Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

A Priori Subcell Limiting Approach for the FR/CPR Method on Unstructured Meshes

A priori subcell limiting approach is developed for high-order flux reconstruction/correction procedure via reconstruction (FR/CPR) methods on two-dimensional unstructured quadrilateral meshes. Firstly, a modified indicator based on modal energy coefficients is proposed to detect troubled cells, where discontinuities exist. Then, troubled cells are decomposed into nonuniform subcells and each subcell has one solution point. A second-order finite difference shock-capturing scheme based on nonuniform nonlinear weighted (NNW) interpolation is constructed to perform the calculation on troubled cells while smooth cells are calculated by the CPR method. Numerical investigations show that the proposed subcell limiting strategy on unstructured quadrilateral meshes is robust in shock-capturing.     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

注意缺陷多动障碍儿童执行功能的评估与干预

ADHD儿童认知障碍的主要特征之一是执行功能损害,涉及包括前额叶皮层在内的特定脑区域及多层级脑网络异常。执行功能按照功能性分为冷-热两方面:冷执行功能损害主要表现于反应抑制、工作记忆以及认知灵活性等;热执行功能损害通常涉及延迟满足、赏罚相关决策、自我调节及情绪调节等。ADHD儿童的执行功能评估应基于可信范式进行文化适应性调整。临床干预不能单一聚焦于冷执行功能,需关注儿童的身体发育以及热执行功能(情绪社会方面)的发展进程,结合其他共病与心理状况,进行全面的动态随访与干预,以达到最佳的长期疗效。     

The role of dark adaptation in understanding early AMD

The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD.Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time.Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.     

30 years of ocular proton therapy,the Nice view

PurposeRadiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization.Materaial and methodsMEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991–2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (～95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract).ResultsAlthough demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice.ConclusionsSome of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.     

基于合作对象探讨我国学术期刊专题/专栏建设

【目的】 了解学术期刊专题/专栏建设的现状,以切实发挥学术期刊专题/专栏建设的作用,为期刊的品牌建设、学术创新、影响力提升和办刊质量提高提供策略。【方法】 采用问卷调查法,对全国范围内397名专题/专栏合作对象(包括期刊主编、编委、审稿人、作者)进行调查,了解他们对期刊专题/专栏建设的态度和意见,从合作对象视角探讨影响学术期刊专题/专栏建设成功率和有效性的因素。【结果】 合作对象态度上,表示支持专题/专栏建设工作的比例较高(71.28%),但供稿率不高(43.37%),存在态度和行为分离的现象。排名前5的供稿率影响因素是期刊被本专业领域研究者认可、期刊被数据库收录情况、期刊影响力、期刊品牌、期刊的处理速度。最优的约稿方式是行业内的学术带头人联系约稿,其次是熟识的专家委托和期刊主编亲自联系进行约稿。合作对象最希望获得的帮助是稿件快速审理发表和确定选题方向。【结论】 为提高学术期刊专题/专栏建设质量,应进一步挖掘重要合作对象的作用,有针对性地选择高供稿率的合作对象;努力挖掘和利用影响合作对象供稿的因素,在期刊品牌建设、扩大影响力方面下功夫;优化约稿方式方法,重视行业学术带头人的作用;同时通过稿件快速审理发表、帮助确定选题并提供发表后推广等服务,提高合作对象对专题/专栏建设工作的认可度和参与度。