Dear Editor,We report a case of multiple evanescent white dot syndrome(MEWDS)relapse following mRNA corona virus disease 2019(COVID-19)vaccination.MEWDS is a choroidal inflammatory disease belonging to the group of“white dot syndromes”group,with an excellent prognosis[1].MEWDS is usually idiopathic,but there have been reports of MEWDS following viral infection or vaccination[1-2].
文摘Dear Editor,Herein,we report a case of a patient who presented with refractory ocular hypertension(OHT)after a dexamethasone implant(DEX-I)injection.Intraocular pressure(IOP)was finally managed after Preserflo Micro Shunt implantation,allowing the continued use of dexamethasone implant.
文摘Gastric cancer associated peritoneal carcinomatosis(GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery( CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in longterm survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.
文摘Prostate multi-parametric magnetic resonance imaging(mpMRI)has shown excellent sensitivity for Gleason7 cancers,especially when their volume is0.5 mL.As a result,performing an mpMRI before prostate biopsy could improve the detection of clinically significant prostate cancer(csPCa)by adding targeted biopsies to systematic biopsies.Currently,there is a consensus that targeted biopsies improve the detection of csPCa in the repeat biopsy setting and at confirmatory biopsy in patients considering active surveillance.Several prospective multicentric controlled trials recently showed that targeted biopsy also improved csPCa detection in biopsy-naǐve patients.The role of mpMRI and targeted biopsy during the follow-up of active surveillance remains unclear.Whether systematic biopsy could be omitted in case of negative mpMRI is also a matter of controversy.mpMRI did show excellent negative predictive values(NPV)in the literature,however,since NPV depends on the prevalence of the disease,negative mpMRI findings should be interpreted in the light of a priori risk for csPCa of the patient.Nomograms combining mpMRI findings and classical risk predictors(age,prostatespecific antigen density,digital rectal examination,etc.)will probably be developed in the future to decide whether a prostate biopsy should be obtained.mpMRI has a good specificity for detecting T3 stage cancers,but its sensitivity is low.It should therefore not be used routinely for staging purposes in low-risk patients.Nomograms combining mpMRI findings and other clinical and biochemical data will also probably be used in the future to better assess the risk of T3 stage disease.
基金Supported by the Labex DEVwe Can (Universitéde Lyon) and PCSI ITMO Cancer INSERM。
文摘Pancreatic ductal adenocarcinoma(PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment(TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy-most commonly using a local high single dose-are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.
基金the Observatoire des Sciences de l’Univers OREME at Montpellier,France(INSU-CNRS).
文摘Background:In Mediterranean mountain socio-ecosystems,both grazing by livestock and the dry season may influence tree regeneration.However,the relative contributions of these drivers are poorly known,even though present and future canopy composition might result from past and present variations in climate and herbivore density.This study aims to test how semi-feral cattle presence and season affect tree regeneration.Methods:The study was conducted using permanent plots inside and outside a cattle exclosure in an old-growth Mediterranean forest.Saplings and seedlings were counted five times per year(winter,early spring,middle spring,summer,fall)and monitored over 7 yrs.Results:Semi-feral cattle exclusion increased Acer,Fagus,Ilex,Pinus,Prunus and Quercus sapling densities and increased Acer,Fraxinus,Ilex,Quercus and Sorbus seedling densities.Interestingly,the dry season did not exert any noticeable effects on the sapling or seedling densities of any of the studied taxa.Discussion:Semi-feral cattle presence may limit tree regeneration through taxon-dependent effects,which suggests that the current decrease in grazing livestock across the Mediterranean basin will modify recruitment processes and,likely,future forest composition.Conclusions:Semi-feral cattle presence acts as a selective driver of tree community composition.
文摘Aims.Return to work(RTW)after breast cancer is a complex process that questions the individual trajectories of patients and stakeholders.Program planning in this context requires relying on appropriate methods like Intervention Mapping(IM)which encompasses such complexity.The aim of the methodological study is to describe an application of IM for both the design and production of a patient guide supporting RTW after breast cancer.Procedure.According to IM,the guide was co-constructed with a Community Advisory Board(CAB)of stakeholders(patients/associations,health professionals,companies,institutions)after considering other options(interactive website,mobile application).The design was done with empirical and theoretical anchoring,guided here by an Ecosystem Process of Change model.A communication agency was chosen to produce the document.Pre-tests were conducted with a representative panel of the target audience to assess the different prototypes elaborated,using questionnaires and a focus group.Results.The final structure of the guide is presented with comments in order to concretely illustrate the management of IM steps 3 and 4.The final structure of the guide is presented,along with a description of its components that target women(according to Prochaska et Di Clemente’s stages of change)and their environment(by use of levers they may activate).The results of the pre-test led to the simplification of the guide and its structure.Conclusion.IM allows a rich integration of experiential knowledge in the planning of complex health and public health programs.The development of the guide has attempted to integrate its aspects,in particular to promote both its implementation and its effects.Reflections are brought about the realistic evaluation of such complex interventions.
基金We acknowledge funding from Agence Nationale de la Recherche under project HiLight(ANR-19-CE24-0020-01)support by the Toulouse computing facility HPC CALMIP(grants p12167 and p19042)the LAAS-CNRS micro and nanotechnologies platform,a member of the French RENATECH network.ICB is partner of the French Investissements d’Avenir program EUR-EIPHI(17-EURE-0002).
文摘Light emission of europium(Eu^(3+))ions placed in the vicinity of optically resonant nanoantennas is usually controlled by tailoring the local density of photon states(LDOS).We show that the polarization and shape of the excitation beam can also be used to manipulate light emission,as azimuthally or radially polarized cylindrical vector beam offers to spatially shape the electric and magnetic fields,in addition to the effect of silicon nanorings(Si-NRs)used as nanoantennas.The photoluminescence(PL)mappings of the Eu^(3+)transitions and the Si phonon mappings are strongly dependent of both the excitation beam and the Si-NR dimensions.The experimental results of Raman scattering and photoluminescence are confirmed by numerical simulations of the near-field intensity in the Si nanoantenna and in the Eu^(3+)-doped film,respectively.The branching ratios obtained from the experimental PL maps also reveal a redistribution of the electric and magnetic emission channels.Our results show that it could be possible to spatially control both electric and magnetic dipolar emission of Eu^(3+)ions by switching the laser beam polarization,hence the near field at the excitation wavelength,and the electric and magnetic LDOS at the emission wavelength.This paves the way for optimized geometries taking advantage of both excitation and emission processes.
基金funded by the National Science and Technology Major Project(No.2017ZX10203207)the National Natural Science Foundation of China(No.81672884)。
文摘Importance:Combination therapies of anti-PD-1 and anti-angiogenesis regimens are emerging rapidly and exhibit more promising anti-tumor efficacy for advanced hepatocellular carcinoma(HCC),and consistently it is the hotspot in clinical studies.Objective:To elaborate several issues which are warranted further consideration as more regimens are being investigated in combination therapies.Evidence Review:We searched PubMed,MEDLINE,Cochrane Library and Google Scholar by 2021 February for publications on combination therapies for HCC.Findings:Several clinical issues are worth reconsidering,such as the evaluation on appropriate primary endpoints in phase III clinical trials as for different practical problems,the translation of surrogate endpoint objective response rate(ORR)benefits into overall survival(OS)benefits,and whether conversion surgery contributes to initial expectations of long-term survival or not.New concepts in novel immunotherapy and targeted therapy in combination with loco-regional therapies may improve overall survival for HCC.Conclusions and Relevance for Reviews:Comprehensive understanding of the mechanism of immunotherapy and targeted therapy contributes to better prognosis of advanced HCC and more explorative combination therapies are needed.
基金Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology(MEXT)support from the Japanese Society for the Promotion of Science(JSPS).
文摘By means of an ultrafast optical technique,we track focused gigahertz coherent phonon pulses in objects down to sub-micron in size.Infrared light pulses illuminating the surface of a single metal-coated silica fibre generate longitudinal-phonon wave packets.Reflection of visible probe light pulses from the fibre surface allows the vibrational modes of the fibre to be detected,and Brillouin optical scattering of partially transmitted light pulses allows the acoustic wavefronts inside the transparent fibre to be continuously monitored.We thereby probe acoustic focusing in the time domain resulting from generation at the curved fibre surface.An analytical model,supported by three-dimensional simulations,suggests that we have followed the focusing of the acoustic beam down to a~150-nm diameter waist inside the fibre.This work significantly narrows the lateral resolution for focusing of picosecond acoustic pulses,normally limited by the diffraction limit of focused optical pulses to~1μm,and thereby opens up a new range of possibilities including nanoscale acoustic microscopy and nanoscale computed tomography.
基金This work was fully funded by the“InstitutÉcocitoyen pour la Connaissance des Pollutions”.
文摘The bioaccumulation of PAHs and metal elements in the indigenous lichens Xanthoria parietina was monitored during two years at a quarterly frequency,in 3 sites of contrasted anthropic influence.The impact of the meteorological factors(temperature,relative humidity,rainfall,wind speed)was first estimated through principal component analysis,and then by stepwise multilinear regressions to include wind directions.The pollutants levels reflected the proximity of atmospheric emissions,in particular from a large industrial harbor.High humidity and mild temperatures,and in a lower extent low wind speed and rainfall,also favored higher concentration levels.The contributions of these meteorological aspects became minor when including wind direction,especially when approaching major emission sources.The bioaccumulation integration time towards meteorological variations was on a seasonal basis(1–2 months)but the wind direction and thus local emissions also relied on a longer time scale(12 months).This showed that the contribution of meteorological conditions may be prevalent in remote places,while secondary in polluted areas,and should be definitely taken into account regarding long-term lichen biomonitoring and inter-annual comparisons.In the same time,a quadruple sampling in each site revealed a high homogeneity among supporting tree species and topography.The resulting uncertainty,including sampling,preparation and analysis was below 30%when comfortable analytical conditions were achieved.Finally,the occurrence of unexpected events such as a major forest fire,permitted to evaluate that this type of short,although intense,events did not have a strong influence on PAH and metals bioaccumulation by lichen.
基金This work was supported by the French National Research Agency(ANR-18-CE32-0005,DIORE).
文摘Carbon catabolite repression(CCR)plays a key role in many physiological and adaptive responses in a broad range of microorganisms that are commonly associated with eukaryotic hosts.When a mixture of different carbon sources is available,CCR,a global regulatory mechanism,inhibits the expression and activity of cellular processes associated with utilization of secondary carbon sources in the presence of the preferred carbon source.CCR is known to be executed by completely different mechanisms in different bacteria,yeast,and fungi.In addition to regulating catabolic genes,CCR also appears to play a key role in the expression of genes involved in plant–microbe interactions.Here,we present a detailed overview of CCR mechanisms in various bacteria.We highlight the role of CCR in beneficial as well as deleterious plant–microbe interactions based on the available literature.In addition,we explore the global distribution of known regulatory mechanisms within bacterial genomes retrieved from public repositories and within metatranscriptomes obtained from different plant rhizospheres.By integrating the available literature and performing targeted meta-analyses,we argue that CCR-regulated substrate use preferences of microorganisms should be considered an important trait involved in prevailing plant–microbe interactions.
基金L.D.acknowledges support from LabEx DAMAS(program“Investissements d’Avenir”,ANR-11-LABX-0008-01)D.R.acknowledges support from LabEx iMUST(ANR-10-LABX-0064)of Universitéde Lyon(program“Investissements d’Avenir”,ANR-11-IDEX-0007)This work was performed using HPC resources from GENCI-CINES computer center under Grant No.A0040906821 and A0040910156 and from PRACE(Partnership for Advanced Computing in Europe)access to AIMODIM project.
文摘A hallmark of low-temperature plasticity in body-centered cubic(BCC)metals is its departure from Schmid’s law.One aspect is that non-glide stresses,which do not produce any driving force on the dislocations,may affect the yield stress.We show here that this effect is due to a variation of the relaxation volume of the 1/2<111>screw dislocations during glide.We predict quantitatively nonglide effects by modeling the dislocation core as an Eshelby inclusion,which couples elastically to the applied stress.This model explains the physical origin of the generalized yield criterion classically used to include non-Schmid effects in constitutive models of BCC plasticity.We use first-principles calculations to properly account for dislocation cores and use tungsten as a reference BCC metal.However,the methodology developed here applies to other BCC metals,other energy models and other solids showing nonglide effects.
文摘Dear Editor,The proto-oncogene MYC has a well-documented role in driving androgen receptor(AR)oncogenic functions in prostate cancer(PCa cells)[1]and was recently reported as a key activator in the regulation of AR transcription[2].Dissecting the mechanisms underlying MYC-mediated AR regulation may be crucial for better understanding PCa development and improving its management.We recently demonstrated that menin,encoded by the MEN1 gene,plays an oncosuppressive role in the generation of ARlow/CD44+microinvasive prostate adenocarcinoma in mice but exerts oncogenic effects specifically in ARdependent human PCa cells,both likely by modulating AR transcription and AR targets[3].We herein wondered whether this oncogenic function of menin would occur through its interaction with other factors known to play a crucial role forAR transcription in PCa,in particular,MYC.