The DIAD Approach to Correlative Synchrotron X‑ray Imaging and Diffraction Analysis of Human Enamel

The Dual Imaging and Diffraction (DIAD) beamline at Diamond Light Source (Didcot, U.K.) implements a correlative approach to the dynamic study of materials based on concurrent analysis of identical sample locations using complementary X-ray modalities to reveal structural detail at various length scales. Namely, the underlying beamline principle and its practical implementation allow the collocation of chosen regions within the sample and their interrogation using real-space imaging (radiography and tomography) and reciprocal space scattering (diffraction). The switching between the two principal modes is made smooth and rapid by design, so that the data collected is interlaced to obtain near-simultaneous multimodal characterization. Different specific photon energies are used for each mode, and the interlacing of acquisition steps allows conducting static and dynamic experiments. Building on the demonstrated realization of this state-of-the-art approach requires further refining of the experimental practice, namely, the methods for gauge volume collocation under different modes of beam–sample interaction. To address this challenge, experiments were conducted at DIAD devoted to the study of human dental enamel, a hierarchical structure composed of hydroxyapatite mineral nanocrystals, as a static sample previously affected by dental caries (tooth decay) as well as under dynamic conditions simulating the process of acid demineralization. Collocation and correlation were achieved between WAXS (wide-angle X-ray scattering), 2D (radiographic), and 3D (tomographic) imaging. While X-ray imaging in 2D or 3D modes reveals real-space details of the sample microstructure, X-ray scattering data for each gauge volume provided statistical nanoscale and ultrastructural polycrystal reciprocal-space information such as phase and preferred orientation (texture). Careful registration of the gauge volume positions recorded during the scans allowed direct covisualization of the data from two modalities. Diffraction gauge volumes were identified and visualized within the tomographic data sets, revealing the underlying local information to support the interpretation of the diffraction patterns. The present implementation of the 4D microscopy paradigm allowed following the progression of demineralization and its correlation with time-dependent WAXS pattern evolution in an approach that is transferable to other material systems

DETERMINING REFERENCE RANGES FOR TREC AND KREC ASSAYS IN IMMUNE DEFICIENCY SCREENING OF NEWBORNS IN RUSSIAN FEDERATION

In this work, we used a reference population of newborns and sampled dried blood spots on Guthrie cards of 2,739 individual samples to determine the reference intervals for TRECs and KRECs values, in order to diagnose primary immunodeficiency by means of neonatal screening. The median absolute values for TRECs and KRECs were 195 (CI95%: 185-206) and 185 (CI95%: 176-197) copies per μl, respectively; the normalized value for TRECs was 2780 (CI95%: 2690-2840), and for KRECs, 2790 (CI95%: 2700-2900) copies per 2 × 105 copies of the albumin gene or 105 cells. The reference interval was calculated for 99 and 99.9 percentiles of total TRECs and KRECs individual values. Due to asymmetric distribution of data, the outliers were filtered off, using the Tukey’s criterion applied after logarithmic transformation of the data. When analyzing absolute values for TREC/KREC (per μL of blood), no “drop-down” TRECs values were identified; for KRECs, 18 experimental values were excluded from further analysis (from 9.8 to 13.5). The outlying values were not identified among the normalized values of TRECs/KRECs. The obtained reference values for TRECs and KRECs (at the 0.1 percentile level) were, respectively, 458 and 32 per 105 cells, or 23 and 17 per μl of blood samples from neonates

TRAL: tandem repeat annotation library.

MOTIVATION: Currently, more than 40 sequence tandem repeat detectors are published, providing heterogeneous, partly complementary, partly conflicting results. RESULTS: We present TRAL, a tandem repeat annotation library that allows running and parsing of various detection outputs, clustering of redundant or overlapping annotations, several statistical frameworks for filtering false positive annotations, and importantly a tandem repeat annotation and refinement module based on circular profile hidden Markov models (cpHMMs). Using TRAL, we evaluated the performance of a multi-step tandem repeat annotation workflow on 547 085 sequences in UniProtKB/Swiss-Prot. The researcher can use these results to predict run-times for specific datasets, and to choose annotation complexity accordingly. AVAILABILITY AND IMPLEMENTATION: TRAL is an open-source Python 3 library and is available, together with documentation and tutorials via http://www.vital-it.ch/software/tral. CONTACT: [email protected]

A framework for employing longitudinally collected multicenter electronic health records to stratify heterogeneous patient populations on disease history

Objective To facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by overcoming electronic health records (EHRs) batch effects. Material and Methods We used 1872 billing codes in EHRs of 102 880 patients from 12 healthcare systems. Using tools borrowed from single-cell omics, we mitigated center-specific batch effects and performed clustering to identify patients with highly similar medical history patterns across the various centers. Our visualization method (PheSpec) depicts the phenotypic profile of clusters, applies a novel filtering of noninformative codes (Ranked Scope Pervasion), and indicates the most distinguishing features. Results We observed 114 clinically meaningful profiles, for example, linking prostate hyperplasia with cancer and diabetes with cardiovascular problems and grouping pediatric developmental disorders. Our framework identified disease subsets, exemplified by 6 "other headache" clusters, where phenotypic profiles suggested different underlying mechanisms: migraine, convulsion, injury, eye problems, joint pain, and pituitary gland disorders. Phenotypic patterns replicated well, with high correlations of >= 0.75 to an average of 6 (2-8) of the 12 different cohorts, demonstrating the consistency with which our method discovers disease history profiles. Discussion Costly clinical research ventures should be based on solid hypotheses. We repurpose methods from single-cell omics to build these hypotheses from observational EHR data, distilling useful information from complex data. Conclusion We establish a generalizable pipeline for the identification and replication of clinically meaningful (sub)phenotypes from widely available high-dimensional billing codes. This approach overcomes datatype problems and produces comprehensive visualizations of validation-ready phenotypes.Molecular Epidemiolog

Transient properties of modified reservoir-induced transparency

Published versio

Smooth Muscle Cell Phenotype Modulation and Contraction on Native and Cross-Linked Polyelectrolyte Multilayers

Smooth muscle cells convert between a motile, proliferative “synthetic ” phenotype and a sessile, “contractile ” phenotype. The ability to manipulate the phenotype of aortic smooth muscle cells with thin biocompatible polyelectrolyte multilayers (PEMUs) with common surface chemical characteristics but varying stiffness was investigated. The stiffness of (PAH/ PAA) PEMUs was varied by heating to form covalent amide bond cross-links between the layers. Atomic force microscopy (AFM) showed that cross-linked PEMUs were thinner than those that were not cross-linked. AFM nanoindentation demonstrated that the Young’s modulus ranged from 6 MPa for hydrated native PEMUs to more than 8 GPa for maximally cross-linked PEMUs. Rat aortic A7r5 smooth muscle cells cultured on native PEMUs exhibited morphology and motility of synthetic cells and expression of the synthetic phenotype markers vimentin, tropomyosin 4, and nonmuscle myosin heavy chain IIB (nmMHCIIB). In comparison, cells cultured on maximally cross-linked PEMUs exhibited the phenotype markers calponin, smooth muscle myosin heavy chain (smMHC), myocardin, transgelin, and smooth muscle R-actin (smActin) that are characteristic of the smooth muscle “contractile ” phenotype. Consistent with those cells being “contractile”, A7r5 cells grown on cross-linked PEMUs produced contractile force when stimulated with a Ca2+ ionophore

Indentation Hardness Measurements at Macro-, Micro-, and Nanoscale: A Critical Overview

The Brinell, Vickers, Meyer, Rockwell, Shore, IHRD, Knoop, Buchholz, and nanoindentation methods used to measure the indentation hardness of materials at different scales are compared, and main issues and misconceptions in the understanding of these methods are comprehensively reviewed and discussed. Basic equations and parameters employed to calculate hardness are clearly explained, and the different international standards for each method are summarized. The limits for each scale are explored, and the different forms to calculate hardness in each method are compared and established. The influence of elasticity and plasticity of the material in each measurement method is reviewed, and the impact of the surface deformation around the indenter on hardness values is examined. The difficulties for practical conversions of hardness values measured by different methods are explained. Finally, main issues in the hardness interpretation at different scales are carefully discussed, like the influence of grain size in polycrystalline materials, indentation size effects at micro-and nanoscale, and the effect of the substrate when calculating thin films hardness. The paper improves the understanding of what hardness means and what hardness measurements imply at different scales.Funding Agencies|Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University ((Faculty Grant SFO Mat LiU) [2009 00971]</p

Инфекции нижних дыхательных путей респираторно-синцитиальной вирусной этиологии у недоношенных детей и детей с бронхолегочной дисплазией

The article is devoted to the study of features of lower respiratory tract infection associated with respiratory syncytial virus. 40 cases of RSV-bronchiolitis in preterm children under year with/without bronchopulmonary dysplasia were analyzed. It was established that disease in those groups of patients had severe course because of the respiratory failure, which dominates in clinical pictures as symptoms of bronchial obstruction and apnea. Treatment of severe RSV-infection often demand admission to intensive care unit, supplemental oxygen and/or mechanical ventilation.Статья посвящена изучению особенностей поражения нижних дыхательных путей при респираторно-синцитиальной вирусной (РСВ) инфекции. Проанализировано 40 случаев РСВ-бронхиолита у недоношенных детей первого года жизни с бронхолегочной дисплазией и без нее. Установлено, что заболевание у данного контингента пациентов имеет тяжелое течение за счет развития дыхательной недостаточности, которая является основным клиническим проявлением, наряду с симптомами бронхиальной обструкции и апноэ. Лечение тяжелой РСВ-инфекции зачастую проводится в условиях отделения реанимации и интенсивной терапии, необходимо проведение оксигенотерапии и искусственной вентиляции легких

Этиология и клинические проявления острых кишечных инфекций у детей, по данным стационара г. Москвы за 2016—2018 гг.

The aim of the study was to study the etiology and clinical manifestations of acute intestinal infections (AII) in children aged 1 month to 18 years old who were hospitalized in the infectious diseases ward of a Moscow city hospital  in 2016—2018.A retrospective analysis of 9076 case histories was performed. Etiological interpretation was carried out using bacteriological examination of feces, latex agglutination reaction, immunochromatographic analysis, polymerase chain reaction (PCR), serological reactions (indirect hemagglutination test).The majority of children hospitalized with AII (62.2%) were 1—6 years of age. The etiology of AII was deciphered in 32% of cases. Acute intestinal infections of viral etiology prevail (64%), among them — rotavirus (73%), less often — norovirus (21%). AII of bacterial etiology accounted for only 14%, among them salmonellosis remains significant (5.6%), and in young children — staphylococcal infection (1.7%). There were also mixed infections (22%), mainly of viral and bacterial etiology. Noteworthy is the increase in the frequency of occurrence of bacterial AII in the winter season. The leading topical diagnosis in the vast majority of patients (85.1%) was gastroenteritis with the development of exsiccosis (77.6%).Целью исследования было изучение этиологии и клинических проявлений острых кишечных инфекций (ОКИ) у детей в возрасте от 1 месяца жизни до 18 лет, госпитализированных в инфекционное отделение стационара города Москвы в 2016—2018  гг. Проведен ретроспективный анализ 9076  историй болезни. Этиологическая расшифровка осуществлялась с использованием бактериологического исследования кала, реакции латекс-агглютинации (РЛА), иммунохроматографического анализа (ИХА), полимеразной цепной реакции (ПЦР), серологических реакций (РНГА, РПГА).Большинство госпитализированных с ОКИ детей (62,2%) были в возрасте 1—6 лет жизни. Этиология ОКИ была расшифрована в 32% случаев. Преобладают острые кишечные инфекции вирусной этиологии (64%), среди них — ротавирусной (73%), реже — норовирусной (21%). ОКИ бактериальной этиологии составили  лишь 14%, среди них значимым остается сальмонеллез (5,6%), а у детей раннего возраста — стафилококковая инфекция (1,7%). Также встречались  микст-инфекции (22%), преимущественно вирусно-бактериальной этиологии. Примечательно увеличение частоты встречаемости бактериальных ОКИ в зимний период года. Ведущим топическим диагнозом у подавляющего большинства больных (85,1%) был гастроэнтерит с развитием эксикоза (77,6%)