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During the COVID-19 pandemic, it is necessary to be wary of the development of pediatric multisystem inflammatory syndrome in children (PMIS) who have had a COVID-19 and had antibodies to the SARS-CoV-2 virus. The aim of this work is to describe two clinical cases in children with antibodies to SARS-CoV-2 against the background of yersiniosis in a 12-year-old child and salmonellosis in a 3-year-old child, which proceeded with a pronounced inflammatory reaction and required a differential diagnosis with multisystem inflammatory syndrome. These bacterial infections proceeded with severe intoxication and fever, had a polymorphic clinical picture with exanthema syndrome, conjunctivitis/scleritis, swelling of the palms/feet, diarrhea and toxic kidney damage, with a pronounced systemic inflammatory reaction – high leukocytosis with neutrophilia and lymphopenia, a significant increase in C-reactive protein, procalcitonin, hypercoagulability (increased fibrinogen, D-dimer). Etiotropic antibiotic therapy led to recovery in both cases. Conclusions: During the COVID-19 pandemic, if antibodies to the SARS-CoV-2 virus are detected in children in the presence of signs of systemic inflammation and corresponding symptoms, the alertness of doctors and a timely comprehensive examination are necessary to exclude bacterial infections, also characterized by signs of systemic inflammation, for the purpose of differential diagnosis of PMIS.

The clinical manifestations of immunodeficiency states (IDS), whether primary or secondary, are extremely nonspecific. The consequence of this is the belated setting of the correct diagnosis and, accordingly, the late start of the necessary therapy. Early detection of IDS is a key factor in the successful treatment of patients with these diseases. Determination of the concentration of TREC and KREC in whole blood and dry blood stains by real-time PCR has already proven its effectiveness for newborns and children in the first year of life. Objective of the study: to determine the concentration reference values of TREC and KREC in peripheral blood and dry spots in children and adolescents aged 1–17 years. Materials and methods of research: 162 conditionally healthy individuals were examined, including 64 at the age of 1–5 years, 47 – 6–11 years old and 51 – 12–17 years old. The concentration of TREC and KREC DNA in peripheral whole blood and dry blood spots on neonatal screening cards was assessed by PCR. Results: reference intervals and threshold values of TREC and KREC content in dry spots and in peripheral whole blood of children and adolescents aged 1–17 years were built and substantiated. Conclusion: the obtained reference values are very convenient for identifying patients with T- and/or B-cell lymphopenia, as well as monitoring the number of naive T- and B-lymphocytes in the peripheral blood of patients with already known diseases in wide pediatric practice.

Objectives Oxytocin (OXT) is widely used to facilitate labor. However, little is known about the effects of perinatal OXT exposure on the developing brain. We investigated the effects of maternal OXT administration on gene expression in perinatal mouse brains. Methods Pregnant C57BL/6 mice were treated with saline or OXT at term (n=6–7/group). Dams and pups were euthanized on gestational day (GD) 18.5 after delivery by C-section. Another set of dams was treated with saline or OXT (n=6–7/group) and allowed to deliver naturally; pups were euthanized on postnatal day 9 (PND9). Perinatal/neonatal brain gene expression was determined using Illumina BeadChip Arrays and real time quantitative PCR. Differential gene expression analyses were performed. In addition, the effect of OXT on neurite outgrowth was assessed using PC12 cells. Results Distinct and sex-specific gene expression patterns were identified in offspring brains following maternal OXT administration at term. The microarray data showed that female GD18.5 brains exhibited more differential changes in gene expression compared to male GD18.5 brains. Specifically, Cnot4 and Frmd4a were significantly reduced by OXT exposure in male and female GD18.5 brains, whereas Mtap1b, Srsf11, and Syn2 were significantly reduced only in female GD18.5 brains. No significant microarray differences were observed in PND9 brains. By quantitative PCR, OXT exposure reduced Oxtr expression in female and male brains on GD18.5 and PND9, respectively. PC12 cell differentiation assays revealed that OXT induced neurite outgrowth. Conclusions Prenatal OXT exposure induces sex-specific differential regulation of several nervous system-related genes and pathways with important neural functions in perinatal brains.

Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and cellular features (pathotypes). One of these pathotypes is defined by high neutrophil infiltration, activation of fibroblasts and vascular remodeling at sites of deep ulceration. Activated fibroblasts in the ulcer bed display neutrophil-chemoattractant properties that are IL-1R, but not TNF, dependent. Pathotype-associated neutrophil and fibroblast signatures are increased in nonresponders to several therapies across four independent cohorts (total n = 343). The identification of distinct, localized, tissular pathotypes will aid precision targeting of current therapeutics and provides a biological rationale for IL-1 signaling blockade in ulcerating disease., Transcriptomic and histological profiling of gut biopsies from multiple independent cohorts of patients with inflammatory bowel disease identifies distinct histopathological, molecular and cellular features associated with treatment response, providing insights for patient stratification and precision therapy.

Ptychography is a scanning coherent diffraction imaging technique that provides high-resolution imaging and complete spatial information of the complex probe and object transmission function. The wavefront error caused by aberrated optics has previously been recovered using ptychography when a highly coherent source is used, but has not been demonstrated with partial coherence due to the multi-modal probe required. Here, we demonstrate that partial coherence can be accounted for in ptychographic reconstructions using the multi-modal approach and assuming that decoherence arises from either the probe or the object. This equivalence recovers coherent (or single state) reconstructions of both the probe and the object even in the presence of partial coherence. We demonstrate this experimentally by using hard x-ray ptychography with a partially coherent source to image a Siemens star test object and to also recover the wavefront error from an aberrated beryllium compound refractive lens. The source properties and resolving capabilities are analyzed, and the wavefront error results are compared with another at-wavelength metrology technique. Our work demonstrates the capability of ptychography to provide high-resolution imaging and optics characterization even in the presence of partial coherence.

Enuresis as an independent pathology in children over 5 years old occurs quite often, and amounts to 5–17% depending on the age. For a long time, the focus of research into this pathology has been on monosymptomatic enuresis, which is both a symptom and the main manifestation of the disease (nighttime urination incontinence). In-depth study into the problem of enuresis was initiated more than 20 years ago by prof. E.L. Vishnevsky in the Moscow City Center of Pathology of urination at the Speransky Children's City Clinical Hospital № 9. As a result of the work carried out jointly at several Russian centres in Moscow, Petrozavodsk, Sevastopol and Anadyr by children’s urologists, neurologists, nephrologists and paediatricians, a conclusion was reached on encuresis as a manifestation of comorbid conditions. The article presents the results of of the clinical studies in children with attention-deficit/hyperactivity disorder (ADHD), overactive bladder (OAB), metabolic nephropathies, and other somatic pathologies in which enuresis was a manifested clinical syndrome. Differential diagnosis and effective treatment tactics in such cases require more thorough research using clinical, neurophysiological and instrumental methods, which makes it possible to establish a diagnosis in a timely manner and administer an adequate therapy.

Neonatal acute kidney injury (AKI) is common in newborns in critical condition in the intensive care units and significantly reduces the chances of recovery. The analysis of attitudes to this problem and the practical experience of pediatric doctors working with newborns regarding the risks of development and outcomes of AKI is an important step in improving the prognosis of the disease. Objective of the study: determination of awareness of the problem of neonatal AKI. Materials and methods of research: the study was carried out in the form of a sociological survey (questionnaire) of doctors (n=63) working in neonatal intensive care units (NICU) (n=34, 54%), and pediatricians not associated with work in the NICU (n=29, 46%). The questionnaire contained 34 questions. 51% of the respondents (n=32) were under 40 years old, 49% – over 40 years old (n=31). Results: there is a lack of awareness of specialists regarding definitions, diagnostics, treatment tactics, prognosis of the disease, as well as insufficient availability of treatment facilities for access to nephrological and dialysis care. 29% (95% CI 14–44%, n=10) NICU doctors and 21% (95% CI 6–36%, n=6) doctors from other departments were unaware of the existing AKI classifications in newborns (p=0,615). 62% (95% CI 46–78%, n=21) of NICU staff and 55% (95% CI 37–73%, n=16) by doctors of other specialties (p=0,785) reported that nephrology counseling was available. The availability of renal replacement therapy was reported by 27% (95% CI 12–42%, n=9) by NICU doctors and 35% (95% CI 18–52%, n=10) by doctors from other departments (p=0,678). Only 52 (83%) (95% CI 74–92%) doctors believe that the child should be examined by a nephrologist. Conclusion: it is necessary to raise awareness among doctors about neonatal AKI.

We consider the task of Inverse Reinforcement Learning in Contextual Markov Decision Processes (MDPs). In this setting, contexts, which define the reward and transition kernel, are sampled from a distribution. In addition, although the reward is a function of the context, it is not provided to the agent. Instead, the agent observes demonstrations from an optimal policy. The goal is to learn the reward mapping, such that the agent will act optimally even when encountering previously unseen contexts, also known as zero-shot transfer. We formulate this problem as a non-differential convex optimization problem and propose a novel algorithm to compute its subgradients. Based on this scheme, we analyze several methods both theoretically, where we compare the sample complexity and scalability, and empirically. Most importantly, we show both theoretically and empirically that our algorithms perform zero-shot transfer (generalize to new and unseen contexts). Specifically, we present empirical experiments in a dynamic treatment regime, where the goal is to learn a reward function which explains the behavior of expert physicians based on recorded data of them treating patients diagnosed with sepsis.

Necrotizing enterocolitis of newborns (NEC) is a severe intestinal disease that occurs against the background of acute hypoxia, violations of normal colonization of the intestine by microflora, leading to necrosis and perforation of the intestinal wall, peritonitis. Frequency of occurrence of 1-5 cases per 1000 live-born children. Most often, premature babies and children with low birth weight get sick. The development of NEC in a child significantly worsens the prognosis and increases mortality. Modern development of medical technology has made it possible to provide assistance to extremely premature newborns, which has led to an increase in the number of patients with NEC who are in a critical condition due to the course of multi-organ failure, including kidney failure, which requires renal replacement therapy (RRT). The main method of RRT used in newborns and young children is peritoneal dialysis (PD). NEC in the initial stages is considered an absolute contraindication for performing invasive manipulations on the abdominal cavity, since the risk of disease progression with the development of complications requiring surgical intervention increases at times. Recently, peritoneal dialysis has also become widespread in deeply premature newborns, who are the main risk group for developing NEC. Peritoneal dialysis in the continuous flow modification eliminates high intra-abdominal tension, one of the provoking factors for the progression of NEC, and in foreign expert studies, there are reports that the dialysis solution improves the intestinal wall trophism. This article presents a clinical case of peritoneal dialysis in flow modification in a 1-month-old child with acute renal damage and necrotizing enterocolitis.

All solid state, thin film Li-NMC batteries produced by Physical Vapour Deposition have the potential to revolutionize the internet of things by integrating ultra-fast charging and high energy densities into small portable devices. In these systems, the integrity of the cathode-solid electrolyte interface is of particular importance, as it determines the internal battery resistance and attainable charge rate. To understand and control the effect of manufacturing parameters on the performance and interface stability in these systems, as well as the mechanisms resulting in interface degradation, a novel approach was used that combined in situ battery lamella charging with electron nano-diffraction and multiphysics Finite Element modeling. Experimentally observed cathode strains and degradation were correlated with deposition parameter-controlled grain orientation, to determine ideal deposition conditions for enhanced thin film battery charging and discharging behavior. It was identified that (104) oriented cathode grains minimize anode-electrolyte interface degradation, while allowing for high charge and discharge rates, as well as significantly reducing the cathode-electrolyte interface resistance. Furthermore, the residual stress state of individual thin film battery layers, as well as the cathode grain orientation were identified as material design parameters to optimize cell performance and durability with potential capacity retention enhancements of up to 28%.

Phantoms are widely used substitutes for various types of soft tissues with mechanically and anatomically matching properties. They can be used as advanced tools for training before the surgical manipulation on human organs such as the brain or liver as part of complex operation planning and preparation. We report 3D printing fabrication and characterization of hydrogel composites based on the combination of two biocompatible materials, namely, polyvinyl alcohol (PVA) and phytagel (PHY). The hydrogels were used for the fabrication of brain phantoms in a multistage procedure based around 3D printing. The main goal of this study is to demonstrate the simple, low cost and relatively fast procedure for the creation of hydrogel organ phantoms of high anatomical and mechanical fidelity made from commonly available materials. To this end, three different types of samples were produced to illustrate the flexibility of hydrogel-based 3D printing approach in mimicking the mechanical properties of human organs: brain, lung, and liver soft tissues. The mechanical response was studied using Deben MicroTest 1 kN mechanical testing device and Q800 Dynamic Mechanical Analyser in compression mode. The results reveal close matching of the dynamic non-linear mechanical response of the phantoms to those of the corresponding natural soft tissues.

This paper presents a summary of recently developed experimental and computational tools to reconstruct residual stress fields and analyze creep in nickel superalloy welds used in aerospace engineering components. This approach combines experimental data with eigenstrain theory to reconstruct stress fields at the macroscopic scale and provided reliable means for numerical prediction of creep behavior of welded components under complex loading conditions. Experimental data in the form of profilometry scans was interpreted using a range of iterative eigenstrain methods that included the adaptation of the contour method and artificial intelligence models for eigenstrain-creep analysis. The integration of principles of artificial intelligence with eigenstrain models allowed highly accurate results to be obtained which were validated by comparison with experimental data obtained using independent techniques such as neutron diffraction. The use of artificial intelligence models is discussed for residual stress reconstruction and creep behavior prediction in annular aeroengine parts manufactured using inertia friction welding. To extend the range of experimental data taken into consideration, the height Digital Image Correlation (hDIC) technique was introduced that utilizes information regarding triaxial displacements obtained from profilometry, allowing deeper and more reliable analysis to be conducted. The hDIC technique was validated using operando tensile testing data.

The pursuit of new nanotechnologies is driven by the demand for miniaturization, ubiquitous computing, increasing connectivity and the Internet of Things (IoT) paradigm, the environmental agenda, and the confluence between microelectronics and biomedical fields. Of particular interest for the present overview are the capabilities of prokaryotic and eukaryotic microorganisms to fabricate numerous nanostructured self-copies from ecologically friendly and renewable raw materials offering new pathways for low energy consumption, smart nanofabrication at production rates that remain unattainable for today’s engineering technologies. The present discussion is focused on the use of stiff and strong nanostructured silica diatom frustules that is widely mooted in the literature in consideration of photonic, photovoltaic, plasmonic, and drug delivery applications. Chemical post-processing routes can be applied to synthesize and deposit nanostructures (Ag, Au, MnO2, ZnO etc.) using templates and substrates of diatomaceous earth and individual diatom frustules. In this concise overview we discuss the background knowledge, motivation and justification for the use of siliceous diatom frustules as a platform for smart nanofabrication, and attempt to anticipate future developments in this field.

Analyzing Oregon agricultural atlases from 1878 to 1958, I show that, despite these texts’ projection of impartial authority, they function to extend a discourse of natural bounty in which agricultural abundance is linked to inherent characteristics of the land, hiding the role of racialized and disenfranchised laborers in production. Using a combination of Agricultural Census data, historical and contemporary records from farmers and agricultural extension services, and GIS software, I demonstrate a method for reconstructing historical and contemporary agricultural labor landscapes, filling in—at least partially—the spatial absence of farmworkers. Using maps I have produced for a limited set of crops as a case study, alongside worker testimonies and ethnographic accounts, I argue that this sort of counter-mapping of the agricultural landscape can form the basis for an alternative spatial narrative of changing landscapes, replacing the depopulated and bountiful nature of conventional agricultural atlases with maps that reveal the agricultural landscape from a worker’s perspective that centers the hidden the toil and suffering entailed in the creation of Oregon’s agricultural bounty.

The review presents the special significance of changes in the intestinal and skin microbiota in the formation of atopic dermatitis (AD) in children. AD is considered as a form of allergic pathology directly related to the state and quality of the microbiota of a growing organism. The microbiota of the skin of patients with AD is characterized by a small species diversity of bacteria; a decrease in the number of actinomycetes and proteobacteria; increased colonization of various types of staphylococci (S. aureus, S. epidermidis, S. haemolyticus, etc). The relationship between the rate of development of AD and violations of the microbiota of the skin in children is shown. The necessity of maintaining high biodiversity of the microbiota of a growing organism as a strategy for optimizing the microecology of children through the use of adaptive probiotics in a healthy microenvironment is substantiated. The restoration of the barrier function of the skin and the normalization of the composition and quality of the intestinal microbiota are determined as the most important task of the general concept of the treatment of AD, where new dermatological cosmetics and proper skin care play an important role. The possibilities of normalizing the microbiome of the affected skin areas to restore the skin barrier with the help of dry skin care cosmetics are shown.

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%).

The eigenstrain theory provides a range of fruitful concepts for advanced modelling of the behaviour of materials and components obtained using sophisticated manufacturing routes, their response to thermal and mechanical loading, and deformation under fatigue and creep conditions. In recent years the method has been shown to be able to provide predictions of residual stresses for a limited range of processing and simulated service conditions for which experimental data is available. The authors recently presented advances in the use of eigenstrain-based analysis to include accurate determination of the domain and boundaries of eigenstrain fields in the weld zone. This approach allowed effective modelling of large-scale components and the determination of volumetric distributions of residual stresses through the use of additional model coefficients that need to be determined. Due to the non-linear dependence of the prediction on these parameters, the algorithm of the decision-making process has a profound influence on the cost of the simulation, and the reliability of its output. To address this challenge, the principles of Artificial Intelligence were adopted for use in the eigenstrain contour method to develop fuzzy Finite Element Model (fFEM) for the eigenstrain the reconstruction of residual stresses in large structures. The deterministic finite element eigenstrain model uses contour measurements for reconstruction process, and the developed fFEM behaves as an artificial agent to determine the coefficients of the deterministic finite element eigenstrain model. As an example application, as-welded and post-weld heat-treated specimens of non-uniform weldments of Inconel Alloy 740H were investigated using the proposed model. The results were verified using displacement measurements and residual stress calculations of the contour method. The determination of model coefficients by artificial agent allowed effective reconstruction of volumetric residual stresses in complex shaped components using limited data without the requirement of costly and destructive multi-cut experimental procedures.

Background Response to targeted therapy varies between patients for largely unknown reasons. Here, we developed and applied an integrative platform using mass spectrometry imaging (MSI), phosphoproteomics, and multiplexed tissue imaging for mapping drug distribution, target engagement, and adaptive response to gain insights into heterogeneous response to therapy. Methods Patient-derived xenograft (PDX) lines of glioblastoma were treated with adavosertib, a Wee1 inhibitor, and tissue drug distribution was measured with MALDI-MSI. Phosphoproteomics was measured in the same tumors to identify biomarkers of drug target engagement and cellular adaptive response. Multiplexed tissue imaging was performed on sister sections to evaluate spatial co-localization of drug and cellular response. The integrated platform was then applied on clinical specimens from glioblastoma patients enrolled in the phase 1 clinical trial. Results PDX tumors exposed to different doses of adavosertib revealed intra- and inter-tumoral heterogeneity of drug distribution and integration of the heterogeneous drug distribution with phosphoproteomics and multiplexed tissue imaging revealed new markers of molecular response to adavosertib. Analysis of paired clinical specimens from patients enrolled in the phase 1 clinical trial informed the translational potential of the identified biomarkers in studying patient’s response to adavosertib. Conclusions The multimodal platform identified a signature of drug efficacy and patient-specific adaptive responses applicable to preclinical and clinical drug development. The information generated by the approach may inform mechanisms of success and failure in future early phase clinical trials, providing information for optimizing clinical trial design and guiding future application into clinical practice.

ObjectivesIn lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.ConclusionsProcurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

In the last decade, perovskite photovoltaics gained popularity as a potential rival for crystalline silicon solar cells, which provide comparable efficiency for lower fabrication costs. However, insufficient stability is still a bottleneck for technology commercialization. One of the key aspects for improving the stability of perovskite solar cells (PSCs) is encapsulating the photoactive material with the hole-transport layer (HTL) with low gas permeability. Recently, it was shown that the double HTL comprising organic and inorganic parts can perform the protective function. Herein, a systematic investigation and comparison of four double HTLs incorporating polytriarylamine and thermally evaporated transition metal oxides in the highest oxidation state are presented. In particular, it was shown that MoOx, WOx, and VOx-based double HTLs provided stable performance of PSCs for 1250 h, while devices with NbOx lost 30% of their initial efficiency after 1000 h. Additionally, the encapsulating properties of all four double HTLs were studied in trilayer stacks with HTL covering perovskite, and insignificant changes in the absorber composition were registered after 1000 h under illumination. Finally, it was demonstrated using ToF-SIMS that the double HTL prevented the migration of perovskite volatile components within the structure. Our findings pave the way towards improved PSC design that ensures their long-term operational stability.

Background Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Methods To identify cellular phenotypes that may be shared across tissues affected by disparate inflammatory diseases, we developed a meta-analysis and integration pipeline that models and removes the effects of technology, tissue of origin, and donor that confound cell-type identification. Using this approach, we integrated > 300,000 single-cell transcriptomic profiles from COVID-19-affected lungs and tissues from healthy subjects and patients with five inflammatory diseases: rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and interstitial lung disease. We tested the association of shared immune states with severe/inflamed status compared to healthy control using mixed-effects modeling. To define environmental factors within these tissues that shape shared macrophage phenotypes, we stimulated human blood-derived macrophages with defined combinations of inflammatory factors, emphasizing in particular antiviral interferons IFN-beta (IFN-β) and IFN-gamma (IFN-γ), and pro-inflammatory cytokines such as TNF. Results We built an immune cell reference consisting of > 300,000 single-cell profiles from 125 healthy or disease-affected donors from COVID-19 and five inflammatory diseases. We observed a CXCL10+ CCL2+ inflammatory macrophage state that is shared and strikingly abundant in severe COVID-19 bronchoalveolar lavage samples, inflamed RA synovium, inflamed CD ileum, and UC colon. These cells exhibited a distinct arrangement of pro-inflammatory and interferon response genes, including elevated levels of CXCL10, CXCL9, CCL2, CCL3, GBP1, STAT1, and IL1B. Further, we found this macrophage phenotype is induced upon co-stimulation by IFN-γ and TNF-α. Conclusions Our integrative analysis identified immune cell states shared across inflamed tissues affected by inflammatory diseases and COVID-19. Our study supports a key role for IFN-γ together with TNF-α in driving an abundant inflammatory macrophage phenotype in severe COVID-19-affected lungs, as well as inflamed RA synovium, CD ileum, and UC colon, which may be targeted by existing immunomodulatory therapies.

Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology, and in situ localisation, we describe heterogeneity of the tissular inflammatory response in IBD treatment failure. Among inflammatory pathotypes, we found high neutrophil infiltration, activation of fibroblasts, and vascular remodelling at sites of deep ulceration was a feature of non-response to several anti-inflammatory therapies. Activated fibroblasts in the ulcer bed display neutrophil chemoattractant properties that are IL-1R- but not TNF-dependent. The identification of distinct, localised, tissular pathotypes associated with treatment non-response will aid precision targeting of current therapeutics and provide a biological rationale for IL-1 signalling blockade in ulcerating disease.

SummaryPro-inflammatory fibroblasts are critical to pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren’s syndrome, and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited the understanding of which pathways are shared by multiple diseases. To investigate, we profiled patient-derived fibroblasts from inflamed and non-inflamed synovium, intestine, lung, and salivary glands with single-cell RNA-sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes. Two shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts were expanded in all inflamed tissues and additionally mapped to dermal analogues in a public atopic dermatitis atlas. We further confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation. This work represents the first cross-tissue, single-cell fibroblast atlas revealing shared pathogenic activation states across four chronic inflammatory diseases.

Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. Our cross-disease analysis revealed that an FCN1+ inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10+ CCL2+ inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1, and IL1B. We found that the CXCL10+ CCL2+ macrophages are transcriptionally similar to blood-derived macrophages stimulated with TNF-α and IFN-γ ex vivo. Our findings suggest that IFN-γ, alongside TNF-α, might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases, which may be targeted by existing immunomodulatory therapies.

Ever since humans engaged in directed manufacturing activities to make tools and utensils, design decorative pieces of jewellery, build dwellings, and fabricate furnishings, they became concerned about surface properties [...]

A retrospective analysis of the etiological structure and clinical manifestations of acute intestinal infections was conducted in 8459 children hospitalized in a specialized infectious disease department at the Children's City Clinical Hospital No.9 in Moscow, in 2015—2017 based on the study of statistical reports of the Children's City Clinical Hospital No.9 for 2015—2017 and 2417 case histories of children aged 1 month to 18 years old.It was found that children with age 1—7 years of age (58.5%) are more likely to have acute intestinal infections and are hospitalized. The etiological interpretation of acute intestinal infections remains at a low level and is 28.6%. The leading causative agents of acute intestinal infections are viruses (83%), mainly rotaviruses (62%), less often noroviruses (18%). Topical diagnosis in the vast majority of patients with acute intestinal infections was gastroenteritis (74.7%), which leads to the development of toxicosis with exsiccosis, especially in young children, which is the reason for hospitalization in the hospital. The share of bacterial diarrhea is small (17%), among them salmonella is significant, and in young children — staphylococcal infection. In recent years, the relevance of identifying campylobacter and clostridium, these pathogens may be the cause of the development of diarrhea with hemoccolitis.

Infections are the leading cause of death for individuals with traumatic spinal cord injury (SCI). Along with increased infection rates, inflammation is often also observed in persons with chronic SCI. Together, immunological changes post-SCI are also poised to impede neurological recovery and mediate common medical consequences of SCI, including atherogenesis and neuropathic pain. The molecular mechanisms contributing to increased infection susceptibility and inflammation in persons living with SCI are poorly understood. Here, we used tools of functional genomics to perform a pilot study to compare whole-blood gene expression in individuals with chronic SCI (≥1 year from initial injury; N = 31) and uninjured individuals (N = 26). We identified 1815 differentially expressed genes in all SCI participants and 2226 differentially expressed genes in persons with SCI rostral to thoracic level 5, compared to uninjured participants. This included marked downregulation of natural killer cell genes and upregulation of the proinflammatory Toll-like receptor signaling pathway. These data provide novel mechanistic insights into the causes underlying the symptoms of immune dysfunction in individuals living with SCI.

The article presents the results of the study of the etiological structure and clinical features of acute intestinal infections of viral, bacterial and mixed etiology in children hospitalized in a specialized department of Children's Clinical Hospital №9 named G. N. Speransky, city of Moscow in 2008—2016. It was found that during 9 years of follow-up, the number of hospitalized patients with acute intestinal infections does not have an obvious tendency to decrease. More than half of hos-pitalized patients are children 1—7 years old. Among the reasons for acute intestinal infections of established etiology, viral agents (rotaviruses and noroviruses) prevail. Among bacterial intestinal infections, the most urgent are salmonellosis, campylobacteriosis and staphylococcal infection.

A 8-year-old child with multiple skeletal injuries after car accident is presented in the article. Extensive right-sided urohematoma with impaired kidney function was diagnosed after 15 days. External drainage of urohematoma, ureteroscopy and examination of the right kidney were consecutively performed within 1.5 months. A complete rupture of the right ureter at the level of pyeloureterostomy was diagnosed. Right kidney autotransplantation with ureteral resection and pyeloureteral anastomosis were performed in 2 months after injury. Duration of surgery was 7.5 hours, cold ischemia - 55 min. Postoperative examination confirmed satisfactory function of the right kidney. This observation is relatively rare and the first in Russia.Представлено клиническое наблюдение ребенка 8 лет, пострадавшего в автокатастрофе и получившего множественные скелетные травмы. Через 15 сут после травмы выявлена обширная урогематома справа со снижением функции почки. В течение 1,5 мес последовательно выполнены наружное дренирование урогематомы, уретероскопия и ревизия правой почки. Диагностирован полный разрыв правого мочеточника на уровне пиелоуретерального соустья. Через 2 мес после травмы произведена аутотрансплантация правой почки с резекцией мочеточника и наложением пиелоуретерального анастомоза. Продолжительность операции составила 7,5 ч, холодовой ишемии - 55 мин. Контроль после операции подтвердил удовлетворительную функцию правой почки. Данное наблюдение сравнительно редкое, в России приводится впервые.

Ptychography has been developed and routinely employed as an at-wavelength metrology method on a low coherence dipole magnet beamline., Ptychography is a scanning coherent diffraction imaging technique which provides high resolution imaging and complete spatial information of the complex electric field probe and sample transmission function. Its ability to accurately determine the illumination probe has led to its use at modern synchrotrons and free-electron lasers as a wavefront-sensing technique for optics alignment, monitoring and correction. Recent developments in the ptychography reconstruction process now incorporate a modal decomposition of the illuminating probe and relax the restriction of using sources with high spatial coherence. In this article a practical implementation of hard X-ray ptychography from a partially coherent X-ray source with a large number of modes is demonstrated experimentally. A strongly diffracting Siemens star test sample is imaged using the focused beam produced by either a Fresnel zone plate or beryllium compound refractive lens. The recovered probe from each optic is back propagated in order to plot the beam caustic and determine the precise focal size and position. The power distribution of the reconstructed probe modes also allows the quantification of the beams coherence and is compared with the values predicted by a Gaussian–Schell model and the optics exit intensity.

4D Printing (4DP) is a term used to denote the ability to control the geometric (shape, dimensions), structural (strength, stiffness), or functional properties of additively manufactured objects via postprocessing. The concept emerged in the 3D printing (3DP) community in the beginning of 2010s. Perhaps the most straightforward manifestation of conferring 4DP capability on a 3D print is via the use of Shape memory effect (SME) in polymers, extensively studied since the 1970s. Using this effect allows expanding the functionality and applications of 3D printed components by triggering specific physical, chemical, and nanostructural phenomena within them. The present Chapter overviews relevant publications focusing on the core mechanisms relating to the SME in additive manufacturing: the nature of polymers suitable for 4DP, the influence of thermal history on polymer supramolecular structure, and the key characteristics of the SME, such as the recovery stress and strain, temperature of activation, reproducibility, etc. The overview also touches upon the diversity of mechanisms of self-healing, self-assembly, self-deployment, etc. that open up the possibilities for use in a range of promising applications, such as sensors and actuators, biomedical implants, mechanical fastening, etc.

Deformation analysis in engineering materials and components is a subject of ongoing enquiry due to its importance for obtaining reliable prediction of strength and durability of structures and assemblies. Whilst optical methods deliver information about surface displacements, X-ray scattering methods have the capability to provide efficient assessment of crystal lattice distortion in the bulk of the component. The height digital image correlation (hDIC) technique is an alternative to conventional digital image correlation that uses the out-of-plane surface height variations for the identification of triaxial deformations. In this study, the hDIC technique was used for the determination of displacements in an aluminium specimen after 3-point bending process that creates a complex deformation state that includes both axial displacements and rotations. The surface of the specimen was prepared for the analysis by electric discharge machining (EDM) technique that has minimal effect on material properties and produces random height profile well-suited for the aim of this study. Surface height variations were measured using deep focus microscopy and used instead of pixel intensity for correlation in the DIC process. The distribution of total of elastic and plastic strains were also calculated by the evolutionary eigenstrain model using 2D X-ray diffraction patterns processed according to the polar transformation method. The agreement between hDIC and polar X-Ray diffraction analyses allowed reliable cross-validation between these two techniques.

50 children aged from 3 to 67 months with acute intestinal infections receiving antibiotic therapy, were clinically and microbiologically examined using gas-liquid chromatographic test with the measurement of short-chain fatty acids (SCFAs) in coprofiltrates. The influence on the biocenosis is assessed upon treatment with an-tidiarrhoeal medication Gelatin tannat (Adiarin), which acts by forming a protective film on the surface of intestinal mucosa preventing loss of body fluids and microbial toxins. 20 children in the control group received antibiotics, sorbents, probiotics. The study has proved the clinical effect of Gelatin tannat, resulting in reduction of time to normalization of diarrhea and intoxication for 2 days, and data on the probiotic effect of the drug, similar to that of probiotics in the control group which expands the indications for the use of Gelatin tannat for prevention of antibiotic-associated diarrhea.

Under homogeneous illumination of thin chalcogenide glass films by polarized light at a wavelength near the band gap ripples form, with a period of the order of 10–15 µm, directed normal to the light polarization. The formation of the ripples cannot be explained by interference phenomena, which predict the ripple periods of the order of light wavelength. Our experimental and theoretical studies of the ripple formation in 1 µm thick As 10 Se 90 chalcogenide films show that the profile variation occurs due to lateral mass transport accelerated by light. The ripple formation is caused by competition between capillary forces and steady state electrostatic forces induced by redistribution of electrons and holes generated by light. Under these driving forces, each harmonic of the film roughness spectrum should exponentially grow or flatten, depending on its frequency. The average period of the ripples corresponds to those harmonics in the roughness spectra, which grow with maximum rate. Light-induced diffusion coefficients have been estimated from the kinetics of the ripple formation.

Modern advanced manufacturing technologies have made possible the tailored design and fabrication of complex nanoscale architectures with anomalous and enhanced properties, including mechanical and optical metamaterials; structured materials which are able to exhibit unusual mechanical and optical properties that are derived from their geometry rather than their intrinsic material properties. In this work, we fabricated for the first time an ultrathin 2D auxetic metamaterial with nanoscale geometric features specifically designed to deform in-plane by using focused-ion-beam milling to introduce patterned nano-slits within a thin membrane. The system was mechanically loaded in-situ and exhibited in-plane dominated deformation up to 5% tensile strain and a Poisson's ratio of −0.78. Furthermore, the porosity and aperture shape of the metamaterial have been shown to change considerably upon the application of strain, with pore dimensions showing a fourfold increase at 5% strain. This mechanically-controlled tuneability makes this metamaterial system an ideal candidate for use as a reconfigurable nano-filter or a nano light-modulator.

Post weld heat treatment (PWHT) process has an important role on fabrication of advanced ultra-supercritical power plant turbines. This process relieves the residual stresses formed as a result of welding by converting elastic strains into creep strains. In order to analyse the residual stress relief mechanism during the PWHT process, a novel simulation approach based on experimental data was developed for the analysis of residual stress states from complex manufacturing processes which are welding and heat treatment. This model uses permanent plastic strains (eigenstrains) formed as a result of welding process to set the initial mechanical state of the sample. The distribution of eigenstrains in the whole body was determined using displacement data obtained from contour measurements. The use of eigenstrains to set the initial residual stress state of the creep model reduced the number of uncertainties. This allowed the use of the principles of artificial intelligence for the development of a new fuzzy finite element model (fFEM) that determines the eigenstrain-creep model parameters through an evolution process. Subsequent to the determination of the model parameters, conditions of the PWHT process are investigated to analyse residual stress relaxation in Inconel Alloy 740H weldments.