HybridMeat - products from animal and plant sources

Consumer diversification and concerns about insufficient protein supply and global malnutrition demand for an exploitation of alternative protein sources such as plant proteins. While manufacturers have made substantial progress in industrially scaled extraction processes and structuring of plant proteins e.g. by extrusion, there is still a lack of information on their fundamental functional and organoleptic properties and interactions with other ingredients in traditional formulations. As a result, food product developers are facing a lot of challenges and are often forced to base their work on trial-and-error rather than mechanistically guided approaches. This is in particular the case for foods where complex raw material requirements and production processes make the manufacture of products with high acceptance and shelf stability not trivial. This includes the design of hybrid meat products that are composed of mixtures of meat and plant proteins. There, traditional meat products are often set as a benchmark, making the performance of such mixed products mostly unsatisfactory. Establishing composition material property functionality relationships may be a first step to overcome these obstacles. Therefore, a variety of plant proteins was assessed for their composition, physicochemical properties, and techno functionalities to gain an understanding of their suitability for the formulation of hybrid meat products. This included their dispersibility, the miscibility of select plant protein fractions with solubilized meat proteins at varying pH and mixing ratios, and the characterization of their odor-active compounds. The latter included powdered as well as extruded plant proteins due to their increasing relevance in the manufacture of hybrid meat and analogue products. Following this, plant proteins were screened in terms of their performance in hybrid meat formulations and during traditional manufacture with a special focus on dry cured products in order to define feasible protein sources and application thresholds. The first part of this thesis showed that aqueous solubility, native pH, and appearance of a variety of 26 plant protein powders from carbohydrate and vegetable oil production correlated with purity and the extraction process. Solubility ranged from as low as 4 % to as high as 100 % based on the protein concentration and prevalence of select protein fractions. For example, large amounts of prolamins (wheat) or glutelins (rice, pumpkin) resulted in low values, while high shares of albumins and globulins promoted moderate to high solubility in sunflower, pea, and potato proteins. A highly soluble (100 %) small molecular weight fraction ( pI) transitioned to two-phased/aggregated ones mediated by interactions (pH ≤ pI) in between individual meat and meat and potato proteins. This resulted in dense, irregularly shaped meat-potato heteroprotein particles, that deviated from the characteristic assembly of pure meat proteins into regular, anisotropic aggregates. A perturbing effect of potato proteins on the structural, organized association of meat proteins below their pI was found. Protein-protein interactions were based on both electrostatics and hydrophobics as shown by variations in surface charge, hydrophobicity, and particle size if sole potato/meat and mixtures were compared. For example, particle size of solubilized meat proteins increased from 18.0 ± 2.9 µm (pH 3.0) to 26.8 ± 9.0 µm (pH 3.0) in 50:50 mixtures. FTIR results confirmed alterations as a function of mixing ratio and pH. Image analysis of microstructures revealed a shift from elongated regular networks towards more disorder and irregularity along with a lower degree of branching. Besides solubility, organoleptic properties influence the suitability of plant proteins as food ingredients. Therefore, odor active compounds of two pea isolates were analyzed by gas chromatography mass spectrometry-olfactometry (GC MS O) after direct immersion stir bar sorptive extraction (DI SBSE), and results were compared to those of their respective extrudates to define changes during dry and wet extrusion. Twenty-four odor-active compounds were found, whereof nine represented major (off-) flavor contributors in peas: hexanal, nonanal, 2 undecanone, (E)-2-octenal, (E, Z)-3,5-octadiene-2-one, (E, E) 2,4 decadienal, 2 pentyl furan, 2-pentyl-pyridine, and γ-nonalactone. The quantity of these nine volatiles was affected distinctively by extrusion. Hexanal was reduced from 3.29 ± 1.05 % (Isolate I) to 0.52 ± 0.02 % (Wet Extrudate I) and (E,Z)-3,5-Octadiene-2-one and (E,E)-2,4-decadienal decreased by 1.5- and 1.8-fold when powdered and dry texturized pea proteins were compared. As a result of the perturbing effect of soluble potato proteins and the higher amount of off flavors in pea isolates compared to their extrudates, use of plant powders as additives was rejected in favor of extruded ones for all subsequent studies. As the focus of this work was the development of dry cured hybrid meat products, the effect of various amounts of extrudates on the traditional formulation and manufacture of this product class was assessed. This included the susceptibility of extrudates towards acid-induced pH changes as compared to pork meat, as well as their behavior in a traditional acidification and drying processes. To that purpose, pork meat and six wet extrudates from peas, pumpkin, or sunflower seeds were analyzed in their proximate composition and subjected to titration starting from the same pH value and using the same acid concentrations. It was shown that wet texturized pumpkin and sunflower proteins had the highest buffering capacity (BC), especially between pH 7.0 and pH 4.5, while pea protein extrudates and pork meat were more prone to acidification and similar in buffering capacity with an average of 881 ± 5 mmol H+/(kg*ΔpH). The obtained data was then used to relate BC with the compositional elements of extrudates such as minerals, proteins, select amino acid, and nonprotein nitrogen. These findings on varying susceptibility towards acids were extended by studies on a minced meat model systems containing pork meat, curing salt, and various amounts (0 to 100 wt%) of wet extrudates and the chemical acidifier Glucono delta-lactone (GDL). It was shown, that increasing concentrations of plant extrudates resulted in a linear increase of the initial (pH0h), intermediate (pH6h), and final (pH48h) pH of minced meat model systems. A sufficient acidification to common target pH values in dry cured meat products (pH ~ 5.0) could be achieved with acidifier amounts of 1.0 wt% up at no more than 15 wt% of extrudates. A mathematical model was proposed to correlate pH, time, acidifier, extrudate concentration, and plant protein origin to aid in the adjustments of formulations at higher extrudate contents, and to describe thresholds of feasible extrudate and acidifier concentrations. The calculated concentrations were then implemented to manufacture dry cured hybrid sausages where meat was partially replaced by 12.5, 25, 37.5, and 50 % of pumpkin seed extrudates. All recipes reached the target pH value with an accuracy of pH 5.0 ± 0.06 thereby validating the proposed mathematical correlations. Hybrid recipes with up to 25 % of extrudates were comparable to the traditional all-meat formulation in both the drying behavior and the distribution of moisture and free water. However, higher meat replacement levels promoted distinct changes in drying behavior and product texture where chewiness, hardness, and cohesiveness decreased by up to 70 %. In conclusion, plant protein functionality differs profoundly from the one of meat proteins, and this functionality also depends on the respective protein source as well as the applied extraction process. Their structuring by extrusion provides beneficial organoleptic changes and eases their incorporation in hybrid formulations. The fundamental characterization of plant proteins in terms of their proximate composition and (physico)chemical properties may be used to establish mathematical correlations to estimate the effect of these novel ingredients in hybrid meat products. Thus, the obtained results offer a valuable basis that manufacturers can draw upon not only to create new foods within this product class but also to broaden and facilitate the application of plant proteins on a large scale.Die Verfügbarkeit von Pflanzenproteinen muss weiter ausgebaut werden, um sich einerseits der zunehmenden Verbraucherdiversifizierung im Lebensmittelbereich anzupassen und andererseits den Problemen der Rohstoffverknappung und des Welthungers entgegenzutreten. Obwohl viele Industrieprozesse zur Extraktion und Strukturierung von Pflanzenproteinen in den letzten Jahren entwickelt wurden, fehlt es immer noch an Kenntnissen über die grundlegenden funktionellen und sensorischen Eigenschaften pflanzlicher Proteine und deren Wechselwirkungen mit anderen Inhaltsstoffen. Dies erschwert eine mechanistisch getriebene Produktentwicklung, vor allem bei Produkten mit komplexen Rohstoffanforderungen und Produktionsprozessen. Infolgedessen werden nach wie vor viele Produktentwicklungen als kostspielige und zeitraubende Trial-and-Error Versuche konzipiert. Dies schließt die Kategorie der Hybridfleischprodukte mit ein, die aus Mischungen tierischer und pflanzlicher Rohstoffe bestehen. Derzeit ist die Akzeptanz derartiger Produkte noch ungenügend, da die qualitativen Attribute von traditionellen Fleisch- und Wurstwaren oft zum Vergleich herangezogen werden. Um zu einem systematischeren Ansatz beim Design von Hybridprodukten zu kommen und qualitativ hochwertigere Hybridlebensmittel herzustellen, ist die Etablierung eines mechanistischen Zusammenhangs zwischen Rohstoffzusammensetzung, physikochemischen Eigenschaften der darin enthaltenen Pflanzenproteine und deren Technofunktionalität notwendig. Im Zuge dieser Dissertation wurden aus diesem Grund eine große Anzahl an Pflanzenproteinen auf ihre funktionellen Eigenschaften und Eignung in Hybridfleischprodukten untersucht. Dies umfasste ihre Löslichkeit und Mischbarkeit mit gelösten Fleischproteinen in Abhängigkeit von pH und Mischungsverhältnis, die Charakterisierung geruchsaktiver Komponenten ausgewählter Pflanzenproteine, deren Veränderung durch Nass- und Trockentexturierung und schließlich die Bestimmung der Produkteigenschaften hybrider Modellformulierungen mit Rohwurstcharakter. Im ersten Teil dieser Arbeit wurde gezeigt, dass Löslichkeit, der native pH Wert, die Farbe und das Erscheinungsbild von Pflanzenproteinen mit ihrer Aufreinigung und dem zugehörigen Extraktionsprozess korrelieren. Hierzu wurden 26 Pflanzenproteinpräparate, die aus der Herstellung von Kohlenhydraten oder Pflanzenölen gewonnen wurden, verwendet. Die Löslichkeit lag zwischen 4 % und 100 % basierend auf der Proteinkonzentration und dem Vorkommen bestimmter Proteinklassen in den Präparaten. So wurde bei einem hohen Anteil an Prolaminen (Weizen) oder Glutelinen (Reis, Kürbis) eine schlechte Löslichkeit festgestellt, wohingegen SonnenblumenErbsen und Kartoffelproteine durch die darin enthaltenen Albumine und Globuline gut bis sehr gut löslich waren. Eine Kartoffelproteinfraktion mit niedrigem Molekulargewicht ( pI) die isotropen Lösungen in einen zwei-phasigen, aggregierten Zustand (pH ≤ pI) übergingen. Es entstanden dichte, unregelmäßig geformte Heteroprotein Partikel, die sich in ihrer Morphologie wesentlich von der für Fleischproteine typischen anisotropen fasrigen Struktur unterschieden. Dies deutete auf einen Störeffekt der Kartoffelproteine auf die typische Selbstassoziation der Fleischproteinen unterhalb ihres pI hin, welcher auf Veränderungen der elektrostatischen (Oberflächenladung) und hydrophoben (Oberflächenhydrophobizität) Protein-Protein Interaktionen zurückgeführt werden konnte. So nahm die Partikelgröße der Fleischproteine im Vergleich zu 50:50 Mischungen von 18.0 ± 2.9 µm (pH 3.0) auf 26.8 ± 9.0 µm (pH 3.0) zu. Eine FTIR Analyse validierte den Zusammenhang der makro- und mikroskopischen Beobachtungen mit Mischungsverhältnis und pH Wert. Eine Bildanalyse verdeutlichte zudem eine Veränderung der länglichen, vernetzten Fleischprotein-Aggregate hin zu ungeordneten und unregelmäßigen Heteroproteinstrukturen mit geringer Anisotropie. Da organoleptische Eigenschaften von großer Bedeutung sind, um die Eignung von Pflanzenproteinen in Lebensmitteln abzuschätzen, wurden zwei Erbsenproteinisolate mit Hilfe von Gaschromatographie kombiniert mit Massenspektroskopie und Olfaktometrie (GC MS-O) untersucht, nachdem sie aus der Lösung an ein Adsorbens gebunden worden waren (DI SBSE). Die Ergebnisse wurden mit denen der daraus produzierten Trocken- und Nassextrudate verglichen, um den Einfluss des Extrusionsprozesses zu bestimmen. Die Analyse identifizierte 24 geruchsaktive Stoffe von denen neun als wesentliche (Off-) Flavor Komponenten in Erbsen bekannt sind: Hexanal, Nonanal, 2 Undecanon, (E) 2 Octenal, (E, Z)-3,5-Octadiene-2-on, (E, E)-2,4-Decadienal, 2 Pentyl furan, 2-Pentyl-pyridin, und γ-Nonalacton. Diese neun Substanzen wurden durch die Extrusion merklich beeinflusst. Hexanal verringerte sich von 3.29 ± 1.05 % (Isolat I) bis auf 0.52 ± 0.02 % (Nassextrudat I) und (E,Z)-3,5-Octadiene-2-on and (E,E)-2,4-Decadienal nahmen um das 1.5- und 1.8-fache ab, wenn die Isolate mit den jeweiligen Trockenextrudaten verglichen wurden. Die darauffolgenden Studien fokussierten sich aufgrund des Störeffektes der Kartoffelproteine und dem höheren Gehalt an Off-Flavor Komponenten in Isolaten auf Extrudate und deren Effekt auf die traditionelle Rezeptur und Herstellung von Produkten mit Rohwurstcharakter. Dies beinhaltete ihre pH-Abhängigkeit und ihr Verhalten während Säuerung- und Trocknung im Vergleich zu tierischen Proteinquellen. Dazu wurden die Zusammensetzung und die Säure Base Eigenschaften (Pufferkapazität) sechs verschiedener Extrudate aus Erbsen, Kürbis- oder Sonnenblumenkernen bestimmt. Kürbis- und Sonnenblumenextrudate zeigten die höchste Pufferkapazität, vor allem im Bereich zwischen pH 7.0 und 4.5. Erbsenextrudate und Schweinefleisch zeigten geringere, aber ähnliche Werte von 881 ± 5 mmol H+/(kg*ΔpH). Eine statistische Analyse der Ergebnisse ergab eine Korrelation der Pufferkapazität mit der Extrudat Zusammensetzung z.B. dem Gehalt an Asche, Proteinen, ausgewählten Aminosäuren und Nicht-Protein Stickstoff. Die gewonnenen Erkenntnisse flossen dann in die nachfolgenden Untersuchungen an Hybridfleischmodellsystemen ein, um so einen Zusammenhang zur Technofunktionlität der Rohstoffe herzustellen. Die Modellsysteme bestanden aus gewolftem Fleisch und Nitritpökelsalzmischungen, denen verschiedene Extrudatkonzentrationen (0 bis 100 wt%) und das chemischen Säuerungsmittel Glucono delta lactone (GDL) zugegeben wurden. Steigende Extrudatkonzentrationen führten dabei zu einem linearen Anstieg des pH Wertes zu Beginn (pH0h), und nach 6 h (pH6h) und 48 h (pH48h) aufgrund der puffernden Wirkung der Proteinextrudate. Typische GDL Konzentrationen (1.0 wt%) ermöglichten eine pH-Wert Senkung auf den für Rohwürste üblichen Wert von pH ~ 5.0, allerdings nur bis zu einer Extrudatkonzentration von nicht mehr als 15 wt%. Für höhere Extrudatgehalte wurde ein mathematisches Modell entwickelt, welches pH, Zeit, GDL und Extrudatkonzentration, sowie den Ursprung des Pflanzenproteins korrelierte. Das Modell wurde bei der Herstellung einer Hybridwurst mit Rohwurstcharaketer validiert, in der 12.5, 25, 37.5 und 50 % Fleisch durch Kürbiskern-Extrudate ersetzt wurde. Alle Formulierungen erreichten den gewünschten pH Wert mit einer Genauigkeit von pH 5.00 ± 0.06. Bis zu einer Fleischreduktion von 25 % waren die Hybride in ihrem Trocknungsverhalten und der Feuchteverteilung mit der rein tierischen Formulierung vergleichbar. Höhere Extrudatkonzentrationen verursachten jedoch merkliche Ungleichverteilungen der Feuchte in den Matrizen und heterogene Produkttexturen. Zusammenfassend zeigen die Studien dieser Dissertation, dass sich Pflanzenproteine hinsichtlich ihrer Funktionalität nicht nur von tierischen Proteinen, sondern auch untereinander aufgrund der verwendeten Proteinquelle und der darin enthaltenen Proteintypen und dem verwendeten Extraktionsprozess unterscheiden können. Ihre Sensorik kann mit Hilfe von Extrusion positiv verändert werden, so dass eine Nutzung als Lebensmittelinhaltsstoff erleichtern wird. Eine grundsätzliche Charakterisierung der Zusammensetzung und der physikochemischen Eigenschaften von Pflanzenproteinen ermöglicht es mathematische Korrelationen zu erstellen, die eine Selektion geeigneter Rohstoffe und Konzentrationen für die Herstellung von Hybridprodukten ermöglicht. Die gewonnenen Erkenntnisse könnten so einen wichtigen Beitrag zur Kommerzialisierung von Hybridfleischprodukten leisten, und damit einen breiteren Einsatz von Pflanzenproteinen ermöglichen

Semi-supervised learning for image classification

Object class recognition is an active topic in computer vision still presenting many challenges. In most approaches, this task is addressed by supervised learning algorithms that need a large quantity of labels to perform well. This leads either to small datasets (< 10,000 images) that capture only a subset of the real-world class distribution (but with a controlled and verified labeling procedure), or to large datasets that are more representative but also add more label noise. Therefore, semi-supervised learning is a promising direction. It requires only few labels while simultaneously making use of the vast amount of images available today. We address object class recognition with semi-supervised learning. These algorithms depend on the underlying structure given by the data, the image description, and the similarity measure, and the quality of the labels. This insight leads to the main research questions of this thesis: Is the structure given by labeled and unlabeled data more important than the algorithm itself? Can we improve this neighborhood structure by a better similarity metric or with more representative unlabeled data? Is there a connection between the quality of labels and the overall performance and how can we get more representative labels? We answer all these questions, i.e., we provide an extensive evaluation, we propose several graph improvements, and we introduce a novel active learning framework to get more representative labels.Objektklassifizierung ist ein aktives Forschungsgebiet in maschineller Bildverarbeitung was bisher nur unzureichend gelöst ist. Die meisten Ansätze versuchen die Aufgabe durch überwachtes Lernen zu lösen. Aber diese Algorithmen benötigen eine hohe Anzahl von Trainingsdaten um gut zu funktionieren. Das führt häufig entweder zu sehr kleinen Datensätzen (< 10,000 Bilder) die nicht die reale Datenverteilung einer Klasse wiedergeben oder zu sehr grossen Datensätzen bei denen man die Korrektheit der Labels nicht mehr garantieren kann. Halbüberwachtes Lernen ist eine gute Alternative zu diesen Methoden, da sie nur sehr wenige Labels benötigen und man gleichzeitig Datenressourcen wie das Internet verwenden kann. In dieser Arbeit adressieren wir Objektklassifizierung mit halbüberwachten Lernverfahren. Diese Algorithmen sind sowohl von der zugrundeliegenden Struktur, die sich aus den Daten, der Bildbeschreibung und der Distanzmasse ergibt, als auch von der Qualität der Labels abhängig. Diese Erkenntnis hat folgende Forschungsfragen aufgeworfen: Ist die Struktur wichtiger als der Algorithmus selbst? Können wir diese Struktur gezielt verbessern z.B. durch eine bessere Metrik oder durch mehr Daten? Gibt es einen Zusammenhang zwischen der Qualität der Labels und der Gesamtperformanz der Algorithmen? In dieser Arbeit beantworten wir diese Fragen indem wir diese Methoden evaluieren. Ausserdem entwickeln wir neue Methoden um die Graphstruktur und die Labels zu verbessern

Molecular mechanisms of xeroderma pigmentosum (XP) proteins

Nucleotide excision repair (NER) is a highly versatile and efficient DNA repair process, which is responsible for the removal of a large number of structurally diverse DNA lesions. Its extreme broad substrate specificity ranges from DNA damages formed upon exposure to ultraviolet radiation to numerous bulky DNA adducts induced by mutagenic environmental chemicals and cytotoxic drugs used in chemotherapy. Defective NER leads to serious diseases, such as xeroderma pigmentosum (XP). Eight XP complementation groups are known of which seven (XPA-XPG) are caused by mutations in genes involved in the NER process. The eighth gene, XPV, codes for the DNA polymerase., which replicates through DNA lesions in a process called translesion synthesis (TLS). Over the past decade, detailed structural information of these DNA repair proteins involved in eukaryotic NER and TLS have emerged. These structures allow us now to understand the molecular mechanism of the NER and TLS processes in quite some detail and we have begun to understand the broad substrate specificity of NER. In this review, we aim to highlight recent advances in the process of damage recognition and repair as well as damage tolerance by the XP proteins

Converging seasonal prevalence dynamics in experimental epidemics

Background Regular seasonal changes in prevalence of infectious diseases are often observed in nature, but the mechanisms are rarely understood. Empirical tests aiming at a better understanding of seasonal prevalence patterns are not feasible for most diseases and thus are widely lacking. Here, we set out to study experimentally the seasonal prevalence in an aquatic host-parasite system. The microsporidian parasite Hamiltosporidium tvärminnensis exhibits pronounced seasonality in natural rock pool populations of its host, Daphnia magna with a regular increase of prevalence during summer and a decrease during winter. An earlier study was, however, unable to test if different starting conditions (initial prevalence) influence the dynamics of the disease in the long term. Here, we aim at testing how the starting prevalence affects the regular prevalence changes over a 4-year period in experimental populations.Results In an outdoor experiment, populations were set up to include the extremes of the prevalence spectrum observed in natural populations: 5% initial prevalence mimicking a newly invading parasite, 100% mimicking a rock pool population founded by infected hosts only, and 50% prevalence which is commonly observed in natural populations in spring. The parasite exhibited similar prevalence changes in all treatments, but seasonal patterns in the 100% treatment differed significantly from those in the 5% and 50% treatments. Populations started with 5% and 50% prevalence exhibited strong and regular seasonality already in the first year. In contrast, the amplitude of changes in the 100% treatment was low throughout the experiment demonstrating the long-lasting effect of initial conditions on prevalence dynamics.Conclusions Our study shows that the time needed to approach the seasonal changes in prevalence depends strongly on the initial prevalence. Because individual D. magna populations in this rock pool metapopulation are mostly short lived, only few populations might ever reach a point where the initial conditions are not visible anymore

Predictors of Dropout in a Digital Intervention for the Prevention and Treatment of Depression in Patients With Chronic Back Pain : Secondary Analysis of Two Randomized Controlled Trials

Peer reviewe

Expression of a Cu,Zn superoxide dismutase typical for familial amyotrophic lateral sclerosis increases the vulnerability of neuroblastoma cells to infectious injury

<p>Abstract</p> <p>Background</p> <p>Infections can aggravate the course of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Mutations in the anti-oxidant enzyme Cu,Zn superoxide dismutase (EC 1.15.1.1, SOD1) are associated with familial ALS. Streptococcus pneumoniae, the most frequent respiratory pathogen, causes damage by the action of the cholesterol-binding virulence factor pneumolysin and by stimulation of the innate immune system, particularly via Toll-like-receptor 2.</p> <p>Methods</p> <p>SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) and SH-SY5Y neuroblastoma cells transfected with wildtype SOD1 were both exposed to pneumolysin and in co-cultures with cultured human macrophages treated with the Toll like receptor 2 agonist N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine × 3 HCl (Pam₃CSK₄). Cell viability and apoptotic cell death were compared morphologically and by in-situ tailing. With the help of the WST-1 test, cell viability was quantified, and by measurement of neuron-specific enolase in the culture supernatant neuronal damage in co-cultures was investigated. Intracellular calcium levels were measured by fluorescence analysis using fura-2 AM.</p> <p>Results</p> <p>SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) were more vulnerable to the neurotoxic action of pneumolysin and to the attack of monocytes stimulated by Pam₃CSK₄ than SH-SY5Y cells transfected with wild-type human SOD1. The enhanced pneumolysin toxicity in G93A-SOD1 neuronal cells depended on the inability of these cells to cope with an increased calcium influx caused by pores formed by pneumolysin. This inability was caused by an impaired capacity of the mitochondria to remove cytoplasmic calcium. Treatment of G93A-SOD1 SH-SY5Y neuroblastoma cells with the antioxidant N-acetylcysteine reduced the toxicity of pneumolysin.</p> <p>Conclusion</p> <p>The particular vulnerability of G93A-SOD1 neuronal cells to hemolysins and inflammation may be partly responsible for the clinical deterioration of ALS patients during infections. These findings link infection and motor neuron disease and suggest early treatment of respiratory infections in ALS patients.</p

International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. Methods ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment

Разработка информационной системы учета и анализа проектной деятельности студента

В статье показан процесс проектирования информационной системы учета и анализа проектной деятельности студента. Проектная деятельность является на сегодняшний день актуальным методом ведения учебной деятельности, который активно внедряется в университеты, в том числе и в ТПУ

Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice

Systemic instigation is a process by which endocrine signals sent from certain tumors (instigators) stimulate BM cells (BMCs), which are mobilized into the circulation and subsequently foster the growth of otherwise indolent carcinoma cells (responders) residing at distant anatomical sites. The identity of the BMCs and their specific contribution or contributions to responder tumor growth have been elusive. Here, we have demonstrated that Scal(+)cKit(-) hematopoietic BMCs of mouse hosts bearing instigating tumors promote the growth of responding tumors that form with a myofibroblast-rich, desmoplastic stroma. Such stroma is almost always observed in malignant human adenocarcinomas and is an indicator of poor prognosis. We then identified granulin (GRN) as the most upregulated gene in instigating Scal(+)cKit(-) BMCs relative to counterpart control cells. The GRN(+) BMCs that were recruited to the responding tumors induced resident tissue fibroblasts to express genes that promoted malignant tumor progression; indeed, treatment with recombinant GRN alone was sufficient to promote desmoplastic responding tumor growth. Further, analysis of tumor tissues from a cohort of breast cancer patients revealed that high GRN expression correlated with the most aggressive triple-negative, basal-like tumor subtype and reduced patient survival. Our data suggest that GRN and the unique hematopoietic BMCs that produce it might serve as novel therapeutic targets