Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.

Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune cells with strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM activity of NK cells engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 NK cells were superior to IL-15 NK cells both in terms of safety and long-term anti-tumor activity, with locoregionally administered IL-15 NK cells proving toxic and ineffective at tumor control. IL-21 NK cells displayed a unique chromatin accessibility signature, with CCAAT/enhancer-binding proteins (C/EBP), especially CEBPD, serving as key transcription factors regulating their enhanced function. Deletion of CEBPD resulted in loss of IL-21 NK cell potency while its overexpression increased NK cell long-term cytotoxicity and metabolic fitness. These results suggest that IL-21, through C/EBP transcription factors, drives epigenetic reprogramming of NK cells, enhancing their anti-tumor efficacy against GBM.

Application of a simplified transesophageal echocardiography examination sequence in high-risk cardiac surgery.

BACKGROUND: In cardiac surgical procedures, patients carrying high-risk profiles are prone to encompass complicated cardiopulmonary bypass (CPB) separation. Intraoperative transesophageal echocardiography (TEE), a readily available tool, is utilized to detect cardiac structural and functional pathologies as well as to facilitate clinical management of CPB separation, especially in the episodes of hemodynamic compromise. However, the conventional TEE examination, always performed in a liberal fashion without any restriction of view acquisition, is relatively time-consuming; there appear its flaws in the context of critically severe status. We therefore developed the perioperative rescue transesophageal echocardiography (PReTEE), a simplified three-view TEE protocol consisting of midesophageal four chamber, midesophageal left ventricular long axis, and transgastric short axis. METHODS: This is a single-center and randomized controlled trial which will be implemented in Peking Union Medical College Hospital, Beijing, China. A total of 46 TEE scans are schemed to be performed by 6 operators participating in and randomly assigned to either the PReTEE or the conventional TEE group. This study is purposed to investigate whether the efficiency of discriminating leading causes of difficult CPB wean-off can be significantly improved via an abbreviated sequence of TEE views. The primary outcome of interest is the difference between the groups of PReTEE and the conventional TEE in the successful discrimination of etiologies in specified 120 s. Cox proportional hazards model will be further employed to calculate the outcome difference. DISCUSSION: The estimated results of this trial are oriented at verifying whether a simplified TEE exam sequence can improve the efficiency of etiologies discrimination during CPB separation in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05960552. Registered on 6 July 2023.

Soil organic carbon formation efficiency from straw/stover and manure input and its drivers: Estimates from long-term data in global croplands.

New soil organic carbon (SOC) formation in cropland from straw/stover or manure input is a vital source of SOC for climate change mitigation. However, location and variations in the efficiency, specifically the ratio of new SOC formation to organic C input (NCE), remain unquantified globally. In this study, the spatial variability of cropland NCE from straw/stover or manure input and explanatory factors were determined by analyzing 897 pairs of long-term field measurements from 404 globally distributed sites and by mapping grid-level cropland NCEs. The global NCE for paddy and upland averaged 13.8% (8.7%-25.1%, 5th-95th percentile) and 10.9% (6.8%-17.3%), respectively. The initial SOC and the clay content of soil, rather than temperature, were the most important factors regulating NCE. A parabola with an apex at approximately 17 g kg-1 between the initial SOC and NCE was resolved, and a positive correlation between soil clay content and NCE was observed. High-resolution mapping of the global NCE derived from manure/straw and insight into NCE dynamics provide a benchmark for diagnosing cropland soil C dynamics under climate change and identifying priority regions and actions for C management.

Bacterial and fungal communities regulated directly and indirectly by tobacco-rape rotation promote tobacco production.

Tobacco continuous cropping is prevalent in intensive tobacco agriculture but often leads to microbial community imbalance, soil nutrient deficiency, and decreased crop productivity. While the tobacco-rape rotation has demonstrated significant benefits in increasing tobacco yield. Microorganisms play a crucial role in soil nutrient cycling and crop productivity. However, the internal mechanism of tobacco-rape rotation affecting tobacco yield through microbe-soil interaction is still unclear. In this study, two treatments, tobacco continuous cropping (TC) and tobacco-rape rotation (TR) were used to investigate how planting systems affect soil microbial diversity and community structure, and whether these changes subsequently affect crop yields. The results showed that compared with TC, TR significantly increased the Shannon index, Chao1 index, ACE index of bacteria and fungi, indicating increased microbial α-diversity. On the one hand, TR may directly affect the bacterial and fungal community structure due to the specificity of root morphology and root exudates in rape. Compared with TC, TR significantly increased the proportion of beneficial bacterial and fungal taxa while significantly reduced soil-borne pathogens. Additionally, TR enhanced the scale and complexity of microbial co-occurrence networks, promoting potential synergies between bacterial OTUs. On the other hand, TR indirectly changed microbial community composition by improving soil chemical properties and changing microbial life history strategies. Compared with TC, TR significantly increased the relative abundance of copiotrophs while reduced oligotrophs. Notably, TR significantly increased tobacco yield by 39.6% compared with TC. The relationships among yield, microbial community and soil chemical properties indicated that planting systems had the greatest total effect on tobacco yield, and the microbial community, particularly bacteria, had the greatest direct effect on tobacco yield. Our findings highlighted the potential of tobacco-rape rotation to increase yield by both directly and indirectly optimizing microbial community structure.

Epidemiologic and genetic associations between primary biliary cholangitis and extrahepatic rheumatic diseases.

Patients with primary biliary cholangitis (PBC) commonly experience extrahepatic rheumatic diseases. However, the epidemiologic and genetic associations as well as causal relationship between PBC and these extrahepatic conditions remain undetermined. In this study, we first conducted systematic review and meta-analyses by analyzing 73 studies comprising 334,963 participants across 17 countries and found strong phenotypic associations between PBC and rheumatic diseases. Next, we utilized large-scale genome-wide association study summary data to define the shared genetic architecture between PBC and rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Sjögren's syndrome (SS). We observed significant genetic correlations between PBC and each of the four rheumatic diseases. Pleiotropy and heritability enrichment analysis suggested the involvement of humoral immunity and interferon-associated processes for the comorbidity. Of note, we identified four variants shared between PBC and RA (rs80200208), SLE (rs9843053), and SSc (rs27524, rs3873182) using cross-trait meta-analysis. Additionally, several pleotropic loci for PBC and rheumatic diseases were found to share causal variants with gut microbes possessing immunoregulatory functions. Finally, Mendelian randomization revealed consistent evidence for a causal effect of PBC on RA, SLE, SSc, and SS, but no or inconsistent evidence for a causal effect of extrahepatic rheumatic diseases on PBC. Our study reveals a profound genetic overlap and causal relationships between PBC and extrahepatic rheumatic diseases, thus providing insights into shared biological mechanisms and novel therapeutic interventions.

Pre-operative prediction of histopathological growth patterns of colorectal cancer liver metastasis using MRI-based radiomic models.

PURPOSE: Histopathological growth patterns (HGPs) of colorectal liver metastases (CRLMs) have prognostic value. However, the differentiation of HGPs relies on postoperative pathology. This study aimed to develop a magnetic resonance imaging (MRI)-based radiomic model to predict HGP pre-operatively, following the latest guidelines. METHODS: This retrospective study included 93 chemotherapy-naïve patients with CRLMs who underwent contrast-enhanced liver MRI and a partial hepatectomy between 2014 and 2022. Radiomic features were extracted from the tumor zone (RTumor), a 2-mm outer ring (RT+2), a 2-mm inner ring (RT-2), and a combined ring (R2+2) on late arterial phase MRI images. Analysis of variance method (ANOVA) and least absolute shrinkage and selection operator (LASSO) algorithms were used for feature selection. Logistic regression with five-fold cross-validation was used for model construction. Receiver operating characteristic curves, calibrated curves, and decision curve analyses were used to assess model performance. DeLong tests were used to compare different models. RESULTS: Twenty-nine desmoplastic and sixty-four non-desmoplastic CRLMs were included. The radiomic models achieved area under the curve (AUC) values of 0.736, 0.906, 0.804, and 0.794 for RTumor, RT-2, RT+2, and R2+2, respectively, in the training cohorts. The AUC values were 0.713, 0.876, 0.785, and 0.777 for RTumor, RT-2, RT+2, and R2+2, respectively, in the validation cohort. RT-2 exhibited the best performance. CONCLUSION: The MRI-based radiomic models could predict HGPs in CRLMs pre-operatively.

Development and interpretation of a multimodal predictive model for prognosis of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It's vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression.

Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.

Advanced gene nanocarriers/scaffolds in nonviral-mediated delivery system for tissue regeneration and repair.

Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

Low estimated glomerular filtration rate and high body mass index are risk factors for acute kidney injury in systemic lupus erythematosus patients after cardiac surgery.

Objective: The occurrence of acute kidney injury (AKI) is common following cardiac surgery, especially among patients characterized with systemic lupus erythematosus (SLE), but studies on this clinical scenario have been limited by the rarity of SLE. We aimed to explore the risk predictors and outcomes with regards to postoperative AKI among cardiac-surgical patients concomitant with SLE. Methods: This was a single-center retrospective study performed in a tertiary hospital. Adult patients diagnosed with SLE who underwent cardiac surgery within the last 22 years were enrolled. Essential variables, including patient-, surgery- and anesthesia-related information, were collected from the medical record system. The definition of AKI was derived from the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Risk predictors suspected to be linked with post-surgical AKI were calculated using the univariable and multivariable analyses. Results: Of all 59 SLE patients undergoing cardiac surgery, 57 were ultimately enrolled into the analysis. AKI occurred in 29 patients (50.9%), who had significantly longer extubation time (median difference 1.0 day, P < 0.001), ICU length of stay (median difference 2.0 days, P = 0.001), postoperative length of stay (median difference 5.0 days, P = 0.026), and more postoperative major complications (odds ratio 10.29, P = 0.025) than the others. Preoperative estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 (odds ratio 5.31, P = 0.021) and body mass index (BMI) ≥ 24 kg/m2 (odds ratio 4.32, P = 0.043) were the only two factors in the multivariable analysis that were significantly correlated with the development of postoperative AKI in patients with SLE after cardiac surgery. Conclusion: AKI in SLE patients after cardiac surgery is common and requires scrutiny, especially in overweight patients with moderate to severe preoperative renal dysfunction.

Gut Microbiota-Derived Butyrate Induces Epigenetic and Metabolic Reprogramming in Myeloid-Derived Suppressor Cells to Alleviate Primary Biliary Cholangitis.

BACKGROUND & AIMS: Gut dysbiosis and myeloid-derived suppressor cells (MDSCs) are implicated in primary biliary cholangitis (PBC) pathogenesis. However, it remains unknown whether gut microbiota or their metabolites can modulate MDSCs homeostasis to rectify immune dysregulation in PBC. METHODS: We measured fecal short-chain fatty acids levels using targeted gas chromatography-mass spectrometry and analyzed circulating MDSCs using flow cytometry in 2 independent PBC cohorts. Human and murine MDSCs were differentiated in vitro in the presence of butyrate, followed by transcriptomic, epigenetic (CUT&Tag-seq and chromatin immunoprecipitation-quantitative polymerase chain reaction), and metabolic (untargeted liquid chromatography-mass spectrometry, mitochondrial stress test, and isotope tracing) analyses. The in vivo role of butyrate-MDSCs was evaluated in a 2-octynoic acid-bovine serum albumin-induced cholangitis murine model. RESULTS: Decreased butyrate levels and defective MDSC function were found in patients with incomplete response to ursodeoxycholic acid, compared with those with adequate response. Butyrate induced expansion and suppressive activity of MDSCs in a manner dependent on PPARD-driven fatty acid ß-oxidation (FAO). Pharmaceutical inhibition or genetic knockdown of the FAO rate-limiting gene CPT1A abolished the effect of butyrate. Furthermore, butyrate inhibited HDAC3 function, leading to enhanced acetylation of lysine 27 on histone H3 at promoter regions of PPARD and FAO genes in MDSCs. Therapeutically, butyrate administration alleviated immune-mediated cholangitis in mice via MDSCs, and adoptive transfer of butyrate-treated MDSCs also displayed protective efficacy. Importantly, reduced expression of FAO genes and impaired mitochondrial physiology were detected in MDSCs from ursodeoxycholic acid nonresponders, and their impaired suppressive function was restored by butyrate. CONCLUSIONS: We identify a critical role for butyrate in modulation of MDSC homeostasis by orchestrating epigenetic and metabolic crosstalk, proposing a novel therapeutic strategy for treating PBC.

Investigating MRI-Associated Biological Aspects of Racial Disparities in Prostate Cancer for African American and White Men.

BACKGROUND: Understanding the characteristics of multiparametric MRI (mpMRI) in patients from different racial/ethnic backgrounds is important for reducing the observed gaps in clinical outcomes. PURPOSE: To investigate the diagnostic performance of mpMRI and quantitative MRI parameters of prostate cancer (PCa) in African American (AA) and matched White (W) men. STUDY TYPE: Retrospective. SUBJECTS: One hundred twenty-nine patients (43 AA, 86 W) with histologically proven PCa who underwent mpMRI before radical prostatectomy. FIELD STRENGTH/SEQUENCE: 3.0 T, T2-weighted turbo spin echo imaging, a single-shot spin-echo EPI sequence diffusion-weighted imaging, and a gradient echo sequence dynamic contrast-enhanced MRI with an ultrafast 3D spoiled gradient-echo sequence. ASSESSMENT: The diagnostic performance of mpMRI in AA and W men was assessed using detection rates (DRs) and positive predictive values (PPVs) in zones defined by the PI-RADS v2.1 prostate sector map. Quantitative MRI parameters, including Ktrans and ve of clinically significant (cs) PCa (Gleason score ≥ 7) tumors were compared between AA and W sub-cohorts after matching age, prostate-specific antigen (PSA), and prostate volume. STATISTICAL TESTS: Weighted Pearson's chi-square and Mann-Whitney U tests with a statistically significant level of 0.05 were used to examine differences in DR and PPV and to compare parameters between AA and matched W men, respectively. RESULTS: A total number of 264 PCa lesions were identified in the study cohort. The PPVs in the peripheral zone (PZ) and posterior prostate of mpMRI for csPCa lesions were significantly higher in AA men than in matched W men (87.8% vs. 68.1% in PZ, and 89.3% vs. 69.6% in posterior prostate). The Ktrans of index csPCa lesions in AA men was significantly higher than in W men (0.25 ± 0.12 vs. 0.20 ± 0.08 min-1; P < 0.01). DATA CONCLUSION: This study demonstrated race-related differences in the diagnostic performances and quantitative MRI measures of csPCa that were not reflected in age, PSA, and prostate volume. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Formyl peptide receptor 1 mitigates colon inflammation and maintains mucosal homeostasis through the inhibition of CREB-C/EBPß-S100a8 signaling.

Excessive inflammatory responses are the main characteristic of ulcerative colitis (UC). Activation of formyl peptide receptor 1 (FPR1) has been found to promote the proliferation and migration of epithelial cells, but its role and therapeutic potential in UC remain unclear. This study observed an increased expression of FPR1 in a mouse model of colitis. Interestingly, FPR1 deficiency exacerbated UC and increased the secretion of the proinflammatory mediator from immune cells (e.g. macrophages), S100a8, a member of the damage-associated molecular patterns. Notably, the administration of the FPR agonist Cmpd43 ameliorated colon injury in a preclinical mice model of UC, likely via inhibiting phosphorylation of cyclic adenosine monophosphate-response element-binding protein and expression of CCAAT/enhancer-binding protein ß, which in turn suppressed the secretion of S100a8. In conclusion, these findings discovered a novel role of FPR1 in the development of colitis and will facilitate the development of FPR1-based pharmacotherapy to treat UC.

Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.

Osteoporosis is a major clinical problem in many autoimmune diseases, including primary biliary cholangitis (PBC), the most common autoimmune liver disease. Osteoporosis is a major cause of fracture and related mortality. However, it remains unclear whether PBC confers a causally risk-increasing effect on osteoporosis. Herein, we aimed to investigate the causal relationship between PBC and osteoporosis and whether the relationship is independent of potential confounders. We performed bidirectional Mendelian randomization (MR) analyses to investigate the association between PBC (8021 cases and 16,489 controls) and osteoporosis in Europeans (the UK Biobank and FinnGen Consortium: 12,787 cases and 726,996 controls). The direct effect of PBC on osteoporosis was estimated using multivariable MR analyses. An independent replication was conducted in East Asians (PBC: 2495 cases and 4283 controls; osteoporosis: 9794 cases and 168,932 controls). Trans-ethnic meta-analysis was performed by pooling the MR estimates of Europeans and East Asians. Inverse-variance weighted analyses revealed that genetic liability to PBC was associated with a higher risk of osteoporosis in Europeans (OR, 1.040; 95% CI, 1.016-1.064; P = 0.001). Furthermore, the causal effect of PBC on osteoporosis persisted after adjusting for BMI, calcium, lipidemic traits, and sex hormones. The causal relationship was further validated in the East Asians (OR, 1.059; 95% CI, 1.023-1.096; P = 0.001). Trans-ethnic meta-analysis confirmed that PBC conferred increased risk on osteoporosis (OR, 1.045; 95% CI, 1.025-1.067; P = 8.17 × 10-6). Our data supports a causal effect of PBC on osteoporosis, and the causality is independent of BMI, calcium, triglycerides, and several sex hormones.

AtPCa-Net: anatomical-aware prostate cancer detection network on multi-parametric MRI.

Multi-parametric MRI (mpMRI) is widely used for prostate cancer (PCa) diagnosis. Deep learning models show good performance in detecting PCa on mpMRI, but domain-specific PCa-related anatomical information is sometimes overlooked and not fully explored even by state-of-the-art deep learning models, causing potential suboptimal performances in PCa detection. Symmetric-related anatomical information is commonly used when distinguishing PCa lesions from other visually similar but benign prostate tissue. In addition, different combinations of mpMRI findings are used for evaluating the aggressiveness of PCa for abnormal findings allocated in different prostate zones. In this study, we investigate these domain-specific anatomical properties in PCa diagnosis and how we can adopt them into the deep learning framework to improve the model's detection performance. We propose an anatomical-aware PCa detection Network (AtPCa-Net) for PCa detection on mpMRI. Experiments show that the AtPCa-Net can better utilize the anatomical-related information, and the proposed anatomical-aware designs help improve the overall model performance on both PCa detection and patient-level classification.

Configurable SNAP microresonators induced by axial pre-strain-assisted CO2 laser exposure.

Flexible engineering of the complex shapes of the surface nanoscale axial photonics (SNAP) bottle microresonators (SBMs) is challenging for future nanophotonic technology applications. Here, we experimentally propose a powerful approach for the one-step fabrication of SBMs with simultaneous negative and positive radius variations, exhibiting a distinctive "bump-well-bump" profile. It is executed by utilizing two focused and symmetrical CO2 laser beams exposed on the fiber surface for only several hundred milliseconds. The spectral characteristics of different eigenmodes are analyzed, providing deep insights into the complex physical processes during the CO2 laser exposure. The shapes of the SBMs can be flexibly adjusted by the exposure time, laser power, and applied pre-strains. As a proof of this technique, the developed approach enables the efficient production of a bat SBM, ensuring a uniform field amplitude of the bat mode over the length exceeding 120 µm with 7% deviation. Our proposed technique provides a powerful technique for the efficient fabrication of SBMs with predetermined shapes, laying the groundwork for its applications on microscale optical signal processing, quantum computing, and so on.

The Heterogeneity of Symptom Burden and Fear of Progression Among Kidney Transplant Recipients: A Latent Class Analysis.

Purpose: Kidney transplant recipients (KTRs) may experience symptoms that increase their fear of progression (FoP), but a dearth of research examines the issue from a patient-centered perspective. Our study aimed to first determine the category of symptom burden, then to explore the differences in characteristics of patients in different subgroups, and finally to analyze the impact of symptom subgroup on FoP. Patients and Methods: Sociodemographic and Clinical Characteristics, Symptom Experience Scale, and Fear of Progression Questionnaire-Short Form were used. Latent class analysis was used to group KTRs according to the occurrence of symptoms. We used multivariate logistic regression to analyze the predictors of different subgroups. The differences in FoP among symptom burden subgroups were analyzed by hierarchical multiple regression. Results: Three subgroups were identified, designated all-high (20.5%), moderate (39.9%), and all-low (39.6%) according to their symptom occurrence. Multivariate logistic regression showed that gender, post-transplant time, per capita monthly income, and hyperuricemia were the factors that distinguished and predicted the all-high subgroup (P < 0.05). Hierarchical multiple regression showed that symptom burden had a significant effect on FoP (class1 vs class3: ß = 0.327, P < 0.001; class2 vs class3: ß = 0.104, P = 0.046), explaining the 8.0% variance of FoP (ΔR2 = 0.080). Conclusion: KTRs generally experience moderate or low symptom burden, and symptom burden is an influencing factor in FoP. Identifying the traits of KTRs with high symptom burden can help clinicians develop targeted management strategies and ease FoP of KTRs.