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Background: Apatinib improves progression-free survival and overall survival with an acceptable safety profile in Chinese patients with chemotherapy-refractory advanced or metastatic gastric cancer. However, the efficacy and safety of apatinib are unclear for elderly patients. This study was undertaken to prospectively investigate the efficacy and safety of apatinib for elderly patients with unresectable advanced or metastatic gastric cancer, who experienced progression to at least one lines of chemotherapy. Methods: This open-label, single-arm, phase II study enrolled patients aged ≥ 60 years with advanced gastric cancer, who experienced progression to one or more lines of chemotherapy at five centers in China. Patients received apatinib in an oral dose of 500mg or 250mg daily according to the research physicians' decision. The primary end point was progression-free survival, and the secondary end points were objective response rate, disease control rate, overall survival, and safety. Results: Forty-eight patients were enrolled between June 2017 and September 2019. The median age was 65.5 years (range 60– 80 years). Twenty-seven patients (56.3%) started treatment with an initial dose of 500 mg and 21 patients (43.7%) with 250 mg. The median progression-free survival and overall survival were 3.00 months (95% confidence interval, 2.17– 3.84) and 8.10 months (95% confidence interval, 4.35– 11.85), respectively. The objective response rate and disease control rate assessed by the investigators were 16.7% and 72.9%, respectively. The common side effects were fatigue (58.3%), hypertension (47.9%), abdominal pain (33.3%), proteinuria (29.2%), leukopenia (22.9%), and neutropenia (20.8%). Hypertension (22.9%) was the major grade 3/4 toxicity. Conclusion: These data suggest that apatinib is effective and relatively tolerable for elderly patients with unresectable advanced or metastatic gastric cancer who have received at least first-line chemotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced fatigue reduces not only the quality of life of patients but also effect their recurrence-free survival rate. Although electroacupuncture can relieve fatigue, it has limited affect on some patients. Therefore, appropriate biomarkers are needed to help screen patients who can benefit from electroacupuncture treatment of fatigue. We conducted this study to explore the predictive ability of SNPs on the efficacy of electroacupuncture in the treatment of fatigue in patients with breast cancer after adjuvant chemotherapy. Our study included breast cancer patients with fatigue after receiving paclitaxel and/or anthracycline based adjuvant chemotherapy. The patients were divided into the electroacupuncture group and the control group. The electroacupuncture treatment group received adjuvant chemotherapy and electroacupuncture treatment, while the control group only received adjuvant chemotherapy, and then compared the fatigue relief degree of two groups. In addition, we used NCBI dbSNP and PharmGKB databases to select fatigue related genes and their SNPs. We collected peripheral blood from the included patients for SNPs typing, and recorded the efficacy of electroacupuncture to analyzed the correlation between different SNPs and therapeutic efficacy. The side effects of electroacupuncture treatment were also recorded. 76 patients in the electroacupuncture group and 48 patients in the control group were enrolled. In the electroacupuncture group, 63 patients (82.9%) experienced moderate to severe fatigue (BFI score > 3). After electroacupuncture treatment, the number of patients with a BFI score of > 3 was 46 (60.5%). Therefore, the fatigue symptoms of 26.9% patients were significantly improved (P < 0.05). In the control group, which did not receive electroacupuncture treatment, 40 of 48 patients had a BFI score of > 3. Following the same observation time used in the electroacupuncture group, 36 patients had a BFI score of > 3 points. Thus, fatigue was not significantly relieved in the control group (83.3% vs. 75.0%, P > 0.05). We included 56 patients in our analysis of the correlation between SNPs and electroacupuncture treatment effects. We divided the patients into an effective group and ineffective group according to therapeutic effects. Our results indicated that the effective rate of electroacupuncture treatment with IL1A rs3783550 AC and CC genotypes was higher than that with other genotypes (AC: 84.6%, CC: 81.8%, AA: 33.0%, P < 0.05). Similarly, the effective rate of electroacupuncture treatment with HTR1A rs6295 GG and CC genotypes was higher than that with other genotypes (GG: 63.0%, CC: 55.6%, GC: 18.2%, P < 0.05). However, no other genotypes were related to the effect of electroacupuncture treatment on fatigue. Our result showed that electroacupuncture has therapeutic effect on fatigue after adjuvant chemotherapy for breast cancer and the side effects are tolerable. In addition, IL1A rs3763550 and HTR1A rss6295 can predict the therapeutic effect of electroacupuncture on fatigue after adjuvant chemotherapy in breast cancer, which helps to better screen patients who can benefit from electroacupuncture treatment. [ABSTRACT FROM AUTHOR]

• Designed a combustion experiment platform that can mimic high-altitude environment. • Revealed the effect of Mg-burning particles on combustion and infrared signatures. • Gas-solid two-phase coupling effects are treated in combustion simulation. • Developed an in-house code to solve the non-isotropic radiative transfer equation. The combustion process of Mg/PTFE/Viton-based pyrotechnics exhibits a complex multiphase flow phenomenon. However, the influence mechanism of metal particles undergoing dynamic diffusion combustion in the flow field on the infrared radiation output characteristics has not yet been elucidated. Systematic experiments and numerical simulations are performed with the combustion and infrared radiation behaviors of the pyrotechnic compositions. A small-scale sealed combustion experiment platform is specially manufactured to mimic the actual ambient pressure at different cruise altitudes. An infrared thermal imager and an infrared thermometer are adopted cooperatively to diagnose the burning process. The Euler-Langrangian method is applied to mathematically describe the gas–solid two-phase interaction in the combustion flow field, and the Eddy Dissipation Concept (EDC) combustion model is employed to simulate the coupling effect of turbulence and chemical reaction in the gas-phase reaction zone. The verified Source Six-Flux (SSF) method based in-house code solves the infrared radiative transfer equation integrating the emission, absorption and scattering effects of participating media. The comparisons with the experimental results demonstrate that the computational model involving heterogeneous reactions established in this paper better approximates the realistic situation. The results reveal that the infrared radiation output capability of dispersed combustion particles in the 2.0–5.5 μm band surpasses that of high-temperature gas molecules under different environmental pressures. The infrared radiation magnitude of both the gaseous phase and the particulate phase decrease significantly with decreasing pressure. The thermal radiation of combustion particles is mainly concentrated in the near- to mid-infrared band, while its emission in the far-infrared band is relatively weak. These scientific findings provide conducive insights for lucubrating the infrared radiation mechanism of pyrotechnics under negative pressure environments, and assist in further promoting the application of MTV pyrotechnics in the field of aerospace. [ABSTRACT FROM AUTHOR]

• The feasibility of applying PTC material to infrared camouflage is discussed for the first time. • The design method of performance parameters of PTC material is proposed. • A heat transfer model of PTC material considering the effect of thermal conductivity is proposed. • The adaptive thermal control performance of PTC material in vacuum environment is studied. In order to protect important military targets from the threat of advanced infrared detection systems and guided weapons, the development of adaptive infrared decoy technology has become a top priority. In this paper, the feasibility of applying PTC material to infrared camouflage of decoy was discussed for the first time. Meanwhile, a design method for performance parameters of PTC materials that satisfy the infrared camouflage was proposed with consideration given to the complex background environment in which the space decoy was located. Taking this as a guide, the room temperature PTC materials that attain the design requirements were prepared. In this paper, the phase change characteristics of the material and the change of thermal conductivity with temperature were considered, and the heat transfer model of the PTC material was further optimized, which was verified by experiments in a vacuum environment. On this basis, the infrared camouflage properties of space decoy based on thermal control of PTC materials were further simulated. The results show that the PTC resistor prepared under the guidance of this design method can achieve a more ideal infrared camouflage effect and higher adaptive temperature control precision than ordinary resistors when applied to space decoy. The research results specify possible directions for the development and thermal control of PTC material. [ABSTRACT FROM AUTHOR]

Purpose: The expression of cytochrome B561 (CYB561) and its role in breast cancer (BC) prognosis remain unclear. We analyzed the differential expression and prognostic value of CYB561 using online databases and a clinical cohort through bioinformatics and immunohistochemistry. Methods: The differential expression of CYB561 and its association with BC were analyzed using the tumor immune estimation resource (TIMER), gene expression profiling interaction analysis2 (GEPIA2), Human Protein Atlas, Cancer Cell Line Encyclopedia, and Kaplan–Meier Plotter website. Important pathways of CYB561 enrichment were explored using gene set enrichment analysis. Immunohistochemistry detected CYB561 expression in normal breast, breast hyperplasia, ductal carcinoma in situ (DCIS), para-cancer, and invasive BC groups. Association between CYB561 expression and BC prognosis was analyzed using Kaplan–Meier and Cox regression analyses. Results: CYB561 mRNA expression was higher in GEPIA and TIMER BC patients than in para-cancer tissues. CYB561 was expressed in the glandular epithelium and myoepithelium, with positive localization in the cytoplasm and cell membrane. CYB561 protein expression significantly differed among the groups. CYB561 expression was correlated with ERBB2/HER2 and infiltrating CD4+ T cells in GEPIA and TIMER BC patients and associated with HER2 status, histological grade, and molecular subtypes in the clinical cohort but not related to tumor-infiltrating lymphocytes. CYB561 mRNA overexpression predicted reduced recurrence-free survival and overall survival in BC. Patients with CYB561 expression had significantly reduced overall survival and increased risk of death. Conclusion: CYB561 can serve as an effective clinical prognostic biomarker for BC. [ABSTRACT FROM AUTHOR]

Background: Granzyme K (GZMK) is a crucial mediator released by immune cells to eliminate tumor cells, playing significant roles in inflammation and tumorigenesis. Despite its importance, the specific role of GZMK in breast cancer and its mechanisms are not well understood. Methods: We utilized data from the TCGA and GEO databases and employed a range of analytical methods including GO, KEGG, GSEA, ssGSEA, and PPI to investigate the impact of GZMK on breast cancer. In vitro studies, including RT-qPCR, CCK-8 assay, cell cycle experiments, apoptosis assays, Celigo scratch assays, Transwell assays, and immunohistochemical methods, were conducted to validate the effects of GZMK on breast cancer cells. Additionally, Cox regression analysis integrating TCGA and our clinical data was used to develop an overall survival (OS) prediction model. Results: Analysis of clinical pathological features revealed significant correlations between GZMK expression and lymph node staging, differentiation grade, and molecular breast cancer subtypes. High GZMK expression was associated with improved OS, progression-free survival (PFS), and recurrence-free survival (RFS), as confirmed by multifactorial Cox regression analysis. Functional and pathway enrichment analyses of genes positively correlated with GZMK highlighted involvement in lymphocyte differentiation, T cell differentiation, and T cell receptor signaling pathways. A robust association between GZMK expression and T cell presence was noted in the breast cancer tumor microenvironment (TME), with strong correlations with ESTIMATEScore (Cor = 0.743, P < 0.001), ImmuneScore (Cor = 0.802, P < 0.001), and StromalScore (Cor = 0.516, P < 0.001). GZMK also showed significant correlations with immune checkpoint molecules, including CTLA4 (Cor = 0.856, P < 0.001), PD-1 (Cor = 0.82, P < 0.001), PD-L1 (Cor = 0.56, P < 0.001), CD48 (Cor = 0.75, P < 0.001), and CCR7 (Cor = 0.856, P < 0.001). Studies indicated that high GZMK expression enhances patient responsiveness to immunotherapy, with higher levels observed in responsive patients compared to non-responsive ones. In vitro experiments confirmed that GZMK promotes cell proliferation, cell division, apoptosis, cell migration, and invasiveness (P < 0.05). Conclusion: Our study provides insights into the differential expression of GZMK in breast cancer and its potential mechanisms in breast cancer pathogenesis. Elevated GZMK expression is associated with improved OS and RFS, suggesting its potential as a prognostic marker for breast cancer survival and as a predictor of the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Currently lacking research to explore the correlation between inflammatory markers and the efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in the treatment of advanced gastric cancer. This study is a retrospective study and included patients with advanced gastric cancer who receiving ICIs combined with chemotherapy from January 2020 to December 2022. We analysed the relationship between systemic inflammatory markers and the efficacy of ICIs combined chemotherapy and constructed a clinical prediction model. A nomogram was constructed based on the results of the bidirectional stepwise regression model. A total of 197 patients were enrolled in the training group, with a median follow‐up period of time 26 months. Kaplan Meier analysis showed that the median OS of patients with low systemic immune‐inflammatory index (SII) and low platelet to lymphocyte ratio (PLR) was superior to those with high SII and PLR. Univariate and multivariate Cox regression analysis showed that SII, NLR, PLR, and N stage as independent prognostic factors for OS. Adding SII to the conventional model improved the predictive ability of the 12‐month OS. A total of 95 patients were included in the validation group, and external validation of the SII‐based nomogram showed favourable predictive performance. Baseline SII, PLR, and N stage may serve as independent predictive factors for survival outcomes in advanced gastric cancer patients undergoing ICIs combined with chemotherapy. The SII‐based nomogram can provide intuitive and accurate prognosis prediction of individual patients. [ABSTRACT FROM AUTHOR]

Extended endocrine therapy (EET) with aromatase inhibitors (AIs) therapy can further reduce the risk of recurrence in breast cancer patients. But the conclusion that whether EET with AIs increases the risk of some side effects compared with nonextended endocrine therapy (NEET) is still controversial and not exhaustive. We searched for Randomized controlled trials (RCT) trials published in EMBASE and PubMed between March 2008 and December 2019. Studies comparing the side effects of adjuvant EET with those of NEET were included. The objective was to determine whether EET with AIs increases the risk of side effects compared with NEET. Overall, 11 trials comprising 24,187 participants were identified. EET with AIs increased the risk of cardiotoxicity [odds ratio (OR) 1.19, 95 % confidence interval (CI) 1.04–1.36; P < 0.05; 438 vs 423], bone pain (OR 1.18, 95 % CI 1.02–1.36; P < 0.05; 446 vs 404), osteoporosis (OR 1.53, 95 % CI 1.35–1.72; P < 0.05; 866 vs 641), fractures (OR 1.33, 95 % CI 1.18–1.50; P < 0.05; 596 vs 438), arthralgia (OR 1.27, 95 % CI 1.19–1.36; P < 0.05; 2404 vs 2060), myalgia (OR 1.29, 95 % CI 1.16–1.43; P < 0.05; 960 vs 776), and hot flashes (OR 1.40, 95 % CI 1.15–1.69; P < 0.05; 2418 vs 2174) and was associated with opposite risk of vaginal bleeding (OR 0.74, 95 % CI 0.59–0.92; P < 0.05; 148 vs 197). However, the extended therapy did not increase the risk of hypertension (OR 1.03, 95 % CI 0.80–1.33; P = 0.80; 364 vs 353), hypercholesterolemia (OR 1.03, 95 % CI 0.91–1.16; P = 0.62; 643 vs 627), vaginal dryness (OR 1.19, 95 % CI 1.00–1.42; P = 0.05; 294 vs 257), fatigue (OR 1.20, 95 % CI 0.96–1.50; P = 0.12; 1501 vs 1462), dizziness (OR 1.04, 95 % CI 0.92–1.17; P = 0.55; 614 vs 595), headaches (OR 1.06, 95 % CI 0.95–1.18; P = 0.30; 885 vs 848), constipation (OR 0.91, 95 % CI 0.79–1.04; P = 0.15; 480 vs 522), nausea (OR 1.83, 95 % CI 0.49–6.83; P =0.37; 340 vs 325), and dyspnea (OR 0.96, 95 % CI 0.82–1.13; P = 0.64; 340 vs 351). The risk of grade ≥ 3 hot flashes increased following extended endocrine therapy (OR 2.01, 95 % CI 1.23–3.29; P < 0.05; 47 vs 23). We observed no evidence for a difference in the risk of grade ≥3 fatigue, arthralgia, myalgia, bone pain, osteoporosis, fractures, hypertension, and headache between both endocrine therapies. Secondary outcomes shows that after receive EET with AIs, patients can benefit from the control of the local recurrence, distant recurrence, contralateral breast cancer, and second cancers. Compared with NEET, EET with AIs significantly increased the risk of cardiotoxicity, bone pain, osteoporosis, fractures, hot flashes, arthralgia, myalgia, and grade ≥3 hot flashes, and EET with AIs can reduced the risks of local recurrence, distant recurrence, contralateral breast cancer, and second cancers. These findings offer an important guide for clinicians and patients. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC. Methods: PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS. Results: We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%). Conclusions: This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR. [ABSTRACT FROM AUTHOR]

α1C-tubulin (TUBA1C) is a member of the α-tubulin family and has served as a potential biomarker in a variety of cancers in many studies. In this study, the gene expression profile of TUBA1C in The Cancer Genome Atlas (TCGA) was extracted for analysis, and the prognostic value of TUBA1C in breast cancer was comprehensively evaluated. The Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression analysis were performed to confirm the correlations between TUBA1C expression and the clinical characteristics of breast cancer patients. The effect of TUBA1C expression on the survival of breast cancer patients was assessed by Kaplan-Meier curve, Cox regression analysis, and the Kaplan-Meier plotter (an online database). The TCGA data set was used for the Gene Set Enrichment Analysis (GSEA). The results confirmed that high TUBA1C expression in breast cancer was closely correlated with survival time, survival status, and tumor size. In addition, elevated TUBA1C expression can predict poor overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Univariate and multivariate analyses (Cox regression analyses) confirmed that TUBA1C was an independent prognostic factor for the OS of breast cancer patients. The GSEA identified that the high TUBA1C expression phenotype was differentially enriched in cell cycle, basal transcription factor, P53 signaling pathway, pathways in cancer, TOLL-like receptor signaling pathway, and NOD-like receptor signaling pathway. In summary, high messenger RNA (mRNA) expression of TUBA1C is an independent risk factor for poor prognosis of breast cancer. [ABSTRACT FROM AUTHOR]

Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8–72.7%; 95% CI, 18–32%) and 36.0% (range, 8.3–63.0%; 95% CI, 31–42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16–5.62), 12.78 (95% CI, 10.24–15.32), and 8.12 (95% CI, 6.48–9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile. [ABSTRACT FROM AUTHOR]

Magnesium/polytetrafluoroethylene/Viton (MTV) fuel-rich pyrolants use the atmospheric oxygen as a complementary oxidizer to sustain and alter the performance of the combustion reaction. The flame diffusion characteristics of MTV fuel-rich pyrolants in the atmospheric environment are studied by a high-speed camera (HSC). The flame temperature and combustion components are measured by using remote sensing Fourier Transform Infrared Spectrometer (FTIR). In order to obtain the combustion component distribution more accurately, an aerobic combustion model containing the oxidation reaction of the excess reactant Mg and carbonaceous species with O2 is established in this study. Eddy dissipation concept (EDC) model is applied to the numerical simulation of the three dimensional anaerobic and aerobic combustion field coupled with Realizable k-ε two-equation turbulence model. The research results show that flame temperature is mainly contributed by anaerobic combustion reaction. The flame structure obtained by the aerobic combustion model is closer to the experimental results, and the result of component distribution calculated by aerobic combustion is more consistent with characteristic spectrum. Therefore, the aerobic combustion model is more suitable for describing the actual MTV flame, and the combustion field can be divided into an anaerobic core zone and an aerobic diffusion zone. [ABSTRACT FROM AUTHOR]

Although platinum-based chemotherapy can improve pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC), the impact on survival of platinum-based neoadjuvant and adjuvant chemotherapy is still controversial. Our meta-analysis aimed at analyzing survival with platinum-based neoadjuvant and adjuvant chemotherapy in patients with TNBC. We searched PubMed, EMBASE, MEDLINE, Cochrane databases, and several major conferences up to January 2021. Fixed and random models were used for our meta-analysis. Disease-free survival (DFS), overall survival (OS), and side effects data were extracted from the included literature in addition to the corresponding pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). A total of nine studies involving 3247 patients were included. The pooled analysis suggested that compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy could further improve DFS (HR = 0.56, 95% CI 0.45–0.67, p < 0.01) and OS (HR = 0.54, 95% CI 0.38–0.70, p < 0.01) in patients with TNBC. The subgroup analysis showed that platinum-based chemotherapy could further improve DFS (HR = 0.59, 95% CI 0.43–0.74, p < 0.01) and OS (HR = 0.61, 95% CI 0.40–0.83, p < 0.01) in neoadjuvant chemotherapy and DFS (HR = 0.53, 95% CI 0.37–0.69, p < 0.01) and OS (HR = 0.46, 95% CI 0.23–0.69, p < 0.01) in adjuvant chemotherapy compared with anthracycline- and/or paclitaxel-based chemotherapy in patients with TNBC. In addition, compared with anthracycline-based chemotherapy, platinum-based chemotherapy without anthracycline chemotherapy could further improve DFS (HR = 0.53, 95% CI 0.37–0.70, p < 0.01) and OS (HR = 0.46, 95%CI 0.19–0.72, p < 0.01) in patients with TNBC. Compared with anthracycline- and/or paclitaxel-based chemotherapy, all-grade diarrhea, fatigue, and grade ≥ 3 anemia were higher in platinum-based chemotherapy. In contrast, all-grade anemia, leukopenia, neutropenia, peripheral neuropathy, myalgia/arthralgia, cardiac toxicity were lower in platinum-based chemotherapy; grade ≥ 3 leukopenia, neutropenia and myalgia/arthralgia were also lower. Compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy was more associated with improved DFS and OS in TNBC patients. The benefit of survival is consistent with platinum-based neoadjuvant and adjuvant chemotherapy. The side effects of platinum-based chemotherapy are tolerable. [ABSTRACT FROM AUTHOR]

Background: The wide use of antibody‐drug conjugates (ADCs) is transforming the cancer‐treatment landscape. Understanding the treatment‐related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies. Methods: We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all‐grade and grade ≥ 3 treatment‐related AEs were the primary outcomes of the analysis. Results: A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any‐grade treatment‐related AEs was 100.0% (95% confidence interval [CI]: 99.9%–100.0%; I2 = 89%) and the incidence of grade ≥ 3 treatment‐related AEs was 6.2% (95% CI: 3.0%–12.4%; I² = 99%). Conclusions: This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components. [ABSTRACT FROM AUTHOR]

Neoadjuvant treatment options for triple-negative breast cancer (TNBC) are abundant, but the efficacy of different combinations of treatment options remains unclear. Our network meta-analysis aimed to evaluate the effectiveness and safety of various neoadjuvant treatment options in patients with TNBC. Literature reports published before March 31, 2022, were retrieved from the PubMed, Embase, Cochrane Library, main oncology conference of the European Society of Medical Oncology, American Society of Clinical Oncology, and San Antonio Breast Cancer Symposium databases. Pairwise and Bayesian network meta-analyses were performed to compare direct and indirect evidence, respectively. The primary outcome was pathological complete response (pCR). Comparison of efficiency between different treatment regimens was made by HRs and 95% confidence intervals (CIs). Overall, 26 studies, including 9714 TNBC patients, were assessed in this network meta-analysis. Results indicated that the pCR of immune checkpoint inhibitors plus platinum-containing regimens is better than other joint regimens. PCR rate of neoadjuvant chemotherapy regimens containing bevacizumab, platinum, poly(ADP-ribose) polymerase inhibitors, and immune checkpoint inhibitors was higher than those of standard chemotherapy agents. By performing a conjoint analysis of the pCR rate and safety endpoints, we found that immune checkpoint inhibitors plus platinum-containing regimens were well balanced in terms of efficacy and toxicity. Considering the efficacy and acceptable adverse events, neoadjuvant chemotherapy based on immune checkpoint inhibitors plus platinum may be considered as an option for patients with TNBC. [ABSTRACT FROM AUTHOR]

The Watson for Oncology (WFO) decision system has been rolled out in many cancers. However, the consistency of treatment for breast cancer is still unclear in relatively economically disadvantaged areas. Patients with postoperative adjuvant stage (January 2017 to December 2017) and advanced-stage breast cancer (January 2014 to December 2018) in northwest of China were included in this study. Patient information was imported to make treatment decisions using Watson version 19.20 analysis and subsequently compared with clinician decisions and analyzed for influencing factors. A total of 263 patients with postoperative adjuvant breast cancer and 200 with advanced breast cancer were included in this study. The overall treatment modality for WFO was in 80.2% and 50.5% agreement with clinicians in the adjuvant and advanced-stage population, respectively. In adjuvant treatment after breast cancer surgery, menopausal status (odds ratio (OR) = 2.89, P = 0.012, 95% CI, 1.260–6.630), histological grade (OR = 0.22, P = 0.019, 95% CI, 0.061–0.781) and tumor stage (OR = 0.22, P = 0.042, 95% CI, 0.050–0.943) were independent factors affecting the concordance between the two stages. In the first-line treatment of advanced breast cancer, hormone receptor status was a factor influencing the consistency of treatment (χ2 = 14.728, P < 0.001). There was good agreement between the WFOs and clinicians' treatment decisions in postoperative adjuvant breast cancer, but poor agreement was observed in patients with advanced breast cancer. [ABSTRACT FROM AUTHOR]

Background: Almost all adjuvant chemotherapy regimens for gastric cancer recommended by guidelines are fluorouracil (5-FU) based, and 5-FU-based adjuvant chemotherapy plays an important role in reducing the recurrence of gastric cancer after surgery. However, the effect of mismatch repair (MMR) status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer remains controversial. Materials and methods: We prospectively included patients with gastric cancer who underwent radical gastrectomy between March 14, 2017 and September 30, 2021. The included patients received 5-FU-based adjuvant chemotherapy or surgery alone. The MMR status of patients was divided into MMR proficient (pMMR) and MMR defective (dMMR) according to four MMR proteins. Peripheral blood was collected for systemic inflammation analysis. The main purpose of this study was to analyze the effect of MMR status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer. We also analyzed the differences in systemic inflammation levels in different MMR status and their impact on survival. Results: A total of 479 patients were enrolled, with a median follow-up period of time was 36 months. In the surgery alone group, dMMR gastric cancer had better disease-free survival (DFS) (hazard ratio [HR] = 4.33, 95% confidence interval [CI] 1.25–15.02, p = 0.02) than pMMR, and in the adjuvant chemotherapy group, there was no significant difference in DFS (HR = 1.16, 95% CI 0.65–2.07, p = 0.61) between dMMR and pMMR gastric cancer. The same results were seen for overall survival (OS). In addition, the result show that in the dMMR group, there was no difference in DFS (HR = 1.62, 95% CI 0.46–5.77, p = 0.45) between patients receiving adjuvant chemotherapy and those receiving surgery alone. In the pMMR group, the DFS values (HR = 0.59, 95%CI 0.35–0.99, p = 0.04) of patients receiving adjuvant chemotherapy were better than those of patients receiving surgery alone, and the same results were observed for OS. In addition, among pMMR patients, patients with a low platelet lymphocyte ratio (PLR) who received 5-FU adjuvant chemotherapy and those with a low neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) who received surgery alone had better DFS and OS. Conclusion: To our knowledge, this is the first prospective study to specifically explore the correlation between MMR and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. The results showed that gastric cancer patients with pMMR can benefit from 5-FU-based adjuvant chemotherapy, but those with dMMR cannot. Among pMMR patients, lower PLR and SII values with surgery alone and lower NLRs in those receiving 5-FU-based adjuvant chemotherapy were associated with higher DFS and OS. [ABSTRACT FROM AUTHOR]

The combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and endocrine treatment has benefited patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer; however, its effects in the neoadjuvant setting for ER + /HER2- early breast cancer (EBC) are unclear. Systematic searches were performed in PubMed, Embase, Cochrane Library, and major oncological meetings for trials of CDK4/6 inhibitors plus neoadjuvant endocrine treatment (NET) vs. NET/neoadjuvant chemotherapy (NACT) alone up to January 30, 2021. We assessed the efficacy of CDK4/6 inhibitors plus NET vs. NET/NACT alone in ER + /HER2- EBC. Six studies that included 803 patients treated with CDK4/6 inhibitors plus NET vs. NET/NACT alone were used. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased the complete cell cycle arrest (CCCA) rate (OR, 9.00; 95% CI, 5.42–14.96; P < 0.001). Nonsignificant differences between CDK4/6 inhibitors and NET/NACT alone occurred in the preoperative endocrine prognostic index (PEPI)-0 rate (OR, 1.13; 95% CI, 0.59–2.18; P = 0.71), pathological complete response (pCR) rate (OR, 0.75; 95% CI, 0.13–4.29; P = 0.74), objective response rate (ORR) (OR, 0.70; 95% CI, 0.21–2.29; P = 0.55), and disease control rate (DCR) (OR, 1.16; 95% CI, 0.47–2.89; P = 0.74). CDK4/6 inhibitors plus NET indicated a high risk of neutropenia (OR, 56.43; 95% CI, 15.76–202.11; P < 0.001) as an adverse effect (AE) and elevated alanine aminotransferase (ALT) level (OR, 15.30; 95% CI, 2.02–115.98; P = 0.008) as grade 3/4 AEs. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased CCCA rate in ER + /HER2- EBC patients. CDK4/6 inhibitors plus NET did not substantially improve the PEPI-0 rate, pCR rate, ORR, or DCR. The combination increased the risk of neutropenia and elevated ALT levels. In the neoadjuvant setting, addition of CDK4/6 inhibitors to NET may be an option for treating ER + /HER2- EBC. [ABSTRACT FROM AUTHOR]

• Designed a combustion experiment platform that can simulate high-altitude environment. • Revealed the intrinsic effect of pressure on the fluorination and oxidation of Mg. • Provided further insight into micro-scale combustion process of Mg particles. • Heterogeneous condensation reactions are innovatively treated in combustion simulation. The exploration of condensed combustion products (CCPs) is essential to reveal the ignition, combustion, and infrared radiation mechanisms of Mg-based (Magnesium/polytetrafluoroethylene/Viton) solid fuels that have been considerably employed in the field of aerospace. Systematic experiments and numerical simulations are performed with the physicochemical properties (including morphology, element distribution, phase composition and particle size distribution) and flow field distribution characteristics of CCPs, respectively. The effects of formulation and pressure on the combustion behaviors of pyrotechnic compositions are thoroughly investigated based on thermal analysis measurements, laser ignition, optical diagnosis and CCPs collection. The results demonstrated that the major solid products for all cases are MgF 2 agglomerates and MgO smoke oxide particles (SOPs). Increasing the Mg content in the formulation is simultaneously beneficial for the reduction of large agglomerates and SOPs. As the pressure is decreased from 0.1 MPa to 0.02 MPa, the volume weighted mean diameter of CCPs increases significantly due to the decrease in burning rate. The numerical model established in this paper better approximates the realistic combustion process by coupling the heterogeneous condensation reactions, and is adopted to predict the distribution of CCPs in the combustion flow field under different experimental conditions. Numerical results reveal that the MgF 2 is mainly distributed in the anaerobic combustion core zone immediately above the burning surface, while MgO is located in the peripheral aerobic combustion diffusion zone. The negative pressure environment has more profound influence on the oxidation reaction of Mg than fluorination reaction. The scientific findings are expected to facilitate the development of more complete combustion and infrared radiation models, while theoretically providing in-depth guidance for the increasing military and civilian application of Mg-based solid fuels. [ABSTRACT FROM AUTHOR]

Poly (aniline) (PANI) is considered an ideal material for the modulation of infrared (IR) radiation due to its excellent electrochromic properties. However, the camphorsulfonic acid doping mechanism which results in emittance modulation is not clearly understood. With the goal of enhancing the IR emittance variation (Δε), a PANI film was synthesized by a chemical oxidation and spraying method, and the doping mechanism of CSA concentration effect on Δε was studied by combining Raman spectra, X-ray photoelectron spectra and density functional theory calculations. The results demonstrate that with increasing camphorsulfonic acid concentration, the effect of the doping concentration on the emittance of PANI/Au films can be divided into two stages: (1) the change in the emittance is mainly caused by the shortening of optical penetration depth either under the state of dopant free (non-doped) or a low CSA doping concentration; (2) the change in emittance is mainly caused by the increase in reflectivity of the PANI layer under the increased doping. Due to the joint action of the two factors, the emittance of the PANI film first increases and then decreases with increasing concentration of CSA, and the maximum Δε (0.45) is realized at 1 M. This paper clarifies the mechanism of PANI films with different CSA dopant concentrations and could provide a way to increase the emittance modulation range by adjusting the concentration of the dopants. • Emittance variation is relevant to the changed of light penetration depth. • Improving of carrier concentration contributes to the shorten of penetration depth. • The carrier concentration evolves with the doping concentration. [ABSTRACT FROM AUTHOR]

• Designed a small-scale negative pressure combustion experiment system. • Revealed the effect of pressure on flame structure and temperature. • Demonstrated the pressure sensitivity of the burning rate under 0.02–0.1 MPa. • Predicted the combustion products distribution characteristics. The present study is devoted to comprehensively evaluating the combustion performance of Mg-based (Magnesium/polytetrafluoroethylene/Viton) solid fuels in high-altitude operating environments. A small-scale sealed CO 2 laser ignition experiment system is designed to produce different negative pressure environments. A high-speed camera (HSC) and an infrared thermal imager are used to cooperatively capture the burning process. The results obtained demonstrate that the area of the flame core zone and the flame temperature increase significantly as the pressure increases. It is conducive to the heat feedback of the gas phase reaction zone to the solid phase heating zone, resulting in an increase in the burning rate. As the Mg content increases, the flame temperature is decreased and the burning rate is increased. The burning rate for the Mg-based solid fuels is found to increase monotonically with ambient pressure and to follow the Vieille's law in the pressure range of 0.02–0.1 MPa. Based on the experiment, a three-dimensional combustion-flow coupling solution model is established including the detailed aerobic combustion reaction kinetic model and the eddy dissipation concept (EDC) model. Numerical simulation results reveal that the content of incompletely reacted Mg increases as the pressure decreases. Conversely, the decreasing behavior of oxygen partial pressure at low pressure reduces the probability of reaction of Mg with O 2 , resulting in a dramatical decrease in the mass fraction of MgO. The scientific findings provide useful insight for the deep understanding of the combustion behavior of Mg-based solid fuels, and support for the increasing demands for both military and civilian applications. [ABSTRACT FROM AUTHOR]

Numerous studies have reported the efficacy of antibody–drug conjugates (ADCs) for treating breast cancer. However, during cytotoxic drug treatment, long-term disabling fatigue is common. Moreover, studies in the relevant literature have indicated that fatigue can significantly increase the incidence of depression and sleep disorders. Therefore, this meta-analysis aims to evaluate the incidence of fatigue in breast cancer survivors treated with ADCs. PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for articles and conference abstracts published before March 16, 2023. Further, two authors independently extracted data from the included studies. The primary outcome of this study was the incidence of all-grade fatigue caused by the use of ADCs in patients with breast cancer. Finally, a random-effects model was used to calculate the incidence and 95% confidence intervals (CIs) of the outcome. Overall, 7963 patients from 31 studies were included in this meta-analysis to assess the incidence of fatigue caused by the use of approved and marketed ADCs in patients with breast cancer. Notably, the incidence of all-grade fatigue during ADC monotherapy was 39.84% (95% CI, 35.09%–44.69%). In subgroup analyses, among ADCs, the incidence of trastuzumab deruxtecan-induced fatigue was the highest, with an all-grade fatigue incidence of 47.05% (95% CI, 42.38%–51.75%). Meanwhile, the incidence of trastuzumab emtansine (T-DM1)-induced all-grade fatigue was 35.17% (95% CI, 28.87%–41.74%), which was the lowest among ADCs. Further, the incidence of all-grade fatigue due to sacituzumab govitecan was 42.82% (95% CI, 34.54%–51.32%), which was higher than that due to T-DM1. Moreover, the incidence of fatigue was higher with T-DM1 combination therapy than with monotherapy. Clinicians have highlighted the high incidence of ADC-related fatigue and its negative impact on patients' physical and mental health, making fatigue an important research variable. The results of this study will further contribute to a comprehensive understanding of ADCs, which have some clinical importance and are of great benefit to patients with breast cancer. [Display omitted] • This is the first meta-analysis assessing the fatigue occurrence rates in breast cancer survivors undergoing ADC drug treatment. • Breast cancer patients undergoing ADC drug treatment experience a higher incidence of all-grade fatigue events. Among them, T-DXd exhibits the highest fatigue occurrence rate,T-DM1 having the lowest fatigue occurrence rate. • The fatigue incidence rate is higher in the combination therapy group compared to the monotherapy group. • The fatigue occurrence rate in phase I and II clinical trials is higher than that in phase III clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients.Methods: After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations.Results: Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32-2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26-2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04-2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69-3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42-2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50-0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3-4 diarrhea (OR: 2.54; 95% CI: 1.21-5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00-1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39-15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02-8.39; P < 0.001).Conclusions: PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC. [ABSTRACT FROM AUTHOR]

Background: The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety.Methods: PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs).Results: A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65-0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53-0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53-0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63-0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44-0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23-3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53-2.64, P < 0.001) and hand-foot syndrome (OR = 8.67, 95% CI 6.70-11.22, P < 0.001).Conclusion: This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the leading cause of cancer-related mortality in women, necessitating the development of novel therapeutic targets. While cytochrome b 561 (CYB561) expression is associated with poor prognosis in BC, the precise role of CYB561 in BC and its potential mechanisms remain unclear. In the present study, we found that CYB561 plays an essential role in BC growth. CYB561 expression was up-regulated in surgically resected cancerous tissues and in six BC cell lines. Lentivirus-mediated CYB561 knockdown in BC cells significantly reduced their proliferation, migration, and invasiveness. CYB561 participates in the regulation of iron metabolism in BC. CYB561 knockdown reduced total iron content, increased ferrous iron content, and down-regulated the expression of proteins associated with iron metabolism (transferrin receptor 1, divalent metal transporter 1, and ferritin heavy chain 1). Conversely, up-regulation of CYB561 through co-incubation with exogenous iron (ferric ammonium citrate) produced contrary outcomes. Additionally, CYB561 activated the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway in BC cells. Down-regulation of CYB561 expression inhibited the Akt/mTOR signaling pathway activity. The application of an mTOR agonist (MHY1485) rescued this negative effect, as well as the inhibitory effect of CYB561 knockdown on cell proliferation. Importantly, the dual mTOR inhibitor MLN0128 (50 nM, 48 h) down-regulated CYB561 expression and the iron metabolism-related proteins transferrin receptor, divalent metal transporter 1, and ferritin heavy chain 1, whereas the mTOR agonist MHY1485 rescued the down-regulation of CYB561 knockdown on iron metabolism-related proteins. We conclude that CYB561 promotes the proliferation of BC cells by regulating iron metabolism through the activation of the Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

In recent times, complicated three-dimensional shape reconstruction from a single RGB image has become a crucial technology in many industries such as Automotive, Healthcare, and Military. It is particularly challenging to reconstruct the complex shape of a military tank. Former methods infer 3D information from 2D images via shape deformation from ellipsoids, which has the problems of local adhesion, uneven surfaces, and distortion of the structure. This study introduces a new single-view 3D shape reconstruction (SVSR) framework with multi-scale feature extraction that splits shape reconstruction into three tasks—camera parameter prediction, initial shape construction, and deformation prediction. The shape-initialization module provides a variable initial shape by predicting the stretch and displacement parameters of each geometric component based on their topological relationships. The shape-deformation module predicts the directional deformation of each vertex. These two modules are dedicated separately to avoid shape adhesion and improve the local detail performance. Silhouette images of the tank's overall shape and local geometric components are employed to eliminate the impact of component shielding and avoid structural distortion via both pixel loss and perceptual loss. Experiments on the main battle tank dataset demonstrate that our method can predict complicated 3D shapes with a low Chamfer distance value (0.0017). Our approach outperforms the other state-of-the-art methods in terms of Chamfer distance and F-score with at least a 10% improvement, with more realistic overall contours and part details. It has huge application prospects in dealing with other complex shape predictions by modifying the shape-initialization module. • A new method was proposed to reconstruct meshes of various complicated tanks from a single image. • Our framework avoids the problems of local adhesion, uneven surface and distortion of structure. • We design a Shape Initialization Module to provide a variable initial shape. • Part loss was designed to optimize the local remodelling of the object. • Multi-scale extraction and multi-path prediction structure optimized the feature processing. [ABSTRACT FROM AUTHOR]

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers. [ABSTRACT FROM AUTHOR]

Antibody–drug conjugates (ADCs) have demonstrated significant efficacy in treating solid tumors. However, the occurrence of ADC drug-associated pneumonitis can limit the use of ADCs or have severe consequences, and we know comparatively little about this. PubMed, EMBASE, and the Cochrane library were exhaustively searched for articles and conference abstracts published before September 30, 2022. Two authors independently extracted data from the included studies. A random-effects model was used to conduct a meta-analysis of the relevant outcomes. Forest plots reflected the incidence rates from each study, and binomial methods were used to calculate the 95 % confidence interval. This meta-analysis included 7732 patients from 39 studies and evaluated the incidence of ADCs drug-associated pneumonitis which have received market approval for the treatment of solid tumors. The total incidence of solid tumors for all-grade pneumonitis was 5.86 % (95 % CI, 3.54–8.66 %) and for grade ≥3 was 0.68 % (95 % CI, 0.18–1.38 %). The incidence of all-grade pneumonitis was 5.08 % (95 % CI, 2.76–7.96 %) and for grade ≥3 was 0.57 % (95 % CI, 0.10–1.29 %) with ADC monotherapy. The incidence of all-grade and grade ≥3 pneumonitis in trastuzumab deruxtecan (T-DXd) was 13.58 % (95 % CI, 9.43–18.29 %) and 2.19 % (95 % CI, 0.94–3.81 %), respectively, the highest in ADC therapy. Total incidence of all-grade pneumonitis was 10.58 % (95 % CI, 4.34–18.81 %) and for grade ≥3 pneumonitis was 1.29 % (95 % CI, 0.22–2.92 %) with ADC combination therapy. The incidence of pneumonitis was higher with combination therapy than with monotherapy in both all-grade and grade ≥3 groups, but there was no statistical significance (P =.138 and P =.281, respectively). The incidence of ADC-associated pneumonitis in non-small cell lung cancer (NSCLC) was 22.18 % (95 % CI, 2.14–52.61 %), the highest among solid tumors. The 11 included studies reported 21 pneumonitis-related deaths. Our findings will assist clinicians in choosing the optimal therapeutic options for patients with solid tumors treated with ADCs. [Display omitted] • This is the first meta-analysis to assess the incidence of pneumonitis caused by approved antibody–drug conjugates (ADCs). • Patients with solid tumors had a higher incidence of all-grade ADC drug-associated pneumonitis, grade ≥3 was relatively rare. • The incidence of pneumonitis varies according to drug and tumor type. [ABSTRACT FROM AUTHOR]

Significant natural fractures develop in deep sandstone reservoirs. However, the previous numerical simulation for matrix acidizing in sandstone rocks always focused on the reactive flow in porous media. A series of responses between multiple types of acids and minerals in fracture and matrix pores have been a significant setback for seeking the mechanism of acid flow in fractured sandstone rocks. This paper, established a multistage reactive-transport model for fractured sandstone rocks based on the two-scale continuum model to explore the effects of fractures on the reactive flow. The weak forms of fluid flow and solute transport equations are derived using the Galerkin method to couple the matrix and fracture domains, and the extended finite element method was used to solve the discretization model. Additionally, we presented numerical simulations under 2D linear flow conditions with specific and sensitive analyses about fracture and matrix properties. Numerical cases showed that the wormhole-shaped structure generated by acid dissolution is hard to develop even in highly heterogeneous fractured sandstone rocks due to the low reaction rate between mud acid and minerals. However, fractures that are not parallel to the flow direction can accelerated acid flow in the formation and reduced Si(OH) 4 precipitation. Increasing the injection rate can not change the dissolution patterns of sandstone, but expanded the acid diffusion range and decreased Si(OH) 4 precipitation in fractured sandstone. • A multistage reactive-transport model of fractured sandstone was developed based on the two-scale continuum model. • The mechanism of acid flow in fractured sandstone rocks was explored. • The effects of the characteristic parameters of fracture and matrix on the acid transport were investigated. • The potential for generating wormhole-like structures in fractured sandstone rocks was analyzed. [ABSTRACT FROM AUTHOR]

Significant natural fractures develop in deep sandstone reservoirs. However, the previous numerical simulation for matrix acidizing in sandstone rocks always focused on the reactive flow in porous media. A series of responses between multiple types of acids and minerals in fracture and matrix pores have been a significant setback for seeking the mechanism of acid flow in fractured sandstone rocks. This paper, established a multistage reactive-transport model for fractured sandstone rocks based on the two-scale continuum model to explore the effects of fractures on the reactive flow. The weak forms of fluid flow and solute transport equations are derived using the Galerkin method to couple the matrix and fracture domains, and the extended finite element method was used to solve the discretization model. Additionally, we presented numerical simulations under 2D linear flow conditions with specific and sensitive analyses about fracture and matrix properties. Numerical cases showed that the wormhole-shaped structure generated by acid dissolution is hard to develop even in highly heterogeneous fractured sandstone rocks due to the low reaction rate between mud acid and minerals. However, fractures that are not parallel to the flow direction can accelerated acid flow in the formation and reduced Si(OH) 4 precipitation. Increasing the injection rate can not change the dissolution patterns of sandstone, but expanded the acid diffusion range and decreased Si(OH) 4 precipitation in fractured sandstone. • A multistage reactive-transport model of fractured sandstone was developed based on the two-scale continuum model. • The mechanism of acid flow in fractured sandstone rocks was explored. • The effects of the characteristic parameters of fracture and matrix on the acid transport were investigated. • The potential for generating wormhole-like structures in fractured sandstone rocks was analyzed. [ABSTRACT FROM AUTHOR]

• A deep learning model to invert thermal boundary parameters is proposed. • The combination of heat transfer and deep learning model is successful. • The proposed hybrid models outperformed the standalone models (CNN, LSTM). • It can effectively solve the complex calculation of traditional inverse methods. Estimating thermal boundary condition parameters in the transient inverse heat transfer problem (IHTP) is characterized by instability and non-uniqueness of the solution. This study formulated a simple method based on deep learning, which can realize multi-dimensional real-time prediction of thermal boundary condition parameters. The proposed model combining convolutional neural network (CNN) and long short-term memory networks (LSTM) allowed estimating multiple time-varying parameters based on the time-varying temperature field image of the target. The data-driven model used the computational fluid dynamics (CFD) method to obtain the numerical data, and the influence weight of the parameters was introduced in the training process to improve the generalization ability of the model. An experiment on the cubic cavity was made to verify the reliability of the proposed model to estimate time-varying parameters. The studies we have performed showed that the proposed hybrid models outperformed the standalone models (CNN, LSTM) in estimating multiple time-varying parameters. In the experimental results, the relative errors of air temperature and humidity were only 2.33% and 4.33%, respectively. These attempts of introducing the deep learning method to the IHTP in the present study were successful and it was significant for the study of the transient inverse heat transfer problem. [ABSTRACT FROM AUTHOR]

In order to research the effect of suction coefficients and directions on suction control, and the relationship between effectiveness and cost of suction, a local suction distribution on the upper surface of the NACA0012 airfoil is designed to control the flow separation. The effectiveness of the designed suction distribution is investigated numerically using Roe scheme and LU-SGS implicit scheme with dual-time-stepping technique. The mechanism of suction control is analyzed by comparing the velocity profiles in the boundary layer. The penalty for utilizing suction control is also estimated. The computational results show that the designed suction distribution is capable of suppressing the flow separations and improving the aerodynamic performances. With the increase of the suction coefficients, the lift-to-drag ratio increases fast firstly and then decrease slowly, while the maximum increase is about 130%. The analysis of energy consumption shows that the cost for using suction to suppress separation flow is relatively small with an appropriate suction coefficient. The effect of suction angles on suction control is obvious. As the suction angle becomes larger, not only the lift-to-drag ratio increases, but also the cost of suction decreases. These results will further help to provide new ideas and methods for flow control design. [ABSTRACT FROM AUTHOR]

In order to solve k-ω type turbulence model equations and Reynolds-averaged Navier-Stokes equations (RANS), cloud reconstruction technology, which can obtain well results from high aspect radio anisotropic cloud of points, is adopted in moving least squares meshless method. With the cloud reconstruction technique and the meshless method, it is realistic to simulate turbulence flows. The turbulence prediction abilities of the k-ω SST (Shear Stress Transport) and the k-ω TNT (Turbulent Non Turbulent) modes are demonstrated on a number of cases including NACA0012 airfoil, RAE2822 airfoil and backward-facing step. It can be found that; for weak advanced pressure gradient flows, the two models have the same ability for prediction; while in shock introduced separation turbulence flows, the SST model show better predicted ability of shock capture than TNT model; for large scale separation flows, there are some differences between the results of the two models and the experimental data, while the overall trends are in good agreement with the experimental data. [ABSTRACT FROM AUTHOR]

• Breast cancer related differentially expressed genes were identified based on TCGA database and GTEx database. • The GIMAP family genes with relatively high diagnostic values for the patients of breast cancer were analyzed. • Immune infiltration of GIMAP family genes obtained, providing selectable targets for breast cancer treatment. Breast cancer is the most common malignancy threatening women's health worldwide. The GTPase IMAP family genes are proteins belonging to the immune-associated nucleotide subfamily of the GTP-binding superfamily and nucleotide-binding proteins. However, little is known about the role of different GTPase IMAP family genes in breast cancer. We obtained differential genes from the GEPIA and UALCAN databases and then used the Kaplan–Meier plotter, The Human Protein Atlas, NetworkAnalyst, STRING, and TIMER to analyze the prognostic value, protein expression, and immune cell infiltration of the GTPase IMAP family in patients with breast cancer. Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly low in breast tumor tissues. In the overall population, patients with high expression of all genes of the GIMAP family had a significantly higher overall survival (OS), with the most significant increase correlated with the GIMAP2 gene (hazard ratio [HR] = 0.45, 95% confidence interval [CI], 0.34–0.59, P = 3.1e−09). However, patients with high expression of the GIMAP family genes in triple-negative breast cancer compared to those with low expression had a significant OS benefit, with the most pronounced benefit correlated with the GIMAP2 gene (HR = 0.37, 95% CI, 0.23–0.59, P = 1.4e−05). GIMAP7 and GIMAP8 were significantly upregulated in breast tumor tissues. The expression of genes in different GIMAP families was positively correlated with the infiltration and expression of six immune cell types (B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells). This study may provide novel insights into the selection of GIMAP family prognostic biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • Question • Will the immunotherapy addition to chemotherapy for metastatic triple-negative breast cancer (mTNBC) compared with standalone chemotherapy increased clinical efficacy? • Findings • This meta-analysis of 4 randomized clinical trials with 3007 patients found that it significantly improved progression-free survival in mTNBC patients with programmed death ligand-1 (PD-L1) positive. • Meaning • This result may provide more options for the treatment of mTNBC patients with PD-L1 positive. One of the front treatment regimens used for metastatic triple-negative breast cancer (mTNBC) is treatment with programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) blockade combine with chemotherapy. However, the results of such studies have been controversial. A systematic searched of PubMed, Embase, Cochrane Library, and the proceedings of the last 5 years of several meetings until February 18, 2021. The primary endpoint was the progression-free survival (PFS) of PD-L1-positive patients treated with PD1/PD-L1 blockade plus chemotherapy compare with chemotherapy. Overall, 4 studies that included a total of 3007 mTNBC patients were analyzed in this meta-analysis. PFS was significantly improved in the PD1/PD-L1 blockade plus chemotherapy group compared with the chemotherapy group in PD-L1-positive mTNBC patients (hazard ratios, (HR), 0.69; 95% CI, 0.59–0.80; P <.001), also in intention-to-treat (ITT) population (HR, 0.82; 95% CI, 0.74–0.90; P <.001). However, no significant benefit in overall survival (OS) was observed regardless of PD-L1 status or ITT population. The immunotherapy plus chemotherapy has higher adverse events (AEs) compared with chemotherapy (all AEs, Odds ratios (ORs), 2.33; 95% CI, 1.50–3.62; P <.001; grade 3-5 AEs, OR, 1.27; 95% CI, 1.04–1.55; P =.019). This meta-analysis showed that the addition of PD1/PD-L1 blockade to chemotherapy improved PFS in PD-L1 positive mTNBC patients, also in the ITT population. However, no significant benefit in OS was observed in patients of PD-L1 positive or in the ITT population after adding PD1/PD-L1 blockade. We found a higher rate of AEs with the addition of PD1/PD-L1 blockers to chemotherapy. [ABSTRACT FROM AUTHOR]

• The study creates a scale measuring language disorder in Mandarin-speaking children. • MCELP-CS is beneficial in language measurement for autistic, CP, and HI children. • MCELP-CS has good internal consistency and excellent structural validity. • The MCELP-CS measured language comprehension and production across domains. To test the psychometric properties of a newly developed Mandarin Clinical Evaluation of Language for Preschooler's Core Scale (MCELP-CS). Data were collected from 379 preschool-aged participants, including 81 children with language disorders associated with clinical conditions. The 155-item MCELP-CS consists of five subscales: vocabulary comprehension (VC), sentence comprehension (SC), vocabulary naming (VN), sentence structure imitation (SSI), and story narration (SN). The scale was used to measure the receptive and expressive language abilities of children aged 3–5 years and 11 months. The Peabody Picture Vocabulary Test-revised (PPVT-R) was used to measure the receptive vocabulary abilities among the children (n = 338). The internal consistency, test-retest reliability, structural validity, convergent validity, and diagnostic accuracy were used to evaluate the scale. Differences between age groups were also examined using analysis of variance. The MCELP-CS had high internal consistency and good test-retest reliability. Fitting indices of the two-factor model from confirmatory factor analysis (CFA), including χ 2 , CFI, TLI, RSEAM, and SRMR, suggested that the model is consistent with the theoretical structure. Significant correlations between the MCELP-CS and PPVT-R showed a high convergent validity. In addition, the scale indicated good diagnostic accuracy in differentiating the language disorders of children with autism, cerebral palsy (CP), and hearing impairment (HI). The MCELP-CS is a reliable and valid diagnostic tool for language disorders of Mandarin-speaking preschool children with autism, CP, and HI. It is appropriate to collect normative data for the MCELP-CS with a large sample population of preschool children. [ABSTRACT FROM AUTHOR]

Acid fracturing is an important method of achieving high-efficiency economic development of carbonate reservoirs. The propagation of acid-etched fractures is affected significantly by geological discontinuities such as natural fractures and limestone caverns. Therefore, acid-etched fractures in carbonate reservoirs also differ greatly in morphology to those inhomogeneous reservoirs. However, no clear propagation mechanism has been available to describe and predict the propagation behavior of acid-etched fractures. In order to investigate the process, based on the extended finite element method, a set of acid-etched fracture propagation models for fracture-vuggy reservoirs, including mechanical, hydro and acid-rock reaction modules, were established. The effect of vuggy, natural fracture and acid on the initiation and propagation of induced fracture, the surface morphology of the acid-etched fractures, the effects of the number of perforation clusters, and natural limestone caverns, were considered. The calculated geometric size of the fracture was compared with the results based on the CGD (Christianovich-Geertsma-Daneshy model) model, for validating the reliability of the present model. The effects of the injection fracturing liquid type and the number of perforation clusters on fracture initiation position, propagation path, and surface morphology were evaluated. The calculation results also were compared with large-scale tri-axial physical experiment data. Finally, the fracture propagation behavior in rock samples containing natural fractures and limestone caverns was simulated in order to examine examining the effects of the limestone caverns with different sizes at different positions on the propagation path of acid-etched fractures. The interaction between induced fractures and limestone caverns was discussed. The induced fractures priority was given to activating natural fractures around the wellbore and extending along the natural fractures and tended to be deflected from the maximum horizontal principal stress direction due to the existence of caverns arrested fractures to a certain degree. • An acid-etched fracture propagation models for fracture-vuggy reservoirs was established. • The initiation and extension mechanisms were discussed. • The artificial fractures tended to initiation from the large size natural fractures near the well. [ABSTRACT FROM AUTHOR]

Stress-dependent permeability (SDP) of naturally fractured tight gas reservoir (NFTGR) has drawn considerable attention in recent decades. The SDP of natural fracture (NF) is quite different from that of the rock matrix (RM) due to the variance NF width and NF filling degree. The SDP of naturally fractures can be obtained by conducting permeability measurement experiments on naturally fractured core plugs (NFCP). However, it is usually impossible to obtain downhole NFCPs due to economic and technical limitations. Our research group obtained various types of naturally fractured downhole core plugs from a NFTGR (Tarim filed, China) and make it possible to investigate the effect of NFs on SDP. The NF types of the downhole core plugs include RM core plug (RMCP), unpenetrated-ring fractured core plug (URFCP), penetrated-vertical fractured core plug (PVFCP), penetrated-incline fractured core plug (PIFCP), unpenetrated-U-type fractured core plug (UUFCP), and multiple fractured core plug (MFCP). We conducted SDP experiments through the application of pressure-pulse-decay (PPD) method. Results showed that the initial permeability of RMCP and MFCP were higher than that of others, and the permeability vanished stress of them were also highest, indicating that the flow resistance of RMCP and MFCP were lower than those of others. It is also shown that the degree of permeability stress-dependent (DPSD) varied from NF types. A modified exponential permeability model was derived to evaluate DPSD of natural fractured core plugs. Two parameters (γ σeff and γ σeff ') were used to describe the DSDP in NFTGR, and the range of which were obtained from the experimental data by regression analysis. The reasonable γ σeff and γ σeff ' range of NFCP were also proposed in this paper. Sensitivity analysis showed that the influence γ σeff ' on SDP was more significant than that of γ σeff. The proposed model can be integrated to reservoir simulators and help to improve of oil and gas production prediction accuracy in NFTGRs. • Real downhole core plugs were used to evaluate the stress dependent permeability. • The degree of stress dependent permeability was evaluated by types of natural fractures. • An analytical model was proposed to assess the stress dependent permeability of naturally fractured reservoir. • Key parameters that control of the stress dependent permeability were identified. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer.Methods: RCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity.Results: Our analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69-0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12-1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66-0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69-0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42-1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47-1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81-1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82-1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81-0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86-1.07; P = 0.47) that among Asian patients.Conclusions: Compared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients. [ABSTRACT FROM AUTHOR]