Marine Oil Pollution Monitoring Based on a Morphological Attention U-Net Using SAR Images.

This study proposed an improved full-scale aggregated MobileUNet (FA-MobileUNet) model to achieve more complete detection results of oil spill areas using synthetic aperture radar (SAR) images. The convolutional block attention module (CBAM) in the FA-MobileUNet was modified based on morphological concepts. By introducing the morphological attention module (MAM), the improved FA-MobileUNet model can reduce the fragments and holes in the detection results, providing complete oil spill areas which were more suitable for describing the location and scope of oil pollution incidents. In addition, to overcome the inherent category imbalance of the dataset, label smoothing was applied in model training to reduce the model's overconfidence in majority class samples while improving the model's generalization ability. The detection performance of the improved FA-MobileUNet model reached an mIoU (mean intersection over union) of 84.55%, which was 17.15% higher than that of the original U-Net model. The effectiveness of the proposed model was then verified using the oil pollution incidents that significantly impacted Taiwan's marine environment. Experimental results showed that the extent of the detected oil spill was consistent with the oil pollution area recorded in the incident reports.

Effect of CO2 Elevation on Tomato Gas Exchange, Root Morphology and Water Use Efficiency under Two N-Fertigation Levels.

Atmospheric elevated CO2 concentration (e[CO2]) decreases plant nitrogen (N) concentration while increasing water use efficiency (WUE), fertigation increases crop nutrition and WUE in crop; yet the interactive effects of e[CO2] coupled with two N-fertigation levels during deficit irrigation on plant gas exchange, root morphology and WUE remain largely elusive. The objective of this study was to explore the physiological and growth responses of ambient [CO2] (a[CO2], 400 ppm) and e[CO2] (800 ppm) tomato plant exposed to two N-fertigation regimes: (1) full irrigation during N-fertigation (FIN); (2) deficit irrigation during N-fertigation (DIN) under two N fertilizer levels (reduced N (N1, 0.5 g pot-1) and adequate N (N2, 1.0 g pot-1). The results indicated that e[CO2] associated with DIN regime induced the lower N2 plant water use (7.28 L plant-1), maintained leaf water potential (-5.07 MPa) and hydraulic conductivity (0.49 mol m-2 s-1 MPa-1), greater tomato growth in terms of leaf area (7152.75 cm2), specific leaf area (223.61 cm2 g-1), stem and total dry matter (19.54 g and 55.48 g). Specific root length and specific root surface area were increased under N1 fertilization, and root tissue density was promoted in both e[CO2] and DIN environments. Moreover, a smaller and denser leaf stomata (4.96 µm2 and 5.37 mm-2) of N1 plant was obtained at e[CO2] integrated with DIN strategy. Meanwhile, this combination would simultaneously reduce stomatal conductance (0.13 mol m-2 s-1) and transpiration rate (1.91 mmol m-2 s-1), enhance leaf ABA concentration (133.05 ng g-1 FW), contributing to an improvement in WUE from stomatal to whole-plant scale under each N level, especially for applying N1 fertilization (125.95 µmol mol-1, 8.41 µmol mmol-1 and 7.15 g L-1). These findings provide valuable information to optimize water and nitrogen fertilizer management and improve plant water use efficiency, responding to the potential resource-limited and CO2-enriched scenario.

Renal glomus tumor: A case report and literature review.

Glomus tumors are rare mesenchymal tumors involving cells from the glomus body, smooth muscle, and vasculature, typically found in distal extremities' skin. This case describes a 54-year-old woman with a history of hypothyroidism and hyperlipidemia, incidentally discovered to have a four-centimeter calcified renal tumor. Surgery was performed due to suspected malignancy. Immunohistochemical staining confirmed a renal glomus tumor, positive for muscle actin and smooth muscle actin (SMA). The tumor was benign, and no adjuvant therapy was needed. The patient remained recurrence-free during follow-up. Renal glomus tumors are predominantly benign, with surgical resection as the primary treatment.

Protective effects of nordalbergin against LPS-induced endotoxemia through inhibiting MAPK/NF-κB signaling pathway, NLRP3 inflammasome activation, and ROS production.

OBJECTIVE: Nordalbergin is a coumarin extracted from Dalbergia sissoo DC. To date, the biological effects of nordalbergin have not been well investigated. To investigate the anti-inflammatory responses and the anti-oxidant abilities of nordalbergin using lipopolysaccharide (LPS)-activated macrophages and LPS-induced sepsis mouse model. MATERIALS AND METHODS: Production of nitrite oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß), reactive oxygen species (ROS), tissue damage and serum inflammatory markers, and the activation of the NLRP3 inflammasome were examined. RESULTS: Our results indicated that nordalbergin reduced the production of NO and pro-inflammatory cytokines in vitro and ex vivo. Nordalbergin also suppressed iNOS and cyclooxygenase-2 expressions, decreased NF-κB activity, and attenuated MAPKs signaling pathway activation by decreasing JNK and p38 phosphorylation by LPS-activated J774A.1 macrophages. Notably, nordalbergin diminished NLRP3 inflammasome activation via repressing the maturation of IL-1ß and caspase-1 and suppressing ROS production by LPS/ATP- and LPS/nigericin-activated J774A.1 macrophages. Furthermore, nordalbergin exhibited protective effects against the infiltration of inflammatory cells and also inhibited the levels of organ damage markers (AST, ALT, BUN) by LPS-challenged mice. CONCLUSION: Nordalbergin possesses anti-inflammatory effects in macrophage-mediated innate immune responses, alleviates ROS production, decreases NLRP3 activation, and exhibits protective effects against LPS-induced tissue damage in mice.

Full-Scale Aggregated MobileUNet: An Improved U-Net Architecture for SAR Oil Spill Detection.

Oil spills are a major threat to marine and coastal environments. Their unique radar backscatter intensity can be captured by synthetic aperture radar (SAR), resulting in dark regions in the images. However, many marine phenomena can lead to erroneous detections of oil spills. In addition, SAR images of the ocean include multiple targets, such as sea surface, land, ships, and oil spills and their look-alikes. The training of a multi-category classifier will encounter significant challenges due to the inherent class imbalance. Addressing this issue requires extracting target features more effectively. In this study, a lightweight U-Net-based model, Full-Scale Aggregated MobileUNet (FA-MobileUNet), was proposed to improve the detection performance for oil spills using SAR images. First, a lightweight MobileNetv3 model was used as the backbone of the U-Net encoder for feature extraction. Next, atrous spatial pyramid pooling (ASPP) and a convolutional block attention module (CBAM) were used to improve the capacity of the network to extract multi-scale features and to increase the speed of module calculation. Finally, full-scale features from the encoder were aggregated to enhance the network's competence in extracting features. The proposed modified network enhanced the extraction and integration of features at different scales to improve the accuracy of detecting diverse marine targets. The experimental results showed that the mean intersection over union (mIoU) of the proposed model reached more than 80% for the detection of five types of marine targets including sea surface, land, ships, and oil spills and their look-alikes. In addition, the IoU of the proposed model reached 75.85 and 72.67% for oil spill and look-alike detection, which was 18.94% and 25.55% higher than that of the original U-Net model, respectively. Compared with other segmentation models, the proposed network can more accurately classify the black regions in SAR images into oil spills and their look-alikes. Furthermore, the detection performance and computational efficiency of the proposed model were also validated against other semantic segmentation models.

Selective therapeutic efficacy of tyrosine kinase inhibitor sorafenib on the restoration of methylglyoxal-induced peritoneal fibrosis.

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects.

Dome-type extracorporeal manual morcellation during laparoscopic uterine surgery: Two years' experience in a teaching hospital.

OBJECTIVE: This study aims to describe the dome-type manual morcellation technique, a modified form of C-type incision, its comparative advantages over existing morcellation methods, the perioperative outcomes of trainees with varying experience levels, and the variables influencing morcellation speed based on our two years of experience. METHODS: This retrospective cohort study included women who underwent laparoscopic myomectomy or hysterectomy using dome-type morcellation for tissue extraction at a tertiary teaching hospital between May 2020 and September 2022. Morcellation was performed by either a single surgeon or a trainee (resident). Basic patient characteristics, perioperative outcomes, and morcellation time and speed were compared between the surgeon and trainee group. Regression models were employed to analyze variables influencing morcellation speed. RESULTS: A total of 41 women were enrolled. Among them, 20 procedures were performed by a surgeon alone, while the remaining 21 procedures were completed by trainees under the surgeon's supervision. The median weight of the specimens was 378 g (range 91-1345 g), and the median time for morcellation was 10 min (range 1-55 min). The median morcellation speed of surgeon and trainees was 70.25 and 31.7 g/min, respectively. Trainees' level of experience was found to be associated with morcellation speed, particularly for soft specimens. Additionally, both incision size and specimen stiffness were significantly associated with morcellation speed. No morcellation-related complications or bag ruptures were observed. CONCLUSION: Dome-type manual morcellation is an intuitive, efficient and safe method for specimen removal and is easy to learn for beginners.

Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy.

Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo, I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46 %, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.

N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance.

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.

Spatially controlled diffusion range of tumor-associated angiogenic factors to develop a tumor model using a microfluidic resistive circuit.

Developing a tumor model with vessels has been a challenge in microfluidics. This difficulty is because cancer cells can overgrow in a co-culture system. The up-regulation of anti-angiogenic factors during the initial tumor development can hinder neovascularization. The standard method is to develop a quiescent vessel network before loading a tumor construct in an adjacent chamber, which simulates the interaction between a tumor and its surrounding vessels. Here, we present a new method that allows a vessel network and a tumor to develop simultaneously in two linked chambers. The physiological environment of these two chambers is controlled by a microfluidic resistive circuit using two symmetric long microchannels. Applying the resistive circuit, a diffusion-dominated environment with a small 2-D pressure gradient is created across the two chambers with velocity <10.9 nm s-1 and Péclet number <6.3 × 10-5. This 2-D pressure gradient creates a V-shaped velocity clamp to confine the tumor-associated angiogenic factors at pores between the two chambers, and it has two functions. At the early stage, vasculogenesis is stimulated to grow a vessel network in the vessel chamber with minimal influence from the tumor that is still developed in the adjacent chamber. At the post-tumor-development stage, the induced steep concentration gradient at pores mimics vessel-tumor interactions to stimulate angiogenesis to grow vessels toward the tumor. Applying this method, we demonstrate that vasculogenic vessels can grow first, followed by stimulating angiogenesis. Angiogenic vessels can grow into stroma tissue up to 1.3 mm long, and vessels can also grow into or wrap around a 625 µm tumor spheroid or a tumor tissue developed from a cell suspension. In summary, our study suggests that the interactions between a developing vasculature and a growing tumor must be controlled differently throughout the tissue development process, including at the early stage when vessels are still forming and at the later stage when the tumor needs to interact with the vessels.

Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH. METHODS: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target. RESULTS: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH.

Foldable paper-based photoelectrochemical biosensor based on etching reaction of CoOOH nanosheets-coated laser-induced PbS/CdS/graphene for sensitive detection of ampicillin.

Timely and rapid detection of antibiotic residues in the environment is conducive to safeguarding human health and promoting an ecological virtuous cycle. A foldable paper-based photoelectrochemical (PEC) sensor was successfully developed for the detection of ampicillin (AMP) based on glutathione/zirconium dioxide hollow nanorods/aptamer (GSH@ZrO2 HS@apt) modified cellulose paper as a reactive zone with laser direct-writing lead sulfide/cadmium sulfide/graphene (PbS/CdS/LIG) as photoelectrode and cobalt hydroxide (CoOOH) as a photoresist material. Initially, AMP was introduced into the paper-based reaction zone as a biogate aptamer, which specifically recognized the target and then left the ZrO2 HS surface, releasing glutathione (GSH) encapsulated inside. Subsequently, the introduction of GSH into the reaction region and etching of CoOOH nanosheets to expose the PbS/CdS/LIG photosensitive material increased photocurrent. Under optimal conditions, the paper-based PEC biosensor showed a linear response to AMP in the range of 5.0 - 2 × 104 pM with a detection limit of 1.36 pM (S/N = 3). In addition, the constructed PEC sensing platform has excellent selectivity, high stability and favorable reproducibility, and can be used to assess AMP residue levels in various real water samples (milk, tap water, river water), indicating its promising application in environmental antibiotic detection.

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes.

INTRODUCTION: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD). METHODS: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC. RESULTS: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference. DISCUSSION: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

Microbacterium abyssi sp. nov. and Microbacterium limosum sp. nov., two new species of the genus Microbacterium, isolated from deep-sea sediment samples.

Two Gram-positive, non-motile, short rod-shaped actinomycete strains, designated as A18JL241T and Y20T, were isolated from deep-sea sediment samples collected from the Southwest Indian Ocean and Western Pacific Ocean, respectively. Both of the isolates were able to grow within the temperature range of 5-40 °C, NaCl concentration range of 0-7  % (w/v) and at pH 6.0-12.0. The two most abundant cellular fatty acids of both strains were anteiso-C15  :  0 and anteiso-C17  :  0. The major polar lipid contents of the two strains were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and one unidentified glycolipid. These two strains shared common chemotaxonomic features comprising MK-10 and MK-12 as the respiratory quinones. The genomic DNA G+C contents of the two strains were 68.1 and 70.4  mol%, respectively. The 16S rRNA gene phylogeny showed that the novel strains formed two distinct sublines within the genus Microbacterium. Strain A18JL241T was most closely related to the type strain of Microbacterium tenebrionis KCTC 49593T (98.8 % sequence similarity), whereas strain Y20T formed a tight cluster with the type strain of Microbacterium schleiferi NBRC 15075T (99.0 %). The orthologous average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values with the type strains of related Microbacterium species were in the range of 74.1-89.1  % and 19.4-36.9  %, respectively, which were below the recognized thresholds of 95-96 % ANI and 70 % dDDH for species definition. Based on the results obtained here, it can be concluded that strains A18JL241T and Y20T represent two novel species of the genus Microbacterium, for which the names Microbacterium abyssi sp. nov. (type strain A18JL241T=JCM 33956T=MCCC 1A16622T) and Microbacterium limosum sp. nov. (type strain Y20T=JCM 33960T=MCCC 1A16747T) are proposed.

Feasibility of High-Cellular-Resolution Full-Field, Artificial-Intelligence-Assisted, Real-Time Optical Coherence Tomography in the Evaluation of Vitiligo: A Prospective Longitudinal Follow-Up Study.

Vitiligo, a psychologically distressing pigmentary disorder characterized by white depigmented patches due to melanocyte loss, necessitates non-invasive tools for early detection and treatment response monitoring. High-cellular-resolution full-field optical coherence tomography (CRFF-OCT) is emerging in pigmentary disorder assessment, but its applicability in vitiligo repigmentation after tissue grafting remains unexplored. To investigate the feasibility of CRFF-OCT for evaluating vitiligo lesions following tissue grafting, our investigation involved ten vitiligo patients who underwent suction blister epidermal grafting and laser ablation at a tertiary center between 2021 and 2022. Over a six-month period, clinical features, dermoscopy, and photography data were recorded. Utilizing CRFF-OCT along with artificial intelligence (AI) applications, repigmentation features were captured and analyzed. The CRFF-OCT analysis revealed a distinct dark band in vitiligo lesion skin, indicating melanin loss. Grafted areas exhibited melanocytes with dendrites around the epidermal-dermal junction and hair follicles. CRFF-OCT demonstrated its efficacy in the early detection of melanocyte recovery and accurate melanin quantification. This study introduces CRFF-OCT as a real-time, non-invasive, and in vivo evaluation tool for assessing vitiligo repigmentation, offering valuable insights into pigmentary disorders and treatment responses.

Role of sentinel lymph node evaluation during hysterectomy for preoperative pathology diagnosis of endometrial intraepithelial neoplasia in a community hospital setting.

OBJECTIVE: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC). METHODS: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling. RESULTS: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups. CONCLUSION: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.

Gasdermin-E-Dependent Non-Canonical Pyroptosis Promotes Drug-Induced Liver Failure by Promoting CPS1 deISGylation and Degradation.

Drug-induced liver injury (DILI) is a significant global health issue that poses high mortality and morbidity risks. One commonly observed cause of DILI is acetaminophen (APAP) overdose. GSDME is an effector protein that induces non-canonical pyroptosis. In this study, the activation of GSDME, but not GSDMD, in the liver tissue of mice and patients with APAP-DILI is reported. Knockout of GSDME, rather than GSDMD, in mice protected them from APAP-DILI. Mice with hepatocyte-specific rescue of GSDME reproduced APAP-induced liver injury. Furthermore, alterations in the immune cell pools observed in APAP-induced DILI, such as the replacement of TIM4+ resident Kupffer cells (KCs) by monocyte-derived KCs, Ly6C+ monocyte infiltration, MerTk+ macrophages depletion, and neutrophil increase, reappeared in mice with hepatocyte-specific rescue of GSDME. Mechanistically, APAP exposure led to a substantial loss of interferon-stimulated gene 15 (ISG15), resulting in deISGylation of carbamoyl phosphate synthetase-1 (CPS1), promoted its degradation via K48-linked ubiquitination, causing ammonia clearance dysfunction. GSDME deletion prevented these effects. Delayed administration of dimethyl-fumarate inhibited GSDME cleavage and alleviated ammonia accumulation, mitigating liver injury. This findings demonstrated a previously uncharacterized role of GSDME in APAP-DILI by promoting pyroptosis and CPS1 deISGylation, suggesting that inhibiting GSDME can be a promising therapeutic option for APAP-DILI.

Chronic Viral Hepatitis B and C Outweigh MASLD in the Associated Risk of Cirrhosis and HCC.

BACKGROUND & AIMS: The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known. METHODS: A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019. RESULTS: In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively. CONCLUSIONS: These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.

Risk of secondary primary malignancies in survivors of upper tract urothelial carcinoma: A nationwide population-based analysis.

BACKGROUND: To investigate the cancer types and risk factors of secondary primary malignancy (SPM) in patients with upper tract urothelial carcinoma (UTUC) in Taiwan. METHODS: Using National Health Insurance Research Dataset and catastrophic illness registry, we enrolled newly diagnosed UTUC patients from 2000 to 2013. Those without catastrophic illness registration were excluded from the study. The cancer types and hazard ratios (HRs) of subsequent SPMs were calculated according to the antecedent malignancy. We analyzed the risk factors for developing SPMs using multivariate Cox proportional hazard models. RESULTS: A total of 9050 UTUC patients were registered and 2187 (24.2%) patients developed SPMs during the study period. As compared with primary UTUC, the relative risk ratios of SPM was 2.5 folds and 18% higher in those with antecedent non-UC malignancy and with bladder cancer history, respectively. Totally, 387 (37.8%) of 1022 UTUC patients with antecedent non-UC malignancy developed subsequent SPM after UTUC diagnosis. The antecedent and subsequent cancer types are similar and kidney cancer is most common, followed by hepatoma. Multivariate analysis showed that a history of antecedent non-UC malignancy is the most unfavorable factor for SPM development (HR, 2.50; 95% CI, 2.23-2.81), followed by liver disease, male gender, antecedent bladder cancer history, age ≥ 75 years, and chronic kidney disease. CONCLUSIONS: Our study, conducted in Taiwan and involving 9050 UTUC patients, meticulously examined the types of SPM and the associated risk factors. Our research unearthed several pivotal discoveries: a preceding history of non-UC malignancies emerged as the single most influential factor contributing to the occurrence of subsequent cancers, followed by liver disease, male gender, antecedent bladder cancer history, age ≥75 years, and chronic kidney disease. Futhermore, kidney cancer emerged as the predominant subsequent malignancy, closely trailed by hepatoma..

Integration of the cancer cell secretome and transcriptome reveals potential noninvasive diagnostic markers for bladder cancer.

PURPOSE: Bladder cancer (BLCA) is a major cancer of the genitourinary system. Although cystoscopy is the standard protocol for diagnosing BLCA clinically, this procedure is invasive and expensive. Several urine-based markers for BLCA have been identified and investigated, but none has shown sufficient sensitivity and specificity. These observations underscore the importance of discovering novel BLCA biomarkers and developing a noninvasive method for detection of BLCA. Exploring the cancer secretome is a good starting point for the development of noninvasive biomarkers for cancer diagnosis. EXPERIMENTAL DESIGN: In this study, we established a comprehensive secretome dataset of five representative BLCA cell lines, BFTC905, TSGH8301, 5637, MGH-U1, and MGH-U4, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression of BLCA-specific secreted proteins at the transcription level was evaluated using the Oncomine cancer microarray database. RESULTS: The expressions of four candidates-COMT, EWSR1, FUSIP1, and TNPO2-were further validated in clinical human specimens. Immunohistochemical analyses confirmed that transportin-2 was highly expressed in tumor cells relative to adjacent noncancerous cells in clinical tissue specimens from BLCA patients, and was significantly elevated in BLCA urine compared with that in urine samples from aged-matched hernia patients (controls). CONCLUSIONS: Collectively, our findings suggest TNPO2 as a potential noninvasive tumor-stage or grade discriminator for BLCA management.