bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Remarkable solutions to impossible problems”: lessons for malaria from the eradication of smallpox
Authors: Cohen Justin M. 
Published: September 2019

AbstractBackgroundMalaria elimination and eventual eradication will require internationally coordinated approaches; sustained engagement from politicians, communities, and funders; efficient organizational structures; innovation and new tools; and well-managed programmes. As governments and the global malaria community seek to achieve these goals, their efforts should be informed by the substantial past experiences of other disease elimination and eradication programmes, including that of the only successful eradication programme of a human pathogen to date: smallpox.MethodsA review of smallpox literature was conducted to evaluate how the smallpox programme addressed seven challenges that will likely confront malaria eradication efforts, including fostering international support for the eradication undertaking, coordinating programmes and facilitating research across the world’s endemic countries, securing sufficient funding, building domestic support for malaria programmes nationally, ensuring strong community support, identifying the most effective programmatic strategies, and managing national elimination programmes efficiently.ResultsReview of 118 publications describing how smallpox programmes overcame these challenges suggests eradication may succeed as a collection of individual country programmes each deriving local solutions to local problems, yet with an important role for the World Health Organization and other international entities to facilitate and coordinate these efforts and encourage new innovations. Publications describing the smallpox experience suggest the importance of avoiding burdensome bureaucracy while employing flexible, problem-solving staff with both technical and operational backgrounds to overcome numerous unforeseen challenges. Smallpox’s hybrid strategy of leveraging basic health services while maintaining certain separate functions to ensure visibility, clear targets, and strong management, aligns with current malaria approaches. Smallpox eradication succeeded by employing data-driven strategies that targeted resources to the places where they were most needed rather than attempting to achieve mass coverage everywhere, a potentially useful lesson for malaria programmes seeking universal coverage with available tools. Finally, lessons from smallpox programmes suggest strong engagement with the private sector and affected communities can help increase the sustainability and reach of today’s malaria programmes.ConclusionsIt remains unclear whether malaria eradication is feasible, but neither was it clear whether smallpox eradication was feasible until it was achieved. To increase chances of success, malaria programmes should seek to strengthen programme management, measurement, and operations, while building flexible means of sharing experiences, tools, and financing internationally.
Direct S-Poly(T) Plus assay in quantification of microRNAs without RNA extraction and its implications in colorectal cancer biomarker studies
Authors: Niu Yanqin , Xia Sijian , Su Mingyang , Dang Quanjin , Kang Kang , Li Li , Gou Deming 
Published: September 2019

AbstractBackgroundAdvances in microRNAs (miRNAs) biomarkers have generated disease markers with potential clinical values. However, none of these published results have been applied in clinic until today. The main reason could be the lack of simple but robust miRNA measurements.MethodsWe built up a simple but ultrasensitive RT-qPCR protocol, Direct S-Poly(T) Plus assay, for detecting miRNAs without RNA purification. In this study, the method was optimized and compared with other RNA purification-based miRNA assays, and the sensitivity was tested. Using Direct S-Poly(T) Plus method, seven potential miRNA biomarkers of colorectal cancer were validated.ResultsIt is possible to detect approximately 100 miRNAs with minimal plasma inputs (20 μl) and time (~ 140 min) with this approach. The sensitivity of this method was 2.7–343-fold higher than that of the stem-loop method, and comparable with S-Poly(T) plus method. 7 validated miRNA biomarkers of colorectal cancer by Direct S-Poly(T) plus assay could discriminate colorectal cancer stage I from healthy individuals, and promised satisfactory discrimination with the area under receiver operating characteristic (ROC) curve ranging from 0.79 to 0.94 (pvalue < 0.001).ConclusionsThis simple and robust protocol may have strong impact on the development of specific miRNAs as biomarkers in clinic.
Comprehensive analysis of aberrantly expressed profiles of mRNA and its relationship with serum galactose-deficient IgA1 level in IgA nephropathy
Authors: Liu Youxia , Liu Xiangchun , Jia Junya , Zheng Jie , Yan Tiekun 
Published: September 2019

Abstract

Background
Immunoglobulin A nephropathy (IgAN) is the leading cause of end-stage kidney disease. Previous mRNA microarray profiling studies of IgAN revealed inconsistent data. We sought to identify the aberrantly expressed genes and biological pathways by integrating IgAN gene expression datasets in blood cells and performing systematically experimental validation. We also explored the relationship between target genes and galactose-deficient IgA1 (Gd-IgA1) in IgAN.

Methods
We retrieved Gene Expression Omnibus (GEO) datasets of IgAN. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional analysis. Deep sequencing on RNA isolated from B cells was used for microarray validation. The relationship between target mRNA expressions and Gd-IgA1 levels in serum were also studied.

Results
Three studies with microarray expression profiling datasets met our inclusion criteria. We identified 655 dyregulated genes, including 319 up-regulated and 336 down-regulated genes in three GEO datasets with a total of 35 patients of IgAN and 19 healthy controls. Based on biological process in GO term, these dyregulated genes are mainly related to pentose-phosphate shunt, non-oxidative branch, post-embryonic camera-type eye development and leukocyte activation. KEGG pathway analysis of microarray data revealed that these aberrantly expressed genes were enriched in human T-cell leukemia virus 1 infection, proteoglycans in cancer, intestinal immune network for IgA production and autophagy. We further performed deep sequencing on mRNAs isolated from B cells of an independent set of five patients with IgAN and three healthy persons with the same clinical and demographic characteristics. Seventy-seven genes overlapped with 655 differentially regulated genes mentioned above, including 43 up-regulated and thirty-four down-regulated genes. We next investigated whether these genes expression correlated with Gd-IgA1 levels in IgAN patients. Pearson correlation analyses showed PTEN (phosphatase and tensin homolog) was the most powerful gene negatively correlated with Gd-IgA1 levels.

Conclusions
These results demonstrated that dyregulated genes in patients with IgAN were enriched in intestinal immune network for IgA production and autophagy process, and PTEN in B cells might be involved in the mechanism of Gd-IgA1 production.
Increased expression of miR-601 is associated with poor prognosis and tumor progression of gastric cancer
Authors: Min Cuili , Zhang Aixia , Qin Jing 
Published: September 2019

AbstractBackgroundMicroRNAs (miRNAs) have been considered to participate in many tumorigenesis, including gastric cancer (GC). Abnormal expression of miR-601 has been reported in GC, but its role is not clear. The goal of this study is to explore the expression patterns, clinical value and functional role of miR-601 in GC.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was conducted to evaluate the expression level of miR-601. The association between miR-601 expression and overall survival was estimated by the Kaplan-Meier survival method. The significance of different variables with respect to survival was analyzed by using the Cox regression assay. Cell experiments were applied to investigate the functional role of miR-601 in GC.ResultsWe found that miR-601 was significantly up-regulated in GC tissues and cells compared with the controls (allP < 0.01). The levels of miR-601 expression were significantly associated with TNM stage, lymph node metastasis, lymphatic invasion, and distant metastasis (allP < 0.05). Kaplan-Meier survival analysis showed that patients in the high miR-601 expression group had poor overall survival (log-rankP = 0.001). Moreover, we confirmed that miR-601, TNM stage, and distant metastasis were independent prognostic factors for GC patients. Overexpression of miR-601 in AGS and SGC-7901 cells by miR-601 mimic transfection significantly promoted the cell proliferation, migration, and invasion (P < 0.05).ConclusionsThe expression level of miR-601 is dramatically up-regulated in GC. The overexpression of miR-601 promotes the tumor progression of GC, and may be a novel prognostic factor for poor survival in GC patients.
Bayesian localization of CNV candidates in WGS data within minutes
Authors: Wiedenhoeft John , Cagan Alex , Kozhemyakina Rimma , Gulevich Rimma , Schliep Alexander 
Published: September 2019

AbstractBackgroundFull Bayesian inference for detecting copy number variants (CNV) from whole-genome sequencing (WGS) data is still largely infeasible due to computational demands. A recently introduced approach to perform Forward–Backward Gibbs sampling using dynamic Haar wavelet compression has alleviated issues of convergence and, to some extent, speed. Yet, the problem remains challenging in practice.ResultsIn this paper, we propose an improved algorithmic framework for this approach. We provide new space-efficient data structures to query sufficient statistics in logarithmic time, based on a linear-time, in-place transform of the data, which also improves on the compression ratio. We also propose a new approach to efficiently store and update marginal state counts obtained from the Gibbs sampler.ConclusionsUsing this approach, we discover several CNV candidates in two rat populations divergently selected for tame and aggressive behavior, consistent with earlier results concerning thedomestication syndromeas well as experimental observations. Computationally, we observe a 29.5-fold decrease in memory, an average 5.8-fold speedup, as well as a 191-fold decrease in minor page faults. We also observe that metrics varied greatly in the old implementation, but not the new one. We conjecture that this is due to the better compression scheme. The fully Bayesian segmentation of the entire WGS data set required 3.5 min and 1.24 GB of memory, and can hence be performed on a commodity laptop.
Thrombus aspiration catheter improve the myocardial reperfusion of STEMI patients with high thrombus load during the emergency PCI operation
Authors: Li Ping , Ruan Jiang-Wen , Liu Ming , Li Si-Yao , Wang Zheng-Dong , Xie Wen-Chao 
Published: September 2019

Abstract

Objective
This study aims to discuss the efficacy and safety of the application of thrombus aspiration catheters during emergency PCI operations for acute ST-elevation myocardial infarction (STEMI) patients with high thrombus load.

Methods
A total of 204 patients diagnosed with acute STEMI and high thrombus load in the Sixth Affiliated Hospital of Guangxi Medical University from July 1, 2016 to June 30, 2017 were selected for the present study. These patients were randomly divided into two groups: thrombus catheter aspiration group (group A, n = 101), and balloon dilatation group (group B, n = 103). The blood flow of the culprit coronary artery in the thrombolysis in myocardial infarction (TIMI) immediately after the emergency PCI operation in these two groups of patients was recorded. Then, an echocardiogram was performed to determine the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) after the operation, and data on major adverse cardiovascular events (MACE) during the 30 days of postoperative follow-up were collected.

Results
The comparative difference between these two groups of patients in terms of hypertension, smoking, diabetes, usage rate of GPIIb/IIIa receptor antagonist, time from hospitalization to balloon dilatation (D2B) and other basic clinical data was not statistically significant (P > 0.05). The postoperative TIMI flow grade of these two groups of patients improved, and the comparative difference between the data obtained from these two groups was statistically significant (P < 0.05). The comparative difference between these two groups in terms of LVEDD and LVEF at 7 days after the operation was not statistically significant (P > 0.05). There was a difference in the occurrence rate of MACE in these two groups of patients during the 30 days of postoperative follow-up, but the comparative difference between these two groups was not statistically significant (P = 0.335).

Conclusion
The application of thrombus aspiration catheter during the emergency PCI operation of STEMI patients with high thrombus load can better improve the myocardial reperfusion. There is no basis for increasing the stroke occurrence risk. However, it obviously fails to improve the recent prognosis and more studies need to explore its effect on myocardial remodeling and major adverse cardiovascular events.
Canine ovarian gonadoblastoma with dysgerminoma overgrowth: a case study and literature review
Authors: Flores Ana R. , Lobo João , Nunes Francisco , Rêma Alexandra , Lopes Paula , Carvalho Luís , Bartosch Carla , Amorim Irina , Gärtner Fátima 
Published: September 2019

Abstract

Background
Gonadoblastoma (GB) is a rare mixed germ cell-sex cord-stromal tumour, first described in humans, commonly found in dysgenetic gonads of intersex patients that have a Y chromosome. However, this entity in not recognized in the WHO classification of tumours of genital system of domestic animals. Herein, we describe a case of ovarian gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour components, in a phenotypically and cytogenetically normal bitch.

Case presentation
A 17-year-old cross-breed bitch had a firm, grey-white multinodular mass in the left ovary. The tumour was submitted to histopathological examination and Y chromosome detected through karyotype analysis and PCR studies. Microscopically, the ovary was almost replaced by an irregular neoplasm composed of three distinct, intermixed elements: dysgerminoma, mixed germ cell-sex cord-stromal tumour resembling human GB and a proliferative sex cord-stromal tumour component. The germ cells of gonadoblastoma and dysgerminoma components were immunoreactive for c-KIT. Sex cord-stromal cells of gonadoblastoma were immunoreactive for α-inhibin. The sex cord-stromal tumour was immunoreactive for AE1/AE3, occasionally for α-inhibin and negative for epithelial membrane antigen (EMA). The karyotype was 78, XX and PCR analysis confirmed the absence of the Y chromosome.

Conclusion
Based on these findings, a diagnosis of gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour was made. This is the first case of ovarian gonadoblastoma in a female dog.
A solution based on melatonin, tryptophan, and vitamin B6 (Melamil Tripto©) for sedation in newborns during brain MRI
Authors: Picone S. , Ariganello P. , Mondì V. , Di Palma F. , Martini L. , Marziali S. , Fariello G. , Paolillo P. 
Published: September 2019

Abstract

Introduction
Melatonin has been studied and used for several years as a sleep-wake cycle modulator in patients with sleep disorders. Experimental evidence has demonstrated the multiple neuroprotective benefits of this indoleamine secreted by the pineal gland. Melatonin is also used in neurological investigations, for its ability to induce sleep in children. In fact, it favors falling asleep during electroencephalogram, Magnetic Resonance Imaging (MRI), and during brainstem auditory evoked potentials. Previous studies are focused on infants and children. No investigation have been performed in neonates, before or during instrumental assessments.

Material and methods
One hundred ten newborns (term and preterm) undergoing brain MRI were enrolled in the study. Thirty minutes before the planned time for the examination, we administered a single dose solution of melatonin- tryptophan-vitamin B6. Twenty minutes after the initial administration of 2 mg, a second dose of 1 mg was administered, if the baby was still awake. If after further 15 min the baby was still not sleeping, an additional dose of 1 mg was administered.

Results
In 106 patients we obtained adequate sedation without adverse events, allowing us to perform an adequate quality MRI, with a median time of 25 min to reach sleeping. Only in three patients MRI could not be performed. In patients having a large weight, higher doses of melatonin were necessary to reach sleeping. Considering the pro kg dose of melatonin, the average dose that induced sleepiness in neonates was 0,64 ± 0.16 mg/Kg.

Conclusion
A solution based on Melatonin- tryptophan-vitamin B6 can be a helpful sedative to administer to neonates undergoing brain MRI, avoiding the use of anesthetics and achieving adequate assessments.
Domestication of the novel alcohologenic acetogen Clostridium sp. AWRP: from isolation to characterization for syngas fermentation
Authors: Lee Joungmin , Lee Jin Woo , Chae Cheol Gi , Kwon Soo Jae , Kim Yun Jae , Lee Jung-Hyun , Lee Hyun Sook 
Published: September 2019

AbstractBackgroundGas-fermenting acetogens have received a great deal of attention for their ability to grow on various syngas and waste gas containing carbon monoxide (CO), producing acetate as the primary metabolite. Among them, someClostridiumspecies, such asC. ljungdahliiandC. autoethanogenum, are of particular interest as they produce fuel alcohols as well. Despite recent efforts, alcohol production by these species is still unsatisfactory due to their low productivity and acetate accumulation, necessitating the isolation of strains with better phenotypes.ResultsIn this study, a novel alcohol-producing acetogen (Clostridiumsp. AWRP) was isolated, and its complete genome was sequenced. This bacterium belongs the same phylogenetic group asC. ljungdahlii,C. autoethanogenum,C. ragsdalei, andC. coskatiibased on 16S rRNA homology; however, the levels of genome-wide average nucleotide identity (gANI) for strain AWRP compared with these strains range between 95 and 96%, suggesting that this strain can be classified as a novel species. In addition, strain AWRP produced a substantial amount of ethanol (70–90 mM) from syngas in batch serum bottle cultures, which was comparable to or even exceeded the typical values obtained using its close relatives cultivated under similar conditions. In a batch bioreactor, strain AWRP produced 119 and 12 mM of ethanol and 2,3-butanediol, respectively, while yielding only 1.4 mM of residual acetate. Interestingly, the alcohologenesis of this strain was strongly affected by oxidoreduction potential (ORP), which has not been reported with other gas-fermenting clostridia.ConclusionConsidering its ethanol production under low oxidoreduction potential (ORP) conditions,Clostridiumsp. AWRP will be an interesting host for biochemical studies to understand the physiology of alcohol-producing acetogens, which will contribute to metabolic engineering of those strains for the production of alcohols and other value-added compounds from syngas.
Recombinant Sj16 protein with novel activity alleviates hepatic granulomatous inflammation and fibrosis induced by Schistosoma japonicum associated with M2 macrophages in a mouse model
Authors: Shen Jia , Wang Lifu , Peng Mei , Liu Zhen , Zhang Beibei , Zhou Tao , Sun Xi , Wu Zhongdao 
Published: September 2019

AbstractBackgroundPotent granulomatous inflammation responses induced by schistosome eggs and resultant fibrosis are the primary causes of morbidity in schistosomiasis. Recombinant Sj16 (rSj16), a 16-kDa protein ofSchistosoma japonicumproduced inEscherichia coli, has been demonstrated to have novel immunoregulatory effectsin vivoandin vitro. Thus, this study investigated the anti-inflammatory and anti-fibrotic effects of rSj16 treatment inS. japonicum-infected mice and demonstrated the immune modulation between the schistosome and the host.MethodsSchistosoma japonicuminfected mice were treated with the rSj16 protein and Sj16 peptide at different time points post-infection to assess their efficacy at the optimal time point. Sj16 peptide and/or Praziquantel (PZQ) treatments were initiated at week 5 post-infection to compare the therapeutic efficacy of each regimen. Hepatic granulomatous inflammation, fibrosis and cytokine production (pro-inflammatory, Th1, Th2, Th17 and regulatory cytokines IL-10) were detected. Moreover, M2 macrophages were measured to illuminate the mechanisms of Sj16.ResultsThe rSj16 protein and Sj16 peptide had significant protective effects inS. japonicum-infected mice, as shown by decreased granuloma formation, areas of collagen deposition and inhibition of pro-inflammatory Th1, Th2 and Th17 cytokine production. These protective activities were more obvious when animals were treated with either the Sj16 protein or peptide at early stages post-infection. Interestingly, the combined treatment of PZQ and Sj16 was more effective and upregulated IL-10 production than administration of PZQ alone in infected mice. Furthermore, the Sj16 treatment alleviated the pathological effects associated with activated M2 macrophages.ConclusionsThis study demonstrates the anti-inflammatory and anti-fibrotic effects of rSj16 in schistosomiasis. Therefore, the combination of rSj16 with PZQ could be a viable and promising therapeutic strategy for schistosomiasis. In addition, this investigation provides additional information on schistosome-mediated immune modulation and host-parasite interactions.