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Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

An accurate target source position is sometimes useful for the pointing observation with the collimated telescopes of the Hard X-ray Modulation Telescope (Insight-HXMT), which is determined by the reliability of the instrumental response. Insight-HXMT has the unique design that all three main payloads (LE, ME and HE) consist of detector groups with three fields of views (FOVs) whose orientations differ by 60°. As the point-spread functions are different at different positions in the FOV coordinates, the count rate ratios between the detector groups depend on the position of an X-ray source in the FOVs. Based on the multi-FOV design, we develop a localization method for an X-ray source in the pointing observation of Insight-HXMT. The accuracy of the method is investigated with the pointing observations of the Crab with different exposures. We find that the statistical error decreases with the exposure, and the systematic error is dominant for the exposure >128 s. With the exposure of 1024 s, the total error is 0.°015 for the Crab. This method can effectively distinguish the Rapid Burster H 1730–333 and Slow Burster GX 354–0, which are only 0.°5 apart and can both contribute to bursts in the light curve obtained by Insight-HXMT. We also apply the pointing observation localization method to locate the X-ray counterpart of FRB 200428 with high precision. The located position is consistent with SGR J1935+2154 within 1σ uncertainty of 10′, which provides important evidence that fast radio bursts can originate from magnetars.

GRO J1008-57, as a Be/X-ray transient pulsar, is considered to have the highest magnetic field in known neutron star X-ray binary systems. Observational data of the X-ray outbursts in GRO J1008-57 from 2017 to 2020 were collected by the Insight-HXMT satellite. In this work, the spin period of the neutron star in GRO J1008-57 was determined to be about 93.28 seconds in August 2017, 93.22 seconds in February 2018, 93.25 seconds in June 2019 and 93.14 seconds in June 2020. GRO J1008-57 evolved in the spin-up process with a mean rate of − ( 2.10 ± 0.05 ) × 10−4 s/d from 2009 – 2018, and turned into a spin down process with a rate of ( 6.7 ± 0.6 ) × 10−5 s/d from Feb 2018 to June 2019. During the type II outburst of 2020, GRO J1008-57 had the spin-up torque again. During the torque reversals, the pulse profiles and continuum X-ray spectra did not change significantly, and the cyclotron resonant scattering feature around 80 keV was only detected during the outbursts in 2017 and 2020. Based on the observed mean spin-up rate, we estimated the inner accretion disk radius in GRO J1008-57 (about 1 - 2 times of the Alfven radius) by comparing different accretion torque models of magnetic neutron stars. During the spin-down process, the magnetic torque should dominate over the matter accreting inflow torque, and we constrained the surface dipole magnetic field B ≥ 6 × 10 12 G for the neutron star in GRO J1008-57, which is consistent with the magnetic field strength obtained by cyclotron line centroid energy.

We report on the Insight-HXMT observations of the new black hole X-ray binary MAXI J1820+070 during its 2018 outburst. Detailed spectral analysis via the continuum fitting method shows an evolution of the inferred spin during its high soft sate. Moreover, the hardness ratio, the non-thermal luminosity and the reflection fraction also undergo an evolution, exactly coincident to the period when the inferred spin transition takes place. The unphysical evolution of the spin is attributed to the evolution of the inner disc, which is caused by the collapse of a hot corona due to condensation mechanism or may be related to the deceleration of a jet-like corona. The studies of the inner disc radius and the relation between the disc luminosity and the inner disc radius suggest that, only at a particular epoch, did the inner edge of the disc reach the innermost stable circular orbit and the spin measurement is reliable. We then constrain the spin of MAXI J1820+070 to be a*=0.2^{+0.2}_{-0.3}. Such a slowly spinning black hole possessing a strong jet suggests that its jet activity is driven mainly by the accretion disc rather than by the black hole spin., Comment: 14 pages, 13 figures, 5 tables, accepted for publication in MNRAS

OBJECTIVE The aim of this study was to build a convolutional neural network (CNN)–based prediction model of glioblastoma (GBM) molecular subtype diagnosis and prognosis with multimodal features. METHODS In total, 222 GBM patients were included in the training set from Sun Yat-sen University Cancer Center (SYSUCC) and 107 GBM patients were included in the validation set from SYSUCC, Xuanwu Hospital Capital Medical University, and the First Hospital of Jilin University. The multimodal model was trained with MR images (pre- and postcontrast T1-weighted images and T2-weighted images), corresponding MRI impression, and clinical patient information. First, the original images were segmented using the Multimodal Brain Tumor Image Segmentation Benchmark toolkit. Convolutional features were extracted using 3D residual deep neural network (ResNet50) and convolutional 3D (C3D). Radiomic features were extracted using pyradiomics. Report texts were converted to word embedding using word2vec. These three types of features were then integrated to train neural networks. Accuracy, precision, recall, and F1-score were used to evaluate the model performance. RESULTS The C3D-based model yielded the highest accuracy of 91.11% in the prediction of IDH1 mutation status. Importantly, the addition of semantics improved precision by 11.21% and recall in MGMT promoter methylation status prediction by 14.28%. The areas under the receiver operating characteristic curves of the C3D-based model in the IDH1, ATRX, MGMT, and 1-year prognosis groups were 0.976, 0.953, 0.955, and 0.976, respectively. In external validation, the C3D-based model showed significant improvement in accuracy in the IDH1, ATRX, MGMT, and 1-year prognosis groups, which were 88.30%, 76.67%, 85.71%, and 85.71%, respectively (compared with 3D ResNet50: 83.51%, 66.67%, 82.14%, and 70.79%, respectively). CONCLUSIONS The authors propose a novel multimodal model integrating C3D, radiomics, and semantics, which had a great performance in predicting IDH1, ATRX, and MGMT molecular subtypes and the 1-year prognosis of GBM.

Fast radio bursts (FRBs) are short pulses observed in radio band from cosmological distances. One class of models invoke soft gamma-ray repeaters (SGRs), or magnetars, as the sources of FRBs. Some radio pulses have been observed from some magnetars, however, no FRB-like events had been detected in association any magnetar burst, including one giant flare. Recently, a pair of FRB-like bursts (FRB 200428 hereafter) separated by milliseconds (ms) were detected from the general direction of the Galactic magnetar SGR J1935+2154. Here we report the detection of a non-thermal X-ray burst in the 1-250 keV energy band with the Insight-HXMT satellite, which we identify as emitted from SGR J1935+2154. The burst showed two hard peaks with a separation of 34 ms, broadly consistent with that of the two bursts in FRB 200428. The delay time between the double radio and X-ray peaks is about 8.57 s, fully consistent with the dispersion delay of FRB 200428. We thus identify the non-thermal X-ray burst is associated with FRB 200428 whose high energy counterpart is the two hard peaks in X-ray. Our results suggest that the non-thermal X-ray burst and FRB 200428 share the same physical origin in an explosive event from SGR J1935+2154., 24 pages, 9 figures, 6 tables; initial submission to a journal on May 9th, 2020. Significant changes include updated localization and detailed spectral evolution of the X-ray burst, and better determination of the two narrow X-ray peaks corresponding to the two radio pulses. Conclusions are strengthened. Nature Astronomy online on Feb. 18, 2021

A black hole X-ray binary produces hard X-ray radiation from its corona and disk when the accreting matter heats up. During an outburst, the disk and corona co-evolves with each other. However, such an evolution is still unclear in both its geometry and dynamics. Here we report the unusual decrease of the reflection fraction in MAXI J1820+070, which is the ratio of the coronal intensity illuminating the disk to the coronal intensity reaching the observer, as the corona is observed to contrast during the decay phase. We postulate a jet-like corona model, in which the corona can be understood as a standing shock where the material flowing through. In this dynamical scenario, the decrease of the reflection fraction is a signature of the corona's bulk velocity. Our findings suggest that as the corona is observed to get closer to the black hole, the coronal material might be outflowing faster., 11 pages, 5 figures; published in Nature Communications; An artist's impression of Figure 5 is updated here, and the animation is available at http://youbei.work/research/

A good hydration status is important to the exercise performance and cognitive function of exercisers.The effective restoration of fluid balance after exercise is helpful to prevent dehydration,maintain body fluid balance,accelerate fatigue recovery,and enhance exercise performance.As the most effective sports nutrition supplement,sports beverage has different ingredients and formulas,and also has various effects.To provide clues for the development of sports beverage,this article reviews the types,components,effects,and mechanisms of sports beverage currently used in post-exercise fluid restoration.

Accurate background estimation is essential for spectral and temporal analysis in astrophysics. In this work, we construct the in-orbit background model for the High-Energy Telescope (HE) of the Hard X-ray Modulation Telescope (dubbed as Insight-HXMT). Based on the two-year blank sky observations of Insight-HXMT/HE, we first investigate the basic properties of the background and find that both the background spectral shape and intensity have long-term evolution at different geographical sites. The entire earth globe is then divided into small grids, each with a typical area of 5x5 square degrees in geographical coordinate system. For each grid, an empirical function is used to describe the long-term evolution of each channel of the background spectrum; the intensity of the background can be variable and a modification factor is introduced to account for this variability by measuring the contemporary flux of the blind detector. For a given pointing observation, the background model is accomplished by integrating over the grids that are passed by the track of the satellite in each orbit. Such a background model is tested with both the blank sky observations and campaigns for observations of a series of celestial sources. The results show an average systematic error of 1.5% for the background energy spectrum (26-100 keV) under a typical exposure of 8 ks, and, 27 pages, 16 figures, accepted by Journal of High Energy Astrophysics

Recently, the system parameters of Cygnus X-1, i.e., the black hole mass M, the orbital inclination i and the source distance D, have been updated. As the input constraints of the continuum-fitting method, it is necessary to refine the spin with these new parameters. The Hard X-ray Modulation Telescope (HXMT, also named Insight) was successfully launched on June 15th, 2017 in China. In this work, we analyzed spectra obtained by the Insight-HXMT during 2017-2018 and re-estimated the spin via the continuum-fitting method. We first re-estimated the spin using old parameters and found the dimensionless spin parameter to be a ⁎ > 0.934 (3σ), which is consistent with previous measurements both from the continuum-fitting and iron-line fitting methods ( Gou et al. 2011 , Gou et al. 2014 ; Fabian et al. 2012 , Walton et al. 2016 , Tomsick et al. 2018 ). Then, when the new parameters were applied, we obtained an increased spin: a ⁎ > 0.967 (3σ), which is also consistent with the recent measurement (Zhao et al. 2020, submitted to ApJ) and also confirms an extreme Kerr black hole lying in this system.

With more than 150 blank sky observations at high Galactic latitude, we make a systematic study to the background of the Low Energy Telescope (LE) of the Hard X-ray Modulation Telescope (dubbed as Insight-HXMT). Both the on-ground simulation and the in-orbit observation indicate that the background spectrum mainly has two components. One is the particle background that dominates above 7 keV and its spectral shape is consistent in every geographical locations. Another is the diffuse X-ray background that dominates below 7 keV and has a stable spectrum less dependent of the sky region. The particle background spectral shape can be obtained from the blind detector data of all the blank sky observations, and the particle background intensity can be measured by the blind detector at 10-12.5 keV. The diffuse X-ray background in the high Galactic latitude can also be obtained from the blank sky spectra after subtracting the particle background. Based on these characteristics, we develop the background model for both the spectrum and the light curve. The systematic error for the background spectrum is investigated with different exposures (T_exp). For the spectrum with T_exp=1 ks, the average systematic errors in 1-7 keV and 1-10 keV are 4.2% and 3.7%, respectively. We also perform the systematic error analyses of the background light curves with different energy bands and time bins. The results show that the systematic errors for the light curves with different time bins are, 24 pages, 17 figures, accepted by Journal of High Energy Astrophysics

The Galactic plane scanning survey is one of the main scientific objectives of the Hard X-ray Modulation Telescope (known as Insight-HXMT). During the two-year operation of Insight-HXMT, more than 1000 scanning observations have been performed and the whole Galactic plane ($\rm 0^{\circ}, Comment: 14 pages, 17 figures, accepted for publication in JHEAP

To know the health status of hydrogen fuel cell, some diagnostics methods are proposed based on the historical status data of the hydrogen fuel cell. As multiple factors would cause the fuel cell problem, feature selection would be necessary during the diagnostics. In this paper, the author tried to apply an enhanced PCA algorithm to generate the proper features. Based on these features, a random forest algorithm is constructed for predicting the health status based on the history data. In this paper, we explore all aspects of hydrogen fuel cell sensor data, and extract several features by performing statistical analysis. We propose an efficient and accurate model for hydrogen fuel cell diagnostics. This model supports pipeline operations from feature selection to final result prediction. Besides, the model can also show which factor is essential for the health status of hydrogen fuel cell.

A new black hole X-ray binary (BHXRB) MAXI J1535-571 was discovered by MAXI during its outburst in 2017. Using observations taken by the first Chinese X-ray satellite, the Hard X-ray Modulation Telescope (dubbed as Insight-HXMT), we perform a joint spectral analysis (2-150 keV) in both energy and time domains. The energy spectra provide the essential input for probing the intrinsic Quasi-Periodic Oscillation (QPO) fractional rms spectra (FRS). Our results show that during the intermediate state, the energy spectra are in general consistent with those reported by Swift/XRT and NuSTAR. However, the QPO FRS become harder and the FRS residuals may suggest the presence of either an additional power-law component in the energy spectrum or a turn-over in the intrinsic QPO FRS at high energies.

We study the 2018 outburst of Aql X-1 via the monitor of all sky X-ray image (MAXI) data. We show that the outburst starting in February 2018 is a member of short-low class in the frame of outburst duration and the peak count rate although the outburst morphology is slightly different from the other fast-rise-exponential-decay (FRED) type outbursts with a milder rising stage. We study the partial accretion in the weak propeller stage of Aql X-1 via the MAXI data of the 2018 outburst. We report on the spectral analysis of 3 observations of Aquila X-1 obtained by Insight – hard X-ray modulation telescope (Insight-HXMT) during the late decay stage of the 2018 outburst. We discuss that the data taken by Insight-HXMT is just after the transition to the weak propeller stage. Our analysis shows the necessity of a comptonization component to take into account the existence of an electron cloud resulting photons partly up-scattered.

We present a detailed timing study of the brightest persistent X-ray source Sco X-1 using the data collected by the Hard X-ray Modulation Telescope ( I n s i g h t -HXMT) from July 2017 to August 2018. A complete Z-track hardness-intensity diagram (HID) is obtained. The normal branch oscillations (NBOs) at ∼ 6 Hz in the lower part of the normal branch (NB) and the flare branch oscillations (FBOs) at ∼ 16 Hz in the beginning part of the flaring branch (FB) are found in observations with the Low Energy X-ray Telescope (LE) and the Medium Energy X-ray Telescope (ME) of I n s i g h t -HXMT, while the horizontal branch oscillations (HBOs) at ∼ 40 Hz and the kilohertz quasi-periodic oscillations (kHz QPOs) at ∼ 800 Hz are found simultaneously above 20 keV for the first time on the horizontal branch (HB) by the High Energy X-ray Telescope (HE) and ME. We find that for all types of the observed QPOs, the centroid frequencies are independent of energy, while the root mean square (rms) increases with energy; the centroid frequencies of both the HBOs and kHz QPOs increase along the Z-track from the top to the bottom of the HB; and the NBOs show soft phase lags increasing with energy. A continuous QPO transition from the FB to NB in ∼ 200 s are also detected. Our results indicate that the non-thermal emission is the origin of all types of QPOs, the innermost region of the accretion disk is non-thermal in nature, and the corona is nonhomogeneous geometrically.

The evidences for the influence of thermonuclear (type-I) X-ray bursts upon the surrounding environments in neutron star low-mass X-ray binaries (LMXB) were detected previously via spectral and timing analyses. Benefitting from a broad energy coverage of Insight-HXMT, we analyze one photospheric radius expansion (PRE) burst, and find an emission excess at soft X-rays. Our spectral analysis shows that, such an excess is not likely relevant to the disk reflection induced by the burst emission and can be attributed to an enhanced pre-burst/persistent emission. We find that the burst and enhanced persistent emissions sum up to exceed Eddington luminosity by ∼ 40 percentages. We speculate that the enhanced emission is from a region beyond the PRE radius, or through the Comptonization of the corona.

Background Estimation of incidence and prognosis of melanomas with brain metastases (MBM) at initial diagnosis based on a large cohort is lacking in current research. This study aims to construct an effective prognostic nomogram for newly diagnosed MBM. Materials and Methods Patients diagnosed with melanomas from Surveillance, Epidemiology, and End Results program between 2010 and 2014 were enrolled in our study. Risk factors predicting brain metastases (BM) were identified using logistic regression analysis. Cox regression analysis was performed to identify prognostic factors of overall survival (OS). Nomogram for estimating 6‐, 9‐, and 12‐month OS was established based on Cox regression analysis. The discriminative ability and calibration of the nomogram were tested using C statistics, calibration plots, and Kaplan‐Meier curves. Results Sixty‐two thousand three hundred and sixty‐nine melanoma patients were enrolled, including 928 with BM. Sex, marital status, insurance status, subsite, surgery of primary sites, radiation, chemotherapy, bone metastases, liver metastases, and lung metastases were associated with MBM at initial diagnosis. On multivariable Cox regression, the following eight variables were incorporated in the prediction of OS: age, unmarried status, absence of surgery to primary sites or unknown, absence of radiation or unknown, absence of chemotherapy or unknown, with bone metastases, with liver metastases, and with lung metastases. The nomogram showed good predictive ability as indicated by discriminative ability and calibration, with the C statistics of 0.716 (95% CI, 0.695‐0.737). Conclusions The incidence and prognosis of MBM patients were well estimated in this study based on a large cohort. The nomogram performed well and could be a useful tool to predict prognosis., This study provided population‐based estimates of the incidence and prognosis for patients of melanoma with brain metastases at initial diagnosis. The nomogram performed well and could be a useful tool to predict prognosis.

Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer.A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival.After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis.The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.

Objective To compare the effects of carbohydrate-electrolyte beverage on post-exercise rehydration of healthy young men in different seasons,and to explore the influence of seasonal adaptability on fluid and electrolyte balance.Methods Fifteen healthy men,aged(24.4±0.5)years,completed 2 trails in a random crossover design both in summer and winter.During recovery,they consumed a drink volume equivalent to 100% of their sweat loss with plain boiled water(the water group)or carbohydrate-electrolyte beverage(the beverage group).Recovery was monitored for further 180 minutes by the collection of blood and urine samples.Results The dehydration time in summer was significantly shorter by about 20 minutes than that in winter(

The High Energy X-ray telescope (HE) on-board the Hard X-ray Modulation Telescope (\textit{Insight}-HXMT) can serve as a wide Field of View (FOV) gamma-ray monitor with high time resolution ($\mu$s) and large effective area (up to thousands cm$^2$). We developed a pipeline to search for Gamma-Ray Bursts (GRBs), using the traditional signal-to-noise ratio (SNR) method for blind search and the coherent search method for targeted search. By taking into account the location and spectrum of the burst and the detector response, the targeted coherent search is more powerful to unveil weak and sub-threshold bursts, especially those in temporal coincidence with Gravitational Wave (GW) events. Based on the original method in literature, we further improved the coherent search to filter out false triggers caused by spikes in light curves, which are commonly seen in gamma-ray instruments (e.g. \textit{Fermi}/GBM, \textit{POLAR}). We show that our improved targeted coherent search method could eliminate almost all false triggers caused by spikes. Based on the first two years of \textit{Insight}-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either \textit{Swift}/BAT or \textit{Fermi}/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of \textit{Insight}-HXMT/HE is increased to about 1.5E-08 erg/cm$^2$ (200 keV$-$3 MeV). We also used this targeted coherent method to search \textit{Insight}-HXMT/HE data for electromagnetic (EM) counterparts of LIGO-Virgo GW events (including O2 and O3a runs). However, we did not find any significant burst associated with GW events., Comment: 12 pages, 14 figures, 5 tables; accepted for publication in MNRAS

We report the energy-resolved broadband timing analysis of the black hole X-ray transient MAXI J1631-479 during its 2019 outburst from February 11 to April 9, using data from the Insight-Hard X-ray Modulation Telescope (Insight-HXMT), which caught the source from its hard intermediate state to the soft state. Thanks to the large effective area of Insight-HXMT at high energies, we are able to present the energy dependence of fast variability up to ~100 keV. Type-C quasi-periodic oscillations (QPOs) with frequency varying between 4.9 Hz and 6.5 Hz are observed in the 1-100 keV energy band. While the QPO fractional rms increases with photon energy from 1 keV to ~10 keV and remains more or less constant from ~10 keV to ~100 keV, the rms of the flat-top noise first increases from 1 keV to ~8 keV then drops to less than 0.1% above ~30 keV. We suggest that the disappearance of the broadband variability above 30 keV could be caused by the non-thermal acceleration in the Comptonizing plasma. At the same time, the QPOs could be produced by the precession of either a small-scale jet or a hot inner flow model., To be published in The Astrophysical Journal

e14014 Background: Nearly all patients (pts) with glioblastoma (GBM) will suffered relapse or disease progression after resection and adjuvant radiotherapy and temozolomide (TMZ). Anlotinib is a new multikinase inhibitors (MKI) blocking angiogenesis and tumor cell proliferation simultaneously and a prospective phase II study was performed to explore the potency of the combination anlotinib and TMZ for pts with relapse or progression GBM. Here, we reports the preliminary results of this study. Methods: This is a prospective, single-arm, open label, phase II study (NCT04547855). Eligible pts were diagnosed with histologically confirmed glioblastoma and experienced relapse or progression for the first time from surgery (including biopsy, partial resection and total resection) and radiotherapy-TMZ therapy (STUPP regimen). Other criteria included 18 to 75 years age, Karnofsky performance status (KPS) ≥ 60% and adequate organ function. The primary endpoint was progression free survival at 6 months (6m-PFS). All pts received orally TMZ (150 mg/m2) from D1-D7 every 2 weeks and anlotinib (12mg, QD) from D1-D14 every 3 weeks until disease progression or unacceptable toxicities. Results: From July 2020 to November 2021, 25 pts were enrolled. The median age was 49 (rang: 23, 62) and the median KPS was 80 (range: 60, 100). Most pts had poor prognostic factors that 17 pts (70.8%) had unmethylated MGMT promoter and 22 pts (91.6%) were IDH wild-type, which 24 pts detected IDH and MGMT status. At the data cutoff date on January 2022, the 6m-PFS was 25.2% and the median PFS was 4.2 months (95% CI, 3.4-5.0m). The median OS reached 9.1 months (95% CI, 8.1-10.2). Tumor response was assessed for all pts. 7 pts achieved partial response and the objective response rate was 28%. 10 pts had stable disease and the disease control rate was 68%. The most common grade 3 or worse adverse events (AEs) was lympyhopenia (48.0%), which may be caused by TMZ. No death was attributed to AEs. Conclusions: Combination of anlotinib and dose-intense temozolomide was tolerable in the treatment of recurrent or progressive glioblastoma. Preliminary results indicated that the efficacy was promising for those miserable pts with worse prognosis factors. Further investigation was ongoing. Clinical trial information: NCT04547855.

In this paper, we presented a detailed timing analysis of a prominent outburst of 4U 0115+63 detected by \textit{Insight}-HXMT in 2017 August. The spin period of the neutron star was determined to be $3.61398\pm 0.00002$ s at MJD 57978. We measured the period variability and extract the orbital elements of the binary system. The angle of periastron evolved with a rate of $0.048\pm0.003$ $yr^{-1}$. The light curves are folded to sketch the pulse profiles in different energy ranges. A multi-peak structure in 1-10 keV is clearly illustrated. We introduced wavelet analysis into our data analysis procedures to study QPO signals and perform a detailed wavelet analysis in many different energy ranges. Through the wavelet spectra, we report the discovery of a QPO at the frequency $\sim 10$ mHz. In addition, the X-ray light curves showed multiple QPOs in the period of $\sim 16-32 $ s and $\sim 67- 200 $ s. We found that the $\sim100$ s QPO was significant in most of the observations and energies. There exist positive relations between X-ray luminosity and their Q-factors and S-factors, while the QPO periods have no correlation with X-ray luminosity. In wavelet phase maps, we found that the pulse phase of $\sim 67- 200 $ s QPO drifting frequently while the $\sim 16-32 $ s QPO scarcely drifting. The dissipation of oscillations from high energy to low energy was also observed. These features of QPOs in 4U 0115+63 provide new challenge to our understanding of their physical origins., 14 pages, 9 figures, and 6 tables. This work has been submitted to MNRAS after the referee's report

After 34 years, the black-hole candidate EXO 1846-031 went into outburst again in 2019. We investigate its spectral properties in the hard intermediate and the soft states with NuSTAR and Insight-HXMT. A reflection component has been detected in the two spectral states but possibly originating from different illumination spectra: in the intermediate state, the illuminating source is attributed to a hard coronal component, which has been commonly observed in other X-ray binaries, whereas in the soft state the reflection is probably produced by the disk self-irradiation. Both cases support EXO 1846-031 as a low inclination system of ~40 degrees. An absorption line is clearly detected at ~7.2 keV in the hard intermediate state, corresponding to a highly ionized disk wind (log {\xi} > 6.1) with a velocity up to 0.06c. Meanwhile, quasi-simultaneous radio emissions have been detected before and after the X-rays, implying the co-existence of disk winds and jets in this system. Additionally, the observed wind in this source is potentially driven by magnetic forces. The absorption line disappeared in the soft state and a narrow emission line appeared at ~6.7 keV on top of the reflection component, which may be evidence for disk winds, but data with the higher spectral resolution are required to examine this., Comment: Accepted for publication in ApJ

Based on Insight-HXMT data, we report on the pulse fraction evolution during the 2017–2018 outburst of the newly discovered first Galactic ultraluminous X-ray (ULX) source Swift J0243.6+6124. The pulse fractions of 19 observation pairs selected in the rising and fading phases with similar luminosity are investigated. The results show a general trend of the pulse fraction increasing with luminosity and energy at supercritical luminosity. However, the relative strength of the pulsation between each pair evolves strongly with luminosity. The pulse fraction in the rising phase is larger at luminosity below 7.71 × 1038 erg s−1, but smaller at above. A transition luminosity is found to be energy independent. Such a phenomenon is first confirmed by Insight-HXMT observations and we speculate that it may have relation with the radiation-pressure-dominated accretion disc.

The Nonlinear propagation of high intensity focused ultrasound(HIFU) at high power can easily lead to waveform distortion and generate high order harmonic. This paper is based on the finite element method to establish the propagation model of high intensity focused ultrasound in biological tissues. Firstly, analyzing the nonlinear characteristic of HIFU propagation in biological tissue. Then, making quantitative comparisons with the nonlinear model in water to obtain the nonlinear characteristics of the focal area. At last, explaining the propagation characteristics of nonlinear ultrasound in biological tissue, and establishing a simulation basis for HIFU in the field treatment for future use.

BackgroundExtranodal natural killer/T-cell lymphoma (ENKTL) is a rare and extremely malignant tumor. The systemic inflammation score (SIS), which is based on the pretreatment level of lymphocyte-to-monocyte ratio (LMR) and serum albumin (Alb), has been shown to be of prognostic value in a number of cancers. We integrate several other pretreatment serum inflammatory indicators, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), serum C-reactive protein (CRP) and albumin (Alb) level, to establish a modified systemic inflammatory scoring system to predict clinical outcomes of ENKTL.MethodsA total of 184 patients with newly diagnosed ENKTL was retrospectively investigated. Systemic inflammatory indexes, including NLR, LMR, CRP, and Alb level were reviewed. Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off value. The associations between cutoff values and overall survival (OS) were analyzed by Kaplan–Meier curves and Cox proportional models.ResultsThe median age of patients was 44.0 years, ranging from 15 to 82 years. There were 129 (70.1%) male patient. About 57.1% of patients had stage III or IV disease. The optimal cut-off values of NLR and LMR in predicting OS were 3.1 and 2.4, respectively. The clinical standard of CRP and Alb levels at 10 and 40 mg/L, respectively, were chosen as the optimal cut-off values. By multivariate analysis, hemophilic syndrome (hazard ratio [HR]: 10.540, 95% confidence interval [CI]: 3.440–32.291, P < 0.001), advanced Ann Arbor stages (III–IV) (HR: 4.606, 95% CI: 1.661–12.774, P = 0.003), paranasal sinus invasion (HR: 2.323, 95% CI: 1.069–5.047, P = 0.033), NLR ≥ 3.1 (HR: 3.019, 95% CI: 1.317–6.923, P = 0.009), Alb level of

We present the observational results from a detailed timing analysis of the black hole candidate EXO 1846–031 during its outburst in 2019 with the observations of Insight-HXMT, NICER and MAXI. This outburst can be classified roughly into four different states. Type-C quasi-periodic oscillations (QPOs) observed by NICER (about 0.1–6 Hz) and Insight-HXMT (about 0.7–8 Hz) are also reported in this work. Meanwhile, we study various physical quantities related to QPO frequency. The QPO rms–frequency relationship in the energy band 1–10 keV indicates that there is a turning pointing in frequency around 2 Hz, which is similar to that of GRS 1915+105. A possible hypothesis for the relationship above may be related to the inclination of the source, which may require a high inclination to explain it. The relationships between QPO frequency and QPO rms, hardness, total fractional rms and count rate have also been found in other transient sources, which can indicate that the origin of type–C QPOs is non-thermal.

Low-frequency quasi-periodic oscillations (LFQPOs) are commonly found in black hole X-ray binaries, and their origin is still under debate. The properties of LFQPOs at high energies (above 30 keV) are closely related to the nature of the accretion flow in the innermost regions, and thus play a crucial role in critically testing various theoretical models. The Hard X-ray Modulation Telescope (Insight-HXMT) is capable of detecting emissions above 30 keV, and is therefore an ideal instrument to do so. Here we report the discovery of LFQPOs above 200 keV in the new black hole MAXI J1820+070 in the X-ray hard state, which allows us to understand the behaviours of LFQPOs at hundreds of kiloelectronvolts. The phase lag of the LFQPO is constant around zero below 30 keV, and becomes a soft lag (that is, the high-energy photons arrive first) above 30 keV. The soft lag gradually increases with energy and reaches ~0.9s in the 150-200 keV band. The detection at energies above 200 keV, the large soft lag and the energy-related behaviors of the LFQPO pose a great challenge for most currently existing models, but suggest that the LFQPO probably originates from the precession of a small-scale jet., 36 pages, 12 figures, 3 tables; published in Nature Astronomy

As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results., 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.04434

We report on our analysis of the 2019 outburst of the X-ray accreting pulsar 4U 1901+03 observed with Insight-HXMT and NICER. Both spectra and pulse profiles evolve significantly in the decaying phase of the outburst. Dozens of flares are observed throughout the outburst. They are more frequent and brighter at the outburst peak. We find that the flares, which have a duration from tens to hundreds of seconds, are generally brighter than the persistent emission by a factor of $\sim$ 1.5. The pulse profile shape during the flares can be significantly different than that of the persistent emission. In particular, a phase shift is clearly observed in many cases. We interpret these findings as direct evidence of changes of the pulsed beam pattern, due to transitions between the sub- and super-critical accretion regimes on a short time scale. We also observe that at comparable luminosities the flares' pulse profiles are rather similar to those of the persistent emission. This indicates that the accretion on the polar cap of the neutron star is mainly determined by the luminosity, i.e., the mass accretion rate., 11 pages, 8 figures, accepted for publication in MNRAS

A link between magnetars and fast radio burst (FRB) sources has finally been established. In this context, one of the open issues is whether/which sources of extra galactic FRBs exhibit X/gamma-ray outbursts and whether it is correlated with radio activity. We aim to constrain possible X/gamma-ray burst activity from one of the nearest extragalactic FRB sources currently known over a broad energy range, by looking for bursts over a range of timescales and energies that are compatible with being powerful flares from extragalactic magnetars. We followed up the as-yet nearest extragalactic FRB source at a mere 149 Mpc distance, the periodic repeater FRB180916.J0158+65, during the active phase on February 4-7, 2020, with the Insight-Hard X-ray Modulation Telescope (HXMT). Taking advantage of the combination of broad band, large effective area, and several independent detectors available, we searched for bursts over a set of timescales from 1 ms to 1.024 s with a sensitive algorithm, that had previously been characterised and optimised. Moreover, through simulations we studied the sensitivity of our technique in the released energy-duration phase space for a set of synthetic flares and assuming different energy spectra. We constrain the possible occurrence of flares in the 1-100 keV energy band to E, 10 pages, 3 figures, accepted by A&A

We investigate the absorption and emission features in observations of GX 301-2 detected with Insight-HXMT/LE in 2017-2019. At different orbital phases, we found prominent Fe Kalpha, Kbeta and Ni Kalpha lines, as well as Compton shoulders and Fe K-shell absorption edges. These features are due to the X-ray reprocessing caused by the interaction between the radiation from the source and surrounding accretion material. According to the ratio of iron lines Kalpha and Kbeta, we infer the accretion material is in a low ionisation state. We find an orbital-dependent local absorption column density, which has a large value and strong variability around the periastron. We explain its variability as a result of inhomogeneities of the accretion environment and/or instabilities of accretion processes. In addition, the variable local column density is correlated with the equivalent width of the iron Kalpha lines throughout the orbit, which suggests that the accretion material near the neutron star is spherically distributed., Comment: 10 pages, 5 figures, 2 tables, accepted for publication in MNRAS

We make the in-orbit calibration to the point-spread functions (PSFs) of the collimators of the Hard X-ray Modulation Telescope with the scanning observation of the Crab. We construct the empirical adjustments to the theoretically calculated geometrical PSFs. The adjustments contain two parts: a rotating matrix to adjust the directional deviation of the collimators and a paraboloidal function to correct the inhomogeneity of the real PSFs. The parameters of the adjusting matrices and paraboloidal functions are determined by fitting the scanning data with lower scanning speed and smaller intervals during the calibration observations. After the PSF calibration, the systematic errors in source localization in the Galactic plane scanning survey are 0.010 deg, 0.015 deg, 0.113 deg for the Low-Energy Telescope (LE), the Medium-Energy telescope (ME) and the High-Energy telescope (HE), respectively; meanwhile, the systematic errors in source flux estimation are 1.8%, 1.6%, 2.7% for LE, ME and HE, respectively., Comment: 15 pages, 27 figures, accepted for publication in JHEAP

Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser473 and Thr308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.

We report on analysis of observations of the bright transient X-ray pulsar \src obtained during its 2017-2018 giant outburst with Insight-HXMT, \emph{NuSTAR}, and \textit{Swift} observatories. We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields., Submitted to MNRAS

We present a study of timing properties of the accreting pulsar 2S 1417-624 observed during its 2018 outburst, based on Swift/BAT, Fermi/GBM, Insight-HXMT and NICER observations. We report a dramatic change of the pulse profiles with luminosity. The morphology of the profile in the range 0.2-10.0keV switches from double to triple peaks at $\sim2.5$ $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$ and from triple to quadruple peaks at $\sim7$ $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$. The profile at high energies (25-100keV) shows significant evolutions as well. We explain this phenomenon according to existing theoretical models. We argue that the first change is related to the transition from the sub to the super-critical accretion regime, while the second to the transition of the accretion disc from the gas-dominated to the radiation pressure-dominated state. Considering the spin-up as well due to the accretion torque, this interpretation allows to estimate the magnetic field self-consistently at $\sim7\times 10^{12}$G., 7 pages, 4 figures, 1 tables, accepted for publication in MNRAS

Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is the active catalytic component of prolyl 4-hydroxylase and plays a crucial role in modulating extracellular matrix hemostasis. P4HA1 has been reported to promote tumor progression by enhancing invasion and angiogenesis. Overexpression of P4HA1 is associated with decreased survival for patients with breast and prostate cancer. However, the prognostic significance of P4HA1 for glioma patients remains undefined.The expression of P4HA1 in 290 gliomas (WHO grade II-IV) and 10 normal brain tissues was examined with TMA-based immunohistochemistry assay. The correlation between P4HA1 expression and clinicopathological parameters as well as the prognosis of glioma patients was investigated.Cytoplasmic expression of P4HA1 is high in 37.93% of all glioma cases, with 44.98% in high-grade gliomas and 19.75% in low-grade gliomas respectively. Increased P4HA1 level was correlated with advanced histological grade (p0.01) and old age (p=0.01). Upregulation of P4HA1, as well as histological grade, was an independent risk factor for unfavorable prognosis. Subgroup analysis demonstrated that high P4HA1 expression was significantly associated with poor prognosis for high-grade gliomas (p0.01) but not for low-grade gliomas.P4HA1 was upregulated in gliomas. High expression of P4HA1 was correlated with the malignancy of gliomas and could serve as a prognostic indicator for patients with high-grade gliomas.

We investigated the functional status of adult supratentorial superficial low-grade glioma (ASS-LGG) after surgery and analyzed its relevant factors to guide the therapeutic strategy and improve the life quality of these patients. Clinical materials from January 2008 to December 2010 in 104 adults with ASS-LGG were analyzed retrospectively. The follow-up period ranged from 6 months to 1.5 years. The logistic regression was used to evaluate the preoperative and postoperative variation of functional status in patients to disclose the relevant factors affecting postoperative functional status, such as age, gender, the duration of symptom, size and location of the tumor, hemisphere, resection degree, and tumor pathologic grade and preoperative Karnofsky performance status (Pre-KPS). Four out of nine candidate factors are related to the postoperative functional status. They are age less than 40 years, the size of tumor less than 5 cm in diameter, tumor located in the right hemisphere, and limited resection of tumor in the eloquent area. It seems more meaningful to evaluate the functional status of the patients with ASS-LGG on the basis of these clinical features, involving age, tumor size, location, and extent of resection.

Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects. The molecular mechanisms were also investigated. We also optimized the delivery methods of bELE. We found that bELE selectively inhibits the proliferation and sphere formation of GSLCs, other than parental glioma cells, and TMZ exerts its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of bELE and TMZ worked better in the xenografts of GSLCs, mimicking the situation of tumorigenesis of human cancer. Notch1 was downregulated with bELE treatment. Our data also demonstrated that the continuous administration of bELE produces an ideal effect to control tumor progression. Our findings have demonstrated, for the first time, that bELE could compensate for TMZ to kill both GSLCs and nonstem-like cancer cells, probably improving the prognosis of glioma patients tremendously. Notch1 might be a downstream target of bELE. Therefore, our data shed light on improving the outcomes of glioma patients by combining bELE and TMZ.

The analysis of exercise and health has become a hot issue that people are paying attention to today. This paper presents an automated method for the complete analysis of weather and air quality and daily exercise volume (number of steps). Firstly, a clustering method based on Fourier transform is used to separate users of different exercise styles, and then the LSTM neural network is used to train the step data and the corresponding weather and air quality data to find the correlation. After testing the real data with multiple exercise styles, the validity of this analysis method can be confirmed. At the same time, the training verification time of the model is also collected, which proves that it has certain advantages in the analysis of large-scale data.