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INTRODUCTION: Accurate determination of the internal length of nasogastric tubes is essential for the safe and effective completion of blind insertions, a routine nursing procedure. The widely used nose-earlobe-xiphoid distance lacks evidence and effectiveness. A recent randomized controlled trial proposed an alternative, the corrected nose-earlobe-xiphoid distance formula. However, its effectiveness in real-world clinical practice has not yet been studied. OBJECTIVE: This study assessed the real-world clinical effectiveness of the corrected nose-earlobe-xiphoid distance formula for determining the internal nasogastric tube length in adult patients admitted to hospitalization or intensive care units. DESIGN: A single-center retrospective clinical effectiveness study was conducted, utilizing routinely collected observational data. SETTING AND MAIN OUTCOME MEASURES: Between October 2020 and November 2022, 358 adult patients in a general hospital requiring a nasogastric feeding tube were included. The primary outcome involved assessing nasogastric tube tip positioning (>3 cm below the lower esophageal sphincter) by an advanced practice nurse through X-ray verification. Secondary outcomes, obtained from patient records for a random subgroup of 100 participants, were reporting clarity and evaluation of the tip position by reviewing radiologists. RESULTS: Following evaluation by an advanced practice nurse, all nasogastric feeding tubes were determined to be correctly positioned. Among the subgroup of 100 tubes, X-ray protocols, as documented by the reviewing radiologists, showed varying levels of reporting clarity for the tube tip: 4.0 % lacked reporting, 33.0 % had ambiguous reporting and 63.0 % had unambiguous reporting. CONCLUSION: The corrected nose-earlobe-xiphoid distance formula demonstrates potential to emerge as a safer alternative to existing methods for determining the internal length of nasogastric tubes. IMPLICATIONS FOR CLINICAL PRACTICE: In addition to healthcare provider education and training, a checklist-based framework is recommended for radiologists to unambiguously report nasogastric tube tip positions.

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Agricultural pesticides, nutrients, and habitat degradation are major causes of insect declines in lowland streams. To effectively conserve and restore stream habitats, standardized stream monitoring data and societal support for freshwater protection are needed. Here, we sampled 137 small stream monitoring sites across Germany, 83 % of which were located in agricultural catchments, with >900 citizen scientists in 96 monitoring groups. Sampling was carried out according to Water Framework Directive standards as part of the citizen science freshwater monitoring program FLOW in spring and summer 2021, 2022 and 2023. The biological indicator SPEARpesticides was used to assess pesticide exposure and effects based on macroinvertebrate community composition. Overall, 58 % of the agricultural monitoring sites failed to achieve a good ecological status in terms of macroinvertebrate community composition and indicated high pesticide exposure (SPEARpesticides status class: 29 % "moderate", 19 % "poor", 11 % "bad"). The indicated pesticide pressure in streams was related to the proportion of arable land in the catchment areas (R2 = 0.23, p < 0.001). Also with regards to hydromorphology, monitoring results revealed that 65 % of the agricultural monitoring sites failed to reach a good status. The database produced by citizen science groups was characterized by a high degree of accuracy, as results obtained by citizen scientists and professionals were highly correlated for SPEARpesticides index (R2 = 0.79, p < 0.001) and hydromorphology index values (R2 = 0.72, p < 0.001). Such citizen-driven monitoring of the status of watercourses could play a crucial role in monitoring and implementing the objectives of the European Water Framework Directive, thus contributing to restoring and protecting freshwater ecosystems.

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The catalytic activity of trypsin-like serine proteases is in many cases regulated by conformational changes initiated by binding of physiological modulators to exosites located distantly from the active site. A trypsin-like serine protease of particular interest is urokinase-type plasminogen activator (uPA), which is involved in extracellular tissue remodeling processes. Herein, we used hydrogen/deuterium exchange mass spectrometry (HDXMS) to study regulation of activity in the catalytic domain of the murine version of uPA (muPA) by two muPA specific monoclonal antibodies. Using a truncated muPA variant (muPA16-243), containing the catalytic domain only, we show that the two monoclonal antibodies, despite binding to an overlapping epitope in the 37s and 70s loops of muPA16-243, stabilize distinct muPA16-243 conformations. Whereas the inhibitory antibody, mU1 was found to increase the conformational flexibility of muPA16-243, the stimulatory antibody, mU3, decreased muPA16-243 conformational flexibility. Furthermore, the HDXMS data unveil the existence of a pathway connecting the 70s loop to the active site region. Using alanine scanning mutagenesis, we further identify the 70s loop as an important exosite for the activation of the physiological uPA substrate plasminogen. Thus, the data presented here reveal important information about dynamics in uPA by demonstrating how various ligands can modulate uPA activity by mediating long-range conformational changes. Moreover, the results provide a possible mechanism of plasminogen activation.

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Although trypsin-like serine proteases have flexible surface-exposed loops and are known to adopt higher and lower activity conformations, structural determinants for the different conformations have remained largely obscure. The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis. We solved five X-ray crystal structures of murine uPA (muPA) in the absence and presence of allosteric molecules and/or substrate-like molecules. The structure of unbound muPA revealed an unsuspected non-chymotrypsin-like protease conformation in which two ß-strands in the core of the protease domain undergoes a major antiparallel-to-parallel conformational transition. We next isolated two anti-muPA nanobodies; an active-site binding nanobody and an allosteric nanobody. Crystal structures of the muPA:nanobody complexes and hydrogen-deuterium exchange mass spectrometry revealed molecular insights about molecular factors controlling the antiparallel-to-parallel equilibrium in muPA. Together with muPA activity assays, the data provide valuable insights into regulatory mechanisms and conformational flexibility of uPA and trypsin-like serine proteases in general.

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OBJECTIVES: The aim was to determine the non-melanoma skin cancer (NMSC) risk in patients with RA or PsA exposed to MTX and other DMARDs. METHODS: Information on medication was collected on 405 patients with RA or PsA in two private rheumatology practices and was matched to comprehensive histologically confirmed cancer registry data for the years 1978-2005. Relative risks (RRs) were estimated by logarithmic binomial modelling, and standardized incidence ratios (SIRs) were calculated from year-, sex- and age-specific rates of NMSC for the local population. RESULTS: Compared with no MTX usage, any MTX usage was associated with a higher rate of at least one histopathologically confirmed NMSC (SIR 4.64, 95% CI: 0.67, 33.2). The SIR was 4.81 (95% CI: 3.60, 6.29) for those receiving a cumulative dose >8000 mg compared with SIR 2.31 (95% CI: 1.58, 2.36) for <5000 mg. An increased risk was shown for both basal cell carcinomas and squamous cell carcinomas, with an apparent dose-response relationship for basal cell carcinomas but not for squamous cell carcinomas. There was an increased risk of NMSC in patients taking CSA (RR = 2.51, 95% CI: 1.23, 5.13) and D-Pen (RR 3.49, 95% CI: 1.34, 4.63) in addition to MTX, but not for patients taking AZA or LEF. CONCLUSION: MTX, and concurrent MTX and CSA or D-Pen use, is associated with an increased risk of NMSC. These results should encourage greater clinical vigilance for NMSC in treated patients with RA and PsA.

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Adolescents with mild to borderline intellectual disability (MBID) often complete schooling without mastering basic math skills, even though basic math is essential for math-related challenges in everyday life. Limited attention to cognitive skills and low executive functioning (EF) may cause this delay. We aimed to improve math skills in an MBID-sample using computerized math training. Also, it was investigated whether EF and math performance were related and whether computerized math training had beneficial effects on EF. The sample consisted of a total of 58 adolescents (12-15 years) from special education. Participants were randomly assigned to either the experimental group or a treatment as usual (TAU) group. In the experimental condition, participants received 5 weeks of training. Math performance and EF were assessed before and after the training period. Math performance improved equally in both groups. However, frequently practicing participants improved more than participants in the control group. Visuo-spatial memory skills were positively related to addition and subtraction skills. Transfer effects from math training to EF were absent. It is concluded that math skills may increase if a reasonable effort in practicing math skills is made. The relation between visuo-spatial memory skills provides opportunities for improving math performance.

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BACKGROUND: Liquid chromatography coupled to mass spectrometry (LC-MS) has become a prominent tool for the analysis of complex proteomics and metabolomics samples. In many applications multiple LC-MS measurements need to be compared, e. g. to improve reliability or to combine results from different samples in a statistical comparative analysis. As in all physical experiments, LC-MS data are affected by uncertainties, and variability of retention time is encountered in all data sets. It is therefore necessary to estimate and correct the underlying distortions of the retention time axis to search for corresponding compounds in different samples. To this end, a variety of so-called LC-MS map alignment algorithms have been developed during the last four years. Most of these approaches are well documented, but they are usually evaluated on very specific samples only. So far, no publication has been assessing different alignment algorithms using a standard LC-MS sample along with commonly used quality criteria. RESULTS: We propose two LC-MS proteomics as well as two LC-MS metabolomics data sets that represent typical alignment scenarios. Furthermore, we introduce a new quality measure for the evaluation of LC-MS alignment algorithms. Using the four data sets to compare six freely available alignment algorithms proposed for the alignment of metabolomics and proteomics LC-MS measurements, we found significant differences with respect to alignment quality, running time, and usability in general. CONCLUSION: The multitude of available alignment methods necessitates the generation of standard data sets and quality measures that allow users as well as developers to benchmark and compare their map alignment tools on a fair basis. Our study represents a first step in this direction. Currently, the installation and evaluation of the "correct" parameter settings can be quite a time-consuming task, and the success of a particular method is still highly dependent on the experience of the user. Therefore, we propose to continue and extend this type of study to a community-wide competition. All data as well as our evaluation scripts are available at http://msbi.ipb-halle.de/msbi/caap.

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BACKGROUND: Mass spectrometry is an essential analytical technique for high-throughput analysis in proteomics and metabolomics. The development of new separation techniques, precise mass analyzers and experimental protocols is a very active field of research. This leads to more complex experimental setups yielding ever increasing amounts of data. Consequently, analysis of the data is currently often the bottleneck for experimental studies. Although software tools for many data analysis tasks are available today, they are often hard to combine with each other or not flexible enough to allow for rapid prototyping of a new analysis workflow. RESULTS: We present OpenMS, a software framework for rapid application development in mass spectrometry. OpenMS has been designed to be portable, easy-to-use and robust while offering a rich functionality ranging from basic data structures to sophisticated algorithms for data analysis. This has already been demonstrated in several studies. CONCLUSION: OpenMS is available under the Lesser GNU Public License (LGPL) from the project website at http://www.openms.de.

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MOTIVATION: Liquid chromatography coupled to mass spectrometry (LC-MS) and combined with tandem mass spectrometry (LC-MS/MS) have become a prominent tool for the analysis of complex proteomic samples. An important step in a typical workflow is the combination of results from multiple LC-MS experiments to improve confidence in the obtained measurements or to compare results from different samples. To do so, a suitable mapping or alignment between the data sets needs to be estimated. The alignment has to correct for variations in mass and elution time which are present in all mass spectrometry experiments. RESULTS: We propose a novel algorithm to align LC-MS samples and to match corresponding ion species across samples. Our algorithm matches landmark signals between two data sets using a geometric technique based on pose clustering. Variations in mass and retention time are corrected by an affine dewarping function estimated from matched landmarks. We use the pairwise dewarping in an algorithm for aligning multiple samples. We show that our pose clustering approach is fast and reliable as compared to previous approaches. It is robust in the presence of noise and able to accurately align samples with only few common ion species. In addition, we can easily handle different kinds of LC-MS data and adopt our algorithm to new mass spectrometry technologies. AVAILABILITY: This algorithm is implemented as part of the OpenMS software library for shotgun proteomics and available under the Lesser GNU Public License (LGPL) at www.openms.de.

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A 9-year-old male Appenzeller mountain dog had progressive severe ataxia and central vestibular syndrome that was localized clinically to the brain stem. The cerebrospinal fluid characteristics were suggestive of hemorrhage into the subarachnoid space. On computed tomography (CT), hyperattenuating masses were found in the left lateral ventricle extending into the cerebrum, and another involving the cerebellum and brainstem. The hyperattenuation of the masses in noncontrast images and the absence of contrast enhancement were consistent with hemorrhage. The dog underwent euthanasia. A metastatic hemangiosarcoma in the brain, causing acute bleeding in the left lateral ventricle and the brainstem, was found. A solitary mass in the left myocardium was thought to be the primary site. CT characteristics of intracranial hemorrhage are reviewed.

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MOTIVATION: Experimental techniques in proteomics have seen rapid development over the last few years. Volume and complexity of the data have both been growing at a similar rate. Accordingly, data management and analysis are one of the major challenges in proteomics. Flexible algorithms are required to handle changing experimental setups and to assist in developing and validating new methods. In order to facilitate these studies, it would be desirable to have a flexible 'toolbox' of versatile and user-friendly applications allowing for rapid construction of computational workflows in proteomics. RESULTS: We describe a set of tools for proteomics data analysis-TOPP, The OpenMS Proteomics Pipeline. TOPP provides a set of computational tools which can be easily combined into analysis pipelines even by non-experts and can be used in proteomics workflows. These applications range from useful utilities (file format conversion, peak picking) over wrapper applications for known applications (e.g. Mascot) to completely new algorithmic techniques for data reduction and data analysis. We anticipate that TOPP will greatly facilitate rapid prototyping of proteomics data evaluation pipelines. As such, we describe the basic concepts and the current abilities of TOPP and illustrate these concepts in the context of two example applications: the identification of peptides from a raw dataset through database search and the complex analysis of a standard addition experiment for the absolute quantitation of biomarkers. The latter example demonstrates TOPP's ability to construct flexible analysis pipelines in support of complex experimental setups. AVAILABILITY: The TOPP components are available as open-source software under the lesser GNU public license (LGPL). Source code is available from the project website at www.OpenMS.de

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A new peak picking algorithm for the analysis of mass spectrometric (MS) data is presented. It is independent of the underlying machine or ionization method, and is able to resolve highly convoluted and asymmetric signals. The method uses the multiscale nature of spectrometric data by first detecting the mass peaks in the wavelet-transformed signal before a given asymmetric peak function is fitted to the raw data. In an optional third stage, the resulting fit can be further improved using techniques from nonlinear optimization. In contrast to currently established techniques (e.g. SNAP, Apex) our algorithm is able to separate overlapping peaks of multiply charged peptides in ESI-MS data of low resolution. Its improved accuracy with respect to peak positions makes it a valuable preprocessing method for MS-based identification and quantification experiments. The method has been validated on a number of different annotated test cases, where it compares favorably in both runtime and accuracy with currently established techniques. An implementation of the algorithm is freely available in our open source framework OpenMS.

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To measure myoglobin, a marker for myocardial infarction, directly in human serum, two-dimensional liquid chromatography in combination with electrospray ionization mass spectrometry was applied as an analytical method. High-abundant serum proteins were depleted by strong anion-exchange chromatography. The myoglobin fraction was digested and injected onto a 60 mm x 0.2 mm i.d. monolithic capillary column for quantitation of selected peptides upon mass spectrometric detection. The addition of known amounts of myoglobin to the serum sample was utilized for calibration, and horse myoglobin was added as an internal standard to improve reproducibility. Calibration graphs were linear and facilitated the reproducible and accurate determination of the myoglobin amount present in serum. Manual data evaluation using integrated peak areas and an automated multistage algorithm fitting two-dimensional models of peptide elution profiles and isotope patterns to the mass spectrometric raw data were compared. When the automated method was applied, a myoglobin concentration of 460 pg/microL serum was determined with a maximum relative deviation from the theoretical value of 10.1% and a maximum relative standard deviation of 13.4%.

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