The Shenshan Group provides important geological information which is vital in unraveling the amalgamation and subsequent rifting processes of South China.While conventional studies have asserted its formation in a su...The Shenshan Group provides important geological information which is vital in unraveling the amalgamation and subsequent rifting processes of South China.While conventional studies have asserted its formation in a subduction setting,the distinct investigation reveals the necessity for reassessment.To address this,the authors employ integrated methods encompassing petrological,zircon U-Pb geochronological,Lu-Hf isotopic and geochemical methods for sedimentary rocks from the upper Shenshan subgroup and Banxi Group.The geochemical results indicate that they were formed through the recycling deposition of intermediate-acidic igneous source material and experienced moderate chemical weathering.Additionally,both sedimentary sequences exhibit characteristics consistent with those formed in an intracontinental extensional rift setting since ca.810 Ma.The provenance analysis indicates that the upper Shenshan subgroup primarily originates from the Yangtze Domain,while the Banxi Group from both the Yangtze and Cathaysia domains.Synthesizing with previous studies,the Shenshan Group should be subdivided into the lower and upper subgroups which represent distinct tectonic backgrounds.The lower subgroup is inferred to have formed in an Early Neoproterozoic fore-arc setting,akin to the Zhoutan group.The upper subgroup corresponds to the Banxi Group,representing the Middle Neoproterozoic postorogenic rift setting,responding to the breakup of Rodinia.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurologica...The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language defi...For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.展开更多
This study investigates the impacts of mixing time,execution procedure,cement dosage(α),and total water-to-cement ratio(W_(Total)/C)on the mixing energy(E)of deep soil mixing(DSM)columns and how E influences the stre...This study investigates the impacts of mixing time,execution procedure,cement dosage(α),and total water-to-cement ratio(W_(Total)/C)on the mixing energy(E)of deep soil mixing(DSM)columns and how E influences the strength of treated sand.Columns with a diameter of 7.5 cm were constructed using three mixing times(130,190,and 250 s),two execution procedures(normal and zigzag),threeαvalues(300,400,and 500 kg/m^(3)),and three W_(Total)/C ratios(2.5,3.0,and 3.5).For comparison,equivalent laboratory samples were also examined.Results revealed that increasing the mixing time andα,adopting the zigzag execution procedure,and reducing the W_(Total)/C ratio increase E.Outcomes indicated that an increase in E from 0.49-0.70 kJ to 0.70-0.90 kJ,0.90-1.10 kJ,and 1.10-1.40 kJ improves the unconfined compressive strength(UCS)of columns on average by 66%,124%,and 179%,respectively,and the secant modulus by 61%,110%,and 152%.Average strain at maximum stress also rises from 0.68%to 0.75%,0.81%,and 0.84%,respectively.The study identified a threshold in the direct relationship between E and the strength ratio(λ),beyond whichλdid not increase significantly with further increases in E.Additionally,at low and high E levels,DSM samples mainly failed by crushing and cracking modes,respectively.In DSM columns withα=500 kg/m^(3)and W_(Total)/C=2.5,increasing average E from 0.77 kJ to 0.95 kJ,1.08 kJ,and 1.28 kJ resulted in a reduction of coefficients of variation of UCS from 30.4%to 27.8%,24.5%,and 21.1%,respectively.展开更多
Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs sur...Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.展开更多
Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine ...Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine in the 1970s significantly improved patient outcomes,leading to a global increase in transplants,including in India,where the practice has grown despite initial challenges.This review pro-vides an extensive overview of HTx,focusing on current practices,technological advancements,and the ongoing challenges the field faces today.It explores the evolution of surgical techniques,such as minimally invasive and robotic-assisted procedures,and the management of posttransplant rejection through tailored immunosuppressive strategies,including new monoclonal antibodies and perso-nalized therapies.The review also highlights emerging innovations such as mechanical circulatory support devices and xenotransplantation as potential solutions to donor shortages while acknowledging the ethical and logistical challenges these approaches entail.Furthermore,the analysis delves into the implications of using extended-criteria donors and the role of multidisciplinary teams in evaluating absolute and relative contraindications.Despite the progress made,the persistent issues of organ scarcity and ethical concerns underscore the need for ongoing research and innovation to further enhance the efficacy,safety,and accessibility of HTx.展开更多
The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the cent...The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.展开更多
The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have ena...The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.展开更多
The connection between climatic factors and grazing is essential for maintaining ecosystem function and vegetation productivity.This study examined the impact of grazing intensity on vegetation across a broad climatic...The connection between climatic factors and grazing is essential for maintaining ecosystem function and vegetation productivity.This study examined the impact of grazing intensity on vegetation across a broad climatic gradient spanning the Espinal,Argentine Low Monte,and Patagonian Steppe ecoregions of Argentina.The research was carried out at eight sampling sites with radial grazing gradients generated around artificial water sources(piospheres),exhibiting two contrasting response patterns of vegetation to grazing pressure.One of the response patterns shows a typical vegetation response to grazing that the vegetation productivity increases with the distance to the water sources(decreasing grazing intensity).The second pattern is found in drier regions,where vegetation presents an inverse productivity response that vegetation productivity is higher near water sources(high grazing intensity)due to increased shrub cover.Vegetation productivity was measured using the Normalized Difference Vegetation Index(NDVI).Vegetation patch structure and cover were determined for each site with high,medium,and low grazing intensities.Results indicated that shrub cover is the primary driver of vegetation productivity,showing contrasting responses to grazing intensity between the two identified patterns.While NDVI proved to be a reliable proxy for shrub cover and total vegetation cover(R2>0.70),it failed to reflect grass cover dynamics.Furthermore,mean annual temperature was more strongly correlated with vegetation cover changes,while grazing intensity significantly altered vegetation patch structure and soil cover distribution.Specifically,in drier regions,high grazing intensity led to larger patches while,in wetter regions,it led to smaller patches(fragmentation).Shrubs,with their deeper roots and drought tolerance,were less preferred and more resistant to grazing in arid environments and thrived under grazing pressure in these arid conditions.Our results underscored the need for adaptive management strategies in grazing systems.Traditional approaches may require significant adjustments,as the efficacy of management hinges on the interplay of specific climatic conditions and the varied responses of vegetation.Furthermore,effective conservation efforts should prioritize the recognition and protection of shrubs given their critical contribution to ecosystem function and biodiversity.Ultimately,this research provides a valuable framework to understand the complex dynamics between grazing and vegetation in arid and semi-arid environments,highlighting that sustainable grazing practices should be tailored to account for both climatic variables and the unique characteristics of different plant communities.展开更多
BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical perf...BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.展开更多
Considering the finite actions of a field on the matter and the space which used to infiltrate their quantum reality at level particle, methods are developed to serve to base the concept of “intentional action” of a...Considering the finite actions of a field on the matter and the space which used to infiltrate their quantum reality at level particle, methods are developed to serve to base the concept of “intentional action” of a field and their ordered and supported effects (synergy) that must be realized for the “organized transformation” of the space and matter. Using path integrals, these transformations are decoded and their quantum principles are shown.展开更多
Pancreatic cystic lesions(PCLs) are increasingly being identified because of the widespread use of highresolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and there...Pancreatic cystic lesions(PCLs) are increasingly being identified because of the widespread use of highresolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and therefore, accurate diagnosis is crucial to determine the best management strategy, either surgical resection or surveillance. However, the current standard of diagnosis is not accurate enough due to limitations of imaging and tissue sampling techniques, which entail the risk of unnecessary burdensome surgery for benign lesions or missed opportunities of prophylactic surgery for potentially malignant PCLs. In the last decade, endoscopic innovations based on endoscopic ultrasonography(EUS) imaging have emerged, aiming to overcome the present limitations. These new EUS-based technologies are contrast harmonic EUS, needle-based confocal endomicroscopy, through-the-needle cystoscopy and through-the needle intracystic biopsy. Here, we present a comprehensive and critical review of these emerging endoscopic tools for the diagnosis of PCLs, with a special emphasis on feasibility, safety and diagnostic performance.展开更多
BACKGROUND Stable angina pectoris,a clinical manifestation of coronary artery disease(CAD),is commonly evaluated using non-invasive diagnostic tools.Traditionally,stress testing modalities such as exercise electrocard...BACKGROUND Stable angina pectoris,a clinical manifestation of coronary artery disease(CAD),is commonly evaluated using non-invasive diagnostic tools.Traditionally,stress testing modalities such as exercise electrocardiography(ECG),myocardial per-fusion imaging(MPI),and stress echocardiography have been the first-line stra-tegies.However,coronary computed tomography angiography(CCTA),an anatomic imaging modality,is increasingly used for its ability to directly visualize coronary artery stenoses and plaque burden.Despite growing adoption,the comparative effectiveness of CCTA and stress testing in terms of diagnostic accuracy,prognostic value,and clinical outcomes in stable angina remains an area of active debate.AIM To compare the diagnostic and prognostic performance of CCTA with various forms of stress testing in adult patients presenting with suspected or confirmed stable angina.METHODS A comprehensive literature search was performed across PubMed,EMBASE,Scopus,and the Cochrane Central Register of Controlled Trials in accordance with the PRISMA guidelines.Only randomized controlled trials(RCT)published in English within the last 15 years were included.Studies involving adult patients(≥18 years)with stable angina or low-risk chest pain were selected.The intervention was CCTA,and the comparators included ECG,MPI,and stress echocardiography.Data were extracted using a standardized process,and study quality was assessed using the Cochrane Risk of Bias 2.0 tool.Due to heterogeneity in outcome measures and modalities,narrative synthesis was employed.RESULTS Five high-quality RCTs encompassing a total of 5551 patients were included.CCTA demonstrated superior diagnostic accuracy and prognostic capability across multiple studies.It was more effective in predicting major adverse cardiac events,including myocardial infarction and cardiac death,and was associated with fewer un-necessary invasive coronary angiographies and better event-free survival.Studies also reported improved revascu-larization rates in patients evaluated with CCTA,particularly within tiered diagnostic protocols.Stress testing,while useful,showed limitations in sensitivity and downstream clinical decision-making.CONCLUSION CCTA offers a diagnostically superior and clinically impactful strategy for the initial evaluation of patients with stable angina,especially those with intermediate pretest probability of CAD.Compared to conventional stress testing,it enhances risk stratification,reduces unnecessary procedures,and may improve long-term outcomes.These findings support its broader integration into diagnostic pathways for stable angina.展开更多
Many spore-forming Bacillus species can cause serious human diseases,because of accidental Bacillusspore infection.Thus,developing an identification strategy with both high sensitivity and specificity is greatly in de...Many spore-forming Bacillus species can cause serious human diseases,because of accidental Bacillusspore infection.Thus,developing an identification strategy with both high sensitivity and specificity is greatly in demand.In this work,we proposed a novel approach named multi-head self-attention mechanism-guided neural network Raman platform to identify living Bacillus spores within a single-cell resolution.The multi-head self-attention mechanism-guided neural network Raman platform was created by combining single-cell Raman spectroscopy,convolutional neural network(CNN),and multi-head self-attention mechanism.To address the limited size of the original spectra dataset,Gaussian noise-based spectra augmentation was employed to increase the number of single-cell Raman spectra datasets for CNN training.Owing to the assistance of both spectra augmentation and multi-head self-attention mechanism,the obtained prediction accuracy of five Bacillus spore species was further improved from 92.29±0.82%to 99.43±0.15%.To figure out the spectra differences covered by the multi-head self-attention mechanism-guided CNN,the relative classification weight from typical Raman bands was visualized via multi-head self-attention mechanism curve.In the process of spectra augmentation from 0 to 1000,the distribution of relative classification weight varied from a discrete state to a more concentrated phase.More importantly,these highlighted four Raman bands(1017,1449,1576,and 1660 cm^(-1))were assigned large weights,showing that the spectra differences in the Raman bands produced the largest contribution to prediction accuracy.It can be foreseen that,our proposed sorting platform has great potential in accurately identifying Bacillus and its related genera species at a single-cell level.展开更多
The accretion of the Panama-ChocóBlock to the South American Plate partially drove the geological setting of the northern Andes.This event occurred in different collisional stages that are recorded in Oligocene-m...The accretion of the Panama-ChocóBlock to the South American Plate partially drove the geological setting of the northern Andes.This event occurred in different collisional stages that are recorded in Oligocene-middle Miocene deformed rocks of the inter-Andean valley between the Western and Central Cordilleras of Colombia.However,uncertainty remains about the age of the latest accretionary phases of the Panama-ChocóBlock.Poorly studied late Miocene volcanic rocks within the northern inter-Andean valley may provide key information to constrain the temporality of that final collision.Here,we study the deformational features of the~12-6 Ma extrusive rocks of the Combia Volcanic Province located in the northwestern Andes(Colombia).We present anisotropy of magnetic susceptibility(AMS)data for pyroclastic and volcanic rocks within the AmagáBasin,an inter-Andean depression with Oligocene-middle Miocene sedimentary rocks that recorded NW-SE compression and NE-SW simple shear caused by the Panama-ChocóBlock collision.We identified that the magnetic fabrics of the extrusive rocks of the Combia Volcanic Province reveal flow directions that indicate the occurrence of ancient volcanoes in the central axis of the AmagáBasin.Some of these fabrics do not contain any deformational features,whereas others record the same structural regime as the Oligocene-middle Miocene sedimentary rocks.We infer that variations in the intensity of the deformation promoted late Miocene local fault reactivations that,in contrast to the Oligocene-middle Miocene deformational events,did not affect the entire AmagáBasin.Age differences among the studied sections can also explain the different deformational patterns identified in the basin.Both interpretations suggest that the most significant collisional events of the Panama-ChocóBlock occurred in the Oligocene-middle Miocene,whereas the formation of the Combia Volcanic Province may have either followed or coincided with the latest stages of the accretion.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
Natural hybridization is known to play a vital role in speciation;however,the mechanisms underlying the early stages of natural hybridization remain unclear.Where two plant species come into contact,two driving forces...Natural hybridization is known to play a vital role in speciation;however,the mechanisms underlying the early stages of natural hybridization remain unclear.Where two plant species come into contact,two driving forces may balance the dynamic consequences of hybridization:fusion by hybridization-mediated gene flow,and separation by reproductive isolation(RI)(Ma et al.,2010a,b;Chang et al.,2022).展开更多
AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active...AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication. METHODS:100 patients with active duodenal ulcer were included in the open,multicentre,randomized study with comparative groups.Patients were randomly assigned to one of the following one-week triple regimes:A) metronidazole 500 mg bid,amoxicillin I g bid and omeprazole 20 mg bid(OAM,n=50)and B)azithromycin 1 god for the first 3 days(total dose 3 g),amoxicillin 1 g bid and omeprazole 20 mg bid(OAA,n=50).Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks.The control endoscopy was performed 8 weeks after the entry.H.pyloriinfection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test. RESULTS:97 patients completed the study according to the protocol(1 patient of the OAM group did not come to the control endoscopy,2 patients of the OAA group stopped the treatment because of mild allergic urticaria).Duodenal ulcers were healed in 48 patients of the OAM group(96 %, C190.5-100 %)and in 46 patients of the OAA group(92 %, CI 89.5-94.5 %)(p=ns).H.pyloHinfection was eradicated in 15 out of 50 patients with OAM(30 %,CI 17-43 %)and in 36 out of 50 patients treated with OAA(72 %;CI 59-85 %) (P<0.001)-ITT analysis.CONCLUSION: The triple therapy with omeprazole, amoxicillin and metronidazole failed to eradicate H.pylori'vc\ the majority of patients, which is an essential argument to withdraw this regimen out of the national recommendations. Macrolide with amoxicillin are preferable to achieve higher eradication rates. Azithromycin (1 g od for the first 3 days) can be considered as a successful component of the triple PPI-based regimen.展开更多
基金supported by the National Natural Science Foundation of China(42372250,42102262 and 41972235)National Key Research and Development Program Project(2023YFF0803701)+1 种基金Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(SML2023SP206)the program of China Scholarship Council。
文摘The Shenshan Group provides important geological information which is vital in unraveling the amalgamation and subsequent rifting processes of South China.While conventional studies have asserted its formation in a subduction setting,the distinct investigation reveals the necessity for reassessment.To address this,the authors employ integrated methods encompassing petrological,zircon U-Pb geochronological,Lu-Hf isotopic and geochemical methods for sedimentary rocks from the upper Shenshan subgroup and Banxi Group.The geochemical results indicate that they were formed through the recycling deposition of intermediate-acidic igneous source material and experienced moderate chemical weathering.Additionally,both sedimentary sequences exhibit characteristics consistent with those formed in an intracontinental extensional rift setting since ca.810 Ma.The provenance analysis indicates that the upper Shenshan subgroup primarily originates from the Yangtze Domain,while the Banxi Group from both the Yangtze and Cathaysia domains.Synthesizing with previous studies,the Shenshan Group should be subdivided into the lower and upper subgroups which represent distinct tectonic backgrounds.The lower subgroup is inferred to have formed in an Early Neoproterozoic fore-arc setting,akin to the Zhoutan group.The upper subgroup corresponds to the Banxi Group,representing the Middle Neoproterozoic postorogenic rift setting,responding to the breakup of Rodinia.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金funded by the Ministerio de Ciencia e Innovación Spain(PID2020-113388RB-I00,AEI/10.13039/501100011033)Consellería de Innovación,Universidades,Ciencia y Sociedad Digital,Generalitat Valenciana(CIPROM/2021/082)+2 种基金co-funded with European Regional Development Funds(ERDF)(PID2020-113388RB-I00,and CIPROM/2021/082)PID2022-136874OB-C33 from MCIN/AEI/10.13039/501100011033by the European Union NextGenerationEU/PRTR(to VF).
文摘The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
文摘For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.
文摘This study investigates the impacts of mixing time,execution procedure,cement dosage(α),and total water-to-cement ratio(W_(Total)/C)on the mixing energy(E)of deep soil mixing(DSM)columns and how E influences the strength of treated sand.Columns with a diameter of 7.5 cm were constructed using three mixing times(130,190,and 250 s),two execution procedures(normal and zigzag),threeαvalues(300,400,and 500 kg/m^(3)),and three W_(Total)/C ratios(2.5,3.0,and 3.5).For comparison,equivalent laboratory samples were also examined.Results revealed that increasing the mixing time andα,adopting the zigzag execution procedure,and reducing the W_(Total)/C ratio increase E.Outcomes indicated that an increase in E from 0.49-0.70 kJ to 0.70-0.90 kJ,0.90-1.10 kJ,and 1.10-1.40 kJ improves the unconfined compressive strength(UCS)of columns on average by 66%,124%,and 179%,respectively,and the secant modulus by 61%,110%,and 152%.Average strain at maximum stress also rises from 0.68%to 0.75%,0.81%,and 0.84%,respectively.The study identified a threshold in the direct relationship between E and the strength ratio(λ),beyond whichλdid not increase significantly with further increases in E.Additionally,at low and high E levels,DSM samples mainly failed by crushing and cracking modes,respectively.In DSM columns withα=500 kg/m^(3)and W_(Total)/C=2.5,increasing average E from 0.77 kJ to 0.95 kJ,1.08 kJ,and 1.28 kJ resulted in a reduction of coefficients of variation of UCS from 30.4%to 27.8%,24.5%,and 21.1%,respectively.
基金supported by the National Natural Science Foundation of China,Nos.82473334(to LZ),82401629(to XL)the Major Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region,No.2022CJE09013(to LZ)+4 种基金Mianyang Science and Technology Bureau(Mianyang Science and Technology Program),No.2023ZYDF097(to LZ)NHC Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX001(to LZ)Spinal Cord Diseases Clinical Medical Center of Yunnan Province,No.2024JSKFKT-16(to BG)the Natural Science Foundation of Sichuan Province,No.2024NSFSC1646(to XL)the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL),2024T170601(to XL)and 2024M76228(to XL).
文摘Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.
文摘Heart transplantation(HTx)is a life-saving procedure for patients with end-stage heart failure and has undergone remarkable advancements since the first succe-ssful transplant in 1967.The introduction of cyclosporine in the 1970s significantly improved patient outcomes,leading to a global increase in transplants,including in India,where the practice has grown despite initial challenges.This review pro-vides an extensive overview of HTx,focusing on current practices,technological advancements,and the ongoing challenges the field faces today.It explores the evolution of surgical techniques,such as minimally invasive and robotic-assisted procedures,and the management of posttransplant rejection through tailored immunosuppressive strategies,including new monoclonal antibodies and perso-nalized therapies.The review also highlights emerging innovations such as mechanical circulatory support devices and xenotransplantation as potential solutions to donor shortages while acknowledging the ethical and logistical challenges these approaches entail.Furthermore,the analysis delves into the implications of using extended-criteria donors and the role of multidisciplinary teams in evaluating absolute and relative contraindications.Despite the progress made,the persistent issues of organ scarcity and ethical concerns underscore the need for ongoing research and innovation to further enhance the efficacy,safety,and accessibility of HTx.
基金supported by the Wellcome Trust(grant No.103852).
文摘The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.
文摘The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.
基金supported by the Universidad Nacional de Río Negro(PI-UNRN 40C-1088)the Consejo Nacional de Investigaciones Científicas y Técnicas(PIP-CONICET 2023-402).
文摘The connection between climatic factors and grazing is essential for maintaining ecosystem function and vegetation productivity.This study examined the impact of grazing intensity on vegetation across a broad climatic gradient spanning the Espinal,Argentine Low Monte,and Patagonian Steppe ecoregions of Argentina.The research was carried out at eight sampling sites with radial grazing gradients generated around artificial water sources(piospheres),exhibiting two contrasting response patterns of vegetation to grazing pressure.One of the response patterns shows a typical vegetation response to grazing that the vegetation productivity increases with the distance to the water sources(decreasing grazing intensity).The second pattern is found in drier regions,where vegetation presents an inverse productivity response that vegetation productivity is higher near water sources(high grazing intensity)due to increased shrub cover.Vegetation productivity was measured using the Normalized Difference Vegetation Index(NDVI).Vegetation patch structure and cover were determined for each site with high,medium,and low grazing intensities.Results indicated that shrub cover is the primary driver of vegetation productivity,showing contrasting responses to grazing intensity between the two identified patterns.While NDVI proved to be a reliable proxy for shrub cover and total vegetation cover(R2>0.70),it failed to reflect grass cover dynamics.Furthermore,mean annual temperature was more strongly correlated with vegetation cover changes,while grazing intensity significantly altered vegetation patch structure and soil cover distribution.Specifically,in drier regions,high grazing intensity led to larger patches while,in wetter regions,it led to smaller patches(fragmentation).Shrubs,with their deeper roots and drought tolerance,were less preferred and more resistant to grazing in arid environments and thrived under grazing pressure in these arid conditions.Our results underscored the need for adaptive management strategies in grazing systems.Traditional approaches may require significant adjustments,as the efficacy of management hinges on the interplay of specific climatic conditions and the varied responses of vegetation.Furthermore,effective conservation efforts should prioritize the recognition and protection of shrubs given their critical contribution to ecosystem function and biodiversity.Ultimately,this research provides a valuable framework to understand the complex dynamics between grazing and vegetation in arid and semi-arid environments,highlighting that sustainable grazing practices should be tailored to account for both climatic variables and the unique characteristics of different plant communities.
文摘BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.
文摘Considering the finite actions of a field on the matter and the space which used to infiltrate their quantum reality at level particle, methods are developed to serve to base the concept of “intentional action” of a field and their ordered and supported effects (synergy) that must be realized for the “organized transformation” of the space and matter. Using path integrals, these transformations are decoded and their quantum principles are shown.
文摘Pancreatic cystic lesions(PCLs) are increasingly being identified because of the widespread use of highresolution abdominal imaging. These cysts encompass a spectrum from malignant disease to benign lesions, and therefore, accurate diagnosis is crucial to determine the best management strategy, either surgical resection or surveillance. However, the current standard of diagnosis is not accurate enough due to limitations of imaging and tissue sampling techniques, which entail the risk of unnecessary burdensome surgery for benign lesions or missed opportunities of prophylactic surgery for potentially malignant PCLs. In the last decade, endoscopic innovations based on endoscopic ultrasonography(EUS) imaging have emerged, aiming to overcome the present limitations. These new EUS-based technologies are contrast harmonic EUS, needle-based confocal endomicroscopy, through-the-needle cystoscopy and through-the needle intracystic biopsy. Here, we present a comprehensive and critical review of these emerging endoscopic tools for the diagnosis of PCLs, with a special emphasis on feasibility, safety and diagnostic performance.
文摘BACKGROUND Stable angina pectoris,a clinical manifestation of coronary artery disease(CAD),is commonly evaluated using non-invasive diagnostic tools.Traditionally,stress testing modalities such as exercise electrocardiography(ECG),myocardial per-fusion imaging(MPI),and stress echocardiography have been the first-line stra-tegies.However,coronary computed tomography angiography(CCTA),an anatomic imaging modality,is increasingly used for its ability to directly visualize coronary artery stenoses and plaque burden.Despite growing adoption,the comparative effectiveness of CCTA and stress testing in terms of diagnostic accuracy,prognostic value,and clinical outcomes in stable angina remains an area of active debate.AIM To compare the diagnostic and prognostic performance of CCTA with various forms of stress testing in adult patients presenting with suspected or confirmed stable angina.METHODS A comprehensive literature search was performed across PubMed,EMBASE,Scopus,and the Cochrane Central Register of Controlled Trials in accordance with the PRISMA guidelines.Only randomized controlled trials(RCT)published in English within the last 15 years were included.Studies involving adult patients(≥18 years)with stable angina or low-risk chest pain were selected.The intervention was CCTA,and the comparators included ECG,MPI,and stress echocardiography.Data were extracted using a standardized process,and study quality was assessed using the Cochrane Risk of Bias 2.0 tool.Due to heterogeneity in outcome measures and modalities,narrative synthesis was employed.RESULTS Five high-quality RCTs encompassing a total of 5551 patients were included.CCTA demonstrated superior diagnostic accuracy and prognostic capability across multiple studies.It was more effective in predicting major adverse cardiac events,including myocardial infarction and cardiac death,and was associated with fewer un-necessary invasive coronary angiographies and better event-free survival.Studies also reported improved revascu-larization rates in patients evaluated with CCTA,particularly within tiered diagnostic protocols.Stress testing,while useful,showed limitations in sensitivity and downstream clinical decision-making.CONCLUSION CCTA offers a diagnostically superior and clinically impactful strategy for the initial evaluation of patients with stable angina,especially those with intermediate pretest probability of CAD.Compared to conventional stress testing,it enhances risk stratification,reduces unnecessary procedures,and may improve long-term outcomes.These findings support its broader integration into diagnostic pathways for stable angina.
基金partially supported by the National Natural Science Foundation of China(62075137)the Guangdong Basic and Applied Basic Research Foundation(2023A1515140161)+3 种基金the Guangxi Natural Science Foundation of China(2021JJB 110003)the Dongguan Science and Technology of Social Development Program(20231800936312)the high-level talent program of Dongguan University of Technology(No.221110080)the Sanming Project of Medicine in Shenzhen(No.SZSM202103014).
文摘Many spore-forming Bacillus species can cause serious human diseases,because of accidental Bacillusspore infection.Thus,developing an identification strategy with both high sensitivity and specificity is greatly in demand.In this work,we proposed a novel approach named multi-head self-attention mechanism-guided neural network Raman platform to identify living Bacillus spores within a single-cell resolution.The multi-head self-attention mechanism-guided neural network Raman platform was created by combining single-cell Raman spectroscopy,convolutional neural network(CNN),and multi-head self-attention mechanism.To address the limited size of the original spectra dataset,Gaussian noise-based spectra augmentation was employed to increase the number of single-cell Raman spectra datasets for CNN training.Owing to the assistance of both spectra augmentation and multi-head self-attention mechanism,the obtained prediction accuracy of five Bacillus spore species was further improved from 92.29±0.82%to 99.43±0.15%.To figure out the spectra differences covered by the multi-head self-attention mechanism-guided CNN,the relative classification weight from typical Raman bands was visualized via multi-head self-attention mechanism curve.In the process of spectra augmentation from 0 to 1000,the distribution of relative classification weight varied from a discrete state to a more concentrated phase.More importantly,these highlighted four Raman bands(1017,1449,1576,and 1660 cm^(-1))were assigned large weights,showing that the spectra differences in the Raman bands produced the largest contribution to prediction accuracy.It can be foreseen that,our proposed sorting platform has great potential in accurately identifying Bacillus and its related genera species at a single-cell level.
基金supported financially by the National Natural Science Foundation of China (Grants W2433104 to V.A.P. and42225402 to J.L.)the China Postdoctoral Science Foundation(Grant 2024M753205 to V.A.P.)+4 种基金the Institute of Geology and Geophysics of the Chinese Academy of Sciences (International Fellowship for Postdoctoral Researchers, Grant 2025PD02 to V.A.P.)an association between ECOS-NORD (France)Colciencias/Icetex (Colombia)(Grant C12U01 to M.I.M.)a junior fellowship scheme of Colciencias (Colombia)(Grant 706-2015 to V.A.P.)supported the undergraduate final project of A.T
文摘The accretion of the Panama-ChocóBlock to the South American Plate partially drove the geological setting of the northern Andes.This event occurred in different collisional stages that are recorded in Oligocene-middle Miocene deformed rocks of the inter-Andean valley between the Western and Central Cordilleras of Colombia.However,uncertainty remains about the age of the latest accretionary phases of the Panama-ChocóBlock.Poorly studied late Miocene volcanic rocks within the northern inter-Andean valley may provide key information to constrain the temporality of that final collision.Here,we study the deformational features of the~12-6 Ma extrusive rocks of the Combia Volcanic Province located in the northwestern Andes(Colombia).We present anisotropy of magnetic susceptibility(AMS)data for pyroclastic and volcanic rocks within the AmagáBasin,an inter-Andean depression with Oligocene-middle Miocene sedimentary rocks that recorded NW-SE compression and NE-SW simple shear caused by the Panama-ChocóBlock collision.We identified that the magnetic fabrics of the extrusive rocks of the Combia Volcanic Province reveal flow directions that indicate the occurrence of ancient volcanoes in the central axis of the AmagáBasin.Some of these fabrics do not contain any deformational features,whereas others record the same structural regime as the Oligocene-middle Miocene sedimentary rocks.We infer that variations in the intensity of the deformation promoted late Miocene local fault reactivations that,in contrast to the Oligocene-middle Miocene deformational events,did not affect the entire AmagáBasin.Age differences among the studied sections can also explain the different deformational patterns identified in the basin.Both interpretations suggest that the most significant collisional events of the Panama-ChocóBlock occurred in the Oligocene-middle Miocene,whereas the formation of the Combia Volcanic Province may have either followed or coincided with the latest stages of the accretion.
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.
基金supported by the National Natural Science Foundation of China(U23A20160,32360336)Guizhou Provincial Key Technology R&D Program(Qian KeHe ZhiCheng[2023]YiBan035).
文摘Natural hybridization is known to play a vital role in speciation;however,the mechanisms underlying the early stages of natural hybridization remain unclear.Where two plant species come into contact,two driving forces may balance the dynamic consequences of hybridization:fusion by hybridization-mediated gene flow,and separation by reproductive isolation(RI)(Ma et al.,2010a,b;Chang et al.,2022).
文摘AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication. METHODS:100 patients with active duodenal ulcer were included in the open,multicentre,randomized study with comparative groups.Patients were randomly assigned to one of the following one-week triple regimes:A) metronidazole 500 mg bid,amoxicillin I g bid and omeprazole 20 mg bid(OAM,n=50)and B)azithromycin 1 god for the first 3 days(total dose 3 g),amoxicillin 1 g bid and omeprazole 20 mg bid(OAA,n=50).Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks.The control endoscopy was performed 8 weeks after the entry.H.pyloriinfection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test. RESULTS:97 patients completed the study according to the protocol(1 patient of the OAM group did not come to the control endoscopy,2 patients of the OAA group stopped the treatment because of mild allergic urticaria).Duodenal ulcers were healed in 48 patients of the OAM group(96 %, C190.5-100 %)and in 46 patients of the OAA group(92 %, CI 89.5-94.5 %)(p=ns).H.pyloHinfection was eradicated in 15 out of 50 patients with OAM(30 %,CI 17-43 %)and in 36 out of 50 patients treated with OAA(72 %;CI 59-85 %) (P<0.001)-ITT analysis.CONCLUSION: The triple therapy with omeprazole, amoxicillin and metronidazole failed to eradicate H.pylori'vc\ the majority of patients, which is an essential argument to withdraw this regimen out of the national recommendations. Macrolide with amoxicillin are preferable to achieve higher eradication rates. Azithromycin (1 g od for the first 3 days) can be considered as a successful component of the triple PPI-based regimen.
