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Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles 1-3 . Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context 4 . Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet 5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data 6 . With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology 7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling., (© 2024. The Author(s).)

Purpose: Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC., Methods: The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software., Results: A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001)., Conclusion: Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To investigate the correlation of melanoma-associated antigen-C gene expression with clinicopathologic characteristics and prognosis in patients with breast cancer through a meta-analysis. PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang and VIP databases were searched from the establishment of the databases to December 2022. The New castle-Ottawa Scale (NOS) was used for literature quality evaluation, and meta-analysis of all studies was performed using Rev Man 5.3 and Stata14.0. A total of 11 studies and 1146 samples were included in the meta-analysis. High expression of MAGE-C gene was significantly correlated with tumor grade (OR = 8.06, 95%CI:4.14-15.67, P < .00001), lymph node metastasis (OR = 8.06, 95%CI:4.14-15.67, P < .00001), tumor type (OR = 0.36, 95%CI: 0.23-0.49, P < .00001), tumor stage (OR = 0.14, 95%CI: 0.05-0.38, P = .0001<.05), ER expression (OR = 0.14, 95%CI: 0.05-0.38, P = .0001<.05), HER-2 expression (OR = 0.24, 95%CI:0.11-0.57, P = .001<.05) and tumor embolus (OR = 0.24, 95%CI:0.11-0.57, P = .001<.05). In addition, the MAGE-C expression was correlated with the reduced overall survival (HR = 2.13, 95%CI: 1.52-2.99, P < .0001), recurrence-free survival (HR = 2.59, 95%CI:1.47-4.56, P = .0010) and metastasis-free survival (OR = 2.52, 95%CI: 1.38-4.59, P = .003). The high expression of MAGE-C gene is closely related to some clinicopathological parameters and poor prognosis of breast cancer, which may be used as a potential biomarker to determine the prognosis of breast cancer., Competing Interests: Disclosure The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Acute myeloid leukemia (AML) is a common leukemia with low cure rate and poor prognosis among pediatric patients. The regulation of AML immune microenvironment and methylation remains to be explored. Pediatric and adult AML patients differ significantly in epigenetic factors, and the efficiency of treatment modalities varies between the two groups of patients., Methods: We collected mRNA, miRNA and DNA methylation data from pediatric AML patients across multiple databases. Differentially expression genes were identified, and a gene-miRNA regulatory network was constructed. Prognostic risk models were established by integrating LASSO and Cox regression, and a nomogram was generated. Based on this model, we investigated tumor-infiltrating immune cells and cell communication, analyzing the biological functions and pathways associated with prognostic factors. Furthermore, the relationships between all prognostic factors and gene modules were explored, and the impact of these factors on treatment modalities was determined., Results: We developed an efficient prognostic risk model and identified HOXA9, SORT1, SH3BP5, mir-224 and mir-335 as biomarkers. We validated these findings in an external dataset and observed a correlation between age and risk in pediatric patients. AML samples with lower risk scores have a better prognosis and higher expression of immune-upregulated biomarkers, and have lower immune scores. Furthermore, we detected discrepancies in immune cell infiltration and interactions between high- and low-risk group samples, which affected the efficacy of immunotherapy. We evaluated all prognostic factors and predicted the effect of immunotherapy and medicine., Conclusion: This study comprehensively investigated the role of methylation signature genes in pediatric AML at the level of genomes and transcriptomes. The research aims to enhance the risk stratification, prognosis evaluation and assessment of treatment effectiveness of AML patients. This study also highlight the uniqueness of pediatric AML and foster the development of new immunotherapy and targeted therapy strategies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: For clinically low-risk stage III colorectal cancer, the decision on cycles of adjuvant chemotherapy after surgery is disputed. The present study investigates the use of additional biomarkers of ploidy and stroma-ratio(PS) to stratify patients with low-risk stage III colorectal cancer, providing a basis for individualized treatment in the future., Methods: This study retrospectively enrolled 198 patients with clinical-low-risk stage III colorectal cancer (T1-3N1M0) and analyzed the DNA ploidy and stroma ratio of FFPE tumor tissues. The patients were divided into PS-low-risk group (Diploidy or Low-stroma) and PS-high-risk group (Non-diploid and High-stroma). For survival analyses, Kaplan-Meier and Cox regression models were used., Results: The results showed that the 5-year DFS of the PS-high-risk group was significantly lower than that in the PS-low-risk group (78.6 vs. 91.2%, HR = 2.606 [95% CI: 1.011-6.717], P = 0.039). Besides, in the PS-low-risk group, the 5 year OS (98.2 vs. 86.7%, P = 0.022; HR = 5.762 [95% CI: 1.281-25.920]) and DFS (95.6, vs 79.9%, P = 0.019; HR = 3.7 [95% CI: 1.24-11.04]) of patients received adjuvant chemotherapy for > 3 months were significantly higher than those received adjuvant chemotherapy for < 3 months. We also found that the PS could stratify the prognosis of patients with dMMR tumors. The 5-year OS (96.3 vs 71.4%, P = 0.037) and DFS (92.6 vs 57.1%, P = 0.015) were higher in the PS-low-risk dMMR patients than those in the PS-high-risk dMMR patients., Conclusion: In this study, we found that PS can predict the prognosis of patients with stage III low-risk CRC. Besides, it may guide the decision on postoperative adjuvant chemotherapy., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Construction of core-shell semiconductor heterojunctions and plasmonic metal/semiconductor heterostructures represents two promising routes to improved light harvesting and promoted charge separation, but their photocatalytic activities are respectively limited by sluggish consumption of charge carriers confined in the cores, and contradictory migration directions of plasmon-induced hot electrons and semiconductor-generated electrons. Herein, a semiconductor/metal/semiconductor stacked core-shell design is demonstrated to overcome these limitations and significantly boost the photoactivity in CO 2  reduction. In this smart design, sandwiched Au serves as a "stone", which "kills two birds" by inducing localized surface plasmon resonance for hot electron generation and mediating unidirectional transmission of conduction band electrons and hot electrons from TiO 2  core to MoS 2  shell. Meanwhile, upward band bending of TiO 2  drives core-to-shell migration of holes through TiO 2 -MoS 2  interface. The co-existence of TiO 2  → Au → MoS 2  electron flow and TiO 2  → MoS 2  hole flow contributes to spatial charge separation on different locations of MoS 2  outer layer for overall redox reactions. Additionally, reduction potential of photoelectrons participating in the CO 2  reduction is elaborately adjusted by tuning the thickness of MoS 2  shell, and thus the product selectivity is delicately regulated. This work provides fresh hints for rationally controlling the charge transfer pathways toward high-efficiency CO 2  photoreduction., (© 2022 Wiley-VCH GmbH.)

Inflammation is a common medical complication in colorectal cancer (CRC) patients, which plays significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICI) is incompletely understood. Here we show that in a patient with high microsatellite instability (MSI-H) CRC and a local inflammatory condition, the primary tumor progresses but its liver metastasis regresses upon Pembrolizumab treatment. In silico investigation prompted by this observation confirms correlation between inflammatory conditions and poor tumor response to PD-1 blockade in MSI-H CRCs, which is further validated in a cohort of 62 patients retrospectively enrolled to our study. Inhibition of local but not systemic immune response is verified in cultures of paired T cells and organoid cells from patients. Single-cell RNA sequencing suggests involvement of neutrophil leukocytes via CD80/CD86-CTLA4 signaling in the suppressive immune microenvironment. In concordance with this finding, elevated neutrophil-to-lymphocyte ratio indicates inhibited immune status and poor tumor response to ICIs. Receiver operating characteristic curve further demonstrates that both inflammatory conditions and a high NLR could predict a poor response to ICIs in MSI- CRCs, and the predictive value could be further increased when these two predictors are combined. Our study thus suggests that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil leukocyte associated immunosuppression and proposes both inflammatory conditions and high neutrophil-to-lymphocyte ratio as clinical features for poor ICI response., (© 2022. The Author(s).)

Background and Objectives: The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM). Methods: A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan-Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS). Results: Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM <0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. < 0.50, HR [95% CI]: 0.67 [0.46-0.99], p = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04-2.05], p = 0.028) and TBS ≥5 (vs. < 5, HR [95% CI]: 1.44 [1.02-2.04], p = 0.038) were associated with worse RFS. Conclusion: PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, He, Li, Zhang, Liu, He, Pan, Lu, Peng and Lin.)

Objective: To investigate the effectiveness of penile up transfer method in the treatment of penoscrotal transposition (PST) in children., Methods: A clinical data of 46 children with PST admitted between January 2015 and March 2021 and met selective criteria was retrospectively analyzed. The M-shaped scrotal flap method was adopted in 21 cases (group A), and the penile up transfer method was adopted in 25 cases (group B). There was no significant difference in age and PST typing between the two groups ( t =0.491, P =0.626; χ 2 =0.710, P =0.790). The operation time and postoperative complications of the two groups were recorded and compared, and the correction effect of PST was evaluated., Results: All operations were successfully completed, and no urethral injury occurred during operation. The operation time was significantly less in group B than in group A [(70.36±9.76) minutes vs . (96.62±13.18) minutes; t =7.553, P =0.000]. All children were followed up 6-33 months (mean, 13.2 months). There were 5 cases (23.8%) of skin necrosis and 6 cases (28.6%) of scar hyperplasia in group A, and 1 case (4.0%) of skin necrosis and 1 case (4.0%) of scar hyperplasia in group B. The incidence of complication was significantly lower in group B than in group A ( χ 2 =3.949, P =0.047; χ 2 =5.341, P =0.021). In the evaluation of PST correction at 6 months after operation, there were 15 cases of complete correction and 6 cases of incomplete correction in group A, 24 cases of complete correction and 1 case of incomplete correction in group B, and the difference was significant ( χ 2 =5.341, P =0.021)., Conclusion: The penis up transfer method is not only easy to correct PST, but also can correct scrotal separation at the same time, with fewer postoperative complications and satisfactory correction effect of penile scrotal appearance.

An estimated 70-80% of cases of colorectal cancer liver metastasis (CRLM) are defined as initially unresectable. "Converting" to no evidence of disease (NED) status may prolong survival. The current study aimed to develop a novel scoring system that predicts the conversion outcome for initially unresectable CRLM. A total of 215 consecutive CRLM patients who received first-line systemic therapy from December 2012 to January 2020 at Sun Yat-sen University Cancer Center were enrolled in the internal cohort. Forty CRLM patients from the database of the Chinese Colorectal Cancer Multidisciplinary Team Alliance were enrolled in the external cohort. A logistic regression model was applied to identify risk factors associated with the conversion outcome. The tumor-to-liver volume ratio (TLVR) was calculated as the total tumor volume divided by the total liver volume, and its cutoff value was 0.23. Three predictors of conversion failure were identified in the internal cohort and incorporated into the C-NED score: poor tumor differentiation (1 point), number of liver metastases > 8 (1 point) and TLVR ≥ 0.23 (1 point). The conversion rate was significantly negatively associated with the C-NED score ( P < 0.001). The C-indexes of the C-NED score for predicting successful conversion outcome in the internal cohort and external cohort were 0.734 (95% confidence interval (CI), 0.668-0.800) and 0.736 (95% CIs, 0.566-0.907), respectively. Median progression-free survival (PFS) time (P = 0.001) and overall survival (OS) time (P = 0.003) were statistically significant different among different C-NED score groups. Our study demonstrated that the C-NED score is an effective scoring system that indicates the actual conversion probability for initially unresectable CRLM patients before treatment, which can serve as a tool that guides optimal first-line management strategies., Competing Interests: None., (AJCR Copyright © 2022.)

Construction of photocatalytic systems with spatially separated dual cocatalysts is considered as a promising route to modulate charge separation/transfer, promote surface redox reactivities, and prevent unwanted reverse reactions. However, past efforts on the loading of spatially separated double-cocatalysts are limited to hollow structured semiconductors with inner/outer surface and monocrystalline semiconductors with different exposed facets. To overcome this limitation, herein, enabled by a unique stacked photocatalyst design, a facile and versatile strategy for spatial separation of redox cocatalysts on various semiconductors without structural and morphological restriction is demonstrated. The smart design begins with the deposition of light-harvesting semiconductors on reduced graphene oxide (rGO) nanosheets, followed with the coverage of Ni(OH) 2 outer layer. The ternary photocatalysts exhibit superior activities and stabilities of H 2 O oxidation and selective CO 2 -to-CO reduction, remarkably surpassing other counterparts. The origin of the enhanced performance is attributed to the synergistic interplay of rGO@Ni(OH) 2 reduction cocatalysts surrounding the semiconductors and Ni(OH) 2 oxidation cocatalysts directly supported by the semiconductors, which mitigates the charge recombination, supplies highly active and selective sites for overall reactions, and preserves the semiconductors from photocorrosion. This work presents a new approach to regulating the position of dual cocatalysts and ameliorating the net efficiency of photoredox catalysis., (© 2021 Wiley-VCH GmbH.)

Introduction: Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs). Methods: One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored. Results: In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival ( p = 0.036 and p = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including "Myc targets," "E2F targets" and "DNA repair" pathways. Conclusion: Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Deng, Yu, Zhao, Peng, Xu, Qin, Xiao, Liu, Li, Fang and Pan.)

Objective: To discuss the effectiveness of modified Brisson surgery in treatment of the severe and obviously obese concealed penis., Methods: A clinical data of 96 boys with severe concealed penis, of 53 cases combined with obviously obese, who were treated by modified Brisson surgery between January 2014 and August 2016, was retrospectively analysed. The children ranged in age from 1 year to 11 years and 9 months, with an average of 5 years and 3 months. The median longitudinal incision of the penis scrotum was used instead of the wedge-shaped skin incision at the junction of the penis and scrotum, which could completely expose the surgical field; fully release and removal of the abnormal meat membrane and fascia around the penis were performed; the propulsion and rotating flaps match the inner sheath of the foreskin was used to completely remove skin stenosis. Postoperative effectiveness was evaluated by Boemers standard., Results: All the incisions healed by first intention and no infection or necrosis of the foreskin flap occurred. Ninety-three cases were discharged from hospital after operation and followed up 1 year to 3 years and 6 months, with an average of 2 years and 4 months. Scrotal hematoma occurred in 2 cases within 48 hours, penile skin edema occurred in 5 cases, and scar hyperplasia in the penis scrotal corner incision occurred in 1 case at 1 month after operation. Postoperative exposure of the penis was good in 90 cases; there was no retraction of the penis in the upright position and sitting position; the family members were satisfied with the appearance of the penis. The penis were partially retracted in 3 cases, that affected the appearance of the penis during the sitting position., Conclusion: The modified Brisson surgery is one of the most effective methods to treat the severe and obviously obese concealed penis, with satisfactory effectiveness and less complication.

Medically complex patients consume a disproportionate amount of care resources in hospitals but still often end up with sub-optimal clinical outcomes. Predicting dynamics of complexity in such patients can potentially help improve the quality of care and reduce utilization of hospital resources. In this work, we model the change prediction of medical complexity using a large dataset of 226K pediatric patients over 5 years from Children's Healthcare of Atlanta (CHOA). We compare different classification methods including logistic regression, random forest, gradient boosting trees, and multilayer perceptron in predicting whether patients will change their complexity status in the last year based on the data from previous years. We achieved an area under the ROC curve (AUC) of 88% for predicting noncomplex patients becoming complex and 74% for predicting complex patients staying complex. We also identify the factors associated with the change in complexity of patients.