Research Priorities to Increase Confidence in and Acceptance of Health Preference Research: What Questions Should be Prioritized Now?

Background And Objective: There has been an increase in the study and use of stated-preference methods to inform medicine development decisions. The objective of this study was to identify prioritized topics and questions relating to health preferences based on the perspective of members of the preference research community.

Methods: Preference research stakeholders from industry, academia, consultancy, health technology assessment/regulatory, and patient organizations were recruited using professional networks and preference-targeted e-mail listservs and surveyed about their perspectives on 19 topics and questions for future studies that would increase acceptance of preference methods and their results by decision makers.

Patients as research partners in preference studies: learnings from IMI-PREFER.

Background: There is growing recognition of the importance of patient and public stakeholder involvement (PPI) in patient preference research. However, limited evidence exists regarding the impact, barriers and enablers of PPI in preference studies. The Innovative Medicines Initiative (IMI)-PREFER project conducted a series of preference case studies which incorporated PPI.

Periostin as a blood biomarker of muscle cell fibrosis, cardiomyopathy and disease severity in myotonic dystrophy type 1.

Background And Purpose: Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy and is caused by an repeat expansion [r(CUG)] located in the 3' untranslated region of the DMPK gene. Symptoms include skeletal and cardiac muscle dysfunction and fibrosis. In DM1, there is a lack of established biomarkers in routine clinical practice.

Estimating conformational landscapes from Cryo-EM particles by 3D Zernike polynomials.

The new developments in Cryo-EM Single Particle Analysis are helping us to understand how the macromolecular structure and function meet to drive biological processes. By capturing many states at the particle level, it is possible to address how macromolecules explore different conformations, information that is classically extracted through 3D classification. However, the limitations of classical approaches prevent us from fully understanding the complete conformational landscape due to the reduced number of discrete states accurately reconstructed.

Barriers to a healthy diet and physical activity in Mexican adults: results from the Mexican Health and Nutrition Survey.

This study aims to (1) identify the most prevalent perceived barriers for healthy eating and performing physical activity among adults in Mexico; and (2) determine the association between perceived barriers, with body mass index (BMI) categories, geo-demographic and socio-economic characteristics. We carried out a cross-sectional, secondary analysis of publicly available data from the Mexican Health and Nutrition Survey 2016. We extracted data from 6406 adults, aged 20-65 years, including: perceived barriers for healthy eating and for performing physical activity, BMI, residence area, region of Mexico, sex, age and socio-economic status.

On bias, variance, overfitting, gold standard and consensus in single-particle analysis by cryo-electron microscopy.

Cryo-electron microscopy (cryoEM) has become a well established technique to elucidate the 3D structures of biological macromolecules. Projection images from thousands of macromolecules that are assumed to be structurally identical are combined into a single 3D map representing the Coulomb potential of the macromolecule under study. This article discusses possible caveats along the image-processing path and how to avoid them to obtain a reliable 3D structure.

Approximating deformation fields for the analysis of continuous heterogeneity of biological macromolecules by 3D Zernike polynomials.

Structural biology has evolved greatly due to the advances introduced in fields like electron microscopy. This image-capturing technique, combined with improved algorithms and current data processing software, allows the recovery of different conformational states of a macromolecule, opening new possibilities for the study of its flexibility and dynamic events. However, the ensemble analysis of these different conformations, and in particular their placement into a common variable space in which the differences and similarities can be easily recognized, is not an easy matter.

Advances in Xmipp for Cryo-Electron Microscopy: From Xmipp to Scipion.

Xmipp is an open-source software package consisting of multiple programs for processing data originating from electron microscopy and electron tomography, designed and managed by the Biocomputing Unit of the Spanish National Center for Biotechnology, although with contributions from many other developers over the world. During its 25 years of existence, Xmipp underwent multiple changes and updates. While there were many publications related to new programs and functionality added to Xmipp, there is no single publication on the Xmipp as a package since 2013.

A study protocol for quantifying patient preferences in neuromuscular disorders: a case study of the IMI PREFER Project.

Patient preference studies are increasingly used to inform decision-making during the medical product lifecycle but are rarely used to inform early stages of drug development.  The primary aim of this study is to quantify treatment preferences of patients with neuromuscular disorders, which represent serious and debilitating conditions with limited or no treatment options available. This quantitative patient preferences study was designed as an online survey, with a cross-over design.

Cryo-EM and Single-Particle Analysis with Scipion.

Cryo-electron microscopy has become one of the most important tools in biological research to reveal the structural information of macromolecules at near-atomic resolution. In single-particle analysis, the vitrified sample is imaged by an electron beam and the detectors at the end of the microscope column produce movies of that sample. These movies contain thousands of images of identical particles in random orientations.

Image Processing in Cryo-Electron Microscopy of Single Particles: The Power of Combining Methods.

Cryo-electron microscopy has established as a mature structural biology technique to elucidate the three-dimensional structure of biological macromolecules. The Coulomb potential of the sample is imaged by an electron beam, and fast semi-conductor detectors produce movies of the sample under study. These movies have to be further processed by a whole pipeline of image-processing algorithms that produce the final structure of the macromolecule.

Associations Between Variant Repeat Interruptions and Clinical Outcomes in Myotonic Dystrophy Type 1.

Objective: To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention.

Methods: Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months.

DeepAlign, a 3D alignment method based on regionalized deep learning for Cryo-EM.

Cryo Electron Microscopy (Cryo-EM) is currently one of the main tools to reveal the structural information of biological specimens at high resolution. Despite the great development of the techniques involved to solve the biological structures with Cryo-EM in the last years, the reconstructed 3D maps can present lower resolution due to errors committed while processing the information acquired by the microscope. One of the main problems comes from the 3D alignment step, which is an error-prone part of the reconstruction workflow due to the very low signal-to-noise ratio (SNR) common in Cryo-EM imaging.

Patient Preferences in Rare Diseases: A Qualitative Study in Neuromuscular Disorders to Inform a Quantitative Preference Study.

Introduction: It has become increasingly important to include patient preference information in decision-making processes for drug development. As neuromuscular disorders represent multisystem, debilitating, and progressive rare diseases with few treatment options, this study aimed to explore unmet health care needs and patient treatment preferences for two neuromuscular disorders, myotonic dystrophy type 1 (DM1) and mitochondrial myopathies (MM) to inform early stages of drug development.

Methods: Fifteen semi-structured interviews and five focus group discussions (FGDs) were held with DM1 and MM adult patients and caregivers.

Algorithmic robustness to preferred orientations in single particle analysis by CryoEM.

The presence of preferred orientations in single particle analysis (SPA) by cryo-Electron Microscopy (cryoEM) is currently one of the hurdles preventing many structural analyses from yielding high-resolution structures. Although the existence of preferred orientations is mostly related to the grid preparation, in this technical note, we show that some image processing algorithms used for angular assignment and three-dimensional (3D) reconstruction are more robust than others to these detrimental conditions. We exemplify this argument with three different data sets in which the presence of preferred orientations hindered achieving a 3D reconstruction without artifacts or, even worse, a 3D reconstruction could never be achieved.

Patient Centricity in Patient Preference Studies: The Patient Perspective.

A factor contributing to the value of patient preference studies is patient centricity. This study aimed to explore how patients want to be involved in the design and conduct of patient preference studies. In addition, we investigated patients' expectations regarding the communication of study results back to patients.

Integration of Cryo-EM Model Building Software in .

Advances in cryo-electron microscopy (cryo-EM) have made it possible to obtain structures of large biological macromolecules at near-atomic resolution. This "resolution revolution" has encouraged the use and development of modeling tools able to produce high-quality atomic models from cryo-EM density maps. Unfortunately, many practical problems appear when combining different packages in the same processing workflow, which make difficult the use of these tools by non-experts and, therefore, reduce their utility.

Re-examining the spectra of macromolecules. Current practice of spectral quasi B-factor flattening.

The analysis of structure factors in 3D cryo-EM Coulomb potential maps and their "enhancement" at the end of the reconstruction process is a well-established practice, normally referred to as sharpening. The aim is to increase contrast and, in this way, to help tracing the atomic model. The most common way to accomplish this enhancement is by means of the so-called B-factor correction, which applies a global filter to boost high frequencies with some dampening considerations related to noise amplification.

Association of sleep, screen time and physical activity with overweight and obesity in Mexico.

Purpose: Approximately 70% of adults in Mexico are overweight or obese. Unhealthy lifestyle behaviors are also prevalent. We examined the association of three lifestyle behaviors with body mass index (BMI) categories in adults from Mexico.

Effective Reduction of Radiation Exposure during Cardiac Catheterization.

Exposure to ionizing radiation during cardiac catheterization can have harmful consequences for patients and for the medical staff involved in the procedures. Minimizing radiation doses during the procedures is essential. We investigated whether fine-tuning the radiation protocol reduces radiation doses in the cardiac catheterization laboratory.

Flexible workflows for on-the-fly electron-microscopy single-particle image processing using Scipion.

Electron microscopy of macromolecular structures is an approach that is in increasing demand in the field of structural biology. The automation of image acquisition has greatly increased the potential throughput of electron microscopy. Here, the focus is on the possibilities in Scipion to implement flexible and robust image-processing workflows that allow the electron-microscope operator and the user to monitor the quality of image acquisition, assessing very simple acquisition measures or obtaining a first estimate of the initial volume, or the data resolution and heterogeneity, without any need for programming skills.

Correction to: Eight years after an international workshop on myotonic dystrophy patient registries: case study of a global collaboration for a rare disease.

The original version of this article [1] unfortunately included an error to an author's name. Author Jordi Díaz-Manera was erroneously presented as Jorge Alberto Diaz Manera. The correct author name has been included in the author list of this Correction article.

Analysis of the functional capacity outcome measures for myotonic dystrophy.

Objectives: Defining clinically relevant outcome measures for myotonic dystrophy type 1 (DM1) that can be valid and feasible for different phenotypes has proven problematic. The Outcome Measures for Myotonic Dystrophy (OMMYD) group proposed a battery of functional outcomes: 6-minute walk test, 30 seconds sit and stand test, timed 10 m walk test, timed 10 m walk/run test, and nine-hole peg test. This, however, required a large-scale investigation, METHODS: A cohort of 213 patients enrolled in the natural history study, PhenoDM1, was analyzed in cross-sectional analysis and subsequently 98 patients were followed for longitudinal analysis.