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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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- Morad, Sadoon, et al.
(författare)
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Hydrothermal alteration of plagioclase in granitic rocks from Proterozoic basement of SE Sweden
- 2010
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Ingår i: Geological Journal. - : Wiley. - 0072-1050 .- 1099-1034. ; 45:1, s. 105-116
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Tidskriftsartikel (refereegranskat)abstract
- Petrographic examinations and electron microprobe analyses of Proterozoic granitic rocks, SE Sweden aimed to characterize and unravel the mechanisms and conditions of plagioclase alterations. These alterations include saussuritization, albitization and replacement of plagioclase by K-feldspar. The hydrothermal alterations, which are inferred to have occurred at ca. 250-400°C, resulted in concomitant formation of Alrich titanite, epidote, calcite, pumpellyite, prehnite and iron oxides. Replacement of plagioclase by K-feldspar occurs in red-stained zones, which have developed close to thin fractures owing to the precipitation of tiny Fe-oxide pigment particles within the altered plagioclase, whereas saussuritized plagioclase has less systematic spatial relationships to these fractures. Albitization of plagioclase occurred in rocks that are poor in biotite compared to rocks that suffered extensive saussuritization. The chemical and textural characterization of various types of plagioclase alterations allows elucidation of the granitic hydrothermal systems. Features of feldspar alteration in the granitic rocks are similar to those encountered in feldspathic sandstones and should hence be considered in studies on diagenetic changes of siliciclastic successions during basin evolution.
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- Lin, Yen-Hung, et al.
(författare)
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A piperidinium salt stabilizes efficient metal-halide perovskite solar cells
- 2020
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 369:6499, s. 96-
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Tidskriftsartikel (refereegranskat)abstract
- Longevity has been a long-standing concern for hybrid perovskite photovoltaics. We demonstrate high-resilience positive-intrinsic-negative perovskite solar cells by incorporating a piperidinium-based ionic compound into the formamidinium-cesium lead-trihalide perovskite absorber. With the bandgap tuned to be well suited for perovskite-on-silicon tandem cells, this piperidinium additive enhances the open-circuit voltage and cell efficiency. This additive also retards compositional segregation into impurity phases and pinhole formation in the perovskite absorber layer during aggressive aging. Under full-spectrum simulated sunlight in ambient atmosphere, our unencapsulated and encapsulated cells retain 80 and 95% of their peak and post-burn-in efficiencies for 1010 and 1200 hours at 60 degrees and 85 degrees C, respectively. Our analysis reveals detailed degradation routes that contribute to the failure of aged cells.
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- Morad, Sadoon, et al.
(författare)
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Hydrothermal alteration of magmatic titanite : Evidence from Proterozoic granitic rocks, Southeastern Sweden
- 2009
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Ingår i: Canadian Mineralogist. - : Mineralogical Association of Canada. - 0008-4476 .- 1499-1276. ; 47:4, s. 801-811
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Tidskriftsartikel (refereegranskat)abstract
- Magmatic titanite in Proterozoic granitic rocks from southeastern Sweden has been subjected to hydrothermal dissolution and replacement by finely crystalline Fe-dominant chlorite and TiO2 (± quartz ± calcite). These alteration patterns require the redistribution of the highly immobile Ti and At on the thin-section scale. The chloritization of titanite involved the formation of an intermediate Al-Fe-rich phase probably comprising intimately intergrown, submicroscopic chlorite and titanite. The creation of microporosity by the hydrothermal alteration of titanite may enhance the diffusive flux of matter, and hence the rate of reactions in granitic rocks. The alteration of titanite is most pronounced in red-stained granitic rock zones enriched in partly dissolved biotite and magnetite, which could have acted as local source of Al, Fe and Mg needed for chlorite formation.
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- Ramadan, Wafaa S, et al.
(författare)
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Interplay between Epigenetics, Expression of Estrogen Receptor- α, HER2/ERBB2 and Sensitivity of Triple Negative Breast Cancer Cells to Hormonal Therapy
- 2018
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 11:1, s. 13-13
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Tidskriftsartikel (refereegranskat)abstract
- Triple negative breast cancer (TNBC) cells are resistant to hormonal/targeted therapies. This study aims to investigate epigenetic differences between TNBC and other types of breast cancer and the effect of epigenetic modulation on the response of TNBC cells to hormonal therapy. Thus, we investigated (i) the expression of different epigenetic markers, (ii) the effect of epigenetic modifying agents on the expression of ERα and HER2/ERBB2 and (iii) the effect on the response to tamoxifen in four breast cancer cell lines with different hormonal receptor status. Our results revealed a differential expression patterns of epigenetic markers in the four breast cancer cells. In TNBC cells, histone deacetylases (HDAC) 1 and 2 were less expressed, whereas HDACs 4 and 6 were overexpressed. Interestingly, treatment with epigenetic modifiers resulted in (i) a pronounced increase in the expression of ERα and HER2/ERBB2 along with (ii) an increase in the sensitivity of TNBC cells to tamoxifen. Collectively, this study indicates a different epigenetic background for TNBC cells, which represses the expression of ERα and HER2/ERBB2. Furthermore, we provide here the rationale for the use of epigenetic modifiers to enhance the response of TNBC to hormonal therapy through upregulation of ERα.
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- Sarteau, A. C., et al.
(författare)
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Changes to care delivery at nine international pediatric diabetes clinics in response to the COVID-19 global pandemic
- 2021
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 463-468
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Tidskriftsartikel (refereegranskat)abstract
- Background Pediatric diabetes clinics around the world rapidly adapted care in response to COVID-19. We explored provider perceptions of care delivery adaptations and challenges for providers and patients across nine international pediatric diabetes clinics. Methods Providers in a quality improvement collaborative completed a questionnaire about clinic adaptations, including roles, care delivery methods, and provider and patient concerns and challenges. We employed a rapid analysis to identify main themes. Results Providers described adaptations within multiple domains of care delivery, including provider roles and workload, clinical encounter and team meeting format, care delivery platforms, self-management technology education, and patient-provider data sharing. Providers reported concerns about potential negative impacts on patients from COVID-19 and the clinical adaptations it required, including fears related to telemedicine efficacy, blood glucose and insulin pump/pen data sharing, and delayed care-seeking. Particular concern was expressed about already vulnerable patients. Simultaneously, providers reported 'silver linings' of adaptations that they perceived as having potential to inform care and self-management recommendations going forward, including time-saving clinic processes, telemedicine, lifestyle changes compelled by COVID-19, and improvements to family and clinic staff literacy around data sharing. Conclusions Providers across diverse clinical settings reported care delivery adaptations in response to COVID-19-particularly telemedicine processes-created challenges and opportunities to improve care quality and patient health. To develop quality care during COVID-19, providers emphasized the importance of generating evidence about which in-person or telemedicine processes were most beneficial for specific care scenarios, and incorporating the unique care needs of the most vulnerable patients.
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- El-Seedi, Hesham, et al.
(författare)
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A Spotlight on the Egyptian Honeybee (Apis mellifera lamarckii)
- 2022
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Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 12:20
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Forskningsöversikt (refereegranskat)abstract
- Egypt has an ongoing long history with beekeeping, which started with the ancient Egyptians making various reliefs and inscriptions of beekeeping on their tombs and temples. The Egyptian honeybee (Apis mellifera lamarckii) is an authentic Egyptian honeybee subspecies utilized in apiculture. A. m. lamarckii is a distinct honeybee subspecies that has a particular body color, size, and high levels of hygienic behavior. Additionally, it has distinctive characteristics; including the presence of the half-queens, an excessive number of swarm cells, high adaptability to climatic conditions, good resistance to specific bee diseases, including the Varro disorder, and continuous breeding during the whole year despite low productivity, using very little propolis, and tending to abscond readily. This review discusses the history of beekeeping in Egypt and its current situation in addition to its morphology, genetic analysis, and distinctive characters, and the defensive behaviors of native A. m. lamarckii subspecies.
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- El-Wekil, Mohamed M., et al.
(författare)
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An innovative dual recognition aptasensor for specific detection of Staphylococcus aureus based on Au/Fe3O4 binary hybrid
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic bacteria cause disease outbreaks and threaten human health, prompting the research on advanced detection assays. Herein, we developed a selective molecular imprinted aptasensor for sensitive and prompt quantitation of Staphylococcus aureus (S. aureus) bacteria. The aptasensor was constructed by immobilization of aptamer on gold nanoparticles modified magnetic nanoparticles (apt-AuNPs@ Fe3O4). A functional monomer (o-phenylenediamine, o-phen) was electro-polymerized on the surface of the as-synthesized nanocomposite in the presence of a template (S. aureus). After removing S. aureus, the formed imprinted sites were available to extract pathogenic bacteria from complicated matrices. The surface morphology of the as-fabricated nanocomposites was characterized using different spectroscopic and electrochemical methods. Moreover, we thoroughly evaluated factors affecting the synthesis and determination procedures. The molecular imprinted aptasensor exhibited a wide linear range of 10(1)-10(7) CFU mL(-1) with a Limit of Detection, LOD (signal to noise = 3) of 1 CFU mL(-1). The aptasensor detected S. aureus in milk, conduit water, and apple juice samples with good recoveries % and satisfactory relative standard deviations (RSDs %) values.
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22. |
- El-Wekil, Mohamed M., et al.
(författare)
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Enzyme-free and label-free strategy for electrochemical oxaliplatin aptasensing by using rGO/MWCNTs loaded with AuPd nanoparticles as signal probes and electro-catalytic enhancers
- 2020
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Ingår i: Talanta. - : Elsevier BV. - 0039-9140 .- 1873-3573. ; 217
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Tidskriftsartikel (refereegranskat)abstract
- An innovative label free electrochemical aptasensor was developed for the analysis of oxaliplatin (OXAL) for the first time. The DNA oligonucleotide (aptamer) was successfully fabricated, by covalently attaching the amino terminus of the functional DNA on the glassy carbon electrode (GCE) surface modified with reduced graphene oxide (rGO) and multi-walled carbon nanotubes (MWCNTs) loaded with AuPd nanoparticles (AuPd NPs@rGO/MWCNTs/GCE). The stepwise assembly process of aptasensor on AuPd NPs@rGO/MWCNTs/GCE was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The aptamer-OXAL complex formation led to inhibition the electron transfer of Fe(CN)63−/4- on the electrode interface, which was clearly observed by decreasing the peak current of the redox probe. Furthermore, we managed to quantitatively measure OXAL by adding different concentrations of OXAL, while monitoring the decrease of differential pulse voltammogram (DPV) responses of the redox probe. Under the optimized conditions, the electrochemical aptasensor exhibited a linear range of 0.1–170.0 nmol L−1 with LOD of 60.0 pmol L−1. Next, we successfully applied the aptasensor calibrated system to determine OXAL in pharmaceutical injection and human biological samples.
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- Irshaid, N M, et al.
(författare)
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Phenotype prediction by DNA-based typing of clinically significant blood group systems in Jordanian blood donors.
- 2002
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Ingår i: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 83:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: During the past 10 years several DNA-typing methods have been developed to complement routine serological typing for determination of polymorphisms in the ABO, RH, KEL, JK and FY blood group genes. However, the molecular basis of blood groups can differ widely between ethnic groups. The purpose of this study was to evaluate selected DNA-based methods for phenotype prediction in a population not previously investigated. MATERIALS AND METHODS: Blood samples from a random sample of Jordanian blood donors were collected and red cells isolated from these blood samples were phenotyped for common ABO (n = 150) and KEL/FY/JK (n = 90) antigens. RHD-negative and -positive donors were selected for RH typing (n = 120 and 30, respectively). DNA was prepared and blood group genotyping performed according to selected methods in current use. Discordant samples required further investigation by extended serology and DNA sequencing. RESULTS: The degree of concordance between phenotype and genotype was high, but some exceptions were noted. Two of 14 A2/A2B samples lacked all mutations associated with known A2 alleles of the ABO system. RH typing revealed four samples with the c(cyt48) marker, causing false-positive RHC typing. A single D-negative sample was positive for D-specific exon 10 markers. The RHD pseudogene was not found in the 150 donors tested. Nine samples revealed discrepancies that were associated with unknown silent or weakly expressing Fyb-like alleles. CONCLUSIONS: With the exception of the FY system, we conclude that the molecular background of the clinically important blood group antigens studied here is similar to that reported for Caucasoids.
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24. |
- Marinkovic, I., et al.
(författare)
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A basic MRI anatomy of the rat brain in coronal sections for practical guidance to neuroscientists
- 2020
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1747
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Tidskriftsartikel (refereegranskat)abstract
- Identification of the brain structures in the magnetic resonance imaging (MRI) of the rat is very important for the experimental work of many neuroscientists. Our intention was to recognize most of the structures without overlapping the MRI sections with the histological templates. Three live rats were used for this study who were examined in a micro-MRI apparatus by performing T2-weighted sequences in serial brain sections. Most of the white matter structures were easily identified, e.g. the anterior commissure, corpus callosum with forceps minor and major, cingulum, external and internal capsules, fornix, stria medullaris and terminalis, cranial nerves, mammillothalamic tract, fasciculus retroflexus, medial and lateral lemniscus, posterior commissure, commissures of the superior and inferior colliculi, medial longitudinal fasciculus, and the cerebral peduncle. Large and small gray matter structures were recognized as well, for example, the anterior olfactory structures, nucleus accumbens, caudate putamen, claustrum, bed nucleus of the stria terminalis, pituitary gland, globus pallidus, amygdala, some midline and intralaminar thalamic nuclei, certain hypothalamic nuclei, hippocampal formation, pineal body, periaqueductal gray matter, lateral and medial geniculate bodies, superior and inferior colliculi, and cranial nerves nuclei. All in all, of the total 160 recognized brain structures, 77 were identified without using the corresponding histological atlases. We believe that our labeled MRI pictures could be an important way for quick orientation for evaluating the effects of the experimental work regarding the rat brain.
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- Nilsson, Jonas, 1970, et al.
(författare)
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Synthetic standard aided quantification and structural characterization of amyloid-beta glycopeptides enriched from cerebrospinal fluid of Alzheimer's disease patients
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- An early pathological hallmark of Alzheimer's disease (AD) is amyloid-beta (A beta) deposits in the brain, which largely consist of up to 43 amino acids long A beta peptides derived from the amyloid precursor protein (APP). We previously identified a series of sialylated Tyr-10 O-glycosylated A beta peptides, 15-20 residues long, from human cerebrospinal fluid (CSF) and observed a relative increase of those in AD vs non-AD patients. We report here on the synthesis and use of an isotopically double-labeled A beta 1-15 glycopeptide, carrying the core 1Gal beta 3GalNAc alpha 1-O-Tyr-10 structure, to (1) identify by HCD LC-MS/MS the definite glycan core 1 structure of immunopurified and desialylated A beta glycopeptides in human CSF and to (2) establish a LC-MS/MS quantification method for desialylated A beta 1-15 (and A beta-17) glycopeptides and to (3) compare the concentrations of these A beta glycopeptides in CSF from 20 AD patients and 20 healthy controls. Although we unambiguously identified the core 1 structures and Tyr-10 attachment sites of the glycopeptides, we did not observe any quantitative differences, determined through both peptide and oxonium ion fragments, of the desialylated A beta 1-15 or A beta 1-17 glycopeptides between the AD and non-AD group. The new quantitative glycoproteomic approach described, using double-labeled glycopeptide standards, will undoubtedly facilitate future studies of glycopeptides as clinical biomarkers but should also embrace sialylated A beta standards to reveal specific sialylation patterns of individual A beta glycopeptides in AD patients and controls.
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26. |
- Ramadan, Q., et al.
(författare)
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A semi-automated BPMN-based framework for detecting conflicts between security, data-minimization, and fairness requirements
- 2020
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Ingår i: Software and Systems Modeling. - : Springer Science and Business Media LLC. - 1619-1366 .- 1619-1374. ; 19, s. 1191-1227
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Tidskriftsartikel (refereegranskat)abstract
- Requirements are inherently prone to conflicts. Security, data-minimization, and fairness requirements are no exception. Importantly, undetected conflicts between such requirements can lead to severe effects, including privacy infringement and legal sanctions. Detecting conflicts between security, data-minimization, and fairness requirements is a challenging task, as such conflicts are context-specific and their detection requires a thorough understanding of the underlying business processes. For example, a process may require anonymous execution of a task that writes data into a secure data storage, where the identity of the writer is needed for the purpose of accountability. Moreover, conflicts not arise from trade-offs between requirements elicited from the stakeholders, but also from misinterpretation of elicited requirements while implementing them in business processes, leading to a non-alignment between the data subjects' requirements and their specifications. Both types of conflicts are substantial challenges for conflict detection. To address these challenges, we propose a BPMN-based framework that supports: (i) the design of business processes considering security, data-minimization and fairness requirements, (ii) the encoding of such requirements as reusable, domain-specific patterns, (iii) the checking of alignment between the encoded requirements and annotated BPMN models based on these patterns, and (iv) the detection of conflicts between the specified requirements in the BPMN models based on a catalog of domain-independent anti-patterns. The security requirements were reused from SecBPMN2, a security-oriented BPMN 2.0 extension, while the fairness and data-minimization parts are new. For formulating our patterns and anti-patterns, we extended a graphical query language called SecBPMN2-Q. We report on the feasibility and the usability of our approach based on a case study featuring a healthcare management system, and an experimental user study.
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27. |
- Wu, Xuanjun, et al.
(författare)
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Protective Epitope Discovery and the Design of MUC1 Based Vaccine for Effective Tumor Protections in Immunotolerant Mice
- 2018
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:48, s. 16596-16609
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Tidskriftsartikel (refereegranskat)abstract
- Human mucin-1 (MUC1) is a highly attractive antigen for the development of anticancer vaccines. However, in human clinical trials of multiple MUC1 based vaccines, despite the generation of anti-MUC1 antibodies, the antibodies often failed to exhibit much binding to tumor presumably due to the challenges in inducing protective immune responses in the immunotolerant environment. To design effective MUC1 based vaccines functioning in immunotolerant hosts, vaccine constructs were first synthesized by covalently linking the powerful bacteriophage Qβ carrier with MUC1 glycopeptides containing 20-22 amino acid residues covering one full length of the tandem repeat region of MUC1. However, IgG antibodies elicited by these first generation constructs in tolerant human MUC1 transgenic (Tg) mice did not bind tumor cells strongly. To overcome this, a peptide array has been synthesized. By profiling binding selectivities of antibodies, the long MUC1 glycopeptide was found to contain immunodominant but nonprotective epitopes. Critical insights were obtained into the identity of the key protective epitope. Redesign of the vaccine focusing on the protective epitope led to a new Qβ-MUC1 construct, which was capable of inducing higher levels of anti-MUC1 IgG antibodies in MUC1.Tg mice to react strongly with and kill a wide range of tumor cells compared to the construct containing the gold standard protein carrier, i.e., keyhole limpet hemocyanin. Vaccination with this new Qβ-MUC1 conjugate led to significant protection of MUC1.Tg mice in both metastatic and solid tumor models. The antibodies exhibited remarkable selectivities toward human breast cancer tissues, suggesting its high translational potential.
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28. |
- Wu, Xuanjun, et al.
(författare)
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Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles
- 2019
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 14:10, s. 2176-2184
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Tidskriftsartikel (refereegranskat)abstract
- Mucin-1 (MUC1) is a highly attractive antigenic target for anticancer vaccines. Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen–Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen. In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized. The bacteriophage Qβ carrier is a powerful carrier for antigen delivery. The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units. The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans. Antibodies induced by Qβ-MUC1-Tf showed strongest binding, with MUC1-expressing melanoma B16-MUC1 cells, and effectively killed these cells in vitro. Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice. This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model. As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
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