Genomic signature for oligometastatic disease in non-small cell lung cancer patients with brain metastases.

Purpose/objectives: Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease. Methods: Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Extracranial oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher's exact tests were used to screen for mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A risk score for the likelihood of oligometastatic disease was generated and correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression. Cox regression was used to determine association between oligometastatic risk score and oligoprogression. Results: 130 patients met study criteria and were included in the analysis. 51 patients (39%) had extracranial oligometastatic disease. Genetic mutations included in the Guardant panel that were associated (p<0.1) with the presence of oligometastatic disease included ATM, JAK2, MAP2K2, and NTRK1, while ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p=0.2). Oligometastatic risk score was significantly associated with the likelihood of oligoprogression based on the Wald chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p=0.03). Conclusions: Elucidation of a genomic signature for extracranial oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients.

Deep Learning Model for Predicting Lung Adenocarcinoma Recurrence from Whole Slide Images.

Lung cancer is the leading cause of cancer-related death in the United States. Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer that can be treated with resection. While resection can be curative, there is a significant risk of recurrence, which necessitates close monitoring and additional treatment planning. Traditionally, microscopic evaluation of tumor grading in resected specimens is a standard pathologic practice that informs subsequent therapy and patient management. However, this approach is labor-intensive and subject to inter-observer variability. To address the challenge of accurately predicting recurrence, we propose a deep learning-based model to predict the 5-year recurrence of LUAD in patients following surgical resection. In our model, we introduce an innovative dual-attention architecture that significantly enhances computational efficiency. Our model demonstrates excellent performance in recurrent risk stratification, achieving a hazard ratio of 2.29 (95% CI: 1.69-3.09, p < 0.005), which outperforms several existing deep learning methods. This study contributes to ongoing efforts to use deep learning models for automatically learning histologic patterns from whole slide images (WSIs) and predicting LUAD recurrence risk, thereby improving the accuracy and efficiency of treatment decision making.

Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-type Non-Small Cell Lung Cancer.

Treatment of non-small cell lung cancer (NSCLC) has drastically changed in recent years owing to the robust anti-cancer effects of immune-checkpoint inhibitors (ICI). However, only 20% of NSCLC patients benefit from ICIs, highlighting the need to uncover the mechanisms mediating resistance. By analyzing the overall survival (OS) and mutational profiles of 424 NSCLC patients who received ICI treatments between 2015 and 2021, we determined that patients carrying a loss of function mutation in neurotrophic tyrosine kinase receptor 1 (NTRK1) had a prolonged OS compared to patients with wild-type NTRK1. Notably, suppression of the NTRK1 pathway by knockdown or Entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models. Comprehensive T cell population analyses demonstrated that stem-like CD4+ T cells and effector CD4+ and CD8+ T cells were highly enriched in anti-PD-1 treated mice bearing tumors with decreased NTRK1 signaling. RNA sequencing revealed that suppression of NTRK1 signaling in tumor cells increased complement C3 expression, which enhanced the recruitment of T cells and myeloid cells and stimulated M1-like macrophage polarization in the tumor. Together, this study demonstrates a role for NTRK1 signaling in regulating crosstalk between tumor cells and immune cells in the tumor microenvironment and provides a potential therapeutic approach to overcomes immunotherapy resistance in NTRK1 wild-type NSCLC patients.

Mutations Associated With High-Grade irAEs in NSCLC Patients Receiving Immunotherapies.

OBJECTIVES: Compared to low-grade irAEs, high-grade irAEs are more often dose-limiting and can alter the long-term treatment options for a patient. Predicting the incidence of high-grade irAEs would help with treatment selection and therapeutic drug monitoring. MATERIALS AND METHODS: We performed a retrospective study of 430 stage III and IV patients with non-small cell lung cancer (NSCLC) who received an immune checkpoint inhibitor (ICI), either with or without chemotherapy, at a single comprehensive cancer center from 2015 to 2022. The study team retrieved sequencing data and complete clinical information, including detailed irAEs medical records. Fisher's exact test was used to determine the association between mutations and the presence or absence of high-grade irAEs. Patients were analyzed separately based on tumor subtypes and sequencing platforms. RESULTS: High-grade and low-grade irAEs occurred in 15.2% and 46.2% of patients, respectively. Respiratory and gastrointestinal irAEs were the 2 most common irAEs. The distribution of patients with or without irAEs was similar between ICI and ICI+chemotherapy-treated patients. By analyzing the mutation data, we identified 5 genes (MYC, TEK, FANCA, FAM123B, and MET) with mutations that were correlated with an increased risk of high-grade irAEs. For the adenocarcinoma subtype, mutations in TEK, MYC, FGF19, RET, and MET were associated with high-grade irAEs; while for the squamous subtype, ERBB2 mutations were associated with high-grade irAEs. CONCLUSION: This study is the first to demonstrate that specific tumor mutations correlate with the incidence of high-grade irAEs in patients with NSCLC treated with an ICI, providing molecular guidance for treatment selection and drug monitoring.

Breathable Wearable Smartsensors Deriving from Interface Self-Assembled Film for Tracking l-Cysteine.

The advent of wearable sensors heralds a transformation in the continuous, noninvasive analysis of biomarkers critical for disease diagnosis and fitness management. Yet, their advancement is hindered by the functional challenges affiliated with their active sensing analysis layer. Predominantly due to suboptimal intrinsic material properties and inconsistent dispersion leading to aggregation, thus compromising sensor repeatability and performance. Herein, an innovative approach to the functionalization of wearable electrochemical sensors was introduced, specifically addressing these limitations. The method involves a proton-induced self-assembly technique at the organic-water (O/W) interface, facilitating the generation of biomarker-responsive films. This research offers flexible, breathable sensor capable of real-time precision tracking l-cysteine (l-Cys) precision tracking. Utilizing an activation mechanism for Prussian blue nanoparticles by hydrogen peroxide, the catalytic core exhibits a specific response to l-Cys. The implications of this study refine the fabrication of film-based analysis electrodes for wearable sensing applications and the broader utilization of two-dimensional materials in functional-specific response films. Findings illuminate the feasibility of this novel strategy for precise biomarker tracking and extend to pave the way for constructing high-performance electrocatalytic analytical interfaces.

IASLC grading system predicts distant metastases for resected lung adenocarcinoma.

AIMS: The International Association for the Study of Lung Cancer (IASLC) has proposed a new histological grading system for invasive lung adenocarcinoma (LUAD). However, the efficacy of this grading system in predicting distant metastases in patients with LUAD remains unexplored. This study aims to assess the potential of the IASLC grading system in predicting the occurrence of brain and bone metastases in patients with resectable LUAD, thereby identifying individuals at high risk of post-surgery distant metastasis. METHODS: We retrospectively analysed clinical data and pathological reports of 174 patients with early-stage LUAD who underwent surgical resection between 2008 and 2015 at our cancer center. Patients were monitored for 5 years, and their bone and brain metastasis-free survival rates were determined. RESULTS: 28 out of 174 patients developed distant metastases in 5 years with a median overall survival of 60 months for metastasis-free patients and 38.3 months for patients with distant metastasis. Tumour grading of all samples was evaluated by both IASLC grading and predominant pattern-based grading systems. Receiver operating characteristic (ROC) curves were used to evaluate the predictive capabilities of the IASLC grading system and tumour stage for distant metastasis. Compared with the predominant pattern-based grading system, the IASLC grading system showed a better correlation with the incidence of distant metastasis and lymphovascular invasion. ROC analyses revealed that the IASLC grading system outperformed tumour stage in predicting distant metastasis. CONCLUSIONS: Our study indicates that the IASLC grading system is capable of predicting the incidence of distant metastasis among patients with early-stage invasive LUAD.

Core Bacterial Taxa Determine Formation of Forage Yield in Fertilized Soil.

Understanding the roles of core bacterial taxa in forage production is crucial for developing sustainable fertilization practices that enhance the soil bacteria and forage yield. This study aims to investigate the impact of different fertilization regimes on soil bacterial community structure and function, with a particular focus on the role of core bacterial taxa in contributing to soil nutrient content and enhancing forage yield. Field experiments and high-throughput sequencing techniques were used to analyze the soil bacterial community structure and function under various fertilization regimes, including six treatments, control with no amendment (CK), double the standard rate of organic manure (T01), the standard rate of organic manure with nitrogen input equal to T04 (T02), half the standard rate of inorganic fertilizer plus half the standard rate of organic manure (T03), the standard rate of inorganic fertilizer reflecting local practice (T04), and double the standard rate of inorganic fertilizer (T05). The results demonstrated that organic manure treatments, particularly T01, significantly increased the forage yield and the diversity of core bacterial taxa. Core taxa from the Actinomycetota, Alphaproteobacteria, and Gammaproteobacteria classes were crucial in enhancing the soil nutrient content, directly correlating with forage yield. Fertilization significantly influenced functions relating to carbon and nitrogen cycling, with core taxa playing central roles. The diversity of core microbiota and soil nutrient levels were key determinants of forage yield variations across treatments. These findings underscore the critical role of core bacterial taxa in agroecosystem productivity and advocate for their consideration in fertilization strategies to optimize forage yield, supporting the shift towards sustainable agricultural practices.

Sex difference in the association between creatinine-to-cystatin C ratio and metabolic syndrome among Chinese adults.

Background: Metabolic syndrome (MetS), characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, affects 20-25% of the global population. The creatinine-to-cystatin C ratio (CCR) is an indicator of skeletal muscle mass. While CCR may play a role in MetS development, sex differences in these associations are not fully understood. Therefore, this study aimed to investigate how CCR levels are associated with MetS in a Chinese adult population, focusing on possible sex disparities. Method: We conducted a retrospective cross-sectional analysis of 9,376 adults from Xiamen Chang Gung Hospital between 2014 to 2016. We examined the relationship between CCR and MetS, adjusting for cardiometabolic risk factors. Results: The prevalence of MetS was 24.7% in males and 18.0% in females. Interestingly, we observed significant sex differences in the association between CCR quartiles and MetS. Females in the lowest CCR quartile had a significantly higher risk of MetS (odds ratio=1.84). Receiver operating characteristic curve analysis revealed acceptable diagnostic power of CCR for MetS in females (area under the curve=0.65) but not in males. Conclusion: Our findings suggest that CCR is an independent risk factor for MetS in females, highlighting the importance of sex-specific assessments when evaluating MetS risk.

Tumor-intrinsic CDC42BPB confers resistance to anti-PD-1 immune checkpoint blockade in breast cancer.

Immune checkpoint blockade has been used to treat breast cancer, but the clinical responses remain relatively poor. We have used the CRISPR-Cas9 kinome knockout library consisting of 763 kinase genes to identify tumor-intrinsic kinases conferring resistance to anti-PD-1 immune checkpoint blockade. We have identified the CDC42BPB kinase as a potential target to overcome the resistance to anti-PD-1 immune checkpoint blockade immunotherapy. We found that CDC42BPB is highly expressed in breast cancer patients who are non-responsive to immunotherapy. Furthermore, a small-molecule pharmacological inhibitor, BDP5290, which targets CDC42BPB, synergized with anti-PD-1 and enhanced tumor cell killing by promoting T cell proliferation in both in vitro and in vivo assays. Moreover, anti-PD-1-resistant breast cancer cells showed higher expression of CDC42BPB, and its inhibition rendered the resistant cells more susceptible to T cell killing in the presence of anti-PD-1. We also found that CDC42BPB phosphorylated AURKA, which in turn upregulated PD-L1 through cMYC. Our results have revealed a robust link between tumor-intrinsic kinase and immunotherapy resistance and have provided a rationale for a unique combination therapy of CDC42BPB inhibition and anti-PD-1 immunotherapy for breast cancer.

The value of 68Ga-PSMA PET/CT in the diagnosis of intracapsular prostate cancer with a poor prognosis.

OBJECTIVE: To evaluate the diagnostic value of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) for intracapsular prostate cancer with a poor prognosis (PPC) and no extracapsular invasion or distant metastasis. METHODS: The PET/CT images and clinical data of 221 patients were retrospectively analyzed. These patients all had clear pathological results. The maximum standard uptake value (SUVmax) of the main lesions was measured at the postprocessing workstation and was tested for correlation with the pathological score. The diagnostic accuracy was calculated using the receiver operating characteristic (ROC) curve, and the best diagnostic threshold was calculated. The correlation between SUVmax and the International Society of Urological Pathology Grade Group (GG) was also analyzed. RESULTS: The pathological results of the 221 patients were 48 benign lesions and 173 malignant lesions, including 81 PPC. Low-, intermediate-, and high-risk prostate cancers made up 21.97% (38/173), 54.33% (94/173), and 23.70% (41/173) of the malignant lesions, respectively. SUVmax and GG were positively correlated (r = 0.54, P < 0.01). The best SUVmax thresholds for 68Ga-PSMA PET/CT for the diagnosis of intracapsular PC and PPC were 7.95 and 13.94, respectively; the specificities were 0.83 and 0.85, the negative predictive values were 0.55 and 0.87, and the areas under the ROC curves were 0.88 and 0.88, respectively. CONCLUSION: 68Ga-PSMA PET/CT has high specificity and NPV in the diagnosis of intracapsular PPC, but the sensitivity for the diagnosis of intracapsular low-risk PC is low, which may cause some cases to be undetected.

Idiopathic young-onset Fahr's disease with schizophrenia-like presentation: a case report.

This case report describes an exceptionally rare case in which a prior diagnosis of schizophrenia was later determined to be early-onset Fahr's disease, linked to a genetic mutation in the SLC20A2 gene. Initially, the patient exhibited symptoms resembling schizophrenia, including aggression and hostility, and was highly susceptible to medication side effects such as restlessness and Parkinsonism. Despite maintaining independent activities of daily living, his neurological examinations revealed hidden weakness on the left side. Following adjustments to the medication regimen, stability was achieved with residual psychotic symptoms under treatment with Risperidone 1.5mg/day, Valproic acid 1500mg/day, and Quetiapine 37.5mg/day. This case underscores the importance of conducting comprehensive imaging studies at the time of initial psychiatric diagnosis, regardless of the apparent typicality of the presentation. Additionally, it emphasizes the need for patience and adherence to the "Start Low and Go Slow" approach in medication management to minimize the risk of exacerbating psychiatric symptoms and aggression.

Thrombosis Rates and Genetic Thrombophilia Risk Among Patients With Advanced Germ Cell Tumors Treated With Chemotherapy.

INTRODUCTION: Men with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). Predictors of VTE may identify patients who would benefit from prophylactic anticoagulation. PATIENTS AND METHODS: Men with advanced GCT (Stage IS, II, III) treated with chemotherapy were identified at 2 centers. High genomic risk was defined from a 5 single nucleotide polymorphism (SNP) germline panel. Logistic regression was used to evaluate the impact of genomic risk on VTE within 6 months of chemotherapy initiation. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was used to build models to predict VTE based on clinical variables and an 86 SNP panel. RESULTS: This 123-patient cohort experienced a VTE rate of 26% with an incidence of high genomic risk of 21%. Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5-3.5, P = .54). Incorporation of clinical variables (Khorana score, N3 status and elevated LDH) resulted in adjusted OR 2.1 (95% CI 0.7-6.5, P = .18). A combined model using clinical variables and 86 SNPs performed similarly (AUC 0.77) compared to clinical variables alone (AUC 0.72). CONCLUSIONS: A previously established 5-SNP panel was not associated with VTE among patients with GCT receiving chemotherapy. However, multivariable models based on clinical variables alone warrant further validation to inform prophylactic anticoagulation strategies.

Benzene-Linked Polymeric Carbon Nitride for Enhanced Photocatalytic Hydrogen Production.

Cross-linking with functional molecular species in polymeric carbon nitride (PCN) could offer a positive strategy that tunes its molecular structure with excellent conductivity to improve photocatalytic activity. Herein, the benzene ring-cross-linked photocatalyst is obtained via the polymerization of urea, melamine, and trimesic acid. Benzene ring-cross-linked PCN narrows the band gap and augments the push-pull effect of carriers, thus enhancing visible light harvesting and transfer easiness of photogenerated electron/hole pairs. Notably, the amount of trimesic acid was optimized during the benzene ring-cross-linked photocatalyst preparation (marked as 01T/A-CN, 02T/A-CN, and 03T/A-CN). Among them, 02T/A-CN photocatalyst achieved an excellent hydrogen production rate of 1931 µmol/h·g, which is higher than that of CN under visible light and beyond most reported. Theoretical calculations further confirmed that the introduction of benzene ring significantly reduces the band gap of PCN, bringing the delocalized electron, a longer intramolecular electron transition distance, and molecular bending. All those factors made benzene ring-cross-linked PCN with improved photocatalytic hydrogen production under visible light irradiation.

Brain metastases from renal cell carcinoma: Effects of novel systemic agents on brain metastasis outcomes.

OBJECTIVE: The objective of this study was to examine survival outcomes in 136 patients with renal cell carcinoma with metastases to the brain who were treated with radiation combined with immunotherapy or tyrosine kinase inhibitor compared to those who were treated with radiation therapy alone. METHODS: The Wake Forest Gamma Knife prospective database was searched for all patients with renal cell carcinoma brain metastases. Outcome measurements included overall survival, determined via the Kaplan-Meier Method, and cumulative incidence of local and distant failure, determined using the Fine Gray competing risks analysis with death as a competing risk for the 136 patients included. RESULTS: Overall survival for the entire population at 6 months, 12 months, and 24 months was 67%, 47% and 30%, respectively. For the TKI (non-immunotherapy-treated) population (n = 37), overall survival was 75%, 61%, and 40% at 6 months, 12 months, and 24 months, respectively. For the immunotherapy-treated population (n = 35), overall survival was 85%, 64%, and 50% at 6 months, 12 months, and 24 months, respectively. Overall survival was significantly increased for patients who received radiation with either immunotherapy or TKI (p < 0.0001). CONCLUSION: Prior series of patients with brain metastases of multiple histologies have demonstrated an improvement in the local efficacy of stereotactic radiosurgery when combined with systemic agents. We found that patients treated with targeted agents and patients treated with immunotherapy demonstrated a trend towards improvement over patients treated in the era prior to the advent of either classes of novel therapies.

Comparison of pharmaceutical properties and biological activities of prednisolone, deflazacort, and vamorolone in DMD disease models.

Duchenne muscular dystrophy (DMD) is a progressive disabling X-linked recessive disorder that causes gradual and irreversible loss of muscle, resulting in early death. The corticosteroids prednisone/prednisolone and deflazacort are used to treat DMD as the standard of care; however, only deflazacort is FDA approved for DMD. The novel atypical corticosteroid vamorolone is being investigated for treatment of DMD. We compared the pharmaceutical properties as well as the efficacy and safety of the three corticosteroids across multiple doses in the B10-mdx DMD mouse model. Pharmacokinetic studies in the mouse and evaluation of p-glycoprotein (P-gP) efflux in a cellular system demonstrated that vamorolone is not a strong P-gp substrate resulting in measurable central nervous system (CNS) exposure in the mouse. In contrast, deflazacort and prednisolone are strong P-gp substrates. All three corticosteroids showed efficacy, but also side effects at efficacious doses. After dosing mdx mice for two weeks, all three corticosteroids induced changes in gene expression in the liver and the muscle, but prednisolone and vamorolone induced more changes in the brain than did deflazacort. Both prednisolone and vamorolone induced depression-like behavior. All three corticosteroids reduced endogenous corticosterone levels, increased glucose levels, and reduced osteocalcin levels. Using micro-computed tomography, femur bone density was decreased, reaching significance with prednisolone. The results of these studies indicate that efficacious doses of vamorolone, are associated with similar side effects as seen with other corticosteroids. Further, because vamorolone is not a strong P-gp substrate, vamorolone distributes into the CNS increasing the potential CNS side-effects.

Delayed Imaging Changes 18 Months or Longer After Stereotactic Radiosurgery for Brain Metastases: Necrosis or Progression.

OBJECTIVE: Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. METHODS: A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. RESULTS: The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. CONCLUSIONS: The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression.

Enteroscopy-Assisted EUS-Guided Trans-gastric Intervention After Roux-en-Y Gastric Bypass Surgery.

Endoscopic ultrasound-directed trans-gastric interventions (EDGI) using lumen apposing metal stent (LAMS) have been increasingly utilized in patients with Roux-en-Y gastric bypass surgery. We present a case of a 71-year-old woman with Roux-en-Y anatomy presenting with choledocholithiasis and enlarged retroperitoneal lymph nodes. Given inability to identify the excluded stomach on routine EUS, enteroscopy was performed with retrograde filling of the excluded stomach to allow for its localization on EUS. The patient underwent LAMS placement to create a jejuno-gastric anastomosis. Subsequently, she had an ERCP (via the LAMS) for removal of bile duct stone and an EUS with fine needle aspiration of the para-aortic lymph node (via the LAMS) confirming malignancy. The LAMS was removed after 2 weeks and the defect closed with APC and clips. An upper GI series obtained at 4 weeks did not show any residual leak. Patient continues to follow up with oncology for workup of primary malignancy.

Treating Multifocal Ureteral Strictures with Combined Techniques: 14 Cases of Initial Experience.

Purpose: To evaluate the safety and feasibility of lingual mucosal graft ureteroplasty (LMGU) combined with ureteral reimplantation (UR) for repairing managing multifocal ureteral strictures (MUS). Methods: Between December 2020 and December 2022, 14 patients underwent LMGU combined with UR. Their perioperative data were collected retrospectively and analyzed. For the proximal diseased ureter, the narrow segment was incised longitudinally to open the ventral wall of ureter, and a lingual mucosal graft was placed as an onlay graft. Meanwhile, UR was applied to treat distal ureteral strictures. Results: Of 14 patients, three (21.4%) had previously undergone a failed ureteral reconstruction. The mean (standard deviation [SD]) proximal stricture length was 4.0 cm (1.56), and distal ureteral stricture length was 4.3 cm (0.94). The mean (SD) operative time was 236 minutes (57), the estimated blood loss was 78 mL (41.5), and the length of postoperative stay was 6 days. One (7%) patient underwent double LMGU to treat proximal 2 segments of ureteral stricture. No open conversions and intraoperative complications occurred. With a mean follow-up of 15 months (range 6-29), the recurrence-free rate was 14/14 (100%). Conclusions: LMGU combined with UR is a feasible and effective technique for managing MUS and can be an alternative to ileal ureteral replacement or renal autotransplantation in some selected patients with MUS.

An Efficient Single Image De-Raining Model With Decoupled Deep Networks.

Single image de-raining is an emerging paradigm for many outdoor computer vision applications since rain streaks can significantly degrade the visibility and render the function compromised. The introduction of deep learning (DL) has brought about substantial advancement on de-raining methods. However, most existing DL-based methods use single homogeneous network architecture to generate de-rained images in a general image restoration manner, ignoring the discrepancy between rain location detection and rain intensity estimation. We find that this discrepancy would cause feature interference and representation ability degradation problems which significantly affect de-raining performance. In this paper, we propose a novel heterogeneous de-raining architecture aiming to decouple rain location detection and rain intensity estimation (DLINet). For these two subtasks, we provide dedicated network structures according to their differential properties to meet their respective performance requirements. To coordinate the decoupled subnetworks, we develop a high-order collaborative network learning the dynamic inter-layer interactions between rain location and intensity. To effectively supervise the decoupled subnetworks during training, we propose a novel training strategy that imposes task-oriented supervision using the label learned via joint training. Extensive experiments on synthetic datasets and real-world rainy scenes demonstrate that the proposed method has great advantages over existing state-of-the-art methods.

Association between N, N-diethyl-m-toluamide exposure and the odds of kidney stones in US adults: a population-based study.

Background: Currently, there is limited research on the specific relationship between N, N-diethyl-m-toluamide (DEET) exposure and the odds of kidney stones. We aimed to investigate the relationship between DEET exposure and the prevalence of kidney stones. Methods: We included 7,567 qualified participants in our research from the 2007-2016 NHANES survey. We carried out three logistic regression models to explore the potential association between DEET exposure and the odds of kidney stones. Spline smoothing with generalized additive models (GAM) was utilized to assess the non-linear relationship and restricted cubic spline (RCS) curves was to determine the dose-response association. Multivariate regression models were used to conduct stratified analysis and sensitivity analysis. Results: Baseline characteristics of study participants presented the distribution of covariables. Regression analysis revealed that the odds of kidney stones were positively associated with the main metabolites of 3-diethyl-carbamoyl benzoic acid (DCBA) (log2) (OR = 1.05, 95% CI 1.02 to 1.08). The fourth quartile of urine DCBA showed a greater risk of kidney stones in the fully adjusted model (OR = 1.36, 95% CI 1.08 to 1.72). Another DEET metabolite of N, N-diethyl-3-hydroxymethylbenzamide (DHMB) was used to confirm the accuracy and stability of the results. The spline smoothing curve represented two main DEET metabolites had similar no-linear relationships and a positive trend with kidney stones proportion. RCS implied that the incidence of kidney stones rose with increasing levels of DEET exposure. High-risk groups on kidney stones were exhibited by stratified analysis under DEET exposure. Conclusion: Our study suggests that DEET exposure is positively associated with odds of kidney stones. Further investigation into the underlying processes of this association is required to guide the prevention and treatment of kidney stones.