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Androgen deprivation therapy (ADT) is the standard therapy for men with advanced prostate cancer (PCa). PCa often responds to ADT and enters a dormancy period, which can be recognized clinically as a minimal residual disease. However, the majority of these patients will eventually experience a relapse in the form of castration-resistant PCa with poor survival. Therefore, ADT-induced dormancy is a unique time window for treatment that can provide a cure. The study of this well-recognized phase of prostate cancer progression is largely hindered by the scarcity of appropriate clinical tissue and clinically relevant preclinical models. Here, we report the utility of unique and clinically relevant patient-derived xenograft models in the study of the intrinsic immune landscape of dormant PCa. Using data from RNA sequencing, we have reconstructed the immune evasion mechanisms that can be utilized by dormant PCa cells. Since dormant PCa cells need to evade the host immune surveillance for survival, our results provide a framework for further study and for devising immunomodulatory mechanisms that can eliminate dormant PCa cells.

Objective We explored the relationship between urinary incontinence (UI) and depression or anxiety. Methods We searched the Cochrane Library, Embase, and PubMed for articles on the association between depression, anxiety, and UI. We calculated pooled 95% confidence intervals (CIs) and odds ratios (ORs). Results Twelve articles (31,462 participants) were included. The UI group had significantly higher depression and anxiety levels than the non-UI group (OR = 1.73, 95%CI: 1.64–1.82, I 2 = 75.5%). In subgroup analysis, depression and anxiety were significantly higher in participants with UI than in those without UI (OR = 1.95, 95%CI: 1.82–2.10, I 2 = 64.3% and OR = 1.54, 95%CI: 1.43–1.65, I 2 = 59.2%, respectively). In subgroup analysis by age, participants with UI had significantly higher depression and anxiety, regardless of age, than the non-UI group (OR = 1.59, 95%CI: 1.29–1.95, I 2 = 59.1% and OR = 1.98, 95%CI: 1.62–2.43, I 2 = 75.5%, respectively). Conclusion Patients with UI had significantly higher depression and anxiety levels than those without UI. Depression and anxiety were higher in patients with UI than in those without UI, regardless of age. Larger sample sizes and more high-quality studies are needed to validate our findings.

Background and Objectives. Pain management following total hip arthroplasty (THA) has been widely investigated; however, the best effective method is yet to be determined. The aim of this prospective, placebo-controlled study was to evaluate the analgesic efficacy of ultrasound-guided QL3 block in patients undergoing THA. Methods. Eighty-eight patients undergoing THA were randomized to receive 0.33% ropivacaine (Group QLB, n = 44) or saline (Group Con, n = 44) for QL3 block. Spinal anesthesia was then performed. Pain intensity was assessed using the visual analog scale (0: no pain to 10: worst possible pain). The primary outcome was pain scores recorded at rest at 3, 6, 12, 24, 36, and 48 h and on standing and walking at 24, 36, and 48 h postoperatively. Secondary outcomes were analgesic consumption, side effects, the 10-meter walking speed on day 6, and patient satisfaction after surgery. Results. Postoperative pain intensity was significantly lower in Group QLB compared to Group Con at rest after 3, 6, 12, 24, 36, and 48 h (p

The study of candidemia in Chinese leukemia patients has been limited. This retrospective study aims to investigate the characteristics and prognostic factors of candidemia among leukemia patients in a Chinese chemotherapy center. From 2009 to 2015, 30 isolates of candidemia were detected in 19 patients with acute leukemia after chemotherapy. The overall incidence of candidemia was 2.12 episode per 1000 admissions. Candida tropicalis was the most common Candida species (n = 17; 89.5%), followed by Candida albicans (n = 2; 10.5%). The most common underlying disease was acute myeloid leukemia (94.7%) and induction chemotherapy phase was the most susceptible stage. The vast majority of candidal infections are endogenous rather than central venous catheter-related. The overall 30-day crude mortality rate was 31.6%. Neutrophil recovery (P = 0.000) and initiation of empiric antifungal treatment before first positive blood culture (P = 0.041) were associated with a significant improvement in overall survival. Although the incidence of candidaemia appears to be quite low in patients with leukemia submitted to intensive chemotherapy, its high mortality rate continues to be a crucial problem despite the availability of new effective antifungal drugs. Early diagnosis followed by rapid antifungal treatment remains the cornerstone of successful management. Catheter removal should be considered on an individual basis. The widespread use of newer antifungal agents as prophylaxis among patients with acute leukemia may result in a decreased candidemia incidence.

Abstract Development of neuroendocrine prostate cancer (NEPC) is emerging as a major problem in clinical management of advanced prostate cancer (PCa). As increasingly potent androgen receptor (AR)‐targeting antiandrogens are more widely used, PCa transdifferentiation into AR‐independent NEPC as a mechanism of treatment resistance becomes more common and precarious, since NEPC is a lethal PCa subtype urgently requiring effective therapy. Reprogrammed glucose metabolism of cancers, that is elevated aerobic glycolysis involving increased lactic acid production/secretion, plays a key role in multiple cancer‐promoting processes and has been implicated in therapeutics development. Here, we examined NEPC glucose metabolism using our unique panel of patient‐derived xenograft PCa models and patient tumors. By calculating metabolic pathway scores using gene expression data, we found that elevated glycolysis coupled to increased lactic acid production/secretion is an important metabolic feature of NEPC. Specific inhibition of expression of MCT4 (a plasma membrane lactic acid transporter) by antisense oligonucleotides led to reduced lactic acid secretion as well as reduced glucose metabolism and NEPC cell proliferation. Taken together, our results indicate that elevated glycolysis coupled to excessive MCT4‐mediated lactic acid secretion is clinically relevant and functionally important to NEPC. Inhibition of MCT4 expression appears to be a promising therapeutic strategy for NEPC.

Objective:To observe the after effect of electroacupuncture (EA) at Jiaji acupoint on the protein expression of P2X4, P2X7 receptors in chronic constriction injury (CCI) rats so as to explore the regularity of electroanalgesia in neuropathic pain.Methods:Twenty-four adult male Sprague Dawley (SD) rats were screened for thermal pain latency and randomly divided into blank group, model group, 1 hour after EA treatment group and 12 hours after EA treatment group, 6 rats in each group. The CCI models were established in the model group, 1 hour after EA treatment group and 12 hours after EA treatment group. The rats in the 1 hour after EA treatment group and 12 hours after EA treatment group were treated with EA at Jiaji acupoint on both sides for 20 minutes on the 7th day after modeling. Each group was redetermined with thermal pain latency after 7 days of modeling and before drawing materials. Spinal cord bulging and the protein expression of P2X4, P2X7 were detected by Western Blot.Results:Compared with the blank group, the thermal pain latency of the model group decreased significantly (PPP>0.05). The protein expression of P2X4, P2X7 level in the model group increased significantly (PPP>0.05).Conclusion:Electroanalgesia might decrease the thermal pain latency through the protein expression of P2X4, P2X7 receptors in CCI rats. The after effect can be extended for one hour or more than one hour, with a certain regularity of aging.

Abstract Racial and ethnic disparities in malignancies attract extensive attention. To investigate whether there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population, data from several prospective AML trials were retrospectively analyzed in this study. We found that there were more patients with core binding factor (CBF) leukemia in Eastern Asian cohorts and there were different CBF leukemia constitutions between them. The ratios of CBF leukemia are 27.7, 22.1, 21.1, and 23.4%, respectively, in our (ChiCTR-TRC-10001202), another Chinese, Korean, and Japanese Eastern Asian cohorts, which are significantly higher than those in ECOG1900, MRC AML15, UK NCRI AML17, HOVON/SAKK AML-42, and German AML2003 (15.5, 12.5, 9.3, 10.2, and 12%, respectively). And CBFbeta-MYH11 occurred more prevalently in HOVON/SAKK AML- 42 and ECOG1900 trials (50.0 and 54.3% of CBF leukemia, respectively) than in Chinese and Japanese trials (20.1 and 20.8%, respectively). The proportion of FLT3-ITD mutation is 11.2% in our cohort, which is lower than that in MRC AML15 and UK NCRI AML17 (24.6 and 17.9%, respectively). Even after excluding the age bias, there are still different incidence rates of mutation between Caucasian and Eastern Asian population. These data suggest that there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population.

In this paper, we propose a niching Pareto ant colony optimization (NPACO) algorithm to solve the bi-objective pathfinding problem. First, based on a planar navigable data model, three different searching area restricted methods are proposed and compared. In addition, a node simplification strategy is introduced to simplify nodes that exist in network branch loops, eliminating the redundant search time in the branch loops. Afterward, we propose the elitist ants and weakened strategy for an ACO to overcome the problem caused by the impact of accumulated pheromone on the suboptimal path and apply the strategy to a PACO for urban city pathfinding. Finally, the niching method is adopted to simultaneously locate and maintain multiple optimal solutions to increase search robustness. The experimental results show that the NPACO with a restricted and simplified search area returns a Pareto optimal solution set that is uniformly distributed along the Pareto frontier with low computational complexity.

Purpose: To evaluate the feasibility and safety of heads-up three-dimensional (3D) vision system for phacoemulsification and intraocular lens (IOL) implantation surgery. Methods: In this prospective, randomized controlled study, 20 eyes with age-related cataract received phacoemulsification and IOL implantation and were randomly divided into “heads-up” 3D vision group and conventional surgery group. Ocular and surgical parameters such as surgery time, pre and postoperative best-corrected visual acuity (BCVA), and corneal endothelial cells density were recorded and statistically analyzed. Results: The result showed significant postoperative improvement of BCVA in both groups. There was no difference in either mean surgery time or postoperative mean endothelial cell density between the 3D group and the conventional group. No major complication occurred during surgery in either group. Conclusion: The heads-up 3D vision system is suitable and safe for cataract phacoemulsification and IOL implantation. This technique can be of widespread use.

Objective:To analyze the reliability of"Practical Process Evaluation Scale"and further more to get the most relevant factors in class of traditional manipulation techniques.Methods:Students were assigned to different groups (three students in each group) in the class of traditional manipulation techniques about the"one-finger scrubbing". The operator scale, model scale and observer scale were designed respectively. In each section, three scales should be completed by three students in each group according to three different roles which was arranged before. This practice was continued for eight weeks, once a week.Results:The reliability analysis showed that the Cronbach's coefficient of operator scale was 0.891, the Cronbach's coefficient of model scale was 0.941, the Cronbach's coefficient of observer scale was 0.774, and the Cronbach's coefficient of total scale was 0.894. The data showed that these scales were high confidence, and have a high internal consistency. The scale factor analysis showed that the most relevant factors in class of traditional manipulation techniques were strength factor, mind factor and limbs factor.Conclusion:In the class of traditional manipulation techniques, "Practical Process Evaluation Scale"is a high-confidence scale, which could accord with the teaching rules of practical training and help to improve students'practical ability, and the most relevant factors should be paid attention to, so as to improve teaching quality effectively.

Objective:To observe the effect of DU1 acupoint on the expression of CypA-ERK1/2 pathway related proteins from the cerebellum of FMR1 gene knockout (KO) mice, so as to explore its mechanism.Methods:Identification of murine gene phenotype by polymerase chain reaction (PCR), and choosing a Fragile X-1(FMR1) deficiency in the KO mice with 28 days after birth, total 24 KO mice were randomly divided into blank group, DU1 acupoint group, DU1 acupoint group with blocking and non-acupoint group, with 6 mice in each group. The blank group was given grab action, the other groups were taken acupuncture intervention. The expression of the related proteins of cerebellar CypA, P-ERK1/2 and ERK1/2 was detected by Western blot method.Results:The expression of CypA in the DU1 acupoint group was significantly higher than that of the non-acupoint group and the blank group (PPP

Abstract Background The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria. Methods We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0. Results The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%). Conclusions Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients. However, acquired resistance to EGFR-TKIs is widely detected across the world, and the exact mechanisms have not been fully demonstrated until now. This study aimed to examine the role of miR-214 in the acquired resistance to erlotinib in NSCLC, and elucidate the underlying mechanisms. qRT-PCR assay detected higher miR-214 expression in the plasma of NSCLC patients with acquired EGFR-TKI resistance than prior to EGFR-TKI therapy, and in the generated erlotinib-resistant HCC827 (HCC827/ER) cells than in HCC827 cells. Bioinformatics analysis and dual-luciferase reporter assay indentified LHX6 as a direct target gene of miR-214, and LHX6 expression was detected to be down-regulated in erlotinib-resistant HCC827 cells. Transwell invasion assay revealed that overexpressing LHX6 reversed the increase in the invasive ability of HCC827 cells induced by miR-214 overexpression, and the CRISPR-Cas9 system-mediated LHX6 knockdown reversed the reduction in the invasion of erlotinib-resistant HCC827 cells caused by miR-214 down-regulation. The results of the present study demonstrate that down-regulation of miR-214 may reverse acquired resistance to erlotinib in NSCLC through mediating its direct target gene LHX6 expression.

Abstract Target-specific next-generation sequencing technology was used to analyze 112 genes in adult patients with acute lymphoblastic leukemia (ALL). This sequencing mainly focused on the specific mutational hotspots. Among the 121 patients, 93 patients were B-ALL (76.9%), and 28 patients (23.1%) were T-ALL. Of the 121 patients, 110 (90.9%) harbored at least one mutation. The five most frequently mutated genes in T-ALL are NOTCH1, JAK3, FBXW7, FAT1, and NRAS. In B-ALL, FAT1, SF1, CRLF2, TET2, and PTPN1 have higher incidence of mutations. Gene mutations are different between Ph+ALL and Ph−ALL patients. B-ALL patients with PTPN11 mutation and T-ALL patients with NOTCH1 and/or FBXW7 mutations showed better survival. But B-ALL with JAK1/JAK2 mutations showed worse survival. The results suggest that gene mutations exist in adult ALL patients universally, they are related with prognosis.

This study reports a 3D freeze-printing method that integrates inkjet printing and freeze casting to control both the microstructure and macroporosity via formation of ice microcrystals during printing. A viscous aqueous ink consisting of a molecular MoS2 precursor (ammonium thiomolybdate) mixed with graphene oxide (GO) nanosheets is used in the printing process. Post-treatments by freeze-drying and reductive thermal annealing convert the printed intermediate mixture into a hybrid structure consisting of MoS2 nanoparticles anchored on the surface of 2D rGO nanosheets in a macroporous framework, which is fully characterized with FESEM, TEM, XRD, Raman spectroscopy and TGA. The resulting hybrid MoS2-rGO aerogels are studied as anodes for sodium ion batteries. They present a high initial specific capacity over 429 mAh/g at C/3.3 rate in the potential range of 2.5–0.10 V (vs Na+/Na). The process involves both reversible 2 Na+ insertion and slow irreversible conversion of MoS2 to metallic Mo. At higher rates, the conversion reaction is suppressed and the electrode is dominated by fast Na+ intercalation with good stability. This demonstrates that the 3D printing technology can be used as a processing technique to control the materials properties for energy storage. Keywords: 3D printing, Hybrid MoS2/graphene aerogel, Freeze-casting, Sodium ion battery, Porous electrode materials

Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). Although HCV clearance has been improved by the advent of direct-acting antiviral agents (DAA), retrospective studies have shown that the risk of subsequent HCC, while considerably decreased compared with active HCV infection, persists after DAA regimens. However, either the mechanisms of how chronic HCV infection causes HCC or the factors responsible for HCC development after viral eradication in patients with DAA treatments remain elusive. We reported an in vitro model of chronic HCV infection and determined Wnt/β-catenin signaling activation due to the inhibition of GSK-3β activity via serine 9 phosphorylation (p-ser9-GSK-3β) leading to stable non-phosphorylated β-catenin. Immunohistochemical staining demonstrated the upregulation of both β-catenin and p-Ser9-GSK-3β in HCV-induced HCC tissues. Chronic HCV infection increased proliferation and colony-forming ability, but knockdown of β-catenin decreased proliferation and increased apoptosis. Unexpectedly, Wnt/β-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3β-mediated β-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/β-catenin signaling for HCV-infected patients.

Hepatitis C virus (HCV) infection promotes autophagic degradation of viral replicative intermediates for sustaining replication and spread. The excessive activation of autophagy can induce cell death and terminate infection without proper regulation. A prior publication from this laboratory showed that an adaptive cellular response to HCV microbial stress inhibits autophagy through beclin 1 degradation. The mechanisms of how secretory and degradative autophagy are regulated during persistent HCV infection is unknown. This study was performed to understand the mechanisms of viral persistence in the absence of degradative autophagy, which is essential for virus survival. Using HCV infection of a CD63-green fluorescence protein (CD63-GFP), labeled stable transfected Huh-7.5 cell, we found that autophagy induction at the early stage of HCV infection increased the degradation of CD63-GFP that favored virus replication. However, the late-stage of persistent HCV infection showed impaired autophagic degradation, leading to the accumulation of CD63-GFP. We found that impaired autophagic degradation promoted the release of extracellular vesicles and exosomes. The impact of blocking the release of extracellular vesicles (EVs) on virus survival was investigated in persistently infected cells and sub-genomic replicon cells. Our study illustrates that blocking EV and exosome release severely suppresses virus replication without effecting host cell viability. Furthermore, we found that blocking EV release triggers interferon lambda 1 secretion. These findings suggest that the release of EVs is an innate immune escape mechanism that promotes persistent HCV infection. We propose that inhibition of extracellular vesicle release can be explored as a potential antiviral strategy for the treatment of HCV and other emerging RNA viruses.

Prostate cancers (PCa) have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment. There is mounting evidence that PCas may undergo an ‘‘Epithelial Immune Cell-like Transition’’ (EIT) by expressing molecules conventionally associated with immune cells (e.g., a variety of cytokines/receptors, immune transcription factors, Ig motifs, and immune checkpoint molecules), which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment. Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development, thus leading to the development of novel immunotherapeutic approaches. Here, we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells, with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa. Furthermore, we summarize current advances in anti-immune checkpoint therapies, and provide perspectives on their potential applicability. Keywords: Prostate cancer, Immune checkpoint, Epithelial immune cell-like transition, Immune suppression, Immune therapy

Metformin, a first-line drug for type 2 diabetes mellitus (T2DM), has been found to reduce depressive symptoms in patients with comorbid depression and other diseases. However, it is largely unclear how metformin ameliorates depressive-like behaviors. Here, we used lipopolysaccharide (LPS) to induce depressive-like behaviors in mice and found that LPS-treated mice exhibited increased immobility in the forced swimming test (FST) and tail suspension test (TST), as well as increased glutamatergic transmission. Furthermore, metformin administration in the LPS-treated mice ameliorated depressive-like behaviors and elevated glutamatergic transmission. Our results suggest that metformin has antidepressant effects and can correct abnormal glutamatergic transmission, providing an insight into the underlying mechanism by which metformin acts against depression.

At present, traditional visual-based surveillance systems are becoming impractical, inefficient, and time-consuming. Automation-based surveillance systems appeared to overcome these limitations. However, the automatic systems have some challenges such as occlusion and retaining images smoothly and continuously. This research proposes a weighted resampling particle filter approach for human tracking to handle these challenges. The primary functions of the proposed system are human detection, human monitoring, and camera control. We used the codebook matching algorithm to define the human region as a target and track it, and we used the practical filter algorithm to follow and extract the target information. Consequently, the obtained information was used to configure the camera control. The experiments were tested in various environments to prove the stability and performance of the proposed system based on the active camera.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. It develops mainly via NE transdifferentiation of prostate adenocarcinoma in response to androgen receptor (AR)-inhibition therapy. The study of NEPC development has been hampered by a lack of clinically relevant models. We previously established a unique and first-in-field patient-derived xenograft (PDX) model of adenocarcinoma (LTL331)-to-NEPC (LTL331R) transdifferentiation. In this study, we applied conditional reprogramming (CR) culture to establish a LTL331 PDX-derived cancer cell line named LTL331_CR_Cell. These cells retain the same genomic mutations as the LTL331 parental tumor. They can be continuously propagated in vitro and can be genetically manipulated. Androgen deprivation treatment on LTL331_CR_Cells had no effect on cell proliferation. Transcriptomic analyses comparing the LTL331_CR_Cell to its parental tumor revealed a profound downregulation of the androgen response pathway and an upregulation of stem and basal cell marker genes. The transcriptome of LTL331_CR_Cells partially resembles that of post-castrated LTL331 xenografts in mice. Notably, when grafted under the renal capsules of male NOD/SCID mice, LTL331_CR_Cells spontaneously gave rise to NEPC tumors. This is evidenced by the histological expression of the NE marker CD56 and the loss of adenocarcinoma markers such as PSA. Transcriptomic analyses of the newly developed NEPC tumors further demonstrate marked enrichment of NEPC signature genes and loss of AR signaling genes. This study provides a novel research tool derived from a unique PDX model. It allows for the investigation of mechanisms underlying NEPC development by enabling gene manipulations ex vivo and subsequent functional evaluations in vivo.

Building extraction and change detection are two important tasks in the remote sensing domain. Change detection between airborne laser scanning data and photogrammetric data is vulnerable to dense matching errors, mis-alignment errors and data gaps. This paper proposes an unsupervised object-based method for integrated building extraction and change detection. Firstly, terrain, roofs and vegetation are extracted from the precise laser point cloud, based on “bottom-up” segmentation and clustering. Secondly, change detection is performed in an object-based bidirectional manner: Heightened buildings and demolished buildings are detected by taking the laser scanning data as reference, while newly-built buildings are detected by taking the dense matching data as reference. Experiments on two urban data sets demonstrate its effectiveness and robustness. The object-based change detection achieves a recall rate of 92.31% and a precision rate of 88.89% for the Rotterdam dataset; it achieves a recall rate of 85.71% and a precision rate of 100% for the Enschede dataset. It can not only extract unchanged building footprints, but also assign heightened or demolished labels to the changed buildings.

Targeted energy management and control is becoming an increasing concern in the building sector. Automatic analyses of thermal data, which minimize the subjectivity of the assessment and allow for large-scale inspections, are therefore of high interest. In this study, we propose an approach for a supervised extraction of façade openings (windows and doors) from photogrammetric 3D point clouds attributed to RGB and thermal infrared (TIR) information. The novelty of the proposed approach is in the combination of thermal information with other available characteristics of data for a classification performed directly in 3D space. Images acquired in visible and thermal infrared spectra serve as input data for the camera pose estimation and the reconstruction of 3D scene geometry. To investigate the relevance of different information types to the classification performance, a Random Forest algorithm is applied to various sets of computed features. The best feature combination is then used as an input for a Conditional Random Field that enables us to incorporate contextual information and consider the interaction between the points. The evaluation executed on a per-point level shows that the fusion of all available information types together with context consideration allows us to extract objects with 90% completeness and 95% correctness. A respective assessment executed on a per-object level shows 97% completeness and 88% accuracy.

Thermal imagery is widely used in various fields of remote sensing. In this study, a novel processing scheme is developed to process the data acquired by the oblique airborne photogrammetric system AOS-Tx8 consisting of four thermal cameras and four RGB cameras with the goal of large-scale area thermal attribute mapping. In order to merge 3D RGB data and 3D thermal data, registration is conducted in four steps: First, thermal and RGB point clouds are generated independently by applying structure from motion (SfM) photogrammetry to both the thermal and RGB imagery. Next, a coarse point cloud registration is performed by the support of georeferencing data (global positioning system, GPS). Subsequently, a fine point cloud registration is conducted by octree-based iterative closest point (ICP). Finally, three different texture mapping strategies are compared. Experimental results showed that the global image pose refinement outperforms the other two strategies at registration accuracy between thermal imagery and RGB point cloud. Potential building thermal leakages in large areas can be fast detected in the generated texture mapping results. Furthermore, a combination of the proposed workflow and the oblique airborne system allows for a detailed thermal analysis of building roofs and facades.

Malignant mesothelioma (MM) is a rare disease often associated with environmental exposure to asbestos and other erionite fibers. MM has a long latency period prior to manifestation and a poor prognosis. The survival post-diagnosis is often less than a year. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. Occupational exposure to asbestos, mining, and migration are reasons that we expect to continue to see growing incidence of mesothelioma in the coming decades. Despite improvements in survival achieved with multimodal therapies and cytoreductive surgeries, less morbid, more effective interventions are needed. Thus, identifying prognostic and predictive biomarkers for MM, and developing novel agents for targeted therapy, are key unmet needs in mesothelioma research and treatment. In this review, we discuss the evolution of pre-clinical model systems developed to study MM and emphasize the remarkable capability of patient-derived xenograft (PDX) MM models in expediting the pre-clinical development of novel therapeutic approaches. PDX disease model systems retain major characteristics of original malignancies with high fidelity, including molecular, histopathological and functional heterogeneities, and as such play major roles in translational research, drug development, and precision medicine.

In view of the difficulty to get mechanical characteristics of shale reservoirs, a quantitative evaluation method based on micro-indentation test technology was proposed to research the meso-mechanical properties of shale. Through micro-indentation test of shale outcrop samples from the Cambrian Longmaxi Formation in the Changning area, Sichuan Basin, the meso-mechanical properties of shale were analyzed, and the relationship between the macro-scale and meso-scale shale mechanical properties was evaluated. The analysis results of micro-indentation tests show that the mesoscopic elastic modulus and indentation hardness are heterogeneous in distribution. The comparison of macro and meso experiments shows that the statistical mean value of meso-elastic modulus is approximate to the value of the macro-elastic modulus. The relationship between composition and mechanical properties of shale was obtained based on the packing density model theory. The result shows that mesoscopic elastic modulus and indentation hardness increase nonlinearly with the increase of the packing density. Based on the hardness-packing density model, the reverse analysis of cohesion and friction angles shows that the mesoscopic value is slightly smaller than the macroscopic value. The micro-indentation test technology can evaluate shale meso-mechanical properties and predict the macro-mechanical properties effectively. Key words: shale, meso-mechanical property, micro-indentation test, elastic modulus, indentation hardness, strength parameters

More potent targeting of the androgen receptor (AR) in advanced prostate cancer is driving an increased incidence of neuroendocrine prostate cancer (NEPC), an aggressive and treatment-resistant AR-negative variant. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. We modeled the development of NEPC from conventional prostatic adenocarcinoma using a patient-derived xenograft and found that the placental gene PEG10 is de-repressed during the adaptive response to AR interference and subsequently highly upregulated in clinical NEPC. We found that the AR and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at distinct stages of NEPC development. In vitro, PEG10 promoted cell-cycle progression from G0/G1 in the context of TP53 loss and regulated Snail expression via TGF-β signaling to promote invasion. Taken together, these findings show the mechanistic relevance of RB1 and TP53 loss in NEPC and suggest PEG10 as a NEPC-specific target.