Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Deepm5C: A deep-learning-based hybrid framework for identifying human RNA N5-methylcytosine sites using a stacking strategy

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Estimating Cost-Effectiveness Using Alternative Preference-Based Scores and Within-Trial Methods: Exploring the Dynamics of the Quality-Adjusted Life-Year Using the EQ-5D 5-Level Version and Recovering Quality of Life Utility Index

ObjectivesThis study aimed to explore quality-adjusted life-year (QALY) and subsequent cost-effectiveness estimates based on the more physical health–focused EQ-5D 5-level version (EQ-5D-5L) value set for England or cross-walked EQ-5D 3-level version UK value set scores or more mental health recovery-focused Recovering Quality of Life Utility Index (ReQoL-UI), when using alternative within-trial statistical methods. We describe possible reasons for the different QALY estimates based on the interaction between item scores, health state profiles, preference-based scores, and mathematical and statistical methods chosen.MethodsQALYs are calculated over 8 weeks from a case study 2:1 (intervention:control) randomized controlled trial in patients with anxiety or depression. Complete case and with missing cases imputed using multiple-imputation analyses are conducted, using unadjusted and regression baseline-adjusted QALYs. Cost-effectiveness is judged using incremental cost-effectiveness ratios and acceptability curves. We use previously established psychometric results to reflect on estimated QALYs.ResultsA total of 361 people (241:120) were randomized. EQ-5D-5L crosswalk produced higher incremental QALYs than the value set for England or ReQoL-UI, which produced similar unadjusted QALYs, but contrasting baseline-adjusted QALYs. Probability of cost-effectiveness <£30 000 per QALY ranged from 6% (complete case ReQoL-UI baseline-adjusted QALYs) to 64.3% (multiple-imputation EQ-5D-5L crosswalk unadjusted QALYs). The control arm improved more on average than the intervention arm on the ReQoL-UI, a result not mirrored on the EQ-5D-5L nor condition-specific (Patient-Health Questionnaire-9, depression; Generalized Anxiety Disorder-7, anxiety) measures.ConclusionsReQoL-UI produced contradictory cost-effectiveness results relative to the EQ-5D-5L. The EQ-5D-5L’s better responsiveness and “anxiety/depression” and “usual activities” items drove the incremental QALY results. The ReQoL-UI’s single physical health item and “personal recovery” construct may have influenced its lower 8-week incremental QALY estimates in this patient sample.     

放疗干预对宫颈癌荷瘤小鼠的抑瘤作用及对Th1/Th2免疫细胞比例的影响

目的探讨放疗干预对宫颈癌荷瘤小鼠的抑瘤作用及其对辅助性T细胞1(Th1)/Th2细胞比例的影响。方法建立宫颈癌荷瘤小鼠模型,随机分为荷瘤组和放疗组,每组各10只,另设对照组10只。放疗组进行放疗干预14天,荷瘤组和对照组不治疗。放疗后4、6、8、10、12、14天测量肿瘤体积;末次治疗后,ELISA法测定血清干扰素-γ(IFN-γ)、白介素-2(IL-2)、IL-4、IL-10含量;计算抑瘤率、胸腺指数和脾脏指数;HE染色观察肿瘤组织学变化;TUNEL染色观察肿瘤组织细胞凋亡情况;流式细胞术检测脾脏Th1/Th2细胞比例;RT-qPCR和Western blot检测脾脏T盒子转录因子(T-bet)、GATA结合蛋白3(GABA-3)mRNA和蛋白表达。结果与荷瘤组比较,放疗组小鼠4、6、8、10、12、14天肿瘤体积及瘤质量减小,血清IL-2、IFN-γ升高,IL-4、IL-10降低,胸腺指数、脾脏指数升高,Th1细胞比例、Th1/Th2增加,Th2细胞比例减少,T-bet mRNA和蛋白及T-bet/GATA-3表达升高,GATA-3 mRNA和蛋白表达降低(P<0.05)。HE染色显示,荷瘤组肿瘤细胞数量较多,核大深染,无明显坏死;放疗组肿瘤细胞数量减少,出现大量坏死组织。TUNEL染色显示,荷瘤组TUNEL阳性细胞较少,放疗组TUNEL阳性细胞明显增多。结论放疗对宫颈癌荷瘤小鼠具有明显抑瘤作用,可能是通过调节T-bet/GATA-3表达,促进Th1/Th2分化平衡,增强机体免疫功能发挥作用。     

Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.