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Objective Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysis A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed.Results The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4+CD45RA+CCR7+ T cells was high in 5/9 cases, and the percentage of CD4+CD45RA−CCR7− T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19+CD38lowCD21low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4+ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8+ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes.Conclusion Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.

Abstract Vascular and neural structures of the retina can be visualized non-invasively and used to predict ocular and systemic pathologies. We set out to evaluate the association of hemoglobin (Hb) levels within the national reference interval with retinal vascular caliber, optical coherence tomography (OCT) and visual field (VF) parameters in the Northern Finland 1966 Birth Cohort (n = 2319, 42.1% male, average age 47 years). The studied parameters were evaluated in Hb quintiles and multivariable linear regression models. The lowest Hb quintile of both sexes presented the narrowest central retinal vein equivalent (CRVE) and the healthiest cardiometabolic profile compared to the other Hb quintiles. In the regression models, CRVE associated positively with Hb levels in both sexes, (B males = 0.068 [0.001; 0.135], B females = 0.087 [0.033; 0.140]), after being adjusted for key cardiometabolic and inflammatory parameters, smoking status, and fellow vessel caliber. No statistically significant associations of Hb levels with central retinal artery equivalent, OCT or VF parameters were detected. In conclusion, Hb levels were positively and specifically associated with CRVE, indicating that Hb levels are an independent factor affecting CRVE and the effect is in parallel with established risk factors for cardiometabolic diseases.

Abstract Acute myeloid leukemia (AML), a heterogeneous and aggressive blood cancer, does not respond well to single-drug therapy. A combination of drugs is required to effectively treat this disease. Computational models are critical for combination therapy discovery due to the tens of thousands of two-drug combinations, even with approved drugs. While predicting synergistic drugs is the focus of current methods, few consider drug efficacy and potential toxicity, which are crucial for treatment success. To find effective new drug candidates, we constructed a bipartite network using patient-derived tumor samples and drugs. The network is based on drug-response screening and summarizes all treatment response heterogeneity as drug response weights. This bipartite network is then projected onto the drug part, resulting in the drug similarity network. Distinct drug clusters were identified using community detection methods, each targeting different biological processes and pathways as revealed by enrichment and pathway analysis of the drugs’ protein targets. Four drugs with the highest efficacy and lowest toxicity from each cluster were selected and tested for drug sensitivity using cell viability assays on various samples. Results show that ruxolitinib-ulixertinib and sapanisertib-LY3009120 are the most effective combinations with the least toxicity and the best synergistic effect on blast cells. These findings lay the foundation for personalized and successful AML therapies, ultimately leading to the development of drug combinations that can be used alongside standard first-line AML treatment.

Abstract Background The aim of this study was to evaluate how diagnostic practice in congenital ichthyoses has evolved during the years 2000–2020 and what kind of gene variants of congenital ichthyosis have been found. Methods The study cohort of this register‐based research consisted of a total of 88 patients, whose diagnostic testing was conducted, and ichthyosis diagnoses set at the Department of Dermatology and the Department of Clinical Genetics at Tampere University Hospital during the years 2000–2020. Results Diagnosis of ichthyosis was confirmed with genetic testing in 33 cases, and with conventional diagnostic methods, such as clinical findings, skin biopsy and family history of ichthyoses, in 55 cases. We observed four novel variants in patients with the clinical diagnoses of congenital ichthyoses. Conclusion When genetic testing became available, it was offered primarily to patients with severe forms of ichthyosis. During the study period next‐generation sequencing became the genetic testing method of choice providing new opportunities in diagnostics.

BackgroundBased on Finnish LDLR-founder variations, the prevalence of familial hypercholesterolemia (FH) in Finland is estimated to be at least 1:600. Patients with FH have increased risk of premature coronary artery disease (CAD) and thus the prevalence of FH is expected to be higher in this subgroup.ObjectiveTo assess the prevalence of monogenic FH in a Finnish cohort of patients with premature CAD and elevated low-density lipoprotein cholesterol (LDL-C) levels.MethodsAmong 28,295 patients undergoing angiography at Heart Hospital at Tampere University Hospital between 2007 and 2017, we identified 162 patients diagnosed with premature CAD (men aged

Atualmente os sistemas agroalimentares têm sido analisados em diversas perspetivas, tanto em termos da eficiência da utilização dos recursos naturais, como pela aplicação de boas práticas na produção de alimentos, a influência das mesmas ao nível da qualidade e segurança alimentar, como também ao nível da sustentabilidade. Contudo, há um elemento fundamental que muitas vezes é negligenciado nesse contexto, designadamente a Ética.

Abstract Rare or novel missense variants in large genes such as TTN and NEB are frequent in the general population, which hampers the interpretation of putative disease-causing biallelic variants in patients with sporadic neuromuscular disorders. Often, when the first initial genetic analysis is performed, the reconstructed haplotype, i.e. phasing information of the variants is missing. Segregation analysis increases the diagnostic turnaround time and is not always possible if samples from family members are lacking. To overcome this difficulty, we investigated how well the linked-read technology succeeded to phase variants in these large genes, and whether it improved the identification of structural variants. Linked-read sequencing data of nemaline myopathy, distal myopathy, and proximal myopathy patients were analyzed for phasing, single nucleotide variants, and structural variants. Variant phasing was successful in the large muscle genes studied. The longest continuous phase blocks were gained using high-quality DNA samples with long DNA fragments. Homozygosity increased the number of phase blocks, especially in exome sequencing samples lacking intronic variation. In our cohort, linked-read sequencing added more information about the structural variation but did not lead to a molecular genetic diagnosis. The linked-read technology can support the clinical diagnosis of neuromuscular and other genetic disorders.

Abstract The eye possesses a paravascular solute transport pathway that is driven by physiological pulsations, resembling the brain glymphatic pathway. We developed synchronous multimodal imaging tools aimed at measuring the driving pulsations of the human eye, using an eye-tracking functional eye camera (FEC) compatible with magnetic resonance imaging (MRI) for measuring eye surface pulsations. Special optics enabled integration of the FEC with MRI-compatible video ophthalmoscopy (MRcVO) for simultaneous retinal imaging along with functional eye MRI imaging (fMREye) of the BOLD (blood oxygen level dependent) contrast. Upon optimizing the fMREye parameters, we measured the power of the physiological (vasomotor, respiratory, and cardiac) eye and brain pulsations by fast Fourier transform (FFT) power analysis. The human eye pulsated in all three physiological pulse bands, most prominently in the respiratory band. The FFT power means of physiological pulsation for two adjacent slices was significantly higher than in one-slice scans (RESP1 vs. RESP2; df = 5, p = 0.045). FEC and MRcVO confirmed the respiratory pulsations at the eye surface and retina. We conclude that in addition to the known cardiovascular pulsation, the human eye also has respiratory and vasomotor pulsation mechanisms, which are now amenable to study using non-invasive multimodal imaging of eye fluidics.

Abstract Background The objectives of this study were to compare oral frailty (OFr) among edentate and dentate older adults living in long-term care facilities (LTCF) and to clarify how edentulism and oral disease burden (ODB) of dentate older adults are associated with OFr. Methods The population of this study comprised 94 edentate and 209 dentate residents in LTCF in Helsinki, Finland, who had previously participated in a nutritional study. The participants underwent a clinical oral examination. The dentate residents were further divided into three ODB groups based on asymptotic dental score. The edentate and different ODB groups were compared with each other regarding demographics and oral and medical findings. OFr was defined as ≥ 2 of following: having a diet of soft/pureed food, residue of food in the oral cavity, inability to keep the mouth open during examination, unclearness of speech, dry mouth. The association between OFr and edentulousness and various levels of ODB was analyzed by a multivariate logistic model. Results Participants with low ODB had significantly less OFr than their edentate peers (p = 0.009). Furthermore, the edentate and dentate with high ODB had similar odds for OFr. Conclusions Edentulousness and high ODB are equally harmful conditions and may predispose to OFr. This study suggests that maintaining healthy natural teeth and good oral health (low ODB) may protect against OFr. Trial registration The Ethics Committee of the Hospital District of Helsinki and Uusimaa approved the protocols for the nutritional status and oral healthcare studies and the merging of the data, including patient medical records (Register number HUS/968/2017).

This systematic literature review employs the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to investigate recent applications of explainable AI (XAI) over the past three years. From an initial pool of 664 articles identified through the Web of Science database, 512 peer-reviewed journal articles met the inclusion criteria—namely, being recent, high-quality XAI application articles published in English—and were analyzed in detail. Both qualitative and quantitative statistical techniques were used to analyze the identified articles: qualitatively by summarizing the characteristics of the included studies based on predefined codes, and quantitatively through statistical analysis of the data. These articles were categorized according to their application domains, techniques, and evaluation methods. Health-related applications were particularly prevalent, with a strong focus on cancer diagnosis, COVID-19 management, and medical imaging. Other significant areas of application included environmental and agricultural management, industrial optimization, cybersecurity, finance, transportation, and entertainment. Additionally, emerging applications in law, education, and social care highlight XAI’s expanding impact. The review reveals a predominant use of local explanation methods, particularly SHAP and LIME, with SHAP being favored for its stability and mathematical guarantees. However, a critical gap in the evaluation of XAI results is identified, as most studies rely on anecdotal evidence or expert opinion rather than robust quantitative metrics. This underscores the urgent need for standardized evaluation frameworks to ensure the reliability and effectiveness of XAI applications. Future research should focus on developing comprehensive evaluation standards and improving the interpretability and stability of explanations. These advancements are essential for addressing the diverse demands of various application domains while ensuring trust and transparency in AI systems.

Background/Objectives: Many older adults living in long-term care (LTC) environments have varying numbers of retained natural teeth. The objective of this study was to assess the disease findings based on tooth type and estimate the role of tooth types in occlusion. Methods: We conducted clinical oral examinations of 276 LTC residents. The disease findings were analyzed for each tooth type and to determine their associations with dementia. Results: In total, 67.8% of the participants had molar teeth. Premolars/canines were often present as residual roots and had caries. Deepened periodontal pockets and higher plaque index (PI) values for molars had odds ratios of 2.5 (95% confidence interval [CI] of 1.59–3.91) and 1.61 (95% CI of 1.29–2.02), respectively. Participants with dementia were more likely to have incisors and premolars/canines in the form of root remnants and higher PI scores for all tooth types (p ≤ 0.01), as well as more deepened periodontal pockets in all teeth (p = 0.029), than those without dementia. The median number of remaining molars per participant was 3 out of a maximum of 12 (95% CI 3.4–4.0); thus, they often lacked occlusal contact. Conclusions: The LTC residents’ molars were more prone to periodontal problems, whereas their premolars/canines often had caries or were present in the form of root remnants, especially in the participants with dementia. People’s teeth should be treated in an easy-to-maintain way before they move into LTC to enable daily oral hygiene measures and maintain oral health.

Background: Measurement of students' self-regulation skills is an active topic in education research, as effective assessment helps devising support interventions to foster academic achievement. Measures based on event tracing usually require large amounts of data (e.g., MOOCs and large courses), while aptitude measures are often qualitative and need careful interpretation. Precise and interpretable evaluation of self-regulation skills in a normal K-12 classroom thus poses a challenge. Objectives: The present study proposes and explores a learning analytics method of combining aptitude and event measures to evaluate student's self-regulation skills. Methods: An explorative learning analytics study was conducted in a junior high school mathematics class (N = 20 students), using a three-lesson intervention with digital learning materials. Students first assessed their self-regulation skills with a self-report questionnaire, after which trace logs and observations of student behaviour were collected. Learning sessions were extracted from trace logs, clustered, and linked to learning strategies. Students were clustered by the self-report results and learning behaviour profiles. Session clusters, student behaviour clusters and assignment grades were also tested for association. Results and Conclusions: The detected session and student behaviour types were linked to learning tactics and strategies found in prior studies. Additionally, association was found between self-reported self-regulation skills and the student behaviour obtained from trace logs. Implications: The results demonstrate the feasibility of concurrently using aptitude and event measures on a classroom scale, providing teachers with a tool to evaluate and support self-regulated learning. Combined with further measures like predictive learning analytics, teachers can obtain an early and highly interpretable picture of at-risk students in their classes.