Circulating microbial content in myeloid malignancy patients is associated with disease subtypes and patient outcomes

Although recent work has described the microbiome in solid tumors, microbial content in hematological malignancies is not well-characterized. Here we analyze existing deep DNA sequence data from the blood and bone marrow of 1870 patients with myeloid malignancies, along with healthy controls, for bacterial, fungal, and viral content. After strict quality filtering, we find evidence for dysbiosis in disease cases, and distinct microbial signatures among disease subtypes. We also find that microbial content is associated with host gene mutations and with myeloblast cell percentages. In patients with low-risk myelodysplastic syndrome, we provide evidence that Epstein-Barr virus status refines risk stratification into more precise categories than the current standard. Motivated by these observations, we construct machine-learning classifiers that can discriminate among disease subtypes based solely on bacterial content. Our study highlights the association between the circulating microbiome and patient outcome, and its relationship with disease subtype

German federal-state-wide seroprevalence study of 1st SARS-CoV-2 pandemic wave shows importance of long-term antibody test performance

Background Reliable data on the adult SARS-CoV-2 infection fatality rate in Germany are still scarce. We performed a federal state-wide cross-sectional seroprevalence study named SaarCoPS, that is representative for the adult population including elderly individuals and nursing home residents in the Saarland. Methods Serum was collected from 2940 adults via stationary or mobile teams during the 1st pandemic wave steady state period. We selected an antibody test system with maximal specificity, also excluding seroreversion effects due to a high longitudinal test performance. For the calculations of infection and fatality rates, we accounted for the delays of seroconversion and death after infection. Results Using a highly specific total antibody test detecting anti-SARS-CoV-2 responses over more than 180 days, we estimate an adult infection rate of 1.02% (95% CI: [0.64; 1.44]), an underreporting rate of 2.68-fold (95% CI: [1.68; 3.79]) and infection fatality rates of 2.09% (95% CI: (1.48; 3.32]) or 0.36% (95% CI: [0.25; 0.59]) in all adults including elderly individuals, or adults younger than 70 years, respectively. Conclusion The study highlights the importance of study design and test performance for seroprevalence studies, particularly when seroprevalences are low. Our results provide a valuable baseline for evaluation of future pandemic dynamics and impact of public health measures on virus spread and human health in comparison to neighbouring countries such as Luxembourg or France

Inter- and intraobserver reliability of the MTM-classification for proximal humeral fractures: A prospective study

<p>Abstract</p> <p>Background</p> <p>A precise modular topographic-morphological (MTM) classification for proximal humeral fractures may address current classification problems. The classification was developed to evaluate whether a very detailed classification exceeding the analysis of fractured parts may be a valuable tool.</p> <p>Methods</p> <p>Three observers classified plain radiographs of 22 fractures using both a simple version (fracture displacement, number of parts) and an extensive version (individual topographic fracture type and morphology) of the MTM classification. Kappa-statistics were used to determine reliability.</p> <p>Results</p> <p>An acceptable reliability was found for the simple version classifying fracture displacement and fractured main parts. Fair interobserver agreement was found for the extensive version with individual topographic fracture type and morphology.</p> <p>Conclusion</p> <p>Although the MTM-classification covers a wide spectrum of fracture types, our results indicate that the precise topographic and morphological description is not delivering reproducible results. Therefore, simplicity in fracture classification may be more useful than extensive approaches, which are not adequately reliable to address current classification problems.</p

Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology

Background: The dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay. Methodology/Principal Findings: A total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina's Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274. Conclusions/Significance: Overall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pig

Insulin resistance, adiponectin and adverse outcomes following elective cardiac surgery: a prospective follow-up study

<p>Abstract</p> <p>Background</p> <p>Insulin resistance and adiponectin are markers of cardio-metabolic disease and associated with adverse cardiovascular outcomes. The present study examined whether preoperative insulin resistance or adiponectin were associated with short- and long-term adverse outcomes in non-diabetic patients undergoing elective cardiac surgery.</p> <p>Methods</p> <p>In a prospective study, we assessed insulin resistance and adiponectin levels from preoperative fasting blood samples in 836 patients undergoing cardiac surgery. Population-based medical registries were used for postoperative follow-up. Outcomes included all-cause death, myocardial infarction or percutaneous coronary intervention, stroke, re-exploration, renal failure, and infections. The ability of insulin resistance and adiponectin to predict clinical adverse outcomes was examined using receiver operating characteristics.</p> <p>Results</p> <p>Neither insulin resistance nor adiponectin were statistically significantly associated with 30-day mortality, but adiponectin was associated with an increased 31-365-day mortality (adjusted odds ratio 2.9 [95% confidence interval 1.3-6.4]) comparing the upper quartile with the three lower quartiles. Insulin resistance was a poor predictor of adverse outcomes. In contrast, the predictive accuracy of adiponectin (area under curve 0.75 [95% confidence interval 0.65-0.85]) was similar to that of the EuroSCORE (area under curve 0.75 [95% confidence interval 0.67-0.83]) and a model including adiponectin and the EuroSCORE had an area under curve of 0.78 [95% confidence interval 0.68-0.88] concerning 31-365-day mortality.</p> <p>Conclusions</p> <p>Elevated adiponectin levels, but not insulin resistance, were associated with increased mortality and appear to be a strong predictor of long-term mortality. Additional studies are warranted to further clarify the possible clinical role of adiponectin assessment in cardiac surgery.</p> <p>Trial Registration</p> <p>The Danish Data Protection Agency; reference no. 2007-41-1514.</p

The force of the sign. Terrorism as a symbolic phenomenon

Seit der radikalen Änderung der weltpolitischen Lage durch das Selbstmordattentat islamistischer Terroristen auf die Supermacht U.S.A. am 11.9.01 versucht die Weltöffentlichkeit, dem Phänomen des Terrorismus durch die verschiedensten Erklärungsstrategien Herr zu werden. Man führt den Kampf der Kulturen oder Religionen an, verweist auf die Ausbeutung der Peripherie des kapitalistischen Weltsystems durch den Hegemon U.S.A. oder pathologisiert bzw. dämonisiert die Taten der Terroristen. Uns scheinen diese Erklärungsstrategien den Machtkonstellationen der postmodernen Gesellschaften nicht gerecht zu werden, da sie ein zentrales soziales Phänomen der vergangenen Jahrzehnte nicht beachten: das Unbehagen an der pluralistischen Gesellschaft und der konsensuell-repräsentativen Demokratie. Um dieses Unbehagen angemessen beschreiben zu können, wollen wir uns ihm aus einer zeichentheoretischen Perspektive nähern, die soziale Formationen nicht durch (kooperative) Arbeit determiniert sieht, sondern durch die Instanz des Codes. Für Jean Baudrillard ist die Wahl des Ziels der beiden Türme bedeutend, die sich wechselseitig reflektieren und das System nach allen Seiten hin abschließen. Mit ihnen wurde das neuralgische Zentrum des Systems getroffen, das sich auf einem binären Code gründet. Die Twintowers bedeuteten nicht nur das Ende jedweder originalen Referenz, sondern auch den Abschluss des Bezeichneten durch die Wiederholung des Zeichens. Der Code führt eine symbolische Verteilung der gesellschaftlichen Körper durch und zielt auf eine möglichst genaue Übereinstimmung der Gemeinschaft mit sich selbst gemäß eines arithmetischen und geometrischen Kalküls. Die integrative Kraft dieses auf dem Identitätsprinzip basierenden Systems scheint immer häufiger nicht mehr in der Lage zu sein, das negative Potential antagonistischer Strategien binden zu können, die in Form von zivilem Ungehorsam, Politik von Minoritäten oder terroristischen Akten die symbolische Ordnung der westlichen Gesellschaften unterhöhlen. In diesem Tagungsband diskutieren wir das Ausmaß der Krise der konsensuellen Demokratie und ihrer Institutionen. Die Aufsätze behandeln folgende Themen: • Die Krise der pluralistischen Gesellschaft: Wie verständlich ist das kulturelle, politische und religiöse Unbehagen am westlichen Wertekanon? • Die Funktion der Medien in der konsensuellen Demokratie; die gesellschaftliche Wirkung der medialen Reproduktion terroristischer Akte; das Bild des Terrorismus in der Populärkultur • Ästhetischer Terror: Die Vernichtung von Sinn und Bedeutung in der zeitgenössischen Kunst und Kunsttheorie • Die politische Logik des Terrorismus (Ziele, Bedingungen u. Legitimität des Terrorismus in Abgrenzung zu alternativen politischen Ausdrucksformen wie z.B. dem zivilen Ungehorsam; die Bedeutung des terroristischen Opfertodes) • Geschichte des Terrorismus (speziell der Terrorismus der RAF) • Terror als irrationale Gewalt (der ontologische Status des Terrorismus)Since the radical changes in international politics caused by the suicide attacks on the USA by Islamic terrorists on the 11th of September in 2001, the world public tries to grasp the phenomenon of „Terrorism“ through different explanatory strategies. These include referring to the clash of cultures and of religions, to the exploitation of the periphery by the capitalist system incarnated by the USA, or pathologizing as well as demonizing the deeds of the terrorists. All these explanatory attempts do not seem to do justice to the actual constellations of power in postmodern societies, because they do not take a widespread social phenomenon of the past decades in consideration: the discomfort with the pluralistic society and with the concurrent-representative democracy. In order to describe this discomfort adequately we would like to approach the phenomenon from a semiotic perspective which does not consider social formations as determined by cooperative work but rather by the authority of the code. For Jean Baudrillard the target was meaningful since the two towers not only reflect each other but also completely close the system. With them the neuralgic center which is based upon the binary code was severely hit. The twin towers not only meant the end of every original reference but also the completion of the signified by the reduplication of the sign. The code conducts a symbolic distribution of the social bodies and aims at an as accurate as possible identification of the community with itself corresponding to an arithmetic and geometric calculus. The system which is based upon the principle of identity does not seem to have the ability to integrate antagonist energies properly. So these antagonist powers undermine the symbolic order of western societies in terms of civil disobedience, politics of minorities or terroristic acts. In this conference transcript we discuss the degree of crisis of consensual democracy and ist institutions. The essays cover the following topics: • The crisis of the pluralistic society: How comprehensible and justified is the cultural, political, and religious discomfort with western values? • The function of mass media in democratic systems: What is the impact of the reproduction of terrorist acts on society? How does popular culture deal with terrorism? • Aesthetic terror: the destruction of sense and meaning in contemporary arts and art theory • The political logic of terrorism (aims, legitimacy of terrorism as opposed to other forms of opposition like civil disobedience; the meaning of the terrorist self-sacrifice death) • History of terrorism (e.g. The German terrorism of the RAF) • Terrorism as an irrational power (ontological status of terrorism

Identification and Clonal Characterisation of a Progenitor Cell Sub-Population in Normal Human Articular Cartilage

Background: Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC), are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage. Methods and Findings: Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect. Conclusions: In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell-based cartilage repair therapies due to its ability to maintain chondrogenicity upon extensive expansion unlike full-depth chondrocytes that lose this ability at only seven population doublings