Background Using Systematic Assessment of Geriatric Elements in Atrial Fibrillation(SAGE-AF) data, determine how well the rich mix of demographic, clinical history, geriatric assessments, and clinically adjudicated ev...Background Using Systematic Assessment of Geriatric Elements in Atrial Fibrillation(SAGE-AF) data, determine how well the rich mix of demographic, clinical history, geriatric assessments, and clinically adjudicated events can predict two-year survival.Methods Subjects were recruited from participating outpatient practices if they had non-valvular AF, were 65 or over with CHA_(2)DS_(2)-VASc scores of at least 2, and were candidates for anticoagulation. Demographics, clinical history, and geriatric qualities of life were assessed by interview and medical records review using standardized protocols and repeated at one and two years. Events identified were abstracted and submitted for adjudication using standard definitions of events and categories. Nonmortality event categories included hospitalizations(cardiovascular, bleeding, other), bleeding(major, clinically relevant non-major, minor), and seven major adverse cardiovascular events.Results The 1245 subjects experienced 1960 events, primarily hospitalizations(935) and/or bleeding(817);114 subjects(9.2%)died during two years of follow-up. Events initially abstracted to more than one category(172) were combined, resulting in 1788unique incidents. Most subjects had zero or one event(69%) and fewer than 7% had more than 3 types. Most variables were significant in bivariate analysis. Using multiple logistic regression with two-year survival as the outcome variable, the best-fit model included event number and type, number of unique incidents, and number of bleeding events(R^(2) = 0.511, C = 93.1) with sensitivity = 97.9% and specificity = 44.7%.Conclusions Two-year survival was high. This model, if validated, could have major implications for treatment of patients with AF. Patients in the large group with no or one event are at very low risk of death(under 2%). The small group with high risk for further complications, including death, deserve reassessment to determine if this trajectory can be altered.展开更多
Complete plastid genomes have been proposed as potential“super-barcodes”for plant identification and delineation,particularly in cases where standard DNA barcodes may be insufficient.However,few studies have systema...Complete plastid genomes have been proposed as potential“super-barcodes”for plant identification and delineation,particularly in cases where standard DNA barcodes may be insufficient.However,few studies have systematically addressed how taxonomic complexity,especially in rapidly radiating lineages with intricate evolutionary histories,might influencethe efficacyof plastome-scale barcodes.Pedicularis is a hyperdiverse genus in the Himalaya-Hengduan Mountains,and previous studies have demonstrated high discriminatory power of the standard barcodes within this genus.Therefore,Pedicularis serves as a model for investigating the key plastome-sequence characteristics and biological phenomena that determine species-discrimination capacity.In this study,we evaluated 292 plastomes representing 96 Pedicularis species to compare the discriminatory power of complete plastid genomes with of standard DNA barcodes.Our results revealed that the traditional standard barcode combination(nrITS+matK+rbcL+trnH-psbA)achieved the highest discrimination rates(81.25%),closely followed by the plastid large single copy(LSC)region(80.21%),then by full plastome,the supermatrix of proteincoding genes,and hypervariable regions(79.17%).Notably,the matK and ycf1 gene alone could discriminate 78.13%of species.Key determinants of species discrimination by integrating alignment length(AL)and the proportion of parsimony-informative sites(PPIS),as well as conserved genes under relaxed selection exhibiting stronger discriminatory capacity.Unlike previous studies that demonstrated superior discrimination rates of plastome-scale barcodes,this study reveals a notable exception of minimal differences between traditional DNA and plastome-scale barcodes that appearing linked to Pedicularis’specificbiological habits and potentially reflectingunique evolutionary patterns in the plastid genome.展开更多
The study of natural hybridization facilitates our understanding of potential adaptive mechanisms in evolution and the process involved in speciation.In this study,we used multiple data types,including morphological t...The study of natural hybridization facilitates our understanding of potential adaptive mechanisms in evolution and the process involved in speciation.In this study,we used multiple data types,including morphological traits,ddRAD-seq and ecological niche data,to investigate the differences among Rhododendron×duclouxii hybrid zones and the mechanisms underlying natural hybridization and possible future evolutionary pathways.Our results show that the origins of each hybrid zone are independent,with variations in hybrid formation,structural characteristics,and patterns of genetic components and morphological trait differentiation.There were no significant differences in morphological traits or genetic variation between the F_(1)and F_(2)generations;however,the range of variation of the F_(2)generation was broader than that of the F_(1)generation.The distribution and ecological characteristics of R.×duclouxii did not significantly differ from those of the two parental species,indicating weak ecological niche preferences between the hybrid and parental taxa.These results imply that the hybrid zones of R.×duclouxii are characterized by considerable variability,with the magnitude of hybridization in each case likely influenced by unique combinations of biological and ecological factors specific to each hybrid zone.We predict that R.×duclouxii hybrid zones will persist and give rise to complex hybrid swarms,each potentially leading to different evolutionary outcomes.展开更多
The red blood cell distribution width(RDW)is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis.Recently,the baseline RDW was found to have clinical significance ...The red blood cell distribution width(RDW)is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis.Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases.A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover).A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis.Further study of RDW may reveal new insight into inflammation mechanisms.In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems.We also present some of the related measurements for their value in predicting clinical outcomes in such conditions.According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count)and current disease severity indices used in clinical practice.展开更多
Additive manufacturing or three dimensional(3D)printing is a promising technique for producing complex geometries and high precision structures from various types of materials.The technique was particularly developed ...Additive manufacturing or three dimensional(3D)printing is a promising technique for producing complex geometries and high precision structures from various types of materials.The technique was particularly developed for polymer materials such as acrylonitrile–butadiene–styrene(ABS)and found its way to different industries such as aerospace,automotive,electronics,medicine and construction.However,during service in outdoor environments,3D printed polymer structures are exposed to different environmental conditions such as UV radiation and moisture,causing a significant degradation in the microstructure and mechanical properties of the structures.This study offers a novel method to improve durability of 3D printed polymer structures against accelerated environmental conditions by deposition of a metallic thin film(i.e.copper)on the structural surface.ABS specimens are 3D printed using fused deposition modeling(FDM)technique and metalized via DC magnetron sputtering.The characterization of durability of 3D printed ABS specimens in outdoor environments is carried out by monitoring flexural properties and microstructure of samples over the course of exposure in a controlled environmental chamber.展开更多
Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve dru...Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas:(1) inhaled drug-aerosol delivery into human lung-airways; and(2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well.Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system.展开更多
BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this d...BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease.Previous studies showed that long noncoding RNAs(lncRNAs)could be involved in autoimmune diseases including CD,but the detailed molecular mechanisms remain unclear.AIM To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD,and to characterize their pathogenic role(s)and related mechanisms.METHODS The differential expression of lncRNAs was screened by high-throughput RNA sequencing,and the top candidate genes were validated in an expanded cohort by real-time PCR.The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis,and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection,real-time PCR,Western blotting analysis,flow cytometry,and cell migration and invasion assays.Finally,these findings were confirmed in vivo using a CD animal model.RESULTS The 3'end of lncRNACNN3-206 and the 3’UTR of Caspase10 contain highaffinity miR212 binding sites.lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients.Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis,migration and invasion in intestinal epithelial cells.Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model.CONCLUSION lncRNACNN3-206 may play a key role in CD pathogenesis.lncRNACNN3-206 could be a therapeutic target for CD treatment.展开更多
The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases （NDDs）, including Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, and Huntington＇s disease （HD）, has been largel...The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases （NDDs）, including Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, and Huntington＇s disease （HD）, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment （MCI） phase of AD： salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD： human epidemiological data indicate that lithium reduc- es AD risk. Animal model studies （AMS） reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD： valproate AMS findings show promise. Pre-symptomatic PD： lithium and valproate AMS findings are encouraging. Early HD： uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD： lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication （valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD） are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.展开更多
Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs(DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis(RA) as monotherapy or in combinatio...Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs(DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis(RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase(JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type Ⅰcytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaL s(ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.展开更多
We examine three simple linear systems from the viewpoint of ergodic theory.We digitize the output and record only the sign of the output at integer times.We show that even with this minimal output we can recover impo...We examine three simple linear systems from the viewpoint of ergodic theory.We digitize the output and record only the sign of the output at integer times.We show that even with this minimal output we can recover important information about the systems.In particular,for a two-dimensional system viewed as a fow on the circle,we can determine the rate of rotation.We then use these results to determine the slope of the trajectories for constant irrational fow on the two-dimensional torus.To achieve this,we randomize the system by partitioning the state space and only recording which partition the state is in at each integer time.We show directly that these systems have entropy zero.Finally,we examine two four-dimensional systems and reduce them to the study of linear fows on the two-dimensional torus.展开更多
Introduction: Health care expenditures in the United States have rapidly risen in the last decade, including orthopaedic induced expenses. This paper addresses the methodology by which clinical evidence is obtained to...Introduction: Health care expenditures in the United States have rapidly risen in the last decade, including orthopaedic induced expenses. This paper addresses the methodology by which clinical evidence is obtained to better direct orthopaedic practice and encourage cost-efficiency. Questions: We conducted this inquiry to answer these questions: 1) Have orthopaedic expenses increased in the United States? 2) Does high grade clinical evidence prevail in orthopaedic literature? 3) Does clinical orthopaedic research include cost in outcome analysis? 4) Does the increase in orthopaedic expenses correlate with cost awareness in orthopaedic literature? Methods: The aggregate hospital charges (national bill) associated with three major orthopaedic procedures were extracted from the Nationwide Inpatient Sample (NIS) website (data available from 1997 to 2008). Using the biomedical search engine PubMed (launched 1996), different types of literature pertaining to general orthopaedic and three major orthopaedic procedures—hip replacement, knee replacement, and spine fusion, were probed regarding level of evidence and cost inclusion. Results: From 1997 to 2008, the national hospital charges for spine fusion increased by 10.4 times while for total knee replacement it increased by 4.9 times and for total/partial hip replacement by 3.4 times. From 1996 to 2010, PubMed indexed 1113 randomized controlled trials (RCTs) related to hip replacement, 942 related to knee replacement and 357 related to spine fusion. During the same period, RCTs related to total/partial hip replacement, total knee replacement and spine fusion procedures have increased by 3 times, 6 times, and 3.4 times, respectively. The percentage of blinded RCTS with cost analysis among all RCTs related to each procedure were 0%, 0.001% and 0.003% for total/partial hip replacement, total knee replacement and spine fusion procedures respectively. The correlation in the national hospital charges of all three procedures individually and their level I literature with cost element was not significant except for spine fusion. Conclusion: To improve literature shortfalls, substantial attention needs to be focused toward more rigorous studies which consider cost efficiency.展开更多
AIM To describe the characteristics of adults who needed to see a doctor in the past year but could not due to the extra cost and assess the impact of limited financial resources on the receipt of routine fecal occult...AIM To describe the characteristics of adults who needed to see a doctor in the past year but could not due to the extra cost and assess the impact of limited financial resources on the receipt of routine fecal occult blood test, sigmoidoscopy, or colonoscopy for colon cancer screening among insured patients. METHODS Data obtained from the 2012 Behavioral Risk Factor Surveillance System included 215436 insured adults age 50-75 years. We computed frequencies, adjusted odds ratios(a ORs), and 95%CIs using SAS v9.3 software. RESULTS Nine percent of the study population needed to see a doctor in the past year but could not because of cost. The numbers were significantly higher among those aged 50-64(P < 0.0001), Non-Hispanic Whites(P < 0.0001), and those with a primary care physician(P < 0.0001) among other factors. Adjusting for possible confounders, a ORs for not seeing the doctor in the past year because of cost were: stool occult blood test within last year a OR = 0.88; 95%CI: 0.76-1.02, sigmoidoscopy within last year a OR = 0.72; 95%CI: 0.48-1.07, colonoscopy within the last year a OR = 0.91; 95%CI: 0.81-1.02. CONCLUSION We found that the limited financial resources within the past 12 mo were significantly associated with colorectal cancer(CRC) non-screening. Patients with risk factors identified in this study should adhere to CRC guidelines and should receive financial help if needed.展开更多
Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of...Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.展开更多
Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration(FDA) recommends the proper disposal of unused prescribed ...Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration(FDA) recommends the proper disposal of unused prescribed medications to maintain safety and prevent environmental hazards. However, many of the current disposal techniques do not properly address safety. A drug disposal pouch containing granular activated carbon offers a unique disposal method to deactivate residual or expired medication in a convenient, effective, and safe manner. A robust and validated method for methylphenidate hydrochloride and loxapine succinate was developed using high-performance liquid chromatography(HPLC) and the deactivation efficiency of the disposal system was tested. Methylphenidate hydrochloride was analyzed on a C18 analytical column(250 mm ?4.60 mm, 100?) using acetonitrile-water(0.05%(v/v) trifluoroacetic acid) as the mobile phase at a flow rate of1.0 mL/min with a run time of 15 min and retention time of 7.8 min. Loxapine succinate was separated on a C8100?(250 mm ? 4.6 mm, 5 mm) column maintained at 25 °C using a flow rate of 1.0 mL/min. The run time was 10 min and the retention time of the drug was around 4.6 min. Mobile phase was composed of acetonitrile and water(0.3% triethylamine) at pH 3.0 as 40:60(v/v). Reference standard solutions(100 mg/mL) for both drugs were prepared by dissolving in mobile phases. These methods provide good linearity(R2? 0.999) over the range of 5–100 mg/mL for methylphenidate hydrochloride and 0.1–100 mg/mL for loxapine succinate. The assay methods were successfully applied to study the deactivation of these drugs.展开更多
This study seeks to investigate the variations associated with lane lateral locations and days of the week in the stochastic and dynamic transition of traffic regimes(DTTR).In the proposed analysis,hierarchical regres...This study seeks to investigate the variations associated with lane lateral locations and days of the week in the stochastic and dynamic transition of traffic regimes(DTTR).In the proposed analysis,hierarchical regression models fitted using Bayesian frameworks were used to calibrate the transition probabilities that describe the DTTR.Datasets of two sites on a freeway facility located in Jacksonville,Florida,were selected for the analysis.The traffic speed thresholds to define traffic regimes were estimated using the Gaussian mixture model(GMM).The GMM revealed that two and three regimes were adequate mixture components for estimating the traffic speed distributions for Site 1 and 2 datasets,respectively.The results of hierarchical regression models show that there is considerable evidence that there are heterogeneity characteristics in the DTTR associated with lateral lane locations.In particular,the hierarchical regressions reveal that the breakdown process is more affected by the variations compared to other evaluated transition processes with the estimated intra-class correlation(ICC)of about 73%.The transition from congestion on-set/dissolution(COD)to the congested regime is estimated with the highest ICC of 49.4%in the three-regime model,and the lowest ICC of 1%was observed on the transition from the congested to COD regime.On the other hand,different days of the week are not found to contribute to the variations(the highest ICC was 1.44%)on the DTTR.These findings can be used in developing effective congestion countermeasures,particularly in the application of intelligent transportation systems,such as dynamic lane-management strategies.展开更多
文摘Background Using Systematic Assessment of Geriatric Elements in Atrial Fibrillation(SAGE-AF) data, determine how well the rich mix of demographic, clinical history, geriatric assessments, and clinically adjudicated events can predict two-year survival.Methods Subjects were recruited from participating outpatient practices if they had non-valvular AF, were 65 or over with CHA_(2)DS_(2)-VASc scores of at least 2, and were candidates for anticoagulation. Demographics, clinical history, and geriatric qualities of life were assessed by interview and medical records review using standardized protocols and repeated at one and two years. Events identified were abstracted and submitted for adjudication using standard definitions of events and categories. Nonmortality event categories included hospitalizations(cardiovascular, bleeding, other), bleeding(major, clinically relevant non-major, minor), and seven major adverse cardiovascular events.Results The 1245 subjects experienced 1960 events, primarily hospitalizations(935) and/or bleeding(817);114 subjects(9.2%)died during two years of follow-up. Events initially abstracted to more than one category(172) were combined, resulting in 1788unique incidents. Most subjects had zero or one event(69%) and fewer than 7% had more than 3 types. Most variables were significant in bivariate analysis. Using multiple logistic regression with two-year survival as the outcome variable, the best-fit model included event number and type, number of unique incidents, and number of bleeding events(R^(2) = 0.511, C = 93.1) with sensitivity = 97.9% and specificity = 44.7%.Conclusions Two-year survival was high. This model, if validated, could have major implications for treatment of patients with AF. Patients in the large group with no or one event are at very low risk of death(under 2%). The small group with high risk for further complications, including death, deserve reassessment to determine if this trajectory can be altered.
基金supported by the National Natural Science Foundation of China(32371700,32071670 and 31870196)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB31000000)+4 种基金the Science and Technology Basic Resources Investigation Program of China(2021FY100200)Yunnan Revitalization Talent Support Program“Young Talent”and“Innovation Team”Projects(202405AS350019)the 14th Five-Year Plan of Xishuangbanna Tropical Botanical Garden,Chinese Academy of Science(XTBG-1450101)the Key R&D program of Yunnan Province,China(202103AC100003)the Key Basic Research program of Yunnan Province,China(202101BC070003).
文摘Complete plastid genomes have been proposed as potential“super-barcodes”for plant identification and delineation,particularly in cases where standard DNA barcodes may be insufficient.However,few studies have systematically addressed how taxonomic complexity,especially in rapidly radiating lineages with intricate evolutionary histories,might influencethe efficacyof plastome-scale barcodes.Pedicularis is a hyperdiverse genus in the Himalaya-Hengduan Mountains,and previous studies have demonstrated high discriminatory power of the standard barcodes within this genus.Therefore,Pedicularis serves as a model for investigating the key plastome-sequence characteristics and biological phenomena that determine species-discrimination capacity.In this study,we evaluated 292 plastomes representing 96 Pedicularis species to compare the discriminatory power of complete plastid genomes with of standard DNA barcodes.Our results revealed that the traditional standard barcode combination(nrITS+matK+rbcL+trnH-psbA)achieved the highest discrimination rates(81.25%),closely followed by the plastid large single copy(LSC)region(80.21%),then by full plastome,the supermatrix of proteincoding genes,and hypervariable regions(79.17%).Notably,the matK and ycf1 gene alone could discriminate 78.13%of species.Key determinants of species discrimination by integrating alignment length(AL)and the proportion of parsimony-informative sites(PPIS),as well as conserved genes under relaxed selection exhibiting stronger discriminatory capacity.Unlike previous studies that demonstrated superior discrimination rates of plastome-scale barcodes,this study reveals a notable exception of minimal differences between traditional DNA and plastome-scale barcodes that appearing linked to Pedicularis’specificbiological habits and potentially reflectingunique evolutionary patterns in the plastid genome.
基金supported by the National Natural Science Foundation of China,China(32300200,31670213,32160240)Postdoctoral Directional Training Foundation of Yunnan Province,China(E33O31C261)+2 种基金the Key Basic Research Program of Yunnan Province,China(202101BC070003)the CAS President’s International Fellowship Initiative,China(2024PVA0087)supported by the Rural and Environment Science and Analytical Services Division of the Scottish Government,United Kingdom.
文摘The study of natural hybridization facilitates our understanding of potential adaptive mechanisms in evolution and the process involved in speciation.In this study,we used multiple data types,including morphological traits,ddRAD-seq and ecological niche data,to investigate the differences among Rhododendron×duclouxii hybrid zones and the mechanisms underlying natural hybridization and possible future evolutionary pathways.Our results show that the origins of each hybrid zone are independent,with variations in hybrid formation,structural characteristics,and patterns of genetic components and morphological trait differentiation.There were no significant differences in morphological traits or genetic variation between the F_(1)and F_(2)generations;however,the range of variation of the F_(2)generation was broader than that of the F_(1)generation.The distribution and ecological characteristics of R.×duclouxii did not significantly differ from those of the two parental species,indicating weak ecological niche preferences between the hybrid and parental taxa.These results imply that the hybrid zones of R.×duclouxii are characterized by considerable variability,with the magnitude of hybridization in each case likely influenced by unique combinations of biological and ecological factors specific to each hybrid zone.We predict that R.×duclouxii hybrid zones will persist and give rise to complex hybrid swarms,each potentially leading to different evolutionary outcomes.
文摘The red blood cell distribution width(RDW)is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis.Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases.A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover).A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis.Further study of RDW may reveal new insight into inflammation mechanisms.In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems.We also present some of the related measurements for their value in predicting clinical outcomes in such conditions.According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count)and current disease severity indices used in clinical practice.
基金Provost Office at Mercer University for SEED grant。
文摘Additive manufacturing or three dimensional(3D)printing is a promising technique for producing complex geometries and high precision structures from various types of materials.The technique was particularly developed for polymer materials such as acrylonitrile–butadiene–styrene(ABS)and found its way to different industries such as aerospace,automotive,electronics,medicine and construction.However,during service in outdoor environments,3D printed polymer structures are exposed to different environmental conditions such as UV radiation and moisture,causing a significant degradation in the microstructure and mechanical properties of the structures.This study offers a novel method to improve durability of 3D printed polymer structures against accelerated environmental conditions by deposition of a metallic thin film(i.e.copper)on the structural surface.ABS specimens are 3D printed using fused deposition modeling(FDM)technique and metalized via DC magnetron sputtering.The characterization of durability of 3D printed ABS specimens in outdoor environments is carried out by monitoring flexural properties and microstructure of samples over the course of exposure in a controlled environmental chamber.
基金Supported by National Science Foundation,No.NSF-CBET 1232988 and ANSYS Inc.(Canonsburg,PA)
文摘Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas:(1) inhaled drug-aerosol delivery into human lung-airways; and(2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well.Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system.
基金Supported by Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX18_0174
文摘BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease.Previous studies showed that long noncoding RNAs(lncRNAs)could be involved in autoimmune diseases including CD,but the detailed molecular mechanisms remain unclear.AIM To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD,and to characterize their pathogenic role(s)and related mechanisms.METHODS The differential expression of lncRNAs was screened by high-throughput RNA sequencing,and the top candidate genes were validated in an expanded cohort by real-time PCR.The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis,and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection,real-time PCR,Western blotting analysis,flow cytometry,and cell migration and invasion assays.Finally,these findings were confirmed in vivo using a CD animal model.RESULTS The 3'end of lncRNACNN3-206 and the 3’UTR of Caspase10 contain highaffinity miR212 binding sites.lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients.Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis,migration and invasion in intestinal epithelial cells.Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model.CONCLUSION lncRNACNN3-206 may play a key role in CD pathogenesis.lncRNACNN3-206 could be a therapeutic target for CD treatment.
文摘The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases （NDDs）, including Alzheimer＇s disease （AD）, Parkinson＇s disease （PD）, and Huntington＇s disease （HD）, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment （MCI） phase of AD： salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD： human epidemiological data indicate that lithium reduc- es AD risk. Animal model studies （AMS） reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD： valproate AMS findings show promise. Pre-symptomatic PD： lithium and valproate AMS findings are encouraging. Early HD： uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD： lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication （valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD） are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.
文摘Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs(DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis(RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase(JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type Ⅰcytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb's mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaL s(ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.
文摘We examine three simple linear systems from the viewpoint of ergodic theory.We digitize the output and record only the sign of the output at integer times.We show that even with this minimal output we can recover important information about the systems.In particular,for a two-dimensional system viewed as a fow on the circle,we can determine the rate of rotation.We then use these results to determine the slope of the trajectories for constant irrational fow on the two-dimensional torus.To achieve this,we randomize the system by partitioning the state space and only recording which partition the state is in at each integer time.We show directly that these systems have entropy zero.Finally,we examine two four-dimensional systems and reduce them to the study of linear fows on the two-dimensional torus.
文摘Introduction: Health care expenditures in the United States have rapidly risen in the last decade, including orthopaedic induced expenses. This paper addresses the methodology by which clinical evidence is obtained to better direct orthopaedic practice and encourage cost-efficiency. Questions: We conducted this inquiry to answer these questions: 1) Have orthopaedic expenses increased in the United States? 2) Does high grade clinical evidence prevail in orthopaedic literature? 3) Does clinical orthopaedic research include cost in outcome analysis? 4) Does the increase in orthopaedic expenses correlate with cost awareness in orthopaedic literature? Methods: The aggregate hospital charges (national bill) associated with three major orthopaedic procedures were extracted from the Nationwide Inpatient Sample (NIS) website (data available from 1997 to 2008). Using the biomedical search engine PubMed (launched 1996), different types of literature pertaining to general orthopaedic and three major orthopaedic procedures—hip replacement, knee replacement, and spine fusion, were probed regarding level of evidence and cost inclusion. Results: From 1997 to 2008, the national hospital charges for spine fusion increased by 10.4 times while for total knee replacement it increased by 4.9 times and for total/partial hip replacement by 3.4 times. From 1996 to 2010, PubMed indexed 1113 randomized controlled trials (RCTs) related to hip replacement, 942 related to knee replacement and 357 related to spine fusion. During the same period, RCTs related to total/partial hip replacement, total knee replacement and spine fusion procedures have increased by 3 times, 6 times, and 3.4 times, respectively. The percentage of blinded RCTS with cost analysis among all RCTs related to each procedure were 0%, 0.001% and 0.003% for total/partial hip replacement, total knee replacement and spine fusion procedures respectively. The correlation in the national hospital charges of all three procedures individually and their level I literature with cost element was not significant except for spine fusion. Conclusion: To improve literature shortfalls, substantial attention needs to be focused toward more rigorous studies which consider cost efficiency.
文摘AIM To describe the characteristics of adults who needed to see a doctor in the past year but could not due to the extra cost and assess the impact of limited financial resources on the receipt of routine fecal occult blood test, sigmoidoscopy, or colonoscopy for colon cancer screening among insured patients. METHODS Data obtained from the 2012 Behavioral Risk Factor Surveillance System included 215436 insured adults age 50-75 years. We computed frequencies, adjusted odds ratios(a ORs), and 95%CIs using SAS v9.3 software. RESULTS Nine percent of the study population needed to see a doctor in the past year but could not because of cost. The numbers were significantly higher among those aged 50-64(P < 0.0001), Non-Hispanic Whites(P < 0.0001), and those with a primary care physician(P < 0.0001) among other factors. Adjusting for possible confounders, a ORs for not seeing the doctor in the past year because of cost were: stool occult blood test within last year a OR = 0.88; 95%CI: 0.76-1.02, sigmoidoscopy within last year a OR = 0.72; 95%CI: 0.48-1.07, colonoscopy within the last year a OR = 0.91; 95%CI: 0.81-1.02. CONCLUSION We found that the limited financial resources within the past 12 mo were significantly associated with colorectal cancer(CRC) non-screening. Patients with risk factors identified in this study should adhere to CRC guidelines and should receive financial help if needed.
文摘Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.
基金funded by Verde Technologies(Minnetonka,MN,USA)as an SBIR PhaseⅡcontract from the National Institute on Drug Abuse(NIDA).Title:In-Home Deactivation System for Psychoactive Drugs(SBIR Phase 2),Contract no.HHSN271201400068C NIDA Reference no.N44DA-14-4420
文摘Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration(FDA) recommends the proper disposal of unused prescribed medications to maintain safety and prevent environmental hazards. However, many of the current disposal techniques do not properly address safety. A drug disposal pouch containing granular activated carbon offers a unique disposal method to deactivate residual or expired medication in a convenient, effective, and safe manner. A robust and validated method for methylphenidate hydrochloride and loxapine succinate was developed using high-performance liquid chromatography(HPLC) and the deactivation efficiency of the disposal system was tested. Methylphenidate hydrochloride was analyzed on a C18 analytical column(250 mm ?4.60 mm, 100?) using acetonitrile-water(0.05%(v/v) trifluoroacetic acid) as the mobile phase at a flow rate of1.0 mL/min with a run time of 15 min and retention time of 7.8 min. Loxapine succinate was separated on a C8100?(250 mm ? 4.6 mm, 5 mm) column maintained at 25 °C using a flow rate of 1.0 mL/min. The run time was 10 min and the retention time of the drug was around 4.6 min. Mobile phase was composed of acetonitrile and water(0.3% triethylamine) at pH 3.0 as 40:60(v/v). Reference standard solutions(100 mg/mL) for both drugs were prepared by dissolving in mobile phases. These methods provide good linearity(R2? 0.999) over the range of 5–100 mg/mL for methylphenidate hydrochloride and 0.1–100 mg/mL for loxapine succinate. The assay methods were successfully applied to study the deactivation of these drugs.
文摘This study seeks to investigate the variations associated with lane lateral locations and days of the week in the stochastic and dynamic transition of traffic regimes(DTTR).In the proposed analysis,hierarchical regression models fitted using Bayesian frameworks were used to calibrate the transition probabilities that describe the DTTR.Datasets of two sites on a freeway facility located in Jacksonville,Florida,were selected for the analysis.The traffic speed thresholds to define traffic regimes were estimated using the Gaussian mixture model(GMM).The GMM revealed that two and three regimes were adequate mixture components for estimating the traffic speed distributions for Site 1 and 2 datasets,respectively.The results of hierarchical regression models show that there is considerable evidence that there are heterogeneity characteristics in the DTTR associated with lateral lane locations.In particular,the hierarchical regressions reveal that the breakdown process is more affected by the variations compared to other evaluated transition processes with the estimated intra-class correlation(ICC)of about 73%.The transition from congestion on-set/dissolution(COD)to the congested regime is estimated with the highest ICC of 49.4%in the three-regime model,and the lowest ICC of 1%was observed on the transition from the congested to COD regime.On the other hand,different days of the week are not found to contribute to the variations(the highest ICC was 1.44%)on the DTTR.These findings can be used in developing effective congestion countermeasures,particularly in the application of intelligent transportation systems,such as dynamic lane-management strategies.
