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The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Philadelphia chromosome (Ph) and is a hallmark of chronic myeloid leukemia (CML). In leukemia cells, Ph not only impairs the physiological signaling pathways but also disrupts genomic stability. This aberrant fusion gene encodes the breakpoint cluster region‐proto‐oncogene tyrosine‐protein kinase (BCR‐ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. The kinase activity is responsible for maintaining proliferation, inhibiting differentiation, and conferring resistance to cell death. During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase, the expression patterns of different BCR‐ABL1 transcripts vary. Each BCR‐ABL1 transcript is present in a distinct leukemia phenotype, which predicts both response to therapy and clinical outcome. Besides CML, the Ph is found in acute lymphoblastic leukemia, acute myeloid leukemia, and mixed‐phenotype acute leukemia. Here, we provide an overview of the clinical presentation and cellular biology of different phenotypes of Ph‐positive leukemia and highlight key findings regarding leukemogenesis.

Background and aimsThe goal of this study was to compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with targeted therapy and PD-(L)1 blockade (triple therapy), either sequentially (SE) or simultaneously (SI), in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC).Approach and resultsFrom January 1, 2018, to June 1, 2022, 575 patients with BCLC stage C HCC who underwent SE or SI triple therapy were retrospectively enrolled. Propensity score matching (PSM; 1:1) was performed to eliminate possible confounder imbalances across cohorts. We used the Kaplan–Meier method and a log-rank test to compare the overall survival (OS) and progression-free survival (PFS) rates between the SI and SE groups. The tumor response and the incidence of adverse events (AEs) were reported. After PSM, 182 patients in each of the two groups were matched. The median OS in the SI group was significantly longer than that in the SE group (28.8 vs. 16.1 months; P = 0.002), and the median PFS was significantly improved in the SI versus SE group (9.6 vs. 7.0 months; P = 0.01). The objective response rate based on the mRECIST was higher in the SI group (58% vs. 37%; P < 0.001). The total incidences of grade 3–4 AEs were 111/182 (60.9%) and 128/182 (70.3%) in the SE and SI groups, respectively. No grade 5 AEs were reported in either group.ConclusionsSimultaneous HAIC plus targeted therapy and PD-(L)1 blockade significantly improved outcomes compared to the sequential regimen in patients with BCLC stage C HCC, with no unexpected AEs.Clinical relevance statement.The patients who received hepatic arterial infusion chemotherapy combined with targeted therapy and PD-(L)1 blockade simultaneously have a better prognosis than those who received it sequentially.

(Cardot) N.P.Balakr. is a woody tree of the Rosaceae family. Interspecific hybridization is prevalent in , and the limited molecular data suggest that the taxonomic status requires further study. Therefore, we assembled and annotated the complete chloroplast genome of . The chloroplast genome of is 160,174 bp in length and consist of 106 genes, including 74 protein-coding genes, 4 rRNA genes and 28 tRNA genes. Phylogenetic analysis revealed that belongs to subg. . The report of the chloroplast genome of enriches genome data and serves as a reference for future classification and genetic diversity.

Objective: The data in regard of the clinical characteristics and diagnosis of somatic cough syndrome in adults were limited. The aim of this study was to fill that gap. Methods: This was a retrospective analysis of patients with somatic cough syndrome. We described clinical characteristics of adult patients with somatic cough syndrome. Results: Twenty-three somatic cough syndrome patients were identified in 543 adult patients with chronic cough. Psychiatric disorder of these patients was identified as anxiety (n = 8), obsessive-compulsive (n = 7), somatoform (n = 6), depression (n = 3), and cognitive bias (n = 1). Twelve patients showed abnormal results of investigations related with common causes of chronic cough, including gastroesophageal reflux, sputum eosinophilia, bronchial hyper-responsiveness, or signs of sinusitis but did not respond to the treatments directed to those conditions. All these patients were ever misdiagnosed as other causes of chronic cough. Compared to 520 non-somatic cough syndrome patients, patients with somatic cough syndrome were younger (32 (29.0–43.0) vs 42.0 (32.0–55.0) years, p = 0.013), longer disease duration (48.0 (19.5–102.0) vs 24.0 (9.0–72.0) months, p = 0.037), more common in dry cough (100% vs 57.6%, p < 0.001), and lower proportion of nocturnal cough (13.0% vs 40.2%, p = 0.009). Common cold (60.9%) was the most common initial trigger of cough and itchy throat (60.9%) was the most common accompanying symptom in patients with somatic cough syndrome. Notably, there were similar distribution in cough triggers and accompanying symptoms between two groups. Conclusion: In spite of much higher proportion of dry cough and smaller proportion of nocturnal cough, adult patients with somatic cough syndrome show similar clinical characteristics with other chronic cough patients, in regard of cough triggers, accompanying symptoms as well as abnormal results of investigations, which should be an important reason for misdiagnosis of somatic cough syndrome. Psychiatric disorder should be addressed in clinical management of chronic cough.

Background As an oncogene, long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) can promote tumor metastasis. Hyperexpression of MALAT1 has been observed in many malignant tumors, including hepatocellular carcinoma (HCC). However, the role and mechanism of MALAT1 in HCC remain unclear. Methods Thirty human HCC and paracancerous tissue specimens were collected, and the human hepatoma cell lines Huh7 and HepG2 were cultured according to standard methods. MALAT1 and Snail family zinc finger (Slug) expression were measured by real‐time PCR, immunohistochemistry, and western blotting. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay verified the direct interaction between miR‐124‐3p and Slug(SNAI2) or MALAT1. Wound healing and transwell assays were performed to examine invasion and migration, and a subcutaneous tumor model was established to measure tumor progression in vivo. Results MALAT1 expression was upregulated in HCC tissues and positively correlated with Slug expression. MALAT1 and miR‐124‐3p bind directly and reversibly to each other. MALAT1 silencing inhibited cell migration and invasion. miR‐124‐3p inhibited HCC metastasis by targeting Slug. Conclusions MALAT1 regulates Slug through miR‐124‐3p, affecting HCC cell metastasis. Thus, the MALAT1/miR‐124‐3p/Slug axis plays an important role in HCC. Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) regulates Slug through miR‐124‐3p, affecting cell migration and cell invasion. Thus, the MALAT1/miR‐124‐3p/Slug axis plays an important role in hepatocellular carcinoma.

In this paper, we define a new problem related to social media, namely, the data-driven engineering of social dynamics. More precisely, given a set of observations from the past, we aim at finding the best short-term intervention that can lead to predefined long-term outcomes. Toward this end, we propose a general formulation that covers two useful engineering tasks as special cases, namely, pattern matching and profit maximization. By incorporating a deep learning model, we derive a solution using convex relaxation and quadratic-programming transformation. Moreover, we propose a data-driven evaluation method in place of the expensive field experiments. Using a Twitter dataset, we demonstrate the effectiveness of our dynamics engineering approach for both pattern matching and profit maximization, and study the multifaceted interplay among several important factors of dynamics engineering, such as solution validity, pattern-matching accuracy, and intervention cost. Finally, the method we propose is general enough to work with multi-dimensional time series, so it can potentially be used in many other applications.

How closely related are two nodes in a graph? How to compute this score quickly, on huge, disk-resident, real graphs? Random walk with restart (RWR) provides a good relevance score between two nodes in a weighted graph, and it has been successfully used in numerous settings, like automatic captioning of images, generalizations to the “connection subgraphs”, personalized PageRank, and many more. However, the straightforward implementations of RWR do not scale for large graphs, requiring either quadratic space and cubic pre-computation time, or slow response time on queries. We propose fast solutions to this problem. The heart of our approach is to exploit two important properties shared by many real graphs: (a) linear correlations and (b) block-wise, community-like structure. We exploit the linearity by using low-rank matrix approximation, and the community structure by graph partitioning, followed by the Sherman–Morrison lemma for matrix inversion. Experimental results on the Corel image and the DBLP dabasets demonstrate that our proposed methods achieve significant savings over the straightforward implementations: they can save several orders of magnitude in pre-computation and storage cost, and they achieve up to 150 × speed up with 90%+ quality preservation.

Surgical simulators need to simulate deformation and cutting of deformable objects. Adaptive octree mesh based cutting methods embed the deformable objects into octree meshes that are recursively refined near the cutting tool trajectory. Deformation is only applied to the octree meshes; thus the deformation instability problem caused by degenerated elements is avoided. Biological tissues and organs usually contain complex internal structures that are ignored by previous work. In this paper the deformable objects are modeled as voxels connected by links and embedded inside adaptive octree meshes. Links swept by the cutting tool are disconnected and object surface meshes are reconstructed from disconnected links. Two novel methods for embedding triangular meshes as internal structures are proposed. The surface mesh embedding method is applicable to arbitrary triangular meshes, but these meshes have no physical properties. The material sub-region embedding method associates the interiors enclosed by the triangular meshes with physical properties, but requires that these meshes are watertight, and have no self-intersections, and their smallest features are larger than a voxel. Some local features are constructed in a pre-calculation stage to increase simulation performance. Simulation tests show that our methods can cut embedded structures in a way consistent with the cutting of the deformable objects. Cut fragments can also deform correctly along with the deformable objects.

Surgical simulators need to simulate deformation and cutting of deformable objects. Adaptive octree mesh based cutting methods embed the deformable objects into octree meshes that are recursively refined near the cutting tool trajectory. Deformation is only applied to the octree meshes;thus the deformation instability problem caused by degenerated elements is avoided. Biological tissues and organs usually contain complex internal structures that are ignored by previous work. In this paper the deformable objects are modeled as voxels connected by links and embedded inside adaptive octree meshes. Links swept by the cutting tool are disconnected and object surface meshes are reconstructed from disconnected links. Two novel methods for embedding triangular meshes as internal structures are proposed. The surface mesh embedding method is applicable to arbitrary triangular meshes, but these meshes have no physical properties. The material sub-region embedding method associates the interiors enclosed by the triangular meshes with physical properties, but requires that these meshes are watertight, and have no self-intersections, and their smallest features are larger than a voxel. Some local features are constructed in a pre-calculation stage to increase simulation performance. Simulation tests show that our methods can cut embedded structures in a way consistent with the cutting of the deformable objects. Cut fragments can also deform correctly along with the deformable objects.

Current applications have produced graphs on the order of hundreds of thousands of nodes and millions of edges. To take advantage of such graphs, one must be able to find patterns, outliers and communities. These tasks are better performed in an interactive environment, where human expertise can guide the process. For large graphs, though, there are some challenges: the excessive processing requirements are prohibitive, and drawing hundred-thousand nodes results in cluttered images hard to comprehend. To cope with these problems, we propose an innovative framework suited for any kind of tree-like graph visual design. GMine integrates (a) a representation for graphs organized as hierarchies of partitions - the concepts of SuperGraph and Graph-Tree; and (b) a graph summarization methodology - CEPS. Our graph representation deals with the problem of tracing the connection aspects of a graph hierarchy with sub linear complexity, allowing one to grasp the neighborhood of a single node or of a group of nodes in a single click. As a proof of concept, the visual environment of GMine is instantiated as a system in which large graphs can be investigated globally and locally.