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Assessing inference to the best explanation posteriors for the estimation of economic agent-based models
Get PDFExplanatory relationships between data and hypotheses have been suggested to play a role in the formation of posterior probabilities. This suggestion was tested in a toy environment and supported by simulations by David H. Glass. We here put forward a variety of inference to the best explanation approaches for determining posterior probabilities by intertwining Bayesian and inference to the best explanation approaches. We then simulate their performances for the estimation of parameters in the Brock and Hommes agent-based model for asset pricing in finance. We find that performances depend on circumstances and also on the evaluation metric. However, most of the time our suggested approaches outperform the Bayesian approach
Knochenmarködem – Ätiologie und Behandlung
Get PDFÜber die letzten Jahrzehnte kam es zu einer deutlichen Zunahme der Diagnose „Knochenmarködem“ (KMÖ). Bei dem KMÖ handelt es sich aber primär um einen radiologisch-deskriptiven Begriff. Ein KMÖ kann durch eine Vielzahl von physiologischen und pathophysiologischen Prozessen ausgelöst werden. Im Rahmen dieser narrativen Übersichtsarbeit soll ein standardisierter Diagnosealgorithmus vorgestellt und die vorhandene Evidenz zu der additiven Therapie zusammengefasst werden.
Der Diagnosealgorithmus basiert auf einer sequenziellen Diagnostik, die neben dem MRT, Röntgen / CT, ein Basislabor, sowie ein differenziertes, endokrinologisches Labor und eine DXA umfasst. Sequenziell werden so traumatische, inflammatorische, septische, mechanisch/degenerative, ischämisch/neurogene, neoplastische, und metabolische Ursachen für das KMÖ abgearbeitet. Erst wenn keine Ursache für das KMÖ gefunden werden konnte, sollte dieses als ein Knochenmarködemsyndrom bezeichnet werden.
Der wichtigste Pfeiler der Therapie des KMÖ ist die Identifikation und Behandlung der zugrundeliegenden Erkrankung. Nur wenn diese adressiert wird, kann eine dauerhafte Heilung erzielt werden. Additiv zu der Therapie der Grunderkrankung, oder beim KMÖS isoliert, können konservative (NSARs ± Immobilisation ± Teilbelastung, Stoßwelle, gepulste elektromagnetische Felder) oder medikamentöse Therapien (Bisphosphonate oder Iloprost) angeboten werden. Alle medikamentösen Therapien sind Off-lable und somit Aufklärungspflichtig. Die chirurgische Therapie hat nach Ansicht der Autor:innen keinen Stellenwert.Over the last decades, there has been a significant increase in the diagnosis of „bone marrow edema“ (BME). BME is primarily a radiological-descriptive term. It can be caused by a variety of physiological and pathophysiological processes. This narrative review aims to present a standardized diagnostic algorithm and summarize the existing evidence on adjunctive therapies.
The diagnostic algorithm is based on a sequential diagnostic approach, which includes MRI, X-ray/CT, basic laboratory tests, a detailed endocrinological laboratory workup, and DXA. This sequential process addresses traumatic, inflammatory, septic, mechanical/degenerative, ischemic/neurogenic, neoplastic, and metabolic causes of BME. Only when no specific cause has been identified, the BME should be classified as a bone marrow edema syndrome (BMES).
The cornerstone of BME therapy is identifying and treating the underlying pathology. Only by addressing the cause long-term recovery can be achieved. In addition to treating the primary disease—or in cases of isolated BMES—adjunctive conservative therapies (e.g., NSAIDs ± immobilization ± partial weight-bearing, shockwave therapy, pulsed electromagnetic fields) or pharmacological treatments (e.g., bisphosphonates or iloprost) may be considered. All pharmacological treatments are off-label and therefore require an informed consent. According to the authors, surgical treatment is not part of BME Management
Developing and characterising bovine decellularized extracellular matrix hydrogels to biofabricate female reproductive tissues
Get PDFThis study investigated the development and characterization of decellularized extracellular matrix (dECM) hydrogels tailored for the biofabrication of female reproductive tissues, specifically targeting ovarian cortex, endometrium, ovarian medulla, and oviduct tissues. We aimed to evaluate the cytocompatibility, biomechanical properties, and overall efficacy of these dECMs in promoting cell viability, proliferation, and morphology using the bovine model. Bovine species provide a valuable model due to their accessibility from slaughterhouse tissues, offering a practical alternative to human samples, which are often limited in availability. Additionally, bovine tissue closely mirrors certain physiological and biological characteristics of humans, making it a relevant model for translational research. Our findings revealed that these dECMs exhibited high biocompatibility with embryo development and cell viability, supporting micro vascularization and cellular morphology without the need for external growth factors. It is important to note that the addition of alginate was crucial for maintaining the structural integrity of the hydrogel during long-term cultures. These hydrogels displayed biomechanical properties that closely mimicked native tissues, which was vital for maintaining their functional integrity and supporting cellular activities. The printability assessments showed that dECMs, particularly those from cortex tissues, achieved high precision in replicating the intended structures, though challenges such as low porosity remained. The bioprinted constructs demonstrated robust cell growth, with over 97% viability observed by day 7, indicating their suitability for cell culture. This work represented a significant advancement in reproductive tissue biofabrication, demonstrating the potential of dECM-based hydrogels in creating structurally and viable tissue constructs. By tailoring each dECM to match the unique biomechanical properties of different tissues, we paved the way for more effective and reliable applications in reproductive medicine and tissue engineering
The genomic architecture of circulating cytokine levels points to drug targets for immune-related diseases
Get PDFSerum anti-NMDA receptor antibodies are linked to memory impairment 12 months after stroke
Get PDFPatients suffering from strokes are at increased risk of developing post-stroke dementia. Serum anti-NMDA receptor autoantibodies (NMDAR1-abs) have been associated with unfavorable post-stroke outcomes. However, their effect on specific cognitive domains remains unclear. We used data from the prospective multicenter DZNE—mechanisms after stroke (DEMDAS) cohort, and measured NMDAR1-abs in serum at baseline. Cognitive function was assessed with a comprehensive neuropsychological test battery at 6- and 12-months follow-up. We employed crude and stepwise confounder adjusted linear and logistic regression models as well as generalized estimating equation models (GEE) to determine the relevance of NMDAR1-abs seropositivity on cognitive function after stroke. 10.2% (58/569) DEMDAS patients were NMDAR1-abs seropositive (IgM:n = 44/IgA:n = 21/IgG:n = 2). Seropositivity was not associated with global cognitive impairment after stroke. However, NMDAR1-abs seropositive patients performed lower in the memory domain (βadjusted = −0.11; 95%CI = −0.57 to −0.03) and were at increased risk for memory impairment (ORadjusted = 3.8; 95%CI = 1.33–10.82) compared to seronegative patients, 12 months after stroke. Further, NMDAR1-abs were linked to memory impairment over time in GEE from 6- to 12-months follow-up (ORadjusted = 2.41; 95%CI = 1.05–5.49). Our data suggests that NMDAR1-abs contribute to memory dysfunction 1 year after stroke while not affecting other cognitive subdomains. Hence, antineuronal autoimmunity may be involved in distinct mechanisms of post-stroke memory impairment. Clinical trial name and registration number: The Determinants of Dementia After Stroke (DEMDAS; study identifier on clinical trials.gov: NCT01334749
Longitudinal association between DNA methylation and type 2 diabetes: Findings from the KORA F4/FF4 study
Get PDFBackground
Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.
Methods
In this longitudinal study, we examined data from the Cooperative Health Research in the Region of Augsburg (KORA) F4 and FF4 studies, conducted approximately seven years apart. Leucocyte DNA methylation was assessed using the Illumina EPIC and 450K arrays. Linear mixed-effects models were employed to identify significant associations between methylation sites and diabetes status, as well as with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homoeostasis model assessment of beta cell function (HOMA-B), and homoeostasis model assessment of insulin resistance (HOMA-IR). Interaction effects between diabetes status and follow-up time were also examined. Additionally, we explored CpG sites associated with persistent prediabetes or T2D, as well as the progression from normal glucose tolerance (NGT) to prediabetes or T2D. Finally, we assessed the associations between the identified CpG sites and their corresponding gene expression levels.
Results
A total of 3,501 observations from 2,556 participants, with methylation measured at least once across two visits, were included in the analyses. We identified 64 sites associated with T2D including 15 novel sites as well as known associations like those with the thioredoxin-interacting protein (TXNIP) and ATP-binding cassette sub-family G member 1 (ABCG1) genes. Of these, eight CpG sites exhibited different rates of annual methylation change between the NGT and T2D groups, and seven CpG sites were linked to the progression from NGT to prediabetes or T2D, including those annotated to mannosidase alpha class 2a member 2 (MAN2A2) and carnitine palmitoyl transferase 1 A (CPT1A). Longitudinal analysis revealed significant associations between methylation and FPG at 128 sites, HbA1c at 41 sites, and HOMA-IR at 57 sites. Additionally, we identified 104 CpG-transcript pairs in whole blood, comprising 40 unique CpG sites and 96 unique gene transcripts.
Conclusions
Our study identified novel differentially methylated loci linked to T2D as well as to changes in diabetes status through a longitudinal approach. We report CpG sites with different rates of annual methylation change and demonstrate that DNA methylation associated with T2D is linked to following transcriptional differences. These findings provide new insights into the molecular mechanisms of diabetes development
The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
Get PDFIn cerebral small vessel disease (cSVD), vascular dysfunction has been associated with cSVD-lesions across the brain. Here we further explore the relation between vascular dysfunction and cSVD-related brain injury. We tested two hypotheses: (1) that complementary measures of abnormal small vessel function relate to decreased white matter integrity, and (2) that local variance in vascular dysfunction relates to local variance in white matter integrity within individual patients.
We included 23 patients with monogenic cSVD (i.e. CADASIL) and 46 patients with sporadic cSVD. With whole-brain analyses, we tested if small vessel flow velocity and reactivity measures from 7T-MRI were associated with global peak-width-of-skeletonized-mean-diffusivity (PSMD). We also tested voxel-wise correlations between reactivity to hypercapnia and mean diffusivity (MD) in white matter.
Whole-brain analyses showed a negative association between blood flow velocity and PSMD for the perforating arteries in the centrum semiovale in CADASIL (p = 0.04) and in the basal ganglia in sporadic cSVD (p = 0.002). Global white matter reactivity to hypercapnia was not associated with PSMD. Within patients, both in CADASIL and sporadic cSVD, we observed significant voxel-wise negative correlations for endothelial-independent vascular reactivity and MD in the white matter.
These findings confirm our hypothesis that small vessel dysfunction in patients with cSVD is associated with microstructural white matter alterations, also at voxel level. The latter may reflect a direct relationship between local small vessel dysfunction and tissue injury
Multiple sclerosis and gut microbiota: Lachnospiraceae from the ileum of MS twins trigger MS-like disease in germfree transgenic mice—An unbiased functional study
Get PDFWe developed a two-tiered strategy aiming to identify gut bacteria functionally linked to the development of multiple sclerosis (MS). First, we compared gut microbial profiles in a cohort of 81 monozygotic twins discordant for MS. This approach allowed to minimize confounding effects by genetic and early environmental factors and identified over 50 differently abundant taxa with the majority of increased taxa within the Firmicutes. These included taxa previously described to be associated with MS (Anaerotruncus colihominis and Eisenbergiella tayi), along with newly identified taxa, such as Copromonas and Acutalibacter. Second, we interrogated the intestinal habitat and functional impact of individual taxa on the development of MS-like disease. In an exploratory approach, we enteroscopically sampled microbiota from different gut segments of selected twin pairs and compared their compositional profiles. To assess their functional potential, samples were orally transferred into germfree transgenic mice prone to develop spontaneous MS-like experimental autoimmune encephalomyelitis (EAE) upon bacterial colonization. We found that MS-derived ileal microbiota induced EAE at substantially higher rates than analogous material from healthy twin donors. Furthermore, female mice were more susceptible to disease development than males. The likely active organisms were identified as Eisenbergiella tayi and Lachnoclostridium, members of the Lachnospiraceae family. Our results identify potentially disease-facilitating bacteria sampled from the ileum of MS affected twins. The experimental strategy may pave the way to functionally understand the role of gut microbiota in initiation of MS
Reduced myelin contributes to cognitive impairment in patients with monogenic small vessel disease
Get PDFIntroduction: Myelin is pivotal for signal transfer and thus cognition. Cerebral small vessel disease (cSVD) is primarily associated with white matter (WM) lesions and diffusion changes; however, myelin alterations and related cognitive impairments in cSVD remain unclear.
Methods: We included 64 patients with familial cSVD (i.e., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]) and 20 cognitively unimpaired individuals. χ separation applied to susceptibility weighted imaging was used to assess myelin and iron within WM hyperintensities, normal appearing WM, and two strategic fiber tracts. Diffusion-based mean diffusivity and free water were analyzed for comparisons. Cognitive impairment was assessed by the Trail Making Test.
Results: CADASIL patients showed reduced myelin within WM hyperintensities and its penumbra in the normal appearing WM. Myelin was moderately correlated with diffusion and iron changes and associated with slower processing speed controlled for diffusion and iron alterations.
Discussion: Myelin constitutes WM alterations distinct from diffusion changes and substantially contributes to explaining cognitive impairment in cSVD
Can AI grade your essays?
No full textThe manual assessment and grading of student writing is a time-consuming yet critical task for teachers. Recent developments in generative AI offer potential solutions to facilitate essay-scoring tasks for teachers. In our study, we evaluate the performance (e.g. alignment and reliability) of both open-source and closed-source LLMs in assessing German student essays, comparing their evaluations to those of 37 teachers across 10 pre-defined criteria (i.e., plot logic, expression). A corpus of 20 real-world essays from Year 7 and 8 students was analyzed using five LLMs: GPT-3.5, GPT-4, o1-preview, LLaMA 3-70B, and Mixtral 8x7B, aiming to provide in-depth insights into LLMs’ scoring capabilities. Closed-source GPT models outperform open-source models in both internal consistency and alignment with human ratings, particularly excelling in language-related criteria. The o1 model outperforms all other LLMs, achieving Spearman’s = .74 with human assessments in the Overall score, and an internal consistency of = .80, though biased towards higher scores. These findings indicate that LLM-based assessment can be a useful tool to reduce teacher workload by supporting the evaluation of essays, especially with regard to language-related criteria. However, due to their tendency to overrate and their remaining issues to capture the content quality, the models require further refinement