Recent years have witnessed a proliferation of quantitative methods for biogeographic inference. In particular, novel parametric approaches represent exciting new opportunities for the study of range evolution. Here, ...Recent years have witnessed a proliferation of quantitative methods for biogeographic inference. In particular, novel parametric approaches represent exciting new opportunities for the study of range evolution. Here, we review a selection of current methods for biogeographic analysis and discuss their respective properties. These methods include generalized parsimony approaches, weighted ancestral area analysis, dispersal-vicariance analysis, the dispersal--extinction--cladogenesis model and other maximum likelihood approaches, and Bayesian stochastic mapping of ancestral ranges, including a novel approach to inferring range evolution in the context of island biogeography. Some of these methods were developed specifically for problems of ancestral range reconstruction, whereas others were designed for more general problems of character state reconstruction and subsequently applied to the study of ancestral ranges. Methods for reconstructing ancestral history on a phylogenetic tree differ not only in the types of ancestral range states that are allowed, but also in the various historical events that may change the ancestral ranges. We explore how the form of allowed ancestral ranges and allowed transitions can both affect the outcome of ancestral range estimation. Finally, we mention some promising avenues for future work in the development of model-based approaches to biogeographic analysis.展开更多
This paper proposes a formation of multiple unmanned aerial vehicles(UAVs)based on the R5DOS(RCC-5 and orientation direction)intersection model.After improving the R5DOS-intersection model,we evenly arranged 16 UAVs i...This paper proposes a formation of multiple unmanned aerial vehicles(UAVs)based on the R5DOS(RCC-5 and orientation direction)intersection model.After improving the R5DOS-intersection model,we evenly arranged 16 UAVs in 16 spatial regions.Compared with those of the rectangular formation model and the grid formation model,the communication costs,time costs,and energy costs of the R5DOS model formation were effectively reduced.At the same time,the operation time of UAV formation was significantly enhanced.The leader-follower method can enhance the robustness of the UAV formation and ensure the integrity of communication during UAV formation operation.Finally,we conducted a simulation experiment on the model and found that the R5DOS model formation was stable and could maintain the desired formation.The randomly generated UAVs could quickly fly to the formation path in a short time,establish formation,and carry out operations.When the leader fails,the follower could travel to the original trajectory of the failed leader in a short time,replace the leader,and continue to communicate and improve the robustness of the formation.To sum up,the UAV formation based on the R5DOS model has the advantages of long operation time,strong endurance,low communication cost,and stable formation,which is of great significance for research on UAV formation.展开更多
Raman spectra of gallium phosphide （GAP） nanosolids （unheated and heat-treated at 598 and 723 K, respectively） were investigated. It was observed that both the longitudinal optical mode （LO） and the transverse o...Raman spectra of gallium phosphide （GAP） nanosolids （unheated and heat-treated at 598 and 723 K, respectively） were investigated. It was observed that both the longitudinal optical mode （LO） and the transverse optical mode （TO） displayed an asymmetry on the low-wavenumber side. The scattering bands were fitted to a sum of four Lorentzians which were assigned to the LO mode, surface phonon mode, TO mode, and a combination of Ga-O-P symmetric bending and sum band formed from the X-point TA ＋ LA phonons, respectively. Analysis of the characteristic of surface phonon mode revealed that the surface phonon peak of the GaP nanosolids could be confirmed. In the infrared spectrum of the GaP nanoparticles, we observed the bands on account of symmetric stretching and bending of PO2, as well as stretching of Ga-O The Raman scattering intensity arising from the Ga-O-P linkages increased as increasing the heat-treatment temperature.展开更多
Polyploid plants typically display advantages on some agronomically important traits over their diploid counterparts.Extensive studies have shown genetic,transcriptomic,and epigenetic dynamics upon polyploidization in...Polyploid plants typically display advantages on some agronomically important traits over their diploid counterparts.Extensive studies have shown genetic,transcriptomic,and epigenetic dynamics upon polyploidization in multiple plant species.However,few studies have unveiled those alternations imposed only by ploidy level,without any interference from heterozygosity.Cultivated potato is highly heterozygous.Thus,in this study,we developed two homozygous autotetraploid lines and one homozygous diploid line in parallel from a homozygous diploid potato.We confirmed their ploidy levels using chloroplast counting and karyotyping.Oligo-FISH and genome re-sequencing validated that these potato lines are nearly homozygous.We investigated variations in phenotypes,transcription,and histone modifications between two ploidies.Both autotetraploid lines produced larger but fewer tubers than the diploid line.Interestingly,each autotetraploid line displayed ploidy-related differential expression for various genes.We also discovered a genomewide enrichment of H3K27ac in genic regions upon whole-genome doubling(WGD).However,such enrichment was not associated with the differential gene expression between two ploidies.The tetraploid lines may exhibit better resistance to cold-induced sweetening(CIS)than the diploid line in tubers,potentially regulated through the expression of CIS-related key genes,which seems to be associated with the levels of H3K4me3 in cold-stored tubers.These findings will help to understand the impacts of autotetraploidization on dynamics of phenotypes,transcription,and histone modifications,as well as on CIS-related genes in response to cold storage.展开更多
Vitamin D is important in multiple aspects of health and its effects are mediated through the Vitamin D Receptor (VDR). We wanted to test the hypothesis that specific haplotypes of the VDR gene are associated with mar...Vitamin D is important in multiple aspects of health and its effects are mediated through the Vitamin D Receptor (VDR). We wanted to test the hypothesis that specific haplotypes of the VDR gene are associated with markers of disease severity, inflammation and bone health in Sickle Cell Disease (SCD). Genotyping was performed on DNA specimens from 1141 study participants in the NIH-funded Silent Infarct Transfusion (SIT) trial. We used the clinical and laboratory data to create separate endothelial dysfunction, vaso-occlusive severity scores and phenotype variables. Seventy-nine Single Nucleotide Polymorphisms (SNP) in the VDR gene and three associated genes—CYP27B1, VD binding protein, retinoid X receptor, were evaluated. The discovery cohort individuals had VDR haplotype information from a prior Genome-Wide Association Study (GWAS). The validation cohort was analyzed for SNPs that were significant in the discovery cohort. The pheno-type data were obtained from the demographic and clinical information of the participants, and were used to create the severity scores, vaso-occlusive score, endothelial dysfunction severity, and overall severity score. Potential gene-gene interactions were analyzed for prediction of disease severity within each severity score. Two SNPs were associated with the overall severity score, 3 SNPs with the endothelial dysfunction severity score and 4 SNPs with the vaso-occlusive severity score. After permutation testing to correct for multiple comparisons, only one of the associations remained significant. SNP rs7965281 was found to be associated with the endothelial dysfunction severity score and remained significant after correcting for multiple comparisons using permutation testing. In the validation cohort, that SNP was again tested for association with each of the severity scores. There was no association with the endothelial or the overall severity score but a trend towards association with the vaso-occlusive severity score (p = 0.02). None of the known functional polymorphisms in the VDR gene were found to have an association with severity in sickle cell disease. Further work analyzing for gene-gene interaction using the same significant SNPs remains to be done in association with inflammatory markers and measure of bone health. Those studies may provide insight on the contribution of VDR polymorphisms to sickle cell disease severity.展开更多
BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor types.Not all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other pall...BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor types.Not all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are limited.AIM To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving chemotherapy.METHODS The National Cancer Database was used to identify patients between 2004-2015.Patients with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were included.Cases with unknown chemotherapy,RT,or nonprimary surgery status were excluded.Kaplan-Meier estimates of OS were calculated.Cox proportional hazards regression models were employed to examine factors influencing survival.RESULTS Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete data.Median age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic center.The majority(72.7%)did not receive other palliative therapies.On both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased mortality.Higher histologic grade and T-stage were also associated with worse OS(P<0.05).CONCLUSION Palliative therapies other than chemotherapy conferred a numerically higher,but not statistically significant difference in OS among patients with metastatic esophageal cancer not receiving chemotherapy.Quality of life metrics,inpatient status,and subgroup analyses are important for examining the role of palliative therapies other than chemotherapy in metastatic esophageal cancer and future studies are warranted.展开更多
BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal cancer.However,not all patients with metastatic disease receive chemotherapy.AIM To evaluate a large canc...BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal cancer.However,not all patients with metastatic disease receive chemotherapy.AIM To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and survival.METHODS We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without chemotherapy.RESULTS A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving chemotherapy.The median follow-up was 69.45 mo.The median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no chemotherapy.Year of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value<0.001],median income>$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving chemotherapy.Modeling the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on OS.Moreover,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic Midwest(HR:1.07,95%CI:1.01-1.14,P=0.032),high CCI(HR for CCI≥2:1.16,95%CI:1.07-1.26,P<0.001),and higher tumor grade(HR for grade 3 vs grade 1:1.28,95%CI:1.14-1.44,P<0.001)and higher T stage(HR for T1 vs T4:0.89,95%CI:0.84-0.95,P<0.001)were independent predictors of worse OS on multivariable analyses.CONCLUSION In this large,retrospective NCDB analysis,we identified several socioeconomic and clinicopathologic predictors for receiving chemotherapy and OS in patients with metastatic esophageal cancer.The benefit of chemotherapy on OS is timedependent and favors early initiation.Focused outreach in lower income and underinsured patients is critical as receipt of chemotherapy is associated with improved OS.展开更多
The rising incidence and death rates linked to Alzheimer's disease(AD)highlight an urgent issue.Genetic screening is celebrated as a significant advancement for its early detection capabilities,pinpointing those a...The rising incidence and death rates linked to Alzheimer's disease(AD)highlight an urgent issue.Genetic screening is celebrated as a significant advancement for its early detection capabilities,pinpointing those at risk before the emergence of symptoms.Yet,the limited availability of these technologies highlights a critical gap in widespread application.This review pivots to the potential of presymptomatic clinical assessments as a readily available,economical,and simple strategy for early detection.Traditionally,AD diagnosis relies on the late-stage identification of cognitive deterioration,functional impairments,and neuropsychiatric symptoms,coinciding with advanced brain degeneration.Conversely,emerging research identifies early indicators preceding significant degeneration,manifesting years before clinical symptoms.We introduce a mnemonic,MEMORIES,to categorize these prodromal:Metabolism changes,Eye/visual impairments,March(refer to gait disturbances),Olfactory dysfunction,Rhythm(blood pressure and heart rate),Insensitivity of the tongue,Ears(hearing loss),and Stool alterations.Recognizing these prodromal through clinical examinations provides a valuable strategy for initiating preventative actions against brain degeneration.This approach advocates for broadening the screening lens beyond genetic screening to encompass clinical evaluations,enhancing early detection and intervention opportunities for AD.展开更多
Crop breeding requires a balance of tradeoffs among key agronomic traits caused by gene pleiotropy.The molecular manipulation of genes can effectively improve target traits,but this may not reduce gene pleiotropy,pote...Crop breeding requires a balance of tradeoffs among key agronomic traits caused by gene pleiotropy.The molecular manipulation of genes can effectively improve target traits,but this may not reduce gene pleiotropy,potentially leading to undesirable traits or even lethal conditions.However,molecular editing of cis-regulatory elements(CREs)of target genes may facilitate the dissection of gene pleiotropy to fine-tune gene expression.In this study,we developed a pipeline,in potato,which employs open chromatin to predict candidate CREs,along with both transient and genetic assays to validate the function of CREs and CRISPR/Cas9 to edit candidate CREs.We used StCDF1 as an example,a key gene for potato tuberization and identified a 288 bp-core promoter region,which showed photoperiodic inducibility.A homozygous CRISPR/Cas9-editing line was established,with two deletions in the core promoter,which displayed a reduced expression level,resulting in late tuberization under both longday and short-day conditions.This pipeline provides an alternative pathway to improve a specific trait with limited downside on other phenotypes.展开更多
Natural products are among the most important sources of lead molecules for drug discovery.With the development of affordable whole-genome sequencing technologies and other‘omics tools,the field of natural products r...Natural products are among the most important sources of lead molecules for drug discovery.With the development of affordable whole-genome sequencing technologies and other‘omics tools,the field of natural products research is currently undergoing a shift in paradigms.While,for decades,mainly analytical and chemical methods gave access to this group of compounds,nowadays genomics-based methods offer complementary approaches to find,identify and characterize such molecules.This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work.In this context,this review gives a summary of tools and databases that currently are available to mine,identify and characterize natural product biosynthesis pathways and their producers based on‘omics data.A web portal called Secondary Metabolite Bioinformatics Portal(SMBP at http://www.secondarymetabolites.org)is introduced to provide a one-stop catalog and links to these bioinformatics resources.In addition,an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field.展开更多
Array comparative genomic hybridization （CGH） has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patien...Array comparative genomic hybridization （CGH） has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome （2GH arrays. A number of highly frequent genomic aberrations were discovered, which may act as ＂drivers＂ of tumor progression. Meanwhile, the genomic profiles of four ＂normal＂ breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.展开更多
基金support from the National Institute of Environmental Health Sciences (USA) training grant to the NCSU Bioinformatics Research Centersupported by National Institutes of Health (USA) grant no.GM070806
文摘Recent years have witnessed a proliferation of quantitative methods for biogeographic inference. In particular, novel parametric approaches represent exciting new opportunities for the study of range evolution. Here, we review a selection of current methods for biogeographic analysis and discuss their respective properties. These methods include generalized parsimony approaches, weighted ancestral area analysis, dispersal-vicariance analysis, the dispersal--extinction--cladogenesis model and other maximum likelihood approaches, and Bayesian stochastic mapping of ancestral ranges, including a novel approach to inferring range evolution in the context of island biogeography. Some of these methods were developed specifically for problems of ancestral range reconstruction, whereas others were designed for more general problems of character state reconstruction and subsequently applied to the study of ancestral ranges. Methods for reconstructing ancestral history on a phylogenetic tree differ not only in the types of ancestral range states that are allowed, but also in the various historical events that may change the ancestral ranges. We explore how the form of allowed ancestral ranges and allowed transitions can both affect the outcome of ancestral range estimation. Finally, we mention some promising avenues for future work in the development of model-based approaches to biogeographic analysis.
基金This study was supported by the National Natural Science Foundation of China(Grant Nos.41601454 and 41671397,URL:http://www.nsfc.gov.cn/)Science and Technology Development Project of Jilin Province,China(Grant No.20191001008XH,URL:http://www.jlkjxm.com/)+2 种基金Science Foundation of Jilin Provincial Education Department,China(Grant No.:JJKH20200329KJ,URL:http://jyt.jl.gov.cn/)Development and Reform Commission Project of Jilin Province,China(Grant No.2020C037-7,URL:http://jldrc.jl.gov.cn/)Ecology and Environment Department Project of Jilin Province,China(Grant Nos.2019-02 and 2020-18,URL:http://sthjt.jl.gov.cn/).
文摘This paper proposes a formation of multiple unmanned aerial vehicles(UAVs)based on the R5DOS(RCC-5 and orientation direction)intersection model.After improving the R5DOS-intersection model,we evenly arranged 16 UAVs in 16 spatial regions.Compared with those of the rectangular formation model and the grid formation model,the communication costs,time costs,and energy costs of the R5DOS model formation were effectively reduced.At the same time,the operation time of UAV formation was significantly enhanced.The leader-follower method can enhance the robustness of the UAV formation and ensure the integrity of communication during UAV formation operation.Finally,we conducted a simulation experiment on the model and found that the R5DOS model formation was stable and could maintain the desired formation.The randomly generated UAVs could quickly fly to the formation path in a short time,establish formation,and carry out operations.When the leader fails,the follower could travel to the original trajectory of the failed leader in a short time,replace the leader,and continue to communicate and improve the robustness of the formation.To sum up,the UAV formation based on the R5DOS model has the advantages of long operation time,strong endurance,low communication cost,and stable formation,which is of great significance for research on UAV formation.
文摘Raman spectra of gallium phosphide （GAP） nanosolids （unheated and heat-treated at 598 and 723 K, respectively） were investigated. It was observed that both the longitudinal optical mode （LO） and the transverse optical mode （TO） displayed an asymmetry on the low-wavenumber side. The scattering bands were fitted to a sum of four Lorentzians which were assigned to the LO mode, surface phonon mode, TO mode, and a combination of Ga-O-P symmetric bending and sum band formed from the X-point TA ＋ LA phonons, respectively. Analysis of the characteristic of surface phonon mode revealed that the surface phonon peak of the GaP nanosolids could be confirmed. In the infrared spectrum of the GaP nanoparticles, we observed the bands on account of symmetric stretching and bending of PO2, as well as stretching of Ga-O The Raman scattering intensity arising from the Ga-O-P linkages increased as increasing the heat-treatment temperature.
基金supported by grants from the National Natural Science Foundation of China(31900386 to Z.Z.)Sichuan Science and Technology Program(2021YFH0025 to Z.Z.and 2021YFYZ0019 to B.Z.and Z.Z.)+1 种基金State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China at Sichuan Agricultural University(SKL-KF202205 to B.Z.)State Key Laboratory of Crop Biology Open Fund(2020KF01 to B.Z.)。
文摘Polyploid plants typically display advantages on some agronomically important traits over their diploid counterparts.Extensive studies have shown genetic,transcriptomic,and epigenetic dynamics upon polyploidization in multiple plant species.However,few studies have unveiled those alternations imposed only by ploidy level,without any interference from heterozygosity.Cultivated potato is highly heterozygous.Thus,in this study,we developed two homozygous autotetraploid lines and one homozygous diploid line in parallel from a homozygous diploid potato.We confirmed their ploidy levels using chloroplast counting and karyotyping.Oligo-FISH and genome re-sequencing validated that these potato lines are nearly homozygous.We investigated variations in phenotypes,transcription,and histone modifications between two ploidies.Both autotetraploid lines produced larger but fewer tubers than the diploid line.Interestingly,each autotetraploid line displayed ploidy-related differential expression for various genes.We also discovered a genomewide enrichment of H3K27ac in genic regions upon whole-genome doubling(WGD).However,such enrichment was not associated with the differential gene expression between two ploidies.The tetraploid lines may exhibit better resistance to cold-induced sweetening(CIS)than the diploid line in tubers,potentially regulated through the expression of CIS-related key genes,which seems to be associated with the levels of H3K4me3 in cold-stored tubers.These findings will help to understand the impacts of autotetraploidization on dynamics of phenotypes,transcription,and histone modifications,as well as on CIS-related genes in response to cold storage.
文摘Vitamin D is important in multiple aspects of health and its effects are mediated through the Vitamin D Receptor (VDR). We wanted to test the hypothesis that specific haplotypes of the VDR gene are associated with markers of disease severity, inflammation and bone health in Sickle Cell Disease (SCD). Genotyping was performed on DNA specimens from 1141 study participants in the NIH-funded Silent Infarct Transfusion (SIT) trial. We used the clinical and laboratory data to create separate endothelial dysfunction, vaso-occlusive severity scores and phenotype variables. Seventy-nine Single Nucleotide Polymorphisms (SNP) in the VDR gene and three associated genes—CYP27B1, VD binding protein, retinoid X receptor, were evaluated. The discovery cohort individuals had VDR haplotype information from a prior Genome-Wide Association Study (GWAS). The validation cohort was analyzed for SNPs that were significant in the discovery cohort. The pheno-type data were obtained from the demographic and clinical information of the participants, and were used to create the severity scores, vaso-occlusive score, endothelial dysfunction severity, and overall severity score. Potential gene-gene interactions were analyzed for prediction of disease severity within each severity score. Two SNPs were associated with the overall severity score, 3 SNPs with the endothelial dysfunction severity score and 4 SNPs with the vaso-occlusive severity score. After permutation testing to correct for multiple comparisons, only one of the associations remained significant. SNP rs7965281 was found to be associated with the endothelial dysfunction severity score and remained significant after correcting for multiple comparisons using permutation testing. In the validation cohort, that SNP was again tested for association with each of the severity scores. There was no association with the endothelial or the overall severity score but a trend towards association with the vaso-occlusive severity score (p = 0.02). None of the known functional polymorphisms in the VDR gene were found to have an association with severity in sickle cell disease. Further work analyzing for gene-gene interaction using the same significant SNPs remains to be done in association with inflammatory markers and measure of bone health. Those studies may provide insight on the contribution of VDR polymorphisms to sickle cell disease severity.
文摘BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor types.Not all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are limited.AIM To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving chemotherapy.METHODS The National Cancer Database was used to identify patients between 2004-2015.Patients with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were included.Cases with unknown chemotherapy,RT,or nonprimary surgery status were excluded.Kaplan-Meier estimates of OS were calculated.Cox proportional hazards regression models were employed to examine factors influencing survival.RESULTS Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete data.Median age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic center.The majority(72.7%)did not receive other palliative therapies.On both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased mortality.Higher histologic grade and T-stage were also associated with worse OS(P<0.05).CONCLUSION Palliative therapies other than chemotherapy conferred a numerically higher,but not statistically significant difference in OS among patients with metastatic esophageal cancer not receiving chemotherapy.Quality of life metrics,inpatient status,and subgroup analyses are important for examining the role of palliative therapies other than chemotherapy in metastatic esophageal cancer and future studies are warranted.
文摘BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal cancer.However,not all patients with metastatic disease receive chemotherapy.AIM To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and survival.METHODS We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without chemotherapy.RESULTS A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving chemotherapy.The median follow-up was 69.45 mo.The median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no chemotherapy.Year of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value<0.001],median income>$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving chemotherapy.Modeling the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on OS.Moreover,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic Midwest(HR:1.07,95%CI:1.01-1.14,P=0.032),high CCI(HR for CCI≥2:1.16,95%CI:1.07-1.26,P<0.001),and higher tumor grade(HR for grade 3 vs grade 1:1.28,95%CI:1.14-1.44,P<0.001)and higher T stage(HR for T1 vs T4:0.89,95%CI:0.84-0.95,P<0.001)were independent predictors of worse OS on multivariable analyses.CONCLUSION In this large,retrospective NCDB analysis,we identified several socioeconomic and clinicopathologic predictors for receiving chemotherapy and OS in patients with metastatic esophageal cancer.The benefit of chemotherapy on OS is timedependent and favors early initiation.Focused outreach in lower income and underinsured patients is critical as receipt of chemotherapy is associated with improved OS.
文摘The rising incidence and death rates linked to Alzheimer's disease(AD)highlight an urgent issue.Genetic screening is celebrated as a significant advancement for its early detection capabilities,pinpointing those at risk before the emergence of symptoms.Yet,the limited availability of these technologies highlights a critical gap in widespread application.This review pivots to the potential of presymptomatic clinical assessments as a readily available,economical,and simple strategy for early detection.Traditionally,AD diagnosis relies on the late-stage identification of cognitive deterioration,functional impairments,and neuropsychiatric symptoms,coinciding with advanced brain degeneration.Conversely,emerging research identifies early indicators preceding significant degeneration,manifesting years before clinical symptoms.We introduce a mnemonic,MEMORIES,to categorize these prodromal:Metabolism changes,Eye/visual impairments,March(refer to gait disturbances),Olfactory dysfunction,Rhythm(blood pressure and heart rate),Insensitivity of the tongue,Ears(hearing loss),and Stool alterations.Recognizing these prodromal through clinical examinations provides a valuable strategy for initiating preventative actions against brain degeneration.This approach advocates for broadening the screening lens beyond genetic screening to encompass clinical evaluations,enhancing early detection and intervention opportunities for AD.
基金supported by grants from the National Natural Science Foundation of China(32170573)Sichuan Science and Technology Program(2021YFYZ0019,2023ZYD0056).
文摘Crop breeding requires a balance of tradeoffs among key agronomic traits caused by gene pleiotropy.The molecular manipulation of genes can effectively improve target traits,but this may not reduce gene pleiotropy,potentially leading to undesirable traits or even lethal conditions.However,molecular editing of cis-regulatory elements(CREs)of target genes may facilitate the dissection of gene pleiotropy to fine-tune gene expression.In this study,we developed a pipeline,in potato,which employs open chromatin to predict candidate CREs,along with both transient and genetic assays to validate the function of CREs and CRISPR/Cas9 to edit candidate CREs.We used StCDF1 as an example,a key gene for potato tuberization and identified a 288 bp-core promoter region,which showed photoperiodic inducibility.A homozygous CRISPR/Cas9-editing line was established,with two deletions in the core promoter,which displayed a reduced expression level,resulting in late tuberization under both longday and short-day conditions.This pipeline provides an alternative pathway to improve a specific trait with limited downside on other phenotypes.
文摘Natural products are among the most important sources of lead molecules for drug discovery.With the development of affordable whole-genome sequencing technologies and other‘omics tools,the field of natural products research is currently undergoing a shift in paradigms.While,for decades,mainly analytical and chemical methods gave access to this group of compounds,nowadays genomics-based methods offer complementary approaches to find,identify and characterize such molecules.This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work.In this context,this review gives a summary of tools and databases that currently are available to mine,identify and characterize natural product biosynthesis pathways and their producers based on‘omics data.A web portal called Secondary Metabolite Bioinformatics Portal(SMBP at http://www.secondarymetabolites.org)is introduced to provide a one-stop catalog and links to these bioinformatics resources.In addition,an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field.
基金supported by the Danish Cancer Soci-ety through the budget of the Institute of Cancer Biol-ogy and by grants from the Danish Medical Research Council, the Natural and Medical Sciences Committee of the Danish Cancer Society, Novo Nordisk, the John and Birthe Meyer Foundation, the Solar Fonden, the Stensbygaard Fonden, the Kai Langeog Gundhild Kai Lange Fond, the will of Edith Stern, and the "Race Against Breast Cancer" ProjectThe support of the Marketing Department at the Danish Cancer Society is greatly appreciatedsupported by a project grant from the Hi-Tech Research and Development Program of China (2006AA02A301)
文摘Array comparative genomic hybridization （CGH） has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome （2GH arrays. A number of highly frequent genomic aberrations were discovered, which may act as ＂drivers＂ of tumor progression. Meanwhile, the genomic profiles of four ＂normal＂ breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.
