To establish a new procedure for 3D geometric reconstruction of the human cornea to obtain a solid model that represents a personalized and in vivo morphology of both the anterior and posterior ...corneal surfaces. This model is later analyzed to obtain geometric variables enabling the characterization of the corneal geometry and establishing a new clinical diagnostic criterion in order to distinguish between healthy corneas and corneas with keratoconus.
The method for the geometric reconstruction of the cornea consists of the following steps: capture and preprocessing of the spatial point clouds provided by the Sirius topographer that represent both anterior and posterior corneal surfaces, reconstruction of the corneal geometric surfaces and generation of the solid model. Later, geometric variables are extracted from the model obtained and statistically analyzed to detect deformations of the cornea.
The variables that achieved the best results in the diagnosis of keratoconus were anterior corneal surface area (ROC area: 0.847, p<0.000, std. error: 0.038, 95% CI: 0.777 to 0.925), posterior corneal surface area (ROC area: 0.807, p<0.000, std. error: 0.042, 95% CI: 0,726 to 0,889), anterior apex deviation (ROC area: 0.735, p<0.000, std. error: 0.053, 95% CI: 0.630 to 0.840) and posterior apex deviation (ROC area: 0.891, p<0.000, std. error: 0.039, 95% CI: 0.8146 to 0.9672).
Geometric modeling enables accurate characterization of the human cornea. Also, from a clinical point of view, the procedure described has established a new approach for the study of eye-related diseases.
Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of ...therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC stroma, but its roles there have not been studied. Here we report functions and molecular pathways of Gal1 that mediate its oncogenic properties in this setting. Genetic ablation of Gal1 in a mouse model of PDAC (EIa-myc mice) dampened tumor progression by inhibiting proliferation, angiogenesis, desmoplasic reaction and by stimulating a tumor-associated immune response, yielding a 20% increase in relative lifesplan. Cellular analyses in vitro and in vivo suggested these effects were mediated through the tumor microenvironment. Importantly, acinar-to-ductal metaplasia, a crucial step for initiation of PDAC, was found to be regulated by Gal1. Mechanistic investigations revealed that Gal1 promoted Hedgehog pathway signaling in PDAC cells and stromal fibroblasts as well as in Ela-myc tumors. Taken together, our findings establish a function for Gal1 in tumor-stroma crosstalk in PDAC and provide a preclinical rationale for Gal1 targeting as a microenvironment-based therapeutic strategy.
To characterize corneal structural changes in keratoconus using a new morphogeometric approach and to evaluate its potential diagnostic ability.
Comparative study including 464 eyes of 464 patients ...(age, 16 and 72 years) divided into two groups: control group (143 healthy eyes) and keratoconus group (321 keratoconus eyes). Topographic information (Sirius, CSO, Italy) was processed with SolidWorks v2012 and a solid model representing the geometry of each cornea was generated. The following parameters were defined: anterior (Aant) and posterior (Apost) corneal surface areas, area of the cornea within the sagittal plane passing through the Z axis and the apex (Aapexant, Aapexpost) and minimum thickness points (Amctant, Amctpost) of the anterior and posterior corneal surfaces, and average distance from the Z axis to the apex (Dapexant, Dapexpost) and minimum thickness points (Dmctant, Dmctpost) of both corneal surfaces.
Significant differences among control and keratoconus group were found in Aapexant, Aapexpost, Amctant, Amctpost, Dapexant, Dapexpost (all p<0.001), Apost (p = 0.014), and Dmctpost (p = 0.035). Significant correlations in keratoconus group were found between Aant and Apost (r = 0.836), Amctant and Amctpost (r = 0.983), and Dmctant and Dmctpost (r = 0.954, all p<0.001). A logistic regression analysis revealed that the detection of keratoconus grade I (Amsler Krumeich) was related to Apost, Atot, Aapexant, Amctant, Amctpost, Dapexpost, Dmctant and Dmctpost (Hosmer-Lemeshow: p>0.05, R2 Nagelkerke: 0.926). The overall percentage of cases correctly classified by the model was 97.30%.
Our morphogeometric approach based on the analysis of the cornea as a solid is useful for the characterization and detection of keratoconus.
Given current high market competitiveness, it is necessary to differentiate between products that perform the same function. For this objective, designer can recur to various sources of inspiration ...in the searching of the more attractive form during the conceptual design stage. One of these sources can be nature, which offers a large number of geometries and textures that can be used from a shape point of view to help the designer in the creative process. This work presents an agent-based approach for a design-aided tool to provide users with some ideas, beginning with simple parts/concepts, and then increasing the complexity level according to the answers offered by designer. The proposed paradigm was implemented using the JADE agent-based platform. In order to validate the platform, several product categories were offered to fifteen different users and a total of sixty design proposals were obtained with the aid of the platform. After evaluating all the proposals, twelve of the sixty designs were finally selected and modelled by a Computer-Aided Design software. The obtained results demonstrate the feasibility of using an agent-based approach to obtain an adaptive intelligent solution to the product conceptual design problem.
The aim of this work was to investigate the effect of feeding ethyl-3-nitrooxy propionate (E3NP) and 3-nitrooxypropanol (3NP), 2 recently developed compounds with potential antimethanogenic activity, ...in vitro and in vivo in nonlactating sheep on ruminal methane production, fermentation pattern, the abundance of major microbial groups, and feed degradability. Three experiments were conducted, 1 in vitro and 2 in vivo. The in vitro batch culture trial (experiment 1) tested 2 doses of E3NP and 3NP (40 and 80μL/L), which showed a substantial reduction of methane production (up to 95%) without affecting concentration of volatile fatty acids (VFA). The 2 in vivo trials were conducted over 16 d (experiment 2) and 30 d (experiment 3) to study their effects in sheep. In experiment 2, 6 adult nonpregnant sheep, with permanent rumen cannula and fed alfalfa hay and oats (60:40), were treated with E3NP at 2 doses (50 and 500mg/animal per day). After 7, 14, and 15 d of treatment, methane emissions were recorded in respiration chambers and rumen fluid samples were collected for VFA analysis and quantification of bacterial, protozoal, and archaeal numbers by real-time PCR. Methane production decreased by 29% compared with the control with the higher dose of E3NP on d 14 to 15. A decrease in the acetate:propionate ratio was observed without detrimental effects on dry matter intake. In experiment 3, 9 adult nonpregnant sheep, with permanent rumen cannula and fed with alfalfa hay and oats (60:40), were treated with E3NP or 3NP at one dose (100mg/animal per day) over 30 d. On d 14 and d 29 to 30, methane emissions were recorded in respiration chambers. Rumen fluid samples were collected on d 29 and 30 for VFA analysis and quantification of bacterial, protozoal, and archaeal numbers by real-time PCR. In addition, on d 22 and 23, samples of oats and alfalfa hay were incubated in the rumen of sheep to determine dry matter ruminal degradation over 24 and 48h, respectively; no effect was observed (78.6, 78.3, and 78.8% of alfalfa and 74.2, 74.0, and 70.6% of oats in control, E3NP, and 3NP groups, respectively). A reduction in methane production was observed for both additives at d 14 and d 29 to 30. In both treatments, the acetate:propionate ratio was significantly decreased. Likewise, total concentrations of the analyzed microbial groups in the rumen showed no difference among treatments and doses for both experiments. Both tested compounds showed promise as methane inhibitors in the rumen, with no detrimental effects on fermentation or intake, which would need to be confirmed in lactating animals.
To identify the questing tick populations in urban and suburban areas from the city of Lugo (NW Spain), ticks were collected monthly by flagging. The presence of Borrelia spp., Rickettsia spp. and ...Anaplasma phagocytophilum also was determined by polymerase chain reaction (PCR) and sequence analysis. Overall, 342 questing ticks were collected; the tick abundance was higher in suburban (95.9%) than in urban areas (4.1%). Ixodes frontalis was the most abundant (86.5%); 88.5% were larvae, 11.1% nymphs and 0.3% adults. All development stages of I. ricinus (7.3%) and adults of Rhipicephalus sanguineus sensu lato (5.8%) and Dermacentor reticulatus (0.3%) were found. Rickettsia spp. (31.9%) was more prevalent than Borrelia spp. (2.7%); no ticks were positive to A. phagocytophilum. Six Rickettsia species were identified (R. slovaca, R. monacensis, R. massiliae, R. raoultii, R. sibirica subsp. mongolitimonae and R. aeschielmanii); Candidatus Rickettsia rioja and two novel Rickettsia species also were detected. In addition, Borrelia turdi (1.8%) and B. valaisiana (0.9%) were identified in Ixodes ticks. This is the first report of R. slovaca in R. sanguineus s.l. and of R. monacensis, R. raoultii, R. slovaca, R. sibirica subsp. mongolitimonae and Ca. R. rioja in I. frontalis. Since most of the pathogens detected are zoonotic, their presence in these areas may have implications for public health.
A higher number of ticks was collected in suburban than in urban areas, being Ixodes frontalis the most commonly detected species.
The results have significant implications for public health since most Rickettsia spp. detected are zoonotic.
This is the first report of the detection of Borrelia spp. and Rickettsia spp. DNA some species in questing I. frontalis.
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) still poses a challenge for biomedicine and public health. To advance the development of effective diagnostic, prognostic, and preventive ...interventions, our study focused on high‐throughput antibody binding epitope mapping of the SARS‐CoV‐2 spike RBD protein by IgA, IgM and IgG antibodies in saliva and sera of different cohorts from healthy uninfected individuals to SARS‐CoV‐2‐infected unvaccinated and vaccinated asymptomatic, recovered, nonsevere, and severe patients. Identified candidate diagnostic (455‐LFRKSNLKPFERD‐467), prognostic (395‐VYADSFVIRGDEV‐407‐C‐KLH, 332‐ITNLCPFGEV‐342‐C‐KLH, 352‐AWNRKRI‐358‐C‐KLH, 524‐VCGPKKSTNLVKN‐536‐KLH), and protective (MKLLE‐487‐NCYFPLQSYGFQPTNGVG‐504‐GGGGS‐446‐GGNYNYLYRLFRKSNLKPFERD‐467) epitopes were validated with sera from prevaccine and postvaccine cohorts. The results identified neutralizing epitopes and support that antibody recognition of linear B‐cell epitopes in RBD protein is associated with antibody isotype and disease symptomatology. The findings in asymptomatic individuals suggest a role for anti‐RBD antibodies in the protective response against SARS‐CoV‐2. The possibility of translating results into diagnostic interventions for the early diagnosis of asymptomatic individuals and prognosis of disease severity provides new tools for COVID‐19 surveillance and evaluation of risks in hospitalized patients. These results, together with other approaches, may contribute to the development of new vaccines for the control of COVID‐19 and other coronavirus‐related diseases using a quantum vaccinomics approach through the combination of protective epitopes.
Recognition of linear B‐cell epitopes in SARS‐CoV‐2 Spike protein is associated with antibody isotype and disease symptomatology. Antibody isotype mapping identified reactive immunodominant epitopes in infected individuals from asymptomatic to severe cases. These results may translate into diagnostic and prognostic interventions for COVID‐19 surveillance and development of new vaccines.
Dengue is transmitted by the Aedes aegypti mosquito as a vector, and a recent outbreak was reported in several districts of Lima, Peru. We conducted a modeling study to explain the transmission ...dynamics of dengue in three of these districts according to the demographics and climatology.
We used the weekly distribution of dengue cases in the Comas, Lurigancho, and Puente Piedra districts, as well as the temperature data to investigate the transmission dynamics. We used maximum likelihood minimization and the human susceptible-infected-recovered and vector susceptible-infected (SIR-SI) model with a Gaussian function for the infectious rate to consider external non-modeled variables.
We found that the adjusted SIR-SI model with the Gaussian transmission rate (for modelling the exogenous variables) captured the behavior of the dengue outbreak in the selected districts. The model explained that the transmission behavior had a strong dependence on the weather, cultural, and demographic variables while other variables determined the start of the outbreak.
The experimental results showed good agreement with the data and model results when a Bayesian-Gaussian transmission rate was employed. The effect of weather was also observed, and a strong qualitative relationship was obtained between the transmission rate and computed effective reproduction number Rt.
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