The chemical journey of Europium(III) through winter rye (Secale cereale L.) – Understanding through mass spectrometry and chemical microscopy

A combination of biochemical preparation methods with microscopic, spectroscopic, and mass spectrometric analysis techniques as contemplating state of the art application, was used for direct visualization, localization, and chemical identification of europium in plants. This works illustrates the chemical journey of europium (Eu(III)) through winter rye (Secale cereale L.), providing insight into the possibilities of speciation for Rare Earth Elements (REE) and trivalent f-elements. Kinetic experiments of contaminated plants show a maximum europium concentration in Secale cereale L. after four days. Transport of the element through the vascular bundle was confirmed with Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDS). For chemical speciation, plants were grown in a liquid nutrition medium, whereby Eu(III) species distribution could be measured by mass spectrometry and luminescence measurements. Both techniques confirm the occurrence of Eu malate species in the nutrition medium, and further analysis of the plant was performed. Luminescence results indicate a change in Eu(III) species distribution from root tip to plant leaves. Microscopic analysis show at least three different Eu(III) species with potential binding to organic and inorganic phosphate groups and a Eu(III) protein complex. With plant root extraction, further europium species could be identified by using Electrospray Ionization Mass Spectrometry (ESI MS). Complexation with malate, citrate, a combined malate-citrate ligand, and aspartate was confirmed mostly in a 1:1 stoichiometry (Eu:ligand). The combination of the used analytical techniques opens new possibilities in direct species analysis, especially regarding to the understanding of rare earth elements (REE) uptake in plants. This work provides a contribution in better understanding of plant mechanisms of the f-elements and their species uptake

Quasar Candidates in the Hubble Deep Field

We focus on the search for unresolved faint quasars and AGN in the crude combine images using a multicolor imaging analysis that has proven very successful in recent years. Quasar selection was carried out both in multicolor space and in "profile space," defined as the multi-parameter space formed by the radial profiles of the objects in the different images. By combining the dither frames available for each filter, we were able to obtain well-sampled radial profiles of the objects and measure their deviation from that of a stellar source. We also generated synthetic quasar spectra in the range 1.0 < z < 5.5 and computed expected quasar colors. We determined that the data are 90% complete for point sources at 26.2, 28.0, 27.8, 26.8 in the F300W, F450W, F606W and F814W filters, respectively. We find 41 compact objects in the HDF: 8 pointlike objects with colors consistent with quasars or stars, 18 stars, and 15 slightly resolved objects, 12 of which have colors consistent with quasars or stars. We estimate the upper limit of unresolved and slightly resolved quasars/AGNs with V < 27.0 and z < 3.5 to be 20 objects (16,200 per deg^2). We find good agreement among authors on the number of stars and the lack of quasar candidates with z > 3.5. We find more quasar candidates than previous work because of our more extensive modeling and use of all of the available color information. (abridged)Comment: We have clarified our discussion and conclusions, added some references and removed the appendix, which is now available from the first author. 37 pages including 10 embedded postscript figures and 6 tables. To appear in the Feb. 99 issue of A

Traditional or regenerative periodontal surgery?-a comparison of the publications between two periodontal journals over time

OBJECTIVES The objective is to compare the amount and content of publications regarding traditional or regenerative periodontal surgery in the years 1982/1983 and 2012/2013 in two leading periodontal journals of North America and Europe. MATERIAL AND METHODS The search was carried out in the Journal of Periodontology and Journal of Clinical Periodontology. Four reviewers screened the articles and allocated the topics with respect to periodontal surgery. The distribution of articles with respect to traditional or regenerative periodontal surgery was then compared between the journals and the respective time periods. RESULTS Out of 1084 screened articles, 145 articles were included. Articles with periodontal surgery content amounted to 18% for the first time period and to 11% for the second time period. In the years 1982/1983, 7% of articles in the Journal of Periodontology and 8% in the Journal of Clinical Periodontology referred to traditional periodontal surgery, while 8% (Journal of Periodontology) and 5% (Journal of Clinical Periodontology) examined regenerative periodontal surgery. The distribution changed 30 years later, with 1% (Journal of Periodontology) and 3% (Journal of Clinical Periodontology) traditional periodontal surgery and 7% and 6% regenerative periodontal surgery content. CONCLUSION While the clinical need for traditional periodontal surgery remained, research in this important field decreased. Publications rather tended to focus on adjunctive regenerative measures. CLINICAL RELEVANCE Periodontal surgery with adjunctive regenerative measures is an established and well-documented clinical procedure. However, with respect to the dominance of horizontal bone loss in periodontally diseased patients, there is a need for ongoing research with focus on traditional periodontal surgery

The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

Measures implemented in the school setting to contain the COVID-19 pandemic

BACKGROUND: In response to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the impact of coronavirus disease 2019 (COVID-19), governments have implemented a variety of measures to control the spread of the virus and the associated disease. Among these, have been measures to control the pandemic in primary and secondary school settings. OBJECTIVES: To assess the effectiveness of measures implemented in the school setting to safely reopen schools, or keep schools open, or both, during the COVID-19 pandemic, with particular focus on the different types of measures implemented in school settings and the outcomes used to measure their impacts on transmission-related outcomes, healthcare utilisation outcomes, other health outcomes as well as societal, economic, and ecological outcomes.  SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Educational Resources Information Center, as well as COVID-19-specific databases, including the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease (indexing preprints) on 9 December 2020. We conducted backward-citation searches with existing reviews. SELECTION CRITERIA: We considered experimental (i.e. randomised controlled trials; RCTs), quasi-experimental, observational and modelling studies assessing the effects of measures implemented in the school setting to safely reopen schools, or keep schools open, or both, during the COVID-19 pandemic. Outcome categories were (i) transmission-related outcomes (e.g. number or proportion of cases); (ii) healthcare utilisation outcomes (e.g. number or proportion of hospitalisations); (iii) other health outcomes (e.g. physical, social and mental health); and (iv) societal, economic and ecological outcomes (e.g. costs, human resources and education). We considered studies that included any population at risk of becoming infected with SARS-CoV-2 and/or developing COVID-19 disease including students, teachers, other school staff, or members of the wider community.  DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full texts. One review author extracted data and critically appraised each study. One additional review author validated the extracted data. To critically appraise included studies, we used the ROBINS-I tool for quasi-experimental and observational studies, the QUADAS-2 tool for observational screening studies, and a bespoke tool for modelling studies. We synthesised findings narratively. Three review authors made an initial assessment of the certainty of evidence with GRADE, and several review authors discussed and agreed on the ratings. MAIN RESULTS: We included 38 unique studies in the analysis, comprising 33 modelling studies, three observational studies, one quasi-experimental and one experimental study with modelling components. Measures fell into four broad categories: (i) measures reducing the opportunity for contacts; (ii) measures making contacts safer; (iii) surveillance and response measures; and (iv) multicomponent measures. As comparators, we encountered the operation of schools with no measures in place, less intense measures in place, single versus multicomponent measures in place, or closure of schools. Across all intervention categories and all study designs, very low- to low-certainty evidence ratings limit our confidence in the findings. Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the model structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to deviations from intended interventions or missing data. Across all categories, few studies reported on implementation or described how measures were implemented. Where we describe effects as 'positive', the direction of the point estimate of the effect favours the intervention(s); 'negative' effects do not favour the intervention.  We found 23 modelling studies assessing measures reducing the opportunity for contacts (i.e. alternating attendance, reduced class size). Most of these studies assessed transmission and healthcare utilisation outcomes, and all of these studies showed a reduction in transmission (e.g. a reduction in the number or proportion of cases, reproduction number) and healthcare utilisation (i.e. fewer hospitalisations) and mixed or negative effects on societal, economic and ecological outcomes (i.e. fewer number of days spent in school). We identified 11 modelling studies and two observational studies assessing measures making contacts safer (i.e. mask wearing, cleaning, handwashing, ventilation). Five studies assessed the impact of combined measures to make contacts safer. They assessed transmission-related, healthcare utilisation, other health, and societal, economic and ecological outcomes. Most of these studies showed a reduction in transmission, and a reduction in hospitalisations; however, studies showed mixed or negative effects on societal, economic and ecological outcomes (i.e. fewer number of days spent in school). We identified 13 modelling studies and one observational study assessing surveillance and response measures, including testing and isolation, and symptomatic screening and isolation. Twelve studies focused on mass testing and isolation measures, while two looked specifically at symptom-based screening and isolation. Outcomes included transmission, healthcare utilisation, other health, and societal, economic and ecological outcomes. Most of these studies showed effects in favour of the intervention in terms of reductions in transmission and hospitalisations, however some showed mixed or negative effects on societal, economic and ecological outcomes (e.g. fewer number of days spent in school). We found three studies that reported outcomes relating to multicomponent measures, where it was not possible to disaggregate the effects of each individual intervention, including one modelling, one observational and one quasi-experimental study. These studies employed interventions, such as physical distancing, modification of school activities, testing, and exemption of high-risk students, using measures such as hand hygiene and mask wearing. Most of these studies showed a reduction in transmission, however some showed mixed or no effects.   As the majority of studies included in the review were modelling studies, there was a lack of empirical, real-world data, which meant that there were very little data on the actual implementation of interventions. AUTHORS' CONCLUSIONS: Our review suggests that a broad range of measures implemented in the school setting can have positive impacts on the transmission of SARS-CoV-2, and on healthcare utilisation outcomes related to COVID-19. The certainty of the evidence for most intervention-outcome combinations is very low, and the true effects of these measures are likely to be substantially different from those reported here. Measures implemented in the school setting may limit the number or proportion of cases and deaths, and may delay the progression of the pandemic. However, they may also lead to negative unintended consequences, such as fewer days spent in school (beyond those intended by the intervention). Further, most studies assessed the effects of a combination of interventions, which could not be disentangled to estimate their specific effects. Studies assessing measures to reduce contacts and to make contacts safer consistently predicted positive effects on transmission and healthcare utilisation, but may reduce the number of days students spent at school. Studies assessing surveillance and response measures predicted reductions in hospitalisations and school days missed due to infection or quarantine, however, there was mixed evidence on resources needed for surveillance. Evidence on multicomponent measures was mixed, mostly due to comparators. The magnitude of effects depends on multiple factors. New studies published since the original search date might heavily influence the overall conclusions and interpretation of findings for this review

The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations