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Chloromethane (CH3Cl) is the most abundant natural chlorinated organic compound in the atmosphere playing an important role in catalyzing stratospheric ozone loss. Vegetation emits the largest amounts of CH3Cl to the atmosphere but its source strength is highly uncertain leading also to large uncertainties in the global budget of CH3Cl. Triple‐element stable isotope analysis may help to reduce uncertainties because it provides additional process‐level information compared to conventional quantification methods. In this study we performed experiments to obtain a first triple‐elemental isotopic fingerprint (2H, 13C, 37Cl) of CH3Cl emitted by a relevant plant species (royal fern, Osmunda regalis). Isotopic values of all three elements showed considerable differences compared to isotopic values of industrially manufactured CH3Cl which bodes well for future applications to distinguish individual sources. Isotopic analysis of potential precursors (rain, methoxy groups) of CH3Cl in plants revealed no measurable change of hydrogen and chlorine isotopic ratios during formation which may provide a simpler route to estimate the isotopic composition of CH3Cl emissions. Plant degradation experiments of CH3Cl were carried out with club moss (Selaginella kraussiana) revealing significant isotopic fractionation for all three elements. The fractionation pattern characterized by epsilon and lambda is inconsistent with known biotic dechlorination reactions indicating a yet unreported biotic degradation mechanism for CH3Cl. Overall, this study provides first insights into the triple‐elemental isotopic fingerprint of plant emissions and degradation. The results may represent important input data for future isotope‐based models to improve global budget estimates of CH3Cl and to explore the yet unknown degradation pathways. Plain Language Summary: Chloromethane is the most abundant chlorinated organic compound in the atmosphere. It contributes to the destruction of the ozone layer that protects us from skin cancer and genetic damage. Currently, we do not have a good understanding of the sources and removal processes of chloromethane in the atmosphere. In this paper, we use a technique that takes advantage of the different varieties of a chemical element. These so‐called isotopes behave differently during chemical reactions that lead to individual isotopic fingerprints depending on the source or removal process. We used isotopic fingerprints of all three chemical elements in chloromethane and showed that chloromethane produced by a plant (royal fern) differs substantially from chloromethane manufactured by industry. Other plant species such as club moss are able to remove chloromethane from the atmosphere but it is often not clear how this occurs. Isotopic analysis revealed that the studied club moss uses a unique, thus far unknown, way to break down chloromethane. This study demonstrates how information extracted from isotopic fingerprints will help to improve our understanding of sources and removal processes of chloromethane in the atmosphere. It can help to better predict how ozone destruction in the stratosphere affects us in the future. Key Points: First triple‐element isotopic characterization of plant CH3Cl emission and degradationPlant degradation experiments suggest another yet unknown transformation pathwayImportant input data for future isotope based models to improve understanding of global CH3Cl budget [ABSTRACT FROM AUTHOR]

We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. B Introduction: b Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity. PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 71.1%, 91.7%, 4.9%, and 3.2% respectively. [Extracted from the article]

B Introduction: b We previously performed global miRNA expression profiling of cHL vs. non-Hodgkin lymphoma (NHL) cell lines and sorted germinal centre B-cells (GCB). Whereas overexpression of miR-148a in three cHL cell lines caused a 32% decrease ( I p i < 0.05) in proliferation in the KM-H2 cell line compared to empty vector transductions. Deregulated hsa-miR-23a-3p and hsa-mir-148a-3p influence key processes in classic Hodgkin lymphoma (cHL) pathogenesis. [Extracted from the article]

Abstract: The objectives of this research were to establish a practicable phenotyping platform for assessing the drought stress response of perennial ryegrass (Lolium perenne L.; Lp), and to use this platform for evaluating the variation for drought tolerance among a panel of 39 diverse Lp populations. A moderate‐to‐strong correlation was assessed between the performance of plants grown in a hydroponics system, where the stress was generated by the addition of polyethylene glycol (PEG), and those grown in the field in a rainout shelter. Following the application of drought stress, tetraploid Lp populations, along with a small number of reference Festulolium and Festuca sp. accessions, were able to develop more shoot and root dry matter than diploid Lp populations. The onset of drought symptoms was also delayed within these accessions and the plants recovered better once drought had been relieved. Although most of the diploid Lp populations were drought susceptible, there was a considerable accession‐to‐accession variation for performance under drought stress conditions. Measuring biomass production and post‐drought recovery in rainout shelter experiments in combination with the assessment of root biomass accumulation in PEG‐supplemented hydroponics represented a viable means of screening Lp germplasm for drought tolerance. [ABSTRACT FROM AUTHOR]

Abstract: Ice nucleation active bacteria have attracted particular attention due to their unique ability to produce specific ice nucleation proteins (INpros), which are the most efficient ice nuclei known as they induce nucleation at temperatures close to 0°C. Our model bacterium Pseudomonas syringae strain R10.79 produced INpros containing 67 tandem repeats, forming the proposed ice‐binding surface. To understand the role of the INpro repeats as well as the role of intermolecular interactions between INpros for their ice nucleation behavior, we produced a truncated version of the protein with only 16 tandem repeats (INpro16R). The purified INpro16R produced oligomers of varying sizes. Immersion freezing ice nucleation behavior of purified INpro16R was characterized by droplet‐freezing assays and in the Leipzig Aerosol Cloud Interaction Simulator. Predominant INpro16R oligomers introduced into Leipzig Aerosol Cloud Interaction Simulator as single particles with diameters of 50 nm or 70 nm were ice nucleation active at temperatures of −26°C and −24°C, respectively. These are much lower temperatures compared to that of intact INpros (−12°C). The data clearly indicated that the number of repeats determines the ice nucleation temperature. In addition, ice nucleation between −9°C and −10°C, comparable to the activity of intact INpro, was caused by higher‐order INpro16R oligomers. This supported previous observations that INpro oligomerization increases the ice‐binding surface, thereby affecting ice nucleation activity. In conclusion, both repeat number and oligomerization contribute in a seemingly independent manner to the nucleation mechanism of INpros. [ABSTRACT FROM AUTHOR]

Background: Chronic diarrhea (CD) is common in dogs, and information on frequency and distribution of primary and secondary causes is lacking. Objectives: To evaluate underlying causes and predictors of outcome in dogs with CD. Animals: One hundred and thirty-six client-owned dogs with CD (≥3 weeks duration). Methods: Retrospective review of medical records (Small Animal Clinic, Freie Universität Berlin, Germany, 09/2009-07/2011). Quantification of final diagnoses and comparison of clinical aspects including disease severity and clinicopathological abnormalities among dogs with clinical remission (either complete [gastrointestinal signs absent] or partial [clinical improvement of gastrointestinal signs and reduced episodes with shortened duration]), and those without recovery. Results: Ninety percent of dogs were diagnosed with a primary enteropathy: inflammatory (71%; of those 66% dietary responsive, 23% idiopathic, 11% antibiotic responsive), infectious (13%), neoplastic (4%), and in one dog each mechanical disease or systemic vasculitis. Secondary causes were diagnosed in 10% of dogs: exocrine pancreatic (6%), endocrine (2%), and in one dog each hepatic, renal, and cardiac disease. In total, 87% of dogs had clinical remission, whereas 13% died or did not respond to treatment: Lack of recovery was frequently recorded for dogs with primary inflammatory (idiopathic) or neoplastic disease and was significantly associated with increased disease severity scores (P = .005), anemia (hematocrit < 40%, P < .001), severe hypoalbuminemia (serum albumin <2.0 g/dL, P = .008), and severe hypocobalaminemia (serum cobalamin concentration <200 pg/mL, P = .006). Conclusions and clinical importance: Inflammatory enteropathies and particularly those of dietary origin were the most common causes of CD in dogs. Findings support the usefulness of hematocrit, and serum albumin and cobalamin concentration as prognostic markers in dogs with CD. [ABSTRACT FROM AUTHOR]

Warfarin is the anticoagulant of choice for venous thromboembolism (VTE) treatment, although its suppression of the endogenous clot-dissolution complex APC:PS may ultimately lead to longer time-to-clot dissolution profiles, resulting in increased risk of re-thrombosis. This detrimental effect might not occur during VTE treatment using other anticoagulants, such as rivaroxaban or enoxaparin, given their different mechanisms of action within the coagulation network. A quantitative systems pharmacology model was developed describing the coagulation network to monitor clotting factor levels under warfarin, enoxaparin, and rivaroxaban treatment. The model allowed for estimation of all factor rate constants and production rates. Predictions of individual coagulation factor time courses under steady-state warfarin, enoxaparin, and rivaroxaban treatment reflected the suppression of protein C and protein S under warfarin compared to rivaroxaban and enoxaparin. The model may be used as a tool during clinical practice to predict effects of anticoagulants on individual clotting factor time courses and optimize antithrombotic therapy. [ABSTRACT FROM AUTHOR]

In this article the multiplicative decomposition of the deformation gradient into one part constrained in the direction of the axis of anisotropy and one part describing the directional deformation is proposed. This leads to a clear division of the deformation and stress states in the direction of anisotropy and a remaining part. The decomposition is explained in detail and a constitutive model of hyper-elasticity is proposed for the case of transversal isotropy, where the behavior of the model is investigated with the aid of simple analytical examples. The model is also investigated for inhomogeneous deformation states using high-order finite elements based on hierarchical shape functions showing the sensitivity of the accuracy of the results in the case of anisotropic media. [ABSTRACT FROM AUTHOR]

Helminths induce strong regulatory and T helper 2-type responses, whereby antibody-derived host protection and regulation are essential components. Lymphatic filariasis is an immune-mediated spectral disease that manifests as two main clinical outcomes: chronic pathology or asymptomatic infection. These outcomes depend on a multitude of factors, including parasite-induced immunoregulation and host genetic background; antibody responses contribute to this outcome. N-glycosylation of the Fc region of antibodies is a post-translational modification required for the structure and molecular function, influencing host inflammatory and regulatory responses. Altered IgG glycosylation correlates with disease, whereby decreased galactosylation is associated with inflammation while increased sialylation is associated with anti-inflammatory responses. We purified N-linked glycans from the Fc region of total IgG from Wuchereria bancrofti-infected patients characterizing the two clinical manifestations (chronic pathology and asymptomatic infection) and compared them to infection-free endemic normals. Using capillary electrophoresis, we found that there was no difference in galactosylation of total IgG between the three groups; however, asymptomatically infected patients had significantly lower levels of disialylated IgG compared to endemic normals and patients with pathology. These data suggest that while galactosylation does not contribute to disease outcome, sialylation may be involved in asymptomatic infection. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability to induce immunoregulatory pathways in their hosts. In particular, administration of ova from the pig whipworm Trichuris suis (T. suis; TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune disorders. Despite these advances, the biological pathways through which TSO therapy modu-lates the host immune system in the context of human disease remain undefined. Methods: We characterized the dominant proteins present in the excretory/secre-tory (E/S) products of first-stage (LI) T. suis larvae (Ts E/S) using LC-MS/MS analysis and examined the immunosuppressive properties of whole larval Ts E/S in vitro and in a murine model of allergic airway disease. Results: Administration of larval Ts E/S proteins in vivo during the allergen sensiti-zation phase was sufficient to suppress airway hyperreactivity, bronchiolar inflam-matory infiltrate and allergen-specific IgE production. Three proteins in larval Ts E/S were unambiguously identified. The immunomodulatory function of larval Ts E/S was found to be partially dependent on the immunoregulatory cytokine IL-10. Conclusions: Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dam-pen allergic airway hyperreactivity. Thus, the therapeutic potential of defined lar-val E/S proteins should be exploited for the treatment of human allergic disorders. [ABSTRACT FROM AUTHOR]

Eight polymorphic microsatellite loci were developed for the brook lamprey Lampetra planeri through 454 sequencing and their usefulness was tested in 45 individuals of both L. planeri and the river lamprey Lampetra fluviatilis. The number of alleles per loci ranged between two and five; the Italian and Irish populations had a mean expected heterozygosity of 0·388 and 0·424 and a mean observed heterozygosity of 0·418 and 0·411, respectively. [ABSTRACT FROM AUTHOR]

In a multicentre randomised trial (German Research Association, grants DFG WA 831/2-1 to 2-6, WO 677/2-1.1 to 2-2.1.; controlled-trials.com ISRCTN97265367), patients with complete molar loss in one jaw received either a partial removable dental prosthesis ( PRDP) with precision attachments or treatment according to the SDA concept aiming at pre-molar occlusion. The objective of this current analysis was to evaluate the influence of different treatments on periodontal health. Linear mixed regression models were fitted to quantify the differences between the treatment groups. The assessment at 5 years encompassed 59 patients ( PRDP group) and 46 patients ( SDA group). For the distal measuring sites of the posterior-most teeth of the study jaw, significant differences were found for the plaque index according to Silness and Löe, vertical clinical attachment loss ( CAL-V), probing pocket depth ( PPD) and bleeding on probing. These differences were small and showed a slightly more unfavourable course in the PRDP group. With CAL-V and PPD, significant differences were also found for the study jaw as a whole. For CAL-V, the estimated group differences over 5 years amounted to 0·27 mm (95% CI 0·05; 0·48; P = 0·016) for the study jaw and 0·25 mm (95% CI 0·05; 0·45; P = 0·014) for the distal sites of the posterior-most teeth. The respective values for PPD were 0·22 mm (95% CI 0·03; 0·41; P = 0·023) and 0·32 mm (95% CI 0·13; 0·5; P = 0·001). It can be concluded that even in a well-maintained patient group statistically significant although minor detrimental effects of PRDPs on periodontal health are measurable. [ABSTRACT FROM AUTHOR]

High-order finite elements are commonly compared with linear element formulations showing that, in terms of the relation between computational time and achievable accuracy, linear element formulations are inferior to high-order elements. On the other hand, the finite element community follows the h-version approach due to its simplicity in implementation. This article compares high-order finite elements based on hierarchic shape functions with low-order mixed element formulations using finite strain hyperelasticity. These comparisons are conducted from the point of view of both accuracy and efficiency as well as highly deformed structures. It also investigates improvements to minimize the overall computational effort such as parallelizing the element assemblage procedure, choosing a starting vector estimator for Newton's method, and investigating the Newton-Chord method. The advantages and disadvantages of both finite element approaches are also discussed. [ABSTRACT FROM AUTHOR]

Many important cultural and religious objects from Asia consist of outer metallic shapes, usually bronze, which fully enclose inner contents made of organic materials such as wood, bark, paper, textile, plants and others. Bronze and other metallic materials, such as copper and silver, are generally more transparent to neutrons than to X-rays. However, organic materials are less transparent to neutrons than to X-rays and therefore organic materials, enclosed by metallic materials, can be made visible with neutrons. Therefore, neutron imaging (radiography and tomography) was found to be an ideal tool for the inspection of objects that consist of metal outside and organic materials inside. This has been successfully demonstrated here with four metallic Tibetan Buddha statues, providing archaeometry with a powerful new tool. The first successful applications of this novel technique are described in this article. Further possible and useful applications of neutron imaging of cultural objects are outlined. [ABSTRACT FROM AUTHOR]

Background Some helminth infections are negatively associated with the prevalence of allergic disorders, arguing for a modulation of allergic reactions by the parasites, depending on the worm species, intensity and phase of infection and the type of disease. Objective The aim of this study was to analyse the influence of a chronic infection with the gastrointestinal nematode Heligmosomoides polygyrus, in a murine model of allergic airway disease and of atopic dermatitis (AD), respectively. Methods Mice were infected with H. polygyrus and systemically sensitized with the model allergen ovalbumin. Subsequently, the animals were challenged with the allergen either via the airways for induction of airway disease, or via skin patches for induction of dermatitis. Results Mice concomitantly infected with H. polygyrus showed diminished eosinophil and lymphocyte recruitment into the lungs and decreased allergen-specific IgE levels when compared with sensitized and airway challenged controls. In addition, animals showed a trend towards reduced airway hyper-reactivity. In contrast, no significant differences in the severity of eczematous skin lesions were observed between infected and control animals in the AD model. Although H. polygyrus infection reduced CD8+ and CD4+ T-cell infiltration into the skin and production of allergen-specific IgE, mast cell recruitment was significantly increased in worm-infected mice in the dermatitis model. The worm infection was associated with significantly elevated numbers of Foxp3+ regulatory T cells (Treg) in peribronchial lymph nodes in H. polygyrus-infected sensitized and airway challenged mice. In contrast, Treg cells were basically absent in eczematous skin and their number was not increased in skin-draining lymph nodes of mice with experimental dermatitis. Conclusion Infection with the gastrointestinal nematode used in our study leads to significant inhibition of mucosa-associated but not cutaneous allergic reactions, pointing to a site specificity of the immunomodulation exerted by helminths. This finding might be an important aspect for future considerations of helminths for treatment of allergic diseases. [ABSTRACT FROM AUTHOR]

This article treats the computation of discretized constitutive models of evolutionary-type (like models of viscoelasticity, plasticity, and viscoplasticity) with quasi-static finite elements using diagonally implicit Runge-Kutta methods (DIRK) combined with the Multilevel-Newton algorithm (MLNA). The main emphasis is on promoting iterative methods, as opposed to the more traditional direct methods, for solving the non-symmetric systems which occur within the DIRK/MLNA. It is shown that iterative solution of the arising sequences of linear systems can be substantially accelerated by various techniques that aim at sharing part of the computational effort throughout the sequence. In this way iterative solution becomes attractive at clearly lower dimensions than the dimensions where direct solvers start to fail for memory reasons. The applications are related to small strain viscoplasticity of a smooth constitutive model for plastics and a finite strain plasticity model with non-linear kinematic hardening developed for metals. [ABSTRACT FROM AUTHOR]

The reproductive biology of Epinephelus coioides was determined from the examination of 1455 individuals collected between July 2005 and June 2007 in the southern Arabian Gulf. Histological preparations of gonads indicated that males were either derived from a juvenile phase or the transition of postspawning females, confirming a diandric protogynous sexual pattern. The spawning season was well defined, occurring once a year during April and early May. Peaks in spawning occurred after the full and new moons and was completed within a single lunar cycle. The presence of mature males over the entire size and age range and the absence of inactive mature females during the spawning season suggested that the population was not constrained by sperm limitation. While specimens undergoing sexual transition were only observed in size and age ranges of 335–685 mm total length ( LT) and 5–6 years, patterns in the proportion of males in size and age classes suggested that sex change occurred at a relatively constant rate after female maturation up to the maximum size (1002 mm LT) and age (11 years). Relationships between reproductive output and capacity with size and age indicated that conventional regulations that equate the mean size at first capture to sexual maturation are unsuitable for the management of E. coioides. The maximum age, small size and young age at sexual maturation ( Lmin= 320 mm LT, 2 years, for females and 242 mm LT, 1 year, for males) conflict with the general pattern for large epinepheline groupers and may be a direct result of the intensive demersal fishery in the southern Arabian Gulf. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the feasibility of a multifaceted strategy to translate evidence-based guidelines for treating nursing home-acquired pneumonia (NHAP) into practice using a small intervention trial. DESIGN: Pre-posttest with untreated control group. SETTING: Two Colorado State Veterans Homes (SVHs) during two influenza seasons. PARTICIPANTS: Eighty-six residents with two or more signs of lower respiratory tract infection. INTERVENTION: Multifaceted, including a formative phase to modify the intervention, institutional-level change emphasizing immunization, and availability of appropriate antibiotics; interactive educational sessions for nurses; and academic detailing. MEASUREMENTS: Subjects' SVH medical records were reviewed for guideline compliance retrospectively for the influenza season before the intervention and prospectively during the intervention. Bivariate comparisons-of-care processes between the intervention and control facility before and after the intervention were made using the Fischer exact test. RESULTS: At the intervention facility, compliance with five of the guidelines improved: influenza vaccination, timely physician response to illness onset, x-ray for patients not being hospitalized, use of appropriate antibiotics, and timely antibiotic initiation for unstable patients. Chest x-ray and appropriate and timely antibiotics were significantly better at the intervention than at the control facility during the intervention year but not during the control year. CONCLUSION: Multifaceted, evidence-based, NHAP guideline implementation improved care processes in a SVH. Guideline implementation should be studied in a national sample of nursing homes to determine whether it improves quality of life and functional outcomes of this debilitating illness for long-term care residents. [ABSTRACT FROM AUTHOR]

Parasitic nematodes are constantly exposed to the immune effector mechanisms of their hosts. One strategy of the worms to cope with these defence reactions is the secretion of modulatory proteins that down-regulate cell-mediated immune responses. We analysed the proliferation of mesenteric lymph node cells of mice infected with Heligmosomoides polygyrus and showed that cellular proliferation was strongly suppressed in the chronic phase of infection. To identify proteins of H. polygyrus that are involved in parasite-induced immunomodulation, worm extract and culture supernatant of adult H. polygyrus were fractionated by gel chromatography and activity of each fraction was determined. One of the fractions (fraction 9) of worm extract as well as worm secretory products inhibited the antigen-specific cellular proliferation by about 40%. This reduced cellular reactivity coincided with a down-regulation of inducible nitric oxide production of mouse macrophages by 57%. Furthermore, fraction 9 contained antigens that were recognized by IgE antibodies of H. polygyrus -infected mice and induced degranulation of an IgE-sensitized basophil cell line. Single proteins of fraction 9 were analysed by mass spectrometry. These data suggest that antigens that are recognised by IgE antibodies might play an important role in immunomodulation exerted by nematode infections. [ABSTRACT FROM AUTHOR]

The authors assessed the impact of severe hepatic impairment on the disposition of fingolimod--a sphingosine-1-phosphate receptor immunomodulator primarily metabolized by CYP4F2--in 6 patients and 6 matched healthy controls who received a single 5-mg oral dose. Compared with healthy controls, severe hepatic-impaired subjects had a doubled area under the concentration time curve (AUC) and 50% prolonged elimination half-life but a similar peak blood concentration. When these data were combined with those from a previous study in mild and moderate hepatic-impaired subjects, there were significant positive correlations between fingolimod AUC versus bilirubin (r = 0.683) and prothrombin time (r = 0.777) and a significant negative correlation versus albumin (r = 0.578), confirming the importance of liver function for fingolimod clearance. For patients with severe hepatic impairment (Child-Pugh class C), a standard first dose of fingolimod could be given followed by a maintenance dose that is reduced by half from the normal maintenance dose. [ABSTRACT FROM AUTHOR]

This paper shows the possibilities offered by the combined use of non-destructive neutron and X-ray beams in archaeological research on metallic finds. The following five artefacts from Swiss excavations were submitted to investigation, each with dedicated aims: a Roman sword, a Roman dagger, an Iron Age bucket, Iron Age spearheads and a Roman finger ring. The images obtained with both methods—neutrons and X-rays—are discussed in length in this paper. The investigations took place at the Paul Scherrer Institute and the archaeologists who studied the objects come from the Universities of Lausanne and Zurich. [ABSTRACT FROM AUTHOR]

The authors assessed the mutual influence of the immunosuppressant everolimus (Certican) and the HMG-CoA reductase inhibitors atorvastatin and pravastatin when coadministered based on pharmacokinetic and pharmacodynamic measures. In this randomized, open-label, three-way crossover study, 24 healthy men received three single-dose oral treatments: 2 mg everolimus, 20 mg atorvastatin (n = 12) or 20 mg pravastatin (n = 12), and the respective statin coadministered with everolimus. Consecutive treatments were separated by a 14-day washout. The pharmacokinetics of all three drugs and total HMG-CoA reductase inhibitors were measured. Everolimus Cmax was reduced by 9% and 10% with atorvastatin and pravastatin coadministration; the corresponding decreases in everolimus AUC were 5% and 6%, respectively. Everolimus coadministration increased the Cmax of atorvastatin by 11% but had no influence on atorvastatin AUC. Coadministration of everolimus with pravastatin was associated with a 10% decrease in pravastatin Cmax and a 5% decrease in the AUC. The elimination half-lives of the two statins were unaffected by everolimus. Changes in total HMG-CoA reductase inhibitors in plasma exhibited generally similar patterns as for the parent statin exposures. Single-dose administrations of everolimus with either atorvastatin or pravastatin did not influence the pharmacokinetics of everolimus, atorvastatin, pravastatin, or total HMG-CoA reductase inhibitors in plasma to a clinically relevant extent. [ABSTRACT FROM AUTHOR]

This article documents the addition of 92 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Anopheles minimus, An. sinensis, An. dirus, Calephelis mutica, Lutjanus kasmira, Murella muralis and Orchestia montagui. These loci were cross-tested on the following species: Calephelis arizonensi, Calephelis borealis, Calephelis nemesis, Calephelis virginiensis and Lutjanus bengalensis. [ABSTRACT FROM AUTHOR]

Here, we report on a novel allele human leukocyte antigen (HLA)-A*240215. This allele differs from HLA-A*240201 by a synonymous nucleotide exchange at nucleotide 255 in exon 2. [ABSTRACT FROM AUTHOR]

In this paper we interpret the finite-element method applied to constitutive models with internal variables as the solution of differential algebraic equations (DAE). With this interpretation we can utilize Diagonal Implicit Runge-Kutta methods (DIRK) as well as a corresponding step-size control and a special solution technique for block-structured systems of equations. This proceeding doesn't affect already developed FE-implementations which are based on the Backward Euler method. Furthermore, the meaning of the consistent tangent operator becomes more obvious. The paper ends with some examples in creep and relaxation tests, where step size control should always be used conditioned by the different time scales. [ABSTRACT FROM AUTHOR]

The new HLA-C*07:108 differs from C*07:01:01 by two transversions in exon 3. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent aggressive B-cell lymphoma. The group is heterogeneous and the outcome is variable. A variety of approaches have been employed with the objective of improving the stratification of DLBCL patients according to their prognosis, based on the cell of origin. Recently, distinct genetic subtypes of DLBCL have been identified. Given the importance of cell migration in immune cells, the objective of this study was to ascertain whether different genetic subtypes of DLBCL exhibit disparate migration abilities. MCD- and EZB-type DLBCL cell lines were subjected to testing to ascertain their basal velocity in straight microchannels and their ability to overcome tight constrictions of 2 μm. The EZB-type cell lines showed superior basal migration velocity and constriction passage time, and a similar trend was observed in live cell imaging of native human DLBCL tissue. In addition, MCD-type DLBCL exhibited significantly elevated levels of nuclear lamin A/C, which is responsible for the stiffness of the nuclear envelope and could thus explain the disparate migration behaviours observed among these subtypes. Our study suggests that different genetic subtypes of DLBCL may not only influence the outcome after therapy but also the motility of the tumour cells., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Mantle cell lymphoma (MCL) is clinically and biologically heterogeneous. While various prognostic features have been proposed, none currently impact therapy selection, particularly in older patients, for whom treatment is primarily dictated by age and comorbidities. Herein, we undertook a comprehensive comparison of clinicopathological features in a cohort of patients 60 years and older, uniformly treated with bendamustine and rituximab, with a median survival of >8 years. The strongest prognostic indicators in this cohort were a high-risk call by a simplified MCL international prognostic index (s-MIPI) (HR: 3.32, 95% CI: 1.65-6.68 compared to low risk), a high-risk call by MCL35 (HR: 10.34, 95% CI: 2.37-45.20 compared to low risk) and blastoid cytology (HR: 4.21, 95% CR: 1.92-9.22 compared to classic). Patients called high risk by both the s-MIPI and MCL35 had the most dismal prognosis (HR: 11.58, 95% CI: 4.10-32.72), while those with high risk by either had a moderate but clinically relevant prognosis (HR: 2.95, 95% CI: 1.49-5.82). A robust assay to assess proliferation, such as MCL35, along with stringent guidelines for cytological evaluation of MCL, in combination with MIPI, may be a strong path to risk-stratify older MCL patients in future clinical trials., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Different studies have characterized the microenvironment and its prognostic impact in classic Hodgkin lymphoma whereas such analyses are pending for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We thus investigated characteristics of tumour cells and microenvironment in NLPHL and evaluated possible correlations with the clinical presentation. Lymph node samples from 152 NLPHL patients who had first-line treatment within the randomized German Hodgkin Study Group HD16-HD18 trials were available and analysed with regard to IgD status and nuclear size of the tumour cells as well as presence of PD1-positive follicular T helper cells and CD163-positive macrophages in the microenvironment. While large tumour cell nuclei and high numbers of PD1-positive follicular T helper cells in the microenvironment were more common in patients presenting with early/intermediate stages than in patients with advanced-stage disease (p < 0.0001, unpaired t-test; p = 0.0022, Mann-Whitney test), no differences between risk groups were observed in terms of the IgD status of the tumour cells and the content of CD163-positive macrophages in the microenvironment. PD1-positive follicular T helper cells were present in both cases with typical and variant growth patterns and rosetting around the tumour cells was observed in 96% of patients, indicating an important role of PD1-positive follicular T helper cells in NLPHL., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Classic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T-cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T-cell lymphoma (ALCL). Since we recently observed differences in the motility of ALCL and cHL tumour cells, here, we aimed to obtain a better understanding of T-cell-derived cHL by investigating their global proteomic profiles and their motility. In a proteomics analysis, when only motility-associated proteins were regarded, T-cell-derived cHL cell lines showed the highest similarity to ALK - ALCL cell lines. In contrast, T-cell-derived cHL cell lines presented a very low overall motility, similar to that observed in conventional cHL. Whereas all ALCL cell lines, as well as T-cell-derived cHL, predominantly presented an amoeboid migration pattern with uropod at the rear, conventional cHL never presented with uropods. The migration of ALCL cell lines was strongly impaired upon application of different inhibitors. This effect was less pronounced in cHL cell lines and almost invisible in T-cell-derived cHL. In summary, our cell line-derived data suggest that based on proteomics and migration behaviour, T-cell-derived cHL is a neoplasm that shares features with both cHL and ALCL and is not an ALCL with low tumour cell content. Complementary clinical studies on this lymphoma are warranted., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0·0354) and splenic involvement (P = 0·0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET-2) tended to be more common (P = 0·1078). Five-year progression-free survival [hazard ratio (HR) = 0·86; 95% confidence interval (CI) = 0·49-1·47] and overall survival (HR = 0·85; 95% CI = 0·49-1·51) did not differ between the groups after study treatment with PET-2-guided escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Thus, advanced NLPHL is often associated with atypical growth patterns but their prognostic impact is compensated by PET-2-guided escalated BEACOPP., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background Myocarditis attributable to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune-related adverse event. Limited data have suggested an association between baseline and on-treatment absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) and the development of other immune-related adverse events; there are no data characterizing the role of ALC and NLR in ICI-associated myocarditis. Methods and Results This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post-ICI immune-related adverse events. We leveraged clinical testing, where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events was also tested. In cases, there was a statistically significant decrease in ALC with myocarditis from baseline (1.6 thousands per cubic milliliter (K/μL); interquartile range, 1.1-1.9 K/μL) to admission (1.1 K/μL; interquartile range, 0.7-1.3 K/μL; P <0.001). Similarly, there was an increase in NLR from baseline (3.5; interquartile range, 2.3-5.4) to admission (6.6; interquartile range, 4.5-14.1; P <0.001). There was no statistically significant change in controls. In follow-up, there were 20 events; larger decreases in ALC (44.6% versus 18.2%; P <0.001) or increases in NLR (156.5% versus 65.1%; P =0.019) were associated with major adverse cardiac events. Conclusions A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR was associated with subsequent major adverse cardiac events.