Indoor air quality(IAQ)is often overlooked,yet a poorly maintained environment can lead to significant health issues and reduced concentration and productivity in work or educational settings.This study presents an in...Indoor air quality(IAQ)is often overlooked,yet a poorly maintained environment can lead to significant health issues and reduced concentration and productivity in work or educational settings.This study presents an innovative control system for mechanical ventilation specifically designed for university classrooms,with the dual goal of enhancing IAQ and increasing energy efficiency.Two classrooms with distinct construction characteristics were analyzed:one with exterior walls and windows,and the other completely underground.For each classroom,a model was developed using DesignBuilder software,which was calibrated with experimental data regarding CO_(2) concentration,temperature,and relative humidity levels.The proposed ventilation system operates based on CO_(2) concentration,relative humidity,and potential for free heating and cooling.In addition,the analysis was conducted for other locations,demonstrating consistent energy savings across different climates and environments,always showing an annual reduction in energy consumption.Results demonstrate that mechanical ventilation,when integrated with heat recovery and free cooling strategies,significantly reduces energy consumption by up to 25%,while also maintaining optimal CO_(2) levels to enhance comfort and air quality.These findings emphasize the essential need for well-designed mechanical ventilation systems to ensure both psychophysical well-being and IAQ in enclosed spaces,particularly in environments intended for extended occupancy,such as classrooms.Furthermore,this approach has broad applicability,as it could be adapted to various building types,thereby contributing to sustainable energy management practices and promoting healthier indoor spaces.This study serves as a model for future designs aiming to balance energy efficiency with indoor air quality,especially relevant in the post-COVID era,where the importance of indoor air quality has become more widely recognized.展开更多
Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emerge...Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.展开更多
A consumption of 46.9 million tons of processed tomatoes was reported in 2022 which is merely 20%of the total consumption.An increase of 3.3%in consumption is predicted from 2024 to 2032.Tomatoes are also rich in iron...A consumption of 46.9 million tons of processed tomatoes was reported in 2022 which is merely 20%of the total consumption.An increase of 3.3%in consumption is predicted from 2024 to 2032.Tomatoes are also rich in iron,potassium,antioxidant lycopene,vitamins A,C and K which are important for preventing cancer,and maintaining blood pressure and glucose levels.Thus,tomatoes are globally important due to their widespread usage and nutritional value.To face the high demand for tomatoes,it is mandatory to investigate the causes of crop loss and minimize them.Diseases are one of the major causes that adversely affect crop yield and degrade the quality of the tomato fruit.This leads to financial losses and affects the livelihood of farmers.Therefore,automatic disease detection at any stage of the tomato plant is a critical issue.Deep learning models introduced in the literature show promising results,but the models are difficult to implement on handheld devices such as mobile phones due to high computational costs and a large number of parameters.Also,most of the models proposed so far work efficiently for images with plain backgrounds where a clear demarcation exists between the background and leaf region.Moreover,the existing techniques lack in recognizing multiple diseases on the same leaf.To address these concerns,we introduce a customized deep learning-based convolution vision transformer model.Themodel achieves an accuracy of 93.51%for classifying tomato leaf images with plain as well as complex backgrounds into 13 categories.It requires a space storage of merely 5.8 MB which is 98.93%,98.33%,and 92.64%less than stateof-the-art visual geometry group,vision transformers,and convolution vision transformermodels,respectively.Its training time of 44 min is 51.12%,74.12%,and 57.7%lower than the above-mentioned models.Thus,it can be deployed on(Internet of Things)IoT-enabled devices,drones,or mobile devices to assist farmers in the real-time monitoring of tomato crops.The periodicmonitoring promotes timely action to prevent the spread of diseases and reduce crop loss.展开更多
Environmental monitoring of airborne formaldehyde (FA) using sensitive methodologies is fundamental to prevent health risks. The objective of this study was to compare three different FA monitoring methods during the ...Environmental monitoring of airborne formaldehyde (FA) using sensitive methodologies is fundamental to prevent health risks. The objective of this study was to compare three different FA monitoring methods during the daily activities of an anatomic pathology laboratory. Daily eight-hour measurements deriving from Radiello® passive diffusive samplers (PDS), NEMo XT continuous optical sensor (COS), and multi-gas 1512 photoacoustic monitor (MPM) were simultaneously compared over a period of 14 working days. Given the different daily distributions of the measurements performed by the three devices, all measurements were time-aligned for comparison purposes. The 95% limit of agreement (LOA) method was applied to estimate the degree of concordance of each device with respect to the others. Formaldehyde arithmetic mean measured using PDS was 32.6 ± 10.4 ppb (range: 19.8 - 62.7). The simultaneous measures performed by COS and MPM were respectively 42.4 ± 44.8 ppb (range: 7.0 - 175.0) and 189.0 ± 163.7 ppb (range: 40.0 - 2895.4). The MPM geometric mean (171.3 ppb) was approximately five times higher than those derived from COS (32.3 ppb) and PDS (31.4 ppb). The results of the LOA method applied to log-transformed FA data showed the same systematic discrepancies between MPM and the other two devices. A good agreement between PDS and COS could lead to a tailored approach according to the individual specificity of these techniques. This tool may be useful for accurately assessing the risk of FA exposure among healthcare workers. However, the limited specificity of the MPM does not support its use as a monitoring method for FA in the workplace.展开更多
To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA...To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA),choledocus extrapancreatic cholangiocarcinoma(EPCCA)and choledocus intrapancreatic cholangiocarcinoma(IPCCA)and,finally,gallbladder carcinoma(GBCCA).CCAs are relatively uncommon but.展开更多
This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty(UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP se...This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty(UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes(Eye OP1). After treatment, the mean intraocular pressure(IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6(all P<0.001). Mean laser flare-cell photometry value steeply increased after surgery from 12.1±7.5 to 64.1±53.9 ph/ms(P=0.001) at day 1, and then progressively decreased to respectively 60.6±49.7 at day 7, 43.5±38.5 at day 14 and 28.2±18.3 at month 1(all P<0.05), returning at levels similar to baseline ones at month 3 and month 6(respectively 16.7±6.2 and 12.8±10.2, both P>0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth(R=-0.568, P=0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.展开更多
Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque dest...Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.展开更多
In this paper,a resilient distributed control scheme against replay attacks for multi-agent networked systems subject to input and state constraints is proposed.The methodological starting point relies on a smart use ...In this paper,a resilient distributed control scheme against replay attacks for multi-agent networked systems subject to input and state constraints is proposed.The methodological starting point relies on a smart use of predictive arguments with a twofold aim:1)Promptly detect malicious agent behaviors affecting normal system operations;2)Apply specific control actions,based on predictive ideas,for mitigating as much as possible undesirable domino effects resulting from adversary operations.Specifically,the multi-agent system is topologically described by a leader-follower digraph characterized by a unique leader and set-theoretic receding horizon control ideas are exploited to develop a distributed algorithm capable to instantaneously recognize the attacked agent.Finally,numerical simulations are carried out to show benefits and effectiveness of the proposed approach.展开更多
1 The need to extend and expand the maternal,neonatal and child health (MNCH) continuum to include preconception health The provision of care along the MNCH continuum is currently the core strategy for reducing m...1 The need to extend and expand the maternal,neonatal and child health (MNCH) continuum to include preconception health The provision of care along the MNCH continuum is currently the core strategy for reducing maternal,neonatal and infant mortality [1-5]. Yet,gaps in the MNCH continuum persist. Reductions in maternal mortality have stagnated in many parts of the world. With the lowering of infant and child mortality,approximately 40% of infant deaths now occur in the neonatal period [6]. Strong scientific evidence indicates that improving women's health before pregnancy would result in better maternal and neonatal health outcomes-specifically,fewer pregnancy complications and a reduction in rates of birth defects,fetal loss,low birth weight and preterm delivery [7]. The WHO estimates that 19% of all maternal deaths are due indirectly to preexisting medical conditions [8]. Furthermore,early prenatal care is too late to prevent many adverse birth outcomes,as organogenesis is completed during the critical first weeks of pregnancy,often before a woman knows that she is pregnant [9]. There is a clear need to strengthen preconception health services.展开更多
Hepatocellular carcinoma(HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progres...Hepatocellular carcinoma(HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progressive increase in the number of scientific studies on this topic. MicroRNAs(miRNAs) are small noncoding RNA that play a role in almost all main cellular pathways. miRNAs are involved in the regulation of expression of the major tumor-related genes in carcinogenesis, acting as oncogenes or tumor suppressor genes. The aim of this review was to identify papers published in 2017 investigating the role of miRNAs in HCC tumorigenesis. miRNAs were classified according to their role in the main molecular pathways involved in HCC tumorigenesis:(1) m TOR;(2) Wnt;(3) JAK/STAT;(4) apoptosis; and(5) MAPK. The role of miRNAs in prognosis/response prediction was taken into consideration. Bearing in mind that the analysis of miRNAs in serum and other body fluids would be crucial for clinical management, the role of circulating miRNAs in HCC patients was also investigated. The most represented mi RNA-regulated pathway in HCC is m TOR, but apoptosis, Wnt, JAK/STAT or MAPK pathways are also influenced by mi RNA expression levels. These miRNAs could thus be used in clinical practice as diagnostic, prognostic or therapeutic targets for HCC treatment.展开更多
Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury(AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. A...Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury(AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. After AKI, inflammation, oxidative stress and excessive deposition of extracellular matrix are the molecular events that ultimately cause the end-stage renal disease. Despite numerous improvement of supportive therapy, the mortality and morbidity among patients remain high. Therefore, exploring novel therapeutic options to treat AKI is mandatory. Numerous evidence in animal models has demonstrated the capability of mesenchymal stem cells(MSCs) to restore kidney function after induced kidney injury. After infusion, MSCs engraft in the injured tissue and release soluble factors and microvesicles that promote cell survival and tissue repairing. Indeed, the main mechanism of action of MSCs in tissue regeneration is the paracrine/endocrine secretion of bioactive molecules. MSCs can be isolated from several tissues, including bone marrow, adipose tissue, and blood cord; pre-treatment procedures to improve MSCs homing and their paracrine function have been also described. This review will focus on the application of cell therapy in AKI and it will summarize preclinical studies in animal models and clinical trials currently ongoing about the use of mesenchymal stem cells after AKI.展开更多
Multi-agent systems are usually equipped with open communication infrastructures to improve interactions efficiency,reliability and sustainability.Although technologically costeffective,this makes them vulnerable to c...Multi-agent systems are usually equipped with open communication infrastructures to improve interactions efficiency,reliability and sustainability.Although technologically costeffective,this makes them vulnerable to cyber-attacks with potentially catastrophic consequences.To this end,we present a novel control architecture capable to deal with the distributed constrained regulation problem in the presence of time-delay attacks on the agents’communication infrastructure.The basic idea consists of orchestrating the interconnected cyber-physical system as a leader-follower configuration so that adequate control actions are computed to isolate the attacked unit before it compromises the system operations.Simulations on a multi-area power system confirm that the proposed control scheme can reconfigure the leader-follower structure in response to denial ofservice(DoS)attacks.展开更多
Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy ...Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic(and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and(intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integratingendoscopy, serology, histology and molecular profiling.展开更多
Rhythmic oscillatory patterns sustain cellular dynamics,driving the concerted action of regulatory molecules,microtubules,and molecular motors.We describe cellular microtubules as oscillators capable of synchronizatio...Rhythmic oscillatory patterns sustain cellular dynamics,driving the concerted action of regulatory molecules,microtubules,and molecular motors.We describe cellular microtubules as oscillators capable of synchronization and swarming,generating mechanical and electric patterns that impact biomolecular recognition.We consider the biological relevance of seeing the inside of cells populated by a network of molecules that behave as bioelectronic circuits and chromophores.We discuss the novel perspectives disclosed by mechanobiology,bioelectromagnetism,and photobiomodulation,both in term of fundamental basic science and in light of the biomedical implication of using physical energies to govern(stem)cell fate.We focus on the feasibility of exploiting atomic force microscopy and hyperspectral imaging to detect signatures of nanomotions and electromagnetic radiation(light),respectively,generated by the stem cells across the specification of their multilineage repertoire.The chance is reported of using these signatures and the diffusive features of physical waves to direct specifically the differentiation program of stem cells in situ,where they already are resident in all the tissues of the human body.We discuss how this strategy may pave the way to a regenerative and precision medicine without the needs for(stem)cell or tissue transplantation.We describe a novel paradigm based upon boosting our inherent ability for self-healing.展开更多
HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit fro...HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs such as Trastuzumab. This manuscript focuses on HER2 in gastric carcinogenesis, on optimal evaluation of HER2 and on the possible causes which may contribute to inaccurate HER2 evaluation. Similarly to breast cancer HER2 evaluation, standardization of HER2 testing in gastric cancer is necessary in diagnostic practice. The three principle aspects which require consideration are:(1) the choice of sample with regards to cancer morphology- intestinal vs diffuse areas;(2) the choice of scoring criteria- use of HER2 scoring criteria specific for gastric cancer; and(3) the choice of HER2 evaluation methods- use of an algorithm in which both immunohistochemistry and in situ hybridization play a role. Problematic issues include:(1) pre-analytic variables with particular emphasis on fixation;(2) recommended methodology for HER2 assessment(immunohistochemistry vs in situ hybridization);(3) HER2 heterogeneity both within the primary tumor and between primary tumor and metastases;(4) reliability of biopsies in HER 2 evaluation; and(5) quantity of sample(FFPE blocks from surgical specimens or endoscopic biopsies) necessary for an adequate assessment.展开更多
Long-term epilepsy associated tumors(LEAT) represent a well known cause of focal epilepsies. Glioneuronaltumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most c...Long-term epilepsy associated tumors(LEAT) represent a well known cause of focal epilepsies. Glioneuronaltumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly ariseing in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic networkwith complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation.展开更多
BACKGROUND The therapeutic approach of metastatic renal cell carcinoma(RCC)represents a real challenge for clinicians,because of the variable clinical course;the recent availability of numerous targeted therapies that...BACKGROUND The therapeutic approach of metastatic renal cell carcinoma(RCC)represents a real challenge for clinicians,because of the variable clinical course;the recent availability of numerous targeted therapies that have significantly improved overall oncological results,but still with a low percentage of complete responses;and the increasing role of metastasectomy(MSX)as an effective strategy to achieve a durable cure,or at least defer initiation of systemic therapies,in selected patients and in the context of multimodality treatment strategies.CA^E SUMMARY We report here the case of a 40-year-old man who was referred to our unit in November 2004 with lung and mediastinal lymph nodes metastases identified during periodic surveillance 6 years after a radical nephrectomy for RCC;he underwent MSX of multiple lung nodules and mediastinal lymphadenectomy,with subsequent systemic therapy with Fluorouracil,Interferon-alpha and Interleukin 2.The subsequent clinical course was characterized by multiple sequential abdominal and thoracic recurrences,successfully treated with multiple systemic treatments,repeated local treatments,including two pancreatic resections,conservative resection and ablation of multiple bilobar liver metastases,resection and stereotactic body radiotherapy of multiple lung metastases.He is alive without evidence of recurrence 20 years after initial nephrectomy and sequential treatment of recurrences in multiple sites,including resection of more than 38 metastases,and 5 years after his last MSX.CONCLUSION This case highlights that effective multimodality therapeutic strategies,including multiple systemic treatments and iterative aggressive surgical resection,can be safely performed with long-term survival in selected patients with multiple metachronous sequential metastases from RCC.展开更多
基金Funding Statement:This research was conducted as part of the Tech4You Project“Technologies for climate change adaptation and quality of life improvement”,n.ECS0000009,CUP H23C22000370006,Italian PNRR,Mission 4,Component 2,Investment 1.5 funded by the European Union-NextGenerationEU.
文摘Indoor air quality(IAQ)is often overlooked,yet a poorly maintained environment can lead to significant health issues and reduced concentration and productivity in work or educational settings.This study presents an innovative control system for mechanical ventilation specifically designed for university classrooms,with the dual goal of enhancing IAQ and increasing energy efficiency.Two classrooms with distinct construction characteristics were analyzed:one with exterior walls and windows,and the other completely underground.For each classroom,a model was developed using DesignBuilder software,which was calibrated with experimental data regarding CO_(2) concentration,temperature,and relative humidity levels.The proposed ventilation system operates based on CO_(2) concentration,relative humidity,and potential for free heating and cooling.In addition,the analysis was conducted for other locations,demonstrating consistent energy savings across different climates and environments,always showing an annual reduction in energy consumption.Results demonstrate that mechanical ventilation,when integrated with heat recovery and free cooling strategies,significantly reduces energy consumption by up to 25%,while also maintaining optimal CO_(2) levels to enhance comfort and air quality.These findings emphasize the essential need for well-designed mechanical ventilation systems to ensure both psychophysical well-being and IAQ in enclosed spaces,particularly in environments intended for extended occupancy,such as classrooms.Furthermore,this approach has broad applicability,as it could be adapted to various building types,thereby contributing to sustainable energy management practices and promoting healthier indoor spaces.This study serves as a model for future designs aiming to balance energy efficiency with indoor air quality,especially relevant in the post-COVID era,where the importance of indoor air quality has become more widely recognized.
文摘Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.
基金the Department of Informatics,Modeling,Electronics and Systems(DIMES)University of Calabria(Grant/Award Number:SIMPATICO_ZUMPANO).
文摘A consumption of 46.9 million tons of processed tomatoes was reported in 2022 which is merely 20%of the total consumption.An increase of 3.3%in consumption is predicted from 2024 to 2032.Tomatoes are also rich in iron,potassium,antioxidant lycopene,vitamins A,C and K which are important for preventing cancer,and maintaining blood pressure and glucose levels.Thus,tomatoes are globally important due to their widespread usage and nutritional value.To face the high demand for tomatoes,it is mandatory to investigate the causes of crop loss and minimize them.Diseases are one of the major causes that adversely affect crop yield and degrade the quality of the tomato fruit.This leads to financial losses and affects the livelihood of farmers.Therefore,automatic disease detection at any stage of the tomato plant is a critical issue.Deep learning models introduced in the literature show promising results,but the models are difficult to implement on handheld devices such as mobile phones due to high computational costs and a large number of parameters.Also,most of the models proposed so far work efficiently for images with plain backgrounds where a clear demarcation exists between the background and leaf region.Moreover,the existing techniques lack in recognizing multiple diseases on the same leaf.To address these concerns,we introduce a customized deep learning-based convolution vision transformer model.Themodel achieves an accuracy of 93.51%for classifying tomato leaf images with plain as well as complex backgrounds into 13 categories.It requires a space storage of merely 5.8 MB which is 98.93%,98.33%,and 92.64%less than stateof-the-art visual geometry group,vision transformers,and convolution vision transformermodels,respectively.Its training time of 44 min is 51.12%,74.12%,and 57.7%lower than the above-mentioned models.Thus,it can be deployed on(Internet of Things)IoT-enabled devices,drones,or mobile devices to assist farmers in the real-time monitoring of tomato crops.The periodicmonitoring promotes timely action to prevent the spread of diseases and reduce crop loss.
文摘Environmental monitoring of airborne formaldehyde (FA) using sensitive methodologies is fundamental to prevent health risks. The objective of this study was to compare three different FA monitoring methods during the daily activities of an anatomic pathology laboratory. Daily eight-hour measurements deriving from Radiello® passive diffusive samplers (PDS), NEMo XT continuous optical sensor (COS), and multi-gas 1512 photoacoustic monitor (MPM) were simultaneously compared over a period of 14 working days. Given the different daily distributions of the measurements performed by the three devices, all measurements were time-aligned for comparison purposes. The 95% limit of agreement (LOA) method was applied to estimate the degree of concordance of each device with respect to the others. Formaldehyde arithmetic mean measured using PDS was 32.6 ± 10.4 ppb (range: 19.8 - 62.7). The simultaneous measures performed by COS and MPM were respectively 42.4 ± 44.8 ppb (range: 7.0 - 175.0) and 189.0 ± 163.7 ppb (range: 40.0 - 2895.4). The MPM geometric mean (171.3 ppb) was approximately five times higher than those derived from COS (32.3 ppb) and PDS (31.4 ppb). The results of the LOA method applied to log-transformed FA data showed the same systematic discrepancies between MPM and the other two devices. A good agreement between PDS and COS could lead to a tailored approach according to the individual specificity of these techniques. This tool may be useful for accurately assessing the risk of FA exposure among healthcare workers. However, the limited specificity of the MPM does not support its use as a monitoring method for FA in the workplace.
基金This study was supported by a grant from the Italian Ministry of Health,Ricerca Corrente Program 2016-2018 to Paola Parente.
文摘To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA),choledocus extrapancreatic cholangiocarcinoma(EPCCA)and choledocus intrapancreatic cholangiocarcinoma(IPCCA)and,finally,gallbladder carcinoma(GBCCA).CCAs are relatively uncommon but.
文摘This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty(UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes(Eye OP1). After treatment, the mean intraocular pressure(IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6(all P<0.001). Mean laser flare-cell photometry value steeply increased after surgery from 12.1±7.5 to 64.1±53.9 ph/ms(P=0.001) at day 1, and then progressively decreased to respectively 60.6±49.7 at day 7, 43.5±38.5 at day 14 and 28.2±18.3 at month 1(all P<0.05), returning at levels similar to baseline ones at month 3 and month 6(respectively 16.7±6.2 and 12.8±10.2, both P>0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth(R=-0.568, P=0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.
基金Supported by FORICA(the FOundation for Advanced Research in Hypertension and Cardiovascular diseases,www.forica.it)
文摘Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.
文摘In this paper,a resilient distributed control scheme against replay attacks for multi-agent networked systems subject to input and state constraints is proposed.The methodological starting point relies on a smart use of predictive arguments with a twofold aim:1)Promptly detect malicious agent behaviors affecting normal system operations;2)Apply specific control actions,based on predictive ideas,for mitigating as much as possible undesirable domino effects resulting from adversary operations.Specifically,the multi-agent system is topologically described by a leader-follower digraph characterized by a unique leader and set-theoretic receding horizon control ideas are exploited to develop a distributed algorithm capable to instantaneously recognize the attacked agent.Finally,numerical simulations are carried out to show benefits and effectiveness of the proposed approach.
文摘1 The need to extend and expand the maternal,neonatal and child health (MNCH) continuum to include preconception health The provision of care along the MNCH continuum is currently the core strategy for reducing maternal,neonatal and infant mortality [1-5]. Yet,gaps in the MNCH continuum persist. Reductions in maternal mortality have stagnated in many parts of the world. With the lowering of infant and child mortality,approximately 40% of infant deaths now occur in the neonatal period [6]. Strong scientific evidence indicates that improving women's health before pregnancy would result in better maternal and neonatal health outcomes-specifically,fewer pregnancy complications and a reduction in rates of birth defects,fetal loss,low birth weight and preterm delivery [7]. The WHO estimates that 19% of all maternal deaths are due indirectly to preexisting medical conditions [8]. Furthermore,early prenatal care is too late to prevent many adverse birth outcomes,as organogenesis is completed during the critical first weeks of pregnancy,often before a woman knows that she is pregnant [9]. There is a clear need to strengthen preconception health services.
文摘Hepatocellular carcinoma(HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progressive increase in the number of scientific studies on this topic. MicroRNAs(miRNAs) are small noncoding RNA that play a role in almost all main cellular pathways. miRNAs are involved in the regulation of expression of the major tumor-related genes in carcinogenesis, acting as oncogenes or tumor suppressor genes. The aim of this review was to identify papers published in 2017 investigating the role of miRNAs in HCC tumorigenesis. miRNAs were classified according to their role in the main molecular pathways involved in HCC tumorigenesis:(1) m TOR;(2) Wnt;(3) JAK/STAT;(4) apoptosis; and(5) MAPK. The role of miRNAs in prognosis/response prediction was taken into consideration. Bearing in mind that the analysis of miRNAs in serum and other body fluids would be crucial for clinical management, the role of circulating miRNAs in HCC patients was also investigated. The most represented mi RNA-regulated pathway in HCC is m TOR, but apoptosis, Wnt, JAK/STAT or MAPK pathways are also influenced by mi RNA expression levels. These miRNAs could thus be used in clinical practice as diagnostic, prognostic or therapeutic targets for HCC treatment.
文摘Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury(AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. After AKI, inflammation, oxidative stress and excessive deposition of extracellular matrix are the molecular events that ultimately cause the end-stage renal disease. Despite numerous improvement of supportive therapy, the mortality and morbidity among patients remain high. Therefore, exploring novel therapeutic options to treat AKI is mandatory. Numerous evidence in animal models has demonstrated the capability of mesenchymal stem cells(MSCs) to restore kidney function after induced kidney injury. After infusion, MSCs engraft in the injured tissue and release soluble factors and microvesicles that promote cell survival and tissue repairing. Indeed, the main mechanism of action of MSCs in tissue regeneration is the paracrine/endocrine secretion of bioactive molecules. MSCs can be isolated from several tissues, including bone marrow, adipose tissue, and blood cord; pre-treatment procedures to improve MSCs homing and their paracrine function have been also described. This review will focus on the application of cell therapy in AKI and it will summarize preclinical studies in animal models and clinical trials currently ongoing about the use of mesenchymal stem cells after AKI.
文摘Multi-agent systems are usually equipped with open communication infrastructures to improve interactions efficiency,reliability and sustainability.Although technologically costeffective,this makes them vulnerable to cyber-attacks with potentially catastrophic consequences.To this end,we present a novel control architecture capable to deal with the distributed constrained regulation problem in the presence of time-delay attacks on the agents’communication infrastructure.The basic idea consists of orchestrating the interconnected cyber-physical system as a leader-follower configuration so that adequate control actions are computed to isolate the attacked unit before it compromises the system operations.Simulations on a multi-area power system confirm that the proposed control scheme can reconfigure the leader-follower structure in response to denial ofservice(DoS)attacks.
基金Supported by A grant from the Italian Association for Cancer Research(partly,AIRC Regional grant 2008 No.6421)published under the auspices of the Healthy Stomach Initiative(HIS)
文摘Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic(and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and(intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integratingendoscopy, serology, histology and molecular profiling.
文摘Rhythmic oscillatory patterns sustain cellular dynamics,driving the concerted action of regulatory molecules,microtubules,and molecular motors.We describe cellular microtubules as oscillators capable of synchronization and swarming,generating mechanical and electric patterns that impact biomolecular recognition.We consider the biological relevance of seeing the inside of cells populated by a network of molecules that behave as bioelectronic circuits and chromophores.We discuss the novel perspectives disclosed by mechanobiology,bioelectromagnetism,and photobiomodulation,both in term of fundamental basic science and in light of the biomedical implication of using physical energies to govern(stem)cell fate.We focus on the feasibility of exploiting atomic force microscopy and hyperspectral imaging to detect signatures of nanomotions and electromagnetic radiation(light),respectively,generated by the stem cells across the specification of their multilineage repertoire.The chance is reported of using these signatures and the diffusive features of physical waves to direct specifically the differentiation program of stem cells in situ,where they already are resident in all the tissues of the human body.We discuss how this strategy may pave the way to a regenerative and precision medicine without the needs for(stem)cell or tissue transplantation.We describe a novel paradigm based upon boosting our inherent ability for self-healing.
文摘HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs such as Trastuzumab. This manuscript focuses on HER2 in gastric carcinogenesis, on optimal evaluation of HER2 and on the possible causes which may contribute to inaccurate HER2 evaluation. Similarly to breast cancer HER2 evaluation, standardization of HER2 testing in gastric cancer is necessary in diagnostic practice. The three principle aspects which require consideration are:(1) the choice of sample with regards to cancer morphology- intestinal vs diffuse areas;(2) the choice of scoring criteria- use of HER2 scoring criteria specific for gastric cancer; and(3) the choice of HER2 evaluation methods- use of an algorithm in which both immunohistochemistry and in situ hybridization play a role. Problematic issues include:(1) pre-analytic variables with particular emphasis on fixation;(2) recommended methodology for HER2 assessment(immunohistochemistry vs in situ hybridization);(3) HER2 heterogeneity both within the primary tumor and between primary tumor and metastases;(4) reliability of biopsies in HER 2 evaluation; and(5) quantity of sample(FFPE blocks from surgical specimens or endoscopic biopsies) necessary for an adequate assessment.
文摘Long-term epilepsy associated tumors(LEAT) represent a well known cause of focal epilepsies. Glioneuronaltumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly ariseing in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic networkwith complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation.
文摘BACKGROUND The therapeutic approach of metastatic renal cell carcinoma(RCC)represents a real challenge for clinicians,because of the variable clinical course;the recent availability of numerous targeted therapies that have significantly improved overall oncological results,but still with a low percentage of complete responses;and the increasing role of metastasectomy(MSX)as an effective strategy to achieve a durable cure,or at least defer initiation of systemic therapies,in selected patients and in the context of multimodality treatment strategies.CA^E SUMMARY We report here the case of a 40-year-old man who was referred to our unit in November 2004 with lung and mediastinal lymph nodes metastases identified during periodic surveillance 6 years after a radical nephrectomy for RCC;he underwent MSX of multiple lung nodules and mediastinal lymphadenectomy,with subsequent systemic therapy with Fluorouracil,Interferon-alpha and Interleukin 2.The subsequent clinical course was characterized by multiple sequential abdominal and thoracic recurrences,successfully treated with multiple systemic treatments,repeated local treatments,including two pancreatic resections,conservative resection and ablation of multiple bilobar liver metastases,resection and stereotactic body radiotherapy of multiple lung metastases.He is alive without evidence of recurrence 20 years after initial nephrectomy and sequential treatment of recurrences in multiple sites,including resection of more than 38 metastases,and 5 years after his last MSX.CONCLUSION This case highlights that effective multimodality therapeutic strategies,including multiple systemic treatments and iterative aggressive surgical resection,can be safely performed with long-term survival in selected patients with multiple metachronous sequential metastases from RCC.
