Since the advent of transcatheter aortic valve replacement(TAVR)in 2002,it has now become the default interventional strategy for symptomatic patients presenting with severe aortic stenosis,particularly in intermediat...Since the advent of transcatheter aortic valve replacement(TAVR)in 2002,it has now become the default interventional strategy for symptomatic patients presenting with severe aortic stenosis,particularly in intermediate to highsurgical risk patients.In 2019,the United States Food and Drug Administration approved TAVR in low-risk patients based on two randomized trials.However,these breakthrough trials excluded patients with certain unfavorable anatomies and odd profiles.While currently there is no randomized study of TAVR in young patients,it may be preferred by the young population given the benefits of early discharge,shorter hospital stay,and expedite recovery.Nonetheless,it is important to ruminate various factors including lifetime expectancy,risk of pacemaker implantation,and the need for future valve or coronary interventions in young cohorts before considering TAVR in these patients.Furthermore,the data on long-term durability(>10 years)of TAVR is still unknown given most of the procedures were initially performed in the high or prohibitive surgical risk population.Thus,this editorial aims to highlight the importance of considering an individualized approach in young patients with consideration of various factors including lifetime expectancy while choosing TAVR against surgical aortic valve replacement.展开更多
BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival outcomes.Currently,there is limited data investigating the significance of socioeconomic status,race/ethnici...BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival outcomes.Currently,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer survival.Data from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to 2016.Socioe-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban population.Survival was calculated with Cox proportional hazards models for death in the 5-year period following diagnosis.RESULTS Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma cases.When analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,P<0.05].Similarly,counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.展开更多
Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the produc...Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.展开更多
Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating im...Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like network with clearly discernable lumens, which is reminiscent of brain microvascular network in vivo. With the novel integrin-binding array system, we identified the specific types of integrins on brain microvascular endothelial cells that mediate cell adhesion and growth followed by functionalizing a 3 D hydrogel culture system using the binding peptides that specifically bind to the identified integrins, leading to robust growth and lumenized microvascular-like network formation of brain microvascular endothelial cells in 3 D culture. This technology can be used for in vitro and in vivo vascularization of transplants or brain lesions to promote brain tissue regeneration following neurological insults.展开更多
Tauopathies encompass a collection of chronic,progressive neurodegenerative diseases,including Alzheimer's disease(AD),chronic traumatic encephalopathy,and corticobasal degeneration,characterized by the accumulati...Tauopathies encompass a collection of chronic,progressive neurodegenerative diseases,including Alzheimer's disease(AD),chronic traumatic encephalopathy,and corticobasal degeneration,characterized by the accumulation of pathogenic aggregates of the microtubule-associated protein tau in neurons and/or glia(Reid et al.,2020).展开更多
Background:Spontaneous heparin-induced thrombocytopenia is a pro-thrombotic syndrome in which anti-heparin antibodies develop without heparin exposure.Case presentation:A 78-year-old man who underwent a successful lum...Background:Spontaneous heparin-induced thrombocytopenia is a pro-thrombotic syndrome in which anti-heparin antibodies develop without heparin exposure.Case presentation:A 78-year-old man who underwent a successful lumbar laminectomy presented to the hospital 5 days after discharge for stroke-like symptoms and was found to have acute infarcts of the bilateral frontal lobes.The patient was found to be severely thrombocytopenic and was incidentally found to have an inferior wall myocardial infarction.Further investigation led to the diagnosis of bilateral lower extremity deep vein thromboses.His overall clinical presentation prompted a detailed hematologic workup that indicated positivity for heparin-induced thrombocy-topenia despite no previous exposure to heparin products.Conclusions:This case illustrates a patient with no prior lifetime heparin exposure who underwent laminectomy with subsequent development of acute infarcts of the bilateral frontal lobes,an inferior wall myocardial infarction,and bilateral lower extremity deep vein thromboses,with concern for sequelae of spontaneous heparin-induced thrombo-cytopenia.展开更多
Background Examining the health outcomes of veterans who have completed the United States Veterans Health Administration’s(VHA’s)Traumatic Brain Injury(TBI)Screening and Evaluation Program may aid in the refinement ...Background Examining the health outcomes of veterans who have completed the United States Veterans Health Administration’s(VHA’s)Traumatic Brain Injury(TBI)Screening and Evaluation Program may aid in the refinement and improvement of clinical care initiatives within the VHA.This study compared self-reported physical functioning,cardiometabolic health conditions,and health care utilization patterns in Million Veteran Program enrollees with TBI Screening and Evaluation Program data(collected between 2007 and 2019),with the goal of enhancing understanding of potentially modifiable health conditions in this population.Methods In this observational cohort study,veterans(n=16,452)were grouped based on the diagnostic outcome of the TBI Screening and Evaluation Program:1)negative TBI screen(Screen^(-));2)positive TBI screen but no confirmed TBI diagnosis[Screen^(+)/Comprehensive TBI Evaluation(CTBIE)^(-)];or 3)positive TBI screen and confirmed TBI diagnosis(Screen^(+)/CTBIE^(+)).Chi-square tests and analysis of covariance were used to explore group differences in physical functioning,cardiometabolic health conditions,and health care utilization patterns,and logistic regressions were used to examine predictors of Screen^(+/-)and CTBIE^(+/-)group status.Results The results showed that veterans in the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups generally reported poorer levels of physical functioning(P’s<0.001,np2=0.02 to 0.03),higher rates of cardiometabolic health conditions(P’s<0.001,φ=0.14 to 0.52),and increased health care utilization(P’s<0.001,φ=0.14 to>0.5)compared with the Screen-group;however,health outcomes were generally comparable between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups.Follow-up analyses confirmed that while physical functioning,hypertension,stroke,healthcare utilization,and prescription medication use reliably distinguished between the Screen-and Screen^(+)groups(P’s<0.02,OR’s 0.78 to 3.38),only physical functioning distinguished between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups(P<0.001,OR 0.99).Conclusions The findings suggest that veterans who screen positive for TBI,regardless of whether they are ultimately diagnosed with TBI,are at greater risk for negative health outcomes,signifying that these veterans represent a vulnerable group that may benefit from increased clinical care and prevention efforts.展开更多
Lisfranc injuries can be difficult injuries to identify and treat, while also being the subject of significant debate on proper surgical management. A narrative literature review was performed using Pubmed and Google ...Lisfranc injuries can be difficult injuries to identify and treat, while also being the subject of significant debate on proper surgical management. A narrative literature review was performed using Pubmed and Google Scholar databases to identify recent studies evaluating open reduction internal fixation vs primary arthrodesis for Lisfranc injuries to further elucidate optimal surgical management. Additional focus was placed removal of hardware after ORIF to identify the need for routine hardware removal as an additional surgery may guide surgeon decision-making. This review showed inconclusive data on the superiority of ORIF vs arthrodesis, as multiple conflicting results exist, though established that functional results are similar between these options. Though both are generally accepted treatment options, there are no well-designed randomized controlled trials directly comparing the two. Retention of hardware after ORIF has been shown to be tolerated, though there is a significant risk of the need for unplanned removal due to pain and hardware breakage.展开更多
We present the development of a bias compensating reinforcement learning(RL)algorithm that optimizes thermal comfort(by minimizing tracking error)and control utilization(by penalizing setpoint deviations)in a multi-zo...We present the development of a bias compensating reinforcement learning(RL)algorithm that optimizes thermal comfort(by minimizing tracking error)and control utilization(by penalizing setpoint deviations)in a multi-zone heating,ventilation,and air-conditioning(HVAC)lab facility subject to unmeasurable disturbances and unknown dynamics.It is shown that the presence of unmeasurable disturbance results in an inconsistent learning equation in traditional RL controllers leading to parameter estimation bias(even with integral action support),and in the extreme case,the divergence of the learning algorithm.We demonstrate this issue by applying the popular Q-learning algorithm to linear quadratic regulation(LQR)of a multi-zone HVAC environment and showing that,even with integral support,the algorithm exhibits bias issue during the learning phase when the HVAC disturbance is unmeasurable due to unknown heat gains,occupancy variations,light sources,and outside weather changes.To address this difficulty,we present a bias compensating learning equation that learns a lumped bias term as a result of disturbances(and possibly other sources)in conjunction with the optimal control parameters.Experimental results show that the proposed scheme not only recovers the bias-free optimal control parameters but it does so without explicitly learning the dynamic model or estimating the disturbances,demonstrating the effectiveness of the algorithm in addressing the above challenges.展开更多
Background: In accordance with its measles elimination strategic plan 2012-2020, the Democratic Republic of the Congo (DRC) organized a follow-up vaccination campaign against measles from October to December 2019 in 2...Background: In accordance with its measles elimination strategic plan 2012-2020, the Democratic Republic of the Congo (DRC) organized a follow-up vaccination campaign against measles from October to December 2019 in 26 provinces. This study aims to establish the contribution of this supplementary vaccination campaign to protecting children against measles. Methods: The survey was carried out in November 2020 among households of the DRC, according to the 2018 revised version of the World Health Organization’s stratified cluster sampling method, using multiple stage sampling. It targeted 280 children aged 6 - 59 months per stratum or province, with 10 children in each of the 28 selected clusters. Data collection using tablets with centralized and real-time data processing was preceded by enumeration to refine the household sampling frame. Clusters and households were selected by random draw. Data collected with CS Pro 7 software were analyzed with SPSS, Epi info 7 and Excel software to determine indicators and make before-after comparisons using the McNemar test, at a precision threshold of 5%. Results: Of the 8535 surveyed children, 89.5% were vaccinatedduring the follow-up campaign and 81.6% were vaccinated before. Only 3.7% had correctly completed campaign vaccination cards. Estimated vaccination coverage increased from 80.8% before the campaign to 92.6% after the campaign (p 0.001). Vaccination coverage after campaign against measles improved in all provinces (p < 0.001) except Bas-Uele and Maniema. Thirteen provinces reached the national coverage target of 95%, compared to five before the campaign. The proportion of zero-dose children dropped significantly after this campaign from 19.2% to 7.4% (p 0.001), and even fell below 1% in six provinces. Conclusion: This measles vaccination campaign improved overall vaccination coverage by 10% and reached more unvaccinated children. Efforts must continue to improve the retention of vaccination card, the adherence of unvaccinated children and the effectiveness of routine vaccination.展开更多
Background A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait,and expression quantitative trait loci(eQTL)studies provide important information to help close that gap...Background A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait,and expression quantitative trait loci(eQTL)studies provide important information to help close that gap.However,two concerns that arise with eQTL analyses using RNA-sequencing data are normalization of data across samples and the data not following a normal distribution.Multiple pipelines have been suggested to address this.For instance,the most recent analysis of the human and farm Genotype-Tissue Expression(GTEx)project proposes using trimmed means of M-values(TMM)to normalize the data followed by an inverse normal transformation.Results In this study,we reasoned that eQTL analysis could be carried out using the same framework used for dif-ferential gene expression(DGE),which uses a negative binomial model,a statistical test feasible for count data.Using the GTEx framework,we identified 35 significant eQTLs(P<5×10^(–8))following the ANOVA model and 39 significant eQTLs(P<5×10^(–8))following the additive model.Using a differential gene expression framework,we identified 930 and six significant eQTLs(P<5×10^(–8))following an analytical framework equivalent to the ANOVA and additive model,respectively.When we compared the two approaches,there was no overlap of significant eQTLs between the two frameworks.Because we defined specific contrasts,we identified trans eQTLs that more closely resembled what we expect from genetic variants showing complete dominance between alleles.Yet,these were not identified by the GTEx framework.Conclusions Our results show that transforming RNA-sequencing data to fit a normal distribution prior to eQTL analysis is not required when the DGE framework is employed.Our proposed approach detected biologically relevant variants that otherwise would not have been identified due to data transformation to fit a normal distribution.展开更多
BACKGROUND Cirrhosis and its complications develop in a subgroup of patients with nonalcoholic fatty liver disease(NASH).Early detection of liver fibrosis represents an important goal of clinical care.AIM To test the ...BACKGROUND Cirrhosis and its complications develop in a subgroup of patients with nonalcoholic fatty liver disease(NASH).Early detection of liver fibrosis represents an important goal of clinical care.AIM To test the hypothesis that the development of cirrhosis in nonalcoholic fatty liver disease patients is preceded by the long-term trends of platelet counts and Fib-4 scores.METHODS We identified all patients in our healthcare system who had undergone fibrosis staging by liver biopsy or magnetic resonance elastography(MRE)for nonalcoholic fatty liver disease during the past decade(n=310).Platelet counts,serum glutamic-pyruvic transaminase and serum glutamic oxalacetic transaminase values preceding the staging tests were extracted from the electronic medical record system,and Fib-4 scores were calculated.Potential predictors of advanced fibrosis were evaluated using multivariate regression analysis.RESULTS Significant decreases in platelet counts and increases in Fib-4 scores were observed in all fibrosis stages,particularly in patients with cirrhosis.In the liver biopsy group,the presence of cirrhosis was best predicted by the combination of the Fib-4 score at the time closest to staging(P<0.0001),the presence of diabetes(P=0.0001),and the correlation coefficient of the preceding timedependent drop in platelet count(P=0.044).In the MRE group,Fib4 score(P=0.0025)and platelet drop(P=0.0373)were significant predictors.In comparison,the time-dependent rise of the Fib-4 score did not contribute in a statistically significant way.CONCLUSION Time-dependent changes in platelet counts and Fib-4 scores contribute to the prediction of cirrhosis in NASH patients with biopsy-or MRE-staged fibrosis.Their incorporation into predictive algorithms may assist in the earlier identification of high-risk patients.展开更多
Cellular angiofibroma is a rare mesenchymal tumor that most commonly presents as an asymptomatic well-circumscribed mass in the vulva. Very few cases have been found in the vagina and even fewer presented with vaginal...Cellular angiofibroma is a rare mesenchymal tumor that most commonly presents as an asymptomatic well-circumscribed mass in the vulva. Very few cases have been found in the vagina and even fewer presented with vaginal bleeding. A 54-year-old female presented to the emergency department with five months of vaginal bleeding and symptomatic anemia requiring blood transfusion. Upon physical examination, she was found to have a firm 4<span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">cm posterior vaginal mass, distinctly distal to the cervix. The mass was resected and diagnosed as a vaginal cellular angiofibroma on pathologic evaluation. The patient did well post</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">operatively with recommended follow-up every six months. The common differential diagnosis for a bleeding vaginal mass includes leiomyoma, angiofibroblastoma, aggressive angiomyxoma, squamous cell carcinoma, and adenocarcinoma. In this case, cellular angiofibroma presented as a vaginal mass with heavy bleeding leading to severe anemia. Early involvement of gynecologic oncology can help to optimize patients’ evaluation and management.</span></span></span>展开更多
BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clin...BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.展开更多
Obtaining nutritious food is becoming increasingly difficult due to the growing urban population and the degradation of soil, water, and air from mechanized and industrialized agricultural techniques. More than half t...Obtaining nutritious food is becoming increasingly difficult due to the growing urban population and the degradation of soil, water, and air from mechanized and industrialized agricultural techniques. More than half the global population resides in urban areas, with not enough surrounding agricultural land to meet food requirements. Food traveling long distances, an average of 1020 miles, has resulted in increased food miles for the average food item in the United States of America, representing wasted resources. The novel GREENBOX technology was invented in response to increasing pressures on food security. Previous studies conducted on GREENBOX technology assessed the technical feasibility of utilizing Lettuce Lactuca sativa ‘Rex Butterhead’. We at the APS Laboratory for Sustainable Food at Florida Gulf Coast University assessed the technical feasibility of growing different leafy green vegetable crops. GREENBOX technology consists of thermally insulated climate-controlled enclosures, an artificial lighting source, a soilless cultivation method (hydroponics), and environmental control modules. We assembled two GREENBOX units to assess the environmental conditions and growth performance of Brassica rapa var. chinensis ‘Li Ren Choi’, Spinach Spinacia oleracea ‘Auroch’, Arugula Eruca sativa ‘Astro’, and Mizuna Brassica Brassica rapa var. japonica. Plugs were cultivated and then transplanted in a randomized manner to the nutrient film technique (NFT) channels, subsequently grown for 30 days to full bloom and ready for harvest. Fertigation was carried out using a standard concentration nutrient solution. Crops were arranged in twelve blocks of four species each. We collected environmental data including daily light integral (DLI, mol/m<sup>2</sup>∙d), temperature (˚C), relative humidity (%), and vapor pressure deficit (VPD, kPa). Collected biomass data included wet weight (g), dry weight (g), leaf area (cm<sup>2</sup>), and chlorophyll concentration (mg/cm<sup>2</sup>). We then derived the Specific Leaf Area (SLA, cm<sup>2</sup>/g). Descriptive statistics were utilized to understand the differences in biomass parameters between the four crops grown. We also compared the performance parameters of our crops with existing peer-reviewed literature and found it superior, if not comparable to commonly found industrial output. We determined that all crops grew to full bloom, demonstrating that GREENBOX technology may be used to grow a variety of different leafy green vegetable crops.展开更多
Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triple...Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world,which is seriously threatening the lives of patients.Due to the rapid development of the disease,patients were in the mid...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world,which is seriously threatening the lives of patients.Due to the rapid development of the disease,patients were in the middle and advanced stages at the time of diagnosis and missed the best time for treatment.With the development of minimally invasive medicine,interventional therapy for advanced HCC has achieved promising results.Transarterial chemoembolization(TACE)and transarterial radioembolization(TARE)are currently recognized as effective treatments.This study aimed to investigate the clinical value and safety of TACE alone and combined with TACE in the treatment of progression in patients with advanced HCC and to find a breakthrough for the early diagnosis and treatment of patients with advanced HCC.AIM To investigate the efficacy and safety of hepatic TACE and TARE in advanced descending hepatectomy.METHODS In this study,218 patients with advanced HCC who were treated in the Zhejiang Provincial People’s Hospital from May 2016 to May 2021 were collected.Of the patients,119 served as the control group and received hepatic TACE,99 served as the observation group and were treated with hepatic TACE combined with TARE.The patients in two groups were compared in terms of lesion inactivation,tumor nodule size,lipiodol deposition,serum alpha-fetoprotein(AFP)level in different periods,postoperative complications,1-year survival rate,and clinical symptoms such as liver pain,fatigue,and abdominal distension,and adverse reactions such as nausea and vomiting.RESULTS The observation group and the control group had good efficacy in treatment efficiency,reduction of tumor nodules,reduction of postoperative AFP value,reduction of postoperative complications,and relief of clinical symptoms.In addition,compared with the control group,the treatment efficiency,reduction of tumor nodules,reduction of AFP value,reduction of postoperative complications,and relief of clinical symptoms in the observation group were better than those in the TACE group alone.Patients in the TACE+TARE group had a higher 1-year survival rate after surgery,lipiodol deposition was significantly increased and the extent of tumor necrosis was expanded.The overall incidence of adverse reactions in the TACE+TARE group was lower than that in the TACE group,and the difference had statistical significance(P<0.05).CONCLUSION Compared with TACE alone,TACE combined with TARE is more effective in the treatment of patients with advanced HCC.It also improves postoperative survival rate,reduces adverse effects,and has a better safety profile.展开更多
Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging e...Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging evidence that salivary micro-ribonucleic acids(miRNAs)may serve as biomarkers of concussion;however,it remains unclear whether concussion-related miRNAs are impacted by exercise.We sought to determine whether40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports.Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.Methods:This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites.Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing.Within-subjects testing was used to identify and exclude miRNAs that changed with either(a)a single episode of exercise(166 samples from 83 individuals)or(b)season-long participation in contact sports(212 samples from 106 individuals).The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression(172 samples from 75 concussed and 97 non-concussed individuals).Results:Two miRNAs(miR-532-5p and miR-182-5p)decreased(adjusted p<0.05)after a single episode of exercise,and 1 miRNA(miR-4510)increased only after contact sports participation.Twenty-three miRNAs changed at the end of a contact sports season.Two of these miRNAs(miR-26b-3p and miR-29c-3p)were associated(R>0.50;adjusted p<0.05)with the number of head impacts sustained in a single football practice.Among the 15 miRNAs not confounded by exercise or season-long contact sports participation,11 demonstrated a significant difference(adjusted p<0.05)between concussed and non-concussed participants,and 6 displayed moderate ability(area under curve>0.70)to identify concussion.A single ratio(miR-27a-5p/miR-30a-3p)displayed the highest accuracy(AUC=0.810,sensitivity=82.4%,specificity=73.3%)for differentiating concussed and non-concussed participants.Accuracy did not differ between participants with SRC and non-SRC(z=0.5,p=0.60).Conclusion:Salivary miRNA levels may accurately identify SRC when not confounded by exercise.Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive,sideline adjunct for SRC assessment.展开更多
We study boundary value problems for fractional integro-differential equations involving Caputo derivative of order α∈ (n-1, n) in Banach spaces. Existence and uniqueness results of solutions are established by vi...We study boundary value problems for fractional integro-differential equations involving Caputo derivative of order α∈ (n-1, n) in Banach spaces. Existence and uniqueness results of solutions are established by virtue of the Holder's inequality, a suitable singular Cronwall's inequality and fixed point theorem via a priori estimate method. At last, examples are given to illustrate the results.展开更多
文摘Since the advent of transcatheter aortic valve replacement(TAVR)in 2002,it has now become the default interventional strategy for symptomatic patients presenting with severe aortic stenosis,particularly in intermediate to highsurgical risk patients.In 2019,the United States Food and Drug Administration approved TAVR in low-risk patients based on two randomized trials.However,these breakthrough trials excluded patients with certain unfavorable anatomies and odd profiles.While currently there is no randomized study of TAVR in young patients,it may be preferred by the young population given the benefits of early discharge,shorter hospital stay,and expedite recovery.Nonetheless,it is important to ruminate various factors including lifetime expectancy,risk of pacemaker implantation,and the need for future valve or coronary interventions in young cohorts before considering TAVR in these patients.Furthermore,the data on long-term durability(>10 years)of TAVR is still unknown given most of the procedures were initially performed in the high or prohibitive surgical risk population.Thus,this editorial aims to highlight the importance of considering an individualized approach in young patients with consideration of various factors including lifetime expectancy while choosing TAVR against surgical aortic valve replacement.
文摘BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival outcomes.Currently,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer survival.Data from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to 2016.Socioe-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban population.Survival was calculated with Cox proportional hazards models for death in the 5-year period following diagnosis.RESULTS Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma cases.When analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,P<0.05].Similarly,counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.
文摘Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.
基金supported by NIH grant RO1 NS093985 (to DS, NZ, XW) and RO1 NS101955 (to DS)the VCU Microscopy Facility,supported,in part,by funding from NIH-NCI Cancer Center Support Grant P30 CA016059。
文摘Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like network with clearly discernable lumens, which is reminiscent of brain microvascular network in vivo. With the novel integrin-binding array system, we identified the specific types of integrins on brain microvascular endothelial cells that mediate cell adhesion and growth followed by functionalizing a 3 D hydrogel culture system using the binding peptides that specifically bind to the identified integrins, leading to robust growth and lumenized microvascular-like network formation of brain microvascular endothelial cells in 3 D culture. This technology can be used for in vitro and in vivo vascularization of transplants or brain lesions to promote brain tissue regeneration following neurological insults.
基金supported by the Department of Defense under award number W81XWH1910344-PRARP-CSRA (to CB)。
文摘Tauopathies encompass a collection of chronic,progressive neurodegenerative diseases,including Alzheimer's disease(AD),chronic traumatic encephalopathy,and corticobasal degeneration,characterized by the accumulation of pathogenic aggregates of the microtubule-associated protein tau in neurons and/or glia(Reid et al.,2020).
文摘Background:Spontaneous heparin-induced thrombocytopenia is a pro-thrombotic syndrome in which anti-heparin antibodies develop without heparin exposure.Case presentation:A 78-year-old man who underwent a successful lumbar laminectomy presented to the hospital 5 days after discharge for stroke-like symptoms and was found to have acute infarcts of the bilateral frontal lobes.The patient was found to be severely thrombocytopenic and was incidentally found to have an inferior wall myocardial infarction.Further investigation led to the diagnosis of bilateral lower extremity deep vein thromboses.His overall clinical presentation prompted a detailed hematologic workup that indicated positivity for heparin-induced thrombocy-topenia despite no previous exposure to heparin products.Conclusions:This case illustrates a patient with no prior lifetime heparin exposure who underwent laminectomy with subsequent development of acute infarcts of the bilateral frontal lobes,an inferior wall myocardial infarction,and bilateral lower extremity deep vein thromboses,with concern for sequelae of spontaneous heparin-induced thrombo-cytopenia.
基金supported by a Career Development Award awarded to Dr. Merritt from the VA Clinical Science Research&Development Service (IK2 CX001952)Dr. Clark received start-up funds from the University of Texas at Austin that further supported this work。
文摘Background Examining the health outcomes of veterans who have completed the United States Veterans Health Administration’s(VHA’s)Traumatic Brain Injury(TBI)Screening and Evaluation Program may aid in the refinement and improvement of clinical care initiatives within the VHA.This study compared self-reported physical functioning,cardiometabolic health conditions,and health care utilization patterns in Million Veteran Program enrollees with TBI Screening and Evaluation Program data(collected between 2007 and 2019),with the goal of enhancing understanding of potentially modifiable health conditions in this population.Methods In this observational cohort study,veterans(n=16,452)were grouped based on the diagnostic outcome of the TBI Screening and Evaluation Program:1)negative TBI screen(Screen^(-));2)positive TBI screen but no confirmed TBI diagnosis[Screen^(+)/Comprehensive TBI Evaluation(CTBIE)^(-)];or 3)positive TBI screen and confirmed TBI diagnosis(Screen^(+)/CTBIE^(+)).Chi-square tests and analysis of covariance were used to explore group differences in physical functioning,cardiometabolic health conditions,and health care utilization patterns,and logistic regressions were used to examine predictors of Screen^(+/-)and CTBIE^(+/-)group status.Results The results showed that veterans in the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups generally reported poorer levels of physical functioning(P’s<0.001,np2=0.02 to 0.03),higher rates of cardiometabolic health conditions(P’s<0.001,φ=0.14 to 0.52),and increased health care utilization(P’s<0.001,φ=0.14 to>0.5)compared with the Screen-group;however,health outcomes were generally comparable between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups.Follow-up analyses confirmed that while physical functioning,hypertension,stroke,healthcare utilization,and prescription medication use reliably distinguished between the Screen-and Screen^(+)groups(P’s<0.02,OR’s 0.78 to 3.38),only physical functioning distinguished between the Screen^(+)/CTBIE^(-)and Screen^(+)/CTBIE^(+)groups(P<0.001,OR 0.99).Conclusions The findings suggest that veterans who screen positive for TBI,regardless of whether they are ultimately diagnosed with TBI,are at greater risk for negative health outcomes,signifying that these veterans represent a vulnerable group that may benefit from increased clinical care and prevention efforts.
文摘Lisfranc injuries can be difficult injuries to identify and treat, while also being the subject of significant debate on proper surgical management. A narrative literature review was performed using Pubmed and Google Scholar databases to identify recent studies evaluating open reduction internal fixation vs primary arthrodesis for Lisfranc injuries to further elucidate optimal surgical management. Additional focus was placed removal of hardware after ORIF to identify the need for routine hardware removal as an additional surgery may guide surgeon decision-making. This review showed inconclusive data on the superiority of ORIF vs arthrodesis, as multiple conflicting results exist, though established that functional results are similar between these options. Though both are generally accepted treatment options, there are no well-designed randomized controlled trials directly comparing the two. Retention of hardware after ORIF has been shown to be tolerated, though there is a significant risk of the need for unplanned removal due to pain and hardware breakage.
文摘We present the development of a bias compensating reinforcement learning(RL)algorithm that optimizes thermal comfort(by minimizing tracking error)and control utilization(by penalizing setpoint deviations)in a multi-zone heating,ventilation,and air-conditioning(HVAC)lab facility subject to unmeasurable disturbances and unknown dynamics.It is shown that the presence of unmeasurable disturbance results in an inconsistent learning equation in traditional RL controllers leading to parameter estimation bias(even with integral action support),and in the extreme case,the divergence of the learning algorithm.We demonstrate this issue by applying the popular Q-learning algorithm to linear quadratic regulation(LQR)of a multi-zone HVAC environment and showing that,even with integral support,the algorithm exhibits bias issue during the learning phase when the HVAC disturbance is unmeasurable due to unknown heat gains,occupancy variations,light sources,and outside weather changes.To address this difficulty,we present a bias compensating learning equation that learns a lumped bias term as a result of disturbances(and possibly other sources)in conjunction with the optimal control parameters.Experimental results show that the proposed scheme not only recovers the bias-free optimal control parameters but it does so without explicitly learning the dynamic model or estimating the disturbances,demonstrating the effectiveness of the algorithm in addressing the above challenges.
文摘Background: In accordance with its measles elimination strategic plan 2012-2020, the Democratic Republic of the Congo (DRC) organized a follow-up vaccination campaign against measles from October to December 2019 in 26 provinces. This study aims to establish the contribution of this supplementary vaccination campaign to protecting children against measles. Methods: The survey was carried out in November 2020 among households of the DRC, according to the 2018 revised version of the World Health Organization’s stratified cluster sampling method, using multiple stage sampling. It targeted 280 children aged 6 - 59 months per stratum or province, with 10 children in each of the 28 selected clusters. Data collection using tablets with centralized and real-time data processing was preceded by enumeration to refine the household sampling frame. Clusters and households were selected by random draw. Data collected with CS Pro 7 software were analyzed with SPSS, Epi info 7 and Excel software to determine indicators and make before-after comparisons using the McNemar test, at a precision threshold of 5%. Results: Of the 8535 surveyed children, 89.5% were vaccinatedduring the follow-up campaign and 81.6% were vaccinated before. Only 3.7% had correctly completed campaign vaccination cards. Estimated vaccination coverage increased from 80.8% before the campaign to 92.6% after the campaign (p 0.001). Vaccination coverage after campaign against measles improved in all provinces (p < 0.001) except Bas-Uele and Maniema. Thirteen provinces reached the national coverage target of 95%, compared to five before the campaign. The proportion of zero-dose children dropped significantly after this campaign from 19.2% to 7.4% (p 0.001), and even fell below 1% in six provinces. Conclusion: This measles vaccination campaign improved overall vaccination coverage by 10% and reached more unvaccinated children. Efforts must continue to improve the retention of vaccination card, the adherence of unvaccinated children and the effectiveness of routine vaccination.
基金partially funded by the Virginia Cattle Industry Board and the Virginia Agriculture CouncilVT Open Access Subvention Fund for the partial support of the publication fees
文摘Background A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait,and expression quantitative trait loci(eQTL)studies provide important information to help close that gap.However,two concerns that arise with eQTL analyses using RNA-sequencing data are normalization of data across samples and the data not following a normal distribution.Multiple pipelines have been suggested to address this.For instance,the most recent analysis of the human and farm Genotype-Tissue Expression(GTEx)project proposes using trimmed means of M-values(TMM)to normalize the data followed by an inverse normal transformation.Results In this study,we reasoned that eQTL analysis could be carried out using the same framework used for dif-ferential gene expression(DGE),which uses a negative binomial model,a statistical test feasible for count data.Using the GTEx framework,we identified 35 significant eQTLs(P<5×10^(–8))following the ANOVA model and 39 significant eQTLs(P<5×10^(–8))following the additive model.Using a differential gene expression framework,we identified 930 and six significant eQTLs(P<5×10^(–8))following an analytical framework equivalent to the ANOVA and additive model,respectively.When we compared the two approaches,there was no overlap of significant eQTLs between the two frameworks.Because we defined specific contrasts,we identified trans eQTLs that more closely resembled what we expect from genetic variants showing complete dominance between alleles.Yet,these were not identified by the GTEx framework.Conclusions Our results show that transforming RNA-sequencing data to fit a normal distribution prior to eQTL analysis is not required when the DGE framework is employed.Our proposed approach detected biologically relevant variants that otherwise would not have been identified due to data transformation to fit a normal distribution.
文摘BACKGROUND Cirrhosis and its complications develop in a subgroup of patients with nonalcoholic fatty liver disease(NASH).Early detection of liver fibrosis represents an important goal of clinical care.AIM To test the hypothesis that the development of cirrhosis in nonalcoholic fatty liver disease patients is preceded by the long-term trends of platelet counts and Fib-4 scores.METHODS We identified all patients in our healthcare system who had undergone fibrosis staging by liver biopsy or magnetic resonance elastography(MRE)for nonalcoholic fatty liver disease during the past decade(n=310).Platelet counts,serum glutamic-pyruvic transaminase and serum glutamic oxalacetic transaminase values preceding the staging tests were extracted from the electronic medical record system,and Fib-4 scores were calculated.Potential predictors of advanced fibrosis were evaluated using multivariate regression analysis.RESULTS Significant decreases in platelet counts and increases in Fib-4 scores were observed in all fibrosis stages,particularly in patients with cirrhosis.In the liver biopsy group,the presence of cirrhosis was best predicted by the combination of the Fib-4 score at the time closest to staging(P<0.0001),the presence of diabetes(P=0.0001),and the correlation coefficient of the preceding timedependent drop in platelet count(P=0.044).In the MRE group,Fib4 score(P=0.0025)and platelet drop(P=0.0373)were significant predictors.In comparison,the time-dependent rise of the Fib-4 score did not contribute in a statistically significant way.CONCLUSION Time-dependent changes in platelet counts and Fib-4 scores contribute to the prediction of cirrhosis in NASH patients with biopsy-or MRE-staged fibrosis.Their incorporation into predictive algorithms may assist in the earlier identification of high-risk patients.
文摘Cellular angiofibroma is a rare mesenchymal tumor that most commonly presents as an asymptomatic well-circumscribed mass in the vulva. Very few cases have been found in the vagina and even fewer presented with vaginal bleeding. A 54-year-old female presented to the emergency department with five months of vaginal bleeding and symptomatic anemia requiring blood transfusion. Upon physical examination, she was found to have a firm 4<span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">cm posterior vaginal mass, distinctly distal to the cervix. The mass was resected and diagnosed as a vaginal cellular angiofibroma on pathologic evaluation. The patient did well post</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">operatively with recommended follow-up every six months. The common differential diagnosis for a bleeding vaginal mass includes leiomyoma, angiofibroblastoma, aggressive angiomyxoma, squamous cell carcinoma, and adenocarcinoma. In this case, cellular angiofibroma presented as a vaginal mass with heavy bleeding leading to severe anemia. Early involvement of gynecologic oncology can help to optimize patients’ evaluation and management.</span></span></span>
文摘BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.
文摘Obtaining nutritious food is becoming increasingly difficult due to the growing urban population and the degradation of soil, water, and air from mechanized and industrialized agricultural techniques. More than half the global population resides in urban areas, with not enough surrounding agricultural land to meet food requirements. Food traveling long distances, an average of 1020 miles, has resulted in increased food miles for the average food item in the United States of America, representing wasted resources. The novel GREENBOX technology was invented in response to increasing pressures on food security. Previous studies conducted on GREENBOX technology assessed the technical feasibility of utilizing Lettuce Lactuca sativa ‘Rex Butterhead’. We at the APS Laboratory for Sustainable Food at Florida Gulf Coast University assessed the technical feasibility of growing different leafy green vegetable crops. GREENBOX technology consists of thermally insulated climate-controlled enclosures, an artificial lighting source, a soilless cultivation method (hydroponics), and environmental control modules. We assembled two GREENBOX units to assess the environmental conditions and growth performance of Brassica rapa var. chinensis ‘Li Ren Choi’, Spinach Spinacia oleracea ‘Auroch’, Arugula Eruca sativa ‘Astro’, and Mizuna Brassica Brassica rapa var. japonica. Plugs were cultivated and then transplanted in a randomized manner to the nutrient film technique (NFT) channels, subsequently grown for 30 days to full bloom and ready for harvest. Fertigation was carried out using a standard concentration nutrient solution. Crops were arranged in twelve blocks of four species each. We collected environmental data including daily light integral (DLI, mol/m<sup>2</sup>∙d), temperature (˚C), relative humidity (%), and vapor pressure deficit (VPD, kPa). Collected biomass data included wet weight (g), dry weight (g), leaf area (cm<sup>2</sup>), and chlorophyll concentration (mg/cm<sup>2</sup>). We then derived the Specific Leaf Area (SLA, cm<sup>2</sup>/g). Descriptive statistics were utilized to understand the differences in biomass parameters between the four crops grown. We also compared the performance parameters of our crops with existing peer-reviewed literature and found it superior, if not comparable to commonly found industrial output. We determined that all crops grew to full bloom, demonstrating that GREENBOX technology may be used to grow a variety of different leafy green vegetable crops.
文摘Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world,which is seriously threatening the lives of patients.Due to the rapid development of the disease,patients were in the middle and advanced stages at the time of diagnosis and missed the best time for treatment.With the development of minimally invasive medicine,interventional therapy for advanced HCC has achieved promising results.Transarterial chemoembolization(TACE)and transarterial radioembolization(TARE)are currently recognized as effective treatments.This study aimed to investigate the clinical value and safety of TACE alone and combined with TACE in the treatment of progression in patients with advanced HCC and to find a breakthrough for the early diagnosis and treatment of patients with advanced HCC.AIM To investigate the efficacy and safety of hepatic TACE and TARE in advanced descending hepatectomy.METHODS In this study,218 patients with advanced HCC who were treated in the Zhejiang Provincial People’s Hospital from May 2016 to May 2021 were collected.Of the patients,119 served as the control group and received hepatic TACE,99 served as the observation group and were treated with hepatic TACE combined with TARE.The patients in two groups were compared in terms of lesion inactivation,tumor nodule size,lipiodol deposition,serum alpha-fetoprotein(AFP)level in different periods,postoperative complications,1-year survival rate,and clinical symptoms such as liver pain,fatigue,and abdominal distension,and adverse reactions such as nausea and vomiting.RESULTS The observation group and the control group had good efficacy in treatment efficiency,reduction of tumor nodules,reduction of postoperative AFP value,reduction of postoperative complications,and relief of clinical symptoms.In addition,compared with the control group,the treatment efficiency,reduction of tumor nodules,reduction of AFP value,reduction of postoperative complications,and relief of clinical symptoms in the observation group were better than those in the TACE group alone.Patients in the TACE+TARE group had a higher 1-year survival rate after surgery,lipiodol deposition was significantly increased and the extent of tumor necrosis was expanded.The overall incidence of adverse reactions in the TACE+TARE group was lower than that in the TACE group,and the difference had statistical significance(P<0.05).CONCLUSION Compared with TACE alone,TACE combined with TARE is more effective in the treatment of patients with advanced HCC.It also improves postoperative survival rate,reduces adverse effects,and has a better safety profile.
基金supported by a sponsored research agreement between Quadrant Biosciences and the Penn State College of Medicine to ACLsupported by the National Center for Advancing Translational Sciences(Grant KL2 TR002015,Grant UL1 TR002014)。
文摘Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging evidence that salivary micro-ribonucleic acids(miRNAs)may serve as biomarkers of concussion;however,it remains unclear whether concussion-related miRNAs are impacted by exercise.We sought to determine whether40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports.Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.Methods:This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites.Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing.Within-subjects testing was used to identify and exclude miRNAs that changed with either(a)a single episode of exercise(166 samples from 83 individuals)or(b)season-long participation in contact sports(212 samples from 106 individuals).The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression(172 samples from 75 concussed and 97 non-concussed individuals).Results:Two miRNAs(miR-532-5p and miR-182-5p)decreased(adjusted p<0.05)after a single episode of exercise,and 1 miRNA(miR-4510)increased only after contact sports participation.Twenty-three miRNAs changed at the end of a contact sports season.Two of these miRNAs(miR-26b-3p and miR-29c-3p)were associated(R>0.50;adjusted p<0.05)with the number of head impacts sustained in a single football practice.Among the 15 miRNAs not confounded by exercise or season-long contact sports participation,11 demonstrated a significant difference(adjusted p<0.05)between concussed and non-concussed participants,and 6 displayed moderate ability(area under curve>0.70)to identify concussion.A single ratio(miR-27a-5p/miR-30a-3p)displayed the highest accuracy(AUC=0.810,sensitivity=82.4%,specificity=73.3%)for differentiating concussed and non-concussed participants.Accuracy did not differ between participants with SRC and non-SRC(z=0.5,p=0.60).Conclusion:Salivary miRNA levels may accurately identify SRC when not confounded by exercise.Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive,sideline adjunct for SRC assessment.
基金supported by Grant In Aid research fund of Virginia Military Instittue, USA
文摘We study boundary value problems for fractional integro-differential equations involving Caputo derivative of order α∈ (n-1, n) in Banach spaces. Existence and uniqueness results of solutions are established by virtue of the Holder's inequality, a suitable singular Cronwall's inequality and fixed point theorem via a priori estimate method. At last, examples are given to illustrate the results.