Programming techniques for improving rule readability for rule-based information extraction natural language processing pipelines of unstructured and semi-structured medical texts.

BACKGROUND: Extraction of medical terms and their corresponding values from semi-structured and unstructured texts of medical reports can be a time-consuming and error-prone process. Methods of natural language processing (NLP) can help define an extraction pipeline for accomplishing a structured format transformation strategy. OBJECTIVES: In this paper, we build an NLP pipeline to extract values of the classification of malignant tumors (TNM) from unstructured and semi-structured pathology reports and import them further to a structured data source for a clinical study. Our research interest is not focused on standard performance metrics like precision, recall, and F-measure on the test and validation data. We discuss how with the help of software programming techniques the readability of rule-based (RB) information extraction (IE) pipelines can be improved, and therefore minimize the time to correct or update the rules, and efficiently import them to another programming language. METHODS: The extract rules were manually programmed with training data of TNM classification and tested in two separate pipelines based on design specifications from domain experts and data curators. Firstly we implemented each rule directly in one line for each extraction item. Secondly, we reprogrammed them in a readable fashion through decomposition and intention-revealing names for the variable declaration. To measure the impact of both methods we measure the time for the fine-tuning and programming of the extractions through test data of semi-structured and unstructured texts. RESULTS: We analyze the benefits of improving through readability of the writing of rules, through parallel programming with regular expressions (REGEX), and the Apache Uima Ruta language (AURL). The time for correcting the readable rules in AURL and REGEX was significantly reduced. Complicated rules in REGEX are decomposed and intention-revealing declarations were reprogrammed in AURL in 5 min. CONCLUSION: We discuss the importance of factor readability and how can it be improved when programming RB text IE pipelines. Independent of the features of the programming language and the tools applied, a readable coding strategy can be proven beneficial for future maintenance and offer an interpretable solution for understanding the extraction and for transferring the rules to other domains and NLP pipelines.

openEHR-to-FHIR: Converting openEHR Compositions to Fast Healthcare Interoperability Resources (FHIR) for the German Corona Consensus Dataset (GECCO).

The German Corona Consensus (GECCO) established a uniform dataset in FHIR format for exchanging and sharing interoperable COVID-19 patient specific data between health information systems (HIS) for universities. For sharing the COVID-19 information with other locations that use openEHR, the data are to be converted in FHIR format. In this paper, we introduce our solution through a web-tool named "openEHR-to-FHIR" that converts compositions from an openEHR repository and stores in their respective GECCO FHIR profiles. The tool provides a REST web service for ad hoc conversion of openEHR compositions to FHIR profiles.

Multifocal motor neuropathy in Austria: a nationwide survey of clinical features and response to treatment.

BACKGROUND AND OBJECTIVES: Multifocal motor neuropathy (MMN) is a rare neuropathy and detailed descriptions of larger patient cohorts are scarce. The objective of this study was to evaluate epidemiological, clinical, and laboratory features of MMN patients and their response to treatment in Austria and to compare these data with those from the literature. METHODS: Anonymized demographic and clinical data about MMN patients until 31.12.2017 were collected from registered Austrian neurologists. Exploratory statistics on clinical and laboratory features as well as treatment regimens and responses were performed. RESULTS: 57 Patients with MMN were identified, resulting in a prevalence of 0.65/100.000. Mean age of onset was 44.1 ± 13.1 years, the diagnostic delay 5.5 ± 8.4 years. In 77% of patients, symptom onset was in the upper limbs, and in 92%, it occurred in distal muscles. Proximal onset was never observed in the lower limbs. At the final follow-up, the majority of patients had atrophy (88%) in affected regions. Definite motor conduction blocks (CB) were found in 54 patients. Anti-GM1-IgM antibodies were present in 43%. Treatment with intravenous immunoglobulins improved muscle strength and INCAT score initially, but at last follow-up, both scores deteriorated to values before treatment. DISCUSSION: The findings of the present study corroborate the previous findings in MMN. Onset typically occurs in the upper limbs and mostly distal, CBs are found in the majority of cases, while anti-GM1-IgM antibodies are detected in only approximately 40%. Our study underlines that the initial good response to treatment fades over time.

An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology.

As heart failure with preserved ejection fraction (HFpEF) rises to epidemic proportions, major steps in patient management and therapeutic development are badly needed. With the current position paper we seek to update our view on HFpEF as a highly complex systemic syndrome, from risk factors and mechanisms to long-term clinical manifestations. We will revise recent advances in animal model development, experimental set-ups and basic and translational science approaches to HFpEF research, highlighting their drawbacks and advantages. Directions are provided for proper model selection as well as for integrative functional evaluation from the in vivo setting to in vitro cell function testing. Additionally, we address new research challenges that require integration of higher-order inter-organ and inter-cell communication to achieve a full systems biology perspective of HFpEF.

Benefits and Barriers of E-Learning for Staff Training in a Medical University.

Learning Management Systems (LMS) are a feasible solution to fulfill the various requirements for e-learning based training in a medical university. Using the LMS ILIAS, the Institute of Diagnostic and Interventional Radiology has designed an e-learning unit about data protection, which has been used by 73% of the department's employees in the first three months. To increase the use of e-learning for staff training, it is necessary to identify barriers and benefits, which encourage the use of e-learning. Therefore, we started an online survey to examine how the employees evaluate this learning opportunity. The results show that 87% of the employees had no technical problems and also competence of Information and Communication Technology (ICT) was no barrier. If anything, reported issues were time shortages and tight schedules. Therefore, short learning modules (less than 20 minutes) are preferred. Furthermore, temporal flexibility for learning is important for 83% of employees.

Influence of repeated subcutaneous G-CSF injections on selected blood parameters relevant for monitoring programmes in sports drug testing.

The use of growth factors in sports is restricted under the terms of the World Anti-Doping Code (WADC). While the beneficial effects of erythropoietin (EPO) on erythropoiesis and therefore its performance-enhancing properties have been well documented and established for decades, the aim of this study was to elucidate the relevance of the cytokine G-CSF in a doping control context, particularly concerning its influence on selected blood parameters representing central aspects of the Athlete Biological Passport. For that purpose, the effect of repeated subcutaneous granulocyte colony-stimulating factor (G-CSF) injections in therapeutic dosages (10 µg/kg/d) on white blood cells, erythrocytes, hemoglobin, hematocrit and percent reticulocytes was analyzed by using commonly employed fluorescence flow cytometry-based approaches. A total of 20 people were tested (14 male, 6 female) and both white blood cell count and reticulocyte percentages were found to significantly increase following a 5-day treatment with G-CSF. Simultaneously, all other volume-dependent parameters (red blood cell count, hemoglobin, hematocrit) slightly but significantly decreased. Due to the relevance of these measurands for the validity of blood tests for doping controls and the anecdotal evidence of G-CSF being potentially misused by elite athletes, G-CSF analyses might be indicated in case of unusually altered blood profiles.

Tubular toxicity in sirolimus- and cyclosporine-based transplant immunosuppression strategies: an ancillary study from a randomized controlled trial.

BACKGROUND: Sirolimus has been promoted as an agent to provide immunosuppression for kidney transplant recipients that, in contrast to calcineurin inhibitors, would not be nephrotoxic. However, several reports have observed proteinuria in patients treated with sirolimus, ranging from low grade to nephrotic range. Accordingly, we compared markers of tubular and glomerular damage in an ancillary study of a randomized trial comparing sirolimus and cyclosporine. STUDY DESIGN: Single-center, open-label, randomized, prospective trial. SETTING & PARTICIPANTS: Patients undergoing cadaveric or living donor kidney transplant at the University Hospital in Basel, Switzerland, between January 2001 and July 2004. INTERVENTION: Immunosuppression regimen consisting of cyclosporine, mycophenolate mofetil, and prednisone versus sirolimus, mycophenolate mofetil, and prednisone. OUTCOMES: The primary outcome was kidney function, assessed using serum creatinine level. Secondary outcomes included patient and graft survival, number of rejections, and evidence of kidney damage, assessed using glomerular and tubular urine biomarker levels. MEASUREMENTS: Urine and serum were collected at 0, 7, 30, and 90 days. Kidney function was estimated using serum creatinine level. Urinary markers included alpha(1)-microglobulin and retinol-binding protein (tubular), transferrin and albumin (glomerular), and semiquantitative assessment of glucosuria. Protocol kidney biopsies were performed at days 90 and 180. RESULTS: There were 63 patients randomly assigned to cyclosporine-based regimens, and 64, to sirolimus-based regimens. Kidney function was similar in both groups, whereas levels of markers associated with glomerular damage (albumin, 19.5 vs 8.96 mg/mmol creatinine; P < 0.001; transferrin, 13.1 vs 5.7 mg/mmol creatinine; P < 0.001) and those associated with tubular damage (alpha(1)-microglobulin, 11 vs 7.6 mg/mmol creatinine; P = 0.004; retinol-binding protein, 19.6 vs 9.6 mg/mmol creatinine; P = 0.002) were higher beginning at day 7 in patients randomly assigned to sirolimus therapy, with similar findings through day 90. Glucosuria incidence was higher in patients randomly assigned to sirolimus therapy beginning by day 30 (65% vs 30% on day 30; P = 0.002; 51% vs 22% on day 90; P < 0.001). On histologic examination, the overall severity of tubular lesions was significantly higher in patients randomly assigned to sirolimus therapy. LIMITATIONS: Small sample size, short-term follow-up likely insufficient to appreciate calcineurin-associated nephropathy. CONCLUSION: Compared with a cyclosporine-based immunosuppression regimen, a sirolimus-based regimen is associated with de novo low-grade glomerular proteinuria, increased excretion of markers associated with tubular damage, and evidence of tubular damage on kidney biopsy.

Erythropoiesis-stimulating agents: development, detection and dangers.

Epoetin alfa, the first member of the family of erythropoiesis stimulating agents (ESAs), was introduced to the market in 1989. Since then development has progressed to epoetins of the third generation. Currently drugs that use alternative approaches to stimulate erythropoiesis are under development. Uptake of all available ESAs into doping has occurred rapidly after their introduction. A multitude of dangers to health are associated with the illicit use of these substances. Different approaches to detect ESAs in doping control have been developed to comply with the very diverse nature of the compounds used. Future developments in the field of ESA require the development of new techniques in doping analysis. This review gives an overview of the development of ESA and its detection methods as well as future developments. [Correction made here after initial online publication]

Comparison of the urinary protein patterns of athletes by 2D-gel electrophoresis and mass spectrometry-a pilot study.

Urinary proteins and exercise-induced proteinuria have been the subject of much research. Proteinuria has been studied in depth after different running and cycling intensities and durations and the different mechanisms of glomerular filtration and tubular dysfunction have been elucidated. The present study was carried out to compare urinary protein profiles of athletes in different sport categories (endurance sport, team sport, strength sport). Doping-control urine samples obtained from in-competition testing and specimens derived from a control group were analysed by means of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significantly deviating protein spots were enzymatically hydrolysed and identified by nanoflow liquid chromatography-orbitrap mass spectrometry. Endurance sport samples demonstrated a significant increase of mainly medium-sized urinary proteins such as transferrin, zinc alpha-2-glycoprotein and prostaglandin H2 D-isomerase (30-80 kDa) in 2D-PAGE experiments. Proteinuria was evident in all samples after protein concentration measurements (protein/creatinine > 15 mg/mmol). Alterations were also observed in strength sport samples, which showed an increase of low molecular weight proteins or protein fragments (<30 kDa, e.g., transthyretin, CD 59 antigen or an N-terminal transferrin fragment). In contrast, the concentration measurements did not imply proteinuria but total protein excretion was in a normal range. The study provides a first overview on 2D maps of the urinary proteome after different types of exercise. Future studies may lead to the establishment of urinary protein maps that are typical for a certain type of sport or even an individual athlete. These maps may complement the blood passport of athletes in doping control.

ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial.

BACKGROUND: Despite all the advantages in the immunosuppressive therapy, kidney transplantation in immunologically high risk patients remains a challenge. Ideally, an induction therapy should provide maximal graft protection, while adverse events rate and costs remain as low as possible. MATERIAL & METHODS: Immunologically high risk kidney recipients with CDC-PRA l 25% within the last 3 years, a positive B-cell CDC-crossmatch or graft loss due to rejection within 3 years following a prior transplantation, were randomized 1:1 to receive ATG-Fresenius (ATG-F) (9 mg/kg day 0; 3 mg/kg day 1-4) or Daclizumab therapy (1 mg/kg day 0, 14, 28, 42, 56) in a pilot study. Additional immunosuppression consisted of cyclosporine, mycophenolate mofetil, and steroids. 11 patients were included in each group. RESULTS: The patient (90% in ATG-F; 100% in Daclizumab) and graft survival (censored for death) (100% in ATG-F; 90% in Daclizumab) and the mean creatinine concentration at 24 months (139+/-68 mol/l in ATG-F; 176+/-103 mol/l in Daclizumab) were similar in both groups. More severe graft rejections (3 vascular rejections in Daclizumab) and adverse events (5.3/patient in ATG-F; 6.7/patient in Daclizumab) were observed in the Daclizumab group. The costs for hospitalization/ day within 24 months were lower in ATG-F (2.32+/-3.51 USD vs. 12.25+/-9.75 USD; p=0.02) resulting in an average cost-difference of more than 10'435 USD /patient. CONCLUSIONS: In this pilot trial, both treatments were comparably successful regarding graft and patient outcome.

The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A.

The immunosuppressive action of the calcineurin inhibitor cyclosporine A (CsA) stems from the inhibition of nuclear factor of activated T cells (NFAT) signaling in T cells. CsA is also used for the treatment of proteinuric kidney diseases. As it stands, the antiproteinuric effect of CsA is attributed to its immunosuppressive action. Here we show that the beneficial effect of CsA on proteinuria is not dependent on NFAT inhibition in T cells, but rather results from the stabilization of the actin cytoskeleton in kidney podocytes. CsA blocks the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho GTPases in podocytes, thereby preserving the phosphorylation-dependent synaptopodin-14-3-3 beta interaction. Preservation of this interaction, in turn, protects synaptopodin from cathepsin L-mediated degradation. These results represent a new view of calcineurin signaling and shed further light on the treatment of proteinuric kidney diseases. Novel calcineurin substrates such as synaptopodin may provide promising starting points for antiproteinuric drugs that avoid the serious side effects of long-term CsA treatment.