Individual trajectories of asthma, obesity and ADHD during the transition from childhood and adolescence to young adulthood

The German Health Interview and Examination Survey for Children and Adolescents (KiGGS) provides comprehensive and reliable data on the health situation of the upcoming generation. The KiGGS cohort accompanies participants from the KiGGS baseline study (2003–2006) into adulthood. Until now, two follow-up surveys of the cohort have been implemented with KiGGS Wave 1 (2009–2012) and KiGGS Wave 2 (2014–2017). In KiGGS Wave 2, the cohort was supplemented by the in-depth study ‘Family and care-specific factors influencing the development, trajectories and effects of mental disorders (especially ADHD), obesity and allergic diseases (especially asthma)’. One aim of the study was to identify individual trajectories of these health disorders. For this purpose, probabilities for typical transitions from the KiGGS baseline study to KiGGS Wave 2 were calculated. An important result is that many participants who had asthma, obesity or ADHD at KiGGS baseline still had the disease more than ten years later: Over a third still had asthma (35%) or ADHD (37%), and almost half were still affected by obesity (47%). The results point to the need for early preventive measures to stop these potentially chronic diseases from developing in childhood and adolescence. ASTHMA · OBESITY · ADHD · TRANSITION · YOUNG ADULTHOOD · KIGG

Over-Expression of LEDGF/p75 in HEp-2 Cells Enhances Autoimmune IgG Response in Patients with Benign Prostatic Hyperplasia : A Novel Diagnostic Approach with Therapeutic Consequence?

Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence

The Critically Endangered western chimpanzee declines by 80%

African large mammals are under extreme pressure from unsustainable hunting and habitat loss. Certain traits make large mammals particularly vulnerable. These include late age at first reproduction, long inter-birth intervals, and low population density. Great apes are a prime example of such vulnerability, exhibiting all of these traits. Here we assess the rate of population change for the western chimpanzee, Pan troglodytes verus, over a 24-year period. As a proxy for change in abundance, we used transect nest count data from 20 different sites archived in the IUCN SSC A.P.E.S. database, representing 25,000 of the estimated remaining 35,000 western chimpanzees. For each of the 20 sites, datasets for 2 different years were available. We estimated site-specific and global population change using Generalized Linear Models. At 12 of these sites, we detected a significant negative trend. The estimated change in the subspecies abundance, as approximated by nest encounter rate, yielded a 6% annual decline and a total decline of 80.2% over the study period from 1990 to 2014. This also resulted in a reduced geographic range of 20% (657,600 vs. 524,100 km2). Poverty, civil conflict, disease pandemics, agriculture, extractive industries, infrastructure development, and lack of law enforcement, are some of the many reasons for the magnitude of threat. Our status update triggered the uplisting of the western chimpanzee to “Critically Endangered” on the IUCN Red List. In 2017, IUCN will start updating the 2003 Action Plan for western chimpanzees and will provide a consensus blueprint for what is needed to save this subspecies. We make a plea for greater commitment to conservation in West Africa across sectors. Needed especially is more robust engagement by national governments, integration of conservation priorities into the private sector and development planning across the region and sustained financial support from donors.Additional co-authors: Emma Normand, Kathryn Shutt-Phillips, Alexander Tickle, Elleni Vendras, Adam Welsh, Erin G. Wessling, Christophe Boesc

Veränderungen der psychischen Gesundheit in der Kinder- und Jugendbevölkerung in Deutschland während der COVID-19- Pandemie – Ergebnisse eines Rapid Reviews

Hintergrund: Dieser Rapid Review untersucht Veränderungen der psychischen Gesundheit von Kindern und Jugendlichen in der Allgemeinbevölkerung in Deutschland während der COVID-19-Pandemie. Methode: Grundlage sind 39 Publikationen, die mittels systematischer Literaturrecherche (Stand 19.11.2021) und Handrecherche identifiziert wurden. Die Datengrundlagen der eingeschlossenen Publikationen wurden bezüglich ihrer Repräsentativität für die Allgemeinbevölkerung systematisiert, die verwendeten Indikatoren hinsichtlich der abgebildeten Konstrukte und ihrer Verlässlichkeit kategorisiert. Ergebnisse: Die große Mehrzahl der Studien bezog sich auf den Pandemiebeginn bis zum Sommerplateau 2020. Aus repräsentativen Studien wurde überwiegend ein hohes Ausmaß an pandemiebezogenen Belastungen, Zunahmen psychischer Auffälligkeiten und Beeinträchtigungen der Lebensqualität berichtet. Nichtrepräsentative Studien zeigten gemischte Ergebnisse. Vulnerable Gruppen ließen sich nur eingeschränkt identifizieren. Routine- und versorgungsbezogene Daten wiesen Rückgänge der ambulanten und stationären Inanspruchnahme während der Pandemiewellen mit Nachholeffekten aus. Kinder und Jugendliche erweisen sich in der Pandemie als vulnerabler im Vergleich zu Erwachsenen. Ihre Belastung variierte jedoch mit den Pandemiewellen und den assoziierten Eindämmungsmaßnahmen. Schlussfolgerungen: Ein zukünftiges vorausschauendes Krisen- und Pandemiemanagement erfordert eine engmaschige und kontinuierliche Surveillance der psychischen Kindergesundheit sowie eine bessere Identifikation von Risikogruppen

TaReCa – Cascade utilization of horticultural biomass for a resource efficient production of valuable bioactive substances

Viele pflanzliche Sekundärmetabolite haben antioxidative oder andere bioaktive Eigenschaften, weshalb sie einerseits wichtige Bestandteile der menschlichen Ernährung sind, andererseits aber auch als pharmazeutische Verbindungen oder als Substrat für die chemische Synthese von bioaktiven Substanzen verwendet werden. Pflanzen induzieren die Produktion solcher nutzbaren Sekundärmetabolite wie z.B. Flavonoiden als Reaktion auf abiotischen Stress. Die Produktion von Gemüse und Früchten in Gewächshäusern hinterlässt große Mengen an ungenutzter pflanzlicher Biomasse, welche eine potentielle Ressource für die Gewinnung wertvoller Metabolite darstellt. Durch eine kaskadenartige Verwendung von Gartenbaukulturen zur Produktion von Früchten und Gemüse mit einer anschließenden Gewinnung hochwertiger Substanzen aus der verbleibenden Restbiomasse würde ein erheblicher Mehrwert generiert. Das Projekt TaReCa bearbeitet die Entwicklung einer maßgeschneiderten Kaskadenverwertung von Paprikapflanzen-Restbiomasse aus dem Gartenbau. Dabei soll der pflanzliche Sekundärmetabolismus durch spezifische abiotische Stressbedingungen nach der Fruchternte gezielt induziert werden, um die Konzentrationen der Zielmetaboliten zu steigern. Durch umweltfreundliche und wirtschaftliche Extraktionsprozesse und eine anschließende Verwertung des verbleibenden Pflanzenmaterials in einer Bioraffinerie wird die Wertschöpfungskette erweitert. Eine Analyse der Anwendungsgebiete sowie Untersuchungen zur Akzeptanz der induzierten Inhaltsstoffe, Prozesse und Technologien werden helfen, das Marktpotenzial der Restbiomasse für die Nutzung in Kaskaden zu evaluieren. Die maßgeschneiderte Nutzung von Gartenbaubiomasse durch Lebensmittelproduktion, Extraktion bioaktiver Sekundärmetabolite und Bioraffinerien kann wirtschaftlich relevante, biobasierte Produkte für industrielle Anwendungen erzeugen und somit zur Entwicklung einer nachhaltigen, effizienten und integrierten Bioökonomie beitragen, ohne mit der Lebensmittelproduktion zu konkurrieren.Many plant secondary metabolites have antioxidant or pharmaceutically relevant properties, which makes them important components of the human diet, but also as pharmaceutical compounds or for the chemical synthesis of bioactive substances. Plants induce the production of secondary metabolites, e.g. flavonoids in response to environmental stress stimuli. The production of vegetables and fruits in greenhouses leaves huge amounts of so far under-utilized biomass after fruit harvest, which is a potential source for production of valuable metabolites. A cascade utilization of horticultural crops to produce fruits and vegetables with subsequent extraction of high quality compounds would generate significant added value. The project TaReCa is working on the development of a tailored cascade utilization of bell pepper plant residues from horticulture. The secondary metabolism will be induced by specific abiotic stress treatments after the last fruit harvest, in order to increase the concentrations of the target metabolites. Eco-friendly and economical extraction processes and subsequent utilization of the remaining plant material in a biorefinery will expand the value chain. An analysis of the application areas as well as studies on the acceptance of the induced ingredients, processes and technologies will help to evaluate the market potential of the residual biomass for the proposed cascaded use. The tailored utilization of horticultural biomass in food production, extraction of bioactive secondary metabolites and biorefineries can produce economically relevant bio-based products for industrial applications and thus contribute to the development of a sustainable, efficient and integrated bioeconomy without competing with food production

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment