Generation of 3D lacrimal gland organoids from human pluripotent stem cells.

Lacrimal glands are the main exocrine glands of the eyes. Situated within the orbit, behind the upper eyelid and towards the temporal side of each eye, they secrete lacrimal fluid as a major component of the tear film. Here we identify cells with characteristics of lacrimal gland primordia that emerge in two-dimensional eye-like organoids cultured from human pluripotent stem cells1. When isolated by cell sorting and grown under defined conditions, the cells form a three-dimensional lacrimal-gland-like tissue organoid with ducts and acini, enabled by budding and branching. Clonal colony analyses indicate that the organoids originate from multipotent ocular surface epithelial stem cells. The organoids exhibit notable similarities to native lacrimal glands on the basis of their morphology, immunolabelling characteristics and gene expression patterns, and undergo functional maturation when transplanted adjacent to the eyes of recipient rats, developing lumina and producing tear-film proteins.

HyGAnno: hybrid graph neural network-based cell type annotation for single-cell ATAC sequencing data.

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno leverages genome-wide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was assessed across various datasets, showcasing its strengths in precise cell annotation, generating interpretable cell embeddings, robustness to noisy reference data and adaptability to tumor tissues.

Ultrasound-guided genitofemoral nerve block for femoral arterial access gain and closure: a randomized controlled trial.

OBJECTIVES: This study aimed to compare the analgesic efficacy and safety of the femoral branch block of the genitofemoral nerve (FBB) versus local infiltration anesthesia (LIA) for femoral arterial access gain and closure. METHODS: Eighty-two patients (age, 64.8 ± 10.9 years; female, 30.5%) undergoing endovascular procedures using 5-Fr femoral sheath were assigned to either FBB (n = 41) or LIA (n = 41). In both groups, 2% lidocaine HCL with 1:100,000 epinephrine was used as an anesthetic solution. Pain scores during access gain and closure were evaluated using a visual analog scale (score 0-10), patient satisfaction levels with the quality of anesthesia were scored on a 7-point Likert scale, and adverse events were recorded. RESULTS: The primary endpoint, pain scores during access closure, was significantly lower in the FBB group than in the LIA group (0.1 ± 0.37 vs 1.73 ± 0.92; p < 0.001). The FBB group also had significantly lower pain scores during access gain compared to the LIA group (0.83 ± 0.83 vs 2.78 ± 1.26; p < 0.001). There was an inverse relationship between pain scores and FBB after adjustment for age, gender, and body mass index (p < 0.001). FBB group reported significantly higher satisfaction with anesthesia quality compared to the LIA group (6.49 ± 0.64 vs 4.05 ± 1.05; p < 0.001). No complications were recognized in either group. CONCLUSIONS: Ultrasound-guided genitofemoral nerve blocks offered better acute pain relief and higher patient satisfaction than LIA during femoral arterial access gain and closure. CLINICAL RELEVANCE STATEMENT: In this prospective randomized controlled trial, ultrasound-guided genitofemoral nerve blocks offered better acute pain relief than local infiltration anesthesia, resulting in enhanced patient satisfaction. KEY POINTS: • FBB provided better pain relief during access gain and closure than LIA. • FBB offered higher patient satisfaction with the quality of anesthesia than LIA. • No anesthesia-related or access site complications were recognized in either treatment group.

Autonomous Interfacial Assembly of Polymer Nanofilms via Surfactant-Regulated Marangoni Instability.

Interfacial polymerization (IP) provides a versatile platform for fabricating defect-free functional nanofilms for various applications, including molecular separation, energy, electronics, and biomedical materials. Unfortunately, coupled with complex natural instability phenomena, the IP mechanism and key parameters underlying the structural evolution of nanofilms, especially in the presence of surfactants as an interface regulator, remain puzzling. Here, we interfacially assembled polymer nanofilm membranes at the free water-oil interface in the presence of differently charged surfactants and comprehensively characterized their structure and properties. Combined with computational simulations, an in situ visualization of interfacial film formation discovered the critical role of Marangoni instability induced by the surfactants via various mechanisms in structurally regulating the nanofilms. Despite their different instability-triggering mechanisms, the delicate control of the surfactants enabled the fabrication of defect-free, ultra-permselective nanofilm membranes. Our study identifies critical IP parameters that allow us to rationally design nanofilms, coatings, and membranes for target applications.

Subcellular expression pattern and clinical significance of CBX2 and CBX7 in breast cancer subtypes.

Chromobox (CBX)2 and CBX7, members of CBX family protein, show diverse expression patterns and contrasting roles in certain cancers. We aimed to investigate the subcellular expression patterns and clinical significances of CBXs in breast cancer (BC) subtypes, which have heterogeneous clinical course and therapeutic responses. Among the subtypes, the triple-negative BC (TNBC) is a heterogeneous group that lacks specific markers. We categorized TNBC into quadruple-negative BC (QNBC) and TNBC, based on androgen receptor (AR) status, to make the groups more homogeneous. Immunohistochemistry for CBX proteins was performed on 323 primary invasive BC tissues and their clinical significances were analyzed. Cytoplasmic CBX2 (CBX2-c) was linked to adverse clinicopathological factors and TNBC and QNBC subtypes. In contrast, nuclear CBX7 (CBX7-n) was associated with favorable parameters and luminal A subtype. CBX2-c expression increased progressively from that in benign lesions to that in in situ carcinomas and invasive cancers, whereas CBX7-n and AR expressions showed sequential downregulation. AR was lower in metastatic tissues compared to matched primary cancer tissues. We speculate that the upregulation of CBX2-c and downregulation of CBX7-n could play a role in breast oncogenesis and an adverse clinical course, suggesting them as potential prognostic markers and therapeutic targets in invasive BCs.

Efficacy and Safety of Triple Therapy of Telmisartan/Amlodipine/Rosuvastatin in Patients with Dyslipidemia and Hypertension: A Multicenter Randomized Clinical Trial.

Background: Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence. Objective: This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy. Methods: This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed. Results: Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (P = 0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were -16.27 (0.93) mm Hg in the TEL/ALD/RSV group, -6.85 (0.92) mm Hg in the ALD/ATV group (LSM difference = -9.42 mm Hg; 95% CI, -11.99 to -6.84; P < .001). For LDL-C level changes, a significant difference was noted between the 2 groups: -50.03% (1.18%) in the TEL/ALD/RSV group, -39.60% (1.17%) in the ALD/ATV group (LSM difference = -10.43%; 95% CI, -13.70 to -7.16; P < .001). No severe adverse events were observed. Conclusions: TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (Curr Ther Res Clin Exp. 2024; XX:XXX-XXX). ClinicalTrials.gov identifier: NCT03860220.

Machine learning-based analysis of multi-omics data on the cloud for investigating gene regulations.

Gene expressions are subtly regulated by quantifiable measures of genetic molecules such as interaction with other genes, methylation, mutations, transcription factor and histone modifications. Integrative analysis of multi-omics data can help scientists understand the condition or patient-specific gene regulation mechanisms. However, analysis of multi-omics data is challenging since it requires not only the analysis of multiple omics data sets but also mining complex relations among different genetic molecules by using state-of-the-art machine learning methods. In addition, analysis of multi-omics data needs quite large computing infrastructure. Moreover, interpretation of the analysis results requires collaboration among many scientists, often requiring reperforming analysis from different perspectives. Many of the aforementioned technical issues can be nicely handled when machine learning tools are deployed on the cloud. In this survey article, we first survey machine learning methods that can be used for gene regulation study, and we categorize them according to five different goals: gene regulatory subnetwork discovery, disease subtype analysis, survival analysis, clinical prediction and visualization. We also summarize the methods in terms of multi-omics input types. Then, we explain why the cloud is potentially a good solution for the analysis of multi-omics data, followed by a survey of two state-of-the-art cloud systems, Galaxy and BioVLAB. Finally, we discuss important issues when the cloud is used for the analysis of multi-omics data for the gene regulation study.

Fresnel-type solid immersion lens for efficient light collection from quantum defects in diamond.

Quantum defects in diamonds have been studied as a promising resource for quantum science. The subtractive fabrication process for improving photon collection efficiency often require excessive milling time that can adversely affect the fabrication accuracy. We designed and fabricated a Fresnel-type solid immersion lens using the focused ion beam. For a 5.8 µm-deep Nitrogen-vacancy (NV-) center, the milling time was highly reduced (1/3 compared to a hemispherical structure), while retaining high photon collection efficiency (> 2.24 compared to a flat surface). In numerical simulation, this benefit of the proposed structure is expected for a wide range of milling depths.

Transverse Magnetization in Spin-Orbit Coupled Antiferromagnets.

Some antiferromagnets under a magnetic field develop magnetization perpendicular to the field as well as more conventional ones parallel to the field. So far, the transverse magnetization (TM) has been attributed to either the spin canting effect or the presence of cluster magnetic multipolar ordering. However, a general theory of TM based on microscopic understanding is still missing. Here, we construct a general microscopic theory of TM in antiferromagnets with cluster magnetic multipolar ordering by considering classical spin Hamiltonians with spin anisotropy that arises from the spin-orbit coupling. First, from general symmetry analysis, we show that TM can appear only when all crystalline symmetries are broken other than the antiunitary mirror, antiunitary twofold rotation, and inversion symmetries. Moreover, by analyzing spin Hamiltonians, we show that TM always appears when the degenerate ground state manifold of the spin Hamiltonian is discrete, as long as it is not prohibited by symmetry. On the other hand, when the degenerate ground state manifold is continuous, TM generally does not appear except when the magnetic field direction and the spin configuration satisfy specific geometric conditions under single-ion anisotropy. Finally, we show that TM can induce the anomalous planar Hall effect, a unique transport phenomenon that can be used to probe multipolar antiferromagnetic structures. We believe that our theory provides a useful guideline for understanding the anomalous magnetic responses of the antiferromagnets with complex magnetic structures.

Early versus delayed bronchial artery embolization for non-massive hemoptysis.

OBJECTIVES: The aims of this study were to compare clinical outcomes of early versus delayed bronchial artery embolization (BAE) for non-massive hemoptysis and to investigate predictors of recurrent hemoptysis. METHODS: From March 2018 to February 2021, 138 consecutive patients (age, 65.5 ± 12.4 years; male, 67.4%) with non-massive hemoptysis underwent BAE. The enrolled patients were divided into an early embolization (EE) group (within the first 24 h, n = 79) and a delayed embolization (DE) group (n = 59). RESULTS: The time to embolization ranged between 0 and 15 days and was shorter in the EE group (0.47 ± 0.5 days) than in the DE group (4.02 ± 2.8 days, p < 0.001). The in-hospital clinical outcomes were not different between the two groups, except for hospital stay and post-embolization hospital stay. The recurrence-free survival in the EE group was significantly better than that in the DE group (p = 0.018). The time to embolization (hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.04-1.42; p = 0.015) and aspergilloma (HR, 6.89; 95% CI, 2.08-22.86; p = 0.002) were predictive factors for recurrent hemoptysis. CONCLUSIONS: BAE is an effective and safe treatment modality for non-massive hemoptysis. An early interventional strategy should be considered in patients presenting with non-massive hemoptysis to reduce the length of hospital stay and early recurrence. A delayed time to embolization and the presence of aspergilloma were independent risk factors for recurrent hemoptysis. KEY POINTS: • Bronchial artery embolization afforded good clinical improvement for treating non-massive hemoptysis without significant complications. • An early interventional strategy should be considered in patients presenting with non-massive hemoptysis to reduce the length of hospital stay and early recurrence. • A delayed time to embolization and the presence of aspergilloma were independent risk factors for recurrent hemoptysis.

Value of multiphase computed tomography for gastrointestinal bleeding before endovascular treatment in hemodynamically unstable patients.

BACKGROUND: There has been no practice-based study regarding the multiphase computed tomography (CT) before endovascular treatment in hemodynamically unstable gastrointestinal bleeding (GIB) and concerns exist regarding the time delay. PURPOSE: To evaluate the clinical efficacy of multiphase CT before endovascular treatment in hemodynamically unstable GIB and to investigate the predictors of angiographic localization and recurrent bleeding. MATERIAL AND METHODS: The multicenter retrospective study included 93 consecutive hemodynamically unstable patients who underwent conventional angiography for non-variceal GIB after failed endoscopic localization. Enrolled patients were divided into a CT group (n = 61) and a non-CT group (n = 32). RESULTS: The clinical characteristics did not differ between the two groups except for the time to angiography (CT group, 14.8±15.1 h; non-CT group, 9.2±11.7 h, P = 0.022). The rate of angiographic localization was significantly higher in the CT group than in the non-CT group only for lower GIB (P = 0.049). Indirect sign was significantly more frequent in the CT group than in the non-CT group (P = 0.014). CT localization was positive predictor (odd ratio [OR] = 7.66; 95% confidence interval [CI] = 2.1-27.94; P = 0.002) and prolonged time to angiography was negative predictor (OR = 0.94; 95% CI = 0.9- 0.98; P = 0.001) for angiographic localization. A higher systolic blood pressure until index angiography (OR = 0.95; 95% CI = 0.91-1; P = 0.044) was associated with a reduced risk of recurrent bleeding. CONCLUSION: In hemodynamically unstable patients, multiphase CT is particularly useful for angiographic localization of lower GIB. It should be considered immediately after failed endoscopic hemostasis to reduce time to angiography.

Machine Learning-Based Proteomics Reveals Ferroptosis in COPD Patient-Derived Airway Epithelial Cells Upon Smoking Exposure.

BACKGROUND: Proteomics and genomics studies have contributed to understanding the pathogenesis of chronic obstructive pulmonary disease (COPD), but previous studies have limitations. Here, using a machine learning (ML) algorithm, we attempted to identify pathways in cultured bronchial epithelial cells of COPD patients that were significantly affected when the cells were exposed to a cigarette smoke extract (CSE). METHODS: Small airway epithelial cells were collected from patients with COPD and those without COPD who underwent bronchoscopy. After expansion through primary cell culture, the cells were treated with or without CSEs, and the proteomics of the cells were analyzed by mass spectrometry. ML-based feature selection was used to determine the most distinctive patterns in the proteomes of COPD and non-COPD cells after exposure to smoke extract. Publicly available single-cell RNA sequencing data from patients with COPD (GSE136831) were used to analyze and validate our findings. RESULTS: Five patients with COPD and five without COPD were enrolled, and 7,953 proteins were detected. Ferroptosis was enriched in both COPD and non-COPD epithelial cells after their exposure to smoke extract. However, the ML-based analysis identified ferroptosis as the most dramatically different response between COPD and non-COPD epithelial cells, adjusted P value = 4.172 × 10-6, showing that epithelial cells from COPD patients are particularly vulnerable to the effects of smoke. Single-cell RNA sequencing data showed that in cells from COPD patients, ferroptosis is enriched in basal, goblet, and club cells in COPD but not in other cell types. CONCLUSION: Our ML-based feature selection from proteomic data reveals ferroptosis to be the most distinctive feature of cultured COPD epithelial cells compared to non-COPD epithelial cells upon exposure to smoke extract.

Double-Pigtail Drainage Catheter: A New Design for Efficient Pleural Drainage.

Background and Objectives: The novel double-pigtail catheter (DPC) has an additional pigtail coiling at the mid-shaft with multiple centripetal side holes. The present study aimed to investigate the advantages and efficacy of DPC in overcoming the complications of conventional single-pigtail catheters (SPC) used to drain pleural effusion. Materials and Methods: Between July 2018 and December 2019, 382 pleural effusion drainage procedures were reviewed retrospectively (DPC, n = 156; SPC without multiple side holes, n = 110; SPC with multiple side holes (SPC + M), n = 116). All patients showed shifting pleural effusions in the decubitus view of the chest radiography. All catheters were 10.2 Fr in diameter. One interventional radiologist performed all procedures and used the same anchoring technique. Complications (dysfunctional retraction, complete dislodgement, blockage, and atraumatic pneumothorax) were compared among the catheters using chi-square and Fisher's exact tests. Clinical success was defined as an improvement in pleural effusion within three days without additional procedures. Survival analysis was performed to calculate the indwelling time. Results: The dysfunctional retraction rate of DPC was significantly lower than that of the other catheters (p < 0.001). Complete dislodgement did not occur in any of the DPC cases. The clinical success rate of DPC (90.1%) was the highest. The estimated indwelling times were nine (95% confidence interval (CI): 7.3-10.7), eight (95% CI: 6.6-9.4), and seven (95% CI: 6.3-7.7) days for SPC, SPC + M, and DPC, respectively, with DPC showing a significant difference (p < 0.05). Conclusions: DPC had a lower dysfunctional retraction rate compared to conventional drainage catheters. Furthermore, DPC was efficient for pleural effusion drainage with a shorter indwelling time.

OpenContami: a web-based application for detecting microbial contaminants in next-generation sequencing data.

SUMMARY: Microorganisms infect and contaminate eukaryotic cells during the course of biological experiments. Because microbes influence host cell biology and may therefore lead to erroneous conclusions, a computational platform that facilitates decontamination is indispensable. Recent studies show that next-generation sequencing (NGS) data can be used to identify the presence of exogenous microbial species. Previously, we proposed an algorithm to improve detection of microbes in NGS data. Here, we developed an online application, OpenContami, which allows researchers easy access to the algorithm via interactive web-based interfaces. We have designed the application by incorporating a database comprising analytical results from a large-scale public dataset and data uploaded by users. The database serves as a reference for assessing user data and provides a list of genera detected from negative blank controls as a 'blacklist', which is useful for studying human infectious diseases. OpenContami offers a comprehensive overview of exogenous species in NGS datasets; as such, it will increase our understanding of the impact of microbial contamination on biological and pathological traits. AVAILABILITY AND IMPLEMENTATION: OpenContami is freely available at: https://openlooper.hgc.jp/opencontami/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BioVLAB-Cancer-Pharmacogenomics: tumor heterogeneity and pharmacogenomics analysis of multi-omics data from tumor on the cloud.

MOTIVATION: Multi-omics data in molecular biology has accumulated rapidly over the years. Such data contains valuable information for research in medicine and drug discovery. Unfortunately, data-driven research in medicine and drug discovery is challenging for a majority of small research labs due to the large volume of data and the complexity of analysis pipeline. RESULTS: We present BioVLAB-Cancer-Pharmacogenomics, a bioinformatics system that facilitates analysis of multi-omics data from breast cancer to analyze and investigate intratumor heterogeneity and pharmacogenomics on Amazon Web Services. Our system takes multi-omics data as input to perform tumor heterogeneity analysis in terms of TCGA data and deconvolve-and-match the tumor gene expression to cell line data in CCLE using DNA methylation profiles. We believe that our system can help small research labs perform analysis of tumor multi-omics without worrying about computational infrastructure and maintenance of databases and tools. AVAILABILITY AND IMPLEMENTATION: http://biohealth.snu.ac.kr/software/biovlab_cancer_pharmacogenomics. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Predicting mechanism of action of novel compounds using compound structure and transcriptomic signature coembedding.

MOTIVATION: Identifying mechanism of actions (MoA) of novel compounds is crucial in drug discovery. Careful understanding of MoA can avoid potential side effects of drug candidates. Efforts have been made to identify MoA using the transcriptomic signatures induced by compounds. However, these approaches fail to reveal MoAs in the absence of actual compound signatures. RESULTS: We present MoAble, which predicts MoAs without requiring compound signatures. We train a deep learning-based coembedding model to map compound signatures and compound structure into the same embedding space. The model generates low-dimensional compound signature representation from the compound structures. To predict MoAs, pathway enrichment analysis is performed based on the connectivity between embedding vectors of compounds and those of genetic perturbation. Results show that MoAble is comparable to the methods that use actual compound signatures. We demonstrate that MoAble can be used to reveal MoAs of novel compounds without measuring compound signatures with the same prediction accuracy as that with measuring them. AVAILABILITY AND IMPLEMENTATION: MoAble is available at https://github.com/dmis-lab/moable. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

HHEX promotes myeloid transformation in cooperation with mutant ASXL1.

Additional sex combs-like 1 (ASXL1), an epigenetic modulator, is frequently mutated in myeloid neoplasms. Recent analyses of mutant ASXL1 conditional knockin (ASXL1-MT-KI) mice suggested that ASXL1-MT alone is insufficient for myeloid transformation. In our previous study, we used retrovirus-mediated insertional mutagenesis, which exhibited the susceptibility of ASXL1-MT-KI hematopoietic cells to transform into myeloid leukemia cells. In this screening, we identified the hematopoietically expressed homeobox (HHEX) gene as one of the common retrovirus integration sites. In this study, we investigated the potential cooperation between ASXL1-MT and HHEX in myeloid leukemogenesis. Expression of HHEX enhanced proliferation of ASXL1-MT-expressing HSPCs by inhibiting apoptosis and blocking differentiation, whereas it showed only modest effect in normal HSPCs. Moreover, ASXL1-MT and HHEX accelerated the development of RUNX1-ETO9a and FLT3-ITD leukemia. Conversely, HHEX depletion profoundly attenuated the colony-forming activity and leukemogenicity of ASXL1-MT-expressing leukemia cells. Mechanistically, we identified MYB and ETV5 as downstream targets for ASXL1-MT and HHEX by using transcriptome and chromatin immunoprecipitation-next-generation sequencing analyses. Moreover, we found that expression of ASXL1-MT enhanced the binding of HHEX to the promoter loci of MYB or ETV5 via reducing H2AK119ub. Depletion of MYB or ETV5 induced apoptosis or differentiation in ASXL1-MT-expressing leukemia cells, respectively. In addition, ectopic expression of MYB or ETV5 reversed the reduced colony-forming activity of HHEX-depleted ASXL1-MT-expressing leukemia cells. These findings indicate that the HHEX-MYB/ETV5 axis promotes myeloid transformation in ASXL1-mutated preleukemia cells.

Transcholecystic management of extrahepatic duct stones in poor candidates for endoscopic or transhepatic approaches.

OBJECTIVES: To investigate transcholecystic management of extrahepatic duct (EHD) stones using balloon ampulloplasty in patients who are poor candidates for endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) and assess its efficacy and safety. METHODS: Forty-one patients who were unable to undergo ERCP or had failed ERCP with non-dilated intrahepatic ducts (IHD) between February 2019 and October 2020 were retrospectively enrolled. After clinical improvement with percutaneous cholecystostomy (PC), EHD stones were managed through cystic duct passage, guidewire unwinding, sheath insertion, and EHD stone removal using balloon ampulloplasty. If the transcholecystic route failed, a transhepatic approach was used according to the pre-existing cholangiogram obtained via PC. We evaluated the technical success rate and complications of each step. RESULTS: The technical success rate for the transcholecystic-only approach was 80.5%. The remaining cases were successfully managed with transhepatic conversion. Multiple stone removal sessions were required in 22% of the cases. One patient with combined IHD stones was initially converted to a transhepatic approach without any transcholecystic removal trial. The technical success rates for each step were as follows: cystic duct passage (38/40, 95%), guidewire unwinding (36/38, 94.7%), sheath insertion (36/36, 100%), and stone removal using balloon ampulloplasty (33/36, 91.7%). The overall clinical success was 97.6% (40/41) without major procedure-related complications. Thereafter, cholecystectomy was successfully performed in patients with concomitant gallstones (n = 20). No postprocedural complications occurred during the follow-up (1-70 days). CONCLUSIONS: Percutaneous EHD stone removal through transcholecystic and transhepatic routes after PC is effective and safe in poor candidates for PTBD or ERCP. KEY POINTS: • This study shows the safety and efficacy of extrahepatic duct (EHD) stones in patients who are poor candidates for initial percutaneous transhepatic biliary drainage and endoscopic retrograde cholangiopancreatography. • The overall technical success for the transcholecystic-only approach was 80.5% (33/41). Including transhepatic conversions, it was 100% (41/41). Stone removal was successful in one session in 78% (32/41) of the patients and in multiple sessions in 28.1% (9/41) of the patients. • Balloon ampulloplasty with stone expulsion using an occlusion balloon catheter is also a safe and effective method for removing EHD stones.

Imaging-Guided Deployment of a Balloon-Based Vascular Closure Device in Routine Clinical Practice.

This study evaluated the feasibility and safety of imaging-guided deployment of a Mynx Control device (Cordis, Miami Lakes, Florida) at the femoral access. A total of 201 Mynx devices were used under imaging guidance in 137 patients (mean age, 64.18 years ± 13.8; male, 68.6%) between June 2020 and February 2022. A 5-F sheath was used in 176 (87.6%) procedures, a 6-F sheath was used in 17 (8.5%) procedures, and a 7-F sheath was used in 8 (4%) procedures. Indicator errors occurred in 9 (4.5%) procedures. However, technical success was achieved via manipulation under imaging guidance in all procedures. The mean time to hemostasis was 3.3 minutes ± 0.5, and the clinical success rate was 100%. The mean length of hospital stay was 7 days ± 7.5. After 4 (2%) procedures, small hematomas reabsorbed spontaneously. Imaging-guided deployment of a Mynx Control device is a feasible and safe option for access site closure. Even after an indicator error, successful hemostasis was achieved via real-time interaction.

A semi-supervised deep learning approach for predicting the functional effects of genomic non-coding variations.

BACKGROUND: Understanding the functional effects of non-coding variants is important as they are often associated with gene-expression alteration and disease development. Over the past few years, many computational tools have been developed to predict their functional impact. However, the intrinsic difficulty in dealing with the scarcity of data leads to the necessity to further improve the algorithms. In this work, we propose a novel method, employing a semi-supervised deep-learning model with pseudo labels, which takes advantage of learning from both experimentally annotated and unannotated data. RESULTS: We prepared known functional non-coding variants with histone marks, DNA accessibility, and sequence context in GM12878, HepG2, and K562 cell lines. Applying our method to the dataset demonstrated its outstanding performance, compared with that of existing tools. Our results also indicated that the semi-supervised model with pseudo labels achieves higher predictive performance than the supervised model without pseudo labels. Interestingly, a model trained with the data in a certain cell line is unlikely to succeed in other cell lines, which implies the cell-type-specific nature of the non-coding variants. Remarkably, we found that DNA accessibility significantly contributes to the functional consequence of variants, which suggests the importance of open chromatin conformation prior to establishing the interaction of non-coding variants with gene regulation. CONCLUSIONS: The semi-supervised deep learning model coupled with pseudo labeling has advantages in studying with limited datasets, which is not unusual in biology. Our study provides an effective approach in finding non-coding mutations potentially associated with various biological phenomena, including human diseases.