B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer.

This study identifies mechanisms mediating responses to immune checkpoint inhibitors using mouse models of triple-negative breast cancer. By creating new mammary tumor models, we find that tumor mutation burden and specific immune cells are associated with response. Further, we developed a rich resource of single-cell RNA-seq and bulk mRNA-seq data of immunotherapy-treated and non-treated tumors from sensitive and resistant murine models. Using this, we uncover that immune checkpoint therapy induces T follicular helper cell activation of B cells to facilitate the anti-tumor response in these models. We also show that B cell activation of T cells and the generation of antibody are key to immunotherapy response and propose a new biomarker for immune checkpoint therapy. In total, this work presents resources of new preclinical models of breast cancer with large mRNA-seq and single-cell RNA-seq datasets annotated for sensitivity to therapy and uncovers new components of response to immune checkpoint inhibitors.

Engineering of NEMO as calcium indicators with large dynamics and high sensitivity.

Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of suboptimal peak signal-to-baseline ratio (SBR) with limited resolution for reporting subtle calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and wide dynamic ranges (>100-fold). NEMO indicators report Ca2+ transients with peak SBRs around 20-fold larger than the top-of-the-range GCaMP6 series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared with GCaMP6s, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times larger in vivo, thereby outperforming most existing state-of-the-art GECIs. Given their high sensitivity and resolution to report intracellular Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes in both mammals and plants.

OncoPubMiner: a platform for mining oncology publications.

Updated and expert-quality knowledge bases are fundamental to biomedical research. A knowledge base established with human participation and subject to multiple inspections is needed to support clinical decision making, especially in the growing field of precision oncology. The number of original publications in this field has risen dramatically with the advances in technology and the evolution of in-depth research. Consequently, the issue of how to gather and mine these articles accurately and efficiently now requires close consideration. In this study, we present OncoPubMiner (https://oncopubminer.chosenmedinfo.com), a free and powerful system that combines text mining, data structure customisation, publication search with online reading and project-centred and team-based data collection to form a one-stop 'keyword in-knowledge out' oncology publication mining platform. The platform was constructed by integrating all open-access abstracts from PubMed and full-text articles from PubMed Central, and it is updated daily. OncoPubMiner makes obtaining precision oncology knowledge from scientific articles straightforward and will assist researchers in efficiently developing structured knowledge base systems and bring us closer to achieving precision oncology goals.

The effect and mechanism of hexokinase-2 on cisplatin resistance in lung cancer cells A549.

BACKGROUND: Hexokinase (HK) is the first rate-limiting enzyme of glycolysis, which can convert glucose to glucose-6-phosphate. There are several subtypes of HK, including HK2, which is highly expressed in a variety of different tumors and is closely associated with survival. METHODS: Non-small cell lung cancer (NSCLC) A549 cells with stable overexpression and knockdown of HK2 were obtained by lentivirus transfection. The effects of overexpression and knockdown of HK2 on proliferation, migration, invasion, and glycolytic activity of A549 cells were investigated. The effects on apoptosis were also analyzed using western blot and flow cytometry. In addition, the mitochondria and cytoplasm were separated and the expression of apoptotic proteins was detected by western blot respectively. RESULTS: Upregulation of HK2 could promote glycolysis, cell proliferation, migration, and invasion, which would be inhibited through the knockdown of HK2. HK2 overexpression contributed to cisplatin resistance, whereas HK2 knockdown enhanced cisplatin-induced apoptosis in A549 cells. CONCLUSIONS: Overexpression of HK2 can promote the proliferation, migration, invasion, and drug resistance of A549 cells by enhancing aerobic glycolysis and inhibiting apoptosis. Reducing HK2 expression or inhibiting HK2 activity can inhibit glycolysis and induce apoptosis in A549 cells, which is expected to be a potential treatment method for NSCLC.

Identification and Evaluation of Olive Phenolics in the Context of Amine Oxidase Enzyme Inhibition and Depression: In Silico Modelling and In Vitro Validation.

The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with Olea europaea, and of these, only a relatively small fraction have been characterised. Utilising the OliveNetTM library, phenolic compounds were investigated as potential inhibitors of the epigenetic modifier lysine-specific demethylase 1 (LSD1). Furthermore, the compounds were screened for inhibition of the structurally similar monoamine oxidases (MAOs) which are directly implicated in the pathophysiology of depression. Molecular docking highlighted that olive phenolics interact with the active site of LSD1 and MAOs. Protein-peptide docking was also performed to evaluate the interaction of the histone H3 peptide with LSD1, in the presence of ligands bound to the substrate-binding cavity. To validate the in silico studies, the inhibitory activity of phenolic compounds was compared to the clinically approved inhibitor tranylcypromine. Our findings indicate that olive phenolics inhibit LSD1 and the MAOs in vitro. Using a cell culture model system with corticosteroid-stimulated human BJ fibroblast cells, the results demonstrate the attenuation of dexamethasone- and hydrocortisone-induced MAO activity by phenolic compounds. The findings were further corroborated using human embryonic stem cell (hESC)-derived neurons stimulated with all-trans retinoic acid. Overall, the results indicate the inhibition of flavin adenine dinucleotide (FAD)-dependent amine oxidases by olive phenolics. More generally, our findings further support at least a partial mechanism accounting for the antidepressant effects associated with EVOO and the Mediterranean diet.

The evolution and heterogeneity of neutrophils in cancers: origins, subsets, functions, orchestrations and clinical applications.

Neutrophils, the most prevalent innate immune cells in humans, have garnered significant attention in recent years due to their involvement in cancer progression. This comprehensive review aimed to elucidate the important roles and underlying mechanisms of neutrophils in cancer from the perspective of their whole life cycle, tracking them from development in the bone marrow to circulation and finally to the tumor microenvironment (TME). Based on an understanding of their heterogeneity, we described the relationship between abnormal neutrophils and clinical manifestations in cancer. Specifically, we explored the function, origin, and polarization of neutrophils within the TME. Furthermore, we also undertook an extensive analysis of the intricate relationship between neutrophils and clinical management, including neutrophil-based clinical treatment strategies. In conclusion, we firmly assert that directing future research endeavors towards comprehending the remarkable heterogeneity exhibited by neutrophils is of paramount importance.

Peripheral Blood IL5RA Gene Expression as a Diagnostic Biomarker for Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus, often diagnosed late because of its challenging symptoms and costly and invasive diagnostic methods.1,2 To address the need for more accessible biomarkers in EoE,3 we aimed to investigate the potential of whole-blood RNA expression as a noninvasive biomarker for diagnosing and monitoring EoE, hypothesizing that genetic signatures in blood could distinguish EoE cases, correlate with disease activity, and predict treatment responses.

Recent development in fabrication and evaluation of phenolic-dietary fiber composites for potential treatment of colonic diseases.

Phenolics have been shown by in vitro and animal studies to have multiple pharmacological effects against various colonic diseases. However, their efficacy against colonic diseases, such as inflammatory bowel diseases, Crohn's disease, and colorectal cancer, is significantly compromised due to their chemical instability and susceptibility to modification along the gastrointestinal tract (GIT) before reaching the colonic site. Dietary fibers are promising candidates that can form phenolic-dietary fiber composites (PDC) to carry phenolics to the colon, as they are natural polysaccharides that are non-digestible in the upper intestinal tract but can be partially or fully degradable by gut microbiota in the colon, triggering the release at this targeted site. In addition, soluble and fermentable dietary fibers confer additional health benefits as prebiotics when used in the PDC fabrication, and the possibility of synergistic relationship between phenolics and fibers in alleviating the disease conditions. The functionalities of PDC need to be characterized in terms of their particle characteristics, molecular interactions, release profiles in simulated digestion and colonic fermentation to fully understand the metabolic fate and health benefits. This review examines recent advancements regarding the approaches for fabrication, characterization, and evaluation of PDC in in vitro conditions.

Universal window size-dependent transition of correlations in complex systems.

Correlation analysis serves as an easy-to-implement estimation approach for the quantification of the interaction or connectivity between different units. Often, pairwise correlations estimated by sliding windows are time-varying (on different window segments) and window size-dependent (on different window sizes). Still, how to choose an appropriate window size remains unclear. This paper offers a framework for studying this fundamental question by observing a critical transition from a chaotic-like state to a nonchaotic state. Specifically, given two time series and a fixed window size, we create a correlation-based series based on nonlinear correlation measurement and sliding windows as an approximation of the time-varying correlations between the original time series. We find that the varying correlations yield a state transition from a chaotic-like state to a nonchaotic state with increasing window size. This window size-dependent transition is analyzed as a universal phenomenon in both model and real-world systems (e.g., climate, financial, and neural systems). More importantly, the transition point provides a quantitative rule for the selection of window sizes. That is, the nonchaotic correlation better allows for many regression-based predictions.

Fibre fermentation and pig faecal microbiota composition are affected by the interaction between sugarcane fibre and (poly)phenols in vitro.

We investigated the effects of (poly)phenol-rich sugarcane extract (PRSE), sugarcane fibre (SCFiber), and the combination of them (PRSE + SCFiber) on the gut microbiota and short-chain fatty acids (SCFA) production using in vitro digestion and pig faecal fermentation. Measuring total phenolic content and antioxidant activity through the in vitro digestion stages showed that PRSE + SCFiber increased the delivery of (poly)phenols to the in vitro colonic fermentation stage compared to PRSE alone. The PRSE + SCFiber modulated the faecal microbiota profile by enhancing the relative abundances of Prevotella, Lactobacillus, and Blautia, and reducing the relative abundance of Streptococcus. PRSE + SCFiber also mitigated the inhibitory effects of PRSE on SCFA production. These results suggest that the inclusion of sugarcane fibre with PRSE could increase the availability of phenolic compounds in the colon and modulate the gut microbiota towards a more favourable profile.

Transport model simulation prediction and environmental risk assessment of pyrethroid insecticides in urban artificial lakes caused by rainfall: A case study of Cloud Mountain Park in subhumid climate zone.

Pyrethroid insecticides are among urban parks' most widely used and harmful insecticides. The advanced prediction method is the key to studying the pollution and diffusion risk of plant conservation insecticides in parks. A two-dimensional advection-dispersion model was established for the North Lake of Cloud Mountain Park in the subhumid area of Hebei Province. The temporal and spatial distribution of lambda-cyhalothrin pollution required by plant growth in artificial lakes under different rainfall intensities and the time of water renewal after rainfall was simulated and predicted. According to the model efficiency (E: 0.98), mean absolute error (MAE: 0.016-0.064 cm), and root mean square error (RMSE: 0.014-0.041 cm), the prediction results showed that the model fits well. The results showed that the concentration of lambda-cyhalothrin in the artificial lake was positively correlated with the increase in rainfall intensity. Under the three scenarios of moderate rain, heavy rain, and rainstorm, the variation of total pollutants into the lake over time conformed to the first-order dynamic equation (R2＞0.97), and the cumulative rates were 0.013 min-1, 0.019 min-1 and 0.022 min-1, respectively. Under light rain, the accumulation rate of lambda-cyhalothrin showed a double-linear relationship, which was in accordance with the second-order kinetic equation (R2＞0.97). The rapid accumulation rate of early-stage rainfall was 0.0024 min-1, and the slow accumulation rate of late-stage rainfall was 0.0019 min-1. The human health risk assessment predicted by the simulation was lower than the hazard value (Rtgn(a-1): 9.65 E-11-1.12 E-10 a-1). However, the potential risk value to aquatic species was higher (RQ: 0.33-23.05). In addition, the increase in rainfall intensity has no significant effect on the acceleration of water renewal time. The two-dimensional dispersion model of pollutants driven by water dynamics provided relevant examples for evaluating the impact of runoff on pesticide scour in parks and supplied scientific support for improving the management of artificial lakes in urban parks.

The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area.

Structural brain changes along the lineage leading to modern Homo sapiens contributed to our distinctive cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens. We find that alleles with evidence of recent positive polygenic selection over the past 2000-3000 years are associated with increased surface area (SA) of the entire cortex, as well as specific regions, including those involved in spoken language and visual processing. Therefore, polygenic selective pressures impact the structure of specific cortical areas even over relatively recent timescales. Moreover, common sequence variation within human gained enhancers active in the prenatal cortex is associated with postnatal global SA. We show that such variation modulates the function of a regulatory element of the developmentally relevant transcription factor HEY2 in human neural progenitor cells and is associated with structural changes in the inferior frontal cortex. These results indicate that non-coding genomic regions active during prenatal cortical development are involved in the evolution of human brain structure and identify novel regulatory elements and genes impacting modern human brain structure.

Impact of Impure Gas on CO2 Capture from Flue Gas Using Carbon Nanotubes: A Molecular Simulation Study.

We used a grand canonical Monte Carlo simulation to study the influence of impurities including water vapor, SO2, and O2 in the flue gas on the adsorption of CO2/N2 mixture in carbon nanotubes (CNTs) and carboxyl doped CNT arrays. In the presence of single impure gas, SO2 yielded the most inhibitions on CO2 adsorption, while the influence of water only occurred at low pressure limit (0.1 bar), where a one-dimensional chain of hydrogen-bonded molecules was formed. Further, O2 was found to hardly affect the adsorption and separation of CO2. With three impurities in flue gas, SO2 still played a major role to suppress the adsorption of CO2 by reducing the adsorption amount significantly. This was mainly because SO2 had a stronger interaction with carbon walls in comparison with CO2. The presence of three impurities in flue gas enhanced the adsorption complexity due to the interactions between different species. Modified by hydrophilic carboxyl groups, a large amount of H2O occupied the adsorption space outside the tube in the carbon nanotube arrays, and SO2 produced competitive adsorption for CO2 in the tube. Both of the two effects inhibited the adsorption of CO2, but improved the selectivity of CO2/N2, and the competition between the two determined the adsorption distribution of CO2 inside and outside the tube. In addition, it was found that (7, 7) CNT always maintained the best CO2/N2 adsorption and separation performance in the presence of impurity gas, for both the cases of single CNT and CNT array.

Comparison between nab-paclitaxel and solvent-based taxanes as neoadjuvant therapy in breast cancer: a systematic review and meta-analysis.

BACKGROUND: To compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the treatment of breast cancer. METHODS: We systematically searched the PubMed, Embase, and Cochrane Central Register databases. Randomized controlled trials (RCTs) and cohort studies, published in English, about the comparison between nab-paclitaxel and sb-taxanes as neoadjuvant therapy in patients with breast cancer were searched up to September 2019. RESULTS: The primary outcome was the proportion of patients with pathological complete response (pCR, defined as ypT0 ypN0 or ypT0/is ypN0). Other main outcomes included long-term survival and adverse events (AEs). Seven studies (five RCTs and two cohorts) and 2949 patients were included. Neoadjuvant nab-paclitaxel improved pCR compared with sb-taxanes (ypT0 ypN0: OR = 1.52, 95%CI: 1.27-1.83, P < 0.001; ypT0/is ypN0: OR = 1.40, 95%CI: 1.17-1.68, P < 0.001). The benefits of nab-paclitaxel on pCR were persistent in HER2-negative, hormone receptor (HR)-positive breast cancer (OR = 1.53, 95%CI: 1.07-2.19, P = 0.020), triple-negative breast cancer (weekly/every 2 weeks regimen; OR = 2.95, 95%CI: 1.54-5.67, P < 0.001), and tumors with Ki-67 > 20% (OR = 1.63, 95%CI: 1.26-2.12, P < 0.001). Patients treated with nab-paclitaxel had better event-free survival (EFS; HR = 0.69, 95%CI: 0.57-0.85, P < 0.001) than with sb-taxanes. There were no differences in most of grade > 3 AEs between nab-paclitaxel and sb-taxanes (all P > 0.05), besides of any grade hypersensitivity (OR = 0.29, 95%CI: 0.11-0.72, P = 0.008), any grade (OR = 2.10, 95%CI: 1.37-3.23, P = 0.001) and grade > 3 (OR = 4.01, 95%CI: 2.51-6.41, P < 0.001) neuropathy. CONCLUSION: Nab-paclitaxel is effective for the treatment of non-metastatic breast cancer in the neoadjuvant setting. Nab-paclitaxel could improve pCR rate and EFS compared with sb-taxanes and with reasonable toxicities.

Comprehensive analysis of immune-related prognostic genes in the tumour microenvironment of hepatocellular carcinoma.

BACKGROUND: The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression. METHODS: In this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA). RESULTS: Seven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored. CONCLUSION: The ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.

Genetic alteration of Chinese patients with rectal mucosal melanoma.

BACKGROUND: Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy. METHODS: 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance. RESULTS: BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735-34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305-97.300), P = 0.005]. CONCLUSIONS: This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.

Recognition and Selectivity Analysis Monitoring of Multicomponent Steroid Estrogen Mixtures in Complex Systems Using a Group-Targeting Environmental Sensor.

The same class of steroid estrogen mixtures, coexisting in the environment of 17ß-estradiol, estrone (E1), and ethinyl estradiol (EE2), have strong ability to disrupt the human endocrine system and are seriously prejudicial to the health of the organism and environmental safety. Herein, a highly sensitive and group-targeting environmental monitoring sensor was fabricated for a comprehensive analysis of multicomponent steroid estrogens (multi-SEs) in complex systems. This breakthrough was based on the highly sensitive photoelectrochemical response composite material CdSe NPs-TiO2 nanotube and highly group-specific aptamers. The optimized procedure exhibited not only high sensitivity in a wide range of concentrations from 0.1 to 50 nM, indeed, the minimum detection limit was 33 pM, but also strong resistance to interference. The affinity and consistent action pockets of this sensor enable selective detection of multi-SEs in complex systems. It subsequently was applied for the analysis of multi-SEs from three real samples in the environment including medical wastewater, river water, and tap water to provide a means to clarify the fate of multi-SEs in the process of migration and transformation. This monitoring sensor has a brilliant application prospect for the identification and monitoring of the same class of endocrine-disrupting chemical mixtures in environmental complex systems.

Determination of Bioelectrical Impedance Thresholds for Early Detection of Breast Cancer-related Lymphedema.

Background: Bioelectrical impedance technology is a common technique used for the early detection of breast cancer-related lymphedema (BCRL). However, studies on the threshold value established by Inbody 720 device (Biospace, Korea) have been extremely limited. We aimed to determine its reference range and cutoff values. Methods: All patients were recruited from October 2017 to October 2019 at the Peking University People's Hospital Breast Center. In total, 82 patients with unilateral BCRL and 1305 healthy subjects were recruited in this study. We measured the extracellular fluid (ECF) ratio, extracellular water (ECW) ratio, as well as the single-frequency bioimpedance analysis (SFBIA) ratios at 1 and 5 kHz with the Inbody 720 device. The Youden index-based cutoff points, mean + 2SD and mean + 3SD values of these four indicators for both dominant and nondominant arms were also calculated. Results: Data were collected from 1387 women, including healthy subjects and patients with lymphedema. All statistical analyses were performed with SPSS. Significant differences were found between the two groups in the ECW, ECF, and SFBIA ratios. For the dominant affected arms, the Youden index-based cutoff points for the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz were 1.009, 1.008, 1.068, and 1.068, respectively. For the nondominant affected arms, the Youden index-based cutoff points were 1.014, 1.013, 1.047, and 1.048, respectively. The mean + 2 standard deviations (SD) and mean + 3SD values were also calculated. Conclusions: We determined the Youden index-based cutoff points, mean + 2SD and mean + 3SD values of the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz for both dominant and nondominant arms with data from 1305 healthy subjects. Next, the Youden index-based cutoff points, the mean + 2SD and mean + 3SD values were used to recognize patients with lymphedema. We found that the Youden index-based cutoff points and the mean + 2SD showed similar identification capacity on lymphedema, and they seemed to distinguish more patients with lymphedema than mean + 3SD values.

Structural decomposition analysis of global carbon emissions: The contributions of domestic and international input changes.

Finding the essential factors driving carbon emissions is vital for the carbon reduction policy-making. Different from the existing research, this paper studied the separate influence of internal and external input structural changes on global carbon emissions. We applied structural decomposition analysis (SDA) to decompose the global carbon emission change into six factors: namely, the carbon emission intensity, the domestic input structure, the international input structure, consumption pattern, consumption volume and population. The results firstly showed that the contributions of different factors to global carbon emissions changed over time. In recent five years, structural changes of domestic inputs became the principle driver of decrease in global carbon emissions. Secondly, the results showed that there were significant differences for countries in their factors for carbon emissions. In India and Russia, domestic input structural change was the major contributor to the decrease in carbon emissions. In Japan and Germany, the most important factor for the increase in carbon emissions was the international input structure. Finally, the results showed the factors for carbon emission changes were correlated to economic development. The international input structural changes significantly increased carbon emissions in high-income countries. Our findings suggested that some countries such as India and Russia, improving the usage efficiency of domestic carbon-intensive products would help reducing carbon emissions. For most high-income countries such as Japan and Germany, they should reduce the dependence on the imported carbon-intensive products by turning the external input sources to countries with technology advantages. In addition, technology exportation of high-income countries would also be beneficial for the global carbon reduction.

Using the axillary reverse mapping technique to screen breast cancer patients with a high risk of lymphedema.

BACKGROUND: Preventing breast cancer-related lymphedema (BCRL) by preserving upper lymphatic drainage is still controversial. Our study aimed to use the axillary reverse mapping (ARM) technique in patients who underwent axillary surgery to analyse the correlation between postoperative residual ARM nodes and the occurrence of lymphedema, select candidates at high risk of developing lymphedema, and analyse the oncologic safety of ARM nodes. METHODS: Patients undergoing sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) from October 2015 to February 2016 at the Peking University People's Hospital Breast Center were prospectively recruited for the study. ARM was performed in all patients before surgery. ARM nodes were separated from SLNB and ALND specimens. Data were collected on the identification of ARM nodes before surgery, number of residual ARM nodes after surgery, nodal status, crossover rate, and correlation between residual ARM nodes and the occurrence of lymphedema. RESULTS: The analysis included 78 patients. Of the 53 patients who underwent SLNB, crossover between ARM nodes and breast sentinel lymph nodes (SLNs) was seen in 22 specimens. The incidence of ARM node metastasis was 1.89% (1/53) and 25% (9/36) in the SLNB and ALND groups, respectively. The number of positive axillary lymph nodes was associated with the involvement of ARM nodes (P = 0.036). The incidence of residual ARM nodes was significantly higher in the SLNB group than in the ALND group (67.6% vs. 37.9%, P = 0.016). The incidence of lymphedema was significantly higher in the ALND group than in the SLNB group (33.3% vs. 5.4%, P = 0.003). CONCLUSIONS: For SLNB, the ARM technique can help to resect SLNs more accurately. However, we do not recommend using the ARM technique to preserve ARM nodes in patients undergoing ALND due to oncologic safety issues. Nevertheless, we can predict patients undergoing axillary surgery who are more likely to have a high risk of lymphedema by assessing residual ARM nodes. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov in February 2016. The clinical trial registration number is NCT02691624.