Active learning of molecular data for task-specific objectives.

Active learning (AL) has shown promise to be a particularly data-efficient machine learning approach. Yet, its performance depends on the application, and it is not clear when AL practitioners can expect computational savings. Here, we carry out a systematic AL performance assessment for three diverse molecular datasets and two common scientific tasks: compiling compact, informative datasets and targeted molecular searches.

Bird tolerance to humans in open tropical ecosystems.

Animal tolerance towards humans can be a key factor facilitating wildlife-human coexistence, yet traits predicting its direction and magnitude across tropical animals are poorly known. Using 10,249 observations for 842 bird species inhabiting open tropical ecosystems in Africa, South America, and Australia, we find that avian tolerance towards humans was lower (i.e.

Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort.

Background: The dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved.

Probabilistic outlier identification for RNA sequencing generalized linear models.

Relative transcript abundance has proven to be a valuable tool for understanding the function of genes in biological systems. For the differential analysis of transcript abundance using RNA sequencing data, the negative binomial model is by far the most frequently adopted. However, common methods that are based on a negative binomial model are not robust to extreme outliers, which we found to be abundant in public datasets.

Qualifying drug dosing regimens in pediatrics using Gaussian processes.

Drug development commonly studies an adult population first and then the pediatric population. The knowledge from the adult population is taken advantage of for the design of the pediatric trials. Adjusted drug doses for these are often derived from adult pharmacokinetic (PK) models which are extrapolated to patients with smaller body size.

lgpr: an interpretable non-parametric method for inferring covariate effects from longitudinal data.

Motivation: Longitudinal study designs are indispensable for studying disease progression. Inferring covariate effects from longitudinal data, however, requires interpretable methods that can model complicated covariance structures and detect non-linear effects of both categorical and continuous covariates, as well as their interactions. Detecting disease effects is hindered by the fact that they often occur rapidly near the disease initiation time, and this time point cannot be exactly observed.

Interindividual variability and lateralization of μ-opioid receptors in the human brain.

Alterations in the brain's μ-opioid receptor (MOR) system have been associated with several neuropsychiatric disorders. Central MOR availability also varies considerably in healthy individuals. Multiple epidemiological factors have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive.

Minimum Mode Saddle Point Searches Using Gaussian Process Regression with Inverse-Distance Covariance Function.

The minimum mode following method can be used to find saddle points on an energy surface by following a direction guided by the lowest curvature mode. Such calculations are often started close to a minimum on the energy surface to find out which transitions can occur from an initial state of the system, but it is also common to start from the vicinity of a first-order saddle point making use of an initial guess based on intuition or more approximate calculations. In systems where accurate evaluations of the energy and its gradient are computationally intensive, it is important to exploit the information of the previous evaluations to enhance the performance.

Nudged Elastic Band Calculations Accelerated with Gaussian Process Regression Based on Inverse Interatomic Distances.

Calculations of minimum energy paths for atomic rearrangements using the nudged elastic band method can be accelerated with Gaussian process regression to reduce the number of energy and atomic force evaluations needed for convergence. Problems can arise, however, when configurations with large forces due to short distance between atoms are included in the data set. Here, a significant improvement to the Gaussian process regression approach is obtained by basing the difference measure between two atomic configurations in the covariance function on the inverted interatomic distances and by adding a new early stopping criterion for the path relaxation phase.

Deep Learning Spectroscopy: Neural Networks for Molecular Excitation Spectra.

Deep learning methods for the prediction of molecular excitation spectra are presented. For the example of the electronic density of states of 132k organic molecules, three different neural network architectures: multilayer perceptron (MLP), convolutional neural network (CNN), and deep tensor neural network (DTNN) are trained and assessed. The inputs for the neural networks are the coordinates and charges of the constituent atoms of each molecule.

An additive Gaussian process regression model for interpretable non-parametric analysis of longitudinal data.

Biomedical research typically involves longitudinal study designs where samples from individuals are measured repeatedly over time and the goal is to identify risk factors (covariates) that are associated with an outcome value. General linear mixed effect models are the standard workhorse for statistical analysis of longitudinal data. However, analysis of longitudinal data can be complicated for reasons such as difficulties in modelling correlated outcome values, functional (time-varying) covariates, nonlinear and non-stationary effects, and model inference.

Effectiveness of three interventions for secondary prevention of low back pain in the occupational health setting - a randomised controlled trial with a natural course control.

Background: We assessed the effectiveness of three interventions that were aimed to reduce non-acute low back pain (LBP) related symptoms in the occupational health setting.

Methods: Based on a survey (n = 2480; response rate 71%) on LBP, we selected a cohort of 193 employees who reported moderate LBP (Visual Analogue Scale VAS > 34 mm) and fulfilled at least one of the following criteria during the past 12 months: sciatica, recurrence of LBP ≥ 2 times, LBP ≥ 2 weeks, or previous sickness absence. A random sample was extracted from the cohort as a control group (Control, n = 50), representing the natural course of LBP.

Characterization and non-parametric modeling of the developing serum proteome during infancy and early childhood.

Children develop rapidly during the first years of life, and understanding the sources and associated levels of variation in the serum proteome is important when using serum proteins as markers for childhood diseases. The aim of this study was to establish a reference model for the evolution of a healthy serum proteome during early childhood. Label-free quantitative proteomics analyses were performed for 103 longitudinal serum samples collected from 15 children at birth and between the ages of 3-36 months.

p95HER2 Methionine 611 Carboxy-Terminal Fragment Is Predictive of Trastuzumab Adjuvant Treatment Benefit in the FinHer Trial.

Expression of p95HER2 (p95), a truncated form of the HER2 receptor, which lacks the trastuzumab binding site but retains kinase activity, has been reported as a prognostic biomarker for poor outcomes in patients with trastuzumab-treated HER2-positive metastatic breast cancer. The impact of p95 expression on trastuzumab treatment efficacy in early HER2-positive breast cancer is less clear. In the current study, p95 was tested as a predictive marker of trastuzumab treatment benefit in the HER2-positive subset of the FinHer adjuvant phase III trial.

Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans.

Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects.

Nudged elastic band calculations accelerated with Gaussian process regression.

Minimum energy paths for transitions such as atomic and/or spin rearrangements in thermalized systems are the transition paths of largest statistical weight. Such paths are frequently calculated using the nudged elastic band method, where an initial path is iteratively shifted to the nearest minimum energy path. The computational effort can be large, especially when ab initio or electron density functional calculations are used to evaluate the energy and atomic forces.

Plasma levels of hepatocyte growth factor and placental growth factor predict mortality in a general population: a prospective cohort study.

Background: Circulating levels of growth factors involved in leucocyte production and angiogenesis could be indicative of underlying aberrations of tissue homeostasis and therefore be utilized as predictors of risk for all-cause cardiovascular disease (CVD) or cancer mortality.

Methods: Baseline plasma levels of a range of growth factors were measured in two cohorts of the population-based FINRISK study (1997 Discovery cohort, N = 8444, aged 25-74; 2002 Replication cohort, N = 2951, aged 51-74 years) using a multiplexed bead array methodology and ELISA. Participants were followed up by linking them to registry data.

SLUG transcription factor: a pro-survival and prognostic factor in gastrointestinal stromal tumour.

Background: The SLUG transcription factor has been linked with the KIT signalling pathway that is important for gastrointestinal stromal tumour (GIST) tumourigenesis. Its clinical significance in GIST is unknown.

Methods: Influence of SLUG expression on cell proliferation and viability were investigated in GIST48 and GIST882 cell lines.

Effect of KIT and PDGFRA Mutations on Survival in Patients With Gastrointestinal Stromal Tumors Treated With Adjuvant Imatinib: An Exploratory Analysis of a Randomized Clinical Trial.

Importance: Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) mutations.

Objective: To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib.

Design, Setting, And Participants: This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial.

Distributed neural signatures of natural audiovisual speech and music in the human auditory cortex.

During a conversation or when listening to music, auditory and visual information are combined automatically into audiovisual objects. However, it is still poorly understood how specific type of visual information shapes neural processing of sounds in lifelike stimulus environments. Here we applied multi-voxel pattern analysis to investigate how naturally matching visual input modulates supratemporal cortex activity during processing of naturalistic acoustic speech, singing and instrumental music.

Cost-effectiveness of providing patients with information on managing mild low-back symptoms in an occupational health setting.

Background: Evidence shows that low back specific patient information is effective in sub-acute low back pain (LBP), but effectiveness and cost-effectiveness (CE) of information in early phase symptoms is not clear. We assessed effectiveness and CE of patient information in mild LBP in the occupational health (OH) setting in a quasi-experimental study.

Methods: A cohort of employees (N = 312, aged <57) with non-specific, mild LBP (Visual Analogue Scale between 10-34 mm) was selected from the respondents of an employee survey (N = 2480; response rate 71 %).

The current duration design for estimating the time to pregnancy distribution: a nonparametric Bayesian perspective.

This paper was inspired by the studies of Niels Keiding and co-authors on estimating the waiting time-to-pregnancy (TTP) distribution, and in particular on using the current duration design in that context. In this design, a cross-sectional sample of women is collected from those who are currently attempting to become pregnant, and then by recording from each the time she has been attempting. Our aim here is to study the identifiability and the estimation of the waiting time distribution on the basis of current duration data.

Gastrointestinal stromal tumor: a method for optimizing the timing of CT scans in the follow-up of cancer patients.

Purpose: To develop a mathematical model to adjust the timing of computed tomography (CT) scans with the hazard of cancer recurrence in time to facilitate early detection of cancer recurrence.

Materials And Methods: The clinical data were extracted from the randomized Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) trial database. The SSG XVIII/AIO trial was registered (trial no.

The influence of selective participation in a physical activity intervention on the generalizability of findings.

Objective: To evaluate factors that characterize employees who did not participate in a physical activity intervention in an occupational setting and assess how selective participation affects inferences from the data.

Methods: Employees were asked to complete a health risk appraisal. The respondents were invited to participate in a physical activity intervention.

Face-to-face information combined with a booklet versus a booklet alone for treatment of mild low-back pain: a randomized controlled trial.

Objective: The aim of this study was to determine the effectiveness of face-to-face information for the treatment of mild low-back pain (LBP) in an occupational health (OH) setting.

Methods: We conducted a 48-month randomized controlled trial (RCT) with two 1:1 allocated parallel groups of forestry company employees. Eligibility criteria included permanent employment, age <57 years, and mild LBP [visual analogue scale (VAS) 10-34 mm] in a survey.