BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human...AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
Basic life support for cardiac arrest associates cardiopulmonary resuscitation(CPR)and defibrillation.CPR relies on chest compressions(CC)and ventilation.Current guidelines on CPR recommend a depth of 5-6 cm at a rhyt...Basic life support for cardiac arrest associates cardiopulmonary resuscitation(CPR)and defibrillation.CPR relies on chest compressions(CC)and ventilation.Current guidelines on CPR recommend a depth of 5-6 cm at a rhythm of 100-120 times/min for CC.[1,2]Interruptions of the CC must be as short as possible and are related to ventilation,defibrillation and turnover of the rescuers.Most of the automated external defibrillators(AEDs)require interruptions of the CC to perform rhythm analysis.Among the numerous marketed models of AEDs,some provide real-time feedback about the quality of the CC.展开更多
Conventional agrochemical plant biostimulants have been used to increase crop yield and stress resistance,andthis strategy continues to be integral to today's farming.While effective,the large-scale implantations ...Conventional agrochemical plant biostimulants have been used to increase crop yield and stress resistance,andthis strategy continues to be integral to today's farming.While effective,the large-scale implantations of theseproducts are not without environmental,ecological,and cost concerns and the associated climate-change challenges.To alleviate this long-standing pressure on agriculture,designing and developing more biocompatible andsustainable plant stimulants are among the primary focuses of agricultural management.Over the recent decades,the field has witnessed significant progress in emerging naturally derived or nature-inspired nano-biostimulantswith large-active-surface areas,including bio-compounds,biopolymers,and nanocarbons.However,the extraction/preparation of these products may apply additional costs or require specific equipment.More recently,thefield's attention has shifted to the sustainable application of chemical-additive-free biostimulants towards practicalapplications in nano-agriculture.Herein,we rationally designed and reported the first evidence and elucidationon biostimulant impacts of plant-self-derived nano-extracts from donor Arabidopsis thaliana as a model forinducing mirror biostimulant activities in conspecific host seeds,seedlings,and plants.Moreover,we assessed theeffect of donor plants'age on short,mid-,and long-term biocompatibility,growth,and development/maturationof the recipient plants for up to around 30 days.As a proof-of-concept,we found these autologous bio-extractscould effectively promote seed sprouting,seedling germination,and the development of soil-drenched plantsof the same types.Our transmission-electron microscopy characterization of root/shoot pieces shows the presenceof multiple phyto-compounds,including microtubules/actin filaments,cell vacuoles,Golgi stacks/endoplasmicreticulum,cell wall polysaccharide-based cellulose fibers,and organic amorphous nanoparticles and clusters ofcarbon quantum dots in the structure of these extracts.This personalized plant stimulation may induce furthergrowth/defense-related mechanisms,setting new paradigms toward reducing the agrochemical inputs.展开更多
Diabetes mellitus represents a major global health issue,driving the need for noninvasive alternatives to traditional blood glucose monitoring methods.Recent advancements in wearable technology have introduced skin-in...Diabetes mellitus represents a major global health issue,driving the need for noninvasive alternatives to traditional blood glucose monitoring methods.Recent advancements in wearable technology have introduced skin-interfaced biosensors capable of analyzing sweat and skin biomarkers,providing innovative solutions for diabetes diagnosis and monitoring.This review comprehensively discusses the current developments in noninvasive wearable biosensors,emphasizing simultaneous detection of biochemical biomarkers(such as glucose,cortisol,lactate,branched-chain amino acids,and cytokines)and physiological signals(including heart rate,blood pressure,and sweat rate)for accurate,personalized diabetes management.We explore innovations in multimodal sensor design,materials science,biorecognition elements,and integration techniques,highlighting the importance of advanced data analytics,artificial intelligence-driven predictive algorithms,and closed-loop therapeutic systems.Additionally,the review addresses ongoing challenges in biomarker validation,sensor stability,user compliance,data privacy,and regulatory considerations.A holistic,multimodal approach enabled by these next-generation wearable biosensors holds significant potential for improving patient outcomes and facilitating proactive healthcare interventions in diabetes management.展开更多
Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal ce...Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.展开更多
Hydrophilicity is critical in Nafion membranes during fuel cell operation as insufficient membrane hydration leads to brittle behavior and a drop in proton conductivity.The incorporation of APTS(3-(aminopro pyl)trieth...Hydrophilicity is critical in Nafion membranes during fuel cell operation as insufficient membrane hydration leads to brittle behavior and a drop in proton conductivity.The incorporation of APTS(3-(aminopro pyl)triethoxysilane)into exfoliated graphene oxide(EGO)by covalent functionalization to be used as filler into Nafion membranes allows higher hydrophilicity for these membranes.This is associated with promoting hydroxyl,carbonyl,siloxane,silane,and amine groups within the EGO-APTS matrix.The incorporation of these materials as Fuel Cell MEAs leads to a significant reduction of the ohmic resistance measured at high frequency resistance(HFR)in electrochemical impedance spectroscopy(EIS)experiments and achieves maximum power densities of 1.33 W cm^(-2)at 60℃ at 100%RH(APTS-EGO,0.2 wt%)and1.33 W cm^(-2)at 60℃ at 70%RH(APTS-EGO,0.3 wt%),which represents an improvement of 190%compared to the commercial Nafion 212 when utilizing low humidification conditions(70%).Moreover,the as-synthesized membrane utilizes lower Nafion ionomer mass,which,in conjunction with the excellent cell performance,has the potential to decrease the cost of the membrane from 87 to 80￡/W as well as a reduction of fluorinated compounds within the membrane.展开更多
Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed asse...Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.展开更多
Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we develop...Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.展开更多
The age at which a woman enters natural menopause has also been associated to death from any cause.Menopause is a natural component of aging that happens between the ages of 45 and 55,with the average menopausal age b...The age at which a woman enters natural menopause has also been associated to death from any cause.Menopause is a natural component of aging that happens between the ages of 45 and 55,with the average menopausal age being 51.Previous research has revealed the age at which women reach menopause,but there is no evidence to support the link between menopause and longevity.We made a study in assessing the limits of maximum lifespan at menopausal age in our previous article.In this paper,we aim to predict the maximum lifespan of women at mean menopausal age.展开更多
In recent years,there has been an increasing need for climate information across diverse sectors of society.This demand has arisen from the necessity to adapt to and mitigate the impacts of climate variability and cha...In recent years,there has been an increasing need for climate information across diverse sectors of society.This demand has arisen from the necessity to adapt to and mitigate the impacts of climate variability and change.Likewise,this period has seen a significant increase in our understanding of the physical processes and mechanisms that drive precipitation and its variability across different regions of Africa.By leveraging a large volume of climate model outputs,numerous studies have investigated the model representation of African precipitation as well as underlying physical processes.These studies have assessed whether the physical processes are well depicted and whether the models are fit for informing mitigation and adaptation strategies.This paper provides a review of the progress in precipitation simulation overAfrica in state-of-the-science climate models and discusses the major issues and challenges that remain.展开更多
With the increasing exploration of oil and gas into deep waters,the necessity for material development increases for lighter conduits such as composite marine risers,in the oil and gas industry.To understand the resea...With the increasing exploration of oil and gas into deep waters,the necessity for material development increases for lighter conduits such as composite marine risers,in the oil and gas industry.To understand the research knowledge on this novel area,there is a need to have a bibliometric analysis on composite marine risers.A research methodology was developed whereby the data retrieval was from SCOPUS database from 1977–2023.Then,VOSviewer was used to visualize the knowledge maps.This study focuses on the progress made by conducting knowledge mapping and scientometric review on composite marine risers.This scientometric analysis on the subject shows current advances,geographical activities by countries,authorship records,collaborations,funders,affiiliations,co‑occurrences,and future research areas.It was observed that the research trends recorded the highest publication volume in the U.S.A.,but less cluster affiiliated,as it was followed by countries like the U.K.,China,Nigeria,Australia and Singapore.Also,thisfiield has more conference papers than journal papers due to the challenge of adaptability,acceptance,qualifiication,and application of composite marine risers in the marine industry.Hence,there is a need for more collaborations on composite marine risers and more funding to enhance the research trend.展开更多
Multi-objective optimization is critical for problem-solving in engineering,economics,and AI.This study introduces the Multi-Objective Chef-Based Optimization Algorithm(MOCBOA),an upgraded version of the Chef-Based Op...Multi-objective optimization is critical for problem-solving in engineering,economics,and AI.This study introduces the Multi-Objective Chef-Based Optimization Algorithm(MOCBOA),an upgraded version of the Chef-Based Optimization Algorithm(CBOA)that addresses distinct objectives.Our approach is unique in systematically examining four dominance relations—Pareto,Epsilon,Cone-epsilon,and Strengthened dominance—to evaluate their influence on sustaining solution variety and driving convergence toward the Pareto front.Our comparison investigation,which was conducted on fifty test problems from the CEC 2021 benchmark and applied to areas such as chemical engineering,mechanical design,and power systems,reveals that the dominance approach used has a considerable impact on the key optimization measures such as the hypervolume metric.This paper provides a solid foundation for determining themost effective dominance approach and significant insights for both theoretical research and practical applications in multi-objective optimization.展开更多
AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease. METHODS:A cohort of patients with inflammatory bowel diseases (42 patie...AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease. METHODS:A cohort of patients with inflammatory bowel diseases (42 patients with Crohn's disease and 10 patients with ulcerative colitis) and gluten sensitive enteropathy (16 patients) from Debrecen,Hungary were enrolled in the study. The diagnosis was made using the formally accepted criteria. Perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA), antiendomysium antibodies (EMA),antigliadin antibodies (AGA) and anti human tissue transglutaminase antibodies (tTGA) were investigated. RESULTS:The results showed that ASCA positivity occurred not only in Crohn's disease but also in Celiac disease and in these cases both the IgG and IgA type antibodies were proved. CONCLUSION:It is conceivable that ASCA positivity correlates with the (auto-) immune inflammation of small intestines and it is a specific marker of Crohn's disease.展开更多
Background:A significant challenge regarding notable historical figures is determining the accuracy of the words and actions attributed to them with the limited available evidence,when their biographers have presented...Background:A significant challenge regarding notable historical figures is determining the accuracy of the words and actions attributed to them with the limited available evidence,when their biographers have presented a biased life assessment.Lauded as a founding suffragette,the first female school principal,and the first white female practicing physician in Canada,Dr.Emily Stowe did not help historians.She destroyed her records,leaving her life story to be told by her daughter,who portrayed her as a heroine–a view that has persisted since the start of the 20th century.To improve the accuracy of assessing the life of Emily Stowe,as much information as possible about Stowe must be collected and interpreted.Methods:Presented is a narrative research method for analyzing historical figures that examines 22 life-changing events in the life of Stowe by answering six types of questions about each event:when,where,who,what,how,and why.Results:This narrative research,representing a psychoanalytic research process,finds that much of the repeated story of Stowe is either exaggerated or likely false.Conclusion:Following the example of Emily Stowe,this unique method is applicable for improving the historical accuracy in assessing the lives of other notable figures.It represents a method extendable to those currently alive,outside the public eye,searching to develop their own narrative.展开更多
AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. ...AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.展开更多
A novel, Ti-6 Al-4 V(Ti64)/Hydroxyapatite(HA at 5% by weight concentration) metal/ceramic composite has been fabricated using electron beam powder bed fusion(EPBF) additive manufacturing(AM): specifically, the commerc...A novel, Ti-6 Al-4 V(Ti64)/Hydroxyapatite(HA at 5% by weight concentration) metal/ceramic composite has been fabricated using electron beam powder bed fusion(EPBF) additive manufacturing(AM): specifically, the commercial electron beam melting(EBM?) process. In addition to solid Ti64 and Ti64/5% HA samples, four different unit cell(model) open-cellular mesh structures for the Ti64/5% HA composite were fabricated having densities ranging from 0.68 to 1.12 g/cm^3, and corresponding Young's moduli ranging from 2.9 to 8.0 GPa, and compressive strengths ranging from ~3 to 11 MPa. The solid Ti64/5%HA composite exhibited an optimal tensile strength of 123 MPa, and elongation of 5.5% in contrast to a maximum compressive strength of 875 MPa. Both the solid composite and mesh samples deformed primarily by brittle deformation, with the mesh samples exhibiting erratic, brittle crushing. Solid, EPBF-fabricated Ti64 samples had a Vickers microindentation hardness of 4.1 GPa while the Ti64/5%HA solid composite exhibited a Vickers microindentation hardness of 6.8 GPa. The lowest density Ti64/5%HA composite mesh strut sections had a Vickers microindentation hardness of 7.1 GPa. Optical metallography(OM) and scanning electron microscopy(SEM) analysis showed the HA dispersoids to be highly segregated along domain or grain boundaries, but homogeneously distributed along alpha(hcp) platelet boundaries within these domains in the Ti64 matrix for both the solid and mesh composites. The alpha platelet width varied from ~5 μm in the EPBF-fabricated Ti64 to ~1.1 m for the Ti64/5%HA mesh strut. The precursor HA powder diameter averaged 5 μm, in contrast to the dispersed HA particle diameters in the Ti64/5%HA composite which averaged 0.5 m. This work highlights the use of EPBF AM as a novel process for fabrication of a true composite structure, consisting of a Ti64 matrix and interspersed and exposed HA domains, which to the authors' knowledge has not been reported before. The results also illustrate the prospects not only for fabricating specialized, novel composite bone replacement scaffolds and implants, through the combination of Ti64 and HA, but also prospects for producing a variety of related metal/ceramic composites using EPBF AM.展开更多
Integrating exhaled breath analysis into the diagnosis of cardiovascular diseases holds significant promise as a valuable tool for future clinical use,particularly for ischemic heart disease(IHD).However,current resea...Integrating exhaled breath analysis into the diagnosis of cardiovascular diseases holds significant promise as a valuable tool for future clinical use,particularly for ischemic heart disease(IHD).However,current research on the volatilome(exhaled breath composition)in heart disease remains underexplored and lacks sufficient evidence to confirm its clinical validity.Key challenges hindering the application of breath analysis in diagnosing IHD include the scarcity of studies(only three published papers to date),substantial methodological bias in two of these studies,and the absence of standardized protocols for clinical imple-mentation.Additionally,inconsistencies in methodologies—such as sample collection,analytical techniques,machine learning(ML)approaches,and result interpretation—vary widely across studies,further complicating their reprodu-cibility and comparability.To address these gaps,there is an urgent need to establish unified guidelines that define best practices for breath sample collection,data analysis,ML integration,and biomarker annotation.Until these challenges are systematically resolved,the widespread adoption of exhaled breath analysis as a reliable diagnostic tool for IHD remains a distant goal rather than an immi-nent reality.展开更多
Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to spe...Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.展开更多
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
文摘Basic life support for cardiac arrest associates cardiopulmonary resuscitation(CPR)and defibrillation.CPR relies on chest compressions(CC)and ventilation.Current guidelines on CPR recommend a depth of 5-6 cm at a rhythm of 100-120 times/min for CC.[1,2]Interruptions of the CC must be as short as possible and are related to ventilation,defibrillation and turnover of the rescuers.Most of the automated external defibrillators(AEDs)require interruptions of the CC to perform rhythm analysis.Among the numerous marketed models of AEDs,some provide real-time feedback about the quality of the CC.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)grant number 525793193Prof.Stefan Eimer and Ms.Marion Basoglu at Goethe University for their assistance in TEM characterization+1 种基金Mr.Holger Schranz for his help in plant cultivation and maintenanceProf.Bruno M.Moerschbacher from the Institute of Plant Biology and Biotechnology at the Münster University。
文摘Conventional agrochemical plant biostimulants have been used to increase crop yield and stress resistance,andthis strategy continues to be integral to today's farming.While effective,the large-scale implantations of theseproducts are not without environmental,ecological,and cost concerns and the associated climate-change challenges.To alleviate this long-standing pressure on agriculture,designing and developing more biocompatible andsustainable plant stimulants are among the primary focuses of agricultural management.Over the recent decades,the field has witnessed significant progress in emerging naturally derived or nature-inspired nano-biostimulantswith large-active-surface areas,including bio-compounds,biopolymers,and nanocarbons.However,the extraction/preparation of these products may apply additional costs or require specific equipment.More recently,thefield's attention has shifted to the sustainable application of chemical-additive-free biostimulants towards practicalapplications in nano-agriculture.Herein,we rationally designed and reported the first evidence and elucidationon biostimulant impacts of plant-self-derived nano-extracts from donor Arabidopsis thaliana as a model forinducing mirror biostimulant activities in conspecific host seeds,seedlings,and plants.Moreover,we assessed theeffect of donor plants'age on short,mid-,and long-term biocompatibility,growth,and development/maturationof the recipient plants for up to around 30 days.As a proof-of-concept,we found these autologous bio-extractscould effectively promote seed sprouting,seedling germination,and the development of soil-drenched plantsof the same types.Our transmission-electron microscopy characterization of root/shoot pieces shows the presenceof multiple phyto-compounds,including microtubules/actin filaments,cell vacuoles,Golgi stacks/endoplasmicreticulum,cell wall polysaccharide-based cellulose fibers,and organic amorphous nanoparticles and clusters ofcarbon quantum dots in the structure of these extracts.This personalized plant stimulation may induce furthergrowth/defense-related mechanisms,setting new paradigms toward reducing the agrochemical inputs.
文摘Diabetes mellitus represents a major global health issue,driving the need for noninvasive alternatives to traditional blood glucose monitoring methods.Recent advancements in wearable technology have introduced skin-interfaced biosensors capable of analyzing sweat and skin biomarkers,providing innovative solutions for diabetes diagnosis and monitoring.This review comprehensively discusses the current developments in noninvasive wearable biosensors,emphasizing simultaneous detection of biochemical biomarkers(such as glucose,cortisol,lactate,branched-chain amino acids,and cytokines)and physiological signals(including heart rate,blood pressure,and sweat rate)for accurate,personalized diabetes management.We explore innovations in multimodal sensor design,materials science,biorecognition elements,and integration techniques,highlighting the importance of advanced data analytics,artificial intelligence-driven predictive algorithms,and closed-loop therapeutic systems.Additionally,the review addresses ongoing challenges in biomarker validation,sensor stability,user compliance,data privacy,and regulatory considerations.A holistic,multimodal approach enabled by these next-generation wearable biosensors holds significant potential for improving patient outcomes and facilitating proactive healthcare interventions in diabetes management.
基金the Scientific and Technological Research Council of Türkiye(TÜBİTAK)Under the International Postdoctoral Research Fellowship Program(2219),No.1059B192400980the National Postdoctoral Research Fellowship Program(2218),No.122C158.
文摘Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.
基金financially supported by the UK Research Council EPRSC EP/W03395X/1the Program grant SynHiSel EP/V047078/1the Hydrogen and Fuel Cells Hub(H_(2)FC SUPERGEN)EP/P024807/1。
文摘Hydrophilicity is critical in Nafion membranes during fuel cell operation as insufficient membrane hydration leads to brittle behavior and a drop in proton conductivity.The incorporation of APTS(3-(aminopro pyl)triethoxysilane)into exfoliated graphene oxide(EGO)by covalent functionalization to be used as filler into Nafion membranes allows higher hydrophilicity for these membranes.This is associated with promoting hydroxyl,carbonyl,siloxane,silane,and amine groups within the EGO-APTS matrix.The incorporation of these materials as Fuel Cell MEAs leads to a significant reduction of the ohmic resistance measured at high frequency resistance(HFR)in electrochemical impedance spectroscopy(EIS)experiments and achieves maximum power densities of 1.33 W cm^(-2)at 60℃ at 100%RH(APTS-EGO,0.2 wt%)and1.33 W cm^(-2)at 60℃ at 70%RH(APTS-EGO,0.3 wt%),which represents an improvement of 190%compared to the commercial Nafion 212 when utilizing low humidification conditions(70%).Moreover,the as-synthesized membrane utilizes lower Nafion ionomer mass,which,in conjunction with the excellent cell performance,has the potential to decrease the cost of the membrane from 87 to 80￡/W as well as a reduction of fluorinated compounds within the membrane.
基金supported by a grant from the Health Research New Zealand(HRC)22/559(to AJG and LB)。
文摘Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.
基金supported partially by the Australian Government through the Australian Research Council Centres of Excellence funding scheme(project CE200100029)。
文摘Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.
文摘The age at which a woman enters natural menopause has also been associated to death from any cause.Menopause is a natural component of aging that happens between the ages of 45 and 55,with the average menopausal age being 51.Previous research has revealed the age at which women reach menopause,but there is no evidence to support the link between menopause and longevity.We made a study in assessing the limits of maximum lifespan at menopausal age in our previous article.In this paper,we aim to predict the maximum lifespan of women at mean menopausal age.
基金the World Climate Research Programme(WCRP),Climate Variability and Predictability(CLIVAR),and Global Energy and Water Exchanges(GEWEX)for facilitating the coordination of African monsoon researchsupport from the Center for Earth System Modeling,Analysis,and Data at the Pennsylvania State Universitythe support of the Office of Science of the U.S.Department of Energy Biological and Environmental Research as part of the Regional&Global Model Analysis(RGMA)program area。
文摘In recent years,there has been an increasing need for climate information across diverse sectors of society.This demand has arisen from the necessity to adapt to and mitigate the impacts of climate variability and change.Likewise,this period has seen a significant increase in our understanding of the physical processes and mechanisms that drive precipitation and its variability across different regions of Africa.By leveraging a large volume of climate model outputs,numerous studies have investigated the model representation of African precipitation as well as underlying physical processes.These studies have assessed whether the physical processes are well depicted and whether the models are fit for informing mitigation and adaptation strategies.This paper provides a review of the progress in precipitation simulation overAfrica in state-of-the-science climate models and discusses the major issues and challenges that remain.
基金support of the School of Engineering,Lancaster University,UK,for the Engineering Department Studentship as well as the Engineering and Physical Sciences Research Council(EPSRC)’s Doctoral Training Centre(DTC)。
文摘With the increasing exploration of oil and gas into deep waters,the necessity for material development increases for lighter conduits such as composite marine risers,in the oil and gas industry.To understand the research knowledge on this novel area,there is a need to have a bibliometric analysis on composite marine risers.A research methodology was developed whereby the data retrieval was from SCOPUS database from 1977–2023.Then,VOSviewer was used to visualize the knowledge maps.This study focuses on the progress made by conducting knowledge mapping and scientometric review on composite marine risers.This scientometric analysis on the subject shows current advances,geographical activities by countries,authorship records,collaborations,funders,affiiliations,co‑occurrences,and future research areas.It was observed that the research trends recorded the highest publication volume in the U.S.A.,but less cluster affiiliated,as it was followed by countries like the U.K.,China,Nigeria,Australia and Singapore.Also,thisfiield has more conference papers than journal papers due to the challenge of adaptability,acceptance,qualifiication,and application of composite marine risers in the marine industry.Hence,there is a need for more collaborations on composite marine risers and more funding to enhance the research trend.
基金funded by Researchers Supporting Programnumber(RSPD2024R809),King Saud University,Riyadh,Saudi Arabia.
文摘Multi-objective optimization is critical for problem-solving in engineering,economics,and AI.This study introduces the Multi-Objective Chef-Based Optimization Algorithm(MOCBOA),an upgraded version of the Chef-Based Optimization Algorithm(CBOA)that addresses distinct objectives.Our approach is unique in systematically examining four dominance relations—Pareto,Epsilon,Cone-epsilon,and Strengthened dominance—to evaluate their influence on sustaining solution variety and driving convergence toward the Pareto front.Our comparison investigation,which was conducted on fifty test problems from the CEC 2021 benchmark and applied to areas such as chemical engineering,mechanical design,and power systems,reveals that the dominance approach used has a considerable impact on the key optimization measures such as the hypervolume metric.This paper provides a solid foundation for determining themost effective dominance approach and significant insights for both theoretical research and practical applications in multi-objective optimization.
文摘AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease. METHODS:A cohort of patients with inflammatory bowel diseases (42 patients with Crohn's disease and 10 patients with ulcerative colitis) and gluten sensitive enteropathy (16 patients) from Debrecen,Hungary were enrolled in the study. The diagnosis was made using the formally accepted criteria. Perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA), antiendomysium antibodies (EMA),antigliadin antibodies (AGA) and anti human tissue transglutaminase antibodies (tTGA) were investigated. RESULTS:The results showed that ASCA positivity occurred not only in Crohn's disease but also in Celiac disease and in these cases both the IgG and IgA type antibodies were proved. CONCLUSION:It is conceivable that ASCA positivity correlates with the (auto-) immune inflammation of small intestines and it is a specific marker of Crohn's disease.
文摘Background:A significant challenge regarding notable historical figures is determining the accuracy of the words and actions attributed to them with the limited available evidence,when their biographers have presented a biased life assessment.Lauded as a founding suffragette,the first female school principal,and the first white female practicing physician in Canada,Dr.Emily Stowe did not help historians.She destroyed her records,leaving her life story to be told by her daughter,who portrayed her as a heroine–a view that has persisted since the start of the 20th century.To improve the accuracy of assessing the life of Emily Stowe,as much information as possible about Stowe must be collected and interpreted.Methods:Presented is a narrative research method for analyzing historical figures that examines 22 life-changing events in the life of Stowe by answering six types of questions about each event:when,where,who,what,how,and why.Results:This narrative research,representing a psychoanalytic research process,finds that much of the repeated story of Stowe is either exaggerated or likely false.Conclusion:Following the example of Emily Stowe,this unique method is applicable for improving the historical accuracy in assessing the lives of other notable figures.It represents a method extendable to those currently alive,outside the public eye,searching to develop their own narrative.
基金Supported by the Grants From Ligue Nationale Contre le Cancer,Comités Départementaux de la Manche,de l'Orne et du Calvados and from Université de Metz
文摘AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.
文摘A novel, Ti-6 Al-4 V(Ti64)/Hydroxyapatite(HA at 5% by weight concentration) metal/ceramic composite has been fabricated using electron beam powder bed fusion(EPBF) additive manufacturing(AM): specifically, the commercial electron beam melting(EBM?) process. In addition to solid Ti64 and Ti64/5% HA samples, four different unit cell(model) open-cellular mesh structures for the Ti64/5% HA composite were fabricated having densities ranging from 0.68 to 1.12 g/cm^3, and corresponding Young's moduli ranging from 2.9 to 8.0 GPa, and compressive strengths ranging from ~3 to 11 MPa. The solid Ti64/5%HA composite exhibited an optimal tensile strength of 123 MPa, and elongation of 5.5% in contrast to a maximum compressive strength of 875 MPa. Both the solid composite and mesh samples deformed primarily by brittle deformation, with the mesh samples exhibiting erratic, brittle crushing. Solid, EPBF-fabricated Ti64 samples had a Vickers microindentation hardness of 4.1 GPa while the Ti64/5%HA solid composite exhibited a Vickers microindentation hardness of 6.8 GPa. The lowest density Ti64/5%HA composite mesh strut sections had a Vickers microindentation hardness of 7.1 GPa. Optical metallography(OM) and scanning electron microscopy(SEM) analysis showed the HA dispersoids to be highly segregated along domain or grain boundaries, but homogeneously distributed along alpha(hcp) platelet boundaries within these domains in the Ti64 matrix for both the solid and mesh composites. The alpha platelet width varied from ~5 μm in the EPBF-fabricated Ti64 to ~1.1 m for the Ti64/5%HA mesh strut. The precursor HA powder diameter averaged 5 μm, in contrast to the dispersed HA particle diameters in the Ti64/5%HA composite which averaged 0.5 m. This work highlights the use of EPBF AM as a novel process for fabrication of a true composite structure, consisting of a Ti64 matrix and interspersed and exposed HA domains, which to the authors' knowledge has not been reported before. The results also illustrate the prospects not only for fabricating specialized, novel composite bone replacement scaffolds and implants, through the combination of Ti64 and HA, but also prospects for producing a variety of related metal/ceramic composites using EPBF AM.
基金Supported by The government assignment,No.1023022600020-6The Ministry of Science and Higher Education of the Russian Federation Within The Framework of State Support for The Creation and Development of World-Class Research Center“Digital Biodesign and Personalized Healthcare,”No.075-15-2022-304RSF grant,No.24-15-00549.
文摘Integrating exhaled breath analysis into the diagnosis of cardiovascular diseases holds significant promise as a valuable tool for future clinical use,particularly for ischemic heart disease(IHD).However,current research on the volatilome(exhaled breath composition)in heart disease remains underexplored and lacks sufficient evidence to confirm its clinical validity.Key challenges hindering the application of breath analysis in diagnosing IHD include the scarcity of studies(only three published papers to date),substantial methodological bias in two of these studies,and the absence of standardized protocols for clinical imple-mentation.Additionally,inconsistencies in methodologies—such as sample collection,analytical techniques,machine learning(ML)approaches,and result interpretation—vary widely across studies,further complicating their reprodu-cibility and comparability.To address these gaps,there is an urgent need to establish unified guidelines that define best practices for breath sample collection,data analysis,ML integration,and biomarker annotation.Until these challenges are systematically resolved,the widespread adoption of exhaled breath analysis as a reliable diagnostic tool for IHD remains a distant goal rather than an immi-nent reality.
文摘Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.
