Prognostic value of KRAS G12V mutation in lung adenocarcinoma stratified by stages and radiological features.

OBJECTIVE: KRAS G12V is one of the most common KRAS mutation variants in lung adenocarcinoma (LUAD), and yet its prognostic value is still unrevealed. In this study, we investigated the clinicopathologic characteristics and prognostic value of the KRAS G12V mutation in LUAD. METHODS: Data of 3829 patients who underwent LUAD resection between 2008 and 2020 were collected. Mutations were classified as wild-type, G12V, or non-G12V. The clinicopathologic characteristics, postoperative outcomes, and recurrence pattern were analyzed among groups. RESULTS: In total, 3554 patients were wild-type and 275 patients harbored a KRAS mutation: 60 patients with G12V (22.2%) and 215 patients with non-G12V (77.8%). The KRAS G12V mutation was more frequent in male patients, older patients (≥60 years), former/current smokers, those patients with radiologic solid nodules, and those with highly invasive histologic subtypes. Tumors carrying KRAS G12V mutation exhibited elevated programmed death-ligand 1 expression in comparison with wild-type tumors. KRAS G12V was more prevalent in older patients and had less lymphovascular invasion compared with other mutation types. FGF3, RET, and KDR co-mutations occurred more frequently in the KRAS G12V group. Multivariate analysis demonstrated that the KRAS G12V mutation was an independent prognostic factor in stage Ⅰ tumors, whereas the KRAS non-G12V mutation was not. KRAS G12V was associated with early recurrence and locoregional recurrence. CONCLUSIONS: The KRAS G12V mutation was associated with aggressive clinical-pathologic phenotype and early recurrence. To note, this mutation exhibited a significantly worse prognosis in patients with part-solid and stage Ⅰ lung adenocarcinoma. Meanwhile, the prognostic significance of KRAS G12C and G12V variants was comparable.

Clinicopathologic features, concurrent genomic alterations, and clinical outcomes of patients with KRAS G12D mutations in resected lung adenocarcinoma.

BACKGROUND: In light of the ongoing clinical development of KRAS G12D-specific inhibitors, we sought to investigate the clinicopathologic, co-occurring genomic features and outcomes of patients with KRAS G12D-mutant lung adenocarcinoma. METHODS: 3828 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations between 2008 and 2020. The association between KRAS G12D and clinicopathologic features, molecular profiles, and outcomes was investigated. RESULTS: 65 patients (1.7%) with KRAS G12D-mutant lung adenocarcinoma were identified. KRAS G12D mutation was more frequent in males, former/current smokers, radiologic solid tumors, and invasive mucinous adenocarcinoma. TP53 and STK11 were the two most frequent concomitant mutations in the KRAS G12D group. KRAS G12D mutation did not appear to be a prognostic factor in resected stage I-III lung adenocarcinomas, while KRAS non-G12D mutation was related to worse survival, especially in stage I tumors. KRAS G12D mutations were associated with positive but low (1-49%) PD-L1 expression compared to negative (<1%), while KRAS non-G12D mutation was associated with high PD-L1 expression (≥50%). TP53 co-mutation indicated higher PD-L1 expression, while STK11 co-mutation had a negligible impact on PD-L1 expression. Furthermore, data mining of MSK datasets from cBioPortal revealed that KRAS G12D and SKT11 co-mutation were associated with a diminished response to immunotherapy. CONCLUSIONS: KRAS G12D-mutant lung adenocarcinoma harbored unique clinicopathologic and genomic characteristics. Despite not being prognostic in resected lung adenocarcinoma, KRAS G12D might be a valuable biomarker in combination with certain co-mutations for identifying relevant subgroups of patients that could eventually influence treatment regimens.

Pathological and radiological T descriptors in invasive lung adenocarcinoma: from correlations to prognostic significance.

Background: The eighth T classification excluded lepidic and ground-glass opacity (GGO) components. Current studies demonstrated lepidic and GGO components showed independent prognostic significances. This study elucidated the correlations and prognostic impacts of pathological and radiological T descriptors in invasive lung adenocarcinoma. Methods: A total of 1,490 patients with invasive lung adenocarcinoma were retrospectively reviewed. Correlation between pathological invasive size (PIS) and radiological solid size (RSS), and lepidic ratio and GGO ratio were comprehensively evaluated. Impacts of these pathological and radiological T descriptors on recurrence-free survival (RFS) were comparatively analyzed. Results: Clinical (c)T-stage was more frequently downstaged than upstaged comparing with the pathological (p)T-stage (28.4% vs. 18.2%). The correlation between PIS and RSS in solid nodule was stronger than that in part-solid nodule (solid: R2=0.750 vs. part-solid: R2=0.355). Some pathological invasive components except solid component were featured as GGO. Among T1 patients, lepidic absent GGO showed better RFS than lepidic present solid nodule (pT1: P=0.001; cT1: P=0.021). Multivariable analysis revealed GGO ratio was an independent prognostic factor for RFS in T1 invasive lung adenocarcinoma, whereas lepidic ratio was not. Conclusions: Among T1 invasive lung adenocarcinoma, GGO ratio showed independent prognostic value for RFS, regardless of RSS. Meanwhile, lepidic ratio was not an independent RFS factor. GGO component rather than lepidic component should be considered as an additional T descriptor.

Corrosion-resistant cobalt phosphide electrocatalysts for salinity tolerance hydrogen evolution.

Seawater electrolysis is a viable method for producing hydrogen on a large scale and low-cost. However, the catalyst activity during the seawater splitting process will dramatically degrade as salt concentrations increasing. Herein, CoP is discovered that could reject chloride ions far from catalyst in electrolyte based on molecular dynamic simulation. Thus, a binder-free electrode is designed and constructed by in-situ growth of homogeneous CoP on rGO nanosheets wrapped around the surface of Ti fiber felt for seawater splitting. As expected, the as-obtained CoP/rGO@Ti electrode exhibits good catalytic activity and stability in alkaline electrolyte. Especially, benefitting from the highly effective repulsive Cl- intrinsic characteristic of CoP, the catalyst maintains good catalytic performance with saturated salt concentration, and the overpotential increasing is less than 28 mV at 10 mA cm-2 from 0 M to saturated NaCl in electrolyte. Furthermore, the catalyst for seawater splitting performs superior corrosion-resistance with a low solubility of 0.04%. This work sheds fresh light into the development of efficient HER catalysts for salinity tolerance hydrogen evolution.

Prognostic Factors for Survival of Stage IB Non-small Cell Lung Cancer Patients: A 10-Year Follow-Up Retrospective Study.

BACKGROUND: This study aimed to determine the prognostic factors for the long-term outcome of stage IB non-small cell lung cancer (NSCLC). METHODS: Surgically resected patients with stage IB NSCLC diagnosed (based on TNM 8th edition) between April 2008 and December 2013 were retrospectively reviewed. The prognosis and possible risk factors among the stage IB NSCLC patients were evaluated. RESULTS: Of the 349 patients identified for the study, 80 (22.9%) received post-surgery adjuvant chemotherapy (ACT). The median follow-up time after surgery was 123.3 months. The 10-year overall survival (OS) rate was 69.6%, and the 10-year recurrence-free survival (RFS) rate was 62.8%. The patients in this cohort were divided into three groups (T1 with visceral pleural invasion [VPI], T2a without VPI, and T2a with VPI), and no significant differences in OS or RFS were found among the groups. Furthermore, survival analysis indicated that the absence of ground-glass opacity (GGO) components portends an adverse long-term OS and RFS. In a subgroup of patients with solid nodules, age older than 65 years (hazard ratio [HR] 1.987; 95% confidence interval [CI] 1.312-3.010; p = 0.001) and ACT (HR 0.392; 95% CI 0.225-0.684; p < 0.001) were independent prognostic factors for OS, whereas lymphovascular invasion (HR 1.792; 95% CI 0.995-3.227; p = 0.052) should be considered as an independent unfavorable prognostic factor for RFS. CONCLUSIONS: As an upstaging factor, VPI did not further stratify prognosis for the stage IB patients in our cohort. The presence of GGO components had a notable impact on a favorable prognosis in stage IB NSCLCs.

Criticality and Neuromorphic Sensing in a Single Memristor.

Resistive random access memory (RRAM) is an important technology for both data storage and neuromorphic computation, where the dynamics of nanoscale conductive filaments lies at the core of the technology. Here, we analyze the current noise of various silicon-based memristors that involves the creation of a percolation path at the intermediate phase of filament growth. Remarkably, we find that these atomic switching events follow scale-free avalanche dynamics with exponents satisfying the criteria for criticality. We further prove that the switching dynamics are universal and show little dependence on device sizes or material features. Utilizing criticality in memristors, we simulate the functionality of hair cells in auditory sensory systems by observing the frequency selectivity of input stimuli with tunable characteristic frequency. We further demonstrate a single-memristor-based sensing primitive for representation of input stimuli that exceeds the theoretical limits dictated by the Nyquist-Shannon theorem.

Prognostic effect of ground-glass opacity in subcentimeter invasive lung adenocarcinoma.

Background: Although subcentimeter nodules represent precursor or minimally invasive lung cancer in most cases, there are still a few that are subcentimeter invasive adenocarcinoma (IAC). The aim of this study was to investigate the prognostic effect of ground-glass opacity (GGO) and the optimal surgical procedure in this special group. Methods: Patients with subcentimeter IAC were enrolled and were categorized into pure GGO, part-solid, and solid nodules based on the radiological appearance. Cox proportional hazards model and the Kaplan-Meier method were used for survival analyses. Results: A total of 247 patients were enrolled. Among them, 66 (26.7%) were in the pure-GGO group, 107 (43.3%) were in the part-solid group, and 74 (30.0%) were in the solid group. Survival analysis demonstrated a significantly worse survival in the solid group. Cox multivariate analyses confirmed that the absence of GGO component was an independent risk factor for worse recurrence-free survival (RFS) and overall survival (OS). As for surgical procedures, lobectomy did not provide a significant better RFS or OS than sublobar resection in the whole cohort or in a subgroup of patients with solid nodules. Conclusions: The radiological appearance stratified the prognosis of IAC with size of smaller than or equal to 1 cm. Sublobar resection may be feasible for subcentimeter IAC, even for those appearing as solid nodules; however, caution should be taken when applying wedge resection.

Prognostic value of KRAS G12C mutation in lung adenocarcinoma stratified by stages and radiological features.

OBJECTIVES: The role of KRAS G12C is of particular interest given the promising clinical activity of KRAS G12C-specific inhibitors. This study comprehensively investigated the clinicopathological characteristics and prognostic value of KRAS G12C mutation in patients with surgically resected lung adenocarcinoma. METHODS: Data were collected on 3828 patients with completely resected primary lung adenocarcinomas who underwent KRAS mutation analysis between 2008 and 2020. The association between KRAS G12C and clinicopathologic characteristics, molecular profiles, recurrence patterns, and postoperative outcome were explored. RESULTS: Two hundred seventy-five patients (7.2%) were confirmed to harbor a KRAS mutation, of whom 83 (30.2%) had the G12C subtype. KRAS G12C was more frequent in men, former/current smokers, radiologic solid nodules, invasive mucinous adenocarcinoma, and solid predominant tumors. KRAS G12C tumors had more lymphovascular invasion and higher programmed death-ligand 1 expression than KRAS wild-type tumors. TP53 (36.8%), STK11 (26.3%), and RET (18.4%) mutations were the 3 most frequent in the KRAS G12C group. Logistic regression analysis showed patients with KRAS G12C mutation were prone to experience early recurrence and locoregional recurrence. KRAS G12C mutation was found to be significantly associated with poor survival after propensity score matching. Stratified analysis showed that the KRAS G12C was an independent prognostic factor in stage I tumors and part-solid lesions, respectively. CONCLUSIONS: The KRAS G12C mutation had a significant prognostic value in stage I lung adenocarcinomas as well as in part-solid tumors. Furthermore, it exhibited a potentially aggressive phenotype associated with early and locoregional recurrence. These findings might be relevant as better KRAS treatments are developed for clinical application.

Scaling information pathways in optical fibers by topological confinement.

Spatial mode-count scalability in optical fibers is of paramount importance for addressing the upcoming information-capacity crunch, reducing energy consumption per bit, and for enabling advanced quantum computing networks, but this scalability is severely limited by perturbative mode mixing. We show an alternative means of light guidance, in which light's orbital angular momentum creates a centrifugal barrier for itself, thereby enabling low-loss transmission of light in a conventionally forbidden regime wherein the mode mixing can be naturally curtailed. This enables kilometer-length-scale transmission of a record ~50 low-loss modes with cross-talk as low as -45 decibels/kilometer and mode areas of ~800 square micrometers over a 130-nanometer telecommunications spectral window. This distinctive light-guidance regime promises to substantially increase the information content per photon for quantum or classical networks.

Monodispersed Pt Sites Supported on NiFe-LDH from Synchronous Anchoring and Reduction for High Efficiency Overall Water Splitting.

Precise design of low-cost, efficient and definite electrocatalysts is the key to sustainable renewable energy. Herein, this work develops a targeted-anchored and subsequent spontaneous-redox strategy to synthesize nickel-iron layered double hydroxide (LDH) nanosheets anchored with monodispersed platinum (Pt) sites (Pt@LDH). Intermediate metal-organic frameworks (MOF)/LDH heterostructure not only provides numerous confine points to guarantee the stability of Pt sites, but also excites the spontaneous reduction for PtII . Electronic structure, charge transfer ability and reaction kinetics of Pt@LDH can be effectively facilitated by the monodispersed Pt moieties. As a result, the optimized Pt@LDH that with the 5% ultra-low content Pt exhibits the significant increment in electrochemical water splitting performance in alkaline media, which only afford low overpotentials of 58 mV at 10 mA cm-2 for hydrogen evolution reaction (HER) and 239 mV at 10 mA cm-2 for oxygen evolution reaction (OER), respectively. In a real device, Pt@LDH can drive an overall water-splitting at low cell voltage of 1.49 V at 10 mA cm-2 , which can be superior to most reported similar LDH-based catalysts. Moreover, the versatility of the method is extended to other MOF precursors and noble metals for the design of ultrathin LDH supported monodispersed noble metal electrocatalysts promoting research interest in material design.

Pregnancy may have little influence on ground-glass opacities suspected for lung adenocarcinoma.

PURPOSE: Owing to the popularity of low-dose computed tomography in lung cancer screening, young women spotted with ground-glass opacities (GGO) is a growing subgroup in clinical practice. We aim to investigate the influence of pregnancy on GGOs suspected for lung adenocarcinoma. METHODS: This retrospective study collected a series of female patients who were pregnant in follow-up of GGO lesions. The last CT images of GGO before pregnancy (CT1) and the first CT images after pregnancy (CT2) were reviewed to assess any radiologic change. Young female patients who were not pregnant in long-term (> 12 months) follow-up of GGO were enrolled as a comparison group. We also enrolled patients who gave birth within 2 years before surgical resection of GGOs. RESULTS: Four patients were enrolled according to the criteria. There was no significant change of the GGOs in all four patients with a median follow-up duration of 45.5 (range 17-86) months. Two patients were diagnosed pathologically to be minimally invasive adenocarcinoma, one was invasive adenocarcinoma and one did not underwent surgery. Six patients were enrolled in the comparison group and no significant change was witnessed in all the nodules. In those patients who gave birth within two years before surgical resection of GGOs, we found that the majority present as preinvasive lesions, and those with invasive adenocarcinomas were bigger in size and possess more solid component radiologically. CONCLUSION: Pregnancy seems to have little impact on GGOs suspected for lung adenocarcinoma. Therefore, pregnancy might be safely planned during the follow-up of GGOs.

Raman gain control in optical fibers with orbital-angular-momentum-induced chirality of light.

Stimulated Raman scattering is a particularly robust nonlinearity, occurring in virtually every material because its spectral linewidth and associated frequency shift do not typically depend on phases or directions (i.e. wavevectors) of the interacting light beams. In amorphous materials such as glass fibers, Raman bandwidths are large, enabling its use as a broadband gain element. This ubiquity makes it a versatile means for achieving optical amplification or realizing lasers over a large range of pulsewidths at user-defined colors. However, this ease of deploying the effect also presents itself as a stubborn source of noise in fiber-based quantum sources or parasitic emission in fiber lasers. Here, we show that orbital angular momentum carrying light beams experiencing spin-orbit interactions yield novel phase-matching criteria for Raman scattering. This enables tailoring its spectral shape (by over half the Raman shift in a given material) as well as strength (by ∼ 100×) simply by controlling light's topological charge - a capability of utility across the multitude of applications where modulating Raman scattering is desired.

Analog Tunnel Memory Based on Programmable Metallization for Passive Neuromorphic Circuits.

Although experimental implementations of memristive crossbar arrays have indicated the potential of these networks for in-memory computing, their performance is generally limited by an intrinsic variability on the device level as a result of the stochastic formation of conducting filaments. A tunnel-type memristive device typically exhibits small switching variations, owing to the relatively uniform interface effect. However, the low mobility of oxygen ions and large depolarization field result in slow operation speed and poor retention. Here, we demonstrate a quantum-tunneling memory with Ag-doped percolating systems, which possesses desired characteristics for large-scale artificial neural networks. The percolating layer suppresses the random formation of conductive filaments, and the nonvolatile modulation of the Fowler-Nordheim tunneling current is enabled by the collective movement of active Ag nanocrystals with high mobility and a minimal depolarization field. Such devices simultaneously possess electroforming-free characteristics, record low switching variabilities (temporal and spatial variation down to 1.6 and 2.1%, respectively), nanosecond operation speed, and long data retention (>104 s at 85 °C). Simulations prove that passive arrays with our analog memory of large current-voltage nonlinearity achieve a high write and recognition accuracy. Thus, our discovery of the unique tunnel memory contributes to an important step toward realizing neuromorphic circuits.

Angular momentum driven dynamics of stimulated Brillouin scattering in multimode fibers.

The strength of stimulated Brillouin scattering (SBS) in optical fibers is largely governed by the spatial overlap between supported optical and acoustic modes, leading to a complicated amalgamation of photon-phonon interactions in multimode fibers. Here, we study SBS dynamics in ring-core fibers that support modes carrying orbital angular momentum (OAM), which result in distinctive characteristics. We find that the OAM SBS response, as well as modal content, strongly depends on the polarization state of the pump, as OAM modes in fiber have distinct propagation dynamics depending on whether the input is circularly or linearly polarized. This is in contrast to conventionally posited wisdom that SBS strength is independent of the pump's input polarization state in an isotropic material. This increased specificity can lead to interesting effects such as spatial phase conjugation even in the presence of stably transmitted, i.e. non-aberrated, spatial pump modes. More generally, we show that using OAM modes yields additional degrees of control over SBS interactions beyond more conventional parameters, such as effective area, acousto-optic spatial overlaps, and material composition.

Remote Measurement of the Angular Velocity Vector Based on Vectorial Doppler Effect Using Air-Core Optical Fiber.

Rotational Doppler effect has made tremendous development in both theoretical and applied research over the last decade. Different from the inertial thinking of focusing on the scalar field dominated by helical phase light, we have revealed a vectorial Doppler effect in our previous work, which is based on the spatially variant polarized light fields to simultaneously acquire the speed and direction of a target. Here, further, we propose a method to construct a flexible and robust velocimeter based on that novel effect by employing an air-core fiber with kilometer-length scale for remotely measuring the vectorial information of angular velocity in situ. In addition, we experimentally substantiate that the measurement system still has commendable accuracy in determining the direction of movement even when the air-core fiber is interfered by the external environment. The demonstrations prove the potential of vectorial Doppler effect in practical scenarios and remote measurements.

Increased Tumor Intrinsic Growth Potential and Decreased Immune Function Orchestrate the Progression of Lung Adenocarcinoma.

Background: The overall 5-year survival of lung cancer was reported to be only ~15%, with lung adenocarcinoma (LUAD) as the main pathological subtype. Before developing into invasive stages, LUAD undergoes pre-invasive stages of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), where surgical resection gives an excellent 5-year survival rate. Given the dramatic decline of prognosis from pre-invasive to invasive stages, a deeper understanding of key molecular changes driving the progression of LUAD is highly needed. Methods: In this study, we performed whole-exome sequencing and RNA sequencing on surgically resected 24 AIS, 74 MIA, 99 LUAD specimens, and their adjacent paired normal tissues. Survival data were obtained by follow-up after surgery. Key molecular events were found by comparing the gene expression profiles of tumors with different stages. Finally, to measure the level of imbalance between tumor intrinsic growth potential and immune microenvironment, a tumor progressive (TP) index was developed to predict tumor progression and patients' survival outcome and validated by external datasets. Results: As tumors progressed to more invasive stages, they acquired higher growth potential, mutational frequency of tumor suppressor genes, somatic copy number alterations, and tumor mutation burden, along with suppressed immune function. To better predict tumor progression and patients' outcome, TP index were built to measure the imbalance between tumor intrinsic growth potential and immune microenvironment. Patients with a higher TP index had significantly worse recurrence-free survival [Hazard ratio (HR), 10.47; 95% CI, 3.21-34.14; p < 0.0001] and overall survival (OS) [Hazard ratio (HR), 4.83e8; 95% CI, 0-Inf; p = 0.0013]. We used The Cancer Genome Atlas (TCGA)-LUAD dataset for validation and found that patients with a higher TP index had significantly worse OS (HR, 1.10; 95% CI, 0.83-1.45; p = 0.048), demonstrating the prognostic value of the TP index for patients with LUAD. Conclusions: The imbalance of tumor intrinsic growth potential and immune function orchestrate the progression of LUAD, which can be measured by TP index. Our study provided new insights into predicting survival of patients with LUAD and new target discovery for LUAD through assessing the imbalance between tumor intrinsic growth potential and immune function.

Comprehensive investigation of lung cancer associated with cystic airspaces: predictive value of morphology.

OBJECTIVES: We comprehensively investigated the morphology patterns of lung cancers associated with cystic airspaces. Our goal was to determine the predictive value of imaging features in a clinical environment. METHODS: We collected information about patients with resected lung cancers associated with cystic airspaces from January 2010 to December 2019. Radiological features, clinicopathological characteristics, gene mutations and survival data were analysed comprehensively. RESULTS: A total of 384 resected lung cancers associated with cystic airspaces were identified and categorized as 4 types: I, thin-wall type (n = 31, 8.1%); II, thick-wall type (n = 113, 29.4%); III, cystic airspace with a nodule type (n = 162, 42.1%) and IV, mixed type (n = 78, 20.3%). There were 27 (7.0%) adenocarcinomas in situ/minimally invasive adenocarcinomas; 237 (61.7%) lung adenocarcinomas; 115 (29.9%) squamous cell carcinomas; and 5 (1.3%) other tumours. The epidermal growth factor receptor mutation rate for type III was the highest (68.4%, P = 0.004). Pre-/minimally invasive adenocarcinomas were commonly featured as thin, pure ground-glass wall-surrounded cystic airspaces with smooth inner surfaces and margins. For patients with lung adenocarcinomas associated with cystic airspaces, type III (odds ratio 2.10; 95% confidence interval 0.55-8.06; P = 0.028) was an independent factor associated with a worse differentiation level. Type I was associated with excellent survival and type II, with the worst prognosis (P < 0.001). Type II (hazard ratio 2.29; 95% confidence interval 1.30-4.04; P = 0.004) was an independent prognostic factor for overall survival. CONCLUSIONS: Morphological patterns could be predictors for gene mutations, invasive status, pathological differentiation and postoperative prognosis for lung adenocarcinomas associated with cystic airspaces.

Detection and treatment of lung adenocarcinoma at pre-/minimally invasive stage: is it lead-time bias?

OBJECTIVES: This study investigates whether lead-time bias contributes to the excellent survival of AIS and MIA. METHODS: We enrolled patients with resected adenocarcinoma from 2008 to 2012. Age, sex, smoke history, surgical approach, radiological features, invasive stage and postoperative follow-up data were documented. 1:1 PSM was performed to balance the influence of sex and smoking status on survival. After matching, the average age of the two groups was compared to calculate the lead time of diagnosis. The gain in life years for adenocarcinoma diagnosed at pre-/minimally invasive stage was estimated by subtracting the "lead time" and "median survival year of IAC" from "the life expectancy of AIS/MIA patients" referring to the Centre for Health and Information. RESULTS: There were 124 AIS/MIA patients and 1148 IAC patients. The frequency of female and never-smoking patients in AIS/MIA group was much higher than that in IAC group. PSM analysis identified 124 patient pairs. No cancer-related death and recurrence were observed among AIS/MIA patients 5 years after surgery. For IAC patients, the 5-year disease-specific survival rate was 73.5% and the median survival is 13.5 years. The average age of AIS/MIA group and IAC group are 53.6 years and 58.2 years, respectively. The lead time between diagnosis of AIS/MIA and IAC is 4.6 years. Referring to the Centre for Health and Information, the life expectancy of patients with AIS/MIA diagnosed at 53.6 years old is 28.9 years. With adjustment for the lead time, the gain in life years for adenocarcinoma diagnosed at pre-/minimally invasive stage is 10.8 years. CONCLUSIONS: With adjustment for the lead time between diagnosis of AIS/MIA and IAC, resecting lung adenocarcinoma at pre-/minimally invasive stage can improve life expectancy. The excellent survival of AIS/MIA is not lead-time bias.

Reliable Memristor Based on Ultrathin Native Silicon Oxide.

Memristors based on two-dimensional (2D) materials can exhibit great scalability and ultralow power consumption, yet the structural and thickness inhomogeneity of ultrathin electrolytes lowers the production yield and reliability of devices. Here, we report that the self-limiting amorphous SiOx (∼2.7 nm) provides a perfect atomically thin electrolyte with high uniformity, featuring a record high production yield. With the guidance of physical modeling, we reveal that the atomic thickness of SiOx enables anomalous resistive switching with a transition to an analog quasi-reset mode, where the filament stability can be further enhanced using Ag-Au nanocomposite electrodes. Such a picojoule memristor shows record low switching variabilities (C2C and D2D variation down to 1.1 and 2.6%, respectively), good retention at a few microsiemens, and high conductance-updating linearity, constituting key metrics for analog neural networks. In addition, the stable high-resistance state is found to be an excellent source for true random numbers of Gaussian distribution. This work opens up opportunities in mass production of Si-compatible memristors for ultradense neuromorphic and security hardware.