Quantitative trait loci for clinical mastitis on chromosomes 2, 6, 14 and 20 in Norwegian Red cattle

Mastitis is the most frequent and costly disease in dairy production and solutions leading to a reduction in the incidence of mastitis are highly demanded. Here a genome-wide association study was performed to identify polymorphisms affecting susceptibility to mastitis. Genotypes for 17 349 SNPs distributed across the 29 bovine autosomal chromosomes from a total of 2589 sires with 1 389 776 daughters with records on clinical mastitis were included in the analysis. Records of occurrence of clinical mastitis were divided into seven time periods in the first three lactations in order to identify quantitative trait loci affecting mastitis susceptibility in particular phases of lactation. The most convincing results from the association mapping were followed up and validated by a combined linkage disequilibrium and linkage analysis. The study revealed quantitative trait loci affecting occurrence of clinical mastitis in the periparturient period on chromosomes 2, 6 and 20 and a quantitative trait locus affecting occurrence of clinical mastitis in late lactation on chromosome 14. None of the quantitative trait loci for clinical mastitis detected in the study seemed to affect lactation average of somatic cell score. The SNPs highly associated with clinical mastitis lie near both the gene encoding interleukin 8 on chromosome 6 and the genes encoding the two interleukin 8 receptors on chromosome 2.     

Quantifying the predictive accuracy of time-to-event models in the presence of competing risks

Prognostic models for time-to-event data play a prominent role in therapy assignment, risk stratification and inter-hospital quality assurance. The assessment of their prognostic value is vital not only for responsible resource allocation, but also for their widespread acceptance. The additional presence of competing risks to the event of interest requires proper handling not only on the model building side, but also during assessment. Research into methods for the evaluation of the prognostic potential of models accounting for competing risks is still needed, as most proposed methods measure either their discrimination or calibration, but do not examine both simultaneously. We adapt the prediction error proposal of Graf et al. (Statistics in Medicine 1999, 18, 2529–2545) and Gerds and Schumacher (Biometrical Journal 2006, 48, 1029–1040) to handle models with competing risks, i.e. more than one possible event type, and introduce a consistent estimator. A simulation study investigating the behaviour of the estimator in small sample size situations and for different levels of censoring together with a real data application follows.     

Approximate nonparametric corrected-score method for joint modeling of survival and longitudinal data measured with error

We consider the problem of jointly modeling survival time and longitudinal data subject to measurement error. The survival times are modeled through the proportional hazards model and a random effects model is assumed for the longitudinal covariate process. Under this framework, we propose an approximate nonparametric corrected-score estimator for the parameter, which describes the association between the time-to-event and the longitudinal covariate. The term nonparametric refers to the fact that assumptions regarding the distribution of the random effects and that of the measurement error are unnecessary. The finite sample size performance of the approximate nonparametric corrected-score estimator is examined through simulation studies and its asymptotic properties are also developed. Furthermore, the proposed estimator and some existing estimators are applied to real data from an AIDS clinical trial.     

Analysis of peripheral blood lymphocyte subsets and prognosis in patients with septic shock

The purpose of the study is to study the relationship between peripheral blood lymphocyte subset proportion and prognosis in patients with septic shock. Fifty‐two patients with septic shock, admitted to the intensive care unit between March 2007 and December 2010, were enrolled in this study. Peripheral blood lymphocyte subset proportions were measured using flow cytometry. The percentage of CD3⁺CD4⁺ T lymphocytes and CD19⁺ lymphocytes, CD4⁺/CD8⁺ T cell ratio were substantially lower in patients with septic shock compared to the control group (P < 0.01). The percentage of CD3⁺CD8⁺ T lymphocytes did not differ significantly between the two groups (P > 0.05). The percentage of CD16⁺CD56⁺ lymphocytes was higher in patients with septic shock than in the control group (P < 0.01). Compared with the survivor group, the percentage of CD3⁺CD4⁺ T lymphocytes and CD19⁺ lymphocytes, CD4⁺/CD8⁺ T cell ratio were clearly lower in the non‐survivor group (P < 0.01). There was no difference in the percentage of CD3⁺CD8⁺ T lymphocytes between the non‐survivor and survivor groups (P > 0.05). The percentage of CD16⁺CD56⁺ lymphocytes was higher in the non‐survivor group than in the survivor group (P < 0.05). The total maximum SOFA score and the delta SOFA score were much higher in the non‐survivor group than in the survivor group (P < 0.01). Immune imbalance occurs in patients with septic shock. Peripheral blood lymphocyte subset proportion and SOFA scores can be used to assess the treatment and prognosis of septic shock.     

Optimal viral immune surveillance evasion strategies

Following cell entry, viruses can be detected by cytotoxic T lymphocytes. These cytotoxic T lymphocytes can induce host cell apoptosis and prevent the propagation of the virus. Viruses with fewer epitopes have a higher survival probability, and are selected through evolution. However, mutations have a fitness cost and on evolutionary periods viruses maintain some epitopes. The number of epitopes in each viral protein is a balance between the selective advantage of having fewer epitopes and the reduced fitness following the epitope removing mutations. We discuss a bioinformatic analysis of the number of epitopes in various viral proteins and propose an optimization framework to explain these numbers. We show, using a genomic analysis and a theoretical optimization framework, that a critical factor affecting the number of presented epitopes is the expression stage in the viral life cycle of the gene coding for the protein. The early expression of epitopes can lead to the destruction of the host cell before budding can take place. We show that a lower number of epitopes is expected in early proteins even if late proteins have a much higher copy number.     

不同程度颅脑疾病患者肠道菌群分析

检测不同程度颅脑疾病患者肠道菌群分布情况, 探讨患者肠道菌群分布与疾病的关系, 为该类患者的治疗提供参考。

通过MiSeq PE2x300 bp高通量测序技术对21例重度颅脑损伤患者(G1组, GCS≤8分)和14例轻度颅脑损伤患者(G2组, GCS > 8分)粪便样本中细菌的16S rRNA基因V3-V4可变区进行定性分析, 并对两组患者肠道菌群进行生物学分类比较、多样性分析和组间物种差异分析。

两组患者肠道菌群多样性差异无统计学意义(均P > 0.05)。G1组患者肠道厌氧球菌属(Anaerococcus)、埃希菌-志贺菌属(Escherichia-Shigella)、链球菌属(Streptococcus)、肠球菌属(Enterococcus)、棒状杆菌属(Corynebacterium)数量高于G2组(均P < 0.05)。

颅脑疾病患者肠道菌群紊乱, 其肠道菌群丰度及多样性显著下降, 有害菌数量升高, 有益菌数量下降。

     

NRS2002评分和血清白蛋白值与门诊肺结核患者病情的相关性

目的 评价NRS2002评分和血清白蛋白（ALB）值与门诊肺结核患者病情的相关性。 方法 选择2017年10月至2018年9月在余姚市人民医院肺结核门诊就诊的290名肺结核患者为研究对象。患者首次就诊时进行NRS2002营养筛查,NRS2002评分≥3分判定为存在营养风险。检测患者血清白蛋白（ALB）值,ALB≤35 g/L判定为营养不足。观察患者NRS2002评分、ALB值与肺结核患者痰液结核分枝杆菌阳性、肺结核空洞等情况的相关性。 结果 NRS2002评分、年龄与肺结核患者的病情相关。NRS2002评分≥3分以及ALB≤35 g/L的患者痰液结核分枝杆菌阳性率和存在肺结核空洞的比例均高于NRS2002评分35 g/L的患者（均P40岁为肺结核患者痰液结核分枝杆菌阳性的危险因素;而年龄、性别、NRS2002评分和ALB值均不是患者肺结核空洞的危险因素。 结论 NRS2002评分≥3分、ALB≤35 g/L的肺结核患者更容易出现痰液结核分枝杆菌阳性情况。肺结核患者营养状况与肺结核患者病情具有一定相关性。     

Integrated scoring approach to assess radiotherapy plan quality for breast cancer treatment

BackgroundProposal of an integrated scoring approach assessing the quality of different treatment techniques in a radiotherapy planning comparison. This scoring method incorporates all dosimetric indices of planning target volumes (PTVs) as well as organs at risk (OARs) and provides a single quantitative measure to select an ideal plan.Materials and methodsThe radiotherapy planning techniques compared were field-in-field (FinF), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), hybrid IMRT (H-IMRT), and hybrid VMAT (H-VMAT). These plans were generated for twenty-five locally advanced left-sided breast cancer patients. The PTVs were prescribed a hypofractionation dose of 40.5 Gy in 15 fractions. The integrated score for each planning technique was calculated using the proposed formula.ResultsAn integrated score value that is close to zero indicates a superior plan. The integrated score that incorporates all dosimetric indices (PTVs and OARs) were 1.37, 1.64, 1.72, 1.18, and 1.24 for FinF, IMRT, VMAT, H-IMRT, and H-VMAT plans, respectively.ConclusionThe proposed integrated scoring approach is scientific to select a better plan and flexible to incorporate the patient-specific clinical demands. This simple tool is useful to quantify the treatment techniques and able to differentiate the acceptable and unacceptable plans.     

Identification of cuproptosis‐related lncRNAs for prognosis and immunotherapy in glioma

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis‐related genes have prognostic predictive value has not been clarified. In this study, uni‐/multi‐variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis‐related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high‐ and low‐risk groups. Either for grade 2–3 or for grade 4, glioma patients with high‐risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high‐risk group was functionally associated with immune responses and cancer‐related pathways. The high‐risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high‐risk group were significantly higher than those in the low‐risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T‐cell co‐stimulation pathways. In conclusion, we established a risk model based on cuproptosis‐related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno‐microenvironment status of glioma.