bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylation data imputation performances under different representations and missingness patterns
Authors: Lena Pietro Di , Sala Claudia , Prodi Andrea , Nardini Christine
Published: April 2020

Background: High-throughput technologies enable the cost-effective collection and analysis of DNA methylation data throughout the human genome. This naturally entails missing values management that can complicate the analysis of the data. Several general and specific imputation methods are suitable for DNA methylation data. However, there are no detailed studies of their performances under different missing data mechanisms â(completely) at random or not- and different representations of DNA methylation levels ($\beta$ and $M$-value). Results: We make an extensive analysis of the imputation performances of seven imputation methods on simulated missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR) methylation data. We further consider imputation performances on the β- and M-value popular representations of methylation levels. Overall, β -values enable better imputation performances than M-values. Imputation accuracy is lower for mid-range β -values, while it is generally more accurate for values at the extremes of the β -value range. The MAR values distribution is on the average more dense in the mid-range in comparison to the expected β -value distribution. As a consequence, MAR values are on average harder to impute. Conclusions: The results of the analysis provide guidelines for the most suitable imputation approaches for DNA methylation data under different representations of DNA methylation levels and different missing data mechanisms.
Further identification of a 140bp sequence from amid intron 9 of human FMR1 gene as a new exon
Authors: Yang Wen-jing , Yan Ai-zhen , Xu Yong-jun , Guo Xiao-yan , Fu Xian-guo , Li Dan , Liao Juan , Zhang Duo , Lan Fenghua
Published: April 2020

Background:the disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein (FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological functions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140 bp exon from the intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and its underlying signaling pathways. Results: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal individuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the genomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic expression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated protein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in mGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed. Conclusions: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal healthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account for the multiple functions of FMRP.
Effect of acupuncture and its influence on cerebral activity in patients with persistent asthma: study protocol for a randomized controlled clinical trial
Authors: Yu Siyi , Dong Xiaohui , Sun Ruirui , He Zhaoxuan , Zhang Chuantao , Chen Mei , Hong Xiaojuan , Lan Lei , Zeng Fang
Published: April 2020

Background
Previous studies suggested that acupuncture was a promising adjunct treatment for asthma. However, the underlying mechanism of acupuncture for asthma remains unclear. The present trial aimed to explore whether and how specific meridian acupuncture works in quality of life and symptomatic improvement by modulating brain function in asthma patients.
Methods : A randomized controlled functional brain imaging trial is currently being conducted in Sichuan, China. In total 48 patients with mild to moderate, persistent asthma will be recruited randomly allocated to two acupuncture groups: acupuncturing at Lung Meridian and acupuncturing at Heart Meridian . The treatment period will last for 4 weeks. The Asthma quality of life questionnaire (AQLQ) is the primary outcome. Asthma control test (ACT), the rate of Peak expiratory flow (PEFR), Forced expiratory volume in 1 second (FEV1), Montreal cognitive assessment (MoCA), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) will also assess the clinical efficacy of different interventions. Functional magnetic resonance imaging (fMRI) scans will be performed to detect cerebral activity changes in each group. The clinical data and fMRI data will be analyzed, respectively. Pearson correlation analysis will be used to assess the association between the changes of cerebral activity features and the improvement of clinical outcomes in each group.
Discussion : The present study has been established on the “meridians-viscera relationship” theory of traditional Chinese medicine and modern central mechanism of acupuncture. The results of this trial would be useful to identify the efficiency of the specific meridian acupuncture for asthma. The investigation of its central mechanism would further expand our knowledge of the acupuncture for asthma.
Trial registration: Chinese Clinical Trial Registry, ChiCTR1900027478. Registered on 15 November 2019.
Premature aging of circulating T cells predicts all-cause mortality in hemodialysis patients
Authors: Xiang Fangfang , Chen Rongyi , Cao Xuesen , Shen Bo , Chen Xiaohong , Ding Xiaoqiang , Zou Jianzhou
Published: April 2020

Background Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system, which is recently concerned as a significant factor for increased risk of various morbidities. Nevertheless, there are few dates explicating the relevancy of T cell senescence to mortality. In this study, we prospectively studied the predictive value of T cell senescence for mortality in hemodialysis patients. Methods Patients who had been on hemodialysis treatment for at least 6 months were enrolled. T cell senescence determined by differentiation status was evaluated by flow cytometry. Survival outcomes were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to evaluate the prognostic impact of T cell premature aging and other clinical factors on all-cause mortality. Results A total of 466 patients (277 man and 169 women) were enrolled in this study. Decreased number of naïve T cell, as the most prominent feature of T cell senescence, did not change in parallel with age in these patients. Decreased absolute count of T cell, naïve T cell, CD4 + naïve T cell were independently associated with all-cause mortality. Decreased percentage of T cell and increased percentage of CD8 + central-memory T cell were also independently associated with all-cause mortality. After including all the T cell parameters in one regression model, only decreased count of naïve T cell was significantly associated with increased mortality in these patients. Conclusion s Aging-associated T cell changes are aggravated in ESRD patients. For the first time, our study demonstrates that naïve T cell depletion is a strong predictor of all-cause mortality in HD patients.
Disequilibrium evolution of the Fructose-1,6-bisphosphatase gene family leads to their functional biodiversity in Gossypium species
Authors: Author) Qun Ge(Former Corresponding , Cūi Yànli , Lǐ Jùnwén , Gōng Jǔwǔ , Lú Quánwěi , Lǐ Péngtāo , Shí Yùzhēn , Shāng Hǎihóng , Liú Àiyīng , Dèng Xiǎoyīng , Pān Jìngtāo , Chén Qúanjiā , Yuan Youlu , Author) Wankui Gong(New Corresponding
Published: April 2020

Background: Fructose-1,6-bisphosphatase (FBP) is a key enzyme in the plant sucrose synthesis pathway, in the Calvin cycle, and plays an important role in photosynthesis regulation in green plants. However, no systemic analysis of FBPs has been reported in Gossypium species.Results: A total of 41 FBP genes from four Gossypium species were identified and analyzed. These FBP genes were sorted into two groups and seven subgroups. Results revealed that FBP family genes were under purifying selection pressure that rendered FBP family members as being conserved evolutionarily, and there was no tandem or fragmental DNA duplication in FBP family genes. Collinearity analysis revealed that a FBP gene was located in a translocated DNA fragment and the whole FBP gene family was under disequilibrium evolution that led to a faster evolutionary progress of the members in G. barbadense and in At subgenome than those in other Gossypium species and in the Dt subgenome, respectively, in this study. Through RNA-seq analyses and qRT-PCR verification, different FBP genes had diversified biological functions in cotton fiber development (two genes in 0 DPA and 1DPA ovules and four genes in 20–25 DPA fibers), in plant responses to Verticillium wilt onset (two genes) and to salt stress (eight genes).Conclusion: The FBP gene family displayed a disequilibrium evolution pattern in Gossypium species, which led to diversified functions affecting not only fiber development, but also responses to Verticillium wilt and salt stress. All of these findings provide the foundation for further study of the function of FBP genes in cotton fiber development and in environmental adaptability.
Relationship of endoscopic lesions of the renal papilla with type of renal stone and 24 h urine analysis
Authors: Arroyo Xavier Arnau Sabaté , Grases Felix , Quetglas Jose Luis Bauza , Garcia Jorge Guimera , Ayala Enrique Pieras
Published: April 2020

BACKGROUND:

Our purpose was to study the relationship of the 3 different types of endoscopic calcifications of the renal papilla (Randall’s plaque, intratubular calcification, papillary crater) with the type of stone and urine analysis.

METHODS:

This prospective study examined 41 patients (age range: 18 to 80 years) who received retrograde intrarenal surgery (RIRS) for renal lithiasis (mean stone size: 15.3 ± 7.2 mm). The renal papilla injuries were endoscopically classified as Randall's plaque, intratubular calcification, or papillary crater. Calculi were classified as uric acid, calcium oxalate monohydrate (COM; papillary and cavity), calcium oxalate dihydrate (COD), or calcium phosphate (CP). A 24 h urine analysis of calcium, oxalate, citrate, phosphate, and pH was performed in all patients. The relationship of each type of papillary injury with type of stone and urine chemistry was determined. Fisher’s exact test and Student’s t-test were used to determine the significance of relationships, and a p value below 0.05 was considered significant.

RESULTS

The most common injury was tubular calcification (78%), followed by Randall’s plaque (58%), and papillary crater (39%). There was no significant relationship of Randall’s plaque with type of stone. However, endoscopic intratubular calcification (p = 0.025) and papillary crater (p = 0.041) were more common in patients with COD and CP stones. There were also significant relationships of papillary crater with hypercalciuria (p = 0.036) and hyperoxaluria (p = 0.024), and of Randall’s plaque with hypocitraturia (p = 0.005).

CONCLUSIONS

There are certain specific relationships between the different types of papillary calcifications that were endoscopically detected with stone chemistry and urine analysis. COD and CP stones were associated with endoscopic tubular calcifications and papillary craters. Hypercalciuria was associated with tubular calcification, and hypocitraturia was associated with Randall’s plaque.
Patient satisfaction and quality of life in breast reconstruction: assessment of outcomes of immediate, delayed, and nonreconstruction.
Authors: Siqueira Hianga Fayssa Fernandes , Teixeira Jorge Luiz de Almeida , Filho Reginaldo da Silva Lessa , Hora Evânia Curvelo , Brasileiro Filipe Ferreira , Borges Kênya de Souza , Brito Érika de Abreu Costa , Lima Marcela Sampaio , Marques Adriane Dórea , Moura Alex Rodrigues , Júnior Tarcizo Costa Figueiredo , de Oliveira Thiago Costa , Vasconcelos Ana Alice Santana , Lima Carlos Anselmo
Published: April 2020

Objectives

This study was conducted aiming to assess the quality of life and satisfaction of women who had mastectomy treated with and without breast reconstruction.

Results

A total of 81 women who had mastectomy were included, of whom 53 (65.4%) underwent breast reconstruction. Quality of life was not significantly better in the reconstruction group than the nonreconstruction group. Satisfaction with the surgically operated breast, whether reconstructed or not, was positively correlated with quality of life (p = 0.004). There was no significant difference in quality of life between women with immediate and late reconstruction. This study showed that the satisfaction of patients with the operated breast, reconstructed or not, is more important in quality of life than whether the breast was reconstructed or not. When we analyzed the quality of life of women who had mastectomy who were dissatisfied with their unreconstructed breasts, we observed that nonreconstruction had a negative impact on the quality of life.
District-level strategies to control the HIV epidemic in Zimbabwe: a practical example of precision public health.
Authors: Makurumidze Richard , Decroo Tom , Lynen Lutgarde , Chinwadzimba Zororo Kudzaishe , Damme Wim Van , Hakim James , Rusakaniko Simbarashe
Published: April 2020

Objective

We conducted a descriptive cross-sectional study using survey and programme data to asses district-level performance along the HIV care cascade (HIV testing target achievement, linkage to ART, ART coverage) in order to formulate district-specific recommendations, taking into consideration prevalence and yield of testing.Results

Data from 60 districts were analysed. Most 48 (80.0%) of districts surpassed 90% of their 2018 HIV testing targets. Linkage to ART was less than 90% in 40 (83.3%) of districts. Half (30) of districts had an ART coverage above 90%. Of 30 districts with suboptimal(<90%) ART coverage, 18 had achieved high HIV testing target achievement but suboptimal linkage to ART, 6 had achieved high HIV testing targets and high linkage to ART, 4 had both suboptimal HIV testing target achievement and linkage to ART and 2 had suboptimal HIV testing target achievement and high linkage to ART. Priority should be given to districts with suboptimal ART coverage. Remediation strategies should be tailored to address the poorly performing stage of the cascade in each district.
Prevalence and significance of potential drug-drug interactions among cancer patients receiving chemotherapy
Authors: Ismail Mohammad , Khan Sehrash , Khan Fahadullah , Noor Sidra , Sajid Hira , Yar Shazia , Rasheed Irum
Published: April 2020

Background: Cancer patients often receive multiple drugs to maximize their therapeutic benefit, treat co-morbidities and counter the adverse effects of chemotherapy. Concomitant administration of multiple drugs increases the risk of drug interactions leading to compromised therapeutic efficacy or safety of therapy. The purpose of this study was to identify the prevalence, levels and predictors of potential drug-drug interactions (pDDIs) among cancer patients.
Methods: Six hundred and seventy-eight patients receiving chemotherapy from two tertiary care hospitals were included in this cross-sectional study. Patient medication profiles were screened for pDDIs using the Micromedex® database. Logistic regression analysis was performed to identify the predictors of pDDIs.
Results: The overall prevalence of pDDIs was 78%, majority of patients had 1-2 pDDIs (39.2%). A total of 1843 pDDIs were detected. Major-pDDIs were most frequent (67.3%) whereas, a significant association of pDDIs was found between >7 all prescribed drugs (p <0.001) and ≥3 anti-cancer drugs (p <0.001). Potential adverse outcomes of these interactions include reduced therapeutic effectiveness, QT interval prolongation, tendon rupture, bone marrow suppression and neurotoxicity.
Conclusions: Major finding of this study is the high prevalence of pDDIs signifying the need of strict patient monitoring for pDDIs among cancer patients. Patients at higher risk to pDDIs include those prescribed with >7 any types of drugs or ≥3 anticancer drugs. Moreover, list of most frequently identified major and moderate interactions will aid health care professional in timely identification and prevention of pDDIs.
Combined lateral peripatellar and posteromedial approaches for Schatzker type IV tibial plateau fractures involving posteromedial plane: A prospective study.
Authors: Zhang Jun , Yin Bo , Zhao Jianmin , Li Yihan , Yin Peng , Guo Tao
Published: April 2020

Objective

The objective of this study to evaluate prospectively the effectiveness of Schatzker type IV tibial plateau fractures involving posteromedial plane managed by combined lateral peripatellar and posteromedial approaches

Materials and methods

We analyzed 18 patients with Schatzker type IV tibial plateau fractures involving posteromedial plane. There were 12 males and 6 females with an average of 38.5 years (range, 25-60 years). The mechanism of injury included traffic accident in 15 patients and falling in 3 patients. The injured lower limbs were right in 11 patients and left in 7 patients. The mean time from injury to surgery was 6.78 days (range, 5-9 days). There were 8 patients with meniscus injuries in our study.

Results

The mean operation time was 3.41 hours (range, 3-4 hours). The mean blood loss was 352.78 ml (range, 300-410 ml). All the injured meniscuses were repaired. All patients were followed up, and the average time of follow up was 16.61 months (range, 14-22 months). Bone union was achieved at a mean of 12 weeks (range, 10-14 weeks). The mean degree of knee extension was 1.11° (range, 0-5°), and the mean degree of knee flexion was 120.56°(range, 110-130°). The mean points of KSS were 83 (range, 74-89 points). According to the criteria of KSS, 14 patients had clinical outcomes rated as excellent and 4 patients were rated as good.

Conclusion

Our results suggested that Combined lateral peripatellar and posteromedial approaches in the treatment of Schatzker type IV tibial plateau fractures involving posteromedial plane acquired satisfying outcomes. It was good for repairing the injured meniscus through our approaches.
Colonisation potential of plantaricin-producing Lactobacillus plantarum SF9C andS-layer-carrying Lactobacillus brevis SF9B among gut microbiota
Authors: Butorac Katarina , Banic Martina , Novak Jasna , Pavunc Andreja Leboš , Uroic Ksenija , Orsolic Nada , Kukolj Marina , Radovic Slobodanka , Scalabrin Simone , Zucko Jurica , Starčevic Antonio , Suskovic Jagoda , Kos Blaženka
Published: April 2020

Background: The influence of an S-layer-carrying strain Lactobacillus brevis SF9B and a plantaricin-producing strain Lactobacillus plantarum SF9C on the gut microbiota composition was evaluated in the rats. Considering the probiotic potential of Lb. brevis SF9B, this study aimed to examine the antibacterial activity of Lb. plantarum SF9C and potential for their in vivo colonisation, which could be the basis for the investigation of their synergistic functionality. Results: A plantaricin-encoding cluster was identified in Lb. plantarum SF9C, a strain which efficiently inhibited the growth of Listeria monocytogenes ATCC®19111™ and Staphylococcus aureus 3048. Contrary to the plantaricin-producing SF9C strain, the S-layer-carrying SF9B strain excluded Escherichia coli 3014 and Salmonella enterica serovar Typhimurium FP1 from adhesion to Caco-2 cells. Finally, DGGE analysis of the V2-V3 region of the 16S rRNA gene confirmed the transit of two selected lactobacilli through the gastrointestinal tract (GIT). Microbiome profiling via the Illumina MiSeq platform revealed the prevalence of Lactobacillus spp. in the gut microbiota of rats suggesting their colonisation potential in GIT.Conclusion: The combined application of Lb. plantarum SF9C and Lb. brevis SF9B could influence the intestinal microbiota composition, which is reflected through the increased abundance of Lactobacillus genus, but also through altered abundances of other bacterial genera, either in the model of healthy or aberrant microbiota of rats. The obtained results contributed to the functional aspects of SF9C and SF9B strains which could be incorporated in the probiotic-containing functional foods and therefore have a beneficial influence on the gut microbiota composition.
Perceptions and predictors of organizational justice among healthcare professionals in academic hospitals in South-eastern Nigeria
Authors: Ghasi Nwanneka Chidinma , Ogbuabor Daniel Chukwuemeka , Onodugo Vincent Aghaegbunam
Published: April 2020

Background Research on organizational justice in hospitals in African countries are limited despite being important for workforce performance and hospital operational efficiency. This paper investigated perceptions and predictors of organizational justice among health professionals in academic hospitals in South-east Nigeria. Methods The study was conducted in two teaching hospitals in Enugu State, South-east Nigeria using mixed-methods design. Randomly sampled 360 health professionals (doctors = 105, nurses = 200 and allied health professionals, AHPs = 55) completed an organizational justice scale. Additionally, semi-structured, in-depth interview with purposively selected 18 health professionals were conducted. Univariate and bivariate statistics and multivariable linear regression were used to analyze quantitative data. Statistical significance was set at alpha 0.05 level. Qualitative data were analyzed thematically using NVivo 11 software. Results The findings revealed moderate to high perception of different dimensions of organizational justice. Doctors showed the highest perception, whereas AHPs had the least perception. Among doctors, age and education predicted distributive justice (adjusted R2 = 22%); hospital ownership and education predicted procedural justice (adjusted R2 = 17%); and hospital ownership predicted interactional justice (adjusted R2 = 42%). Among nurses, age, gender and marital status predicted distributive justice (adjusted R2 = 41%); hospital ownership, age and gender predicted procedural justice (adjusted R2 = 28%); and hospital ownership, age, marital status and tenure predicted interactional justice (R2 = 35%). Among AHPs, marital status predicted distributive justice (adjusted R2 = 5%), while hospital ownership and tenure predicted interactional justice (adjusted R2 =15%). Qualitative findings indicate that nurses and AHPs perceive as unfair, differences in pay, access to hospital resources, training, work schedule, participation in decision-making and enforcement of policies between doctors and other health professionals due to medical dominance. Overall, supervisors have a culture of limited information sharing with, and disrespectful treatment of, their junior colleagues. Conclusion Perceptions of organizational justice range from moderate to high and predictors vary among different healthcare professionals. Addressing specific socio-demographic factors that significantly influenced perceptions of organizational justice among different categories of health professionals and departure from physician-centered culture would improve perceptions of organizational justice among health professionals in Nigeria and similar settings.
Patient-specific instrument assisted calcaneal fracture minimally invasive internal fixation can carry out preoperative plan accurately and quickly: a retrospective study
Authors: Wang Chenggong , Xu Can , Li Mingqing , Li Hui , Xiao Han , Zhong Da , Liu Hua
Published: April 2020

Background: Almost all of the traditional calcaneal fracture minimally invasive internal fixations (MIIF) require a lot of intraoperative fluoroscopy, moreover, the fracture recovery of many patients is not considered ideal. Therefore, we designed a new surgical procedure through the digital surgical simulation and made patient-specific instrument (PSI) for calcaneal fracture patients before surgery, and then we manage the operation through the assistance of PSI during the whole process. The purpose of this study is to verify whether the PSI assisted calcaneal fracture minimally invasive internal fixation can carry out preoperative plan accurately and quickly. Methods: We retrospectively analyzed the Sanders type III or IV fresh calcaneal fracture patients who had been performed MIIF assisted by the PSI in our hospital during January 2016 to December 2018. We collected and analyzed perioperative data including intraoperative fluoroscopy times, whether the internal fixation actual usage (IFAU) same as preoperative plan, surgical time and situation of complication; and collected and analyzed the data of preoperative actual measurement, preoperative-plan and postoperative actual measurement from X-rays and CT, including Böhler angle, Gissane angle, subtalar joint width, calcaneus valgus angle and calcaneal volume overlapping ratio. All patients had been followed up and their AOFAS score had been recorded. Then we performed statistical analyses. Results: The intraoperative fluoroscopy times was 3.95±1.78, the condition of IFAU in 16 patients (16 feet) was the same as preoperative plan, the surgery time was 28.16±10.70 min, no patients developed complications. The preoperative plan Böhler angle, Gissane angle, subtalar joint width and calcaneus valgus angle were not significant different from the postoperative; the preoperative Böhler angle, Gissane angle, subtalar joint width and calcaneus valgus angle were all significant different from the postoperative. The calcaneal volume overlapping ratio with preoperative design was 91.2±2.3%. The AOFAS score of all patients gradually increased as time goes on, and difference of the AOFAS scores between all time-points were significant. Conclusions: The new patient-specific instrument assisted calcaneal fracture minimally invasive internal fixation can carry out the preoperative plan accurately and quickly.
High Hip Center Technique in Total Hip Arthroplasty for Crowe Type II-III Developmental Dysplasia: Results of Midterm Follow-up
Authors: Shen Junmin , Zhou Yonggang , Sun Jingyang , Ma Haiyang , Du Yinqiao , Li Tiejian
Published: April 2020

Background: High hip center technique is still controversial about the survivorship of prothesis and postoperative complications. We aimed to show the utility of high hip center technique used in patients with Crowe II-III developmental dysplasia of the hip at the midterm follow-up and evaluated the clinical and radiographic results between different heights of hip center.Methods: We retrospectively evaluated 69 patients (85 hips) with Crowe II-III dysplasia who underwent a high hip center cementless total hip arthroplasty at a mean follow up of 8.9 years (range, 6.0-14.1years). The patients were divided into two groups according to the height of hip center, respectively group A (≥22mm and <28mm) and group B (≥28mm). Radiographic, functional and survivorship outcomes were evaluated.Results: There were no statistically significant differences between two groups in horizontal distance, offset, abductor lever arm, leg length discrepancy and cup inclination. At the final follow up, the mean WOMAC and Harris hip score were significantly improved in both groups. Of the 85 hips, 7 hips (8.2%) showed a positive Trendelenburg sign. Besides, 6 patients (8.7%) presented with a limp. No significant differences were shown regarding the Harris hip score, WOMAC score, Trendelenburg sign and limp between two groups. The Kaplan-Meier implants survivorship rates at the final follow-up for all-causes revisions in group A and group B were similar (96.7% [95% confidence interval, 90.5%-100%] and 96.2% [95% confidence interval, 89.0%-100%], respectively).Conclusions: The high hip center technique is a valuable alternative to achieve excellent midterm results for Crowe II-III developmental dysplasia of the hip.
Full-length transcriptome sequencing of the identified fruit shape-related genes of the Olecranon honey peach
Authors: Liu Jianliang , Bao Yao , Wang Qin , Liu Huifan
Published: April 2020

Background: The Olecranon honey peach shaped like an eagle’s beak. In this study, full-length transcriptome sequencing of the Olecranon honey peach and its bud mutant variant was performed by Oxford Nanopore Technologies to comparatively analyze the differentially expressed genes and the transcriptome to identify important fruit shape-related genes. Results: Full-length transcriptome sequencing was performed to analyze the two peaches. A consensus isoform was obtained and compared to the reference genome for an elimination of redundancy analysis. As a result, a final set of 58 596 transcript sequences was obtained. A total of 21 745 simple sequence repeats were obtained, and 18 322 alternative splicing (AS) events were identified. The comparative analysis of the non-redundant transcript revealed 2530 new gene loci and 37 364 novel transcripts. A total of 457 genes were differentially expressed in the two groups, including 169 up-regulated genes and 288 down-regulated genes. A total of 1519 transcripts were differentially expressed, of which 552 were up-regulated and 997 were down-regulated. Conclusions: In the case of the plant hormone signal transduction pathway identified by the KEGG annotation, our analyses revealed that differential expression of genes 9229 , 26004 , 22504 , 2822 , 2826 , 2824 , ONT.1953 , ONT.1950 , and ONT.1953 was related to the shape of the peach and may regulate the production of large fruit, via endogenous hormones, secondary metabolites, and signal transduction. This study provides useful information on the shape-related genes and transcripts in the Olecranon honey peach.
Construction of SSR linkage maps and identification of QTL for resistance to root rot in sweetpotato (Ipomoea batatas (L.) Lam.)
Authors: Ma Zhimin , Gao Wenchuan , Liu Lanfu , Liu Minghui , Zhao Ning , Han Meikun , Wang Zhao , Jiao Weijing , Gao Zhiyuan , Hu Yaya , Liu Qingchang
Published: April 2020

Background: Sweetpotato root rot is a devastating disease caused by Fusarium solani that causes significant yield losses of sweetpotato in China. There is currently no effective method to control the disease. The breeding of resistant varieties is the most effective and economic way to control the disease. To date, quantitative trait locus (QTL) for resistance to root rot have not been reported and the biological mechanisms of resistance remain unclear in sweetpotato. Thus, it is necessary and worthwhile to identify resistance loci to help develop disease-resistant varieties.
Results: In this study, we constructed genetic linkage maps of sweetpotato using a mapping population consisting of 300 individuals derived from a cross between Jizishu 1 and Longshu 9 by simple sequence repeat (SSR) markers, and mapped seven QTLs for resistance to root rot. In total, 484 and 573 polymorphic SSR markers were grouped into 90 linkage groups for Jizishu 1 and Longshu 9, respectively. The total map distance for Jizishu 1 was 3,974.24 cM, with an average marker distance of 8.23 cM. The total map distance for Longshu 9 was 5,163.35 cM, with an average marker distance of 9.01 cM. Five QTLs ( qRRM_1 , qRRM_2 , qRRM_3, qRRM_4 , and qRRM_5 ) were located in five linkage groups of Jizishu 1 map explaining 52.6-57.0% of the variation. Two QTLs ( qRRF_1 and qRRF_2 ) were mapped on two linkage groups of Longshu 9 explaining 57.6% and 53.6% of the variation. 71.4 % of the QTLs had a positive effect on the variation. Three of the seven QTLs, qRRM_3 , qRRF_1 , and qRRF_2 , were colocalized with markers IES43-5mt, IES68-6fs**, and IES108-1fs, respectively.
Conclusions: To our knowledge, this is the first report on the construction of a genetic linkage map for purple sweetpotato (Jizishu 1) and the identification of QTLs associated with resistance to root rot in sweetpotato using SSR markers. These QTLs will have practical significance for the fine mapping of root rot resistance genes and play an important role in sweetpotato marker-assisted breeding.
Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer
Authors: Altunel Erdem , Roghani Roham S. , Chen Kai-Yuan , Kim So Young , McCall Shannon , Ware Kathryn E. , Shen Xiling , Somarelli Jason A. , Hsu David S.
Published: April 2020

Background: Metastatic colorectal cancer (CRC) continues to be a major health problem, and current treatments are primarily for disease control and palliation of symptoms. In this study, we developed a precision medicine strategy to discover novel therapeutics for patients with CRC. Methods: Six matched low-passage cell lines and patient-derived xenografts (PDX) were established from CRC patients undergoing resection of their cancer. High-throughput drug screens using a 119 FDA-approved oncology drug library were performed on these cell lines, which were then validated in vivo in matched PDXs. RNA-Seq analysis was then performed to identify predictors of response. Results: Our study revealed marked differences in response to standard-of-care agents across patients and pinpointed druggable pathways to treat CRC. Among these pathways co-targeting of fibroblast growth factor receptor (FGFR), SRC, platelet derived growth factor receptor (PDGFR), or vascular endothelial growth factor receptor (VEGFR) signaling was found to be an effective strategy. Molecular analyses revealed potential predictors of response to these druggable pathways. Conclusions: Our data suggests that the use of matched low-passage cell lines and PDXs is a promising strategy to identify new therapies and pathways to treat metastatic CRC.
The MD-PhD Program In Geneva: A 10-year Analysis Of Demographics And Outcomes
Authors: Rocha Andre Dos Santos , Combescure Cristophe , Negro Francesco
Published: April 2020

Background: MD-PhD programs are research-oriented degrees that empower medical doctors with in-depth scientific skills. ‘Physician-scientists’ graduating from these programs are expected to highly contribute to biomedical research and academic medicine, alongside clinical practice. In that respect, however, there is limited knowledge about the outcomes and careers of the MD-PhD workforce, particularly in Europe. In the present study, we surveyed the MD-PhD graduates from the University of Geneva between 2010 and 2019.Methods: A cross-sectional survey was performed in April 2019, targeting all medical doctors who had obtained the MD-PhD degree from the University of Geneva since 2010. Features, career outcomes and opinions of MD-PhD graduates were assessed through an online anonymous questionnaire.Results: Twenty-one questionnaires were collected from 31 MD-PhD graduates (response rate 65.5 %). Most respondents (57.1%) had performed an MD-PhD training in basic sciences; however, only 14.3% had pursued this type of research thereafter. Most of the respondents were holding a position at a University hospital (90.5%), although a significant number of them were no longer doing research in their current position (28.6%) and 85.7% were facing obstacles and challenges to combine clinical duties and research. Despite this, the majority declared that the MD-PhD degree had given them an edge during the career (85.7%). Conclusions: The physician-scientists who graduated from the MD-PhD program in Geneva were globally satisfied with their training. However, many challenges and obstacles to combine clinical duties and research were reported by MD-PhD graduates, precluding the implementation of research activities in their current position.
Network Pharmacology and Molecular docking Analysis on Mechanisms and Molecular Targets of LongChaiJiangXue Formula for Treatment of Polycythemia Vera
Authors: Ming Jing , Zhu Shirong , Li Yujin , Liu Weiyi , Jiang Yunyao , Hu Xiaomei
Published: April 2020

Background: LongChaiJiangXue formula (LCJX) has the effect of not only clearing up excessive erythrocytes but also relieving clinical symptoms of Polycythemia vera (PV). Material/Methods: The chemical constitution of LCJX was identified from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Seven hundred and fifty-nine targets were identified and a total of 248 targets were screened out after discarding duplication and genes without any ID in databases. GeneCards database, OMIM database, and GEO database were searched for differential expression genes. The network was built by Cytoscape (3.7.2) software and the protein-protein interaction (PPI) networks of PV and LCJX were merged by https://string-db.org . Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was processed by the R platform. The molecular docking technology was used to further analyze the intense of the assosiation of the compounds and targets. Results: 73 compounds of LCJX were chosen as the candidate active compounds. The compound-targets network contained 105 nods and 216 edges that presented the interaction of agents and targets. The PPI network of LCJX targets involved 59 nodes and 168 edges. The network showed that the key nodes were concentrated in signal transducer and activator of transcription-3(STAT-3), interleukin-6(IL-6), Janus kinase 2(JAK2), and vascular endothelial growth factor-A(VEGFA). The most enriched terms in the GO analysis in the GO biological processes(BP) were reactive oxygen species metabolic process, response to lipopolysaccharide, and response to oxidative stress. According to GO molecular functions(MF), the central nodes were generally enriched in cytokine receptor binding, cytokine activity, and heme binding. Regarding the GO cell components(CC), the terms included vesicle lumen, cytoplasmic vesicle lumen, and secretory granule lumen. In light of the KEGG enrichment analysis, the Hepatitis B, AGE-RAGE signaling pathway in diabetic complications, Kaposi sarcoma-associated herpesvirus infection, measles, Human cytomegalovirus infection, and JAK-STAT signaling pathway were significantly enriched. The molecular docking technology found that puerarin and saikosaponin A had relative stronger affinity with VEGFA, HIF-1A, JAK2 and STAT3 than other compounds in terms of the binding free energy. Conclusions: The effect of LCJX on PV is achieved through a series of complex mechanisms. Network pharmacology and molecular docking are powerful tools to reveal the effect of compound Chinese medicine on the disease.
A Confirmatory Factor Analysis of the knowledge, attitude and practice questionnaire towards prevention of Respiratory tract infections during Hajj and Umrah
Authors: Goni Mohammd Dauda , Naing Nyi Nyi , Hasan Habsah , Wan-Arfah Nadiah , Deris Zakuan Zainy , Arifin Wan Nor , Baaba Aisha Abubakar , Njaka Stanley
Published: April 2020

Background Respiratory tract infections are one of the common infection associated with Hajj pilgrimage that is of great public health and global concern. This study is aimed at determining the factor structure of the knowledge, attitude and practice questionnaire for the prevention of respiratory tract infections during Hajj by confirmatory factor analysis (CFA). Methods A multistage cluster sampling method was conducted on Malaysian Umrah pilgrims during the weekly Umrah orientation course. A total of 200 Umrah pilgrims participated in the study. The KAP questionnaire was distributed to pilgrims at the beginning of the orientation and retrieved immediately at the end of the orientation. The robust maximum likelihood was used for the estimation due to the multivariate normality assumption violation. A two-factor model was tested for measurement model validity and construct validity for each of the attitude and practice domains. Results CFA of a 25-item in total, two-factor model yielded adequate goodness-of-fit values. The measurement model also showed a good convergent and discriminant validity after model re-specification. A two-factor model was tested for measurement model validity and construct validity for each of the attitude and practice domains. Conclusion The KAP questionnaire was proven to have a valid measurement model and reliable constructs. It was deemed suitable for use to measure the KAP of Hajj and Umrah pilgrims towards the prevention of respiratory tract infections.
Exploration of a novel prognostic risk signatures and immune checkpoint molecules in endometrial carcinoma microenvironment
Authors: Liu Jinhui , Nie Sipei , Wu Zhipeng , Li Siyue , Jiang Yi , Wan Yicong , Meng Huangyang , Zhou Shulin , Cheng Wenjun
Published: April 2020

Background: Endometrial carcinoma (EC) is one of the common female malignancies. The effectiveness of immunotherapy in treating EC remains to be testified. Methods: In our present study, we explored the underlying mechanism through tumor microenvironment (TME) and immune-related genes in EC. Based on The Cancer Genome Atlas (TCGA) database to screen immune-related differentially expressed genes (DEGs). Then, survival analysis, functional annotations and interpreted interaction network of these genes were further investigated for the underlying regulation mechanisms. Moreover, we used a conjoint Cox regression analysis to built the immune-related prognostic risk signatures and identify the candidate prognostic biomarkers. Based on the risk model, we further explored the predictive value of risk signatures by exploring the tumor-infiltrating immune cells, prognostic immune checkpoints modulators, and checkpoint inhibitors in TME. Results: As a result, we found 799 up-regulated and 139 down-regulated immune-related and differentially expressed genes of EC. Based on the 225 prognostic DEGs, we built two risk models based on key prognostic immune-related genes, which identified respectively for overall survival and disease-free survival. Gene set enrichment analysis revealed immune-related pathways were mostly enriched in gene sets of the low-risk group, and the nomograms were constructed based on the risk models. By analyzing the immune status in low- and high- group of EC patients , we found higher immune cell infiltration and activation in low risk tumor tissues, which might cause lower tumor purity and contribute to better prognosis of EC. By analyzing the immune checkpoint molecules, we found both the expression and immunophenoscore of immune checkpoints PD-1, CTLA4, PD-L1 and PD-L2 increased significantly in low-risk group. In addition, the low-risk group were found display higher tumor mutational burden. Conclusions: Our study suggested that high-immune TME might prevent the progression of EC, which indicated the possibility of immunotherapy to fight against EC.
Associated factors with awareness, treatment and control of hypertension among 3,579 hypertensive adults in China: data from the China Health and Nutrition Survey
Authors: Wei junxiang , Xin Bo , Li Yan , Wang Youfa
Published: April 2020

Background: Hypertension prevalence is high and rising in China, but it is inadequately controlled. This study investigated hypertension awareness, treatment, and control and their associated factors among Chinese adults. Methods: Data collected from the 2011 China Health and Nutrition Survey (CHNS) from 12,991 Chinese adults were used. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg, self-reported prior diagnosed hypertension, or taking antihypertensive medications. Hypertension awareness, treatment, and control were defined as a self-reported diagnosis of hypertension, current use of antihypertensive medication, and blood pressure < 140/90 mm Hg, respectively. Multivariate logistic regression was performed to examine factors associated with hypertension awareness, treatment, and control. Results: Overall, 3,579 (27.6%) of the CHNS adult participants had hypertension, of whom 55.7% were aware of their diagnosis, 46.5% were treated with antihypertensive medications, but only 20.3% had their blood pressure controlled. Rates of hypertension awareness and treatment varied across population subgroups; higher likelihood was associated with being female (OR = 1.37; 95%CI, 1.12-1.66), older age (1.57; 1.65-4.02), urban residence (1.50; 1.14-1.97), living in the Eastern region (1.52; 1.14-2.01), having overweight/obesity (1.99; 1.39-2.84), and engaging in less healthy lifestyles. Lower control rate was associated with obesity (0.56; 0.42-0.76) and minority ethnicity (0.52; 0.31-0.86). Conclusion: Hypertension is a major public health burden in China. Rates of hypertension awareness, treatment, and control are still low despite efforts that have been made. More intensive screening and treatment intervention programs are needed in the future.
Intensity of end-of-life health care and 30-day mortality after systemic anti-cancer treatment in patients with advanced lung cancer
Authors: Oselin Kersti , Pisarev Heti , Ilau Keit , Kiivet Raul-Allan
Published: April 2020

Background: We aimed to study the mortality and intensity of health care in patients with advanced lung cancer assigned to systemic anti-cancer treatment (SACT) compared with patients who were not eligible for SACT (no-SACT). Methods: A retrospective cohort of lung cancer patients, who were treated at the North Estonia Medical Centre from 2015–2017, was linked to population-based health care data from the Estonian Health Insurance Fund. We calculated 14- and 30-day mortality after SACT and used a composite measure of intensity of care, comprised from the following: emergency department visit, admission to hospital, admission to intensive care unit, receipt of radiotherapy or systemic treatment. Results: The median overall survival (OS) of patients who received at least one cycle of SACT (n = 489) was 9.1 months and in patients with no-SACT (n = 289) 1.3 months (hazard ratio [HR]=4.23, 95% CI=3.60-5.00). In the SACT group 6.7% and 14.7% of patients died within 14 days and 30 days after the last cycle, respectively. During the final 30 days of life, intensive EOL care was received by 69.9% of the SACT patients and 43.7% of the no-SACT patients (p < 0.001). Among SACT patients, sepsis, bacterial infection and/or neutropenia had a significant adverse effect on survival (HR=1.7, 95% CI=1.3-2.21, p < 0.001), whereas the use of the granulocyte colony stimulating growth factor reduced the risk of death (HR= 0.71, 95% CI=0.55-0.93, p = 0.013). Conclusions: Significant proportions of patients with advanced lung cancer continue to receive intensive care near death. Our results highlight that neutropenia and infectious complications are still the primary cause of early SACT-related death.