Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsi...Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL 5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide“click”chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.展开更多
As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming cle...As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of cSVD.The term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).展开更多
Historically,"big pharma"did most central nervous system drug discovery R&D in-house.Yet,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(...Historically,"big pharma"did most central nervous system drug discovery R&D in-house.Yet,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).展开更多
BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chroni...BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chronic gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ systems.The impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ systems.AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.METHODS Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical Center.Validated questionnaires and data from patient files were used to quantify the six dimensions of PH.Internal consistency was tested with McDonald’s Omega.Zero-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered significant.RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population.Regarding quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB disorders.Intercorrelation scores between the six dimensions were only very weak to weak,forcing us to quantify each domain separately.CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients.Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.展开更多
In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity ...In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.展开更多
AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopa...AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopausal female BC patients with OM volunteered to take part in this study between July 2012 and July 2022.Women with BC who are menopausal were found to have an OM incidence of 1.6%.Furthermore,CA-153,CA-125,and apolipoprotein A(Apo A)all contributed to OM in women with BC who are postmenopausal according to binary logistic regression.Receiver operating curve(ROC)analysis was used to assess the diagnostic value of OM in patients with BC.RESULTS:Both CA-153 and CA-153+CA-125 showed a higher sensitivity of 95.45%,whereas CA-153+Apo A illustrated the highest specificity of 99.02%.Moreover,CA-153 and CA-153+CA-125 had higher areas under the curve(AUC)of 0.973.CONCLUSION:The data indicate that the serum concentrations of CA-153 exhibited the most significant predictors of the diagnosis of OM in menopausal women with BC.The current study researches the utility of risk factors in predicting of OM in menopausal BC women and put forward the latest suggestions on their clinical application.展开更多
The current study aimed to evaluate the first aid knowledge and general awareness of bleeding control, and their relations with different variables among the population of Jazan City, Saudi Arabia, in 2023. A cross-se...The current study aimed to evaluate the first aid knowledge and general awareness of bleeding control, and their relations with different variables among the population of Jazan City, Saudi Arabia, in 2023. A cross-sectional study was conducted in Jazan City, Saudi Arabia between April 2023 and May 2023. Participants, >13 years old, living in Jazan City, were self-enrolled. Data collection was carried out by distributing a self-reported online survey questionnaire via email and social media apps. A validated, pretested online self-report questionnaire was used for data collection, with data analysis performed using (MS) Excel 2022 and SPSS version 26. A Chi-square test was used to determine the association of sociodemographic variables and Bleeding Control (BC) knowledge with, significance set at p < 0.05. A total of 250 participants completed the questionnaire, predominantly aged between 16 - 25 years, with 152 (60.8%) being male, and about 90% being Saudi citizens. Only 53 (21.2%) participated in previous first aid training concentrating on bleeding control. Only 76 (30.4%) of participants had good knowledge, while 131 (52.4%) exhibited positive attitude towards BC first aid. There were no statistically significant associations between BC knowledge and age, gender, occupation, nationality, and education. However, a significant association was observed between previous BC training and knowledge (Chi-test = 40.373, d.f = 1, p = 0.000) at p < 0.05. Conclusion: The prevalence of poor knowledge of bleeding control among community members in Jazan City was high. The findings of this study should be carefully considered by various healthcare organizations to implement educational first-aid programs and activities aimed at enhancing community awareness and knowledge of bleeding control.展开更多
Introduction and Significance: Burn injury (BI) is a considerable health issue which is responsible for around 300,000 deaths and affecting about 11 million people every year worldwide. In Saudi Arabia, the prevalence...Introduction and Significance: Burn injury (BI) is a considerable health issue which is responsible for around 300,000 deaths and affecting about 11 million people every year worldwide. In Saudi Arabia, the prevalence of BIs array from 112 to 518 per 100,000 per year. The appropriate awareness of performing first aid could facilitate to improve the outcomes of burns. Purpose and Objectives: To appraise the community that acknowledges burns, first aid, and associated factors among the community population in Jazan City, Saudi Arabia. The paper aims to identify limitations to encourage additional research and persuade legislators to develop improved burn-injury care recommendations and training programs. Materials and Methods: An observational-based sample survey was conducted among the people who live in Jazan City aging 13 years or more, during April 5 to May 5, 2023. Data collection was done by a validated online self-administrated questionnaire sent randomly to community members in different parts of Jazan City via social media platforms. Collected data were coded and cleaned by an excel program, and finally exported on SPSS 26.0 software. The variables were analyzed using descriptive statistics like frequencies and percentages. Also, the Chi-square test was used to investigate the relation between different variables, with a significance value of P Results: This study included 243 participants (about 62%) among them were mostly male participants (151) having a university degree. The majority of participants 75% did not take any form of BFA training in the past. This study shows that 69.9% of the participants have inadequate awareness, despite 72% having a constructive attitude towards burn first aid. Previous burn-related first aid training was significantly associated with participants’ knowledge of BFA at a p-value less than 0.05. Conclusion: This study indicates a high frequency of Jazan population having inadequate knowledge of burn first aid despite the high prevalence of a favorable attitude. There is a need to develop an effective nationwide burn prevention program and early burn first aid treatment in Saudi Arabia and promote a consistent guideline for burn first aid.展开更多
AIM:To study functional brain abnormalities in patients with hypertensive retinopathy(HR)and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations(fALFFs)method.METHO...AIM:To study functional brain abnormalities in patients with hypertensive retinopathy(HR)and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations(fALFFs)method.METHODS:Twenty HR patients and 20 healthy controls(HCs)were respectively recruited.The age,gender,and educational background characteristics of the two groups were similar.After functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the fALFF method.Receiver operating characteristic(ROC)curve analysis was used to classify the data.Further,we used Pearson’s correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR.RESULTS:The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus(RO-MFG)and right lingual gyrus.In contrast,the values of fALFFs in the left middle temporal gyrus(MTG),left superior temporal pole(STP),left middle frontal gyrus(MFG),left superior marginal gyrus(SMG),left superior parietal lobule(SPL),and right supplementary motor area(SMA)were higher in the HR group.The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group(P<0.001).The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores(r=0.9232;P<0.0001)and depression scores(r=0.9682;P<0.0001).CONCLUSION:fALFF values in multiple brain regions of HR patients are abnormal,suggesting that these brain regions in HR patients may be dysfunctional,which may help to reveal the pathophysiological mechanisms of HR.展开更多
AIM:To study functional brain abnormalities in patients with eye trauma(ET)and to discuss the pathophysiological mechanisms of ET.METHODS:Totally 31 ET patients and 31 healthy controls(HCs)were recruited.The age,gende...AIM:To study functional brain abnormalities in patients with eye trauma(ET)and to discuss the pathophysiological mechanisms of ET.METHODS:Totally 31 ET patients and 31 healthy controls(HCs)were recruited.The age,gender,and educational background characteristics of the two groups were similar.After functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the functional connectivity(FC)method.Receiver operating characteristic(ROC)curve analysis was used to classify the data.Pearson’s correlation analysis was used to explore the relationship between FC values in specific brain regions and clinical behaviors in patients with ET.RESULTS:Significantly increased FC between several regions was identified including the medial prefrontal cortex(MPFC)and left hippocampus formations(HF),the MPFC and left inferior parietal lobule(IPL),the left IPL and left medial temporal lobe(MTL),the left IPL and right MTL,and the right IPL and left MTL.No decreased region-to-region connectivity was detected in default mode network(DMN)sub-regions in patients with ET.Compared with HCs,ET patients exhibited significantly increased FC between several paired DMN regions,as follows:posterior cingulate cortex(PCC)and right HF(HF.R,t=2.196,P=0.032),right inferior parietal cortices(IPC.R)and left MTL(MTL.L,t=2.243,P=0.029),and right MTL(MTL.R)and HF.R(t=2.236,P=0.029).CONCLUSION:FC values in multiple brain regions of ET patients are abnormal,suggesting that these brain regions in ET patients may be dysfunctional,which may help to reveal the pathophysiological mechanisms of ET.展开更多
BACKGROUND Artificial intelligence(AI)has potential in the optical diagnosis of colorectal polyps.AIM To evaluate the feasibility of the real-time use of the computer-aided diagnosis system(CADx)AI for ColoRectal Poly...BACKGROUND Artificial intelligence(AI)has potential in the optical diagnosis of colorectal polyps.AIM To evaluate the feasibility of the real-time use of the computer-aided diagnosis system(CADx)AI for ColoRectal Polyps(AI4CRP)for the optical diagnosis of diminutive colorectal polyps and to compare the performance with CAD EYE^(TM)(Fujifilm,Tokyo,Japan).CADx influence on the optical diagnosis of an expert endoscopist was also investigated.METHODS AI4CRP was developed in-house and CAD EYE was proprietary software provided by Fujifilm.Both CADxsystems exploit convolutional neural networks.Colorectal polyps were characterized as benign or premalignant and histopathology was used as gold standard.AI4CRP provided an objective assessment of its characterization by presenting a calibrated confidence characterization value(range 0.0-1.0).A predefined cut-off value of 0.6 was set with values<0.6 indicating benign and values≥0.6 indicating premalignant colorectal polyps.Low confidence characterizations were defined as values 40%around the cut-off value of 0.6(<0.36 and>0.76).Self-critical AI4CRP’s diagnostic performances excluded low confidence characterizations.RESULTS AI4CRP use was feasible and performed on 30 patients with 51 colorectal polyps.Self-critical AI4CRP,excluding 14 low confidence characterizations[27.5%(14/51)],had a diagnostic accuracy of 89.2%,sensitivity of 89.7%,and specificity of 87.5%,which was higher compared to AI4CRP.CAD EYE had a 83.7%diagnostic accuracy,74.2%sensitivity,and 100.0%specificity.Diagnostic performances of the endoscopist alone(before AI)increased nonsignificantly after reviewing the CADx characterizations of both AI4CRP and CAD EYE(AI-assisted endoscopist).Diagnostic performances of the AI-assisted endoscopist were higher compared to both CADx-systems,except for specificity for which CAD EYE performed best.CONCLUSION Real-time use of AI4CRP was feasible.Objective confidence values provided by a CADx is novel and self-critical AI4CRP showed higher diagnostic performances compared to AI4CRP.展开更多
AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography ...AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.展开更多
BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As ...BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As a con-sequence,the quality and completeness of the report are highly dependent on the training and experience of the examiners.AIM To develop a structured MRI and EAUS template(SMART)reporting the minimum dataset of information for the treatment of anal fistulas.METHODS This modified Delphi survey based on the RAND-UCLA appropriateness for consensus-building was conducted between May and August 2023.One hundred and fifty-one articles selected from a systematic review of the lite-rature formed the database to generate the evidence-based statements for the Delphi study.Fourteen questions were anonymously voted by an interdisciplinary multidisciplinary group for a maximum of three iterative rounds.The degree of agreement was scored on a numeric 0–10 scale.Group consensus was defined as a score≥8 for≥80%of the panelists.RESULTS Eleven scientific societies(3 radiological and 8 surgical)endorsed the study.After three rounds of voting,the experts(69 colorectal surgeons,23 radiologists,2 anatomists,and 1 gastroenterologist)achieved consensus for 12 of 14 statements(85.7%).Based on the results of the Delphi process,the six following features of anal fistulas were included in the SMART:Primary tract,secondary extension,internal opening,presence of collection,coexisting le-sions,and sphincters morphology.CONCLUSION A structured template,SMART,was developed to standardize imaging reporting of fistula-in-ano in a simple,systematic,time-efficient way,providing the minimum dataset of information and visual diagram useful to refer-ring physicians.展开更多
BACKGROUND Reaching the Selecting Therapeutic Targets in Inflammatory Bowel Disease-II(STRIDE-II)therapeutic targets for inflammatory bowel disease(IBD)requires an interdisciplinary approach.Lifestyle interventions fo...BACKGROUND Reaching the Selecting Therapeutic Targets in Inflammatory Bowel Disease-II(STRIDE-II)therapeutic targets for inflammatory bowel disease(IBD)requires an interdisciplinary approach.Lifestyle interventions focusing on enhancing and preserving health-related physical fitness(HRPF)may aid in improving subjective health,decreasing disability,or even controlling inflammation.However,ambiguity remains about the status and impact of HRPF(i.e.body composition,cardiorespiratory fitness,muscular strength,muscular endurance,and flexibility)in IBD patients,hindering the development of physical activity and physical exercise training guidelines.AIM To review HRPF components in IBD patients and the impact of physical activity and physical exercise training interventions on HRPF.METHODS A systematic search in multiple databases was conducted for original studies that included patients with IBD,assessed one or more HRPF components,and/or evaluated physical activity or physical exercise training interventions.RESULTS Sixty-eight articles were included.No study examined the complete concept of HRPF,and considerable heterogeneity existed in assessment methods,with frequent use of non-validated tests.According to studies that used gold standard tests,cardiorespiratory fitness seemed to be reduced,but findings on muscular strength and endurance were inconsistent.A limited number of studies that evaluated physical activity or physical exercise training interventions reported effects on HRPF,overall showing a positive impact.CONCLUSION We performed a scoping review using a systematic and iterative approach to identify and synthesize an emerging body of literature on health-related physical fitness in patients with IBD,highlighting several research gaps and opportunities for future research.Findings of this review revealed a gap in the literature regarding the accurate assessment of HRPF in patients with IBD and highlighted important methodological limitations of studies that evaluated physical activity or physical exercise training interventions.This scoping review is a step towards performing studies and systematic reviews in the future,which was not possible at present given the heterogeneity in endpoints and designs of the available studies on this topic.Future well-designed studies are required to determine the optimal training paradigm for improving HRPF in patients with IBD before guidelines can be developed and integrated into the therapeutic strategy.展开更多
基金the European Research Council starting grant “Cell Hybridge” for financial support under the Horizon2020 framework program (Grant#637308)the Province of Limburg for support and funding
文摘Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL 5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide“click”chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.
文摘As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of cSVD.The term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).
基金funded by the FWO(1S34321N)the Fondation Charcot Stichting(to TV and RS)。
文摘Historically,"big pharma"did most central nervous system drug discovery R&D in-house.Yet,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).
文摘BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chronic gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ systems.The impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ systems.AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.METHODS Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical Center.Validated questionnaires and data from patient files were used to quantify the six dimensions of PH.Internal consistency was tested with McDonald’s Omega.Zero-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered significant.RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population.Regarding quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB disorders.Intercorrelation scores between the six dimensions were only very weak to weak,forcing us to quantify each domain separately.CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients.Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.
文摘In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Jiangxi Key R&D Program of Jiangxi Province(No.20223BBH80014)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2022B258)Science and Technology Project of Jiangxi Health Commission(No.202210017).
文摘AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopausal female BC patients with OM volunteered to take part in this study between July 2012 and July 2022.Women with BC who are menopausal were found to have an OM incidence of 1.6%.Furthermore,CA-153,CA-125,and apolipoprotein A(Apo A)all contributed to OM in women with BC who are postmenopausal according to binary logistic regression.Receiver operating curve(ROC)analysis was used to assess the diagnostic value of OM in patients with BC.RESULTS:Both CA-153 and CA-153+CA-125 showed a higher sensitivity of 95.45%,whereas CA-153+Apo A illustrated the highest specificity of 99.02%.Moreover,CA-153 and CA-153+CA-125 had higher areas under the curve(AUC)of 0.973.CONCLUSION:The data indicate that the serum concentrations of CA-153 exhibited the most significant predictors of the diagnosis of OM in menopausal women with BC.The current study researches the utility of risk factors in predicting of OM in menopausal BC women and put forward the latest suggestions on their clinical application.
文摘The current study aimed to evaluate the first aid knowledge and general awareness of bleeding control, and their relations with different variables among the population of Jazan City, Saudi Arabia, in 2023. A cross-sectional study was conducted in Jazan City, Saudi Arabia between April 2023 and May 2023. Participants, >13 years old, living in Jazan City, were self-enrolled. Data collection was carried out by distributing a self-reported online survey questionnaire via email and social media apps. A validated, pretested online self-report questionnaire was used for data collection, with data analysis performed using (MS) Excel 2022 and SPSS version 26. A Chi-square test was used to determine the association of sociodemographic variables and Bleeding Control (BC) knowledge with, significance set at p < 0.05. A total of 250 participants completed the questionnaire, predominantly aged between 16 - 25 years, with 152 (60.8%) being male, and about 90% being Saudi citizens. Only 53 (21.2%) participated in previous first aid training concentrating on bleeding control. Only 76 (30.4%) of participants had good knowledge, while 131 (52.4%) exhibited positive attitude towards BC first aid. There were no statistically significant associations between BC knowledge and age, gender, occupation, nationality, and education. However, a significant association was observed between previous BC training and knowledge (Chi-test = 40.373, d.f = 1, p = 0.000) at p < 0.05. Conclusion: The prevalence of poor knowledge of bleeding control among community members in Jazan City was high. The findings of this study should be carefully considered by various healthcare organizations to implement educational first-aid programs and activities aimed at enhancing community awareness and knowledge of bleeding control.
文摘Introduction and Significance: Burn injury (BI) is a considerable health issue which is responsible for around 300,000 deaths and affecting about 11 million people every year worldwide. In Saudi Arabia, the prevalence of BIs array from 112 to 518 per 100,000 per year. The appropriate awareness of performing first aid could facilitate to improve the outcomes of burns. Purpose and Objectives: To appraise the community that acknowledges burns, first aid, and associated factors among the community population in Jazan City, Saudi Arabia. The paper aims to identify limitations to encourage additional research and persuade legislators to develop improved burn-injury care recommendations and training programs. Materials and Methods: An observational-based sample survey was conducted among the people who live in Jazan City aging 13 years or more, during April 5 to May 5, 2023. Data collection was done by a validated online self-administrated questionnaire sent randomly to community members in different parts of Jazan City via social media platforms. Collected data were coded and cleaned by an excel program, and finally exported on SPSS 26.0 software. The variables were analyzed using descriptive statistics like frequencies and percentages. Also, the Chi-square test was used to investigate the relation between different variables, with a significance value of P Results: This study included 243 participants (about 62%) among them were mostly male participants (151) having a university degree. The majority of participants 75% did not take any form of BFA training in the past. This study shows that 69.9% of the participants have inadequate awareness, despite 72% having a constructive attitude towards burn first aid. Previous burn-related first aid training was significantly associated with participants’ knowledge of BFA at a p-value less than 0.05. Conclusion: This study indicates a high frequency of Jazan population having inadequate knowledge of burn first aid despite the high prevalence of a favorable attitude. There is a need to develop an effective nationwide burn prevention program and early burn first aid treatment in Saudi Arabia and promote a consistent guideline for burn first aid.
基金Supported by National Natural Science Foundation of China(No.82160195)Jiangxi Double-Thousand Plan High-Level Talent Project of Science and Technology Innovation(No.jxsq2023201036)+2 种基金Key R&D Program of Jiangxi Province(No.20223BBH80014)Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2022B258)Science and Technology Project of Jiangxi Health Commission(No.202210017).
文摘AIM:To study functional brain abnormalities in patients with hypertensive retinopathy(HR)and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations(fALFFs)method.METHODS:Twenty HR patients and 20 healthy controls(HCs)were respectively recruited.The age,gender,and educational background characteristics of the two groups were similar.After functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the fALFF method.Receiver operating characteristic(ROC)curve analysis was used to classify the data.Further,we used Pearson’s correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR.RESULTS:The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus(RO-MFG)and right lingual gyrus.In contrast,the values of fALFFs in the left middle temporal gyrus(MTG),left superior temporal pole(STP),left middle frontal gyrus(MFG),left superior marginal gyrus(SMG),left superior parietal lobule(SPL),and right supplementary motor area(SMA)were higher in the HR group.The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group(P<0.001).The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores(r=0.9232;P<0.0001)and depression scores(r=0.9682;P<0.0001).CONCLUSION:fALFF values in multiple brain regions of HR patients are abnormal,suggesting that these brain regions in HR patients may be dysfunctional,which may help to reveal the pathophysiological mechanisms of HR.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Key R&D Program of Jiangxi Province(No.20223BBH80014)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2022B258)Science and Technology Project of Jiangxi Health Commission(No.202210017).
文摘AIM:To study functional brain abnormalities in patients with eye trauma(ET)and to discuss the pathophysiological mechanisms of ET.METHODS:Totally 31 ET patients and 31 healthy controls(HCs)were recruited.The age,gender,and educational background characteristics of the two groups were similar.After functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the functional connectivity(FC)method.Receiver operating characteristic(ROC)curve analysis was used to classify the data.Pearson’s correlation analysis was used to explore the relationship between FC values in specific brain regions and clinical behaviors in patients with ET.RESULTS:Significantly increased FC between several regions was identified including the medial prefrontal cortex(MPFC)and left hippocampus formations(HF),the MPFC and left inferior parietal lobule(IPL),the left IPL and left medial temporal lobe(MTL),the left IPL and right MTL,and the right IPL and left MTL.No decreased region-to-region connectivity was detected in default mode network(DMN)sub-regions in patients with ET.Compared with HCs,ET patients exhibited significantly increased FC between several paired DMN regions,as follows:posterior cingulate cortex(PCC)and right HF(HF.R,t=2.196,P=0.032),right inferior parietal cortices(IPC.R)and left MTL(MTL.L,t=2.243,P=0.029),and right MTL(MTL.R)and HF.R(t=2.236,P=0.029).CONCLUSION:FC values in multiple brain regions of ET patients are abnormal,suggesting that these brain regions in ET patients may be dysfunctional,which may help to reveal the pathophysiological mechanisms of ET.
文摘BACKGROUND Artificial intelligence(AI)has potential in the optical diagnosis of colorectal polyps.AIM To evaluate the feasibility of the real-time use of the computer-aided diagnosis system(CADx)AI for ColoRectal Polyps(AI4CRP)for the optical diagnosis of diminutive colorectal polyps and to compare the performance with CAD EYE^(TM)(Fujifilm,Tokyo,Japan).CADx influence on the optical diagnosis of an expert endoscopist was also investigated.METHODS AI4CRP was developed in-house and CAD EYE was proprietary software provided by Fujifilm.Both CADxsystems exploit convolutional neural networks.Colorectal polyps were characterized as benign or premalignant and histopathology was used as gold standard.AI4CRP provided an objective assessment of its characterization by presenting a calibrated confidence characterization value(range 0.0-1.0).A predefined cut-off value of 0.6 was set with values<0.6 indicating benign and values≥0.6 indicating premalignant colorectal polyps.Low confidence characterizations were defined as values 40%around the cut-off value of 0.6(<0.36 and>0.76).Self-critical AI4CRP’s diagnostic performances excluded low confidence characterizations.RESULTS AI4CRP use was feasible and performed on 30 patients with 51 colorectal polyps.Self-critical AI4CRP,excluding 14 low confidence characterizations[27.5%(14/51)],had a diagnostic accuracy of 89.2%,sensitivity of 89.7%,and specificity of 87.5%,which was higher compared to AI4CRP.CAD EYE had a 83.7%diagnostic accuracy,74.2%sensitivity,and 100.0%specificity.Diagnostic performances of the endoscopist alone(before AI)increased nonsignificantly after reviewing the CADx characterizations of both AI4CRP and CAD EYE(AI-assisted endoscopist).Diagnostic performances of the AI-assisted endoscopist were higher compared to both CADx-systems,except for specificity for which CAD EYE performed best.CONCLUSION Real-time use of AI4CRP was feasible.Objective confidence values provided by a CADx is novel and self-critical AI4CRP showed higher diagnostic performances compared to AI4CRP.
基金Supported by National Natural Science Foundation of China(No.82160195)Key R&D Program of Jiangxi Province(No.20223BBH80014)General Science and Technology Program of the Department of Traditional Chinese Medicine,Jiangxi Provincial Health Commission(No.2017A241).
文摘AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.
文摘BACKGROUND There is still considerable heterogeneity regarding which features of cryptoglandular anal fistula on magnetic resonance imaging(MRI)and endoanal ultrasound(EAUS)are relevant to surgical decision-making.As a con-sequence,the quality and completeness of the report are highly dependent on the training and experience of the examiners.AIM To develop a structured MRI and EAUS template(SMART)reporting the minimum dataset of information for the treatment of anal fistulas.METHODS This modified Delphi survey based on the RAND-UCLA appropriateness for consensus-building was conducted between May and August 2023.One hundred and fifty-one articles selected from a systematic review of the lite-rature formed the database to generate the evidence-based statements for the Delphi study.Fourteen questions were anonymously voted by an interdisciplinary multidisciplinary group for a maximum of three iterative rounds.The degree of agreement was scored on a numeric 0–10 scale.Group consensus was defined as a score≥8 for≥80%of the panelists.RESULTS Eleven scientific societies(3 radiological and 8 surgical)endorsed the study.After three rounds of voting,the experts(69 colorectal surgeons,23 radiologists,2 anatomists,and 1 gastroenterologist)achieved consensus for 12 of 14 statements(85.7%).Based on the results of the Delphi process,the six following features of anal fistulas were included in the SMART:Primary tract,secondary extension,internal opening,presence of collection,coexisting le-sions,and sphincters morphology.CONCLUSION A structured template,SMART,was developed to standardize imaging reporting of fistula-in-ano in a simple,systematic,time-efficient way,providing the minimum dataset of information and visual diagram useful to refer-ring physicians.
文摘BACKGROUND Reaching the Selecting Therapeutic Targets in Inflammatory Bowel Disease-II(STRIDE-II)therapeutic targets for inflammatory bowel disease(IBD)requires an interdisciplinary approach.Lifestyle interventions focusing on enhancing and preserving health-related physical fitness(HRPF)may aid in improving subjective health,decreasing disability,or even controlling inflammation.However,ambiguity remains about the status and impact of HRPF(i.e.body composition,cardiorespiratory fitness,muscular strength,muscular endurance,and flexibility)in IBD patients,hindering the development of physical activity and physical exercise training guidelines.AIM To review HRPF components in IBD patients and the impact of physical activity and physical exercise training interventions on HRPF.METHODS A systematic search in multiple databases was conducted for original studies that included patients with IBD,assessed one or more HRPF components,and/or evaluated physical activity or physical exercise training interventions.RESULTS Sixty-eight articles were included.No study examined the complete concept of HRPF,and considerable heterogeneity existed in assessment methods,with frequent use of non-validated tests.According to studies that used gold standard tests,cardiorespiratory fitness seemed to be reduced,but findings on muscular strength and endurance were inconsistent.A limited number of studies that evaluated physical activity or physical exercise training interventions reported effects on HRPF,overall showing a positive impact.CONCLUSION We performed a scoping review using a systematic and iterative approach to identify and synthesize an emerging body of literature on health-related physical fitness in patients with IBD,highlighting several research gaps and opportunities for future research.Findings of this review revealed a gap in the literature regarding the accurate assessment of HRPF in patients with IBD and highlighted important methodological limitations of studies that evaluated physical activity or physical exercise training interventions.This scoping review is a step towards performing studies and systematic reviews in the future,which was not possible at present given the heterogeneity in endpoints and designs of the available studies on this topic.Future well-designed studies are required to determine the optimal training paradigm for improving HRPF in patients with IBD before guidelines can be developed and integrated into the therapeutic strategy.
