Radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer: Analysis of an other-cause mortality matched cohort.

OBJECTIVE: Comparative effectiveness studies comparing trimodal therapy (TMT) to radical cystectomy (RC) are typically hindered by selection bias where TMT is usually reserved to patients with poor overall health status. We developed a novel approach by matching patients based on their calculated other-cause mortality (OCM) risk. Using this homogeneous cohort, we tested the impact of TMT vs RC on cancer-specific mortality (CSM). MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) 2004-2018 database was queried to identify patients diagnosed with cT2-4N0M0 muscle-invasive bladder cancer (MIBC). A Fine-Gray competing-risk regression model calculating the 5-year OCM risk was used to create a 1:1 propensity-score matched-cohort of patients treated with RC or TMT. Cumulative incidence and competing-risk regression analyses tested the impact of treatment type (RC vs TMT) on CSM. Patients were further stratified according to clinical T stage (cT2 vs cT3-4) in sensitivity analyses. RESULTS: We identified 6,587 patients (76%) treated with RC and 2,057 (24%) with TMT. The median follow-up was 3.0 years. In the unmatched-cohort, 5-year OCM and CSM rates were 14% and 40% for RC vs 23% and 47% in TMT group, respectively (all P < 0.001). Our matched-cohort included 4,074 patients, equally distributed for treatment type, with no difference in 5-year OCM (HR: 0.98, 95% CI: 0.86-1.11, P = 0.714). In clinical-stage specific sensitivity analyses, 5-year CSM rate was significantly worse for cT2N0M0 patients treated with TMT (HR: 1.52, 95% CI: 1.21-1.91, P < 0.001) than those treated with RC. For cT3-4N0M0 patients, there was no difference in CSM among the 2 approaches (HR: 0.98, 95% CI: 0.63-1.52, P = 0.900). CONCLUSIONS: Our findings demonstrate an oncologic advantage of RC over TMT for cT2 MIBC patients. Conversely, we did not find a cancer-specific survival difference for cT3-T4 MIBC patients, regardless of treatment.

GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in breast cancer patients.

Resistance to DNA-damaging agents is a major unsolved challenge for breast cancer patients undergoing chemotherapy. Here, we show that elevated expression of transcriptional repressor GATA binding 1 (TRPS1) is associated with lower drug sensitivity, reduced response rate, and poor prognosis in chemotherapy-treated breast cancer patients. Mechanistically, elevated TRPS1 expression promotes hyperactivity of DNA damage repair (DDR) in breast cancer cells. We provide evidence that TRPS1 dynamically localizes to DNA breaks in a Ku70- and Ku80-dependent manner, and that TRPS1 is a new member of the DDR protein family. We also discover that the dynamics of TRPS1 assembly at DNA breaks is regulated by its reversible PARylation in the DDR, and that mutations of the PARylation sites on TRPS1 lead to increased sensitivity to chemotherapeutic drugs. Taken together, our findings provide new mechanistic insights into the DDR and chemoresistance in breast cancer patients and identify TRPS1 as a critical DDR protein. TRPS1 may also be considered as a target to improve chemo-sensitization strategies and, consequently, clinical outcomes for breast cancer patients.

Transition-Metal-Free Direct α-Arylation of Weinreb-type Amides with Arylboronic Acids through Aza-oxyallyl Cation Intermediates.

Here, we report an efficient transition-metal-free C(sp2)-C(sp3) Suzuki-Miyaura-type cross-coupling between α-halo Weinreb-type amides and arylboronic acids. The reaction is carried out by capturing active aza-oxyallyl cation (AOAC) with arylboronic acid to form a boron "ate" complex, followed by 1,4-migration to give α-aryl amides with good yields.

Pyroptosis-related gene GSDMC indicates poor prognosis and promotes tumor progression by activating the AKT/mTOR pathway in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is one of the most common malignant tumors of the respiratory. Pyroptosis plays an essential role in cancer, but there is limited research investigating pyroptosis in LUSC. In this study, pyroptosis-related genes were observed to have extensive multiomics alterations in LUSC through analysis of the TCGA database. Utilizing machine learning for selection and verifying expression levels, GSDMC was chosen as the critical gene for further experiments. Our research found that GSDMC is overexpressed in LUSC tissues and cells, and is associated with poor prognosis. Knockdown of GSDMC in LUSC inhibits cell proliferation, invasion, metastasis, chemotherapeutic sensitivity, and reduced tumor formation in nude mice, accompanied by downregulation of proliferative and EMT-related protein expression. However, these effects were counteracted in cells where GSDMC is overexpressed. Mechanistically, the oncogenic role of GSDMC is primarily achieved through the activation of the AKT/mTOR pathway, and this effect can be significantly reversed by rapamycin. Finally, SMAD4's interaction with the promoter region of GSDMC results in the suppression of GSDMC expression. In summary, our study through bioinformatics and experimental approaches not only proves that SMAD4 regulates the protumorigenic role of GSDMC through transcriptional targeting, but also indicates the possibility of developing the SMAD4/GSDMC/AKT/mTOR signaling axis as a potential biomarker and treatment target for LUSC.

Biologic and genomic characterization of a novel virulent Aeromonas hydrophila phage phiA051, with high homology to prophages.

Introduction: Aeromonas hydrophila is particularly harmful to freshwater aquaculture, and the search for phage is an effective biological control method, but reports of possible temperate phages and their mutants are rare in this field. In this study, a virulent phage highly homologous to prophage in the genomes of A. hydrophila was collected and preliminary biological characterization was carried out to understand its nature. Materials and methods: Water samples taken from eel ponds in Fujian, China were combined with the strain. Spot test method and double-layer agar plate assay was used for confirmation and purification. Phage virions were observed using transmission electron microscope. A total of 68 strains of Aeromonas spp. were used to determine the host range. MOI groups of 1,000, 100, 10, 1, 0.1, 0.01, 0.001, 0.0001, 0.00001 were prepared to detect the optimal MOI. The conditions of thermal stability assay were set as 30, 40, 50, 60, 70 and 80°C for 1 h, respectively, and conditions of acid and alkali stability assay were set as 2.0, 4.0, 6.0, 8.0, 10.0 and 12.0 of pH. MOI of 0.01 and 0.1, respectively, are set to determine the inhibitory capacity of phage. Results: A novel virulent A. hydrophila phage designated phiA051 has been isolated from aquaculture water. Electron microscopic observation showed that the phage phiA051 was composed of an icosahedral capsid. The phage phiA051 possesses an optimal multiplicity of infection (MOI) of 0.01, and its burst size was 108 PFU/cell. The phage maintained a high viability at temperatures of 30-50°C or pH 6.0-10.0 for 1 h. Phage phiA051 has certain potentials in rapidly inhibiting the spread of pathogen early in the outbreak, and it has a linear dsDNA with GC content of 60.55% and a total length of 32,212 bp, including 46 ORFs. Discussion: The phage phiA051 behaved as a virulent phage. However, the BLASTN result showed that 23 of the top 25 hits were genomes of Aeromonas strains. It was suggested that phiA051 was probably derived from some prophage in the chromosome of Aeromonas. Further investigation of the mechanism how phage phiA051 transforms from a temperate phage to a virulent phage will provide a unique perspective and idea to explore the potential of prophages.

Assessment of the gender gap in urology industry payments: An Open Payments Program data analysis.

PURPOSE: The Open Payments Program (OPP), established in 2013 under the Sunshine Act, mandated medical device and pharmaceutical manufacturers to submit records of financial incentives given to physicians for public availability. The study aims to characterize the gap in real general and real research payments between man and woman urologists. MATERIALS AND METHODS: The study sample included all urologists in the United States who received at least one general or research payment in the OPP database from 2015 to 2021. Recipients were identified using the National Provider Identifier and National Downloadable File datasets. Payments were analyzed by geography, year, payment type, and years since graduation. Multivariable analysis on odds of being in above the median in terms of money received was done with gender as a covariate. This analysis was also completed for all academic urologists. RESULTS: There was a total of 15,980 urologists; 13.6% were woman, and 86.4% were man. Compared to man urologists, woman urologists were less likely to be in the top half of total payments received (odds ratio [OR] 0.62) when adjusted for other variables. When looking at academic urologists, 18.1% were woman and 81.9% were man. However, woman academic urologists were even less likely to be in the top 50% of payments received (OR 0.55). CONCLUSIONS: This study is the first to characterize the difference in industry payments between man and woman urologists. The results should be utilized to educate physicians and industry, in order to achieve equitable engagement and funding for woman urologists.

FOXP4 is a Direct YAP1 Target that Promotes Gastric Cancer Stemness and Drives Metastasis.

The Hippo-YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo-YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer (GC). As the Hippo-YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it. Here, we identified a vital role of FOXP4 in YAP1-driven gastric carcinogenesis by maintaining stemness and promoting peritoneal metastasis. Loss of FOXP4 impaired GC spheroid formation and reduced stemness marker expression, while FOXP4 upregulation potentiated cancer cell stemness. RNA-seq analysis revealed SOX12 as downstream target of FOXP4, and functional studies established that SOX12 supports stemness in YAP1-induced carcinogenesis. A small molecule screen identified 42-(2-Tetrazolyl)rapamycin as a FOXP4 inhibitor, and targeting FOXP4 suppressed GC tumor growth and enhanced the efficacy of 5-FU chemotherapy in vivo. Collectively, these findings revealed that FOXP4 upregulation by YAP1 in GC regulates stemness and tumorigenesis by upregulating SOX12. Targeting the YAP1-FOXP4-SOX12 axis represents a potential therapeutic strategy for GC.

Surgeon Skill and Perioperative Outcomes in Robot-Assisted Partial Nephrectomy.

Importance: Technical skill in complex surgical procedures may affect clinical outcomes, and there is growing interest in understanding the clinical implications of surgeon proficiency levels. Objectives: To determine whether surgeon scores representing technical skills of robot-assisted kidney surgery are associated with patient outcomes. Design, Setting, and Participants: This quality improvement study included 10 urological surgeons participating in a surgical collaborative in Michigan from July 2021 to September 2022. Each surgeon submitted up to 7 videos of themselves performing robot-assisted partial nephrectomy. Videos were segmented into 6 key steps, yielding 127 video clips for analysis. Each video clip was deidentified and distributed to at least 3 of the 24 blinded peer surgeons from the collaborative who also perform robot-assisted partial nephrectomy. Reviewers rated technical skill and provided written feedback. Statistical analysis was performed from May 2023 to January 2024. Main Outcomes and Measures: Reviewers scored each video clip using a validated instrument to assess technical skill for partial nephrectomy on a scale of 1 to 5 (higher scores indicating greater skill). For all submitting surgeons, outcomes from a clinical registry were assessed for length of stay (LOS) greater than 3 days, estimated blood loss (EBL) greater than 500 mL, warm ischemia time (WIT) greater than 30 minutes, positive surgical margin (PSM), 30-day emergency department (ED) visits, and 30-day readmission. Results: Among the 27 unique surgeons who participated in this study as reviewers and/or individuals performing the procedures, 3 (11%) were female, and the median age was 47 (IQR, 39-52) years. Risk-adjusted outcomes were associated with scores representing surgeon skills. The overall performance score ranged from 3.5 to 4.7 points with a mean (SD) of 4.1 (0.4) points. Greater skill was correlated with significantly lower rates of LOS greater than 3 days (-6.8% [95% CI, -8.3% to -5.2%]), EBL greater than 500 mL (-2.6% [95% CI, -3.0% to -2.1%]), PSM (-8.2% [95% CI, -9.2% to -7.2%]), ED visits (-3.9% [95% CI, -5.0% to -2.8%]), and readmissions (-5.7% [95% CI, -6.9% to -4.6%]) (P < .001 for all). Higher overall score was also associated with higher partial nephrectomy volume (ß coefficient, 11.4 [95% CI, 10.0-12.7]; P < .001). Conclusions and Relevance: In this quality improvement study on video-based evaluation of robot-assisted partial nephrectomy, higher technical skill was associated with lower rates of adverse clinical outcomes. These findings suggest that video-based evaluation plays a role in assessing surgical skill and can be used in quality improvement initiatives to improve patient care.

The Effect of Minority Stress Processes on Smoking for Lesbian, Gay, Bisexual, Transgender, and Queer Individuals: A Systematic Review.

Purpose: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals are more likely to smoke than non-LGBTQ individuals. Smoking has been posited as a coping mechanism for LGBTQ individuals facing minority stress. However, the exact relationship between minority stress and smoking behaviors among LGBTQ individuals is unclear. Therefore, the purpose of this systematic review was to examine how minority stress processes are associated with smoking behaviors for LGBTQ individuals. Methods: Searches of the PubMed and PsycINFO databases were conducted for smoking-, LGBTQ-, and minority stress-related terms. No date, geographic, or language limits were used. For inclusion, the study must have (1) been written in English, (2) had an LGBTQ group as the study population or a component of the study population, (3) assessed the cigarette smoking status of patients, and (4) assessed at least one minority stress-related process (internalized stigma, perceived stigma, or prejudice events). Results: The final review included 44 articles. Aside from two outlier studies, all of the reviewed studies exhibited that increased levels of minority stress processes (internalized queerphobia, perceived stigma, and prejudice events) were associated with increased probability of cigarette use in LGBTQ individuals. Increased minority stress was also associated with greater psychological distress/mental health decline. Conclusion: The findings of this review suggest that minority stress processes represent a contributing factor to smoking health disparities in LGBTQ populations. These results highlight the need for smoking cessation and prevention programs to address minority stress and improve smoking disparities in these populations.

Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients.

Background: Early research indicates that cancer patients are more vulnerable to adverse outcomes and mortality when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, the specific attributes of SARS-CoV-2 in lung Adenocarcinoma (LUAD) have not been extensively and methodically examined. Methods: We acquired 322 SARS-CoV-2 infection-related genes (CRGs) from the Human Protein Atlas database. Using an integrative machine learning approach with 10 algorithms, we developed a SARS-CoV-2 score (Cov-2S) signature across The Cancer Genome Atlas and datasets GSE72094, GSE68465, and GSE31210. Comprehensive multi-omics analysis, including assessments of genetic mutations and copy number variations, was conducted to deepen our understanding of the prognosis signature. We also analyzed the response of different Cov-2S subgroups to immunotherapy and identified targeted drugs for these subgroups, advancing personalized medicine strategies. The expression of Cov-2S genes was confirmed through qRT-PCR, with GGH emerging as a critical gene for further functional studies to elucidate its role in LUAD. Results: Out of 34 differentially expressed CRGs identified, 16 correlated with overall survival. We utilized 10 machine learning algorithms, creating 101 combinations, and selected the RFS as the optimal algorithm for constructing a Cov-2S based on the average C-index across four cohorts. This was achieved after integrating several essential clinicopathological features and 58 established signatures. We observed significant differences in biological functions and immune cell statuses within the tumor microenvironments of high and low Cov-2S groups. Notably, patients with a lower Cov-2S showed enhanced sensitivity to immunotherapy. We also identified five potential drugs targeting Cov-2S. In vitro experiments revealed a significant upregulation of GGH in LUAD, and its knockdown markedly inhibited tumor cell proliferation, migration, and invasion. Conclusion: Our research has pioneered the development of a consensus Cov-2S signature by employing an innovative approach with 10 machine learning algorithms for LUAD. Cov-2S reliably forecasts the prognosis, mirrors the tumor's local immune condition, and supports clinical decision-making in tumor therapies.

Study on the factors affecting the mechanical properties of antler under quasi-static compression.

In the natural environment, antlers have a significant mechanical structure that protects the deer head from injury. In this paper, the mechanical properties of antlers were evaluated through quasi-static compression tests and microstructural observation of samples from antlers, and the relationship between the sampling position, load direction, and microstructure and their mechanical properties were investigated. Compression experiments confirmed that the tines had the strongest mechanical properties, followed by the main beams and finally the brow tines. The mechanical properties of the test specimens subjected to axial compression were higher than those of lateral compression. The axial load test of the longitudinal sample of the tine of the antler has the best mechanical properties. Its specific energy absorption is 51.33 J/g, the peak crushing force is 1.26 kN, and the mean crushing force is 1.47 kN. There are many tubular structures in the transverse sections of antlers, and the distribution of fibers in the vertical direction is laminar with alternating rows forming a helical structure. Tubular structures were found to be prevalent in some of the better biomechanical structures by comparison. Numerical modeling simulations to describe the effect of tubular structures on the mechanical properties of antlers. The simulation results show that the increase in the size of the tubular structure improves its energy absorption within the variation of a 20% increase in the size of the long and short axis. These findings provide a theoretical and experimental basis for the design of energy-absorbing structures. RESEARCH HIGHLIGHTS: In this paper, transverse and longitudinal samples were taken from the main beam, tine, and brow tine of antlers, and axial and lateral compression were carried out, respectively. In this paper, quasi-static compression experiments were carried out on antler samples to study the effects of sampling position, loading direction, and microstructure on antler mechanical properties. By means of microstructure observation and numerical modeling, it is determined that the size of the antler Havel tube has an effect on its mechanical properties.

Simulating PDT of port-wine stains in the in vivo chicken wattle model using Hemoporfin and radiation at 532 nm: Comparison of a LED and a laser source.

Port-wine stain (PWS) birthmarks are congenital capillary malformations occurring in 0.3 %∼0.5 % of newborns. Hemoporfin-mediated vascular-acting photodynamic therapy (Hemoporfin PDT) is an emerging option for treating PWS. This in vivo study aimed to compare laser and light-emitting diodes (LED) as light source for Hemoporfin PDT. Chicken wattles were used as the animal model. Color and histopathological changes were evaluated after combining Hemoporfin with KTP laser or LED light source of 532 nm at the same doses. Both PDT approaches could induce significant vascular injury and color bleaching. Although the use of the laser resulted in a greater vascular clearance, the LED showed more uniform distribution both in the beam profiles and tissue reaction and exhibited better safety. This in vivo study suggests that the LED is a favorable choice for larger PWS lesion.

Aqueous biphasic systems developed with deep eutectic solvents and polymer for the efficient extraction of pigments from beverages.

Novel aqueous biphasic systems (ABSs) developed with benzyl-based quaternary ammonium salts-deep eutectic solvents (DESs) and polypropylene glycol (PPG) were herein proposed. The liquid-liquid equilibrium and the partitioning behavior of pigments in the systems were addressed. The results suggested that the shorter the carbon chain length of the DES, the easier to form two phases. The analysis of mixed samples showed that the selective separation was achieved in the ABSs, including 99.47% of tartrazine in the DES-rich phase and 98.47% of sudan III in the PPG-rich phase. Additionally, the systems were successfully applied to the extraction of pigments from the actual beverage samples with recoveries ranging from 93.43% to 102.15%. Furthermore, the study on the separation mechanism indicated that the hydrogen bonding played a significant role in the separation process. All the above results highlight the proposed DES/polymer-based ABSs have great advantages in selective and high-performance separation of pigments from beverages.

Conversion to Radical Nephrectomy From Robotic Partial Nephrectomy Is Most Commonly Due to Anatomic and Oncologic Complexity.

PURPOSE: Partial nephrectomy is standard-of-care treatment for small renal masses. As utilization of partial nephrectomy increases and includes larger and complex tumors, the risk of conversion to radical nephrectomy likely increases. We evaluated incidence and reason for conversion to radical nephrectomy in patients scheduled for partial nephrectomy by surgeons participating in MUSIC (the Michigan Urologic Surgery Improvement Collaborative). MATERIALS AND METHODS: All patients in whom robotic partial nephrectomy was planned were stratified by completed procedure (robotic partial nephrectomy vs radical nephrectomy). Preoperative and intraoperative records were reviewed for preoperative assessment of difficulty and reason for conversion. Patient, tumor, pathologic, and practice variables were compared between cohorts. RESULTS: Of 650 patients scheduled for robotic partial nephrectomy, conversion to radical nephrectomy occurred in 27 (4.2%) patients. No conversions to open were reported. Preoperative documentation indicated a plan for possible conversion in 18 (67%) patients including partial with possible radical (n = 8), partial vs radical (n = 6), or likely radical nephrectomy (n = 4). Intraoperative documentation indicated that only 5 (19%) conversions were secondary to bleeding, with the remaining conversions due to tumor complexity and/or oncologic concerns. Patients undergoing conversion had larger (4.7 vs 2.8 cm, P < .001) and higher-complexity tumors (64% vs 6%, P < .001) with R.E.N.A.L. (for radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry score ≥ 10. The converted cases had a higher rate of ≥ pT3 (27% vs 8.4%, P = .008). CONCLUSIONS: There was a low rate of conversion from robotic partial to radical nephrectomy in the MUSIC-KIDNEY (Kidney mass: Identifying and Defining Necessary Evaluation and therapY) collaborative, and an even lower risk of conversion due to uncontrolled bleeding. Targeted review of each conversion identified appropriate decision-making based on oncologic risk in most cases.

The role of long noncoding RNAs in ocular angiogenesis and vascular oculopathy.

BACKGROUND: Long noncoding RNAs (lncRNAs) are RNA transcripts over 200 nucleotides in length that do not code for proteins. Initially considered a genomic mystery, an increasing number of lncRNAs have been shown to have vital roles in physiological and pathological conditions by regulating gene expression through diverse mechanisms depending on their subcellular localization. Dysregulated angiogenesis is responsible for various vascular oculopathies, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and corneal neovascularization. While anti-VEGF treatment is available, it is not curative, and long-term outcomes are suboptimal, and some patients are unresponsive. To better understand these diseases, researchers have investigated the role of lncRNAs in regulating angiogenesis and models of vascular oculopathies. This review summarizes recent research on lncRNAs in ocular angiogenesis, including the pro-angiogenic lncRNAs ANRIL, HOTAIR, HOTTIP, H19, IPW, MALAT1, MIAT, NEAT1, and TUG1, the anti-angiogenic lncRNAs MEG3 and PKNY, and the human/primate specific lncRNAs lncEGFL7OS, discussing their functions and mechanisms of action in vascular oculopathies.

Transcriptome-Based Identification of the SaR2R3-MYB Gene Family in Sophora alopecuroides and Function Analysis of SaR2R3-MYB15 in Salt Stress Tolerance.

As one of the most prominent gene families, R2R3-MYB transcription factors significantly regulate biochemical and physiological processes under salt stress. However, in Sophora alopecuroides, a perennial herb known for its exceptional saline alkali resistance, the comprehensive identification and characterization of SaR2R3-MYB genes and their potential functions in response to salt stress have yet to be determined. We investigated the expression profiles and biological functions of SaR2R3-MYB transcription factors in response to salt stress, utilizing a transcriptome-wide mining method. Our analysis identified 28 SaR2R3-MYB transcription factors, all sharing a highly conserved R2R3 domain, which were further divided into 28 subgroups through phylogenetic analysis. Some SaR2R3-MYB transcription factors showed induction under salt stress, with SaR2R3-MYB15 emerging as a potential regulator based on analysis of the protein-protein interaction network. Validation revealed the transcriptional activity and nuclear localization of SaR2R3-MYB15. Remarkably, overexpression of SaR2R3-MYB15 in transgenic plants could increase the activity of antioxidant enzymes and the accumulation of proline but decrease the content of malondialdehyde (MDA), compared with wild-type plants. Moreover, several salt stress-related genes showed higher expression levels in transgenic plants, implying their potential to enhance salt tolerance. Our findings shed light on the role of SaR2R3-MYB genes in salt tolerance in S. alopecuroides.

Research on Indoor Environment Prediction of Pig House Based on OTDBO-TCN-GRU Algorithm.

Temperature and humidity, along with concentrations of ammonia and hydrogen sulfide, are critical environmental factors that significantly influence the growth and health of pigs within porcine habitats. The ability to accurately predict these environmental variables in pig houses is pivotal, as it provides crucial decision-making support for the precise and targeted regulation of the internal environmental conditions. This approach ensures an optimal living environment, essential for the well-being and healthy development of the pigs. The existing methodologies for forecasting environmental factors in pig houses are currently hampered by issues of low predictive accuracy and significant fluctuations in environmental conditions. To address these challenges in this study, a hybrid model incorporating the improved dung beetle algorithm (DBO), temporal convolutional networks (TCNs), and gated recurrent units (GRUs) is proposed for the prediction and optimization of environmental factors in pig barns. The model enhances the global search capability of DBO by introducing the Osprey Eagle optimization algorithm (OOA). The hybrid model uses the optimization capability of DBO to initially fit the time-series data of environmental factors, and subsequently combines the long-term dependence capture capability of TCNs and the non-linear sequence processing capability of GRUs to accurately predict the residuals of the DBO fit. In the prediction of ammonia concentration, the OTDBO-TCN-GRU model shows excellent performance with mean absolute error (MAE), mean square error (MSE), and coefficient of determination (R2) of 0.0474, 0.0039, and 0.9871, respectively. Compared with the DBO-TCN-GRU model, OTDBO-TCN-GRU achieves significant reductions of 37.2% and 66.7% in MAE and MSE, respectively, while the R2 value is improved by 2.5%. Compared with the OOA model, the OTDBO-TCN-GRU achieved 48.7% and 74.2% reductions in the MAE and MSE metrics, respectively, while the R2 value improved by 3.6%. In addition, the improved OTDBO-TCN-GRU model has a prediction error of less than 0.3 mg/m3 for environmental gases compared with other algorithms, and has less influence on sudden environmental changes, which shows the robustness and adaptability of the model for environmental prediction. Therefore, the OTDBO-TCN-GRU model, as proposed in this study, optimizes the predictive performance of environmental factor time series and offers substantial decision support for environmental control in pig houses.

CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.

Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle-type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6-HMGCS1-YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non-alcoholic fatty liver diseases- associated HCC.

The evolving management of small renal masses.

Small renal masses (SRMs) are a heterogeneous group of tumours with varying metastatic potential. The increasing use and improving quality of abdominal imaging have led to increasingly early diagnosis of incidental SRMs that are asymptomatic and organ confined. Despite improvements in imaging and the growing use of renal mass biopsy, diagnosis of malignancy before treatment remains challenging. Management of SRMs has shifted away from radical nephrectomy, with active surveillance and nephron-sparing surgery taking over as the primary modalities of treatment. The optimal treatment strategy for SRMs continues to evolve as factors affecting short-term and long-term outcomes in this patient cohort are elucidated through studies from prospective data registries. Evidence from rapidly evolving research in biomarkers, imaging modalities, and machine learning shows promise in improving understanding of the biology and management of this patient cohort.

Practice-Level Variation in Opioid-Free Discharge Following Surgery for T1 Renal Masses: A MUSIC-KIDNEY Analysis.

INTRODUCTION: Opioid prescription following surgery has played a role in the current opioid epidemic. We evaluated practice-level variation in opioid prescribing following surgery for cT1 renal masses and examined the relationships between opioid-free discharge and postoperative emergency department (ED) visits and readmissions. METHODS: We retrospectively examined all T1 renal mass (RM) patients with data regarding postoperative opioid prescriptions within the Michigan Urological Surgery Improvement Collaborative-Kidney Mass: Identifying and Defining Necessary Evaluation and Therapy (MUSIC-KIDNEY) registry from April 2021 to March 2023. Patients were stratified into those who received opioids at discharge and those with opioid-free discharge. Associations with patient, tumor, and surgical factors were evaluated. Rates of postoperative ED visits and readmissions within 30 days were compared between cohorts. Practice-level variation was assessed. RESULTS: Of 414 patients who underwent surgery for T1 RM across 15 practices in MUSIC-KIDNEY, 23.7% had opioid-free discharge. Practice-level variation in rates of opioid-free discharge ranged from 6.7% to 55.0%. For patients prescribed opioids, the median number of pills was 10 (IQR 6-12). Patients with cT1b masses were more likely to have opioid-free discharge (44.9% vs 32%, OR 0.44; 95% CI 0.22-0.89). Rates of 30-day ED visits (7.0% vs 3.1%) and readmissions (4.1% vs 2.0%) were lower in the opioid-free discharge group but did not reach statistical significance. CONCLUSIONS: MUSIC-KIDNEY data suggest opioid-free discharge is not associated with increased rates of postoperative ED visits or readmissions. There exists wide practice-level variation in opioid prescriptions following surgery for T1 RM in the state of Michigan. Similar variation likely exists throughout the United States, and best surgical practice suggests reduction in opioid prescribing after nephrectomy.