Rationally Designed L12-Pt2RhFe Intermetallic Catalyst with High CO-Tolerance for Alkaline Methanol Electrooxidation.

It is a grand challenge to deep understanding of and precise control over functional sites for the rational design of highly efficient catalysts for methanol electrooxidation. Here, an L12-Pt2RhFe intermetallic catalyst with integrated functional components is demonstrated, which exhibits exceptional CO tolerance. The Pt2RhFe/C achieves a superior mass activity of 6.43 A mgPt -1, which is 2.23-fold and 3.53-fold higher than those of PtRu/C and Pt/C. Impressively, the Pt2RhFe/C exhibits a significant enhancement in durability owing to its high CO-tolerance and stability. Density functional theory calculations reveal that high performance of Pt2RhFe intermetallic catalyst arises from the synergistic effect: the strong OH binding energy (OHBE) at Fe sites induce stably adsorbed OH species and thus facilitate the dehydrogenation step of methanol via rapid hydrogen transfer, while moderate OHBE at Rh sites promote the formation of the transition state (Pt-CO···OH-Rh) with a low activation barrier for CO removal. This work provides new insights into the role of OH binding strength in the removal of CO species, which is beneficial for the rational design of highly efficient catalysts.

Mid-infrared ultrashort pulses generated from a hybrid mode-locked Er:ZBLAN fiber laser.

By combining nonlinear polarization rotation (NPR) and semiconductor saturable absorber, we report a hybrid mode-locked Er:ZBLAN fiber oscillator at 2.8 µm. Stable 325-fs mode-locked pulses with an average power of 131 mW and a record signal-to-noise ratio of 79 dB at the fundamental frequency of 55.4 MHz are generated. Numerical simulations are carried out based on the modified coupled nonlinear Schrödinger equations, and offer new insights into the underlying dynamics of pulse generation. The simulations indicate that compared with Er:ZBLAN fiber lasers mode-locked by NPR alone, the hybrid mode-locked Er:ZBLAN fiber oscillator allows a wider range and a lower threshold of the pump power while maintaining the ultrashort pulse width. Moreover, we numerically demonstrate that the hybrid mode-locked oscillator is less sensitive to the variation of polarization states, which will increase its robustness against environmental disturbance. This is the first time that the hybrid mode-locking technique is applied in the mid-infrared, opening up new opportunities for the development of stable ultrafast mid-infrared laser sources and practical applications outside the laboratory.

High-energy femtosecond pulse generation from a hybrid mode-locked large-mode-area Er:ZBLAN fiber laser.

We report a hybrid mode-locked fiber laser at 2.8 µm based on a large-mode-area Er:ZBLAN fiber. Reliable self-starting mode-locking is achieved via the combination of nonlinear polarization rotation and a semiconductor saturable absorber. Stable mode-locked pulses with a pulse energy of 9.4 nJ and a pulse duration of 325 fs are generated. To the best of our knowledge, this is the highest pulse energy directly generated from a femtosecond mode-locked fluoride fiber laser (MLFFL) to date. The measured M2 factors are below 1.13, indicating a nearly diffraction-limited beam quality. Demonstration of this laser provides a feasible scheme for the pulse energy scaling of mid-infrared MLFFLs. Moreover, a peculiar multi-soliton mode-locking state is also observed, in which the time interval between the solitons varies irregularly from tens of picoseconds to several nanoseconds.

Average-power (4.13 W) 59 fs mid-infrared pulses from a fluoride fiber laser system.

We report a high-average-power mid-infrared ultrafast laser system consisting of a fluoride fiber mode-locked oscillator and a nonlinear amplifier. A backward pumping scheme was used in the amplifier to simultaneously realize pulse amplification and self-compression. The input signal polarization was demonstrated to play an important role in the self-compression process. Through the optimization of input polarization, a 4.13 W average-power 59 fs pulse at 2.8 µm was achieved, with an estimated pulse energy of 42.2 nJ and a peak power of 715 kW. To the best of our knowledge, this is the highest average-power pulse with sub-100-fs duration generated from a mid-infrared fiber laser system to date.

Production and characterization of GPC3-N protein and its nanobody.

Glypican-3 (GPC3) has a promise to be the diagnostic biomarker as well as therapeutic target for hepatocellular carcinoma (HCC). Nanobody have the great potential in clinical diagnosis and treatment for their characteristics of small size, high solubility, stability, manipulability, binding advantages, and ease of production. In this study, the recombinant glypican-3-N terminal (GPC3-N) protein was expressed as inclusion body in E. coli BL21(DE3)pLysS cells and then purified, which is then used as the immunogen to construct nanobody phage library. The positive clone (named MF15) was obtained by four rounds of bio-panning, and then transformed into the E. coil TOP10F' cells to express nanobody protein, with the molecular weight of 19 kDa. Both Western blot and immunofluorescence analysis revealed that bacterially expressed GPC3-N protein is biologically active, and MF15 could specifically recognized native GPC3 expressed in HepG2 cells. The results in this study would provide the technical support for the development of diagnostic kits and antibody drugs targeting GPC3.

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial.

Importance: Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). Objective: To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. Design, Setting, and Participants: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Interventions: Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). Main Outcomes and Measures: The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Results: Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Conclusions and Relevance: Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02633202.

Apatinib for the treatment of metastatic or locoregionally recurrent nasopharyngeal carcinoma after failure of chemotherapy: A multicenter, single-arm, prospective phase 2 study.

BACKGROUND: The authors aimed to investigate the efficacy and safety of apatinib in patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma (NPC). METHODS: A multicenter, single-arm, prospective phase 2 study was conducted on patients (18-70 years of age) with metastatic or recurrent NPC who had failed chemotherapy. Patients with recurrent disease involving vascular structure invasion were excluded. All enrolled patients received apatinib (500 mg daily) in continuous 4-week cycles until disease progression or development of unacceptable toxicity. The primary end point of this study was objective response rate (ORR), and the secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. This study was registered with ClinicalTrials.gov (NCT03130270). RESULTS: Between January 2017 and June 2018, 33 patients were enrolled. At the end of the data collection (May 20, 2020), the 33 patients had completed a total of 261.2 cycles of apatinib. Although 12 patients achieved a partial response, no patient achieved a complete response; thus, the ORR in the 33 patients was 36.4% (95% CI, 19.0%-53.7%). At the end of follow-up (median, 30 months; 95% CI, 24.9-35.1), median OS and median PFS were 16 months (95% CI, 14.6-17.4 months) and 5.0 months (95% CI, 3.6-6.4 months), respectively. The most common adverse events (grade 1/2) were hand-foot syndrome (18 [54.5%]), hypertension (14 [42.4%]), oral ulcer (8 [24.2%]), and proteinuria (4 [12.1%]). Two patients (1 with diabetes and 1 with hypertension) developed cerebral infarction. Grade 3/4 toxicities were uncommon. CONCLUSIONS: Apatinib shows promising activity, with manageable toxicities, in patients with metastatic or locoregionally recurrent NPC. Further evaluation of apatinib in large-scale studies is warranted. LAY SUMMARY: Clinical studies on vascular endothelial growth factor receptor (VEGFR)-targeted therapy for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. A recent preclinical study that evaluated apatinib in models of NPC showed a high objective response rate and a favorable safety profile. Our data further confirmed good efficacy in patients with lung metastasis. Further studies of the efficacy and safety of apatinib combined with immune checkpoint inhibitors or chemotherapy in NPC is warranted.

Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study.

BACKGROUND: Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy. METHODS: This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015-2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy. RESULTS: A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033). CONCLUSION: For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation. TRIAL REGISTRATION: The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Nonparaxial propagation of the chirped Airy vortex beams in uniaxial crystal orthogonal to the optical axis.

We study both analytically and numerically nonparaxial propagation dynamics of the Chirped Airy vortex (CAiV) beams in uniaxial crystal orthogonal to the optical axis. The propagation trajectory, the intensity, the radiation forces, the Poynting vector and the angular momentum (AM) of the CAiV beams are illustrated by numerical examples. The influences of the ratio of the extraordinary refractive index to the ordinary refractive index, the linear chirp factor and the quadratic chirp factor on the nonparaxial evolution of the CAiV beams are examined in detail. Results show that the linear chirp factor provides an intensity concentration, which is totally different with the influence of the quadratic chirp. Besides, the uniaxial crystals with different refractive index ratios can be used to control the intensity of optical lobes. Moreover, the value and the direction of the radiation forces depend on the propagation distance and the chirp factor. The chirp factor acting on the Poynting vector and the AM mainly occurs in the direction of vectors. The nonparaxial propagation characteristics of the CAiV beams provide a convenient method to the intensity modulation and the optical manipulation of micro particles.

An AgPd NP-based lateral flow immunoassay for simultaneous detection of glycocholic acid and alpha-fetoprotein.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, ranking third in cancer deaths. Early diagnosis of HCC markers is imperative for effective prognosis and treatment. This study explores the utility of glycocholic acid (GCA) and alpha-fetoprotein (AFP) as biomarkers for liver diseases, with a specific focus on their simultaneous detection for enhanced diagnostic and prognostic capabilities. Harnessing the benefits of lateral flow immunoassay (LFIA), such as operational simplicity, speed, and accuracy, we engineered AgPd nanocomposites with antibodies targeting GCA and AFP. Under the optimized conditions, the visual detection limit for GCA was established at 50 ng mL-1 and the cut-off value at 104 ng mL-1. And for AFP, the visual detection limit was 0.1 ng mL-1 and the cut-off value was 500 ng mL-1. The accuracy and feasibility of the strips were validated through the detection of 39 actual serum samples. The results highlight the potential of LFIA as a rapid and effective tool for clinical diagnosis. The developed LFIA method not only demonstrates accuracy and feasibility but also presents a promising avenue for the early diagnosis of hepatocellular carcinoma.

Dual lateral flow assay based on PdRu nanocages for human Papillomavirus detection.

Cervical cancer is one of the most common gynecological malignancies, with the vast majority of which being caused by persistent infection with Human Papillomavirus (HPV) 16 and 18. The current available HPV detection methods are sensitive and genotyped but are restricted by expensive instruments and skilled personnel. The development of an easy-to-use, rapid, and cost-friendly analysis method for HPV is of great need. Herein, hollow palladium-ruthenium nanocages modified with two oligonucleotides (PdRu capture probes) were constructed for genotyping and simultaneous detection of target nucleic acids HPV16 and HPV18 by dual lateral flow assay (DLFA). PdRu capture probes were endowed with bi-functions for the first time, which could be used to output signals and hybridize target nucleic acids. Under optimized conditions, the PdRu based-DLFA with detection limits of 0.93 nM and 0.19 nM, respectively, exhibited convenient operation, and high sensitivity. Meanwhile, the DLFA achieved excellent rapid detection within 20 min, which was attributed to capture probes that can be directly bound to amplification-free target nucleic acids. Therefore, the development of PdRu-based DLFA can be utilized for rapid, sensitive, and simultaneous genotyping detection of HPV16 and HPV18, showing great application for nucleic acid detection.

Constructing a Topologically Adaptable Solid Electrolyte Interphase for a Highly Reversible Zinc Anode.

The performance of aqueous zinc metal batteries is significantly compromised by the stability of the solid electrolyte interphase (SEI), which is intimately linked to the structure of the electrical double layer (EDL) between the zinc anode and electrolyte. Furthermore, understanding the mechanical behavior of SEI is crucial, as it governs its response to stress induced by volume changes, fracture, or deformation. In this study, we introduce l-glutamine (Gln) as an additive to regulate the adsorbed environment of the EDL and in situ produce a hybrid SEI consisting of ZnS and Gln-related species. The results of the nanoindentation test indicate that the hybrid SEI exhibits a low modulus and low hardness, alongside exceptional shape recovery capability, which effectively limits side reactions and enables topological adaptation to volume fluctuations in zinc anodes during zinc ion plating/stripping, thereby enabling Zn//Zn symmetric cells to exhibit an ultralong cycle life of 4000 h in coin cells and a high cumulative capacity of 18,000 mA h in pouch cells. More importantly, the superiority of the formulated strategy is further demonstrated in Zn//NH4V4O10 full cells at different N/P ratios of 5.2, 4.9, 3.5, and 2.4. This provides a promising approach for future interfacial modulation in aqueous battery chemistry.

Microstructure and morphology of the soldering interface of Sn-2.0Ag-1.5Zn low Ag content lead-free solder ball and different substrates.

Eutectic Sn-Ag-Cu lead-free solder has limited applications due to cost and reliability issues. Sn-Ag-Zn solder has the advantages of low melting point, good mechanical properties and reliable welding interface. However, the research system of low silver content Sn-Ag-Zn solder is incomplete. In this paper, Sn-2.0Ag-1.5Zn low silver content alloy solder is soldered to different substrates. The interfacial reaction after soldering and the microstructure and reliability under different aging treatment conditions are studied. Sn-2.0Ag-1.5Zn solder is made into solder balls by direct melting method. The solder balls are placed in a solder strength tester to be heated and welded to the substrate, and then the solder joints are placed in a heating furnace for aging treatment. The results show that the solder is soldered to the bare Cu substrate, and a dense double-layer Intermetallic Compound (IMC) structure of Cu5Zn8 and Ag3Sn is formed at the interface after aging treatment. The double-layer structure blocks each other, limiting the development of copper-tin IMCs. The solder is soldered with the Cu substrate electroplated with Ni barrier layer, and the soldering interface forms a thin layer of Ni3Sn4 metal compound. After aging for 1000 h, the thickness of Ni3Sn4 is about 1 µm, the thickness of Ni barrier layer is kept at 2-3 µm, and the barrier effect of Ni barrier layer is stable. Sn-2.0Ag-1.5Zn solder has excellent loss performance in long aging treatment. It has good heat-resistance aging treatment, good quality of solder connection, high interface reliability and less environmental pollution. The low silver content in Sn-2.0Ag-1.5Zn solder results in a significant cost reduction. Coarse IMC Ag3Sn is not easily formed. The optimized ratio of Ag and Zn in Sn-2.0Ag-1.5Zn solder improves the strength and toughness of the solder joint. The performance has been improved, and it is a very promising alloy solder.

Intrathyroidal Thymic Carcinoma: A Retrospective Case Series Study.

OBJECTIVE: Intrathyroidal thymic carcinoma (ITC) is a rare low-grade malignant thyroid tumor. There is neither sufficient understanding of this tumor nor its clinical treatment. This study is to explore the clinicopathological features, treatment, and prognosis of ITC and thereby provide a reference for the diagnosis and treatment of the disease. METHODS: The clinical, pathological, therapeutic, and prognostic data of 13 patients with ITC were retrospectively analyzed. RESULTS: The case series comprised 7 males and 6 females, with an average age of 51.9 ± 10.1 years. After surgical resection, all patients received post-operative neck radiotherapy at dosages of 60-66 Gy. Five patients with level VI lymph node metastasis additionally received 6 courses of cisplatin chemotherapy. All patients were followed-up for 21-132 months (median = 66 months), and all of them survived without recurrence or metastasis. CONCLUSIONS: The diagnosis of ITC depends mainly on pathological and immunohistochemical results, particularly CD5 positive staining. Surgical resection is the preferred primary treatment modality which can be supplemented with radiotherapy and chemotherapy to reduce the risk of recurrence and metastasis.

A Four-Gene Signature Model Improves the Prediction of Distant Metastasis in Patients with Nasopharyngeal Carcinoma: A Retrospective, Three-Center Observational Study.

Background: Similar to that in other malignant tumors, distant metastasis is one of the most important causes of poor prognosis in nasopharyngeal carcinoma (NPC). However, the genetic hallmarks and networks that regulate the distant metastasis of NPC are not fully understood. Methods: In this study, we performed high-throughput screening of mRNA expression profiles in 92 NPC samples collected from 3hospitals and detected the mRNA expression levels of 31,503 genes in these samples. Gene functional enrichment analyses were performed using gene set enrichment analysis (GSEA). Least absolute shrinkage and selection operator (LASSO) was applied to select prognostic genes and a Cox proportional hazards regression model including these genes was constructed to predict prognosis. The Kaplan-Meier curve and time-dependent receiver operating characteristic (ROC) curve were plotted to assess the performance of this model. Univariate and multivariate analyses were performed using the Cox proportion hazard model to test the independence of prognostic effect of gene model and other clinical features. Results: A total of 1837 differentially expressed genes between patients with and without distant metastasis were identified in the training cohort, including 869 upregulated genes and 968 downregulated genes. Six gene sets, including the Wnt/ß catenin signaling pathway, hedgehog (Hh) signaling pathway, Notch signaling pathway, mitotic spindle, apical surface, and estrogen response late, were enriched in patients with distant metastasis. A four-gene signature model was constructed in the training cohort, and according to the time-dependent ROC curve, this model had certain accuracy in predicting distant metastasis-free survival (DMFS) in both the training and validation cohorts. Conclusion: We developed a four-gene signature model that can evaluate the distant metastasis risk of NPC patients and may also provide novel therapeutic targets for NPC treatment in the near future.

Analytical Modeling and Validation of a Preloaded Piezoceramic Current Output.

Energy harvesting using piezoceramic has drawn a lot of attention in recent years. Its potential usage in microelectromechanical systems is starting to become a reality thanks to the development of an integrated circuit. An accurate equivalent circuit of piezoceramic is important in energy harvesting and the sensing system. A piezoceramic is always considered to be a current source according to empirical testing, instead of the derivation from its piezoelectric characteristics, which lacks accuracy under complicated mechanical excitation situations. In this study, a new current output model is developed to accurately estimate its value under various kinds of stimulation. Considering the frequency, amplitude and preload variation imposed on a piezoceramic, the multivariate model parameters are obtained in relation to piezo coefficients. Using this model, the current output could be easily calculated without experimental testing in order to quickly estimate the output power in energy harvesting whatever its geometric shape and the various excitations.

Programmable Color in a Free-Standing Photonic Microgel Film with Ultra-Fast Response.

In this work, a free-standing microgel film with programmable and angle-independent structural color is prepared via a simple but effective method. Dried poly(styrene-N-isopropylacrylamide-acrylic acid) (pStNIPAAmAA) microgels were stabilized by inter-microgel crosslinking, and thus, only microgels were used to build the optical hydrogel. The free-standing microgel film displayed tunable structural color by the swelling/deswelling of the microgels under external stimuli, such as temperature, pH, ionic strength, and organic solvent. Moreover, the structural color of the film is angle-independent for the disordered microgel arrays. It is worth noting that programmable color stripes which have the panther chameleon's ability to change skin color are successfully fabricated by patterning microgels with different thermoresponsivities. More importantly, the microgel film has an ultrafast response to temperature (1.41 s from 20 to 40 °C) and pH (2.24 s from pH 8.3 to pH 2.0), much faster than that of most optical materials reported in previous studies.

A dosimetric and radiobiological evaluation of VMAT following mastectomy for patients with left-sided breast cancer.

BACKGROUND: To compare the dosimetric, normal tissue complication probability (NTCP), secondary cancer complication probabilities (SCCP), and excess absolute risk (EAR) differences of volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for left-sided breast cancer after mastectomy. METHODS AND MATERIALS: Thirty patients with left-sided breast cancer treated with post-mastectomy radiation therapy (PMRT) were randomly enrolled in this study. Both IMRT and VMAT treatment plans were created for each patient. Planning target volume (PTV) doses for the chest wall and internal mammary nodes, PTV1, and PTV of the supraclavicular nodes, PTV2, of 50 Gy were prescribed in 25 fractions. The plans were evaluated based on PTV1 and PTV2 coverage, homogeneity index (HI), conformity index, conformity number (CN), dose to organs at risk, NTCP, SCCP, EAR, number of monitors units, and beam delivery time. RESULTS: VMAT resulted in more homogeneous chest wall coverage than did IMRT. The percent volume of PTV1 that received the prescribed dose of VMRT and IMRT was 95.9 ± 1.2% and 94.5 ± 1.6%, respectively (p < 0.001). The HI was 0.11 ± 0.01 for VMAT and 0.12 ± 0.02 for IMRT, respectively (p = 0.001). The VMAT plan had better conformity (CN: 0.84 ± 0.02 vs. 0.78 ± 0.04, p < 0.001) in PTV compared with IMRT. As opposed to IMRT plans, VMAT delivered a lower mean dose to the ipsilateral lung (11.5 Gy vs 12.6 Gy) and heart (5.2 Gy vs 6.0 Gy) and significantly reduced the V5, V10, V20, V30, and V40 of the ipsilateral lung and heart; only the differences in V5 of the ipsilateral lung did not reach statistical significance (p = 0.409). Although the volume of the ipsilateral lung and heart encompassed by the 2.5 Gy isodose line (V2.5) was increased by 6.7% and 7.7% (p < 0.001, p = 0.002), the NTCP was decreased by 0.8% and 0.6%, and SCCP and EAR were decreased by 1.9% and 0.1% for the ipsilateral lung. No significant differences were observed in the contralateral lung/breast V2.5, V5, V10, V20, mean dose, SCCP, and EAR. Finally, VMAT reduced the number of monitor units by 31.5% and the treatment time by 71.4%, as compared with IMRT. CONCLUSIONS: Compared with IMRT, VMAT is the optimal technique for PMRT patients with left-sided breast cancer due to better target coverage, a lower dose delivered, NTCP, SCCP, and EAR to the ipsilateral lung and heart, similar doses delivered to the contralateral lung and breast, fewer monitor units and a shorter delivery time.

Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases.

BACKGROUND: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). METHODS: Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training (N = 9,259) and two validation cohorts (N = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts. RESULTS: We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival (p < 0.001 for all): AHR1, T1N0; AHR2A, T1N1/T2-3N0 cfEBV DNA < 2,000 (EBVlow); AHR2B, T1N1/T2-3N0 cfEBV DNA ⩾ 2,000 (EBVhigh) and T1-2N2/T2-3N1 EBVlow; AHR3, T1-2N2/T2-3N1 EBVhigh and T3N2/T4N0 EBVlow; AHR4, T3N2/T4 N0-1 EBVhigh and T1-3N3/T4N1-3 EBVlow; AHR5, T1-3N3/T4 N2-3 EBVhigh. Our AHR model outperformed the published RPA models and TNM stage with better hazard consistency (1.35 versus 3.98-12.67), hazard discrimination (5.29 versus 6.69-13.35), explained variation (0.248 versus 0.164-0.225), balance (0.385 versus 0.438-0.749) and C-index (0.707 versus 0.662-0.700). In addition, our AHR model was superior to the TNM stage for risk stratification of OS in two validation cohorts (p < 0.001 for both). CONCLUSION: Herein, we developed and validated a risk classification system that combines the AJCC/UICC 8th edition TN-stage classification and cfEBV DNA for non-metastatic NPC. Our new clinicomolecular model provides improved OS prediction over the current staging system.

Vibration characteristic analysis of single-cylinder two-stroke engine and mounting system optimization design.

Compared with four-stroke engines, single-cylinder two-stroke engines have the characteristics of small inertia, high rotational speed, and wide excitation frequency range. However, the structural vibration and noise generated by the two-stroke engine are very violent. Hence, it is necessary to reduce the vibration and noise of the single-cylinder two-stroke engine. Based on the design theory of the engine mounting system, the excitation frequency, direction, and magnitude of a single-cylinder two-stroke engine are analyzed. The rubber isolator is selected as the new mount element, and the dynamic model of the engine powertrain mounting system is established based on ADAMS software. Based on the sensitivity analysis of the design variables of the mounting system, the natural frequency of the mounting system is used as an objective, and the three-directional stiffness of the mounting system is taken as design variables for the optimization problem. The optimization model is solved by the sequential quadratic programming method. The results show that the maximum frequency of the mounting system after optimization is less than 1/2 of the excitation frequency, and the isolation effect is achieved. The dynamic model and the optimization method presented in this article would provide a useful tool for the design and optimization of mounting system for the single-cylinder two-stroke engine to reduce vibration from the engine to the engine support.