A near-zero quiescent power breeze wake-up anemometer based on a rolling-bearing triboelectric nanogenerator.

Wind sensors have always played an irreplaceable role in environmental information monitoring and are expected to operate with lower power consumption to extend service lifetime. Here, we propose a breeze wake-up anemometer (B-WA) based on a rolling-bearing triboelectric nanogenerator (RB-TENG) with extremely low static power. The B-WA consists of two RB-TENGs, a self-waking-up module (SWM), a signal processing module (SPM), and a wireless transmission unit. The two RB-TENGs are employed for system activation and wind-speed sensing. Once the ambient wind-speed exceeds 2 m/s, the wake TENG (W-TENG) and the SWM can wake up the system within 0.96 s. At the same time, the SPM starts to calculate the signal frequency from the measured TENG (M-TENG) to monitor the wind speed with a sensitivity of 9.45 Hz/(m/s). After the wind stops, the SWM can switch off the B-WA within 0.52 s to decrease the system energy loss. In quiescent on-duty mode, the operating power of the B-WA is less than 30 nW, which can greatly extend the service lifetime of the B-WA. By integrating triboelectric devices and rolling bearings, this work has realized an ultralow quiescent power and self-waked-up wireless wind-speed monitoring system, which has foreseeable applications in remote weather monitoring, IoT nodes, and so on.

Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial.

BACKGROUND: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. METHODS: Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). RESULTS: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. CONCLUSIONS: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.

Downstaging guided neoadjuvant strategy shift and bladder preservation in locally advanced bladder cancer: A case report.

Background: The study of bladder preservation for muscle-invasive bladder cancer (MIBC) mainly focuses on the T2 stage, which remains difficult in the T3 and T4 stage. Pembrolizumab has been applied as neoadjuvant therapy followed by radical cystectomy for MIBC, gaining encouraging results in the phase II study. Disitamab vedotin, an antibody-drug conjugate (ADC), also achieved promising efficacy for refractory bladder cancer. However, the neoadjuvant therapy strategy of these drugs for bladder sparing remains further exploration. Case presentation: A patient with locally advanced MIBC at our institute underwent a neoadjuvant therapeutic regimen followed by transurethral resection of bladder tumor (TURBT) and concurrent chemoradiotherapy. In light of limited initial efficacy, we enacted an adaptive shift in the neoadjuvant treatment strategy, transitioning from a combination of gemcitabine, cis-platinum, and pembrolizumab to disitamab vedotin with pembrolizumab. This approach ultimately achieved bladder preservation, complete response, and a remarkable 1-year disease-free survival (DFS). Conclusion: Proactive evaluation in the early stages of tumor downstaging can serve as a guiding principle for neoadjuvant strategies. This is the first successful case of neoadjuvant pembrolizumab combined with disitamab vedotin and chemotherapy in MIBC patients achieving complete response and bladder preservation.

Multifunctional bimetallic MOF with oxygen vacancy synthesized by microplasma for rapid total antioxidant capacity assessment in agricultural products.

The assessment of total antioxidant capacity (TAC) is crucial for evaluating overall antioxidant potential, predicting the risk of chronic diseases, guiding dietary and nutritional interventions, and studying the effectiveness of antioxidants. However, achieving rapid TAC assessment with high sensitivity and stability remains a challenge. In this study, Ce/Fe-MOF with abundant oxygen vacancies was synthesized using microplasma for TAC determination. The microplasma synthesis method was rapid (30 min) and cost-effective. The presence of oxygen vacancies and the collaboration between iron and cerium in Ce/Fe-MOF not only enhanced the catalyst's efficiency but also conferred multiple enzyme-like properties: peroxidase-like, oxidase-like, and superoxide dismutase mimetic activities. Consequently, a simple colorimetric assay was established for TAC determination in vegetables and fruits, featuring a short analysis time of 15 min, a good linear range of 5-60 µM, a low detection limit of 1.3 µM and a good recovery of 91 %-107 %. This method holds promise for rapid TAC assessment in agricultural products.

Reporting of tumor lysis syndrome with targeted therapy for hepatic cancer in the FDA adverse events reporting system.

BACKGROUND: Hepatic cancer is a common cancer in clinical practice. Current drug therapies for this condition include targeted therapy, chemotherapy, and immunotherapy. Tumor lysis syndrome (TLS) is the most serious complication of oncology treatment. According to the literature, several cases reported TLS occurred with targeted therapies for hepatic cancer. METHODS: Reporting odds ratio and information component were used to measure the disproportionate signals for TLS associated with targeted therapies, using data from the FDA's Adverse Event Reporting System (FAERS). A stepwise sensitivity analysis was conducted to test the robustness of signals. Time-to-onset analysis was used to describe the latency of TLS events associated with targeted therapies. The Bradford Hill criteria were used to perform a global assessment of the evidence. RESULTS: Sorafenib, lenvatinib, cabozantinib, and bevacizumab showed higher disproportionate signals for TLS than chemotherapy. The median number of days to TLS occurrence after drug therapy was 5.5, 6.5, and 6.5 days for sorafenib, lenvatinib, and bevacizumab, respectively. CONCLUSIONS: There is a significant association between tumor lysis syndrome and targeted therapies for hepatic carcinoma, with particularly strong signals for sorafenib and lenvatinib. Clinicians should be aware of the potential for tumor lysis syndrome in targeted therapies for hepatic carcinoma.

Impacts of land use/cover and slope on the spatial distribution and ecological risk of trace metals in soils affected by smelting emissions.

The soil contamination around smelting sites shows high spatial heterogeneity. This study investigated the impacts of distance, land use/cover types, land slopes, wind direction, and soil properties on the distribution and ecological risk of trace metals in the soil around a copper smelter. The results demonstrated that the average concentrations of As, Cd, Cu, Pb, and Zn were 248.0, 16.8, 502.4, 885.6, and 250.2 g mg kg-1, respectively, higher than their background values. The hotspots of trace metals were primarily distributed in the soil of smelting production areas, runoff pollution areas, and areas in the dominant wind direction. The concentrations of trace metals decreased with the distance to the smelting production area. An exponential decay regression revealed that, depending on the metal species, the influence distances of smelting emissions on trace metals in soil ranged from 450 to 1000 m. Land use/cover types and land slopes significantly affected trace element concentrations in the soil around the smelter. High concentrations of trace metals were observed in farmland, grassland, and flatland areas. The average concentrations of trace metals in the soil decreased in the order of flat land > gentle slope > steep slope. Soil pH values were significantly positively correlated with Cd, Cu, Pb, Zn, and As, and SOM was significantly positively correlated with Cd, Pb, and Zn in the soil. Trace metals in the soil of the study area posed a significant ecological risk. The primary factors influencing the distribution of ecological risk, as determined by the Ctree analysis, were land slope, soil pH, and distance to the source. These results can support the rapid identification of high-risk sites and facilitate risk prevention and control around smelting sites.

The canonical single-stranded DNA-binding protein is not an essential replication factor but an RNA chaperon in Saccharolobus islandicus.

Single-stranded DNA-binding proteins (SSBs) have been regarded as indispensable replication factors. Herein, we report that the genes encoding the canonical SSB (SisSSB) and the non-canonical SSB (SisDBP) in Saccharolobus islandicus REY15A are not essential for cell viability. Interestingly, at a lower temperature (55°C), the protein level of SisSSB increases and the growth of ΔSisssb and ΔSisssbΔSisdbp is retarded. SisSSB exhibits melting activity on dsRNA and DNA/RNA hybrid in vitro and is able to melt RNA hairpin in Escherichia coli. Furthermore, the core SisSSB domain is able to complement the absence of cold-shock proteins in E. coli. Importantly, these activities are conserved in the canonical SSBs from Crenarchaeota species that lack bacterial Csp homologs. Overall, our study has clarified the function of the archaeal canonical SSBs which do not function as a DNA-processing factor, but play a role in the processes requiring melting of dsRNA or DNA/RNA hybrid.

Effects of Simulated Reclaimed Water on Soil Particle Sizes and Cd Adsorption and Migration in Soils at Smelting Sites.

This work studied the vertical migration characteristics of Cd in soil profiles from a zinc smelting site under the influence of simulated reclaimed water containing NaCl and Na2SO4. The isothermal adsorption curves of Cd in the soils of miscellaneous fill and weathered slate well fitted the Freundlich and Langmuir models, with R2 ranging from 0.991 to 0.998. The maximum adsorption capacity of Cd in the soils decreased significantly under the salt ion treatments with NaCl and Na2SO4. After leaching, the Cd concentrations in the leachates and Cd contents in the subsoil layers of 10-60 cm followed the order NaCl treatment > Na2SO4 treatment > CK (p < 0.05), suggesting that the salt ions promoted the vertical migration of exogenous Cd. The proportion of coarse particles (> 0.02 mm) decreased, while that of fine particles (< 0.02 mm) increased under salt ion treatments (p < 0.05). The morphological characterization indicated that salt ions accelerated the erosion and fragmentation of coarse particles to form fine particles. The use of reclaimed water to flush smelting sites may increase the risk of Cd migration with small-sized soil particles from the soil to groundwater.

Dual-layer spectral-detector CT for predicting microsatellite instability status and prognosis in locally advanced gastric cancer.

OBJECTIVE: To construct and validate a prediction model based on dual-layer detector spectral CT (DLCT) and clinico-radiologic features to predict the microsatellite instability (MSI) status of gastric cancer (GC) and to explore the relationship between the prediction results and patient prognosis. METHODS: A total of 264 GC patients who underwent preoperative DLCT examination were randomly allocated into the training set (n = 187) and validation set (n = 80). Clinico-radiologic features and DLCT parameters were used to build the clinical and DLCT model through multivariate logistic regression analysis. A combined DLCT parameter (CDLCT) was constructed to predict MSI. A combined prediction model was constructed using multivariate logistic regression analysis by integrating the significant clinico-radiologic features and CDLCT. The Kaplan-Meier survival analysis was used to explore the prognostic significant of the prediction results of the combined model. RESULTS: In this study, there were 70 (26.52%) MSI-high (MSI-H) GC patients. Tumor location and CT_N staging were independent risk factors for MSI-H. In the validation set, the area under the curve (AUC) of the clinical model and DLCT model for predicting MSI status was 0.721 and 0.837, respectively. The combined model achieved a high prediction efficacy in the validation set, with AUC, sensitivity, and specificity of 0.879, 78.95%, and 75.4%, respectively. Survival analysis demonstrated that the combined model could stratify GC patients according to recurrence-free survival (p = 0.010). CONCLUSION: The combined model provides an efficient tool for predicting the MSI status of GC noninvasively and tumor recurrence risk stratification after surgery. CRITICAL RELEVANCE STATEMENT: MSI is an important molecular subtype in gastric cancer (GC). But MSI can only be evaluated using biopsy or postoperative tumor tissues. Our study developed a combined model based on DLCT which could effectively predict MSI preoperatively. Our result also showed that the combined model could stratify patients according to recurrence-free survival. It may be valuable for clinicians in choosing appropriate treatment strategies to avoid tumor recurrence and predicting clinical prognosis in GC. KEY POINTS: • Tumor location and CT_N staging were independent predictors for MSI-H in GC. • Quantitative DLCT parameters showed potential in predicting MSI status in GC. • The combined model integrating clinico-radiologic features and CDLCT could improve the predictive performance. • The prediction results could stratify the risk of tumor recurrence after surgery.

Downregulation of VPS13C promotes cisplatin resistance in cervical cancer by upregulating GSTP1.

Cisplatin resistance remains a major obstacle limiting the effectiveness of chemotherapy in cervical cancer. However, the underlying mechanism of cisplatin resistance is still unclear. In this study, we demonstrate that vacuolar protein sorting 13 homolog C (VPS13C) deficiency promotes cisplatin resistance in cervical cancer. Moreover, through an RNA sequencing screen, VPS13C deficiency was identified as negatively correlated with the high expression of glutathione S-transferase pi gene (GSTP1). Mechanistically, loss of VPS13C contributes to cisplatin resistance by influencing the expression of GSTP1 and inhibiting the downstream c-Jun N-terminal kinase (JNK) pathway. In addition, targeting GSTP1 with the inhibitor NBDHEX effectively rescued the cisplatin resistance induced by VPS13C deficiency. Overall, our findings provide insights into the underlying mechanisms of VPS13C in cisplatin resistance and identify VPS13C as a promising candidate for the treatment of chemoresistance in cervical cancer.

The FHA domain protein ArnA functions as a global DNA damage response repressor in the hyperthermophilic archaeon Saccharolobus islandicus.

Forkhead-associated (FHA) domain proteins specifically recognize phosphorylated threonine via the FHA domain and are involved in signal transduction in various processes especially DNA damage response (DDR) and cell cycle regulation in eukaryotes. Although FHA domain proteins are found in prokaryotes, archaea, and bacteria, their functions are far less clear as compared to the eukaryotic counterparts, and it has not been studied whether archaeal FHA proteins play a role in DDR. Here, we have characterized an FHA protein from the hyperthermophilic Crenarchaeon Saccharolobus islandicus (SisArnA) by genetic, biochemical, and transcriptomic approaches. We find that ΔSisarnA exhibits higher resistance to DNA damage agent 4-nitroquinoline 1-oxide (NQO). The transcription of ups genes, encoding the proteins for pili-mediated cell aggregation and cell survival after DDR, is elevated in ΔSisarnA. The interactions of SisArnA with two predicted partners, SisvWA1 (SisArnB) and SisvWA2 (designated as SisArnE), were enhanced by phosphorylation in vitro. ΔSisarnB displays higher resistance to NQO than the wild type. In addition, the interaction between SisArnA and SisArnB, which is reduced in the NQO-treated cells, is indispensable for DNA binding in vitro. These indicate that SisArnA and SisArnB work together to inhibit the expression of ups genes in vivo. Interestingly, ΔSisarnE is more sensitive to NQO than the wild type, and the interaction between SisArnA and SisArnE is strengthened after NQO treatment, suggesting a positive role of SisArnE in DDR. Finally, transcriptomic analysis reveals that SisArnA represses a number of genes, implying that archaea apply the FHA/phospho-peptide recognition module for extensive transcriptional regulation. IMPORTANCE Cellular adaption to diverse environmental stresses requires a signal sensor and transducer for cell survival. Protein phosphorylation and its recognition by forkhead-associated (FHA) domain proteins are widely used for signal transduction in eukaryotes. Although FHA proteins exist in archaea and bacteria, investigation of their functions, especially those in DNA damage response (DDR), is limited. Therefore, the evolution and functional conservation of FHA proteins in the three domains of life is still a mystery. Here, we find that an FHA protein from the hyperthermophilic Crenarchaeon Saccharolobus islandicus (SisArnA) represses the transcription of pili genes together with its phosphorylated partner SisArnB. SisArnA derepression facilitates DNA exchange and repair in the presence of DNA damage. The fact that more genes including a dozen of those involved in DDR are found to be regulated by SisArnA implies that the FHA/phosphorylation module may serve as an important signal transduction pathway for transcriptional regulation in archaeal DDR.

Model development and probabilistic risks of cadmium transport in slag-soil-groundwater systems with heterogeneous conditions.

Prediction of the long-term risk of trace metals leaching from soils at smelting sites is essential for groundwater protection. Herein, a mass balance-based stochastic model was developed to simulate the transport and probabilistic risks of trace metals in heterogeneous slag-soil-groundwater systems. The model was applied to a smelting slag yard with three stacking scenarios, including (A) fixed stacking amount, (B) stacking amount increasing yearly, and (C) slag removal after 20 years. The simulations suggested that the leaching flux and net accumulation of Cd in soils of the slag yard and abandoned farmland were greatest for scenario (B), which was followed by scenarios (A) and (C). In the slag yard, a plateau occurred in the Cd leaching flux curves, followed by a sharp increase. After 100 years of leaching, only scenario (B) had a high probabilistic risk (>99.9 %) of threatening groundwater safety under heterogeneous conditions. <11.1 % of the exogenous Cd may leach into groundwater under the worst scenario. The key parameters affecting Cd leaching risk include runoff interception rate (IRCR), input flux from slag release (I), and stacking time (ST). The simulation results were consistent with the values measured in a field investigation and laboratory leaching experiments. The results should help guide remediation objectives and measures to minimize the leaching risk at smelting sites.

Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer to transform effectively EMVI and MRF from positive to negative: results of a long-term single center phase 2 clinical trial.

PURPOSE: Chemoradiotherapy (CRT) remains the standard treatment for locally advanced rectal cancer (LARC). This phase 2 clinical trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in LARC. PATIENTS AND METHODS: The patients with LARC (the lower edge more than 5 cm from the anal verge) received up to 5 cycles of mFOLFOXIRI. MRI was performed to assess the baseline and postchemotherapy TN stage. Radical resection was performed within 4-6 weeks from the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2 and a positive CRM. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: From February 2016 to March 2019, 50 patients were enrolled. Forty-eight (96%) were clinically node-positive, 28 (56.5%) with MRF invasion and 39 (78.4%) were EMVI positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range,1-5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients with cN + achieved a pathological node-negative status. The proportions of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively. Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or > toxicities included neutrocytopenia (50%), leukopenia (14%) and diarrhea (12%) during the neoadjuvant chemotherapy period. Clinically meaningful postoperative complications included pneumonia (n = 1), pelvic infection (n = 1) and anastomotic fistula (n = 1). With a median follow-up time of 51.2 months, local recurrences and distant metastases were confirmed in 3 (6.5%) and 9 (19.6%) of cases, respectively. The 3-year disease free survival (DFS) and overall survival (OS)rates were 75.8% and 86.8%. CONCLUSION: Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect and seemed to be effective in eliminating EMVI and transforming the positive MRF to negative in LARC. The survival results are promising. The long-term follow-up showed promising DFS and OS rates accompanied by a favorable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03443661, 23/02/2018.

Combined CT and serum CA19-9 for stratifying risk for progression in patients with locally advanced pancreatic cancer receiving intraoperative radiotherapy.

Background and purpose: The aim of this study was to evaluate the significance of baseline computed tomography (CT) imaging features and carbohydrate antigen 19-9 (CA19-9) in predicting prognosis of locally advanced pancreatic cancer (LAPC) receiving intraoperative radiotherapy (IORT) and to establish a progression risk nomogram that helps to identify the potential beneficiary of IORT. Methods: A total of 88 LAPC patients with IORT as their initial treatment were enrolled retrospectively. Clinical data and CT imaging features were analyzed. Cox regression analyses were performed to identify the independent risk factors for progression-free survival (PFS) and to establish a nomogram. A risk-score was calculated by the coefficients of the regression model to stratify the risk of progression. Results: Multivariate analyses revealed that relative enhanced value in portal-venous phase (REV-PVP), peripancreatic fat infiltration, necrosis, and CA19-9 were significantly associated with PFS (all p < 0.05). The nomogram was constructed according to the above variables and showed a good performance in predicting the risk of progression with a concordance index (C-index) of 0.779. Our nomogram stratified patients with LAPC into low- and high-risk groups with distinct differences in progression after IORT (p < 0.001). Conclusion: The integrated nomogram would help clinicians to identify appropriate patients who might benefit from IORT before treatment and to adapt an individualized treatment strategy.

Exploration of the immunogenetic landscape of hyperprogressive disease after combined immunotherapy in cancer patients.

The immune-genetic changes that occur in cancer patients experiencing hyperprogressive disease (HPD) during combined immunotherapy are unclear. In this study, HPD patients with pre- and post-HPD samples and non-HPD patients with solid tumors were molecularly characterized by genetic and tumor immune microenvironment (TiME) analyses of paired samples by whole-exome sequencing, RNA sequencing, and multiplex immunofluorescence. The genetic analysis of paired samples showed that almost all the tumor driver gene mutations were preserved between pre- and post-HPD tumors. HPD patients had higher frequencies of mutations in TP53 and CNN2, and a significantly higher mutant-allele tumor heterogeneity than non-HPD patients. Tumor IL-6 mRNA was upregulated in post-HPD samples vs. pre-HPD, accompanied by a potential immune suppressive TiME with an elevated M2/M1 ratio. Salvage treatment with irinotecan plus bevacizumab was effective in one HPD patient, who experienced prolonged survival. These genetic features and TiME characteristics might help identify the features of HPD after immunotherapy.

Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial.

Background: This study aimed to evaluate the efficacy and safety of a new combination of nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) for patients with advanced biliary tract carcinoma (BTC). Methods: Patients were treated with nab-paclitaxel at a dose of 125 mg/m2 on day 1 and 8, and S-1, 80 to 120 mg/day on days 1-14 of a 21-day cycle. Treatments were repeated until disease progression or unacceptable toxicity occurred. The primary endpoint was objective response rate (ORR). The secondary endpoints were median progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: The number of patients enrolled were 54, and 51 patients were evaluated for efficacy. A total of 14 patients achieved partial response (PR) with an ORR of 27.5%. The ORR varied by sites, with 53.8% (7/13) for gallbladder carcinoma, 18.4% (7/38) for cholangiocarcinoma. The most common grade 3 or 4 toxicities were neutropenia and stomatitis. The median PFS and OS were 6.0 and 13.2 months, respectively. Conclusions: The combination of nab-paclitaxel with S-1 showed explicit antitumor activities and favorable safety profile in advanced BTC and could serve as a potential non-platinum and -gemcitabine-based regimen.

Impact of Vanadium-Containing Stone Coal Smelting on Trace Metals in an Agricultural Soil-Vegetable System: Accumulation, Transfer, and Health Risks.

Dietary exposure to trace metals (TMs) through vegetable consumption has been identified as a potential risk to human health. Fifty-one paired agricultural soil and leaf vegetable samples were collected around V-containing stone coal smelting sites in Hunan Province, China, to study the contamination and transfer characteristics of TMs (Cd, Cr, Cu, Pb, V, and Zn) in the soil-vegetable system. The health risk to local residents through vegetable ingestion was evaluated using Monte Carlo simulations. The results showed that 96.2%, 23.1%, 53.8%, 30.8%, 96.2%, and 69.2% of the soil samples had Cd, Cr, Cu, Pb, V, and Zn contents exceeding their related maximum allowable values, respectively. Cadmium and V were the primary pollutants based on the Igeo values. Moreover, 46.9% and 48.4% of vegetable samples exceeded the maximum permissible levels for Cd and Pb, respectively. There was a negative correlation between the bioaccumulation factors for Cd and V of the vegetable and soil physicochemical properties, including pH, organic matter, and free Fe2O3 content. Ingestion of garland chrysanthemum and pak choi posed high health risks, and Cd, V, and Pb were the primary contributors. These findings will help design strategies to minimize contamination and human exposure to soil-vegetable systems caused by V-containing stone coal smelting.

[Characteristics and Risk Assessment of Heavy Metals in the Soil Around Copper Smelting Sites].

Copper smelting can cause heavy metal pollution in surrounding soil and threaten human health. This study examined the characteristics, distribution, and health risk of heavy metals in soil with different land uses around 40 copper smelting sites at home and abroad by collecting published literature data. The results showed that the mean values of ω(As), ω(Cd), ω(Cu), ω(Pb), and ω(Zn) in the soil around the copper smelting sites were 196, 10.5, 1948, 604, and 853 mg·kg-1, respectively. The order of Igeo was Cd(5.63)>Cu(3.88)>As(2.96)>Pb(2.30)>Zn(1.27), and the accumulation of Cd and Cu was the most serious. High Nemero index (NIPI) values were found in the soil around smelting sites with a long history of smelting, outdated process, and insufficient environmental protection measures. Significant correlations were found between the concentrations of heavy metals in the soil, which decreased with the sampling distance. The heavy metals mainly accumulated within 2-3 km from the smelting sites. Compared with the smelting history, scale, and process, land use type had a lower effect on soil heavy metal concentrations. The heavy metals in the soil around copper smelters may pose carcinogenic and non-carcinogenic risks on residents. The high health risks were mainly caused by As and Pb in smelting production areas, and Pb in woodland. These results may guide the risk prevention of heavy metal pollution in the soil around smelting sites.

Less aggressive treatment for less aggressive disease? A retrospective single-center study of pulmonary-limited metastases associated with colorectal cancer.

OBJECTIVE: To explore the appropriate treatment strategies, clinical outcomes, and prognostic factors of patients with pulmonary-limited metastases derived from colorectal cancer (CRC), usually manifested as a less aggressive course. METHODS: A retrospective review was conducted in 331 CRC patients diagnosed with pulmonary-limited metastases at a single institution between January 2011 and November 2017. The Kaplan-Meier method was used to calculate the overall survival (OS). Further analysis was conducted according to treatment modalities. Univariate and multivariate analyses were used to determine potential prognostic factors influencing OS. RESULTS: With a median follow-up time of 38.6 months, the median OS in all patients was 45.2 months. A total of 163 patients received intensive local treatment with a median OS of 76.4 months, whereas 168 patients received palliative systemic treatment with a median OS of 29.7 months. The median OS was 68.9 months for patients treated with radiotherapy/radiofrequency ablation, with similar efficacy compared to surgery group, whose OS had not reached yet. No survival benefits were observed from the additional targeted therapy in systemic treatment group. The prognostic analysis demonstrated unilateral/bilateral lesions, synchronous/metachronous metastases, intensive local treatment, and resection of primary lesion that were significantly associated with survival of patients. CONCLUSIONS: Intensive local treatment alone for pulmonary lesions was associated with excellent survival in certain patients with CRC presented with metastases confined to lungs. Doublet systemic chemotherapy as the first-line treatment also revealed satisfied efficacy and safety.

Statistical inference and power analysis for direct and spillover effects in two-stage randomized experiments.

Two-stage randomized experiments become an increasingly popular experimental design for causal inference when the outcome of one unit may be affected by the treatment assignments of other units in the same cluster. In this paper, we provide a methodological framework for general tools of statistical inference and power analysis for two-stage randomized experiments. Under the randomization-based framework, we consider the estimation of a new direct effect of interest as well as the average direct and spillover effects studied in the literature. We provide unbiased estimators of these causal quantities and their conservative variance estimators in a general setting. Using these results, we then develop hypothesis testing procedures and derive sample size formulas. We theoretically compare the two-stage randomized design with the completely randomized and cluster randomized designs, which represent two limiting designs. Finally, we conduct simulation studies to evaluate the empirical performance of our sample size formulas. For empirical illustration, the proposed methodology is applied to the randomized evaluation of the Indian National Health Insurance Program. An open-source software package is available for implementing the proposed methodology.