Data sharing considerations to maximise use of pathogen biological and genomics resources data for public health.

Public sector data associated with health is a highly valuable resource with multiple potential end-users, from health practitioners, researchers, public bodies, policy makers and industry. Data for infectious disease agents is used for epidemiological investigations, disease tracking and assessing emerging biological threats. Yet, there are challenges in collating and re-using it. Data may be derived from multiple sources, generated and collected for different purposes. While public sector data should be open access, providers from public health settings or from agriculture, food or environment sources have sensitivity criteria to meet with ethical restrictions in how the data can be reused. Yet, sharable datasets need to describe the pathogens with sufficient contextual metadata for maximal utility, e.g. associated disease or disease potential and the pathogen source. As data comprises the physical resources of pathogen collections and potentially associated sequences, there is an added emerging technical issue of integration of 'omics 'big data'. Thus, there is a need to identify suitable means to integrate and safely access diverse data for pathogens. Established genomics alliances and platforms interpret and meet the challenges in different ways depending on their own context. Nonetheless, their templates and frameworks provide a solution for adaption to pathogen datasets.

Metal fluorides-multi-functional tools for the study of phosphoryl transfer enzymes, a practical guide.

Enzymes facilitating the transfer of phosphate groups constitute the most extensive protein families across all kingdoms of life. They make up approximately 10% of the proteins found in the human genome. Understanding the mechanisms by which enzymes catalyze these reactions is essential in characterizing the processes they regulate. Metal fluorides can be used as multifunctional tools to study these enzymes. These ionic species bear the same charge as phosphate and the transferring phosphoryl group and, in addition, allow the enzyme to be trapped in catalytically important states with spectroscopically sensitive atoms interacting directly with active site residues. The ionic nature of these phosphate surrogates also allows their removal and replacement with other analogs. Here, we describe the best practices to obtain these complexes, their use in NMR, X-ray crystallography, cryo-EM, and SAXS and describe a new metal fluoride, scandium tetrafluoride, which has significant anomalous signal using soft X-rays.

Perceptions of the attributes of new long-acting HIV pre-exposure prophylaxis formulations compared with a daily, oral dose among South African young women: a qualitative study.

Oral PrEP is highly effective against the acquisition of HIV but is underutilised by young women. New options, like the monthly dapivirine vaginal ring (DVR) and injectable long-acting cabotegravir (CAB-LA), are emerging. However, little is known about young women's perceptions of these alternatives. This qualitative study explored perceptions of the attributes of PrEP technologies in South Africa. Young women accessing sexual health services were purposively selected to participate in 22 in-depth interviews, five focus group discussions and two workshops using the nominal group technique, between August 2022 and March 2023. A thematic approach guided by the diffusion of innovation attributes, including relative advantage, compatibility with the student's lives, complexity of the technology, and trialability, was used for data analysis. The DVR was the least preferred because of lower efficacy, the perceived complexity of inserting it in the vagina and some safety concerns. Oral PrEP, which some had tried and discontinued, was least compatible with students' busy schedules. Integrating PrEP and contraceptives with similar return visit patterns could enhance service delivery. Intensive deman-creation campaigns will be needed to increase PrEP utilisation and dispel myths about the vaginal ring.

Electromagnetic Enantiomer: Chiral Nanophotonic Cavities for Inducing Chemical Asymmetry.

Chiral molecules, a cornerstone of chemical sciences with applications ranging from pharmaceuticals to molecular electronics, come in mirror-image pairs called enantiomers. However, their synthesis often requires complex control of their molecular geometry. We propose a strategy called "electromagnetic enantiomers" for inducing chirality in molecules located within engineered nanocavities using light, eliminating the need for intricate molecular design. This approach works by exploiting the strong coupling between a nonchiral molecule and a chiral mode within a nanocavity. We provide evidence for this strong coupling through angular emission patterns verified by numerical simulations and with complementary evidence provided by luminescence lifetime measurements. In simpler terms, our hypothesis suggests that chiral properties can be conveyed on to a molecule with a suitable chromophore by placing it within a specially designed chiral nanocavity that is significantly larger (hundreds of nanometers) than the molecule itself. To demonstrate this concept, we showcase an application in display technology, achieving efficient emission of circularly polarized light from a nonchiral molecule. The electromagnetic enantiomer concept offers a simpler approach to chiral control, potentially opening doors for asymmetric synthesis.

Activated platelets retain and protect most of their factor XIII-A cargo from proteolytic activation and degradation.

Platelet factor (F)XIII-A is a major cytoplasmic protein (~3% of total) representing ~50% of total circulating FXIII. However, mobilization of FXIII-A during platelet activation is not well defined. To determine mechanisms mediating the retention versus release of platelet FXIII-A, platelets from healthy humans and mice (F13a1-/-, Fga-/-, Plg-/-, Stim1fl/fl, Pf4-Cre and respective controls) were stimulated with thrombin, convulxin+thrombin, or calcium ionophore (A23187), in the absence or presence of inhibitors of transglutaminase activity, mRNA translation, microtubule rearrangement, calpain, and Rho GTPase. Platelet releasates and pellets were separated by (ultra)centrifugation. FXIII-A was detected by immunoblotting and immunofluorescence microscopy. Even following strong dual agonist (convulxin+thrombin) stimulation of human platelets, >80% platelet FXIII-A remained associated with the platelet pellet. In contrast, essentially all tissue factor pathway inhibitor, another cytoplasmic protein in platelets, was released to the supernatant. Pellet-associated FXIII-A was not due to de novo synthesis via platelet F13A1 mRNA. The proportion of platelet FXIII-A retained by, versus released from, activated platelets was partly dependent on STIM1 signaling, microtubule rearrangement, calpain, and RhoA activation, but did not depend on the presence of fibrinogen or plasminogen. Immunofluorescence microscopy confirmed the presence of considerable FXIII-A within the activated platelets. Whereas released FXIII-A was cleaved to FXIII-A* and could be degraded by plasmin, platelet-associated FXIII-A remained uncleaved. Retention of substantial platelet-derived FXIII-A by activated platelets, and its reduced susceptibility to thrombin- and plasmin-mediated proteolysis, suggests platelet FXIII-A is a protected pool with biological role(s) that differs from plasma FXIII.

Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset.

Co-observation of a gene variant with a pathogenic variant in another gene that explains the disease presentation has been designated as evidence against pathogenicity for commonly used variant classification guidelines. Multiple variant curation expert panels have specified, from consensus opinion, that this evidence type is not applicable for the classification of breast cancer predisposition gene variants. Statistical analysis of sequence data for 55,815 individuals diagnosed with breast cancer from the BRIDGES sequencing project was undertaken to formally assess the utility of co-observation data for germline variant classification. Our analysis included expected loss-of-function variants in 11 breast cancer predisposition genes and pathogenic missense variants in BRCA1, BRCA2, and TP53. We assessed whether co-observation of pathogenic variants in two different genes occurred more or less often than expected under the assumption of independence. Co-observation of pathogenic variants in each of BRCA1, BRCA2, and PALB2 with the remaining genes was less frequent than expected. This evidence for depletion remained after adjustment for age at diagnosis, study design (familial versus population-based), and country. Co-observation of a variant of uncertain significance in BRCA1, BRCA2, or PALB2 with a pathogenic variant in another breast cancer gene equated to supporting evidence against pathogenicity following criterion strength assignment based on the likelihood ratio and showed utility in reclassification of missense BRCA1 and BRCA2 variants identified in BRIDGES. Our approach has applicability for assessing the value of co-observation as a predictor of variant pathogenicity in other clinical contexts, including for gene-specific guidelines developed by ClinGen Variant Curation Expert Panels.

Effector-specific improvements in action prediction in left-handed individuals after short-term physical practice.

Research has established the influence of short-term physical practice for enhancing action prediction in right-handed (RH) individuals. In addition to benefits of physical practice for these later assessed perceptual-cognitive skills, effector-specific interference has been shown through action-incongruent secondary tasks (motor interference tasks). Here we investigated this experience-driven facilitation of action predictions and effector-specific interference in left-handed (LH) novices, before and after practicing a dart throwing task. Participants watched either RH (n = 19) or LH (n = 24) videos of temporally occluded dart throws, across a control condition and three secondary-task conditions: tone-monitoring, RH or LH force monitoring. These conditions were completed before and after physical practice throwing with the LH. Significantly greater improvement in prediction accuracy was shown post-practice for the LH- versus RH-video group. Consistent with previous work, effector-specific interference was shown, exclusive to the LH-video group. Only when doing the LH force monitoring task did the LH-video group show secondary task interference in prediction accuracy. These data support the idea that short-term physical practice resulted in the development of an effector-specific motor representation. The results are also consistent with other work in RH individuals (showing RH motor interference) and hence rule out the interpretation that these effector specific effects are due to the disruption of more generalized motor processes, thought to be lateralized to the left-hemisphere of the brain.

ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors.

PURPOSE: PARP inhibitors (PARPi) are effective in homologous recombination repair (HRR) defective (HRD) cancers. To (re)sensitise HRR proficient (HRP) tumours to PARPi combinations with other drugs are being explored. Our aim was to determine the mechanism underpinning the sensitisation to PARPi by inhibitors of cell cycle checkpoint kinases ATR, CHK1 and WEE1. EXPERIMENTAL DESIGN: A panel of HRD and HRP cells (including matched BRCA1 or 2 mutant and corrected pairs) and ovarian cancer ascites cells were used. Rucaparib (PARPi) induced replication stress (RS) and HRR (immunofluorescence microscopy for γH2AX and RAD51 foci, respectively), cell cycle changes (flow cytometry), activation of ATR, CHK1 and WEE1 (Western Blot for pCHK1S345, pCHK1S296 and pCDK1Y15, respectively) and cytotoxicity (colony formation assay) was determined, followed by investigations of the impact on all of these parameters by inhibitors of ATR (VE-821, 1 µM), CHK1 (PF-477736, 50 nM) and WEE1 (MK-1775, 100 nM). RESULTS: Rucaparib induced RS (3 to10-fold), S-phase accumulation (2-fold) and ATR, CHK1 and WEE1 activation (up to 3-fold), and VE-821, PF-477736 and MK-1775 inhibited their targets and abrogated these rucaparib-induced cell cycle changes in HRP and HRD cells. Rucaparib activated HRR in HRP cells only and was (60-1,000x) more cytotoxic to HRD cells. VE-821, PF-477736 and MK-1775 blocked HRR and sensitised HRP but not HRD cells and primary ovarian ascites to rucaparib. CONCLUSIONS: Our data indicate that, rather than acting via abrogation of cell cycle checkpoints, ATR, CHK1 and WEE1 inhibitors cause an HRD phenotype and hence "induced synthetic lethality" with PARPi.

Sustained predation pressure may prevent the loss of anti-predator traits from havened populations.

Conservation havens free of invasive predators are increasingly relied upon for fauna conservation, although havened populations can lose anti-predator traits, likely making them less suitable for life 'beyond the fence'. Sustaining low levels of mammalian predator pressure inside havens may prevent the loss of anti-predator traits from havened populations. We opportunistically compared behavioural and morphological anti-predator traits between four woylie (Bettongia penicillata ogilbyi) populations- one haven isolated from all mammalian predators, one haven containing a native mammalian predator (chuditch; Dasyurus geoffroii), and their respective non-havened counterparts (each containing both chuditch and invasive predators). Havened woylies existing without mammalian predators were smaller (shorter hindfeet, smaller body weight) and less reactive (consumed more food from fox-treated and control feeding stations, less agitated during human handling) than a non-havened reference population. However, in the haven containing chuditch, we found no difference in behaviour or morphology compared to the adjacent non-havened population. Across populations, anti-predator responses tended to appear stronger at sites with higher predator activity, suggestive of an adaptive response across a gradient of predation pressure. Our findings suggest that maintaining mammalian predation pressure in conservation havens could be effective for preventing or slowing the loss of anti-predator traits from these populations.

Non-symbolic estimation of big and small ratios with accurate and noisy feedback.

The ratio of two magnitudes can take one of two values depending on the order they are operated on: a 'big' ratio of the larger to smaller magnitude, or a 'small' ratio of the smaller to larger. Although big and small ratio scales have different metric properties and carry divergent predictions for perceptual comparison tasks, no psychophysical studies have directly compared them. Two experiments are reported in which subjects implicitly learned to compare pairs of brightnesses and line lengths by non-symbolic feedback based on the scaled big ratio, small ratio or difference of the magnitudes presented. Results of Experiment 1 showed all three operations were learned quickly and estimated with a high degree of accuracy that did not significantly differ across groups or between intensive and extensive modalities, though regressions on individual data suggested an overall predisposition towards differences. Experiment 2 tested whether subjects learned to estimate the operation trained or to associate stimulus pairs with correct responses. For each operation, Gaussian noise was added to the feedback that was constant for repetitions of each pair. For all subjects, coefficients for the added noise component were negative when entered in a regression model alongside the trained differences or ratios, and were statistically significant in 80% of individual cases. Thus, subjects learned to estimate the comparative operations and effectively ignored or suppressed the added noise. These results suggest the perceptual system is highly flexible in its capacity for non-symbolic computation, which may reflect a deeper connection between perceptual structure and mathematics.

Dicobalt(ii) helices kill colon cancer cells via enantiomer-specific mechanisms; DNA damage or microtubule disruption.

Highly diastereoselective self-assembly reactions give both enantiomers (Λ and Δ) of anti-parallel triple-stranded bimetallic Co(ii) and Co(iii) cationic helices, without the need for resolution; the first such reaction for Co. The complexes are water soluble and stable, even in the case of Co(ii). Studies in a range of cancer and healthy cell lines indicate high activity and selectivity, and substantial differences between enantiomers. The oxidation state has little effect, and correspondingly, Co(iii) compounds are reduced to Co(ii) e.g. by glutathione. In HCT116 colon cancer cells the Λ enantiomer induces dose-dependent G2-M arrest in the cell cycle and disrupts microtubule architectures. This Co(ii) Λ enantiomer is ca. five times more potent than the isostructural Fe(ii) compound. Since the measured cellular uptakes are similar this implies a higher affinity of the Co system for the intracellular target(s); while the two systems are isostructural they have substantially different charge distributions as shown by calculated hydrophobicity maps. In contrast to the Λ enantiomer, Δ-Co(ii) induces G1 arrest in HCT116 cells, efficiently inhibits the topoisomerase I-catalyzed relaxation of supercoiled plasmid DNA, and, unlike the isostructural Fe(ii) system, causes DNA damage. It thus seems very likely that redox chemistry plays a role in the latter.

Suppression of astrocyte BMP signaling improves fragile X syndrome molecular signatures and functional deficits.

Fragile X syndrome (FXS) is a monogenic neurodevelopmental disorder with manifestations spanning molecular, neuroanatomical, and behavioral changes. Astrocytes contribute to FXS pathogenesis and show hundreds of dysregulated genes and proteins; targeting upstream pathways mediating astrocyte changes in FXS could therefore be a point of intervention. To address this, we focused on the bone morphogenetic protein (BMP) pathway, which is upregulated in FXS astrocytes. We generated a conditional KO (cKO) of Smad4 in astrocytes to suppress BMP signaling, and found this lessens audiogenic seizure severity in FXS mice. To ask how this occurs on a molecular level, we performed in vivo transcriptomic and proteomic profiling of cortical astrocytes, finding upregulation of metabolic pathways, and downregulation of secretory machinery and secreted proteins in FXS astrocytes, with these alterations no longer present when BMP signaling is suppressed. Functionally, astrocyte Smad4 cKO restores deficits in inhibitory synapses present in FXS auditory cortex. Thus, astrocytes contribute to FXS molecular and functional phenotypes, and targeting astrocytes can mitigate FXS symptoms.

The "what, why, and how?" of story completion in health services research: a scoping review.

BACKGROUND: The story completion method provides a different way of doing qualitative research. We note the emergent popularity of this method in health-related research, while much remains to be negotiated in terms of best practices for such studies. This scoping review aims to provide a synthesis on how researchers have used the story completion method in health services research. We offer implications for research and practice for further discussion by the scholarly community. METHODS: We used the JBI methodology for scoping reviews. Six databases were searched for published literature till March 1, 2023: Medline, Embase, CINAHL, PsycINFO, SAGE Journals Online databases, and SAGE Research Methods. We included primary studies of any study design using the story completion method in health services research. RESULTS: A total of 17 studies were included. Findings suggest that the story completion method is useful for research on sensitive topics, and affords the use of comparative study designs and large sample sizes which may be difficult with conventional qualitative research methods. More than 80% of included studies used story completion as the sole method. However, the data collected from this method were limited in terms of the inferences that can be drawn; and richness of participant responses may vary widely. Less than 30% of included studies reported piloting of the story stems. Most studies were conducted online and analyzed qualitatively, though the story stem design and sample size varied widely. CONCLUSION: The story completion method, with its attendant affordances for larger sample sizes, comparative study designs, and streamlined data collection is an innovative and useful stand-alone or adjunct qualitative method for health services research.

Effects of outdoor recreational physical challenges on general self-efficacy: A randomized controlled trial.

Outdoor programs involving recreational physical challenges are becoming increasingly popular for training and development purposes among adults, but rigorous studies investigating their effectiveness remain scarce. A randomized controlled trial was conducted to evaluate the effects of an outdoor adventure-based program on measures of self-efficacy, resilience, risk-taking propensity, and perceived stress. Participants were randomly assigned either to an intervention condition (half-day high ropes course) or a wait-list control group. Measures were taken at baseline and four days post-intervention and on the day to measure intervention perceptions. Significant increases in self-efficacy and risk-taking propensity were observed for the intervention arm compared to the control arm. Greater intervention engagement and affective valence ratings were associated with self-efficacy change. These findings highlight the practical relevance of adventure-based experiences for organizations and educational institutions seeking to enhance young adults' self-confidence. Additionally, they emphasize the importance of tailoring interventions to individual needs and ensuring positive participant experiences to achieve desired outcomes.

Next-generation risk assessment read-across case study: application of a 10-step framework to derive a safe concentration of daidzein in a body lotion.

Introduction: We performed an exposure-based Next Generation Risk Assessment case read-across study using New Approach Methodologies (NAMs) to determine the highest safe concentration of daidzein in a body lotion, based on its similarities with its structural analogue, genistein. Two assumptions were: (1) daidzein is a new chemical and its dietary intake omitted; (2) only in vitro data were used for daidzein, while in vitro and legacy in vivo data for genistein were considered. Methods: The 10-step tiered approach evaluating systemic toxicity included toxicokinetics NAMs: PBPK models and in vitro biokinetics measurements in cells used for toxicogenomics and toxicodynamic NAMs: pharmacology profiling (i.e., interaction with molecular targets), toxicogenomics and EATS assays (endocrine disruption endpoints). Whole body rat and human PBPK models were used to convert external doses of genistein to plasma concentrations and in vitro Points of Departure (PoD) to external doses. The PBPK human dermal module was refined using in vitro human skin metabolism and penetration data. Results: The most relevant endpoint for daidzein was from the ERα assay (Lowest Observed Effective Concentration was 100 ± 0.0 nM), which was converted to an in vitro PoD of 33 nM. After application of a safety factor of 3.3 for intra-individual variability, the safe concentration of daidzein was estimated to be 10 nM. This was extrapolated to an external dose of 0.5 µg/cm2 for a body lotion and face cream, equating to a concentration of 0.1%. Discussion: When in vitro PoD of 33 nM for daidzein was converted to an external oral dose in rats, the value correlated with the in vivo NOAEL. This increased confidence that the rat oral PBPK model provided accurate estimates of internal and external exposure and that the in vitro PoD was relevant in the safety assessment of both chemicals. When plasma concentrations estimated from applications of 0.1% and 0.02% daidzein were used to calculate bioactivity exposure ratios, values were >1, indicating a good margin between exposure and concentrations causing adverse effects. In conclusion, this case study highlights the use of NAMs in a 10-step tiered workflow to conclude that the highest safe concentration of daidzein in a body lotion is 0.1%.

Correction: Development of the Bristol Rabbit Pain Scale (BRPS): A multidimensional composite pain scale specific to rabbits (Oryctolagus cuniculus).

[This corrects the article DOI: 10.1371/journal.pone.0252417.].

Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses.

Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.

Development of mental health first aid guidelines for psychosis for Brazil: A Delphi expert consensus study.

Psychotic symptoms can be highly debilitating for those experiencing them. Community members, including family and friends, can play a crucial role in providing support to a person during the early stages of psychosis, provided they have the necessary resources. Mental health first aid guidelines for psychosis have been developed for high-income countries and this study aimed to adapt those guidelines for Brazil. A Delphi expert consensus method was used to gather the views and opinions of 28 health professionals and 24 individuals with lived experience of psychosis in Brazil over two survey rounds. Firstly, 403 statements were translated from English to Brazilian-Portuguese. In the Round 1 survey, participants were asked to rate each statement based on how important they believed it was for it to be included in the Brazilian guidelines. They were also asked to suggest new actions if they wished. Consensus was reached on 257 statements. Eight new statements were created and endorsed from panelists' comments, and a further 45 statements were unique to the Brazilian guidelines. There was a modest level of similarity between the English-language and Brazilian guidelines. However, the Brazilian guidelines had a greater focus on the importance of family support for people with psychosis and stigma as a possible barrier for openly discussing help-seeking actions for mental health problems in Brazil.

Identifying patients at risk for depression after radical cystectomy.

INTRODUCTION: We aimed to assess rates of depression in patients with bladder cancer undergoing radical cystectomy and identify its predictors. METHODS: Depressive symptoms in 42 consecutive patients were evaluated using the Beck's Depression Inventory (BDI) on the day prior to surgery, postoperative day (POD) 6, six weeks after surgery, and 12-18 months postoperatively. RESULTS: Fifteen patients (36%) presented with BDI scores ≥10 before the operation; this rate increased to 64% on POD 6 and 69% at six weeks post-surgery. Depression score rose from a preoperative median of seven to 11 on POD 6 (p=0.003) and to 15 at six weeks after surgery (p=0.001). Patients who arrived with a BDI score of <10 had a higher increase in the BDI at six weeks compared to patients with depressive symptoms prior to surgery (average increase of 9.8 vs. 0.8, p<0.01). Age, gender, type of diversion, and complications were not associated with depression at presentation or progression of depression. Patients who did not receive neoadjuvant chemotherapy tended to be at increased risk for depression progression (57.1% vs. 14.3%, p=0.093). Twenty-four patients completed a fourth questionnaire 12-18 months postoperatively. The median BDI score was eight; three patients with disease recurrence had a higher increase in the BDI score (average 12.7 vs. -5.2, p<0.01). CONCLUSIONS: Depression among patients facing cystectomy is high, and postoperative progression is substantial. Patients without depressive symptoms preoperatively are at increased risk of developing postoperative depression. After 12-18 months, the most influential risk factor for depression is recurrence. These findings highlight the need to consider interventions in selected patients.