Business Process Modelling(BPM)is essential for analyzing,improving,and automating the flow of information within organizations,but traditional approaches based on manual interpretation are slow,error-prone,and requir...Business Process Modelling(BPM)is essential for analyzing,improving,and automating the flow of information within organizations,but traditional approaches based on manual interpretation are slow,error-prone,and require a high level of expertise.This article proposes an innovative alternative solution that overcomes these limitations by automatically generating comprehensive Business Process Modelling and Notation(BPMN)diagrams solely from verbal descriptions of the processes to be modeled,utilizing Large Language Models(LLMs)and multimodal Artificial Intelligence(AI).Experimental results,based on video recordings of process explanations provided by an expert from an organization(in this case,the Commercial Courts of a public justice administration),demonstrate that the proposed methodology successfully enables the automatic generation of complete and accurate BPMN diagrams,leading to significant improvements in the speed,accuracy,and accessibility of process modeling.This research makes a substantial contribution to the field of business process modeling,as its methodology is groundbreaking in its use of LLMs and multimodal AI capabilities to handle different types of source material(text and video),combining several tools to minimize the number of queries and reduce the complexity of the prompts required for the automatic generation of successful BPMN diagrams.展开更多
The variation in temperature on the island of Gran Canaria is studied using the method applied to the nearby island of Tenerife [1]. An upward warming trend of 0.09°C ± 0.05°C (α = 0.01) was seen from ...The variation in temperature on the island of Gran Canaria is studied using the method applied to the nearby island of Tenerife [1]. An upward warming trend of 0.09°C ± 0.05°C (α = 0.01) was seen from 1946 to date, which has accelerated since the seventies to 0.17°C ± 0.10°C (α = 0.01). The increase was higher at night (0.11°C ± 0.05°C) than by day (0.08°C ± 0.06°C), so the temperature range decreased slightly. These values are similar to those of Tenerife and the time series of anomalies for the two islands are highly correlated. On the coast the same relationship to the sea surface temperature was found as in Tenerife, but in the mid-altitude areas to windward, some differences were detected that are hypothetically attributable to the different relief of the two islands.展开更多
Functionally graded cellular structures(FGCSs)have a multitude of applications to a wide range of industries.Utilising the ever-progressing technology of additive manufacturing(AM),FGCSs can be applied to control mate...Functionally graded cellular structures(FGCSs)have a multitude of applications to a wide range of industries.Utilising the ever-progressing technology of additive manufacturing(AM),FGCSs can be applied to control material grading and achieve the desired mechanical properties.The current study explores the design and optimisation of FGCSs for AM,with a focus on improving the compression and impact performance of below knee(BK)prosthetic limbs made of thermoplastic polyurethane(TPU).A multiscale research methodology integrating topology optimization(TO),finite element analysis(FEA),and design of experiments(Do E)was adopted to optimise lattice structures in terms of stiffness and lightweight properties.Two-unit cell designs were considered in the study:Schwarz P gyroid and body-centered cubic(BCC).Response surface methodology(RSM)was implemented to analyse the effect of minimum and maximum cell wall thickness,cell size,and unit cell type on the mechanical performance of TPU FGCS structures.The results indicated that a Schwarz P FGCS structure with cell size,minimum and maximum cell wall thickness of 6,0.9 and 2.8 mm,respectively,could be optimal for a compromise between performance and weight.In this optimized case,stiffness and volume fraction values of 684 N/mm and 0.64 were obtained,respectively.The study also presents a proof-of-concept design for a BK prosthetic damper,highlighting the potential of FGCSs to enhance patient comfort,reduce manufacturing costs,and enable personalised designs through 3D scanning and AM.The obtained results could be a step forward towards the incorporation of AM technologies in prosthetics,offering a pathway to lightweight,cost-effective,and functionally tailored solutions.展开更多
The article examines the physical,petrographic,mineralogical,and microstructural properties of mortar samples taken from a medieval structure located in northwestern Anatolia.Six mortar samples collected from the stru...The article examines the physical,petrographic,mineralogical,and microstructural properties of mortar samples taken from a medieval structure located in northwestern Anatolia.Six mortar samples collected from the structure were analyzed using advanced techniques such as acid loss,ignition loss,sieve analysis,physical analyses,polarizing and stereo microscope observations,SEM-EDS,XRD,and TGA.The mortars examined exhibit hydraulic properties.The hydraulic character of the mortars is mainly provided by brick dust and aggregates exhibiting pozzolanic activity.Acid loss and ignition loss analyses indicate that the binder-aggregate ratios vary between 1:1 and 1:3.The elemental and mineral composition of these mortars was analyzed using EDS and XRD,respectively.Analytical techniques revealed the presence of quartz,feldspar,muscovite,biotite,vaterite,and aragonite crystals.The results were supported by thermogravimetric analysis.This study provides important references for the formulation of compatible repair mortars to ensure the proper preservation of materials used in masonry walls of large-scale structures in similar geographical areas.It is intended that this study,based on the examination of mortar samples taken from the structure,will contribute to future research.展开更多
This article analyses the relationship between PM_(10) concentrations inside and outside two schools in Barreiro,Portugal:Primary School No.5 and D.Luís Mendonça Furtado Basic School.The main objective was t...This article analyses the relationship between PM_(10) concentrations inside and outside two schools in Barreiro,Portugal:Primary School No.5 and D.Luís Mendonça Furtado Basic School.The main objective was to understand the impact of external and internal sources on indoor air quality(IAQ)in school environments.Monitoring campaigns were carried out in different indoor spaces,including classrooms,the gym,and the canteen,and the results were compared with PM_(10) levels outside the building.At Primary School No.5,indoor PM10 concentrations were consistently higher than the outdoor values measured on Avenida do Bocage,with an average Indoor/Outdoor(I/O)ratio of 2.2,indicating a significant impact of indoor activities on particle levels.Similarly,at the D.Luís Mendonça Furtado Basic School,there was an increase in PM_(10) and PM_(2:5) concentrations during school hours,with the highest I/O ratio(3.04)recorded on school days.In the evenings and at weekends,when the spaces were unoccupied,particle concentrations dropped considerably,reaching an I/O ratio of 0.70.Said results suggest that indoor activities are a determining factor for particle levels in indoor air,emphasizing the need for ventilation and pollution control strategies in schools to protect the health of students and staff.展开更多
Neurodegeneration involves a wide range of neuropathological alterations affecting the integrity,physiology,and architecture of neural cells.Many studies have demonstrated neurodegeneration in different animals.In the...Neurodegeneration involves a wide range of neuropathological alterations affecting the integrity,physiology,and architecture of neural cells.Many studies have demonstrated neurodegeneration in different animals.In the case of Alzheimer's disease(AD),spontaneous animal models should display two neurohistopathological hallmarks:the deposition ofβ-amyloid and the arrangement of neurofibrillary tangles.However,no natural animal models that fulfill these conditions have been reported and most research into AD has been performed using transgenic rodents.Recent studies have also demonstrated that toothed whales-homeothermic,long-lived,top predatory marine mammals-show neuropathological signs of AD-like pathology.The neuropathological hallmarks in these cetaceans could help to better understand their endangered health as well as neurodegenerative diseases in humans.This systematic review analyzes all the literature published to date on this trending topic and the proposed causes for neurodegeneration in these iconic marine mammals are approached in the context of One Health/Planetary Health and translational medicine.展开更多
Semisubmersible naval ships are versatile military crafts that combine the advantageous features of high-speed planing crafts and submarines.At-surface,these ships are designed to provide sufficient speed and maneuver...Semisubmersible naval ships are versatile military crafts that combine the advantageous features of high-speed planing crafts and submarines.At-surface,these ships are designed to provide sufficient speed and maneuverability.Additionally,they can perform shallow dives,offering low visual and acoustic detectability.Therefore,the hydrodynamic design of a semisubmersible naval ship should address at-surface and submerged conditions.In this study,Numerical analyses were performed using a semisubmersible hull form to analyze its hydrodynamic features,including resistance,powering,and maneuvering.The simulations were conducted with Star CCM+version 2302,a commercial package program that solves URANS equations using the SST k-ωturbulence model.The flow analysis was divided into two parts:at-surface simulations and shallowly submerged simulations.At-surface simulations cover the resistance,powering,trim,and sinkage at transition and planing regimes,with corresponding Froude numbers ranging from 0.42 to 1.69.Shallowly submerged simulations were performed at seven different submergence depths,ranging from D/LOA=0.0635 to D/LOA=0.635,and at two different speeds with Froude numbers of 0.21 and 0.33.The behaviors of the hydrodynamic forces and pitching moment for different operation depths were comprehensively analyzed.The results of the numerical analyses provide valuable insights into the hydrodynamic performance of semisubmersible naval ships,highlighting the critical factors influencing their resistance,powering,and maneuvering capabilities in both at-surface and submerged conditions.展开更多
Urban environments have challenging characteristics for bird acoustic communication.High levels of anthropogenic noise,as well as vegetation structure(e.g.,in urban parks),can potentially affect the song frequency cha...Urban environments have challenging characteristics for bird acoustic communication.High levels of anthropogenic noise,as well as vegetation structure(e.g.,in urban parks),can potentially affect the song frequency characteristics of several bird species.An additional factor such as the abundance of conspecific and heterospecific vocalizing birds may play an important role in determining the structure of bird songs.In this study,we analyzed whether noise levels,vegetation percentage,and abundance of conspecifics and heterospecifics influence the song characteristics of three syntopic songbird species:House Finch(Haemorhous mexicanus),Rufouscollared Sparrow(Zonotrichia capensis),and House Sparrow(Passer domesticus)living in urban sites.We recorded songs of these species and measured the peak frequency and entropy of their songs at 14 sites in the city of San Cristobal de Las Casas,Chiapas,Mexico.We found that the song peak frequency of House Finch and House Sparrow's songs was negatively related to the vegetation.The peak frequency of neither of the three species correlated with the average noise level.However,the abundances of conspecific and heterospecific were related to the peak frequency of the three species'songs.The entropy of the House Finch and House Sparrow songs was positively and negatively related,respectively,to noise levels.House Sparrow song entropy was negatively related to the percentage of vegetation.Song entropy of House Finches was negatively associated to conspecific and House Sparrow abundance.Song entropy of Rufous-collared Sparrows was positively related to conspecific abundance.In conclusion,the song peak frequency and song entropy of the three songbird species were differentially related to urban noise,vegetation,and conspecific and heterospecific abundance,suggesting these factors influence bird song characteristics.展开更多
BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an invasive endoscopic procedure used mainly to treat hepato-pancreato-biliary(HPB)diseases.The need for ERCP has increased with the rising number of H...BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an invasive endoscopic procedure used mainly to treat hepato-pancreato-biliary(HPB)diseases.The need for ERCP has increased with the rising number of HPB diseases over the past decade.Thus,due to increased demand,ERCP is performed at more centers.Currently,it is performed by general surgeons,gastroenterology and invasive radiology specialists in the United States and Europe as recommended by the British Society of Gastroenterology(BSG).AIM To present the results of ERCP procedures from fourteen surgical centers in Türkiye.METHODS Fourteen surgical centers performing ERCP were included in the present study.The age,gender,ERCP indication,success status,post-ERCP complications,ERCP reports and the files of 66993 patients who underwent ERCP were collected from the participating centers.The results are discussed according to the targets declared by the BSG,which are volume load per annum,proportion of successful cannulation(>85%),bile duct clearance rate(>75%),stenting rate for strictures(>80%)and complications(<6%).RESULTS A total of 66993 ERCP procedures were performed in the centers included in the study up to August 2024.29250(43.6%)of the procedures were performed urgently,especially for suppurative cholangitis,biliary tract injuries,etc.The remaining 37743(56.4%)cases were performed electively.50.2%of the patients were female and 49.8%were male.The average ages were 56.5 years for women and 55.9 years for men.General anesthesia was used in 84.1%of the patients while sedation was used in 15.9%.The indications were bile duct stone(78.7%),pancreatic tumor(3.9%),papillary tumor(3.3%),cholangiocarcinoma(2.6%),Oddi sphincter dysfunction(2.4%),bile leakage after cholecystectomy(2%),bile leakage after hydatid cyst surgery(1.9%),biliary stricture(1.7%),and other diseases(3.1%).Hyperamylasemia and post-ERCP pancreatitis were the most common complications as observed in 8.1%of the patients.They were usually self-limited and responded to supportive measures.The frequency of the other complications was also consistent with the literature.CONCLUSION There is a huge shortage of ERCP endoscopists worldwide due to insufficient ERCP training and centers especially in developing and underdeveloped countries.As patients requiring ERCP usually present to surgical practitioners,the incorporation of surgeons into this training program is an effective and reliable solution.The BSG recommends the incorporation of surgeons and radiologists in addition to gastroenterology specialists.This study is the first to present the results of ERCP procedures from fourteen surgical centers throughout Türkiye.The results suggest that the surgical centers included were able to achieve the targets set by the BSG.This study demonstrated that the surgical ERCP units in the present work have reached satisfactory results and provided a reliable and successful ERCP service.There are currently no issues regarding the validity and appropriateness of the surgeons performing ERCP.Therefore,ERCP training should be encouraged in surgeons and more surgical ERCP centers should be provided.展开更多
Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessi...Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessing therapeutic efficacy and monitoring acupuncture treatment.Methods miRNA microarray data(CEL and TXT formats)were acquired from human and murine RA models,with the latter undergoing acupuncture treatment.Data were normalized using the robust multi-array average(RMA)method and analyzed for differential expression.Differential expression analysis identified miRNAs through a comparative analysis of RA human tissues,acupuncture-treated murine RA models,and a bibliographic search for miRNAs implicated in RA pathogenesis and acupuncture treatment.Bioinformatics analysis was performed to identify potential target genes for each miRNA and signaling pathways via search tools for the Retrieval of Interacting Genes/Proteins(STRING)and ShinyGO.Gene-drug interaction analysis was performed through Drug-Gene Interaction Database(DGIdb)screening.Interaction networks were constructed with the Cytoscape v3.10.3 software.Results The hsa-miR-125a-5p and hsa-miR-125b-5p were identified as potential biomarkers associated with RA pathogenesis,presenting 468 and 455 target genes,respectively.These genes were enriched in 20 signaling pathways,including Janus kinasa-signal transducer and activator of transcription(JAK-STAT),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase-protein kinase B(PI3K-Akt),and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway,which have been associated with RA pathogenesis and progression.Drug-gene interaction networks revealed that 22 genes were significantly associated with 58 RA treatment drugs,among which 13 genes interacted with members of the hsa-miR-125 family.Conclusion The hsa-miR-125a-5p and hsa-miR-125b-5p demonstrate critical regulatory role in RA pathogenesis by modulating signaling pathways,including JAK-STAT,MAPK,PI3K-Akt,and NF-κB.Our findings show that the hsa-miR-125a-5p and hsa-miR-125b-5p exhibit differential expression patterns in response to pharmacological intervention in various diseases,including RA management.This suggests their potential roles as biomarkers for monitoring acupuncture treatment.Although existing evidence indicates that acupuncture can modify miRNA expression profiles,rigorous validation through biological models remains essential to confirm these results.展开更多
We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive muco...We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease(GVHD). Balloon dilation,corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease,ulceration,esophageal webs,casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.展开更多
AIM:To evaluate the association of metabolic syndrome(MS) and colorectal cancer and adenomas in a Western country,where the incidence of MS is over 27%.METHODS:This was a prospective study between March 2013 and March...AIM:To evaluate the association of metabolic syndrome(MS) and colorectal cancer and adenomas in a Western country,where the incidence of MS is over 27%.METHODS:This was a prospective study between March 2013 and March 2014.MS was diagnosed according to the National Cholesterol Education ProgramATP III.Demographic characteristics,anthropometric measurements,metabolic risk factors,and colonoscopic pathologic findings were assessed in patients with MS(group 1) who underwent routine colonoscopy at our department.This data was compared with consecutive patients without metabolic syndrome(group 2),with no differences regarding sex and age.Patients with incomplete colonoscopy,family history,or past history of colorectal neoplasm were excluded.Informed consent was obtained and the ethics committee approved this study.Statistical analysis was performed using Student's t-test and χ2 test,with a P value ≤ 0.05 being considered statistically significant.RESULTS:Of 258 patients,129 had MS;51% males;mean-age 67.1 years(50-87).Among the MS group,94% had high blood pressure,91% had increased waist circumference,60% had diabetes,55% had low high-density lipoprotein cholesterol level,50% had increased triglyceride level,and 54% were obese [body mass index(BMI) 30 kg/m2].51% presented 4 criteria of MS.MS was associated with increased prevalence of adenomas(43% vs 25%,P = 0.004) and colorectal cancer(13% vs 5%,P = 0.027),compared with patients without MS.MS was also positively associated with multiple(≥ 3) adenomas(35% vs 9%,P = 0.024) and sessile adenomas(69% vs 53%,P = 0.05).No difference existed between location(P = 0.086),grade of dysplasia(P = 0.196),or size(P= 0.841) of adenomas.In addition,no difference was found between BMI(P = 0.078),smoking(P = 0.146),alcohol consumption(P = 0.231),and the presence of adenomas.CONCLUSION:MS is positively associated with adenomas and colorectal cancer.However,there is not enough information in western European countries to justify screening in patients with MS.To our knowledge,no previous study has evaluated this association in Portuguese patients.展开更多
Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in scree...Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.展开更多
AIM: To investigate the safety and efficacy of intravitreal dexamethasone implants(Ozurdex?/DEX) in patients with diabetic macular edema(DME) either na?ve or nonna?ve to anti-VEGF therapies who switched to DEX implant...AIM: To investigate the safety and efficacy of intravitreal dexamethasone implants(Ozurdex?/DEX) in patients with diabetic macular edema(DME) either na?ve or nonna?ve to anti-VEGF therapies who switched to DEX implant independent of response to anti-vascular endothelial growth factors(anti-VEGFs).METHODS: This was an audit retrospective review of medical records of patients with DME who switched to the DEX intravitreal implant. Patients were divided into 2 groups: patients na?ve to antiangiogenic therapy and patients who were previously treated with anti-VEGFs. Data regarding demographics, changes in mean best-corrected visual acuity(BCVA), central macular thickness(CMT), and intraocular pressure(IOP) was collected over 6 mo. The demographic data mean changes in BCVA, CMT, and IOP were compared. Six-month follow-up data of 47 patients(57 eyes), who either switched to DEX implant irrespective of response to previous treatments or were treatment na?ve before receiving DEX implant, was collected.RESULTS: Improvement in mean BCVA was observed from 1-4 mo after injection with a decreased effect at month 6 as expected, with better outcomes in na?ve compared to non-na?ve patients. A statistically relevant decrease in mean CMT was observed during the follow-up period. An increase in mean IOP was observed in the first 2 mo after DEX therapy. The mean number of injections of the overall population during the 6 mo was 1.3. A subgroup analysis showed no relevant difference between phakic versus pseudophakic patients relative to measured outcomes. There was no cataract progression during the follow-up period and no adverse events reported.CONCLUSION: This real-life setting study shows that intravitreal DEX implant is effective and safe. The timings of greater therapeutic impact are concordant with previous studies and suggest that earlier treatment with corticosteroids may have an additional benefit in na?ve patients.展开更多
AIM:To assess the appropriate use and the diagnostic yield of upper gastrointestinal endoscopy and colonoscopy in this subgroup of patients.METHODS:In total,789 consecutive outpatients referred for gastrointestinal(GI...AIM:To assess the appropriate use and the diagnostic yield of upper gastrointestinal endoscopy and colonoscopy in this subgroup of patients.METHODS:In total,789 consecutive outpatients referred for gastrointestinal(GI) endoscopy [381 for esophagogastroduodenoscopy(EGD) and 408 for colonoscopy] were prospectively enrolled in the study.The American Society for Gastrointestinal Endoscopy(ASGE) guidelines were used to assess the relationship between appropriateness and the presence of relevant endoscopic f indings.RESULTS:The overall inappropriate rate was 13.3%.The indications for EGD and colonoscopy were,respectively,appropriate in 82.7% and 82.6% of the exams,uncertain in 5.8% and 2.4% and inappropriate in 11.5% and 15%.The diagnostic yield was signif icant higher forEGDs and colonoscopies judged appropriate and uncertain when compared with those considered inappropriate(EGD:36.6% vs 36.4% vs 11.4%,P = 0.004;Colonoscopy:24.3% vs 20.0% vs 3.3%,P = 0.001).Of the 25 malignant lesions detected,all but one was detected in exams judged appropriate or uncertain.CONCLUSION:This study shows a good adherence to ASGE guidelines by the referring physicians and a significant increase of the diagnostic yield in appropriate examinations,namely in detecting neoplastic lesions.It underscores the importance that the appropriateness of the indication assumes in assuring high-quality GI endoscopic procedures.展开更多
Dengue virus infection continues to be major public health problem in large part of world.The epidemiology of dengue viral infection is becoming increasingly complex and has substantially changed over almost past six ...Dengue virus infection continues to be major public health problem in large part of world.The epidemiology of dengue viral infection is becoming increasingly complex and has substantially changed over almost past six decades not only in terms of prevalent strains and geographical locations but also in terms of disease severity and atypical presentations.Though liver is the most common organ affected but is generally asymptomatic.We present a case of infant with severe dengue who died of fulminant hepatic failure and showed pan lobular necrosis on post mortem liver biopsy.The case is being presented to highlight life threatening complication of dengue in young children,and dengue viral infection as a cause of acute liver failure in endemic areas.Thus dengue fever should also be considered as one of the differential diagnosis in children presenting with fever and fulminant hepatic failure in endemic regions.展开更多
Candida endocarditis is extremely rare in term neonates,and gall bladder involvement due to candidemia has never been reported amongst neonates and infants.A term,appropriate for gestational age neonate developed Cand...Candida endocarditis is extremely rare in term neonates,and gall bladder involvement due to candidemia has never been reported amongst neonates and infants.A term,appropriate for gestational age neonate developed Candida tropicalis blood stream infection in second week of life.He was started on conventional amphotericin B.However,he failed to show any clinical improvement,and candidemia keep on persisting.Repeat sanctuary sites screening revealed multiple echogenic masses in heart(vegetations) and gall bladder.On changing the treatment to liposomal amphotericin B and fluconazole,he recovered clinically,echogenic masses in gall bladder disappeared,and intracardiac vegetations decreased in size.展开更多
Bone remodeling is precisely coordinated by bone resorption and formation.Apoptotic osteoclasts generate large amounts of apoptotic bodies(ABs)marking the end of the bone resorption phase,whereas the functions of oste...Bone remodeling is precisely coordinated by bone resorption and formation.Apoptotic osteoclasts generate large amounts of apoptotic bodies(ABs)marking the end of the bone resorption phase,whereas the functions of osteoclast-derived ABs remain largely unknown.Here,we identified the molecular profile of ABs derived from osteoclasts at distinct differentiation stages and investigated their corresponding functions.ABs were isolated from apoptotic bone marrow macrophages,preosteoclasts,and mature osteoclasts induced by staurosporine.Proteomic signature analysis with liquid chromatography-tandem mass spectrometry suggested marked protein cargo differences among the different ABs.Further bioinformatic analysis showed that the proteomic signatures of the ABs were highly similar to those of their parental cells.Functionally,pOC-ABs induced endothelial progenitor cell differentiation and increased CD31hiEmcnhi endothelial cell formation in a murine bone defect model via their PDGF-BB cargo.mOC-ABs induced osteogenic differentiation of mesenchymal stem cells and facilitated osteogenesis via RANKL reverse signaling.In summary,we mapped the detailed proteomic landscapes of ABs derived from osteoclasts and showed that their potential biological roles are important in coupling bone formation with resorption during bone remodeling.展开更多
BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combinat...BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.展开更多
基金funded by Fundación CajaCanarias and Fundación Bancaria“la Caixa”,grant number 2023DIG11.
文摘Business Process Modelling(BPM)is essential for analyzing,improving,and automating the flow of information within organizations,but traditional approaches based on manual interpretation are slow,error-prone,and require a high level of expertise.This article proposes an innovative alternative solution that overcomes these limitations by automatically generating comprehensive Business Process Modelling and Notation(BPMN)diagrams solely from verbal descriptions of the processes to be modeled,utilizing Large Language Models(LLMs)and multimodal Artificial Intelligence(AI).Experimental results,based on video recordings of process explanations provided by an expert from an organization(in this case,the Commercial Courts of a public justice administration),demonstrate that the proposed methodology successfully enables the automatic generation of complete and accurate BPMN diagrams,leading to significant improvements in the speed,accuracy,and accessibility of process modeling.This research makes a substantial contribution to the field of business process modeling,as its methodology is groundbreaking in its use of LLMs and multimodal AI capabilities to handle different types of source material(text and video),combining several tools to minimize the number of queries and reduce the complexity of the prompts required for the automatic generation of successful BPMN diagrams.
文摘The variation in temperature on the island of Gran Canaria is studied using the method applied to the nearby island of Tenerife [1]. An upward warming trend of 0.09°C ± 0.05°C (α = 0.01) was seen from 1946 to date, which has accelerated since the seventies to 0.17°C ± 0.10°C (α = 0.01). The increase was higher at night (0.11°C ± 0.05°C) than by day (0.08°C ± 0.06°C), so the temperature range decreased slightly. These values are similar to those of Tenerife and the time series of anomalies for the two islands are highly correlated. On the coast the same relationship to the sea surface temperature was found as in Tenerife, but in the mid-altitude areas to windward, some differences were detected that are hypothetically attributable to the different relief of the two islands.
基金financially supported and funded by the Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University(IMSIU)(No.IMSIU-DDRSP2503)。
文摘Functionally graded cellular structures(FGCSs)have a multitude of applications to a wide range of industries.Utilising the ever-progressing technology of additive manufacturing(AM),FGCSs can be applied to control material grading and achieve the desired mechanical properties.The current study explores the design and optimisation of FGCSs for AM,with a focus on improving the compression and impact performance of below knee(BK)prosthetic limbs made of thermoplastic polyurethane(TPU).A multiscale research methodology integrating topology optimization(TO),finite element analysis(FEA),and design of experiments(Do E)was adopted to optimise lattice structures in terms of stiffness and lightweight properties.Two-unit cell designs were considered in the study:Schwarz P gyroid and body-centered cubic(BCC).Response surface methodology(RSM)was implemented to analyse the effect of minimum and maximum cell wall thickness,cell size,and unit cell type on the mechanical performance of TPU FGCS structures.The results indicated that a Schwarz P FGCS structure with cell size,minimum and maximum cell wall thickness of 6,0.9 and 2.8 mm,respectively,could be optimal for a compromise between performance and weight.In this optimized case,stiffness and volume fraction values of 684 N/mm and 0.64 were obtained,respectively.The study also presents a proof-of-concept design for a BK prosthetic damper,highlighting the potential of FGCSs to enhance patient comfort,reduce manufacturing costs,and enable personalised designs through 3D scanning and AM.The obtained results could be a step forward towards the incorporation of AM technologies in prosthetics,offering a pathway to lightweight,cost-effective,and functionally tailored solutions.
文摘The article examines the physical,petrographic,mineralogical,and microstructural properties of mortar samples taken from a medieval structure located in northwestern Anatolia.Six mortar samples collected from the structure were analyzed using advanced techniques such as acid loss,ignition loss,sieve analysis,physical analyses,polarizing and stereo microscope observations,SEM-EDS,XRD,and TGA.The mortars examined exhibit hydraulic properties.The hydraulic character of the mortars is mainly provided by brick dust and aggregates exhibiting pozzolanic activity.Acid loss and ignition loss analyses indicate that the binder-aggregate ratios vary between 1:1 and 1:3.The elemental and mineral composition of these mortars was analyzed using EDS and XRD,respectively.Analytical techniques revealed the presence of quartz,feldspar,muscovite,biotite,vaterite,and aragonite crystals.The results were supported by thermogravimetric analysis.This study provides important references for the formulation of compatible repair mortars to ensure the proper preservation of materials used in masonry walls of large-scale structures in similar geographical areas.It is intended that this study,based on the examination of mortar samples taken from the structure,will contribute to future research.
文摘This article analyses the relationship between PM_(10) concentrations inside and outside two schools in Barreiro,Portugal:Primary School No.5 and D.Luís Mendonça Furtado Basic School.The main objective was to understand the impact of external and internal sources on indoor air quality(IAQ)in school environments.Monitoring campaigns were carried out in different indoor spaces,including classrooms,the gym,and the canteen,and the results were compared with PM_(10) levels outside the building.At Primary School No.5,indoor PM10 concentrations were consistently higher than the outdoor values measured on Avenida do Bocage,with an average Indoor/Outdoor(I/O)ratio of 2.2,indicating a significant impact of indoor activities on particle levels.Similarly,at the D.Luís Mendonça Furtado Basic School,there was an increase in PM_(10) and PM_(2:5) concentrations during school hours,with the highest I/O ratio(3.04)recorded on school days.In the evenings and at weekends,when the spaces were unoccupied,particle concentrations dropped considerably,reaching an I/O ratio of 0.70.Said results suggest that indoor activities are a determining factor for particle levels in indoor air,emphasizing the need for ventilation and pollution control strategies in schools to protect the health of students and staff.
文摘Neurodegeneration involves a wide range of neuropathological alterations affecting the integrity,physiology,and architecture of neural cells.Many studies have demonstrated neurodegeneration in different animals.In the case of Alzheimer's disease(AD),spontaneous animal models should display two neurohistopathological hallmarks:the deposition ofβ-amyloid and the arrangement of neurofibrillary tangles.However,no natural animal models that fulfill these conditions have been reported and most research into AD has been performed using transgenic rodents.Recent studies have also demonstrated that toothed whales-homeothermic,long-lived,top predatory marine mammals-show neuropathological signs of AD-like pathology.The neuropathological hallmarks in these cetaceans could help to better understand their endangered health as well as neurodegenerative diseases in humans.This systematic review analyzes all the literature published to date on this trending topic and the proposed causes for neurodegeneration in these iconic marine mammals are approached in the context of One Health/Planetary Health and translational medicine.
文摘Semisubmersible naval ships are versatile military crafts that combine the advantageous features of high-speed planing crafts and submarines.At-surface,these ships are designed to provide sufficient speed and maneuverability.Additionally,they can perform shallow dives,offering low visual and acoustic detectability.Therefore,the hydrodynamic design of a semisubmersible naval ship should address at-surface and submerged conditions.In this study,Numerical analyses were performed using a semisubmersible hull form to analyze its hydrodynamic features,including resistance,powering,and maneuvering.The simulations were conducted with Star CCM+version 2302,a commercial package program that solves URANS equations using the SST k-ωturbulence model.The flow analysis was divided into two parts:at-surface simulations and shallowly submerged simulations.At-surface simulations cover the resistance,powering,trim,and sinkage at transition and planing regimes,with corresponding Froude numbers ranging from 0.42 to 1.69.Shallowly submerged simulations were performed at seven different submergence depths,ranging from D/LOA=0.0635 to D/LOA=0.635,and at two different speeds with Froude numbers of 0.21 and 0.33.The behaviors of the hydrodynamic forces and pitching moment for different operation depths were comprehensively analyzed.The results of the numerical analyses provide valuable insights into the hydrodynamic performance of semisubmersible naval ships,highlighting the critical factors influencing their resistance,powering,and maneuvering capabilities in both at-surface and submerged conditions.
基金the Consejo Nacional de Humanidades,Ciencias y Tecnologías (CONAHCYT)of Mexico for providing funding for graduate studies of X.D.L. (No.001283)El Colegio de la Frontera Sur for PATM graduate fellowship for fieldwork。
文摘Urban environments have challenging characteristics for bird acoustic communication.High levels of anthropogenic noise,as well as vegetation structure(e.g.,in urban parks),can potentially affect the song frequency characteristics of several bird species.An additional factor such as the abundance of conspecific and heterospecific vocalizing birds may play an important role in determining the structure of bird songs.In this study,we analyzed whether noise levels,vegetation percentage,and abundance of conspecifics and heterospecifics influence the song characteristics of three syntopic songbird species:House Finch(Haemorhous mexicanus),Rufouscollared Sparrow(Zonotrichia capensis),and House Sparrow(Passer domesticus)living in urban sites.We recorded songs of these species and measured the peak frequency and entropy of their songs at 14 sites in the city of San Cristobal de Las Casas,Chiapas,Mexico.We found that the song peak frequency of House Finch and House Sparrow's songs was negatively related to the vegetation.The peak frequency of neither of the three species correlated with the average noise level.However,the abundances of conspecific and heterospecific were related to the peak frequency of the three species'songs.The entropy of the House Finch and House Sparrow songs was positively and negatively related,respectively,to noise levels.House Sparrow song entropy was negatively related to the percentage of vegetation.Song entropy of House Finches was negatively associated to conspecific and House Sparrow abundance.Song entropy of Rufous-collared Sparrows was positively related to conspecific abundance.In conclusion,the song peak frequency and song entropy of the three songbird species were differentially related to urban noise,vegetation,and conspecific and heterospecific abundance,suggesting these factors influence bird song characteristics.
文摘BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an invasive endoscopic procedure used mainly to treat hepato-pancreato-biliary(HPB)diseases.The need for ERCP has increased with the rising number of HPB diseases over the past decade.Thus,due to increased demand,ERCP is performed at more centers.Currently,it is performed by general surgeons,gastroenterology and invasive radiology specialists in the United States and Europe as recommended by the British Society of Gastroenterology(BSG).AIM To present the results of ERCP procedures from fourteen surgical centers in Türkiye.METHODS Fourteen surgical centers performing ERCP were included in the present study.The age,gender,ERCP indication,success status,post-ERCP complications,ERCP reports and the files of 66993 patients who underwent ERCP were collected from the participating centers.The results are discussed according to the targets declared by the BSG,which are volume load per annum,proportion of successful cannulation(>85%),bile duct clearance rate(>75%),stenting rate for strictures(>80%)and complications(<6%).RESULTS A total of 66993 ERCP procedures were performed in the centers included in the study up to August 2024.29250(43.6%)of the procedures were performed urgently,especially for suppurative cholangitis,biliary tract injuries,etc.The remaining 37743(56.4%)cases were performed electively.50.2%of the patients were female and 49.8%were male.The average ages were 56.5 years for women and 55.9 years for men.General anesthesia was used in 84.1%of the patients while sedation was used in 15.9%.The indications were bile duct stone(78.7%),pancreatic tumor(3.9%),papillary tumor(3.3%),cholangiocarcinoma(2.6%),Oddi sphincter dysfunction(2.4%),bile leakage after cholecystectomy(2%),bile leakage after hydatid cyst surgery(1.9%),biliary stricture(1.7%),and other diseases(3.1%).Hyperamylasemia and post-ERCP pancreatitis were the most common complications as observed in 8.1%of the patients.They were usually self-limited and responded to supportive measures.The frequency of the other complications was also consistent with the literature.CONCLUSION There is a huge shortage of ERCP endoscopists worldwide due to insufficient ERCP training and centers especially in developing and underdeveloped countries.As patients requiring ERCP usually present to surgical practitioners,the incorporation of surgeons into this training program is an effective and reliable solution.The BSG recommends the incorporation of surgeons and radiologists in addition to gastroenterology specialists.This study is the first to present the results of ERCP procedures from fourteen surgical centers throughout Türkiye.The results suggest that the surgical centers included were able to achieve the targets set by the BSG.This study demonstrated that the surgical ERCP units in the present work have reached satisfactory results and provided a reliable and successful ERCP service.There are currently no issues regarding the validity and appropriateness of the surgeons performing ERCP.Therefore,ERCP training should be encouraged in surgeons and more surgical ERCP centers should be provided.
基金Programa de Investigadores e Investigadoras of the Consejo Mexiquense de Ciencia y Tecnología(COMECYT)(EESP2024-0038)。
文摘Objective To perform an in silico bioinformatics analysis to identify differentially expressed microRNAs(miRNAs)implicated in rheumatoid arthritis(RA)pathogenesis and evaluate their potential as biomarkers for assessing therapeutic efficacy and monitoring acupuncture treatment.Methods miRNA microarray data(CEL and TXT formats)were acquired from human and murine RA models,with the latter undergoing acupuncture treatment.Data were normalized using the robust multi-array average(RMA)method and analyzed for differential expression.Differential expression analysis identified miRNAs through a comparative analysis of RA human tissues,acupuncture-treated murine RA models,and a bibliographic search for miRNAs implicated in RA pathogenesis and acupuncture treatment.Bioinformatics analysis was performed to identify potential target genes for each miRNA and signaling pathways via search tools for the Retrieval of Interacting Genes/Proteins(STRING)and ShinyGO.Gene-drug interaction analysis was performed through Drug-Gene Interaction Database(DGIdb)screening.Interaction networks were constructed with the Cytoscape v3.10.3 software.Results The hsa-miR-125a-5p and hsa-miR-125b-5p were identified as potential biomarkers associated with RA pathogenesis,presenting 468 and 455 target genes,respectively.These genes were enriched in 20 signaling pathways,including Janus kinasa-signal transducer and activator of transcription(JAK-STAT),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase-protein kinase B(PI3K-Akt),and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway,which have been associated with RA pathogenesis and progression.Drug-gene interaction networks revealed that 22 genes were significantly associated with 58 RA treatment drugs,among which 13 genes interacted with members of the hsa-miR-125 family.Conclusion The hsa-miR-125a-5p and hsa-miR-125b-5p demonstrate critical regulatory role in RA pathogenesis by modulating signaling pathways,including JAK-STAT,MAPK,PI3K-Akt,and NF-κB.Our findings show that the hsa-miR-125a-5p and hsa-miR-125b-5p exhibit differential expression patterns in response to pharmacological intervention in various diseases,including RA management.This suggests their potential roles as biomarkers for monitoring acupuncture treatment.Although existing evidence indicates that acupuncture can modify miRNA expression profiles,rigorous validation through biological models remains essential to confirm these results.
文摘We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease(GVHD). Balloon dilation,corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease,ulceration,esophageal webs,casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.
文摘AIM:To evaluate the association of metabolic syndrome(MS) and colorectal cancer and adenomas in a Western country,where the incidence of MS is over 27%.METHODS:This was a prospective study between March 2013 and March 2014.MS was diagnosed according to the National Cholesterol Education ProgramATP III.Demographic characteristics,anthropometric measurements,metabolic risk factors,and colonoscopic pathologic findings were assessed in patients with MS(group 1) who underwent routine colonoscopy at our department.This data was compared with consecutive patients without metabolic syndrome(group 2),with no differences regarding sex and age.Patients with incomplete colonoscopy,family history,or past history of colorectal neoplasm were excluded.Informed consent was obtained and the ethics committee approved this study.Statistical analysis was performed using Student's t-test and χ2 test,with a P value ≤ 0.05 being considered statistically significant.RESULTS:Of 258 patients,129 had MS;51% males;mean-age 67.1 years(50-87).Among the MS group,94% had high blood pressure,91% had increased waist circumference,60% had diabetes,55% had low high-density lipoprotein cholesterol level,50% had increased triglyceride level,and 54% were obese [body mass index(BMI) 30 kg/m2].51% presented 4 criteria of MS.MS was associated with increased prevalence of adenomas(43% vs 25%,P = 0.004) and colorectal cancer(13% vs 5%,P = 0.027),compared with patients without MS.MS was also positively associated with multiple(≥ 3) adenomas(35% vs 9%,P = 0.024) and sessile adenomas(69% vs 53%,P = 0.05).No difference existed between location(P = 0.086),grade of dysplasia(P = 0.196),or size(P= 0.841) of adenomas.In addition,no difference was found between BMI(P = 0.078),smoking(P = 0.146),alcohol consumption(P = 0.231),and the presence of adenomas.CONCLUSION:MS is positively associated with adenomas and colorectal cancer.However,there is not enough information in western European countries to justify screening in patients with MS.To our knowledge,no previous study has evaluated this association in Portuguese patients.
文摘Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.
文摘AIM: To investigate the safety and efficacy of intravitreal dexamethasone implants(Ozurdex?/DEX) in patients with diabetic macular edema(DME) either na?ve or nonna?ve to anti-VEGF therapies who switched to DEX implant independent of response to anti-vascular endothelial growth factors(anti-VEGFs).METHODS: This was an audit retrospective review of medical records of patients with DME who switched to the DEX intravitreal implant. Patients were divided into 2 groups: patients na?ve to antiangiogenic therapy and patients who were previously treated with anti-VEGFs. Data regarding demographics, changes in mean best-corrected visual acuity(BCVA), central macular thickness(CMT), and intraocular pressure(IOP) was collected over 6 mo. The demographic data mean changes in BCVA, CMT, and IOP were compared. Six-month follow-up data of 47 patients(57 eyes), who either switched to DEX implant irrespective of response to previous treatments or were treatment na?ve before receiving DEX implant, was collected.RESULTS: Improvement in mean BCVA was observed from 1-4 mo after injection with a decreased effect at month 6 as expected, with better outcomes in na?ve compared to non-na?ve patients. A statistically relevant decrease in mean CMT was observed during the follow-up period. An increase in mean IOP was observed in the first 2 mo after DEX therapy. The mean number of injections of the overall population during the 6 mo was 1.3. A subgroup analysis showed no relevant difference between phakic versus pseudophakic patients relative to measured outcomes. There was no cataract progression during the follow-up period and no adverse events reported.CONCLUSION: This real-life setting study shows that intravitreal DEX implant is effective and safe. The timings of greater therapeutic impact are concordant with previous studies and suggest that earlier treatment with corticosteroids may have an additional benefit in na?ve patients.
文摘AIM:To assess the appropriate use and the diagnostic yield of upper gastrointestinal endoscopy and colonoscopy in this subgroup of patients.METHODS:In total,789 consecutive outpatients referred for gastrointestinal(GI) endoscopy [381 for esophagogastroduodenoscopy(EGD) and 408 for colonoscopy] were prospectively enrolled in the study.The American Society for Gastrointestinal Endoscopy(ASGE) guidelines were used to assess the relationship between appropriateness and the presence of relevant endoscopic f indings.RESULTS:The overall inappropriate rate was 13.3%.The indications for EGD and colonoscopy were,respectively,appropriate in 82.7% and 82.6% of the exams,uncertain in 5.8% and 2.4% and inappropriate in 11.5% and 15%.The diagnostic yield was signif icant higher forEGDs and colonoscopies judged appropriate and uncertain when compared with those considered inappropriate(EGD:36.6% vs 36.4% vs 11.4%,P = 0.004;Colonoscopy:24.3% vs 20.0% vs 3.3%,P = 0.001).Of the 25 malignant lesions detected,all but one was detected in exams judged appropriate or uncertain.CONCLUSION:This study shows a good adherence to ASGE guidelines by the referring physicians and a significant increase of the diagnostic yield in appropriate examinations,namely in detecting neoplastic lesions.It underscores the importance that the appropriateness of the indication assumes in assuring high-quality GI endoscopic procedures.
文摘Dengue virus infection continues to be major public health problem in large part of world.The epidemiology of dengue viral infection is becoming increasingly complex and has substantially changed over almost past six decades not only in terms of prevalent strains and geographical locations but also in terms of disease severity and atypical presentations.Though liver is the most common organ affected but is generally asymptomatic.We present a case of infant with severe dengue who died of fulminant hepatic failure and showed pan lobular necrosis on post mortem liver biopsy.The case is being presented to highlight life threatening complication of dengue in young children,and dengue viral infection as a cause of acute liver failure in endemic areas.Thus dengue fever should also be considered as one of the differential diagnosis in children presenting with fever and fulminant hepatic failure in endemic regions.
文摘Candida endocarditis is extremely rare in term neonates,and gall bladder involvement due to candidemia has never been reported amongst neonates and infants.A term,appropriate for gestational age neonate developed Candida tropicalis blood stream infection in second week of life.He was started on conventional amphotericin B.However,he failed to show any clinical improvement,and candidemia keep on persisting.Repeat sanctuary sites screening revealed multiple echogenic masses in heart(vegetations) and gall bladder.On changing the treatment to liposomal amphotericin B and fluconazole,he recovered clinically,echogenic masses in gall bladder disappeared,and intracardiac vegetations decreased in size.
基金This work was funded by a grant from the National Natural Science Foundation of China(81802166)a grant from the State Key Program of National Natural Science of China(81930067)a first-class General Financial Grant from the China Postdoctoral Science Foundation(2017M613315).
文摘Bone remodeling is precisely coordinated by bone resorption and formation.Apoptotic osteoclasts generate large amounts of apoptotic bodies(ABs)marking the end of the bone resorption phase,whereas the functions of osteoclast-derived ABs remain largely unknown.Here,we identified the molecular profile of ABs derived from osteoclasts at distinct differentiation stages and investigated their corresponding functions.ABs were isolated from apoptotic bone marrow macrophages,preosteoclasts,and mature osteoclasts induced by staurosporine.Proteomic signature analysis with liquid chromatography-tandem mass spectrometry suggested marked protein cargo differences among the different ABs.Further bioinformatic analysis showed that the proteomic signatures of the ABs were highly similar to those of their parental cells.Functionally,pOC-ABs induced endothelial progenitor cell differentiation and increased CD31hiEmcnhi endothelial cell formation in a murine bone defect model via their PDGF-BB cargo.mOC-ABs induced osteogenic differentiation of mesenchymal stem cells and facilitated osteogenesis via RANKL reverse signaling.In summary,we mapped the detailed proteomic landscapes of ABs derived from osteoclasts and showed that their potential biological roles are important in coupling bone formation with resorption during bone remodeling.
文摘BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.
