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Survival is one of the most important endpoints in cancer therapy, and parametric survival analysis could comprehensively reveal the overall result of disease progression, drug efficacy, toxicity as well as their interactions. In this study we investigated the efficacy and toxicity of dexamethasone (DEX) combined with gemcitabine (GEM) in pancreatic cancer xenograft. Nude mice bearing SW1990 pancreatic cancer cells derived tumor were treated with DEX (4 mg/kg, i.g.) and GEM (15 mg/kg, i.v.) alone or in combination repeatedly (QD, Q3D, Q7D) until the death of animal or the end of study. Tumor volumes and net body weight (NBW) were assessed every other day. Taking NBW as a systemic safety indicator, an integrated pharmacokinetic/pharmacodynamic (PK/PD) model was developed to quantitatively describe the impact of tumor size and systemic safety on animal survival. The PK/PD models with time course data for tumor size and NBW were established, respectively, in a sequential manner; a parametric time-to-event (TTE) model was also developed based on the longitudinal PK/PD models to describe the survival results of the SW1990 tumor-bearing mice. These models were evaluated and externally validated. Only the mice with good tumor growth inhibition and relatively stable NBW had an improved survival result after DEX and GEM combination therapy, and the simulations based on the parametric TTE model showed that NBW played more important role in animals' survival compared with tumor size. The established model in this study demonstrates that tumor size was not always the most important reason for cancer-related death, and parametric survival analysis together with safety issues was also important in the evaluation of oncology therapies in preclinical studies.

N6-methyladenosine (m6A), the most abundant mRNA modification in mammals, is involved in the metabolism of mRNA. KIAA1429 is regarded as the largest m6A methyltransferase and plays an important role in m6A modification. However, the prognostic value and function of KIAA1429 in colorectal cancer (CRC) are unclear. Quantitative real-time PCR and immunohistochemical assays were performed to evaluate the expression of KIAA1429 in CRC tissues. Kaplan-Meier survival curves and log-rank tests were used to assess the association between KIAA1429 expression and the prognosis of patients with CRC. CCK-8 assays, colony formation assays, cell cycle assays, and xenograft experiments were performed to investigate the effect of KIAA1429 on cell proliferation. RNA immunoprecipitation, methylated RNA immunoprecipitation assays, and RNA stability assays were conducted to explore the underlying mechanism. KIAA1429 was significantly upregulated in CRC tissues compared with adjacent normal tissues. Patients with higher expression of KIAA1429 had shorter overall survival than those with lower expression. Functionally, KIAA1429 promoted CRC cell proliferation in vitro and in vivo. Mechanistically, KIAA1429 negatively regulated the expression of WEE1 by decreasing its stability in an m6A-independent manner by binding to the third segment in the 3'-UTR of WEE1 mRNA. Moreover, butyrate decreased the expression of KIAA1429 by downregulating the level of the transcription factor NFκB1. Our findings indicated that KIAA1429 plays an oncogenic role in CRC cells by inhibiting the expression of WEE1 in an m6A-independent manner and is associated with poor survival in CRC patients. These results suggested that KIAA1429 might be a potential prognostic marker for CRC.

We devised a new method for asymmetric cyclopropanation by employing (

BACKGROUND Malignant solitary fibrous tumors (SFTs) account for 15%-20% of all SFTs, and malignant SFTs arising from the greater omentum are extremely rare. Most malignant SFTs of the greater omentum are diagnosed via pathological examinations after surgery. In this study, we report a case of malignant omental SFT and review the published literature on this rare malignancy. CASE SUMMARY A 64-year-old female presented with an abdominal mass, and underwent exploratory surgery, during which a huge tumor originating from the greater omentum and intraperitoneal implants were identified and resected. The results of the pathological examination, immunohistochemistry staining, and gene sequencing led to the diagnosis of malignant SFT of the greater omentum. The patient died one and a half years later due to tumor recurrence and metastasis. CONCLUSION This is the first report of the application of gene sequencing in the diagnosis of malignant SFTs of the greater omentum.

Environmental pollution has become more diversified in recent years as technologies for urbanization is increasingly more advanced. Several environmental factors such as air and water pollutants have been linked to allergic symptoms. For instance, because of industrialization for city development in many countries, polluted soil or tiny particles in the air could result in an even more hazardous environment for people to reside. Aside from the aspects of environmental issues, other newly emerging factors such as the electromagnetic field (EMF) also require further investigation. Here, in this narrative review, we focused on allergens from atmospheric and water pollution, hygiene improvement, changes in food trend, and residential environmental pollution. Current evidences regarding the association between various pollutants and the potential clinical diseases could be induced. For people with high skin exposure to air pollutants such as PM 2.5, PM 10, or sulfur dioxide, potential onset of dermatological allergic events should be alerted. The mechanisms involved in allergic diseases are being discussed and summarized. Interactions between immunological mechanisms and clinical implications could potentially provide clearer view to the association between allergic status and pollutants. Moreover, understanding the mechanistic role of allergens can raise awareness to global environment and public health.

Human immunodeficiency virus (HIV) exploits the sequence variation and structural dynamics of the envelope glycoprotein gp120 to evade the immune attack of neutralization antibodies, contributing to various HIV neutralization phenotypes. Although the HIV neutralization phenotype has been experimentally characterized, the roles of rapid sequence variability and significant structural dynamics of gp120 are not well understood. Here, 45 prefusion gp120 from different HIV strains belong to three tiers of sensitive, moderate, and resistant neutralization phenotype are structurally modeled by homology modeling and then investigated by molecular dynamics (MD) simulations and graph machine learning (ML). Our results show that the structural deviations, population distribution, and conformational flexibility of gp120 are related to the HIV neutralization phenotype. Per-residue dynamics indicate the local regions especially in the second structural elements with high-flexibility, may be responsible for the HIV neutralization phenotype. Moreover, a graph ML model with the attention mechanism was trained to explore inherent representation related to the classification of the HIV neutralization phenotype, further distinguishing the strong related gp120 sequence variation together with structural dynamics in the HIV neutralization phenotype. Our study not only deciphers gp120 sequence variation and structural dynamics in the HIV neutralization phenotype but also explores complex relationships between the sequence, structure, and dynamics of protein by combining MD simulations and ML.

The muon collider provides a unique opportunity to study the vector boson scattering processes and dimension-8 operators contributing to anomalous quartic gauge couplings~(aQGCs). Because of the cleaner final state, it is easier to decode subprocess and certain operator couplings at a muon collider. We attempt to identify the anomalous $WWWW$ coupling in the exclusive $WW\to WW$ scattering in this paper. Since one aQGC can be induced by multiple dimension-8 operators, the study of one coupling can help to confine different operators. Meanwhile, singling out the $WW\to WW$ process can help to study the unitarity bounds. The vector boson scattering process corresponding to the anomalous $WWWW$ coupling is $\mu^+\mu^-\to \nu\nu\bar{\nu}\bar{\nu}\ell^+\ell^-$, with four (anti-)neutrinos in the final state, which brings troubles in phenomenological studies. In this paper, the machine learning method is used to tackle this problem. We find that, using the artificial neural network can extract the $W^+W^-\to W^+W^-$ contribution, and is helpful to reconstruct the center of mass energy of the subprocess which is important in the study of the Standard Model effective field theory. The sensitivities and the expected constraints on the dimension-8 operators at the muon collider with $\sqrt{s}=30$ TeV are presented. We demonstrate that the artificial neural networks exhibit great potential in the phenomenological study of processes with multiple neutrinos in the final state., Comment: 33 pages, 11 figures, 8 tables

The search of new physics~(NP) beyond the Standard Model is one of the most important tasks of high energy physics. A common characteristic of the NP signals is that they are usually few and kinematically different. We use a model independent strategy to study the phenomenology of NP by directly picking out and studying the kinematically unusual events. For this purpose, the isolation forest~(IF) algorithm is applied, which is found to be efficient in identifying the signal events of the anomalous quartic gauge couplings~(aQGCs). The IF algorithm can also be used to constraint the coefficients of aQGCs. As a machine learning algorithm, the IF algorithm shows a good prospect in the future studies of NP., Comment: 19 pages, 10 figures

In this paper, we investigate the contributions of anomalous quartic gauge couplings (aQGCs) to $Z\gamma jj$ production at the Large Hadron Collider (LHC) in the context of Standard Model effective theory (SMEFT). When energy scale is large, the validity of SMEFT becomes an important issue. To ensure the validity, the unitarity bound is applied in a model independent approach, which is found to have significant suppressive effects on the signals of $O_{M_i}$ operators. The kinematic and polarization features of the aQGC signals are also studied. The polarization effect is useful to highlight the signals of $O_{T_i}$ operators. The sensitivity estimates on dimension-8 operators with unitarity bounds at $\sqrt{s}=14$ TeV are obtained., Comment: 25 pages, 6 figures

We explore the signals of axion-like particles (ALPs) via the process e + e − → aγ → 3γ at the Circular Electron Positron Collider (CEPC). The expected sensitivities of the CEPC with the center of mass energy s = 240 GeV for the ALP parameter space are obtained. Our results show that the promising sensitivities of the CEPC to the coupling g aγγ are in the range of 3.25 × 10−5 GeV−1 to 3.7 × 10−4 GeV−1 with the ALP mass m a from 2.9 GeV to 190 GeV.

We investigate the prospects for discovering axion-like particles (ALPs) via a light-by-light (LBL) scattering at two colliders, the future circular collider (FCC-ee) and circular electron-positron collider (CEPC). The promising sensitivities to the effective ALP-photon coupling $g_{a\gamma\gamma}$ are obtained. Our numerical results show that the FCC-ee and CEPC might be more sensitive to the ALPs with mass 2 GeV $\sim$ 10 GeV than the LHC and CLIC., Comment: 16 pages, 9 figures, 3 tables. Submitted to Physical Review D

The dynamic responses of sandwich structures with MHS(metal hollow sphere)and closed cell aluminum foams under blast loading were simulated numerically by employing the finite element software ANSYS/LS-DYNA. Both sandwich panels and sandwich spheres were modeled. Some factors that determine the blast resistance of the sandwich structures were investigated. According to the parametric studies, the sandwich structures with thin inner face sheet and thick outer face sheet have stronger blast resistance than others. Also the results show that sandwich structures with interlaced hollow spheres have a better performance than those with paratactic hollow spheres. Moreover, it's inferred that the density graded core with the biggest density as the first impact layer and the least density as the last layer has more benefits in energy absorption. The comparison between sandwich structures with metal hollow spheres and those with aluminum foams was studied experimentally and numerically and the results demonstrate that structures with aluminum foam have advantage in energy absorption but structures with MHS are stronger and can undertake more TNT.

Air pollution is one of the most serious environment pollution. 8 typical landscape plants, in Suzhou City, were selected to quantitative study their dust-capturing capacities, and the morphological traits of their leaves were observed under a SEM (scanning electron microscope). The paper showed that there were great differences in the dust-capturing capability of garden trees, and the dust-capturing capacities of garden trees in different seasons were in the order of May > August > November; the leaves of Cinnamomum camphora (L.) Pres, Camellia japonica L. and Euonymus japonicus Thunb. var. Ovatus Aureus had smooth surfaces or tubercles, whose dust-capturing capacities were poor, while the leaf of Loropetalum chinense(R.Br.) Oliv.Var. rubrum Yieh had many wrinkled form of cuticle, deep grooves, trichomes and high stomata desity which were favor of dust-retained, thus its dust- capturing capacity was stronger. The results can be seen as a possibility of select suitable species for urban environment.

The vector boson scattering at the Large Hadron Collider (LHC) is sensitive to anomalous quartic gauge couplings (aQGCs). In this paper, we investigate the aQGC contribution to $ W \gamma jj$ production at the LHC with $\sqrt{s}=13$ TeV in the context of an effective field theory (EFT). The unitarity bound is applied as a cut on the energy scale of this production process, which is found to have significant suppressive effects on the signals. To enhance the statistical significance, we analyse the kinematic and polarization features of the aQGC signals in detail. We find that the polarization effects induced by the aQGCs are unique and can discriminate the signals from the SM backgrounds well. With the proposed event selection strategy, we obtain the constraints on the coefficients of dimension-8 operators with current luminosity. The results indicate that the process $pp \to W \gamma jj$ is powerful for searching for the $O_{M_{2,3,4,5}}$ and $O_{T_{5,6,7}}$ operators., Comment: 29 pages, 11 figures, 7 tables, to be published in Chinese Physics C

Currently, conventional seismic inversions are mostly premised on well data, and there exist uncertainty in seismic inversions in areas with few fixed wells. After years of production practice, well-seismic cooperative inversion under the constraint of pseudo wells is a more effective method for reservoir prediction in areas with few fixed wells and complex phase spread changes. Nevertheless, the selection of locations of conventional pseudo wells only takes into account the spatial distribution of wells but seldom considers the changes of phase spreads; curves of pseudo wells are mostly derived from sparse pulse inversion with relatively low longitudinal resolution, which cannot accurately reflect the vertical and horizontal variation characteristics of the reservoir; there is no effective quality control method to prove the reliability of the curve after selecting the pseudo well. To solve the above-mentioned problems, this thesis acquires pseudo-wave impedance curves with high-frequency components by means of waveform difference inversion, controls quality and optimizes the location of pseudo wells under the guidance of geological results, and performs phase control inversion under the constraint of high-frequency pseudo-wave impedance curves, which greatly enhances the vertical and horizontal resolution of inversion, solves the problem of fine reservoir prediction in areas with few fixed wells, and offers strong support for high-speed and efficient development of oil and gas.

Bone diseases, which mainly affect whole-body skeleton, also influence the metabolism, turnover, and remodeling of cranial and maxillofacial bone, resulting in unnormal bone volume, bone mineral density, biomechanical strength, and osseo-healing of mandible as well as maxillary. Thus, bone diseases influence dental implant treatment. Here, we introduce related bone diseases and treatment suggestions for these patients. Moreover, as one of the most important treatments for these diseases, antiresorptive and antiangiogenic drugs are usually used in these cases. However, these two treatments might result in MRONJ. So, we also introduce the incident, cautions for MRONJ, and dental implant treatment in this part. Following these suggestions might minimalize the risk of developing related complications.

ObjectiveTo investigate the association between the Tangshan earthquake and depression after 37 years.Design and settingA cross-sectional study conducted in Tangshan from 2013 to 2014.ParticipantsThe sample included 5024 participants born before 28 July 1976 the date of the Tangshan earthquake, with available data on their earthquake experiences and depression 37 years post-earthquake.Outcomes and variablesThe outcome was depression measured using the Center for Epidemiological Study and Depression Scale. The independent variable was earthquake experience, which was classified into three groups: no earthquake experience, earthquake experience without bereavement and earthquake experience with bereavement. Multivariable logistic regression analysis was used to evaluate the association between earthquake experience and depression after adjusting for gender, age at the time of the earthquake, smoking status, drinking status, education, income, residence in Tangshan 1 to 2 years post-earthquake, hypertension, diabetes and dyslipidaemia.ResultsOf the 5024 participants, 641 experienced the Tangshan earthquake, and 98 experienced bereavement due to the earthquake. 37 years after the earthquake, survivors who had lost relatives during the earthquake were nearly three times (OR 2.82, 95% CI 1.24 to 6.39) as likely to have depression as those who had not experienced the earthquake, while those who had not lost relatives were 1.69 times as likely (OR 1.69, 95% CI 0.93 to 3.08). Stratified analyses showed that earthquake was significantly associated with depression in women with (OR 3.51, 95% CI 1.21 to 10.16) or without bereavement (OR 3.07, 95% CI 1.44 to 6.56) but not in men; this association was also significant in individuals over 18 years old at the time of the earthquake with (OR 13.16, 95% CI 3.08 to 56.3) or without bereavement (OR 3.39, 95% CI 1.31 to 8.87) but not in individuals less than 18 years old.Conclusions37 years after the Tangshan earthquake, earthquake experience was associated with depression among bereaved survivors, women and individuals over 18 years old at the time of the earthquake.

Vector-like quarks (VLQs) are predicted in many new physics scenarios beyond the standard model (SM). We consider a search strategy for vector-like bottom quark (VLQ-$B$) at the LHC in a model independent fashion. Our analysis is based on single production of VLQ-$B$ with decaying to the $ Zb$ mode. The production cross sections and the signal significance $SS$ are calculated, and the observability of the VLQ-$B$ signal is investigated. Our numerical results show that the possible signals of the VLQ-$B$ with electric charge of $Q_B= -1/3$, which is the $SU(2)$ singlet, might be detected via the process $pp \to B \to Z~(\to l^+ l^-) b$ at the upgraded LHC., 11 pages, 10 figures, references added, version accepted by PLB

Compared with the traditional magnetic bubble, skyrmion has smaller size, better stability therefore is considered as a very promising candidate for future memory devices. When skyrmions are manipulated, erased and created, the density of skyrmions can be varied, however the relationship between the radii and the densities of skyrmions needs more exploration. In this paper, we study this problem both theoretically and by using the lattice simulation. The average radius of skyrmions as a function of material parameters, the strength of external magnetic field and the density of skyrmions is obtained and verified. With this explicit function, the skyrmion radius can be easily predicted, which is helpful for the future study of skyrmion memory devices., 17 pages, 10 figures

The perovskite oxide Bi0.5Na0.5MnxTi1-xO3, Bi0.5Na0.5NbxTi1-xO3, Bi0.5Na0.5 (Mn0.5Nb0.5)xTi1-xO3 and Bi0.5Na0.5TiO3 ceramics (x=0.25%) were prepared via the conventional solid state reaction method. The role of Mn as an acceptor, Nb as a donor and (Mn0.5Nb0.5) substitution at B site in BNT lead-free piezoceramics was investigated. The (Mn0.5Nb0.5) substitution led to the inhibited of reduction of Ti4+ to Ti3+ and gave rise to large defect-dipole clusters containing highly localized electrons which should be responsible for the increase of Tc and Td. The ferroelectric properties and field-induced strains were both improved by Mn-acceptor and (Mn0.5Nb0.5) co-doped. The fatigue-resistant properties of Nb doped BNT ceramics were comparable to BNT ceramics, Mn doped ceramics were found to have significantly improved fatigue-resistant properties, while almost no profound fatigue was observed in BNT-MnNb ceramics after switching over 106 cycles at room temperature.

As the only exposed viral protein at the membrane surface of HIV, envelope glycoprotein gp120 is responsible for recognizing host cells and mediating virus-cell membrane fusion. Available structures of gp120 indicate that it exhibits two distinct conformational states, called closed and open states. Although experimental data demonstrates that CD4 binding stabilizes open state of gp120, detailed structural dynamics and kinetics of gp120 during this process remain elusive. Here, two open-state gp120 simulation systems, one without any ligands (ligand-free) and the other complexed with CD4 (CD4-bound), were subjected to microsecond-scale molecular dynamics simulations following the conformational transitions and allosteric pathways of gp120 evaluated by using the Markov state model and a network-based method, respectively. Our results provide an atomic-resolution description of gp120 conformational transitions, suggesting that gp120 is intrinsically dynamic from the open state to closed state, whereas CD4 binding blocks these transitions. Consistent with experimental structures, five metastable conformations with different orientations of the V1/V2 region and V3 loop have been extracted. The binding of CD4 significantly enhances allosteric communications from the CD4-binding site to V3 loop and β20-21 hairpin, resulting in high-affinity interactions with coreceptors and activation of the conformational transitions switcher, respectively. This study will facilitate the structural understanding of the CD4-binding effects on conformational transitions and allosteric pathways of gp120.

We explore the possibility of searching for axionlike particle (ALP) by $ep$ collisions via the subprocess $e^{-}\gamma \rightarrow e^{-}a \rightarrow e^{-}\gamma\gamma$. Sensitivities to the effective ALP-photon coupling $g_{a\gamma\gamma}$ for its mass in the range of 10 GeV $< M_{a}< 3$ TeV are obtained for the LHeC and its high-energy upgrade, FCC-eh. Comparing to existing bounds on the ALP free parameters, we find that the bounds given by $ep$ colliders are competitive and complementary to other colliders., Comment: 11 pages, 3 figures

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases with a high prevalence in the general population. The association between NAFLD and cardiovascular disease has been well addressed in previous studies. However, whether NAFLD is associated with carotid artery disease in a community-based Chinese population remained unclear. The aim of this study was to investigate the association between NAFLD and carotid artery disease. Methods: A total of 2612 participants (1091 men and 1521 women) aged 40 years and older from Jidong of Tangshan city (China) were selected for this study. NAFLD was diagnosed by abdominal ultrasonography. The presence of carotid stenosis or plaque was evaluated by carotid artery ultrasonography. Logistic regression was used to analyze the association between NAFLD and carotid artery disease. Results: Participants with NAFLD have a higher prevalence of carotid stenosis (12.9% vs. 4.6%) and carotid plaque (21.9% vs. 15.0%) than those without NAFLD. After adjusting for age, gender, smoking status, income, physical activity, diabetes, hypertension, triglyceride, waist-hip ratio, and high-density lipoprotein, NAFLD is significantly associated with carotid stenosis (odds ratio [OR]: 2.06, 95% confidence interval [CI]: 1.45–2.91), but the association between NAFLD and carotid plaque is not statistically significant (OR: 1.10, 95% CI: 0.86–1.40). Conclusion: A significant association between NAFLD and carotid stenosis is found in a Chinese population. Key words: Association; Carotid Artery Disease; Carotid Stenosis; Nonalcoholic Fatty Liver Disease

BackgroundInsomnia is one of the main symptoms of sleep disorders. Previous studies have suggested that alcohol intake is associated with several adverse health outcomes. The association between alcohol consumption and insomnia has been addressed in several studies with different results. However, whether gender may modify the association between alcohol consumption and insomnia is not clear. This study will focus on gender differences in the relationship between alcohol consumption and insomnia.MethodsThe final study includes 8081 subjects aged between 18 and 65 years from the Jidong cohort. The data on alcohol consumption is collected by questionnaires, and insomnia problems are assessed using the entire 8-item Athens Insomnia Scale (AIS-8). Logistic analysis is used to evaluate the association between alcohol consumption and insomnia.ResultsAmong the 8081 participants in this study, 2618 (32.4%) are alcohol drinkers, including 2424 males and 194 females. The prevalence of insomnia is 9.6% in the male and 10.6% in the female. The adjusted odds ratios (ORs) with 95% confidence interval (CI) of mild-to-moderate drinkers and heavy drinkers for insomnia are 1.27 (1.02-1.58) and 1.02 (0.79-1.32), respectively. Heavy alcohol consumption is significantly correlated with insomnia in the female, after controlling for potential confounding factors (OR: 2.11, 95% CI: 1.28-3.49, p for interaction = 0.002).ConclusionA significant association between alcohol consumption and insomnia is found in females, but not in males from the northern Chinese population.

This paper studied commercial space of the Shanghai Railway Station. It summed up construction and development of history railway and railway passenger transportation. It clarified commercial activities of major railway terminal. It summarized appropriate scale and location of different business activities by the tightness of characteristics different commercial activities as well as problems and deficiencies of existing large passenger commercial space. It identified the source of the problem by several field researches on Shanghai Railway Station. This paper summarized different layout features of the passenger terminal commercial space design history and analyzed the differences and reasons. Finally this paper presented specific strategies and ideas of a large railway passenger commercial space design combined with their views of trends for railway passenger comprehensive development.