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1
Grzebisz, Witold. "Site-Specific Nutrient Management." Agronomy 11, no. 4 (April 13, 2021): 752. http://dx.doi.org/10.3390/agronomy11040752.
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The editorial introduces to a Special Issue entitled ”Site-Specific Nutrient Management. The concept of the nitrogen gap (NG) is as a core challenge for an effective realization of the so called “twin objectives” in sustainable agriculture. This special issue stresses on some hot spots in crop production, being responsible in the yield gap development, that farmers have to take control. The yield gap cannot be ameliorated without the synchronization of the in-season requirements of the currently grown crop for N with its three-dimensional variability in a supply on a field (temporal, spatial and vertical). A recognition of soil fertility status in the rooted zone, which includes availability of both mineral N and nutrients decisive for its uptake, is the first step in the NG amelioration. The sustainability in soil fertility, as a prerequisite of N fertilizer application, requires a wise strategy of organic matter management, based on farmyard manure, and/or cultivation of legumes. The soil fertility status, irrespectively of the World region determines ways of the N rate optimization. The division of a particular field into homogenous productive units is the primary step in the NG cover. It can be delineated, using both data on soil physico-chemical properties of the soil rooted zone, and then validated by using satellite spectral images of the crop biomass in a well-defined stage of its growth, decisive for yield. The proposed set of diagnostic tools is a basis for elaboration an effective agronomic decision support system.
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Pearson, Clare, Veronique Poirier, Karen Fitzgerald, Greg Rubin, and Willie Hamilton. "Cross-sectional study using primary care and cancer registration data to investigate patients with cancer presenting with non-specific symptoms." BMJ Open 10, no. 1 (January 2020): e033008. http://dx.doi.org/10.1136/bmjopen-2019-033008.
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IntroductionPatients presenting to primary care with site-specific alarm symptoms can be referred onto urgent suspected cancer pathways, whereas those with non-specific symptoms currently have no dedicated referral routes leading to delays in cancer diagnosis and poorer outcomes. Pilot Multidisciplinary Diagnostic Centres (MDCs) provide a referral route for such patients in England.ObjectivesThis work aimed to use linked primary care and cancer registration data to describe diagnostic pathways for patients similar to those being referred into MDCs and compare them to patients presenting with more specific symptoms.MethodsThis cross-sectional study linked primary care data from the National Cancer Diagnosis Audit (NCDA) to national cancer registration and Route to Diagnosis records. Patient symptoms recorded in the NCDA were used to allocate patients to one of two groups - those presenting with symptoms mirroring referral criteria of MDCs (non-specific but concerning symptoms (NSCS)) and those with at least one site-specific alarm symptom (non-NSCS). Descriptive analyses compared the two groups and regression analysis by group investigated associations with long primary care intervals (PCIs).ResultsPatients with NSCS were more likely to be diagnosed at later stage (32% stage 4, compared with 21% in non-NSCS) and via an emergency presentation (34% vs 16%). These patients also had more multiple pre-referral general practitioner consultations (59% vs 43%) and primary care-led diagnostics (blood tests: 57% vs 35%). Patients with NSCS had higher odds of having longer PCIs (adjusted OR: 1.24 (1.11 to 1.36)). Patients with lung and urological cancers also had higher odds of longer PCIs overall and in both groups.ConclusionsDifferences in the diagnostic pathway show that patients with symptoms mirroring the MDC referral criteria could benefit from a new referral pathway.
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Raza, Shaan M., Paul W. Gidley, Michael E. Kupferman, Ehab Y. Hanna, Shirley Y. Su, and Franco DeMonte. "Site-Specific Considerations in the Surgical Management of Skull Base Chondrosarcomas." Operative Neurosurgery 14, no. 6 (September 9, 2017): 611–19. http://dx.doi.org/10.1093/ons/opx171.
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Abstract BACKGROUND Numerous approaches have been reported in the management of skull base chondrosarcomas. Data are lacking for surgical outcomes by the tumor site of origin. OBJECTIVE To provide insight into outcomes by site of origin and factors affecting resection in order to aid in surgical approach selection. METHODS A retrospective review was conducted of 49 patients with chondrosarcoma treated at our institution. Charts were reviewed for tumor- and treatment-related factors. Extent of resection was the primary outcome, while neurological function and surgical complications were secondary outcomes. Statistical analyses were performed assessing variables for their impact on the primary outcome. RESULTS The gross total resection rate for the overall cohort was 67.3%, and 97.8% of patients were either neurologically stable or improved postoperatively. A petroclival site of origin had lower rates of resection vs all other sites (P < .05). Histology and previous surgery did not predict outcome (P > .05), while previous radiotherapy and cavernous sinus invasion correlated with a subtotal resection (P < .05). In the petroclival cohort, clival, jugular tubercle, and soft tissue involvement correlated with a subtotal resection (P < .05). An endoscopic endonasal transpterygoid approach alone or combined with a transcranial approach yielded the highest resection rates for petroclival tumors (P < .05). CONCLUSION Chondrosarcomas pose unique challenges based on the site of origin and pattern of extension. While current surgical strategies appear to yield adequate results at a majority of skull base sites, petroclival tumors represent a particular cohort in which improvement is needed. Based on our analysis, strategies incorporating both endoscopic and transcranial skull base approaches are likely necessary to achieve optimal outcomes.
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Molnar, Sheri, Stan E. Dosso, and John F. Cassidy. "Uncertainty of linear earthquake site amplification via Bayesian inversion of surface seismic data." GEOPHYSICS 78, no. 3 (May 1, 2013): WB37—WB48. http://dx.doi.org/10.1190/geo2012-0345.1.
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We examine uncertainty in predicted linear 1D site amplification due to uncertainty in shear-wave velocity ([Formula: see text]) structure quantified from Bayesian (probabilistic) inversion of microtremor array dispersion data. Based on a sample of [Formula: see text] profiles drawn from the posterior probability density of the microtremor inversion, probability distributions are computed for common predictors of site amplification including [Formula: see text] (traveltime average [Formula: see text] to a depth [Formula: see text]) and amplification spectra based on seismic impedance variations and full transverse shear-wave effects. These methods are applicable for any site, but the resulting probabilistic site amplification analyses are specific to the two sediment sites studied here with strongly contrasting geology in high population centers of British Columbia, Canada. The site amplification probability distributions for the two sites are shown to be more informative than amplification estimated for a single best-fit [Formula: see text] profile by characterizing the uncertainty and therefore level of confidence in the predictions. The shear-wave amplification probability spectra are evaluated by comparison to empirical earthquake and microtremor spectral ratios, with generally good agreement in resonant peak frequencies and amplification levels, providing confidence that the primary influence of site-specific structure is accounted for appropriately. The wider implication here is that proper characterization of the [Formula: see text] profile uncertainty distribution from inversion of cost-effective surface wave dispersion data is beneficial in the application of said profiles to the prediction of earthquake site response and its uncertainty, as required for probabilistic seismic hazard assessment.
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Samaržija, Ivana. "Site-Specific and Common Prostate Cancer Metastasis Genes as Suggested by Meta-Analysis of Gene Expression Data." Life 11, no. 7 (June 30, 2021): 636. http://dx.doi.org/10.3390/life11070636.
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Anticancer therapies mainly target primary tumor growth and little attention is given to the events driving metastasis formation. Metastatic prostate cancer, in comparison to localized disease, has a much worse prognosis. In the work presented here, groups of genes that are common to prostate cancer metastatic cells from bones, lymph nodes, and liver and those that are site-specific were delineated. The purpose of the study was to dissect potential markers and targets of anticancer therapies considering the common characteristics and differences in transcriptional programs of metastatic cells from different secondary sites. To that end, a meta-analysis of gene expression data of prostate cancer datasets from the GEO database was conducted. Genes with differential expression in all metastatic sites analyzed belong to the class of filaments, focal adhesion, and androgen receptor signaling. Bone metastases undergo the largest transcriptional changes that are highly enriched for the term of the chemokine signaling pathway, while lymph node metastasis show perturbation in signaling cascades. Liver metastases change the expression of genes in a way that is reminiscent of processes that take place in the target organ. Survival analysis for the common hub genes revealed involvements in prostate cancer prognosis and suggested potential biomarkers.
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Deng, Yang, Aiqun Li, and Dongming Feng. "Fatigue performance investigation for hangers of suspension bridges based on site-specific vehicle loads." Structural Health Monitoring 18, no. 3 (July 17, 2018): 934–48. http://dx.doi.org/10.1177/1475921718786710.
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Hangers or suspenders of a suspension bridge are the primary load-carrying members and are vital to the structural integrity and service life of the bridge. Site-specific vehicle loads monitored by the weigh-in-motion system can assist to obtain the operational cyclic stresses of hangers. Differing from most existing studies, herein, a framework for fatigue performance investigation for hangers of suspension bridges is proposed utilizing the full information of the weigh-in-motion data. This framework includes four steps: (1) generate influence surfaces for hangers, (2) reconstruct vehicular loading flows based on the weigh-in-motion data, (3) calculate time histories of hanger tension forces, and (4) evaluate fatigue damages and predict fatigue lives. Critical issues, such as the loading configuration of trucks, the threshold of the gross vehicle weight, and the time step for stress calculation, have been studied and discussed in detail. Based on 8-month weigh-in-motion data of a prototype suspension bridge, it is shown that the fatigue damage of hangers can be evaluated day by day, and subsequently the fatigue lives can be predicted. The correlation between the fatigue damages and vehicular loads is also investigated in this study.
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Shashni, Rajesh, M. Zuhaib Qayyum, V. Vishalini, Debashish Dey, and Ranjan Sen. "Redundancy of primary RNA-binding functions of the bacterial transcription terminator Rho." Nucleic Acids Research 42, no. 15 (July 31, 2014): 9677–90. http://dx.doi.org/10.1093/nar/gku690.
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Abstract The bacterial transcription terminator, Rho, terminates transcription at half of the operons. According to the classical model derived from in vitro assays on a few terminators, Rho is recruited to the transcription elongation complex (EC) by recognizing specific sites (rut) on the nascent RNA. Here, we explored the mode of in vivo recruitment process of Rho. We show that sequence specific recognition of the rut site, in majority of the Rho-dependent terminators, can be compromised to a great extent without seriously affecting the genome-wide termination function as well as the viability of Escherichia coli. These terminators function optimally only through a NusG-assisted recruitment and activation of Rho. Our data also indicate that at these terminators, Rho-EC-bound NusG interaction facilitates the isomerization of Rho into a translocase-competent form by stabilizing the interactions of mRNA with the secondary RNA binding site, thereby overcoming the defects of the primary RNA binding functions.
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Mizukami, Takuro, Masaki Takahashi, Yu Sunakawa, Satoshi Yuki, Yoshinori Kagawa, Atsuo Takashima, Kyoko Kato, et al. "Identification of site-specific genome alterations in metastatic colorectal cancer: Sub-study 003 of the SCRUM-Japan GI-SCREEN." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 578. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.578.
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578 Background: Primary tumor sidedness is known to be an independent prognostic factor and a predictor for the efficacy of anti-EGFR antibody. However, limited information is available regarding the role of primary tumor site for the treatment of metastatic colorectal cancer (mCRC) patients (pts), including gene mutation profiles, prognosis, and prediction for treatment. This study was conducted as a sub-study of the SCRUM-Japan GI-SCREEN, the Nationwide Cancer Genome Screening Project in Japan. Methods: Among participants of the GI-Screen 2013-01-CRC, untreated pts with mCRC which samples were collected from primary site were eligible. DNA and RNA were extracted from FFPE tumor samples and then were analyzed by the Oncomine Cancer Research Panel detecting gene mutations, copy number variants (CNV), and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. Results: Among 1011 enrolled pts from Feb. 2015 to Mar 2017, a total of 561 samples were analyzed (median age, 66.0 years; 232 [41.4 %] female). Frequency of female, undifferentiated, mucinous or signet ring cell subtype were gradually increased as the primary site became the right side. Median site-specific survival was 22.4 months (m) in the cecum, 25.3 m in the ascending colon, 21.2 m in the transverse colon, 72.5 m in the descending colon, 36.5 m in the sigmoid colon, and 39.6 m in the rectum. Gene alterations differed in each primary site. Among frequently observed gene alterations, FBXW7 mutation in rectum, ATM mutation in transverse colon, BRAF and SMAD4 mutations in ascending colon significantly contributed to poor prognosis. Conclusions: This study revealed the site-specific survival and gene alterations in Japanese mCRC pts. These novel knowledges provide an intriguing background to investigate new targeted approaches in these pts and represent the progress toward precision medicine. We will analyze the site-specific therapeutic effect of molecular targeting agents, including anti-EGFR antibody. Clinical trial information: UMIN000031242.
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Sollazzo, Giuseppe, Sonia Longo, Maurizio Cellura, and Clara Celauro. "Impact Analysis Using Life Cycle Assessment of Asphalt Production from Primary Data." Sustainability 12, no. 24 (December 9, 2020): 10171. http://dx.doi.org/10.3390/su122410171.
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Road construction and maintenance have a great impact on the environment, owing to the huge volumes of resources involved. Consequently, current production procedures and technologies must be properly investigated, for identifying and quantifying the life cycle environmental impacts produced. In this paper, primary data, i.e., site-specific data directly collected or measured on a reference plant, are analyzed for calculating the impact of the production of a hot mix asphalt. The analysis is performed in a from “cradle to gate” approach to estimate the environmental burdens of the production process in an average plant, representative of the existing technology in Italy and Southern Europe. The research outcomes are useful to increase reliability in quantification of asphalt production impacts and the contribution of each component. The results represent a reference basis for producers, designers, and contractors in the decisional phases, identifying the most critical aspects in the current practice and the possible improvements for reducing impacts of road industries. In this regard, efficient energy technologies for reducing the production temperature (such as warm mix asphalt) and burned fuels are proven to assure relevant improvements in the environmental performance.
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Wanner, Miriam, Katarina L. Matthes, Dimitri Korol, Silvia Dehler, and Sabine Rohrmann. "Indicators of Data Quality at the Cancer Registry Zurich and Zug in Switzerland." BioMed Research International 2018 (June 13, 2018): 1–11. http://dx.doi.org/10.1155/2018/7656197.
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Data quality is an important issue in cancer registration. This paper provides a comprehensive overview of the four main data quality indicators (comparability, validity, timeliness, and completeness) for the Cancer Registry Zurich and Zug (Switzerland). We extracted all malignant cancer cases (excluding non-melanoma skin cancer) diagnosed between 1980 and 2014 in the canton of Zurich. Methods included the proportion of morphologically verified cases (MV%), the proportion of DCN and DCO cases (2009–2014), cases with primary site uncertain (PSU%), the stability of incidence rates over time, age-specific incidence rates for childhood cancer, and mortality:incidence (MI) ratios. The DCO rate decreased from 6.4% in 1997 to 0.8% in 2014 and was <5% since 2000. MV% was 95.5% in 2014. PSU% was <3% over the whole period. The incidence rate of all tumours increased over time with site-specific fluctuations. The overall M:I ratio decreased from 0.58 in 1980 to 0.37 in 2014. Overall, data quality of the Cancer Registry Zurich and Zug was acceptable according to the methods presented in this review. Most indicators improved over time with low DCO rates, high MV%, low PSU%, relatively low M:I ratios and age-specific incidence of childhood cancer within reference ranges.
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Minunno, F., M. Peltoniemi, S. Launiainen, M. Aurela, A. Lindroth, A. Lohila, I. Mammarella, K. Minkkinen, and A. Mäkelä. "A simplified gross primary production and evapotranspiration model for boreal coniferous forests – is a generic calibration sufficient?" Geoscientific Model Development Discussions 8, no. 7 (July 2, 2015): 5089–137. http://dx.doi.org/10.5194/gmdd-8-5089-2015.
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Abstract. The problem of model complexity has been lively debated in environmental sciences as well as in the forest modelling community. Simple models are less input demanding and their calibration involves a lower number of parameters, but they might be suitable only at local scale. In this work we calibrated a simplified ecosystem process model (PRELES) to data from multiple sites and we tested if PRELES can be used at regional scale to estimate the carbon and water fluxes of Boreal conifer forests. We compared a multi-site (M-S) with site-specific (S-S) calibrations. Model calibrations and evaluations were carried out by the means of the Bayesian method; Bayesian calibration (BC) and Bayesian model comparison (BMC) were used to quantify the uncertainty in model parameters and model structure. To evaluate model performances BMC results were combined with more classical analysis of model-data mismatch (M-DM). Evapotranspiration (ET) and gross primary production (GPP) measurements collected in 10 sites of Finland and Sweden were used in the study. Calibration results showed that similar estimates were obtained for the parameters at which model outputs are most sensitive. No significant differences were encountered in the predictions of the multi-site and site-specific versions of PRELES with exception of a site with agricultural history (Alkkia). Although PRELES predicted GPP better than evapotranspiration, we concluded that the model can be reliably used at regional scale to simulate carbon and water fluxes of Boreal forests. Our analyses underlined also the importance of using long and carefully collected flux datasets in model calibration. In fact, even a single site can provide model calibrations that can be applied at a wider spatial scale, since it covers a wide range of variability in climatic conditions.
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Li, Yinghua, Danna Xie, Xiaojing Chen, Teng Hu, Simin Lu, and Yunwei Han. "Prognostic Value of the Site of Distant Metastasis and Surgical Interventions in Metastatic Gastric Cancer: A Population-Based Study." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382096413. http://dx.doi.org/10.1177/1533033820964131.
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Background: Studies on the prognostic significance of site-specific distant metastasis, multiple-site metastases, and the impact of surgery of the primary tumor and metastatic lesion on survival outcomes of patients with metastatic gastric cancer (GC) remain elusive. Therefore, this study aimed to investigate the prognostic significance of the site of distant metastasis among patients with metastatic GC. Furthermore, the effect of surgery of the primary tumor and metastatic lesion on the prognosis of metastatic GC was also analyzed. Methods: The data of 4,221 eligible patients, who were diagnosed with metastatic GC between 2010 and 2015, were identified from the Surveillance Epidemiology and End Results (SEER) database. Multivariate logistic regression analysis was performed to assess the association between potential prognostic factors, including the site of metastasis and surgery, and survival of patients with metastatic GC. Overall survival (OS) and cause-specific survival (CSS) were determined using the Kaplan-Meier survival curves and differences were assessed using the Log-rank test. Results: Out of the total 4,221 GC patients with definite organ metastases, 3312 patients had single-site metastasis while 909 patients had multiple-site metastases. GC patients with single-site metastasis of liver or lung exhibited better CSS and OS compared to those with bone metastasis. Furthermore, GC patients with liver metastasis benefited from surgery of both the primary and metastatic lesions, while those with lung metastasis benefited from surgery of metastasis resection only. Multivariate Cox regression analysis revealed that GC patients with single-site metastasis, well-differentiated tumors, GC patients who underwent surgery of the primary tumor and those who received chemotherapy exhibited favorable prognosis. Conclusions: The site of metastasis was an independent prognostic factor for metastatic GC. Surgery had survival benefits in certain cases of metastatic GC; however, further studies are warranted to clarify these benefits in carefully selected patients.
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Li, H., K. Qu, K. Tokoro, Y. Ren, J. Y. Liu, A. Sferruzza, and R. Bender. "Identification of cancer of unknown primary with gene expression profiling." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 10052. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.10052.
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10052 Background: Patients with metastatic cancer of unknown primary (CUP) generally have a poor prognosis, with a median survival of 2–10 months. Conventional diagnostic approaches for identifying the primary tumor site are successful in only 20%-30% of cases; however, such identification provides prognostic information and helps with selection of tumor-specific therapy, leading to improved survival. Recent studies indicate that gene expression-based classification of CUP is highly successful in predicting the site of origin. We report herein development and validation of a method that determines the site of tumor origin by comparing the gene expression profiles of CUP cases to those in a database created from known tumor types. Methods: RNA extracted from frozen and formalin-fixed, paraffin-embedded (FFPE) tissue wasis purified and amplified using the Paradise Reagent System System (Arcturus, Mountain View, CA). Following reverse-transcription, cDNA products wereare used in a semi-quantitative real-time PCR to detect 87 tumor-associated genes and 5 reference genes in an ABI PRISM 7900HT Detection System (Applied Biosystems, Foster City, CA). Gene expression data wereare then compared to those in a database, composed of gene expression profiles of 571 samples from 39 different tumor types, using k-nearest neighbor analysis to predict the most likely site of tumor origin. Intra- and interassay reproducibility was determined. Frozen and FFPE tissues (n=57) from a well-characterized, independent sample set were also tested in a blinded manner to further validate the method. Results: Based on the real-time PCR cycle threshold, the intra- and interassay reproducibility ranged from 0.1%-4.3% and 0.5%-8.2%, respectively. The primary tumor type was identified in 77% of cases. The assay determined the correct tumor type in 88% (44/50) of the samples. Seven samples were not reported: 3 failed to amplify adequately and 4 had an unacceptably low confidence level. Conclusions: We have shown that gene expression profiling can determine the most likely site of tumor origin. Our data suggest that this new method is able tomay identify the primary site of tumor origin in 77% of CUP cases. No significant financial relationships to disclose.
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Kamel, Mohamed Gomaa, Amr Ehab El-Qushayri, Ahmed Kamal Sayed, and Nguyen Tien Huy. "Using the primary site as a prognostic tool for nodal mantle cell lymphoma: a SEER-based study." Journal of Comparative Effectiveness Research 9, no. 12 (August 2020): 861–76. http://dx.doi.org/10.2217/cer-2020-0083.
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Background: Nodal mantle cell lymphoma (NMCL) has a worse survival than extra-nodal mantle cell lymphoma. Materials & methods: A cohort study was conducted to evaluate the primary site role as a mortality predictor using data from 1983 to 2011 from the Surveillance, Epidemiology, and End Results (SEER) database. Results: Most patients had NMCL in multiple regions (71.9%). There was a significantly increased incidence of NMCL cases over years with 83.2% of them occurred between 1998 and 2011. The mean survival was 52.9 months with overall survival/cancer-specific survival rate of 29.2/42.9%, respectively. Lymph nodes of intrathoracic and multiple regions had a worse overall survival while the head, face and neck, intra-abdominal, pelvic, inguinal region and leg as well as multiple regions had worse cancer-specific survival. Conclusion: NMCL primary site can serve as a prognostic factor. We encourage adding it to MCL International Prognostic Index.
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Steiner, Laurie A., Vincent Schulz, Yelena Maksimova, Nancy E. Seidel, David M. Bodine, and Patrick G. Gallagher. "Unbiased Identification of Functional Barrier Insulators in Primary Human Erythroid Cells,." Blood 118, no. 21 (November 18, 2011): 3385. http://dx.doi.org/10.1182/blood.v118.21.3385.3385.
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Abstract Abstract 3385 Barrier insulators function to actively maintain the boundaries between heterochromatin and euchromatin. They are critical for regulation of cell-type specific gene expression in normal development and differentiation. Mutations that disrupt barrier insulator function have been associated with developmental disorders, malignancies, and inherited hemolytic anemias. Barrier insulators are poorly understood in mammalian cells, with much of the available data coming from model organisms. In vertebrates, the best characterized barrier insulator is the 5' hypersensitive site in the LCR of the chicken β-globin gene cluster (cHS4). In cHS4, barrier insulator function is mediated by binding of the upstream stimulatory factor (USF) proteins, which bind specific DNA sequences and recruit multiple regulatory proteins, including histone aceytltranserases (HATs) and histone methyltransferases (MTs), which maintain DNA in a euchromatin state. The cHS4 barrier also recruits the protein VEZF1, recently shown to mediate protection of DNA from methylation. We hypothesize that there is a common regulatory signature for cell-type specific barrier insulators characterized by binding of the USF proteins, with recruitment of HATs, MTs, and other proteins in the genome of human erythroid cells. To test this hypothesis, we utilized chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) to generate genome-wide maps of barrier-associated proteins and histone modifications in primary human erythroid cells (R3/R4 stage). Regions where barrier-associated proteins co-localize, representing potential barrier insulators, were identified then subjected to functional analysis in position effect variegation (PEV) assays. Genome-wide, 3825 sites bound the USF proteins USF1 and USF2 with their associated MTs (PRMT1/PRMT4), and HATs (P300, PCAF, SRC1). The genome-wide binding of VEZF1 was compared to the binding of the USFs, MTs, and HATs. VEZF1 bound 1129 (30%) of the potential barrier sites. The role of CTCF in barrier insulators is controversial. It is dispensable for cHS4 barrier function in chicken erythroid cells, but in human cells, it marks chromatin boundaries in a cell-type specific manner. CTCF ChIP-seq in erythroid cells revealed that a very large number of the barrier-associated sites (3382, 88%) bound CTCF. Together, 1167 sites bound all 9 factors. These sites were located primarily in gene promoters (42%) and 5' untranslated regions (23%), consistent with data from Drosophila, where barriers are frequently associated with gene promoters. Active barriers are associated with an “open” chromatin structure and lack CpG methylation, thus these epigenetic marks were assessed at the predicted barrier sites. The majority of sites, 96%, had the active histone mark H3K4me2, while only 0.02% were positive for the repressive histone mark H3K27me3. To assess CpG methylation, methyl binding domain pull down was coupled with massively parallel sequencing (MethylSeq). 3676 regions of CpG methylation were identified, but none overlapped with the barrier signature. PEV assays, which assesses the ability of a region of DNA to protect a reporter gene from heterochromatin-mediated silencing, were used to determine if selected sites identified by ChIP-seq studies had barrier insulator function in vivo. Constructs containing an EF1alpha promoter directing an EGFP reporter gene-IRES-hygromycin cassette were flanked by potential barriers and stably transfected into K562 cells. Results from single copy clones were normalized to the cHS4 positive control. Sites tested included an intergenic site on chromosome 11 located >100kb from any known gene (site 1), which bound the USFs, PRMTs, PCAF, SRC1, and CTCF, and a site in intron 1 of the band 3 gene (site 2), which bound the USFs, PRMT4, P300, PCAF, and SRC1. Both sites were shown to have barrier activity (site 1 x2= 6.77, p<0.01 and site 2 x2= 3.30, p<0.06), demonstrating that our molecular signature can predict functional barrier insulators. The orientation dependence of vertebrate barrier elements has never been described. When site 1 and 2 were analyzed in the opposite orientation relative to the direction of transcription, neither had barrier function. Unbiased identification of barrier insulators on a genome wide scale will provide novel insights into normal erythropoiesis and its perturbation in human disease. Disclosures: No relevant conflicts of interest to declare.
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McDaniel, Jaydene, Steven McDaniel, Beanca Jhanine Samiano, Matthew Marrujo, Karl Kingsley, and Katherine M. Howard. "Microbial Screening Reveals Oral Site-Specific Locations of the Periodontal Pathogen Selenomonas noxia." Current Issues in Molecular Biology 43, no. 1 (June 12, 2021): 353–64. http://dx.doi.org/10.3390/cimb43010029.
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Introduction: Selenomonas noxia (SN) is an important periodontal pathogen, associated with gingivitis and periodontitis. Many studies have found associations between SN and indicators of poor health outcomes, such as smoking, low socioeconomic status and obesity. However, less is known about the prevalence of this organism and more specifically about other oral site-specific locations that may harbor this organism. Methods: Using an existing patient repository (n = 47) of DNA isolated from saliva and other oral sites (n = 235), including the dorsum of the tongue, lower lingual incisor, upper buccal molar and gingival crevicular fluid (GCF), molecular screening for SN was performed. Screening results were analyzed for associations between demographic variables (age, sex, race/ethnicity) and clinical information (body mass index or BMI, presence of orthodontic brackets, primary/mixed/permanent dentition). Results: qPCR screening revealed a total of n = 62/235 sites or 26.3% harboring SN with saliva and GCF (either alone or in combination with one or more sites) most often observed (Saliva, n = 23/27 or 85.18%, GCF, n = 14/27 or 51%). Analysis of site-specific data revealed most positive results were found among saliva and GCF alone or in combination, with fewer positive results observed among the tongue (33.3%), lower lingual incisor (29.6%), and upper buccal molar (25.9%). No significant associations were found between demographic or clinical variables and presence of SN at any site. Conclusions: These results may be among the first to describe site-specific locations of S. noxia among various additional oral biofilm sites. These data may represent a significant advancement in our understanding of the sites and locations that harbor this organism, which may be important for our understanding of the prevalence and distribution of these organisms among patients of different ages undergoing different types of oral treatments, such as orthodontic treatment or therapy.
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Veazey, Ronald S., Marie-Claire Gauduin, Keith G. Mansfield, Irene C. Tham, John D. Altman, Jeffrey D. Lifson, Andrew A. Lackner, and R. Paul Johnson. "Emergence and Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells in the Intestines of Macaques during Primary Infection." Journal of Virology 75, no. 21 (November 1, 2001): 10515–19. http://dx.doi.org/10.1128/jvi.75.21.10515-10519.2001.
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ABSTRACT In this report, three Mamu-A*01+ rhesus macaques were examined to compare the emergence of simian immunodeficiency virus (SIV)-specific CD8+ T cells in the intestines and blood in early SIV infection using a major histocompatibility complex class I tetramer complexed with the Gag181–189 peptide. Fourteen days after intravenous inoculation with SIVmac251, large numbers of SIV Gag181–189-specific CD8+ T cells were detected in the intestinal mucosa (3.1 to 11.5% of CD3+CD8+ lymphocytes) as well as in the blood (3.1 to 13.4%) of all three macaques. By 21 days postinoculation, levels of tetramer-binding cells had dropped in both the intestines and blood. At day 63, however, levels of SIV Gag181–189-specific CD8+ T cells in the intestines had rebounded in all three macaques to levels that were higher (8.6 to 18.7%) than those at day 21. In contrast, percentages of tetramer-binding cells in the peripheral blood remained comparatively stable (2.5 to 4.5%) at this time point. In summary, SIV Gag181–189-specific CD8+ T cells appeared in both the intestinal mucosa and peripheral blood at a comparable rate and magnitude in primary SIV infection. Given that the intestine is a major site of early viral replication as well as the site where most of the total body lymphocyte pool resides, these data indicate that it is also an early and important site of development of antiviral immune responses.
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Liu, Jiaqi L., Emily V. Walker, Yuba Raj Paudel, Faith G. Davis, and Yan Yuan. "Brain Metastases among Cancer Patients Diagnosed from 2010–2017 in Canada: Incidence Proportion at Diagnosis and Estimated Lifetime Incidence." Current Oncology 29, no. 3 (March 18, 2022): 2091–105. http://dx.doi.org/10.3390/curroncol29030169.
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The incidence of BM among Canadian cancer patients is unknown. We aimed to estimate IP of BM at the time of cancer diagnosis and during the lifetime of patients with selected primary cancers. Data on BM at diagnosis from 2010–2017 was obtained from the CCR. Site-specific IPs of BM were estimated from provincial registries containing ≥90% complete data on BM. The CCR IP estimates and the IP estimates from literature were applied to the total diagnosed primary cancers to estimate the number of concurrent BM and lifetime BM from 2010–2017 in Canada, respectively. The annual average number of patients with BM at diagnosis from all cancer sites was approximately 3227. The site-specific IPs of BM at diagnosis were: lung (9.42%; 95% CI: 9.16–9.68%), esophageal (1.58%; 95% CI: 1.15–2.02%), kidney/renal pelvis (1.33%; 95% CI: 1.12–1.54%), skin melanoma (0.73%; 95% CI: 0.61–0.84%), colorectal (0.22%; 95% CI: 0.18–0.26%), and breast (0.21%; 95% CI: 0.17–0.24%). Approximately 76,546 lifetime BM cases (or 5.70% of selected fifteen primary cancers sites) were estimated to have occurred from the 2010–2017 cancer patient cohort. These findings reflect results of population analyses in the US and Denmark. We recommend improved standardization of the collection of BM data within the CCR.
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Adamo, Irene, Edgar Ortiz-Malavasi, Robin Chazdon, Priscila Chaverri, Hans ter Steege, and József Geml. "Soil Fungal Community Composition Correlates with Site-Specific Abiotic Factors, Tree Community Structure, and Forest Age in Regenerating Tropical Rainforests." Biology 10, no. 11 (October 31, 2021): 1120. http://dx.doi.org/10.3390/biology10111120.
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Successional dynamics of plants and animals during tropical forest regeneration have been thoroughly studied, while fungal compositional dynamics during tropical forest succession remain unknown, despite the crucial roles of fungi in ecological processes. We combined tree data and soil fungal DNA metabarcoding data to compare richness and community composition along secondary forest succession in Costa Rica and assessed the potential roles of abiotic factors influencing them. We found a strong coupling of tree and soil fungal community structure in wet tropical primary and regenerating secondary forests. Forest age, edaphic variables, and regional differences in climatic conditions all had significant effects on tree and fungal richness and community composition in all functional groups. Furthermore, we observed larger site-to-site compositional differences and greater influence of edaphic and climatic factors in secondary than in primary forests. The results suggest greater environmental heterogeneity and greater stochasticity in community assembly in the early stages of secondary forest succession and a certain convergence on a set of taxa with a competitive advantage in the more persisting environmental conditions in old-growth forests. Our work provides unprecedented insights into the successional dynamics of fungal communities during secondary tropical forest succession.
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Marquardt, André, Philip Kollmannsberger, Markus Krebs, Antonella Argentiero, Markus Knott, Antonio Giovanni Solimando, and Alexander Georg Kerscher. "Visual Clustering of Transcriptomic Data from Primary and Metastatic Tumors—Dependencies and Novel Pitfalls." Genes 13, no. 8 (July 26, 2022): 1335. http://dx.doi.org/10.3390/genes13081335.
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Personalized oncology is a rapidly evolving area and offers cancer patients therapy options that are more specific than ever. However, there is still a lack of understanding regarding transcriptomic similarities or differences of metastases and corresponding primary sites. Applying two unsupervised dimension reduction methods (t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP)) on three datasets of metastases (n = 682 samples) with three different data transformations (unprocessed, log10 as well as log10 + 1 transformed values), we visualized potential underlying clusters. Additionally, we analyzed two datasets (n = 616 samples) containing metastases and primary tumors of one entity, to point out potential familiarities. Using these methods, no tight link between the site of resection and cluster formation outcome could be demonstrated, or for datasets consisting of solely metastasis or mixed datasets. Instead, dimension reduction methods and data transformation significantly impacted visual clustering results. Our findings strongly suggest data transformation to be considered as another key element in the interpretation of visual clustering approaches along with initialization and different parameters. Furthermore, the results highlight the need for a more thorough examination of parameters used in the analysis of clusters.
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Tucker-Kulesza, Stacey E., Gretchen F. Sassenrath, Tri Tran, Weston Koehn, and Lauren Erickson. "Site-Specific Erodibility in Claypan Soils: Dependence on Subsoil Characteristics." Applied Engineering in Agriculture 33, no. 5 (2017): 705–18. http://dx.doi.org/10.13031/aea.12120.
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Abstract. Soil erosion is a primary factor limiting the productive capacity of many crop production fields and contributing to sediment and nutrient impairments of water bodies. Loss of topsoil is especially critical for areas of limited topsoil depth, such as the claypan area of the central United States. More than a century of conventional agricultural practices have eroded the topsoil and, in places, exposed the unproductive clay layer. This clay layer is impervious, limiting water infiltration and root penetration, and severely restricting agricultural productivity. Previous studies have documented changes in topsoil thickness using apparent electrical conductivity (ECa). However, that methodology is limited by its shallow depth of measurement within the soil profile, and as such cannot adequately explore factors within the soil profile that potentially contribute to topsoil erosion. In this study, we identified areas of limited topsoil depth using crop yields and ECa. Two areas within the production field varying in crop production and ECa were selected for detailed measurements using Electrical Resistivity Tomography. This methodology allowed delineation of soil stratigraphy to a depth of 5.3 m. The erodibility of undisturbed soil samples from the two areas were measured in an Erosion Function Apparatus to obtain the critical shear stress, or the applied stress at which soil begins to erode. Based on resistivity measurement, the highly productive region of the field had a thick (1.0-2.0 m) soil layer of saturated clayey sand soil over a uniform sandy material, with minimal clay layer. This soil had a critical shear stress of 12 Pa. The extent of historical erosion was evident in the poorly-producing area, as only a thin band of topsoil material remained over a thicker clay layer. The unproductive area with exposed clay layer had a critical shear stress of 128 Pa, indicating it was more resistant to erosion than the highly productive region. The clay layer was found to extend to 1.3-1.5 m in depth in the soil profile in the poorly producing area. Below this layer was a layer with similar resistivity to the high-producing region. The data reveal the extent of historical erosion within the crop production field and highlight significant variability in measured soil properties within a field of identical production practices. While spatial variations in topsoil have long been considered in developing management practices to improve soil health and productive capacity, our results indicate the importance of identifying variability of subsoil characteristics to address long-term impacts on soil erosion and productivity. Keywords: Soil erosion, Soil electrical conductivity, Claypan soil, Productive capacity, Electrical resistivity tomography.
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Larsson, Susanna C., Siddhartha Kar, John R. B. Perry, Paul Carter, Mathew Vithayathil, Amy M. Mason, Douglas F. Easton, and Stephen Burgess. "Serum Estradiol and 20 Site-Specific Cancers in Women: Mendelian Randomization Study." Journal of Clinical Endocrinology & Metabolism 107, no. 2 (October 3, 2021): e467-e474. http://dx.doi.org/10.1210/clinem/dgab713.
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Abstract Context The causal role of endogenous estradiol in cancers other than breast and endometrial cancer remains unclear. Objective This Mendelian randomization study assessed the causal associations of endogenous 17β-estradiol (E2), the most potent estrogen, with cancer risk in women. Methods As primary genetic instrument, we used a genetic variant in the CYP19A1 gene that is strongly associated with serum E2 levels. Summary statistics genetic data for the association of the E2 variant with breast, endometrial, and ovarian cancer were obtained from large-scale consortia. We additionally estimated the associations of the E2 variant with any and 20 site-specific cancers in 198 825 women of European descent in UK Biobank. Odds ratios (OR) of cancer per 0.01 unit increase in log-transformed serum E2 levels in pmol/L were estimated using the Wald ratio. Results Genetic predisposition to higher serum E2 levels was associated with increased risk of estrogen receptor (ER)-positive breast cancer (OR 1.02; 95% CI, 1.01-1.03; P = 2.5 × 10−3), endometrial cancer overall (OR 1.09; 95% CI, 1.06-1.11; P = 7.3 × 10−13), and endometrial cancer of the endometrioid histology subtype (OR 1.10; 95% CI, 1.07-1.13; P = 2.1 × 10−11). There were suggestive associations with breast cancer overall (OR 1.01; 95% CI, 1.00-1.02; P = 0.02), ovarian cancer of the endometrioid subtype (OR 1.05; 95% CI, 1.01-1.10; P = 0.02), and stomach cancer (OR 1.12; 95% CI, 1.00-1.26; P = 0.05), but no significant association with other cancers. Conclusion This study supports a role of E2 in the development of ER-positive breast cancer and endometrioid endometrial cancer but found no strong association with other cancers in women.
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Kuppel, S., P. Peylin, F. Maignan, F. Chevallier, G. Kiely, L. Montagnani, and A. Cescatti. "Model–data fusion across ecosystems: from multisite optimizations to global simulations." Geoscientific Model Development 7, no. 6 (November 10, 2014): 2581–97. http://dx.doi.org/10.5194/gmd-7-2581-2014.
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Abstract. This study uses a variational data assimilation framework to simultaneously constrain a global ecosystem model with eddy covariance measurements of daily net ecosystem exchange (NEE) and latent heat (LE) fluxes from a large number of sites grouped in seven plant functional types (PFTs). It is an attempt to bridge the gap between the numerous site-specific parameter optimization works found in the literature and the generic parameterization used by most land surface models within each PFT. The present multisite approach allows deriving PFT-generic sets of optimized parameters enhancing the agreement between measured and simulated fluxes at most of the sites considered, with performances often comparable to those of the corresponding site-specific optimizations. Besides reducing the PFT-averaged model–data root-mean-square difference (RMSD) and the associated daily output uncertainty, the optimization improves the simulated CO2 balance at tropical and temperate forests sites. The major site-level NEE adjustments at the seasonal scale are reduced amplitude in C3 grasslands and boreal forests, increased seasonality in temperate evergreen forests, and better model–data phasing in temperate deciduous broadleaf forests. Conversely, the poorer performances in tropical evergreen broadleaf forests points to deficiencies regarding the modelling of phenology and soil water stress for this PFT. An evaluation with data-oriented estimates of photosynthesis (GPP – gross primary productivity) and ecosystem respiration (Reco) rates indicates distinctively improved simulations of both gross fluxes. The multisite parameter sets are then tested against CO2 concentrations measured at 53 locations around the globe, showing significant adjustments of the modelled seasonality of atmospheric CO2 concentration, whose relevance seems PFT-dependent, along with an improved interannual variability. Lastly, a global-scale evaluation with remote sensing NDVI (normalized difference vegetation index) measurements indicates an improvement of the simulated seasonal variations of the foliar cover for all considered PFTs.
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Li, Fu Jun, Ranu Surolia, Huashi Li, Zheng Wang, Gang Liu, Rui-Ming Liu, Sergey B. Mirov, Mohammad Athar, Victor J. Thannickal, and Veena B. Antony. "Low-dose cadmium exposure induces peribronchiolar fibrosis through site-specific phosphorylation of vimentin." American Journal of Physiology-Lung Cellular and Molecular Physiology 313, no. 1 (July 1, 2017): L80—L91. http://dx.doi.org/10.1152/ajplung.00087.2017.
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Exposure to cadmium (Cd) has been associated with development of chronic obstructive lung disease (COPD). The mechanisms and signaling pathways whereby Cd causes pathological peribronchiolar fibrosis, airway remodeling, and subsequent airflow obstruction remain unclear. We aimed to evaluate whether low-dose Cd exposure induces vimentin phosphorylation and Yes-associated protein 1 (YAP1) activation leading to peribronchiolar fibrosis and subsequent airway remodeling. Our data demonstrate that Cd induces myofibroblast differentiation and extracellular matrix (ECM) deposition around small (<2 mm in diameter) airways. Upon Cd exposure, α-smooth muscle actin (α-SMA) expression and the production of ECM proteins, including fibronectin and collagen-1, are markedly induced in primary human lung fibroblasts. Cd induces Smad2/3 activation and the translocation of both Smad2/3 and Yes-associated protein 1 (YAP1) into the nucleus. In parallel, Cd induces AKT and cdc2 phosphorylation and downstream vimentin phosphorylation at Ser39 and Ser55, respectively. AKT and cdc2 inhibitors block Cd-induced vimentin fragmentation and secretion in association with inhibition of α-SMA expression, ECM deposition, and collagen secretion. Furthermore, vimentin silencing abrogates Cd-induced α-SMA expression and decreases ECM production. Vimentin-deficient mice are protected from Cd-induced peribronchiolar fibrosis and remodeling. These findings identify two specific sites on vimentin that are phosphorylated by Cd and highlight the functional significance of vimentin phosphorylation in YAP1/Smad3 signaling that mediates Cd-induced peribronchiolar fibrosis and airway remodeling.
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Schiessl, Andreas, Richard Müller, Rebekka Volk, Konrad Zimmer, Patrick Breun, and Frank Schultmann. "Integrating site-specific environmental impact assessment in supplier selection: exemplary application to steel procurement." Journal of Business Economics 90, no. 9 (February 25, 2020): 1409–57. http://dx.doi.org/10.1007/s11573-020-00967-1.
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Abstract In times of fast-growing stakeholder interest in sustainability, the ecological and social perspective of industrial companies and its products is gaining increasing importance. In particular, the emission of greenhouse gases (GHG) in the automotive industry has come to the forefront of public and governmental attention. The transport sector accounts for 27% of all European GHG emissions and constitutes the largest emitter of CO2e (CO2 equivalents) among all energy demanding technologies. Due to increasingly efficient combustion engines and technology innovation towards e-mobility, the emissions from car manufacturing gain in importance. So far little focus has been laid upon the emissions created throughout the production process in automotive supply chains from a purchasing perspective. The purchasing of raw material from environmentally efficient suppliers can constitute a possibility to significantly reduce CO2e emissions in automotive supply chains and thus contribute to the two degrees global warming goal. Supplier selection decisions, which cover approximately 75% of the value adding process of a car, are today mainly cost and quality-driven. In order to integrate CO2e as decision criterion for supplier selections, site-specific and comparable data on CO2e emissions from the upstream supply chain is necessary, but currently lacking. To estimate CO2e emissions of steel suppliers’ production sites, a model has been developed to estimate manufacturing processes on a site-specific level without the necessity of confidential primary data. The model is applied on 22 integrated steel mills in EU-15. The results, which can be transferred and used for various products and industries, e.g. the construction industry, demonstrate the partially large disparities of manufacturing efficiency regarding CO2e emissions among steel manufacturers due to different levels of process integration and internal process know-how. A range between 1879 and 2990 (kg CO2e/t crude steel) has been revealed. Finally, the estimated data on CO2e performance of suppliers is applied in a case study of supplier selection of a German automobile manufacturer in order to simulate environmental as well as economic effects.
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Palombo, Fabio, Andrea Monciotti, Alessandra Recchia, Riccardo Cortese, Gennaro Ciliberto, and Nicola La Monica. "Site-Specific Integration in Mammalian Cells Mediated by a New Hybrid Baculovirus–Adeno-Associated Virus Vector." Journal of Virology 72, no. 6 (June 1, 1998): 5025–34. http://dx.doi.org/10.1128/jvi.72.6.5025-5034.1998.
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ABSTRACT Baculovirus can transiently transduce primary human and rat hepatocytes, as well as a subset of stable cell lines. To prolong transgene expression, we have developed new hybrid vectors which associate key elements from adeno-associated virus (AAV) with the elevated transducing capacity of baculovirus. The hybrid vectors contain a transgene cassette composed of the β-galactosidase (β-Gal) reporter gene and the hygromycin resistance (Hygr) gene flanked by the AAV inverted terminal repeats (ITRs), which are necessary for AAV replication and integration in the host genome. Constructs were derived both with and without the AAVrep gene under the p5 and p19 promoters cloned in different positions with respect to the baculovirus polyheidrin promoter. A high-titer preparation of baculovirus-AAV (Bac-AAV) chimeric virus containing the ITR–Hygr–β-Gal sequence was obtained with insect cells only when the rep gene was placed in an antisense orientation to the polyheidrin promoter. Infection of 293 cells with Bac-AAV virus expressing the rep gene results in a 10- to 50-fold increase in the number of Hygr stable cell clones. Additionally, rep expression determined the localization of the transgene cassette in the aavs1 site in approximately 41% of cases as detected by both Southern blotting and fluorescent in situ hybridization analysis. Moreover, site-specific integration of the ITR-flanked DNA was also detected by PCR amplification of the ITR-aavs1 junction in transduced human fibroblasts. These data indicate that Bac-AAV hybrid vectors can allow permanent, nontoxic gene delivery of DNA constructs for ex vivo treatment of primary human cells.
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Pohl, Marie O., Idoia Busnadiego, Verena Kufner, Irina Glas, Umut Karakus, Stefan Schmutz, Maryam Zaheri, et al. "SARS-CoV-2 variants reveal features critical for replication in primary human cells." PLOS Biology 19, no. 3 (March 24, 2021): e3001006. http://dx.doi.org/10.1371/journal.pbio.3001006.
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Since entering the human population, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; the causative agent of Coronavirus Disease 2019 [COVID-19]) has spread worldwide, causing >100 million infections and >2 million deaths. While large-scale sequencing efforts have identified numerous genetic variants in SARS-CoV-2 during its circulation, it remains largely unclear whether many of these changes impact adaptation, replication, or transmission of the virus. Here, we characterized 14 different low-passage replication-competent human SARS-CoV-2 isolates representing all major European clades observed during the first pandemic wave in early 2020. By integrating viral sequencing data from patient material, virus stocks, and passaging experiments, together with kinetic virus replication data from nonhuman Vero-CCL81 cells and primary differentiated human bronchial epithelial cells (BEpCs), we observed several SARS-CoV-2 features that associate with distinct phenotypes. Notably, naturally occurring variants in Orf3a (Q57H) and nsp2 (T85I) were associated with poor replication in Vero-CCL81 cells but not in BEpCs, while SARS-CoV-2 isolates expressing the Spike D614G variant generally exhibited enhanced replication abilities in BEpCs. Strikingly, low-passage Vero-derived stock preparation of 3 SARS-CoV-2 isolates selected for substitutions at positions 5/6 of E and were highly attenuated in BEpCs, revealing a key cell-specific function to this region. Rare isolate-specific deletions were also observed in the Spike furin cleavage site during Vero-CCL81 passage, but these were rapidly selected against in BEpCs, underscoring the importance of this site for SARS-CoV-2 replication in primary human cells. Overall, our study uncovers sequence features in SARS-CoV-2 variants that determine cell-specific replication and highlights the need to monitor SARS-CoV-2 stocks carefully when phenotyping newly emerging variants or potential variants of concern.
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Penuela, Maria, Nirav Patil, Gino Cioffi, Carol Kruchko, and Jill S. Barnholtz-Sloan. "EPID-29. CAUSES OF DEATH FOR PRIMARY BRAIN AND CNS TUMOR PATIENTS IN THE UNITED STATES (2001 – 2016): A POPULATION BASED STUDY." Neuro-Oncology 22, Supplement_2 (November 2020): ii84—ii85. http://dx.doi.org/10.1093/neuonc/noaa215.347.
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Abstract BACKGROUND Population-based data on the various causes of death among Primary Brain and CNS tumor patients are lacking. We evaluated the causes of death for all eligible patients using the National Program of Cancer Registries (NPCR) data. METHODS The population-based cancer survival data collected by the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) were used to analyze the causes of death for patients of all ages with primary brain and CNS tumors diagnosed between 2001 and 2016. Patients for whom the cause of death was not listed on the death certificate or whose state death certificate was not available were excluded. Additional analyses to identify factors associated with brain tumor-specific mortality for the most common malignant (Glioblastoma) and non-malignant (Meningioma) were performed using univariable and multivariable logistic regression analysis. RESULTS Major cause of death for patients with malignant tumors was death due to brain and other CNS tumors (49.29%), and for non-malignant tumors were other benign and malignant tumors (31.5%) and heart disease (17.9%). Overall mortality was 36.4% (n=331,953) in patients with Primary Brain and CNS Tumors during the study period. Specifically, 163,621 (49.29%) patients died due to brain and other CNS tumors. A significant proportion of patients with malignant tumors had brain tumor-specific mortality compared to non-malignant tumors (75.4% in malignant vs 4.2% in non-malignant). The factors associated with brain specific mortality in Glioblastoma patients were Age (p< 0.001), Race (p< 0.001) and Primary Site (p< 0.001). Further, the factors associated with brain specific mortality in Non-malignant Meningioma patients were Age (p< 0.001), Sex (p< 0.001), Race (p< 0.001) and Primary Site (P< 0.001). CONCLUSION Cause of death attributed to the brain tumor was significantly higher in malignant brain tumors compared to non-malignant brain tumors.
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Strongman, Helen, Rachael Williams, and Krishnan Bhaskaran. "What are the implications of using individual and combined sources of routinely collected data to identify and characterise incident site-specific cancers? a concordance and validation study using linked English electronic health records data." BMJ Open 10, no. 8 (August 2020): e037719. http://dx.doi.org/10.1136/bmjopen-2020-037719.
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ObjectivesTo describe the benefits and limitations of using individual and combinations of linked English electronic health data to identify incident cancers.Design and settingOur descriptive study uses linked English Clinical Practice Research Datalink primary care; cancer registration; hospitalisation and death registration data.Participants and measuresWe implemented case definitions to identify first site-specific cancers at the 20 most common sites, based on the first ever cancer diagnosis recorded in each individual or commonly used combination of data sources between 2000 and 2014. We calculated positive predictive values and sensitivities of each definition, compared with a gold standard algorithm that used information from all linked data sets to identify first cancers. We described completeness of grade and stage information in the cancer registration data set.Results165 953 gold standard cancers were identified. Positive predictive values of all case definitions were ≥80% and ≥94% for the four most common cancers (breast, lung, colorectal and prostate). Sensitivity for case definitions that used cancer registration alone or in combination was ≥92% for the four most common cancers and ≥80% across all cancer sites except bladder cancer (65% using cancer registration alone). For case definitions using linked primary care, hospitalisation and death registration data, sensitivity was ≥89% for the four most common cancers, and ≥80% for all cancer sites except kidney (69%), oral cavity (76%) and ovarian cancer (78%). When primary care or hospitalisation data were used alone, sensitivities were generally lower and diagnosis dates were delayed. Completeness of staging data in cancer registration data was high from 2012 (minimum 76.0% in 2012 and 86.4% in 2014 for the four most common cancers).ConclusionsAscertainment of incident cancers was good when using cancer registration data alone or in combination with other data sets, and for the majority of cancers when using a combination of primary care, hospitalisation and death registration data.
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MOIMAZ, Suzely Adas Saliba, Lúcia Maria Lima Lemos de MELO, Cléa Adas Saliba GARBIN, Artênio José Ísper GARBIN, and Nemre Adas SALIBA. "Oral health assessment protocol in primary care." RGO - Revista Gaúcha de Odontologia 63, no. 4 (December 2015): 446–54. http://dx.doi.org/10.1590/1981-863720150003000113012.
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Objective: The aim of this study was to analyze the oral health service performance in a certain municipality and also to develop a diagnostic evaluation protocol of Oral Health in Primary Care. Methods: This is a descriptive, quantitative and qualitative research. The research site chosen was in the city of Pereira Barreto, State of São Paulo Brazil, since it makes use of the Family Health Strategy as the structuring care model of the Health Care System in 100% of the population as well as oral health teams implemented and oral health secondary care. Data were obtained through interviews with the manager, six dentists, six oral health assistants and six community health workers. Document analysis of the Municipal Health Plan was also conducted along with the Dental Health Agenda and on-site observation of the dental structure. Results: The city Health Plan presents a detailed description of the municipality general situation, the oral health agenda recommends, in its implementation phase, the three main areas as a core in Family Health Strategy as follows: health unit, family and community.The survey found that the main form of access of the population to services was the spontaneous demand and there were only two Family Health teams without focus on oral health. Conclusion: The analysis of the service performed; made possible to develop a protocol with specific Oral Health dimensions to support the manager in defining intervention strategies
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Beebe, Caroline. "Standard Descriptive Vocabulary and Archaeology Digital Data Collection." Advances in Archaeological Practice 5, no. 3 (July 19, 2017): 250–64. http://dx.doi.org/10.1017/aap.2017.15.
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ABSTRACTArchaeology has embraced the shift to digital technology for collecting, analyzing, and sharing data. Digital repositories are now recognized as essential for data stewardship and are setting standards for data deposition. These new technologies and systems support the scientific need for reproducible results through intra-cultural as well as cross-cultural hypothesis testing. Methods of digital data collection in the field, however, are often site specific, restricted by the limited availability of digital technologies, or not well suited for creating systems that support the requirements of the new digital information paradigm. As a small science project, the Chau Hiix Project in Belize will provide examples of the pitfalls in and insights about shifting to digital technology to make its primary data shareable and reusable. These experiences suggest the need for an international collaborative agenda that develops digital data description standards based on controlled vocabulary, facet analysis, and crosswalks implemented at the analog point of collection.
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Hayashi, Hidetoshi, Yuichi Takiguchi, Hironobu Minami, Kohei Akiyoshi, Yoshihiko Segawa, Hiroki Ueda, Yasuo Iwamoto, et al. "NGSCUP: Phase II trial of site-specific treatment based on gene expression and mutation profiling by next generation sequencing (NGS) for patients (pts) with cancer of unknown primary site (CUP)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15577-e15577. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15577.
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e15577 Background: Although gene profiling is a promising diagnostic technique to determine the tissue of origin for pts with CUP, we reported that site-specific treatment based on gene profiling using microarray did not result in an improvement the survival compared with empirical therapy in the previous randomized phase 2 trial (Hayashi, et. al, JCO 2019). Recently, we have established new integrative diagnostic system combined the gene expression from RNA-sequencing and mutation/copy number variation data from targeted genomic-sequencing using NGS. We have performed a single-arm phase 2 study to assess the efficacy of site-specific therapy determined by this system in previously untreated pts with CUP. Methods: Comprehensive gene profiling was performed by NGS, and an established algorithm was applied to predict tumor origin. Pts with CUP was received site-specific chemotherapy determined by the predicted site. The primary endpoint was one-year survival rate. Results: A total of 111 pts was enrolled and all had sufficient biopsy tissue for gene profiling. Efficacy analysis was performed for 97 pts who received site-specific treatment. Cancer types most commonly predicted were lung (21%), liver (15%), kidney (15%), and colorectal cancer (12%). The one-year survival rate, median overall survival (OS), and progression free survival (PFS) was 53.1% (95%CI, 42.6-62.5%), 13.7 months (95% CI, 9.3-19.7 months), and 5.2 months (95% CI, 3.3-7.1 months), respectively. Median OS (15.7 versus 11.0 months, P = .078) and PFS (5.5 versus 2.8 months, P = .019) were better for predicted tumor types categorized as more responsive types than for less responsive ones. Conclusions: Site-specific treatment based on NGS demonstrated promising efficacy. Pts with CUP predicted to have more responsive tumor types had longer survival compared with pts with less responsive tumor types, suggesting that molecular tumor profiling by both DNA and RNA testing contributes to the management of pts with CUP. Clinical trial information: UMIN051180009.
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Remigius, W. Dheelibun, and Anand Natarajan. "Identification of wind turbine main-shaft torsional loads from high-frequency SCADA (supervisory control and data acquisition) measurements using an inverse-problem approach." Wind Energy Science 6, no. 6 (November 5, 2021): 1401–12. http://dx.doi.org/10.5194/wes-6-1401-2021.
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Abstract. To assess the structural health and remaining useful life of wind turbines within wind farms, the site-specific structural response and modal parameters of the primary structures are required. In this regard, a novel inverse-problem-based methodology is proposed here to identify the dynamic quantities of the drivetrain main shaft, i.e. torsional displacement and coupled stiffness. As a model-based approach, an inverse problem of a mathematical model concerning the coupled-shaft torsional dynamics with high-frequency SCADA (supervisory control and data acquisition) measurements as input is solved. It involves Tikhonov regularisation to minimise the measurement noise and irregularities on the shaft torsional displacement obtained from measured rotor and generator speed. Subsequently, the regularised torsional displacement along with necessary SCADA measurements is used as an input to the mathematical model, and a model-based system identification method called the collage method is employed to estimate the coupled torsional stiffness. It is also demonstrated that the estimated shaft torsional displacement and coupled stiffness can be used to identify the site-specific main-shaft torsional loads. It is shown that the torsional loads estimated by the proposed methodology is in good agreement with the aeroelastic simulations of the Vestas V52 wind turbine. Upon successful verification, the proposed methodology is applied to the V52 turbine to identify the site-specific main-shaft torsional loads and damage-equivalent load. Since the proposed methodology does not require a design basis or additional measurement sensors, it can be directly applied to wind turbines within a wind farm that possess high-frequency SCADA measurements.
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Heatherington, Craig, Alistair Grinham, Irene Penesis, Scott Hunter, and Remo Cossu. "Geotechnical Approach to Early-Stage Site Characterisation of Shallow Wave Energy Sites." Journal of Marine Science and Engineering 9, no. 6 (May 31, 2021): 605. http://dx.doi.org/10.3390/jmse9060605.
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Marine renewable energy is still in its infancy and poses serious challenges due to the harsh marine conditions encountered for wave or tidal installations and the survivability of devices. Geophysical and hydrodynamic initial site surveys need to be able to provide repeatable, reliable, and economical solutions. An oscillating water column wave energy converter is to be installed on the west coast of King Island, Tasmania. The location is in a high-energy nearshore environment to take advantage of sustained shoaling non-breaking waves of the Southern Ocean and required site-specific information for the deployment. We provide insight into scalable geophysical site surveys capable of capturing large amounts of data within a short time frame. This data was incorporated into a site suitability model, utilising seabed slope, sediment depth, and water depth to provide the terrain analysis needed to match deployment-specific characteristics. In addition, short-term hydrology and geotechnical work found a highly energetic seabed (near seafloor water velocities <1 m/s) with sufficient bearing capacity (6 MPa). In a highly energetic environment, care was taken to collect the relevant data needed for an assessment of critical information to an emerging technology companies primary project. This is in addition to the malleable methodology for a site suitability model that can incorporate various weighted parameters to prioritise the location for shallow wave energy sites in general.
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Spokas, Kurt, and Frank Forcella. "Estimating hourly incoming solar radiation from limited meteorological data." Weed Science 54, no. 1 (February 2006): 182–89. http://dx.doi.org/10.1614/ws-05-098r.1.
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Two major properties that determine weed seed germination are soil temperature and moisture content. Incident radiation is the primary variable controlling energy input to the soil system and thereby influences both moisture and temperature profiles. However, many agricultural field sites lack proper instrumentation to measure solar radiation directly. To overcome this shortcoming, an empirical model was developed to estimate total incident solar radiation (beam and diffuse) with hourly time steps. Input parameters for the model are latitude, longitude, and elevation of the field site, along with daily precipitation with daily minimum and maximum air temperatures. Field validation of this model was conducted at a total of 18 sites, where sufficient meteorological data were available for validation, allowing a total of 42 individual yearly comparisons. The model performed well, with an average Pearson correlation of 0.92, modeling index of 0.95, modeling efficiency of 0.80, root mean square error of 111 W m−2, and a mean absolute error of 56 W m−2. These results compare favorably to other developed empirical solar radiation models but with the advantage of predicting hourly solar radiation for the entire year based on limited climatic data and no site-specific calibration requirement. This solar radiation prediction tool can be integrated into dormancy, germination, and growth models to improve microclimate-based simulation of development of weeds and other plants.
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Zhong, Miaochun, Farhana Zerin Khan, Xianghong He, Lingfei Cui, Kefeng Lei, and Minghua Ge. "Impact of Lung Metastasis versus Metastasis of Bone, Brain, or Liver on Overall Survival and Thyroid Cancer-Specific Survival of Thyroid Cancer Patients: A Population-Based Study." Cancers 14, no. 13 (June 26, 2022): 3133. http://dx.doi.org/10.3390/cancers14133133.
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We investigate the impact of lung metastasis versus metastasis of bone, brain, or liver on overall survival (OS) and thyroid cancer-specific survival (TCSS) in patients with thyroid cancer (TC). Therefore, de-identified SEER 18 registry data of primary TC patients diagnosed between 2010 and 2016 were analyzed. The primary outcome was the prognosis of TC patients with lung metastasis compared with other sites. The secondary outcomes included the prognosis comparison between patients with and without surgery and between single and multiple metastasis sites. Isolated lung metastasis was associated with worse OS and TCSS than bone metastasis (both p < 0.05) and was associated with worse OS than liver metastasis (p = 0.0467). Surgery performed either for the primary or distant site was associated with better OS and TCSS in patients with metastasis of lung or bone (p < 0.05). Isolated lung metastasis was related to better OS and TCSS than lung–liver, lung–brain, and lung–other multiple metastases. The multivariable analysis revealed that age < 55 years, surgery to the primary site, and to the distant site(s) were associated with better outcomes, while T4 and Tx were associated with worse outcomes. Nevertheless, it revealed that the other race (i.e., any race other than white, black, or unknown) and male gender were associated with better TCSS only (p < 0.05). Isolated lung metastasis is associated with a worse prognosis in TC patients compared with bone or liver metastasis. Surgery performed either for the primary or distant site(s) is associated with better survival outcomes in TC patients with metastasis of lung or bone.
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Barlow, Ellen L., Michael Jackson, and Neville F. Hacker. "The Prognostic Role of the Surgical Margins in Squamous Vulvar Cancer: A Retrospective Australian Study." Cancers 12, no. 11 (November 14, 2020): 3375. http://dx.doi.org/10.3390/cancers12113375.
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For the last 30 years at the Royal Hospital for Women, unifocal vulvar squamous cancers have been treated by radical local excision, aiming to achieve a histopathological margin of ≥8 mm, equating to a surgical margin of 1 cm. The need for a margin of this width has recently been challenged. We aimed to determine the long-term outcome following this conservative approach, and the relationship between vulvar recurrences and surgical margins. Data were obtained retrospectively on 345 patients treated primarily with surgery for squamous vulvar cancer between 1987 and 2017. Median follow-up was 93 months. Five-year disease-specific survival was 86%. Of 78 vulvar recurrences, 33 (42.3%) were at the primary site and 45 (57.7%) at a remote site. In multivariable analysis, a margin < 5 mm showed a higher risk of all vulvar (Hazard ratio (HR), 2.29; CI, 1.12−4.70), and primary site recurrences (subdistribution hazard ratio (SHR), 15.20; CI, 5.21−44.26), while those with a margin of 5 to <8 mm had a higher risk of a primary site recurrence (SHR, 8.92; CI, 3.26−24.43), and a lower risk of remote site recurrence. Excision margins < 8 mm treated by re-excision or radiation therapy had a significantly decreased risk of recurrence. Guidelines should continue to recommend a surgical margin of 1 cm.
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Wang, Yanhong, Yi Ouyang, Jingjing Su, Zhigang Bai, Qunrong Cai, and Xinping Cao. "Role of locoregional surgery in treating FIGO 2009 stage IVB cervical cancer patients: a population-based study." BMJ Open 11, no. 8 (August 2021): e042364. http://dx.doi.org/10.1136/bmjopen-2020-042364.
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ObjectiveWe aimed to analyse the clinical value of primary site surgery in improving the cancer-specific survival (CSS) and overall survival (OS) of initial metastatic cervical cancer patients.DesignA population-based retrospective study.SettingNational Cancer Institute’s Surveillance, Epidemiology and End Results database.ParticipantsWe analysed 1390 patients with the International Federation of Gynecology and Obstetrics 2009 stage IVB cervical cancer with complete clinical data treated between 2010 and 2016.InterventionsPrimary site surgery.MeasuresPropensity score matching (PSM) with a ratio of 1:2 was used to balance measure covariates of comparison groups. Survival time was calculated using Kaplan-Meier methods and compared by the log-rank test. To eliminate the bias of site-specific metastasis, clinicopathological factors and subsequent therapy on survival analysis, subgroup analyses stratified by metastasis type, clinicopathological factors and subsequent therapy were employed to evaluate the effect of cervical surgery on survival. Combination of directed acyclic graph and change-in-estimate procedures was performed to indentified confounders, and Cox regression was used to assess the survival benefit of cervical surgery for primary metastatic cervical cancer patients. The consistency of our findings was evaluated through sensitivity analysis.ResultsMatching resulted in two comparison groups with minor differences in most variables. Pre-and-post-PSM, the median CSS and OS in the surgery group were 1.3 and 1.5, 1.1 and 1.2 times of those in the non-surgery group, respectively. Primary site surgery conferred prognosis superiority for patients with metastases to distant lymph node and other sites rather than organ metastases. After PSM and adjusting confounders, local surgery reduced the cancer related and overall mortality rates by 31% and 30%, respectively.ConclusionsSurgical procedures could promote survival in patients with primary metastatic cervical cancer and should be considered a therapeutic option for carefully chosen patients.
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Andrade, Lesley, Kathy Moran, Susan J. Snelling, Darshaka Malaviarachchi, Joanne Beyers, Kelsie Near, and Janis Randall Simpson. "Beyond BMI: a feasibility study implementing NutriSTEP in primary care practices using electronic medical records (EMRs)." Health Promotion and Chronic Disease Prevention in Canada 40, no. 1 (January 2020): 1–10. http://dx.doi.org/10.24095/hpcdp.40.1.01.
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Introduction Primary care providers have a role to play in supporting the development of healthy eating habits, particularly in a child’s early years. This study examined the feasibility of implementing the NutriSTEP® screen—a 17-item nutrition risk screening tool validated for use with both toddler and preschooler populations—integrated with an electronic medical record (EMR) in primary care practices in Ontario, Canada, to inform primary care decision-making and public health surveillance. Methods Five primary care practices implemented the NutriSTEP screen as a standardized form into their EMRs. To understand practitioners’ experiences with delivery and assess factors associated with successful implementation, we conducted semi-structured qualitative interviews with primary care providers who were most knowledgeable about NutriSTEP implementation at their site. We assessed the quality of the extracted patient EMR data by determining the number of fully completed NutriSTEP screens and documented growth measurements of children. Results Primary care practices implemented the NutriSTEP screen as part of a variety of routine clinical contacts; specific data collection processes varied by site. Valid NutriSTEP screen data were captured in the EMRs of 80% of primary care practices. Approximately 90% of records had valid NutriSTEP screen completions and 70% of records had both valid NutriSTEP screen completions and valid growth measurements. Conclusion Integration of NutriSTEP as a standardized EMR form is feasible in primary care practices, although implementation varied in our study. The application of EMR-integrated NutriSTEP screening as part of a comprehensive childhood healthy weights surveillance system warrants further exploration.
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Paudel, Yuba Raj, Emily Walker, Trenton Smith, Yan Yuan, Alan Nichol, and Faith Davis. "OTHR-07. ESTIMATING INCIDENCE PROPORTION OF BRAIN METASTASES AT DIAGNOSIS AND LIFETIME INCIDENCE AMONG CANCER PATIENTS DIAGNOSED FROM 2010–2015 IN CANADA." Neuro-Oncology Advances 1, Supplement_1 (August 2019): i19. http://dx.doi.org/10.1093/noajnl/vdz014.084.
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Abstract INTRODUCTION: The incidence of brain metastases (BM) among Canadian cancer patients is unknown. We aimed to estimate the incidence proportion (IP) of BM at the time of all cancer diagnoses and during follow-up of cancer patients with the top six primary tumours that are most likely to metastasize to the brain. METHODS: Data on BM at diagnosis from 2010–2015 was obtained from the Canadian Cancer Registry (CCR). Site-specific IPs of BM was estimated for patients from provincial registries that achieved ≥90% complete data. These estimates were applied to the total number of newly diagnosed primary cancers to estimate total number of BM at diagnosis from 2010–2015 in Canada. To estimate the number of lifetime BM that arise from six selected primary cancers including lung, breast, skin melanoma, colorectal, kidney/renal pelvis and esophagus, we applied IP estimates reported in the literature. RESULTS: We identified 1,105,905 cancer cases in the CCR from 2010–2015, of which 519,950 (47%) were from the six primaries. The annual average number of patients with BMs at diagnosis from all cancer sites was approximately 2,800 and was highest for lung cancer(2,400).The site-specific IPs of BM at diagnosis were: lung (9.6%;95% CI: 9.3–10.0%), esophageal (2%;95%CI:1.5–2.7%), kidney/renal pelvis (1.3%;95%CI:1.0–1.5%), skin melanoma (1.1%;95%CI:0.9–1.3%), colorectal (0.3%;95%CI:0.2–0.3%), and breast (0.2%;95%CI:0.2–0.3%).Using clinical and population data from the literature, we estimated that nearly 7,400 lifetime BM cases occur annually for these six primaries. CONCLUSIONS: Each year in Canada, approximately 2,800 BMs from all primary cancers are found at the time of diagnosis and approximately 7,400 lifetime BM occur annually from the six selected primary tumours.
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Grange, F., M. W. Bekkenk, J. Wechsler, C. J. L. M. Meijer, L. Cerroni, M. Bernengo, J. Bosq, et al. "Prognostic Factors in Primary Cutaneous Large B-Cell Lymphomas: A European Multicenter Study." Journal of Clinical Oncology 19, no. 16 (August 15, 2001): 3602–10. http://dx.doi.org/10.1200/jco.2001.19.16.3602.
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PURPOSE: Most primary cutaneous B-cell lymphomas have an excellent prognosis. However, primary cutaneous large B-cell lymphomas (PCLBCLs) of the leg have been recognized as a distinct entity with a poorer prognosis in the European Organization for Research and Treatment of Cancer (EORTC) classification. This distinction on the basis of site has been debated. Our aim was to identify independent prognostic factors in a large European multicenter series of PCLBCL.PATIENTS AND METHODS: The clinical and histologic data of 145 patients with PCLBCL were evaluated. According to the EORTC classification, 48 patients had a PCLBCL of the leg and 97 had a primary cutaneous follicle center-cell lymphoma (PCFCCL). Data from both groups were compared. Univariate and multivariate analyses of specific survival were performed using a Cox proportional hazards model.RESULTS: Compared with PCFCCL, PCLBCL-leg were characterized by an older age of onset, a more recent history of skin lesions, a more frequent predominance of tumor cells with round nuclei and positive bcl-2 staining, and a poorer 5-year disease-specific survival rate (52% v 94%; P < .0001). Univariate survival analysis in the entire study group showed that older age, a more recent onset of skin lesions, the location on the leg, multiple skin lesions, and the round-cell morphology were significantly related to death. In multivariate analysis, the round-cell morphology (P < .0001), the location on the leg (P = .002), and multiple skin lesions (P = .01) remained independent prognostic factors. The round-cell morphology was an adverse prognostic factor both in PCLBCL-leg and in PCFCCL, whereas multiple skin lesions were associated with a poor prognosis only in patients with PCLBCL-leg.CONCLUSION: With site, morphology, and number of tumors taken into account, guidelines for the management of PCLBCL are presented.
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Felix, Ashley Sinclair, Faina Linkov, George Larry Maxwell, Camille Ragin, and Emanuela Taioli. "Racial Disparities in Risk of Second Primary Cancers in Patients With Endometrial Cancer: Analysis of SEER Data." International Journal of Gynecologic Cancer 21, no. 2 (January 2011): 309–15. http://dx.doi.org/10.1097/igc.0b013e318206a098.
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Introduction:Endometrial cancer (EC) is the most common gynecologic cancer in the United States. Racial disparities in the incidence and mortality of this cancer are apparent; black women are less likely to develop this malignancy and yet are more likely to die when diagnosed. Racial differences of second primary cancer (SPC) have not been examined, and the goal of this study was to examine these differences.Methods:With the use of the National Cancer Institute's Surveillance, Epidemiology, and End Results database, SPC risk in white patients and black patients with EC was compared to the general population and to women with other primary cancers. Standardized incidence ratios (SIRs) of SPC (overall and by tumor site) with 95% confidence intervals were calculated. Poisson regression was used to estimate the race-specific risk of SPC in EC cases treated with radiotherapy versus nonirradiated cases.Results:The analysis included 11,047 patients with EC diagnosed between 1973 and 2007 that developed an SPC. Overall risk of SPC in white women with EC was significantly lower than that in the general population (SIR = 0.85; 95% CI, 0.84-0.87) but significantly higher in black women with EC (SIR = 1.19; 95% CI, 1.08-1.31). White women with EC treated with radiotherapy were more likely to develop SPC compared with nonirradiated cases (incidence rate ratio [IRR], 1.18; 95% CI, 1.14-1.23).Conclusions:This is the first analysis of race-specific SPC risk in EC cases, and it suggests differences between white women and black women with EC. Although exploratory, these data provide important clues about the etiology of SPC in patients with EC. This analysis also highlights the need for careful monitoring after diagnosis and treatment of EC.
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Zibordi, Giuseppe, Frédéric Mélin, Jean-François Berthon, Brent Holben, Ilya Slutsker, David Giles, Davide D’Alimonte, et al. "AERONET-OC: A Network for the Validation of Ocean Color Primary Products." Journal of Atmospheric and Oceanic Technology 26, no. 8 (August 1, 2009): 1634–51. http://dx.doi.org/10.1175/2009jtecho654.1.
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Abstract The ocean color component of the Aerosol Robotic Network (AERONET-OC) has been implemented to support long-term satellite ocean color investigations through cross-site consistent and accurate measurements collected by autonomous radiometer systems deployed on offshore fixed platforms. The AERONET-OC data products are the normalized water-leaving radiances determined at various center wavelengths in the visible and near-infrared spectral regions. These data complement atmospheric AERONET aerosol products, such as optical thickness, size distribution, single scattering albedo, and phase function. This work describes in detail this new AERONET component and its specific elements including measurement method, instrument calibration, processing scheme, quality assurance, uncertainties, data archive, and products accessibility. Additionally, the atmospheric and bio-optical features of the sites currently included in AERONET-OC are briefly summarized. After illustrating the application of AERONET-OC data to the validation of primary satellite products over a variety of complex coastal waters, recommendations are then provided for the identification of new deployment sites most suitable to support satellite ocean color missions.
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Mu, Yi, Jonathan R. Edwards, Teresa C. Horan, Sandra I. Berrios-Torres, and Scott K. Fridkin. "Improving Risk-Adjusted Measures of Surgical Site Infection for the National Healthcare Safely Network." Infection Control & Hospital Epidemiology 32, no. 10 (October 2011): 970–86. http://dx.doi.org/10.1086/662016.
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Background.The National Healthcare Safety Network (NHSN) has provided simple risk adjustment of surgical site infection (SSI) rates to participating hospitals to facilitate quality improvement activities; improved risk models were developed and evaluated.Methods.Data reported to the NHSN for all operative procedures performed from January 1, 2006, through December 31, 2008, were analyzed. Only SSIs related to the primary incision site were included. A common set of patient- and hospital-specific variables were evaluated as potential SSI risk factors by univariate analysis. Some ific variables were available for inclusion. Stepwise logistic regression was used to develop the specific risk models by procedure category. Bootstrap resampling was used to validate the models, and the c-index was used to compare the predictive power of new procedure-specific risk models with that of the models with the NHSN risk index as the only variable (NHSN risk index model).Results.From January 1, 2006, through December 31, 2008, 847 hospitals in 43 states reported a total of 849,659 procedures and 16,147 primary incisional SSIs (risk, 1.90%) among 39 operative procedure categories. Overall, the median c-index of the new procedure-specific risk was greater (0.67 [range, 0.59–0.85]) than the median c-index of the NHSN risk index models (0.60 [range, 0.51–0.77]); for 33 of 39 procedures, the new procedure-specific models yielded a higher c-index than did the NHSN risk index models.Conclusions.A set of new risk models developed using existing data elements collected through the NHSN improves predictive performance, compared with the traditional NHSN risk index stratification.
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Block, KL, K. Ravid, QH Phung, and M. Poncz. "Characterization of regulatory elements in the 5'-flanking region of the rat GPIIb gene by studies in a primary rat marrow culture system." Blood 84, no. 10 (November 15, 1994): 3385–93. http://dx.doi.org/10.1182/blood.v84.10.3385.3385.
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Abstract Glycoprotein (GP)IIb/IIIa, an integrin complex found on the surface of platelets, is a receptor for fibrinogen and other ligands, and is involved in platelet aggregation. Because GPIIb is specifically expressed in megakaryocytes, we have studied the 52-flanking region of the rat (r) GPIIb gene as a model of a megakaryocyte-specific gene. The studies presented here used a rat marrow expression system, which allows the study of primary cells undergoing terminal differentiation into megakaryocytes. The determination of megakaryocyte-specific expression of DNA constructs was possible by immunomagnetically separating megakaryocytes from total bone marrow cells. Transient expression constructs, containing varying lengths of the 52-flanking region from -39 to -912 bp, localized a regulatory element between -460 and -439 bp upstream of the transcriptional start site. This region contains a GATA consensus binding element between -457 and -454 (GATA454). Further constructs demonstrated that this GATA binding element was indeed essential for expression. A 25-bp substitution, covering the region -450 to -426 immediately downstream of the GATA454, demonstrated that this region was essential for full expression, which suggests that this region may interact with the GATA454 site in promoting high-level lineage-specific expression. To define regulatory elements between the GATA454 and the transcriptional start site further, we tested additional constructs derived from the original -912 construct; each of which contained the GATA454 but had different 50-bp deletions from -450 to the start site. Virtually all of these constructs continued to show high-level tissue-specific expression. The deleted -150 to -101 construct had twice the level of expression of the full-length wild-type construct; therefore, this region may contain a negative regulatory element. Comparison of our data with expression studies performed with the 52-region of the human GPIIb gene using HEL cells, a cell line with some megakaryocytic properties, demonstrates significant differences, which may reflect our use of primary rate bone marrow cells. In particular, our study points to the importance of the GATA454 for high levels of GPIIb expression in developing megakaryocytes.
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Block, KL, K. Ravid, QH Phung, and M. Poncz. "Characterization of regulatory elements in the 5'-flanking region of the rat GPIIb gene by studies in a primary rat marrow culture system." Blood 84, no. 10 (November 15, 1994): 3385–93. http://dx.doi.org/10.1182/blood.v84.10.3385.bloodjournal84103385.
Full textAbstract:
Glycoprotein (GP)IIb/IIIa, an integrin complex found on the surface of platelets, is a receptor for fibrinogen and other ligands, and is involved in platelet aggregation. Because GPIIb is specifically expressed in megakaryocytes, we have studied the 52-flanking region of the rat (r) GPIIb gene as a model of a megakaryocyte-specific gene. The studies presented here used a rat marrow expression system, which allows the study of primary cells undergoing terminal differentiation into megakaryocytes. The determination of megakaryocyte-specific expression of DNA constructs was possible by immunomagnetically separating megakaryocytes from total bone marrow cells. Transient expression constructs, containing varying lengths of the 52-flanking region from -39 to -912 bp, localized a regulatory element between -460 and -439 bp upstream of the transcriptional start site. This region contains a GATA consensus binding element between -457 and -454 (GATA454). Further constructs demonstrated that this GATA binding element was indeed essential for expression. A 25-bp substitution, covering the region -450 to -426 immediately downstream of the GATA454, demonstrated that this region was essential for full expression, which suggests that this region may interact with the GATA454 site in promoting high-level lineage-specific expression. To define regulatory elements between the GATA454 and the transcriptional start site further, we tested additional constructs derived from the original -912 construct; each of which contained the GATA454 but had different 50-bp deletions from -450 to the start site. Virtually all of these constructs continued to show high-level tissue-specific expression. The deleted -150 to -101 construct had twice the level of expression of the full-length wild-type construct; therefore, this region may contain a negative regulatory element. Comparison of our data with expression studies performed with the 52-region of the human GPIIb gene using HEL cells, a cell line with some megakaryocytic properties, demonstrates significant differences, which may reflect our use of primary rate bone marrow cells. In particular, our study points to the importance of the GATA454 for high levels of GPIIb expression in developing megakaryocytes.
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Addo-Fordjour, Patrick, and Zakaria B. Rahmad. "Mixed Species Allometric Models for Estimating above-Ground Liana Biomass in Tropical Primary and Secondary Forests, Ghana." ISRN Forestry 2013 (September 14, 2013): 1–9. http://dx.doi.org/10.1155/2013/153587.
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The study developed allometric models for estimating liana stem and total above-ground (TAGB) biomass in primary and secondary forests in the Asenanyo Forest Reserve, Ghana. Liana biomass was determined for 50 individuals for each forest using destructive sampling. Various predictors involving liana diameter and length were run against liana biomass in regression analysis, and R2, RMSE, and Furnival's index of fit (FI) were used for model comparison. The equations comprised models fitted to untransformed and log-transformed data. Forest type had a significant influence (P<0.05) on liana allometric models in the current study, resulting in the development of forest-type-specific equations. There were significant and strong linear relationships between liana biomass and the predictors in both forests (R2>0.970). Liana diameter was a better predictor of biomass than liana length. Generally, the models which were based on log-transformed data showed better fit (higher FI values) than those fitted to untransformed data. Comparison of the site specific models in the current study with previously published models indicated that the models of the current study differed from the previous ones. This indicates the need for forest specific equations to be used for accurate determination of above-ground liana biomass.
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Wang, Y., S. M. Camp, M. Niwano, X. Shen, J. C. Bakowska, X. O. Breakefield, and P. D. Allen. "Herpes Simplex Virus Type 1/Adeno-Associated Virus rep+ Hybrid Amplicon Vector Improves the Stability of Transgene Expression in Human Cells by Site-Specific Integration." Journal of Virology 76, no. 14 (July 15, 2002): 7150–62. http://dx.doi.org/10.1128/jvi.76.14.7150-7162.2002.
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ABSTRACT Herpes simplex virus type 1 (HSV-1) amplicon vectors are promising gene delivery tools, but their utility in gene therapy has been impeded to some extent by their inability to achieve stable transgene expression. In this study, we examined the possibility of improving transduction stability in cultured human cells via site-specific genomic integration mediated by adeno-associated virus (AAV) Rep and inverted terminal repeats (ITRs). A rep − HSV/AAV hybrid amplicon vector was made by inserting a transgene cassette flanked with AAV ITRs into an HSV-1 amplicon backbone, and a rep + HSV/AAV hybrid amplicon was made by inserting rep68/78 outside the rep − vector 3′ AAV ITR sequence. Both vectors also had a pair of loxP sites flanking the ITRs. The resulting hybrid amplicon vectors were successfully packaged and compared to a standard amplicon vector for stable transduction frequency (STF) in human 293 and Gli36 cell lines and primary myoblasts. The rep +, but not the rep −, hybrid vector improved STF in all three types of cells; 84% of Gli36 and 40% of 293 stable clones transduced by the rep + hybrid vector integrated the transgene into the AAVS1 site. Due to the difficulty in expanding primary myoblasts, we did not assess site-specific integration in these cells. A strategy to attempt further improvement of STF by “deconcatenating” the hybrid amplicon DNA via Cre-loxP recombination was tested, but it did not increase STF. These data demonstrate that introducing the integrating elements of AAV into HSV-1 amplicon vectors can significantly improve their ability to achieve stable gene transduction by conferring the AAV-like capability of site-specific genomic integration in dividing cells.
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Horlings, H. M., M. O. Warmoes, J. M. Kerst, H. Helgason, D. De Jong, and L. Van ’t Veer. "Successful classification of metastatic carcinoma of known primary using the CUPPRINT." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 20028. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.20028.
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20028 Background: It is critical for treatment decisions of metastatic disease to identify the primary tumor of the metastases, since the choice of optimal therapy depends on the correct diagnosis of the primary. Routine diagnostic evaluation is not sufficient to detect the primary site in 2–4% of all patients with pathology proven malignancy who present with metastatic disease. Currently the diagnostic yield is approximately between 20% and 30% for these patients. Microarray-based gene expression profiling has shown great promise to improve this. Methods: A microarray database was constructed of 497 frozen and 127 paraffin embedded (FFPE) samples representing 51 tumor types of both primary and metastatic tumors. The microarray database contained 22,000 gene-expression measurements for each sample. From the microarray database, we used an algorithm to search for gene combinations optimal for multi-tumor classification. This optimal gene-set was printed on 8-pack slides. These “1 × 3” glass slides contain eight mini-arrays with 1900 probes allowing for 8 simultaneous hybridizations, CUPPRINT. A k-nearest-neighbor-algorithm using this optimal gene-set was developed to discriminate between the 51 tumor types. We have independently verified the accuracy of this classification algorithm using FFPE samples from patients with metastases from 90 known and 50 unknown primary carcinomas. The expression data will be compared with clinicopathological data and an additional immunological panel of cytokeratin 7, cytokeratin 20, carcinogen embryonic antigen, CD 10, thyroid transcription factor 1, renal cell carcinoma, thyrogobulin, calcitonin, estrogen, progesterone, prostate specific antigen and CA 125. Results: The microarray based assay was able to classify correctly the primary site in 36 of 41 samples done so far (88% accuracy). The immunological panel showed a discriminative immunophenotype in 73% of these cases. For 49 known and 50 unknown primary tumors comparison between gene expression and clinicopathological investigations is currently pending. Conclusion: CUPPRINT, a microarrays based assay, is capable to accurately determine the tumor site of origin for a metastatic lesion. [Table: see text]
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Serth, Jürgen, Inga Peters, Olga Katzendorn, Tu N. Dang, Joana Moog, Zarife Balli, Christel Reese, et al. "Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS)." International Journal of Molecular Sciences 23, no. 19 (September 23, 2022): 11190. http://dx.doi.org/10.3390/ijms231911190.
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Approximately 21% of patients with renal cell cancer (RCC) present with synchronous metastatic disease at the time of diagnosis, and metachronous metastatic disease occurs in 20–50% of cases within 5 years. Recent advances in adjuvant treatment of aggressive RCC following surgery suggest that biomarker-based prediction of risk for distant metastasis could improve patient selection. Biometrical analysis of TCGA-KIRC data identified candidate loci in the NK6 homeobox 2 gene (NKX6-2) that are hypermethylated in primary metastatic RCC. Analyses of NKX6-2 DNA methylation in three gene regions including a total of 16 CpG sites in 154 tumor-adjacent normal tissue, 189 RCC, and 194 metastatic tissue samples from 95 metastasized RCC patients revealed highly significant tumor-specific, primary metastatic-specific, and metastatic tissue-specific hypermethylation of NKX6-2. Combined CpG site methylation data for NKX6-2 and metastasis-associated genes (INA, NHLH2, and THBS4) demonstrated similarity between metastatic tissues and metastatic primary RCC tissues. The random forest method and evaluation of an unknown test cohort of tissues using receiver operator characteristic curve analysis revealed that metastatic tissues can be differentiated by a median area under the curve of 0.86 (p = 1.7 × 10−8–7.5 × 10−3) in 1000 random runs. Analysis of variable importance demonstrated an above median contribution for decision-making of at least one CpG site in each of the genes, suggesting superior informativity for sites annotated to NHLH2 and NKX6-2. Thus, DNA methylation of NKX6-2 is associated with the metastatic state of RCC tissues and contributes to a four-gene-based statistical predictor of tumoral and metastatic renal tissues.