Towards automated processing of clinical Finnish: Sublanguage analysis and a rule-based parser

Introduction

In this paper, we present steps taken towards more efficient automated processing of clinical Finnish, focusing on daily nursing notes in a Finnish Intensive Care Unit (ICU). First, we analyze ICU Finnish as a sublanguage, identifying its specific features facilitating, for example, the development of a specialized syntactic analyser. The identified features include frequent omission of finite verbs, limitations in allowed syntactic structures, and domain-specific vocabulary. Second, we develop a formal grammar and a parser for ICU Finnish, thus providing better tools for the development of further applications in the clinical domain.

Methods

The grammar is implemented in the LKB system in a typed feature structure formalism. The lexicon is automatically generated based on the output of the FinTWOL morphological analyzer adapted to the clinical domain. As an additional experiment, we study the effect of using Finnish constraint grammar to reduce the size of the lexicon. The parser construction thus makes efficient use of existing resources for Finnish.

Results

The grammar currently covers 76.6% of ICU Finnish sentences, producing highly accurate best-parse analyzes with F-score of 91.1%. We find that building a parser for the highly specialized domain sublanguage is not only feasible, but also surprisingly efficient, given an existing morphological analyzer with broad vocabulary coverage. The resulting parser enables a deeper analysis of the text than was previously possible.     

Human Infection with Avian Influenza A(H9N2) Virus,Cambodia, February 2021

In February 2021, routine sentinel surveillance for influenza-like illness in Cambodia detected a human avian influenza A(H9N2) virus infection. Investigations identified no recent H9N2 virus infections in 43 close contacts. One chicken sample from the infected child’s house was positive for H9N2 virus and genetically similar to the human virus.     

Radiosynthesis and in vivo evaluation of [11C]-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A

IntroductionSince MAO-A is an enzyme involved in the metabolism of neurotransmitters, fluctuations in MAO-A functionality are associated with psychiatric and neurological disorders as well as with tobacco addiction and behaviour. This study reports the radiolabelling of two [¹¹C]-labelled pyrrole-2-carboxamide derivates, RS 2315 and RS 2360, along with the characterization of their in vivo properties.MethodsThe radiolabelling of [¹¹C]-RS 2315 and [¹¹C]-RS 2360 was accomplished by alkylation of their amide precursors with [¹¹C]CH₃I. Biodistribution, blocking and metabolite studies of both tracers were performed in NMRI mice. Finally, a PET study in Sprague-Dawley rats was performed for [¹¹C]-RS 2360.ResultsBoth tracers were obtained in a radiochemical yield of approximately 30% with radiochemical purity of >98%. Biodistribution studies showed high brain uptake followed by rapid brain clearance for both radiotracers. In the brain, [¹¹C]-RS 2360 was more stable than [¹¹C]-RS 2315. Blocking studies in mice could not demonstrate specificity of [¹¹C]-RS 2315 towards MAO-A or MAO-B. The blocking and imaging study with [¹¹C]-RS 2360 on the other hand indicated specific binding in MAO-A at the earliest time points.Conclusions[¹¹C]-RS 2315 displayed a high nonspecific binding and is therefore not suitable for visualization of MAO-A in vivo. [¹¹C]-RS 2360 on the other hand has potential for mapping MAO-A since specific binding is demonstrated.     

In vivo evaluation of [123I]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine,an iodinated SPECT tracer for imaging the P-gp transporter

IntroductionP-glycoprotein (P-gp) is an energy-dependent transporter that contributes to the efflux of a wide range of xenobiotics at the blood–brain barrier playing a role in drug-resistance or therapy failure. In this study, we evaluated [¹²³I]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine ([¹²³I]-FMIP) as a novel single photon emission computed tomography (SPECT) tracer for imaging P-gp at the brain in vivo.MethodsThe tissue distribution and brain uptake as well as the metabolic profile of [¹²³I]-FMIP in wild-type and mdr1a (?/?) mice after pretreatment with physiological saline or cyclosporin A (CsA) (50 mg/kg) was investigated. The influence of increasing doses CsA on brain uptake of [¹²³I]-FMIP was explored. μSPECT images of mice brain after injection of 11.1 MBq [¹²³I]-FMIP were obtained for different treatment strategies thereby using the Milabs U-SPECT-II.ResultsModulation of P-gp with CsA (50 mg/kg) as well as mdr1a gene depletion resulted in significant increase in cerebral uptake of [¹²³I]-FMIP with only minor effect on blood activity. [¹²³I]-FMIP is relative stable in vivo with >80% intact [¹²³I]-FMIP in brain at 60 min p.i. in the different treatment regiments. A dose-dependent sigmoidal increase in brain uptake of [¹²³I]-FMIP with increasing doses of CsA was observed. In vivo region of interest-based SPECT measurements correlated well with the observations of the biodistribution studies.ConclusionsThese findings indicate that [¹²³I]-FMIP can be applied to assess the efficacy of newly developed P-gp modulators. It is also suggested that [¹²³I]-FMIP is a promising SPECT tracer for imaging P-gp at the blood-brain barrier.     

Epigenetic sampling effects: nephrectomy modifies the clear cell renal cell cancer methylome

Purpose

Currently, it is unclear to what extent sampling procedures affect the epigenome. Here, this phenomenon was evaluated by studying the impact of artery ligation on DNA methylation in clear cell renal cancer.

Methods

DNA methylation profiles between vascularised tumour biopsy samples and devascularised nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort.

Results

We found that six genes were differentially methylated in the test samples, of which four were linked to ischaemia or hypoxia (REXO1L1, TLR4, hsa-mir-1299, ANKRD2). Three of these genes were also found to be significantly differentially methylated in the validation cohort, indicating that the observed effects are genuine.

Conclusion

Tissue ischaemia during normal surgical removal of tumour can cause epigenetic changes. Based on these results, we conclude that the impact of sampling procedures in clinical epigenetic studies should be considered and discussed, particularly after inducing hypoxia/ischaemia, which occurs in most oncological surgery procedures through which tissues are collected for translational research.

     

Drug fever as an adverse effect of acitretin in complicated psoriasis patient

We present a case of a 63‐year old man with severe chronic plaque psoriasis and a recent history of lung cancer, wherein fever appeared suddenly after initiation of treatment with low dose acitretin. Tumor recurrence or infection was not found during extensive examinations, nevertheless the patient was empirically treated with broad‐spectrum antibiotics without any effect on fever. Immediately after discontinuation of acitretin therapy, the fever disappeared. The patient was followed for next 2 years, during this period similar problems did not reappear, although there has been a relapse of psoriasis and the patient was switched later on biological treatment.     

Induction of lymphatic endothelial cell differentiation in embryoid bodies

The molecular mechanisms that regulate the formation of the lymphatic vascular system remain poorly characterized. Whereas studies in embryonic stem (ES) cells have provided major new insights into the mechanisms of blood vessel formation, the development of lymphatic endothelium has not been previously observed. We established embryoid bodies (EBs) from murine ES cells in the presence or absence of lymphangiogenic growth factors. We found that lymphatic endothelial cells develop at day 18 after EB formation. These cells express CD31 and the lymphatic lineage markers Prox-1 and Lyve-1, but not the vascular marker MECA-32, and they frequently sprout from preexisting blood vessels. Lymphatic vessel formation was potently promoted by VEGF-A and VEGF-C but not by bFGF. Our results reveal, for the first time, that ES cells can differentiate into lymphatic endothelial cells, and they identify the EB assay as a powerful new tool to dissect the molecular mechanisms that control lymphatic vessel formation.     

Costs of patient management of visceral leishmaniasis in Muzaffarpur, Bihar, India

OBJECTIVES: To identify and quantify the direct and indirect economic cost of treatment for visceral leishmaniasis (VL) with conventional Amphotericin B deoxycholate, currently the first-line treatment in Muzaffarpur. METHODS: Costs of patient management for VL were estimated from a societal and household perspective by means of a questionnaire designed for this study, interviews and financial reports. RESULTS: The total cost of care per episode of VL from the societal perspective was estimated at US$355, equivalent to 58% of annual household income. The largest cost category was medical costs (55%), followed by indirect costs (36%) and non-medical costs (9%). The cost from the household perspective was equivalent to US$217. The largest cost category was indirect costs (59%), followed by medical costs (27%) and non-medical costs (15%). Loss of income because of illness and hospitalization and expenses for drugs were the largest cost components. CONCLUSIONS: The economic costs related to VL are substantial, both to society and the patient. Public health authorities in Bihar should focus on policies that detect VL in the early stage and implement interventions that minimize the burden to households affected by VL.