Erratum to "The influence of ecological factors on cnidarian venoms" [Toxicon: X 9-10C (2021) 100067].

[This corrects the article DOI: 10.1016/j.toxcx.2021.100067.].

Resonant X-ray photoelectron spectroscopy: identification of atomic contributions to valence states.

Valence electronic structure is crucial for understanding and predicting reactivity. Valence non-resonant X-ray photoelectron spectroscopy (NRXPS) provides a direct method for probing the overall valence electronic structure. However, it is often difficult to separate the varying contributions to NRXPS; for example, contributions of solutes in solvents or functional groups in complex molecules. In this work we show that valence resonant X-ray photoelectron spectroscopy (RXPS) is a vital tool for obtaining atomic contributions to valence states. We combine RXPS with NRXPS and density functional theory calculations to demonstrate the validity of using RXPS to identify atomic contributions for a range of solutes (both neutral and ionic) and solvents (both molecular solvents and ionic liquids). Furthermore, the one-electron picture of RXPS holds for all of the closed shell molecules/ions studied, although the situation for an open-shell metal complex is more complicated. The factors needed to obtain a strong RXPS signal are investigated in order to predict the types of systems RXPS will work best for; a balance of element electronegativity and bonding type is found to be important. Additionally, the dependence of RXPS spectra on both varying solvation environment and varying local-covalent bonding is probed. We find that RXPS is a promising fingerprint method for identifying species in solution, due to the spectral shape having a strong dependence on local-covalency but a weak dependence on the solvation environment.

Inducing metamorphosis in the irukandji jellyfish Carukia barnesi.

Here we utilize chemical ecology as a tool to manipulate the biological system of a small, but highly venomous to humans, cubozoan jellyfish, Carukia barnesi. We trialled a range of chemical reagents including indole compounds, 9-cis-retinoic acid and lugols solution to induce metamorphosis between the polyp and medusa life stages. An optimum method was determined resulting in a 90% metamorphosis rate to healthy medusa by exposing the polyps to 1 µM of 5-methoxy-2-methylindole for 24 h. Of note is that chemical exposure time significantly impacts health and metamorphosis rates in this species. We also present a theoretical mechanism for the chemical/biological interactions occurring during metamorphosis. This is a significant methodological advancement which now enables rearing of this animal en mass in aquaria-a world first for this species-which will subsequently supply and facilitate venom research into this understudied jellyfish.

Implications of bleaching on cnidarian venom ecology.

Cnidarian bleaching research often focuses on the effects on a cnidarian's physiological health and fitness, whilst little focus has been towards the impacts of these events on their venom ecology. Given the importance of a cnidarian's venom to their survival and the increasing threat of bleaching events, it is important to understand the effects that this threat may have on this important aspect of their ecology as it may have unforeseen impacts on their ability to catch prey and defend themselves. This review aims to explore evidence that suggests that bleaching may impact on each of the key aspects of a cnidarians' venom ecology: cnidae, venom composition, and venom toxicity. Additionally, the resulting energy deficit, compensatory heterotrophic feeding, and increased defensive measures have been highlighted as possible ecological factors driving these changes. Suggestions are also made to guide the success of research in this field into the future, specifically in regards to selecting a study organism, the importance of accurate symbiont and cnidae identification, use of appropriate bleaching methods, determination of bleaching, and animal handling. Ultimately, this review highlights a significant and important gap in our knowledge into how cnidarians are, and will, continue to be impacted by bleaching stress.

Central nervous system manifestations of systemic haematological malignancies and key differentials.

Central nervous system (CNS) involvement by haematological malignancies is uncommon, and generally associated with a poor prognosis. Neuroimaging plays a key role in the accurate diagnosis, including in the critical differentiation from other processes such as infection and treatment-related toxicity. This review illustrates a variety of manifestations of CNS involvement by haematological malignancies and relevant differential diagnoses. CNS involvement can be seen in lymphoma (both primary and secondary), Waldenström macroglobulinaemia, multiple myeloma, leukaemia, and the malignant histiocytoses. The typical patterns vary between the different disorders, for example, in the most common sites of involvement and the relative frequency of parenchymal and meningeal involvement. Adjacent structures may also be involved. Nevertheless, there is some overlap in the imaging appearances, with common features including pre-contrast hyperdensity on computed tomography (CT), diffusion restriction, and avid post-contrast enhancement. In the post-treatment context, it is also important to distinguish between disease relapse and post-treatment effects. This includes opportunistic infections and the effects of chemotherapy and/or radiotherapy, including toxic effects and radiotherapy-induced neoplasms.

The influence of ecological factors on cnidarian venoms.

Venom research is often focussed on medical relevance, novel compounds and venom evolution, whilst studying the relationship between a venom and its environment - venom ecology - has been conducted to a lesser extent. Given the projected environmental changes envisioned to occur with global warming, it is pertinent now more than ever, to highlight this topic. Here we review literature examining the influence of ecological factors such as environmental temperature, salinity, ontogeny, geographic location and diet on cnidarian venoms. This review provides an exclusive focus on the cnidarian phylum and encompasses all available published, peer-reviewed literature to our knowledge regarding the ecological factors influencing venom. We find a startling lack of research into the effects of both environmental and biological factors on venoms, with very few to no studies available per category. Importantly, research does exist that suggest these ecological processes may influence other marine or terrestrial venoms, thus we recommend future research is needed to explore this concept in cnidarians.

Evaluation of the Impact of Magnetic Resonance Imaging with Susceptibility-weighted Imaging for Screening and Surveillance of Radiation-induced Cavernomas in Long-term Survivors of Malignancy.

AIMS: Radiation-induced cavernomas (RIC) are common late toxicities in long-term survivors of malignancy following cerebral irradiation. However, the natural history of RIC is poorly described. We report the first series of long-term surveillance of RIC using modern magnetic resonance imaging (MRI) including highly sensitive susceptibility-weighted imaging (SWI). The aims of this research were to better characterise the natural history of RIC and investigate the utility of MRI-SWI for screening and surveillance. MATERIALS AND METHODS: Eligibility required long-term survivors of malignancy with previous exposure to cerebral irradiation and RIC identified on MRI-SWI surveillance. The number and size of RIC were reported on Baseline MRI-SWI and last Follow-up MRI-SWI. RESULTS: In total, 113 long-term survivors with RIC underwent MRI-SWI surveillance; 109 (96%) were asymptomatic at the time of RIC diagnosis. The median age at cerebral irradiation was 9.3 years; the median radiotherapy dose was 50.4 Gy. The median time from cerebral irradiation to Baseline MRI-SWI was 17.9 years. On Baseline MRI-SWI, RIC multiplicity was present in 89% of patients; 34% had >10 RIC; 65% had RIC ≥4 mm. The median follow-up from Baseline MRI-SWI was 7.3 years. On Follow-up MRI-SWI, 96% of patients had multiple RIC; 62% had >10 RIC; 72% had RIC ≥4 mm. Of the 109 asymptomatic patients at RIC diagnosis, 96% remained free from RIC-related symptoms at 10 years. Only two required neurosurgical intervention for RIC; there was no RIC-related mortality. CONCLUSIONS: RIC are commonly multiple, asymptomatic and typically increase in size and number over time. Our findings suggest that MRI-SWI for screening of RIC is unlikely to influence longer term intervention in asymptomatic cancer survivors. In the absence of neurological symptoms, assessment or monitoring of RIC are insufficient indications for MRI-SWI surveillance for long-term survivors of malignancy with past exposure to cerebral irradiation.

Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: an international, multi-centre propensity-score-matched study.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.

Data processing in NMR relaxometry using the matrix pencil.

The matrix pencil method (MPM) is explored for stable, reproducible data processing in nuclear magnetic resonance (NMR) relaxometry. Data from one-dimensional and two-dimensional relaxometry experiments designed to measure transverse relaxation T2, longitudinal relaxation T1, diffusion coefficient D values, and their correlations in a standard olive oil/water mixture serve as a platform available to any NMR spectroscopist to compare the performance of the MPM to the benchmark inverse Laplace transform (ILT). The data from two practical examples, including the drying of a solvent polymer system and the enzymatic digestion of polysialic acid, were also explored with the MPM and ILT. In the cases considered here, the MPM appears to outperform the ILT in terms of resolution and stability in the determination of fundamental constants for complex materials and mixtures.

Trained facilitators' experiences with structured advance care planning conversations in oncology: an international focus group study within the ACTION trial.

BACKGROUND: In oncology, Health Care Professionals often experience conducting Advance Care Planning (ACP) conversations as difficult and are hesitant to start them. A structured approach could help to overcome this. In the ACTION trial, a Phase III multi-center cluster-randomized clinical trial in six European countries (Belgium, Denmark, Italy, the Netherlands, Slovenia, United Kingdom), patients with advanced lung or colorectal cancer are invited to have one or two structured ACP conversations with a trained facilitator. It is unclear how trained facilitators experience conducting structured ACP conversations. This study aims to understand how facilitators experience delivering the ACTION Respecting Choices (RC) ACP conversation. METHODS: A qualitative study involving focus groups with RC facilitators. Focus group interviews were recorded, transcribed, anonymized, translated into English, and thematically analysed, supported by NVivo 11. The international research team was involved in data analysis from initial coding and discussion towards final themes. RESULTS: Seven focus groups were conducted, involving 28 of in total 39 trained facilitators, with different professional backgrounds from all participating countries. Alongside some cultural differences, six themes were identified. These reflect that most facilitators welcomed the opportunity to participate in the ACTION trial, seeing it as a means of learning new skills in an important area. The RC script was seen as supportive to ask questions, including those perceived as difficult to ask, but was also experienced as a barrier to a spontaneous conversation. Facilitators noticed that most patients were positive about their ACTION RC ACP conversation, which had prompted them to become aware of their wishes and to share these with others. The facilitators observed that it took patients substantial effort to have these conversations. In response, facilitators took responsibility for enabling patients to experience a conversation from which they could benefit. Facilitators emphasized the need for training, support and advanced communication skills to be able to work with the script. CONCLUSIONS: Facilitators experienced benefits and challenges in conducting scripted ACP conversations. They mentioned the importance of being skilled and experienced in carrying out ACP conversations in order to be able to explore the patients' preferences while staying attuned to patients' needs. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry 63110516 ( ISRCTN63110516 ) per 10/3/2014.

Vulnerability of seagrass blue carbon to microbial attack following exposure to warming and oxygen.

Seagrass meadows store globally-significant quantities of organic 'blue' carbon. These blue carbon stocks are potentially vulnerable to anthropogenic stressors (e.g. coastal development, climate change). Here, we tested the impact of oxygen exposure and warming (major consequences of human disturbance) on rates of microbial carbon break-down in seagrass sediments. Active microbes occurred throughout seagrass sediment profiles, but deep, ancient sediments (~5000 yrs. old) contained only 3% of the abundance of active microbes as young, surface sediments (<2 yrs. old). Metagenomic analysis revealed that microbial community structure and function changed with depth, with a shift from proteobacteria and high levels of genes involved in sulfur cycling in the near surface samples, to a higher proportion of firmicutes and euraracheota and genes involved in methanogenesis at depth. Ancient carbon consisted almost entirely (97%) of carbon considered 'thermally recalcitrant', and therefore presumably inaccessible to microbial attack. Experimental warming had little impact on carbon; however, exposure of ancient sediments to oxygen increased microbial abundance, carbon uptake and sediment carbon turnover (34-38 fold). Overall, this study provides detailed characterization of seagrass blue carbon (chemical stability, age, associated microbes) and suggests that environmental disturbances that expose coastal sediments to oxygen (e.g. dredging) have the capacity to diminish seagrass sediment carbon stocks by facilitating microbial remineralisation.

Staff perception of obstacles and facilitators when providing end of life care in critical care units of two teaching hospitals: A survey design.

OBJECTIVE: To determine perceptions of Jordanian critical care staff about obstacles and facilitators to end-of-life care. RESEARCH METHODOLOGY: The "National Survey of Critical Care Nurses' Perceptions of End-of-Life Care" was adapted and distributed to 143 critical care nurses (n = 110) and physicians (n = 33) in two Jordanian hospitals. Nurses and physicians completed items about perceived obstacles to end-of-life care. Nurses only completed items about facilitators to end-of-life care. RESULTS: The overall response rate was 72.7% (n = 104/143). Seventy-six nurses (69.1%) and 28 physicians (84.5%) responded. Nurses and physicians agreed that the highest scoring obstacles were: 'family members who do not understand what life-saving measures mean' and the 'poor design of critical care units'. Other highly scoring obstacles related to clinicians' behaviours, characteristics and attitudes. Nurses perceived the highest scoring facilitator was 'family members who accepted that the patient was dying'. CONCLUSION: There is a need to further explore the issues underlying perceptions about clinicians' behaviours, which were perceived to be key barriers to quality end-of-life care and to find acceptable solutions that fit with Islamic culture. It is the first time that the survey has been used to gather perceptions of doctors and nurses in a non-western culture.

"Reversible" myelodysplastic syndrome or ineffectual clonal haematopoiesis? - add(6p) myeloid neoplasm with a spontaneous cytogenetic remission.

Cytotoxic chemotherapy has inherent mutagenic potential and alters the bone marrow microenvironment after therapy. In some cases, this potentiates expansion of an aberrant clone and may lead to a therapy-related myeloid neoplasm if the clone overcomes selective pressure. We present the case of a 43-year-old woman diagnosed with an indolent, therapy-related myeloid neoplasm with an isolated chromosome 6p abnormality following treatment for de novo Acute Myeloid Leukaemia (AML), who manifest a sustained spontaneous cytogenetic remission two years later, possibly due to an ineffectual or non-dominant founding clone. This case reminds us to be mindful of the possibility that clonal haematopoiesis may not always equate to clinically relevant disease, even in the setting of an abnormal clonal karyotype.

Advance care planning: A systematic review about experiences of patients with a life-threatening or life-limiting illness.

BACKGROUND: Advance care planning is seen as an important strategy to improve end-of-life communication and the quality of life of patients and their relatives. However, the frequency of advance care planning conversations in practice remains low. In-depth understanding of patients' experiences with advance care planning might provide clues to optimise its value to patients and improve implementation. AIM: To synthesise and describe the research findings on the experiences with advance care planning of patients with a life-threatening or life-limiting illness. DESIGN: A systematic literature review, using an iterative search strategy. A thematic synthesis was conducted and was supported by NVivo 11. DATA SOURCES: The search was performed in MEDLINE, Embase, PsycINFO and CINAHL on 7 November 2016. RESULTS: Of the 3555 articles found, 20 were included. We identified three themes in patients' experiences with advance care planning. 'Ambivalence' refers to patients simultaneously experiencing benefits from advance care planning as well as unpleasant feelings. 'Readiness' for advance care planning is a necessary prerequisite for taking up its benefits but can also be promoted by the process of advance care planning itself. 'Openness' refers to patients' need to feel comfortable in being open about their preferences for future care towards relevant others. CONCLUSION: Although participation in advance care planning can be accompanied by unpleasant feelings, many patients reported benefits of advance care planning as well. This suggests a need for advance care planning to be personalised in a form which is both feasible and relevant at moments suitable for the individual patient.

Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials.

Background: Patients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed overall survival (OS) stratified by progression-free survival (PFS) at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration. Patients and methods: PFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs). Results: A total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0-34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively. Conclusion: Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.

Dancing partners at the ball: Rational selection of next generation anti-CD20 antibodies for combination therapy of chronic lymphocytic leukemia in the novel agents era.

The anti-CD20 antibodies represent a major advancement in the therapeutic options available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab and obinutuzumab to various chemotherapy regimens has led to considerable improvements in both response and survival. Ocaratuzumab, veltuzumab and ublituximab are currently being explored within the trial setting. We review the current status of these antibodies, and discuss how their mechanisms of action may impact on the choice of combinations with novel small molecule agents.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.