Development and Assessment of a Novel Ulcerative Colitis-Specific Quality of Life Questionnaire: A Prospective, Multi-Institutional Study.

PURPOSE: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC. MATERIALS AND METHODS: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach's alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes. RESULTS: A Cronbach's alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ). CONCLUSION: The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement.

Dual Immune Checkpoint Inhibition in Patients With Aggressive Thyroid Carcinoma: A Phase 2 Nonrandomized Clinical Trial.

Importance: Aggressive thyroid carcinoma, including radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC), are associated with significant morbidity and mortality and have limited therapeutic options. Distinct immune profiles have been identified in thyroid cancer subtypes suggesting they may be susceptible to immune checkpoint inhibition. Objective: To evaluate the efficacy of anti-programmed cell death 1 nivolumab and anti-cytotoxic lymphocyte-associated protein 4 ipilimumab in patients with aggressive thyroid carcinoma. Design, Setting, and Participants: This phase 2 nonrandomized clinical trial enrolled patients with RAIR DTC in a single center from October 2017 to May 2019, with exploratory cohorts in MTC and ATC. The data were analyzed between June 2021 and September 2023. Intervention: Intravenous nivolumab, 3 mg/kg, every 2 weeks and ipilimumab, 1 mg/kg, every 6 weeks until disease progression, intolerable adverse events, or a maximum duration of 2 years. Main Outcomes and Measures: The primary end point of the study was objective response rate (ORR) in RAIR DTC, which was scored according to RECIST (Response Evaluation Criteria in Solid Tumours), version 1.1. Key secondary end points included safety, progression-free survival, overall survival, and biomarker analyses. Results: A total of 51 patients were registered, and 49 patients were evaluable for analysis. The median (range) age was 65 years (30-88 years), and 25 participants (51%) were female. ORR in the DTC cohort was 9.4% (3/32 [95% CI, 2.8%-28.5%]), with all partial responses in either oncocytic carcinoma (2/6 [33.0%]) or poorly differentiated thyroid carcinoma (1/5 [20.0%]). Clinical benefit rates were 62.5% (20/32) in the overall DTC cohort, including 83.3% (5/6) in oncocytic carcinoma and 40% (2/5) in poorly differentiated thyroid carcinoma. ORR in the exploratory ATC cohort was 30.0% (3/10 [95% CI, 6.7%-65.2%]), with a clinical benefit rates of 50.0% (5/10). No responses were observed in the exploratory MTC cohort. The safety profile was similar to prior reports with dual immune checkpoint inhibition (pruritus, rash, diarrhea, fatigue, and elevation of lipase and liver enzymes). The presence of NRAS tumor genetic sequence variations, but not BRAF V600E, was associated with worse outcomes. Conclusions and Relevance: This phase 2 nonrandomized clinical trial reported clinical activity of dual immune checkpoint inhibition in aggressive thyroid cancer. The study did not meet its end point in the primary population of RAIR DTC and does not support further investigation in non-biomarker-selected DTC. However, the signal observed in ATC may merit further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT03246958.

Combined high-rate contact stabilization and chemically enhanced primary treatment for enhanced recovery of organic matter and biogas from sewage.

This study examined integrating high-rate contact stabilization (HRCS) and chemically enhanced primary treatment (CEPT) for wastewater to improve the carbon recovery rate (CRR). Enhancing chemical oxygen demand (COD) removal efficiency was hypothesized to improve the CRR. The evaluation covered serial HRCS-CEPT, serial CEPT-HRCS, and single-stage carbon recovery (Single-CR). The COD removal efficiencies for individual HRCS and CEPT were 50.3 % and 56.2 %, respectively. The serial CEPT-HRCS system failed in the HRCS process due to poor settling, resulting in microbial washout. However, the serial HRCS-CEPT system achieved the highest COD removal efficiency (84.5 %). The Single-CR system exhibited the highest CRR of 0.780 ± 0.083 g-CODCH4/g-CODinf, identifying it as the most promising process for energy-positive wastewater treatment. The selective pressure in the high-rate system resulted in a simplified and specialized bacterial community, mainly comprising microorganisms with high polyhydroxyalkanoate storage capacity, such as Lactococcus sp., Enterobacter sp., and Acinetobacter sp.

Distinctive CD39+CD9+ lung interstitial macrophages suppress IL-23/Th17-mediated neutrophilic asthma by inhibiting NETosis.

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39+CD9+ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39+CD9+ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39+CD9+ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39+CD9+ IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39+CD9+ IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.

Thiatruxene-Based Conductive MOF: Harnessing Sulfur Chemistry for Enhanced Proton Transport.

Functionalizing the organic building blocks of electrically conductive MOFs (EC-MOFs) can be a powerful method for adjusting the electronic structure and introducing a specific chemistry. However, designing EC-MOF linkers with reactive functional groups for postsynthetic modification is challenging due to the requirements of d-p conjugation. This work addresses such design limitations by synthesizing an EC-MOF, Cu-thiatruxene (Cu-thiaTRX). This conductive framework incorporated a truxene-based linker with heterocyclic sulfur, allowing for efficient conjugation and an electrical conductivity of 2.2 × 10-2 S cm-1. Harnessing sulfur chemistry in Cu-thiaTRX involves a two-step postsynthetic modification: oxidation and SNAr. The sulfinic groups introduced in the framework enabled tunable proton conductivity, leading to a 200-fold improvement. These results highlight the importance of a rational linker design for functionalization.

The Efficacy of a Home-Based, Augmented Reality Dual-Task Platform for Cognitive-Motor Training in Elderly Patients: A Pilot Observational Study.

OBJECTIVE: This study introduces a novel home-based dual-task platform incorporating augmented reality (AR), COGNIMO, aimed at simultaneously enhancing cognition and physical abilities. The purpose of this study was to assess the effectiveness of this intervention in enhancing cognitive and physical abilities in elderly individuals with subjective cognitive decline, mild cognitive impairment (MCI), and mild Alzheimer's dementia. METHODS: A 12-week observational study enrolled 57 participants aged 60-85 years. Primary outcomes included changes in cognitive scores (Korean Mini-Mental State Examination, 2nd edition [K-MMSE-2] and Korean-Montreal Cognitive Assessment [K-MoCA]), while secondary outcomes measured physical parameters and depression scores between baseline and week 12 in the active and the control groups. RESULTS: Of 57 participants, 49 completed the study. The active group (≥12 sessions) exhibited significant improvement in K-MoCA compared to the control group (<12 sessions) (p=0.004), while K-MMSE-2 score changes showed no significant difference (p=0.579). Positive correlations between training sessions and K-MoCA changes were observed (r=0.31, p=0.038), emphasizing a dose-response relationship. Subgroup analyses revealed a distinction in cognitive changes, particularly in the MCI group. CONCLUSION: The COGNIMO platform showed positive effects on cognitive function in MCI patients, suggesting potential benefits for this population. The study highlights the potential of AR-integrated home-based interventions for cognitive enhancement in elderly individuals, underlining the need for further trials in the future.

Cell states and neighborhoods in distinct clinical stages of primary and metastatic esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a highly lethal cancer of the upper gastrointestinal tract with rising incidence in western populations. To decipher EAC disease progression and therapeutic response, we performed multiomic analyses of a cohort of primary and metastatic EAC tumors, incorporating single-nuclei transcriptomic and chromatin accessibility sequencing, along with spatial profiling. We identified tumor microenvironmental features previously described to associate with therapy response. We identified five malignant cell programs, including undifferentiated, intermediate, differentiated, epithelial-to-mesenchymal transition, and cycling programs, which were associated with differential epigenetic plasticity and clinical outcomes, and for which we inferred candidate transcription factor regulons. Furthermore, we revealed diverse spatial localizations of malignant cells expressing their associated transcriptional programs and predicted their significant interactions with microenvironmental cell types. We validated our findings in three external single-cell RNA-seq and three bulk RNA-seq studies. Altogether, our findings advance the understanding of EAC heterogeneity, disease progression, and therapeutic response.

Cascade Hydroxyl Radical-Generating and Ferroptosis-Inducing Nanofiber System for the Therapy of Oral Squamous Cell Carcinoma.

Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H2O2 generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction.

Prevalence and risk factors for gallstone and renal stone formation in patients with intestinal Behçet's disease.

BACKGROUND/AIMS: The association between inflammatory bowel disease (IBD) and gallstone and renal stone formation has been established. However, few studies have investigated this association in patients with intestinal Behçet's disease (BD). We aimed to examine the prevalence of gallstones and renal stones in patients with intestinal BD and identify potential risk factors. METHODS: We analyzed gallstone and renal stone occurrences in 553 patients diagnosed with intestinal BD who had undergone cross-sectional imaging examinations between March 2005 and April 2021 at the IBD Center, Severance Hospital, Seoul, South Korea. Logistic regression models were used to identify risk factors for gallstone and renal stone formation. RESULTS: Of 553 patients over a mean 12.1-year duration, 141 (25.4%) patients had gallstones and 35 (6.3%) had renal stones. In multivariate logistic regression analysis, disease duration > 19 years (OR 2.91, 95% CI 1.56-5.44, 0.002). No significant correlation 0.001), prior intestinal BD-related surgery (OR 2.29, 95% CI 1.42-3.68, p < 0.001), and disease activity index for intestinal BD scores ≥ 75 (OR 2.23, 95% CI 1.12-4.45, p = 0.022) were associated with increased gallstone occurrence. A positive correlation was observed between renal stones, disease duration > 19 years (OR 5.61, 95% CI 1.98-15.90, p = 0.001) and frequent hospitalization (> 3 times) (OR 3.29, 95% CI 1.52-7.13, p = 0.002). No significant correlation was observed between gallstone and renal stone occurrence. CONCLUSION: These findings contribute to greater understanding concerning gallstone and renal stone prevalence and associated risk factors in patients with intestinal BD.

Intravascular Casting Radiopaque Hydrogel Systems for Transarterial Chemo/Cascade Catalytic/Embolization Therapy of Hepatocellular Carcinoma.

This paper introduces catheter-directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion-crosslinked hyaluronic acid-dopamine (HD) with glucose oxidase (for glucose decomposition to H2O2 in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X-ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X-ray fluoroscopy. Mn4+ (from MnO2) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O2 generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn2+. The gelation time-controlled, catheter-injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC-bearing animal models. The developed radiopaque/injectable/embolic/sol-to-gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.

Advancing Electrically Conductive Metal-Organic Frameworks for Photocatalytic Energy Conversion.

ConspectusPhotocatalytic energy conversion is a pivotal process for harnessing solar energy to produce chemicals and presents a sustainable alternative to fossil fuels. Key strategies to enhance photocatalytic efficiency include facilitating mass transport and reactant adsorption, improving light absorption, and promoting electron and hole separation to suppress electron-hole recombination. This Account delves into the potential advantages of electrically conductive metal-organic frameworks (EC-MOFs) in photocatalytic energy conversion and examines how manipulating electronic structures and controlling morphology and defects affect their unique properties, potentially impacting photocatalytic efficiency and selectivity. Moreover, with a proof-of-concept study of photocatalytic hydrogen peroxide production by manipulating the EC-MOF's electronic structure, we highlight the potential of the strategies outlined in this Account.EC-MOFs not only possess porosity and surface areas like conventional MOFs, but exhibit electronic conductivity through d-p conjugation between ligands and metal nodes, enabling effective charge transport. Their narrow band gaps also allow for visible light absorption, making them promising candidates for efficient photocatalysts. In EC-MOFs, the modular design of metal nodes and ligands allows fine-tuning of both the electronic structure and physical properties, including controlling the particle morphology, which is essential for optimizing band positions and improving charge transport to achieve efficient and selective photocatalytic energy conversion.Despite their potential as photocatalysts, modulating the electronic structure or controlling the morphology of EC-MOFs is nontrivial, as their fast growth kinetics make them prone to defect formation, impacting mass and charge transport. To fully leverage the photocatalytic potential of EC-MOFs, we discuss our group's efforts to manipulate their electronic structures and develop effective synthetic strategies for morphology control and defect healing. For tuning electronic structures, diversifying the combinations of metals and linkers available for EC-MOF synthesis has been explored. Next, we suggest that synthesizing ligand-based solid solutions will enable continuous tuning of the band positions, demonstrating the potential to distinguish between photocatalytic reactions with similar redox potentials. Lastly, we present incorporating a donor-acceptor system in an EC-MOF to spatially separate photogenerated carriers, which could suppress electron-hole recombination. As a synthetic strategy for morphology control, we demonstrated that electrosynthesis can modify particle morphology, enhancing electrochemical surface area, which will be beneficial for reactant adsorption. Finally, we suggest a defect healing strategy that will enhance charge transport by reducing charge traps on defects, potentially improving the photocatalytic efficiency.Our vision in this Account is to introduce EC-MOFs as an efficient platform for photocatalytic energy conversion. Although EC-MOFs are a new class of semiconductor materials and have not been extensively studied for photocatalytic energy conversion, their inherent light absorption and electron transport properties indicate significant photocatalytic potential. We envision that employing modular molecular design to control electronic structures and applying effective synthetic strategies to customize morphology and defect repair can promote charge separation, electron transfer to potential reactants, and mass transport to realize high selectivity and efficiency in EC-MOF-based photocatalysts. This effort not only lays the foundation for the rational design and synthesis of EC-MOFs, but has the potential to advance their use in photocatalytic energy conversion.

Start-up strategy of single-stage partial nitrification-anammox process for anaerobic digestion effluent.

The objective of this study was to improve the nitrogen removal efficiency and reduce the start-up period of a single-stage partial nitritation-anammox (SPNA) system using iron particle-integrated anammox granules (IP-IAGs). Anammox granules were enriched in sequencing batch and expanded granular sludge bed (EGSB) reactors. The EGSB reactor produced larger and more uniform granules with higher specific anammox activity. IP-IAGs were then inoculated into a two-stage partial nitritation-anammox reactor treating anaerobic digestion (AD) effluent, followed by an internal recirculation strategy to acclimate the granules to oxygen exposure for SPNA. Finally, the SPNA process operated to treat real AD effluent under optimal conditions of 0.05 L/min aeration intensity (0.01 vvm) and 24 h of hydraulic retention time, achieving TNRE of 86.01 ± 2.64 % and nitrogen removal rate of 0.74 ± 0.04 kg-N/m3·d for 101 d.

Enhancement of Lithium-Mediated Nitrogen Reduction by Modifying Center Atom of Tetraalkyl-Type Ionic Liquids.

The lithium-mediated nitrogen reduction reaction (Li-NRR) offers a viable alternative to the Haber-Bosch process for ammonia production. However, ethanol, a common proton carrier in Li-NRR, exhibits electrochemical instability, leading to oxidation at the anode or byproduct formation at the cathode. This study replaces alcoholic proton carriers with ionic liquids (ILs), specifically tetrabutylphosphonium chloride (TBPCl) and tetrabutylammonium chloride (TBACl), to examine how the electronegativity differences between the central atom and adjacent carbon of the cation affect catalytic performance. The results show that switching the central atom in tetraalkyl-type ILs markedly enhances performance, specifically resulting in a 1.45-fold increase in Faradaic efficiency (FE) with the transition from phosphonium to ammonium cation of ILs. Additionally, optimal IL concentrations in the electrolyte are identified to maximize ammonia yield. TBACl, in particular, demonstrates enhanced ammonia production and operational stability, achieving an ammonia yield rate of 13.60 nmol/cm2/s, an FE of 39.5 %, and operational stability for over 12 h under conditions of 10 mA/cm2 and 10 atm. This research underscores the potential of precise IL modifications for more efficient and sustainable Li-NRR.

Small-molecule probe for IBD risk variant GPR65 I231L alters cytokine signaling networks through positive allosteric modulation.

The proton-sensing heterotrimeric guanine nucleotide-binding protein-coupled receptor GPR65 is expressed in immune cells and regulates tissue homeostasis in response to decreased extracellular pH, which occurs in the context of inflammation and tumorigenesis. Genome-wide association studies linked GPR65 to several autoimmune and inflammatory diseases such as multiple sclerosis and inflammatory bowel disease (IBD). The loss-of-function GPR65 I231L IBD risk variant alters cellular metabolism, impairs protective tissue functions, and increases proinflammatory cytokine production. Hypothesizing that a small molecule designed to potentiate GPR65 at subphysiological pH could decrease inflammatory responses, we found positive allosteric modulators of GPR65 that engage and activate both human and mouse orthologs of the receptor. We observed that the chemical probe BRD5075 alters cytokine and chemokine programs in dendritic cells, establishing that immune signaling can be modulated by targeting GPR65. Our investigation offers improved chemical probes to further interrogate the biology of human GPR65 and its clinically relevant genetic variants.

Red Fluorescence from Organic Microdots: Leveraging Foldamer-Linked Azobenzene for Enhanced Stability and Intensity in Bioimaging Applications.

Azobenzene, while relevant, has faced constraints in biological system applications due to its suboptimal quantum yield and short-wavelength emission. This study presents a pioneering strategy for fabricating organic microdots by coupling foldamer-linked azobenzene, resulting in robust fluorescence intensity and stability, especially in aggregated states, thereby showing promise for bioimaging applications. Comprehensive experimental and computational examinations elucidate the mechanisms underpinning enhanced photostability and fluorescence efficacy. In vitro and in vivo evaluations disclose that the external layer of cis-azo-foldamer microdots performs a self-sacrificial function during photo-bleaching. Consequently, these red-fluorescent microdots demonstrate extraordinary structural and photochemical stabilities over extended periods. The conjugation of a ß-peptide foldamer to the azobenzene chromophore through a glycine linker instigates a blue-shifted and amplified π*-n transition. Molecular dynamics simulations reveal that the aggregated state of cis-azo-foldamers fortifies the stability of cis isomers, thereby augmenting fluorescence efficiency. This investigation furnishes crucial insights into conceptualizing novel, biologically inspired materials, promising stable and enduring imaging applications, and carries implications for diverse arenas such as medical diagnostics, drug delivery, and sensing technologies.

Multilevel Conductance States of Vapor-Transport-Deposited Sb2S3 Memristors Achieved via Electrical and Optical Modulation.

The pursuit of advanced brain-inspired electronic devices and memory technologies has led to explore novel materials by processing multimodal and multilevel tailored conductive properties as the next generation of semiconductor platforms, due to von Neumann architecture limits. Among such materials, antimony sulfide (Sb2S3) thin films exhibit outstanding optical and electronic properties, and therefore, they are ideal for applications such as thin-film solar cells and nonvolatile memory systems. This study investigates the conduction modulation and memory functionalities of Sb2S3 thin films deposited via the vapor transport deposition technique. Experimental results indicate that the Ag/Sb2S3/Pt device possesses properties suitable for memory applications, including low operational voltages, robust endurance, and reliable switching behavior. Further, the reproducibility and stability of these properties across different device batches validate the reliability of these devices for practical implementation. Moreover, Sb2S3-based memristors exhibit artificial neuroplasticity with prolonged stability, promising considerable advancements in neuromorphic computing. Leveraging the photosensitivity of Sb2S3 enables the Ag/Sb2S3/Pt device to exhibit significant low operating potential and conductivity modulation under optical stimulation for memory applications. This research highlights the potential applications of Sb2S3 in future memory devices and optoelectronics and in shaping electronics with versatility.

The concept of onychodermis containing onychofibroblasts has histological (microanatomical), immunohistochemical as well as molecular basis.

The terms "onychofibroblast" (nail-specific fibroblast) and onychodermis (nail-specific dermis) were first introduced in 2006 and 2012, respectively, based on distinctive histologic and immunohistochemical features from the dermis of the surrounding skin and have been demonstrated in multiple studies. Recently, based on molecular research, the definition of onychodermis containing onychofibroblasts has been expanded to encompass the area located between the nail matrix and bed epithelium and periosteum. Single-cell RNA sequencing and in situ hybridization demonstrated that onychofibroblasts within the onychodermis express the genes including RSPO4, MSX1, WIF-1, and BMP5, which are implicated in nail formation and/or in disorders with nail phenotype. A mutation in RSPO4, a component of the Wnt signaling pathway, causes anonychia congenita. Nail matrix onychodermis and nail bed onychodermis share many similar characteristics which differ from the surrounding normal dermis of the skin. Comparative spatial transcriptomic and single-cell analyses of human nail units and hair follicles suggest that onychodermis is the counterpart of follicular dermal papilla, which plays a key role in hair follicle growth and morphogenesis. Onychomatricoma, as a nail-specific tumor, has been demonstrated to be a mesenchymal tumor that originates from onychofibroblasts and is associated with the upregulation of Wnt signaling. Collectively, the onychodermis and onychofibroblasts play crucial roles in nail development and these specialized nail mesenchymal elements are key components in the pathogenesis of onychomatricoma. The concept of onychodermis containing onychofibroblasts is very important for nail biology and pathology.

Somatic structural variants drive distinct modes of oncogenesis in melanoma.

The diversity of structural variants (SVs) in melanoma and how they impact oncogenesis are incompletely known. We performed harmonized analysis of SVs across melanoma histologic and genomic subtypes, and we identified distinct global properties between subtypes. These included the frequency and size of SVs and SV classes, their relation to chromothripsis events, and the impact on cancer-related genes of SVs that alter topologically associated domain (TAD) boundaries. Following our prior identification of double-stranded break repair deficiency in a subset of triple-wild-type cutaneous melanoma, we identified MRE11 and NBN loss-of-function SVs in melanomas with this mutational signature. Experimental knockouts of MRE11 and NBN, followed by olaparib cell viability assays in melanoma cells, indicated that dysregulation of each of these genes may cause sensitivity to PARP inhibitors in cutaneous melanomas. Broadly, harmonized analysis of melanoma SVs revealed distinct global genomic properties and molecular drivers, which may have biological and therapeutic impact.

Discordance Rate and Risk Factor of Other Diagnostic Modalities for Small Bowel Tumors Detected by Device-Assisted Enteroscopy: A Korean Association for the Study of Intestinal Disease (KASID) Multicenter Study.

Background/Aims: Despite advances in imaging and endoscopic technology, diagnostic modalities for small bowel tumors are simultaneously performed. We investigated the discrepancy rate between each modality and predictive factors of discrepancy in patients with definite small bowel tumors. Methods: Data of patients with definite small bowel tumors who underwent both device-assisted enteroscopy (DAE) and computed tomography (CT) were retrieved from web-based enteroscopy registry database in Korea. Predictive risk factors associated with discrepancy were analyzed using logistic regression analysis. Results: Among 998 patients, 210 (21.0%) were diagnosed with small bowel tumor using DAE, in 193 patients with definite small bowel tumor, DAE and CT were performed. Of these patients, 12 (6.2%) showed discrepancy between examinations. Among 49 patients who underwent DAE and video capsule endoscopy (VCE) examination, 13 (26.5%) showed discrepancy between examinations. No significant independent risk factors were associated with concordance between DAE and CT in multivariate logistic regression analysis among the patients. In a multivariate logistic regression analysis, red blood cell transfusion was negatively associated with concordance between DAE and VCE in patients with small bowel tumor (odds ratio, 0.163; 95% confidence interval, 0.026 to 1.004; p=0.050). Conclusions: For small bowel tumors, the discrepancy rate between DAE and CT was 6.2%, and 26.5% between DAE and VCE. Despite developments in cross-sectional imaging (VCE and DAE modalities), discrepancies still exist. For small bowel bleeding that require significant transfusion while showing insignificant VCE findings, DAE should be considered as the next diagnostic approach, considering the possibility of missed small bowel tumor.