Polo like kinase 2 tumour suppressor and cancer biomarker: new perspectives on drug sensitivity/resistance in ovarian cancer

The polo-like kinase PLK2 has recently been identified as a potential theranostic marker in the management of chemotherapy sensitive cancers. The methylation status of the PLK2 CpG island varies with sensitivity to paclitaxel and platinum in ovarian cancer cell lines. Importantly, extrapolation of these in vitro data to the clinical setting confirms that the methylation status of the PLK2 CpG island predicts outcomes in patients treated with carboplatin and paclitaxel chemotherapy. A second cell cycle regulator, p57Kip2, is also subject to epigenetic silencing in carboplatin resistance in vitro and in vivo, emphasising that cell cycle regulators are important determinants of sensitivity to chemotherapeutic agents and providing insights into the phenomenon of collateral drug sensitivity in oncology. Understanding the mechanistic basis and identification of robust biomarkers to predict collateral sensitivity may inform optimal use of chemotherapy in patients receiving multiple lines of treatment

Folk and Popular Music of Brazil

Both general interest in Brazilian popular music in North America and pertinent research agendas in Brazil and abroad have led to varied new publications. In the musical arena itself, vital new phenomena have appeared, and international attention to Brazil\u27s popular music has significantly increased. As far as sound recording is concerned, the past decade has witnessed the consolidation of the digital age, and the CD has become the preferred vehicle, though the limited buying power of the bulk of the Brazilian population has determined the continued mass manufacture of cassette tapes as well as vinyl LPs in Brazil. In sum, changing conditions of production and consumption, fresh ideas and styles in music-making, and on-going efforts in scholarship, all validate the present revised and expanded edition of the specialized bibliography

Single electron charging of impurity sites visualized by scanning gate experiments on a quantum point contact

A quantum point contact (QPC) patterned on a two-dimensional electron gas is investigated with a scanning gate setup operated at a temperature of 300 mK. The conductance of the point contact is recorded while the local potential is modified by scanning the tip. Single electron charging of impurities induced by the local potential is observed as a stepwise conductance change of the constriction. By selectively changing the state of some of these impurities, it is possible to observe changes in transmission resonances of the QPC. The location of such impurities is determined, and their density is estimated to be below 50 per \mu m^2, corresponding to less than 1 % of the doping concentration

Vacancy Tuning in Li,V-Substituted Lyonsites

© 2020 Taylor & Francis Group, LLC. The lyonsite structure, characterized by the formula A 4 M 3O12, is a relatively understudied tunneled crystal structure. This host structure is known to be compositionally flexible, able to incorporate a number of cations in various oxidation states into the A site. In the parent compound Co3.75V1.5Mo1.5O12, it is apparent that a stoichiometric vacancy of 0.25 is unavoidable as a result of Coulombic repulsion. This work focuses on the systematic elimination of vacancies by chemically introducing guest Li ions while maintaining host integrity. A full solid solution was found to exist with the formula □0.25–1/8xLi x Co3.75–7/8xV1.5–3/4xMo1.5+3/4xO12 (0 ≤ x ≤ 2), terminating at the known end member Li2Co2Mo3O12. Lattice refinements on PXRD data confirmed the isostructural nature of the whole series, and detailed structural analysis revealed that competition between Li and Co in the same crystallographic site is unequal, with Li exhibiting a stronger site preference for larger interstitial sites. Diffuse reflectance analysis revealed that the optical band gap is directly tunable with x, and supporting structure-property relationships were also explored via magnetometry and dielectric measurements

Combining Charlson and Elixhauser scores with varying lookback predicated mortality better than using individual scores

Objective: To investigate variation in the presence of secondary diagnosis codes in Charlson and Elixhauser comorbidity scores and assess whether including a 1-year lookback period improved prognostic adjustment by these scores individually, and combined, for 30-day mortality. Study Design and Setting: We analyzed inpatient admissions from January 1, 2007 to May 18, 2018 in Oxfordshire, UK. Comorbidity scores were calculated using secondary diagnostic codes in the diagnostic-dominant episode, and primary and secondary codes from the year before. Associations between scores and 30-day mortality were investigated using Cox models with natural cubic splines for nonlinearity, assessing fit using Akaike Information Criteria. Results: The 1-year lookback improved model fit for Charlson and Elixhauser scores vs. using diagnostic-dominant methods. Including both, and allowing nonlinearity, improved model fit further. The diagnosis-dominant Charlson score and Elixhauser score using a 1-year lookback, and their interaction, provided the best comorbidity adjustment (reduction in AIC: 761 from best single score model). Conclusion: The Charlson and Elixhauser score calculated using primary and secondary diagnostic codes from 1-year lookback with secondary diagnostic codes from the current episode improved individual predictive ability. Ideally, comorbidities should be adjusted for using both the Charlson (diagnostic-dominant) and Elixhauser (1-year lookback) scores, incorporating nonlinearity and interactions for optimal confounding control

Design principles governing the development of theranostic anticancer agents and their nanoformulations with photoacoustic properties

The unmet need to develop novel approaches for cancer diagnosis and treatment has led to the evolution of theranostic agents, which usually include, in addition to the anticancer drug, an imaging agent based mostly on fluorescent agents. Over the past few years, a non-invasive photoacoustic imaging modality has been effectively integrated into theranostic agents. Herein, we shed light on the design principles governing the development of theranostic agents with photoacoustic properties, which can be formulated into nanocarriers to enhance their potency. Specifically, we provide an extensive analysis of their individual constituents including the imaging dyes, drugs, linkers, targeting moieties, and their formulation into nanocarriers. Along these lines, we present numerous relevant paradigms. Finally, we discuss the clinical relevance of the specific strategy, as also the limitations and future perspectives, and through this review, we envisage paving the way for the development of theranostic agents endowed with photoacoustic properties as effective anticancer medicines

Short-term genome stability of serial Clostridium difficile ribotype 027 isolates in an experimental gut model and recurrent human disease

Copyright: © 2013 Eyre et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedClostridium difficile whole genome sequencing has the potential to identify related isolates, even among otherwise indistinguishable strains, but interpretation depends on understanding genomic variation within isolates and individuals.Serial isolates from two scenarios were whole genome sequenced. Firstly, 62 isolates from 29 timepoints from three in vitro gut models, inoculated with a NAP1/027 strain. Secondly, 122 isolates from 44 patients (2–8 samples/patient) with mostly recurrent/on-going symptomatic NAP-1/027 C. difficile infection. Reference-based mapping was used to identify single nucleotide variants (SNVs).Across three gut model inductions, two with antibiotic treatment, total 137 days, only two new SNVs became established. Pre-existing minority SNVs became dominant in two models. Several SNVs were detected, only present in the minority of colonies at one/two timepoints. The median (inter-quartile range) [range] time between patients’ first and last samples was 60 (29.5–118.5) [0–561] days. Within-patient C. difficile evolution was 0.45 SNVs/called genome/year (95%CI 0.00–1.28) and within-host diversity was 0.28 SNVs/called genome (0.05–0.53). 26/28 gut model and patient SNVs were non-synonymous, affecting a range of gene targets.The consistency of whole genome sequencing data from gut model C. difficile isolates, and the high stability of genomic sequences in isolates from patients, supports the use of whole genome sequencing in detailed transmission investigations.Peer reviewe

Health system interventions to integrate genetic testing in routine oncology services: A systematic review

Background Integration of genetic testing into routine oncology care could improve access to testing. This systematic review investigated interventions and the tailored implementation strategies aimed at increasing access to genetic counselling and testing and identifying hereditary cancer in oncology. Methods The search strategy results were reported using the PRISMA statement and four electronic databases were searched. Eligible studies included routine genetic testing for breast and ovarian cancer or uptake after universal tumour screening for colorectal or endometrial cancer. The titles and abstracts were reviewed and the full text articles screened for eligibility. Data extraction was preformed using a designed template and study appraisal was assessed using an adapted Newcastle Ottawa Scale. Extracted data were mapped to Proctor’s et al outcomes and the Consolidated Framework for Implementation Research and qualitatively synthesised. Results Twenty-seven studies, published up to May 2020, met the inclusion criteria. Twenty-five studies ranged from poor (72%), fair to good (28%) quality. Most interventions identified were complex (multiple components) such as; patient or health professional education, interdisciplinary practice and a documentation or system change. Forty-eight percent of studies with complex interventions demonstrated on average a 35% increase in access to genetic counselling and a 15% increase in testing completion. Mapping of study outcomes showed that 70% and 32% of the studies aligned with either the service and client or the implementation level outcome and 96% to the process or inner setting domains of the Consolidated Framework for Implementation Research. Conclusion Existing evidence suggests that complex interventions have a potentially positive effect towards genetic counselling and testing completion rates in oncology services. Studies of sound methodological quality that explore a greater breadth of pre and post implementation outcomes and informed by theory are needed. Such research could inform future service delivery models for the integration of genetics into oncology services

Plasmid classification in an era of whole-genome sequencing: application in studies of antibiotic resistance epidemiology

Plasmids are extra-chromosomal genetic elements ubiquitous in bacteria, and commonly transmissible between host cells. Their genomes include variable repertoires of ‘accessory genes,’ such as antibiotic resistance genes, as well as ‘backbone’ loci which are largely conserved within plasmid families, and often involved in key plasmid-specific functions (e.g., replication, stable inheritance, mobility). Classifying plasmids into different types according to their phylogenetic relatedness provides insight into the epidemiology of plasmid-mediated antibiotic resistance. Current typing schemes exploit backbone loci associated with replication (replicon typing), or plasmid mobility (MOB typing). Conventional PCR-based methods for plasmid typing remain widely used. With the emergence of whole-genome sequencing (WGS), large datasets can be analyzed using in silico plasmid typing methods. However, short reads from popular high-throughput sequencers can be challenging to assemble, so complete plasmid sequences may not be accurately reconstructed. Therefore, localizing resistance genes to specific plasmids may be difficult, limiting epidemiological insight. Long-read sequencing will become increasingly popular as costs decline, especially when resolving accurate plasmid structures is the primary goal. This review discusses the application of plasmid classification in WGS-based studies of antibiotic resistance epidemiology; novel in silico plasmid analysis tools are highlighted. Due to the diverse and plastic nature of plasmid genomes, current typing schemes do not classify all plasmids, and identifying conserved, phylogenetically concordant genes for subtyping and phylogenetics is challenging. Analyzing plasmids as nodes in a network that represents gene-sharing relationships between plasmids provides a complementary way to assess plasmid diversity, and allows inferences about horizontal gene transfer to be made

COVID-19 pandemic impact on adolescent mental health: a reassessment accounting for development

Current prospective reports suggest a pandemic-related increase in adolescent mental health problems. We examine whether age-related change over 11-14 years accounts for this increase. Mothers and adolescents in a UK-based birth cohort (Wirral Child Health and Development Study; WCHADS; N = 737) reported on adolescent depression and behavioural problems pre-pandemic (December 2019-March 2020), mid-pandemic (June 2020-March 2021) and late pandemic (July 2021-March 2022). Analysis used repeated measures models for over-dispersed Poisson counts with an adolescent-specific intercept with age as a time-varying covariate. Maturational curves for girls, but not for boys, showed a significant increase in self-reported depression symptoms over ages 11-14 years. Behavioural problems decreased for both. After adjusting for age-related change, girls' depression increased by only 13% at mid-pandemic and returned to near pre-pandemic level at late pandemic (mid versus late - 12%), whereas boys' depression increased by 31% and remained elevated (mid versus late 1%). Age-adjusted behavioural problems increased for both (girls 40%, boys 41%) and worsened from mid- to late pandemic (girls 33%, boys 18%). Initial reports of a pandemic-related increase in depression in young adolescent girls could be explained by a natural maturational rise. In contrast, maturational decreases in boys' depression and both boys' and girls' behavioural problems may mask an effect of the pandemic