Biomarker Index Research Articles

Depositional environment of the Late Santonian lacustrine source rocks in the Songliao Basin (NE China): Implications from organic geochemical analyses

The Songliao Basin (SLB) located in northeastern China is one of the largest Cretaceous continental sedimentary basins in the world. The SLB is filled with sediments deposited in the Upper Jurassic, the Lower Cretaceous and the Upper Cretaceous epochs. The Nenjiang Formation (K2n) is subdivided into five members, where Member 2 (K2n2) was deposited in the late Santonian in the lower part of the Nenjiang Formation. This member is characterized by a thick succession of organic-rich source rocks. However, the complexity of the depositional environment raises questions about the specific factors that drove this accumulation of organic material. Here, we present data on the total organic carbon (TOC) contents and their stable carbon isotope values (δ13Corg), as well as biomarker data from 50 outcrop samples collected from the Yuewangcheng (YWC) section, in the southeastern SLB. According to the variations of the bulk organic parameters (TOC and δ13Corg) and biomarker indices, the profile could be divided into three stages (stages I–III). The distribution of biomarkers (n-alkanes, steranes and hopanes) and δ13Corg values indicate that the organic matter (OM) in the Lower K2n2 is derived largely from algae and macrophytes, with a minor input from bacteria and land plants. The water column was stratified, as indicated by the presence of gammacerane. Variations in the pristane/phytane (Pr/Ph) and aryl isoprenoids relative to phenanthrene ratio (A-i/P) suggest that bottom waters were anoxic during Stage I (31.5–26.0 m) and Stage II (26.0–16.3 m), with the anoxic layer impinging on the euphotic zone and a relative oxic environment at Stage III (16.3–0 m). This brackish environment persisted in the water over the interval represented by the section, as reflected by methytrimethyltridecyl chromans (MTTCs) Index (MTTCI) and α-MTTC/γ-MTTC ratios. Marine transgressions, with subsequent seawater incursions, can be detected with the presence of 24-n-propyl-cholestanes and 24-isopropyl-cholestanes in the Lower K2n2 sediments, especially during Stage I. These seawater incursions are closely correlated with anoxic conditions and the deposition of organic-rich source rocks.

Overexpression of SSH1 in gastric adenocarcinoma and its correlation with clinicopathological features.

Gastric adenocarcinoma is known to be the fourth most common cancer type and the second cause of cancer-related deaths. Movement and invasion of cancer cells is one of the major characteristics of the cancer phenotype that various types of network regulate this. Expression levels of slingshot diphosphatase 1 (SSH1) gene has been modulated in this pathway. SSH1 acts as a dephosphorylation and activator of cofilin that this regulating and activating by SSH1 can play a major role in the mobility and migration of the cell. The aim of this study was to compare the expression level of SSH1 genes between tumor and corresponding adjacent non tumor gastric tissues and healthy tissue of gastric adenocarcinoma. In this study, mRNA of 40 gastric adenocarcinoma and corresponding adjacent non tumor gastric tissues and 15 healthy biopsy samples was extracted, then after cDNA synthesis, real-time polymerase chain reaction was performed to measure gene expression. According to REST analysis, the relative expression of SSH1 was significantly increased in gastric cancer tissues compared to the corresponding adjacent non tumor gastric tissue samples and normal tissue. Nevertheless, the result revealed no substantial correlation between the expression levels of SSH1 with clinical features. The biomarker index for SSH1 was obtained as 0.89. The results obtained from investigating SSH1 expression are indicative of significant changes in the expression of this gene in gastric adenocarcinoma. This gene can also be used as a biomarker for gastric cancer.

Effects of different endurance exercise modalities on retinal vessel diameters in unipolar depression

BackgroundPsychiatric disorders are associated with a high prevalence of cardiovascular disease. Regular exercise is known to reduce depressive symptoms and improve vascular function, in turn lowering cardiovascular risk. We aimed to investigate the effects of different exercise modalities on retinal vessel diameters as a microvascular biomarker and depression severity index in patients suffering from unipolar depression. Methods23 patients (female: 19, male: 4, age: 36.7, Beck-Depression-Inventory-II (BDI-II) score: 30.7) were enrolled in this two-armed randomized controlled trial. Static vessel analysis was performed to obtain central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents and the arterio-venous diameter ratio (AVR). Maximal bicycle ergometer exercise testing yielded maximal fitness parameters. Patients were assigned to either high intensity low volume (HILV) or moderate continuous aerobic training (MCT). Both intervention groups trained three times a week during a 4-week intervention period. ResultsModerate interaction effects were found for AVR (ɳp2 = 0.12) whereby HILV showed a larger increase in AVR (HILV: pre: 0.89 (0.04), post: 0.91 (0.04), SMD = −0.50) compared to MCT (MCT: pre: 0.85 (0.06), post: 0.86 (0.05), SMD = −0.18). Parallel group trials revealed a 67% possibly beneficial effect of HILV over MCT. Moderate interaction effects on depression severity reduction (ɳp2 = 0.06) were found, whereby the effect size was slightly larger in MCT. ConclusionBoth exercise interventions improved AVR as well as BDI-II. HILV may be more effective in improving cerebrovascular health. The exercise-induced effects on retinal vessel diameter changes were relatively small and the clinical relevance remains to be investigated in larger and longer-term exercise trials.

Characterizing blue carbon stocks in Thalassia testudinum meadows subjected to different phosphorus supplies: A lignin biomarker approach

AbstractSeagrass meadows represent globally important stores of carbon. However, environmental heterogeneity in shallow, estuarine environments may shape the quantity, composition, and postdepositional processing of organic carbon stocks (Corg) in such meadows. Along a persistent gradient in total phosphorus concentrations in the water column and a parallel gradient in seagrass morphology, we measured bulk carbon parameters (Corg, dry bulk density, %Corg, Corg : N, δ13C) and lignin biomarkers in Thalassia testudinum tissues and in the sediments beneath these meadows in three coastal systems. We found Corg stocks and sources differed among coastal systems, but the aforementioned parameters were not consistently related to either standing stocks of seagrass or historical nutrient concentrations. We estimated that seagrasses contributed 30–53% of the total sedimentary Corg in these three coastal systems, with the remainder derived from allochthonous sources. The coastal system with intermediate phosphorus concentrations and aboveground seagrass stock had more Corg overall, more Corg from seagrass, and sediments with lower bulk density. A consistent negative relationship between dry bulk density and %Corg suggested hydrodynamics exerted a strong influence on stocks and sources of sedimentary Corg. Lignin biomarkers refined our understanding of sources of Corg and postdepositional processing of seagrass tissues. Phenolic acid‐to‐aldehyde ratios were high in fresh T. testudinum tissues. Lower values in sediments indicated seagrass tissues undergo extensive loss of acidic lignin phenols after deposition resulting in a need for lignin biomarker indices designed for estuarine sediments. Future studies of seagrass Corg should account for hydrodynamic setting, especially when investigating influences of environmental heterogeneity.

Abstract 2017: Phenotypic plasticity and class switching in ovarian cancer

Abstract The multifaceted evolution of cancer involves differential responses of tumor cell populations to intrinsic and extrinsic stimuli. Numerous reports have examined the role of epithelial-mesenchymal transition (EMT) in the progression of high-grade serous ovarian carcinoma (HGSC). An earlier study from our group successfully resolved molecular subclasses in HGSC wherein metastasis was mediated by cooperative cell migration in the epithelial subclass and EMT in the mesenchymal subclass. We now explore the transcriptional circuitry in expression datasets and cell lines regulating these states. This led to the identification that Tcf21 and Slug expression correlated with the epithelial and mesenchymal phenotypes, respectively, and inversely correlated with each other. Probing the differential altered localization and expression of TCF21 and Slug further resolved a spectrum of intermediary phenotypic states along the epithelial to mesenchymal spectrum, each of which is associated with the expression of specific markers. Further, functional assays reveal the inherent plasticity of each phenotype with migratory mechanisms emerging as a differential parameter. Rigidity and high degree of differentiation of the epithelial and mesenchymal state is evident from a lack of responsiveness to specific microenvironmental conditions. Importantly, such cellular plasticity induced shifts from a steady-state phenotype following modulation of the microenvironment only in the intermediate phenotypes to exhibit flexibility to transit towards either the two ends of the spectrum. Specifically, a tendency to acquire an epithelial phenotype on growth factor deprivation was noted. The effects of BMP7 and TGFβ to induce epithelial or mesenchymal phenotypes, respectively, were also noted exclusively within the intermediary states. The stress generated by chemotherapeutic agents like paclitaxel led to enrichment of and dominant effects of the epithelial state. We further queried if this plasticity is also a feature of HGSC tumors. Marker expression (Tcf21, E-cadherin, Parp1, Slug, Anxa2 and Hyaluronan) was scored based on their frequency, intensity and location in tumors to derive a definitive scoring system comprising biomarker and tumor class indices. Application of such scoring could effectively stratifiy 95 human HGSC cases comprising primary and metastatic tumors into epithelial and mesenchymal classes, and further resolve a third class likely to represent the intermediate states. A salient feature noted was that metastases and chemotherapy could lead to class switching. Our study thus provides a comprehensive view of the intrinsic and extrinsic molecular events governing cellular plasticity in HGSC. Citation Format: Sharmila A. Bapat, Sagar Varankar, Swapnil Kamble. Phenotypic plasticity and class switching in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2017.

Aberrant Middle Prefrontal-Motor Cortex Connectivity Mediates Motor Inhibitory Biomarker in Schizophrenia

BackgroundInhibitory deficits in motor cortex in schizophrenia have been well demonstrated using short-interval intracortical inhibition (SICI) by transcranial magnetic stimulation. However, it remains unknown whether these deficits originate from dysfunction of motor cortex itself or reflect abnormal modulations of motor cortex by other schizophrenia-related brain areas. MethodsThe study was completed by 24 patients with schizophrenia spectrum disorders and 30 healthy control subjects. SICI was obtained by delivering transcranial magnetic stimulation over the left motor cortex. Resting-state functional magnetic resonance imaging and diffusion tensor imaging fractional anisotropy were used to measure functional connectivity (FC) and white matter microstructures, respectively. Stimulation sites for SICI at motor cortex were used as the seeds to obtain whole-brain FC maps. Clinical symptoms were assessed with the Brief Psychiatric Rating Scale. ResultsIn schizophrenia, left prefrontal cortex–motor cortex FC was inversely associated with SICI but positively associated with the underlying white matter microstructure at the left corona radiata and also associated with overall symptoms (all corrected p < .05). Mediation analysis showed that the prefrontal-motor cortex FC significantly mediated the corona radiata white matter effects on SICI (p = .007). ConclusionsHigher resting-state left prefrontal-motor cortex FC, accompanied by a higher fractional anisotropy of left corona radiata, predicted fewer inhibitory deficits, suggesting that the inhibitory deficits in motor cortex in schizophrenia may in part be mediated by a top-down prefrontal influence. SICI may serve as a robust biomarker indexing inhibitory dysfunction at anatomic as well as circuitry levels in schizophrenia.

The Holocene isotopic record of aquatic cellulose from Lake Äntu Sinijärv, Estonia: Influence of changing climate and organic-matter sources

The well characterized oxygen-isotopic fractionation during cellulose biosynthesis has been utilised by numerous studies of stable isotopes in fine-grained aquatic cellulose. We measured the δ13Ccellulose and δ18Ocellulose values of bulk cellulose and moss fragments from an ∼11.4ka-long core obtained from a shallow, productive, spring-fed, hardwater lake, Äntu Sinijärv, Estonia (59˚3.8′N; 26˚14.5′E; 94.6 m a.s.l.; maximum depth 7.3 m), in order to reconstruct regional Holocene climate and lake-basin evolution. Isotopically, the modern waterbody is a well-behaved, open, hydrological system with negligible evaporative effects. Cellulose-isotope records were compared with down-core measurements of loss-on-ignition (LOI), carbonate and mineral contents, total organic carbon (TOC), total nitrogen (TN), C/N ratio, δ13CTOC, biomarker indices (Palg and Paq), published palaeoecological data and a δ18Ocarbonate record from the same palaeolake. Green microalgae, freshwater macroalgae (Chara) and aquatic bryophytes were important sources of sedimentary cellulose during different phases in the environmental history of the lake. Although a strong palaeoclimatic imprint can be detected in the δ18Ocellulose record from Äntu Sinijärv, notably the Preboreal oscillation, the 8.2ka event and an unnamed cold oscillation ∼3.25ka BP, the isotopic signal of these events may have been amplified by increases in 18O-depleted spring snowmelt. In contrast, δ13Ccellulose was tightly coupled to the Holocene evolution of terrestrial ecosystems and soils by significant inputs of biogenic carbon from the catchment and sublacustrine springs. During the early Holocene, ∼11 – 9ka BP, the δ18Ocellulose and δ18Ocarbonate records diverge markedly, which can be attributed to “no-analogue” seasonal, climatic, hydrological and isotopic conditions resulting from orbital forcing and residual ice-sheet impacts.

Test-retest reliability of short-interval intracortical inhibition and intracortical facilitation in patients with schizophrenia

Impaired short-interval intracortical inhibition (SICI) elicited by paired-pulse TMS (ppTMS) has emerged as one of the most consistent TMS findings in patients with schizophrenia. Reduction of SICI has been reproducibly found, suggesting that SICI may be a new biomarker indexing the inhibitory dysfunction in schizophrenia. This study evaluated whether SICI has the test-retest reliability suitable for clinical trial and research applications. SICIs, intracortical facilitation (ICF), and other ppTMS effects were obtained using inter-stimulus intervals (ISIs) from 1 to 500 ms, on 2 occasions about 3–4 weeks apart in patients with schizophrenia and healthy individuals. Acceptable test-retest reliabilities were found for SICI (at 1 and 3 ms ISIs) in both patients and controls (all intraclass correlation coefficients r > 0.6). However, test-retest reliability in longer ISIs and in ICF were modest or poor. To our knowledge, this is the first study demonstrated the acceptable reliability of SICI measure in patients with schizophrenia. The data support SICI as a reliable biomarker for schizophrenia.

Sex consideration in diet-biomarker-related indices: a systematic review.

An index of biomarkers derived from dietary factors (diet-biomarker-related index) identifies foods and nutrients that encompass physiological potentials and provides scientific evidence for dietary patterns that increase the risk of disease associated with specific biomarkers. Although men and women have different dietary patterns and physiological characteristics, sex is not often considered when investigators develop a diet-biomarker-related index. We aimed to review whether epidemiological studies developed diet-biomarker-related indices in a sex-specific way. We systematically searched for epidemiological studies that developed diet-biomarker-related indices, including (i) biomarker prediction indices that include dietary factors as explanatory variables and (ii) dietary patterns to explain biomarker variations, in the PubMed and EMBASE databases. We qualitatively reviewed the sex consideration in index development. We identified seventy-nine studies that developed a diet-biomarker-related index. We found that fifty-four studies included both men and women. Of these fifty-four studies, twenty-nine (53·7 %) did not consider sex, eleven (20·3 %) included sex in the development model, seven (13·0 %) considered sex but did not include sex in the development model, and seven (13·0 %) derived a diet-biomarker-related index for men and women separately. A list of selected dietary factors that explained levels of biomarkers generally differed by sex in the studies that developed a diet-biomarker-related index in a sex-specific way. Most studies that included both men and women did not develop the diet-biomarker-related index in a sex-specific way. Further research is needed to identify whether a sex-specific diet-biomarker-related index is more predictive of the disease of interest than an index without sex consideration.

The validity, stability, and utility of measuring uric acid in saliva.

Serum uric acid (UA) is associated with many health conditions, including kidney, cardiovascular, and metabolic disorders. We examined the validity and stability of salivary UA as a noninvasive measure of serum UA. Using serum and salivary UA data from healthy adults (n=99), we examined the UA serum-saliva correlation, and UA associations with adiponectin and C-reactive protein. Using longitudinal data from young adults (n=182), we examined salivary UA stability. We found robust positive serum-saliva correlations for UA. UA and adiponectin were inversely related in serum and saliva. Salivary UA was relatively stable; 62-66% of variance could be attributed to a latent trait-like component. Salivary UA may be an important biomarker indexing health and disease risk.

Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology

Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer’s disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. In 915 patients, CSF Ng was evaluated across several different neurodegenerative diseases. Of these 915 patients, 116 had a neuropathologically confirmed definitive diagnosis and the relation between CSF Ng and topographical distribution of different pathologies in the brain was evaluated. CSF Ng was specifically increased in ADD compared to eight other neurodegenerative diseases, including Parkinson’s disease (p < 0.0001), frontotemporal dementia (p < 0.0001), and amyotrophic lateral sclerosis (p = 0.0002). Similar results were obtained in neuropathologically confirmed cases. Using a biomarker index to evaluate whether CSF Ng contributed diagnostic information to the core AD CSF biomarkers (amyloid β (Aβ), t-tau, and p-tau), we show that Ng significantly increased the discrimination between AD and several other disorders. Higher CSF Ng levels were positively associated with greater Aβ neuritic plaque (Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuritic plaque score, p = 0.0002) and tau tangle pathology (Braak neurofibrillary tangles staging, p = 0.0007) scores. In the hippocampus and amygdala, two brain regions heavily affected in ADD with high expression of Ng, CSF Ng was associated with plaque (p = 0.0006 and p < 0.0001), but not with tangle, α-synuclein, or TAR DNA-binding protein 43 loads. These data support that CSF Ng is increased specifically in ADD, that high CSF Ng concentrations likely reflect synaptic dysfunction and that CSF Ng is associated with β-amyloid plaque pathology.

Association of Biomarker and Physiologic Indices With Mortality in Older Adults: Cardiovascular Health Study.

A goal of gerontology is discovering aging phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that strongly and independently associated with mortality and that statistically attenuated chronologic age could be used to define such a phenotype. We determined the association of a Biomarker Index (BI) with mortality and compared it with a validated Physiologic Index (PI) in older adults. The indices were constructed in the Cardiovascular Health Study, mean (SD) age 74.5 (5.1) years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, insulin-like growth factor-binding protein 3, amino-terminal pro-B-type natriuretic peptide, dehydroepiandrosterone sulfate, and interleukin-6, and was built in test (N = 2,197) and validation (N = 1,124) samples. The PI included carotid intima-media thickness, pulmonary capacity, brain white matter grade, cystatin-C, and fasting glucose. Multivariable Cox proportional hazards models predicting death were calculated with 10 years of follow-up. In separate age-adjusted models, the hazard ratio for mortality per point of the BI was 1.30 (95% confidence interval 1.25, 1.34) and the BI attenuated age by 25%. The hazard ratio for the PI was 1.28 (1.24, 1.33; 29% age attenuation). In the same model, the hazard ratio for the BI was 1.23 (1.18, 1.28) and for the PI was 1.22 (1.17, 1.26), and age was attenuated 42.5%. Associations persisted after further adjustment. The BI and PI were significantly and independently associated with mortality. Both attenuated the age effect on mortality substantially. The indices may be feasible phenotypes for developing interventions hoping to alter the trajectory of aging.

Myeloperoxidase, superoxide dismutase‐3, cardiometabolic risk factors, and distal sensorimotor polyneuropathy: The KORA F4/FF4 study

Oxidative stress has been proposed as important pathomechanism of cardiometabolic diseases and distal sensorimotor polyneuropathy (DSPN). However, the relevance of biomarkers of oxidative stress has not been investigated in this context. Therefore, this study aimed to assess the association of the prooxidant myeloperoxidase (MPO) and the antioxidant extracellular superoxide dismutase (SOD3) with cardiometabolic risk factors and with prevalence and incidence of DSPN. Cross-sectional analyses comprised 1069 participants (40.3% with prediabetes and 20.5% with type 2 diabetes) of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006-2008), 181 of whom had DSPN at baseline. Prospective analyses included 524 individuals without DSPN at baseline who also participated in the KORA FF4 study (2013-2014), 132 of whom developed DSPN during the 6.5-year follow-up. Serum MPO and SOD3 were measured by ELISA, and their association with cardiometabolic risk factors and DSPN were estimated by using linear and logistic regression analyses. Higher MPO and SOD levels showed multiple positive associations with cardiometabolic risk factors including age, indices of obesity, insulin resistance, serum lipids, renal dysfunction, and biomarkers of inflammation. Higher MPO levels were associated with prevalent DSPN (fully adjusted OR 1.38 [95% CI 1.10; 1.72] per doubling of MPO). Higher baseline SOD3 levels were related to incident DSPN (age and sex-adjusted OR 2.14 [1.02; 4.48] per doubling of SOD3), which was partially explained by cardiometabolic risk factors. Systemic levels of both pro- and antioxidant enzymes appear involved in cardiometabolic risk and development of DSPN.

Hydrocarbon accumulation and formation of composite reservoirs in KL16-1 of Laizhou Bay Sag, Bohai Sea, China

The Laizhou Bay Sag, one of the oil-bearing sags with large exploration potential in the South Bohai Sea of China, contains two sets of high-quality hydrocarbon source rocks, i.e. Member 3 and Member 4 of Shahejie Fm (E2s3 and E2s4). As an important hydrocarbon accumulation zone in the sag, the KL16-1 low bulge is found to have oil reservoirs in the Neogene Guantao Fm (N1g), the Paleogene Dongying Fm (E3d), the Paleogene Shahejie Fm (E2s), and the Mesozoic buried hill formation. It is characterized by distinct features of composite reservoirs. Nonetheless, its hydrocarbon accumulation process and mechanism are unknown yet. In this paper, the hydrocarbon generation modelling of source rocks, combined with the characteristics of oil-source rock biomarker compounds and fluid inclusions, is used to restore the hydrocarbon accumulation process in the KL16-1 low bulge. Crude oil in all three KL16-1 plays is characterized by low Pr/Ph, low gammacerane, high 4-methyl sterane and high dinosterane. In other words, it is oil of low maturity to maturity. As the biomarker index of the oil is very similar to that of the E2s3 source rocks, it is thought that E2s3 is the primary source rock layer, while E2s4 is the secondary source rock layer. In addition, episodic oil and gas charging happened in two phases under high pressure in the late period (from 5.0 Ma till now).

Abstract P1-06-10: Correlative analysis of breast cancer index (BCI) restratification of 21-gene recurrence score (RS) in patients with hormone receptor-positive (HR+), node-negative breast cancer

Abstract Background: In a cross-stratification analysis performed within the TransATAC cohort, Breast Cancer Index (BCI) and 21-gene Recurrence Score (RS) had a concordance of 58.2% (Sestak et al., Clin Cancer Res, 2016). Restratification by BCI of the low and intermediate RS risk groups led to subgroups with significantly different rates (P &amp;lt; 0.001 and P = 0.003, respectively); in contrast, restratified subgroups created by RS of BCI risk groups did not differ significantly. The objective of this study was to analyze the concordance of BCI and RS test results in HR+, node-negative (LN-) patients tested in the real-world setting and to investigate molecular, clinical, and pathologic correlates within discrepant cases. Methods: This study utilized a subset of cases from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database which contains clinicopathologic and molecular variables from clinical cases submitted for BCI testing. Clinicopathologic variables, abstracted from pathology reports, were available for a subset of cases. This analysis evaluated cases from LN- patients with available RS data. Concordance was evaluated between BCI Prognostic risk groups (Low, High) and RS risk groups (Low, Intermediate, High based on TAILOR Rx cutpoints [0-10, 11-25, and 26+]). Fisher's Exact tests were used to compare molecular (HoxB13/IL17BR [H/I] endocrine response biomarker and Molecular Grade Index [MGI] proliferation marker) and clinicopathologic (age, grade, size, HER2, Ki67) data in discrepant risk groups. Results: There were 456 LN- patients included. Median age was 58.0y (range 27.2-84.0y; 73.9% ≥50y); 33.1%/50.1%/16.8% were grade 1/2/3; and 24.0%/59.5%/15.3% were T1ab/T1c/T2. BCI classified 47.8% (n=218) of patients as Low Risk vs 52.2% (n=238) as High Risk. RS classified 17.1% (n=78), 67.1% (n=306), and 15.8% (n=72) of patients as Low, Intermediate, and High Risk, respectively. BCI restratified RS-Low patients as high risk in 17.1% of cases, restratified RS-Intermediate as Low Risk in 48.4% and High Risk in 51.6%, and restratified RS-High as Low risk in 20.8% of cases. In RS-Low patients, only H/I (P=0.0004) and MGI (P=0.047) were significantly correlated with restratification to BCI-High Risk. In RS-Intermediate patients, H/I (P&amp;lt;0.0001), MGI (P&amp;lt;0.0001), grade (P&amp;lt;0.0001), and Ki67 &amp;gt;20% (P=0.0003) were significantly correlated with restratification by BCI to High or Low Risk. In RS-High patients, H/I (P=0.0008), MGI (P&amp;lt;0.0001), grade (P=0.016) were significantly correlated with restratification to Low Risk. Conclusion: BCI restratified a substantial proportion of patients in each RS risk group. Based on previous studies demonstrating that BCI has improved prognostic ability for assessment of risk of late distant recurrence (Sgroi et al., Lancet Oncol, 2013), these results highlight the clinical utility of BCI within all RS risk groups. The estrogen signaling pathway biomarker H/I and proliferative biomarkers (MGI, grade, Ki67) were associated with restratification by BCI, while age, HER2 status, and tumor size were not. Citation Format: Yan F, Master AK, Israel MA, Liu J, Schnabel CA, Hurvitz S, Gadi VK. Correlative analysis of breast cancer index (BCI) restratification of 21-gene recurrence score (RS) in patients with hormone receptor-positive (HR+), node-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-10.

太阳辐射影响高原生态系统的湖泊沉积生物标志物证据

太阳活动与地球生态系统之间的联系是学术界较少谈及但却十分重要的论题。本文尝试利用青藏高原东部湖泊沉积物中高等植物生物标志物指标探讨高原生态系统与太阳活动之间的关系。结果表明高等植物来源正构烷烃和正构脂肪醇的碳优势指数(CPI)及平均碳链长度(ACL)敏感地响应了总太阳辐照度(TSI)的变化，忠实地记录了青藏高原东部近900 a来四次太阳活动极小期。因此我们认为高原湖泊生态系统波动背后的驱动力实质上是太阳辐射强度的变化。 The relationship between solar activity and the terrestrial ecosystem is an important topic but less mentioned in previous studies. Herein, we applied the biomarker index deduced from the n-alkanes and n-alkanols in lake sediments which are believed to be derived from higher plant exploring the relationship between the solar activity and plateau ecosystem. The results show that the conventional biomarker indexes including carbon preference index (CPI) and average chain length (ACL) sensitively respond to the total solar irradiation (TSI) variation and faithfully recorded four solar minimum periods during the last 900 a. So it is considered that the driving force behind the fluctuations of plateau lacustrine ecosystem is essentially the change in solar radiation intensity.

Right Atrial Deformation in Predicting Outcomes in Pediatric Pulmonary Hypertension.

Elevated right atrial (RA) pressure is a risk factor for mortality, and RA size is prognostic of adverse outcomes in pulmonary hypertension (PH). There is limited data on phasic RA function (reservoir, conduit, and pump) in pediatric PH. We sought to evaluate (1) the RA function in pediatric PH patients compared with controls, (2) compare the RA deformation indices with Doppler indices of diastolic dysfunction, functional capacity, biomarkers, invasive hemodynamics, and right ventricular functional indices, and (3) evaluate the potential of RA deformation indices to predict clinical outcomes. Sixty-six PH patients (mean age 7.9±4.7 years) were compared with 36 controls (7.7±4.4 years). RA and right ventricular deformation indices were obtained using 2-dimensional speckle tracking (2DCPA; TomTec, Germany). RA strain, strain rates, emptying fraction, and right ventricular longitudinal strain were measured. RA function was impaired in PH patients versus controls (P<0.001). There were significant associations between RA function with invasive hemodynamics (P<0.01). RA reservoir, pump function, the rate of RA filling, and atrial minimum volume predicted adverse clinical outcomes (hazard ratio [HR], 0.15; confidence interval [CI], 0.03-0.73; P<0.01; HR, 0.05; CI, 0.003-0.43; P<0.004; HR, 0.04; CI, 0.006-0.56; P<0.01; and HR, 8.6; CI, 1.6-37.2; P<0.01, respectively). RA deformation properties are significantly altered in pediatric PH patients. Progressive worsening of RA reservoir and conduit functions is related to changes in right ventricular diastolic dysfunction. RA reservoir function, pump function, the rate of atrial filling, and atrial minimum volume emerged as outcome predictors in pediatric PH.

Acid pretreatment increased lipid biomarker extractability: a case study to reveal soil organic matter input from rubber trees after long‐term cultivation

The lipids extractable by organic solvents are important components of soil organic matter (SOM) and were used to trace the sources and degradation of SOM. Previous studies have suggested soil mineral protection of lipids, which might decrease the efficiency of extraction of some lipid compounds by organic solvents. Therefore, in this study we applied a mild acid treatment to remove most of the reactive mineral particles without altering SOM chemical structures. The SOM information provided by lipid biomarkers was different before and after acid treatment in this research. Because of the various chemical contents of lipids, the presence of reactive minerals might alter lipid biomarker signals considerably and could lead to the wrong conclusions. Based on lipid biomarker information obtained through acid‐aided extraction, we identified that the source for alkanoic acids was different from that for alkanols and alkanes. Alkanoic acids were derived from both original vegetation (bamboos) and new inputs from fresh rubber tree tissues, whereas alkanols and alkanes were mainly from the original vegetation. Various biomarker indices indicated an extended degradation of lipids after intensive rubber tree cultivation. The leaching of short‐chain aliphatic lipids and the new input of alkanoic acids in the surface soil were also considered to avoid the incorrect orientation of biomarker information. This study suggested that although the new input from rubber trees was evident in cultivated soil, cultivation activities might enhance the degradation of SOM and accelerate its turnover. The cycling of SOM thus needs to be investigated carefully to protect the ecosystems affected by intense human activity.Highlights The extractability of lipids is enhanced after removal of reactive minerals. Various biomarkers indicate enhanced lipid degradation after cultivation. New input of SOM from rubber trees is suggested by alkanoic acid biomarkers. Cultivation activities accelerate SOM degradation and turnover.

Clinical significance of the serum biomarker index detection in children with Henoch-Schonlein purpura

ObjectiveTo explore a panel of serum biomarkers for laboratory diagnosis of pediatric Henoch-Schönlein purpura (HSP). MethodsThe blood white blood cells (WBC) and serum levels of serum amyloid A (SAA), interleukin 6 (IL-6), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin E (IgE), C-reactive protein (CRP), complement component 3 (C3), complement component 4 (C4), and ASO (anti-streptolysin O) were detected in 127 patients with Henoch-Schonlein purpura (HSP), 110 cases of septicemia patients, and 121 healthy volunteers. The diagnostic ability of biomarkers selected from HSP and septicemia patients was analyzed by ROC curve. By designing the calculation model, the biomarker index was calculated for laboratory diagnosis of HSP and differential diagnosis between HSP and septicemia. ResultsThe levels of serum WBC, CRP, IL-6 and SAA in the septicemia patients were significantly higher than those in the control group (p<0.05). Compared with the healthy individuals, serum levels of WBC, CRP, IL-6, SAA, IgA and IgM were significantly increased in patients with HSP (p<0.05). The area under the curve (AUC) of SAA, IgA, IgM, WBC, IL-6, and CRP in the patients with HSP was 0.964, 0.855, 0.849, 0.787, 0.765, and 0.622, respectively. The values of SAA, IgA, IgM, WBC, IL-6, and CRP in septicemia patients were 0.700, 0.428, 0.689, 0.682, 0.891, and 0.853, respectively. Biomarker index=SAA+IgA/4000+IgM/4000×0.4CRPmean valueCRPi. The biomarker index in HSP patients was significantly higher than that of the healthy controls. However, the biomarker index in septicemia patients was significantly lower than the control. ConclusionThe biomarker index of HSP patients is higher than that of the control group. While in the infectious disease represented by septicemia, it is decreased. The detection of biomarker index could exclude the interference of infection as the auxiliary examination to HSP patients.

Improved method for simultaneous determination of saturated and aromatic biomarkers, organosulfur compounds and diamondoids in crude oils by GC–MS/MS

An improved GC–MS/MS method was developed for simultaneous determination of various types of molecular markers in whole crudes without the need for laborious group-type separation and discrete analyses of the diverse fractions. The ability to simultaneously identify and accurately quantify the numerous saturated and aromatic biomarkers, the organosulfur compounds (OSC) and the diamondoids in a single step was attained through use of expanded multiple reaction monitoring (MRM) transitions in specific time windows. The optimization was achieved through improving GC separation and selective choice of precursor and product ions, collision energies, dwell time, and time windows in the MRM settings. The method was tested using four crude oils of diverse types, densities and maturities: a heavy crude from Sicily (18° API), an intermediate-density crude from the Arabian Gulf (33° API), a light black oil from California (39° API), and a light condensate from Wyoming (53° API). The improvements were validated by checking accuracy and precision using three spiking levels of standard compounds into the oils. Comparison of the results of the single-step GC–MS/MS method with the results from traditional multi-step approaches indicates that the single-step GC–MS/MS approach achieved higher resolution, higher specificity and sensitivity, higher accuracy and precision for calculation of the common biomarker indices. Additionally, the single-step approach precluded the loss of light-end components during sample preparation and minimized co-elution problems in molecular analyses.