bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Analysis for the Reconstruction of Porous Media Using Multiple-Point Statistics
Authors: Xie Qing , Xu Jianping , Yuan Yuanda , Niu Cong
Published: October 2020

The pore structure reconstruction of the porous media is of great importance to the research of mechanisms of fluid flow in porous media. To capture the large-scale patterns in the pore space, the multiple-point statistical technique is generally adopted for porous media reconstruction. Commonly, two different schemes, i.e., the single-grid scheme and the multiple-grid scheme, can be applied for simulation realization. The selection between this two schemes and a proper data template size have thus become a new research issue, and the performance of the characteristic reproduction of the training image using this two schemes must be quantified. In this paper, a series of multiple-point statistics simulation basing on a 2D micro-CT sandstone image are proceeded using both single- and multiple-grid schemes, and different data templates are adapted for porous media reconstruction. Further, to quantify the impact of the computational schemes and setting of the data template to the simulation realizations, a number of measurements considering the pore diameter, porosity, connectivity, and permeability are implemented to fully analyze the results obtained. Results show that by using the single-point statistical method, a large template is necessary to reproduce large-scale structures. The multiple-grid template method may bring great benefits to simulation efficiency over the simple data template method, as well as the recovery of the pore long-range geometric features and seepage characteristics. With the extension of the template for the multiple-grid scheme, the simulation results show lack of variations to some extent.
Preventive Transhepatic Tract Embolisation after Percutaneous Biliary Interventions: A Systematic Review
Authors: Schmitz Daniel , Chang De-Hua , Rudi Jochen , Hetjens Svetlana , Ebert Matthias P. A.
Published: October 2020

Preventive transhepatic tract embolisation (PTTE) after percutaneous biliary intervention (PBI) may reduce adverse events. The aim of this systematic review was to analyse feasibility, safety, and efficacy of PTTE with different embolic agents. A systematic literature research was performed according to the PRISMA guidelines. The identified studies were analysed concerning study quality, number of cases, indication, embolic agent, embolisation technique, success, and embolisation-related adverse events. Out of 62 identified records, 7 studies of mainly moderate study quality published through 2019 were included for further analysis. Cyanoacrylate (n = 4), gelatin sponge (n = 2), and coils (n = 1) were used as embolic agents in a total number of 314 patients. Technical success was 96–100%. Embolisation-related adverse events (glue migration, pain) occurred in 10/314 (3.2%) patients. Reduction of PBI-related pain was approved by one controlled study; haemorrhage events were reduced but not clearly significant. Overall, biliary leak, transhepatic bleeding, and PBI-related pain occurred in 7/201 (3.5%), 1/293 (0.3%), and 17/46 (36.9%) documented patients after PTTE. Adverse events which likely could not have been prevented by PTTE occurred in 23/180 (12.8%) patients. Embolic agents were not compared. In conclusion, PTTE is feasible and safe. It is effective concerning the prevention of PBI-related pain, and it may be effective concerning haemorrhage. Prevention of biliary leak is not proven. It remains unclear which embolic agent should be preferred. A prospective randomised trial including all preventable adverse events is lacking.
A Review of the Engineering Properties of Metakaolin Based Concrete: Towards Combatting Chloride Attack in Coastal/Marine Structures
Authors: Pillay Deveshan L. , Olalusi Oladimeji B. , Awoyera Paul O. , Rondon Carlos , Echeverría Ana María , Kolawole John Temitope
Published: October 2020

Changing human lifestyle and increasing urbanisation are contributory factors to the high demand for concrete construction materials across the globe. With the imminent developments in the unpopulated marine/coastal zones, higher installation of concrete facilities is still expected. However, poor design and construction procedures coupled with inadequate materials selection and exposure to aggressive environmental conditions, such as chloride laden environments, often result in the reduced aesthetic and structural performance of concrete. Deterioration of reinforced concrete structures located in a coastal/marine setting can influence the safety, economic, and sustainability aspects of society. Hence, there is an increased need for alternate binder systems with the ability to reduce the effects of chloride attack in concrete. This paper presents a critical review of the engineering properties of metakaolin (MK) based concrete exposed to chloride attack. The key advantages and limitations of using MK for concrete production purposes were outlined and evaluated. Areas for future research were also highlighted in this paper. Based on the favourable 28‐day compressive strength (73–84 MPa) and durability performance documented across the numerous past year studies that were reviewed, it can be concluded that MK is a viable alternate binder material for combatting chloride attack in coastal/marine concrete structures. This, in conjunction with its lack of chemical CO2 emissions, proves that MK can be used to improve the serviceability and sustainability states of marine structures. The viewpoint of this review will guide concrete constructors and researchers on a possible framework for the utilisation of metakaolin for enhancing durability concrete in aggressive environments.
Superpixel Spectral Unmixing for Hyperspectral Image Superresolution Using a Coupled Encoder-Decoder Network
Authors: Zhang Shao-lei , Fu Guang-yuan , Wang Hong-qiao , Zhao Yu-qing
Published: October 2020

In this paper, we propose a novel hyperspectral image superresolution method based on superpixel spectral unmixing using a coupled encoder-decoder network. The hyperspectral image and multispectral images are fused to generate high-resolution hyperspectral images through the spectral unmixing framework with low-rank constraint. Specifically, the endmember and abundance information is extracted via a coupled encoder-decoder network integrating the priori for unmixing. The coupled network consists of two encoders and one shared decoder, where spectral information is preserved through the encoder. The multispectral image is clustered into superpixels to explore self-similarity, and then, the superpixels are unmixed to obtain an abundance matrix. By imposing a low-rank constraint on the abundance matrix, we further improve the superresolution performance. Experiments on the CAVE and Harvard datasets indicate that our superresolution method outperforms the other compared methods in terms of quantitative evaluation and visual quality.
New Application Task Offloading Algorithms for Edge, Fog, and Cloud Computing Paradigms
Authors: Kim Sungwook
Published: October 2020

In the last few years, we have seen an exponential increase in the number of computation-intensive applications, which have resulted in the popularity of fog and cloud computing paradigms among smart-chip-embedded mobile devices. These devices can partially offload computation tasks either using the fog system or using the cloud system. In this study, we design a new task offloading scheme by considering the challenges of future edge, fog and cloud computing paradigms. To provide an effective solution toward an appropriate task offloading problem, we focus on two cooperative bargaining game solutions—Tempered Aspirations Bargaining Solution (TABS) and Gupta-Livne Bargaining Solution (GLBS). To maximize the application service quality, a proper bargaining solution should be properly selected. In the proposed scheme, the TABS method is used for time-sensitive offloading services, and the GLBS method is applied to ensure computation-oriented offloading services. The primary advantage of our bargaining-based approach is to provide an axiom-based strategic solution for the task offloading problem while dynamically responding to the current network environments. Extensive simulation studies are conducted to demonstrate the effectiveness of the proposed scheme, and the superior performance over existing schemes is observed. Finally, we show prime directions for future work and potential research issues.
Open-Ended Coaxial Cable Selection for Measurement of Liquid Dielectric Properties via the Reflection Method
Authors: Wang Jingchen , Lim Eng Gee , Leach Mark Paul , Wang Zhao , Man Ka Lok
Published: October 2020

An open-ended coaxial cable is used to measure the dielectric properties of lossy liquid. The method which is based on the measurement of the reflection coefficient of the open-ended cable makes it easy to operate and postprocess. To meet the accuracy requirements, the dimensions of the coaxial cable need to be taken into consideration; therefore, it is necessary to select an appropriate coaxial cable for the measurement. This paper investigates the influence of cable dimensions on dielectric measurement accuracy. With careful choice of the coaxial cable, the relative error of calculated results can be less than 0.1%.
Numerical Simulation and Symmetry Reduction of a Two-Component Reaction-Diffusion System
Authors: Li Jina , Ji Xuehui
Published: October 2020

In this paper, the symmetry classification and symmetry reduction of a two-component reaction-diffusion system are investigated, the reaction-diffusion system can be reduced to system of ordinary differential equations, and the solutions and numerical simulation will be showed by examples.
Nonlinear Noise Compensation in an Integration System of Fiber-Wireless Communication and Free Space Optical Communication
Authors: Chen Long , Liu Miao , Tang Zhijun
Published: October 2020

We propose and experiment an integration system of fiber-wireless communication and free space optical (FSO) communication based on nonlinear noise compensation. This integration system, combining the benefits of FSO communication and high-frequency wireless communication, as well as the high-frequency efficiency and anti-interference to multipath fading of the multicarriers orthogonal frequency division multiplexing (OFDM) modulation, can increase the capacity and flexibility of the system. The nonlinear equalizer is employed to compensate the distortion caused by the beating between OFDM signal subcarriers in the combination system. Up to 1-Gbaud 16QAM discrete multitone (DMT) OFDM signal can be first transmitted over the distance of 100-m single-mode fiber (SMF), then delivered over the distance of 100-m FSO link, and finally, transmitted over the distance of 4 m wireless. The bit-error-ratio (BER) of the OFDM signal in the integration system can be less than the hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10−3. The experiment shows that the nonlinear equalizer can work well compatible with the combination system and can improve the transmission performance by 0.7-dB receiving sensitivity in the combination system.
Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma
Authors: Turner Joel G. , Cui Yan , Bauer Alexis A. , Dawson Jana L. , Gomez Juan A. , Kim Jongphil , Cubitt Christopher L. , Nishihori Taiga , Dalton William S. , Sullivan Daniel M.
Published: October 2020

High-dose chemotherapy with melphalan followed by autologous transplantation is a first-line treatment for multiple myeloma. Here, we present preclinical evidence that this treatment may be significantly improved by the addition of exportin 1 inhibitors (XPO1i). The XPO1i selinexor, eltanexor, and KOS-2464 sensitized human multiple myeloma cells to melphalan. Human 8226 and U266 multiple myeloma cell lines and melphalan-resistant cell lines (8226-LR5 and U266-LR6) were highly sensitized to melphalan by XPO1i. Multiple myeloma cells from newly diagnosed and relapsed/refractory multiple myeloma patients were also sensitized by XPO1i to melphalan. In NOD/SCIDγ mice challenged with either parental 8226 or U266 multiple myeloma and melphalan-resistant multiple myeloma tumors, XPO1i/melphalan combination treatments demonstrated stronger synergistic antitumor effects than single-agent melphalan with minimal toxicity. Synergistic cell death resulted from increased XPO1i/melphalan-induced DNA damage in a dose-dependent manner and decreased DNA repair. In addition, repair of melphalan-induced DNA damage was inhibited by selinexor, which decreased melphalan-induced monoubiquitination of FANCD2 in multiple myeloma cells. Knockdown of FANCD2 was found to replicate the effect of selinexor when used with melphalan, increasing DNA damage (γH2AX) by inhibiting DNA repair. Thus, combination therapies that include selinexor or eltanexor with melphalan may have the potential to improve treatment outcomes of multiple myeloma in melphalan-resistant and newly diagnosed patients. The combination of selinexor and melphalan is currently being investigated in the context of high-dose chemotherapy and autologous transplant (NCT02780609).

Significance:

Inhibition of exportin 1 with selinexor synergistically sensitizes human multiple myeloma to melphalan by inhibiting Fanconi anemia pathway-mediated DNA repair.
Inhibition of IL1β by Canakinumab May Be Effective against Diverse Molecular Subtypes of Lung Cancer: An Exploratory Analysis of the CANTOS Trial
Authors: Wong Connie C. , Baum Jason , Silvestro Angela , Beste Michael T. , Bharani-Dharan Bharani , Xu Siyan , Wang Ying A. , Wang Xiaoshan , Prescott Margaret F. , Krajkovich Lynne , Dugan Margaret , Ridker Paul M. , Martin Anne-Marie , Svensson Eric C.
Published: October 2020

In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), inhibition of the IL1β inflammatory pathway by canakinumab has been shown to significantly reduce lung cancer incidence and mortality. Here we performed molecular characterization of CANTOS patients who developed lung cancer during the study, including circulating tumor DNA (ctDNA) and soluble inflammatory biomarker analysis. Catalogue of Somatic Mutations in Cancer (COSMIC) database ctDNA mutations were detected in 65% (46/71) of the CANTOS patients with lung cancer, with 51% (36/71) having detectable ctDNA at the time point closest to lung cancer diagnosis and 43% (29/67) having detectable ctDNA at trial randomization. Mutations commonly found in lung cancer were observed with no evidence of enrichment in any mutation following canakinumab treatment. Median time to lung cancer diagnosis in patients with (n = 29) versus without (n = 38) detectable COSMIC ctDNA mutations at baseline was 407 days versus 837 days (P = 0.011). For serum inflammatory biomarker analysis, circulating levels of C-reactive protein (CRP), IL6, IL18, IL1 receptor antagonist, TNFα, leptin, adiponectin, fibrinogen, and plasminogen activator inhibitor-1 were determined. Patients with the highest level of baseline CRP or IL6, both downstream of IL1β signaling, trended toward a shorter time to lung cancer diagnosis. Other inflammation markers outside of the IL1β pathway at baseline did not trend with time to lung cancer diagnosis. These results provide further evidence for the importance of IL1β-mediated protumor inflammation in lung cancer and suggest canakinumab's effect may be mediated in part by delaying disease progression of diverse molecular subtypes of lung cancer.

Significance:

These findings suggest that targeting the IL1β inflammatory pathway might be critical in reducing tumor-promoting inflammation and lung cancer incidence.
A Global and Integrated Analysis of CINSARC-Associated Genetic Defects
Authors: Lesluyes Tom , Chibon Frédéric
Published: October 2020

The Complexity Index in Sarcomas (CINSARC) signature is a transcriptomic marker that identifies high-risk soft-tissue sarcomas and is associated with high metastatic potential. During the last decade, CINSARC has been successfully developed and validated and is currently being assessed in two prospective phase III clinical trials for stratification of therapy. Although the link between CINSARC expression and tumor aggressiveness is well established, questions remain about how CINSARC genes are regulated. In this study, we leveraged a The Cancer Genome Atlas multiomics study on sarcomas with complex genetics to appraise the association between CINSARC profile, genomic features, and two potential regulation mechanisms, DNA methylation and miRNA expression. CINSARC expression was associated with an increase of ploidy, intratumor heterogeneity, copy-number alteration, altered expression of 37 miRNAs, and a decrease of DNA methylation. These genetic changes are not independent, but rather act together to promote or repress CINSARC expression. These findings depict new insights into CINSARC regulation.

Significance:

These findings demonstrate that CINSARC is associated with a variety of genomic aberrations that contribute to higher risk for metastasis and may serve as a prognostic factor in sarcomas and beyond.
Field Carcinogenesis in Cancer Evolution: What the Cell Is Going On?
Authors: Sinjab Ansam , Han Guangchun , Wang Linghua , Kadara Humam
Published: October 2020

Field carcinogenesis describes the prevalence of tumor-related alterations in normal appearing tissues. Here, we summarize recent efforts in profiling molecular field dynamics for resolving early events in cancer evolution. We also highlight gaps in our knowledge of the molecular and cellular heterogeneity of field carcinogenesis and propose directions to tackle these voids using single-cell–based approaches and unique tissue sampling models. By interrogating both the mutagenized epithelium and its microenvironment, we surmise that single-cell–guided studies will help chart the spatiotemporal molecular and cellular “atlas” of field carcinogenesis, will further delineate preneoplastic initiation and progression, and will help identify cancer prevention and early intervention targets.
Fibroblast-Derived IL33 Facilitates Breast Cancer Metastasis by Modifying the Immune Microenvironment and Driving Type 2 Immunity
Authors: Shani Ophir , Vorobyov Tatiana , Monteran Lea , Lavie Dor , Cohen Noam , Raz Yael , Tsarfaty Galia , Avivi Camila , Barshack Iris , Erez Neta
Published: October 2020

Lungs are one of the main sites of breast cancer metastasis. The metastatic microenvironment is essential to facilitate growth of disseminated tumor cells. Cancer-associated fibroblasts (CAF) are prominent players in the microenvironment of breast cancer. However, their role in the formation of a permissive metastatic niche is unresolved. Here we show that IL33 is upregulated in metastases-associated fibroblasts in mouse models of spontaneous breast cancer metastasis and in patients with breast cancer with lung metastasis. Upregulation of IL33 instigated type 2 inflammation in the metastatic microenvironment and mediated recruitment of eosinophils, neutrophils, and inflammatory monocytes to lung metastases. Importantly, targeting of IL33 in vivo resulted in inhibition of lung metastasis and significant attenuation of immune cell recruitment and type 2 immunity. These findings demonstrate a key function of IL33 in facilitating lung metastatic relapse by modulating the immune microenvironment. Our study shows a novel interaction axis between CAF and immune cells and reveals the central role of CAF in establishing a hospitable inflammatory niche in lung metastasis.

Significance:

This study elucidates a novel role for fibroblast-derived IL33 in facilitating breast cancer lung metastasis by modifying the immune microenvironment at the metastatic niche toward type 2 inflammation.
Sequential Prostate Magnetic Resonance Imaging in Newly Diagnosed High-risk Prostate Cancer Treated with Neoadjuvant Enzalutamide is Predictive of Therapeutic Response
Authors: Karzai Fatima , Walker Stephanie M. , Wilkinson Scott , Madan Ravi A. , Shih Joanna H. , Merino Maria J. , Harmon Stephanie A. , VanderWeele David J. , Cordes Lisa M. , Carrabba Nicole V. , Bright John R. , Terrigino Nicolas T. , Chun Guinevere , Bilusic Marijo , Couvillon Anna , Hankin Amy , Williams Monique N. , Lis Rosina T. , Ye Huihui , Choyke Peter L. , Gulley James L. , Sowalsky Adam G. , Turkbey Baris , Pinto Peter A. , Dahut William L.
Published: October 2020

Purpose:

For high-risk prostate cancer, standard treatment options include radical prostatectomy (RP) or radiotherapy plus androgen deprivation therapy (ADT). Despite definitive therapy, many patients will have disease recurrence. Imaging has the potential to better define characteristics of response and resistance. In this study, we evaluated prostate multiparametric MRI (mpMRI) before and after neoadjuvant enzalutamide plus ADT.

Patients and Methods:

Men with localized intermediate- or high-risk prostate cancer underwent a baseline mpMRI and mpMRI-targeted biopsy followed by a second mpMRI after 6 months of enzalutamide and ADT prior to RP. Specimens were sectioned in the same plane as mpMRI using patient-specific 3D-printed molds to permit mpMRI-targeted biopsies to be compared with the same lesion from the RP. Specimens were analyzed for imaging and histologic correlates of response.

Results:

Of 39 patients enrolled, 36 completed imaging and RP. Most patients (92%) had high-risk disease. Fifty-eight lesions were detected on baseline mpMRI, of which 40 (69%) remained measurable at 6-month follow-up imaging. Fifty-five of 59 lesions (93%) demonstrated >50% volume reduction on posttreatment mpMRI. Three of 59 lesions (5%) demonstrated growth in size at follow-up imaging, with two lesions increasing more than 3-fold in volume. On whole-mount pathology, 15 patients demonstrated minimal residual disease (MRD) of <0.05 cc or pathologic complete response. Low initial mpMRI relative tumor burden was most predictive of MRD on final pathology.

Conclusions:

Low relative lesion volume at baseline mpMRI was predictive of pathologic response. A subset of patients had limited response. Selection of patients based on these metrics may improve outcomes in high-risk disease.
A Space–Time Continuum for Immunotherapy Biomarkers in Gastroesophageal Cancer?
Authors: Klempner Samuel J. , Upadhyay Vivek , Chao Joseph
Published: October 2020

In an annotated series of gastroesophageal adenocarcinomas differences in PD-L1 expression and tumor mutation burden occur between both paired contemporaneous primary and metastatic biopsies and pre/posttreatment samples. This work has implications for optimizing patient selection, serial testing, need for mechanistic understanding, and may underlie variable responses to checkpoint inhibitors in gastroesophageal cancers.

See related article by Zhou et al., p. 6453
Inhibition of EZH2 Enhances the Antitumor Efficacy of Metformin in Prostate Cancer
Authors: Kong Yifan , Zhang Yanquan , Mao Fengyi , Zhang Zhuangzhuang , Li Zhiguo , Wang Ruixin , Liu Jinghui , Liu Xiaoqi
Published: October 2020

Upregulation of EZH2 is associated with advanced stage and poor prognosis of prostate cancer; therefore, it is likely to be a promising therapeutic target. Metformin, a drug that has been used to treat type 2 diabetes, was found to have antineoplastic activity in different cancers. Herein, we report that the combination of metformin and the EZH2 inhibitor GSK126 exerts synergistic inhibition on prostate cancer cell growth, both in vitro and in vivo. Mechanistically, we identify that metformin can reduce EZH2 expression through upregulating miR-26a-5p, which is antagonized by androgen receptor (AR). Furthermore, we show that AR binds to the promoter of miR-26a-5p and suppresses its transcription. Although metformin can remove AR from the miR-26a-5p promoter, the interaction between AR and EZH2, which usually exists in androgen-refractory prostate cancer cells, strongly impedes the removal. However, GSK126 can inhibit the methyltransferase-dependent interaction between AR and EZH2, thus restoring metformin's efficacy in androgen-refractory prostate cancer cells. Collectively, our finding suggests that the combination of metformin and GSK126 would be an effective approach for future prostate cancer therapy, and particularly effective for AR-positive castration-resistant prostate cancer.
Assessment of and Interventions for Women at High Risk for Breast or Ovarian Cancer: A Survey of Primary Care Physicians
Authors: Samimi Goli , Heckman-Stoddard Brandy M. , Holmberg Christine , Tennant Bethany , Sheppard Bonny Bloodgood , Coa Kisha I. , Kay Shelley S. , Ford Leslie G. , Szabo Eva , Minasian Lori M.
Published: October 2020

As clinical guidelines for cancer prevention refer individuals to primary care physicians (PCP) for risk assessment and clinical management, PCPs may be expected to play an increasing role in cancer prevention. It is crucial that PCPs are adequately supported to assess an individual’s cancer risk and make appropriate recommendations. The objective of this study is to assess use, familiarity, attitude, and behaviors of PCPs regarding breast and ovarian cancer risk and prevention, to better understand the factors that influence their prescribing behaviors. We conducted a cross-sectional, web-based survey of PCPs in the United States, recruited from an opt-in healthcare provider panel. Invitations were sent in batches until the target sample size of 750 respondents (250 each for obstetrics/gynecology, internal medicine, and family medicine) was met. Self-reported use of breast/ovarian cancer risk assessments was low (34.7%–59.2%) compared with discussion of cancer family history (96.9%), breast exams (87.1%), and mammograms (92.8%). Although most respondents (48.0%–66.8%) were familiar with cancer prevention interventions, respondents who reported to be less familiar were more likely to report cautious attitudes. When presented with hypothetical cases depicting patients at different breast/ovarian cancer risks, up to 34.0% of respondents did not select any of the clinically recommended course(s) of action. This survey suggests that PCP use of breast/ovarian cancer risk assessment tools and ability to translate the perceived risks to clinical actions is variable. Improving implementation of cancer risk assessment and clinical management guidelines within primary care may be necessary to improve the appropriate prescribing of cancer prevention interventions.

Prevention Relevance: Primary care physicians are becoming more involved in cancer prevention management, so it is important that cancer risk assessment and medical society guideline recommendations for cancer prevention are better integrated into primary care to improve appropriate prescribing of cancer prevention interventions and help reduce cancer risk.
Immune Remodeling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection
Authors: Pires Ana , Greenshields-Watson Alexander , Jones Emma , Smart Kathryn , Lauder Sarah N. , Somerville Michelle , Milutinovic Stefan , Kendrick Howard , Hindley James P. , French Rhiannon , Smalley Matthew J. , Watkins William J. , Andrews Robert , Godkin Andrew , Gallimore Awen
Published: October 2020

The nature of the tumor microenvironment (TME) influences the ability of tumor-specific T cells to control tumor growth. In this study, we performed an unbiased comparison of the TME of regulatory T-cell (Treg)–replete and Treg-depleted carcinogen-induced tumors, including Treg-depleted responding (regressing) and non-responding (growing) tumors. This analysis revealed an inverse relationship between extracellular matrix (ECM) and T-cell infiltrates where responding tumors were T-cell rich and ECM poor, whereas the converse was observed in non-responder tumors. For this reason, we hypothesized that the ECM acted as a barrier to successful T-cell infiltration and tumor rejection. However, further experiments revealed that this was not the case but instead showed that an effective T-cell response dramatically altered the density of ECM in the TME. Along with loss of ECM and high numbers of infiltrating T cells, responder tumors were distinguished by the development of lymphatic and blood vessel networks with specialized immune function. ECM-rich tumors exhibited a stem cell–like gene expression profile and superior tumor-initiating capacity, whereas such features were absent in responder tumors. Overall, these findings define an extended role for an effective immune response, not just in direct killing of tumor cells but in widescale remodeling of the TME to favor loss of ECM, elimination of cancer stem cells, and propagation of adaptive immunity.
The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment
Authors: Väyrynen Juha P. , Haruki Koichiro , Lau Mai Chan , Väyrynen Sara A. , Zhong Rong , Dias Costa Andressa , Borowsky Jennifer , Zhao Melissa , Fujiyoshi Kenji , Arima Kota , Twombly Tyler S. , Kishikawa Junko , Gu Simeng , Aminmozaffari Saina , Shi Shanshan , Baba Yoshifumi , Akimoto Naohiko , Ugai Tomotaka , Da Silva Annacarolina , Guerriero Jennifer L. , Song Mingyang , Wu Kana , Chan Andrew T. , Nishihara Reiko , Fuchs Charles S. , Meyerhardt Jeffrey A. , Giannakis Marios , Ogino Shuji , Nowak Jonathan A.
Published: October 2020

Macrophages are among the most common cells in the colorectal cancer microenvironment, but their prognostic significance is incompletely understood. Using multiplexed immunofluorescence for CD68, CD86, IRF5, MAF, MRC1 (CD206), and KRT (cytokeratins) combined with digital image analysis and machine learning, we assessed the polarization spectrum of tumor-associated macrophages in 931 colorectal carcinomas. We then applied Cox proportional hazards regression to assess prognostic survival associations of intraepithelial and stromal densities of M1-like and M2-like macrophages while controlling for potential confounders, including stage and microsatellite instability status. We found that high tumor stromal density of M2-like macrophages was associated with worse cancer-specific survival, whereas tumor stromal density of M1-like macrophages was not significantly associated with better cancer-specific survival. High M1:M2 density ratio in tumor stroma was associated with better cancer-specific survival. Overall macrophage densities in tumor intraepithelial or stromal regions were not prognostic. These findings suggested that macrophage polarization state, rather than their overall density, was associated with cancer-specific survival, with M1- and M2-like macrophage phenotypes exhibiting distinct prognostic roles. These results highlight the utility of a multimarker strategy to assess the macrophage polarization at single-cell resolution within the tumor microenvironment.
Precision Therapy of Pancreatic Cancer: From Bench to Bedside
Authors: Ciecielski Katrin Jana , Berninger Alexandra , Algül Hana
Published: October 2020

Background: Pancreatic ductal adenocarcinoma (PDAC), with a mortality rate of 94% and a 5-year-survival rate of only 8%, is one of the deadliest cancer entities worldwide, and early diagnostic methods as well as effective therapies are urgently needed. Summary: This review summarizes current clinical procedure and recent developments of oncological therapy in the palliative setting of metastatic PDAC. It further gives examples of successful, as well as failed, targeted therapy approaches and finally discusses promising ongoing research into the decade-old question of the “undruggability” of KRAS. Key Messages: Bench-driven concepts change the clinical landscape from “one size fits all” towards precision medicine. With growing insight into the molecular mechanisms of pancreatic cancer the era of targeted therapy in PDAC is gaining a new momentum.
LncRNA MALAT1 Promotes STAT3-Mediated Endothelial Inflammation by Counteracting the Function of miR-590
Authors: Zhou Qing , Run Qi , Li Chen-Yu , Xiong Xiang-Yu , Wu Xiao-Lin
Published: October 2020

The excessive production of inflammatory mediators by vascular endothelial cells (ECs) greatly contributes to the development of atherosclerosis. In this study, we explored the potential effect of lncRNA MALAT1 on endothelial inflammation. First, the EC inflammation model was constructed by treating human umbilical vein ECs (HUVECs) and human coronary artery ECs (HCAECs) with oxidized low-density lipoprotein (ox-LDL), which confirmed the role of MALAT1 in the inflammatory activity. Then MALAT1 was overexpressed in HUVECs and HCAECs, and the levels of inflammatory mediators and nitric oxide (NO) were examined by Western blotting, ELISA, and NO detection assay. The migration ability was confirmed by wound healing assay. The interactions among MALAT1, miR-590, and STAT3 were predicted by bioinformatics analysis and verified by qRT-PCR, Western blotting, or dual-luciferase reporter assay. MALAT1 was upregulated in ECs treated with ox-LDL, and knockdown of MALAT1 significantly inhibited ox-LDL-induced inflammation. MALAT1 overexpression potentiated the inflammatory activities of ECs, including enhanced production of inflammatory cytokines (IL-6, IL-8, and TNF-α) and adhesion molecules (VCAM1 and ICAM1), and decreased NO level and cell migratory ability. Mechanistically, MALAT1 could directly downregulate miR-590, and miR-590 could bind to the 3′-UTR of STAT3 to repress its expression. Additionally, overexpression of MALAT1-mediated inflammation was largely abrogated by the concomitant overexpression of miR-590. miR-590 knockdown activated the inflammatory response, which was reversed by STAT3 inhibition. Thus, MALAT1 serves as a proinflammatory lncRNA in ECs through regulating the miR-590/STAT3 axis, suggesting that MALAT1 may be a promising therapeutic target during the treatment of atherosclerosis.
Interatrial Block Predicts Atrial Fibrillation and Total Mortality in Patients with Cardiac Resynchronization Therapy
Authors: Jacobsson Jonatan , Carlson Jonas , Reitan Christian , Borgquist Rasmus , Platonov Pyotr G.
Published: October 2020

Background: Interatrial block (IAB) and abnormal P-wave terminal force in lead V1 (PTFV1) are electrocardiographic (ECG) abnormalities that have been shown to be associated with new-onset atrial fibrillation (AF) and death. However, their prognostic importance has not been proven in cardiac resynchronization therapy (CRT) recipients. Objective: To assess if IAB and abnormal PTFV1 are associated with new-onset AF or death in CRT recipients. Methods: CRT recipients with sinus rhythm ECG at CRT implantation and no AF history were included (n = 210). Automated analysis of P-wave duration (PWD) and morphology classified patients as having either no IAB (PWD <120 ms), partial IAB (pIAB: PWD ≥120 ms, positive P waves in leads II and aVF), or advanced IAB (aIAB: PWD ≥120 ms and biphasic or negative P wave in leads II or aVF). PTFV1 >0.04 mm•s was considered abnormal. Adjusted Cox regression analyses were performed to assess the impact of IAB and abnormal PTFV1 on the primary endpoint new-onset AF, death, or heart transplant (HTx) and the secondary endpoint death or HTx at 5 years of follow-up. Results: IAB was found in 45% of all patients and independently predicted the primary endpoint with HR 1.9 (95% CI 1.2–2.9, p = 0.004) and the secondary endpoint with HR 2.1 (95% CI 1.2–3.4, p = 0.006). Abnormal PTFV1 was not associated with the endpoints. Conclusions: IAB is associated with new-onset AF and death in CRT recipients and may be helpful in the risk stratification in the context of heart failure management. Abnormal PTFV1 did not demonstrate any prognostic value.
Effect of Progressive Resistance Training on Circulating Adipogenesis-, Myogenesis-, and Inflammation-Related microRNAs in Healthy Older Adults: An Exploratory Study
Authors: Liu Hung-Wen , Cheng Hao-Chien , Tsai Shun-Hsi , Sun Wen-Hsien
Published: October 2020

Background: Functional and physiological adaptations induced by resistance training have been extensively studied in older adults. However, microRNA (miRNA) as the novel regulator in protective effects remains poorly understood. Objective: The purpose of an exploratory study was to analyze the response of a panel of circulating miRNAs to adaptations mediated by resistance training. Methods: Ten healthy older adults (age: 67.6 ± 2.2 years, 7 women and 3 men) without previous experience in resistance training were recruited. Blood samples were collected at baseline and after a 12-week resistance training. Next-generation sequencing was used to determine circulating miRNA responses to chronic resistance training. Results: After the 12-week training, physical functions including grip strength, lower body strength and endurance, and walking capacity were improved in the older adults, while the serum levels of leptin (from 18.1 ± 20.0 to 14.9 ± 17.6 ng/mL, p = 0.029) and tumor necrosis factor alpha (TNFα; from 4.4 ± 0.6 to 4.0 ± 0.6 pg/mL, p < 0.001) were significantly decreased. In addition, adipogenesis-related miRNAs (miR-103a-3p, -103b, -143-5p, -146b-3p, -146b-5p, -17-5p, -181a-2-3p, -181b-5p, -199a-5p, -204-3p, and -378c), anti-adipogenesis-related miRNAs (miR-155-3p, -448, and -363-3p), myogenesis-related miRNAs (miR-125b-1-3p, -128-3p, -133a-3p, 155-3p, -181a-2-3p, -181b-5p, -199a-5p, -223-3p, and -499a-5p), and inflammation-related miRNAs (miR-146b-3p, -146b-5p, -155-3p, -181a-2-3p, and -181b-5p) were changed significantly in the older adults after training (fold change >2, p < 0.05). The log2 fold change of miRNA-125-1-3p was inversely correlated with delta walking time (R = –0.685, p = 0.029) and change in insulin-like growth factor 1 (R = –0.644, p = 0.044). Conclusions: Our results can help explain the link between specific circulating miRNAs and beneficial effects of resistance training on functional and physiological adaptations in older adults.
СПРОМОЖНІСТЬ РЕФОРМОВАНОЇ СИСТЕМИ ОХОРОНИ ЗДОРОВ’Я м. КИЄВА ДО НАДАННЯ МЕДИЧНОЇ ДОПОМОГИ ХВОРИМ НА ЦЕРЕБРАЛЬНИЙ ІНСУЛЬТ
Authors: Prokopiv М. М. , Slabkiy G. O. , Yatsina А. Т.
Published: October 2020

Мета: дослідити рівень спроможності реформованої системи охорони здоров’я м. Києва до надання медичної допомоги хворим на церебральний інсульт.

Матеріали і методи. При проведенні даного дослідження використано статистичний метод, метод структурно-логічного аналізу та метод системного підходу. Матеріалами дослідження слугували дані галузевої статистичної звітності по м. Києву за 2014–2018 рр., укладені договори між закладами охорони здоров’я м. Києва та Національною службою охорони здоров’я України, починаючи з 1 квітня 2020 р.

Результати. За умов впровадження системи державних фінансових гарантій медичного обслуговування населення для надання медичної допомоги населенню з гострими мозковими інсультами заклади охорони здоров’я з 1 квітня 2020 р. укладають договори з Національною службою охорони здоров’я України відповідно до пакетів медичних послуг за напрямами «Медична допомога при гострому мозковому інсульті» та «Медична реабілітація дорослих та дітей від трьох років з ураженням нервової системи», які включають специфікацію надання та умови закупівлі медичних послуг. Дані пакети є недостатньо досконалими і потребують у майбутньому перегляду.

Для надання стаціонарної медичної допомоги при гострому мозковому інсульті система охорони здоров’я м. Києва має достатні госпітальні ресурси, але в більшості вони знаходяться в різних закладах охорони здоров’я, що створює перешкоди до надання якісної допомоги при різних формах інсультів та до недостатньо раціонального використання наявних ресурсів. При цьому тільки в двох закладах охорони здоров’я із десяти підрозділи візуалізації патологічного процесу працюють цілодобово, в тому числі у вихідні та святкові дні, а в решті закладів – у режимі роботи лікаря в денний час, що не дає можливості виконати умови договорів із Національною службою охорони здоров’я України, коли візуалізація процесу повинна здійснюватися протягом 60 хв перебування в лікарні.

Висновки. Отримані в ході дослідження результати вказують на недостатню спроможність реформованої системи охорони здоров’я в м. Києві забезпечити хворих на церебральні інсульти доступною та якісною медичною допомогою, в тому числі реабілітаційними послугами.
ФАРМАКОЕКОНОМІЧНІ АСПЕКТИ ТЕРАПІЇ ХВОРОБИ ПАРКІНСОНА
Authors: Khubetova I. V.
Published: October 2020

Мета: визначити фармакоекономічні характеристики застосування зареєстрованих в Україні протипаркінсонічних засобів.

Матеріали і методи. Інформацію про вартість та об’єми продажу протипаркінсонічних лікарських засобів отримано з відкритих джерел. Розраховували середню вартість лікування на місяць з урахуванням рекомендованих максимальних та мінімальних доз.

Інформацію про фактичний стан прескрибції протипаркінсонічних засобів отримано шляхом ретроспективного аналізу призначень Обласного консультативно-діагностичного центру екстрапірамідних розладів за 2015–2020 рр. Cтатистичну обробку проводили за допомогою програмного забезпечення Statistica 10.0 (Dell StatSoft Inc., США).

Результати. При аналізі реальної практики призначень протипаркінсонічних засобів встановлено, що найчастіше пацієнтам призначали препарати леводопи і праміпексол, при цьому 6,6 % пацієнтів на момент включення в реєстр взагалі не отримували ніякої терапії. На монотерапії перебували 18,4 % пацієнтів, два препарати отримували 15,4 %, три – 8,9 % пацієнтів, 2,5 % хворих одночасно отримували більше 3 препаратів. Найдоступнішим економічно в якості монотерапії є застосування холінергічних засобів і амантадину. Молодим пацієнтам, залежно від переважаючих клінічних проявів, можуть застосовувати агоністи дофаміну та інгібітори МАО-В, а пацієнтам похилого віку та хворим молодого віку з когнітивними порушеннями застосовують препарати леводопи, в тому числі комбіновані.

Висновки. Доведено, що фармакоекономічний ефект від терапії є вищим при ранньому початку лікування хвороби Паркінсона. Монотерапія на ранніх стадіях цієї хвороби є більш економічно ефективною, аніж застосування комбінацій препаратів. Наявність дискінезій на пізніх стадіях хвороби Паркінсона збільшує прямі видатки на медикаментозне лікування вдвічі.
ДИСПЛАЗІЯ СПОЛУЧНОЇ ТКАНИНИ ТА АРТЕРІАЛЬНА ГІПЕРТЕНЗІЯ: СУЧАСНИЙ ПОГЛЯД НА ПРОБЛЕМУ
Authors: Bentsa T. M.
Published: October 2020

Артеріальна гіпертензія (АГ) займає провідне місце в структурі смертності, збільшує ризик розвитку атеросклеротичних і серцево-судинних ускладнень. Характерною особливістю АГ є висока частота коморбідності. Пацієнти з АГ, як правило, мають одну або декілька супутніх патологій. Коморбідність призводить до взаємного впливу на перебіг захворювань, характер і тяжкість ускладнень, нерідко утруднює діагностику, визначає цільові значення артеріального тиску і особливості вибору антигіпертензивних препаратів. Основна частина. Одним із факторів ризику, який відіграє важливу роль у патогенезі, але є недостатньо вивченим з погляду розвитку та прогресування АГ, є наявність дисплазії сполучної тканини (ДСТ). Пацієнти з ДСТ частіше мають артеріальну гіпотензію або нейроциркуляторну дистонію, але згодом у цих молодих людей часто формується синдром АГ. Основа формування АГ, поєднаної з ДСТ – дисфункція судинного ендотелію артеріального кровообігу, вираження якої залежить від тривалості, ступеня тяжкості АГ, наявності атерогенних дисліпідемій, ефективності антигіпертензивної терапії та її ангіопротекторної активності. Висновок. Наявність у пацієнта коморбідності, зокрема, поєднання ДСТ та АГ, потребує індивідуального підходу, комплексної діагностики (клінічних, генеалогічних і лабораторно-інструментальних досліджень) та лікування з урахуванням обох наявних патологій.
АНАЛІЗ МОРФОЛОГІЧНИХ ЗМІН СЛИЗОВОЇ ОБОЛОНКИ СЕЧОВОГО МІХУРА ЖІНОК РАННЬОГО ТА ПІЗНЬОГО МЕНОПАУЗАЛЬНОГО ПЕРІОДІВ ЗАЛЕЖНО ВІД ГОРМОНАЛЬНОГО СТАТУСУ
Authors: Bidovanets B. Yu. , Bodnar Ya. Ya. , Golovata T. K. , Pryshliak A. M.
Published: October 2020

На сьогодні дизурія у жінок перименопаузального періоду є однією із найсерйозніших проблем медицини. Тісний анатомо-функціональний зв’язок сечової системи із репродуктивними органами жінок та їх нейроендокринною системою потребує застосування комплексних методів дослідження у випадках різних патологічних станів, у тому числі зумовлених віковими змінами жіночого організму.

Мета – вивчення морфологічних змін слизової оболонки сечового міхура у жінок раннього та пізнього менопаузального періодів та їх залежність від рівнів прогестерону та естрадіолу.

Матеріал і методи. Досліджено біоптати слизової оболонки сечового міхура в ділянці трикутника та лівої бокової стінки у 62 жінок. З них до групи пацієнток раннього менопаузального періоду віднесено 20, пізнього менопаузального періоду – 28 пацієнток. Контрольну групу складали 14 жінок репродуктивного періоду в віці 35–45 років. Застосовані гістологічний та біохімічний методи дослідження.

Результати. Доведено, що в слизовій оболонці сечового міхура при дизурії у жінок перименопаузального періоду виникають виразні дистрофічні та дегенеративні пошкодження, які супроводжуються запальними реакціями у власній пластинці та компенсаторними гіперпластичними процесами. Рівень гормонів прогресивно знижується в обох групах пацієнток порівняно з групою контролю.

Висновки. У обстежених жінок раннього та пізнього менопаузального періодів рівень зниження гормонів має пряму відповідність із ступенем вираження морфологічних проявів.
ЕФЕКТИВНІСТЬ УЛЬТРАЗВУКОВОЇ ДІАГНОСТИКИ ТУБЕРКУЛЬОЗНОЇ ЕМПІЄМИ ПЛЕВРИ
Authors: Коshak Yu. F.
Published: October 2020

Представлено перший ефективний аналіз ранньої діагностики хворих на туберкульозну емпієму плеври за допомогою ультразвукового дослідження органів грудної клітки. Проаналізовано ультразвукові особливості стадійності, локалізації в діагностиці туберкульозної емпієми плеври в залежності від статі, віку, початку, перебігу та поширеності нагноєння.

Мета – покращити результати ультразвукової діагностики хворих із туберкульозною емпіємою плеври шляхом проведення аналізу цінності стандартних методів діагностики.

Матеріал і методи. Проведений ретроспективний аналіз 685 випадків туберкульозної емпієми плеври у пацієнтів, які за останні 10 років отримали стаціонарне лікування у фтизіохірургічному відділенні «ТОПД». Усім хворим були проведені необхідні клінічні, лабораторні та інструментальні, включаючи ультразвукові, рентгенологічні та імунологічні методи обстеження.

Результати. Встановлено, що ультразвукове дослідження має цілий ряд переваг і є високоінформативним методом діагностики плеврального нагноєння. За даними ехосканувального дослідження можна спрогнозувати характер плеврального випоту.

Висновки. Лише у 51,2 % хворих на туберкульозну емпієму плеври захворювання було діагностовано своєчасно, тобто на стадії можливого малоінвазивного хірургічного лікування. Найбільші діагностичні труднощі трапляються у пацієнтів з локалізацією емпієми плеври у зоні активних туберкульозних або метатуберкульозних змін. У 48,7 % хворих туберкульозна емпієма була діагностована на пізній стадії гнійного процесу, що підтверджує необхідність широкого застосування в діагностиці ультразвукового дослідження.