TeCoMiner: Topic Discovery Through Term Community Detection

This note is a short description of TeCoMiner, an interactive tool for exploring the topic content of text collections. Unlike other topic modeling tools, TeCoMiner is not based on some generative probabilistic model but on topological considerations about co-occurrence networks of terms. We outline the methods used for identifying topics, describe the features of the tool, and sketch an application, using a corpus of policy related scientific news on environmental issues published by the European Commission over the last decade.Comment: 8 pages, 4 figure

Nachhaltige Lieferketten: global kooperative Regionalwirtschaften für Wohlstand und Resilienz

Zwei Drittel des heutigen Welthandels gründen auf globalen Wertschöpfungsketten und Versorgungsnetzen. Rein regionalwirtschaftlich organisierte Lieferketten haben in den letzten Jahrzehnten an Bedeutung verloren. Die Auswirkungen dieser globalisierten Strukturen sind vielfältig: Zum einen haben sie beschäftigungsfördernde Effekte und wirken wohlstandsstiftend. Zum anderen existieren entlang der Lieferketten extreme soziale, ökologische und ökonomische Schieflagen. Die COVID-19-Pandemie zeigt in erheblichem Maße, wie fragil bestehende Lieferkettensysteme sind. Der Lockdown unterbricht noch immer komplexe Lieferketten und viele Probleme der bestehenden Produktions- und Konsumweise verschärfen sich weiterhin. COVID-19 ist ein Beispiel einer der möglichen Krisen, welche die globalen und vernetzten Wertschöpfungsketten kurzfristig erschüttern kann. Andere Krisen entwickeln sich schleichender und damit weniger schnell erkennbar, wie etwa der globale Klimawandel. So unterschiedlich sie sind, haben die Krisen eines gemein: Sie zeigen die Verletzlichkeit globaler Gesellschafts- und Wirtschaftsstrukturen auf und verdeutlichen die Wirkungen globalen Handels auf die Regionen und Menschen der Welt. Die globale Nachhaltigkeitsstrategie setzt genau hier an - sie zielt darauf ab, Unterschiede und Ungleichheit in Chancen und Lebensqualität grundlegend zu vermindern. Deshalb sollte die Umsetzung der Nachhaltigkeitsziele auf internationaler, nationaler und regionaler Ebene eine Antwort auf solche Krisen sein. Da durch die Covid-19-Pandemie zeitgleich die komplette Welt in eine Umbruchsituation gedrängt wurde, bietet die Reaktion darauf an, Nachhaltigkeit als zentrale politische Resilienz-Strategie zu nutzen. Im Zuge der Corona-Pandemie flammte die Diskussion um resiliente Kommunen auf. Diese sollten sich stärker an regional- und kreislaufwirtschaftlichen Ansätzen orientieren, um angesichts solcher Pandemien die Versorgung weiterhin gewährleisten zu können. So wichtig und richtig die Entwicklung eigener regionalwirtschaftlicher und kreislauforientierter Ansätze im Kern ist, so wenig resilient ist es, wenn deren Entwicklung nicht unter globaler und nachhaltiger Perspektive erfolgt. Ziel sollten menschengerechte, nachhaltige und transparente Lieferketten sein, die auch bei plötzlich veränderten Rahmenbedingungen und Krisen richtungssicher die Versorgungssicherheit zur Deckung von Grundbedürfnissen und Daseinsvorsorge sicherstellen können. Das vorliegende Diskussionspapier zeichnet als Zukunftsszenario global kooperative, kreislauforientierte Regionalwirtschaften, die weltweite Ungleichheiten in Chancen und Lebensqualität grundlegend vermindern und dabei gleichsam die natürlichen Lebensgrundlagen dauerhaft bewahrt werden

Spontaneous antral follicle formation and metaphase II oocyte from a non-stimulated prepubertal ovarian tissue xenotransplant

Background Current strategies in cancer treatment have markedly increased the rates of remission and survival for cancer patients, but are often associated with subsequent sterility. While there are various options available to an adult female depending on the patient’s particular situation, the only realistic option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue. This is the first report of a morphologically mature oocyte collected from non-stimulated prepubertal ovarian tissue xenotransplants. Methods Ovarian tissue from a 6 year old patient suffering from nephroblastoma was removed and cryopreserved for fertility preservation. The frozen-thawed ovarian tissue fragments were xenotransplanted to bilaterally oophorectomized severe combined immunodeficiency (SCID) mice to assess follicle development. Results Antral follicle formation occurred post-xenotransplantation in a single ovarian fragment without exogenous hormone stimulation. A morphologically maturing oocyte was harvested from these follicles. Conclusions Prepubertal human ovarian follicles and oocytes can be matured after xenotransplantation even without exogenous hormone stimulation. These results indicate that tissue collected from prepubertal patients can support fertility in cancer survivors

A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study

The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m(2) doxorubicin or equivalent were allowed. Left ventricular ejection fraction of > 50 % was required. Patients received PLD 50 mg/m(2) every 28 days or capecitabine 1250 mg/m(2) twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838-1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %;P = 0.31). Both PLD and capecitabine are effective first-line agents for MBC

Low Energy Electron Irradiation Is a Potent Alternative to Gamma Irradiation for the Inactivation of (CAR-)NK-92 Cells in ATMP Manufacturing

Background: With increasing clinical use of NK-92 cells and their CAR-modified derivatives in cancer immunotherapy, there is a growing demand for efficient production processes of these “off-the-shelf” therapeutics. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cell proliferation has to be inactivated before transfusion. This is commonly achieved by gamma irradiation. Recently, we showed proof of concept that low energy electron irradiation (LEEI) is a new method for NK-92 inactivation. LEEI has several advantages over gamma irradiation, including a faster reaction time, a more reproducible dose rate and much less requirements on radiation shielding. Here, LEEI was further evaluated as a promising alternative to gamma irradiation yielding cells with highly maintained cytotoxic effector function. Methods: Effectiveness and efficiency of LEEI and gamma irradiation were analyzed using NK-92 and CD123-directed CAR-NK-92 cells. LEE-irradiated cells were extensively characterized and compared to gamma-irradiated cells via flow cytometry, cytotoxicity assays, and comet assays, amongst others. Results: Our results show that both irradiation methods caused a progressive decrease in cell viability and are, therefore, suitable for inhibition of cell proliferation. Notably, the NKmediated specific lysis of tumor cells was maintained at stable levels for three days postirradiation, with a trend towards higher activities after LEEI treatment as compared to gamma irradiation. Both gamma irradiation as well as LEEI led to substantial DNA damage and an accumulation of irradiated cells in the G2/M cell cycle phases. In addition, transcriptomic analysis of irradiated cells revealed approximately 12-fold more differentially expressed genes two hours after gamma irradiation, compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in surface expression of CD56, but no changes in the levels of the activating receptors NKp46, NKG2D, or NKp30. Conclusions: The presented data show that LEEI inactivates (CAR-)NK-92 cells as efficiently as gamma irradiation, but with less impact on the overall gene expression. Due to logistic advantages, LEEI might provide a superior alternative for the manufacture of (CAR-)NK-92 cells for clinical application

Risk knowledge of people with relapsing-remitting multiple sclerosis:Results of an international survey

Background Adequate disease and treatment-related risk knowledge of people with Multiple Sclerosis (pwMS) is a prerequisite for informed choices in medical encounters. Previous work showed that MS risk knowledge is low among pwMS and role preferences are different in Italy and Germany. Objective We investigated the level of risk knowledge and role preferences in 8 countries and assessed putative variables associated with risk knowledge. Methods An online-survey was performed based on the Risk knowledge questionnaire for people with relapsing-remitting MS (RIKNO 2.0), the electronic Control Preference Scale (eCPS), and other patient questionnaires. Inclusion criteria of participants were: (1) age 18 years, (2) a diagnosis of relapsing-remitting MS (RRMS), (3) being in a decision making process for a disease modifying drug. Results Of 1939 participants from Germany, Italy, the Netherlands, Serbia, Spain and Turkey, 986 (51%) (mean age 38.6 years [range 18–67], 77% women, 7.8 years of disease duration) completed the RIKNO 2.0, with a mean of 41% correct answers. There were less than 50 participants in the UK and Estonia and data were not analysed. Risk knowledge differed across countries (p &lt; 0.001). Variables significantly associated with higher risk knowledge were higher education (p &lt; 0.001), previous experience with disease modifying drugs (p = 0.001), correct answer to a medical data interpretation question (p &lt; 0.001), while higher fear for wheelchair dependency was negatively associated to risk knowledge (p = 0.001). Conclusion MS risk knowledge was overall low and differed across participating countries. These data indicate that information is an unmet need of most pwMS.</p

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis