Traditional systemic treatment options in advanced low-grade serous ovarian cancer after successful cytoreduction: a systematic review and meta-analysis

Objective: We performed a systematic literature review and a subsequent meta-analysis to compare traditional treatment options, i.e., antihormonal and cytotoxic, in LGSOC. Methods: We conducted a systematic literature review in MEDBASE and MEDLINE between September 2000 and June 2021 for women who received cytotoxic chemotherapy and/or antihormonal treatment after primary cytoreduction due to stage II–IV LGSOC and also at relapse. PFS and OS were calculated depending on the type of their adjuvant treatment. For each endpoint in the meta-analysis, pooled HR was calculated using the random effect model with the inverse variance weighted method. Only primary patients were included in the subsequent meta-analysis due to the small number of studies in the relapsed setting. Results: Five eligible first-line studies were included. Systemic chemotherapy failed to provide a significant OS benefit when compared to no systemic treatment (pooled HR = 1.01, 95% CI [0.79, 1.29]) after successful cytoreduction. Moreover, systemic chemotherapy followed by antihormonal treatment also did not result to a significant PFS or OS benefit when compared to systemic chemotherapy alone (for PSF: pooled HR = 0.59, 95% CI [0.33, 1.04]; for OS: pooled HR = 0.83, 95% CI [0.50, 1.39]). There were insufficient data from studies in the recurrent setting to allow their inclusion in the meta-analysis. Conclusions: In this meta-analysis, we failed to identify a traditional cytotoxic or antihormonal systemic treatment option that was associated with a significant OS or PFS benefit when administered following successful cytoreduction for advanced LGSOC. Prospective randomized studies are urgently warranted to define optimal adjuvant options in this challenging disease

Analysis of Virion Structural Components Reveals Vestiges of the Ancestral Ichnovirus Genome

Many thousands of endoparasitic wasp species are known to inject polydnavirus (PDV) particles into their caterpillar host during oviposition, causing immune and developmental dysfunctions that benefit the wasp larva. PDVs associated with braconid and ichneumonid wasps, bracoviruses and ichnoviruses respectively, both deliver multiple circular dsDNA molecules to the caterpillar. These molecules contain virulence genes but lack core genes typically involved in particle production. This is not completely unexpected given that no PDV replication takes place in the caterpillar. Particle production is confined to the wasp ovary where viral DNAs are generated from proviral copies maintained within the wasp genome. We recently showed that the genes involved in bracovirus particle production reside within the wasp genome and are related to nudiviruses. In the present work we characterized genes involved in ichnovirus particle production by analyzing the components of purified Hyposoter didymator Ichnovirus particles by LC-MS/MS and studying their organization in the wasp genome. Their products are conserved among ichnovirus-associated wasps and constitute a specific set of proteins in the virosphere. Strikingly, these genes are clustered in specialized regions of the wasp genome which are amplified along with proviral DNA during virus particle replication, but are not packaged in the particles. Clearly our results show that ichnoviruses and bracoviruses particles originated from different viral entities, thus providing an example of convergent evolution where two groups of wasps have independently domesticated viruses to deliver genes into their hosts

'Being there' for women with metastatic breast cancer: a pan-European patient survey

BACKGROUND: Understanding their experiences of diagnosis is integral to improving the quality of care for women living with advanced/metastatic breast cancer. METHODS: A survey, initiated in March 2011, was conducted in two stages. First, the views of 47 breast cancer-related patient groups in eight European countries were sought on standards of breast cancer care and unmet needs of patients. Findings were used to develop a patient-centric survey to capture personal experiences of advanced breast cancer to determine insights into the ‘trade-off' between extending overall survival and side effects associated with its treatment. The second online survey was open to women with locally advanced or metastatic breast cancer, or their carers, and responders were recruited through local patient groups. Data were collected via anonymous local language questionnaires. RESULTS: The online stage II survey received a total of 230 responses from 17 European countries: 94% of respondents had locally advanced or metastatic breast cancer and 6% were adult carers. Although the overall experience of care was generally good/excellent (77%), gaps were still perceived in terms of treatment choice and information provision. Treatment choice for patients was felt to be lacking by 32% of responders. In addition, 68% of those who responded would have liked more information about future medical treatments and research, with 57% wishing to receive this information from their oncologist. Two-thirds (66%) of women with advanced breast cancer, or their carers, believed life-extending treatment to be important so that they can spend more time with family and friends, and 67% said that the treatment was worthwhile, despite potential associated side effects. CONCLUSION: These findings show a continuing need to provide women with advanced breast cancer with better information and emphasise the importance that these patients often place on prolonging survival

Vivienne Westwood and the ethics of consuming fashion

Our paper examines ethical consumption using the case study of Vivienne Westwood, the fashion designer, and her eponymous firm, and shows how consumers of fashion might be considered ethical. The fashion industry has figured prominently in ethical debates, notably its role in encouraging overconsumption of resources and promoting an idealised lifestyle that is often neither materially nor psychically sustainable for consumers (Buchholz, 1998). We acknowledge this, yet suggest the purchase and use of clothing carries with it the potential to be ethical insofar as customers find themselves personally implicated with and caring for a designers' work

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Bioformulation of microbial biocontrol agents for a sustainable agriculture

The application of microbial based biopesticides has become a sustainable alternative to the use of chemicals to prevent yield losses due to plant pathogens. However, microbial based biopesticides are often unsuccessfully formulated and do not meet the demanding regulatory standards required by the agencies, which hinders their commercialization. Hence, an outline on the approaches to attain more effective formulations might be useful for the development of future more effective products. With this aim, this chapter reports the current state of biocontrol strategies and describes the principles of microbial biocontrol formulations. Emphasis is placed on techniques and tools available for the development and characterisation of microbial products. To provide glimpses on the possible formulations, the different existing additives, carriers, inoculation techniques and formulation types are exhaustively reviewed. Finally, requirements and principles for efficacy evaluation of plant protection products in the European Union are include

Cooperative Binding

Molecular binding is an interaction between molecules that results in a stable association between those molecules. Cooperative binding occurs if the number of binding sites of a macromolecule that are occupied by a specific type of ligand is a nonlinear function of this ligand’s concentration. This can be due, for instance, to an affinity for the ligand that depends on the amount of ligand bound. Cooperativity can be positive (supralinear) or negative (infralinear). Cooperative binding is most often observed in proteins, but nucleic acids can also exhibit cooperative binding, for instance of transcription factors. Cooperative binding has been shown to be the mechanism underlying a large range of biochemical and physiological processes

Genetic and immune landscape evolution in MMR-deficient colorectal cancer.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve. All cases had high truncal mutation burdens. Despite pervasive ITH, driver aberrations showed a clear hierarchy. Those in WNT/β-catenin, mitogen-activated protein kinase, and TGF-β receptor family genes were almost always truncal. Immune evasion (IE) drivers, such as inactivation of genes involved in antigen presentation or IFN-γ signalling, were predominantly subclonal and showed parallel evolution. These IE drivers have been implicated in immune checkpoint inhibitor resistance or sensitivity. Clonality assessments are therefore important for the development of predictive immunotherapy biomarkers in MMRd CRCs. Phylogenetic analysis identified three distinct patterns of IE driver evolution: pan-tumour evolution, subclonal evolution, and evolutionary stasis. These, but neither mutation burdens nor heterogeneity metrics, significantly correlated with T-cell densities, which were used as a surrogate marker of tumour immunogenicity. Furthermore, this revealed that genetic and T-cell infiltrates coevolve in MMRd CRCs. Low T-cell densities in the subgroup without any known IE drivers may indicate an, as yet unknown, IE mechanism. PD-L1 was expressed in the tumour microenvironment in most samples and correlated with T-cell densities. However, PD-L1 expression in cancer cells was independent of T-cell densities but strongly associated with loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and may contribute to a higher recurrence risk of MMRd CRCs with impaired CDX2 expression. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Thermodynamic model of hardness: Particular case of boron-rich solids

A number of successful theoretical models of hardness have been developed recently. A thermodynamic model of hardness, which supposes the intrinsic character of correlation between hardness and thermodynamic properties of solids, allows one to predict hardness of known or even hypothetical solids from the data on Gibbs energy of atomization of the elements, which implicitly determine the energy density per chemical bonding. The only structural data needed is the coordination number of the atoms in a lattice. Using this approach, the hardness of known and hypothetical polymorphs of pure boron and a number of boron-rich solids has been calculated. The thermodynamic interpretation of the bonding energy allows one to predict the hardness as a function of thermodynamic parameters. In particular, the excellent agreement between experimental and calculated values has been observed not only for the room- temperature values of the Vickers hardness of stoichiometric compounds, but also for its temperature and concentration dependencies