Similarity search is an important function in many applications, which usually focuses on measuring the similarity between objects with the same type. However, in many scenarios, we need to measure the relatedness between objects with different types. With the surge of study on heterogeneous networks, the relevance measure on objects with different types becomes increasingly important. In this paper, we study the relevance search problem in heterogeneous networks, where the task is to measure the relatedness of heterogeneous objects (including objects with the same type or different types). A novel measure HeteSim is proposed, which has the following attributes: (1) a uniform measure: it can measure the relatedness of objects with the same or different types in a uniform framework; (2) a path-constrained measure: the relatedness of object pairs are defined based on the search path that connect two objects through following a sequence of node types; (3) a semi-metric measure: HeteSim has some good properties (e.g., self-maximum and symmetric), that are crucial to many data mining tasks. Moreover, we analyze the computation characteristics of HeteSim and propose the corresponding quick computation strategies. Empirical studies show that HeteSim can effectively and efficiently evaluate the relatedness of heterogeneous objects.

BaCKgRoUND aND aIMS: Cancer-associated fibroblasts (CAFs) are key players in multicellular, stromal-dependent alterations leading to HCC pathogenesis. However, the intricate crosstalk between CAFs and other components in the tumor microenvironment (TME) remains unclear. This study aimed to investigate the cellular crosstalk among CAFs, tumor cells, and tumor-associated neutrophils (TANs) during different stages of HCC pathogenesis. appRoaCH aND ReSUltS: In the HCC-TME, CAFderived cardiotrophin-like cytokine factor 1 (CLCF1) increased chemokine (C-X-C motif ) ligand 6 (CXCL6) and TGFβ secretion in tumor cells, which subsequently promoted tumor cell stemness in an autocrine manner and TAN infiltration and polarization in a paracrine manner. Moreover, CXCL6 and TGFβ secreted by HCC cells activated extracellular signal-regulated kinase (ERK) 1/2 signaling of CAFs to produce more CLCF1, thus forming a positive feedback loop to accelerate HCC progression. Inhibition of ERK1/2 or CLCF1/ciliary neurotrophic factor receptor signaling efficiently impaired CLCF1-mediated crosstalk among CAFs, tumor cells, and TANs both in vitro and in vivo. In clinical samples, up-regulation of the CLCF1−CXCL6/TGFβ axis exhibited a marked correlation with increased cancer stem cells, "N2"-polarized TANs, tumor stage, and poor prognosis. CoNClUSIoNS:This study reveals a cytokine-mediated cellular crosstalk and clinical network involving the CLCF1− CXCL6/TGFβ axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. These results may support the CLCF1 cascade as a potential prognostic biomarker and suggest that selective blockade of CLCF1/ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC. (Hepatology 2021;73:1717-1735. M ore than 80% of HCCs are characterized by extensive liver fibrosis caused by the activation, proliferation, and accumulation of fibroblasts. (1) A hallmark feature of the tumor microenvironment (TME) of HCC is the mass of cancer-associated fibroblasts (CAFs), which has been extensively reported to influence HCC progression. (1)

In the afternoon of 15 July 2007, a thunderstorm was initiated within a line of cumulus clouds which formed parallel to the crest of the Black Forest mountains during the Intensive Observation Period (IOP) 8b of the Convective and Orographicallyinduced Precipitation Study (COPS). This paper extends the analysis of processes that led to convection initiation (CI), i.e. the transition from shallow to deep convection, on this day with the data from several COPS instruments that have not been considered in previous studies. In particular, the boundary-layer structure, lids and the water-vapour field in the pre-convective environment of the event are discussed. For this purpose, we investigated measurements of water-vapour lidars, temperature lidars and wind lidars, profiles from radiosondes, in situ aircraft data and gridded data of weather stations as well as GPS integrated-water-vapour data and satellite imagery. Thermally driven circulation systems formed over both the Black Forest and the Vosges mountain ranges which resulted in local convergence zones. These superimposed with the large-scale convergence in the Black Forest area. In the presence of sufficient moisture and updraught, clouds formed close to the mountain crests. The related latent-heat release allowed larger thermals to be produced, which may have had a positive feedback on stabilizing these convergence zones as a whole. We believe that differences in the moisture field explain why convection remained shallow and sparse over the Vosges mountains because these differences were responsible for differences in convective inhibition (CIN). The stationary location of the convergence zone over the southern Black Forest was probably decisive for CI because it constantly transported sensible and latent heat into the area in which CI took place.

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Proliferating cell nuclear antigen (PCNA) is reported as a famous marker in various tumors. A couple of articles have been published about the clinical function of PCNA on cancer progression; however, these results are conflicting in some degree. Thus, it is crucial to perform a systematic review and meta-analysis to identify their real actions. Here, we took cervical cancer and glioma as example and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (95 % CIs). In the present study, the PCNA expression in cervical cancer and gliomas patients was both correlated with 5-year-overall survival (OS) (HR = 4.41, 95 % CI 2.71-7.17, p = 0.000; HR = 4.40, 95 % CI 3.00-6.47, p = 0.000; respectively). In addition, a fixed effect model revealed a significant association between PCNA and FIGO stage (OR = 4.48, 95 % CI 3.48-5.77, p = 0.000) or WHO grade (OR = 5.64, 95 % CI 4.15-7.68, p = 0.000), rather than age (OR = 1.01, 95 % CI 0.71-1.43, p = 0.957; OR = 1.00, 95 % CI 0.80-1.24, p = 0.989; respectively). No heterogeneity was observed across all studies. According to funnel plot, no publication bias was reported. In conclusion, our systematic review suggests that PCNA expression is significantly associated with poor 5-year survival, advanced stage or higher WHO grade, which might be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target in cervical cancer, gliomas, or even more cancers.

Adjuvant chemotherapy after surgery is the standard treatment modality for stage III and part of stage II or stage IV colorectal cancer (CRC) patients. However, the 5-year overall survival (OS) rate remains unsatisfactory. Thus, developing combination therapies is essential to improve the prognosis of patients with CRC. The present study aimed to determine the effect of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with CRC. 122 patients with CRC treated with postoperative adjuvant chemotherapy were retrospectively included in this study. Among them, 62 patients received adjuvant chemotherapy only (control group), while the other 60 patients, with similar demographic and clinical characteristics, received adjuvant chemotherapy and sequential CIK cell immunotherapy (CIK group). Survival analysis showed significantly improved disease free survival (DFS) and OS rates in the CIK group compared with the control group (log-rank test, P = .0024; P = .008, respectively). Univariate and multivariate analyses indicated that sequential CIK cell treatment was an independent prognostic factor for patients' DFS and OS. Subgroup analyses showed that sequential CIK cell treatment significantly improved the DFS and OS of patients with high-risk T4 stage and insufficient chemotherapy duration. In conclusion, these data indicate that sequential adjuvant CIK cell treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with CRC, particularly for patients with highrisk T4 stage and insufficient chemotherapy duration.

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