BACKGROUND & AIMS: :We report the case of a 60-year-old man who first presented with transient difficulty of word recall. Subsequent MRI revealed an invasive brain tumor in the left frontal lobe. The patient underwent open biopsy, and diffuse astrocytoma(WHO grade II)was diagnosed. However, the malignant potential of this tumor was not particularly low because of a few enhancement on preoperative evaluation, and radiation therapy was initially performed. Four months after ending irradiation, temozolomide treatment was introduced for tumor regrowth. After another 2 months, combined chemotherapy with bevacizumab was also started due to tumor enlargement, which was evaluated as malignant transformation to glioblastoma. Two focal lesions with signal hyperintensity on DWI appeared in the frontal and temporal lobes at different locations 3 months after starting bevacizumab. The left temporal lesion subsequently changed to a ring-enhanced tumor, and glioblastoma(WHO grade IV)was finally diagnosed at decompressive surgery. Another frontal lesion, however, continued to maintain a favorable course without any changes in signal despite appearing as similar signal-hyperintense lesions. The temporal hyperintense lesion may undergo malignant transformation into glioblastoma with typical radiological appearance. Recent studies on image changes following bevacizumab treatment have attracted widespread attention, and the clinical significance of such hyperintense lesions has gained attention. This present case was thought to be valuable because of the contradistinctive aspects at the same time, in which the hyperintense lesions of the frontal and temporal lobes seemed to represent antitumor activity or drug refractory effects based on bevacizumab treatment.

背景与目标： : 我们报告了一名60岁男子的案例，该男子首次出现短暂的单词回忆困难。随后的MRI显示左额叶有浸润性脑肿瘤。患者接受了开放性活检，并诊断为弥漫性星形细胞瘤 (WHO II级)。然而，由于术前评估的增强作用，该肿瘤的恶性潜能并不是特别低，并且最初进行了放射治疗。放疗结束四个月后，替莫唑胺治疗肿瘤再生。另外2个月后，由于肿瘤扩大，贝伐单抗联合化疗也开始，这被评估为恶性转化为胶质母细胞瘤。开始使用贝伐单抗3个月后，在不同位置的额叶和颞叶出现了两个DWI信号高信号的局灶性病变。左颞部病变随后变为环状增强肿瘤，最终在减压手术中诊断为胶质母细胞瘤 (WHO IV级)。然而，尽管出现类似的信号高信号病变，但另一额叶病变继续保持良好的病程，而信号没有任何变化。颞高强度病变可能会发生恶性转化为具有典型放射学外观的胶质母细胞瘤。近年来关于贝伐单抗治疗后图像变化的研究引起了广泛关注，此类高强度病变的临床意义也引起了人们的关注。由于同时存在不同的方面，因此本病例被认为是有价值的，其中额叶和颞叶的高强度病变似乎代表了基于贝伐单抗治疗的抗肿瘤活性或药物难治性作用。

BACKGROUND & AIMS: OBJECTIVES:To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health Initiative (WHI) randomized trial. METHODS:Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up. RESULTS:Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors. CONCLUSION:A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:Successful hemodialysis requires reliable vascular access that can deliver adequate blood flow. An arteriovenous fistula is preferred for access because of its longevity and low frequency of complications, but up to 60% of arteriovenous fistulas created surgically are never suitable for hemodialysis because of nonmaturation (insufficient vascular dilatation). Decreased arterial elasticity may impair dilatation, thereby affecting fistula maturation. This study evaluated the feasibility of brachial artery elasticity measurement in patients with chronic kidney disease obtained during routine pre-operative mapping ultrasound (US) imaging before hemodialysis access placement and compared the measurements to those obtained in healthy volunteers. METHODS:Brachial artery functional US studies were collected from 75 patients undergoing routine preoperative mapping for hemodialysis access and 50 healthy volunteers. Vascular strain was calculated from the change in intima-media thickness between end systole and end diastole, and vascular stress was estimated from the pulse pressure. Assuming a linear elastic medium, the elastic modulus was estimated as the ratio of vascular stress to strain. RESULTS:Elastic modulus measurements were significantly higher in patients than in volunteers (130 versus 100 kPa; P = .01). With combined volunteer and patient data, there was a significant correlation between elasticity and systolic blood pressure (R2 = 0.23; P < .001). Elasticity was correlated with age in volunteers but not in patients (R2 = 0.14; P = .017; R2 < .001; P = .829, respectively). CONCLUSIONS:This analysis of clinical arterial vessel biomechanics shows that a noninvasive US measurement can detect elastic modulus differences between patients with chronic kidney disease and healthy individuals. Future studies will correlate the elastic modulus with histologic characteristics and eventual arteriovenous fistula maturation, which may provide supplemental information on arterial biomechanical properties as a useful addition to current predictors of fistula success.

背景与目标：

BACKGROUND & AIMS: :Comparative analysis is the preferred method of inferring RNA secondary structure, but its use requires considerable expertise and manual effort. As the importance of secondary structure for accurate sequence alignment and phylogenetic analysis becomes increasingly realised, the need for secondary structure models for diverse taxonomic groups becomes more pressing. The number of available structures bears little relation to the relative diversity or importance of the different taxonomic groups. Insects, for example, comprise the largest group of animals and yet are very poorly represented in secondary structure databases. This paper explores the utility of maximum weighted matching (MWM) to help automate the process of comparative analysis by inferring secondary structure for insect mitochondrial small subunit (12S) rRNA sequences. By combining information on correlated changes in substitutions and helix dot plots, MWM can rapidly generate plausible models of secondary structure. These models can be further refined using standard comparative techniques. This paper presents a secondary structure model for insect 12S rRNA based on an alignment of 225 insect sequences and an alignment for 16 exemplar insect sequences. This alignment is used as a template for a web server that automatically generates secondary structures for insect sequences.

背景与目标： : 比较分析是推断RNA二级结构的首选方法，但其使用需要相当的专业知识和人工努力。随着二级结构对于准确的序列比对和系统发育分析的重要性日益认识，对用于不同分类组的二级结构模型的需求变得越来越迫切。可用结构的数量与不同分类组的相对多样性或重要性几乎没有关系。例如，昆虫是最大的动物群体，但在二级结构数据库中的代表性很差。本文探讨了最大加权匹配 (MWM) 通过推断昆虫线粒体小亚基 (12S) rRNA序列的二级结构来帮助自动化比较分析过程的效用。通过结合有关取代和螺旋点图的相关变化的信息，MWM可以快速生成二级结构的合理模型。这些模型可以使用标准的比较技术进一步完善。本文基于225昆虫序列的比对和16个示例性昆虫序列的比对，提出了昆虫12S rRNA的二级结构模型。此对齐方式用作web服务器的模板，该模板会自动生成昆虫序列的二级结构。

BACKGROUND & AIMS: :High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and malignant ovarian tumor.To identify co-expression modules and hub genes correlated with platinum-based chemotherapy resistant and sensitive HGSOC, we performed weighted gene co-expression network analysis (WGCNA) on microarray data of HGSOC with 12 resistant samples and 16 sensitive samples of GSE51373 dataset.A total of 5122 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that the module salmon (cor = 0.50), magenta (cor = 0.49), and black (cor = 0.45) were discovered associated with chemotherapy resistant, and the significance for these platinum-resistant modules were validated in the GSE63885 dataset. Given that the black module was validated to be the most related one, hub genes of this module, alcohol dehydrogenase 1B, cadherin 11, and vestigial like family member 3were revealed to be expressional related with platinum resistance, and could serve as prognostic markers for ovarian cancer.Our analysis might provide insight for molecular mechanisms of platinum-based chemotherapy resistance and treatment response in ovarian cancer.

背景与目标： 高级别浆液性卵巢癌 (HGSOC) 是最常见和最恶性的卵巢肿瘤。为了确定与铂类化疗耐药和敏感的HGSOC相关的共表达模块和hub基因，我们对HGSOC的微阵列数据进行了加权基因共表达网络分析 (WGCNA)，其中GSE51373数据集的12个耐药样品和16个敏感样品。WGCNA共包含5122个基因，并鉴定了16个模块。模块-性状分析发现模块鲑鱼 (cor  =   0.50) 、品红色 (cor  =   0.49) 和黑色 (cor  =   0.45) 与化疗耐药相关，并在GSE63885数据集验证了这些耐铂模块的意义。鉴于黑色模块被证实是最相关的一个，该模块的中枢基因，乙醇脱氢酶1B，钙粘蛋白11和残留样家族成员3被发现与铂类抗性表达相关，并可作为卵巢癌的预后指标，我们的分析可能为卵巢癌铂类化疗耐药的分子机制和治疗反应提供深入的研究。

BACKGROUND & AIMS: :This paper proposes a new sequential weighted least squares (SWLS) method for positron emission tomography (PET) reconstruction. The SWLS algorithm is noniterative and can be considered as equivalent to the penalized WLS (PWLS) method under certain initial conditions. However, a full implementation of SWLS is computationally intensive. To overcome this problem, we propose a simplified SWLS as a reasonable alternative to the SWLS. The performance of this SWLS method is evaluated in experiments using both simulated and clinical data. The results show that the method can be advantageously compared with the original SWLS both in computation time and reconstruction quality.

背景与目标： : 本文提出了一种新的顺序加权最小二乘 (SWLS) 方法，用于正电子发射断层扫描 (PET) 重建。SWLS算法是非迭代的，在某些初始条件下可以视为等效于惩罚WLS (PWLS) 方法。但是，SWLS的完整实现需要大量计算。为了克服这个问题，我们提出了一种简化的SWLS作为SWLS的合理替代方案。使用模拟和临床数据在实验中评估了该SWLS方法的性能。结果表明，该方法在计算时间和重建质量上都可以与原始SWLS进行比较。

BACKGROUND & AIMS: BACKGROUND:It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations. AIMS:To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence. METHOD:Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study). RESULTS:Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA. CONCLUSIONS:A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.

背景与目标：

BACKGROUND & AIMS: BACKGROUND AND PURPOSE:The roles of DTI and dynamic susceptibility contrast-enhanced-PWI in predicting the angiographic vascularity of meningiomas have not been studied. We aimed to investigate if these 2 techniques could reflect the angiographic vascularity of meningiomas. MATERIALS AND METHODS:Thirty-two consecutive patients with meningiomas who had preoperative dynamic susceptibility contrast-enhanced-PWI, DTI, and conventional angiography were retrospectively included. The correlations between angiographic vascularity of meningiomas, classified with a 4-point grading scale, and the clinical or imaging variables-age and sex of patient, as well as size, CBV, fractional anisotropy, and ADC of meningiomas-were analyzed. The meningiomas were dichotomized into high-vascularity and low-vascularity groups. The differences in clinical and imaging variables between the 2 groups were compared. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of these variables. RESULTS:In meningiomas, angiographic vascularity correlated positively with CBV but negatively with fractional anisotropy. High-vascularity meningiomas demonstrated significantly higher CBV but lower fractional anisotropy as compared with low-vascularity meningiomas. In differentiating between the 2 groups, the area under the curve values were 0.991 for CBV and 0.934 for fractional anisotropy on receiver operating characteristic curve analysis. CONCLUSIONS:CBV and fractional anisotropy correlate well with angiographic vascularity of meningiomas. They may differentiate between low-vascularity and high-vascularity meningiomas.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To evaluate the performance of diffusion-weighted imaging (DWI) against the reference standard of gadolinium-enhanced T1-weighted imaging (Gd-T1-WI) in children. METHODS:Thirty-nine consecutive patients (mean age 5.7 years) with suspected acute pyelonephritis underwent magnetic resonance imaging (MRI) including DWI and (the reference standard) Gd-T1-WI. Each study was read in double-blinded fashion by two radiologists. Each kidney was graded as normal or abnormal. Sensitivity and specificity of DWI were computed. Agreement between sequences and interobserver reproducibility were calculated (Cohen κ statistic and the McNemar tests). RESULTS:Thirty-two kidneys (41 %) had hypo-enhancing areas on Gd-T1-W images. The sensitivity and specificity of DWI were 100 % (32/32) and 93.5 % (43/46). DWI demonstrated excellent agreement (κ = 0.92,) with Gd-T1-W, with no significant difference (P = 0.25) in detection of abnormal lesions. Interobserver reproducibility was excellent with DWI (κ = 0.79). CONCLUSION:DWI enabled similar detection of abnormal areas to Gd-T1-WI and may provide an injection-free means of evaluation of acute pyelonephritis. KEY POINTS:• Diffusion weighted magnetic resonance imaging (DWI) can confirm acute pyelonepritis. • DWI provided comparable results to gadolinium enhanced T1-W MRI in acute pyelonepritis. • Contrast medium injection could be avoided for diagnosing acute pyelonephritis by MRI. • MRI with T2-WI and DWI provide a fast and comprehensive diagnostic tool.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:In the United States, chronic obstructive pulmonary disease (COPD) diagnosis is often a lengthy process, and consequently results in delays in treatment in early stages. Disease progression and complication may result in increased levels of healthcare service use. To understand the economic burden of COPD prior to diagnosis in the U.S., trends in utilization and costs during the period before initial COPD diagnosis were compared with matched controls. METHODS:A retrospective case-control study was conducted using medical and pharmacy claims data from a large managed care health plan representing a base population of over 30 million covered lives in the U.S. COPD patients with at least 12 months of continuous enrollment and aged 40 years or older were identified (n=28,968) and matched to up to three random controls (n=81,322) by age, gender, region of plans and index date. Multivariate regression models were used to estimate average incremental service use and cost between COPD patients and controls. Moreover, trends in utilization and costs for the COPD patients were examined over 36 months before diagnosis. RESULTS:COPD patients used 1.5-1.6 times more inpatient/emergency department (IP/ED) services and office visits compared to control patients. The average incremental annual costs for IP/ED services, office visits, and medical and pharmacy services were estimated at $550, $238, $1438 and $401, respectively, after adjusting for age, gender, region and comorbid conditions. The 36-month trend analysis showed that COPD patients' healthcare utilization and costs increased gradually over time, often with a marked increase in the month before COPD diagnosis. CONCLUSIONS:COPD patients in the U.S. consumed substantial healthcare services and costs prior to diagnosis. More timely diagnosis and subsequent treatment may avoid costly healthcare utilization and unnecessary mortality and morbidity post-diagnosis.

背景与目标：

BACKGROUND & AIMS: PURPOSE:To investigate the contribution of perfusion-weighted MR imaging (PWI) by using the relative cerebral blood volume (rCBV) ratio in the differential diagnosis of various intracranial space-occupying lesions. MATERIALS AND METHODS:This study involved 105 patients with lesions (high-grade glioma (N=26), low-grade glioma (N=11), meningioma (N=23), metastasis (N=25), hemangioblastoma (N=6), pyogenic abscess (N=4), schwannoma (N=5), and lymphoma (N=5)). The patients were examined with a T2*-weighted (T2*W) gradient-echo single-shot EPI sequence. The rCBV ratios of the lesions were obtained by dividing the values obtained from the normal white matter. Statistical analysis was performed with the Mann-Whitney U-test. A P-value less than 0.05 was considered statistically significant. RESULTS:The rCBV ratio was 5.76+/-3.35 in high-grade gliomas, 1.69+/-0.51 in low-grade gliomas, 8.02+/-3.89 in meningiomas, 5.27+/-3.22 in metastases, 11.36+/-4.41 in hemangioblastomas, 0.76+/-0.12 in abscesses, 1.10+/-0.32 in lymphomas, and 3.23+/-0.81 in schwannomas. The rCBV ratios were used to discriminate between 1) high- and low-grade gliomas (P<0.001), 2) hemangioblastomas and metastases (P<0.05), 3) abscesses from high-grade gliomas and metastases (P<0.001), 4) schwannomas and meningiomas (P<0.001), 5) lymphomas from high-grade gliomas and metastases (P<0.001), and 6) typical meningiomas and atypical meningiomas (P<0.01). CONCLUSION:rCBV ratios can help discriminate intracranial space-occupying lesions by demonstrating lesion vascularity. It is possible to discriminate between 1) high- and low-grade gliomas, 2) hemangioblastomas and other intracranial posterior fossa masses, 3) abscesses from high-grade gliomas and metastases, 4) schwannomas and meningiomas, 5) lymphomas and high-grade gliomas and metastases, and 6) typical and atypical meningiomas.

背景与目标：

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Using an instrument to measure physical functioning that was normed to the U.S. population, data were obtained from patients with a new diagnosis of breast, colon, lung, and prostate cancer. Two questions were addressed: (a) after controlling for age, and number of comorbid conditions, do site and stage of cancer predict functional limitations prior to diagnosis; (b) using age adjusted national norms on physical functioning, how well do age, number of comorbid conditions, stage, treatment and cluster of symptoms (pain, fatigue, and insomnia) explain changes in physical function between 3 months prior to and 8 weeks following diagnosis? METHODS:Patients 65 years of age and older were accrued from 24 community oncology settings. Consenting patients were interviewed within 8 weeks of initial treatment. The SF-36 was used to measure physical functioning. Comorbidity and symptom experience were assessed through patient report and site and stage of cancer from record audits. RESULTS:Prior to diagnosis of cancer, patients were comparable in physical functioning to the U.S. population aged 55-64, a full decade younger than the sample of cancer patients. Site and stage of disease did not account for variations in physical functioning prior to diagnosis. Compared against national norms, patients with more extensive treatments (surgery plus adjuvant therapy) reported greater loss in functioning. Pain, fatigue, and insomnia had a consistent and significant effect on losses in functioning unrelated to patients' treatments or their comorbid conditions. CONCLUSIONS:Site and stage of cancer prior to diagnosis do not affect functioning. Older cancer patients report higher functioning than their counterparts in the U.S. population. Changes in functioning following diagnosis varied by cancer site. Treatments were related to loss in functioning, but comorbidity was not. Pain, fatigue, and insomnia were significant and independent predictors of change in patient functioning. This underscores the importance of interventions to manage symptoms early in the course of treatment for individuals.

背景与目标：

BACKGROUND & AIMS: :We report the serial magnetic resonance imaging (MRI) findings in a case of methanol intoxication. A 50-year-old man who had accidentally ingested methanol was admitted to our institution. The patient was almost blind, and became comatose. The MRI showed bilateral putaminal lesions with restricted diffusion. The MRI, which was performed on the third day after admission, showed new lesions in the subcortical white matter. The patient's general condition improved. His visual acuity, however, did not improve.

背景与目标： : 我们报告了甲醇中毒情况下的连续磁共振成像 (MRI) 发现。一名意外摄入甲醇的50岁男子被我们机构录取。病人几乎失明，昏迷了。MRI显示双侧皮损扩散受限。入院后第三天进行的MRI显示皮质下白质有新病变。患者的一般情况有所改善。但是，他的视力没有改善。

BACKGROUND & AIMS: :It has long been observed that trimethylamine N-oxide (TMAO) and urea demonstrate dramatically different properties in a protein folding process. Even with the enormous theoretical and experimental research work on these two osmolytes, various aspects of their underlying mechanisms still remain largely elusive. In this paper, we propose to use the weighted persistent homology to systematically study the osmolytes molecular aggregation and their hydrogen-bonding network from a local topological perspective. We consider two weighted models, i.e., localized persistent homology (LPH) and interactive persistent homology (IPH). Boltzmann persistent entropy (BPE) is proposed to quantitatively characterize the topological features from LPH and IPH, together with persistent Betti number (PBN). More specifically, from the localized persistent homology models, we have found that TMAO and urea have very different local topology. TMAO is found to exhibit a local network structure. With the concentration increase, the circle elements in these networks show a clear increase in their total numbers and a decrease in their relative sizes. In contrast, urea shows two types of local topological patterns, i.e., local clusters around 6 Å and a few global circle elements at around 12 Å. From the interactive persistent homology models, it has been found that our persistent radial distribution function (PRDF) from the global-scale IPH has same physical properties as the traditional radial distribution function. Moreover, PRDFs from the local-scale IPH can also be generated and used to characterize the local interaction information. Other than the clear difference of the first peak value of PRDFs at filtration size 4 Å, TMAO and urea also shows very different behaviors at the second peak region from filtration size 5 Å to 10 Å. These differences are also reflected in the PBNs and BPEs of the local-scale IPH. These localized topological information has never been revealed before. Since graphs can be transferred into simplicial complexes by the clique complex, our weighted persistent homology models can be used in the analysis of various networks and graphs from any molecular structures and aggregation systems.

背景与目标： : 长期以来，人们观察到三甲胺N-氧化物 (TMAO) 和尿素在蛋白质折叠过程中表现出截然不同的特性。即使对这两种渗透物进行了大量的理论和实验研究，其潜在机制的各个方面仍然难以捉摸。在本文中，我们建议使用加权持久性同源性从局部拓扑角度系统地研究渗透压分子聚集及其氢键网络。我们考虑两个加权模型，即局部持久同源性 (LPH) 和交互式持久同源性 (IPH)。提出了玻尔兹曼持久熵 (BPE) 来定量表征LPH和IPH的拓扑特征以及持久Betti数 (PBN)。更具体地说，从局部持久同源性模型中，我们发现TMAO和urea具有非常不同的局部拓扑。发现TMAO具有本地网络结构。随着浓度的增加，这些网络中的圆元素显示出其总数的明显增加和相对大小的减小。相比之下，尿素显示了两种类型的局部拓扑模式，即6å 附近的局部簇和12å 附近的一些全局圆元素。从交互式持久同源性模型中发现，我们来自全局尺度IPH的持久径向分布函数 (PRDF) 具有与传统径向分布函数相同的物理性质。此外，还可以生成来自本地尺度IPH的prdf，并将其用于表征本地交互信息。除了在过滤尺寸为4å 时PRDFs的第一个峰值的明显差异外，TMAO和尿素在第二个峰值区域也显示出从过滤尺寸5å 到10å 的非常不同的行为。这些差异也反映在本地规模IPH的pbn和bpe中。这些局部化的拓扑信息以前从未被揭示过。由于图形可以通过集团复合体转移到简单的复合物中，因此我们的加权持久同源性模型可以用于分析来自任何分子结构和聚集系统的各种网络和图形。

BACKGROUND & AIMS: :The purpose of in vivo-in vitro correlation (IVIVC) modeling is described. These models are usually fitted to deconvoluted data rather than the raw plasma drug concentration/time data. Such a two-stage analysis is undesirable because the deconvolution step is unstable and because the fitted model predicts the fraction of a dosage unit dissolved/absorbed in vivo which generally is not the primary focus of our attention. Interest usually centers on the plasma drug concentration or some function of it (e.g., AUC, Cmax). Incorporation of a convolution step into the model overcomes these difficulties. Odds, hazards, and reversed hazards models which include a convolution step are described. The identity model (which states that average in vivo and in vitro dissolution/time curves are coincident or directly superimposable) is a special case of these models. The odds model and the identity model were fitted to data sets for two different products using nonlinear mixed effects model fitting software. Results show that the odds model describes both data sets reasonably well and is a significantly better fit than the identity model in each case.

背景与目标： : 描述了体内-体外相关 (IVIVC) 建模的目的。这些模型通常适合去卷积数据，而不是原始血浆药物浓度/时间数据。这种两阶段分析是不希望的，因为去卷积步骤是不稳定的，并且因为拟合模型预测了体内溶解/吸收的剂量单位的分数，这通常不是我们关注的主要焦点。兴趣通常集中在血浆药物浓度或其某些功能 (例如AUC，Cmax) 上。将卷积步骤合并到模型中可以克服这些困难。描述了包括卷积步骤的赔率，危害和反向危害模型。身份模型 (指出平均体内和体外溶出度/时间曲线是一致的或可直接叠加的) 是这些模型的特例。使用非线性混合效应模型拟合软件将赔率模型和身份模型拟合到两种不同产品的数据集。结果表明，赔率模型可以很好地描述这两个数据集，并且在每种情况下都比身份模型更好。