Atrial fibrillation(AF)is the most common arrhythmia in humans,affecting more than 40 million people worldwide.Radiofrequency catheter ablation(RFCA)was first introduced as a treatment for AF by Haïssaguerre M in...Atrial fibrillation(AF)is the most common arrhythmia in humans,affecting more than 40 million people worldwide.Radiofrequency catheter ablation(RFCA)was first introduced as a treatment for AF by Haïssaguerre M in the late 1990s.This procedure quickly became the treatment of choice,especially for symptomatic patients with AF refractory to medication.However,up to 45%of patients may experience AF recurrence within 12 months after RFCA.In this setting,AF recurrence is likely multifactorial,including atrial remodeling,local fibrosis or incomplete ablation due to failure in locating the trigger.Additionally,patients with obesity,sleep apnea,hypertension,or diabetes are at an increased risk of AF recurrence after RFCA.Inflammation is increasingly recognized as a potential key factor in AF recurrence and may arise both from the healing response of heart tissue post-ablation or from chronic low-grade inflammation,as observed in many risk factors.Here,we present an original study by Wang et al,which investigated the combination of the systemic immune-inflammation index-a marker developed to assess overall inflammatory status-and the APPLE score,designed to predict AF recurrence following RFCA.The study found that using both indicators together improved the accuracy of AF recurrence prediction.These findings underscore the significant role of inflammation in cardiovascular disease and demonstrated its impact on AF recurrence after RFCA.Further research is warranted to validate the combined use of these two scores in clinical settings for predicting AF recurrence following catheter ablation.展开更多
Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucid...Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.展开更多
Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is ...Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.展开更多
The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centere...The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.展开更多
The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by ...The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.展开更多
Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis.This is also reflected by the widespread expression of two familie...Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis.This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2)with numerous subtypes.In the last few decades,there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions.Mainly,signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies.Thus,interference with P2 receptors may be a promising strategy for the modulation of immune responses.Although only a few clinical studies have been conducted in isolated entities with limited success,preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases.Despite the association of P2 receptors with several disorders from this field,the use of P2 receptor antagonists in clinical therapy is still very scarce.In this narrative review,we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes.We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events.Using suramin,a non-specific purinergic inhibitor,as an example,we further show that off-target effects could be responsible for observed effects in immunological settings,which may have interesting implications.Overall,we believe that it is worthwhile to further investigate this hitherto underexplored area.展开更多
We present a class of arbitrarily high order fully explicit kinetic numerical methods in compressible fluid dynamics,both in time and space,which include the relaxation schemes by Jin and Xin.These methods can use the...We present a class of arbitrarily high order fully explicit kinetic numerical methods in compressible fluid dynamics,both in time and space,which include the relaxation schemes by Jin and Xin.These methods can use the CFL number larger or equal to unity on regular Cartesian meshes for the multi-dimensional case.These kinetic models depend on a small parameter that can be seen as a"Knudsen"number.The method is asymptotic preserving in this Knudsen number.Also,the computational costs of the method are of the same order of a fully explicit scheme.This work is the extension of Abgrall et al.(2022)[3]to multidimensional systems.We have assessed our method on several problems for two-dimensional scalar problems and Euler equations and the scheme has proven to be robust and to achieve the theoretically predicted high order of accuracy on smooth solutions.展开更多
The human brain has exceedingly high metabolic demands.The cerebral vasculature has the critical task of providing sufficient blood supply to meet this demand.The sudden interruption of blood flow to the brain,as obse...The human brain has exceedingly high metabolic demands.The cerebral vasculature has the critical task of providing sufficient blood supply to meet this demand.The sudden interruption of blood flow to the brain,as observed during ischemic stroke,results in acute neurological injury with devastating consequences-a high rate of adult disability and death.Ischemic stroke is thus a vascular disorder with a dramatic neurological impact.There is an urgent need for more effective disease management to combat stroke as current treatment paradigms,focusing on vascular recanalization and neuroprotection,have only limited clinical success.Since accumulating data suggests successful long-term neuroprotection is unlikely to be achievable without a functional microvascular network,strategies that reduce endothelial dysfunction could be indispensable.Encouragingly,very recent evidence highlighted herein suggests protecting the humble pericyte may be a new approach to reaching this goal.展开更多
The deferred correction(DeC)is an iterative procedure,characterized by increasing the accuracy at each iteration,which can be used to design numerical methods for systems of ODEs.The main advantage of such framework i...The deferred correction(DeC)is an iterative procedure,characterized by increasing the accuracy at each iteration,which can be used to design numerical methods for systems of ODEs.The main advantage of such framework is the automatic way of getting arbitrarily high order methods,which can be put in the Runge-Kutta(RK)form.The drawback is the larger computational cost with respect to the most used RK methods.To reduce such cost,in an explicit setting,we propose an efcient modifcation:we introduce interpolation processes between the DeC iterations,decreasing the computational cost associated to the low order ones.We provide the Butcher tableaux of the new modifed methods and we study their stability,showing that in some cases the computational advantage does not afect the stability.The fexibility of the novel modifcation allows nontrivial applications to PDEs and construction of adaptive methods.The good performances of the introduced methods are broadly tested on several benchmarks both in ODE and PDE contexts.展开更多
Sustainable intensification of cultivated land use(SICLU) and large-scale operations(LSO) are widely acknowledged strategies for enhancing agricultural performance.However,the existing literature has faced challenges ...Sustainable intensification of cultivated land use(SICLU) and large-scale operations(LSO) are widely acknowledged strategies for enhancing agricultural performance.However,the existing literature has faced challenges in precisely defining SICLU and constructing comprehensive indicators,which has hindered the exploration of factors influencing LSO within the SICLU framework.To address this gap,we integrated self-efficacy theory into the design of an index framework for evaluating SICLU.We subsequently employed econometric models to analyze the significant factors that impact LSO.Our findings reveal that SICLU can be divided into four key dimensions:intensive management,efficient output,resource conservation,and ecological environment optimization.Furthermore,it is crucial to incorporate belief-based cognitive factors into the index system,as farmers’ understanding of fertilizer and pesticide application significantly influences their willingness to engage in LSO.Moreover,we identify grain market turnover as the most influential factor in promoting LSO,with single-factor contribution rates reaching 70.9% for cultivated land transfer willingness and 62.5% for the total planting areas.Interestingly,unlike irrigation and agricultural machinery inputs,increased labor inputs correspond to larger planting areas for farmers.This trend may be attributed to reduced labor availability because of rural labor migration,whereas the reduction in irrigation and agricultural input is contingent on innovations in production practices and the transfer of cultivated land management rights.Importantly,SICLU dynamically influences LSO,with each index related to SICLU having an optimal range that fosters LSO.These insights offer valuable guidance for policymakers,emphasizing farmers as their central focus,with the adjustment of input and output factors as a means to achieve LSO as the ultimate goal.In conclusion,we propose research avenues for further enriching the SICLU framework to ensure that it aligns with the specific characteristics of regional agricultural development.展开更多
Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital hea...Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)procedures.We sought to evaluate the safety and efficacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP procedures.Methods and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of Zurich Heart Center between January 2019 and December 2022 was observed and analyzed.During the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound guidance.At the end of the procedure,a single Z-stitch was performed at the puncture site.We eval-uated the incidence of in-hospital complications associated with femoral access puncture in this population.Among 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP procedures.The median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousfistula,venous or arterial thrombosis.Conclusion:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.展开更多
Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseas...Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.展开更多
BACKGROUND When patients with a failed hip arthroplasty are unsuitable for reimplantation,Girdlestone resection arthroplasty(GRA)is a viable treatment option.We report on a patient who was treated with a GRA due to a ...BACKGROUND When patients with a failed hip arthroplasty are unsuitable for reimplantation,Girdlestone resection arthroplasty(GRA)is a viable treatment option.We report on a patient who was treated with a GRA due to a periprosthetic infection.We discovered partial paralysis of the quadriceps muscle in this patient.We investigated the femoral nerve anatomy,particularly the nerve entry points,to better understand this phenomenon.AIM To reveal the femoral nerve anatomy with respect to severe proximal migration after GRA.METHODS Eight cadaveric hemipelves were investigated.The branches of the femoral nerve were dissected and traced distally.The GRA was performed by the direct anterior approach.Axial stress to the lower extremity was applied,and the relative movement of the femur was recorded.The femoral nerve and its entry points were assessed.RESULTS GRA led to a 3.8 cm shift of the femur in vertical direction,a 1.8 cm shift in the dorsal direction,and a 2.3 cm shift in the lateral direction.A 36.5°external shift was observed.This caused stress to the lateral division of the femoral nerve.We observed migration of the femoral nerve entry point at the following locations:(1)Vastus medialis(5.3 mm);(2)The medial part of the vastus intermedius(5.4 mm);(3)The lateral part of the vastus intermedius(16.3 mm);(4)Rectus femoris(23.1 mm);(5)Tensor vastus intermedius(30.8 mm);and(6)Vastus lateralis(28.8 mm).CONCLUSION Migration of the femur after GRA altered the anatomy of the femoral nerve.Stress occurred at the lateral nerve division leading to poor functional results.展开更多
BACKGROUND The auricle,or auricula,defines the visible boundaries of the external ear and is essential in forensic investigations,including facial reconstruction and human remains identification.Beyond its forensic si...BACKGROUND The auricle,or auricula,defines the visible boundaries of the external ear and is essential in forensic investigations,including facial reconstruction and human remains identification.Beyond its forensic significance,auricular morphology attracts interest from various fields,such as medicine and industry.The size of the ears is culturally associated with health and longevity,while surgical techniques for ear reconstruction address both congenital and aesthetic concerns.AIM To determine whether known correlations with various measurements and observations regarding sex and age could also be established through computed tomography(CT).METHODS Computed tomography scans of the head from 342 females and 329 males aged 18 to 97 years(mean=60±19 years)were included in this study.Different auricular lengths,widths and perimeters were measured for both sides.Additionally,the preauricular area was assessed using three-dimensional volume rendering tech-nique images.RESULTS The measured auricular dimensions in centimeters are presented as mean values(right/left)for males(length 16.91±0.51/6.93±0.52;length 22.83±0.35/2.84±0.34;width 13.94±0.32/4.01±0.36;width 23.51±0.34/3.46±0.31;perimeter 17.66±1.25/17.71±1.28)and females(length 16.44±0.5/6.48±0.51;length 22.7±0.32/2.71±0.33;width 13.6±0.32/3.68±0.31;width 23.3±0.3/3.26±0.27;perimeter 16.36±1.2/16.46±1.2).A positive correlation with age was shown in all measurements,with the highest value for perimeter in both,males(r-value:right/left:0.49/0.47)and females(r-value:right/left:0.53/0.53).After confounding factors were excluded,the preauricular vertical line was first seen at 45 years.The mean age for males with preauricular vertical lines was 66.65±10.92 years(95%CI:63.99-69.3),while without vertical lines,it was 44.48±16.15 years(95%CI:41.21-47.74);for females,it was 70.18±12.44 years(95%CI:68.9-71.46)with and 47.87±17.09 years(95%CI:45.96-49.78)without vertical lines.CONCLUSION In this study,we pioneered the use of CT volumetric data to examine human auricle morphology and we achieved a precise 3D(pre-)auricular assessment.Sex-specific positive correlations between ear dimensions and age,as well as the mean age for the appearance of preauricular lines,were identified,providing valuable insights into the capabilities of modern CT devices.展开更多
Phylogenetic niche conservatism posits that species tend to retain ancestral ecological traits and distributions,which has been broadly tested for lineages originating in tropical climates but has been rarely tested f...Phylogenetic niche conservatism posits that species tend to retain ancestral ecological traits and distributions,which has been broadly tested for lineages originating in tropical climates but has been rarely tested for lineages that originated and diversified in temperate climates.Liverworts are thought to originate in temperate climates.Mean lineage age reflects evolutionary history of biological communities.Here,using regional liverwort floras across a long latitudinal gradient from tropical to arctic climates in North America,we test the age-component of the temperate niche conservatism hypothesis.Mean genus age(MGA)was estimated for each of 76 regional floras of liverworts.We related MGA to climatic variables for North America as a whole and for its eastern and western parts separately,and used variation partitioning analysis to assess the relative importance of temperature-versus precipitationrelated variables and of climate extremes versus seasonality on MGA.We found that older genera of liverworts tend to concentrate in humid regions of intermediate temperatures in the range of 10℃-20℃,from which liverworts have adapted to and diversified into more arid,colder,and hotter regions,supporting the temperate niche conservatism hypothesis.We also found that across North America the MGA of liverwort assemblages is more strongly affected by precipitation-related variables than by temperature-related variables,and is more strongly affected by climate extremes than by climate seasonality.Geographic patterns of the MGA of liverworts are consistent with the temperate niche conservatism hypothesis,rather than the tropical niche conservatism hypothesis,the latter of which is broadly supported by angiosperms.展开更多
Here we provide a preliminary assessment of dietary and habitat requirements of two sympatric primate taxa, a "simple-stomached" and "complex-stomached" species (Rhinopithecus bieti Colobinae vs. Macaca mulatta C...Here we provide a preliminary assessment of dietary and habitat requirements of two sympatric primate taxa, a "simple-stomached" and "complex-stomached" species (Rhinopithecus bieti Colobinae vs. Macaca mulatta Cercopithecinae), as a basis for illuminating how the two coexist. Of ca. 22 plant food species consumed by the macaques, at least 16 were also eaten by the snub-nosed monkeys. Both species showed a preference for fruits. While the snub-nosed monkeys did not utilize any resources associated with human communities, rhesus macaques did occasionally raid agricultural crops. The mean elevation of the snub-nosed monkey group was 3,218 m, while the mean elevation of the macaque group was 2,995 m. Macaques were also spotted on meadows whereas snub-nosed monkeys evidently avoided these. For both species, mixed deciduous broadleaf/conifer forest was the most frequently used ecotype, but whereas evergreen broadleaf forest (Cyclobalanopsis community) accounted for only 3% of the location records of the snub-nosed monkeys, it accounted for 36% of the location records of the macaques. Groups of the two species usually kept a considerable spatial distance from one another (mean 2.4 km). One close encounter and confrontation between groups of the two species resulted in the macaque group moving away. Our findings suggest that the coexistence of the two taxa is facilitated via differential macrohabitat use and spatial avoidance. Although divergent habitat-use strategies may reflect interspecific competition, they may also merely reflect different physiological or ecological requirements.展开更多
AIM: To study the association of three common ABCB11 and ABCC2 polymorphisms (ABCB11: 1331T〉C→V444A; ABCC2: 3563T〉A → V1188E and 4544G 〉A → C1515Y) with intrahepatic cholestasis of pregnancy (ICP) and con...AIM: To study the association of three common ABCB11 and ABCC2 polymorphisms (ABCB11: 1331T〉C→V444A; ABCC2: 3563T〉A → V1188E and 4544G 〉A → C1515Y) with intrahepatic cholestasis of pregnancy (ICP) and contraceptive-induced cholestasis (CIC). METHODS: ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS: The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls: C allele 76.2% (CI, 58.0-94.4) vs 51.3% (CI 35.8-66.7), respectively (P = 0.0007); and CC allele 57.1% (CI 36.0-78.3) vs 20% (CI 7.6-32.4), respectively (P = 0.0065). All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION: Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.展开更多
文摘Atrial fibrillation(AF)is the most common arrhythmia in humans,affecting more than 40 million people worldwide.Radiofrequency catheter ablation(RFCA)was first introduced as a treatment for AF by Haïssaguerre M in the late 1990s.This procedure quickly became the treatment of choice,especially for symptomatic patients with AF refractory to medication.However,up to 45%of patients may experience AF recurrence within 12 months after RFCA.In this setting,AF recurrence is likely multifactorial,including atrial remodeling,local fibrosis or incomplete ablation due to failure in locating the trigger.Additionally,patients with obesity,sleep apnea,hypertension,or diabetes are at an increased risk of AF recurrence after RFCA.Inflammation is increasingly recognized as a potential key factor in AF recurrence and may arise both from the healing response of heart tissue post-ablation or from chronic low-grade inflammation,as observed in many risk factors.Here,we present an original study by Wang et al,which investigated the combination of the systemic immune-inflammation index-a marker developed to assess overall inflammatory status-and the APPLE score,designed to predict AF recurrence following RFCA.The study found that using both indicators together improved the accuracy of AF recurrence prediction.These findings underscore the significant role of inflammation in cardiovascular disease and demonstrated its impact on AF recurrence after RFCA.Further research is warranted to validate the combined use of these two scores in clinical settings for predicting AF recurrence following catheter ablation.
基金financially supported by National Natural Science Foundation of China (32160801)China Agriculture Research System (CARS-39-12)+1 种基金Young Talent Fund of Association for Science and Technology in Shaanxi, China (2023-6-2-1)“Double-chain” project on livestock breeding (2022GDTSLD-46)
文摘Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.
文摘Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.
文摘The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.
文摘The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.
基金supported by the UZH Postdoc grant(to MH)the Foundation for Research in Science at the University of Zurich(to MTW)。
文摘Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis.This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2)with numerous subtypes.In the last few decades,there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions.Mainly,signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies.Thus,interference with P2 receptors may be a promising strategy for the modulation of immune responses.Although only a few clinical studies have been conducted in isolated entities with limited success,preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases.Despite the association of P2 receptors with several disorders from this field,the use of P2 receptor antagonists in clinical therapy is still very scarce.In this narrative review,we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes.We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events.Using suramin,a non-specific purinergic inhibitor,as an example,we further show that off-target effects could be responsible for observed effects in immunological settings,which may have interesting implications.Overall,we believe that it is worthwhile to further investigate this hitherto underexplored area.
基金funded by the SNF project 200020_204917 entitled"Structure preserving and fast methods for hyperbolic systems of conservation laws".
文摘We present a class of arbitrarily high order fully explicit kinetic numerical methods in compressible fluid dynamics,both in time and space,which include the relaxation schemes by Jin and Xin.These methods can use the CFL number larger or equal to unity on regular Cartesian meshes for the multi-dimensional case.These kinetic models depend on a small parameter that can be seen as a"Knudsen"number.The method is asymptotic preserving in this Knudsen number.Also,the computational costs of the method are of the same order of a fully explicit scheme.This work is the extension of Abgrall et al.(2022)[3]to multidimensional systems.We have assessed our method on several problems for two-dimensional scalar problems and Euler equations and the scheme has proven to be robust and to achieve the theoretically predicted high order of accuracy on smooth solutions.
基金supported by Swiss National Science Foundation grant 31003A_150062(to OOO).
文摘The human brain has exceedingly high metabolic demands.The cerebral vasculature has the critical task of providing sufficient blood supply to meet this demand.The sudden interruption of blood flow to the brain,as observed during ischemic stroke,results in acute neurological injury with devastating consequences-a high rate of adult disability and death.Ischemic stroke is thus a vascular disorder with a dramatic neurological impact.There is an urgent need for more effective disease management to combat stroke as current treatment paradigms,focusing on vascular recanalization and neuroprotection,have only limited clinical success.Since accumulating data suggests successful long-term neuroprotection is unlikely to be achievable without a functional microvascular network,strategies that reduce endothelial dysfunction could be indispensable.Encouragingly,very recent evidence highlighted herein suggests protecting the humble pericyte may be a new approach to reaching this goal.
文摘The deferred correction(DeC)is an iterative procedure,characterized by increasing the accuracy at each iteration,which can be used to design numerical methods for systems of ODEs.The main advantage of such framework is the automatic way of getting arbitrarily high order methods,which can be put in the Runge-Kutta(RK)form.The drawback is the larger computational cost with respect to the most used RK methods.To reduce such cost,in an explicit setting,we propose an efcient modifcation:we introduce interpolation processes between the DeC iterations,decreasing the computational cost associated to the low order ones.We provide the Butcher tableaux of the new modifed methods and we study their stability,showing that in some cases the computational advantage does not afect the stability.The fexibility of the novel modifcation allows nontrivial applications to PDEs and construction of adaptive methods.The good performances of the introduced methods are broadly tested on several benchmarks both in ODE and PDE contexts.
基金Under the auspices of National Natural Science Foundation of China(No.42071226,41671176)Taishan Scholars Youth Expert Support Plan of Shandong Province(No.TSQN202306183)。
文摘Sustainable intensification of cultivated land use(SICLU) and large-scale operations(LSO) are widely acknowledged strategies for enhancing agricultural performance.However,the existing literature has faced challenges in precisely defining SICLU and constructing comprehensive indicators,which has hindered the exploration of factors influencing LSO within the SICLU framework.To address this gap,we integrated self-efficacy theory into the design of an index framework for evaluating SICLU.We subsequently employed econometric models to analyze the significant factors that impact LSO.Our findings reveal that SICLU can be divided into four key dimensions:intensive management,efficient output,resource conservation,and ecological environment optimization.Furthermore,it is crucial to incorporate belief-based cognitive factors into the index system,as farmers’ understanding of fertilizer and pesticide application significantly influences their willingness to engage in LSO.Moreover,we identify grain market turnover as the most influential factor in promoting LSO,with single-factor contribution rates reaching 70.9% for cultivated land transfer willingness and 62.5% for the total planting areas.Interestingly,unlike irrigation and agricultural machinery inputs,increased labor inputs correspond to larger planting areas for farmers.This trend may be attributed to reduced labor availability because of rural labor migration,whereas the reduction in irrigation and agricultural input is contingent on innovations in production practices and the transfer of cultivated land management rights.Importantly,SICLU dynamically influences LSO,with each index related to SICLU having an optimal range that fosters LSO.These insights offer valuable guidance for policymakers,emphasizing farmers as their central focus,with the adjustment of input and output factors as a means to achieve LSO as the ultimate goal.In conclusion,we propose research avenues for further enriching the SICLU framework to ensure that it aligns with the specific characteristics of regional agricultural development.
基金This study complied with the Declaration of Helsinki and was approved by the local Ethics Committee(Cantonal Ethics Committee Zurich,Nr.2016-00116).All patients signed informed consent for the procedure and the use of clinical data for scientific study.
文摘Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)procedures.We sought to evaluate the safety and efficacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP procedures.Methods and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of Zurich Heart Center between January 2019 and December 2022 was observed and analyzed.During the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound guidance.At the end of the procedure,a single Z-stitch was performed at the puncture site.We eval-uated the incidence of in-hospital complications associated with femoral access puncture in this population.Among 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP procedures.The median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousfistula,venous or arterial thrombosis.Conclusion:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.
基金RN received funding from Swiss Centre for Applied Human ToxicologyHelmut Hortun Stiftung。
文摘Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.
文摘BACKGROUND When patients with a failed hip arthroplasty are unsuitable for reimplantation,Girdlestone resection arthroplasty(GRA)is a viable treatment option.We report on a patient who was treated with a GRA due to a periprosthetic infection.We discovered partial paralysis of the quadriceps muscle in this patient.We investigated the femoral nerve anatomy,particularly the nerve entry points,to better understand this phenomenon.AIM To reveal the femoral nerve anatomy with respect to severe proximal migration after GRA.METHODS Eight cadaveric hemipelves were investigated.The branches of the femoral nerve were dissected and traced distally.The GRA was performed by the direct anterior approach.Axial stress to the lower extremity was applied,and the relative movement of the femur was recorded.The femoral nerve and its entry points were assessed.RESULTS GRA led to a 3.8 cm shift of the femur in vertical direction,a 1.8 cm shift in the dorsal direction,and a 2.3 cm shift in the lateral direction.A 36.5°external shift was observed.This caused stress to the lateral division of the femoral nerve.We observed migration of the femoral nerve entry point at the following locations:(1)Vastus medialis(5.3 mm);(2)The medial part of the vastus intermedius(5.4 mm);(3)The lateral part of the vastus intermedius(16.3 mm);(4)Rectus femoris(23.1 mm);(5)Tensor vastus intermedius(30.8 mm);and(6)Vastus lateralis(28.8 mm).CONCLUSION Migration of the femur after GRA altered the anatomy of the femoral nerve.Stress occurred at the lateral nerve division leading to poor functional results.
基金Supported by Schulz B received funding from Guerbet AG,No.8050.
文摘BACKGROUND The auricle,or auricula,defines the visible boundaries of the external ear and is essential in forensic investigations,including facial reconstruction and human remains identification.Beyond its forensic significance,auricular morphology attracts interest from various fields,such as medicine and industry.The size of the ears is culturally associated with health and longevity,while surgical techniques for ear reconstruction address both congenital and aesthetic concerns.AIM To determine whether known correlations with various measurements and observations regarding sex and age could also be established through computed tomography(CT).METHODS Computed tomography scans of the head from 342 females and 329 males aged 18 to 97 years(mean=60±19 years)were included in this study.Different auricular lengths,widths and perimeters were measured for both sides.Additionally,the preauricular area was assessed using three-dimensional volume rendering tech-nique images.RESULTS The measured auricular dimensions in centimeters are presented as mean values(right/left)for males(length 16.91±0.51/6.93±0.52;length 22.83±0.35/2.84±0.34;width 13.94±0.32/4.01±0.36;width 23.51±0.34/3.46±0.31;perimeter 17.66±1.25/17.71±1.28)and females(length 16.44±0.5/6.48±0.51;length 22.7±0.32/2.71±0.33;width 13.6±0.32/3.68±0.31;width 23.3±0.3/3.26±0.27;perimeter 16.36±1.2/16.46±1.2).A positive correlation with age was shown in all measurements,with the highest value for perimeter in both,males(r-value:right/left:0.49/0.47)and females(r-value:right/left:0.53/0.53).After confounding factors were excluded,the preauricular vertical line was first seen at 45 years.The mean age for males with preauricular vertical lines was 66.65±10.92 years(95%CI:63.99-69.3),while without vertical lines,it was 44.48±16.15 years(95%CI:41.21-47.74);for females,it was 70.18±12.44 years(95%CI:68.9-71.46)with and 47.87±17.09 years(95%CI:45.96-49.78)without vertical lines.CONCLUSION In this study,we pioneered the use of CT volumetric data to examine human auricle morphology and we achieved a precise 3D(pre-)auricular assessment.Sex-specific positive correlations between ear dimensions and age,as well as the mean age for the appearance of preauricular lines,were identified,providing valuable insights into the capabilities of modern CT devices.
文摘Phylogenetic niche conservatism posits that species tend to retain ancestral ecological traits and distributions,which has been broadly tested for lineages originating in tropical climates but has been rarely tested for lineages that originated and diversified in temperate climates.Liverworts are thought to originate in temperate climates.Mean lineage age reflects evolutionary history of biological communities.Here,using regional liverwort floras across a long latitudinal gradient from tropical to arctic climates in North America,we test the age-component of the temperate niche conservatism hypothesis.Mean genus age(MGA)was estimated for each of 76 regional floras of liverworts.We related MGA to climatic variables for North America as a whole and for its eastern and western parts separately,and used variation partitioning analysis to assess the relative importance of temperature-versus precipitationrelated variables and of climate extremes versus seasonality on MGA.We found that older genera of liverworts tend to concentrate in humid regions of intermediate temperatures in the range of 10℃-20℃,from which liverworts have adapted to and diversified into more arid,colder,and hotter regions,supporting the temperate niche conservatism hypothesis.We also found that across North America the MGA of liverwort assemblages is more strongly affected by precipitation-related variables than by temperature-related variables,and is more strongly affected by climate extremes than by climate seasonality.Geographic patterns of the MGA of liverworts are consistent with the temperate niche conservatism hypothesis,rather than the tropical niche conservatism hypothesis,the latter of which is broadly supported by angiosperms.
文摘Here we provide a preliminary assessment of dietary and habitat requirements of two sympatric primate taxa, a "simple-stomached" and "complex-stomached" species (Rhinopithecus bieti Colobinae vs. Macaca mulatta Cercopithecinae), as a basis for illuminating how the two coexist. Of ca. 22 plant food species consumed by the macaques, at least 16 were also eaten by the snub-nosed monkeys. Both species showed a preference for fruits. While the snub-nosed monkeys did not utilize any resources associated with human communities, rhesus macaques did occasionally raid agricultural crops. The mean elevation of the snub-nosed monkey group was 3,218 m, while the mean elevation of the macaque group was 2,995 m. Macaques were also spotted on meadows whereas snub-nosed monkeys evidently avoided these. For both species, mixed deciduous broadleaf/conifer forest was the most frequently used ecotype, but whereas evergreen broadleaf forest (Cyclobalanopsis community) accounted for only 3% of the location records of the snub-nosed monkeys, it accounted for 36% of the location records of the macaques. Groups of the two species usually kept a considerable spatial distance from one another (mean 2.4 km). One close encounter and confrontation between groups of the two species resulted in the macaque group moving away. Our findings suggest that the coexistence of the two taxa is facilitated via differential macrohabitat use and spatial avoidance. Although divergent habitat-use strategies may reflect interspecific competition, they may also merely reflect different physiological or ecological requirements.
基金Supported by Grants from the Gebert Rüf Foundation, the Forschungskredit of the University Zurichthe Swiss National Science Foundation, Grants PP00B-108511/1 and 31-64140.00
文摘AIM: To study the association of three common ABCB11 and ABCC2 polymorphisms (ABCB11: 1331T〉C→V444A; ABCC2: 3563T〉A → V1188E and 4544G 〉A → C1515Y) with intrahepatic cholestasis of pregnancy (ICP) and contraceptive-induced cholestasis (CIC). METHODS: ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS: The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls: C allele 76.2% (CI, 58.0-94.4) vs 51.3% (CI 35.8-66.7), respectively (P = 0.0007); and CC allele 57.1% (CI 36.0-78.3) vs 20% (CI 7.6-32.4), respectively (P = 0.0065). All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION: Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.