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.

Two-in-one strategy for optimizing chemical and structural properties of carbon felt electrodes for vanadium redox flow batteries.

Vanadium redox flow batteries (VRFBs) have received significant attention for use in large-scale energy storage systems (ESSs) because of their long cycle life, flexible capacity, power design, and safety. However, the poor electrochemical activity of the conventionally used carbon felt electrode results in low energy efficiency of the VRFBs and consequently impedes their commercialization. In this study, a carbon felt (CF) electrode with numerous nanopores and robust oxygen-containing functional groups at its edge sites is designed to improve the electrochemical activity of a carbon felt electrode. To achieve this, Ni metal nanoparticles were initially precipitated on the surface of the CF electrode, followed by etching of the precipitated Ni nanoparticles on the CF electrode using sulfuric acid. The resulting CF electrode had a specific surface area eight times larger than that of the pristine CF electrode. In addition, the oxygen-containing functional groups anchored at the graphite edge sites of the nanopores can act as robust electrocatalysts for VO2+/VO2+ and V2+/V3+ redox reactions. Consequently, the VRFB cell with the resulting carbon felt electrode can deliver a high energy efficiency of 86.2% at the current density of 60 mA cm-2, which is 20% higher than that of the VRFB cell with the conventionally heat-treated CF electrode. Furthermore, the VRFB cell with the resultant carbon felt electrodes showed stable cycling performance with no considerable energy efficiency loss over 200 charge-discharge cycles. In addition, even at a high current density of 160 mA cm-2 , the developed carbon felt electrode can achieve an energy efficiency of 70.1%.

This work reveals the importance of the robust graphite edge-site oxygen functional group and the holey structure of the ET-CF electrode, emphasizing that high VRFB efficiency can be achieved by engineering both the structure and surface properties of the carbon felt electrode.

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.

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.

Role of helicity in the nonenzymatic template-directed primer extension of DNA.

Complexing a DNA primer with an RNA template showed improved nonenzymatic template-directed primer extension, attributed to a shift in the DNA helicity from a B-type towards an A-type helix. A 2-fold (deoxyadenosine) and 4.5-fold (deoxycytidine) increase in conversion from initial DNA primer to a primer + 1 nucleotide product was observed.

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.

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.

Prediction of Implant Size Based on Breast Volume Using Mammography with Fully Automated Measurements and Breast MRI.

BACKGROUND: Determination of implant size is crucial for patients with breast cancer undergoing one-stage breast reconstruction. The purpose of this study is to predict the implant size based on the breast volume measured by mammography (MG) with a fully automated method, and by breast magnetic resonance imaging (MRI) with a semi-automated method, in breast cancer patients with direct-to-implant reconstruction. PATIENTS AND METHODS: This retrospective study included 84 patients with breast cancer who underwent direct-to-implant reconstruction after nipple-sparing or skin-sparing mastectomy and preoperative MG and MRI between April 2015 and April 2019. Breast volume was measured using (a) MG with a fully automated commercial software and (b) MRI with an in-house semi-automated software program. Multivariable regression analyses including breast volume and patient weight (P < 0.05 in univariable analysis) were conducted to predict implant size. RESULTS: MG and MRI breast volume was highly correlated with both implant size (correlation coefficient 0.862 and 0.867, respectively; P values < 0.001) and specimen weight (correlation coefficient 0.802 and 0.852, respectively; P values < 0.001). Mean absolute difference between the MR breast volume and implant size was 160 cc, which was significantly higher than that between the MG breast volume and implant size of 118 cc (P < 0.001). On multivariable analyses, only breast volume measured by both MG and MRI was significantly associated with implant size in any implant type (all P values < 0.001). CONCLUSION: Breast volume measured by MG and MRI can be used to predict appropriate implant size in breast cancer patients undergoing direct-to-implant reconstruction in an efficient and objective manner.

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.

Primary versus modified secondary closure techniques for persistent tracheocutaneous fistula in pediatric patients.

PURPOSE: This study aimed at compating two closure techniques for tracheocutaneous fistulas (TCFs) in pediatric patients. METHODS: A total of 106 consecutive pediatric patients who underwent closure of a persistent TCF between April 2007 and February 2021 at a tertiary pediatric hospital were evaluated, and 103 pediatric patients aged between 12 months and 18 years were included. The clinical characteristics, perioperative outcomes, and postoperative outcomes were compared between TCF closure by primary closure (Group 1) and a modified secondary healing technique (Group 2). RESULTS: Of the 103 patients, 58 were classified into Group 1, and 45 into Group 2. The mean age at tracheostomy and TCF closure was significantly younger in Group 2, and the interval between decannulation to TCF closure was significantly shorter in Group 2. Procedural time and hospital stay were significantly shorter in Group 2 than Group 1. Group 2 had a significantly lower complication rate, need for revision surgery, and recannulation rate than Group 1. CONCLUSIONS: Modified secondary healing was more efficient in terms of procedural time and hospital stay, and safer (i.e., fewer complications). It is an effective surgical technique for closing a persistent TCF in younger patients more quickly after decannulation compared to primary closure.

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.

Nitrates administered by spray versus tablet: comparison of coronary vasodilation on CT angiography.

OBJECTIVES: To compare the coronary vasodilation effects of spray with those induced by tablet administration in coronary CT angiography (CCTA). METHODS: A total of 2024 patients who underwent CCTA were identified for this retrospective study, including 828 patients with spray (spray group) and 1169 with tablets (tablet group). Of these, 93 patients underwent CCTA at least twice using both spray and tablets. The number of measurable segments and diameters of all 18 segments was measured. The number of measurable segments was compared between groups. RESULTS: No statistically significant differences were evident between these two groups in terms of clinical characteristics. All coronary segments except the ramus intermedius (RI) and left posterior descending artery (L-PDA) were significantly larger in the spray group than in the tablet group (all p < 0.001). In peripheral and branch vessels, as well as in central and main coronary arteries, the diameters were significantly larger in the spray group than in the tablet group (all p < 0.001). Although not always statistically significant, all coronary segments tended to be more measurable on CCTA with spray than with tablet. In the subgroup that underwent CCTA twice using both spray and tablets, all coronary segments except the RI, obtuse marginal artery 2 (OM2), and L-PDA were significantly larger in the spray group than in the tablet group (all p < 0.05). CONCLUSION: Lingual isosorbide dinitrate (ISDN) spray was more efficacious than sublingual nitroglycerin (NTG) tablets in coronary vasodilation for CCTA. Therefore, lingual ISDN spray should be preferred over sublingual NTG tablets for CCTA. KEY POINTS: • Lingual ISDN spray was more efficacious than sublingual NTG tablet for coronary vasodilation in coronary CT angiography, even in elderly patients. • The diameters of all coronary segments except RI and L-PDA were significantly larger, and there were significantly more coronary segments greater than 1.5 mm, except RI and L-PDA, in the spray group than in the tablet group in the whole study group. • Even in peripheral and branch vessels, the diameters of coronary arteries were significantly larger in the spray group than in the tablet group, and they were also larger in elderly patients.

Oncological outcomes of preoperatively unexpected malignant tumors of the parotid gland.

PURPOSE: Unexpected parotid cancers are often encountered due to inaccuracies in the preoperative evaluation. This study aimed to examine the clinical characteristics and oncological outcomes of these cancers and to propose the appropriate management strategy. METHODS: This is a multicenter case series study in which a total of 302 patients were diagnosed postoperatively with parotid cancers between 2003 and 2017. Of these, 85 cases without evidence of malignancy prior to surgery but identified as malignant on postoperative pathology were included. RESULTS: Of 85 patients, 76 and 9 underwent superficial and total parotidectomy, respectively. A positive resection margin was present in 24.7% of the cases. Postoperative radiotherapy was administered to 43.6% of patients; 4.2% had a local recurrence, and no patients died of the disease. The 5-year overall and relapse-free survival rates were 100.0% and 95.2%, respectively. Patients who underwent piecemeal resection had significantly poorer oncologic outcomes. Age, sex, histologic grade, T stage, extracapsular extension, resection margin status, and postoperative radiotherapy did not affect recurrence and survival. CONCLUSION: Preoperatively unexpected parotid cancers had excellent local control and overall survival despite positive or close resection margin, with or without postoperative radiotherapy. Therefore, patients with unexpected parotid malignancies may benefit from less aggressive postoperative management option.

Inferring the choreography of parental genomes during fertilization from ultralarge-scale whole-transcriptome analysis.

Fertilization precisely choreographs parental genomes by using gamete-derived cellular factors and activating genome regulatory programs. However, the mechanism remains elusive owing to the technical difficulties of preparing large numbers of high-quality preimplantation cells. Here, we collected >14 × 10(4) high-quality mouse metaphase II oocytes and used these to establish detailed transcriptional profiles for four early embryo stages and parthenogenetic development. By combining these profiles with other public resources, we found evidence that gene silencing appeared to be mediated in part by noncoding RNAs and that this was a prerequisite for post-fertilization development. Notably, we identified 817 genes that were differentially expressed in embryos after fertilization compared with parthenotes. The regulation of these genes was distinctly different from those expressed in parthenotes, suggesting functional specialization of particular transcription factors prior to first cell cleavage. We identified five transcription factors that were potentially necessary for developmental progression: Foxd1, Nkx2-5, Sox18, Myod1, and Runx1. Our very large-scale whole-transcriptome profile of early mouse embryos yielded a novel and valuable resource for studies in developmental biology and stem cell research. The database is available at http://dbtmee.hgc.jp.

Correction to: RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes.

An amendment to this paper has been published and can be accessed via the original article.