Personalized Model to Predict Small for Gestational Age at Delivery Using Fetal Biometrics, Maternal Characteristics, and Pregnancy Biomarkers: A Retrospective Cohort Study of Births Assisted at a Spanish Hospital.

Small for gestational age (SGA) is defined as a newborn with a birth weight for gestational age < 10th percentile. Routine third-trimester ultrasound screening for fetal growth assessment has detection rates (DR) from 50 to 80%. For this reason, the addition of other markers is being studied, such as maternal characteristics, biochemical values, and biophysical models, in order to create personalized combinations that can increase the predictive capacity of the ultrasound.

O-fucosylation stabilizes the TSR3 motif in thrombospondin-1 by interacting with nearby amino acids and protecting a disulfide bond.

Thrombospondin type-1 repeats (TSRs) are small protein motifs containing six conserved cysteines forming three disulfide bonds that can be modified with an O-linked fucose. Protein O-fucosyltransferase 2 (POFUT2) catalyzes the addition of O-fucose to TSRs containing the appropriate consensus sequence, and the O-fucose modification can be elongated to a Glucose-Fucose disaccharide with the addition of glucose by β3-glucosyltransferase (B3GLCT). Elimination of Pofut2 in mice results in embryonic lethality in mice, highlighting the biological significance of O-fucose modification on TSRs.

A Need for a Paradigm Shift in Healthy Nutrition Research.

Research in the field of sustainable and healthy nutrition is calling for the application of the latest advances in seemingly unrelated domains such as complex systems and network sciences on the one hand and big data and artificial intelligence on the other. This is because the confluence of these fields, whose methodologies have experienced explosive growth in the last few years, promises to solve some of the more challenging problems in sustainable and healthy nutrition, i.e.

A metapopulation approach to identify targets for Wolbachia-based dengue control.

Over the last decade, the release of Wolbachia-infected Aedes aegypti into the natural habitat of this mosquito species has become the most sustainable and long-lasting technique to prevent and control vector-borne diseases, such as dengue, zika, or chikungunya. However, the limited resources to generate such mosquitoes and their effective distribution in large areas dominated by the Aedes aegypti vector represent a challenge for policymakers. Here, we introduce a mathematical framework for the spread of dengue in which competition between wild and Wolbachia-infected mosquitoes, the cross-contagion patterns between humans and vectors, the heterogeneous distribution of the human population in different areas, and the mobility flows between them are combined.

Atomic and Specificity Details of Mucin 1 -Glycosylation Process by Multiple Polypeptide GalNAc-Transferase Isoforms Unveiled by NMR and Molecular Modeling.

The large family of polypeptide GalNAc-transferases (GalNAc-Ts) controls with precision how GalNAc -glycans are added in the tandem repeat regions of mucins (, MUC1). However, the structural features behind the creation of well-defined and clustered patterns of -glycans in mucins are poorly understood. In this context, herein, we disclose the full process of MUC1 -glycosylation by GalNAc-T2/T3/T4 isoforms by NMR spectroscopy assisted by molecular modeling protocols.

The interconnection between independent reactive control policies drives the stringency of local containment.

The lack of medical treatments and vaccines upon the arrival of the SARS-CoV-2 virus has made non-pharmaceutical interventions the best allies in safeguarding human lives in the face of the COVID-19 pandemic. Here we propose a self-organized epidemic model with multi-scale control policies that are relaxed or strengthened depending on the extent of the epidemic outbreak. We show that optimizing the balance between the effects of epidemic control and the associated socio-economic cost is strongly linked to the stringency of control measures.

Statistical characterization of a good biomarker in oncology.

Objective: The  aim of this article is to review and illustrate the attributes that analyze the performance of a predictive model, suchas discrimination, calibration and clinical utility.

Material And Methods: To illustrate a biomarkervalidation process, we analyzed 216 patientsrecruited in the Miguel Servet University Hospital Zaragoza, Spain. The outcome of the study was clinicallysignificant prostate cancer (Gleason ≥ 7).

Testosterone Recovery after Androgen Deprivation Therapy in Prostate Cancer: Building a Predictive Model.

Purpose: To analyze the variability, associated actors, and the design of nomograms for individualized testosterone recovery after cessation of androgen deprivation therapy (ADT).

Materials And Methods: A longitudinal study was carried out with 208 patients in the period 2003 to 2019. Castrated and normogonadic testosterone levels were defined as 0.

Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies.

Protein misfolding is a general hallmark of protein deposition diseases, such as Alzheimer's disease or Parkinson's disease, in which different types of aggregated species (oligomers, protofibrils and fibrils) are generated by the cells. Despite widespread interest, the relationship between oligomers and fibrils in the aggregation process and spreading remains elusive. A large variety of experimental evidences supported the idea that soluble oligomeric species of different proteins might be more toxic than the larger fibrillar forms.

Modeling the effects of social distancing on the large-scale spreading of diseases.

To contain the propagation of emerging diseases that are transmissible from human to human, non-pharmaceutical interventions (NPIs) aimed at reducing the interactions between humans are usually implemented. One example of the latter kind of measures is social distancing, which can be either policy-driven or can arise endogenously in the population as a consequence of the fear of infection. However, if NPIs are lifted before the population reaches herd immunity, further re-introductions of the pathogen would lead to secondary infections.

Differences in the spatial landscape of urban mobility: Gender and socioeconomic perspectives.

Many of our routines and activities are linked to our ability to move; be it commuting to work, shopping for groceries, or meeting friends. Yet, factors that limit the individuals' ability to fully realise their mobility needs will ultimately affect the opportunities they can have access to (e.g.

The Pathological G51D Mutation in Alpha-Synuclein Oligomers Confers Distinct Structural Attributes and Cellular Toxicity.

A wide variety of oligomeric structures are formed during the aggregation of proteins associated with neurodegenerative diseases. Such soluble oligomers are believed to be key toxic species in the related disorders; therefore, identification of the structural determinants of toxicity is of upmost importance. Here, we analysed toxic oligomers of α-synuclein and its pathological variants in order to identify structural features that could be related to toxicity and found a novel structural polymorphism within G51D oligomers.

Beyond Dunbar circles: a continuous description of social relationships and resource allocation.

We discuss the structure of human relationship patterns in terms of a new formalism that allows to study resource allocation problems where the cost of the resource may take continuous values. This is in contrast with the main focus of previous studies where relationships were classified in a few, discrete layers (known as Dunbar's circles) with the cost being the same within each layer. We show that with our continuum approach we can identify a parameter [Formula: see text] that is the equivalent of the ratio of relationships between adjacent circles in the discrete case, with a value [Formula: see text].

Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor.

AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor's ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms.

Molecular simulations of proteins: From simplified physical interactions to complex biological phenomena.

Molecular dynamics simulation is the most popular computational technique for investigating the structural and dynamical behaviour of proteins, in search of the molecular basis of their function. Far from being a completely settled field of research, simulations are still evolving to best capture the essential features of the atomic interactions that govern a protein's inner motions. Modern force fields are becoming increasingly accurate in providing a physical description adequate to this purpose, and allow us to model complex biological systems under fairly realistic conditions.

Insight on molecular pathogenesis and pharmacochaperoning potential in phosphomannomutase 2 deficiency, provided by novel human phosphomannomutase 2 structures.

Phosphomannomutase 2 (PMM2) deficiency, the most frequent congenital disorder of glycosylation (PMM2-CDG), is a severe condition, which has no cure. Due to the identification of destabilizing mutations, our group aims at increasing residual activity in PMM2-CDG patients, searching for pharmacochaperones. Detailed structural knowledge of hPMM2 might help identify variants amenable to pharmacochaperoning.

Discovery of Diverse Natural Products as Inhibitors of SARS-CoV-2 M Protease through Virtual Screening.

SARS-CoV-2 is a type of coronavirus responsible for the international outbreak of respiratory illness termed COVID-19 that forced the World Health Organization to declare a pandemic infectious disease situation of international concern at the beginning of 2020. The need for a swift response against COVID-19 prompted to consider different sources to identify bioactive compounds that can be used as therapeutic agents, including available drugs and natural products. Accordingly, this work reports the results of a virtual screening process aimed at identifying antiviral natural product inhibitors of the SARS-CoV-2 M viral protease.

Teaching Urology to Undergraduates: A Prospective Survey of What General Practitioners Need to Know.

Background: Higher education training in Medicine has considerably evolved in recent years. One of its main goals has been to ensure the training of students as future adequately qualified general practitioners (GPs). Tools need to be developed to evaluate and improve the teaching of Urology at the undergraduate level.

Reduced Growth in Non-Small for Gestational Age Fetuses from 35 Weeks of Gestation to Birth and Perinatal Outcomes.

Objective: This study aimed to assess reduced fetal growth between 35 weeks of gestation and birth in non-small for gestational age fetuses associated with adverse perinatal outcomes (APOs).

Material And Method: It is a retrospective cohort study of 9,164 non-small for gestational age fetuses estimated by ultrasound at 35 weeks. The difference between the birth weight percentile and the estimated percentile weight (EPW) at 35 weeks of gestation was calculated, and we studied the relationship of this difference with the appearance of APO.

l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells.

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine.

Structure determination of GPCRs: cryo-EM compared with X-ray crystallography.

G protein-coupled receptors (GPCRs) are the largest single family of cell surface receptors encoded by the human genome and they play pivotal roles in co-ordinating cellular systems throughout the human body, making them ideal drug targets. Structural biology has played a key role in defining how receptors are activated and signal through G proteins and β-arrestins. The application of structure-based drug design (SBDD) is now yielding novel compounds targeting GPCRs.

Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds.

Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (K = 0.81 μM).

Absence of SARS-CoV-2 Antibodies in Natural Environment Exposure in Sheep in Close Contact with Humans.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the zoonotic causative agent of coronavirus disease 2019 (COVID-19) that has caused a pandemic situation with millions of infected humans worldwide. Among domestic animals, there have been limited studies regarding the transmissibility and exposure to the infection in natural conditions. Some animals are exposed and/or susceptible to SARS-CoV-2 infection, such as cats, ferrets and dogs.

Prediction of Late-Onset Small for Gestational Age and Fetal Growth Restriction by Fetal Biometry at 35 Weeks and Impact of Ultrasound-Delivery Interval: Comparison of Six Fetal Growth Standards.

Small-for-gestational-age (SGA) infants have been associated with increased risk of adverse perinatal outcomes (APOs). In this work, we assess the predictive ability of the ultrasound-estimated percentile weight (EPW) at 35 weeks of gestational age to predict late-onset SGA and APOs, according to six growth standards, and whether the ultrasound-delivery interval influences the detection rate. To this purpose, we analyze a retrospective cohort study of 9585 singleton pregnancies.