O2 supplementation disambiguation in clinical narratives to support retrospective COVID-19 studies.

BACKGROUND: Oxygen saturation, a key indicator of COVID-19 severity, poses challenges, especially in cases of silent hypoxemia. Electronic health records (EHRs) often contain supplemental oxygen information within clinical narratives. Streamlining patient identification based on oxygen levels is crucial for COVID-19 research, underscoring the need for automated classifiers in discharge summaries to ease the manual review burden on physicians. METHOD: We analysed text lines extracted from anonymised COVID-19 patient discharge summaries in German to perform a binary classification task, differentiating patients who received oxygen supplementation and those who did not. Various machine learning (ML) algorithms, including classical ML to deep learning (DL) models, were compared. Classifier decisions were explained using Local Interpretable Model-agnostic Explanations (LIME), which visualize the model decisions. RESULT: Classical ML to DL models achieved comparable performance in classification, with an F-measure varying between 0.942 and 0.955, whereas the classical ML approaches were faster. Visualisation of embedding representation of input data reveals notable variations in the encoding patterns between classic and DL encoders. Furthermore, LIME explanations provide insights into the most relevant features at token level that contribute to these observed differences. CONCLUSION: Despite a general tendency towards deep learning, these use cases show that classical approaches yield comparable results at lower computational cost. Model prediction explanations using LIME in textual and visual layouts provided a qualitative explanation for the model performance.

Neuropeptide S Encodes Stimulus Salience in the Paraventricular Thalamus.

Evaluation of stimulus salience is critical for any higher organism, as it allows for prioritizing of vital information, preparation of responses, and formation of valuable memory. The paraventricular nucleus of the thalamus (PVT) has recently been identified as an integrator of stimulus salience but the neurochemical basis and afferent input regarding salience signaling have remained elusive. Here we report that neuropeptide S (NPS) signaling in the PVT is necessary for stimulus salience encoding, including aversive, neutral and reinforcing sensory input. Taking advantage of a striking deficit of both NPS receptor (NPSR1) and NPS precursor knockout mice in fear extinction or novel object memory formation, we demonstrate that intra-PVT injections of NPS can rescue the phenotype in NPS precursor knockout mice by increasing the salience of otherwise low-intensity stimuli, while intra-PVT injections of NPSR1 antagonist in wild type mice partially replicates the knockout phenotype. The PVT appears to provide stimulus salience encoding in a dose- and NPS-dependent manner. PVT NPSR1 neurons recruit the nucleus accumbens shell and structures in the prefrontal cortex and amygdala, which were previously linked to the brain salience network. Overall, these results demonstrate that stimulus salience encoding is critically associated with NPS activity in the PVT.

Head and Tail Oxidized Terpenoid Esters from Androconia of Heliconius erato Butterflies.

Heliconius erato is a neotropical butterfly species that is part of a complex mimicry ring, with colorful wing patterns. For intraspecific communication, males use pheromones that are released from two different scent-emitting structures. Scent glands located near the abdominal claspers of males, containing antiaphrodisiac pheromones, release a highly complex mixture of compounds that is transferred to females during mating, rendering them unattractive to other males. On the other hand, androconia, scent-emitting scale areas on the wings of male butterflies, release a structurally more restricted set of compounds that likely serves an aphrodisiac role. We report here on two structurally related compounds that are the major androconial constituents, produced in high amounts and are not volatile due to their high molecular mass. Their structures were established by extensive analysis of mass, infrared, and NMR spectra, as well as microderivatization reactions of the natural extract. After establishing synthetic access, the compounds were unequivocally identified as two unusual head and tail oxidized terpenoids, (4E,8E,12E)-4,8,12-trimethyl-16-oxoheptadeca-4,8,12-trien-1-yl oleate (1) and stearate (2). Although behavioral assays are necessary to fully comprehend their role in the chemical communication of the species, hypotheses for their use by the butterflies are also discussed.

Antibacterial phloroglucinols derivatives from the leaves of Mallotus oppositifolius (Geisler) Müll. Arg. (Euphorbiaceae).

From the ethno-medicinally used leaves of Mallotus oppositifolius, four acylphloroglucinol derivatives, namely Acronyculatin SU (1-3) and Mallotojaponin D (4) were isolated along with seven known compounds (5-11). Structures were elucidated by comprehensive spectroscopic analyses and HRMS data. Absolute configurations were assigned by careful comparison of their specific optical rotation with those of closely related compounds. Compounds 1, 2, 6 and 11 demonstrated inhibitory activity against the bacterial strains E. coli, S. aureus, S. typhi, P. aeruginosa with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50 µg/ml.

Design Considerations for a Knowledge Graph: The WATRIMed Use Case.

The World Health Organization estimates that as much as 80% of the population uses Traditional Medicine (TM) in some form, and in particular, herbal-based Traditional Medicine (HTM). However, TM is mostly orally transmitted and suffers from lack of standardizations and lack of computable TM data. Shareable standards could enable computational support of TM data management. In this paper, we outline the design and development of the West African Herbal Traditional Medicine (WATRIMed) Knowledge Graph (KG), which is an effort for bringing West Africa TM to the digital world and help establishing bridges with conventional medicine. WATRIMed entities have been enriched with knowledge from external publicly available knowledge bases and further mapped with the BioTopLite Upper Level Ontology. As of result, the model of the publicly available KG currently comprises 472 Concepts and 75 Properties (57 object properties and 18 data properties). It describes formally 115 medicinal plants, 179 chemical compounds and 67 recipes.

Neural mechanisms of training an auditory event-related potential task in a brain-computer interface context.

Effective use of brain-computer interfaces (BCIs) typically requires training. Improved understanding of the neural mechanisms underlying BCI training will facilitate optimisation of BCIs. The current study examined the neural mechanisms related to training for electroencephalography (EEG)-based communication with an auditory event-related potential (ERP) BCI. Neural mechanisms of training in 10 healthy volunteers were assessed with functional magnetic resonance imaging (fMRI) during an auditory ERP-based BCI task before (t1) and after (t5) three ERP-BCI training sessions outside the fMRI scanner (t2, t3, and t4). Attended stimuli were contrasted with ignored stimuli in the first-level fMRI data analysis (t1 and t5); the training effect was verified using the EEG data (t2-t4); and brain activation was contrasted before and after training in the second-level fMRI data analysis (t1 vs. t5). Training increased the communication speed from 2.9 bits/min (t2) to 4 bits/min (t4). Strong activation was found in the putamen, supplementary motor area (SMA), and superior temporal gyrus (STG) associated with attention to the stimuli. Training led to decreased activation in the superior frontal gyrus and stronger haemodynamic rebound in the STG and supramarginal gyrus. The neural mechanisms of ERP-BCI training indicate improved stimulus perception and reduced mental workload. The ERP task used in the current study showed overlapping activations with a motor imagery based BCI task from a previous study on the neural mechanisms of BCI training in the SMA and putamen. This suggests commonalities between the neural mechanisms of training for both BCI paradigms.

The effects of kratom on restraint-stress-induced analgesia and its mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa and its extracts are called kratom (dried leaves, extract). They contain several alkaloids with an affinity for different opioid receptors. They are used in traditional medicine for the treatment of different diseases, as a substitute by opiate addicts, and to mitigate opioid withdrawal symptoms. Apart from their medical properties, they are used to enhance physical endurance and as a means of overcoming stress. PURPOSE: The aim of this study was to determine the mechanisms underlying the effects of kratom on restraint-stress-induced analgesia which occurs during or following exposure to a stressful or fearful stimulus. METHODS: To gain further insights into the action of kratom on stress, we conducted experiments using restraint stress as a test system and stress-induced analgesia as a test parameter. Using transgenic mu opioid-receptor (MOR) deficient mice, we studied the involvement of this receptor type. We used nor-binaltorphimine (BNT), an antagonist at kappa opioid receptors (KOR), to study functions of this type of receptor. Membrane potential assay was also employed to measure the intrinsic activity of kratom in comparison to U50,488, a highly selective kappa agonist. RESULTS: Treatment with kratom diminished stress-induced analgesia in wildtype and MOR knockout animals. Pretreatment of MOR deficient mice with BNT resulted in similar effects. In comparison to U50,488, kratom exhibited negligible intrinsic activity at KOR alone. CONCLUSIONS: The results suggest that the use of kratom as a pharmacological tool to mitigate withdrawal symptoms is related to its action on KOR.

Sexual Deception in the Eucera-Pollinated Ophrys leochroma: A Chemical Intermediate between Wasp- and Andrena-Pollinated Species.

Ophrys flowers mimic sex pheromones of attractive females of their pollinators and attract males, which attempt to copulate with the flower and thereby pollinate it. Virgin females and orchid flowers are known to use the same chemical compounds in order to attract males. The composition of the sex pheromone and its floral analogue, however, vary between pollinator genera. Wasp-pollinated Ophrys species attract their pollinators by using polar hydroxy acids, whereas Andrena-pollinated species use a mixture of non-polar hydrocarbons. The phylogeny of Ophrys shows that its evolution was marked by episodes of rapid diversification coinciding with shifts to different pollinator groups: from wasps to Eucera and consequently to Andrena and other bees. To gain further insights, we studied pollinator attraction in O. leochroma in the context of intra- and inter-generic pollinator shifts, radiation, and diversification in the genus Ophrys. Our model species, O. leochroma, is pollinated by Eucera kullenbergi males and lies in the phylogeny between the wasp and Andrena-pollinated species; therefore, it is a remarkable point to understand pollinator shifts. We collected surface extracts of attractive E. kullenbergi females and labellum extracts of O. leochroma and analyzed them by using gas chromatography with electroantennographic detection (GC-EAD) and gas chromatography coupled with mass spectrometry (GC-MS). We also performed field bioassays. Our results show that O. leochroma mimics the sex pheromone of its pollinator's female by using aldehydes, alcohols, fatty acids, and non-polar compounds (hydrocarbons). Therefore, in terms of the chemistry of pollinator attraction, Eucera-pollinated Ophrys species might represent an intermediate stage between wasp- and Andrena-pollinated orchid species.

Responsiveness of cats (Felidae) to silver vine (Actinidia polygama), Tatarian honeysuckle (Lonicera tatarica), valerian (Valeriana officinalis) and catnip (Nepeta cataria).

BACKGROUND: Olfactory stimulation is an often overlooked method of environmental enrichment for cats in captivity. The best known example of olfactory enrichment is the use of catnip, a plant that can cause an apparently euphoric reaction in domestic cats and most of the Pantherinae. It has long been known that some domestic cats and most tigers do not respond to catnip. Although many anecdotes exist of other plants with similar effects, data are lacking about the number of cats that respond to these plants, and if cats that do not respond to catnip respond to any of them. Furthermore, much is still unknown about which chemicals in these plants cause this response. METHODS: We tested catnip, silver vine, Tatarian honeysuckle and valerian root on 100 domestic cats and observed their response. Each cat was offered all four plant materials and a control, multiple times. Catnip and silver vine also were offered to nine tigers. The plant materials were analyzed by gas chromatography coupled with mass spectrometry to quantify concentrations of compounds believed to exert stimulating effects on cats. RESULTS: Nearly all domestic cats responded positively to olfactory enrichment. In agreement with previous studies, one out of every three cats did not respond to catnip. Almost 80% of the domestic cats responded to silver vine and about 50% to Tatarian honeysuckle and valerian root. Although cats predominantly responded to fruit galls of the silver vine plant, some also responded positively to its wood. Of the cats that did not respond to catnip, almost 75% did respond to silver vine and about one out of three to Tatarian honeysuckle. Unlike domestic cats, tigers were either not interested in silver vine or responded disapprovingly. The amount of nepetalactone was highest in catnip and only present at marginal levels in the other plants. Silver vine contained the highest concentrations of all other compounds tested. CONCLUSIONS: Olfactory enrichment for cats may have great potential. Silver vine powder from dried fruit galls and catnip were most popular among domestic cats. Silver vine and Tatarian honeysuckle appear to be good alternatives to catnip for domestic cats that do not respond to catnip.

TNM-O: ontology support for staging of malignant tumours.

BACKGROUND: Objectives of this work are to (1) present an ontological framework for the TNM classification system, (2) exemplify this framework by an ontology for colon and rectum tumours, and (3) evaluate this ontology by assigning TNM classes to real world pathology data. METHODS: The TNM ontology uses the Foundational Model of Anatomy for anatomical entities and BioTopLite 2 as a domain top-level ontology. General rules for the TNM classification system and the specific TNM classification for colorectal tumours were axiomatised in description logic. Case-based information was collected from tumour documentation practice in the Comprehensive Cancer Centre of a large university hospital. Based on the ontology, a module was developed that classifies pathology data. RESULTS: TNM was represented as an information artefact, which consists of single representational units. Corresponding to every representational unit, tumours and tumour aggregates were defined. Tumour aggregates consist of the primary tumour and, if existing, of infiltrated regional lymph nodes and distant metastases. TNM codes depend on the location and certain qualities of the primary tumour (T), the infiltrated regional lymph nodes (N) and the existence of distant metastases (M). Tumour data from clinical and pathological documentation were successfully classified with the ontology. CONCLUSION: A first version of the TNM Ontology represents the TNM system for the description of the anatomical extent of malignant tumours. The present work demonstrates its representational power and completeness as well as its applicability for classification of instance data.

Social Media as Catalyzer for Connected Health: Hype or Hope? Perspectives from IMIA Working Groups.

The Internet and social media are becoming ubiquitous technologies that are transforming the health sector. Social media has become an avenue for accessing, creating and sharing health information among patients and healthcare professionals. Furthermore, social media has become a key feature in many eHealth solutions, including wearable technologies, Big Data solutions, eLearning systems, Serious Games, Medical imaging, etc. These hyper-connected technologies are facilitating a paradigm shift towards more connected health. In this panel, representatives of different IMIA Working Groups will explore how both hope and hype contribute to social media's catalyzing role in creating connected health solutions.

Research Resource: Real-Time Analysis of Somatostatin and Dopamine Receptor Signaling in Pituitary Cells Using a Fluorescence-Based Membrane Potential Assay.

Stable somatostatin analogues and dopamine receptor agonists are the mainstay for the pharmacological treatment of functional pituitary adenomas; however, only a few cellular assays have been developed to detect receptor activation of novel compounds without disrupting cells to obtain the second messenger content. Here, we adapted a novel fluorescence-based membrane potential assay to characterize receptor signaling in a time-dependent manner. This minimally invasive technique provides a robust and reliable read-out for ligand-induced receptor activation in permanent and primary pituitary cells. The mouse corticotropic cell line AtT-20 endogenously expresses both the somatostatin receptors 2 (sst2) and 5 (sst5). Exposure of wild-type AtT-20 cells to the sst2- and sst5-selective agonists BIM-23120 and BIM-23268, respectively, promoted a pertussis toxin- and tertiapin-Q-sensitive reduction in fluorescent signal intensity, which is indicative of activation of G protein-coupled inwardly rectifying potassium (GIRK) channels. After heterologous expression, sst1, sst3, and sst4 receptors also coupled to GIRK channels in AtT-20 cells. Similar activation of GIRK channels by dopamine required overexpression of dopamine D2 receptors (D2Rs). Interestingly, the presence of D2Rs in AtT-20 cells strongly facilitated GIRK channel activation elicited by the sst2-D2 chimeric ligand BIM-23A760, suggesting a synergistic action of sst2 and D2Rs. Furthermore, stable somatostatin analogues produced strong responses in primary pituitary cultures from wild-type mice; however, in cultures from sst2 receptor-deficient mice, only pasireotide and somatoprim, but not octreotide, induced a reduction in fluorescent signal intensity, suggesting that octreotide mediates its pharmacological action primarily via the sst2 receptor.

Functional anatomy of the colonic bioreactor: Impact of antibiotics and Saccharomyces boulardii on bacterial composition in human fecal cylinders.

Sections of fecal cylinders were analyzed using fluorescence in situ hybridization targeting 180 bacterial groups. Samples were collected from three groups of women (N=20 each) treated for bacterial vaginosis with ciprofloxacin+metronidazole. Group A only received the combined antibiotic regimen, whereas the A/Sb group received concomitant Saccharomyces boulardii CNCM I-745 treatment, and the A_Sb group received S. boulardii prophylaxis following the 14-day antibiotic course. The number of stool cylinders analyzed was 188 out of 228 in group A, 170 out of 228 in group A/Sb, and 172 out of 216 in group A_Sb. The colonic biomass was organized into a separate mucus layer with no bacteria, a 10-30µm broad unstirred transitional layer enriched with bacteria, and a patchy fermentative area that mixed digestive leftovers with bacteria. The antibiotics suppressed bacteria mainly in the fermentative area, whereas abundant bacterial clades retreated to the transitional mucus and survived. As a result, the total concentration of bacteria decreased only by one order. These effects were lasting, since the overall recovery of the microbial mass, bacterial diversity and concentrations were still below pre-antibiotic values 4 months after the end of antibiotic treatment. Sb-prophylaxis markedly reduced antibiotic effects and improved the recovery rates. Since the colon is a sophisticated bioreactor, the study indicated that the spatial anatomy of its biomass was crucial for its function.

1-Acyl-3-0-[ß-glucopyranosyl-(1"-+ 6')-ß-glucopyranosyl]-glycerols and Cordycedipeptides B and C, New Metabolites from Bacillus pumilus.

Four 1-monoacyl-3-0-[ß-glucopyranosyl-( ->6)-ß-glucopyranosyl]-glycerols (1) and four 1,2-diacyl-3-0-[p-glucopyranosyl-(1->6)-p-glucopyranosyl]- glycerols (2a) with acyl residues consisting of 1:1 mixtures of 1-iso-pentadecanoyl- and 1 -anteiso-pentadecanoyl residues and the respective heptadecanoic acid isomers s as main components, have been characterized in the extracts of Bacillus pumilus strain DKS 1. Twenty-seven further metabolites, among them the diketopiperazines cordycedipeptide A (3), B (4), and C (5), were obtained. All compounds were elucidated by NMR and MS techniques and fully characterized and tested for antimicrobial activity against Legionella pneumophila.

Integrated care: an Information Model for Patient Safety and Vigilance Reporting Systems.

Quality management information systems for safety as a whole or for specific vigilances share the same information types but are not interoperable. An international initiative tries to develop an integrated information model for patient safety and vigilance reporting to support a global approach of heath care quality.

Pseudomonas strains naturally associated with potato plants produce volatiles with high potential for inhibition of Phytophthora infestans.

Bacteria emit volatile organic compounds with a wide range of effects on bacteria, fungi, plants, and animals. The antifungal potential of bacterial volatiles has been investigated with a broad span of phytopathogenic organisms, yet the reaction of oomycetes to these volatile signals is largely unknown. For instance, the response of the late blight-causing agent and most devastating oomycete pathogen worldwide, Phytophthora infestans, to bacterial volatiles has not been assessed so far. In this work, we analyzed this response and compared it to that of selected fungal and bacterial potato pathogens, using newly isolated, potato-associated bacterial strains as volatile emitters. P. infestans was highly susceptible to bacterial volatiles, while fungal and bacterial pathogens were less sensitive. Cyanogenic Pseudomonas strains were the most active, leading to complete growth inhibition, yet noncyanogenic ones also produced antioomycete volatiles. Headspace analysis of the emitted volatiles revealed 1-undecene as a compound produced by strains inducing volatile-mediated P. infestans growth inhibition. Supplying pure 1-undecene to P. infestans significantly reduced mycelial growth, sporangium formation, germination, and zoospore release in a dose-dependent manner. This work demonstrates the high sensitivity of P. infestans to bacterial volatiles and opens new perspectives for sustainable control of this devastating pathogen.

Does chloride channel accessory 3 have a role in arthritis pain? A study on murine antigen-induced arthritis.

Calcium-activated chloride channels (CaCCs) are thought to regulate neuronal excitability, and recently chloride (Cl(-)) regulation in DRG neurons has attracted much attention in pain research. Furthermore, the activity of CaCCs is modified by a family of CLCA proteins. In acute antigen-induced arthritis (AIA), a remarkable up-regulation of the murine chloride channel accessory 3 (mClca3) was shown in dorsal root ganglion (DRG) neurons. Therefore we tested the hypothesis that mClca3 is involved in arthritic pain perception. In mClca3 knock-out mice and wild-type control mice, AIA was induced and measures of inflammation and pain were assessed. In the very acute phase of AIA, joint swelling was reduced in mClca3 knock-out mice. This effect disappeared during the course of AIA. We could not show significant differences in mechanical hyperalgesia between both groups of mice, neither at the acute nor at the chronic stage (21 days of AIA). Additional experiments on thermal hyperalgesia in wild-type and mClca3 knock-out mice in the first 3 days of AIA did not show a difference either. In addition, niflumic acid, an antagonist at CaCCs, did not significantly influence hyperalgesia during AIA. Thus, we were not able to provide evidence for a role of CaCCs, and in particular of mClca3, on the expression of arthritis or inflammation-evoked hyperalgesia.

Mass spectrometry identification of alkyl-substituted pyrazines produced by Pseudomonas spp. isolates obtained from wine corks.

We investigated the pyrazine production of 23 Pseudomonas isolates obtained from cork in order to assess their implications in off-flavour development. Off-flavour development in cork stoppers is a crucial process in maintaining the high quality of some wines. Pyrazine production was analyzed by headspace solid-phase-microextraction (HS-SPME) and gas chromatography coupled with mass spectrometry (GC-MS). Five out of the 23 isolates, i.e. Pseudomonas koreensis TCA20, Pseudomonas palleroniana TCA16, Pseudomonas putida TCA23 and N7, and Pseudomonas stutzeri TRA27a were able to produce branched alkyl-substituted pyrazines. For isolates N7 and TCA16, 14 compounds could be identified as pyrazines. The use of mineral media supplemented with different carbon and nitrogen sources resulted in changes in the pyrazine production capacity. In the two strains the amount of pyrazines produced was higher with glucose and decreased significantly with lactate. In all cases, 2,5-di(1-methylethyl)pyrazine was found to be dominant and independent of amino acid addition, suggesting a completely de novo synthesis. Aroma descriptions of most alkyl substituted pyrazines include mild vegetal aromas, not necessarily undesirable for the cork manufacturing industry. Methoxypyrazines, exhibiting earthy and musty aromas, could not be detected in any of the strains analysed.

(±)-Asarinin.

Asarinin, C(20)H(18)O(6), was isolated as a racemate from the shrub Zanthoxylum alatum. Both forms of the enantiomerically pure substance, (+)- and (-)-asarinin, have been the subject of a total of five previous structure determinations that are essentially identical except for the absolute stereochemistry. However, there seems to be some confusion in the literature concerning these structure determinations of asarinin and also those of its stereoisomer sesamin. The molecular structure of racemic asarinin differs from that of the pure enantiomers in the orientation of one ring system. In the packing of the racemate, molecules are linked by C-H...O interactions to form ribbons parallel to [101].

From concept representations to ontologies: a paradigm shift in health informatics?

OBJECTIVES: This work aims at uncovering challenges in biomedical knowledge representation research by providing an understanding of what was historically called "medical concept representation" and used as the name for a working group of the International Medical Informatics Association. METHODS: Bibliometrics, text mining, and a social media survey compare the research done in this area between two periods, before and after 2000. RESULTS: Both the opinion of socially active groups of researchers and the interpretation of bibliometric data since 1988 suggest that the focus of research has moved from "medical concept representation" to "medical ontologies". CONCLUSIONS: It remains debatable whether the observed change amounts to a paradigm shift or whether it simply reflects changes in naming, following the natural evolution of ontology research and engineering activities in the 1990s. The availability of powerful tools to handle ontologies devoted to certain areas of biomedicine has not resulted in a large-scale breakthrough beyond advances in basic research.