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The development of comprehensive picture archive and communication systems (PACS) has mainly been limited to proprietary developments by vendors, though a number of freely available software projects have addressed specific image management tasks. The openSourcePACS project aims to provide an open source, common foundation upon which not only can a basic PACS be readily implemented, but to also support the evolution of new PACs functionality through the development of novel imaging applications and services. open Source PACS consists of four main software modules: 1) image order entry, which enables the ordering and tracking of structured image requisitions; 2) an agent-based image server framework that coordinates distributed image services including routing, image processing, and querying beyond the present digital image and communications in medicine (DICOM) capabilities; 3) an image viewer, supporting standard display and image manipulation tools, DICOM presentation states, and structured reporting; and 4) reporting and result dissemination, supplying web-based widgets for creating integrated reports. All components are implemented using Java to encourage cross-platform deployment. To demonstrate the usage of openSourcePACS, a preliminary application supporting primary care/specialist communication was developed and is described herein. Ultimately, the goal of openSourcePACS is to promote the wide-scale development and usage of PACS and imaging applications within academic and research communities.

BACKGROUND: The Japanese Red Cross (JRC) implemented a fully automated pooling and nucleic acid amplification test (NAT) system for testing seronegative donations. The JRC sample repository and repeat blood donations allowed for lookback and follow-up studies of hepatitis B virus (HBV) DNA-positive donors, who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antigen in the JRC screening system. STUDY DESIGN AND METHODS: From February 1, 2000, to March 31, 2003, 17,314,486 units were tested in 50-sample pools with a semiautomated multiplex assay system (AMPLINAT MPX test, Roche). During this period, 328 HBV DNA-positive donations were found. From 26 of these donors, sequential samples were available at short intervals. This enabled us to examine the dynamics of viral markers in acute HBV infection. The length of detectable periods of plasma viremia and antigenemia were estimated by regression analysis from the results obtained in the quantitative polymerase chain reaction assay (JRC) and HBsAg enzyme immunoassay (Auszyme II, AxSYM, Abbott) and chemiluminescence immunoassay (Abbott). RESULTS: The median length of detectable HBV DNA in individual donation and 20-sample minipool (MP) NAT format was estimated to be 74 and 50 days, respectively, whereas the median length of detectable HBsAg was estimated to be 42 days. Six of the 26 donors were infected with mutant viruses, and 3 of these 6 donors did not develop detectable HBsAg during the entire observation period, despite a moderately high viral load of 10(4) to 10(5) HBV DNA copies per mL. CONCLUSION: Transmission of mutant virus may cause occult HBV infection in the acute stage. HBV NAT, even in MP configuration, is more effective than HBsAg testing and capable of interdicting infected donors in the pre- and post-HBsAg window periods. [ABSTRACT FROM AUTHOR]

An autism-associated gene Shank3 encodes multiple splicing isoforms, Shank3a-f. We have recently reported that Shank3a/b-knockout mice were more susceptible to kainic acid-induced seizures than wild-type mice at 4 weeks of age. Little is known, however, about how the N-terminal and ankyrin repeat domains (NT-Ank) of Shank3a/b regulate multiple molecular signals in the developing brain. To explore the functional roles of Shank3a/b, we performed a mass spectrometry-based proteomic search for proteins interacting with GFP-tagged NT-Ank. In this study, NT-Ank was predicted to form a variety of complexes with a total of 348 proteins, in which RNA-binding (n = 102), spliceosome (n = 22), and ribosome-associated molecules (n = 9) were significantly enriched. Among them, an X-linked intellectual disability-associated protein, Nono, was identified as a NT-Ank-binding protein. Coimmunoprecipitation assays validated the interaction of Shank3 with Nono in the mouse brain. In agreement with these data, the thalamus of Shank3a/b-knockout mice aberrantly expressed splicing isoforms of autism-associated genes, Nrxn1 and Eif4G1, before and after seizures with kainic acid treatment. These data indicate that Shank3 interacts with multiple RNA-binding proteins in the postnatal brain, thereby regulating the homeostatic expression of splicing isoforms for autism-associated genes after birth., (© 2024 The Author(s). Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

GNAO1 encodes G protein subunit alpha O1 (Gαo). Pathogenic variations in GNAO1 cause developmental delay, intractable seizures, and progressive involuntary movements from early infancy. Because the functional role of GNAO1 in the developing brain remains unclear, therapeutic strategies are still unestablished for patients presenting with GNAO1-associated encephalopathy. We herein report that siRNA-mediated depletion of Gnao1 perturbs the expression of transcripts associated with Rho GTPase signaling in Neuro2a cells. Consistently, siRNA treatment hampered neurite outgrowth and extension. Growth cone formation was markedly disrupted in monolayer neurons differentiated from iPSCs from a patient with a pathogenic variant of Gαo (p.G203R). This variant disabled neuro-spherical assembly, acquisition of the organized structure, and polarized signals of phospho-MLC2 in cortical organoids from the patient's iPSCs. We confirmed that the Rho kinase inhibitor Y27632 restored these morphological phenotypes. Thus, Gαo determines the self-organizing process of the developing brain by regulating the Rho-associated pathway. These data suggest that Rho GTPase pathway might be an alternative target of therapy for patients with GNAO1-associated encephalopathy., (© 2024. The Author(s).)

Pathogenic variants in ATP1A3, the gene encoding the α3 subunit of the Na+/K+-ATPase, cause alternating hemiplegia of childhood (AHC) and related disorders. Impairments in Na+/K+-ATPase activity are associated with the clinical phenotype. However, it remains unclear whether additional mechanisms are involved in the exaggerated symptoms under stressed conditions in patients with AHC. We herein report that the intracellular loop (ICL) of ATP1A3 interacted with RNA-binding proteins, such as Eif4g (encoded by Eif4g1), Pabpc1 and Fmrp (encoded by Fmr1), in mouse Neuro2a cells. Both the siRNA-mediated depletion of Atp1a3 and ectopic expression of the p.R756C variant of human ATP1A3-ICL in Neuro2a cells resulted in excessive phosphorylation of ribosomal protein S6 (encoded by Rps6) and increased susceptibility to heat stress. In agreement with these findings, induced pluripotent stem cells (iPSCs) from a patient with the p.R756C variant were more vulnerable to heat stress than control iPSCs. Neurons established from the patient-derived iPSCs showed lower calcium influxes in responses to stimulation with ATP than those in control iPSCs. These data indicate that inefficient protein synthesis contributes to the progressive and deteriorating phenotypes in patients with the p.R756C variant among a variety of ATP1A3-related disorders., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Objective: This study aims to facilitate the creation of quality standardized nursing statements in South Korea's hospitals using algorithmic generation based on the International Classifications of Nursing Practice (ICNP) and evaluation through Large Language Models., Materials and Methods: We algorithmically generated 15 972 statements related to acute respiratory care using 117 concepts and concept composition models of ICNP. Human reviewers, Generative Pre-trained Transformers 4.0 (GPT-4.0), and Bio_Clinical Bidirectional Encoder Representations from Transformers (BERT) evaluated the generated statements for validity. The evaluation by GPT-4.0 and Bio_ClinicalBERT was conducted with and without contextual information and training., Results: Of the generated statements, 2207 were deemed valid by expert reviewers. GPT-4.0 showed a zero-shot  AUC of 0.857, which aggravated with contextual information. Bio_ClinicalBERT, after training, significantly improved, reaching an AUC of 0.998., Conclusion: Bio_ClinicalBERT effectively validates auto-generated nursing statements, offering a promising solution to enhance and streamline healthcare documentation processes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50-deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function.

Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14 high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) are a promising cell source for regenerative medicine and drug discovery. However, the use of animal models for studying human cardiomyocytes derived from hiPSCs in vivo is limited and challenging. Given the shared properties between humans and zebrafish, their ethical advantages over mammalian models, and their immature immune system that is rejection-free against xenografted human cells, zebrafish provide a suitable alternative model for xenograft studies. We microinjected fluorescence-labeled cardiac lineage cells derived from hiPSCs, specifically mesoderm or cardiac mesoderm cells, into the yolk and the area proximal to the outflow tract of the linear heart at 24 hours post-fertilization (hpf). The cells injected into the yolk survived and did not migrate to other tissues. In contrast, the cells injected contiguous with the outflow tract of the linear heart migrated into the pericardial cavity and heart. After 1 day post injection (1 dpi, 22-24 hpi), the injected cells migrated into the pericardial cavity and heart. Importantly, we observed heartbeat-like movements of some injected cells in the zebrafish heart after 1 dpi. These results suggested successful xenografting of hiPSC-derived cardiac lineage cells into the zebrafish embryo heart. Thus, we developed a valuable tool using zebrafish embryos as a model organism for investigating the molecular and cellular mechanisms involved in the grafting process. This is essential in developing cell transplantation-based cardiac therapeutics as well as for drug testing, notably contributing to advancements in the field of cardio-medicine., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kiyoshi Ohnuma reports financial support was provided by Japan Society for the Promotion of Science. Chinmoy Patra reports financial support was provided by Japan Society for the Promotion of Science. Mika Takahi reports financial support was provided by Nagaoka University of Technology Development Education Research Promotion Association., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Epileptic seizures are distinct but frequent comorbidities in children with autism spectrum disorder (ASD). The hyperexcitability of cortical and subcortical neurons appears to be involved in both phenotypes. However, little information is available concerning which genes are involved and how they regulate the excitability of the thalamocortical network. In this study, we investigate whether an ASD-associated gene, SH3 and multiple ankyrin repeat domains 3 (Shank3), plays a unique role in the postnatal development of thalamocortical neurons. We herein report that Shank3a/b, the splicing isoforms of mouse Shank3, were uniquely expressed in the thalamic nuclei, peaking from two to four weeks after birth. Shank3a/b-knockout mice showed lower parvalbumin signals in the thalamic nuclei. Consistently, Shank3a/b-knockout mice were more susceptible to generalized seizures than wild-type mice after kainic acid treatments. Together, these data indicate that NT-Ank domain of Shank3a/b regulates molecular pathways that protect thalamocortical neurons from hyperexcitability during the early postnatal period of mice., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

The blood-brain barrier (BBB), which is comprised of brain capillary endothelial cells, plays a pivotal role in the transport of drugs from the blood to the brain. Therefore, an analysis of proteins in the endothelial cells, such as transporters and tight junction proteins, which contribute to BBB function, is important for the development of therapeutics for the treatment of brain diseases. However, gene transfection into the vascular endothelial cells of the BBB is fraught with difficulties, even in vitro. We report herein on the development of lipid nanoparticles (LNPs), in which mRNA is encapsulated in a nano-sized capsule composed of a pH-activated and reductive environment-responsive lipid-like material (ssPalm). We evaluated the efficiency of mRNA delivery into non-polarized human brain capillary endothelial cells, hCMEC/D3 cells. The ssPalm LNPs permitted marker genes (GFP) to be transferred into nearly 100% of the cells, with low toxicity in higher concentration. A proteomic analysis indicated that the ssPalm-LNP had less effect on global cell signaling pathways than a Lipofectamine MessengerMAX/GFP-encoding mRNA complex (LFN), a commercially available transfection reagent, even at higher mRNA concentrations.