bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating effects of preoperative inflammatory biomarkers on predicting survival outcomes of intrahepatic cholangiocarcinoma after curative resection
Authors: Zhang Zeyu , Zhou Yufan , Hu Kuan , Huang Yun 
Published: October 2020

Abstract
Introduction
Intrahepatic cholangiocarcinoma (ICC) stands as the second most common malignant tumor in the liver with poor patient prognosis. Increasing evidences have shown that inflammation plays a significant role in tumor progression, angiogenesis, and metastasis. However, the prognosis significance of inflammatory biomarkers on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is poorly recognized.

Methods
ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were investigated.

Results
Receiver operating characteristic (ROC) curves showed no significance in NLR, PLR, and LMR in RFS and OS, while significant results were shown on SII in both RFS (P = 0.035) and OS (P = 0.034) with areas under ROC curve as 0.63 (95%CI 0.52–0.74) and 0.62 (95%CI 0.51–0.72), respectively. Kaplan-Meier curves revealed a statistically significant better survival data in SII-low groups on both RFS (P < 0.001) and OS (P < 0.001). The univariate and multivariate analyses revealed that higher level of SII was independently associated with both poorer RFS time and OS time. However, no significant result was shown on NLR, PLR, or LMR.

Conclusion
SII is an effective prognostic factor for predicting the prognosis of ICC patient undergone curative hepatectomy, while NLR, PLR, and LMR are not associated with clinical outcomes of these patients.
Efficient control of Japanese encephalitis virus in the central nervous system of infected pigs occurs in the absence of a pronounced inflammatory immune response
Authors: Redant Valerie , Favoreel Herman W. , Dallmeier Kai , Van Campe Willem , De Regge Nick 
Published: October 2020

Abstract

Background
Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia. JEV infection of mice and humans can lead to an uncontrolled inflammatory response in the central nervous system (CNS), resulting in a detrimental outcome. Pigs act as important amplification and reservoir hosts, and JEV infection of pigs is mostly subclinical. Information on virus spread in the CNS and immune responses controlling JEV infection in the CNS of pigs, however remains scarce.

Methods
Nine-week-old pigs were inoculated intranasal or intradermal with a relevant dose of 105 TCID50 of JEV genotype 3 Nakayama strain. Clinical signs were assessed daily, and viral spread was followed by RT-qPCR. mRNA expression profiles were determined to study immune responses in the CNS.

Results
Besides a delay of 2 days to reach the peak viremia upon intranasal compared to intradermal inoculation, the overall virus spread via both inoculation routes was highly similar. JEV appearance in lymphoid and visceral organs was in line with a blood-borne JEV dissemination. JEV showed a particular tropism to the CNS but without the induction of neurological signs. JEV entry in the CNS probably occurred via different hematogenous and neuronal pathways, but replication in the brain was mostly efficiently suppressed and associated with a type I IFN-independent activation of OAS1 expression. In the olfactory bulb and thalamus, where JEV replication was not completely controlled by this mechanism, a short but strong induction of chemokine gene expression was detected. An increased IFNy expression was simultaneously observed, probably originating from infiltrating T cells, correlating with a fast suppression of JEV replication. The chemokine response was however not associated with the induction of a strong inflammatory response, nor was an induction of the NLRP3 inflammasome observed.

Conclusions
These findings indicate that an adequate antiviral response and an attenuated inflammatory response contribute to a favorable outcome of JEV infection in pigs and help to explain the limited neurological disease compared to other hosts. We show that the NLRP3 inflammasome, a key mediator of neurologic disease in mice, is not upregulated in pigs, further supporting its important role in JEV infections.
Spinal neuronal excitability and neuroinflammation in a model of chemotherapeutic neuropathic pain: targeting the resolution pathways
Authors: Meesawatsom Pongsatorn , Hathway Gareth , Bennett Andrew , Constantin-Teodosiu Dumitru , Chapman Victoria 
Published: October 2020

Abstract
Background
Neuroinflammation is a critical feature of sensitisation of spinal nociceptive processing in chronic pain states. We hypothesised that the resolvin pathways, a unique endogenous control system, may ameliorate aberrant spinal processing of somatosensory inputs associated with chemotherapy-induced neuropathic pain (CINP).

Method
The paclitaxel (PCX) model of CINP was established in male Sprague-Dawley rats and compared to control rats (n = 23 and 22, respectively). Behavioural pain responses were measured, and either single unit electrophysiological recordings of dorsal horn wide dynamic range (WDR) neurones were performed, or mRNA microarray analysis of the dorsal horn of the spinal cord was undertaken.

Results
PCX rats exhibited significant changes in behavioural responses to mechanical and cold stimuli. A higher proportion of WDR neurones in PCX rats were polymodal (generating post-discharge following a non-noxious mechanical stimulus, responding to non-noxious cold and exhibiting spontaneous activity) compared to control (p < 0.05). Microarray analysis revealed changes in proinflammatory pathways (Tlr, Tnfrsf1a, Nlrp1a, Cxcr1, Cxcr5, Ccr1, Cx3cr1) and anti-inflammatory lipid resolvin pathways (Alox5ap, Cyp2j4 and Ptgr1) compared to control (p < 0.05). Ingenuity pathway analysis predicted changes in glutamatergic and astrocyte signaling in the PCX group. Activation of the resolvin system via the spinal administration of aspirin-triggered resolvin D1 (AT-RvD1) markedly inhibited (73 ± 7% inhibition) normally non-noxious mechanically (8 g) evoked responses of WDR neurones only in PCX rats, whilst leaving responses to noxious mechanically induced stimuli intact. Inhibitory effects of AT-RvD1were comparable in magnitude to spinal morphine (84 ± 4% inhibition).

Conclusion
The PCX model of CINP was associated with mechanical allodynia, altered neuronal responses and dysregulation of pro- and anti-inflammatory signalling in the spinal dorsal horn. The resolvin AT-RvD1 selectively inhibited low weight mechanical-evoked responses of WDR neurones in PCX rats, but not in controls. Our data support the targeting of spinal neuroinflammation via the activation of the resolvin system as a new therapeutic approach for CINP.
The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease
Authors: McCarthy Micheline , Raval Ami P. 
Published: October 2020

AbstractThe peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.
Infertility policy analysis: a comparative study of selected lower middle- middle- and high-income countries
Authors: Morshed-Behbahani Bahar , Lamyian Minoor , Joulaei Hassan , Rashidi Batool Hossein , Montazeri Ali 
Published: October 2020

Abstract
Background
Infertility has recently become a salient but neglected global issue. Policies to address the sexual and reproductive health and rights (SRHR) are vital, especially in lower middle and middle-income countries (LMICs). Hence, the aim of this study was to compare the national infertility policies in the selected countries (LMICs comparing with high-income) to determine gaps or to confirm desirable policies in the given health systems.

Methods
This study has executed a comparative policy analysis of infertility services using the universal health coverage framework (financial protection, population coverage, and service features) in three scopes (prevention, treatment, and supportive care). Seven countries that had infertility programs in their health sectors were selected.

Results
The results showed that financial protection was good in high and middle-income countries, but in a lower middle income, and in one high-income country was poor. The findings also showed that health systems in the same countries had no infertility services for men. Preventive and supportive care services were neglected in LMICs by governments.

Conclusion
The findings indicate that income is not the only factor that fulfills universal health coverage for infertility care services. Perhaps to achieve equity in infertility care services, it should be seen as a universal human right to accomplish the right to have a child and to have a life with physical and mental health for all men and women.
Detection and stage classification of Plasmodium falciparum from images of Giemsa stained thin blood films using random forest classifiers
Authors: Abbas Syed Saiden , Dijkstra Tjeerd M. H. 
Published: October 2020

AbstractBackgroundThe conventional method for the diagnosis of malaria parasites is the microscopic examination of stained blood films, which is time consuming and requires expertise. We introduce computer-based image segmentation and life stage classification with a random forest classifier. Segmentation and stage classification are performed on a large dataset of malaria parasites with ground truth labels provided by experts.MethodsWe made use of Giemsa stained images obtained from the blood of 16 patients infected with Plasmodium falciparum. Experts labeled the parasite types from each of the images. We applied a two-step approach: image segmentation followed by life stage classification. In segmentation, we classified each pixel as a parasite or non-parasite pixel using a random forest classifier. Performance was evaluated with classification accuracy, Dice coefficient and free-response receiver operating characteristic (FROC) analysis. In life stage classification, we classified each of the segmented objects into one of 8 classes: 6 parasite life stages, early ring, late ring or early trophozoite, mid trophozoite, early schizont, late schizont or segmented, and two other classes, white blood cell or debris.ResultsOur segmentation method gives an average cross-validated Dice coefficient of 0.82 which is a 13% improvement compared to the Otsu method. The Otsu method achieved a True Positive Fraction (TPF) of 0.925 at the expense of a False Positive Rate (FPR) of 2.45. At the same TPF of 0.925, our method achieved an FPR of 0.92, an improvement by more than a factor two. We find that inclusion of average intensity of the whole image as feature for the random forest considerably improves segmentation performance. We obtain an overall accuracy of 58.8%when classifying all life stages. Stages are mostly confused with their neighboring stages. When we reduce the life stages to ring, trophozoite and schizont only, we obtain an accuracy of 82.7%.ConclusionPixel classification gives better segmentation performance than the conventional Otsu method. Effects of staining and background variations can be reduced with the inclusion of average intensity features. The proposed method and data set can be used in the development of automatic tools for the detection and stage classification of malaria parasites. The data set is publicly available as a benchmark for future studies.
Gastric adenocarcinoma of the fundic gland type: clinicopathological features of eight patients treated with endoscopic submucosal dissection
Authors: Li Chengfang , Wu Xinglong , Yang Shuang , Yang Xiaorong , Yao Jin , Zheng Hong 
Published: October 2020

Abstract
Background
Gastric adenocarcinoma of the fundic gland type (GA-FG) has been added to the 2019 edition of the World Health Organization’s list of digestive system-associated cancers. This lesion differentiates toward the fundic gland and mostly involves chief cell-predominant differentiation with low-grade cytology. Clinicians and pathologists are still unaware of this rare disease; consequently, some cases are incorrectly diagnosed. This study aimed to investigate the clinicopathological features of GA-FG using retrospective analyses of endoscopic and pathological findings.

Materials and methods
Samples were collected from patients diagnosed with GA-FG. The clinical courses of all patients were monitored prospectively and reviewed retrospectively. Available clinical information, endoscopic features, pathological appearance, and follow-up data were assessed. Immunohistochemistry [mucin (MUC) 2, MUC5, MUC6, P53, CDX2, Ki67, SYN, CD56, CGA, β-catenin, and pepsinogen-I] was examined using Envision two-step method.

Results
Eight cases of endoscopic submucosal dissection (ESD) were obtained from our institution. Patient age ranged from 48 to 80 years (mean, 65 years). Some patients were on acid-suppressing medication. Most lesions were located in the upper third (n = 7) and one was in the middle third of the stomach. Six lesions were of the superficial flat type, whereas two were of the superficial elevated type. Narrow-band imaging using magnifying endoscopy showed irregular microvascular patterns (MVPs) in four cases and regular MVPs in the remaining cases. All lesions were primarily solitary and ~ 6 mm in diameter (largest, 12 mm). The main body of the tumors were localized in the mucosal layer, of which six cases invade into the submucosal layer. Well-formed glands of chief cells were predominant. Tumor cells were positive for pepsinogen-I, MUC6, SYN, and CD56. Lymphatic and vascular infiltration and metastatic and recurrent disease were not observed in any case.

Conclusion
GA-FG, a well-differentiated adenocarcinoma with mild atypia, can be completely removed using ESD, with a favorable prognosis in patients.
Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking
Authors: Li Jialin , Luo Hua , Liu Xinkui , Zhang Jingyuan , Zhou Wei , Guo Siyu , Chen Xiuping , Liu Yingying , Jia Shanshan , Wang Haojia , Li Bingbing , Cheng Guoliang , Wu Jiarui 
Published: October 2020

AbstractBackgroundYuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.MethodsThe active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein–protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.ResultsThe study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds.ConclusionThis novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.
Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer—results from the randomized phase III SUCCESS-A trial
Authors: de Gregorio Amelie , Häberle Lothar , Fasching Peter A. , Müller Volkmar , Schrader Iris , Lorenz Ralf , Forstbauer Helmut , Friedl Thomas W. P. , Bauer Emanuel , de Gregorio Nikolaus , Deniz Miriam , Fink Visnja , Bekes Inga , Andergassen Ulrich , Schneeweiss Andreas , Tesch Hans , Mahner Sven , Brucker Sara Y. , Blohmer Jens-Uwe , Fehm Tanja N. , Heinrich Georg , Lato Krisztian , Beckmann Matthias W. , Rack Brigitte , Janni Wolfgang 
Published: October 2020

Abstract
Background
When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients.

Methods
A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety.

Results
No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively.

Conclusion
Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting.

Trial registration
Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.
A new blind color watermarking based on a psychovisual model
Authors: Lefevre Pascal , Alleysson David , Carre Philippe 
Published: October 2020

AbstractIn this paper, we address the problem of the use of a human visual system (HVS) model to improve watermark invisibility. We propose a new color watermarking algorithm based on the minimization of the perception of color differences. This algorithm is based on a psychovisual model of the dynamics of cone photoreceptors. We used this model to determine the discrimination power of the human for a particular color and thus the best strategy to modify color pixels. Results were obtained on a color version of the lattice quantization index modulation (LQIM) method and showed improvements on psychovisual invisibility and robustness against several image distortions.
Design of a culture medium for optimal growth of the bacterium Pseudoxanthomonas indica H32 allowing its production as biopesticide and biofertilizer
Authors: Morales-Borrell Dayana , González-Fernández Nemecio , Mora-González Néstor , Pérez-Heredia Carlos , Campal-Espinosa Ana , Bover-Fuentes Eddy , Salazar-Gómez Eladio , Morales-Espinosa Yissel 
Published: October 2020

AbstractCulture medium composition is one of the most important parameters to analyze in biotechnological processes with industrial purposes. The aim of this study was to design of a culture medium for optimal growth of the bacterium Pseudoxanthomonas indica H32 allowing its production as biopesticide and biofertilizer. The influence of several carbon and nitrogen sources and their molar ratios on P. indica H32 growth was investigated. The effect of different micronutrients such as mineral salts and vitamin on P. indica H32 growth was determined as well. A mixture design based on Design-Expert 10.0 Software was performed to optimize the culture medium concentration. Finally, in the designed medium, an attribute of the biological mechanism of action of the P. indica H32 against nematodes, was evaluated: the hydrogen sulfide production. It was found that tested carbon/nitrogen ratios were not a significant influence on P. indica H32 growth. Growth of P. indica H32 was favored with use of sucrose, yeast extract and phosphate buffer without the addition of any tested micronutrients. An optimal concentration of 10 g/L sucrose and 5 g/L yeast extract were obtained at a cost of 0.10 $/L. In this concentration, the specific growth rate (µ) and maximal optical density (Xmax) were equal to 0.439 h− 1 and 8.00 respectively. It was evidenced that under the culture conditions used, P. indica H32 produced hydrogen sulfide. The designed medium led to a 1.08 $/L reduction of costs in comparison to LB medium. These results were critical to carry on with biotechnological development of P. indica H32 as a bioproduct.