Non-ionic deep eutectic solvents(DESs)are non-ionic designer solvents with various applications in catalysis,extraction,carbon capture,and pharmaceuticals.However,discovering new DES candidates is challenging due to a...Non-ionic deep eutectic solvents(DESs)are non-ionic designer solvents with various applications in catalysis,extraction,carbon capture,and pharmaceuticals.However,discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES formation.The search for DES relies heavily on intuition or trial-and-error processes,leading to low success rates or missed opportunities.Recognizing that hydrogen bonds(HBs)play a central role in DES formation,we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning(ML)models to discover new DES systems.We first analyze the HB properties of 38 known DES and 111 known non-DES systems using their molecular dynamics(MD)simulation trajectories.The analysis reveals that DES systems have two unique features compared to non-DES systems:The DESs have①more imbalance between the numbers of the two intra-component HBs and②more and stronger inter-component HBs.Based on these results,we develop 30 ML models using ten algorithms and three types of HB-based descriptors.The model performance is first benchmarked using the average and minimal receiver operating characteristic(ROC)-area under the curve(AUC)values.We also analyze the importance of individual features in the models,and the results are consistent with the simulation-based statistical analysis.Finally,we validate the models using the experimental data of 34 systems.The extra trees forest model outperforms the other models in the validation,with an ROC-AUC of 0.88.Our work illustrates the importance of HBs in DES formation and shows the potential of ML in discovering new DESs.展开更多
The pyramid wavefront sensor(PWFS)can provide the sensitivity needed for demanding adaptive optics applications,such as imaging exoplanets using the future extremely large telescopes of over 30 m of diameter(D).Howeve...The pyramid wavefront sensor(PWFS)can provide the sensitivity needed for demanding adaptive optics applications,such as imaging exoplanets using the future extremely large telescopes of over 30 m of diameter(D).However,its exquisite sensitivity has a limited linear range of operation,or dynamic range,although it can be extended through the use of beam modulation—despite sacrificing sensitivity and requiring additional optical hardware.Inspired by artificial intelligence techniques,this work proposes to train an optical layer—comprising a passive diffractive element placed at a conjugated Fourier plane of the pyramid prism—to boost the linear response of the pyramid sensor without the need for cumbersome modulation.We develop an end-2-end simulation to train the diffractive element,which acts as an optical preconditioner to the traditional least-square modal phase estimation process.Simulation results with a large range of turbulence conditions show a noticeable improvement in the aberration estimation performance equivalent to over 3λ∕D of modulation when using the optically preconditioned deep PWFS(DPWFS).Experimental results validate the advantages of using the designed optical layer,where the DPWFS can pair the performance of a traditional PWFS with 2λ∕D of modulation.Designing and adding an optical preconditioner to the PWFS is just the tip of the iceberg,since the proposed deep optics methodology can be used for the design of a completely new generation of wavefront sensors that can better fit the demands of sophisticated adaptive optics applications such as ground-to-space and underwater optical communications and imaging through scattering media.展开更多
At present,it is impossible to deny the existence of artificial intelligence in various areas of social life,understood as the simulation of expert human intelligence from computer processes that involve learning,reas...At present,it is impossible to deny the existence of artificial intelligence in various areas of social life,understood as the simulation of expert human intelligence from computer processes that involve learning,reasoning,and self-correction,its benefits to the medical field,in particular,are innumerable,but their incorporation into health systems has been gradual for many reasons.According to the above,this research analyzed artificial intelligence based on resilient leadership in the health sector,for which qualitative research was carried out with a documentary-bibliographic design with printed and electronic documentary sources with theoretical contributions fromÁvila,Mayer,and Quesada[1],Morgan[2],Villa[3],and Finol[4],among others.It is highlighted that resilient leadership has become a strategic factor in all organizations,since times of uncertainty and changes lead institutions to properly manage the incorporation of technologies specifically AI,achieving in this way that the centers and professionals in the field of health assume the needs of the contexts and the innovations of the same.It is concluded that resilient leadership will allow artificial intelligence in the health sector to generate higher levels of learning and adaptability to the transformations that are necessary,whose resistance would make its application difficult and in the long run it will leave behind professionals who refuse to assume the contributions of these innovative techniques in medical practice.展开更多
Macadamia nuts (Macadamia integrifolia) grown in Venezuela have showed an average total fat content of 70%. Oleic acid (18:1) was the main monounsaturated fatty acid (MUFA) (51.3%), followed by palmitoleic acid (16:1,...Macadamia nuts (Macadamia integrifolia) grown in Venezuela have showed an average total fat content of 70%. Oleic acid (18:1) was the main monounsaturated fatty acid (MUFA) (51.3%), followed by palmitoleic acid (16:1, 22.6%). The content of polyunsaturated fatty acids (PUFAs), C18:2 and C18:3 represented 5.4%. Thus, MUFAs and PUFAs together constituted more than 80% of the total fatty acids present. Trans-vaccenic acid was also present (3%). As regards to other phytochemical compounds, tocopherols and tocotrienols were not found in the sample, but the presence of squalene was detected.The antioxidant activity (44.2%) of the extract was produced by the phytochemicals present.展开更多
Control of nonlinear systems is challenging in realtime.Decision making,performed many times per second,must ensure system safety.Designing input to perform a task often involves solving a nonlinear system of differen...Control of nonlinear systems is challenging in realtime.Decision making,performed many times per second,must ensure system safety.Designing input to perform a task often involves solving a nonlinear system of differential equations,which is a computationally intensive,if not intractable problem.This article proposes sampling-based task learning for controlaffine nonlinear systems through the combined learning of both state and action-value functions in a model-free approximate value iteration setting with continuous inputs.A quadratic negative definite state-value function implies the existence of a unique maximum of the action-value function at any state.This allows the replacement of the standard greedy policy with a computationally efficient policy approximation that guarantees progression to a goal state without knowledge of the system dynamics.The policy approximation is consistent,i.e.,it does not depend on the action samples used to calculate it.This method is appropriate for mechanical systems with high-dimensional input spaces and unknown dynamics performing Constraint-Balancing Tasks.We verify it both in simulation and experimentally for an Unmanned Aerial Vehicles(UAVs) carrying a suspended load,and in simulation,for the rendezvous of heterogeneous robots.展开更多
Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver ... Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver transplantation and major hepatic resection. For these reasons, numerous PC strategies have been evaluated in experimental models of ischemia-reperfusion liver injury, which have not been transferred to clinical application due to side effects, toxicity and difficulties in implementation, with the exception of the controversial ischemic PC. In recent years, our group has undertaken the assessment of alternate experimental liver PC protocols that might have application in the clinical setting. These include thyroid hormone (T3), n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), or iron, which suppressed liver damage due to the 1 h ischemia-20 h reperfusion protocol. T3, n-3 LCPUFA and iron are hormetic agents that trigger biologically beneficial effects in the low-dose range, whose multifactorial mechanisms of action are discussed in the work.展开更多
Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Me...Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.展开更多
The current study is based on the DEM computer simulation of three experimental test devices with different dimensions to determine the difference in the results of the formation of shear and repose angles that the pa...The current study is based on the DEM computer simulation of three experimental test devices with different dimensions to determine the difference in the results of the formation of shear and repose angles that the particles experience when grouped under the action of the gravitational force. In this respect, the experimental test devices with different height, width, and depth were geometrically modeled with iron pellet particles using morphology and a granulometric variation from 6 mm to 9 mm of equivalent diameter in its spherical shape. Depending on the results obtained, a reliable size of the experimental test device will be available to obtain the necessary data for a correct adjustment of the calibration parameters for the DEM simulation of mining-metallurgical processes that use granulated material of iron pellet.展开更多
Arsenic (As) is the most important contaminant of the environment in northern Chile. The purpose of the present work is to study As-toxicity symptoms on Lupino microcarpus (lupine), an annual legume plant that constit...Arsenic (As) is the most important contaminant of the environment in northern Chile. The purpose of the present work is to study As-toxicity symptoms on Lupino microcarpus (lupine), an annual legume plant that constitutes part of the desert community of the pre-Andean area of the Antofagasta Region, Chile. This plant species is cultivated in As-agricultural soil collected from Chiu Chiu (northern Chile) which is classified as arid soils. Control soil (0 - 20 cm depth) is collected from an area located in the central zone of Chile, which is classified as molli soil. The main physic-chemical characteristics of As-soil and the control soil are determined. Eighteen plastic pots of 1.6 L (fifteen for experimental and three for control) are filled with As-soil and control soil treatments. Two plants are cultivated in each pot and then separated leaves and roots for As-analysis. Visual As-toxicity symptoms such as foliar chlorosis, necrosis of the leaf tips and margins, leaf wilting and stunted are determined. Total As concentrations in soils where lupine is cultivated, reach levels between 5.3 - 14.2 mg·kg<sup>-1</sup> d.w. (control soil As-level: 3.1 mg·kg<sup>-1</sup>). Roots show higher As-concentration than leaves, both experimental plants as control plants (2.28 - 9.1 mg·kg<sup>-1</sup> d.w., and 0.76 mg·kg<sup>-1</sup> d.w., respectively) and low values of transport index (TI) (0.16 - 0.34). All of visual As-toxicity symptoms determined is showed by lupin cultivated in As-agricultural soils. Neither control lupin plant suffers any toxicity symptoms. The results indicate that lupine plants do not resist contamination and accumulated higher levels of As in roots. Lupine can be used in the phytostabilisation of As immobilizing it by microbial activity in agricultural soil.展开更多
In this paper, the generation and control of turbulences in a wind tunnel, for design, analysis and testing of test objects are proposed. Modifications to the wind tunnel are made in order to generate the turbulences ...In this paper, the generation and control of turbulences in a wind tunnel, for design, analysis and testing of test objects are proposed. Modifications to the wind tunnel are made in order to generate the turbulences in the test chamber. Specifically, for the turbulence analysis, the reflective symmetry concept is used in order to group the different turbulences cases generated in the wind tunnel test chamber. The Ansys software is used in order to model and analyze the wind tunnel. Specific platform or module known as Fluent is used for the analysis of the turbulence generated in the wind tunnel. To design proposal of a wind tunnel capable to generate and controlling turbulences is exposed in this paper. For this, the controller design and verification are performed by means of simulations. To obtain the control law structure, the inversion concept is used. The proposed control law is validated via a co-simulation implemented in the Simplorer module, with the aim of combining the power electronics part, controller and engine, with the proposed model wind tunnel.展开更多
It is not common to start suffering from syncopes after age 50. They are mainly male patients who present causes other than vasovagal syncope, which predominates at an early age. Orthostatic hypotension is the predomi...It is not common to start suffering from syncopes after age 50. They are mainly male patients who present causes other than vasovagal syncope, which predominates at an early age. Orthostatic hypotension is the predominant causal factor, which is attributed in many cases to advanced age, metabolic, cardiovascular or neurological diseases, to failure of baroreflexes, all of the above may be associated with the use of hypotensive drugs alone or in combination with psychotropic drugs. Furthermore, causes such as carotid sinus syncope, postprandial syncope and situational syncope become more frequent. Therefore, as people age, they present a favorable pathological terrain for the production of syncope. The older you are, the more likely you are to start with syncope. Finding the definitive diagnosis for their syncopes can be difficult, given the multiplicity of interacting factors. Their study is more exhaustive and requires a good anamnesis, knowing the drugs used by the patient, concomitant diseases and careful surveillance to get closer to the diagnosis.展开更多
Background:Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders.Effective therapeutic strategies are an unmet need for these disorder...Background:Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders.Effective therapeutic strategies are an unmet need for these disorders.Polyphenols,such as quercetin and resveratrol,are plant-derived compounds that activate sirtuins(SIRTs)and have shown promising results in some models of neuronal death,although their effects have been scarcely tested in models of motor neuron degeneration.Methods:In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA)into the rat spinal cord tissue.Quercetin and resveratrol were co-infused with AMPA and motor behavior and muscle strength were assessed daily for up to ten days.Then,animals were fixed and lumbar spinal cord tissue was analyzed by histological and immunocytological procedures.Results:We found that the chronic infusion of AMPA[1 mM]caused a progressive motor neuron degeneration,accompanied by astrogliosis and microgliosis,and motor deficits and paralysis of the rear limbs.Quercetin infusion ameliorated AMPA-induced paralysis,rescued motor neurons,and prevented both astrogliosis and microgliosis,and these protective effects were prevented by EX527,a very selective SIRT1 inhibitor.In contrast,neither resveratrol nor EX527 alone improved motor behavior deficits or reduced motor neuron degeneration,albeit both reduced gliosis.Conclusions:These results suggest that quercetin exerts its beneficial effects through a SIRT1-mediated mechanism,and thus SIRT1 plays an important role in excitotoxic neurodegeneration and therefore its pharmacological modulation might provide opportunities for therapy in motor neuron disorders.展开更多
This study aims to monitor diagnostic accuracy amongst Jordanian mammography readers and identify parameters linked to higher levels of performance. In this study, we have used the Breast Screen Reader Assessment Stra...This study aims to monitor diagnostic accuracy amongst Jordanian mammography readers and identify parameters linked to higher levels of performance. In this study, we have used the Breast Screen Reader Assessment Strategy (BREAST) platform to facilitate 27 radiologists in reading a case set of 60 digital mammograms, 20 of which included cancers. Each case consisted of the four standard cranio-caudal (CC) and medio-lateral oblique (MLO) projections. All radiologists were registered to read mammograms at their workplace by the Jordanian Ministry of Health. Each reader was asked to locate any malignancies, provide a confidence rating using a scale of 1 - 5, and identify the type of appearance. All images were displayed using 8 MP monitor, supported by radiology workstations with full image manipulation facilities. Results were evaluated using Jackknife Alternative Free-Response Receiver Operating Characteristic (JAFROC). Demographics obtained from each radiologist regarding their experience, qualifications and breast-reading activities were correlated against JAFROC scores using Spearman techniques. The results showed that the mean JAFROC score was 0. 52 (95% confidence interval (CI): 0.46, 0.58);location sensitivity score was 0. 41 (95% CI: 0.41, 0.56);specificity score was 0.73 (95% CI: 0.68, 0.83). Higher performance in term of JAFROC scores was directly related to number of years since professional qualification (r = 0.433;p = 0.024), number of years reading breast images (r = 0.62;r = 0.001) and number of mammography images read per year (r = 0.69;p = 0.001). On the other hand, higher performance was inversely linked to the frequency of reading other modalities per week (r = -0.48;p = 0.010). No other statistical differences were significant. Finally, higher radiologists’ performance in cancer detection is correlated with increasing the number of mammograms reads per week.展开更多
Anabolic androgenic steroids (AAS) have several adverse effects on the cardiovascular system that may lead to a sudden cardiac death (SCD).We herein report a case involving a 24-year-old male,AAS abuser with intramusc...Anabolic androgenic steroids (AAS) have several adverse effects on the cardiovascular system that may lead to a sudden cardiac death (SCD).We herein report a case involving a 24-year-old male,AAS abuser with intramuscular delivery in the 6 months before,who suffered a cardiorespiratory arrest at home's bathtub when returning from New Year's party.A forensic autopsy was performed according to the guidelines of the Association for European Cardiovascular Pathology (AECVP).The body showed hypertrophy of skeletal musculature,with low amount of subcutaneous fat and no signs of injury (body mass index,BMh 26.8 kg/m^(2)).On internal examination,there were multiorgan congestion,acute pulmonary edema,and cardiomegaly (420 g) with severe coronary atherosclerosis and superimposed acute occlusive thrombosis at the left main trunk and left anterior descendant.Areas of scarring were located at the intersection between the posterior wall and the posterior third of the septum (postero-septal).At histology,acute myocardial infarction at the anterior third of the septum and the anterior wall,and subacute myocardial infarction at apical septum and apical posterior wall were detected.Other findings were small intramyocardial vessel disease and myocytes hypertrophy.Chemicotoxicological analysis in blood showed ethanol ((0.90 ±0.05) g/L),stanazolol (11.31 μg/L),nandrolone (2.05μg/L) and testosterone (<1.00μg/L).When confronted with a sudden death in a young athlete we must pay attention to the physical phenotype that may suggest AAS abuse and perform a detailed examination of the heart.Chemicotoxicological analysis is a key to establish the relationship between SCD and AAS abuse.展开更多
Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the o...Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the oxidative pathway, which generates acetaldehyde and involves the enzymes alcohol dehydrogenase and possibly cytochrome P4502E1. Additionally, ethanol can be metabolized via a nonoxidative pathway involving fatty acid ethyl ester synthases. Metabolism of ethanol by acinar and other pancreatic cells and the consequent generation of toxic metabolites, are postulated to play an important role in the development of alcohol-related acute and chronic pancreatic injury. This current work will review some recent advances in the knowledge about ethanol actions on the exocrine pancreas and its relationship to inflammatory disease and cancer.展开更多
Objective:To determine whether birth weights are lower at high altitudes,and whether gestational age at birth and a population’s length of residence mitigate the effect of high altitude. Methods:The birth weights of ...Objective:To determine whether birth weights are lower at high altitudes,and whether gestational age at birth and a population’s length of residence mitigate the effect of high altitude. Methods:The birth weights of 84,173 neonates recorded in the Peruvian Perinatal Information SystemDatabase were analyzed between 1995 and 2002 for the cities of Lima (150 m),Huancayo (3280 m),Cuzco (3400 m),and Juliaca (3800 m). Results:Birth weight was lower at high altitude,but there was no linear relation between altitude of residence and birth weight. Mean birth weight was higher in Juliaca than in Huancayo. There were no significant differences between the 4 cities regarding birth weights of infants born between 28 and 35 weeks of gestation. However,for infants born between 36 and 42 weeks,birth weight was lower at higher altitudes. This may be due to inadequate maternal oxygenation later in pregnancy at high altitude. In the multivariate analysis,after controlling for maternal age,marital status,parity,body mass index,pre-eclampsia or hemorrhage during pregnancy,and education,as well as sex of the newborn and gestational age at birth,birth weightwas lower in all cities located at a higher altitude than Lima. Yet,longer residence at high altitudes may play a protective role. Juliaca (3800 m),where the population has resided the longest,had the lowest reduction in birth weight compared with Lima (150 m); Cuzco had intermediate values; and Huancayo (3280 m),where the population has resided the shortest,had the highest reduction in birth weight. Conclusions:Birth weight reduction,which is independent of socioeconomic factors,occurs only in births at term and may be less severe in populations that have resided longer at high altitudes.展开更多
Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularizatio...Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.展开更多
During decades, gypsum has been employed as construction material for its versatility and particle size. In the present work, the possibility of developing gypsum panels with the incorporation of pumice and polypropyl...During decades, gypsum has been employed as construction material for its versatility and particle size. In the present work, the possibility of developing gypsum panels with the incorporation of pumice and polypropylene as alternative materials has been investigated. Pumice as well as polypropylene allows obtaining lighter panels than those on the market and with a lower production cost. Each one of these materials was characterized separately. In the case of gypsum and pumice, their granulometry, pH and humidity were determined, whereas polypropylene was characterized by a traction-deformation essay. Then, panels composition （gypsum and pumice concentration）, particle size, water temperature and the way polypropylene was added, was assessed. Panels with a 70% of gypsum, with a particle size of 198 btm and with polypropylene added in a laminar fashion, presented a compressive strength of 350 kPa, which accords to the norm ASTM 1396 and with market requirements. Finally, it was proposed a block diagram of the process for the fabrication of 100 kg/day of formulated panels.展开更多
The study was carried out in healthy Chilean volunteers in order to compare the pharmacokinetics （rate and extent absorption） of two commercial oral formulations of 50 mg hydrochlorothiazide. Thirty nine subjects we...The study was carried out in healthy Chilean volunteers in order to compare the pharmacokinetics （rate and extent absorption） of two commercial oral formulations of 50 mg hydrochlorothiazide. Thirty nine subjects were administered hydrochlorothiazide tablets of test （T） and reference （R） formulation in a single blind, randomized, fasting, 2 × 2 crossover study, seven washout days. Blood samples were taken during a 48 h period after drug administration. Plasma concentrations were quantified by HPLC-MS/MS. The primary parameters log-transformed Cmax （maximum plasma concentration）, A UC0-t and A UC0-∞ （area under the plasma concentration-time curve from zero to the last time and zero to infinity） were tested for bioequivalence considering the ratios of geometric means （test/reference）; whereas tmax （the time of maximum plasma concentration） was analyzed nonparametrically. The 90% confidence intervals for the geometric mean values of test/reference ratios for Cmax, A UCo.t and A UC0-∞ were 95.37%, 93.59% and 96.34%, respectively, and were located within the bioequivalence acceptance range of 80-125%, as were tmax and elimination constants. Together, we conclude that the test formulation of the hydrochlorothiazide 50 mg tablet is bioequivalent to the reference product and suitable for generic prescription.展开更多
基金supported by Ignite Research Collaborations(IRC),Startup funds,and the UK Artificial Intelligence(AI)in Medicine Research Alliance Pilot(NCATS UL1TR001998 and NCI P30 CA177558)。
文摘Non-ionic deep eutectic solvents(DESs)are non-ionic designer solvents with various applications in catalysis,extraction,carbon capture,and pharmaceuticals.However,discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES formation.The search for DES relies heavily on intuition or trial-and-error processes,leading to low success rates or missed opportunities.Recognizing that hydrogen bonds(HBs)play a central role in DES formation,we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning(ML)models to discover new DES systems.We first analyze the HB properties of 38 known DES and 111 known non-DES systems using their molecular dynamics(MD)simulation trajectories.The analysis reveals that DES systems have two unique features compared to non-DES systems:The DESs have①more imbalance between the numbers of the two intra-component HBs and②more and stronger inter-component HBs.Based on these results,we develop 30 ML models using ten algorithms and three types of HB-based descriptors.The model performance is first benchmarked using the average and minimal receiver operating characteristic(ROC)-area under the curve(AUC)values.We also analyze the importance of individual features in the models,and the results are consistent with the simulation-based statistical analysis.Finally,we validate the models using the experimental data of 34 systems.The extra trees forest model outperforms the other models in the validation,with an ROC-AUC of 0.88.Our work illustrates the importance of HBs in DES formation and shows the potential of ML in discovering new DESs.
基金Fondos de Desarrollo de la Astronomía Nacional(ALMA200008,QUIMAL220006)Agencia Nacional de Investigación y Desarrollo(ANILLO ATE220022,DOCTORADO NACIONAL 2022-21221399,ECOS200010,MAGISTER NACIONAL 2023-22230841,STIC2020004)Fondo Nacional de Desarrollo Científico y Tecnológico(EXPLORACION 13220234,POSTDOCTORADO 3220561)。
文摘The pyramid wavefront sensor(PWFS)can provide the sensitivity needed for demanding adaptive optics applications,such as imaging exoplanets using the future extremely large telescopes of over 30 m of diameter(D).However,its exquisite sensitivity has a limited linear range of operation,or dynamic range,although it can be extended through the use of beam modulation—despite sacrificing sensitivity and requiring additional optical hardware.Inspired by artificial intelligence techniques,this work proposes to train an optical layer—comprising a passive diffractive element placed at a conjugated Fourier plane of the pyramid prism—to boost the linear response of the pyramid sensor without the need for cumbersome modulation.We develop an end-2-end simulation to train the diffractive element,which acts as an optical preconditioner to the traditional least-square modal phase estimation process.Simulation results with a large range of turbulence conditions show a noticeable improvement in the aberration estimation performance equivalent to over 3λ∕D of modulation when using the optically preconditioned deep PWFS(DPWFS).Experimental results validate the advantages of using the designed optical layer,where the DPWFS can pair the performance of a traditional PWFS with 2λ∕D of modulation.Designing and adding an optical preconditioner to the PWFS is just the tip of the iceberg,since the proposed deep optics methodology can be used for the design of a completely new generation of wavefront sensors that can better fit the demands of sophisticated adaptive optics applications such as ground-to-space and underwater optical communications and imaging through scattering media.
文摘At present,it is impossible to deny the existence of artificial intelligence in various areas of social life,understood as the simulation of expert human intelligence from computer processes that involve learning,reasoning,and self-correction,its benefits to the medical field,in particular,are innumerable,but their incorporation into health systems has been gradual for many reasons.According to the above,this research analyzed artificial intelligence based on resilient leadership in the health sector,for which qualitative research was carried out with a documentary-bibliographic design with printed and electronic documentary sources with theoretical contributions fromÁvila,Mayer,and Quesada[1],Morgan[2],Villa[3],and Finol[4],among others.It is highlighted that resilient leadership has become a strategic factor in all organizations,since times of uncertainty and changes lead institutions to properly manage the incorporation of technologies specifically AI,achieving in this way that the centers and professionals in the field of health assume the needs of the contexts and the innovations of the same.It is concluded that resilient leadership will allow artificial intelligence in the health sector to generate higher levels of learning and adaptability to the transformations that are necessary,whose resistance would make its application difficult and in the long run it will leave behind professionals who refuse to assume the contributions of these innovative techniques in medical practice.
文摘Macadamia nuts (Macadamia integrifolia) grown in Venezuela have showed an average total fat content of 70%. Oleic acid (18:1) was the main monounsaturated fatty acid (MUFA) (51.3%), followed by palmitoleic acid (16:1, 22.6%). The content of polyunsaturated fatty acids (PUFAs), C18:2 and C18:3 represented 5.4%. Thus, MUFAs and PUFAs together constituted more than 80% of the total fatty acids present. Trans-vaccenic acid was also present (3%). As regards to other phytochemical compounds, tocopherols and tocotrienols were not found in the sample, but the presence of squalene was detected.The antioxidant activity (44.2%) of the extract was produced by the phytochemicals present.
文摘Control of nonlinear systems is challenging in realtime.Decision making,performed many times per second,must ensure system safety.Designing input to perform a task often involves solving a nonlinear system of differential equations,which is a computationally intensive,if not intractable problem.This article proposes sampling-based task learning for controlaffine nonlinear systems through the combined learning of both state and action-value functions in a model-free approximate value iteration setting with continuous inputs.A quadratic negative definite state-value function implies the existence of a unique maximum of the action-value function at any state.This allows the replacement of the standard greedy policy with a computationally efficient policy approximation that guarantees progression to a goal state without knowledge of the system dynamics.The policy approximation is consistent,i.e.,it does not depend on the action samples used to calculate it.This method is appropriate for mechanical systems with high-dimensional input spaces and unknown dynamics performing Constraint-Balancing Tasks.We verify it both in simulation and experimentally for an Unmanned Aerial Vehicles(UAVs) carrying a suspended load,and in simulation,for the rendezvous of heterogeneous robots.
基金Supported by Grants No. 1110006 to Fernández V to No. 1110043 to Tapia GNo. 1090020 to Videla LA from FONDECYT, Chile
文摘 Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver transplantation and major hepatic resection. For these reasons, numerous PC strategies have been evaluated in experimental models of ischemia-reperfusion liver injury, which have not been transferred to clinical application due to side effects, toxicity and difficulties in implementation, with the exception of the controversial ischemic PC. In recent years, our group has undertaken the assessment of alternate experimental liver PC protocols that might have application in the clinical setting. These include thyroid hormone (T3), n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), or iron, which suppressed liver damage due to the 1 h ischemia-20 h reperfusion protocol. T3, n-3 LCPUFA and iron are hormetic agents that trigger biologically beneficial effects in the low-dose range, whose multifactorial mechanisms of action are discussed in the work.
文摘Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.
文摘The current study is based on the DEM computer simulation of three experimental test devices with different dimensions to determine the difference in the results of the formation of shear and repose angles that the particles experience when grouped under the action of the gravitational force. In this respect, the experimental test devices with different height, width, and depth were geometrically modeled with iron pellet particles using morphology and a granulometric variation from 6 mm to 9 mm of equivalent diameter in its spherical shape. Depending on the results obtained, a reliable size of the experimental test device will be available to obtain the necessary data for a correct adjustment of the calibration parameters for the DEM simulation of mining-metallurgical processes that use granulated material of iron pellet.
文摘Arsenic (As) is the most important contaminant of the environment in northern Chile. The purpose of the present work is to study As-toxicity symptoms on Lupino microcarpus (lupine), an annual legume plant that constitutes part of the desert community of the pre-Andean area of the Antofagasta Region, Chile. This plant species is cultivated in As-agricultural soil collected from Chiu Chiu (northern Chile) which is classified as arid soils. Control soil (0 - 20 cm depth) is collected from an area located in the central zone of Chile, which is classified as molli soil. The main physic-chemical characteristics of As-soil and the control soil are determined. Eighteen plastic pots of 1.6 L (fifteen for experimental and three for control) are filled with As-soil and control soil treatments. Two plants are cultivated in each pot and then separated leaves and roots for As-analysis. Visual As-toxicity symptoms such as foliar chlorosis, necrosis of the leaf tips and margins, leaf wilting and stunted are determined. Total As concentrations in soils where lupine is cultivated, reach levels between 5.3 - 14.2 mg·kg<sup>-1</sup> d.w. (control soil As-level: 3.1 mg·kg<sup>-1</sup>). Roots show higher As-concentration than leaves, both experimental plants as control plants (2.28 - 9.1 mg·kg<sup>-1</sup> d.w., and 0.76 mg·kg<sup>-1</sup> d.w., respectively) and low values of transport index (TI) (0.16 - 0.34). All of visual As-toxicity symptoms determined is showed by lupin cultivated in As-agricultural soils. Neither control lupin plant suffers any toxicity symptoms. The results indicate that lupine plants do not resist contamination and accumulated higher levels of As in roots. Lupine can be used in the phytostabilisation of As immobilizing it by microbial activity in agricultural soil.
文摘In this paper, the generation and control of turbulences in a wind tunnel, for design, analysis and testing of test objects are proposed. Modifications to the wind tunnel are made in order to generate the turbulences in the test chamber. Specifically, for the turbulence analysis, the reflective symmetry concept is used in order to group the different turbulences cases generated in the wind tunnel test chamber. The Ansys software is used in order to model and analyze the wind tunnel. Specific platform or module known as Fluent is used for the analysis of the turbulence generated in the wind tunnel. To design proposal of a wind tunnel capable to generate and controlling turbulences is exposed in this paper. For this, the controller design and verification are performed by means of simulations. To obtain the control law structure, the inversion concept is used. The proposed control law is validated via a co-simulation implemented in the Simplorer module, with the aim of combining the power electronics part, controller and engine, with the proposed model wind tunnel.
文摘It is not common to start suffering from syncopes after age 50. They are mainly male patients who present causes other than vasovagal syncope, which predominates at an early age. Orthostatic hypotension is the predominant causal factor, which is attributed in many cases to advanced age, metabolic, cardiovascular or neurological diseases, to failure of baroreflexes, all of the above may be associated with the use of hypotensive drugs alone or in combination with psychotropic drugs. Furthermore, causes such as carotid sinus syncope, postprandial syncope and situational syncope become more frequent. Therefore, as people age, they present a favorable pathological terrain for the production of syncope. The older you are, the more likely you are to start with syncope. Finding the definitive diagnosis for their syncopes can be difficult, given the multiplicity of interacting factors. Their study is more exhaustive and requires a good anamnesis, knowing the drugs used by the patient, concomitant diseases and careful surveillance to get closer to the diagnosis.
基金This work was done under the auspice of Consejo Nacional de Ciencia y Tecnología(CONACyT,protocol approval number 240817)of Dirección General de Asuntos del Personal Académico(DGAPA),UNAM(protocol approval number IN204516).RLG is recipient of a CONACyT doctoral scholarship.
文摘Background:Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders.Effective therapeutic strategies are an unmet need for these disorders.Polyphenols,such as quercetin and resveratrol,are plant-derived compounds that activate sirtuins(SIRTs)and have shown promising results in some models of neuronal death,although their effects have been scarcely tested in models of motor neuron degeneration.Methods:In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA)into the rat spinal cord tissue.Quercetin and resveratrol were co-infused with AMPA and motor behavior and muscle strength were assessed daily for up to ten days.Then,animals were fixed and lumbar spinal cord tissue was analyzed by histological and immunocytological procedures.Results:We found that the chronic infusion of AMPA[1 mM]caused a progressive motor neuron degeneration,accompanied by astrogliosis and microgliosis,and motor deficits and paralysis of the rear limbs.Quercetin infusion ameliorated AMPA-induced paralysis,rescued motor neurons,and prevented both astrogliosis and microgliosis,and these protective effects were prevented by EX527,a very selective SIRT1 inhibitor.In contrast,neither resveratrol nor EX527 alone improved motor behavior deficits or reduced motor neuron degeneration,albeit both reduced gliosis.Conclusions:These results suggest that quercetin exerts its beneficial effects through a SIRT1-mediated mechanism,and thus SIRT1 plays an important role in excitotoxic neurodegeneration and therefore its pharmacological modulation might provide opportunities for therapy in motor neuron disorders.
文摘This study aims to monitor diagnostic accuracy amongst Jordanian mammography readers and identify parameters linked to higher levels of performance. In this study, we have used the Breast Screen Reader Assessment Strategy (BREAST) platform to facilitate 27 radiologists in reading a case set of 60 digital mammograms, 20 of which included cancers. Each case consisted of the four standard cranio-caudal (CC) and medio-lateral oblique (MLO) projections. All radiologists were registered to read mammograms at their workplace by the Jordanian Ministry of Health. Each reader was asked to locate any malignancies, provide a confidence rating using a scale of 1 - 5, and identify the type of appearance. All images were displayed using 8 MP monitor, supported by radiology workstations with full image manipulation facilities. Results were evaluated using Jackknife Alternative Free-Response Receiver Operating Characteristic (JAFROC). Demographics obtained from each radiologist regarding their experience, qualifications and breast-reading activities were correlated against JAFROC scores using Spearman techniques. The results showed that the mean JAFROC score was 0. 52 (95% confidence interval (CI): 0.46, 0.58);location sensitivity score was 0. 41 (95% CI: 0.41, 0.56);specificity score was 0.73 (95% CI: 0.68, 0.83). Higher performance in term of JAFROC scores was directly related to number of years since professional qualification (r = 0.433;p = 0.024), number of years reading breast images (r = 0.62;r = 0.001) and number of mammography images read per year (r = 0.69;p = 0.001). On the other hand, higher performance was inversely linked to the frequency of reading other modalities per week (r = -0.48;p = 0.010). No other statistical differences were significant. Finally, higher radiologists’ performance in cancer detection is correlated with increasing the number of mammograms reads per week.
文摘Anabolic androgenic steroids (AAS) have several adverse effects on the cardiovascular system that may lead to a sudden cardiac death (SCD).We herein report a case involving a 24-year-old male,AAS abuser with intramuscular delivery in the 6 months before,who suffered a cardiorespiratory arrest at home's bathtub when returning from New Year's party.A forensic autopsy was performed according to the guidelines of the Association for European Cardiovascular Pathology (AECVP).The body showed hypertrophy of skeletal musculature,with low amount of subcutaneous fat and no signs of injury (body mass index,BMh 26.8 kg/m^(2)).On internal examination,there were multiorgan congestion,acute pulmonary edema,and cardiomegaly (420 g) with severe coronary atherosclerosis and superimposed acute occlusive thrombosis at the left main trunk and left anterior descendant.Areas of scarring were located at the intersection between the posterior wall and the posterior third of the septum (postero-septal).At histology,acute myocardial infarction at the anterior third of the septum and the anterior wall,and subacute myocardial infarction at apical septum and apical posterior wall were detected.Other findings were small intramyocardial vessel disease and myocytes hypertrophy.Chemicotoxicological analysis in blood showed ethanol ((0.90 ±0.05) g/L),stanazolol (11.31 μg/L),nandrolone (2.05μg/L) and testosterone (<1.00μg/L).When confronted with a sudden death in a young athlete we must pay attention to the physical phenotype that may suggest AAS abuse and perform a detailed examination of the heart.Chemicotoxicological analysis is a key to establish the relationship between SCD and AAS abuse.
基金Supported by Junta de Extremadura-FEDER, PRI08A018
文摘Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the oxidative pathway, which generates acetaldehyde and involves the enzymes alcohol dehydrogenase and possibly cytochrome P4502E1. Additionally, ethanol can be metabolized via a nonoxidative pathway involving fatty acid ethyl ester synthases. Metabolism of ethanol by acinar and other pancreatic cells and the consequent generation of toxic metabolites, are postulated to play an important role in the development of alcohol-related acute and chronic pancreatic injury. This current work will review some recent advances in the knowledge about ethanol actions on the exocrine pancreas and its relationship to inflammatory disease and cancer.
文摘Objective:To determine whether birth weights are lower at high altitudes,and whether gestational age at birth and a population’s length of residence mitigate the effect of high altitude. Methods:The birth weights of 84,173 neonates recorded in the Peruvian Perinatal Information SystemDatabase were analyzed between 1995 and 2002 for the cities of Lima (150 m),Huancayo (3280 m),Cuzco (3400 m),and Juliaca (3800 m). Results:Birth weight was lower at high altitude,but there was no linear relation between altitude of residence and birth weight. Mean birth weight was higher in Juliaca than in Huancayo. There were no significant differences between the 4 cities regarding birth weights of infants born between 28 and 35 weeks of gestation. However,for infants born between 36 and 42 weeks,birth weight was lower at higher altitudes. This may be due to inadequate maternal oxygenation later in pregnancy at high altitude. In the multivariate analysis,after controlling for maternal age,marital status,parity,body mass index,pre-eclampsia or hemorrhage during pregnancy,and education,as well as sex of the newborn and gestational age at birth,birth weightwas lower in all cities located at a higher altitude than Lima. Yet,longer residence at high altitudes may play a protective role. Juliaca (3800 m),where the population has resided the longest,had the lowest reduction in birth weight compared with Lima (150 m); Cuzco had intermediate values; and Huancayo (3280 m),where the population has resided the shortest,had the highest reduction in birth weight. Conclusions:Birth weight reduction,which is independent of socioeconomic factors,occurs only in births at term and may be less severe in populations that have resided longer at high altitudes.
文摘Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.
文摘During decades, gypsum has been employed as construction material for its versatility and particle size. In the present work, the possibility of developing gypsum panels with the incorporation of pumice and polypropylene as alternative materials has been investigated. Pumice as well as polypropylene allows obtaining lighter panels than those on the market and with a lower production cost. Each one of these materials was characterized separately. In the case of gypsum and pumice, their granulometry, pH and humidity were determined, whereas polypropylene was characterized by a traction-deformation essay. Then, panels composition （gypsum and pumice concentration）, particle size, water temperature and the way polypropylene was added, was assessed. Panels with a 70% of gypsum, with a particle size of 198 btm and with polypropylene added in a laminar fashion, presented a compressive strength of 350 kPa, which accords to the norm ASTM 1396 and with market requirements. Finally, it was proposed a block diagram of the process for the fabrication of 100 kg/day of formulated panels.
文摘The study was carried out in healthy Chilean volunteers in order to compare the pharmacokinetics （rate and extent absorption） of two commercial oral formulations of 50 mg hydrochlorothiazide. Thirty nine subjects were administered hydrochlorothiazide tablets of test （T） and reference （R） formulation in a single blind, randomized, fasting, 2 × 2 crossover study, seven washout days. Blood samples were taken during a 48 h period after drug administration. Plasma concentrations were quantified by HPLC-MS/MS. The primary parameters log-transformed Cmax （maximum plasma concentration）, A UC0-t and A UC0-∞ （area under the plasma concentration-time curve from zero to the last time and zero to infinity） were tested for bioequivalence considering the ratios of geometric means （test/reference）; whereas tmax （the time of maximum plasma concentration） was analyzed nonparametrically. The 90% confidence intervals for the geometric mean values of test/reference ratios for Cmax, A UCo.t and A UC0-∞ were 95.37%, 93.59% and 96.34%, respectively, and were located within the bioequivalence acceptance range of 80-125%, as were tmax and elimination constants. Together, we conclude that the test formulation of the hydrochlorothiazide 50 mg tablet is bioequivalent to the reference product and suitable for generic prescription.
