Pancreatic ductal adenocarcinoma is characterized by a complex microenvironment. In this issue of Cancer Cell, Chen and colleagues define an oncogenic role of tumor-cell-produced collagen I ...homotrimers, wherein tumor development is promoted by integrin α3/β1-dependent activation of tumor cell signaling and modulation of tumor microbiome and immunity.
Pancreatic ductal adenocarcinoma is characterized by a complex microenvironment. In this issue of Cancer Cell, Chen and colleagues define an oncogenic role of tumor-cell-produced collagen I homotrimers, wherein tumor development is promoted by integrin α3/β1-dependent activation of tumor cell signaling and modulation of tumor microbiome and immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hypoglycaemic events, particularly nocturnal, affect health-related quality of life (HRQoL) via acute symptoms, altered behaviour and fear of future events. We examined the respective disutility ...associated with a single event of daytime, nocturnal, severe and non-severe hypoglycaemia.
Representative samples were taken from Canada, Germany, Sweden, the United States and the United Kingdom. Individuals completed an internet-based questionnaire designed to quantify the HRQoL associated with different diabetes- and/or hypoglycaemia-related health states. HRQoL was measured on a utility scale: 1 (perfect health) to 0 (death) using the time trade-off method. Three populations were studied: 8286 respondents from the general population; 551 people with type 1 diabetes; and 1603 with type 2 diabetes. Respondents traded life expectancy for improved health states and evaluated the health states of well-controlled diabetes and diabetes with non-severe/severe and daytime/nocturnal hypoglycaemic events.
In the general population, non-severe nocturnal hypoglycaemic events were associated with a 0.007 disutility compared with 0.004 for non-severe daytime episodes, equivalent to a significant 63% increase in negative impact. Severe daytime and nocturnal events were associated with a 0.057 and a 0.062 disutility, respectively, which were not significantly different.
This study applies an established health economic methodology to derive disutilities associated with hypoglycaemia stratified by onset time and severity using a large multinational population. It reveals substantial individual and cumulative detrimental effects of hypoglycaemic events - particularly nocturnal - on HRQoL, reinforcing the clinical imperative of avoiding hypoglycaemia.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group.
Systematic review and ...meta-analysis.
Primary studies were identified based on The Cochrane Database of Systematic Reviews investigating the effect of exercise therapy.
At least two of the authors independently evaluated all identified reviews and primary studies. Randomised controlled trials were included if they compared any exercise therapy intervention with a non-exercising control. Two authors independently extracted data. The RR of serious and non-serious adverse events was estimated separately.
180 Cochrane reviews were included and from these, 773 primary studies were identified. Of these, 378 studies (n=38 368 participants) reported serious adverse events and 375 studies (n=38 517 participants) reported non-serious adverse events. We found no increase in risk of serious adverse events (RR=0.96 (95%CI 0.90 to 1.02, I
: 0.0%) due to exercise therapy. There was, however, an increase in non-serious adverse events (RR=1.19 (95%CI 1.09 to 1.30, I
: 0.0%). The number needed to treat for an additional harmful outcome for non-serious adverse events was 6 95%CI 4 to 11).
Participating in an exercise intervention increased the relative risk of non-serious adverse events, but not of serious adverse events. Exercise therapy may therefore be recommended as a relatively safe intervention.PROSPERO registration numberCRD42014014819.
Enterotoxigenic E. coli (ETEC) susceptibility in pigs is highly influenced by their genotype. The aim of this study was to determine the association between CHCF1 genotype and ETEC F4ab ...susceptibility in experimentally infected pigs.
We investigated ETEC diarrhea development in CHCF1 heterozygous susceptible (RS) (n = 12 pigs) compared to CHCF1 homozygous resistant (RR) (n = 12 pigs) for six days after ETEC F4ab challenge. Afterwards, we genotyped with MUC4 and MUC13 markers to relate performance in identifying ETEC F4ab diarrhea susceptible pigs.
In the CHCF1 RS group, 12/12 pigs developed ETEC diarrhea compared with 0/12 pigs in the CHCF1 RR group. Weight gain was lower in CHCF1 RS pigs compared with RR pigs (mean ± SD: 208 ± 323 g and 987 ± 615 g, p = 0.0007). Further, the shedding of hemolytic E. coli was significantly higher in CHCF1 RS pigs from 2 to 6 days post inoculation and they shed the challenge strain for more days (mean ± SD: 3.5 ± 1.6 days versus 0.5 ± 0.5 days, p < 0.0001). Twelve pigs with ETEC diarrhea were misclassified as resistant with the MUC4 marker and four pigs without ETEC diarrhea were misclassified as susceptible with the MUC13 marker.
We found complete association between CHCF1 genotype and ETEC diarrhea development in pigs from a herd with Danbred genetics. The CHCF1 marker was more likely to determine the true host susceptibility to ETEC F4ab than the other markers. The marker shows potential for improving reliability of PWD challenge models and potentially for use in breeding for ETEC F4ab/ac resistance.
•The genetic marker CHCF1 was in full linkage disequilibrium with clinical ETEC F4ab susceptibility.•CHCF1 genotyping enabled screening of pigs susceptible to ETEC F4ab infection for the challenge trial.•MUC4 and MUC13 markers did not correctly classify clinical ETEC F4ab susceptibility in as many pigs as the CHCF1 marker.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Post-weaning diarrhea in pigs is a considerable challenge in the pig farming industry due to its effect on animal welfare and production costs, as well as the large volume of antibiotics, which are ...used to treat diarrhea in pigs after weaning. Previous studies have revealed loci on SSC6 and SSC13 associated with susceptibility to specific diarrhea causing pathogens. This study aimed to identify new genetic loci for resistance to diarrhea based on phenotypic data. In depth clinical characterization of diarrhea was performed in 257 pigs belonging to two herds during the first 14 days post weaning. The daily diarrhea assessments were used for the classification of pigs into case and control groups. Pigs were assigned to case and control groups based only on the incidence of diarrhea in the second week of the study in order to differentiate between differences in etiology. Genome-wide association studies and metabolomics association analysis were performed in order to identify new biological determinants for diarrhea susceptibility. With the present work, we revealed a new locus for diarrhea resistance on SSC16. Furthermore, studies of metabolomics in the same pigs revealed one metabolite associated with diarrhea.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We generated cell lines resistant to BRAF inhibitors and show that the EGF receptor (EGFR)-SRC family kinase (SFK)-STAT3 signaling pathway was upregulated in these cells. In addition to driving ...proliferation of resistant cells, this pathway also stimulated invasion and metastasis. EGFR inhibitors cooperated with BRAF inhibitors to block the growth of the resistant cells in vitro and in vivo, and monotherapy with the broad specificity tyrosine kinase inhibitor dasatinib blocked growth and metastasis in vivo. We analyzed tumors from patients with intrinsic or acquired resistance to vemurafenib and observed increased EGFR and SFK activity. Furthermore, dasatinib blocked the growth and metastasis of one of the resistant tumors in immunocompromised mice. Our data show that BRAF inhibitor-mediated activation of EGFR-SFK-STAT3 signaling can mediate resistance in patients with BRAF-mutant melanoma. We describe 2 treatments that seem to overcome this resistance and could deliver therapeutic efficacy in patients with drug-resistant BRAF-mutant melanoma.
Therapies that target the driver oncogenes in cancer can achieve remarkable responses if patients are stratified for treatment. However, as with conventional therapies, patients often develop acquired resistance to targeted therapies, and a proportion of patients are intrinsically resistant and fail to respond despite the presence of an appropriate driver oncogene mutation. We found that the EGFR/SFK pathway mediated resistance to vemurafenib in BRAF -mutant melanoma and that BRAF and EGFR or SFK inhibition blocked proliferation and invasion of these resistant tumors, providing potentially effective therapeutic options for these patients.
In liberalized power markets, there are significant power price fluctuations due to independently varying changes in demand and supply, the latter being substantial in systems with high wind power ...penetration. In such systems, hydrogen production by grid connected electrolysis can be cost optimized by operating an electrolyzer part time. This paper presents a study on the minimization of the hydrogen production price and its dependence on estimated power price fluctuations. The calculation of power price fluctuations is based on a parameterization of existing data on wind power production, power consumption and power price evolution in the West Danish power market area. The price for hydrogen is derived as a function of the optimal electrolyzer operation hours per year for four different wind penetration scenarios. It is found to amount to 0.41–0.45
€/Nm
3. The study further discusses the hydrogen price sensitivity towards investment costs and the contribution from non-wind power sources.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Effects of exercise in patients with breast cancer have been thoroughly investigated. The aim was to explore differences in effects regarding type, delivery mode and extensiveness (e.g. intensity; ...volume) of the interventions.
We searched for randomised controlled trials including patients with breast cancer receiving systemic treatment, exercise-based interventions, and measures on patient reported- and objectively measured outcomes.
Exercise showed significant and moderate effects on the primary outcomes quality of life and physical function, Standardised Mean Difference: 0.52 (95 % CI 0.38–0.65) and 0.52 (95 % CI 0.38–0.66), respectively. Type of exercise had little influence on the effects, however combined aerobic- and resistance exercise seemed superior for increasing physical function, compared to aerobic or resistance exercise. Supervised interventions were superior to partly and unsupervised. Extensiveness of the intervention only influenced physical function.
Supervised interventions, more than type or extensiveness of interventions, seem to increase effects.
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•Exercise effectively increases quality of life, irrespective of exercise type.•Supervised exercise interventions are most effective.•Extensiveness of exercise interventions has very little influence on the effects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Fragrances are among the most common contact allergens in children. Cosmetic products are the most frequent source of skin exposure.
Objective
To investigate exposure to fragrance ...allergens among Danish children, based on a sample of 1179 cosmetic products marketed for children.
Methods
Information regarding cosmetic products marketed to children was obtained using a non‐profit smartphone application registry, with data from December 2015 to November 2022.
Results
The number of validated products was 26 537, of which 1349 marketed for children. After elimination of duplicates, 1179 (4.4%) individual products remained. The majority 53.8% (634/1179) of the products were fragranced. The highest frequency of declared fragrances was found in ‘Facial care’‐products: 93.0% (80/86), of which 97.7% were lip balms. The highest number of labelled fragrances in one single product (
n
= 16) was found in a baby perfume. Fragrance mix I (FMI) or II (FMII) allergens were found in 25.3% (298/1179) of the products. Limonene and linalool were the two most frequently labelled fragrance allergens.
Conclusion
Children can be exposed to a vast number of fragrance allergens from scented cosmetic products. Allergens from FM I and FMII are widely used in cosmetic products marketed to children. Patch testing with FMI and FMII remains relevant in children.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
10.
Simplistic pathways or complex networks? Jørgensen, Claus; Linding, Rune
Current opinion in genetics & development,
02/2010, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Signaling events are frequently described in textbooks as linear cascades. However, in reality, input cues are processed by dynamic and context-specific networks, which are assembled from numerous ...signaling molecules. Diseases, such as cancer, are typically associated with multiple genomic alterations that likely change the structure and dynamics of cellular signaling networks. To assess the impact of such genomic alterations on the structure of signaling networks and on the ability of cells to accurately translate environmental cues into phenotypic changes, we argue studies must be conducted on a network level. Advances in technologies and computational approaches for data integration have permitted network studies of signaling events in both cancer and normal cells. Here we will review recent advances and how they have impacted our view on signaling networks with a specific angle on signal processing in cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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