bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges and opportunities in the continuity of care for hypertension: a mixed-methods study embedded in a primary health care intervention in Tajikistan
Authors: Chukwuma Adanna , Gong Estelle , Latypova Mutriba , Fraser-Hurt Nicole 
Published: December 2019

AbstractBackgroundHypertension, a significant risk factor for ischemic heart disease and other chronic conditions, is the third-highest cause of death and disability in Tajikistan. Thus, ensuring the early detection and appropriate management of hypertension is a core element of strategies to improve population health in Tajikistan. For a strategy to be successful, it should be informed by the causes of gaps in service delivery and feasible solutions to these challenges. The objective of this study was to undertake a systematic assessment of hypertension case detection and retention in care within Tajikistan’s primary health care system, and to identify challenges and appropriate solutions.MethodsOur mixed methods study drew on the cascade of care framework to examine patient progression through the recommended stages of hypertension care. We triangulated data from household surveys and facility registries within Tajikistan’s Health Services Improvement Project (HSIP) to describe the cascade. Focus group discussions with local HSIP stakeholders identified the barriers to and facilitators for care. Drawing on global empirical evidence on effective interventions and stakeholder judgments on the feasibility of implementation, we developed recommendations to improve hypertension service delivery that were informed by our quantitative and qualitative findings.ResultsWe review the results for the case detection stage of the cascade of care, which had the most significant gaps. Of the half a million people with hypertension in Khatlon and Sogd Oblasts (administrative regions), about 10% have been diagnosed in Khatlon and only 5% in Sogd. Barriers to case detection include misinformation about hypertension, ambiguous protocols, and limited delivery capacity. Solutions identified to these challenges were mobilizing faith-based organizations, scaling up screening through health caravans, task-shifting to increase provider supply, and introducing job aids for providers.ConclusionsTranslating findings on discontinuities in care for hypertension and other chronic diseases to actionable policy insights can be facilitated by collaboration with local stakeholders, triangulation of data sources, and identifying the intersection between the feasible and the effective in defining solutions to service delivery challenges.
Medical infrared thermal imaging of canine appendicular bone neoplasia
Authors: Sung J. , Loughin C. , Marino D. , Leyva F. , Dewey C. , Umbaugh S. , Lesser M. 
Published: December 2019

Abstract
Background
Medical infrared thermal imaging (MITI) is a noninvasive imaging modality used in veterinary medicine as a screening tool for musculoskeletal and neurological disease processes. An infrared camera measures the surface body heat and produces a color map that represents the heat distribution. Local trauma or disease can impair the autonomic nervous system, which leads to changes in the local dermal microcirculation and subsequent alteration of surface body heat. Disruption of autonomic flow to the cutaneous vasculature at deeper levels can also result in asymmetric thermographic results. The purpose of this study was to evaluate surface temperature differences between limbs affected by bone neoplasia and their normal contralateral limbs.

Results
A statistically significant difference in average temperature was noted between regions of interest of the two groups (paired difference: 0.53 C° ± 0.14; P = 0.0005). In addition, pattern recognition analysis yielded a 75–100% success rate in lesion identification.

Conclusions
Significant alterations noted with average temperature and thermographic patterns indicate that MITI can document discernible changes associated with the presence of canine appendicular bone tumors. While MITI cannot be used as the sole diagnostic tool for bone cancer, it can be used as a screening modality and may be applicable in early detection of cancer.
S-15 in combination of Akt inhibitor promotes the expansion of CD45RA−CCR7+ tumor infiltrating lymphocytes with high cytotoxic potential and downregulating PD-1+Tim-3+ cells as well as regulatory T cells
Authors: Xu Benling , Yuan Long , Chen Guangyu , Li Tiepeng , Zhou Jinxue , Zhang Chengjuan , Qin Peng , Muthana Musleh M. , Wang Shengdian , Du Xuexiang , Gao Quanli 
Published: December 2019

Abstract
Background
Autologous tumor-infiltrating lymphocytes (Tils) immunotherapy is a promising treatment in patients with advanced hepatocellular cancer. Although Tils treatment has shown great promise, their persistence and the efficacy after adoptive-transfer are insufficient and remain a challenge. Studies have demonstrated that IL-15 and Akt inhibitor can regulate T cell differentiation and memory. Here, we constructed S-15 (Super human IL-15), a fusion protein consisting of human IL-15, the sushi domain of the IL-15 receptor α chain and human IgG-Fc. Herein we compared the effects of S-15 with IL-2 or in combination with Akti on the expansion and activation of Tils.

Methods
Hepatocellular cancer tissues were obtained from 6 patients, Tils were expanded using IL-2, IL-2/S-15, IL-2/Akti or in combination IL-2/S-15/Akti. At day 10, anti-CD3 antibody was added to the culture media and expanded to day 25. The composition, exhaustion and T-cell differentiation markers (CD45RA/CCR7) were analyzed by flow cytometry.

Results
We found that IL-2/S-15/Akti expanded Tils and showed the highest percentage of central memory CD45RA−CCR7+ phenotype prior to anti-CD3 antibody activation and after anti-CD3 antibody activation. T cells cultured with IL-2/S-15/Akti exhibited a mixture of CD4+, CD8+, and CD3+CD4−CD8− T cells; S-15 in combination with Akt inhibitor downregulated the expression of PD-1+Tim-3+ on Tils and decreased the Tregs in Tils. Additionally, the Tils expanded in the presence of the Akt inhibitor and S-15 showed enhanced antitumor activity as indicated by the increase in IFN-γ producing tumor infiltrating CD8+ T cells and without comprising the Tils expansion.

Conclusion
Our study elucidates that IL-2/S-15/Akti expanded Tils and represent a viable source for the cellular therapy for patients with hepatocellular cancer.
Validation of Plasmodium falciparum dUTPase as the target of 5′-tritylated deoxyuridine analogues with anti-malarial activity
Authors: Pérez-Moreno Guiomar , Sánchez-Carrasco Paula , Ruiz-Pérez Luis Miguel , Johansson Nils Gunnar , Müller Sylke , Baragaña Beatriz , Hampton Shahienaz Emma , Gilbert Ian Hugh , Kaiser Marcel , Sarkar Sandipan , Pandurangan Thiyagamurthy , Kumar Vijeesh , González-Pacanowska Dolores 
Published: December 2019

Abstract
Background
Malaria remains as a major global problem, being one of the infectious diseases that engender highest mortality across the world. Due to the appearance of resistance and the lack of an effective vaccine, the search of novel anti-malarials is required. Deoxyuridine 5′-triphosphate nucleotido-hydrolase (dUTPase) is responsible for the hydrolysis of dUTP to dUMP within the parasite and has been proposed as an essential step in pyrimidine metabolism by providing dUMP for thymidylate biosynthesis. In this work, efforts to validate dUTPase as a drug target in Plasmodium falciparum are reported.

Methods
To investigate the role of PfdUTPase in cell survival different strategies to generate knockout mutants were used. For validation of PfdUTPase as the intracellular target of four inhibitors of the enzyme, mutants overexpressing PfdUTPase and HsdUTPase were created and the IC50 for each cell line with each compound was determined. The effect of these compounds on dUTP and dTTP levels from P. falciparum was measured using a DNA polymerase assay. Detailed localization studies by indirect immunofluorescence microscopy and live cell imaging were also performed using a cell line overexpressing a Pfdut-GFP fusion protein.

Results
Different attempts of disruption of the dut gene of P. falciparum were unsuccessful while a 3′ replacement construct could recombine correctly in the locus suggesting that the enzyme is essential. The four 5′-tritylated deoxyuridine analogues described are potent inhibitors of the P. falciparum dUTPase and exhibit antiplasmodial activity. Overexpression of the Plasmodium and human enzymes conferred resistance against selective compounds, providing chemical validation of the target and confirming that indeed dUTPase inhibition is involved in anti-malarial activity. In addition, incubation with these inhibitors was associated with a depletion of the dTTP pool corroborating the central role of dUTPase in dTTP synthesis. PfdUTPase is mainly localized in the cytosol.

Conclusion
These results strongly confirm the pivotal and essential role of dUTPase in pyrimidine biosynthesis of P. falciparum intraerythrocytic stages.
A new method for detecting the outer corneal contour in images from an ultra-fast Scheimpflug camera
Authors: Jędzierowska Magdalena , Koprowski Robert , Wilczyński Sławomir , Krysik Katarzyna 
Published: December 2019

Abstract
Background
The Corvis® ST tonometer is an innovative device which, by combining a classic non-contact tonometer with an ultra-fast Scheimpflug camera, provides a number of parameters allowing for the assessment of corneal biomechanics. The acquired biomechanical parameters improve medical diagnosis of selected eye diseases. One of the key elements in biomechanical measurements is the correct corneal contour detection, which is the basis for further calculations. The presented study deals with the problem of outer corneal edge detection based on a series of images from the afore-mentioned device. Corneal contour detection is the first and extremely important stage in the acquisition and analysis of corneal dynamic parameters.

Result
A total of 15,400 images from the Corvis® ST tonometer acquired from 110 patients undergoing routine ophthalmologic examinations were analysed. A method of outer corneal edge detection on the basis of a series of images from the Corvis® ST was proposed. The method was compared with known and commonly used edge detectors: Sobel, Roberts, and Canny operators, as well as others, known from the literature. The analysis was carried out in MATLAB® version 9.0.0.341360 (R2016a) with the Image Processing Toolbox (version 9.4) and the Neural Network Toolbox (version 9.0). The method presented in this paper provided the smallest values of the mean error (0.16%), stability (standard deviation 0.19%) and resistance to noise, characteristic for Corvis® ST tonometry tests, compared to the methods known from the literature. The errors were 5.78 ± 9.19%, 3.43 ± 6.21%, and 1.26 ± 3.11% for the Roberts, Sobel, and Canny methods, respectively.

Conclusions
The proposed new method for detecting the outer corneal contour increases the accuracy of intraocular pressure measurements. It can be used to analyse dynamic parameters of the cornea.
The respective parts of incidence and lethality in socioeconomic differences in cancer mortality. An analysis of the French network Cancer registries (FRANCIM) data
Authors:   the French Network of Cancer Registries (FRANCIM), Bryere Joséphine , Tron Laure , Menvielle Gwenn , Launoy Guy 
Published: December 2019

Abstract
Background
To determine relevant public health actions and to guide intervention priorities, it is of great importance to assess the relative contribution of incidence and lethality to social inequalities in cancer mortality.

Methods
The study population comprised 185,518 cases of cancer diagnosed between 2006 and 2009 recorded in the French registries. Survival was known for each patient (endpoint: 30/06/2013). Deprivation was assessed using the European Deprivation Index. We studied the influence of deprivation on mortality, incidence and lethality rates and quantified the respective proportions of incidence and lethality in social inequalities in mortality by calculating attributable deaths.

Results
For cancers with social inequalities both in incidence and lethality, excess mortality in deprived was mainly caused by social inequalities in incidence (e.g. men lung cancer: 87% of excess deaths in the deprived caused by inequalities in incidence). Proportions were more balanced for some cancer sites (e.g. cervical cancer: 56% incidence, 44% lethality). For cancer sites with a higher incidence in the least deprived (e.g. breast cancer), the excess-lethality in deprived leads entirely the higher mortality among the deprived.

Conclusions
Most of the excess mortality in deprived is due to the excess incidence of tobacco-dependent cancers and the excess lethality of screenable cancers.
Deletion of the Mir-106b~ 25 MicroRNA cluster attenuates atherosclerosis in Apolipoprotein E knockout mice
Authors: Semo Jonathan , Chernin Gil , Jonas Michael , Shimoni Sara , George Jacob 
Published: December 2019

Abstract
Background
MicroRNAs are short non-coding RNAs that regulate gene expression. The aim of this study was to gain an understanding of the possible role of the miR-106b~ 25 microRNA cluster in regulating atherosclerosis in mice.

Methods
MiR-106b~ 25 knockout mice were outcrossed into Apolipoprotein E (ApoE) knockout background to generate double knockout mice. At 36 weeks of age, lesion size was evaluated in the aortic sinus by oil-red-O staining.

Results
Lesion size was 2-fold smaller in double KO mice in comparison to ApoE KO mice. In addition, collagen staining showed a trend towards a stable plaque phenotype in the double KO mice. Lipid profiling of plasma samples of double KO and ApoE KO mice using FPLC revealed over 2-fold decrease in Very low density lipoprotein (VLDL) cholesterol content and a 50% decrease in low density lipoprotein (LDL) cholesterol content in double KO mice. By using target prediction software, we have identified several possible targets for the miR-106b~ 25 cluster including the VLDL and LDL receptors. We found that upon feeding miR-106b~ 25 KO mice with high fat diet, the expression of LDL and VLDL receptors was higher than in the wild-type mice, suggesting the miR-106b~ 25 cluster regulates atherosclerosis by influencing clearance of VLDL and LDL from the plasma.

Conclusions
We identified the miR-106b~ 25 cluster as a novel regulator of atherosclerosis in ApoE KO mice, presumably by regulating plasma cholesterol levels.
Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair
Authors: Xie Hong-Yan , Zhang Tai-Mei , Hu Shu-Yuan , Shao Zhi-Ming , Li Da-Qiang 
Published: December 2019

AbstractDecondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzyme, is required for nucleosome destabilization after DNA damage through loosening the histone-DNA interaction. Depletion of MORC2 attenuates phosphorylated histone H2AX (γH2AX) focal formation, compromises the recruitment of DNA repair proteins, BRCA1, 53BP1, and Rad51, to sites of DNA damage, and consequently reduces cell survival following treatment with DNA-damaging chemotherapeutic drug camptothecin (CPT). Furthermore, we demonstrate that MORC2 can form a homodimer through its C-terminal coiled-coil (CC) domain, a process that is enhanced in response to CPT-induced DNA damage. Deletion of the C-terminal CC domain in MORC2 disrupts its homodimer formation and impairs its ability to destabilize histone-DNA interaction after DNA damage. Consistently, expression of dimerization-defective MORC2 mutant results in impaired the recruitment of DNA repair proteins to damaged chromatin and decreased cell survival after CPT treatment. Together, these findings uncover a new mechanism for MORC2 in modulating chromatin dynamics and DDR signaling through its c-terminal dimerization.
Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application
Authors: Zhang Zhiqiao , He Tingshan , Huang Liwen , Ouyang Yanling , Li Jing , Huang Yiyan , Wang Peng , Ding Jianqiang 
Published: December 2019

Abstract
Background
The current study aimed to construct competing endogenous RNA (ceRNA) regulation network and develop two precision medicine predictive tools for colorectal cancer (CRC).

Methods
Differentially expressed (DE) analyses were performed between CRC tissues and normal tissues. A ceRNA regulation network was constructed based on DElncRNAs, DEmiRNAs, and DEmRNAs.

Results
Fifteen mRNAs (ENDOU, MFN2, FASLG, SHOC2, VEGFA, ZFPM2, HOXC6, KLK10, DDIT4, LPGAT1, BEX4, DENND5B, PHF20L1, HSP90B1, and PSPC1) were identified as prognostic biomarkers for CRC by multivariate Cox regression. Then a Fifteen-mRNA signature was developed to predict overall survival for CRC patients. Concordance indexes were 0.817, 0.838, and 0.825 for 1-, 2- and 3-year overall survival. Patients with high risk scores have worse OS compared with patients with low risk scores.

Conclusion
The current study provided deeper understanding of prognosis-related ceRNA regulatory network for CRC. Two precision medicine predictive tools named Smart Cancer Survival Predictive System and Gene Survival Analysis Screen System were constructed for CRC. These two precision medicine predictive tools can provide valuable precious individual mortality risk prediction before surgery and improve the individualized treatment decision-making.
Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis/chronic fatigue syndrome patients
Authors: Balinas Cassandra , Cabanas Helene , Staines Donald , Marshall-Gradisnik Sonya 
Published: December 2019

AbstractBackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is hallmarked by a significant reduction in natural killer (NK) cell cytotoxicity, a mechanism tightly regulated by calcium (Ca2+). Interestingly, interleukin-2 (IL-2) increases NK cell cytotoxicity. Transient receptor potential melastatin 2 (TRPM2) ion channels are fundamental for Ca2+signalling in NK cells. This pilot investigation aimed to characterise TRPM2 and CD38 surface expression in vitro on NK cells in ME/CFS patients. This investigation furthermore examined the pharmaceutical effect of 8-bromoadenosine phosphoribose (8-Br-ADPR) andN6-Benzoyladenosine-3′,5′-cyclic monophosphate (N6-Bnz-cAMP) on TRPM2 and CD38 surface expression and NK cell cytotoxicity between ME/CFS and healthy control (HC) participants.MethodsTen ME/CFS patients (43.45 ± 12.36) and 10 HCs (43 ± 12.27) were age and sex-matched. Isolated NK cells were labelled with fluorescent antibodies to determine baseline and drug-treated TRPM2 and CD38 surface expression on NK cell subsets. Following IL-2 stimulation, NK cell cytotoxicity was measured following 8-Br-ADPR andN6-Bnz-cAMP drug treatments by flow cytometry.ResultsBaseline TRPM2 and CD38 surface expression was significantly higher on NK cell subsets in ME/CFS patients compared with HCs. Post IL-2 stimulation, TRPM2 and CD38 surface expression solely decreased on the CD56DimCD16+subset. 8-Br-ADPR treatment significantly reduced TRPM2 surface expression on the CD56BrightCD16Dim/−subset within the ME/CFS group. Baseline cell cytotoxicity was significantly reduced in ME/CFS patients, however no changes were observed post drug treatment in either group.ConclusionOverexpression of TRPM2 on NK cells may function as a compensatory mechanism to alert a dysregulation in Ca2+homeostasis to enhance NK cell function in ME/CFS, such as NK cell cytotoxicity. As no improvement in NK cell cytotoxicity was observed within the ME/CFS group, an impairment in the TRPM2 ion channel may be present in ME/CFS patients, resulting in alterations in [Ca2+]imobilisation and influx, which is fundamental in driving NK cell cytotoxicity. Differential expression of TRPM2 between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in ME/CFS.
The prognostic role of circulating CD8+ T cell proliferation in patients with untreated extensive stage small cell lung cancer
Authors: An Ning , Wang Haoyi , Jia Wenxiao , Jing Wang , Liu Chao , Zhu Hui , Yu Jinming 
Published: December 2019

Abstract
Background
Immunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression.

Methods
This study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. The percentages and proliferation potential of T lymphocyte subpopulations from peripheral blood were measured.

Results
CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) were elevated in ED-SCLC patients compared with healthy controls (p = 0.0083). In contrast, the percentages of CD3+ and CD3+CD4+ T cells were significantly lower in SCLC patients (p < 0.001; p = 0.0014). The proliferation (%divided) of CD8+ T cells of SCLC patients was suppressed compared with healthy controls (p = 0.0058), but not of CD4+ T cells (p = 0.1611). Multivariate analyses showed that the %divided of CD8+ T cells is an independent predictor for PFS (HR: 4.342, 95% CI 1.324–14.245; p = 0.015). The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8+ T cells (p = 0.0225, r = − 0.379; p = 0.0003, r = − 0.464).

Conclusion
The present study indicates that SCLC patients have impaired immunity in peripheral blood, and the proliferation potential of circulating CD8+ T cells is a significant predicator for PFS.