A new family of quantile regression models applied to nutritional data.

This paper introduces a new family of quantile regression models whose response variable follows a reparameterized Marshall-Olkin distribution indexed by quantile, scale, and asymmetry parameters. The family has arisen by applying the Marshall-Olkin approach to distributions belonging to the location-scale family. Models of higher flexibility and whose structure is similar to generalized linear models were generated by quantile reparameterization. The maximum likelihood (ML) method is presented for the estimation of the model parameters, and simulation studies evaluated the performance of the ML estimators. The advantages of the family are illustrated through an application to a set of nutritional data, whose results indicate it is a good alternative for modeling slightly asymmetric response variables with support on the real line.

A prospective longitudinal approach to examine the association between social position in childhood, adolescence, and adulthood with the control of hypertension during adulthood.

Introduction: Hypertension is one of the main concerns in public health, since it is related with increased morbidity, and potential years of life lost in addition to loss of quality of life. This study aimed to assess: (1) the distribution of indicators of life course SEP in a cohort of Colombian patients with hypertension and (2) to assess the association of life course SEP and control of hypertension among this cohort of patients. Methods: Data were obtained using the baseline survey of 258 patients from the Social Determinants and Inequities in the Control of Blood Hypertension Program (ProDSICHA). Mother occupation and housing conditions were measured with the Event History Calendar. Mother educational level was measured with the questionnaire developed by the Project on Ethnicity and Race in Latin America (PERLA). Socioeconomic position during adulthood was measured using education, occupation, and income level based in the MacArthur Network. Results: The group with a higher lifelong social position and the group of lower lifelong social position showed better control of hypertension (OR = 1.21; p <0.05; OR = 1.33; p < .05, respectively) compared to those whose social position throughout life varied the most. No statistical differences were found in the relations between single lifetime social position variables, and hypertension control in the three time points analyzed. Discussion: These findings warrant further research to deeper our understanding on the role of a multidimensional and cumulative approach of social position in hypertension control.

Mutations in AGBL5 associated with Retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) is the leading cause of heritable retinal visual impairment. Clinically, it is characterized by a variable onset of progressive night blindness and visual field constriction. RP is characterized by wide genetic heterogeneity with a broad range of potential genes involved in the genesis of this disease. Very few cases have been reported of RP due to pathogenic variants in AGBL5. MATERIALS AND METHODS: We report two patients with RP and bilallelic pathogenic variants in AGBL5. RESULTS: Genetic sequencing showed one homozygous AGBL5 missense variant in one patient and a homozygous nonsense variant in the other. These patients presented with progressive peripheral vision loss and nyctalopia. Their RP phenotypes were similar to previous reports in literature. CONCLUSION: These two cases provide further evidence regarding the relationship of pathogenic variants in AGBL5 as a cause of autosomal recessive RP.

Underrepresentation of Low- and Middle-Income Nations in Ophthalmology Journals: A Critical Analysis on Diversity, Equity, and Global Representation.

Purpose: Low- to middle-income nations contain more than 80% of the world's population; however, only 4% of articles in ophthalmology journals belong to these countries. We aim to analyze the global diversity of the editorial boards of ophthalmology journals. Methods: Cross-sectional study, including all journals in the Ophthalmology section of the SCImago Journal & Country Rank (SJR). Journals were classified according to the country of origin, SJR interquartile range (Q1-Q4), impact factor, and open-access policy. Global diversity among journals was determined by the country of affiliation of editors-in-chief and editorial board members. Nations were classified by income according to the World Bank's 2022 system. The association between editorial diversity and the journal's metrics and country of origin was analyzed using the χ2 test and the Mann-Whitney U test. Results: A total of 116 journals were included and 83.6% belonged to high-income nations. Only 18 (13.3%) editors-in-chief and 582 (13.5%) board members were affiliated with middle-income nations. The most prevalent middle-income countries in editorial boards were Brazil (n = 184, 4.26%), India (n = 150, 3.47%), Turkey (n = 42, 0.97%), and Iran (n = 36, 0.83%). Only 40 (1.07%) editorial board members of Q1 journals were affiliated with non-high-income nations, most belonging to India (n = 28, 70%). Journals from middle-income nations had a statistically significant lower prevalence in the first- and second-quartile ranking (P < 0.001) and a higher proportion of open-access policies (P = 0.019). Conclusions: A clear underrepresentation of low- to middle-income nations was observed in ophthalmology journals. Promoting editorial diversity and minimizing the possibility of editorial bias could lead to greater exposure to real-world data from resource-constrained settings. Translational Relevance: The documented underrepresentation of low- to middle-income nations in ophthalmology journals highlights the importance of promoting diversity and inclusion.

Cardiovascular disease prevention capacity in Colombian local health departments.

Prevention capacity of local health organisations is associated with the performance and outcomes in public health. In Colombia, where cardiovascular disease is the leading cause of morbidity and mortality, there is limited knowledge about the capacity of local health departments to prevent this condition. Efforts are needed to address problems, potential solutions and expected outcomes regarding cardiovascular disease. In this study, a conceptual model for cardiovascular disease prevention capacity in Colombian local health departments was developed, a questionnaire based on this model was validated, the overall cardiovascular disease prevention capacity in a subsample of these organisations was measured, and the association between cardiovascular disease prevention capacity and political, population, and organisational factors was examined. Once the acceptable performance of the questionnaire was verified, variability in cardiovascular prevention capacity was found among a subsample of local health departments. Furthermore, this study provides primary evidence regarding the association between the size of local health departments and overall cardiovascular disease prevention capacity in Colombia. Future studies should focus on measuring this capacity on a larger scale and developing, implementing, and evaluating interventions aimed at strengthening cardiovascular prevention capacity in Colombian local jurisdictions.

Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans.

In several long-lived Caenorhabditis elegans strains, such as insulin/IGF-1 receptor daf-2 mutants, enhanced proteostatic mechanisms are accompanied by elevated intestinal lipid stores, but their role in longevity is unclear. Here, while determining the regulatory network of the selective autophagy receptor SQST-1/SQSTM1, we uncovered an important role for lipid droplets in proteostasis and longevity. Using genome-wide RNAi screening, we identified several SQST-1 modulators, including lipid droplets-associated and aggregation-prone proteins. Expansion of intestinal lipid droplets by silencing the conserved cytosolic triacylglycerol lipase gene atgl-1/ATGL enhanced autophagy, and extended lifespan. Notably, a substantial amount of ubiquitinated proteins were found on lipid droplets. Reducing lipid droplet levels exacerbated the proteostatic collapse when autophagy or proteasome function was compromised, and significantly reduced the lifespan of long-lived daf-2 animals. Altogether, our study uncovered a key role for lipid droplets in C. elegans as a proteostatic mediator that modulates ubiquitinated protein accumulation, facilitates autophagy, and promotes longevity.

CLSoilMaps: A national soil gridded database of physical and hydraulic soil properties for Chile.

Spatially explicit soil information is crucial for comprehending and managing many of Earth´s processes related to carbon, water, and other biogeochemical cycles. We introduced a gridded database of soil physical properties and hydraulic parameters at 100 meters spatial resolution. It covers the continental area of Chile and binational basins shared with Argentina for six standardized depths following the specifications of the GlobalSoilMap project. We generated soil maps based on digital soil mapping techniques based on more than 4000 observations, including unpublished data from remote areas. These maps were used as input for the pedotransfer function Rosetta V3 to obtain predictions of soil hydraulic properties, such as field capacity, permanent wilting point, total available water capacity, and other parameters of the water retention curve. The trained models outperformed several other DSM studies applied at the national and regional scale for soil physical properties (nRMSE ranging from 6.93% to 15.7%) and delivered acceptable predictions (nRMSE ranging from 10.4% to 15.6%) for soil hydraulic properties, making them suitable for countless environmental studies.

Synthesis of Quinazolin-2,4,6-triamine Derivatives as Non-purine Xanthine Oxidase Inhibitors and Exploration of Their Toxicological Potential.

In this work, a new set of quinazolin-2,4,6-triamine derivatives were synthesized to explore their potential biological activity as xanthine oxidase (XO) inhibitors, superoxide scavengers and screening of their toxicological profile. Among all the synthesized compounds, B1 exhibited better inhibitory activity against bovine xanthine oxidase (bXO) than allopurinol (IC50 =1.56 µM and IC50 =6.99 µM, respectively). As superoxide scavengers, B1, B2 and B13 exhibited a better effect than allopurinol (97.3 %, 82.1 %, 87.4 % and 69.4 %, respectively). Regarding the toxicological profile, B1 was less cytotoxic than methotrexate on HCT-15 cancer cells. Apoptosis results obtained in cells of female and male mice, showed that B1 and B2 presented a similar behaviour to CrO3 (positive control) with respect to the average frequency to induce apoptosis; while B13 apoptosis induced effect was similar to DMSO and control group. Finally, B1, B2, B13 did not induce genotoxicity in a micronuclei murine model compared to CrO3 .

Inverse Miniemulsion Enables the Continuous-Flow Synthesis of Controlled Ultra-High Molecular Weight Polymers.

We report the controlled synthesis of ultra-high molecular weight (UHMW) polymers (Mn ≥ 106 g/mol) via continuous flow in a tubular reactor. At high monomer conversion, UHMW polymers in homogeneous batch polymerization exhibit high viscosities that pose challenges for employing continuous flow reactors. However, under heterogeneous inverse miniemulsion (IME) conditions, UHMW polymers can be produced within the dispersed phase, while the viscosity of the heterogeneous mixture remains approximately the same as the viscosity of the continuous phase. Conducting such IME polymerizations in flow results in a faster rate of polymerization compared to batch IME polymerizations while still providing excellent control over molecular weight up to 106 g/mol. Crucial emulsion parameters, such as particle size and stability under continuous flow conditions, were examined using dynamic light scattering. A range of poly(N,N-dimethylacrylamide) and poly(4-acryloylmorpholine) polymers with molecular weights of 104-106 g/mol (D ≤ 1.31) were produced by this method using water-soluble trithiocarbonates as photoiniferters.

Improved inference for MCP-Mod approach using time-to-event endpoints with small sample sizes.

The Multiple Comparison Procedures with Modeling Techniques (MCP-Mod) framework has been recently approved by the U.S. Food, Administration, and European Medicines Agency as fit-for-purpose for phase II studies. Nonetheless, this approach relies on the asymptotic properties of Maximum Likelihood (ML) estimators, which might not be reasonable for small sample sizes. In this paper, we derived improved ML estimators and correction for their covariance matrices in the censored Weibull regression model based on the corrective and preventive approaches. We performed two simulation studies to evaluate ML and improved ML estimators with their covariance matrices in (i) a regression framework (ii) the Multiple Comparison Procedures with Modeling Techniques framework. We have shown that improved ML estimators are less biased than ML estimators yielding Wald-type statistics that controls type I error without loss of power in both frameworks. Therefore, we recommend the use of improved ML estimators in the MCP-Mod approach to control type I error at nominal value for sample sizes ranging from 5 to 25 subjects per dose.

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors.

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

Time and Frequency Repolarization Domains in Elderly Candidates to Transcatheter Aortic Valve Replacement.

Background and aim: Aortic valve stenosis (AVS) is a well-known risk factor for sudden cardiac death. Therefore, some non-invasive, electrocardiographic markers are capable to stratify the risk of sudden death at rest and during light mental challenge [mini-mental state examination (MMSE) administration]. Method: We compared short period RR, QT and Te intervals variability in 42 candidates to and 12 age-matched hypertensive control patients at rest and during mental challenge. Results: At rest, AVS patients showed a higher QT standard deviation (sd), QT low frequency power (LF), QT High Frequency (HF), Tpeak-Tend intervals sd (Te sd) and Te HF than the control group. During mental challenge AVS group showed a decrease of RR mean and RR HF, expressed in normalized units (NU), and an increase of RR total power (TP), RR LF, RR LF NU, RR LF, HF ratio (LF/HF). During this same mental test, QT sd, QT LF, QT HF, Te sd, Te LF, Te HF, QT variability index (VI), TeVI, QT normalized variance (VN) were higher in AVS patients than the control group. During mental challenge Te LF (r:0.825, p<0.05) was significantly associated to: serum albumin (ß:-0.473, p<0.001), MMSE (ß:-0.267, p:0.038), diastolic blood pressure (ß:-0.443, p:0.03) and cardiac index (ß:-0.303, p:0.029). Conclusion: AVS patients showed temporal dispersion of ventricular repolarization phase, useful maker to individuate high risk patients. MMSE administration induced a sympathetic sinus activation and vagal deactivation in AVS subjects. Frailty and mental function influenced Te HF and Te LF.

Comparison of Four Arteries for Invasive Blood Pressure Measurements and Dixtal 2010 Oscillometric Values in Horses Anesthetized With Isoflurane: Does the Artery Matter?

This study evaluated the agreement between invasive blood pressure (IBP) values measured in three different arteries and by an oscillometric device (NIBP) with the ones from the transverse facial artery (FA). Six horses (424.2 ± 40.7 kg) were sedated with xylazine (0.6 mg/kg IV), induced with ketamine (2 mg/kg IV) and midazolam (0.1 mg/kg IV), and maintained with isoflurane (1.2 MAC) for 90 minutes in lateral recumbency. FA, auricular artery (AA), lateral digital artery (LDA), and metatarsal artery (MA) were catheterized, and a standard adult cuff was placed on the tail. IBP and NIBP values were recorded at 30, 45, 60, 75, and 90 minutes of anesthesia. Data were analyzed with Shapiro-Wilk and Repeated-Measures Bland-Altman. Values for FA (mm Hg) were 85.4 ± 10.3 for SAP, 70.6 ± 9.3 for MAP, and 58.5 ± 9.5 for DAP. Mean bias and 95% Limit of agreement (LOA) for AA were -1.7 (-29.0 to 25.6), 2.2 (-18.4 to 22.9), 1.9 (-18.2 to 22.0), for LDA: 1.4 (-25.1 to 27.8), 2.9 (-19.3 to 25.0), 2.3 (-18.4 to 22.9), for MA: -3.2 (-28.3 to 22.0), 2.7 (-16.6 to 22.1), 4.9 (-13.8 to 22.2), and for NIBP: -5.7 (-28.3 to 16.9), 7.9 (-9.5 to 25.3), 17.2 (-2.4 to 36.8), for SAP, MAP and DAP respectively. There is a reasonable bias for IBP values among the arteries evaluated, however a wide LOA, demonstrating the arteries are not interchangeable. NIBP method from Dixtal 2010 results in inaccurate blood pressure values in horses.

A general class of promotion time cure rate models with a new biological interpretation.

Over the last decades, the challenges in survival models have been changing considerably and full probabilistic modeling is crucial in many medical applications. Motivated from a new biological interpretation of cancer metastasis, we introduce a general method for obtaining more flexible cure rate models. The proposal model extended the promotion time cure rate model. Furthermore, it includes several well-known models as special cases and defines many new special models. We derive several properties of the hazard function for the proposed model and establish mathematical relationships with the promotion time cure rate model. We consider a frequentist approach to perform inferences, and the maximum likelihood method is employed to estimate the model parameters. Simulation studies are conducted to evaluate its performance with a discussion of the obtained results. A real dataset from population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil, is discussed in detail.

Genetics of the anterior segment dysgenesis.

The anterior segment dysgeneses are a broad group of heterogeneous disorders characterized by developmental abnormalities of the anterior segment of the eye, including primary congenital aphakia, Peters sequence, aniridia, and Axenfeld-Rieger spectrum. These conditions can have overlapping phenotypes and both genotypic and phenotypic heterogeneity. This article provides a strategy for both phenotyping and then genotyping using a targeted stepwise approach.

Análisis de la presión plantar durante la carrera en el sitio en diferentes superficies / Analysis of Plantar Pressure during the Running in Place over Different Surfaces

El objetivo de este trabajo es evaluar en 36 corredores aficionados, la fuerza y las presiones del pie sobre tres superficies comúnmente empleadas para el entrenamiento de la carrera en el sitio (césped artificial, suelo técnico de caucho y trampolín plano). Los valores de fuerza y presión se registraron mediante plantillas instrumentadas (Gebiomized® Munster, Germany). Se obtuvieron los siguientes parámetros: Fuerza máxima (N) y picos de presión (N/cm2) en 6 zonas específicas del pie. Según los resultados, la fuerza máxima ejercida por el pie dominante en césped artificial (657 N) y en suelo técnico de caucho (692,5 N) fue significativamente superior al registrado sobre el trampolín (262 N). Respecto a la presión, la mayor parte de la presión ejercida por el pie en superficies duras (césped artificial y suelo técnico de caucho), se observó en las cabezas de los metatarsianos, mientras que en el trampolín la presión se repartió entre estas y el calcáneo. (AU)

The objective of this study is to evaluate the Maximum Force and Peak Pressure of the foot on three surfaces commonly used for running in place training (artificial turf, rubber floor and flat trampoline). Force and pressure were recorded in 36 amateur runners using instrumented insoles (Gebiomized® Munster, Germany). The following parameters were obtained: Maximum Force (N) and Peak Pressure (N/cm2) in 6 specific areas of the foot. According to the results, the maximum force exerted by the dominant foot on artificial turf (657 N) and rubber floor (692.5 N) was significantly higher than the recorded on the trampoline (262 N). Regarding the pressure, most of the pressure exerted by the foot on hard surfaces (artificial turf and technical floor), was observed in the heads of the metatarsals, while in the trampoline the pressure was distributed in the heads of the metatarsals and the calcaneus. (AU)

Evaluating and mitigating clinical samples matrix effects on TX-TL cell-free performance.

Cell-free biosensors are promising tools for medical diagnostics, yet their performance can be affected by matrix effects arising from the sample itself or from external components. Here we systematically evaluate the performance and robustness of cell-free systems in serum, plasma, urine, and saliva using two reporter systems, sfGFP and luciferase. In all cases, clinical samples have a strong inhibitory effect. Of the different inhibitors, only RNase inhibitor mitigated matrix effects. However, we found that the recovery potential of RNase inhibitor was partially muted by interference from glycerol contained in the commercial buffer. We solved this issue by designing a strain producing an RNase inhibitor protein requiring no additional step in extract preparation. Furthermore, our new extract yielded higher reporter levels than previous conditions and tempered interpatient variability associated with matrix effects. This systematic evaluation and improvements of cell-free system robustness unified across many types of clinical samples is a significant step towards developing cell-free diagnostics for a wide range of conditions.

Síndrome de Evans y embarazo: reporte de un caso / Evans syndrome and pregnancy: a case report

Resumen El síndrome de Evans es una enfermedad conformada por la presencia simultánea o secuencial de trombocitopenia inmunitaria y anemia hemolítica autoinmunitaria, que puede ser primaria o secundaria a otra patología. Es una afección poco frecuente, por lo que es necesario tener una alta sospecha, y descartar otras patologías que cursan con dichas alteraciones hematológicas, para hacer el diagnóstico. Su manejo representa un desafío terapéutico dado su curso crónico y recidivante. La presentación durante el embarazo se asocia a morbilidad materna y fetal. A continuación presentamos el caso de una gestante en quien se pesquisó trombocitopenia severa aislada al ingreso al control prenatal, y que en el curso del embarazo desarrolló AHAI conformando un síndrome de Evans, que se consideró secundario a LES incompleto al realizar el estudio reumatológico. Debido a la pobre respuesta al tratamiento médico con corticoides e inmunosupresores, la mayor parte del embarazo se mantuvo hospitalizada para observación, ajuste y cambio de terapia, siendo necesario recurrir a manejo quirúrgico con esplenectomía.

Abstract Evans syndrome is a rare entity formed by the simultaneous or sequential presence of immune thrombocytopenia and autoimmune hemolytic anemia, which can be primary or secondary to another pathology. The presentation of this disease during pregnancy is associated with maternal and fetal morbidity. The syndrome's diagnosis requires a high suspicion and the ruling out of other pathologies that can happen with the same hematological alterations. The management represents a therapeutic challenge because of its chronic and recurrent course. Below we present the case of a pregnant woman in whom isolated severe thrombocytopenia was detected at admission for prenatal control, and who developed AIHA during the pregnancy, forming Evans syndrome, which was considered secondary to incomplete SLE when performing the rheumatological study. Due to the poor response to medical treatment with corticosteroids and immunosuppressants, the patient was hospitalized for most of her pregnancy for observation, adjustment and change of therapy, and even it was necessary resort to surgical management with splenectomy.

Short-Period Temporal Dispersion Repolarization Markers in Elderly Patients with Decompensated Heart Failure.

Objectives: Aging and chronic heart failure (CHF) are responsible for the temporal inhomogeneity of electrocardiogram (ECG) repolarization phase. In the past, short period repolarization-dispersion parameters were used as makers of mortality risk in different heart diseases, yet. Aim of this work was to evaluate risk of mortality or worsening condition in CHF elderly subjects by mean of these repo-larization variables. Method: An observational, prospective cohort study was performed, collecting 5 minutes ECG recordings to assess the mean and standard deviation (SD) of the following variables: QT end (QTe), QT peak (QTp) and T peak to T end (Te) in 117 decompensated CHF (age range: from 49 to 103 years). 30-day mortality and high levels of NT-pro BNP (<75 percentile) were considered markers of decompensated CHF. Results: A total of 27 patients (23%) died during the 30-day follow-up (overall mortality rate 23%). Te mean (odd ratio (OR): 1.04, 95% confidence limit (Cl 7u): 1.02-1.09, p<0.01), NT-pro BNP (OR: 1.00, 95% cl: 1.00-1.00, p<0.01) and LVMI (OR : 0.98, 95% cl: 0.96-0.10, p<0.05) were associated to risk of mortality at the multivariable logistic analysis. On the contrary, the same statistical analysis selected TeSD (OR: 1.36, 95% cl: 1.16-1.59, p<0.001) and LVEF (OR: 0.91, 95% cl: 0.87-0.95, p<0.001) as marker of decompensated CHF. Conclusion: In decompensated CHF elderly subjects, Te mean seem be associated to mortality and TeSD could be considered a risk factor for CHF worsening and complications. These evidences could provide useful tools for telemonitoring CHF elderly patients, amelio-rating treatments and outcomes.