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Annals of Vascular Diseases Jun 2024Hereditary aortic aneurysms and dissections, such as Marfan syndrome, differ in that they occur in younger patients without generally recognized risk factors, have a... (Review)
Review
Hereditary aortic aneurysms and dissections, such as Marfan syndrome, differ in that they occur in younger patients without generally recognized risk factors, have a predilection for the thoracic rather than the abdominal aorta, and are at risk for dissection even at smaller aortic diameters. Early diagnosis, careful follow-up, and early intervention, such as medication to reduce aortic root growth and prophylactic aortic replacement to prevent fatal aortic dissection, are essential for a better prognosis. Molecular genetic testing is extremely useful for early diagnosis. However, in actual clinical practice, the question often arises as to when and to which patient genetic testing should be offered since the outcome of the tests can have important implications for the patient and the relatives. Pre- and post-test genetic counseling is essential for early intervention to be effective. (This article is a secondary translation of Jpn J Vasc Surg 2023; 32: 261-267.).
PubMed: 38919319
DOI: 10.3400/avd.ra.24-00013 -
Annals of Vascular Diseases Jun 2024A 79-year-old man underwent 1-debranched thoracic endovascular aortic repair (TEVAR) for a saccular aneurysm of the distal arch of the aorta. Computed tomography...
A 79-year-old man underwent 1-debranched thoracic endovascular aortic repair (TEVAR) for a saccular aneurysm of the distal arch of the aorta. Computed tomography performed 3 years after surgery revealed a significant displacement of the distal side of the stent graft and severe deformity due to displacement of the aorta. There were no obvious findings after aortic dissection. Endovascular treatment was selected, and surgery was performed semiemergency. Additional TEVAR was performed to restore the aortic shape and displacement to its normal position.
PubMed: 38919318
DOI: 10.3400/avd.cr.23-00081 -
Plant Communications Jun 2024Genome-wide association study (GWAS) identifies trait-associated loci, but due in part to slow decay of linkage disequilibrium (LD), identifying the causal genes can be...
Genome-wide association study (GWAS) identifies trait-associated loci, but due in part to slow decay of linkage disequilibrium (LD), identifying the causal genes can be a bottleneck. Transcriptome-wide association study (TWAS) addresses this by identifying gene expression-phenotype associations or integrating gene expression quantitative trait loci (eQTLs) with GWAS results. Here, we used self-pollinated soybean (Glycine max [L.] Merr.) as a model to evaluate the application of TWAS in the genetic dissection of traits in plant species with slow LD decay. We generated RNA-Seq data of a soybean diversity panel, and identified the genetic expression regulation of 29,286 genes in soybean. Different TWAS solutions were less affected by LD and robust with source of expression that identified known genes related to traits from different development stages and tissues. A novel gene named pod color L2 was identified via TWAS and functionally validated by genome editing. By introducing the new exon proportion feature, we significantly improved the detection of expression variations resulting from structural variations and alternative splicing. As a result, the genes identified by our TWAS approach exhibited a diverse range of causal variations, including SNP, insertion/deletion, gene fusion, copy number variation, and alternative splicing. Using our TWAS approach, we identified genes associated with flowering time, including both previously known genes and novel genes that had not previously linked to this trait before, providing complementary insights with GWAS. In summary, this study supports the application of TWAS for candidate gene identification in species with low rates of LD decay.
PubMed: 38918950
DOI: 10.1016/j.xplc.2024.101010 -
Journal of Cardiothoracic Surgery Jun 2024A bronchopleural fistula (BPF) occurs when an abnormal connection forms between the bronchial tubes and pleural cavity, often due to surgery, infection, trauma,...
BACKGROUND
A bronchopleural fistula (BPF) occurs when an abnormal connection forms between the bronchial tubes and pleural cavity, often due to surgery, infection, trauma, radiation, or chemotherapy. The outcomes of both surgical and bronchoscopic treatments frequently prove to be unsatisfactory.
CASE PRESENTATION
Here, we report a case of successful bronchoscopic free fat pad transplantation combined with platelet-rich plasma, effectively addressing a post-lobectomy BPF. Contrast-enhanced chest tomography revealed pleural thickening with heterogeneous consolidations over the right upper and middle lobes, indicative of destructive lung damage and bronchiectasis. The patient underwent thoracoscopic bilobectomy of the lungs. During surgery, severe adhesions and calcification of the chest wall and lung parenchyma were observed. The entire hilar structure was calcified, presenting challenges for dissection, despite the assistance of energy devices. Bronchoscopic intervention was required, during which two abdominal subcutaneous fat pads were retrieved.
CONCLUSION
This innovative approach offers promise in the management of BPF and signals potential advancements in enhancing treatment efficacy and patient recovery.
Topics: Humans; Bronchial Fistula; Pleural Diseases; Bronchoscopy; Platelet-Rich Plasma; Male; Adipose Tissue; Middle Aged; Pneumonectomy
PubMed: 38918864
DOI: 10.1186/s13019-024-02900-x -
Journal of Cardiothoracic Surgery Jun 2024Pleural solitary fibrous tumors (pSFTs) are rare mesenchymal pleural tumors with rich vascularity. Surgical resection is the cornerstone of pSFTs treatment, requiring...
BACKGROUND
Pleural solitary fibrous tumors (pSFTs) are rare mesenchymal pleural tumors with rich vascularity. Surgical resection is the cornerstone of pSFTs treatment, requiring careful preoperative imaging to delineate lesion extent and vascular supply including contrast-enhanced computed tomography and other examinations depending on its size and characteristics.
CASE PRESENTATION
The patient was a 34-year-old female with a mass measuring approximately 67 × 42 × 65 mm in the left posterior mediastinum. Intraoperatively, the mass demonstrated rich vascularity. Two veins originating from the abdominal cavity entered the lower pole, one converged from the superior pole, draining into the brachiocephalic vein. Additionally, two arteries arose directly from the descending aorta, while several veins drained into the intercostal veins. In response to unexpected intraoperative vascular findings, vascular clips and silk threads were used to ligate them. Subsequently, the tumor was successfully dissected, with approximately 600 ml of blood loss recorded during the 4-hour surgery. The patient exhibited a satisfactory postoperative recovery, and follow-up spanning over six months revealed no indications of recurrence or metastasis.
CONCLUSIONS
We firstly present a case of successful resection of a pSFT in a 34-year-old woman with a distinct feeding vessel arising from the descending aorta and describe the related surgical procedures. This case highlights preoperative evaluation of mass vascularity based on contrast-enhanced computed tomography. When blood supply is challenging to clarify, angiography can offer additional details, especially for giant pSFTs. Despite this, thorough intraoperative exploration remains essential to detect unexpected vessels. Appropriate interventions should be customized based on the vascular origins and the surrounding anatomical structures.
Topics: Humans; Female; Adult; Aorta, Thoracic; Solitary Fibrous Tumor, Pleural; Tomography, X-Ray Computed
PubMed: 38918857
DOI: 10.1186/s13019-024-02872-y -
Scientific Reports Jun 2024Early-life exposure to environmental toxicants like Benzo[a]pyrene (BaP) is associated with several health consequences in vertebrates (i.e., impaired or altered...
Early-life exposure to environmental toxicants like Benzo[a]pyrene (BaP) is associated with several health consequences in vertebrates (i.e., impaired or altered neurophysiological and behavioral development). Although toxicant impacts were initially studied relative to host physiology, recent studies suggest that the gut microbiome is a possible target and/or mediator of behavioral responses to chemical exposure in organisms, via the gut-brain axis. However, the connection between BaP exposure, gut microbiota, and developmental neurotoxicity remains understudied. Using a zebrafish model, we determined whether the gut microbiome influences BaP impacts on behavior development. Embryonic zebrafish were treated with increasing concentrations of BaP and allowed to grow to the larval life stage, during which they underwent behavioral testing and intestinal dissection for gut microbiome profiling via high-throughput sequencing. We found that exposure affected larval zebrafish microbiome diversity and composition in a manner tied to behavioral development: increasing concentrations of BaP were associated with increased taxonomic diversity, exposure was associated with unweighted UniFrac distance, and microbiome diversity and exposure predicted larval behavior. Further, a gnotobiotic zebrafish experiment clarified whether microbiome presence was associated with BaP exposure response and behavioral changes. We found that gut microbiome state altered the relationship between BaP exposure concentration and behavioral response. These results support the idea that the zebrafish gut microbiome is a determinant of the developmental neurotoxicity that results from chemical exposure.
Topics: Animals; Zebrafish; Benzo(a)pyrene; Gastrointestinal Microbiome; Behavior, Animal; Larva
PubMed: 38918492
DOI: 10.1038/s41598-024-65610-3 -
Scientific Reports Jun 2024Aspect-Based Sentiment Analysis (ABSA) represents a fine-grained approach to sentiment analysis, aiming to pinpoint and evaluate sentiments associated with specific...
Aspect-Based Sentiment Analysis (ABSA) represents a fine-grained approach to sentiment analysis, aiming to pinpoint and evaluate sentiments associated with specific aspects within a text. ABSA encompasses a set of sub-tasks that together facilitate a detailed understanding of the multifaceted sentiment expressions. These tasks include aspect and opinion terms extraction (ATE and OTE), classification of sentiment at the aspect level (ALSC), the coupling of aspect and opinion terms extraction (AOE and AOPE), and the challenging integration of these elements into sentiment triplets (ASTE). Our research introduces a comprehensive framework capable of addressing the entire gamut of ABSA sub-tasks. This framework leverages the contextual strengths of BERT for nuanced language comprehension and employs a biaffine attention mechanism for the precise delineation of word relationships. To address the relational complexity inherent in ABSA, we incorporate a Multi-Layered Enhanced Graph Convolutional Network (MLEGCN) that utilizes advanced linguistic features to refine the model's interpretive capabilities. We also introduce a systematic refinement approach within MLEGCN to enhance word-pair representations, which leverages the implicit outcomes of aspect and opinion extractions to ascertain the compatibility of word pairs. We conduct extensive experiments on benchmark datasets, where our model significantly outperforms existing approaches. Our contributions establish a new paradigm for sentiment analysis, offering a robust tool for the nuanced extraction of sentiment information across diverse text corpora. This work is anticipated to have significant implications for the advancement of sentiment analysis technology, providing deeper insights into consumer preferences and opinions for a wide range of applications.
PubMed: 38918461
DOI: 10.1038/s41598-024-61886-7 -
Nature Communications Jun 2024Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype...
Large national-level electronic health record (EHR) datasets offer new opportunities for disentangling the role of genes and environment through deep phenotype information and approximate pedigree structures. Here we use the approximate geographical locations of patients as a proxy for spatially correlated community-level environmental risk factors. We develop a spatial mixed linear effect (SMILE) model that incorporates both genetics and environmental contribution. We extract EHR and geographical locations from 257,620 nuclear families and compile 1083 disease outcome measurements from the MarketScan dataset. We augment the EHR with publicly available environmental data, including levels of particulate matter 2.5 (PM), nitrogen dioxide (NO), climate, and sociodemographic data. We refine the estimates of genetic heritability and quantify community-level environmental contributions. We also use wind speed and direction as instrumental variables to assess the causal effects of air pollution. In total, we find PM or NO have statistically significant causal effects on 135 diseases, including respiratory, musculoskeletal, digestive, metabolic, and sleep disorders, where PM and NO tend to affect biologically distinct disease categories. These analyses showcase several robust strategies for jointly modeling genetic and environmental effects on disease risk using large EHR datasets and will benefit upcoming biobank studies in the era of precision medicine.
Topics: Humans; Air Pollution; Particulate Matter; Nitrogen Dioxide; Risk Factors; Environmental Exposure; Male; Female; Electronic Health Records; Air Pollutants; Genetic Predisposition to Disease; Gene-Environment Interaction; Middle Aged; Adult
PubMed: 38918381
DOI: 10.1038/s41467-024-49566-6 -
Acta Neuropathologica Jun 2024Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human...
Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APP mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator.
Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell (iPSC)-derived neurons carrying the familial AD APP mutation after cell injection into the mouse forebrain. APP mutant iPSCs and isogenic controls were differentiated into neurons revealing enhanced Aβ production, elevated phospho-tau, and impaired neurite outgrowth in APP neurons. Two months after transplantation, APP and control neural cells showed robust engraftment but at 12 months post-injection, APP grafts were smaller and demonstrated impaired neurite outgrowth compared to controls, while plaque and tangle pathology were not seen. Single-nucleus RNA-sequencing of micro-dissected grafts, performed 2 months after cell injection, identified significantly altered transcriptome signatures in APP iPSC-derived neurons pointing towards dysregulated synaptic function and axon guidance. Interestingly, APP neurons showed an increased expression of genes, many of which are also upregulated in postmortem neurons of AD patients including the transmembrane protein LINGO2. Downregulation of LINGO2 in cultured APP neurons rescued neurite outgrowth deficits and reversed key AD-associated transcriptional changes related but not limited to synaptic function, apoptosis and cellular senescence. These results provide important insights into transcriptional dysregulation in xenografted APP neurons linked to synaptic function, and they indicate that LINGO2 may represent a potential therapeutic target in AD.
Topics: Humans; Induced Pluripotent Stem Cells; Alzheimer Disease; Neurons; Transcriptome; Animals; Amyloid beta-Protein Precursor; Mice; Nerve Tissue Proteins; Mutation; Membrane Proteins; Synapses; Amyloid beta-Peptides; Signal Transduction
PubMed: 38918213
DOI: 10.1007/s00401-024-02755-5 -
The Korean Journal of Gastroenterology... Jun 2024This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent...
This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent dysphagia. The cause was initially diagnosed as a 10 cm pedunculated lesion extending from the upper esophageal sphincter to the mid-esophagus. An ESD was chosen over traditional surgery because it is less invasive. The procedure involved a precise submucosal injection and excision with special techniques to manage bleeding from a central vessel. Despite the extraction challenges owing to the size of the lesion, it was successfully removed orally. A histopathological examination of the 8.3×4.2×2.3 cm specimen revealed the characteristic features of a well-differentiated liposarcoma, including MDM2 and CDK4 positivity. The follow-up revealed no recurrence, and active surveillance has been performed since. This report highlights the versatility of ESD in treating significant esophageal tumors and provides evidence for its efficacy as a minimally invasive alternative.
Topics: Humans; Male; Esophageal Neoplasms; Middle Aged; Endoscopic Mucosal Resection; Liposarcoma; Tomography, X-Ray Computed; Cyclin-Dependent Kinase 4; Proto-Oncogene Proteins c-mdm2; Esophagoscopy
PubMed: 38918037
DOI: 10.4166/kjg.2024.047