| 1. |
- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 2. |
- Cornelissen, Johannes H C, et al.
(författare)
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Global negative vegetation feedback to climate warming responses of leaf litter decomposition rates in cold biomes
- 2007
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 10:7, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- Whether climate change will turn cold biomes from large long-term carbon sinks into sources is hotly debated because of the great potential for ecosystem-mediated feedbacks to global climate. Critical are the direction, magnitude and generality of climate responses of plant litter decomposition. Here, we present the first quantitative analysis of the major climate-change-related drivers of litter decomposition rates in cold northern biomes worldwide.Leaf litters collected from the predominant species in 33 global change manipulation experiments in circum-arctic-alpine ecosystems were incubated simultaneously in two contrasting arctic life zones. We demonstrate that longer-term, large-scale changes to leaf litter decomposition will be driven primarily by both direct warming effects and concomitant shifts in plant growth form composition, with a much smaller role for changes in litter quality within species. Specifically, the ongoing warming-induced expansion of shrubs with recalcitrant leaf litter across cold biomes would constitute a negative feedback to global warming. Depending on the strength of other (previously reported) positive feedbacks of shrub expansion on soil carbon turnover, this may partly counteract direct warming enhancement of litter decomposition.
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| 3. |
- Noresson, A. L., et al.
(författare)
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Designing interactions by control of protein-ligand complex conformation : Tuning arginine-arene interaction geometry for enhanced electrostatic protein-ligand interactions
- 2018
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 9:4, s. 1014-1021
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Tidskriftsartikel (refereegranskat)abstract
- We investigated galectin-3 binding to 3-benzamido-2-O-sulfo-galactoside and -thiodigalactoside ligands using a combination of site-specific mutagenesis, X-ray crystallography, computational approaches, and binding thermodynamics measurements. The results reveal a conformational variability in a surface-exposed arginine (R144) side chain in response to different aromatic C3-substituents of bound galactoside-based ligands. Fluorinated C3-benzamido substituents induced a shift in the side-chain conformation of R144 to allow for an entropically favored electrostatic interaction between its guanidine group and the 2-O-sulfate of the ligand. By contrast, binding of ligands with non-fluorinated substituents did not trigger a conformational change of R144. Hence, a sulfate-arginine electrostatic interaction can be tuned by the choice of ligand C3-benzamido structures to favor specific interaction modes and geometries. These results have important general implications for ligand design, as the proper choice of arginine-aromatic interacting partners opens up for ligand-controlled protein conformation that in turn may be systematically exploited in ligand design.
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| 4. |
- Ottoson, Jakob, et al.
(författare)
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Removal of viruses, parasitic protozoa microbial indicators and correlation with process indicators in conventional and membrane processes in a wastewater pilot plant
- 2006
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 40:7, s. 1449-1457
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate variations in the occurrence and removal of enterovirus and norovirus genomes, Giardia cysts, Cryptosporidium oocysts and the most commonly used faecal indicators in a Swedish wastewater pilot plant. Paired samples were taken from the inlet and outlet of each treatment line: tertiary filtration, membrane bioreactor (MBR) and upflow anaerobic sludge blankets (UASB). (Oo)cysts and indicators were enumerated using standard methods and viruses using RT-PCR. Giardia cysts and enteroviruses were constantly detected, mean numbers 10(3.11) cysts and 10(4.0) PCR units L-1, respectively. Oocysts were found in 5/19 samples, mean number 5 L-1. Noroviruses were found in 6/7 influent samples, with an average titre of 10(3 28) L-1, during winter, but only in 2/15 in the rest of the year (mean 200 L-1). MBR treatment removed indicators more efficiently than did the other two lines, with 5 log removal of E. coli. Human virus genome removal did not differ between the MBR and tertiary treatment line. Microorganism removal in UASB was significantly lower for all the organisms studied. E. coli, enterococci and Cl. perfringens removal was correlated (p < 0.05) with enterovirus genome removal, with R-values around 0.4. However, values for removal of indicators were more strongly correlated to each other. Removal of viruses based on enumeration using RT-PCR probably underestimates infectious virion removal.
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| 5. |
- Owings, T. M., et al.
(författare)
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Plantar pressures in diabetic patients with foot ulcers which have remained healed
- 2009
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Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 26:11, s. 1141-1146
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Tidskriftsartikel (refereegranskat)abstract
- Aims The recurrence of foot ulcers is a significant problem in people with diabetic neuropathy. The purpose of this study was to measure in-shoe plantar pressures and other characteristics in a group of neuropathic patients with diabetes who had prior foot ulcers which had remained healed. Methods This was an epidemiological cohort study of patients from diabetes clinics of two Swedish hospitals. From a database of 2625 eligible patients, 190 surviving patients with prior plantar ulcers of the forefoot (hallux or metatarsal heads) caused by repetitive stress were identified and 49 patients agreed to participate. Barefoot and in-shoe plantar pressures were measured during walking. Data on foot deformity, activity profiles and self-reported behaviour were also collected. Results Mean barefoot plantar peak pressure at the prior ulcer site (556 kPa) was lower than in other published series, although the range was large (107-1192 kPa). Mean in-shoe peak pressure at this location averaged 207 kPa when measured with an insole sensor. Barefoot peak pressure only predicted similar to 35% of the variance of in-shoe peak pressure, indicating variation in the efficacy of the individual footwear prescriptions (primarily extra-depth shoes with custom insoles). Conclusions We propose that the mean value for in-shoe pressures reported in these patients be used as a target in footwear prescription for patients with prior ulcers. Although plantar pressure is only one factor in a multifaceted strategy to prevent ulcer recurrence, the quantitative focus on pressure reduction in footwear is likely to have beneficial effects.
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| 6. |
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| 7. |
- Weijers-Dall, T D M, et al.
(författare)
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Measurements of the stopping forces for heavy ions in Ge, Ag and Au using novel 'polka-dot' detectors
- 2006
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 251:2, s. 352-360
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of the stopping forces for C-14, N-14 and O-16 ions in Ge and Au, for N-14 and F-19 ions in Ag, as well as for F-19 ions in Au have been made, respectively. A novel technique, reported recently, using PIN diodes coated directly with the stopping medium in a polka dot pattern was used. This provided a set of precise, self-consistent measurements on the same stopping medium. Results show small but significant deviations from SRIM stopping predictions and are also compared to a recently-developed empirical stopping force predictor.
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| 8. |
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| 9. |
- Hashimoto, A, et al.
(författare)
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Simulation of Convective Drying of Wet Porous Materials
- 2003
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Ingår i: Drying Technology. - 1532-2300. ; 21:8, s. 1411-1431
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Tidskriftsartikel (refereegranskat)abstract
- A simulation model for convective drying of wet porous materials was developed. For the simulation, we measured the moisture diffusivities within them and applied a modified Dubinin-Astakhov equation to the moisture sorption data for a membrane filter. The simulation results not accounting for internal mass transfer resistance were quite different from the experimental ones. The drying characteristics calculated by a shrinking core model with effective moisture diffusivity represented a much lower drying rate and much higher temperatures, respectively, than the experimental ones. This meant that we must consider the plural moisture transport mechanisms within the samples. Therefore, we calculated the drying rate and temperatures with an apparent overall mass transfer coefficient damping with a decrease in the moisture content. The results accounting for the hygroscopic effects broadly agreed with the experimental ones by the evaluation.
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| 10. |
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| 11. |
- Persson, Frank, 1970, et al.
(författare)
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Characterisation of the behaviour of particles in biofilters for pre-treatment of drinking water
- 2005
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 39:16, s. 3791-3800
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Tidskriftsartikel (refereegranskat)abstract
- Biofiltration of surface water was examined using granular activated carbon (GAC) and expanded clay (EC). Particle removal was 60-90%, measured by flow cytometry, which enabled discrimination between total- and autofluorescent particles (microalgae) in size ranges of 0.4-1 and 1-15 mu m, and measured by on-line particle counting. Total particles were removed at a higher degree than autofluorescent particles. The biofilters were also challenged with 1 mu m fluorescent microspheres with hydrophobic and hydrophilic surface characteristics and bacteriophages (Salmonella typhimurium 2813). Added microspheres were removed at 97-99% (hydrophobic) and 85-89% (hydrophilic) after 5 hydraulic residence times (HRT) and microspheres retained in the biofilter media were slowly detaching into the filtrate for a long time after the addition. Removal of bacteriophages (5 HRT) was considerably lower at 40-59%, and no long-lasting detachment was observed. A comparison of experimental data with theoretical predictions for removal of particles in clean granular media filters revealed a similar or higher removal of particles around 1 mu m in size than predicted, while bacteriophages were removed at a similar or lesser extent than predicted. The results highlight the selectivity and dynamic behaviour of the particle removal processes and have implications for operation and microbial risk assessment of a treatment train with biofilters as pre-treatment. (c) 2005 Elsevier Ltd. All rights reserved.
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| 12. |
- Rasmusson, J., et al.
(författare)
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LORA - a new airborne imaging radar sensor
- 2005
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Ingår i: Proc. RVK 05, Radiovetenskap och kommunikation, Linköping, Sweden, June 14-16 2005. ; , s. 531-534
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Rasmusson, J.R., et al.
(författare)
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Bistatic VHF and UHF SAR for urban environments
- 2007
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Ingår i: Proceedings of SPIE -- Volume 6547, Radar Sensor Technology XI, James L. Kurtz, Robert J. Tan, Editors, 654705, May 2, 2007. ; 6547
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Stenström, P, et al.
(författare)
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Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.
- 2020
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Ingår i: BJS open. - 2474-9842. ; 4:5, s. 943-953
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Tidskriftsartikel (refereegranskat)abstract
- Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes.An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken.Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age.Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.
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| 15. |
- Verteramo, Maria Luisa, et al.
(författare)
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Interplay between Conformational Entropy and Solvation Entropy in Protein-Ligand Binding
- 2019
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 141:5, s. 2012-2026
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the driving forces underlying molecular recognition is of fundamental importance in chemistry and biology. The challenge is to unravel the binding thermodynamics into separate contributions and to interpret these in molecular terms. Entropic contributions to the free energy of binding are particularly difficult to assess in this regard. Here we pinpoint the molecular determinants underlying differences in ligand affinity to the carbohydrate recognition domain of galectin-3, using a combination of isothermal titration calorimetry, X-ray crystallography, NMR relaxation, and molecular dynamics simulations followed by conformational entropy and grid inhomogeneous solvation theory (GIST) analyses. Using a pair of diastereomeric ligands that have essentially identical chemical potential in the unbound state, we reduced the problem of dissecting the thermodynamics to a comparison of the two protein-ligand complexes. While the free energies of binding are nearly equal for the R and S diastereomers, greater differences are observed for the enthalpy and entropy, which consequently exhibit compensatory behavior, Δ ΔH°(R - S) = -5 ± 1 kJ/mol and -T Δ ΔS°(R - S) = 3 ± 1 kJ/mol. NMR relaxation experiments and molecular dynamics simulations indicate that the protein in complex with the S-stereoisomer has greater conformational entropy than in the R-complex. GIST calculations reveal additional, but smaller, contributions from solvation entropy, again in favor of the S-complex. Thus, conformational entropy apparently dominates over solvation entropy in dictating the difference in the overall entropy of binding. This case highlights an interplay between conformational entropy and solvation entropy, pointing to both opportunities and challenges in drug design.
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| 16. |
- Westrell, Therese, et al.
(författare)
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QMRA (quantitative microbial risk assessment) and HACCP (hazard analysis critical control points) for management of pathogens in wastewater and sewage sludge treatment and reuse
- 2004
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Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 50:2, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Hazard Analysis and Critical Control Points (HACCP) was applied for identifying and controlling exposure to pathogenic microorganisms encountered during normal sludge and wastewater handling at a 12,500 m3/d treatment plant utilising tertiary wastewater treatment and mesophilic sludge digestion. The hazardous scenarios considered were human exposure during treatment, handling, soil application and crop consumption, and exposure via water at the wetland-area and recreational swimming. A quantitative microbial risk assessment (QMRA), including rotavirus, adenovirus, haemorrhagic E. coli, Salmonella, Giardia and Cryptosporidium, was performed in order to prioritise pathogen hazards for control purposes. Human exposures were treated as individual risks but also related to the endemic situation in the general population. The highest individual health risk from a single exposure was via aerosols for workers at the belt press for sludge dewatering (virus infection risk = 1). The largest impact on the community would arise if children ingested sludge at the unprotected storage site, although in the worst-case situation the largest number of infections would arise through vegetables fertilised with sludge and eaten raw (not allowed in Sweden). Acceptable risk for various hazardous scenarios, treatment and/or reuse strategies could be tested in the model.
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| 17. |
- Zach, D., et al.
(författare)
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Anxiety and depression among women with newly diagnosed vulvar cancer - A nationwide longitudinal study
- 2024
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 103:2, s. 396-406
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Our objective was to investigate the trajectories of anxiety, depression, emotional and social functioning in women with newly diagnosed vulvar cancer from the time of diagnosis to 12 months after treatment. A further aim was to identify risk factors for high levels of anxiety.Material and methods: PROVE (PROspective Vulvar Cancer Evaluation) is a nationwide longitudinal cohort study investigating quality of life in women with newly diagnosed vulvar cancer by the following validated patient-reported outcome measures at diagnosis, and 3 and 12 months after treatment: The Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Vulvar module VU34. Mean scores, changes over time and associations were analyzed by generalized estimated equations and log-linear regression models, adjusted for possible confounders.Results: Between 2019 and 2021, 105 (69%) women completed the questionnaires at all three time points. At diagnosis, 42% of the women reported elevated anxiety levels, decreasing significantly to 30% during the first 12 months. Insomnia, persisting vulvar symptoms and high information needs were significantly associated with a high level of anxiety (relative risk [RR] 2.1, 95% CI 1.2-3.7 for insomnia; RR 2.8, 95% CI 1.7-4.6 for vulvar symptoms, RR 2.7, 95% CI 1.5-4.9 for information needs). We found a trend towards a higher level of anxiety in younger women (<65 years: RR 1.5, 95% CI 1.0-2.5). Participants reported a low and stable prevalence of depression (14%) and high social functioning throughout the study period.Conclusions: Women with newly diagnosed vulvar cancer report a high level of anxiety at diagnosis. Despite a significant improvement, anxiety remains widely prevalent during the first year of follow-up. Targeting insomnia, vulvar symptoms and unmet needs may decrease anxiety during surveillance.
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