HunFlair2 in a cross-corpus evaluation of biomedical named entity recognition and normalization tools.

MOTIVATION: With the exponential growth of the life sciences literature, biomedical text mining (BTM) has become an essential technology for accelerating the extraction of insights from publications. The identification of entities in texts, such as diseases or genes, and their normalization, i.e. grounding them in knowledge base, are crucial steps in any BTM pipeline to enable information aggregation from multiple documents. However, tools for these two steps are rarely applied in the same context in which they were developed. Instead, they are applied "in the wild", i.e. on application-dependent text collections from moderately to extremely different from those used for training, varying e.g. in focus, genre or text type. This raises the question whether the reported performance, usually obtained by training and evaluating on different partitions of the same corpus, can be trusted for downstream applications. RESULTS: Here, we report on the results of a carefully designed cross-corpus benchmark for entity recognition and normalization, where tools were applied systematically to corpora not used during their training. Based on a survey of 28 published systems, we selected five, based on pre-defined criteria like feature richness and availability, for an in-depth analysis on three publicly available corpora covering four entity types. Our results present a mixed picture and show that cross-corpus performance is significantly lower than the in-corpus performance. HunFlair2, the redesigned and extended successor of the HunFlair tool, showed the best performance on average, being closely followed by PubTator Central. Our results indicate that users of BTM tools should expect a lower performance than the original published one when applying tools in "the wild" and show that further research is necessary for more robust BTM tools. AVAILABILITY AND IMPLEMENTATION: All our models are integrated into the NLP framework flair: Https://github.com/flairNLP/flair. Code to reproduce our results is available at: Https://github.com/hu-ner/hunflair2-experiments. SUPPLEMENTARY INFORMATION: Supplementary information are available at Bioinformatics online.

Aspirin Stimulates the Osteogenic Differentiation of Human Adipose Tissue-Derived Stem Cells In Vitro.

This study investigates the impact of acetylsalicylic acid (ASA), also known as aspirin, on adipose tissue-derived stem cells (ASCs), aiming to elucidate its dose-dependent effects on morphology, viability, proliferation, and osteogenic differentiation. Isolated and characterized human ASCs were exposed to 0 µM, 100 µM, 200 µM, 400 µM, 800 µM, 1000 µM, 10,000 µM, and 16,000 µM of ASA in vitro. Cell morphology, viability, and proliferation were evaluated with fluorescent live/dead staining, alamarBlue viability reagent, and CyQUANT® cell proliferation assay, respectively. Osteogenic differentiation under stimulation with 400 µM or 1000 µM of ASA was assessed with alizarin red staining and qPCR of selected osteogenic differentiation markers (RUNX2, SPP1, ALPL, BGLAP) over a 3- and 21-day-period. ASA doses ≤ 1000 µM showed no significant impact on cell viability and proliferation. Live/dead staining revealed a visible reduction in viable cell confluency for ASA concentrations ≥ 1000 µM. Doses of 10,000 µM and 16,000 µM of ASA exhibited a strong cytotoxic and anti-proliferative effect in ASCs. Alizarin red staining revealed enhanced calcium accretion under the influence of ASA, which was macro- and microscopically visible and significant for 1000 µM of ASA (p = 0.0092) in quantification if compared to osteogenic differentiation without ASA addition over a 21-day-period. This enhancement correlated with a more pronounced upregulation of osteogenic markers under ASA exposure (ns). Our results indicate a stimulatory effect of 1000 µM of ASA on the osteogenic differentiation of ASCs. Further research is needed to elucidate the precise molecular mechanisms underlying this effect; however, this discovery suggests promising opportunities for enhancing bone tissue engineering with ASCs as cell source.

Diagnostic power of ChatGPT 4 in distal radius fracture detection through wrist radiographs.

Distal radius fractures rank among the most prevalent fractures in humans, necessitating accurate radiological imaging and interpretation for optimal diagnosis and treatment. In addition to human radiologists, artificial intelligence systems are increasingly employed for radiological assessments. Since 2023, ChatGPT 4 has offered image analysis capabilities, which can also be used for the analysis of wrist radiographs. This study evaluates the diagnostic power of ChatGPT 4 in identifying distal radius fractures, comparing it with a board-certified radiologist, a hand surgery resident, a medical student, and the well-established AI Gleamer BoneView™. Results demonstrate ChatGPT 4's good diagnostic accuracy (sensitivity 0.88, specificity 0.98, diagnostic power (AUC) 0.93), surpassing the medical student (sensitivity 0.98, specificity 0.72, diagnostic power (AUC) 0.85; p = 0.04) significantly. Nevertheless, the diagnostic power of ChatGPT 4 lags behind the hand surgery resident (sensitivity 0.99, specificity 0.98, diagnostic power (AUC) 0.985; p = 0.014) and Gleamer BoneView™(sensitivity 1.00, specificity 0.98, diagnostic power (AUC) 0.99; p = 0.006). This study highlights the utility and potential applications of artificial intelligence in modern medicine, emphasizing ChatGPT 4 as a valuable tool for enhancing diagnostic capabilities in the field of medical imaging.

Biocompatibility of Synechococcus sp. PCC 7002 with Human Dermal Cells In Vitro.

Being the green gold of the future, cyanobacteria have recently attracted considerable interest worldwide. This study investigates the adaptability and biocompatibility of the cyanobacterial strain Synechococcus sp. PCC 7002 with human dermal cells, focusing on its potential application in biomedical contexts. First, we investigated the adaptability of Synechococcus PCC 7002 bacteria to human cell culture conditions. Next, we evaluated the biocompatibility of cyanobacteria with common dermal cells, like 3T3 fibroblasts and HaCaT keratinocytes. Therefore, cells were directly and indirectly cocultured with the corresponding cells, and we measured metabolic activity (AlamarBlue assay) and proliferation (cell count and PicoGreen assay). The lactate dehydrogenase (LDH) assay was performed to determine the cytotoxic effect of cyanobacteria and their nutrition medium on human dermal cells. The cyanobacteria exhibited exponential growth under conventional human cell culture conditions, with the temperature and medium composition not affecting their viability. In addition, the effect of illumination on the proliferation capacity was investigated, showing a significant impact of light exposure on bacterial growth. The measured oxygen production under hypoxic conditions demonstrated a sufficient oxygen supply for further tissue engineering approaches depending on the number of bacteria. There were no significant adverse effects on human cell viability and growth under coculture conditions, whereas the LDH assay assessed signs of cytotoxicity regarding 3T3 fibroblasts after 2 days of coculturing. These negative effects were dismissed after 4 days. The findings highlight the potential of Synechococcus sp. PCC 7002 for integration into biomedical approaches. We found no cytotoxicity of cyanobacteria on 3T3 fibroblasts and HaCaT keratinocytes, thus paving the way for further in vivo studies to assess long-term effects and systemic reactions.

Microvascular Muscle vs. Fascio-Cutaneous Free Flaps for Reconstruction of Plantar Load-Bearing Foot Defects-An International Survey.

Background: The reconstruction of plantar load-bearing foot defects faces many plastic surgeons with a major challenge. The optimal patient- and defect-oriented reconstructive strategy must be selected. Methods: To analyze the current trends and recommendations in reconstruction of plantar load-bearing foot defects, we conducted an international survey among plastic surgeons querying them about their recommendations and experiences. Results: The survey revealed that the most common strategies for reconstruction of the foot sole are locoregional and microvascular free flaps, emphasizing the relevance of plastic surgery. Among microvascular free flaps, muscle and fascio-cutaneous free flaps are by far the most frequently used. The target qualities of the reconstructed tissue to be considered are manifold, with adherence being the most frequently mentioned. We observed a noteworthy correlation between the utilization of muscle flaps and a preference for adherence. In addition, we identified a substantial correlation between the usage of fascio-cutaneous free flaps and further target qualities, such as good skin quality and sensitivity. Conclusions: Our findings provide insights into the clinical reality and highlight important aspects that must be considered in reconstruction of the weight-bearing areas of the foot providing support in the selection of the appropriate therapy.

[Searching for Evidence: A Systematic Review of the Pathology of Lipoedema]. / Auf der Suche nach der Evidenz: Eine systematische Übersichtsarbeit zur Pathologie des Lipödems.

BACKGROUND: Lipoedema is a symmetrically localised, painful hypertrophy of subcutaneous adipose tissue in the extremities with marked disproportion to the trunk, and almost exclusively affects females. Despite being first described over 80 years ago, the aetiology and pathogenesis of the disease are largely unknown and are currently the subject of intensive research efforts. METHODS: To summarise the current evidence-based literature on the cellular pathologies and aetiology of lipoedema, a PRISMA-based systematic review was conducted within the National Library of Medicine and Cochrane databases. RESULTS: A total of 53 studies were identified and included in this review. The results were classified and summarised into categories. CONCLUSION: Although there has been a significant increase in research activity and recent publication of extensive studies with a histological and molecular genetic focus, the fundamental aetiology and pathology of lipoedema remains largely unclear. The current data shows discrepancies across studies, particularly with regard to the "oedematous" component of lipoedema. The frequently present comorbidities "lymphoedema" and "obesity", primarily in advanced stages of lipoedema, complicate the diagnostic differentiation and clear definition of study cohorts in scientific research.

[Breast implant-associated squamous cell carcinoma: a systematic literature review]. / Brustimplantat assoziiertes Plattenepithelkarzinom (BIA-SCC) ­ eine systematische Literaturübersicht.

BACKGROUND: Breast implant-associated squamous cell carcinoma (BIA-SCC) is being discussed as a distinct malignant tumour entity originating from the implant capsule. The FDA and the ASPS published a safety communication on BIA-SCC in 2022, with a first case report of BIA-SCC having been published in the 1990s. This manuscript summarises the current scientific data on this rare tumour entity. MATERIAL AND METHODS: This systematic literature review from two independent databases includes all publications of cases with histopathologically confirmed BIA-SCC. Data extraction included study design, demographic data, implant information and details regarding diagnosis and treatment. RESULTS: Nineteen cases of BIA-SCC with a mean age of 57±10 years were reported in 16 publications. In most cases, the indication was aesthetic augmentation (n=13). Both silicone (n=11) and saline (n=7) implants with different surfaces (smooth n=3, textured n=3, polyurethane n=1) were used. Symptoms such as unilateral swelling (n=18), pain (n=14) and erythema (n=5) occurred on an average of 23±9 years after implantation. Imaging showed fluid collection (n=8) or a tumour mass (n=4) around the breast implant. The most common surgical treatment was explantation with capsulectomy. Metastasis was described in 6 cases. CONCLUSIONS: BIA-SCC is a malignant tumour entity associated with breast implant capsules. Based on current low-quality data (level of evidence class V), no definitive conclusion regarding correlation and causality of SCC in patients with breast implants can be drawn. There is an urgent need for national and international breast implant and breast cancer registries to obtain valid data on the incidence, pathogenesis and clinical presentation of rare tumour entities.

The use of commercial fibrin glue in dermal replacement material reduces angiogenic and lymphangiogenic gene and protein expression in vitro.

BACKGROUND: Commercial fibrin glue is increasingly finding its way into clinical practice in surgeries to seal anastomosis, and initiate hemostasis or tissue repair. Human biological glue is also being discussed as a possible cell carrier. To date, there are only a few studies addressing the effects of fibrin glue on the cell-molecular level. This study examines the effects of fibrin glue on angiogenesis and lymphangiogenesis, as well as adipose-derived stem cells (ASCs) with a focus on gene and protein expression in scaffolds regularly used for tissue engineering approaches. METHODS: Collagen-based dermal regeneration matrices (DRM) were seeded with human umbilical vein endothelial cells (HUVEC), human dermal lymphatic endothelial cells (LECs), or adipose-derived stem cells (ASC) and fixed with or without fibrin glue according to the experimental group. Cultures were maintained for 1 and 7 days. Finally, angiogenic and lymphangiogenic gene and protein expression were measured with special regard to subtypes of vascular endothelial growth factor (VEGF) and corresponding receptors using Multiplex-qPCR and ELISA assays. In addition, the hypoxia-induced factor 1-alpha (HIF1a) mediated intracellular signaling pathways were included in assessments to analyze a hypoxic encapsulating effect of fibrin polymers. RESULTS: All cell types reacted to fibrin glue application with an alteration of gene and protein expression. In particular, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor B (VEGFB), vascular endothelial growth factor C (VEGFC), vascular endothelial growth receptor 1 (VEGFR1/FLT1), vascular endothelial growth receptor 2 (VEGFR2/KDR), vascular endothelial growth receptor 3 (VEGFR3/FLT4) and Prospero Homeobox 1 (PROX1) were depressed significantly depending on fibrin glue. Especially short-term fibrin effect led to a continuous downregulation of respective gene and protein expression in HUVECs, LECs, and ASCs. CONCLUSION: Our findings demonstrate the impact of fibrin glue application in dermal regeneration with special regard to angiogenesis and lymphangiogenesis. In particular, a short fibrin treatment of 24 hours led to a decrease in gene and protein levels of LECS, HUVECs, and ASCs. In contrast, the long-term application showed less effect on gene and protein expressions. Therefore, this work demonstrated the negative effects of fibrin-treated cells in tissue engineering approaches and could affect wound healing during dermal regeneration.

Adipose-Derived Stem Cells Improve Angiogenesis and Lymphangiogenesis in a Hypoxic Dermal Regeneration Model In Vitro.

Background and Objectives: Impaired wound healing represents an unsolved medical issue with a high impact on patients' quality of life and global health care. Even though hypoxia is a significant limiting factor for wound healing, it reveals stimulating effects in gene and protein expression at cellular levels. In particular, hypoxically treated human adipose tissue-derived stem cells (ASCs) have previously been used to stimulate tissue regeneration. Therefore, we hypothesized that they could promote lymphangiogenesis or angiogenesis. Materials and Methods: Dermal regeneration matrices were seeded with human umbilical vein endothelial cells (HUVECs) or human dermal lymphatic endothelial cells (LECs) that were merged with ASCs. Cultures were maintained for 24 h and 7 days under normoxic or hypoxic conditions. Finally, gene and protein expression were measured regarding subtypes of VEGF, corresponding receptors, and intracellular signaling pathways, especially hypoxia-inducible factor-mediated pathways using multiplex-RT-qPCR and ELISA assays. Results: All cell types reacted to hypoxia with an alteration of gene expression. In particular, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor B (VEGFB), vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 1 (VEGFR1/FLT1), vascular endothelial growth factor receptor 2 (VEGFR2/KDR), vascular endothelial growth factor receptor 3 (VEGFR3/FLT4), and prospero homeobox 1 (PROX1) were overexpressed significantly depending on upregulation of hypoxia-inducible factor 1 alpha (HIF-1a). Moreover, co-cultures with ASCs showed a more intense change in gene and protein expression profiles and gained enhanced angiogenic and lymphangiogenic potential. In particular, long-term hypoxia led to continuous stimulation of HUVECs by ASCs. Conclusions: Our findings demonstrated the benefit of hypoxic conditioned ASCs in dermal regeneration concerning angiogenesis and lymphangiogenesis. Even a short hypoxic treatment of 24 h led to the stimulation of LECs and HUVECs in an ASC-co-culture. Long-term hypoxia showed a continuous influence on gene expressions. Therefore, this work emphasizes the supporting effects of hypoxia-conditioned-ASC-loaded collagen scaffolds on wound healing in dermal regeneration.

Use of photosynthetic transgenic cyanobacteria to promote lymphangiogenesis in scaffolds for dermal regeneration.

Impaired wound healing represents an unsolved medical need with a high impact on patients´ quality of life and global health care. Even though its causes are diverse, ischemic-hypoxic conditions and exacerbated inflammation are shared pathological features responsible for obstructing tissue restoration. In line with this, it has been suggested that promoting a normoxic pro-regenerative environment and accelerating inflammation resolution, by reinstating the lymphatic fluid transport, could allow the wound healing process to be resumed. Our group was first to demonstrate the functional use of scaffolds seeded with photosynthetic microorganisms to supply tissues with oxygen. Moreover, we previously proposed a photosynthetic gene therapy strategy to create scaffolds that deliver other therapeutic molecules, such as recombinant human growth factors into the wound area. In the present work, we introduce the use of transgenic Synechococcus sp. PCC 7002 cyanobacteria (SynHA), which can produce oxygen and lymphangiogenic hyaluronic acid, in photosynthetic biomaterials. We show that the co-culture of lymphatic endothelial cells with SynHA promotes their survival and proliferation under hypoxic conditions. Also, hyaluronic acid secreted by the cyanobacteria enhanced their lymphangiogenic potential as shown by changes to their gene expression profile, the presence of lymphangiogenic protein markers and their capacity to build lymph vessel tubes. Finally, by seeding SynHA into collagen-based dermal regeneration materials, we developed a viable photosynthetic scaffold that promotes lymphangiogenesis in vitro under hypoxic conditions. The results obtained in this study lay the groundwork for future tissue engineering applications using transgenic cyanobacteria that could become a therapeutic alternative for chronic wound treatment. STATEMENT OF SIGNIFICANCE: In this study, we introduce the use of transgenic Synechococcus sp. PCC 7002 (SynHA) cyanobacteria, which were genetically engineered to produce hyaluronic acid, to create lymphangiogenic photosynthetic scaffolds for dermal regeneration. Our results confirmed that SynHA cyanobacteria maintain their photosynthetic capacity under standard human cell culture conditions and efficiently proliferate when seeded inside fibrin-collagen scaffolds. Moreover, we show that SynHA supported the viability of co-cultured lymphatic endothelial cells (LECs) under hypoxic conditions by providing them with photosynthetic-derived oxygen, while cyanobacteria-derived hyaluronic acid stimulated the lymphangiogenic capacity of LECs. Since tissue hypoxia and impaired lymphatic drainage are two key factors that directly affect wound healing, our results suggest that lymphangiogenic photosynthetic biomaterials could become a treatment option for chronic wound management.

Anomalous Magnetotransport in Disordered Structures: Classical Edge-State Percolation.

By event-driven molecular dynamics simulations we investigate magnetotransport in a two-dimensional model with randomly distributed scatterers close to the field-induced localization transition. This transition is generated by percolating skipping orbits along the edges of obstacle clusters. The dynamic exponents differ significantly from those of the conventional transport problem on percolating systems, thus establishing a new dynamic universality class. This difference is tentatively attributed to a weak-link scenario, which emerges naturally due to barely overlapping edge trajectories. We make predictions for the frequency-dependent conductivity and discuss implications for active colloidal circle swimmers in a hetegogeneous environment.

Physical Forces between Humans and How Humans Attract and Repel Each Other Based on Their Social Interactions in an Online World.

Physical interactions between particles are the result of the exchange of gauge bosons. Human interactions are mediated by the exchange of messages, goods, money, promises, hostilities, etc. While in the physical world interactions and their associated forces have immediate dynamical consequences (Newton's laws) the situation is not clear for human interactions. Here we quantify the relative acceleration between humans who interact through the exchange of messages, goods and hostilities in a massive multiplayer online game. For this game we have complete information about all interactions (exchange events) between about 430,000 players, and about their trajectories (movements) in the metric space of the game universe at any point in time. We use this information to derive "interaction potentials" for communication, trade and attacks and show that they are harmonic in nature. Individuals who exchange messages and trade goods generally attract each other and start to separate immediately after exchange events end. The form of the interaction potential for attacks mirrors the usual "hit-and-run" tactics of aggressive players. By measuring interaction intensities as a function of distance, velocity and acceleration, we show that "forces" between players are directly related to the number of exchange events. We find an approximate power-law decay of the likelihood for interactions as a function of distance, which is in accordance with previous real world empirical work. We show that the obtained potentials can be understood with a simple model assuming an exchange-driven force in combination with a distance-dependent exchange rate.

A brief intervention utilising visual feedback reduces pain and enhances tactile acuity in CLBP patients.

BACKGROUND: Chronic low back pain (CLBP) is a serious health problem in industrialised countries and the efficacy of current treatment options is unsatisfying. OBJECTIVE: The present study examines the effects of a combined intervention that utilizes visual feedback, motion and sensory discrimination training in CLBP patients. METHODS: Thirty patients of an outpatient orthopaedic rehabilitation unit were randomly assigned to either feedback or control group. In addition to standard treatment, patients of the feedback group received 6 feedback sessions where they watched the image of their back during a brief 2-point discrimination training and, after that, while they were tilting their pelvis up and down on the left and right side using their lumbar musculus multifidus solely. The control group received 6 sessions consisting of 2 units of physiotherapy, relaxation training and movement training (walking) each. RESULTS: A significant effect on self-reported pain and sensory discrimination threshold could be found for the feedback intervention, while, as expected, other pain related variables, like pain anxiety, pain vigilance, depression and cognitive appraisal of pain remained unchanged. CONCLUSIONS: These findings imply that very simple feedback interventions without major technical requirements could be a valuable supplement to standard treatment in CLBP.

Detection of the elite structure in a virtual multiplex social system by means of a generalised K-core.

Elites are subgroups of individuals within a society that have the ability and means to influence, lead, govern, and shape societies. Members of elites are often well connected individuals, which enables them to impose their influence to many and to quickly gather, process, and spread information. Here we argue that elites are not only composed of highly connected individuals, but also of intermediaries connecting hubs to form a cohesive and structured elite-subgroup at the core of a social network. For this purpose we present a generalization of the K-core algorithm that allows to identify a social core that is composed of well-connected hubs together with their 'connectors'. We show the validity of the idea in the framework of a virtual world defined by a massive multiplayer online game, on which we have complete information of various social networks. Exploiting this multiplex structure, we find that the hubs of the generalised K-core identify those individuals that are high social performers in terms of a series of indicators that are available in the game. In addition, using a combined strategy which involves the generalised Kcore and the recently introduced M-core, the elites of the different 'nations' present in the game are perfectly identified as modules of the generalised K-core. Interesting sudden shifts in the composition of the elite cores are observed at deep levels. We show that elite detection with the traditional K-core is not possible in a reliable way. The proposed method might be useful in a series of more general applications, such as community detection.

Fractal multi-level organisation of human groups in a virtual world.

Humans are fundamentally social. They form societies which consist of hierarchically layered nested groups of various quality, size, and structure. The anthropologic literature has classified these groups as support cliques, sympathy groups, bands, cognitive groups, tribes, linguistic groups, and so on. Anthropologic data show that, on average, each group consists of approximately three subgroups. However, a general understanding of the structural dependence of groups at different layers is largely missing. We extend these early findings to a very large high-precision large-scale internet-based social network data. We analyse the organisational structure of a complete, multi-relational, large social multiplex network of a human society consisting of about 400,000 odd players of an open-ended massive multiplayer online game for which we know all about their various group memberships at different layers. Remarkably, the online players' society exhibits the same type of structured hierarchical layers as found in hunter-gatherer societies. Our findings suggest that the hierarchical organisation of human society is deeply nested in human psychology.

Behavioral and network origins of wealth inequality: insights from a virtual world.

Almost universally, wealth is not distributed uniformly within societies or economies. Even though wealth data have been collected in various forms for centuries, the origins for the observed wealth-disparity and social inequality are not yet fully understood. Especially the impact and connections of human behavior on wealth could so far not be inferred from data. Here we study wealth data from the virtual economy of the massive multiplayer online game (MMOG) Pardus. This data not only contains every player's wealth at every point in time, but also all actions over a timespan of almost a decade. We find that wealth distributions in the virtual world are very similar to those in Western countries. In particular we find an approximate exponential distribution for low wealth levels and a power-law tail for high levels. The Gini index is found to be g = 0.65, which is close to the indices of many Western countries. We find that wealth-increase rates depend on the time when players entered the game. Players that entered the game early on tend to have remarkably higher wealth-increase rates than those who joined later. Studying the players' positions within their social networks, we find that the local position in the trade network is most relevant for wealth. Wealthy people have high in- and out-degrees in the trade network, relatively low nearest-neighbor degrees, and low clustering coefficients. Wealthy players have many mutual friendships and are socially well respected by others, but spend more time on business than on socializing. Wealthy players have few personal enemies, but show animosity towards players that behave as public enemies. We find that players that are not organized within social groups are significantly poorer on average. We observe that "political" status and wealth go hand in hand.