Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.展开更多
Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomatern...Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomaternal communication,supporting early embryonic development.This study aimed to:(i)compare the protein cargo of uterine fluid EVs(UF-EVs)from CYCLIC and PREGNANT heifers;(ii)characterize the protein profile of conditioned medium(CM)-EVs from endometrial explants cultured alone(EXPL)or co-cultured with five d 7 blastocysts(EXPL+EMB)in vitro;and(iii)compare the EV protein cargo between the in vivo and in vitro models(i.e.,EXPL vs.CYCLIC and EXPL+EMB vs.PREGNANT).Results We identified 1,459 and 1,752 proteins in the UF-EVs of CYCLIC and PREGNANT heifers,respectively.Among these,12 were exclusive to CYCLIC,and 18 were exclusive to PREGNANT.Among the 1,329 proteins identified in both groups,16 were differently abundant;ten were more abundant,and six were less abundant in UF-EVs from PREGNANT heifers.In vivo,the changes in UF-EV protein cargo induced by the presence of a blastocyst were related to inflammatory and immune responses,endometrial receptivity,and support of early embryonic development by promoting cell polarity,cell–cell adhesion,and stem cell differentiation.In vitro,we identified 1,501 proteins in the CM-EVs from EXPL,1,975 in the CM-EVs from EXPL+EMB,and 82 in the CM-EVs from EMB.Additionally,50 proteins were unique to EXPL+EMB,and another 33 were differentially abundant due to the synergistic interaction between the embryo and the endometrium.These proteins are involved in embryonic development,regulation of stem cell differentiation,establishment and maintenance of cell polarity,interferon tau(IFNT)-mediated cell signaling,endometrial receptivity,and immune modulation.Although there are qualitative and quantitative differences between in vivo and in vitro-derived EVs,UF-EVs from CYCLIC heifers compared to CM-EVs from EXPL,as well as UFEVs from PREGNANT heifers compared to CM-EVs from EXPL+EMB shared common proteins.Conclusions These findings highlight the pivotal role of EVs in embryo-maternal communication,suggesting that their protein cargo may actively contribute to the modulation of the uterine environment to support early embryonic development.Understanding these molecular interactions could provide valuable insights into the mechanisms of implantation and pregnancy establishment.展开更多
The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifact...The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse event...Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse events,and earlier revision.Therefore,it is essential to try to avoid LLD when implanting a THA.Several studies focus on this issue,including the following:Accelerometer-based portable navigation system,preoperative digital templating,robot-assisted surgery,the anatomical marker positioning method(shoulder-to-shoulder)and the artificial intelligence-based three-dimensional planning software system.The aforementioned methods should be familiar to surgeons who perform THA procedures,as a fundamental objective of this surgical intervention is to avoid LLD.展开更多
Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are...Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are increasingly ineffective due to resistance and pose environmental risks.In this study,we identified two immunogenic epitopes derived from the B.cinerea cell death-inducing protein BcCrh1 and used them to engineer disease-resistant plants through a novel,spatially compartmentalized dual-epitope immune activation strategy.The first epitope is derived from a 35-amino acid intracellular peptide that exhibits both immunogenicity and cell death-inducing activity,which was mutated to separate these two properties.The second peptide represents an immunogenic portion of the protein that activates extracellular plant immunity.Transcriptomic and metabolomic analyses revealed that these epitopes trigger complementary defense pathways,and their co-expression integrates these responses into a robust,multilayered immunity,providing significantly enhanced protection compared with individual expression.Although constitutive expression of two epitopes conferred resistance,it also led to growth penalties.In contrast,pathogen-inducible expression of two epitopes preserved normal plant development while maintaining strong resistance to both B.cinerea and Pseudomonas syringae in Arabidopsis and tomato.This inducible strategy offers a major advantage by minimizing fitness costs while maximizing protection,highlighting the potential of spatially and temporally targeted epitope-based immune activation for durable and sustainable crop protection.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accoun...Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accounting for 80%of the overall noncutaneous melanomas.Clinically,it remains silent in about 30%of the cases;when symptomatic,it generally causes metamorphopsia(painless loss or distortion of vision)and/or photopsia(flashing or flickering of light in the visual field).Discoloration of the iris,astigmatism,glaucoma,and even blindness are other,less common clinical manifestations.Several pathophysiological mechanisms underlie the development of UM.Genetic mutations,involving especially the G protein subunit alpha q(GNAQ),guanine nucleotide-binding protein subunit alpha-11(GNA11),BRCA1 associated deubiquitinase 1(BAP1),splicing factor 3b subunit 1(SF3B1),and eukaryotic translation initiation factor 1A,X-linked(EIF1AX)genes as well as the MAPK/ERK signaling pathway genes,have been largely associated with the development of UM.Chromosomal aberrations,inflammatory and immunological alterations are often concurrent factors for the development and progression of UM.Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs.This review aims to present the latest advances in the clinical molecular pathology of UM,along with the resulting targeted,immunological,and other therapies that have been introduced or are currently under investigation.展开更多
Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This st...Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This study proposes a novel end-to-end disparity estimation model to address these challenges.Our approach combines a Pseudo-Siamese neural network architecture with pyramid dilated convolutions,integrating multi-scale image information to enhance robustness against lighting interferences.This study introduces a Pseudo-Siamese structure-based disparity regression model that simplifies left-right image comparison,improving accuracy and efficiency.The model was evaluated using a dataset of stereo endoscopic videos captured by the Da Vinci surgical robot,comprising simulated silicone heart sequences and real heart video data.Experimental results demonstrate significant improvement in the network’s resistance to lighting interference without substantially increasing parameters.Moreover,the model exhibited faster convergence during training,contributing to overall performance enhancement.This study advances endoscopic image processing accuracy and has potential implications for surgical robot applications in complex environments.展开更多
Mobile communications are reaching out to every aspect of our daily life,necessitating highefficiency data transmission and support for diverse data types and communication scenarios.Polar codes have emerged as a prom...Mobile communications are reaching out to every aspect of our daily life,necessitating highefficiency data transmission and support for diverse data types and communication scenarios.Polar codes have emerged as a promising solution due to their outstanding error-correction performance and low complexity.Unequal error protection(UEP)involves nonuniform error safeguarding for distinct data segments,achieving a fine balance between error resilience and resource allocation,which ultimately enhancing system performance and efficiency.In this paper,we propose a novel class of UEP rateless polar codes.The codes are designed based on matrix extension of polar codes,and elegant mapping and duplication operations are designed to achieve UEP property while preserving the overall performance of conventional polar codes.Superior UEP performance is attained without significant modifications to conventional polar codes,making it straightforward for compatibility with existing polar codes.A theoretical analysis is conducted on the block error rate and throughput efficiency performance.To the best of our knowledge,this work provides the first theoretical performance analysis of UEP rateless polar codes.Simulation results show that the proposed codes significantly outperform existing polar coding schemes in both block error rate and throughput efficiency.展开更多
In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a to...In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.展开更多
This study presents the design,construction,and thermal evaluation of a solar-powered cocoa roaster based on a Parabolic Cylinder Collector(PCC)with dual-axis solar tracking.The system integrates three functional subs...This study presents the design,construction,and thermal evaluation of a solar-powered cocoa roaster based on a Parabolic Cylinder Collector(PCC)with dual-axis solar tracking.The system integrates three functional subsystems:the cylindrical-parabolic reflecting surface,the stainless-steel absorber tube,and a microcontrollerbased tracking mechanism.The prototype enables continuous acquisition of key thermal variables(solar irradiance,ambient temperature,absorber surface temperature,and bean temperature),allowing a detailed characterization of heat transfer processes during roasting.Roasting experiments were conducted at controlled durations of 40,55,and 70 min between 10:00 and 14:00 h.Maximum roasting temperatures of 125℃–137℃ were reached under average irradiance levels of 685.7–930.5 W m−2.The lowest final moisture content was 2.19%,within the recommended range for high-quality cocoa.Longer roasting durations promoted thermal energy accumulation within the absorber tube,enhancing convective and radiative heat transfer to the bean mass even under fluctuating irradiance.The experimental trends reveal a strong coupling between irradiance variability,absorber temperature,and internal air-beam heat transfer.Comparison with reference parabolic trough collector studies indicate that,although the process-level roasting efficiency(3.83%–7.45%)is lower than conventional collector-level thermal efficiencies,the operating temperatures and moisture-reduction rates align with the thermal requirements of food-processing systems rather than high-enthalpy solar applications.These results also demonstrate the potential of coupling PCC-based solar concentration with lowtemperature convective–radiative roasting processes.Overall,the findings confirm the feasibility of implementing PCC-based roasting technologies in rural or off-grid regions,where solar-driven heat transfer offers a sustainable,low-cost alternative to fossil-fuel-based roasting systems,enabling a controlled thermophysical environment for cocoa transformation.展开更多
Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-in...Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.展开更多
Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excess...Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excessive optical surfaces,reduced light throughput,and instrumental polarization.To address these limitations,we propose an embedded solar adaptive optics telescope(ESAOT)that intrinsically incorporates the solar AO(SAO)subsystem within the telescope's optical train,featuring a co-designed correction chain with a single Hartmann-Shack full-wavefront sensor(HS f-WFS)and a deformable secondary mirror(DSM).The HS f-WFS uses temporal-spatial hybrid sampling technique to simultane-ously resolve tip-tilt and high-order aberrations,while the DSM performs real-time compensation through adaptive modal optimization.This unified architecture achieves symmetrical polarization suppression and high system throughput by min-imizing optical surfaces.A 600 mm ESAOT prototype incorporating a 12×12 micro-lens array HS f-WFS and 61-actuator piezoelectric DSM has been developed and successfully conducted on-sky photospheric observations.Validations in-cluding turbulence simulations,optical bench testing,and practical observations at the Lijiang observatory collectively confirm the system's capability to maintain aboutλ/10 wavefront error during active region tracking.This architectural breakthrough of the ESAOT addresses long-standing SAO integration challenges in solar astronomy and provides scala-bility analyses confirming direct applicability to the existing and future large solar observation facilities.展开更多
This paper presents a nonlinear micropolar nonclassical continuum theory (MPNCCT) for finite deformation, finite strain deformation physics of thermosviscoelastic solid medium with memory (polymeric micropolar solids)...This paper presents a nonlinear micropolar nonclassical continuum theory (MPNCCT) for finite deformation, finite strain deformation physics of thermosviscoelastic solid medium with memory (polymeric micropolar solids) based on classical rotations cΘand their rates. Contravariant second Piola-Kirchhoff stress and moment tensors, in conjunction with finite deformation measures derived by the authors in recent paper, are utilized in deriving the conservation and balance laws and the constitutive theories based on conjugate pairs in entropy inequality and the representation theorem. This nonlinear MPNCCT for TVES with rheology: 1) incorporates nonlinear ordered rate dissipation mechanism based on Green’s strain rates up to order n;2) also incorporates an additional ordered rate dissipation mechanism due to microconstituents, the viscosity of the medium and the rates of the symmetric part of the rotation gradient (of cΘ) tensor up to order n, referred to as micropolar dissipation or micropolar viscous dissipation mechanism;3) incorporates the primary mechanism of memory or rheology due to long chain molecules of the polymer and the viscosity of the medium by using the contravaraint second Piola-Kirchhoff stress tensor and its rates up to order m, resulting in a relaxation spectrum;4) incorporates second mechanism of memory or rheology due to nonclassical physics, interaction of microconstituents with the viscous medium and long chain molecules by considering rates of the contravariant second Piola-Kirchhoff moment tensor up to order m, resulting in relaxation of second Piola-Kirchhoff moment tensor. This results in another relaxation spectrum for the second Piola-Kirchhoff moment tensor due to microconstituents, referred to as micropolar relaxation spectrum consisting of micropolar relaxation time constants of the material. This nonlinear MPNCCT for TVES with memory is thermodynamically and mathematically consistent, and the mathematical model consisting of conservation and balance laws and the constitutive theories has closure and naturally reduces to linear MPNCCT based on infinitesimal deformation assumption. BMM is the essential balance law for all MPNCCT and is used in the present work as well. In the absence of this balance law, a valid thermodynamically and mathematically consistent nonlinear MPNCCT is not possible. The nonlinear MPNCCT based on rotations (cΘ+αΘ) and αΘ(ignoring cΘ) is not considered due to the fact that even the linear MPNCCT based on these rotations is invalid and is thermodynamically and mathematically inconsistent MPNCCT.展开更多
BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We ...BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.展开更多
As artificial Intelligence(AI)continues to expand exponentially,particularly with the emergence of generative pre-trained transformers(GPT)based on a transformer’s architecture,which has revolutionized data processin...As artificial Intelligence(AI)continues to expand exponentially,particularly with the emergence of generative pre-trained transformers(GPT)based on a transformer’s architecture,which has revolutionized data processing and enabled significant improvements in various applications.This document seeks to investigate the security vulnerabilities detection in the source code using a range of large language models(LLM).Our primary objective is to evaluate the effectiveness of Static Application Security Testing(SAST)by applying various techniques such as prompt persona,structure outputs and zero-shot.To the selection of the LLMs(CodeLlama 7B,DeepSeek coder 7B,Gemini 1.5 Flash,Gemini 2.0 Flash,Mistral 7b Instruct,Phi 38b Mini 128K instruct,Qwen 2.5 coder,StartCoder 27B)with comparison and combination with Find Security Bugs.The evaluation method will involve using a selected dataset containing vulnerabilities,and the results to provide insights for different scenarios according to the software criticality(Business critical,non-critical,minimum effort,best effort)In detail,the main objectives of this study are to investigate if large language models outperform or exceed the capabilities of traditional static analysis tools,if the combining LLMs with Static Application Security Testing(SAST)tools lead to an improvement and the possibility that local machine learning models on a normal computer produce reliable results.Summarizing the most important conclusions of the research,it can be said that while it is true that the results have improved depending on the size of the LLM for business-critical software,the best results have been obtained by SAST analysis.This differs in“NonCritical,”“Best Effort,”and“Minimum Effort”scenarios,where the combination of LLM(Gemini)+SAST has obtained better results.展开更多
Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks...Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.展开更多
Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treat...Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treatment and nursing care have greatly improved the life expectancy of individuals with DS.However,as they age,their risk of developing Alzheimer’s disease(AD)increases considerably(Antonarakis et al.,2020).展开更多
Background:We present a case of two major complications following insertion of a nephrostomy managed in a minimally invasive way.Our case is the first in the literature to describe this minimally invasive treatment te...Background:We present a case of two major complications following insertion of a nephrostomy managed in a minimally invasive way.Our case is the first in the literature to describe this minimally invasive treatment technique for colon perforation in a completely asymptomatic patient.Case Description:A 75-year-old female patient with a history of bilateral obstructive uropathy secondary to bilateral radiation-induced ureteric strictures attended for bilateral nephrostomy placement.The patient had a history of endometrial cancer,treated previously by total hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemo-radiotherapy and brachytherapy.Her recovery had been further complicated by the development of radiation cystitis,small bowel resection,and short gut syndrome.The strictures had previously been managed with bilateral double J stents,which have now failed.A left-sided nephrostomy insertion was performed.ACT-scan prompted by a repeat deterioration in renal function revealed a right-sided hydronephrosis and suggested transcolic passage of the previously placed leftsided nephrostomy.She had remained clinically well and apyretic.A right-sided nephrostomy was inserted,and the left re-sited following a colonoscopy-guided nephrostomy removal and clip occlusion of the nephrostomy tract.The patient then developed a pseudoaneurysm,which was managed with embolization.The patient was able to return home with corrected kidney function.The three-monthly checks for changes in nephrostomy catheters did not reveal any complications.Conclusions:The patient therefore presented with two major complications of nephrostomy placement:colonic perforation and pseudoaneurysm,classified as Clavien IIIb and IIIa,respectively.Multidisciplinary management,including urologists,gastroenterologists,general surgeons,and radiologists,enabled a minimally invasive management.Minimally invasive management with endoscopic clip placement appears to be a safe alternative to directed fistula of colonic perforation.展开更多
基金supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
基金supported by research projects:PID2019-111641RB-I00 and PID2023-149027OB-I00 funded by MCIN/AEI/10.13039/501100011033/to DR and PRE2020-094452 to RM。
文摘Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomaternal communication,supporting early embryonic development.This study aimed to:(i)compare the protein cargo of uterine fluid EVs(UF-EVs)from CYCLIC and PREGNANT heifers;(ii)characterize the protein profile of conditioned medium(CM)-EVs from endometrial explants cultured alone(EXPL)or co-cultured with five d 7 blastocysts(EXPL+EMB)in vitro;and(iii)compare the EV protein cargo between the in vivo and in vitro models(i.e.,EXPL vs.CYCLIC and EXPL+EMB vs.PREGNANT).Results We identified 1,459 and 1,752 proteins in the UF-EVs of CYCLIC and PREGNANT heifers,respectively.Among these,12 were exclusive to CYCLIC,and 18 were exclusive to PREGNANT.Among the 1,329 proteins identified in both groups,16 were differently abundant;ten were more abundant,and six were less abundant in UF-EVs from PREGNANT heifers.In vivo,the changes in UF-EV protein cargo induced by the presence of a blastocyst were related to inflammatory and immune responses,endometrial receptivity,and support of early embryonic development by promoting cell polarity,cell–cell adhesion,and stem cell differentiation.In vitro,we identified 1,501 proteins in the CM-EVs from EXPL,1,975 in the CM-EVs from EXPL+EMB,and 82 in the CM-EVs from EMB.Additionally,50 proteins were unique to EXPL+EMB,and another 33 were differentially abundant due to the synergistic interaction between the embryo and the endometrium.These proteins are involved in embryonic development,regulation of stem cell differentiation,establishment and maintenance of cell polarity,interferon tau(IFNT)-mediated cell signaling,endometrial receptivity,and immune modulation.Although there are qualitative and quantitative differences between in vivo and in vitro-derived EVs,UF-EVs from CYCLIC heifers compared to CM-EVs from EXPL,as well as UFEVs from PREGNANT heifers compared to CM-EVs from EXPL+EMB shared common proteins.Conclusions These findings highlight the pivotal role of EVs in embryo-maternal communication,suggesting that their protein cargo may actively contribute to the modulation of the uterine environment to support early embryonic development.Understanding these molecular interactions could provide valuable insights into the mechanisms of implantation and pregnancy establishment.
文摘The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
文摘Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse events,and earlier revision.Therefore,it is essential to try to avoid LLD when implanting a THA.Several studies focus on this issue,including the following:Accelerometer-based portable navigation system,preoperative digital templating,robot-assisted surgery,the anatomical marker positioning method(shoulder-to-shoulder)and the artificial intelligence-based three-dimensional planning software system.The aforementioned methods should be familiar to surgeons who perform THA procedures,as a fundamental objective of this surgical intervention is to avoid LLD.
基金supported by the National Natural Science Foundation of China(grant no.32372514)the Research and Innovation Initiatives of WHPU(grant no.2024J02)+1 种基金Y.L.(202108280009)was funded by the China Scholarship Councilsupported by BARD(grant no.5261-20C)to A.S and T.M.
文摘Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are increasingly ineffective due to resistance and pose environmental risks.In this study,we identified two immunogenic epitopes derived from the B.cinerea cell death-inducing protein BcCrh1 and used them to engineer disease-resistant plants through a novel,spatially compartmentalized dual-epitope immune activation strategy.The first epitope is derived from a 35-amino acid intracellular peptide that exhibits both immunogenicity and cell death-inducing activity,which was mutated to separate these two properties.The second peptide represents an immunogenic portion of the protein that activates extracellular plant immunity.Transcriptomic and metabolomic analyses revealed that these epitopes trigger complementary defense pathways,and their co-expression integrates these responses into a robust,multilayered immunity,providing significantly enhanced protection compared with individual expression.Although constitutive expression of two epitopes conferred resistance,it also led to growth penalties.In contrast,pathogen-inducible expression of two epitopes preserved normal plant development while maintaining strong resistance to both B.cinerea and Pseudomonas syringae in Arabidopsis and tomato.This inducible strategy offers a major advantage by minimizing fitness costs while maximizing protection,highlighting the potential of spatially and temporally targeted epitope-based immune activation for durable and sustainable crop protection.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
文摘Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accounting for 80%of the overall noncutaneous melanomas.Clinically,it remains silent in about 30%of the cases;when symptomatic,it generally causes metamorphopsia(painless loss or distortion of vision)and/or photopsia(flashing or flickering of light in the visual field).Discoloration of the iris,astigmatism,glaucoma,and even blindness are other,less common clinical manifestations.Several pathophysiological mechanisms underlie the development of UM.Genetic mutations,involving especially the G protein subunit alpha q(GNAQ),guanine nucleotide-binding protein subunit alpha-11(GNA11),BRCA1 associated deubiquitinase 1(BAP1),splicing factor 3b subunit 1(SF3B1),and eukaryotic translation initiation factor 1A,X-linked(EIF1AX)genes as well as the MAPK/ERK signaling pathway genes,have been largely associated with the development of UM.Chromosomal aberrations,inflammatory and immunological alterations are often concurrent factors for the development and progression of UM.Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs.This review aims to present the latest advances in the clinical molecular pathology of UM,along with the resulting targeted,immunological,and other therapies that have been introduced or are currently under investigation.
基金Supported by Sichuan Science and Technology Program(2023YFSY0026,2023YFH0004)Supported by the Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korean government(MSIT)(No.RS-2022-00155885,Artificial Intelligence Convergence Innovation Human Resources Development(Hanyang University ERICA)).
文摘Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This study proposes a novel end-to-end disparity estimation model to address these challenges.Our approach combines a Pseudo-Siamese neural network architecture with pyramid dilated convolutions,integrating multi-scale image information to enhance robustness against lighting interferences.This study introduces a Pseudo-Siamese structure-based disparity regression model that simplifies left-right image comparison,improving accuracy and efficiency.The model was evaluated using a dataset of stereo endoscopic videos captured by the Da Vinci surgical robot,comprising simulated silicone heart sequences and real heart video data.Experimental results demonstrate significant improvement in the network’s resistance to lighting interference without substantially increasing parameters.Moreover,the model exhibited faster convergence during training,contributing to overall performance enhancement.This study advances endoscopic image processing accuracy and has potential implications for surgical robot applications in complex environments.
基金supported by National Natural Science Foundation of China(No.62301008)China Postdoctoral Science Foundation(No.2022M720272)New Cornerstone Science Foundation through the XPLORER PRIZE。
文摘Mobile communications are reaching out to every aspect of our daily life,necessitating highefficiency data transmission and support for diverse data types and communication scenarios.Polar codes have emerged as a promising solution due to their outstanding error-correction performance and low complexity.Unequal error protection(UEP)involves nonuniform error safeguarding for distinct data segments,achieving a fine balance between error resilience and resource allocation,which ultimately enhancing system performance and efficiency.In this paper,we propose a novel class of UEP rateless polar codes.The codes are designed based on matrix extension of polar codes,and elegant mapping and duplication operations are designed to achieve UEP property while preserving the overall performance of conventional polar codes.Superior UEP performance is attained without significant modifications to conventional polar codes,making it straightforward for compatibility with existing polar codes.A theoretical analysis is conducted on the block error rate and throughput efficiency performance.To the best of our knowledge,this work provides the first theoretical performance analysis of UEP rateless polar codes.Simulation results show that the proposed codes significantly outperform existing polar coding schemes in both block error rate and throughput efficiency.
文摘In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.
基金the Program for Teaching Development(PRODEP)for funding the project UJAT-PTC-251(Development and Evaluation of a Cocoa Roaster in the Tabasco Region).
文摘This study presents the design,construction,and thermal evaluation of a solar-powered cocoa roaster based on a Parabolic Cylinder Collector(PCC)with dual-axis solar tracking.The system integrates three functional subsystems:the cylindrical-parabolic reflecting surface,the stainless-steel absorber tube,and a microcontrollerbased tracking mechanism.The prototype enables continuous acquisition of key thermal variables(solar irradiance,ambient temperature,absorber surface temperature,and bean temperature),allowing a detailed characterization of heat transfer processes during roasting.Roasting experiments were conducted at controlled durations of 40,55,and 70 min between 10:00 and 14:00 h.Maximum roasting temperatures of 125℃–137℃ were reached under average irradiance levels of 685.7–930.5 W m−2.The lowest final moisture content was 2.19%,within the recommended range for high-quality cocoa.Longer roasting durations promoted thermal energy accumulation within the absorber tube,enhancing convective and radiative heat transfer to the bean mass even under fluctuating irradiance.The experimental trends reveal a strong coupling between irradiance variability,absorber temperature,and internal air-beam heat transfer.Comparison with reference parabolic trough collector studies indicate that,although the process-level roasting efficiency(3.83%–7.45%)is lower than conventional collector-level thermal efficiencies,the operating temperatures and moisture-reduction rates align with the thermal requirements of food-processing systems rather than high-enthalpy solar applications.These results also demonstrate the potential of coupling PCC-based solar concentration with lowtemperature convective–radiative roasting processes.Overall,the findings confirm the feasibility of implementing PCC-based roasting technologies in rural or off-grid regions,where solar-driven heat transfer offers a sustainable,low-cost alternative to fossil-fuel-based roasting systems,enabling a controlled thermophysical environment for cocoa transformation.
基金supported by grants from the Knut and Alice Wallenberg foundation(P-OB,JRZ,and AK)the Swedish Research Council(JRZ and AK),Centrum för idrottsforskning(AK and JRZ)+7 种基金the NovoNordisk Foundation Metabolic Stress Associated Molecules(MSAM)consortium NNF15SA0018346 and Metabolite-related Inflammation and Disease(MeRIAD)consortium Grant number 0064142(AK)the Swedish Diabetes Foundation(AK and JRZ)the European Foundation for the Study of Diabetes(JRZ and AK)the Region Stockholm(ALF project)(JRZ and KC)the Strategic Research Program in Diabetes at Karolinska Institutet(JRZ and AK)supported by the Strategic Research Programme in Diabetes(SRP Diabetes)for use of the Seahorse flux analyzer.Human islets were made possible through the Juvenile Diabetes Research Foundation(JDRF)award 31-2008-416(European Coordinating Infrastructure for Islet Transplantation(ECIT),Islet for Basic Research program)AK holds a Distinguished Investigator Grant within Endocrinology and Metabolism from the Novo Nordisk Foundation(NNF24OC0088739)JRZ received the 2024 European Association for the Study of Diabetes(ESAD)-Novo Nordisk Foundation Diabetes Prize for Excellence(NNF24SA0092609).
文摘Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.
基金support from the National Science Foundation of China(NSFC)(Grants No.12293031 and No.61905252)the National Science Foundation for Distinguished Young Scholars(Grant No.12022308)the National Key R&D Program of China(Grants No.2021YFC2202200 and No.2021YFC2202204).
文摘Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excessive optical surfaces,reduced light throughput,and instrumental polarization.To address these limitations,we propose an embedded solar adaptive optics telescope(ESAOT)that intrinsically incorporates the solar AO(SAO)subsystem within the telescope's optical train,featuring a co-designed correction chain with a single Hartmann-Shack full-wavefront sensor(HS f-WFS)and a deformable secondary mirror(DSM).The HS f-WFS uses temporal-spatial hybrid sampling technique to simultane-ously resolve tip-tilt and high-order aberrations,while the DSM performs real-time compensation through adaptive modal optimization.This unified architecture achieves symmetrical polarization suppression and high system throughput by min-imizing optical surfaces.A 600 mm ESAOT prototype incorporating a 12×12 micro-lens array HS f-WFS and 61-actuator piezoelectric DSM has been developed and successfully conducted on-sky photospheric observations.Validations in-cluding turbulence simulations,optical bench testing,and practical observations at the Lijiang observatory collectively confirm the system's capability to maintain aboutλ/10 wavefront error during active region tracking.This architectural breakthrough of the ESAOT addresses long-standing SAO integration challenges in solar astronomy and provides scala-bility analyses confirming direct applicability to the existing and future large solar observation facilities.
文摘This paper presents a nonlinear micropolar nonclassical continuum theory (MPNCCT) for finite deformation, finite strain deformation physics of thermosviscoelastic solid medium with memory (polymeric micropolar solids) based on classical rotations cΘand their rates. Contravariant second Piola-Kirchhoff stress and moment tensors, in conjunction with finite deformation measures derived by the authors in recent paper, are utilized in deriving the conservation and balance laws and the constitutive theories based on conjugate pairs in entropy inequality and the representation theorem. This nonlinear MPNCCT for TVES with rheology: 1) incorporates nonlinear ordered rate dissipation mechanism based on Green’s strain rates up to order n;2) also incorporates an additional ordered rate dissipation mechanism due to microconstituents, the viscosity of the medium and the rates of the symmetric part of the rotation gradient (of cΘ) tensor up to order n, referred to as micropolar dissipation or micropolar viscous dissipation mechanism;3) incorporates the primary mechanism of memory or rheology due to long chain molecules of the polymer and the viscosity of the medium by using the contravaraint second Piola-Kirchhoff stress tensor and its rates up to order m, resulting in a relaxation spectrum;4) incorporates second mechanism of memory or rheology due to nonclassical physics, interaction of microconstituents with the viscous medium and long chain molecules by considering rates of the contravariant second Piola-Kirchhoff moment tensor up to order m, resulting in relaxation of second Piola-Kirchhoff moment tensor. This results in another relaxation spectrum for the second Piola-Kirchhoff moment tensor due to microconstituents, referred to as micropolar relaxation spectrum consisting of micropolar relaxation time constants of the material. This nonlinear MPNCCT for TVES with memory is thermodynamically and mathematically consistent, and the mathematical model consisting of conservation and balance laws and the constitutive theories has closure and naturally reduces to linear MPNCCT based on infinitesimal deformation assumption. BMM is the essential balance law for all MPNCCT and is used in the present work as well. In the absence of this balance law, a valid thermodynamically and mathematically consistent nonlinear MPNCCT is not possible. The nonlinear MPNCCT based on rotations (cΘ+αΘ) and αΘ(ignoring cΘ) is not considered due to the fact that even the linear MPNCCT based on these rotations is invalid and is thermodynamically and mathematically inconsistent MPNCCT.
文摘BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.
文摘As artificial Intelligence(AI)continues to expand exponentially,particularly with the emergence of generative pre-trained transformers(GPT)based on a transformer’s architecture,which has revolutionized data processing and enabled significant improvements in various applications.This document seeks to investigate the security vulnerabilities detection in the source code using a range of large language models(LLM).Our primary objective is to evaluate the effectiveness of Static Application Security Testing(SAST)by applying various techniques such as prompt persona,structure outputs and zero-shot.To the selection of the LLMs(CodeLlama 7B,DeepSeek coder 7B,Gemini 1.5 Flash,Gemini 2.0 Flash,Mistral 7b Instruct,Phi 38b Mini 128K instruct,Qwen 2.5 coder,StartCoder 27B)with comparison and combination with Find Security Bugs.The evaluation method will involve using a selected dataset containing vulnerabilities,and the results to provide insights for different scenarios according to the software criticality(Business critical,non-critical,minimum effort,best effort)In detail,the main objectives of this study are to investigate if large language models outperform or exceed the capabilities of traditional static analysis tools,if the combining LLMs with Static Application Security Testing(SAST)tools lead to an improvement and the possibility that local machine learning models on a normal computer produce reliable results.Summarizing the most important conclusions of the research,it can be said that while it is true that the results have improved depending on the size of the LLM for business-critical software,the best results have been obtained by SAST analysis.This differs in“NonCritical,”“Best Effort,”and“Minimum Effort”scenarios,where the combination of LLM(Gemini)+SAST has obtained better results.
基金supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA218603
文摘Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.
文摘Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treatment and nursing care have greatly improved the life expectancy of individuals with DS.However,as they age,their risk of developing Alzheimer’s disease(AD)increases considerably(Antonarakis et al.,2020).
文摘Background:We present a case of two major complications following insertion of a nephrostomy managed in a minimally invasive way.Our case is the first in the literature to describe this minimally invasive treatment technique for colon perforation in a completely asymptomatic patient.Case Description:A 75-year-old female patient with a history of bilateral obstructive uropathy secondary to bilateral radiation-induced ureteric strictures attended for bilateral nephrostomy placement.The patient had a history of endometrial cancer,treated previously by total hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemo-radiotherapy and brachytherapy.Her recovery had been further complicated by the development of radiation cystitis,small bowel resection,and short gut syndrome.The strictures had previously been managed with bilateral double J stents,which have now failed.A left-sided nephrostomy insertion was performed.ACT-scan prompted by a repeat deterioration in renal function revealed a right-sided hydronephrosis and suggested transcolic passage of the previously placed leftsided nephrostomy.She had remained clinically well and apyretic.A right-sided nephrostomy was inserted,and the left re-sited following a colonoscopy-guided nephrostomy removal and clip occlusion of the nephrostomy tract.The patient then developed a pseudoaneurysm,which was managed with embolization.The patient was able to return home with corrected kidney function.The three-monthly checks for changes in nephrostomy catheters did not reveal any complications.Conclusions:The patient therefore presented with two major complications of nephrostomy placement:colonic perforation and pseudoaneurysm,classified as Clavien IIIb and IIIa,respectively.Multidisciplinary management,including urologists,gastroenterologists,general surgeons,and radiologists,enabled a minimally invasive management.Minimally invasive management with endoscopic clip placement appears to be a safe alternative to directed fistula of colonic perforation.
