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The objective of this work was to assess how the cow pregnancy depends on the type of service as, race and follicular development in cattle with dual purpose in the Ecuadorian Amazon. The 341 records of the individual services were evaluated from January 2015 to December 2015 that corresponds to cows of different genotypes and cross: Brown Swiss (BS) n = 135, Charolais (Ch) n = 24, Holstein Friesian (HF) n = 104, Jersey (J) n = 12, Normando (N) n = 21, x Brown Swiss Holstein Friesian (HFxBS) n = 35 and Holstein Friesian x Normando (HFxN) n = 10. The work was conducted in the Cantons and Santa Clara which is located in the Pastaza Province (Ecuador). The Two insemination techniques were performed: a estrus detected (natural) 136 cows and a Insemination Time (TAI). The independent variables are "Race" (BS, CH, HF, J, HFxBS and HFxN), the "Technical Service" (N and IATF) and "Follicular Development" (DF). An additive model was adjusted and it was not significant for the interactions between independent variables and the result of the model. It was found that the variable DF is the only that contributes significantly to the model. That is, pregnancy is significantly affected by follicular development (p-value

Juan Carlos Miralles-López,1,2 Francisco J Alvarez-Gutiérrez,3 Julio Delgado-Romero,4 Santiago Quirce,5,6 Jose Gregorio Soto-Campos,7 Ruben Andújar-Espinosa,2,8 Sheila Cabrejos-Perotti,2,9 Manuel Castilla-Martínez,2,10 Isabel Flores-Martín,2,11 Manuel José Pajarón-Fernández,2,12 José Valverde-Molina2,13,14 1Allergy Department, University General Hospital Reina Sofia, Murcia, Spain; 2Severe Asthma Association of the Region of Murcia. ASGRAMUR, Murcia, Spain; 3Medical and Surgical Unit of Respiratory Diseases, Hospital Universitario Virgen Del Rocío, Seville, Spain; 4Allergology Clinical Management Unit, Hospital Virgen Macarena, Seville, Spain; 5Department of Allergy, La Paz University Hospital, IdiPAZ, Madrid, Spain; 6CIBER of Respiratory Diseases (CIBERES), Madrid, Spain; 7Pneumology and Allergy Clinical Management Unit, University Hospital of Jerez, Jerez, Spain; 8Pulmonology Department. H. U. Virgen de la Arrixaca, Murcia, Spain; 9Allergy Department, University General Hospital Santa Lucia, Cartagena, Spain; 10Pulmonology Department, University General Hospital Los Arcos, San Javier, Spain; 11Allergy Department, Hospital Comarcal del Noroeste, Caravaca, Murcia, Spain; 12Allergy Department, Hospital de la Vega Lorenzo Guirao, Cieza, Spain; 13Paediatrics Department, University General Hospital Santa Lucia (Cartagena University Hospital Complex), Cartagena, Spain; 14IMIB Biomedical Research Institute, Murcia, SpainCorrespondence: Juan Carlos Miralles-López, Allergy Department, University General Hospital Reina Sofia, Murcia, Spain, Email juancmiralleslopez@gmail.comPurpose: With the advent of biological therapies, emerging concepts regarding establishing new targets in asthma management, such as disease modification, have entered the debate among the scientific community. The definitions that form the conceptual basis of this goal need to be agreed upon.Methods: A multidisciplinary expert group was assembled as the steering committee. A systematic literature review was conducted to identify the scientific background for constructing appropriate definitions. Based on the literature review and the clinical experience of the experts, the committee built a list of statements that could be applied to establish the definition of disease modification in asthma. After that, a Delphi validation was performed to assess the appropriateness of the list of statements. The questionnaire included a total of 22 statements, divided into “Essential criteria for disease modification in asthma” (5 statements) and “Disease modification indicators and other considerations” (17 statements). Panelists used a 9-point Likert scale to measure agreement on each statement. The cut-off point for high consensus was defined as a minimum score of 7 and had to be reached by at least two-thirds of the experts.Results: A total of 192 asthma experts voted on statements anonymously. Of those, 104 (54%) were Pneumologists, 65 (34%) were allergologists, and 23 (12%) were Pediatricians. An interim analysis of round 1 data was performed. All statements reached consensus on the first round, with a median score above 7 in all cases.Conclusion: In conclusion, in this Delphi study, a large number of experts in the management of severe asthma from different specialties agreed on the clinical-functional and pathophysiological aspects to be considered in order to try to achieve disease modification.Keywords: severe asthma, disease modification, delphi process, remission

The objective of the present work was to estimate and assess trends in greenhouse gas (GHG) emissions, particularly methane (CH4) and nitrous oxide (N2O), from dairy cows in Mexico from the base year of 1970 to 2010. Empirical and mechanistic models were used to estimate enteric methane emissions based on chemical composition of diets. Methane from manure was calculated using Intergovernmental Panel for Climate Change (IPCC) and US Environmental Protection Agency recommended equations. N2O emission was calculated according to IPCC recommendations. Compared with the 1970s, current management practices using modern dairy cows increased feed conversion efficiency 32% and milk yield 62%. GHG emission intensity (i.e. emissions per unit of product) was reduced 30%, 25% and 30% for CH4, N2O and total emissions, respectively. The study showed that although GHG emissions in absolute terms increased in the past 40 years, emission intensity decreased due to higher level of production. This trend is likely to continue in the future, assuming milk production follows the same increasing trend as in other countries in North America. © 2014 CSIRO.

Objectives Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA ( mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus ( HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/ HCV-coinfected patients on pegylated interferon ( pegIFN) plus ribavirin ( RBV). Methods We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B ( IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response ( SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data. Results The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 ( P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype. Conclusions European mtDNA haplogroups were not related to HCV treatment response in HIV/ HCV-coinfected patients on pegIFN-α/ RBV therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of IL28B polymorphisms and severity of liver disease among human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients.Methods: We carried out a cross-sectional study on 223 patients. Liver biopsies were evaluated according to Metavir score. IL28B polymorphisms (rs12980275, rs8099917, rs7248668, and rs11881222) were genotyped using GoldenGate(®) assay.Results: IL28B polymorphisms were in strong linkage disequilibrium, especially the couples rs12980275/rs11881222 and rs8099917/rs7248668. For all patients, the rs12980275 A allele increased the odds for significant fibrosis (F ≥ 2) odds ratio (OR) = 1.68; p = 0.018) and more rapid fibrosis progression (FPR ≥ 0.075 fibrosis units/year) (OR = 1.64; p = 0.035), and decreased the odds for liver steatosis (OR = 0.61; p = 0.046). Furthermore, the rs8099917 T allele increased the odds for F ≥ 2 (OR = 1.93; p = 0.020), FPR ≥ 0.075 (OR = 2.08; p = 0.021), and elevated ALT (≥80 IU/l) (OR = 1.78; p = 0.048). For HCV-genotype 1 patients, rs12980275 A and rs8099917 T alleles decreased the odds for liver steatosis (OR = 0.22; p < 0.001 and OR = 0.39; p = 0.048; respectively). For HCV-genotype 3 patients, the rs12980275 A allele increased the odds for F ≥ 2 ((OR = 6.30; p = 0.012), FPR ≥ 0.075 (OR = 6.40; p = 0.025), and elevated ALT (OR = 4.12; p = 0.037); and the rs8099917 T allele also increased the odds for F ≥ 2 (OR = 7.56; p = 0.027), FPR ≥ 0.075 (OR = 50.8; p = 0.012), and elevated ALT (OR = 5.39; p = 0.043). However, we did not find significant trends in patients infected with HCV-genotype 4.Conclusion: The major alleles of IL28B (rs12980275 A, rs11881222 A, rs8099917 T, and rs7248668 G) are associated with increased odds of liver disease severity in HIV patients infected with HCV-genotype 3. In contrast, HCV-genotype 1 patients carrying the major alleles of IL28B polymorphisms had lower odds for liver steatosis. [ABSTRACT FROM AUTHOR]

Salvador Pastor-Idoate,1,2 Irene Rodríguez-Hernández,2,3 Jimena Rojas,1 Lucia Gonzalez-Buendia,1 Santiago Delgado-Tirado,1,4 Jose Carlos López,1 Rogelio González-Sarmiento,2,3 Jose C Pastor1,4 1IOBA Eye Institute, University of Valladolid, Valladolid, 2Molecular Medicine Unit, Department of Medicine, 3Molecular and Cellular Cancer Biology Institute, High Council of Scientific Research, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, 4Department of Ophthalmology, Hospital Clínico Universitario, Valladolid, Spain Purpose: The objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA) in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R) (T>C), previously associated with proliferative vitreoretinopathy (PVR) development.Materials and methods: Total RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD) and three healthy control eyes were subjected to immunohistochemistry (IHC) with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed.Results: RT-PCR analysis revealed no significant levels of messenger RNA (mRNA) LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells.Conclusion: Although results suggest lack of functionality, the differences found in IHC study and its strong association with PVR and its relationship with tumor necrosis factor locus, warrant further studies and could justify the use of this polymorphism as a valid biomarker to identify high-risk patients to develop PVR after RD. Keywords: proliferative vitreoretinopathy, lymphotoxin alpha, tumor necrosis factor alpha, inflammation, cytokines, polymorphism

Presents an approximation of the exact solution of the non-symmetric matrix Riccati equation with analytic coefficients by a rational matrix function with a prefixed accuracy. Initial value problems for Riccati differential systems; A priori error bounds.

José Carlos López López,1 Nieves Fernández Alonso,1 Juan Cuevas Álvarez,1,2 Tomás García-Caballero,2 José Carlos Pastor Jimeno3 1Ocular Pathology Laboratory, Instituto Universitario de Oftalmobiología Aplicada (IOBA), University of Valladolid, Valladolid, Spain; 2Department of Pathology, Hospital Clínico Universitario, Santiago de Compostela, Spain; 3Retina Group, Instituto Universitario de Oftalmobiología Aplicada (IOBA), University of Valladolid, Hospital Clínico Universitario, Valladolid, Spain Purpose: We evaluated the expression of the neural markers, neuron-specific enolase, and synaptophysin, as a tool to confirm the diagnosis of retinoblastoma (RB) in undifferentiated and advanced tumors. Additionally, we determined whether the extent of RB-associated protein (pRb) expression is helpful in assessing the prognosis in RB patients. Methods: Conventional whole tissue section and tissue microarray immunohistochemistry for neuron-specific enolase, synaptophysin, and pRb were carried out in a series of 22 RBs. Results: Neuron-specific enolase and synaptophysin were expressed in 75%–100% of the tumor cells, and the staining intensity was strong. Two RBs expressed pRb in 75%–100% of the tumor cells, also with strong staining intensity. Concordance between the immunohistochemical outcomes for whole tissue staining and tissue microarray staining was 76.2% for neuron-specific enolase, 85.7% for synaptophysin, and 80.0% for pRb. Conclusion: Neuron-specific enolase and synaptophysin have the potential to be useful markers for the diagnosis of RBs. Extensive and strong pRb staining is not associated with less aggressive tumor behavior according to the pathologic classification of RBs. Keywords: retinoblastoma, immunohistochemistry, neuron-specific enolase, synaptophysin, pRb

In 2022, the US Centers for Disease Control and Prevention commissioned the National Academies of Sciences, Engineering, and Medicine to assess the role of community-level wastewater-based epidemiology (WBE) beyond COVID-19. WBE is recognized as a promising mechanism for promptly identifying infectious diseases, including COVID-19 and other novel pathogens. An important conclusion from this initiative is the critical importance of maintaining equity and expanding access to fully realize the benefits of wastewater surveillance for marginalized communities. To address this need, we propose an optimization framework that strategically allocates wastewater monitoring resources at the wastewater treatment plant (WWTP) level, ensuring more effective and equitable distribution of surveillance efforts to serve underserved populations. The purpose of the framework is to obtain a balanced spatial distribution, inclusive population coverage, and efficient representation of disadvantaged groups in the allocation of resources for WBE. Furthermore, the framework concentrates on areas with high population density and gives priority to vulnerable regions, as well as identifying signals that display significant variations from other monitored sources. The optimization objective is to maximize a weighted combination of these critical factors. This problem is formulated as an integer optimization problem and solved using simulated annealing. We evaluate various scenarios, considering different weighting factors, to optimize the allocation of WWTPs with monitoring systems. This optimization framework provides an opportunity to enhance WBE by providing customized monitoring strategies created to address specific priorities and situations, thus enhancing the decision-making processes in public health responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The popularity of genomic selection as an efficient and cost-effective approach to estimate breeding values continues to increase, due in part to the significant saving in phenotyping. Ridge regression is one of the most popular methods used for genomic prediction; however, its efficiency (in terms of prediction performance) depends on the appropriate tunning of the penalization parameter. In this paper we propose a novel, more efficient method to select the optimal penalization parameter for Ridge regression. We compared the proposed method with the conventional method to select the penalization parameter in 14 real data sets and we found that in 13 of these, the proposed method outperformed the conventional method and across data sets the gains in prediction accuracy in terms of Pearson's correlation was of 56.15%, with not-gains observed in terms of normalized mean square error. Finally, our results show evidence of the potential of the proposed method, and we encourage its adoption to improve the selection of candidate lines in the context of plant breeding., Competing Interests: Conflicts of interest. The author(s) declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

The distinction between noncancerous and cancerous breast tissues is challenging in clinical settings, and discovering new proteomics-based biomarkers remains underexplored. Through a pilot proteomic study (discovery cohort), we aimed to identify a protein signature indicative of breast cancer for subsequent validation using six published proteomics/transcriptomics data sets (validation cohorts). Sequential window acquisition of all theoretical (SWATH)-based mass spectrometry revealed 370 differentially abundant proteins between noncancerous tissue and breast cancer. Protein-protein interaction-based networks and enrichment analyses revealed dysregulation in pathways associated with extracellular matrix organization, platelet degranulation, the innate immune system, and RNA metabolism in breast cancer. Through multivariate unsupervised analysis, we identified a four-protein signature (OGN, LUM, DCN, and COL14A1) capable of distinguishing breast cancer. This dysregulation pattern was consistently verified across diverse proteomics and transcriptomics data sets. Dysregulation magnitude was notably higher in poor-prognosis breast cancer subtypes like Basal-Like and HER2 compared to Luminal A. Diagnostic evaluation (receiver operating characteristic (ROC) curves) of the signature in distinguishing breast cancer from noncancerous tissue revealed area under the curve (AUC) ranging from 0.87 to 0.9 with predictive accuracy of 80% to 82%. Upon stratifying, to solely include the Basal-Like/Triple-Negative subtype, the ROC AUC increased to 0.922-0.959 with predictive accuracy of 84.2%-89%. These findings suggest a potential role for the identified signature in distinguishing cancerous from noncancerous breast tissue, offering insights into enhancing diagnostic accuracy.

Objective: Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms., Methods: Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms., Results: 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up., Conclusion: In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission., Competing Interests: Declaration of competing interest Disclosures that might be interpreted as constituting possible conflict(s) of interest for the study: Javier Loricera had consultation fees/participation in company-sponsored speaker´s bureau from Roche, Galápagos, Novartis, UCB Pharma, MSD, Celgene, Astra Zeneca, and Grünenthal and received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos. Paloma Vela research funding/consulting and conferences fees from: Abbvie, Roche, Amgen, Novartis, Lilly, Pfizer, GSK. Susana Romero-Yuste has received grants/recents supports from Abbvie, Astra-Zeneca, Bristol, Janssen, Lilly, Roche, Sandoz, Sanofi, UCB. Eugenio De Miguel Research funding/consulting and conferences fees from: Abbvie, Novartis, Pfizer, Roche, Janssen, Lilly, MSD, BMS, UCB, Grünenthal and Sanofi. Iván Ferraz-Amaro would like to acknowledge that he has received grants/research supports from Abbvie, MSD, Janssen, and Roche, as well as consultation fees from company sponsored speakers bureaus associated with Abbvie, Pfizer, Roche, Sanofi, Celgene, and MSD. Fernando López-Gutiérrez received support for attending meetings and/or travel from Janssen, Abbvie, Roche, Novartis, MSD, UCB Pharma, Celgene, Lilly, Pfizer, Galápagos. Santos Castañeda has received research support from MSD and Pfizer and had consultation fees/participation in company-sponsored speaker's bureau from BMS, Eli-Lilly, Roche, Gedeon-Richter, Grünenthal Pharma and UCB. Ricardo Blanco received grants/research support from AbbVie, MSD, and Roche, and had consultation fees/participation in a company-sponsored speaker's bureau from AbbVie, Pfizer, Roche, GSK, Lilly, UCB, Bristol-Myers, Novartis, Janssen, UCB and MSD. The following authors did not declare financial disclosure: Adrián Martín-Gutiérrez, Javier Narváez, Vicente Aldasoro, Olga Maiz, Eva Galíndez-Agirregoikoa, Jesús C. Fernández-López, Julio Sánchez-Martín, Patricia Moya, Cristina Campos., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The most stable conformer of laser-ablated diflunisal has been isolated in a supersonic expansion and experimentally detected through high-resolution chirped-pulse rotational spectroscopy. State-of-the-art chemical calculations allowed to understand the nature of the strong stabilization of the detected conformer and its atropisomer among a total of sixteen theoretically predicted conformers and confirmed the presence of a resonance assisted hydrogen bond (RAHB) between the hydroxyl hydrogen atom and the carbonyl oxygen atom of the carboxylic acid group. The comparison of the experimental data from this work and the information found in the literature about the molecule in condensed phases corroborates the existence of these two atropisomers and is contextualized within the complexation arrangement of diflunisal with relevant proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)