Early work supports chemoaffinity with one contradictory result

Recently, generalized modules for membrane antigens (GMMA) technology has been proposed as an alternative approach to traditional glycoconjugate vaccines for O-antigen delivery. Saccharide length is a well-known parameter that can impact the immune response induced by glycoconjugates both in terms of magnitude and quality. However, the criticality of O-antigen length on the immune response induced by GMMA-based vaccines has not been fully elucidated. Here, Shigella and Salmonella GMMA-producing strains were further mutated in order to display homogeneous polysaccharide populations of different sizes on a GMMA surface. Resulting GMMA were compared in mice immunization studies. Athymic nude mice were also used to investigate the involvement of T-cells in the immune response elicited. In contrast with what has been reported for traditional glycoconjugate vaccines and independent of the pathogen and the sugar structural characteristics, O-antigen length did not result in being a critical parameter for GMMA immunogenicity. This work supports the identification of critical quality attributes to optimize GMMA vaccine design and improve vaccine efficacy and gives insights on the nature of the immune response induced by GMMA.

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Expression of BARD1 β Isoform in Selected Pediatric Tumors

Genes ◽

10.3390/genes12020168 ◽

2021 ◽

Vol 12 (2) ◽

pp. 168

Author(s):

Anna Jasiak ◽

Natalia Krawczyńska ◽

Mariola Iliszko ◽

Katarzyna Czarnota ◽

Kamil Buczkowski ◽

...

Keyword(s):

Pediatric Cancer ◽

Genome Stability ◽

Cell Cycle Control ◽

Reverse Transcriptase Gene ◽

Neoplastic Tissue ◽

Adult Type ◽

Qpcr Method ◽

New Treatments ◽

First Time ◽

Work Supports

Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is BARD1 (BRCA1 Associated RING Domain 1)—a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on BARD1 significance in childhood cancer is limited. This study determines the expression level of BARD1 and its isoform beta (β) in three different histogenetic groups of pediatric cancer—neuroblastic tumours, and for the first time in chosen germ cell tumours (GCT), and rhabdomyosarcoma (RMS), using the qPCR method. We found higher expression of beta isoform in tumour compared to healthy tissue with no such changes concerning BARD1 full-length. Additionally, differences in expression of BARD1 β between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of BARD1 β characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the TERT (Telomerase Reverse Transcriptase) gene. In two RMS cases we found deep decrease of BARD1 β in post-chemotherapy samples. This work supports the oncogenicity of the beta isoform in pediatric tumours, as well as demonstrates the differences in its expression depending on the histological type of neoplasm, and the level of maturation in neuroblastic tumours.

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Population Density or Populations Size. Which Factor Determines Urban Traffic Congestion?

Sustainability ◽

10.3390/su13084280 ◽

2021 ◽

Vol 13 (8) ◽

pp. 4280

Author(s):

Yu Sang Chang ◽

Sung Jun Jo ◽

Yoo-Taek Lee ◽

Yoonji Lee

Keyword(s):

Population Density ◽

Population Size ◽

Traffic Congestion ◽

Critical Role ◽

Small Population ◽

High Density ◽

Urban Traffic ◽

Contradictory Result ◽

Low Density

A large number of articles have documented that as population density of cities increases, car use declines and public transit use rises. These articles had a significant impact of promoting high-density compact urban development to mitigate traffic congestion. Another approach followed by other researchers used the urban scaling model to indicate that traffic congestion increases as population size of cities increases, thus generating a possible contradictory result. Therefore, this study examines the role of both density and population size on traffic congestion in 164 global cities by the use of Stochastic Impacts by Regression on Population, Affluence and Technology model. We divide 164 cities into the two subgroups of 66 low density cities and 98 high density cities for analysis. The findings from the subgroups analysis indicated a clear-cut difference on the critical role of density in low-density cities and the exclusive role of population size in high-density cities. Furthermore, using threshold regression model, 164 cities are divided into the two regions of large and small population cities to determine population scale advantage of traffic congestion. Our findings highlight the importance of including analysis of subgroups based on density and/or population size in future studies of traffic congestion.

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EXTH-30. EXPANDING THE UTILITY OF PRE-CLINICAL CONTRAST ENHANCED CT (CE-CT) FOR TUMOR DETECTION IN ORTHOTOPIC GBM MODELS USING RADIOMICS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.384 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii93-ii93

Author(s):

Kate Connor ◽

Emer Conroy ◽

Kieron White ◽

Liam Shiels ◽

William Gallagher ◽

...

Keyword(s):

Imaging Modality ◽

Texture Features ◽

Tumor Detection ◽

Contrast Enhanced Ct ◽

Contrast Enhanced ◽

Pet Ct ◽

Enhanced Ct ◽

Magnetic Resonance Imaging Mri ◽

Work Supports ◽

Selection Of

Abstract Despite magnetic resonance imaging (MRI) being the gold-standard imaging modality in the glioblastoma (GBM) setting, the availability of rodent MRI scanners is relatively limited. CT is a clinically relevant alternative which is more widely available in the pre-clinic. To study the utility of contrast-enhanced (CE)-CT in GBM xenograft modelling, we optimized CT protocols on two instruments (IVIS-SPECTRUM-CT;TRIUMPH-PET/CT) with/without delivery of contrast. As radiomics analysis may facilitate earlier detection of tumors by CT alone, allowing for deeper analyses of tumor characteristics, we established a radiomic pipeline for extraction and selection of tumor specific CT-derived radiomic features (inc. first order statistics/texture features). U87R-Luc2 GBM cells were implanted orthotopically into NOD/SCID mice (n=25) and tumor growth monitored via weekly BLI. Concurrently mice underwent four rounds of CE-CT (IV iomeprol/iopamidol; 50kV-scan). N=45 CE-CT images were semi-automatically delineated and radiomic features were extracted (Pyradiomics 2.2.0) at each imaging timepoint. Differences between normal and tumor tissue were analyzed using recursive selection. Using either CT instrument/contrast, tumors > 0.4cm3 were not detectable until week-9 post-implantation. Radiomic analysis identified three features (waveletHHH_firstorder_Median, original_glcm_Correlation and waveletLHL_firstorder_Median) at week-3 and -6 which may be early indicators of tumor presence. These features are now being assessed in CE-CT scans collected pre- and post-temozolomide treatment in a syngeneic model of mesenchymal GBM. Nevertheless, BLI is significantly more sensitive than CE-CT (either visually or using radiomic-enhanced CT feature extraction) with luciferase-positive tumors detectable at week-1. In conclusion, U87R-Luc2 tumors > 0.4cm3 are only detectable by Week-8 using CE-CT and either CT instrument studied. Nevertheless, radiomic analysis has defined features which may allow for earlier tumor detection at Week-3, thus expanding the utility of CT in the preclinical setting. Overall, this work supports the discovery of putative prognostic pre-clinical CT-derived radiomic signatures which may ultimately be assessed as early disease markers in patient datasets.

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‘Story of one’s life and a tree of friends’ – understanding millennials’ information behaviour in social networks

Journal of Information Science ◽

10.1177/0165551512453381 ◽

2012 ◽

Vol 38 (5) ◽

pp. 489-497 ◽

Cited By ~ 7

Author(s):

Pam Read ◽

Chirag Shah ◽

Lupita S-O’Brien ◽

Jaqueline Woolcott

Keyword(s):

Social Relationships ◽

Social Space ◽

New Technology ◽

Social Groups ◽

Social Value ◽

Face To Face ◽

Comprehensive Literature Review ◽

The Social ◽

Rich Data ◽

Work Supports

Exploring ways in which new technology impacts adolescents’ information behaviours and creates a social space requires holistic investigation. A qualitative study of 21 seniors in an upper-middle-class suburban high school revealed highly individualized use of Facebook and its features. These included: (i) Friends groups of 50—3700 members, with even the largest groups representative primarily of face-to-face connections, and (ii) a clear articulation within those groups of various categories, each with its own distinct communicative channel and style. A meaningful connection was found between the social value of various social network (SN)-mediated relationships and the communicative modes used to maintain and enhance them. Through a comprehensive literature review and clearly grounded analysis of rich data, this work supports the contention that adolescent social groups in which SNs are embedded form a distinct domain, and establishes a rationale for further investigation of adolescents’ contextualized use of SNs within social relationships.

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Effects of asulam spraying on non-target ferns

Canadian Journal of Botany ◽

10.1139/b05-127 ◽

2005 ◽

Vol 83 (12) ◽

pp. 1622-1629 ◽

Cited By ~ 7

Author(s):

J.K. Rowntree ◽

E. Sheffield

Keyword(s):

Experimental Evidence ◽

Application Rate ◽

Field Application ◽

Pteridium Aquilinum ◽

Buffer Zones ◽

Application Rates ◽

Highly Sensitive ◽

Fern Species ◽

Aerial Spraying ◽

Work Supports

The systemic herbicide asulam is used extensively to control the weedy fern bracken ( Pteridium aquilinum (L.) Kuhn). Other ferns were thought to be highly sensitive to asulam exposure, but there has been a dearth of experimental evidence. Eight fern species were exposed to asulam spray at three different application rates or a control of water. Asulam was applied at the recommended field application rate for bracken clearance, and at two further rates corresponding to 10 and 50 m downwind of an aerial spray event. Damage was assessed over two seasons. All ferns tested were severely damaged by exposure to the highest application rate, but sensitivity varied between species. Maximum damage occurred 1 year after spraying, and limited signs of recovery could be seen by the second season. The effects of adding the adjuvant Agral® to applications of asulam were tested on the threatened pteridophyte Pilularia globulifera L. No damage additional to that caused by exposure to asulam was observed. This work supports the view that 50 m buffer zones are sufficient to protect sensitive ferns from the effects of aerial spraying with asulam, provided that drift-reducing nozzles are used and the manufacturer’s application guidelines are observed.

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Family experiences with non-therapeutic research on dying patients in the intensive care unit

Journal of Medical Ethics ◽

10.1136/medethics-2021-107311 ◽

2021 ◽

pp. medethics-2021-107311

Author(s):

Amanda van Beinum ◽

Nick Murphy ◽

Charles Weijer ◽

Vanessa Gruben ◽

Aimee Sarti ◽

...

Keyword(s):

Intensive Care ◽

Intrinsic Value ◽

Family Members ◽

Research Participation ◽

Decision Makers ◽

Minimal Risk ◽

Dying Patients ◽

Therapeutic Study ◽

Therapeutic Research ◽

Work Supports

Experiences of substitute decision-makers with requests for consent to non-therapeutic research participation during the dying process, including to what degree such requests are perceived as burdensome, have not been well described. In this study, we explored the lived experiences of family members who consented to non-therapeutic research participation on behalf of an imminently dying patient.We interviewed 33 family members involved in surrogate research consent decisions for dying patients in intensive care. Non-therapeutic research involved continuous physiological monitoring of dying patients prior to and for 30 min following cessation of circulation. At some study centres participation involved installation of bedside computers. At one centre electroencephalogram monitoring was used with a subset of participants. Aside from additional monitoring, the research protocol did not involve deviations from usual end-of-life care.Thematic analysis of interviews suggests most family members did not perceive this minimal-risk, non-therapeutic study to affect their time with patients during the dying process, nor did they perceive research consent as an additional burden. In our analysis, consenting for participation in perimortem research offered families of the dying an opportunity to affirm the intrinsic value of patients’ lives and contributions. This opportunity may be particularly important for families of patients who consented to organ donation but did not proceed to organ retrieval.Our work supports concerns that traditional models of informed consent fail to account for possible benefits and harms of perimortem research to surviving families. Further research into consent models which integrate patient and family perspectives is needed.

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Application of the direct peptide reactivity assay (DPRA) to inorganic compounds: a case study of platinum species

Toxicology Research ◽

10.1039/c9tx00242a ◽

2019 ◽

Vol 8 (6) ◽

pp. 802-814

Author(s):

Jocelyn D. C. Hemming ◽

Mark Hosford ◽

Martin M. Shafer

Keyword(s):

High Throughput Screening ◽

Inorganic Compounds ◽

High Reactivity ◽

Limited Attention ◽

Adverse Outcome Pathway ◽

Platinum Compounds ◽

Metal Compounds ◽

Work Supports ◽

Platinum Species

Abstract The in chemico Direct Peptide Reactivity Assay (DPRA) was developed as a non-animal, relatively high throughput, screening tool for skin sensitization potential. Although the Adverse Outcome Pathway (AOP) for respiratory sensitization remains to be fully elucidated, it is recognized that the molecular initiation event for both skin and respiratory sensitization to low molecular weight chemicals involves haptenation with proteins. The DPRA examines the reactivity of a test compound to two model peptides (containing either cysteine or lysine) and consequently is able to screen for both skin and respiratory sensitization potential. The DPRA was primarily developed for and validated with organic compounds and assessment of the applicability of the assay to metal compounds has received only limited attention. This paper reports the successful application of the DPRA to a series of platinum compounds, including hexachloroplatinate and tetrachloroplatinate salts, which are some of the most potent chemical respiratory sensitizers known. Eleven platinum compounds were evaluated using the DPRA protocol as detailed by Lalko et al., with only minor modification. Two palladium compounds with structures similar to that of the platinum species studied and cobalt chloride were additionally tested for comparison. The hexachloroplatinate and tetrachloroplatinate salts showed exceptionally high reactivity with the cysteine peptide (EC15 values of 1.4 and 14 μM, respectively). However, for platinum compounds (e.g. hydrogen hexahydroxyplatinate and tetraammineplatinum) where clinical and epidemiological evidence indicates limited sensitization potential, the cysteine DPRA showed only minor or no reactivity (EC15 values of 24 600 and >30 000 μM, respectively). The outcomes of the lysine peptide assays were less robust and where EC15 was measurable, values were substantially higher than the corresponding results from the cysteine assay. This work supports the value of in chemico peptide reactivity as a metric for assessment of platinum sensitization potential and therefore in screening of new platinum compounds for low or absent sensitization potential. Additional studies are required to determine whether the DPRA may be successfully applied to other metals. We provide details on method modifications and precautions important to the success of the DPRA in the assessment of metal reactivity.

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Lymph nodes go with the flow

Journal of Experimental Medicine ◽

10.1084/jem.20181898 ◽

2018 ◽

Vol 215 (11) ◽

pp. 2699-2701 ◽

Cited By ~ 1

Author(s):

Rafael S. Czepielewski ◽

Gwendalyn J. Randolph

Keyword(s):

Lymph Nodes ◽

Lymphatic Vasculature ◽

Work Supports

In this issue, Bovay et al. (https://doi.org/10.1084/jem.20180217) invoke a compelling model of interplay between the venous and lymphatic vasculature in regulating the developmental genesis and early expansion of LNs. This work supports an emerging model that lymph–venous crosstalk supports LN functionality at all stages.

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