Thousands of conductance levels in memristors integrated on CMOS.

Neural networks based on memristive devices1-3 have the ability to improve throughput and energy efficiency for machine learning4,5 and artificial intelligence6, especially in edge applications7-21. Because training a neural network model from scratch is costly in terms of hardware resources, time and energy, it is impractical to do it individually on billions of memristive neural networks distributed at the edge. A practical approach would be to download the synaptic weights obtained from the cloud training and program them directly into memristors for the commercialization of edge applications. Some post-tuning in memristor conductance could be done afterwards or during applications to adapt to specific situations. Therefore, in neural network applications, memristors require high-precision programmability to guarantee uniform and accurate performance across a large number of memristive networks22-28. This requires many distinguishable conductance levels on each memristive device, not only laboratory-made devices but also devices fabricated in factories. Analog memristors with many conductance states also benefit other applications, such as neural network training, scientific computing and even 'mortal computing'25,29,30. Here we report 2,048 conductance levels achieved with memristors in fully integrated chips with 256 × 256 memristor arrays monolithically integrated on complementary metal-oxide-semiconductor (CMOS) circuits in a commercial foundry. We have identified the underlying physics that previously limited the number of conductance levels that could be achieved in memristors and developed electrical operation protocols to avoid such limitations. These results provide insights into the fundamental understanding of the microscopic picture of memristive switching as well as approaches to enable high-precision memristors for various applications. Fig. 1 HIGH-PRECISION MEMRISTOR FOR NEUROMORPHIC COMPUTING.: a, Proposed scheme of the large-scale application of memristive neural networks for edge computing. Neural network training is performed in the cloud. The obtained weights are downloaded and accurately programmed into a massive number of memristor arrays distributed at the edge, which imposes high-precision requirements on memristive devices. b, An eight-inch wafer with memristors fabricated by a commercial semiconductor manufacturer. c, High-resolution transmission electron microscopy image of the cross-section view of a memristor. Pt and Ta serve as the bottom electrode (BE) and top electrode (TE), respectively. Scale bars, 1 µm and 100 nm (inset). d, Magnification of the memristor material stack. Scale bar, 5 nm. e, As-programmed (blue) and after-denoising (red) currents of a memristor are read by a constant voltage (0.2 V). The denoising process eliminated the large-amplitude RTN observed in the as-programmed state (see Methods). f, Magnification of three nearest-neighbour states after denoising. The current of each state was read by a constant voltage (0.2 V). No large-amplitude RTN was observed, and all of the states can be clearly distinguished. g, An individual memristor on the chip was tuned into 2,048 resistance levels by high-resolution off-chip driving circuitry, and each resistance level was read by a d.c. voltage sweeping from 0 to 0.2 V. The target resistance was set from 50 µS to 4,144 µS with a 2-µS interval between neighbouring levels. All readings at 0.2 V are less than 1 µS from the target conductance. Bottom inset, magnification of the resistance levels. Top inset, experimental results of an entire 256 × 256 array programmed by its 6-bit on-chip circuitry into 64 32 × 32 blocks, and each block is programmed into one of the 64 conductance levels. Each of the 256 × 256 memristors has been previously switched over one million cycles, demonstrating the high endurance and robustness of the devices.

Suppression of black-hole growth by strong outflows at redshifts 5.8-6.6.

Bright quasars, powered by accretion onto billion-solar-mass black holes, already existed at the epoch of reionization, when the Universe was 0.5-1 billion years old1. How these black holes formed in such a short time is the subject of debate, particularly as they lie above the correlation between black-hole mass and galaxy dynamical mass2,3 in the local Universe. What slowed down black-hole growth, leading towards the symbiotic growth observed in the local Universe, and when this process started, has hitherto not been known, although black-hole feedback is a likely driver4. Here we report optical and near-infrared observations of a sample of quasars at redshifts 5.8 ≲ z ≲ 6.6. About half of the quasar spectra reveal broad, blueshifted absorption line troughs, tracing black-hole-driven winds with extreme outflow velocities, up to 17% of the speed of light. The fraction of quasars with such outflow winds at z ≳ 5.8 is ≈2.4 times higher than at z ≈ 2-4. We infer that outflows at z ≳ 5.8 inject large amounts of energy into the interstellar medium and suppress nuclear gas accretion, slowing down black-hole growth. The outflow phase may then mark the beginning of substantial black-hole feedback. The red optical colours of outflow quasars at z ≳ 5.8 indeed suggest that these systems are dusty and may be caught during an initial quenching phase of obscured accretion5.

A repeating fast radio burst source in a globular cluster.

Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.

Fully hardware-implemented memristor convolutional neural network.

Memristor-enabled neuromorphic computing systems provide a fast and energy-efficient approach to training neural networks1-4. However, convolutional neural networks (CNNs)-one of the most important models for image recognition5-have not yet been fully hardware-implemented using memristor crossbars, which are cross-point arrays with a memristor device at each intersection. Moreover, achieving software-comparable results is highly challenging owing to the poor yield, large variation and other non-ideal characteristics of devices6-9. Here we report the fabrication of high-yield, high-performance and uniform memristor crossbar arrays for the implementation of CNNs, which integrate eight 2,048-cell memristor arrays to improve parallel-computing efficiency. In addition, we propose an effective hybrid-training method to adapt to device imperfections and improve the overall system performance. We built a five-layer memristor-based CNN to perform MNIST10 image recognition, and achieved a high accuracy of more than 96 per cent. In addition to parallel convolutions using different kernels with shared inputs, replication of multiple identical kernels in memristor arrays was demonstrated for processing different inputs in parallel. The memristor-based CNN neuromorphic system has an energy efficiency more than two orders of magnitude greater than that of state-of-the-art graphics-processing units, and is shown to be scalable to larger networks, such as residual neural networks. Our results are expected to enable a viable memristor-based non-von Neumann hardware solution for deep neural networks and edge computing.

Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

A splice acceptor variant in RGS6 associated with intellectual disability, microcephaly, and cataracts disproportionately promotes expression of a subset of RGS6 isoforms.

Intellectual disability (ID) is associated with an increased risk of developing psychiatric disorders, suggesting a common underlying genetic factor. Importantly, altered signaling and/or expression of regulator of G protein signaling 6 (RGS6) is associated with ID and numerous psychiatric disorders. RGS6 is highly conserved and undergoes complex alternative mRNA splicing producing ~36 protein isoforms with high sequence similarity historically necessitating a global approach in functional studies. However, our recent analysis in mice revealed RGS6 is most highly expressed in CNS with RGS6L(+GGL) isoforms predominating. A previously reported genetic variant in intron 17 of RGS6 (c.1369-1G>C), associated with ID, may provide further clues into RGS6L(+GGL) isoform functional delineation. This variant was predicted to alter a highly conserved canonical 3' acceptor site creating an alternative branch point within exon 18 (included in a subset of RGS6L(+GGL) transcripts) and a frameshift forming an early stop codon. We previously identified this alternative splice site and demonstrated its use generates RGS6Lζ(+GGL) isoforms. Here, we show that the c.1369-1G>C variant disrupts the canonical, preferred (>90%) intron 17 splice site and leads to the exclusive use of the alternate exon 18 splice site, inducing disproportionate expression of a subset of isoforms, particularly RGS6Lζ(+GGL). Furthermore, RGS6 global knockout mice do not exhibit ID. Thus, ID caused by the c.1369-1G>C variant likely results from altered RGS6 isoform expression, rather than RGS6 isoform loss. In summary, these studies highlight the importance of proper RGS6 splicing and identify a previously unrecognized role of G protein signaling in ID.

Unveiling the temperature-dependent thermoelectric properties of the undoped and Na-doped monolayer SnSe allotropes: a comparative study.

Motivated by the excellent thermoelectric (TE) performance of bulk SnSe, extensive attention has been drawn to the TE properties of the monolayer SnSe. To uncover the fundamental mechanism of manipulating the TE performance of the SnSe monolayer, we perform a systematic study on the TE properties of five monolayer SnSe allotropes such asα-,ß-,γ-,δ-, andε-SnSe based on the density functional theory and the non-equilibrium Green's functions. By comparing the TE properties of the Na-doped SnSe allotropes with the undoped ones, the influences of the Na doping and the temperature on the TE properties are deeply investigated. It is shown that the figure of meritZTwill increase as the temperature increases, which is the same for almost all the Na-doped and undoped cases. The Na doping can enhance or suppress theZTin different SnSe allotropes at different temperatures, implying the presence of the anomalous suppression of theZT. The Na doping inducedZTsuppression may be caused basically by the sharp decrease of the power factor and the weak decrease of the electronic thermal conductance, rather than by the decrease of the phononic thermal conductance. We hope this work will be able to enrich the understanding of the manipulation of TE properties by means of dimensions, structurization, doping, and temperature.

Photo-induced structural dynamics of o-nitrophenol by ultrafast electron diffraction.

The photo-induced dynamics of o-nitrophenol, particularly its photolysis, has garnered significant scientific interest as a potential source of nitrous acid in the atmosphere. Although the photolysis products and preceding photo-induced electronic structure dynamics have been investigated extensively, the nuclear dynamics accompanying the non-radiative relaxation of o-nitrophenol on the ultrafast timescale, which include an intramolecular proton transfer step, have not been experimentally resolved. Herein, we present a direct observation of the ultrafast nuclear motions mediating photo-relaxation using ultrafast electron diffraction. This work spatiotemporally resolves the loss of planarity which enables access to a conical intersection between the first excited state and the ground state after the proton transfer step, on the femtosecond timescale and with sub-Angstrom resolution. Our observations, supported by ab initio multiple spawning simulations, provide new insights into the proton transfer mediated relaxation mechanism in o-nitrophenol.

Evaluation of brain iron deposition in different cerebral arteries of acute ischaemic stroke patients using quantitative susceptibility mapping.

AIM: To investigate differences in iron deposition between infarct and normal cerebral arterial regions in acute ischaemic stroke (AIS) patients using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Forty healthy controls and 40 AIS patients were recruited, and their QSM images were obtained. There were seven regions of interest (ROIs) in AIS patients, including the infarct regions of responsible arteries (R1), the non-infarct regions of responsible arteries (R2), the contralateral symmetrical sites of lesions (R3), and the non-responsible cerebral arterial regions (R4, R5, R6, R7). For the healthy controls, the cerebral arterial regions corresponding to the AIS patient group were selected as ROIs. The differences in corresponding ROI susceptibilities between AIS patients and healthy controls and the differences in susceptibilities between infarcted and non-infarct regions in AIS patients were compared. RESULTS: The susceptibilities of infarct regions in AIS patients were significantly higher than those in healthy controls (p<0.0001). There was no significant difference in non-infarct regions between the two groups (p>0.05). The susceptibility of the infarct regions in AIS patients was significantly higher than those of the non-infarct region of responsible artery and non-responsible cerebral arterial regions (p<0.01). CONCLUSIONS: Abnormal iron deposition detected by QSM in the infarct regions of AIS patients may not affect iron levels in the non-infarct regions of responsible arteries and normal cerebral arteries, which may open the door for potential new diagnostic and treatment strategies.

Changes in brain susceptibility in Wilson's disease patients: a quantitative susceptibility mapping study.

AIM: To assess changes in the susceptibility of the caudate nucleus (CN), putamen, and globus pallidus (GP) in patients with neurological and hepatic Wilson's disease (WD) by quantitative susceptibility mapping (QSM). MATERIAL AND METHODS: The brain MRI images of 33 patients diagnosed with WD and 20 age-matched controls were analysed retrospectively. All participants underwent brain T1-weighted, T2-weighted, and QSM imaging using a 1.5 T magnetic resonance imaging (MRI) machine. QSM maps were evaluated with the STISuite toolbox. The quantitative susceptibility levels of the CN, putamen, and GP were analysed using region of interest analysis on QSM maps. Differences among neurological WD patients, hepatic patients, and controls were determined. RESULTS: Susceptibility levels were significantly higher for all examined structures (CN, putamen and GP) in patients with neurological WD compared with controls (all p<0.05) and hepatic WD patients (all p<0.05). No statistically significant differences were found in susceptibility levels between patients with hepatic WD and controls (all p>0.05). CONCLUSION: The QSM technique is a valuable tool for detecting changes in brain susceptibility in WD patients, indicating abnormal metal deposition. Notably, the current findings suggest that neurological WD patients exhibit more severe susceptibility changes compared with hepatic WD patients. Therefore, QSM can be utilised as a complementary method to detect brain injury in WD patients.

Prognostic value of the baseline magnetic resonance score in patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy.

AIM: To investigate the prognostic value of the composite posterior circulation Acute Stroke Prognosis Early Computed tomography (CT) Score (ASPECTS)-Collaterals (pcASCO) score, which combines diffusion-weighted imaging (DWI) posterior circulation ASPECTS (pcASPECTS) and the magnetic resonance angiography (MRA)-collateral circulation score at baseline among patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy. MATERIALS AND METHODS: Patients with acute posterior circulation ischaemic stroke who underwent mechanical thrombectomy were analysed retrospectively. The DWI-pcASPECTS and MRA-collateral circulation score before treatment and the modified Rankin Scale (mRS) at 90 days after treatment were used as the endpoints. An mRS ≤2 was defined as a good prognosis, and an mRS ≥3 was defined as a poor prognosis. Multivariate logistic regression was used to analyse independent predictors of functional outcome 90 days after mechanical thrombectomy. RESULTS: Mechanical thrombectomy was performed in 57 patients; 38 patients had a good prognosis, 19 patients had a poor prognosis, and 33 patients were successfully recanalised. Univariate logistic regression found that National Institute of Health Stroke Scale (NIHSS) score (OR: 1.18, p<0.001), pcASPECTS (OR: 1.91, p=0.028) and pcASCO score (OR: 0.51, p=0.001) were factors of good functional outcome. Receiver operating characteristic curve (ROC curve) analysis showed that the diagnostic efficiency of the NIHSS and pcASCO was better (AUC = 0.88, 0.83, p<0.05) than that of the pcASPECTS (AUC = 0.65). The prediction model was established by age, NIHSS, and pcASCO, and the diagnostic efficiency of the prediction model was better (AUC = 0.94). CONCLUSIONS: The composite MR-pcASCO score can be used as an important predictor of the prognosis of patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy.

Deep learning-based fully automatic screening of carotid artery plaques in computed tomography angiography: a multicenter study.

AIM: To develop and validate a deep learning (DL) algorithm for the automated detection and classification of carotid artery plaques (CAPs) on computed tomography angiography (CTA) images. MATERIALS AND METHODS: This retrospective study enrolled 400 patients (300 in the Center Ⅰ and 100 in Ⅱ). Three radiologists co-labeled CAPs, and their revised calcification status (noncalcified, mixed, and calcified) was regarded as ground truth. Center Ⅰ patients were randomly divided into training and internal validation datasets, while Center Ⅱ patients served as the external validation dataset. Carotid artery regions were segmented using a modified 3D-UNet network, followed by CAPs detection and classification using a ResUNet-based architecture in a two-step DL system. The DL model's detection and classification performance were evaluated on the validation dataset using precision-recall curve, free-response receiver operating characteristic (fROC) curve, Cohen's kappa, and ROC curve analysis. RESULTS: The DL model had achieved 83.4% sensitivity at 3.0 false positives (FPs)/CTA scan in internal validation and 78.9% in external validation. F1-scores were 0.764 and 0.769 at the optimal threshold, and area under fROC curves were 0.756 and 0.738, respectively, indicating good overall accuracy for CAP detection. The DL model also showed good performance for the ternary classification of CAPs, with Cohen's kappa achieved 0.728 and 0.703 in both validation datasets. CONCLUSION: This study demonstrated the feasibility of using a fully automated DL-based algorithm for the detection and ternary classification of CAPs, which could be helpful for the workloads of radiologists.

Relationship between pericoronary fat-attenuation values quantified by coronary computed tomography angiography and coronary artery disease severity.

AIM: To explore the relationship between pericoronary fat-attenuation index (FAI) values and coronary artery disease (CAD) severity measured using coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study retrospectively included 428 patients with CAD who were eligible and underwent CCTA at our hospital. CAD severity on CCTA images including obstructive stenosis and extensive lesions, and segment stenosis and involvement score (SSS, SIS), and CAD-RADS classification were assessed. FAI values for left anterior descending (LAD), left circumflex (LCX) branches, and right coronary artery (RCA) were quantified using fully automated software. The relationship between FAI values and CAD severity was assessed using univariate and multivariate regression models. RESULTS: Univariate analyses showed that sex and current smoking were associated with elevated FAILAD and FAILCX values (all P<0.05), whereas CAD severity was not relevant (all P>0.05). Not only clinical factors such as sex, current smoking, and hypertension were associated with elevated FAIRCA, but also indicators to assess CAD severity including obstructive stenosis, SIS, and SSS were related to it (all P<0.05). Multivariate analysis demonstrated that after correcting for the effects of other conventional cardiovascular risk factors and CCTA imaging features, current smoking was an independent risk factor for elevated FAI values (odds ratio [OR] = 0.569, 0.458, and 0.517; all P<0.05), whereas that SSS (OR=1.041, P=0.027) for elevated FAIRCA values. CONCLUSION: Following correction for conventional cardiovascular risk factors and imaging characteristics, current smoking was an independent clinical risk factor for elevated FAI values, and SSS was an independent risk factor for elevated FAIRCA values.

Added value of spectral computed tomography quantitative parameters for differentiating tuberculosis-associated fibrosing mediastinitis from endobronchial lung cancer: initial results.

OBJECTIVE: The objective of this study was to explore the added value of spectral computed tomography (CT) parameters to conventional CT features for differentiating tuberculosis-associated fibrosing mediastinitis (TB-associated FM) from endobronchial lung cancer (EBLC). METHODS: Chest spectral CT enhancement images from 109 patients with atelectasis were analyzed retrospectively. These patients were divided into two distinct categories: the TB-associated FM group (n = 77) and the EBLC group (n = 32), based on bronchoscopy and/or pathological findings. The selection of spectrum parameters was optimized with the least absolute shrinkage and selection operator regression analysis. The relationship between the spectrum parameters and conventional parameters was explored using Pearson's correlation. Multivariate logistic regression analysis was used to build spectrum model. The spectrum parameters in the spectrum model were replaced with their corresponding conventional parameters to build the conventional model. Diagnostic performances were evaluated using receiver operating characteristic curve analyses. RESULTS: There was a moderate correlation between the parameters ㏒(L-AEFNIC) - ㏒(L-AEFC) (r= 0.419; p< 0.0001), ㏒(O-AEF40KeV) - ㏒(O-AEFC) (r= 0.475; p< 0.0001), [L-A-hydroxyapatite {HAP}(I)] - (L-U-CT) (r= 0.604; p< 0.0001), {arterial enhancement fraction (AEF) derived from normalized iodine concentration (NIC) of lymph node (L-AEFNIC), AEF derived from CT40KeV of bronchial obstruction (O-AEF40KeV), arterial-phase Hydroxyapatite (Iodine) concentration of lymph node [L-A-HAP(I)], AEF derived from conventional CT (AEFC), unenhanced CT value (U-CT)}. Spectrum model could improve diagnostic performances compared to conventional model (area under curve: 0.965 vs 0.916, p= 0.038). CONCLUSION: There was a moderate correlation between spectrum parameters and conventional parameters. Integrating conventional CT features with spectrum parameters could further improve the ability in differentiating TB-associated FM from EBLC.

Bioactivity and genome analysis of Bacillus amyloliquefaciens GL18 isolated from the rhizosphere of Kobresia myosuroides in an alpine meadow.

The unique eco-environment of the Qinghai-Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 107 cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and ß-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[Exploration of the method and efficacy of treatments for intractable pelvic pain caused by rectal or bladder fistula].

Objective: To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods: A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results: Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment (P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments (P＜0.001). Conclusions: Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

[Application of cardiac magnetic resonance imaging in subclinical systemic sclerosis primary heart involvement].

Objectives: Primary cardiac involvement (SSc-PHI) in systemic sclerosis is an important prognostic factor. We aimed to characterize and identify subclinical SSc-PHI using cardiovascular MRI to determine whether disease severity and serum biomarkers are associated with subclinical SSc-PHI. Methods: A total of 26 patients with SSc who had no history of cardiovascular disease or pulmonary hypertension underwent 3 T-enhanced cardiovascular MRI. Measurements included native T1, extracellular volume, advanced gadolinium enhancement, T2 mapping, and left ventricular volume function. Troponin T and N telencephalic natriuretic peptide precursors were also determined. Results: LGE was observed in 13 of 26 patients (50.0%), suggesting focal fibrosis, and T2 mapping was significantly higher in the dcSSc group than in the lcSSc group (P=0.009). Left ventricular volume and function were within the normal range in all patients, but final systolic left ventricular volume was significantly higher in dcSSc than in lcSSc (P=0.021). The modified Rodnan skin score (mRSS) was significantly higher in patients with LGE focal fibrosis (P=0.019). Logistic regression analysis confirmed the association between mRSS and LGE (OR=1.224, P=0.037). In multivariate analysis, T2 mapping was negatively correlated with disease course, and was correlated with dcSSc and fingertip ulcer (R2=0.711, P=0.018, P=0.013, P=0.030). Troponin T was correlated with T2 mapping (r=0.555, P=0.049). Conclusions: Subclinical SSc-PHI is characterized by diffuse and focal myocardial fibrosis, but preserves myocardial systolic function. Subclinical SSC-Phi is associated with TNT, SSc disease severity, and complex peripheral vascular disease. These data provide information for identifying individuals at risk of SSc-PHI.

[Efficacy of rituximab therapy for 10 patients suffering from systemic lupus erythematosus with intestinal involvement].

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.