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  • Caretta, Martina Angela, et al. (author)
  • Water
  • 2022
  • In: Climate Change 2022: Impacts, Adaptation and Vulnerability : Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change - Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change.
  • Book chapter (other academic/artistic)
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3.
  • Suliman, S., et al. (author)
  • Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
  • 2016
  • In: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 95, s. 11-21
  • Journal article (peer-reviewed)abstract
    • This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOKLuc) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOKLuc previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOKLuc + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOKLuc both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOKLuc + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOKLuc, while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
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  • Butterfield, B. J., et al. (author)
  • Alpine cushion plants inhibit the loss of phylogenetic diversity in severe environments
  • 2013
  • In: Ecology Letters. - : Wiley. - 1461-0248 .- 1461-023X. ; 16:4, s. 478-486
  • Journal article (peer-reviewed)abstract
    • Biotic interactions can shape phylogenetic community structure (PCS). However, we do not know how the asymmetric effects of foundation species on communities extend to effects on PCS. We assessed PCS of alpine plant communities around the world, both within cushion plant foundation species and adjacent open ground, and compared the effects of foundation species and climate on alpha (within-microsite), beta (between open and cushion) and gamma (open and cushion combined) PCS. In the open, alpha PCS shifted from highly related to distantly related with increasing potential productivity. However, we found no relationship between gamma PCS and climate, due to divergence in phylogenetic composition between cushion and open sub-communities in severe environments, as demonstrated by increasing phylo-beta diversity. Thus, foundation species functioned as micro-refugia by facilitating less stress-tolerant lineages in severe environments, erasing a global productivity – phylogenetic diversity relationship that would go undetected without accounting for this important biotic interaction.
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  • Cavieres, Lohengrin A., et al. (author)
  • Facilitative plant interactions and climate simultaneously drive alpine plant diversity
  • 2014
  • In: Ecology Letters. - : Wiley. - 1461-0248 .- 1461-023X. ; 17:2, s. 193-202
  • Journal article (peer-reviewed)abstract
    • Interactions among species determine local-scale diversity, but local interactions are thought to have minor effects at larger scales. However, quantitative comparisons of the importance of biotic interactions relative to other drivers are rarely made at larger scales. Using a data set spanning 78 sites and five continents, we assessed the relative importance of biotic interactions and climate in determining plant diversity in alpine ecosystems dominated by nurse-plant cushion species. Climate variables related with water balance showed the highest correlation with richness at the global scale. Strikingly, although the effect of cushion species on diversity was lower than that of climate, its contribution was still substantial. In particular, cushion species enhanced species richness more in systems with inherently impoverished local diversity. Nurse species appear to act as a ‘safety net’ sustaining diversity under harsh conditions, demonstrating that climate and species interactions should be integrated when predicting future biodiversity effects of climate change.
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  • Holtedahl, Knut, et al. (author)
  • Abdominal symptoms and cancer in the Abdomen : Prospective cohort study in European primary care
  • 2018
  • In: British Journal of General Practice. - : ROYAL COLL GENERAL PRACTITIONERS. - 0960-1643 .- 1478-5242. ; 68:670, s. 301-310
  • Research review (peer-reviewed)abstract
    • Background: Different abdominal symptoms may signal cancer, but their role is unclear. Aim: To examine associations between abdominal symptoms and subsequent cancer diagnosed in the abdominal region. Design and setting: Prospective cohort study comprising 493 GPs from surgeries in Norway, Denmark, Sweden, Scotland, Belgium, and the Netherlands. Method: Over a 10-day period, the GPs recorded consecutive consultations and noted: patients who presented with abdominal symptoms pre-specified on the registration form; additional data on non-specific symptoms; and features of the consultation. Eight months later, data on all cancer diagnoses among all study patients in the participating general practices were requested from the GPs. Results: Consultations with 61 802 patients were recorded and abdominal symptoms were documented in 6264 (10.1%) patients. Malignancy, both abdominal and non-abdominal, was subsequently diagnosed in 511 patients (0.8%). Among patients with a new cancer in the abdomen (n = 251), 175 (69.7%) were diagnosed within 180 days after consultation. In a multivariate model, the highest sex- and age-adjusted hazard ratio (HR) was for the single symptom of rectal bleeding (HR 19.1, 95% confidence interval = 8.7 to 41.7). Positive predictive values of >3% were found for macroscopic haematuria, rectal bleeding, and involuntary weight loss, with variations according to age and sex. The three symptoms relating to irregular bleeding had particularly high specificity in terms of colorectal, uterine, and bladder cancer. Conclusions: A patient with undiagnosed cancer may present with symptoms or no symptoms. Irregular bleeding must always be explained. Abdominal pain occurs with all types of abdominal cancer and several symptoms may signal colorectal cancer. The findings are important as they influence how GPs think and act, and how they can contribute to an earlier diagnosis of cancer.
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  • Holtedahl, K., et al. (author)
  • Abdominal symptoms in general practice: Frequency, cancer suspicions raised, and actions taken by GPs in six European countries. Cohort study with prospective registration of cancer
  • 2017
  • In: Heliyon. - : Elsevier BV. - 2405-8440. ; 3:6
  • Journal article (peer-reviewed)abstract
    • Background Abdominal symptoms are diagnostically challenging to general practitioners (GPs): although common, they may indicate cancer. In a prospective cohort of patients, we examined abdominal symptom frequency, initial diagnostic suspicion, and actions of GPs in response to abdominal symptoms. Methods Over a 10-day period, 493 GPs in Norway, Denmark, Sweden, Belgium, the Netherlands, and Scotland, recorded consecutive consultations: sex, date of birth and any specified abdominal symptoms. For patients with abdominal symptoms, additional data on non-specific symptoms, GPs’ diagnostic suspicion, and features of the consultation were noted. Data on all cancer diagnoses among all included patients were requested from the GPs eight months later. Findings Consultations with 61802 patients were recorded. Abdominal symptoms were recorded in 6264 (10.1%) patients. A subsequent malignancy was reported in 511 patients (0.8%): 441 (86.3%) had a new cancer, 70 (13.7%) a recurrent cancer. Abdominal symptoms were noted in 129 (25.2%) of cancer patients (P < 0.001), rising to 34.5% for the 89 patients with cancer located in the abdominal region. PPV for any cancer given any abdominal symptom was 2.1%. In symptomatic patients diagnosed with cancer, GPs noted a suspicion of cancer for 85 (65.9%) versus 1895 (30.9%) when there was no subsequent cancer (P < 0.001). No suspicion was noted in 32 (24.8%) cancer patients. The GP's intuitive cancer suspicion was independently associated with a subsequent new cancer diagnosis (OR 2.11, 95% CI 1.15–3.89). Laboratory tests were ordered for 45.4% of symptomatic patients, imaging for 10.4%, referral or hospitalization for 20.0%: all were more frequent in subsequent cancer patients (P < 0.001). Interpretation Abdominal symptoms pointed to abdominal cancers rather than to other cancers. However, the finding of abdominal symptoms in only one third of patients with an abdominal cancer, and the lack of cancer suspicion in a quarter of symptomatic cancer patients, provide challenges for GPs’ diagnostic thinking and referral practices. © 2017 The Authors
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12.
  • Holtedahl, K., et al. (author)
  • Symptoms and signs of colorectal cancer, with differences between proximal and distal colon cancer: a prospective cohort study of diagnostic accuracy in primary care
  • 2021
  • In: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 22:1
  • Journal article (peer-reviewed)abstract
    • Background: In an abdominal symptom study in primary care in six European countries, 511 cases of cancer were recorded prospectively among 61,802 patients 16years and older in Norway, Denmark, Sweden, Netherlands, Belgium and Scotland. Colorectal cancer is one of the main types of cancer associated with abdominal symptoms; hence, an in-depth subgroup analysis of the 94 colorectal cancers was carried out in order to study variation in symptom presentation among cancers in different anatomical locations. Method: Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. Follow-up data were provided by the GP after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. Fisher’s exact test was used to analyse differences between groups. Results: Almost all symptoms recorded could indicate colorectal cancer. ‘Rectal bleeding’ had a specificity of 99.4% and a PPV of 4.0%. Faecal occult blood in stool (FOBT) or anaemia may indicate gastrointestinal bleeding: when these symptoms and signs were combined, sensitivity reached 57.5%, with 69.2% for cancer in the distal colon. For proximal colon cancers, none of 18 patients had ‘Rectal bleeding’ at the initial consultation, but three of the 18 did so at a later consultation. ‘Abdominal pain, lower part’, ‘Constipation’ and ‘Distended abdomen, bloating’ were less specific and also less sensitive than ‘Rectal bleeding’, and with PPV between 0.7% and 1.9%. Conclusions: Apart from rectal bleeding, single symptoms did not reach the PPV 3% NICE threshold. However, supplementary information such as a positive FOBT or persistent symptoms may revise the PPV upwards. If a colorectal cancer is suspected by the GP despite few symptoms, the total clinical picture may still reach the NICE PPV threshold of 3% and justify a specific referral. © 2021, The Author(s).
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  • Holtedahl, Knut, et al. (author)
  • Symptoms and signs of urogenital cancer in primary care
  • 2023
  • In: BMC primary care. - : BMC. - 2731-4553. ; 24:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Urogenital cancers are common, accounting for approximately 20% of cancer incidence globally. Cancers belonging to the same organ system often present with similar symptoms, making initial management challenging. In this study, 511 cases of cancer were recorded after the date of consultation among 61,802 randomly selected patients presenting in primary care in six European countries: a subgroup analysis of urogenital cancers was carried out in order to study variation in symptom presentation. METHODS: Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. The general practitioner (GP) provided follow-up data after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. RESULTS: The most common symptoms were mainly associated with one or two specific types of cancer: 'Macroscopic haematuria' with bladder or renal cancer (combined sensitivity 28.3%), 'Increased urinary frequency' with bladder (sensitivity 13.3%) or prostatic (sensitivity 32.1%) cancer, or to uterine body (sensitivity 14.3%) cancer, 'Unexpected genital bleeding' with uterine cancer (cervix, sensitivity 20.0%, uterine body, sensitivity 71.4%). 'Distended abdomen, bloating' had sensitivity 62.5% (based on eight cases of ovarian cancer). In ovarian cancer, increased abdominal circumference and a palpable tumour also were important diagnostic elements. Specificity for 'Macroscopic haematuria' was 99.8% (99.7-99.8). PPV>3% was noted for 'Macroscopic haematuria' and bladder or renal cancer combined, for bladder cancer in male patients. In males aged 55-74, PPV=7.1% for 'Macroscopic haematuria' and bladder cancer. Abdominal pain was an infrequent symptom in urogenital cancers. CONCLUSIONS: Most types of urogenital cancer present with rather specific symptoms. If the GP considers ovarian cancer, increased abdominal circumference should be actively determined. Several cases were clarified through the GP's clinical examination, or laboratory investigations.
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  • Kikvidze, Zaal, et al. (author)
  • The effects of foundation species on community assembly: a global study on alpine cushion plant communities
  • 2015
  • In: Ecology. - : Ecological Society of America. - 0012-9658. ; 96:8, s. 2064-2069
  • Journal article (peer-reviewed)abstract
    • Foundation species can change plant community structure by modulating important ecological processes such as community assembly, yet this topic is poorly understood. In alpine systems, cushion plants commonly act as foundation species by ameliorating local conditions. Here, we analyze diversity patterns of species' assembly within cushions and in adjacent surrounding open substrates (83 sites across five continents) calculating floristic dissimilarity between replicate plots, and using linear models to analyze relationships between microhabitats and species diversity. Floristic dissimilarity did not change across biogeographic regions, but was consistently lower in the cushions than in the open microhabitat. Cushion plants appear to enable recruitment of many relatively stress-intolerant species that otherwise would not establish in these communities, yet the niche space constructed by cushion plants supports a more homogeneous composition of species than the niche space beyond the cushion's influence. As a result, cushion plants support higher α-diversity and a larger species pool, but harbor assemblies with lower ?-diversity than open microhabitats. We conclude that habitats with and without dominant foundation species can strongly differ in the processes that drive species recruitment, and thus the relationship between local and regional species diversity.
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  • Rush, Jeffrey S., et al. (author)
  • PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides
  • 2021
  • Other publication (other academic/artistic)abstract
    • The cell wall of the human bacterial pathogen Group A Streptococcus (GAS) consists of peptidoglycan decorated with the Lancefield group A carbohydrate (GAC). GAC is a promising target for the development of GAS vaccines. In this study, employing chemical, compositional, and NMR methods, we show that GAC is attached to peptidoglycan via glucosamine 1-phosphate. This structural feature makes the GAC-peptidoglycan linkage highly sensitive to cleavage by nitrous acid and resistant to mild acid conditions. Using this characteristic of the GAS cell wall, we identify PplD as a protein required for deacetylation of linkage N-acetylglucosamine (GlcNAc). X-ray structural analysis indicates that PplD performs catalysis via a modified acid/base mechanism. Genetic surveys in silico together with functional analysis indicate that PplD homologs deacetylate the polysaccharide linkage in many streptococcal species. We further demonstrate that introduction of positive charges to the cell wall by GlcNAc deacetylation protects GAS against host cationic antimicrobial proteins.
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journal article (16)
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peer-reviewed (17)
other academic/artistic (3)
Author/Editor
Parajuli, R (8)
Weiderpass, E (5)
Bjerkaas, E (5)
Gram, IT (5)
Månsson, Jörgen, 195 ... (4)
Parajuli, A (4)
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Weller, David (2)
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Le Marchand, L (2)
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Ridenour, Wendy M. (2)
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