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Freeway logistics plays a pivotal role in economic development. Although the rapid development in big data and artificial intelligence motivates long-haul freeway logistics towards informatization and intellectualization, the transportation of bulk commodities still faces serious challenges arisen from dispersed freight demands and the lack of co-ordination among different operators. The present study thereby proposed intelligent algorithms for truck dispatching for freeway logistics. Specifically, our contributions include the establishment of mathematical models for full-truckload (FTL) and less-than-truckload (LTL) transportation modes, respectively, and the introduction of reinforcement learning with deep Q-networks tailored for each transportation mode to improve the decision-making in order acceptance and truck repositioning. Simulation experiments based on the real-world freeway logistics data collected in Guiyang, China show that our algorithms improved operational profitability substantially with a 76% and 30% revenue increase for FTL and LTL modes, respectively, compared with single-stage optimization. These results demonstrate the potential of reinforcement learning in revolutionizing freeway logistics and should lay a foundation for future research in intelligent logistics systems.

Abstract Kidney injury from high-altitude polycythemia (HAPC) is common, yet few studies have explored effective treatments. This research assessed the renal benefits of therapeutic erythrocytapheresis (TE) in HAPC patients, analyzing the efficacy of single versus multiple treatments. From 2017 to 2023, 631 patients undergoing TE were included. Findings showed notable improvements in hemoglobin levels (median: 228.00 vs. 169.00 g/L, p

3D packaging mainly uses TSVs (Through Silicon via) to vertically interconnect multiple chips, achieving the purpose of signal transmission and electrical connection. As a popular advanced packaging method, its research is of great significance. Although stacked chips can achieve stronger performance in smaller spaces, they can also cause a series of reliability issues, among which thermal stress and warping due to differences in the thermal expansion coefficients of materials can even lead to chip failure. Therefore, it is highly valuable to simulate and analyze the entire 3D packaging model.In this study, the thermal stress and deformation of the whole three-dimensional package model were simulated by finite element analysis. The results showed that there were significant stress and deformation effects at the joint of the TSV structure at normal temperature, and the stress and deformation reached 209.99 MPa and 0.0018519 mm, respectively. After that, the temperature of the double-sided package system containing 3D package under electrothermal coupling conditions was optimized by heat dissipation design, which verified the ‘quantity first’ scheme of heat dissipation fins and reduced the temperature by 40 %.

Abstract Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.

Tick-borne rickettsial disease (TBRD) is a perilous acute infection that often eludes diagnosis in its early stages. The triad of knowledge, attitudes, and practices (KAPs) among medical professionals is key to reducing missed diagnosis rates. Therefore, a meticulous evaluation of KAPs is imperative. This study aimed to delve into the understanding of TBRD and explore the beliefs and practices related to personal prevention methods among individuals in Lu’an, a hotspot for TBRD. During the summer months of 2023, convenience sampling was employed by circulating a confidential questionnaire to 1,206 participants in the endemic regions of China. This questionnaire painted a comprehensive picture of the participants’ sociodemographic profiles and their KAPs levels vis-à-vis TBRD. The findings revealed that participants scored a mere 55.78% in knowledge, while their attitudes and practices garnered impressive scores of 90.09% and 90.83%, respectively. Upon further analysis using multiple linear regression, several intriguing patterns emerged. Male participants, employed in the Infectious Disease Department, held vice-senior or higher titles, or had prior medical training demonstrated superior knowledge scores. On the other hand, medical personnel who were younger than 30, possessed graduate degrees or higher qualifications, and had training excelled in attitudes and practices. Notably, when employing the Boston Consulting Group (BCG) matrix, a significant distribution of medical personnel was observed across the four quadrants. Specifically, 37.43%, 13.19%, 19.61%, and 29.77% fell into the first, second, third, and fourth quadrants. This survey underscores the commendable attitudes and practices of medical staff towards TBRD in endemic regions of China. However, their knowledge level remains wanting and demands urgent improvement.

Urban ventilation corridors are designed to enhance air quality, alleviate urban thermal conditions, reduce pollution and energy consumption, as well as improve human comfort within cities. They play a pivotal role in mitigating environmental impacts, particularly in densely populated urban areas. Based on satellite remote sensing data, meteorological observations, basic geographic information of Zhengzhou City and its surroundings, and urban planning data, we analyzed the urban wind environment, urban heat island, ecological cold sources, and ventilation potential. The findings reveal several key insights: (1) Dominant winds in Zhengzhou City predominantly originate from the northwest, northeast, and south, influenced by topography and the monsoon climate, with seasonal variations. These wind patterns are crucial considerations for designing primary ventilation corridors. (2) The urban heat island exhibits a polycentric spatial distribution, with intensity decreasing from the city center towards the periphery. Ecological cold sources, primarily situated in the city outskirts, act as reservoirs of fresh air that mitigate the urban heat island effect through designated corridors. (3) A preliminary corridor system, termed “eight primary and thirteen secondary corridors”, is proposed for Zhengzhou City based on an integrated assessment of ventilation potential, urban surface roughness, and sky view factor. This research contributes to advancing the understanding of urban ventilation systems and provides practical insights for policymakers, urban planners, and researchers seeking sustainable solutions to mitigate climate impacts in rapidly urbanizing environments in the region.

Abstract To provide evidence-based medicine references for formulating prevention and control policies in plateau areas, we explore the characteristics of anemia patients in Tibet (the plateau areas of China), especially those located at an altitude above 4500 m. We collected clinical data from 379 Tibetan anemia patients over the age of 18 years. We found those female patients accounted for the majority of Tibetan anemia patients. Almost half of the anemia patients aged from 28 to 47 years. The percentage of severe anemia and extremely severe anemia was 45.4% and 2.4%, respectively. 88.7% of patients are engaged in agriculture and animal husbandry, and 81.5% of patients just graduated from primary school or below. The most common causes of anemia were nutritional anemia, especially iron-deficiency anemia. At high-altitude localities, folic acid-deficiency anemia needs more attention. Overall, this study showed that altitude influences the incidence, severity, and cause of anemia. Peasants and herdsmen, low education levels, young and middle-aged women, and nutrition status should be paid attention to in future anemia control.

Abstract Proton exchange membrane fuel cells (PEMFCs) have garnered significant attention due to their high efficiency and low emissions. However, PEMFC always suffers mass transfer and water management in performance improvement. Herein, an integrated gas diffusion layer (GDL) with wavy channel and micro‐tunneled rib is designed and prepared to achieve faster and gentler mass transfer and excellent water management capability by laser engraving. Outstandingly, the new integrated GDL can use the back pressure of air as low as 0 and 50 kPa to respectively achieve 80% and 90% of fuel cell performance realized under pure oxygen. Such high performance is mainly due to the turbulent flow caused by wavy channel and express removing pathway of liquid water provided by micro‐tunneled rib. Moreover, the new integrated GDL also shows wide humidity tolerance from 40% to 100% and a very high specific volume power density of 16,300 W L−1 due to the thin thickness of new integrated GDL. This new integrated GDL is expected to be widely used in PEMFC and other energy conversion devices.

Methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type (NKTCL). We explored the efficacy and safety of reduced-intensity, non-intravenous etoposide, dexamethasone, and pegaspargase (ESA) with sandwiched radiotherapy. This multicenter, randomized, phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China. Patients were randomly assigned (1:1) to receive ESA (pegaspargase 2,500 IU/m2 intramuscularly on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2–4) or MESA (methotrexate 1 g/m2 intravenously on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2–4, and pegaspargase 2,500 IU/m2 intramuscularly on day 5) regimen (four cycles), combined with sandwiched radiotherapy. The primary endpoint was overall response rate (ORR). The non-inferiority margin was −10.0%. From March 16, 2016, to July 17, 2020, 256 patients underwent randomization, and 248 (ESA [n = 125] or MESA [n = 123]) made up the modified intention-to-treat population. The ORR was 88.8% (95% confidence interval [CI], 81.9–93.7) for ESA with sandwiched radiotherapy and 86.2% (95% CI, 78.8–91.7) for MESA with sandwiched radiotherapy, with an absolute rate difference of 2.6% (95% CI, −5.6–10.9), meeting the non-inferiority criteria. Per-protocol and sensitivity analysis supported this result. Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.

Abstract Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising novel therapeutic approach. However, primary and secondary resistance to CAR-T cell therapy is commonly encountered in various clinical trials. Despite the comprehensive studies to elucidate the mechanisms of resistance, effective resolution in clinical practice is still elusive. Inadequate persistence and subsequent loss of infused CAR-T cells are proposed major resistance mechanism associated with CAR-T cell treatment failure. Thus, we generated CAR-T cells armored with IL-7 to prolong the persistence of infused T-cells, particularly CD4 + T cells, and enhanced anti-tumor response. IL-7 increased CAR-T-cell persistence in vivo and contributed to the distinct T-cell cytotoxicity profile. Using mass cytometry (CyTOF), we further assessed the phenotypic and metabolic profiles of IL-7-secreting CAR-T cells, along with conventional CAR-T cells at the single-cell level. With in-depth analysis, we found that IL-7 maintained CAR-T cells in a less differentiated T-cell state, regulated distinct metabolic activity, and prevented CAR-T-cell exhaustion, which could be essential for CAR-T cells to maintain their metabolic fitness and anti-tumor response. Our findings thus provided clinical rationale to exploit IL-7 signaling for modulation and metabolic reprogramming of T-cell function to enhance CAR-T cell persistence and induce durable remission upon CAR-T cell therapy.

Sterile alpha and HEAT/Armadillo motif-containing protein (SARM) is conserved in evolution and negatively regulates TRIF-dependent Toll signaling in mammals. The SARM protein from Litopenaeus vannamei and its Drosophila orthologue Ectoderm-expressed (Ect4) are also involved in immune defense against pathogen infection. However, the functional mechanism of the protective effect remains unclear. In this study, we show that Ect4 is essential for the viral load in flies after a Drosophila C virus (DCV) infection. Viral load is increased in Ect4 mutants resulting in higher mortality rates than wild-type. Overexpression of Ect4 leads to a suppression of virus replication and thus improves the survival rate of the animals. Ect4 is required for the viral induction of STAT-responsive genes, TotA and TotM. Furthermore, Ect4 interacts with Stat92E, affecting the tyrosine phosphorylation and nuclear translocation of Stat92E in S2 cells. Altogether, our study identifies the adaptor protein Ect4 of the Toll pathway contributes to resistance to viral infection and regulates JAK/STAT signaling pathway.

Eco-city and green building are the global development strategies today. In order to improve the management level of green buildings in the urbanization process, a reciprocal symbiosis evaluation index model is proposed based on the theory of urban ecology. On this basis, the collaborative relationship model between Eco-city and green building is established, and the green building management framework based on the collaborative theory is constructed. The expert survey method was used to determine the evaluation indicators and analyze the relationship between various city subsystems. Then, the analytic hierarchy process is used to build a three-level evaluation index system, including the target layer, the criterion layer, and the index layer. The weight of the evaluation index system is calculated by combining of the chromatography method and the entropy weight method, and a scientific evaluation index system is established. The gray comprehensive evaluation method is used to evaluate the construction of the green building management system. Based on the index system, the analytic hierarchy process is used to calculate different weight coefficients, which makes the evaluation model easy to use and lays a foundation for subsequent research.

Real-world evidence on the effectiveness of COVID-19 vaccines marketed in China against the Omicron BA.2.2 variant remains scarce. A case–control study was conducted to estimate the vaccine effectiveness (VE) of COVID-19 vaccines marketed in China (inactivated vaccines, an Ad5-nCoV vaccine, and a recombinant protein vaccine). There were 414 cases infected with SARS-CoV-2 and 828 close contacts whose test results were consecutively negative as controls during the outbreak of the Omicron variant in Lu’an City, Anhui Province, China, in April 2022. The overall adjusted VE against Omicron BA.2.2 variant infection in the vaccinated group with any COVID-19 vaccine was 35.0% (95% CI: −9.1–61.3%), whereas the adjusted VE for booster vaccination was 51.6% (95% CI: 15.2–72.4%). Subgroup analysis showed that the overall adjusted VE of the Ad5-nCoV vaccine (65.8%, 95% CI: 12.8–86.6%) during the outbreak while any dose of inactivated vaccines and recombinant protein vaccine offered no protection. The adjusted VE of three-dose inactivated vaccines was 48.0% (95% CI: 8.0–70.6%), and the two-dose Ad5-nCoV vaccine was 62.9% (95% CI: 1.8–86%). There is no protection from a three-dose recombinant protein vaccine. COVID-19 vaccines offered 46.8% (95% CI: 9.5–68.7%) protection from infection within six months. There were statistically significant differences between the VEs of heterologous booster (VE = 76.4%, 95% CI: 14.3–93.5%) and homologous booster vaccination (VE = 51.8%, 95% CI: 9.6–74.3%) (P = .036). Booster vaccination of COVID-19 vaccines offered more protection than full vaccination. A booster vaccination campaign for a booster dose after three doses of a recombinant protein vaccine must be urgently conducted.

The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious medical problem worldwide. Acquired OXA-48-like carbapenemases encoded by plasmids are important causes of carbapenem resistance in K. pneumoniae. To explore the links between plasmids and blaOXA-48-like genes in K. pneumoniae, we systematically analyzed the variants of blaOXA-48-like plasmid replicon types, phylogenetic patterns, geographic distribution, conjugative transfer regions, and the genetic environments surrounding blaOXA-48-like of 191 blaOXA-48-like-harboring plasmids, which were identified from 4451 plasmids of K. pneumoniae downloaded from GenBank. Our results showed that seven different variants of blaOXA-48-like genes were identified from the 191 blaOXA-48-like-harboring plasmids in K. pneumoniae, with blaOXA-48, blaOXA-232, and blaOXA-181 being highly prevalent. In K. pneumoniae, blaOXA-48 was mainly carried by the composite transposon Tn1999.2 located on IncL/M-type conjugative plasmids, which were mainly geographically distributed in Switzerland, Germany, and China. In K. pneumoniae, the blaOXA-232 gene was mainly carried by 6.1-kb ColKP3-type mobilizable plasmids, which were mainly isolated in India. In K. pneumoniae, blaOXA-181 was mainly carried by a group of 50-kb ColKP3-IncX3 hybrid conjugative plasmids and a group of small ColKP3-type mobilizable plasmids with lengths of 5.9–9.3 kb, the former was sporadically discovered in China, South Korea, India, and Czech Republic, while the latter was almost all isolated in India. In addition, five blaOXA-245-harboring 65.9-kb IncL plasmids of K. pneumoniae isolated in Spain were found to have the genetic context of blaOXA-245 more complicated than that of blaOXA-48-harboring IncL/M-type plasmids, with two copies of IS1R inserted both upstream and downstream of blaOXA-245-lysR. These findings enhance our understanding of the genetic diversity of blaOXA-48-like-harboring plasmids in K. pneumoniae.

In order to explore the impact of reflow soldering process on power device packaging, a 3D package model based on insulated gate bipolar transistor (IGBT) module was established using DesignModeler, and then ANSYS software was used to perform thermal-structural coupling analysis on the IGBT module, stress distribution and warpage distribution of the IGBT module were obtained by combining the unit life and death method with the solder Anand model, and finally the warpage and stress distribution of different component thicknesses were compared using the orthogonal analysis method. The results show that the warpage of the IGBT module decreases with the increase of the thickness of the substrate, increases with the increase of the thickness of the DBC copper layer, and first increases and then decreases with the increase of the thickness of the Nano silver solder layer. The thickness of the solder layer has the greatest influence on the warpage of the module, and the thickness of the Nano silver solder layer has the least influence on the warpage of the module. The parameters of each component has no major influence on the residual stress of the solder layer. After comprehensive consideration, the optimal material parameters were obtained, and the warpage results are reduced about by 77.24%, compared with the initial parameters, which provides a reference for the package design of the IGBT module.

Gallium nitride (GaN) power devices have many benefits, including high power density, small footprint, high operating voltage, and excellent power gain capability. However, in contrast to silicon carbide (SiC), its performance and reliability can be negatively impacted by its low thermal conductivity, which can cause overheating. Hence, it is necessary to provide a reliable and workable thermal management model. In this paper, a model of a flip-chip packing (FCP) GaN chip was established, and it was assigned to the Ag sinter paste structure. The different solder bumps and under bump metallurgy (UBM) were considered. The results indicated that the FCP GaN chip with underfill was a promising method because it not only reduced the size of the package model but also reduced thermal stress. When the chip was in operation, the thermal stress was about 79 MPa, only 38.77% of the Ag sinter paste structure, lower than any of the GaN chip packaging methods currently in use. Moreover, the thermal condition of the module often has little to do with the material of the UBM. Additionally, nano-silver was found to be the most suitable bump material for FCP GaN chip. Temperature shock experiments were also conducted with different UBM materials when nano-silver was used as bump. It was found that Al as UBM is a more reliable option.

Solder layer void is one of the main failure causes of power semiconductor devices, which will seriously affect the reliability of the devices. In this study, a 3D model of IGBT (Insulated Gate Bipolar Transistor) packaging was built by DesignModeler. Based on ANSYS Workbench, the influence of void size, location, solder layer type, and thickness on the temperature distribution of the IGBT module was simulated. The results show that the larger the void radius, the higher the temperature of the IGBT module. The closer the void is to the center of the solder layer, the higher the temperature of the module. The void on the top corner of the solder layer had the greatest impact on the junction temperature of the IGBT module, and the shape of the void is also one of the factors that affect the temperature of the module. The denser the void distribution, the higher the temperature of the module. The temperature of the IGBT module was reduced from 62.656 °C to 59.697 °C by using nanosilver solder paste, and the overall heat dissipation performance of the module was improved by 5%. The temperature of the module increased linearly with the increase in solder layer thickness, and the temperature increased by 0.8 °C for every 0.025 mm increase in solder layer thickness. The simulation results have a guiding significance for improving the thermal stability of IGBT modules.

Abstract Background Diffuse large B‐cell lymphoma (DLBCL) patients refractory to rituximab‐based immunochemotherapy have a dismal prognosis. However, the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries. To validate the definition and outcomes of refractory DLBCL in China, we conducted a multicenter, retrospective cohort study. Methods The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL (REAL‐TREND) study was performed using real‐world data from 8 centers in China. DLBCL patients with curative intent were included in the REAL‐TREND dataset. Overall survival (OS) was estimated using the Kaplan‐Meier method and compared by the log‐rank test. Due to heterogeneity in response rates among different centers, the response rates of refractory patients were pooled using random‐effect models. Multivariate survival analysis was performed using the Cox regression model. Results A total of 2778 DLBCL patients diagnosed between January, 2010 and December, 2015 were enrolled to this study. After validating previous definitions, the SCHOLAR‐1 study was most suitable to define refractory DLBCL. The estimated 5‐year cumulative incidence of refractory patients was 20% (95% confidence Interval [CI] = 18%‐22%). After the determination of refractory disease, overall response rate and complete remission rate were 30% (95% CI = 22%‐38%) and 9% (95% CI = 4%‐15%), respectively. Patients with either no response to immunochemotherapy or relapse within 12 months after stem‐cell transplantation had inferior survival with a median OS of 5.9 months (95% CI = 5.5‐7.1 months) and 2‐year OS rate of 16% (95% CI = 12%‐20%). International prognostic index score 4‐5 (hazard ratio [HR] = 2.22; 95% CI = 1.47‐3.35), central nervous system relapse (HR = 1.43; 95% CI = 1.04‐1.97), and best response status (HR = 2.68; 95% CI = 1.42‐5.03 for partial remission. HR = 5.97, 95% CI = 3.21‐11.11 for stable disease/progressive disease) were independent unfavorable prognostic factors. Conclusions This is the first large‐scale Asian cohort study focusing on outcomes of refractory DLBCL. The definition of the SCHOLAR‐1 study identifies patients with homogenously inferior survival, thus is appropriate to select refractory DLBCL. Due to poor clinical outcomes in the rituximab era, patients with refractory DLBCL may be potential candidates for novel treatment modalities.

The incidence of diffuse large B-cell lymphoma (DLBCL) increases by age and older DLBCL are commonly related to poor prognosis. However, the clinical and biological features of older DLBCL patients remain to be determined. A total of 2,445 patients with newly diagnosed DLBCL were enrolled for clinical data analysis according to age at diagnosis, with tumor samples of 1,150 patients assessed by DNA sequencing and 385 patients by RNA sequencing. Older DLBCL presented advanced disease stage, elevated serum lactate dehydrogenase, poor performance status, multiple extranodal involvement, high percentage of double expressor subtype, and adverse clinical outcome. According to molecular features, age was positively correlated with the oncogenic mutations of PIM1, MYD88, BTG2, CD79B, TET2, BTG1, CREBBP, TBL1XR1, and with the MYD88-like genetic subtype. These oncogenic mutations were involved in B-cell receptor/NF-κB signaling, B-cell differentiation, and histone acetylation based on biological functions. Older DLBCL also manifested reduction in CD4+ naïve T and CD8+ naïve T cells, and also increased recruitment of exhausted T cells and macrophages, leading to immunosuppressive tumor microenvironment. Our work thus contributes to the understanding of aging-related oncogenic mutations and tumor microenvironment alterations in lymphoma progression, and may provide new insights to mechanism-based targeted therapy in DLBCL.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma and related to autoimmune diseases (AIDs). Primary B-cell receptor-mediated AIDs are associated with poor clinical outcome of DLBCL. To further determine the role of immunological alterations on disease progression, our study integrated genomic and transcriptomic analyses on DLBCL with multiple abnormal immunologic markers.MethodsThe clinical data of 1,792 patients with newly diagnosed DLBCL were collected, with DNA- and RNA-sequencing conducted for 164 and 127 patients, respectively. Frequent gene mutations and the involved dysregulated pathways, along with gene expression pattern and tumor microenvironment alternations, were analyzed and compared based on the immune status of the patients.ResultsDLBCL with multiple abnormal immunologic markers demonstrated a variety of characteristics including elevated serum lactic dehydrogenase level, inferior prognosis, and dysregulated cell cycle and immune response, as well as activated oxidative phosphorylation pathway and increased Th1/Th2 and Th17/Treg ratios, which were highly similar as those that occur in AIDs.ConclusionsWe piloted the description of the clinical and genetic features of DLBCL with multiple abnormal immunologic markers, illustrated possible mechanisms of disease progression, and provided a clinical rationale of mechanism-based targeted therapy in this subset of DLBCL.

PurposeThe aim of the study was to delineate the disease characteristics, the initial treatment patterns, and survival in patients with mantle cell lymphoma (MCL) managed in the real world.MethodsData of 518 MCL patients from 5 major Chinese Hematology Centers in the period from 2007 to 2017 were retrospectively analyzed.ResultsThe median age was 58 years. Of the patients, 88.6% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–1 and 80.7% had advanced-stage disease. Ki67 expression was

Urbanization is a complex economic and social phenomenon. Recently, rapid urbanization has not only caused rapid economic development in China, it has also posed a major threat to the ecological environment. Therefore, this study aims to determine how urbanization and its internal structure affect ecological efficiency (eco-efficiency) using panel data from China’s 30 provinces from 2008 to 2017. First, the eco-efficiencies of 30 provinces in China were calculated using the super slack-based measure model (super-SBM model). Then, the entropy method was used to measure the comprehensive level of urbanization from different dimensions. Finally, the Spatial Durbin model was used to analyze the impact mechanisms of urbanization dimensions and the internal structure effect of each dimension on eco-efficiency. The results show that, from 2008 to 2017, the comprehensive level of China's urbanization in each dimension showed an upward trend, while the average eco-efficiency declined slightly. Further, local eco-efficiency exhibited a negative spatial effect on the surrounding areas. In particular, the local social urbanization level inhibited the eco-efficiency of the surrounding areas, while the local population urbanization level promoted the eco-efficiency of the surrounding areas. Moreover, population and ecological urbanization had significant positive impacts on local eco-efficiency, while social and spatial urbanization had significant negative impacts.

The clinical and molecular characteristics of localized diffuse large B-cell lymphoma (DLBCL) with single nodal (SN) or single extranodal (SE) involvement remain largely elusive in the rituximab era. The clinical data of 181 patients from a retrospective cohort and 108 patients from a phase 3 randomized trial NHL-001 (NCT01852435) were reviewed. Meanwhile, genetic aberrations, gene expression pattern, and tumor immunophenotype profile were revealed by DNA and RNA sequencing of 116 and 53 patients, respectively. SE patients showed similar clinicopathological features as SN patients, except for an increased percentage of low-intermediate risk in the National Comprehensive Cancer Network–International Prognostic Index. According to the molecular features, increased MPEG1 mutations were observed in SN patients, while SE patients were associated with upregulation of TGF-β signaling pathway and downregulation of T-cell receptor signaling pathway. SE patients also presented immunosuppressive status with lower activity of killing of cancer cells and recruiting dendritic cells. Extranodal involvement had no influence on progression-free survival (PFS) or overall survival (OS) in localized DLBCL. Serum lactate dehydrogenase >3 upper limit of normal was an independent adverse prognostic factor for OS, and ATM mutations were related to inferior PFS. Although the overall prognosis is satisfactory, specific clinical, genetic, and microenvironmental factors should be considered for future personalized treatment in localized DLBCL.

Abstract Background We sought to assess reporting in China’s Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system’s detection of respiratory infections of public health significance. Methods From February 29–May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. Results Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive.

Background: This study aimed to investigate the association of pre-treatment inflammatory status with survival time and to develop a prognostic nomogram incorporating inflammatory cytokines in non-Hodgkin's lymphoma. Methods: A total of 228 patients with diffuse large B-cell lymphoma (DLBCL) received R-CHOP-based regimens from a prospective randomized study (NCT01852435) were included as a training cohort. Other cohorts of 886 lymphoma patients were served as validation cohorts. Lymphocyte-monocyte ratio (LMR), serum levels of soluble interleukin s(IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α), were assessed before treatment. Least absolute shrinkage and selection operator (LASSO) regression were used to select variables for nomogram of overall survival (OS). The predictive accuracy of the nomogram was determined by concordance index (C-index). Findings: The nomogram included lactate dehydrogenase (LDH), sIL-2R, TNF-α and decreased LMR. The C-index of the nomogram for OS prediction were range from 0.61 to 0.86 for training cohort of DLBCL and validation cohorts of DLBCL, PTCL, NKTCL and ASCT, which were superior to the predictive power of International Prognostic Index (IPI, 0.67 to 0.84) or NCCN-IPI (0.59 to 0.78), but not in those of indolent lymphoma like FL and MALT. Interpretations: The nomogram incorporating inflammatory cytokines provides a useful tool for risk stratification in aggressive non-Hodgkin's lymphomas. Fund: National Natural Science Foundation of China, the Shanghai Commission of Science and Technology, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of SHDC, and Chang Jiang Scholars Program. Keywords: Non-Hodgkin's lymphoma, Lymphocyte-monocyte ratio, Interleukin-2 receptor, Tumor necrosis factor-α, Prognosis

Plasmablastic lymphoma (PBL) is a rare and aggressive hematological malignancy. PBL commonly occurs in immune incompetent patients, such as those with human immunodeficiency virus (HIV), post-transplant status, or immunosenescence. Given its rarity, there is no specific standard treatment for PBL. However, small case series have shown that intensive chemotherapies combined with anti-myeloma agents such as bortezomib and lenalidomide were effective in treating PBL. Unfortunately, some fragile patients could not tolerate intensive chemotherapeutic regimens, especially the elderly patients. Here we presented a 76-year-old female PBL patient refractory to miniCHOP regimen combined with bortezomib but achieved complete remission when treated with tislelizumab combined with lenalidomide, indicating that immune therapy may be a potential treatment for PBL. To our knowledge, this is the first chemoresistant PBL patient that has been successfully treated with checkpoint inhibitor plus lenalidomide, thus providing new insight towards PBL management.

Background Studies have shown that discharged Coronavirus disease 2019 (COVID-19) patients have retested positive for SARS-CoV-2 during a follow-up RT-PCR test. We sought to assess the results of continued nucleic acid testing for SARS-CoV-2 patients in COVID-19 patients after they were discharged in Lu’an, China. Methods We conducted RT-PCR tests on sputum, throat swabs, fecal or anal swabs, and urine samples collected from 67 COVID-19 patients following discharge. Samples were collected on the 7th and 14th days following discharge. Patients testing positive on the 7th or 14th day were retested after 24 hours until they tested negative twice. Results Seventeen (17/67, 25.4%) discharged COVID-19 patients had a positive RT-PCR retest for SARS-CoV-2. Among them, 14 (82.4%) were sputum positive, five (29.4%) were throat swab positive, seven (41.2%) were fecal or anal swab positive, one (5.9%) was urine sample positive, five (29.4%) were both sputum and throat swab positive, four (23.5%) were both sputum and fecal test positive, and one (5.9%) was positive of all four specimens. The shortest period of time between discharge and the last positive test was 7 days, the longest was 48 days, and the median was 16 days. The proportion of positive fecal or anal swab tests increased from the third week. The median Cq cut-off values after onset were 26.7 after the first week, 37.7 the second to sixth week, and 40 after the sixth week. There were no significant differences between the RT-PCR retest positive group and the unrecovered positive group. Conclusions There was a high proportion of patients who retested positive for COVID-19. Discharge criteria have remained fairly consistent so we encourage regions affected by COVID-19 to appropriately amend their current criteria.

As the main spatial carrier for people’s social activities, street space occupies an important position in the urban space. However, under the direction of traffic-driven urban planning, the social function of street space has been neglected, resulting in the gradual loss of vitality. In mountainous cities with rugged terrain, the factors influencing the vitality of streets may be different compared to those in plain areas. In order to explore the influence mechanism of street vitality in mountainous cities, a new quantitative research method based on the new data environment and a Bayesian network is proposed. In this study, Python and GIS are used to obtain spatial data of streets, and Bayesian networks are used to construct street vitality models to identify important influencing factors and causal relationships between influencing factors. The results demonstrate strong causal dependencies between the factors influencing street vitality in mountainous cities. The mechanism of influence of street vitality revolves around functionality and street texture in terms of its own environment and external environment, respectively. The combination of factor group with functional density as the root node achieved the maximum probability of high vitality of the street. The results of this study have implications for community or urban planners with respect to urban regeneration and street vitality promotion.

As mobile device location data become increasingly available, new analyses are revealing the significant changes of mobility pattern when an unplanned event happened. With different control policies from local and state government, the COVID-19 outbreak has dramatically changed mobility behavior in affected cities. This study has been investigating the impact of COVID-19 on the number of people involved in crashes accounting for the intensity of different control measures using Negative Binomial (NB) method. Based on a comprehensive dataset of people involved in crashes aggregated in New York City during January 1, 2020 to May 24, 2020, people involved in crashes with respect to travel behavior, traffic characteristics and socio-demographic characteristics are found. The results show that the average person miles traveled on the main traffic mode per person per day, percentage of work trip have positive effect on person involved in crashes. On the contrary, unemployment rate and inflation rate have negative effects on person involved in crashes. Interestingly, different level of control policies during COVID-19 outbreak are closely associated with safety awareness, driving and travel behavior, and thus has an indirect influence on the frequency of crashes. Comparing to other three control policies including emergence declare, limits on mass gatherings, and ban on all nonessential gathering, the negative relationship between stay-at-home policy implemented in New York City from March 20, 2020 and the number of people involved crashes is found in our study.

ObjectivesThe present study aims to compare the diagnostic efficacy of MR, 18F-FDG PET/CT, and 18F-FDG PET/MR for the local detection of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).Patients and MethodsThirty-six patients with histologically proven early-stage ENKTL were enrolled from a phase 2 study (Cohort A). Eight nasopharyngeal anatomical regions from each patient were imaged using 18F-FDG PET/CT and MR. A further nine patients were prospectively enrolled from a multicenter, phase 3 study; these patients underwent 18F-FDG PET/CT and PET/MR after a single 18F-FDG injection (Cohort B). Region-based sensitivity and specificity were calculated. The standardized uptake values (SUV) obtained from PET/CT and PET/MR were compared, and the relationship between the SUV and apparent diffusion coefficients (ADC) of PET/MR were analyzed.ResultsIn Cohort A, of the 288 anatomic regions, 86 demonstrated lymphoma involvement. All lesions were detected by 18F-FDG PET/CT, while only 70 were detected by MR. 18F-FDG PET/CT exhibited a higher sensitivity than MR (100% vs. 81.4%, χ2 = 17.641, P < 0.001) for local detection of malignancies. The specificity of 18F-FDG PET/CT and MR were 98.5 and 97.5%, respectively (χ2 = 0.510, P = 0.475). The accuracy of 18F-FDG PET/CT was 99.0% and the accuracy of MR was 92.7% (χ2 = 14.087, P < 0.001). In Cohort B, 72 anatomical regions were analyzed. PET/CT and PET/MR have a sensitivity of 100% and a specificity of 92.5%. The two methods were consistent (κ = 0.833, P < 0.001). There was a significant correlation between PET/MR SUVmax and PET/CT SUVmax (r = 0.711, P < 0.001), and SUVmean (r = 0.685, P < 0.001). No correlation was observed between the SUV and the ADC.ConclusionIn early-stage ENKTL, nasopharyngeal MR showed a lower sensitivity and a similar specificity when compared with 18F-FDG PET/CT. PET/MR showed similar performance compared with PET/CT.

With the increase of power level and integration in electric vehicle controllers, the heat flux of the key silicon-based IGBT (Insulated Gate Bipolar Transistor) device has reached its physical limit. At present, third-generation semiconductor devices including SiC MOSFETs (Metal-Oxide-Semiconductor Field-Effect Transistor) are gradually replacing the dominant IGBT module. The hybrid IGBT module consists of both and can improve the performance and reduce the cost of controllers. Limits due to the installation space, location, and other conditions in the car make it difficult to meet the requirements of controllers with an air-cooled heatsink due to their large size and limited heat dissipation capacity. A smaller and more powerful water-cooled heatsink case is required to ensure the heat dissipation of the IGBT in the controller. Based on previous experience in finite element numerical simulation, hydrodynamics calculation, and heat transfer calculation, ANSYS Workbench finite element software was used to analyze the thermal resistance of each structure inside the module and the heatsink structure. The fluid characteristics and heat transfer performance of three different flow channel structures were analyzed, and the design of the cooling flow fin was improved to provide a reference for the heat dissipation of the hybrid IGBT module.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a severe viral disease caused by SFTSV. It is important to estimate the rate of missed SFTS diagnosis and to further understand the actual incidence in high endemic areas in China. Methods This study was conducted in two high SFTS endemic provinces in 2015. Patients hospitalized in 2014 or within 1 year before investigation were selected after considering their clinical manifestations, specifically, fever, platelet, and white blood cell. During retrospective investigation, sera were collected to detect SFTSV antibodies to assess SFTSV infection. To further understand SFTSV infection, acute phase sera were detected; SFTSV infection rate among a healthy population was also investigated to determine the basic infection level. Results In total, 246 hospitalized cases were included, including 83 cases (33.7%) with fever, thrombocytopenia and leukopenia, 38 cases (15.4%) with fever and thrombocytopenia but without leukopenia, and 125 cases (50.8%) without fever but with thrombocytopenia and leukopenia. In total, 13 patients (5.3%) were SFTSV IgM antibody-positive, 48 (19.5%) were IgG-positive. Of the 13 IgM-positive cases, 11 (84.6%) were IgG-positive (9 with titres ≥1:400). Seropositive rates of antibodies were high (8.4% for IgM and 30.1% for IgG) in patients with fever, thrombocytopenia and leukopenia. Furthermore, among IgG-positive cases in this group, 76% (19/25) of patients’ IgG antibody titres were ≥1:400. Additionally, 28 of 246 cases were initially diagnosed with suspected SFTS and were then excluded, and 218 patients were never diagnosed with SFTS; the seropositive rates of IgM and IgG in these two groups were 25% and 67.9% and 2.8% and 13.3%, respectively. These rates were 64.3% and 21.4% in 14 sera collected during acute phase of the 28 cases mentioned above. Seropositive rate of SFTSV IgG was only 1.3% in the patient-matched healthy group, and no IgM antibody was detected. A preliminary estimate of 8.3% of SFTS cases were missed in SFTS high endemic provinces. Conclusions The actual SFTS incidence was underestimated. Effective measures such as adding a new SFTS case category - “SFTS clinical diagnosis cases” or using serological detection methods during acute phase should be considered to avoid missed diagnoses.

This study fully addressed the modifiable areal unit problem (MAUP) that was well-known in geography but generally ignored by safety analysis. The basic issue of MAUP was introduced firstly with a case study to explicitly demonstrate the existence of the problem in macro level crash modeling, and then four potential strategies, i.e., using disaggregate data as possible, capturing spatial non-stationarity, designing optimal zoning systems, conducting sensitivity analysis to report the scope and magnitude of MAUP, were proposed and illustrated in an integrated way, followed by the future research directions. Results revealed that more efforts are desired to calibrate the state-of-art modeling technique at various levels of aggregation based on spatial homogeneity in traffic safety, transport characteristics, and demographical factors. The awareness of this problem in traffic safety domain is expected to the delineation of basic spatial units (e.g. the traffic safety analysis zones), as well as to provide new insights into the nature of MAUP in statistics and geography.

LEDs are widely used in medicine, navigation and landscape lighting. The development of high-power LED is a severe challenge to LED heat dissipation. In this review, packaging technology and packaging structure are reviewed in terms of the thermal performance of LED packaging, and related technologies that promote heat dissipation in LED packaging are introduced. The design of three components to enhance heat dissipation in LED packaging is described: substrate, lens and phosphor layer. By conducting a summary of the technology and structure of the package, the defects of LED package technology and structure are deeply investigated, and the package is prospected. This has reference value for the heat dissipation design of the LED package and helps to improve the design and manufacture of the LED package.

By studying the substrate material, structure, chip distribution, and array form of the multi-chip light-emitting diode (LED) package, the heat-dissipation capacity of the LED package is improved. Finite element analysis and steady-state thermal analysis are used to simulate and analyze LED packages with different materials and structures. Using the theory of LED illuminance and uniformity, the illuminance of some structures is computed. The results show that the change of substrate material and structure can greatly impact heat dissipation, while changing array forms has little effect on heat dissipation. By improving the spatial distribution of the chip, the temperature superposition problem of the substrate is solved, and the illuminance and uniformity are improved while dissipating heat. The LED filaments of the combined, equidistant, chip-distribution mode have improved heat dissipation. The S-type equal difference has the highest illumination and high illumination uniformity.

BackgroundPerceived as a minor transportation mode mainly for recreation, cycling and its related safety issues have not been treated as a citywide concern in Hong Kong and have thus received inadequate research efforts. Our study aimed to illuminate the safety challenges faced by cyclists in Hong Kong.MethodsWe examined the police crash records from 1998 to 2017 and developed a Bayesian Poisson state space model to evaluate the longitudinal change in traffic injuries to cyclists. We then used quasi-induced exposure to measure the annual relative risk of crash involvement for cycling. Based on an officially published travel characteristics survey, we further measured the risk of injury for cycling per minutes cycled.ResultsBetween 1998 and 2017, Hong Kong witnessed a more than twofold increase in the number of cyclist injuries, with an average annual increase rate of 5.18% (95% CI: 0.53%-12.77%). By 2017, cyclists were 2.21 (1.82-2.69) times more likely to be involved in traffic crashes than in 1998. Per 10 million minutes, the injury rates for cycling were 28.64 (27.43-29.70) and 42.54 (41.07-44.02) on weekdays during 2001-2003 and 2010-2012. After adjusting for sex and age groups, cyclists were 1.95 (1.43-2.61) times more likely to be injured in 2010-2012 than in 2001-2003. Per minutes traveled, cyclists also sustained significantly higher risks of fatality and injury than pedestrians, private car drivers and passengers, taxi passengers, public bus passengers, and minibus passengers. A comparison of Hong Kong with other regions suggests that Hong Kong is among the most dangerous areas for cycling in terms of fatality rate per minutes cycled.ConclusionsCyclist injuries have become a substantial public health burden in Hong Kong. A range of countermeasures with proven effectiveness should be promptly implemented to improve the safety of these vulnerable road users.

This research addresses the mathematical solution of the elastic catenary, a fundamental problem in offshore mooring engineering. A novel exact solution in a non-Lagrangian form is developed through rigorous mathematical derivation, distinguishing it from classical Lagrangian solutions. The procedure is reported in detail, and the resulting expressions are applied to analyze the mooring system of a reference floating turbine. A general approach is introduced to solve the transcendental equations associated with catenary mooring problems. The newly derived formulae exhibit greater applicability to geometry-to-force problems compared to existing Lagrangian expressions, making them particularly useful for conceptual designs and front-end engineering. In summary, this work provides valuable new insights into the exact solution of the elastic catenary, enhancing understanding and enabling practical applications in the field of floating wind turbines. [ABSTRACT FROM AUTHOR]