The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English.

Open-Source Artificial Intelligence System Supports Diagnosis of Mendelian Diseases in Acutely Ill Infants.

Mendelian disorders are prevalent in neonatal and pediatric intensive care units and are a leading cause of morbidity and mortality in these settings. Current diagnostic pipelines that integrate phenotypic and genotypic data are expert-dependent and time-intensive. Artificial intelligence (AI) tools may help address these challenges.

Adaptive proton therapy.

Radiation therapy treatments are typically planned based on a single image set, assuming that the patient's anatomy and its position relative to the delivery system remains constant during the course of treatment. Similarly, the prescription dose assumes constant biological dose-response over the treatment course. However, variations can and do occur on multiple time scales.

Phen2Gene: rapid phenotype-driven gene prioritization for rare diseases.

Human Phenotype Ontology (HPO) terms are increasingly used in diagnostic settings to aid in the characterization of patient phenotypes. The HPO annotation database is updated frequently and can provide detailed phenotype knowledge on various human diseases, and many HPO terms are now mapped to candidate causal genes with binary relationships. To further improve the genetic diagnosis of rare diseases, we incorporated these HPO annotations, gene-disease databases and gene-gene databases in a probabilistic model to build a novel HPO-driven gene prioritization tool, Phen2Gene.

Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.

During adipogenesis, preadipocytes' cytoskeleton reorganizes in parallel with lipid accumulation. Failure to do so may impact the ability of adipose tissue (AT) to shift between lipid storage and mobilization. Here, we identify cytoskeletal transgelin 2 (TAGLN2) as a protein expressed in AT and associated with obesity and inflammation, being normalized upon weight loss.

Correction: Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

[This corrects the article DOI: 10.1371/journal.pone.

[Gender differences in the mortality of people with type 2 diabetes: Asturias Study 2018].

Objective: To investigate the influence of gender on mortality according to the presence or absence of type 2 diabetes mellitus (DM2) and other cardiovascular risk factors in the Asturias Study cohort.

Method: The Asturias Study (started in 1998) is an observational, prospective cohort study of a representative sample of a population of Asturias aged 30-75 years. The population was divided into groups according to the presence or absence of DM2 and according to gender to assess control of cardiovascular risk factors.

Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

People who develop type 2 diabetes (T2D) are known to have a higher mortality risk. We estimated all-cause, cardiovascular, and cancer mortality-risks in our patient cohort according to categories of impaired glucose metabolism. This 18-year retrospective analysis included a region-wide, representative sample of a population aged 30-75 years.

Online adaption approaches for intensity modulated proton therapy for head and neck patients based on cone beam CTs and Monte Carlo simulations.

To develop an online plan adaptation algorithm for intensity modulated proton therapy (IMPT) based on fast Monte Carlo dose calculation and cone beam CT (CBCT) imaging. A cohort of ten head and neck cancer patients with an average of six CBCT scans were studied. To adapt the treatment plan to the new patient geometry, contours were propagated to the CBCTs with a vector field (VF) calculated with deformable image registration between the CT and the CBCTs.

Density overwrites of internal tumor volumes in intensity modulated proton therapy plans for mobile lung tumors.

The purpose of this study was to investigate internal tumor volume density overwrite strategies to minimize intensity modulated proton therapy (IMPT) plan degradation of mobile lung tumors. Four planning paradigms were compared for nine lung cancer patients. Internal gross tumor volume (IGTV) and internal clinical target volume (ICTV) structures were defined encompassing their respective volumes in every 4DCT phase.

Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer.

Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution.

Methods And Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan.

Recent developments and comprehensive evaluations of a GPU-based Monte Carlo package for proton therapy.

Monte Carlo (MC) simulation is commonly considered as the most accurate dose calculation method for proton therapy. Aiming at achieving fast MC dose calculations for clinical applications, we have previously developed a graphics-processing unit (GPU)-based MC tool, gPMC. In this paper, we report our recent updates on gPMC in terms of its accuracy, portability, and functionality, as well as comprehensive tests on this tool.

Genetic variations of the bitter taste receptor TAS2R38 are associated with obesity and impact on single immune traits.

Scope: Changes in genetic variations affecting the taste receptor, type 2, member 38 (TAS2R38) may identify the interacting mechanism leading to obesity and potential associations with proteins partaking in innate immunity, such as surfactant protein D (SPD) and mannan-binding lectin (MBL).

Methods And Results: We evaluated haplotypes of the bitter-taste receptor TAS2R38 in an identification sample of 210 women in different weight conditions, including anorexia nervosa and obesity. The association with SPD and MBL was tested in an independent sample picturing general population (n = 534).

Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects.

Introduction: A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans.

Hypertensive patients in a general practice setting: comparative analysis between controlled and uncontrolled hypertension.

Objective: To study the differences between controlled and uncontrolled hypertensive patients.

Methods: This was a cross-sectional observational study of the hypertensive population on the lists of three general practitioners in the district of Coimbra in central Portugal in 2013, with a margin of error of 6% and 95% confidence interval in each sample, organized in ascending order of health care user numbers. Data were gathered electronically by the investigators after approval by the Regional Health Authority's ethics committee.

Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes.

Context: Surfactant protein-D (SP-D) is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs) affecting SP-D with insulin resistance and type 2 diabetes (T2D).

Research Design And Methods: We evaluated a common genetic variant located in the SP-D coding region (rs721917, Met(31)Thr) in a sample of T2D patients and non-diabetic controls (n = 2,711).

Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene-diet interactions.

Objective: Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing.

Design And Subjects: THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial).

Targeting the association of calgranulin B (S100A9) with insulin resistance and type 2 diabetes.

Calgranulin B (S100A9) was recognized as a candidate type 2 diabetes (T2D) gene in the genomic profiling of muscle from a rodent model of T2D and identifying the human orthologs of genes localized in T2D susceptibility regions. Circulating and S100A9 expressions in muscle and adipose tissue, isolated fat cells, and mouse models were evaluated. A common 5'-upstream single-nucleotide polymorphism (SNP; rs3014866) for S100A9 was analyzed, as well as the effects of weight loss and treatments in vitro with recombinant S100A9.

Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes.

Objective: Increased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.

Design: We performed both cross-sectional and longitudinal (diet-induced weight loss) studies.

Factors determining weight gain in adults and relation with glucose tolerance.

Objective: Modifications in lifestyle, diet and certain clinical events are major contributors for the high prevalence of obesity. The aim of this study was to assess factors associated with weight gain in a population of Spanish adults.

Design: The study was undertaken in two population-based cohorts from the north and the south of Spain (baseline and after 6 years).

[Glucose tolerance and plasma testosterone concentrations in men. Results of the Asturias Study].

Background And Objective: Studies in men have demonstrated a correlation between serum concentrations of androgens and sex hormone binding globulin (SHBG) with the presence of impaired glucose tolerance, diabetes and metabolic syndrome. The aim of this study was to evaluate circulating levels of total testosterone, SHBG, and bioavailable testosterone in the cohort of the Asturias Study and their association with the degree of glucose tolerance and metabolic syndrome.

Patients And Methods: The study population consisted of 282 men aged 36 to 85 years old with normal concentrations of total testosterone.

Vitamin D deficiency in Spain: a population-based cohort study.

Background: Vitamin D deficiency is common worldwide. No homogenous reference values have yet been established and no studies of values have been conducted in Spain involving a large number of participants.

Objective: To study the population concentrations of vitamin D in a representative sample of the Spanish population.

HbA(1c) in the prediction of type 2 diabetes compared with fasting and 2-h post-challenge plasma glucose: The Asturias study (1998-2005).

Aim: Fasting plasma glucose (FPG) and the 2-h post-challenge plasma glucose (2hPG) are commonly used to identify those at risk of type 2 diabetes. However, the role of HbA(1c) in this prediction has still not been ascertained.

Methods: The Asturias study is a prospective population-based survey of diabetes and cardiovascular risk factors.

Surfactant protein d, a marker of lung innate immunity, is positively associated with insulin sensitivity.

Objective: Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations.

Research Design And Methods: Serum SP-D was evaluated in four different cohorts.

Environmental and genetic factors influence the relationship between circulating IL-10 and obesity phenotypes.

Interleukin-10 (IL-10) is a centrally operating anti-inflammatory cytokine that plays a crucial role in the regulation of the innate immune system. It has strong inactivating properties on the inflammatory host response and has been related with viral persistence. We aimed to evaluate the association among circulating IL-10, obesity phenotypes, IL-10 and IL-10R1 gene polymorphisms, and the environmental exposure to viral infection.