Technical outcomes and postprocedural courses of mucosal incision-assisted biopsy for possible gastric gastrointestinal stromal tumors: A series of 48 cases (with video).

Objective: Mucosal incision-assisted biopsy (MIAB) has been introduced as an alternative to endoscopic ultrasound-guided fine needle aspiration for tissue sampling of subepithelial lesions. However, there have been few reports on MIAB, and the evidence is lacking, particularly in small lesions. In this case series, we investigated the technical outcomes and postprocedural influences of MIAB for gastric subepithelial lesions 10 mm or greater in size. Methods: We retrospectively reviewed cases with the intraluminal growth type of possible gastrointestinal stromal tumors, in which MIAB was performed at a single institution between October 2020 and August 2022. Technical success, adverse events, and clinical courses following the procedure were evaluated. Results: In 48 MIAB cases with a median tumor diameter of 16 mm, the success rate of tissue sampling and the diagnostic rate were 96% and 92%, respectively. Two biopsies were considered sufficient for making the definitive diagnosis. Postoperative bleeding occurred in one case (2%). In 24 cases, surgery has performed a median of two months after MIAB, and no unfavorable findings caused by MIAB were seen intraoperatively. Finally, 23 cases were histologically diagnosed as gastrointestinal stromal tumors, and no patients who underwent MIAB experienced recurrence or metastasis during a median observation period of 13 months. Conclusions: The data indicated that MIAB appears feasible, safe, and useful for histological diagnosis of gastric intraluminal growth types of possible gastrointestinal stromal tumors, even those of a small size. Postprocedural clinical effects were considered negligible.

Small bowel capsule endoscopy examination and open access database with artificial intelligence: The SEE-artificial intelligence project.

Objectives: Artificial intelligence (AI) may be practical for image classification of small bowel capsule endoscopy (CE). However, creating a functional AI model is challenging. We attempted to create a dataset and an object detection CE AI model to explore modeling problems to assist in reading small bowel CE. Methods: We extracted 18,481 images from 523 small bowel CE procedures performed at Kyushu University Hospital from September 2014 to June 2021. We annotated 12,320 images with 23,033 disease lesions, combined them with 6161 normal images as the dataset, and examined the characteristics. Based on the dataset, we created an object detection AI model using YOLO v5 and we tested validation. Results: We annotated the dataset with 12 types of annotations, and multiple annotation types were observed in the same image. We test validated our AI model with 1396 images, and sensitivity for all 12 types of annotations was about 91%, with 1375 true positives, 659 false positives, and 120 false negatives detected. The highest sensitivity for individual annotations was 97%, and the highest area under the receiver operating characteristic curve was 0.98, but the quality of detection varied depending on the specific annotation. Conclusions: Object detection AI model in small bowel CE using YOLO v5 may provide effective and easy-to-understand reading assistance. In this SEE-AI project, we open our dataset, the weights of the AI model, and a demonstration to experience our AI. We look forward to further improving the AI model in the future.

Hox dosage and morphological diversification during development and evolution.

Hox genes encode for evolutionary conserved transcription factors that have long fascinated biologists since the observation of the first homeotic transformations in flies. Hox genes are developmental architects that instruct the formation of various and precise morphologies along the body axes in cnidarian and bilaterian species. In contrast to these highly specific developmental functions, Hox genes encode for proteins that display poorly selective DNA-binding properties in vitro. This "Hox paradox" has been partially solved with the discovery of the TALE-class cofactors, which interact with all Hox members and form versatile Hox/TALE protein complexes on DNA. Here, we describe the role of the Hox dosage as an additional molecular strategy contributing to further resolve the Hox paradox. We present several cases where the Hox dosage is involved in the formation of different morphologies in invertebrates and vertebrates, with a particular emphasis on flight appendages in insects. We also discuss how the Hox dosage could be interpreted in different types of target enhancers within the nuclear environment in vivo. Altogether our survey underlines the Hox dosage as a key mechanism for shaping Hox molecular function during development and evolution.

TALE transcription factors: Cofactors no more.

Exd/PBX, Hth/MEIS and PREP proteins belong to the TALE (three-amino-acid loop extension) superclass of transcription factors (TFs) with an atypical homedomain (HD). Originally discovered as "cofactors" to HOX proteins, revisiting their traditional role in light of genome-wide experiments reveals a strong and reproducible pattern of HOX and TALE co-occupancy across diverse embryonic tissues. While confirming that TALE increases HOX specificity and selectivity in vivo, this wider outlook also reveals novel aspects of HOX:TALE collaboration, namely that HOX TFs generally require pre-bound TALE factors to access their functional binding sites in vivo. In contrast to the restricted expression domains of HOX TFs, TALE factors are largely ubiquitous, and PBX and PREP are expressed at the earliest developmental stages. PBX and MEIS control development of many organs and tissues and their dysregulation is associated with congenital disease and cancer. Accordingly, many instances of TALE cooperation with non HOX TFs have been documented in various systems. The model that emerges from these studies is that TALE TFs create a permissive chromatin platform that is selected by tissue-restricted TFs for binding. In turn, HOX and other tissue-restricted TFs selectively convert a ubiquitous pool of low affinity TALE binding events into high confidence, tissue-restricted binding events associated with transcriptional activation. As a result, TALE:TF complexes are associated with active chromatin and domain/lineage-specific gene activity. TALE ubiquitous expression and broad genomic occupancy, as well as the increasing examples of TALE tissue-specific partners, reveal a universal and obligatory role for TALE in the control of tissue and lineage-specific transcriptional programs, beyond their initial discovery as HOX co-factors.

Hox function and specificity - A tissue centric view.

Since their discovery, the Hox genes, with their incredible power to reprogram the identity of complete body regions, a phenomenon called homeosis, have captured the fascination of many biologists. Recent research has provided new insights into the function of Hox proteins in different germ layers and the mechanisms they employ to control tissue morphogenesis. We focus in this review on the ectoderm and mesoderm to highlight new findings and discuss them with regards to established concepts of Hox target gene regulation. Furthermore, we highlight the molecular mechanisms involved the transcriptional repression of specific groups of Hox target genes, and summarize the role of Hox mediated gene silencing in tissue development. Finally, we reflect on recent findings identifying a large number of tissue-specific Hox interactor partners, which open up new avenues and directions towards a better understanding of Hox function and specificity in different tissues.

The pioneering function of the hox transcription factors.

Ever since the discovery that the Hox family of transcription factors establish morphological diversity in the developing embryo, major efforts have been directed towards understanding Hox-dependent patterning. This has led to important discoveries, notably on the mechanisms underlying the collinear expression of Hox genes and Hox binding specificity. More recently, several studies have provided evidence that Hox factors have the capacity to bind their targets in an inaccessible chromatin context and trigger the switch to an accessible, transcriptional permissive, chromatin state. In this review, we provide an overview of the evidences supporting that Hox factors behave as pioneer factors and discuss the potential mechanisms implicated in Hox pioneer activity as well as the significance of this functional property in Hox-dependent patterning.

Hox genes in spiders: Their significance for development and evolution.

Hox genes are known for their role in the specification of typical body plan features in animals. Evolutionary changes in Hox gene function are believed to be involved in the emergence of the diverse body plans we observe in animals today. Spiders share many body plan features with other arthropods, but also have numerous unique traits of their own. Studies of spider Hox genes have already provided insights into evolutionarily conserved and derived features of the spider body plan and their genetic basis. However, many aspects of Hox gene biology have been insufficiently studied in spiders so far. In this review, we highlight previous comparative studies of Hox genes in spiders and their significance for our understanding of the evolution of the spider body plan. We also identify aspects of Hox gene biology that need to be studied in greater detail. Many spider Hox genes have not been investigated beyond their mRNA expression patterns, and the role of Hox genes with apparently plesiomorphic or dual functions, like ftz and Hox3 is still unclear. Spiders have a duplicated Hox gene cluster, but possible sub- or neofunctionalisation of duplicates have not yet been studied systematically. Future research should therefore focus on these issues, in addition to the role of Polycomb and trithorax-mediated regulation, the identification of regulatory regions, cofactors or spider-specific target genes, and the significance of non-coding RNAs transcribed from within the Hox cluster and even from the antisense strand of particular Hox genes.

Evolution of the insect Hox gene cluster: Comparative analysis across 243 species.

The Hox gene cluster is an iconic example of evolutionary conservation between divergent animal lineages, providing evidence for ancient similarities in the genetic control of embryonic development. However, there are differences between taxa in gene order, gene number and genomic organisation implying conservation is not absolute. There are also examples of radical functional change of Hox genes; for example, the ftz, zen and bcd genes in insects play roles in segmentation, extraembryonic membrane formation and body polarity, rather than specification of anteroposterior position. There have been detailed descriptions of Hox genes and Hox gene clusters in several insect species, including important model systems, but a large-scale overview has been lacking. Here we extend these studies using the publicly-available complete genome sequences of 243 insect species from 13 orders. We show that the insect Hox cluster is characterised by large intergenic distances, consistently extreme in Odonata, Orthoptera, Hemiptera and Trichoptera, and always larger between the 'posterior' Hox genes. We find duplications of ftz and zen in many species and multiple independent cluster breaks, although certain modules of neighbouring genes are rarely broken apart suggesting some organisational constraints. As more high-quality genomes are obtained, a challenge will be to relate structural genomic changes to phenotypic change across insect phylogeny.

Hox, homology, and parsimony: An organismal perspective.

Hox genes are important regulators in animal development. They often show a mosaic of conserved (e.g., longitudinal axis patterning) and lineage-specific novel functions (e.g., development of skeletal, sensory, or locomotory systems). Despite extensive research over the past decades, it remains controversial at which node in the animal tree of life the Hox cluster evolved. Its presence already in the last common metazoan ancestor has been proposed, although the genomes of both putative earliest extant metazoan offshoots, the ctenophores and the poriferans, are devoid of Hox sequences. The lack of Hox genes in the supposedly "simple"-built poriferans and their low number in cnidarians and the basally branching bilaterians, the xenacoelomorphs, seems to support the classical notion that the number of Hox genes is correlated with the degree of animal complexity. However, the 4-fold increase of the Hox cluster in xiphosurans, a basally branching chelicerate clade, as well as the situation in some teleost fishes that show a multitude of Hox genes compared to, e.g., human, demonstrates, that there is no per se direct correlation between organismal complexity and Hox number. Traditional approaches have tried to base homology on the morphological level on shared expression profiles of individual genes, but recent data have shown that, in particular with respect to Hox and other regulatory genes, complex gene-gene interactions rather than expression signatures of individual genes alone are responsible for shaping morphological traits during ontogeny. Accordingly, for sound homology assessments and reconstructions of character evolution on organ system level, additional independent datasets (e.g., morphological, developmental) need to be included in any such analyses. If supported by solid data, proposed structural homology should be regarded as valid and not be rejected solely on the grounds of non-parsimonious distribution of the character over a given phylogenetic topology.

Establishing and maintaining Hox profiles during spinal cord development.

The chromosomally-arrayed Hox gene family plays central roles in embryonic patterning and the specification of cell identities throughout the animal kingdom. In vertebrates, the relatively large number of Hox genes and pervasive expression throughout the body has hindered understanding of their biological roles during differentiation. Studies on the subtype diversification of spinal motor neurons (MNs) have provided a tractable system to explore the function of Hox genes during differentiation, and have provided an entry point to explore how neuronal fate determinants contribute to motor circuit assembly. Recent work, using both in vitro and in vivo models of MN subtype differentiation, have revealed how patterning morphogens and regulation of chromatin structure determine cell-type specific programs of gene expression. These studies have not only shed light on basic mechanisms of rostrocaudal patterning in vertebrates, but also have illuminated mechanistic principles of gene regulation that likely operate in the development and maintenance of terminal fates in other systems.

Diagnostic and therapeutic strategies for colorectal tumor with positive muscle-retracting sign.

Objectives: Endoscopic submucosal dissection (ESD) for colorectal tumors with positive muscle-retracting (MR) sign often results in incomplete resection or discontinuation owing to the difficulty of submucosal dissection. The present study aimed to evaluate the usefulness of endoscopic ultrasonography (EUS) in diagnosing the MR sign and performing ESD using the pocket-creation method (PCM). Methods: Thirty-six cases of colorectal tumors with positive MR sign during ESD between January 2015 and December 2021 were retrospectively reviewed. Cases were divided into two groups: 1) the conventional method (CM) group, comprising 29 cases, and 2) the PCM group with seven cases, in which preoperative EUS and ESD using PCM were performed. Treatment outcomes were compared between the groups. The diagnostic yield of EUS for the MR sign was evaluated among large sessile tumors >20 mm in which preoperative EUS was performed. Results: Histologic diagnosis was adenoma or Tis carcinoma in 12 cases (33%), T1 carcinoma in 18 cases (50%), T2 carcinoma in four cases (11%), and unevaluable in two cases (6%). The sensitivity and specificity of the EUS-MR sign for large sessile tumors were 87.5% and 83.3%, respectively. ESD was achieved in all cases in the PCM group, although it was discontinued in eight cases (28%) in the CM group. There were significant differences between the PCM and CM groups in en bloc resection (100% vs. 48%, p = 0.013) and R0 resection rates (71% vs. 31%, p = 0.049). Conclusion: The MR sign can be predicted by preoperative EUS, and ESD using PCM allows en bloc resection.

Higher detectability of gastric cancer after Helicobacter pylori eradication in texture and color enhancement imaging mode 2 in screening endoscopy.

Objectives: The utility of texture and color enhancement imaging (TXI) in detecting gastric cancer (GC) has been investigated. However, few reports exist on TXI mode2 (TXI2) used for detecting GC; this study investigated the efficacy of TXI2 in GC detection during screening endoscopy. Methods: This study enrolled 13,440 participants with confirmed Helicobacter pylori (H. pylori) infection status who underwent screening endoscopy by 20 endoscopists in our health screening center. The participants were divided into two groups: one group was observed using white light imaging (WLI) only by 17 endoscopists (WLI group, 10,745 participants), and the other group was observed using TXI2 only by the other three endoscopists (TXI2 group, 2695 participants). We analyzed the detection rate and the characteristics of GC. In addition, considering the bias due to the diagnostic ability, we analyzed the subset of the WLI group where the participants were evaluated by the top three endoscopists based on their GC detection rate (Expert-WLI group, 2792 participants) for comparison with the TXI2 group. Results: Fifty patients were diagnosed with GC. The GC detection rates were 0.68% and 0.71% in the Expert-WLI and TXI2 groups, respectively. In patients who underwent screening endoscopy after H. pylori eradication, the detection rates of differentiated GC, L-region lesions, and surface depressed-type lesions were 0.52%, 0%, and 0.43% in the Expert-WLI group and 1.36%, 0.78%, and 1.36% in the TXI2 group, respectively. Conclusions: In screening endoscopy, the detectability of differentiated GC and L-region lesions and surface depressed-type lesions after H. pylori eradication was higher in TXI2.

Overlooked CO2 emissions induced by air pollution control devices in coal-fired power plants.

China's efforts to mitigate air pollution from its large-scale coal-fired power plants (CFPPs) have involved the widespread use of air pollution control devices (APCDs). However, the operation of these devices relies on substantial electricity generated by CFPPs, resulting in indirect CO2 emissions. The extent of CO2 emissions caused by APCDs in China remains uncertain. Here, using a plant-level dataset, we quantified the CO2 emissions associated with electricity consumption by APCDs in China's CFPPs. Our findings reveal a significant rise in CO2 emissions attributed to APCDs, increasing from 1.48 Mt in 2000 to 51.7 Mt in 2020. Moreover, the contribution of APCDs to total CO2 emissions from coal-fired power generation escalated from 0.12% to 1.19%. Among the APCDs, desulfurization devices accounted for approximately 80% of the CO2 emissions, followed by dust removal and denitration devices. Scenario analysis indicates that the lifespan of CFPPs will profoundly impact future emissions, with Nei Mongol, Shanxi, and Shandong provinces projected to exhibit the highest emissions. Our study emphasizes the urgent need for a comprehensive assessment of environmental policies and provides valuable insights for the integrated management of air pollutants and carbon emissions in CFPPs.

Zipper repair of 3 cm iatrogenic colonic perforation with dual-channel endoscope and twin grasper-assisted titanium clip.

A 53-year-old man undergoing painless colonoscopy for long-term diarrhea. After colonoscopy withdrawing to the sigmoid colon, a local perforation was found, about 3 cm in size, oval in shape. We used a two-channel endoscope and grip to pull the edges of the intestinal wall on both sides of the perforation site to close together, and then repair the 3 cm oval perforation of the colon through multiple ordinary titanium clips. The patient had no obvious infection after surgery and recovered well after 1 month of follow-up. Preliminary experience has shown that using multiple titanium clips under dual-channel endoscope to zipper suture can effectively repair 3 cm iatrogenic colonic perforations.

Dabigatran-induced esophagitis with full circumferential blue pigmentation.

Dabigatran is a useful and widely used drug for stroke prevention in patients with atrial fibrillation. However, it has been reported to cause esophagitis. Herein, we report the case of a 77-year-old man with dabigatran-induced esophagitis with blue pigmentation, which is known to be a rare adverse effect. The patient presented to our hospital with a tightness of the chest and anorexia. Computed tomography revealed a thickening of the entire esophageal wall, with an upper esophageal predominance. Esophagogastroduodenoscopy was performed, which showed that the cervical and upper thoracic esophagus had blue pigmentation with edematous changes, partial narrowing, and longitudinal sloping. We replaced dabigatran with edoxaban, a similar anticoagulation medication. The patient was closely monitored for 1 month after switching to edoxaban. The follow-up esophagogastroduodenoscopy showed marked improvements, revealing resolution of the bluish discoloration and edematous changes, and the patient's complaints regarding the tightness of the chest and anorexia were also resolved. It is important to recognize that such side effects can occur with dabigatran, a drug that is frequently used in daily practice. Considering the fact that strong edematous changes can cause indigo carmine pigmentation associated with dabigatran stagnation, we recommend switching to another anticoagulant if esophagitis occurs during dabigatran administration.

Endoscopic landmarks corresponding to anatomical landmarks for esophageal subsite classification.

Objectives: Individual treatment strategies for esophageal cancer have been investigated based on the anatomical subsite classification. Accurate subsite classification based on these anatomical landmarks is thus important. We investigated the suitability of the existing endoscopic classification and explored alternative landmarks for esophageal subsite classification. Methods: Patients who received endoscopic ultrasonography (and computed tomography scans for surveillance of esophageal cancer treatment or esophageal submucosal tumors were included. Distances between anatomical landmarks, including the inferior cricoid cartilage border, superior border of the sternum, and tracheal bifurcation, were measured using a combination of endoscopic ultrasonography, computed tomography, and other information. Results: The mean (standard deviation) distances from the superior incisor dentition to the pharynx-esophagus, cervical-upper thoracic esophagus, and upper-middle thoracic esophagus boundaries were 16.9 (1.7), 21.7 (1.9), and 29.0 (1.9) cm, respectively. However, variances in the differences between the mean and individual distances were large (2.8, 3.4, and 3.7, respectively), mainly because of differences in body height. However, variances in the differences between individual distances and novel endoscopic landmarks, including the lower end of the pyriform sinus and lower end of compression of the left main bronchus, were lower (1.7, 1.2, and 0.6, respectively). Conclusions: Existing indicators of esophageal subsite boundaries were not consistent with anatomical boundaries. Modification of the distance from the superior incisor dentition based on average distances from anatomical landmarks or the use of alternative endoscopic landmarks is recommended to provide more suitable anatomical boundaries.

Endoscopic ultrasound-guided hepaticogastrostomy versus choledochoduodenostomy for malignant biliary obstruction: A meta-analysis.

Objectives: Endoscopic ultrasound (EUS)-guided biliary drainage encompasses techniques such as EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided choledochoduodenostomy (EUS-CDS). This meta-analysis compared the efficacy of EUS-CDS with that of EUS-HGS for the treatment of biliary obstruction. Methods: A systematic meta-analysis of all relevant articles listed was performed by searching the Cochrane Library, PubMed, and Google Scholar databases. We used random effects or fixed effects models to compare success rates, adverse events, procedure times, and time to recurrent biliary obstruction after EUS-CDS and EUS-HGS. Results: This meta-analysis included 18 eligible studies. There was no significant difference between EUS-CDS and EUS-HGS with respect to technical success rate (odds ratio [OR] 1.04; 95% confidence interval [CI] 0.62-1.73) and clinical success rate (OR 0.66; 95% CI 0.43-1.04), or with respect to total procedure-related adverse events (OR 1.39; 95% CI 1.00-1.93). Subgroup analysis of adverse events revealed that the rate of recurrent biliary obstruction (RBO) was significantly higher for EUS-HGS (OR 2.95; 95% CI 1.54-5.64). There was no significant difference between the two methods with respect to time to recurrent biliary obstruction (mean difference -11.93 days; 95% CI -47.77-23.91). However, the procedure time was longer for EUS-HGS (mean difference, 3.21 min; 95% CI 1.24-5.19). Conclusion: EUS-CDS and EUS-HGS are comparable in terms of technical success, clinical success, and rate of adverse events; however, EUS-CDS is superior with respect to procedure time and preventing RBO.

Safety of full bowel preparation and colonoscopy in elderly patients with ulcerative colitis: A real-world multicenter retrospective cohort study.

Background: The number of elderly patients with ulcerative colitis (UC) has been increasing worldwide. Complications are common in elderly patients who undergo colonoscopy, raising doubts about whether colonoscopy should be performed in the same way in this age group as in younger patients. The aim of this study was to determine the safety of full bowel preparation and colonoscopy in elderly patients with UC. Methods: We retrospectively reviewed a cohort of patients with UC who had visited any of the 12 hospitals and were registered in our inflammatory bowel disease database. We compared complications associated with colonoscopy and bowel preparation and relapse of UC after colonoscopy in 133 patients aged ≥65 years with UC (the elderly group) and 116 randomly selected patients aged <65 years with UC (the non-elderly group). Results: Nine elderly patients were not referred for colonoscopy by their physicians because of poor performance status or advanced age. There was no significant between-group difference in the complication rate (p = 0.57) or frequency of relapse of UC after colonoscopy (p = 0.67). Conclusions: The findings of this study indicate that colonoscopy can be performed as safely in elderly patients with UC as in their younger counterparts. However, our results also indicate that colonoscopy is often avoided in elderly patients, possibly because of concerns about safety.

3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration.

The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO32-, osteogenic effects of Sr2+ and Zn2+, and antibacterial effects of SeO32- and Zn2+. In vitro studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. In vivo tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection.