Search

Summary We are interested in the development of surrogate models for the prediction of field saturations using a fully convolutional encoder/decoder network based on the dense convolutional network (DenseNet; Huang et al. 2017), similar to the approaches used for image/image-regression tasks in deep learning. In the surrogate model, the encoder network automatically extracts the multiscale features from the raw input data, and the decoder network then uses these data to recover the input image resolution at the output of the model. The input of multiple influencing factors is considered to make our surrogate model more consistent with the physical laws, which has achieved good results in the prediction of output fields in our experiments. Various reservoir parameters including the static reservoir properties (i.e., permeability field) and dynamic reservoir properties (i.e., well placement) are used as input features, and the water-saturation distributions in different periods are taken as the output. Compared with traditional numerical reservoir simulation, which has a high computational cost and is time consuming, not only does it present the same precision, but it costs less time. At the same time, it can also be used for production optimization and history matching.

Background An increasing number of clinical trials require biomarker-driven patient stratification, especially for revolutionary immune checkpoint blockade therapy. Due to the complicated interaction between a tumor and its microenvironment, single biomarkers, such as PDL1 protein level, tumor mutational burden (TMB), single gene mutation and expression, are far from satisfactory for response prediction or patient stratification. Recently, combinatorial biomarkers were reported to be more precise and powerful for predicting therapy response and identifying potential target populations with superior survival. However, there is a lack of dedicated tools for such combinatorial biomarker analysis. Results Here, we present dualmarker, an R package designed to facilitate the data exploration for dual biomarker combinations. Given two biomarkers, dualmarker comprehensively visualizes their association with drug response and patient survival through 14 types of plots, such as boxplots, scatterplots, ROCs, and Kaplan–Meier plots. Using logistic regression and Cox regression models, dualmarker evaluated the superiority of dual markers over single markers by comparing the data fitness of dual-marker versus single-marker models, which was utilized for de novo searching for new biomarker pairs. We demonstrated this straightforward workflow and comprehensive capability by using public biomarker data from one bladder cancer patient cohort (IMvigor210 study); we confirmed the previously reported biomarker pair TMB/TGF-beta signature and CXCL13 expression/ARID1A mutation for response and survival analyses, respectively. In addition, dualmarker de novo identified new biomarker partners, for example, in overall survival modelling, the model with combination of HMGB1 expression and ARID1A mutation had statistically better goodness-of-fit than the model with either HMGB1 or ARID1A as single marker. Conclusions The dualmarker package is an open-source tool for the visualization and identification of combinatorial dual biomarkers. It streamlines the dual marker analysis flow into user-friendly functions and can be used for data exploration and hypothesis generation. Its code is freely available at GitHub at https://github.com/maxiaopeng/dualmarker under MIT license.

Reactive oxygen species (ROS) as well-known endogenous stimuli has been widely used to activate drug delivery systems (DDSs) for tumor-specific therapy. Unfortunately, endogenous ROS in the tumor microenvironment (TME) is not enough to achieve effective therapeutic efficacy and cancer cells have adapted to high oxidative stress by upregulating glutathione (GSH) level. Herein, we devised a novel ROS-activable self-immolative prodrug CASDB with both GSH-depletion ability and ROS self-supply competence. Then, an stimuli-responsive nanoplatform integrating CASDB with clinical chemotherapeutics mitoxantrone (MTO) and PLGA was fabricated (denoted as CMPs) through nanoprecipitation method. The CMPs could achieve desired accumulation at tumor tissues through enhanced permeability and retention (EPR) effects. Then the accumulated CMPs could induce tumor cell apoptosis efficiently. Especially, ROS in tumor sites could trigger the immolation of CASDB to generate CA and quinone methide (QM). Then CA and QM cooperatively promoted damage of mitochondria due to oxidative stress and led to cancer cells more sensitive to MTO. Accordingly, MTO could perturb cellular microenvironment of cancer cells then promote the degradation of CASDB. The experiment results demonstrated that CMPs were ideal for desirable synergetic tumor-specific anticancer therapy with negligible systemic toxicity. The half-maximal inhibitory concentrations (IC50) value of CMPs was 6.53 μM, while the IC50 values of MTO was 14.76 μM. And the CMPs group showed the strongest tumor suppressor effect with the tumor sizes increased to 1.2-fold (Control group: 20.6-fold, MTO only: 3.0-fold). This study should be inspirational for designing efficient prodrugs to overcome the handicaps of traditional chemotherapy.

SummaryAlthough researchers have applied many methods to history matching, such as Monte Carlo methods, ensemble-based methods, and optimization algorithms, history matching fractured reservoirs is still challenging. The key challenges are effectively representing the fracture network and coping with large amounts of reservoir-model parameters. With increasing numbers of fractures, the dimension becomes larger, resulting in heavy computational work in the inversion of fractures. This paper proposes a new characterization method for the multiscale fracture network, and a powerful dimensionality-reduction method by means of an autoencoder for model parameters. The characterization method of the fracture network is dependent on the length, orientation, and position of fractures, including large-scale and small-scale fractures. To significantly reduce the dimension of parameters, the deep sparse autoencoder (DSAE) transforms the input to the low-dimensional latent variables through encoding and decoding. Integrated with the greedy layer-wise algorithm, we set up a DSAE and then take the latent variables as optimization variables. The performance of the DSAE with fewer activating nodes is excellent because it reduces the redundant information of the input and avoids overfitting. Then, we adopt the ensemble smoother (ES) with multiple data assimilation (ES-MDA) to solve this minimization problem. We test our proposed method in three synthetic reservoir history-matching problems, compared with the no-dimensionality-reduction method and the principal-component analysis (PCA). The numerical results show that the characterization method integrated with the DSAE could simplify the fracture network, preserve the distribution of fractures during the update, and improve the quality of history matching naturally fractured reservoirs.

SummaryReservoir connectivity analysis plays an essential role in controlling water cut in the middle and later stages of reservoir development. The traditional analysis methods, such as well test and tracer, may result in interruption and high reservoir development costs. Analyzing connectivity through history data is an advisable alternative method because the fluctuation of data reflects interwell interference. However, most of the former data-driven methods, such as capacitance and resistance model (CRM), estimate connectivity using formulas in relatively simple forms, leading to inadequate expression for underground interwell flow. In this paper, an interpretable recurrent graph neural network (GNN) is proposed to construct an interacting process imitating the real interwell flow regularity and overcoming the weakness in previous methods. In contrast, it is formed by a deep enough neural network structure with a relatively larger number of parameters when compared with the CRM model. In detail, this method makes the first use of both rate information and bottomhole pressure (BHP) to completely describe the hidden state of wells and the energy information exchanged among them, which are then continually updated in spatial and temporal ways.Meanwhile, a self-defined recurrent structure deals with the time lag and attenuation phenomenon as it records the residual energy from past timestamps. Finally, it calculates BHP for each production well with the manually specified production rate as extra input data. Detailed results are presented in two examples. Our proposed method shows significant advantages to other methods due to its reasonable structure and great ability to fit nonlinear mapping.

Although a number of therapeutic strategies have been applied in cancer therapy, treatment for cancer metastasis is challenging due to unsatisfactory cure rate and easy cancer recurrence. In our wo...

Summary History matching is a typical inverse problem that adjusts the uncertainty parameters of the reservoir numerical model with limited dynamic response data. In most situations, various parameter combinations can result in the same data fit, termed as nonuniqueness of inversion. It is desirable to find as many global or local optima as possible in a single optimization run, which may help to reveal the distribution of the uncertainty parameters in the posterior space, which is particularly important for robust optimization, risk analysis, and decision making in reservoir management. However, many factors, such as the nonlinearity of inversion problems and the time-consuming numerical simulation, limit the performance of most existing inverse algorithms. In this paper, we propose a novel data-driven niching differential evolution algorithm with adaptive parameter control for nonuniqueness of inversion, called DNDE-APC. On the basis of a differential evolution (DE) framework, the proposed algorithm integrates a clustering approach, niching technique, and local surrogate assistant method, which is designed to balance exploration and convergence in solving the multimodal inverse problems. Empirical studies on three benchmark problems demonstrate that the proposed algorithm is able to locate multiple solutions for complex multimodal problems on a limited computational budget. Integrated with convolutional variational autoencoder (CVAE) for parameterization of the high-dimensional uncertainty parameters, a history matching workflow is developed. The effectiveness of the proposed workflow is validated with heterogeneous waterflooding reservoir case studies. By analyzing the fitting and prediction of production data, history-matched realizations, the distribution of inversion parameters, and uncertainty quantization of forecasts, the results indicate that the new method can effectively tackle the nonuniqueness of inversion, and the prediction result is more robust.

In this study, we found a green method to obtain aryl nitriles from aromatic aldehyde in water. This simple process was modified from a conventional method. Compared with those approaches, we used water as the solvent instead of harmful chemical reagents. In this one-pot conversion, we got twenty-five aryl nitriles conveniently with pollution to the environment being minimized. Furthermore, we confirmed the reaction mechanism by capturing the intermediates, aldoximes.

To explore the clinical characteristics and prognosis of COVID‐19 patients with cerebral stroke. A total of 2474 COVID‐19 patients from February 10th to March 24th, 2020 were admitted and treated in two branches (Optic Valley and Sino‐French New City branch) of the Tongji Hospital. Data on the clinical characteristics, laboratory parameters and prognosis of COVID‐19 patients with or without cerebral stroke were collected and comparatively analysed. Of the 2474 COVID‐19 patients, 113 (4.7%) patients had cerebral stroke, and 25 (1.0%) patients had new‐onset stroke. Eighty‐eight (77.9%) patients in the previous‐stroke group had cerebral ischaemia, while 25 (22.1%) patients in the new‐onset stroke group had cerebral ischaemia. Most COVID‐19 patients with stroke were elderly with more comorbidities, such as hypertension, diabetes and heart diseases than patients without stroke. Laboratory examinations showed hypercoagulation and elevated serum parameters such as IL‐6, cTnI, NT pro‐BNP and BUN. Consciousness disorders, a long disease course and poor prognosis were also more commonly observed in stroke patients. The mortality rate of stroke patients was almost double (12.4% vs 6.9%) that of patients without stroke. In addition, age, male sex and hypertension were independent predictors for new cerebral stroke in COVID‐19 patients. In conclusion, the high risk of new‐onset stroke must be taken into consideration when treating COVID‐19 patients with an elderly age combined with a history of hypertension. These patients are more vulnerable to multiorgan dysfunction and an overactivated inflammatory response, in turn leading to an unfavourable outcome and higher mortality rate.

Sub-30 nm lanthanide-doped KLu2F7 upconversion (UC) nanorods were synthesized using a hightemperature coprecipitation method. Highly uniform morphologies, a small size distribution and the desirable orthorhombic crystalline phase was achieved by controlling the reaction temperature; while control over the UC luminescence color was achieved by changing the dopant activator. Orthorhombic KLu2F7 nanorods showed excellent potential as a host phase for future UC luminescence materials in applications such as bioimaging.

Objectives This phase 2 study explored tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy as first-line treatment of advanced lung cancer. Material and Methods Eligible patients had histologically/cytologically confirmed advanced/metastatic nonsquamous non-small cell lung cancer (NSQ), squamous NSCLC (SQ), or extensive-stage small cell lung cancer (SCLC). All patients received tislelizumab 200 mg in combination with 4–6 cycles of platinum-doublet. The NSQ cohort received pemetrexed + platinum Q3W for 4 cycles followed by pemetrexed maintenance, the SQ cohort received paclitaxel + platinum (A) or gemcitabine + platinum (B) Q3W, and the SCLC cohort received etoposide + platinum Q3W. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Progression-free survival (PFS) and tolerability profile were secondary endpoints; exploratory endpoints included overall survival (OS) and predictive biomarkers. Results Fifty-four patients (NSQ, n = 16; SQ = 21 [SQ-A, n = 15; SQ-B, n = 6]; SCLC, n = 17) were enrolled; as of February 25, 2019, 14 remained on treatment. Confirmed ORRs were 44% (NSQ), 80% (SQ-A), 67% (SQ-B), and 77% (SCLC). Median PFS were 9.0 months (NSQ), 7.0 months (SQ-A), and 6.9 months (SCLC); PFS in SQ-B are not mature. Median OS was not reached in all cohorts except for SCLC (15.6 months). Common treatment-emergent AEs included anemia (79.6%, n = 43) and decreased white blood cell count (74.1%, n = 40). Gene expression analyses revealed distinct patterns by histology type; lower tumor inflammation signature levels were observed among nonresponding patients with NSQ and SCLC. Conclusions Tislelizumab plus chemotherapy demonstrated encouraging antitumor activity, was generally well tolerated, and distinct immune- and cell cycle–related gene signatures were associated with efficacy across cohorts.

Background: MicroRNAs (miRNAs) act as a critical role in cancer pathogenesis, while the potential of miR-449b-5p in breast carcinoma remains to be fully inquired. Therefore, we purposed to probe the mechanism governing miR-449b-5p in breast cancer. Methods: Reverse transcription-PCR (RTPCR) was adopted to examine miR-449b-5p expression level in breast carcinoma. The functional experiments were implemented to estimate the role of miR-449b-5p in cell growth and migration. The interplay of miR-449b-5p with FLOT2 was validated with luciferase reporter assay. Results: miR-449b-5p level was markedly lessened in the tissue samples and cell lines of breast carcinoma. Overexpression of miR-449b-5p contributed to suppression of cell growth and migration whereas induced apoptosis in SKBr-3 and MCF-7 cells. Moreover, luciferase reporter experiment suggested that FLOT2 had a negative correlation with miR-449b-5p expression. Functionally, ectopic expression of FLOT2 reversed repressive effects of miR-449b-5p mimic on malignant behaviors of breast carcinoma cells. Conclusion: miR-449b-5p hindered cell proliferation, migration and facilitated cell apoptosis of breast carcinoma through targeting FLOT2. Our findings may offer a potent target for the therapy of breast carcinoma.

Summary Efficient identification and characterization of fracture networks are crucial for the exploitation of fractured media such as naturally fractured reservoirs. Using the information obtained from borehole logs, core images, and outcrops, fracture geometries can be roughly estimated. However, this estimation always has uncertainty, which can be decreased using inverse modeling. Following the Bayes framework, a common practice for inverse modeling is to sample from the posterior distribution of uncertain parameters, given the observational data. However, a challenge for fractured reservoirs is that the fractures often occur on different scales, and these fractures form an irregular network structure that is difficult to model and predict. In this work, a multiscale-parameterization method is developed to model the fracture network. Based on this parameterization method, we present a novel history-matching approach using a data-driven evolutionary algorithm to explore the Bayesian posterior space and decrease the uncertainties of the model parameters. Empirical studies on hypothetical and outcrop-based cases demonstrate that the proposed method can model and estimate the complex multiscale-fracture network on a limited computational budget.

It is of great scientific significance to reveal the flow characteristics of dentiform emitters and to optimize the channel structure of emitters to improve the anti-clogging properties of emitters, which contribute to improving the working performance of irrigation systems. The study was carried out using computational fluid dynamics (CFD) simulations, combined with the physical test in the laboratory. First, this paper analyzes the distributions of flow velocity, kinetic energy in turbulence, and physical particle trajectories inside the different structural emitters based on CFD simulations, and based on the simulation results, a dentiform emitter optimization scheme was proposed, and two-channel structures, including the structurally improved emitter, were arranged to conduct indoor tests for verification. The result shows that the maximum kinetic energy in turbulence in the flow channel appeared in the main flow area and that the area of strongest energy dissipation in turbulence was at the tooth tip. The main flow area was largest for the emitter with the triangular channel, and the turbulence energy of the low-speed region was highest for the circular trapezoidal structure. The results suggested a scheme for further optimization of the dentiform emitter. For the optimized channel structure, the maximum value of turbulent kinetic energy was increased by about 19–101% compared with the other four flow channels. The area of the main flow region and the kinetic energy in turbulence in the low-speed area in the emitter were increased. In addition, the range of kinetic energy in turbulence was increased by 52–200% in the low-speed region of the channel. The transport rate of physical particles was increased, and the transport distance and residence time of the particles were reduced. The physical test results show that the optimized channel structure emitter achieved a decrease in the clogging probability compared with the other four structures. Therefore, increasing the area of the main flow region and the low-speed area in the flow channel is an effective physical way of physically improving the anti-clogging performance of the emitter.

Immune checkpoint blockade (ICB) therapy has shown promising antitumor effects, but its immune response rate remains unsatisfactory. In recent years, chemotherapy has been proven to have synergistic effects with ICB therapy because some chemotherapeutic agents can enhance the immunogenicity of tumor cells by inducing immunogenic cell death (ICD). However, it cannot be ignored that chemotherapy often shows limited therapeutic efficacy due to high cytotoxicity, drug resistance, and some other side effects. Herein, we report a strategy to improve cancer immunotherapy by utilizing red blood cell-based vaccines (RBC-vaccines) where chemotherapy-induced tumor antigens (cAgs) are anchored onto red blood cells (RBCs) via the EDC/NHS-mediated amine coupling reaction. In this work, RBC-vaccines administered subcutaneously are primarily devoured by dendritic cells (DCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment by increasing the infiltration of intratumoral CD8

The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-CoV-2 variants, including Omicron, are required to be identified as soon as the samples are identified as ‘positive’. Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time, we have developed MOPCS (Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) with the ‘gene scissors’ clustered regularly interspaced short palindromic repeat (CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification, within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-CoV-2, and mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) and BA.1 (a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.

Mitochondria are involved in many cellular activities, including energy metabolism and biosynthesis of nucleotides, fatty acids and amino acids. Mitochondrial morphology is a key factor in dictating mitochondrial functions. Here, we report that the acyl-CoA-binding protein (ACBP) Acb1 in the fission yeast Schizosaccharomyces pombe is required for the maintenance of tubular mitochondrial morphology and proper mitochondrial respiration. The absence of Acb1 causes severe mitochondrial fragmentation in a dynamin-related protein Dnm1-dependent manner and impairs mitochondrial respiration. Moreover, Acb1 regulates the remodelling of lipid droplets in nutrient-rich conditions. Importantly, Acb1 promotes cell survival when cells are cultured in nutrient-rich medium. Hence, our findings establish roles of ACBP in regulating mitochondria, lipid droplets and cell viability.

Moyamoya disease (MMD) is characterized by frequent migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) in the intima layer of blood vessels. However, the underlying mechanism is unclear. Toll-like receptor (TLR) 7 is abundantly expressed in smooth muscle cells (SMCs) in multiple vascular diseases, which might be linked to the disease-associated vascular remodeling. In the present study, the expression of TLR7 in MMD vessels was examined using the superficial temporal artery (STA) and middle cerebral artery (MCA) from MMD patients. Furthermore, the effect of TLR7 activation on the VSMC phenotype switch in vitro and vascular remodeling in vivo was assessed using a 9.4Tesla MRI. Our results demonstrated that the TLR7 and microRNA Let-7c expression are upregulated in VSMCs and the plasma of MMD patients, respectively. Additionally, TLR7 stimulation by Let-7c or Imiquimod induces a synthetic phenotype switch in VSMCs. Mechanistic studies revealed that Akt/mTOR signaling is responsible for this TLR-induced VSMC phenotypic switch. The Let-7c or Imiquimod treatment also resulted in reduced blood flow of internal carotid arteries (ICAs) in an in vivo model, while TLR7 inhibition attenuated the ICA stenosis. Besides, Let-7c was also found to be elevated in the hypoxic endothelial cells. Taken together, our study demonstrates that Let-7c released by endothelial cells under hypoxic conditions may activate TLR7 on VSMCs, ultimately leading to the phenotype switch and vascular wall remodeling. These findings thus elucidate the putative mechanisms underlying progressive stenosis of blood vessels in MMD and provide prospective therapeutic targets for further exploration.

Septins are a family of filament-forming GTP-binding proteins that regulate fundamental cellular activities, such as cytokinesis and cell polarity. In general, septin filaments function as barriers and scaffolds on the cell cortex. However, little is known about the mechanism that governs the recruitment and localization of the septin complex to the cell cortex. Here, we identified the Cdc42 GTPase-activating protein Rga6 as a key protein involved in promoting the localization of the septin complex to the cell cortex in the fission yeast Schizosaccharomyces pombe. Rga6 interacts with the septin complex and partially colocalizes with the septin complex on the cell cortex. Live-cell microscopy analysis further showed septin enrichment at the cortical regions adjacent to the growing cell tip. The septin enrichment likely plays a crucial role in confining active Cdc42 to the growing cell tip. Hence, our findings support a model whereby Rga6 regulates polarized cell growth partly through promoting targeted localization of the septin complex on the cell cortex. This article has an associated First Person interview with the first author of the paper.

Although a number of therapeutic strategies have been applied in cancer therapy, treatment for cancer metastasis is challenging due to unsatisfactory cure rate and easy cancer recurrence. In our work, nanocomposites (NCs) based on polypyrrole-coated mesoporous TiO

537 Background: Tislelizumab, a humanized monoclonal antibody that targets programmed cell death protein 1 (PD-1), has shown promising activity in the treatment of advanced urothelial bladder cancer (UBC). Recent studies suggest that liver metastases (LM) are associated with reduced effectiveness of PD-1/PD-L1 therapies (Yu, et al. Nat Med. 2021;27[1]:152-164). We evaluated how LM correlate with survival outcomes and the tumor immune microenvironment in UBC patients treated with tislelizumab in the BGB-A317-204 trial (NCT04004221). Methods: Cox regression was used to evaluate the effect of LM on overall survival (OS). Other key baseline characteristics were further included as covariates in the model to investigate the adjusted effect of LM and the interactions of LM with them. Gene expression profiling and multiplex immunohistochemistry (mIHC) analysis were performed on baseline tumor samples. Gene expression differences between LM positive (LM+) and LM negative (LM–) patients were compared by Wilcoxon rank-sum test for continuous biomarkers, and Fisher’s exact test for categorical biomarkers. All P-values reported in this post-hoc exploratory analysis were descriptive, without multiplicity adjustment. A result of P

Background In patients with papillary thyroid cancer (PTC), cervical lymph node metastasis (LNM) must be carefully assessed to determine the extent of lymph node dissection required and patient prognosis. Few studies attempted to determine whether the ultrasound (US) appearance of the primary thyroid tumor could be used to predict cervical lymph node involvement. This study aimed to identify the US features of the tumor that could predict cervical LNM in patients with PTC. Methods This was a retrospective study of patients with pathologically confirmed PTC. We evaluated the following US characteristics: lobe, isthmus, and tumor size; tumor position; parenchymal echogenicity; the number of lesions (i.e., tumor multifocality); parenchymal and lesional vascularity; tumor margins and shape; calcifications; capsular extension; tumor consistency; and the lymph nodes along the carotid vessels. The patients were grouped as no LNM (NLNM), central LNM (CLNM) alone, and lateral LNM (LLNM) with/without CLNM, according to the postoperative pathological examination. Results Totally, 247 patients, there were 67 men and 180 women. Tumor size of > 10 mm was significantly more common in the CLNM (70.2%) and LLNM groups (89.6%) than in the NLNM group (45.4%). At US, capsular extension > 50% was most common in the LLNM group (35.4%). The multivariable analysis revealed that age (OR = 0.203, 95%CI: 0.095–0.431, P P = 0.023) were independently associated with CLNM compared with NLNM. In addition, age (OR = 0.277, 95%CI: 0.127–0.603, P = 0.001), tumor size (OR = 6.069, 95%CI: 2.075–17.75, P = 0.001), and capsular extension (OR = 2.09, 95%CI: 1.326–3.294, P = 0.001) were independently associated with LLNM compared with NLNM. Conclusion Percentage of capsular extension at ultrasound is associated with LLNM. US-guided puncture cytology and eluent thyroglobulin examination could be performed as appropriate to minimize the missed diagnosis of LNM.

BackgroundNeoadjuvant chemotherapy (NAC) has been expanded to hormone receptor (HR) positive breast cancer (BC) patients with operable disease, to increase the likelihood of breast-conserving surgery. Genomic profiling at baseline would reveal NAC response relevant genomic features and signaling pathways, guiding clinical NAC utilization based on patients’ genomic characteristics.MethodsWe prospectively studied stage II/III BC patients who were eligible for breast-conserving surgery. Patients received epirubicin and cyclophosphamide for 4 cycles, followed by another 4-cycle docetaxel, and human epidermal growth factor receptor (HER2) positive patients were additionally treated with herceptin when using docetaxel (EC-T(H)). NAC responses were evaluated as pathologic complete response (pCR) or non-pathologic complete response (non-pCR). Genomic features related to NAC responses were identified by profiling baseline tumor tissues sampled one day before NAC, using whole-exome sequencing. Differentially expressed genes and up-/down-regulated pathways were investigated by performing RNA-sequencing.ResultsA total of 25 stage II/III BC patients were enrolled, including 5 patients ultimately evaluated as pCR and 20 patients evaluated as non-pCR. PIK3CA (48%) and TP53 (40%) mutations were enriched in patients not achieving pCR. Mutated phosphatidylinositol-3-kinase-AKT (PI3K-AKT) pathway and homologous recombinational repair pathway were also more frequently observed in patients evaluated as non-pCR. Significant arm-level amplifications (8q24.23 and 17q12) and deletions (1p32.2, 4p14, 7q11.23, 10q21.3, 11q23.3, etc.) were identified among patients not achieving pCR, while patients achieving pCR displayed no significant copy number alterations. Significantly up-regulated expression of PI3K-AKT pathway genes was also detected among patients failed to achieve pCR, compared to patients achieving pCR.ConclusionCompared to BC patients achieving pCR to NAC, aberrant activation of PI3K-AKT pathway genes were more frequently observed in patients not achieving pCR, consistent with the significant up-regulation of PI3K-AKT pathway gene expression in the non-pCR subgroup. Together, these findings indicate that upregulated PI3K-AKT pathway serves as a potential indicator of lack of response to NAC in stage II/III BC patients, and other effective therapeutic options are urgently needed for those resistant patients.

Background Chinese residents’ practical work experiences are different from those described in Western studies. To explore potential mechanisms underlying the effects of doctor-patient relationships on medical residents’ work engagement, verifying a posited mediating effect of role overload, and moderating effect of conflict avoidance, in the Chinese context. Methods Based on the conservation of resources theory, a composite model was constructed. This study’s data were collected from four different Chinese tertiary hospitals; 195 residents undergoing regularization training took this survey. Hierarchical moderated and mediated regression analyses were utilized. Results Doctor-patient relationship were found to be positively related to residents’ work engagement (β=0.31, p≤0.001). Role overload partially mediated the effect of these relationships on work engagement, and the moderating role of conflict avoidance in the relationship between doctor-patient relationship and conflict avoidance was negative. Conclusion Maintaining good doctor-patient relationship can prompt residents to increase their engagement in work in order to meet their patients’ needs. Furthermore, role overload has a particular influence in early career stages. Not only is it necessary for residents to gain a sense of recognition and support while they carry out their job responsibilities, especially while dealing with complex doctor-patient relationship, but it is also important to create work environments that can help residents shape their professional competency.

The outbreak of the infection of 2019 novel coronavirus disease (COVID­‐19) has become a challenging public health threat worldwide. Limited data are available for pregnant women with COVID‐19 pneumonia. We report a case of a convalescing pregnant woman diagnosed with COVID‐19 infection 37 days before delivery in the third trimester. A live birth without severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection was performed successfully via the vagina. The findings from our case indicate that there is no intrauterine transmission in this woman who developed COVID‐19 pneumonia in late pregnancy., Highlights The newborn was delivered by vaginal delivery, different from most of the cases.The results showed that intrauterine vertical transmission was not observed in our case.Our finding will be helpful for formulating the principles of obstetric treatment for pregnant women with COVID‐19.

There is an urgent need to seek colossal dielectric materials with better dielectric properties because of the rapid development of the electronics industry. In this work, ( M 0.5 Nb 0.5 ) 0.01 Ti 0.99 O 2 ( M = Al, In, Eu) ceramics are synthesized by traditional solid-state reaction, and recorded as ANTO, INTO and ENTO ceramics, respectively. The effects of different radius acceptor ions on the phase structure, microstructure and dielectric properties of TiO 2 based ceramics are investigated. It is found that all samples are rutile phases without the generation of the second phase, but the difference of ion radius resulted in lattice distortion of different degrees, which affects the defect structure in the material. The dielectric properties of the materials are related to the defect structure in the material, and the ability to localize electrons in different defect structures is different. The dielectric properties of ANTO ceramics are similar to those of un-doped TiO 2 ; INTO ceramics have the lowest dielectric loss (0.039), the best temperature and frequency stability, and there are no dielectric loss peak near the room temperature; The ENTO ceramics has the maximum permittivity (2.01 × 10 5 ).

The Aurora A inhibitor alisertib shows encouraging activities in clinical trials against advanced breast cancer. However, it remains unclear whether and how the inflammatory microenvironment is involved in its efficacy. Here, we demonstrated that inhibition of Aurora A directly reshaped the immune microenvironment through removal of tumor-promoting myeloid cells and enrichment of anticancer T lymphocytes, which established a tumor-suppressive microenvironment and significantly contributed to the regression of murine mammary tumors. Mechanistically, alisertib treatment triggered apoptosis in myeloid-derived suppressor cells (MDSC) and macrophages, resulting in their elimination from tumors. Furthermore, alisertib treatment disrupted the immunosuppressive functions of MDSC by inhibiting Stat3-mediated ROS production. These alterations led to significant increases of active CD8+ and CD4+ T lymphocytes, which efficiently inhibited the proliferation of tumor cells. Intriguingly, alisertib combined with PD-L1 blockade showed synergistic efficacy in the treatment of mammary tumors. These results detail the effects of Aurora A inhibition on the immune microenvironment and provide a novel chemo-immunotherapy strategy for advanced breast cancers. Significance: These findings show that inhibition of Aurora A facilitates an anticancer immune microenvironment, which can suppress tumor progression and enhance anti–PD-L1 therapy in breast cancer. See related commentary by Rivoltini et al., p. 3169

The search for colossal dielectric constant materials is imperative because of their potential for promising applications for the areas of device miniaturization and energy storage. In this work, (Nd0.5Nb0.5)xTi1-xO2 ceramics is prepared via the solid-state reaction route. The microstructure, crystal structures, and dielectric properties of (Nd0.5Nb0.5)xTi1-xO2 ceramics are investigated. It is proved that schottky barrier exists at grain boundary by measuring impedance spectrum of different DC biases and C-V curve. The grain boundary characteristics of the ceramics are studied. It is found that the proper second phase is beneficial to increase the grain boundary resistance and restrain the long range movement of electrons, so that the material keeps low dielectric loss and improves the temperature stability. But too much of second phase will deteriorate performance due to excessive space charges. In addition, all the (Nd0.5Nb0.5)xTi1-xO2 ceramics displays a colossal dielectric constant (>104), especially a high dielectric constant (2.55 × 104) and low dielectric loss (0.023) at 1 kHz and room temperature which can be obtain in (Nd0.5Nb0.5)xTi1-xO2 ceramic with x = 3%. The dielectric properties of (Nd0.5Nb0.5)xTi1-xO2 ceramics can be explained by internal barrier layer capacitor (IBLC) model, which can be optimized by balancing grain size, barrier height and barrier width.

Confocal laser scanning microscopy (CLSM) is expected to exhibit a better imaging performance in the second near-infrared (NIR-II) windows with weak tissue scattering and autofluorescence. However, the indium gallium arsenide (InGaAs) detectors currently used for imaging in the NIR-II region are prohibitively expensive, hampering its extensive biomedical applications. In this study, a novel NIR-II CLSM system is developed by using the inexpensive silicon photomultiplier (SiPM) that can perform the multicolor biological imaging in vivo. Using IR-780 iodide as the contrast agent, the NIR-II imaging capability of constructed CLSM is inspected, demonstrating a spatial resolution of 1.68 µm (close to the diffraction limit) and a fluorophore detection sensitivity as low as 100 nm. In particular, it is discovered that the multicolor imaging performance in both NIR-I and NIR-II windows is comparable to those from multialkali and InGaAs photomultiplier tubes. In addition, 3D NIR-II CLSM is also conducted for in vivo imaging of the vascular structure in mouse ear and subcutaneous tumors. To the best of authors' knowledge, this is the first time that a low-cost detector based on a SiPM has been used for microscopic imaging of trailing fluorescence signals in the NIR-II region of an NIR fluorescent probe.

Sugar beet is one of the main sugar crops and an important cash crop in the three northern regions of China (Northeast China, North China, and Northwest China). As an arid region, Xinjiang lacks water resources. The establishment of a reasonable drip-irrigation system for sugar beet in Xinjiang can not only achieve the goal of high quality and high yield, but is also crucial for the efficient utilization of water and fertilizer. This research was implemented in the experimental field of the Xinjiang Academy of Agricultural Sciences’ Sugar Beet Improvement Center in Manas County, Xinjiang, from the year 2019. Taking ST 15140 sugar beet as the experimental variety, a field study was conducted to investigate the effects of different irrigation and fertilization methods on the yield and sugar content of sugar beets. Ten treatments of two irrigation levels (W1: 4500 m3 ha−1, W2: 5400 m3 ha−1) and five fertilization methods (F1, F2, F3, F4, and F5) were carried out in a randomized block design with three replications. The yield and sugar content; growth indicators such as leaf photosynthetic rate, stomatal conductance, chlorophyll content and intercellular CO2 concentration; and fertilizer-use efficiency (nitrogen-use efficiency (NUE), phosphorus-use efficiency (PUE), and potassium-use efficiency (KUE)) during the sugar beet growing seasons were determined. The results indicated that the W1F3 (4500 m3 ha−1, N 229.5 kg ha−1 + P2O5 180 kg ha−1 + K2O 202.5 kg ha−1 + hydroquinone 229.5 g ha−1) treatment had the highest yield and sugar content of 132.20 Mg ha−1 and 15.61%, respectively. For crop growth indicators, the photosynthetic rate (33.27 μmol m−2 s−1) and the stomatal conductance (252.67 mmol m−2 s−1) under W1F3 were both the highest among all of the treatments. The fertilizer-use efficiency in W1F3 was in the following order: KUE > NUE > PUE. The highest KUE (128.10%) and NUE (65.49%) occurred under W1F3 at the sugar accumulation stage of the crop growing season. In addition, K determined the yield and sugar content of sugar beet by influencing growth factors such as the photosynthetic rate, chlorophyll content, intercellular CO2 concentration, along with the KUE, which explained 30.2%, 5.1%, 10%, and 14.7% of the variation in yield and sugar content, respectively. The results of this study indicated that the application of an inhibitor with optimized-minus-N fertilization under lower irrigation (W1F3) was the optimal treatment. Above all, K determined the yield and sugar contents of sugar beets, emphasizing the pivotal role of K in the growth, physiological processes, and output of sugar beets.

The biocompatible nanosystem integrating hemin into black phosphorus nanosheets was ingeniously constructed through the easy modified strategy. Taking advantage of the enhanced permeability and retention (EPR) effect, the designed nanosystem could accumulate into the tumor location, leading to attractive cytotoxicity through the enhanced photodynamic therapy (PDT) ascribing to the catalytic oxygen supply and GSH depletion of hemin. Simultaneously, combining PDT and photothermal therapy (PTT) showed an apparent promotion in anti-tumor effect. Moreover, inflammatory response and immune activation amplified anti-tumor effect, which could compensate limitations of exogenous therapy (i.e., limited tissue depth and intensity-dependent curation effect) and potentiate the efficiency of the endogenous immune-activating behavior. Especially, the designed nanosystem degraded followed by being metabolized in the blood circulation. By and large, this constructed nanosystem provides the new insight into designing biocompatible nanomaterials and paves the ideal way for anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Biocompatible nanomaterials-based synergistic tumor therapy offers the potential application prospect. Taking advantage of degradable black phosphorus, the nanosystem integrating hemin into black phosphorus for the enhanced photodynamic therapy and synergistic photothermal-photodynamic activating inflammation-immune response was developed and the results demonstrate that tumor growth was inhibited followed by activating inflammatory factors and leading to satisfactory immune response.

In recent years, more and more research enthusiasm has been devoted to the development of emerging two-dimensional (2D) monoelement materials (Xenes) and explored potential applications in various fields, especially biomedicine and bioimaging. The inspiring results attribute to their excellent physicochemical properties, including adjustable band gap, surface electronic layout characteristics, and so on, making it easier for surface modification in order to meet designated needs. As a popular interdisciplinary research frontier, a variety of methods for fabricating 2D Xenes have recently been adopted for pre-preparing future practical bioimaging applications, which implies that these materials will have broad clinical application prospects in the future. In this review, we will concentrate on the family of 2D Xenes and summarize their fabrication and modification methods firstly. Then, their applications in bioimaging as nanocarriers will be described according to the Periodic Table of Elements. In addition, current challenges and prospects for further clinical applications will be under discussion and use black phosphorus as a typical example. At last, general conclusion will be made that it is worth expecting that 2D Xenes will play a key role in the next generation of oncologic bioimaging in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

History matching is an important part of reservoir numerical simulation research and the basis for predicting oilfield development performance. At present, integrated smoother and ensemble Kalman filter methods are the mainstream methods of history matching. However, these data assimilation algorithms need to be based on Gaussian assumptions and cannot guarantee the geological authenticity of the modified model. Therefore, to achieve end-to-end processing of dynamic data to modify the reservoir model, while ensuring that the distribution of data does not need to be restricted by Gaussian distribution, this paper proposes the use of the deep conditional generative adversarial network (CGAN) method for automatic reservoir history matching for the first time. The mapping relationship between static geological reservoir parameters and dynamic production data is found through the training generative network, which reduces the uncertainty of the reservoir model obtained by automatic history matching and explains parallel offline processing. The numerical simulation results show that the prediction results on the 2D two-phase flow model are consistent with the results of the proposed deep conditional generative adversarial network method.

History matching can provide reliable numerical models for reservoir management and development by assimilating the historical production data into prior geological realizations. It is usually a typical inverse problem with multiple solutions. However, efficiently obtaining multiple posterior solutions is still challenging for most existing history matching algorithms. In this paper, we present a novel algorithm to tackle this problem, which integrates the niching technique and surrogate-assisted method into the particle swarm optimization (PSO), in which, the niching technique can improve the exploration ability and maintain the diversity of the population, while the surrogate-assisted method is focused on accelerating the convergence. Additionally, the convolutional variational autoencoder (CVAE), a deep learning model, is adopted to map the high-dimensional spatially uncertain parameters such as permeability and porosity to low-dimensional latent variables. Experimental results show that the proposed algorithm has good convergence and sampling ability for history matching problems.

Taxanes are widely used in chemotherapy, but intrinsic and acquired resistance limit the clinical outcomes. Studies showed tumor interaction with suppressive macrophages plays a key role in taxane resistance, yet therapeutic strategies that deplete or repolarize macrophages are challenging. Here we uncovered a novel tumor-macrophage interaction via Notch2-Jag1 justacrine signaling that can be targeted to sensitize paclitaxel response without affecting the broad macrophage functions. Using translatome profiling, we identified Notch2 upregulation during taxol-induced prolonged mitosis. Notch2 was subsequently activated in the post-mitotic G1 phase by Jag1 expressed on neighboring macrophages, which promoted tumor cell survival by upregulating p38 and anti-apoptotic proteins. Notch2 also upregulated cytokines that further recruited Jag1-expressing macrophages. By targeting this Notch2-Jag1 interaction with a pan-Notch inhibitor, RO4929097, taxol resistance was significantly attenuated in multiple mouse tumor models. Our results point to combining Notch inhibitor with taxane as an effective strategy to selectively disrupt tumor-macrophage interaction underlying chemoresistance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide and causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here, we obtained the complex structure of RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2), and further evaluated the binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in RaTG13 RBD with their counterparts in SARS-CoV-2 RBD, we found that residue 501, the major position found in VOCs 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 MAb, CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host-adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spill-over of CoVs., Structural and molecular analysis of the receptor binding domain of RaTG13, a coronavirus closely related phylogenetically to SARS-CoV-2, bound to the human receptor ACE2 as well as ACE-2 orthologs in 24 other species provides a framework to understand its host range as well as the basis of antibody cross-reactivity between the two viruses.

Background: High tumor mutational burden (TMB-H) is associated with elevated neoantigen expression across tumors, linked with an improved response to PD-(L)1 inhibitors. Here we report data from the final analysis of a Phase 1 trial that enrolled patients (pts) with various solid tumors treated with tislelizumab (NCT02407990). We evaluated the association of TMB with clinical outcomes, integrative biomarker analysis of genomic alterations and gene expression profiling by TMB status. Methods:451 pts were enrolled and treated with different doses of tislelizumab. Baseline tumor tissue was evaluated for gene expression (HTG EdgeSeq Precision Immuno-Oncology Panel) and genomic profiling (FoundationOne CDx). TMB-H and gene hyperamplification (HA) were defined as ≥ 10 mutations/Mb and a minimum of copy number gain > 5, respectively. Associations with progression-free survival (PFS) and overall survival (OS) were examined using Cox proportional hazards models. Results: The overall objective response rate was 13.3% (95% CI: 10.3, 16.8), median (m) PFS 2.1 months (95% CI: 2.1, 2.7), and mOS 10.3 months (95% CI: 8.5, 11.6). Improved clinical outcomes were observed in pts with TMB-H tumors (n=43, 16.2% of TMB evaluable pts), and response was further enriched in pts without gene HA (TMB-H/HA-) (Table). This population showed elevated cytotoxic T-cell activity and interferon signaling in the TME, along with fewer hyper-amplified genes in RTK-RAS-PI3K pathway. This was validated in an independent PD-(L)1 inhibitor treated pan-cancer cohort (n=837): TMB-H/HA-(n=139) had longer OS than TMB-H/HA+ (n=89) (mOS: 34 vs 15 months, P=0.07). Conclusions: The combination of TMB and HA was found to be predictive of clinical benefit across various solid tumor types, treated with tislelizumab. This joint algorithm, as reported by one clinically approved assay, may provide new insights to the identification of pts who are most likely to gain benefit from PD-(L)1 blockade. Clinical outcomes in pts subgroups by TMB and HA status TMB-H TMB-L Overall HA- HA+ Overall HA- HA+ n (% in TMB BEP [N=266]) 43 (16.2) 20 (7.5) 23 (8.6) 223 (83.8) 103 (38.7) 120 (45.1) ORR, % (95% CI) 32.6 (19.1, 48.5) 50.0 (27.2, 72.8) 17.4 (5.0, 38.8) 10.3 (6.7, 15.1) 11.7 (6.2, 19.5) 9.2 (4.7, 15.8) mPFS, months (95% CI) 8.3 (2.0,11.5) 15.1 (8.1, NR) (2.0, 1.2, 8.3) 2.1 (2.0, 2.1) 2.1 (2.1, 4.0) 2.0 (2.0, 2.1) mOS, months (95% CI) 20.1 (10.3, 37.4) 30.9 (11.1, NR) 9.7 (2.8, 23.8) 11.1 (7.7, 11.9) 13.9 (11.1, 18.2) 6.7 (5.6, 8.1) BEP, biomarker evaluable population; CI, confidence interval; HA, hyperamplification; NR, not reached; ORR, objective response rate; mOS, median overall survival; mPFS, median progression-free survival; TMB-H, high tumor mutational burden; TMB-L, low tumor mutational burden Citation Format: Sanjeev Deva, Michael Millward, Michael Friedlander, Hui K. Gan, Lisa G. Hovarth, Jong-Seok Lee, Andrew Hill, Shahneen Sandhu, Liang Liang, Jingwen Shi, Yun Zhang, Yang Shi, Xiaopeng Ma, Xikun Wu, Zhirong Shen, Jayesh Desai. The combination of hyper-amplification and tumor mutational burden as a pan-cancer biomarker in patients treated with tislelizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB511.

Background: Functionally activated immune cells (ICs) in the tumor microenvironment (TME) are critical to antitumor efficacy. Here, we report association between ICs and the clinical efficacy of tislelizumab (TIS), an anti-programmed cell death protein 1 monoclonal antibody, by examining tumor tissues from various tumor types in three pooled Phase 1/2 studies (NCT02407990, NCT04068519, NCT04004221). Methods:Available baseline tumor tissues from patients (pts) with advanced solid tumors who received TIS were tested with either multiplex-immunohistochemistry (m-IHC) (n=67, Opal automation Multiplex IHC kit) or gene expression profile (n=629, HTG EdgeSeq Precision Immuno-Oncology Panel). High/low cell density/signature scores were defined per median score, respectively. Median overall survival (OS) was estimated by the Kaplan-Meier method and log rank test was used to compare survival curves between pts with different biomarker levels. Results: Pts with a high CD68 density (CD68Hi) (n=34) had a longer OS compared with pts who had a low CD68 density (n=33), with a median OS of 15.0 vs 10.4 months, p=0.11. A weak association was observed between survival and CD8 cell density. When the two cell types were combined as a composite biomarker, pts with high CD8 (CD8Hi) and CD68Hi showed the longest OS (Table). A consistent finding was confirmed in the gene expression population (Table). Further TME analysis revealed that pts with CD8Hi and CD68Hi signature showed most elevated CD8 T cell cytotoxicity (CD8A, GNLY, GZMA, GZMB), T cell trafficking (CXCL9, CXCL10, CCL4, CCL5), MHCI antigen presentation (TAP1, TAP2, HLA.A/B/C) signatures/genes, and enriched expression of pro-inflammatory macrophage polarization pathway (STAT1, SLAMF7/8, ISG15). Conclusion: Co-enrichment of CD8 T cells and macrophages were associated with survival benefit and an immune-activated TME in pts with various tumor types treated with TIS. This observation warrants further investigation. Association between ICs and the clinical efficacy of TIS m-IHC analysis CD8Hi/CD68 Hi (n=24) CD8 Hi/CD68Lo (n=10) CD8 Lo/CD68Hi (n=10) CD8 Lo/CD68Lo (n=23) Median OS, months (95% CI) 15.7 (8.5, NA) 5.1 (0.8, 10.8) 6.3 (1.8, NA) 11.2 (4.0, 17.6) Gene expression analysis CD8Hi/CD68 Hi (n=202) CD8 Hi/CD68Lo (n=113) CD8 Lo/CD68Hi (n=113) CD8 Lo/CD68Lo (n=201) Median OS, months (95% CI) 14.9 (11.2, 19.2) 11.1 (7.1, 13.5) 7.7 (5.6, 11.4) 9.8 (7.4, 11.6) p value* 0.00033 *p value obtained from log-rank test CI, confidence interval; Hi, high density; IC, immune cell; m-IHC, multiplex immunohistochemistry; Lo, low density; NA, not available; OS, overall survival; TIS, tislelizumab Citation Format: Wei Shen, Tengfei Liu, Yang Shi, Jingwen Shi, Dan Wang, Liang Liang, Silu Yang, Xiaopeng Ma, Wei Jin, Pei Zhang, Ruiqi Huang, Yun Zhang, Zhirong Shen. CD8 T cells and macrophage abundances associated with clinical benefit of tislelizumab in various tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB514.