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Sökning: WFRF:(Goodwin P)

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44.
  • Rubinstein, Yaffa R., et al. (författare)
  • The case for open science : rare diseases
  • 2020
  • Ingår i: JAMIA Open. - : Oxford University Press (OUP). - 2574-2531. ; 3:3, s. 472-486
  • Forskningsöversikt (refereegranskat)abstract
    • The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally.
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45.
  • Sandberg Wollheim, Magnhild, et al. (författare)
  • Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis.
  • 2005
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 65:6, s. 802-806
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although patients with multiple sclerosis (MS) are advised to stop interferon (IFN) beta-1a therapy before becoming pregnant, some patients become pregnant while on treatment. Methods: We examined individual patient data from eight clinical trials with IFN beta-1a. Results: Of 3,361 women in the studies, 69 pregnancies were reported, of which 41 were patients receiving (or who had stopped receiving within 2 weeks prior to conception) IFN beta-1a (in utero exposure group), 22 were patients who discontinued IFN beta-1a treatment more than 2 weeks before conception (previous exposure group), and six were patients receiving placebo. The 41 in utero exposure pregnancies resulted in 20 healthy full-term infants, one healthy premature infant, nine induced abortions, eight spontaneous abortions, one fetal death, and one congenital anomaly (hydrocephalus). One patient was lost to follow-up. The 22 previous exposure pregnancies resulted in 20 full-term healthy infants, one healthy premature infant, and one birth-related congenital anomaly (Erb palsy) Conclusions: The majority (21/31) of pregnancies that had the potential to go to full term produced healthy infants. The rate of spontaneous abortion was higher, but not significantly so, in the in utero exposure group compared to general population estimates. Until more exposure data become available, patients remain advised to stop IFN beta therapy before becoming pregnant.
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46.
  • Strittmatter, Nicole, et al. (författare)
  • Method To Visualize the Intratumor Distribution and Impact of Gemcitabine in Pancreatic Ductal Adenocarcinoma by Multimodal Imaging
  • 2022
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:3, s. 1795-1803
  • Tidskriftsartikel (refereegranskat)abstract
    • Gemcitabine (dFdC) is a common treatment for pancreatic cancer; however, it is thought that treatment may fail because tumor stroma prevents drug distribution to tumor cells. Gemcitabine is a pro-drug with active metabolites generated intracellularly; therefore, visualizing the distribution of parent drug as well as its metabolites is important. A multimodal imaging approach was developed using spatially coregistered mass spectrometry imaging (MSI), imaging mass cytometry (IMC), multiplex immunofluorescence microscopy (mIF), and hematoxylin and eosin (H&E) staining to assess the local distribution and metabolism of gemcitabine in tumors from a genetically engineered mouse model of pancreatic cancer (KPC) allowing for comparisons between effects in the tumor tissue and its microenvironment. Mass spectrometry imaging (MSI) enabled the visualization of the distribution of gemcitabine (100 mg/kg), its phosphorylated metabolites dFdCMP, dFdCDP and dFdCTP, and the inactive metabolite dFdU. Distribution was compared to small-molecule ATR inhibitor AZD6738 (25 mg/kg), which was codosed. Gemcitabine metabolites showed heterogeneous distribution within the tumor, which was different from the parent compound. The highest abundance of dFdCMP, dFdCDP, and dFdCTP correlated with distribution of endogenous AMP, ADP, and ATP in viable tumor cell regions, showing that gemcitabine active metabolites are reaching the tumor cell compartment, while AZD6738 was located to nonviable tumor regions. The method revealed that the generation of active, phosphorylated dFdC metabolites as well as treatment-induced DNA damage primarily correlated with sites of high proliferation in KPC PDAC tumor tissue, rather than sites of high parent drug abundance.
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47.
  • Tjin, Anna, et al. (författare)
  • Role strain and COVID-era burden among South Asian caregivers of individuals with brain health conditions and disabilities
  • 2022
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:S8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The COVID-19 pandemic has renewed attention to the conflicting demands placed on caregivers worldwide. Nowhere is this more evident than in South Asia, where cultural norms and a scarcity of long-term care facilities have made the home the locus of caregiving for individuals with brain health conditions and disabilities. A hidden cost of this informal arrangement is the burden experienced by the primary caregiver. This may be exacerbated when traditional caregiving expectations clash with personal aspirations outside the family. Method: The COVID-19 pandemic has renewed attention to the conflicting demands placed on caregivers worldwide. Nowhere is this more evident than in South Asia, where cultural norms and a scarcity of long-term care facilities have made the home the locus of caregiving for individuals with brain health conditions and disabilities. A hidden cost of this informal arrangement is the burden experienced by the primary caregiver. This may be exacerbated when traditional caregiving expectations clash with personal aspirations outside the family. Result: The COVID-19 pandemic has renewed attention to the conflicting demands placed on caregivers worldwide. Nowhere is this more evident than in South Asia, where cultural norms and a scarcity of long-term care facilities have made the home the locus of caregiving for individuals with brain health conditions and disabilities. A hidden cost of this informal arrangement is the burden experienced by the primary caregiver. This may be exacerbated when traditional caregiving expectations clash with personal aspirations outside the family. Conclusion: Role strain may be a significant driver of burden when the caretaker’s educational and professional potential collide with traditional South Asian family obligations. The burden reported by our respondents suggests that role strain may elevate stress among young, educated caregivers. Our results, therefore, provide indirect evidence concerning the changing economic and socio-cultural context of caregiving in South Asian households.
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48.
  • Wadt, K. A. W., et al. (författare)
  • A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma
  • 2015
  • Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 88:3, s. 267-272
  • Tidskriftsartikel (refereegranskat)abstract
    • We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.
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