Dopamine-integrated all-hydrogel multi-electrode arrays for neural activity recording.

Investigation of brain neural circuits is essential for deciphering the diagnostics and therapeutics of neurodegenerative diseases. The main concerns with traditional rigid metal electrodes include intrinsic mechanical mismatch between sensing electrodes and tissues, unavoidable foreign body responses, and inadequate spatiotemporal resolution, resulting in a deficiency of sensing performance. All-hydrogel neural electrodes with multi-electrode arrays (MEAs) suggest a viable way to modulate the trade-off between tissue-mechanical compliance and excellent spatiotemporal recording capacity, but still face the issues of insufficient conductivity and unstable interlayer bonding. Herein, we constructed a four-layer all-hydrogel neural electrode, by sandwiching a conductive hydrogel layer within two encapsulation hydrogel layers, with a shielding hydrogel layer located on top. We introduce a dual-strategy treatment to induce controllable phase separation in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogel, which achieved ultra-high conductivity (up to 4176 S cm-1) comparable to that of metals and precise spatial resolution (∼15 µm) suitable for single neuron recording. In addition, the utilization of polyphenol chemistry mediated adaptive adhesion endowed this neural electrode with flexible and stable interlayer bonding among conductive-encapsulation-shielding layers and the tissue-electrode interface. Consequently, the all-hydrogel neural electrode exhibited a tenfold higher signal-to-noise ratio than a commercial silver electrode, realized the recording of weak neural activity signals within single and multiple neurons in epileptic rats, and applied man-made stimulation to the cerebral cortex of rats during seizures. This work provides a useful tool to understand the development, function and treatment of neurodegenerative diseases.

Flexible Temperature Sensor with High Reproducibility and Wireless Closed-Loop System for Decoupled Multimodal Health Monitoring and Personalized Thermoregulation.

Temperature and pulse waves are two fundamental indicators of body health. Specifically, thermoresistive flexible temperature sensors are one of the most applied sensors. However, they suffer from poor reproducibility of resistivity; and decoupling temperature from pressure/strain is still challenging. Besides, autonomous thermoregulation by wearable sensory systems is in high demand, but conventional commercial apparatuses are cumbersome and not suitable for long-term portable use. Here, a material-design strategy is developed to overcome the problem of poor reproducibility of resistivity by tuning the thermal expansion coefficient to nearly zero, precluding the detriment caused by shape expansion/shrinkage with temperature variation and achieving high reproducibility. The strategy also obtains more reliable sensitivity and higher stability, and the designed thermoresistive fiber has strain-insensitive sensing performance and fast response/recovery time. A smart textile woven by the thermoresistive fiber can decouple temperature and pulse without crosstalk; and a flexible wireless closed-loop system comprising the smart textile, a heating textile, a flexible diminutive control patch, and a smartphone is designed and constructed to monitor health status in real-time and autonomously regulate body temperature. This work offers a new route to circumvent temperature-sensitive effects for flexible sensors and new insights for personalized thermoregulation.

Impact of prior SARS-CoV-2 infection on postoperative recovery in patients with hepatocellular carcinoma resection.

BACKGROUND: The impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC) remains uncertain given the lack of sufficient evidence. AIM: To investigate the impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who were pathologically diagnosed with HCC and underwent elective partial hepatectomy in Guangdong Provincial People's Hospital between January 2022 and April 2023 were enrolled in this retrospective cohort study. The patients were divided into two groups based on their history of SARS-CoV-2 infection. Rehabilitation parameters, including postoperative liver function, incidence of complications, and hospitalization expenses, were compared between the two groups. Propensity score matching (PSM) was performed to reduce confounding bias. RESULTS: We included 172 patients (58 with and 114 without prior SARS-CoV-2 infection) who underwent liver resection for HCC. No significant differences in the rehabilitation parameters were observed between the two groups. After PSM, 58 patients were selected from each group to form the new comparative groups. Similar results were obtained within the population after PSM. CONCLUSION: Prior SARS-CoV-2 infection does not appear to affect postoperative rehabilitation, including liver function, postoperative complications, or hospitalization expenses among patients with HCC after elective partial hepatectomy.

Fundamental Understanding of Interface Chemistry and Electrical Contact Properties of Bi and MoS2.

The interface properties and thermal stability of bismuth (Bi) contacts on molybdenum disulfide (MoS2) shed light on their behavior under various deposition conditions and temperatures. The examination involves extensive techniques including X-ray photoelectron spectroscopy, scanning tunneling microscopy (STM), and scanning tunneling spectroscopy (STS). Bi contacts formed a van der Waals interface on MoS2 regardless of deposition conditions, such as ultrahigh vacuum (UHV, 3 × 10-11 mbar) and high vacuum (HV, 4 × 10-6 mbar), while the oxidation on MoS2 has been observed. However, the semimetallic properties of Bi suppress the impact of defect states, including oxidized-MoS2 and vacancies. Notably, the n-type characteristic of Bi/MoS2 remains unaffected, and no significant changes in the local density of states near the conduction band minimum are observed despite the presence of defects detected by STM and STS. As a result, the Fermi level (EF) resides below the conduction band of MoS2. The study also examines the impact of annealing on the contact interface, revealing no interface reaction between Bi and MoS2 up to 300 °C. These findings enhance our understanding of semimetal (Bi) contacts on MoS2, with implications for improving the performance and reliability of electronic devices.

Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis.

Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. Here, we establish that aging of the immune system, regardless of the age of the stroma and tumor, drives lung cancer progression. Hematopoietic aging enhances emergency myelopoiesis, resulting in the local accumulation of myeloid progenitor-like cells in lung tumors. These cells are a major source of IL-1⍺ that drives the enhanced myeloid response. The age-associated decline of DNMT3A enhances IL-1⍺ production, and disrupting IL-1R1 signaling early during tumor development normalized myelopoiesis and slowed the growth of lung, colonic, and pancreatic tumors. In human tumors, we identified an enrichment for IL-1⍺-expressing monocyte-derived macrophages linked to age, poorer survival, and recurrence, unraveling how aging promotes cancer and offering actionable therapeutic strategies.

A transformer-based deep learning model for early prediction of lymph node metastasis in locally advanced gastric cancer after neoadjuvant chemotherapy using pretreatment CT images.

Background: Early prediction of lymph node status after neoadjuvant chemotherapy (NAC) facilitates promptly optimization of treatment strategies. This study aimed to develop and validate a deep learning network (DLN) using baseline computed tomography images to predict lymph node metastasis (LNM) after NAC in patients with locally advanced gastric cancer (LAGC). Methods: A total of 1205 LAGC patients were retrospectively recruited from three hospitals between January 2013 and March 2023, constituting a training cohort, an internal validation cohort, and two external validation cohorts. A transformer-based DLN was developed using 3D tumor images to predict LNM after NAC. A clinical model was constructed through multivariate logistic regression analysis as a baseline for subsequent comparisons. The performance of the models was evaluated through discrimination, calibration, and clinical applicability. Furthermore, Kaplan-Meier survival analysis was conducted to assess overall survival (OS) of LAGC patients at two follow-up centers. Findings: The DLN outperformed the clinical model and demonstrated a robust performance for predicting LNM in the training and validation cohorts, with areas under the curve (AUCs) of 0.804 (95% confidence interval [CI], 0.752-0.849), 0.748 (95% CI, 0.660-0.830), 0.788 (95% CI, 0.735-0.835), and 0.766 (95% CI, 0.717-0.814), respectively. Decision curve analysis exhibited a high net clinical benefit of the DLN. Moreover, the DLN was significantly associated with the OS of LAGC patients [Center 1: hazard ratio (HR), 1.789, P < 0.001; Center 2:HR, 1.776, P = 0.013]. Interpretation: The transformer-based DLN provides early and effective prediction of LNM and survival outcomes in LAGC patients receiving NAC, with promise to guide individualized therapy. Future prospective multicenter studies are warranted to further validate our model. Funding: National Natural Science Foundation of China (NO. 82373432, 82171923, 82202142), Project Funded by China Postdoctoral Science Foundation (NO. 2022M720857), Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (NO. U22A20345), National Science Fund for Distinguished Young Scholars of China (NO. 81925023), Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (NO. 2022B1212010011), High-level Hospital Construction Project (NO. DFJHBF202105), Natural Science Foundation of Guangdong Province for Distinguished Young Scholars (NO. 2024B1515020091).

The First Case of Lynch Syndrome-Associated Penile Cancer Harboring a Heterozygous PMS2 Frameshift Variant.

INTRODUCTION: Penile squamous cell carcinoma (PSCC) is a rare malignancy in men with poor survival in metastatic disease. Lynch syndrome (LS) is a cancer predisposition, autosomal-dominant, inherited disorder that arises from loss of function variants in mismatch repair genes. CASE PRESENTATION: Here, we reported a PSCC patient who was suspected with LS caused by a heterozygous PMS2 D526Afs*69 variant. A 57-year-old male with PSCC underwent pelvic lymph node dissection and bilateral groin lymph node dissection due to metastatic disease. He has a family history of colon cancer and brain cancer. Comprehensive genomic sequencing of his tumor specimen identified 19 somatic mutations with a high tumor mutation burden (14.03 mutations per Mb) and a high frequency of microsatellite instability. Additionally, a germline PMS2 D526Afs*69 mutation was identified in the peripheral blood sample. Immunohistochemistry analysis showed complete loss of PMS2 and MLH1 expression in his tumor. CONCLUSION: These observations provided evidence suggesting that PSCC could be part of the LS spectrum.

Combination of Cytologic Findings and Circulating Tumor DNA From Cerebrospinal Fluid Revealed SCLC Transformation in Patients With Leptomeningeal Metastases of Lung Adenocarcinoma.

Introduction: Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce. Methods: We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing. Results: Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the EGFR mutation, including four patients with EGFR exon 19 deletion and three patients with EGFR exon 21 L858R mutation. Another patient harbored ERBB2 insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that TP53 and RB1 mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0-17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2-29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0-5.9 mo). Conclusions: SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

Magnetic shielding properties of an iron-based nanocrystalline alloy for induction heating systems.

A nanocrystalline alloy, with an iron-based composition (Fe58.5Si16.7B6.5Nb5.1Cu13.2) and a Curie temperature of 570 °C, was investigated for its effectiveness as magnetic shielding films in an induction heating system. The primary focus of the research was to evaluate the shielding performance of the 3-turned (9-layered) shielding films with dimensions of 135 mm × 17 mm × 0.15 mm. Upon winding, these films formed a cylindrical structure that enveloped the coil, with a diameter of 13.9 mm and a height of 17 mm. The results showed that increasing the degree of fragmentation within the nanocrystalline shielding films significantly reduced the magnetic permeability by decreasing the real component from 11,500 to 400 and the imaginary part from 2800 to 20. However, a lower degree of fragmentation led to a 10 % increase in the resistance (Rs) of the heating module, although this effect was less pronounced as the relative permeability continued to increase. Furthermore, observations on preheating time to a set temperature of 400 °C and total energy consumption over a duration of 250s revealed an initial downward trend, followed by a rapid increase that even exceeded the initial values as the magnetic permeability of the nanocrystalline shielding films augmented. Notably, the study emphasized that nanocrystalline shielding films with a relative permeability value of 1000 demonstrated exceptional magnetic shielding performance, resulting in a 12.5 % reduction in preheat time and 7 % less energy consumption during preheating. In addition to empirical findings, the study developed a theoretical model elucidating the shielding mechanism inherent in induction heating systems. This model serves as a robust framework for the application of nanocrystalline shielding materials in such systems, laying the groundwork for enhanced magnetic shielding capabilities in future applications.

On-Chip Synthesis of Quasi-2D Semimetals from Multi-Layer Chalcogenides.

Reducing the dimensions of materials from three to two, or quasi-two, provides a fertile platform for exploring emergent quantum phenomena and developing next-generation electronic devices. However, growing high-quality, ultrathin, quasi2D materials in a templated fashion on an arbitrary substrate is challenging. Here, the study demonstrates a simple and reproducible on-chip approach for synthesizing non-layered, nanometer-thick, quasi-2D semimetals. In one implementation, this method starts with thin semiconducting InSe flakes of below 20 nm in thickness with nickel deposited on top, followed by a low-temperature annealing step that results in a controlled transformation of the layered InSe to a non-layered, crystalline semimetal via reaction with the laterally diffusing nickel. Atomic resolution microscopy reveals the transformed semimetal to be Ni3In2Se2 with a Kagome-lattice structure. Moreover, it is demonstrated that this synthesis method is generalizable by transforming 2D layered chalcogenides such as SnS and SnSe employing Ni and Co to non-layered semimetals, paving the way for engineering novel types of devices.

Patterns of failure and the subsequent treatment after progression on first-line immunotherapy monotherapy in advanced non-small cell lung cancer: a retrospective study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the recommended first-line treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, data on the failure patterns of first-line ICIs monotherapy is limited, and the optimal strategy for subsequent treatment remains controversial. METHODS: Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and October 2021 were identified. The progressive sites were recorded to analyze failure patterns. Post-progression survival (PPS) was compared between different treatment regimens. RESULTS: A total of 121 patients receiving first-line ICIs monotherapy were identified, with a median progression-free survival of 8.6 months. Sixty-five patients had available imaging at diagnosis as well as progressive disease, with 56.9% showing oligoprogression. For those with progression in existing lesions, the most common sites were the liver (77.8%) and lung parenchyma (62.5%), while progression with new lesions frequently occurred in the liver (32.0%). Fifty patients with recorded subsequent treatment were included in the analysis of subsequent treatment patterns. Patients treated with anti-angiogenesis therapy could get better PPS (HR: 0.275, P = 0.013). Isolated oligoprogression occurred most often in the lung parenchyma and intracranial lesions. More than half of these patients continued immunotherapy after local treatment, with a 2.5-year PPS rate of 51.4%. CONCLUSION: The liver was the most common site of progression on first-line ICIs monotherapy. Anti-angiogenesis-based therapy might be an optimal regimen at the time of progression. Patients with isolated oligoprogressive could still benefit from immunotherapy after local treatment.

Arsenic trioxide and p97 inhibitor synergize against acute myeloid leukemia by targeting nascent polypeptides and activating the ZAKα-JNK pathway.

Arsenic trioxide (ATO) has exhibited remarkable efficacy in treating acute promyelocytic leukemia (APL), primarily through promoting the degradation of the PML-RARα fusion protein. However, ATO alone fails to confer any survival benefit to non-APL acute myeloid leukemia (AML) patients and exhibits limited efficacy when used in combination with other agents. Here, we explored the general toxicity mechanisms of ATO in APL and potential drugs that could be combined with ATO to exhibit synergistic lethal effects on other AML. We demonstrated that PML-RARα degradation and ROS upregulation were insufficient to cause APL cell death. Based on the protein synthesis of different AML cells and their sensitivity to ATO, we established a correlation between ATO-induced cell death and protein synthesis. Our findings indicated that ATO induced cell death by damaging nascent polypeptides and causing ribosome stalling, accompanied by the activation of the ZAKα-JNK pathway. Furthermore, ATO-induced stress activated the GCN2-ATF4 pathway, and ribosome-associated quality control cleared damaged proteins with the assistance of p97. Importantly, our data revealed that inhibiting p97 enhanced the effectiveness of ATO in killing AML cells. These explorations paved the way for identifying optimal synthetic lethal drugs to enhance ATO treatment on non-APL AML.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma: A network meta-analysis.

BACKGROUND: With the rapid progress of systematic therapy for hepatocellular carcinoma (HCC), therapeutic strategies combining hepatic arterial infusion chemotherapy (HAIC) with systematic therapy arised increasing concentrations. However, there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC. AIM: To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC. METHODS: A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study. The outcomes of interest comprised overall survival (OS), progression-free survival (PFS), tumor response and adverse events. Hazard ratios (HR) and odds ratios (OR) with a 95% confidence interval (CI) were calculated and agents were ranked based on their ranking probability. RESULTS: HAIC outperformed Sorafenib (HR = 0.55, 95%CI: 0.42-0.72; HR = 0.51, 95%CI: 0.33-0.78; OR = 2.86, 95%CI: 1.37-5.98; OR = 5.45, 95%CI: 3.57-8.30; OR = 7.15, 95%CI: 4.06-12.58; OR = 2.89, 95%CI: 1.99-4.19; OR = 0.48, 95%CI: 0.25-0.92, respectively) and transarterial chemoembolization (TACE) (HR = 0.50, 95%CI: 0.33-0.75; HR = 0.62, 95%CI: 0.39-0.98; OR = 3.08, 95%CI: 1.36-6.98; OR = 2.07, 95%CI: 1.54-2.80; OR = 3.16, 95%CI: 1.71-5.85; OR = 2.67, 95%CI: 1.59-4.50; OR = 0.16, 95%CI: 0.05-0.54, respectively) in terms of efficacy and safety. HAIC + lenvatinib + ablation, HAIC + ablation, HAIC + anti- programmed cell death 1 (PD-1), and HAIC + radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone. HAIC + TACE + S-1, HAIC + lenvatinib, HAIC + PD-1, HAIC + TACE, and HAIC + sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC. HAIC + PD-1, HAIC + TACE + S-1 and HAIC + TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone. CONCLUSION: HAIC proved more effective and safer than sorafenib and TACE. Furthermore, combined with other interventions, HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Ternary Content-Addressable Memory Based on a Single Two-Dimensional Transistor for Memory-Augmented Learning.

Ternary content-addressable memory (TCAM) is promising for data-intensive artificial intelligence applications due to its large-scale parallel in-memory computing capabilities. However, it is still challenging to build a reliable TCAM cell from a single circuit component. Here, we demonstrate a single transistor TCAM based on a floating-gate two-dimensional (2D) ambipolar MoTe2 field-effect transistor with graphene contacts. Our bottom graphene contacts scheme enables gate modulation of the contact Schottky barrier heights, facilitating carrier injection for both electrons and holes. The 2D nature of our channel and contact materials provides device scaling potentials beyond silicon. By integration with a floating-gate stack, a highly reliable nonvolatile memory is achieved. Our TCAM cell exhibits a resistance ratio larger than 1000 and symmetrical complementary states, allowing the implementation of large-scale TCAM arrays. Finally, we show through circuit simulations that in-memory Hamming distance computation is readily achievable based on our TCAM with array sizes up to 128 cells.

Low Contact Resistance on Monolayer MoS2 Field-Effect Transistors Achieved by CMOS-Compatible Metal Contacts.

Contact engineering on monolayer layer (ML) semiconducting transition metal dichalcogenides (TMDs) is considered the most challenging problem toward using these materials as a transistor channel in future advanced technology nodes. The typically observed strong Fermi-level pinning induced in part by the reaction of the source/drain contact metal and the ML TMD frequently results in a large Schottky barrier height, which limits the electrical performance of ML TMD field-effect transistors (FETs). However, at a microscopic level, little is known about how interface defects or reaction sites impact the electrical performance of ML TMD FETs. In this work, we have performed statistically meaningful electrical measurements on at least 120 FETs combined with careful surface analysis to unveil contact resistance dependence on interface chemistry. In particular, we achieved a low contact resistance for ML MoS2 FETs with ultrahigh-vacuum (UHV, 3 × 10-11 mbar) deposited Ni contacts, ∼500 Ω·µm, which is 5 times lower than the contact resistance achieved when deposited under high-vacuum (HV, 3 × 10-6 mbar) conditions. These electrical results strongly correlate with our surface analysis observations. X-ray photoelectron spectroscopy (XPS) revealed significant bonding species between Ni and MoS2 under UHV conditions compared to that under HV. We also studied the Bi/MoS2 interface under UHV and HV deposition conditions. Different from the case of Ni, we do not observe a difference in contact resistance or interface chemistry between contacts deposited under UHV and HV. Finally, this article also explores the thermal stability and reliability of the two contact metals employed here.

Lipid-associated macrophages for osimertinib resistance and leptomeningeal metastases in NSCLC.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

Second primary malignancy for early-stage head and neck squamous cell carcinoma by SEER17 registries.

OBJECTIVE: Investigating treatment modalities' association with second primary malignancy risk in early-stage head and neck squamous cell carcinoma (HNSCC). METHODS: Data of 5-year survivors of early-stage (stages I-II, seventh TNM staging manual) HNSCC from 2000 to 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio and excess absolute risk were used to assess second primary malignancy (SPM) development externally. Relative risk was estimated to compare SPM risk within groups. Fine-Gray's model estimated cumulative incidence of second primary malignancy. RESULTS: Overall, 8957 5-year survivors with early-stage HNSCC were enrolled. Patients receiving definitive radiotherapy had poorer survival than surgery patients. Surgery correlated with lower risk of second primary malignancy (RR = 0.89, 95% CI 0.80-0.99), especially for oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39-0.82). Differences in the risk of second primary malignancy among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect risk of second primary malignancy within each subgroup. CONCLUSIONS: Surgery led to better survival and lower risk of second primary malignancy compared to definitive radiotherapy in 5-year survivors. Incidence and sites of second primary malignancy varied by primary sites, emphasizing targeted long-term surveillance's importance.

The profile of blood microbiome in new-onset type 1 diabetes children.

Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.