Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Characterization of Pediatric Mixed Phenotype Acute Leukemia (MPAL)

Abstract Background/Aim: Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy in which the leukemic cells cannot be assigned to any specific lineage. The lack of well-defined, pathogenetically relevant diagnostic criteria makes the clinical handling of MPAL patients challenging. We herein report the genetic findings in bone marrow cells from two pediatric MPAL patients. Patients and Methods: Bone marrow cells were examined using G-banding, array comparative genomic hybridization, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization. Results: In the first patient, the genetic analyses revealed structural aberrations of chromosomal bands 8p11, 10p11, 11q21, and 17p11, the chimeras MLLT10::PICALM and PICALM::MLLT10, and imbalances (gains/losses) on chromosomes 2, 4, 8, 13, and 21. A submicroscopic deletion in 21q was also found including the RUNX1 locus. In the second patient, there were structural aberrations of chromosome bands 1p32, 8p11, 12p13, 20p13, and 20q11, the chimeras ETV6::LEXM and NCOA6::ETV6, and imbalances on chromosomes 2, 8, 11, 12, 16, 19, X, and Y. Conclusion: The leukemic cells from both MPAL patients carried chromosome aberrations resulting in fusion genes as well as genomic imbalances resulting in gain and losses of many gene loci. The detected fusion genes probably represent the main leukemogenic events, although the gains and losses are also likely to play a role in leukemogenesis.
Bottom-Up Analysis of Telemonitoring Costs: A Case Study in Slovenian Primary Care

ABSTRACT Introduction Telemonitoring improves clinical outcomes in patients with arterial hypertension (AH) and type 2 diabetes (T2D), however, cost structure analyses are lacking. This study seeks to explore the cost structure of telemonitoring for the elderly with AH and T2D in primary care and identify factors influencing costs for potential future expansions. Methods Infrastructure, operational, patient participation, and out-of-pocket costs were determined using a bottom-up approach. Infrastructure costs were determined by dividing equipment and telemonitoring platform expenses by the number of participants. Operational and patient participation costs were determined by considering patient training time, data measurement/review time, and teleconsultation time. The change in out-of-pocket costs was assessed in both groups using a structured questionnaire and 12-month expenditure data. Statistical analysis employed an unpaired sample t-test, Mann-Whitney U test, and chi-square test. Results A total of 117 patients aged 71.4±4.7 years were included in the study. The telemonitoring intervention incurred an annual infrastructure costs of €489.4 and operational costs of €97.3 (95% CI 85.7-109.0) per patient. Patient annual participation costs were €215.6 (95% CI 190.9-241.1). Average annual out-of-pocket costs for both groups were €345 (95% CI 221-469). After 12 months the telemonitoring group reported significantly lower out-of-pocket costs (€132 vs. €545, p<0.001), driven by reduced spending on food, dietary supplements, medical equipment, and specialist check-ups compared to the standard care group. Conclusion To optimise the cost structure of telemonitoring, strategies like shortening the telemonitoring period, developing a national telemonitoring platform, using patient devices, integrating artificial intelligence into platforms, and involving nurse practitioners as telemedicine centre coordinators should be explored.
Prediction in SVO and SOV languages: processing and typological considerations

Abstract In this study, we tested the possibility that different word orders engender different processing preferences. Our key hypothesis was that a head-initial language like English (SVO) allows more prediction compared to a head-final language like Japanese (SOV). In Experiment 1, English and Japanese native speakers completed a cloze task in which they heard a sentence fragment (SV_ in English and SO_ in Japanese) and had to complete it with the word they thought best. We assessed cloze probability of the words produced and voice onset times. Experiment 2 examined written completions in English, in which we compared the cloze probabilities in SV_ fragments versus OS_ fragments. Following the central hypothesis, this experiment allowed us to determine (within language) whether there is more prediction from a noun and verb compared to two nouns. Finally, in Experiment 3, we compared written completions in English and Japanese, in which the stimuli given to participants were identical (SV_ in English and S_V in Japanese). Results across all three experiments were consistent with greater prediction in English. We argue that prediction is one important factor in processing, that it is relied on more in English than in Japanese, and that prediction will be especially favored in languages like English in which the verb regularly precedes its direct object.
Validation of the Slovene Version of the Stop-Bang Questionnaire in a Primary Practice Setting

ABSTRACT Aim The aim of our study was to validate the Slovene translation of the STOP-BANG (SBQ) questionnaire for use in the primary practice setting. Methods We recruited 158 randomly selected visitors at four primary practice clinics who came to the practice for any reason. Participants completed the Slovene SBQ and underwent type 3 respiratory polygraphy, which was analysed by an experienced somnologist. The SBQ was previously translated in to Slovene and validated for the sleep clinic. Results Of 158 participants, 153 had valid recordings. The mean age of the participants was 49.5 years (±13.0 years), and 47.7% were male. OSA was identified in 49.0% of the participants. The questionnaire, with a cutoff of ≥3, demonstrated an area under the curve of 0.823 for any OSA (REI≥5), 0.819 for moderate and severe OSA (REI≥15) and 0.847 for severe OSA (REI≥30). Sensitivity was 65.3%, 81.8%, and 90.0%, and specificity was 87.2%, 73.3% and 65.0% for any, moderate to severe and severe OSA, respectively. Conclusions The Slovene translation of the SBQ is a reliable instrument for OSA risk stratification in the primary practice setting.
Interprofessional Education with Simulations in Primary Care

ABSTRACT The introduction of interprofessional primary care (IPC) as a model of collaborative patient care is increasingly vital in the context of complex healthcare systems and the growing needs of patients. Its benefits include improved patient outcomes, enhanced efficiency, and reduced costs. However, the successful implementation of IPC faces challenges due to the differences in training and backgrounds among healthcare professionals, emphasising the importance of effective teamwork and collaborative education. Educational approaches utilising simulations have gained prominence, particularly in addressing the challenges of interprofessional primary care. Notably, simulations facilitate team learning, enhancing team management and confidence, which ultimately leads to improved performance in real-life scenarios. They also contribute to patient safety by providing comprehensive training and creating a safe environment for professionals to practice and refine their skills without risking real patient harm. Moreover, simulations promote psychological safety, allowing healthcare workers to manage stress effectively and prepare for critical situations. Ethical considerations are met through simulation-based education, ensuring patient confidentiality, and creating a standardised and just learning environment for all students. Simulations contribute to promoting equity in medical education by providing equal access to high-quality training opportunities for all healthcare professionals. In conclusion, successful IPC implementation requires a comprehensive approach that includes interprofessional education and the integration of simulations as an essential component of the curriculum at all levels of healthcare education. This approach fosters effective communication, teamwork, and confidence among primary care teams, ultimately leading to improved patient care and outcomes.
Dual-branch Multitask Fusion Network for Offline Chinese Writer Identification

Chinese characters are complex and contain discriminative information, meaning that their writers have the potential to be recognized using less text. In this study, offline Chinese writer identification based on a single character was investigated. To extract comprehensive features to model Chinese characters, explicit and implicit information as well as global and local features are of interest. A dual-branch multitask fusion network is proposed which contains two branches for global and local feature extraction simultaneously, and introduces auxiliary tasks to help the main task. Content recognition, stroke number estimation, and stroke recognition are considered as three auxiliary tasks for explicit information. The main task extracts implicit information of writer identity. The experimental results validated the positive influences of auxiliary tasks on the writer identification task, with the stroke number estimation task being most helpful. In-depth research was conducted to investigate the influencing factors in Chinese writer identification, with respect to character complexity, stroke importance, and character number, which provides a systematic reference for the actual application of neural networks in Chinese writer identification.
The Computational Method for Supporting Thai VerbNet Construction

VerbNet is a lexical resource for verbs that has many applications in natural language processing tasks, especially ones that require information about both the syntactic behavior and the semantics of verbs. This paper presents an attempt to construct the first version of a Thai VerbNet corpus via data enrichment of the existing lexical resource. This corpus contains the annotation at both the syntactic and semantic levels, where verbs are tagged with frames within the verb class hierarchy and their arguments are labeled with the semantic role. We discuss the technical aspect of the construction process of Thai VerbNet and survey different semantic role labeling methods to make this process fully automatic. We also investigate the linguistic aspect of the computed verb classes and the results show the potential in assisting semantic classification and analysis. At the current stage, we have built the verb class hierarchy consisting of 28 verb classes from 112 unique concept frames over 490 unique verbs using our association rule learning method on Thai verbs.
Gamification Research Focus in Learning Mathematics

Gamification in the educational process is implementing gaming elements into activities that are usually unrelated to games to increase student motivation and student participation in learning. This study aims to examine the research landscape related to Gamification in mathematics learning from 2013 to 2023. The method used in this research is a literature review with a bibliometric analysis approach using Vosviewer. The Scopus database was used for the literature review, which included 61 documents that met the criteria and were analysed. According to the findings, 2021 was the year with the most Gamification-related publications, and Spain accounted for the most. Spain, United States, Mexico, and Colombia have the most extensive international cooperation on this topic. Based on the cluster displayed, research on Gamification in mathematics learning has some specific focus, namely (1) The integration of ICT and collaboration in digital technology-related projects, (2) the implementation of Gamification in educational settings to increase student engagement and motivation, and (3) serious game as a strategy for learning mathematical concept. The next researcher is advised to look into how well Gamification can improve cognitive abilities and how different Gamification techniques affect students' motivation and academic success on diverse educational levels.
A Research Investigates the Utilization of Single-Beam Sonar Search for Object Recognition of Drowning Incidents in Underwater Environments -Using Tainan City as a Case Study

According to WHO (2021), drowning accounted for 7% of all injury-related deaths and was the third leading cause of unintentional injury deaths worldwide in 2019 [1]. The Fire Department of Tainan City, Taiwan reported that over 50 people drown each year in various bodies of water, with streams (36%), canals (22%), offshore areas (12%), and fish farms (11%) being the most frequent locations. These areas often have poor visibility and are difficult to navigate, making it challenging for lifeboats to be deployed in rescue efforts. Research by Tipton and Golden (2011) has shown that the survival rate of drowning victims is influenced by water temperature, salinity, submersion time, and age. Despite this, current underwater search methods are time-consuming [2]. Thus, there is an urgent need to develop a fast, safe, and effective approach to search for drowning victims in invisible waters. This paper uses observational and experimental methods, employing a telescopic rod and a fishing line to hook a single-beam sonar, to measure and scan underwater images. The objective is to identify different drowning postures and exact underwater positions, and to verify the feasibility of actual underwater search for drowning in the future.
Modulation of the spatiotemporal dynamics of striatal direct pathway neurons and motor output by mGluR5

Striatal spiny projection neurons (SPNs) integrate glutamatergic input from motor cortex and thalamus with various neuromodulatory signals to regulate motor output. In vivo Ca2+ imaging has demonstrated that spatially compact clusters of direct and indirect pathway SPNs (dSPNs and iSPNs) co-activate during spontaneous movement. This co-activity is statistically greater between neurons in close proximity, correlates with the animal’s behavioral state, and could, in part, reflect shared excitatory inputs. However, whether and how synaptic mechanism have a role in generating this distinctive spatiotemporal activity is unknown. Here, we show that the Group I metabotropic glutamate receptor 5 (mGluR5) plays a key role in the formation and regulation of spatially clustered SPN co-activity. Pharmacological modulation of mGluR5 signaling bidirectionally altered movement and spatially clustered dynamics, but not mean activity levels of dSPNs. Targeted deletion of mGluR5 in dSPNs recapitulated the effects on spatiotemporal neural dynamics and movement demonstrating a striatal specific effect of mGluR5. These changes in locomotion and neural ensemble dynamics were also correlated with changes in dSPNs synaptic properties in the cKO mice. Together results suggest excitatory synaptic function influences motor function by shaping the characteristic spatially clustered patterns of co-activity that typify dSPN activation in vivo.
Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade

Metastatic cutaneous melanoma is a fatal skin cancer. Resistance to targeted and immune therapies limits the benefits of current treatments. Identifying and adding anti-resistance agents to current treatment protocols can potentially improve clinical responses. Myocardin-related transcription factor (MRTF) is a transcriptional coactivator whose activity is indirectly regulated by actin and the Rho family of GTPases. We previously demonstrated that development of BRAF inhibitor (BRAFi) resistance frequently activates the Rho/MRTF pathway in human and mouse BRAFV600E melanomas. In clinical trials, pre-treatment with BRAFi reduces the benefit of immune therapies. We aimed to test the efficacy of concurrent treatment with our MRTF pathway inhibitor CCG-257081 and anti-PD1 in vivo and to examine its effects on the melanoma immune microenvironment. Because MRTF pathway activation upregulates the expression of immune checkpoint inhibitor genes/proteins, we asked whether CCG-257081 can improve the response to immune checkpoint blockade. CCG-257081 reduced the expression of PDL1 in BRAFi-resistant melanoma cells and decreased surface PDL1 levels on both BRAFi- sensitive and -resistant melanoma cells. Using our recently described murine vemurafenib-resistant melanoma model, we found that CCG-257081, in combination with anti-PD1 immune therapy, reduced tumor growth and increased survival. Moreover, anti-PD1/CCG-257081 co-treatment increased infiltration of CD8+ T cells and B cells into the tumor microenvironment and reduced tumor-associated macrophages. Here, we propose CCG-257081 as an anti-resistance and immune therapy-enhancing anti-melanoma agent. Novelty and Impact We present a study that provides evidence for a new combined approach for targeting BRAF inhibitor-resistant melanoma. Pharmacological inhibition of the resistance-inducing Rho/MRTF pathway using CCG-257081 enhanced the response to PD1/PDL-1 blockade in vivo. These results indicate a role of the Rho/MRTF pathway in regulating tumor-immune interactions. Thus, CCG-257081 emerges as a potential new anti-resistance agent that can improve the response to immune checkpoint inhibitors in advanced melanoma and, possibly, other cancers.
Phylogenetic distribution and experimental characterization of corrinoid production and dependence in soil bacterial isolates

Soil microbial communities impact carbon sequestration and release, biogeochemical cycling, and agricultural yields. These global effects rely on metabolic interactions that modulate community composition and function. However, the physicochemical and taxonomic complexity of soil and the scarcity of available isolates for phenotypic testing are significant barriers to studying soil microbial interactions. Corrinoids—the vitamin B12 family of cofactors—are critical for microbial metabolism, yet they are synthesized by only a subset of microbiome members. Here, we evaluated corrinoid production and dependence in soil bacteria as a model to investigate the ecological roles of microbes involved in metabolic interactions. We isolated and characterized a taxonomically diverse collection of 161 soil bacteria from a single study site. Most corrinoid-dependent bacteria in the collection prefer B12 over other corrinoids, while all tested producers synthesize B12, indicating metabolic compatibility between producers and dependents in the collection. Furthermore, a subset of producers release B12 at levels sufficient to support dependent isolates in laboratory culture at estimated ratios of up to 1,000 dependents per producer. Within our isolate collection, we did not find strong phylogenetic patterns in corrinoid production or dependence. Upon investigating trends in the phylogenetic dispersion of corrinoid metabolism categories across sequenced bacteria from various environments, we found that these traits are conserved in 47 out of 85 genera. Together, these phenotypic and genomic results provide evidence for corrinoid-based metabolic interactions among bacteria and provide a framework for the study of nutrient-sharing ecological interactions in microbial communities.
An agarose disk electroporation method for ex vivo retinal tissue cultured at the air-liquid interface reveals electrical stimulus-induced cell cycle reentry in retinal cells

It is advantageous to culture the ex vivo murine retina along with many other tissue types at the air-liquid interface. However, gene delivery to these cultures can be challenging. Electroporation is a fast and robust method of gene delivery, but typically requires submergence in a liquid buffer to allow electric current flow. We have developed a submergence-free electroporation technique using that allows for efficient gene delivery to the ex vivo murine retina. This method advances our ability to use ex vivo retinal tissue for genetic studies and can easily be adapted for any tissue cultured at an air-liquid interface. Use of this method has revealed valuable insights on the state of ex vivo retinal tissues and the effects of electrical stimulation on retinal cells. Motivation Tissues cultured at the air-liquid interface, such as retinal tissue, are adhered to a filter membrane with media underneath but not fully submerged. If tissues are fully submerged in liquid, they detach from the membrane and become damaged. Electroporation typically requires tissue submergence for electric current flow. We have developed a submergence-free electroporation method using an agarose disk for electric current delivery that can efficiently and consistently electroporate ex vivo retinal tissue cultured at an air-liquid interface without the need to submerge the tissue and disrupt the culture system.
Trophic microRNA: Precursor and mature microRNA ingestion downregulates the target transcripts and hampers larval development in Plutella xylostella

MicroRNAs (miRNAs) are post-transcriptional gene regulators. In the miRNA pathway’s cytoplasmic part, the miRNA is processed from a hairpin-structured precursor (pre-miRNA) to a double-stranded (ds) mature RNA and ultimately to a single-stranded mature miRNA. In insects, ingesting these two ds forms can regulate the target gene expression; this inspired the trophic miRNA’s use as a functional genomics and pest management tool. However, systematic studies enabling comparisons of pre- and mature forms, dosages, administration times, and instar-wise effects on target transcripts and phenotypes, which can help develop a miRNA administration method, are unavailable due to the different focuses of the previous investigations. We investigated the impact of trophically delivered Px-let-7 miRNA on the Brassicaceae pest, Plutella xylostella, to compare the efficacies of its pre- and ds-mature forms. Continuous feeding on the miRNA-supplemented diet suppressed expressions of FTZ-F1 and E74, the target ecdysone pathway genes. Both the pre-let-7 and mature let-7 miRNA forms similarly downregulated the target transcripts in all four larval instars. Pre-let-7 and let-7 ingestions decreased P. xylostella’s larval mass and instar duration and increased mortality in all instars, exhibiting adverse effects on larval growth and development. Pre-miRNA processing Dicer-1 was upregulated upon pre-let-7 ingestion, indicating the miRNA uptake by the midgut cells. The scrambled sequence controls did not affect the target transcripts, suggesting the sequence-specific targeting by the mature miRNA and hairpin cassette’s non-involvement in the target downregulation. This work provides a framework for miRNA and target gene function analyses and potentiates the trophic miRNA’s utility in pest management.
Chromatin Remodeling and Epigenetic Modifications in Planar Cell Migration

The cell nucleus plays a critical role in cell migration by its deformability under forces, by acting as a piston that activates mechanosensitive channels, and also by serving as a ruler tailoring cell response to spatial constraints. Cell nuclear mechanics determine the mechanobiology of static and migrating cells. Here, we report that intranuclear chromatin architecture plays a previously unknown role during cell migration on planar substrates. By inhibiting histone deacetylation, which compacts chromatin, and a methyltransferase, which affects chromatin remodeling and chromatin compaction, we showed that cell migration speed and persistence drastically slowed wound closure efficiency in an in vitro scratch wound assay. Chromatin remodeling was visualized and quantified during cell migration, which may be intertwined with nuclear mechanics and shape. Inhibition disrupts remodeling and other unknown roles in chromatin, thus affecting the speed and persistence of cell migration. Interestingly, cytoskeletal stress fiber formation and cell shape were not visibly affected by chromatin modifications, suggesting an exclusive nuclear mechanobiological role in cell migration. These findings provide new insights into how aging and other degenerative conditions affect the plasticity of chromatin architecture and hence its effect on cell migration efficiency.