Native cellulose model films containing both amorphous and crystalline cellulose I regions were prepared by spin-coating aqueous cellulose nanofibril dispersions onto silica substrates. Nanofibrils ...from wood pulp with low and high charge density were used to prepare the model films. Because the low charged nanofibrils did not fully cover the silica substrates, an anchoring substance was selected to improve the coverage. The model surfaces were characterized using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The effect of nanofibril charge density, electrolyte concentration, and pH on swelling and surface interactions of the model film was studied by quartz crystal microbalance with dissipation (QCM-D) and AFM force measurements. The results showed that the best coverage for the low charged fibrils was achieved by using 3-aminopropyltrimethoxysilane (APTS) as an anchoring substance and hence it was chosen as the anchor. The AFM and XPS measurements showed that the fibrils are covering the substrates. Charge density of the fibrils affected the morphology of the model surfaces. The low charged fibrils formed a network structure while the highly charged fibrils formed denser film structure. The average thickness of the films corresponded to a monolayer of fibrils, and the average rms roughness of the films was 4 and 2 nm for the low and high charged nanofibril films, respectively. The model surfaces were stable in QCM-D swelling experiments, and the behavior of the nanofibril surfaces at different electrolyte concentrations and pHs correlated with other studies and the theories of Donnan. The AFM force measurements with the model surfaces showed well reproducible results, and the swelling results correlated with the swelling observed by QCM-D. Both steric and electrostatic forces were observed and the influence of steric forces increased as the films were swelling due to changes in pH and electrolyte concentration. These films differ from previous model cellulose films due to their chemical composition (crystalline cellulose I and amorphous regions) and fibrillar structure and hence serve as excellent models for the pulp fiber surface.
The severity of the COVID‐19 pandemic and subsequent mitigation strategies have varied across the Nordic countries. In a joint Nordic population‐based effort, we compared patterns of new cancer cases ...and notifications between the Nordic countries during 2020. We used pathology notifications to cancer registries in Denmark, the Faroe Islands, Finland, Iceland, Norway and Sweden to determine monthly numbers of pathology notifications of malignant and in situ tumours from January to December 2020 compared to 2019 (2017‐2019 for Iceland and the Faroe Islands). We compared new cancer cases per month based on unique individuals with pathology notifications. In April and May 2020, the numbers of new malignant cases declined in all Nordic countries, except the Faroe Islands, compared to previous year(s). The largest reduction was observed in Sweden (May: −31.2%, 95% CI −33.9, −28.3), followed by significant declines in Finland, Denmark and Norway, and a nonsignificant decline in Iceland. In Denmark, Norway, Sweden and Finland the reporting rates during the second half of 2020 rose to almost the same level as in 2019. However, in Sweden and Finland, the increase did not compensate for the spring decline (annual reduction −6.2% and −3.6%, respectively). Overall, similar patterns were observed for in situ tumours. The COVID‐19 pandemic led to a decline in rates of new cancer cases in Sweden, Finland, Denmark and Norway, with the most pronounced reduction in Sweden. Possible explanations include the severity of the pandemic, temporary halting of screening activities and changes in healthcare seeking behaviour.
What's new?
The severity of the COVID‐19 pandemic and subsequent mitigation strategies have varied across the Nordic countries. This is the first international comparison of cancer notification rates during the first year of the COVID‐19 pandemic, including six countries with similar tax‐funded healthcare systems and population‐based cancer reporting. The findings suggest that, despite differences in pandemic mitigation efforts, the severity of the pandemic may have had a larger effect on cancer detection than strict societal restrictions. In all countries, it will be of importance to monitor future trends in late‐stage cancer incidence and survival.
An elevated level of macrophage inhibitory cytokine-1 (MIC-1) is reported in the sera of patients with metastatic prostate cancer compared with that of benign diseases and healthy adults. We ...investigated the mechanistic role of MIC-1 overexpression in the metastasis of prostate cancer cells. Our study showed a progressive increase in secretory MIC-1 production correlated with the increase in the metastatic potential of PC-3 and LNPCa prostate cancer metastatic variants. Further, the in vitro studies using 'loss-' and 'gain'-of-function approaches showed that ectopic overexpression of MIC-1 (PC-3-MIC-1) and forced downregulation of MIC-1(PC-3M-siMIC-1) enhanced and reduced the motility and invasiveness of these cells, respectively. Supporting our in vitro observations, all the mice orthotopically implanted with PC-3-MIC-1 cells developed metastasis compared with none in the PC-3-vector group. Our results showed that MIC-1 overexpression was associated with apparent changes in actin organization. In addition, an enhanced phosphorylation of focal adhesion kinase (FAK) and guanosine-5'-triphosphate (GTP)-bound RhoA was also seen; however, no significant change was observed in total FAK and RhoA levels in the PC-3-MIC-1 cells. Altogether, our findings show that MIC-1 has a role in prostate cancer metastasis, in part, by promoting the motility of these cells. Activation of the FAK-RhoA signaling pathway is involved in MIC-1-mediated actin reorganization, and thus, leads to an increase in the motility of prostate cancer cells.
Purpose
Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs ...with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs).
Methods
This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI).
Results
Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34).
Conclusion
There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.
Here, we use a novel space-by-time approach to study large-scale changes in phytoplankton species distribution in Swedish boreal lakes in response to climate variability. Using phytoplankton samples ...from 27 lakes, evenly distributed across Sweden, all relatively unimpacted by anthropogenic disturbance and sampled annually between 1996 and 2010, we found significant shifts in the geographical distribution of 18 species. We also found significant changes in the prevalence of 45 species (33 became more common and 12 less common) over the study period. Using species distribution models and phytoplankton samples from 60 lakes sampled at least twice between 1992 and 2010, we evaluated the importance of climate variability and other environmental variables on species distribution. We found that temperature (e.g., extreme events and the duration of the growing season) was the most important predictor for species detections. Many cyanobacteria, chlorophytes, and, to a lesser extent, diatoms and zygnematophytes, showed congruent and positive responses to temperature. In contrast, precipitation explained little variation and was important only for a few taxa (e.g., Staurodesmus spp., Trachelomonas volvocina). At the community level, our results suggest a change in community composition at temperatures over 20 °C and growing seasons longer than 40 days. We conclude that climate is an important driver of the distributional patterns of individual phytoplankton species and may drive changes in community composition in minimally disturbed boreal lakes.
To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer.
Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 ...premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years.
In estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio HR, 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (
= .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit.
This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.
Despite its promise as a highly useful therapy for pancreatic cancer (PC), the addition of external beam radiation therapy to PC treatment has shown varying success in clinical trials. Understanding ...PC radioresistance and discovery of methods to sensitise PC to radiation will increase patient survival and improve quality of life. In this study, we identified PC radioresistance-associated pathways using global, unbiased techniques.
Radioresistant cells were generated by sequential irradiation and recovery, and global genome cDNA microarray analysis was performed to identify differentially expressed genes in radiosensitive and radioresistant cells. Ingenuity pathway analysis was performed to discover cellular pathways and functions associated with differential radioresponse and identify potential small-molecule inhibitors for radiosensitisation. The expression of FDPS, one of the most differentially expressed genes, was determined in human PC tissues by IHC and the impact of its pharmacological inhibition with zoledronic acid (ZOL, Zometa) on radiosensitivity was determined by colony-forming assays. The radiosensitising effect of Zol in vivo was determined using allograft transplantation mouse model.
Microarray analysis indicated that 11 genes (FDPS, ACAT2, AG2, CLDN7, DHCR7, ELFN2, FASN, SC4MOL, SIX6, SLC12A2, and SQLE) were consistently associated with radioresistance in the cell lines, a majority of which are involved in cholesterol biosynthesis. We demonstrated that knockdown of farnesyl diphosphate synthase (FDPS), a branchpoint enzyme of the cholesterol synthesis pathway, radiosensitised PC cells. FDPS was significantly overexpressed in human PC tumour tissues compared with healthy pancreas samples. Also, pharmacologic inhibition of FDPS by ZOL radiosensitised PC cell lines, with a radiation enhancement ratio between 1.26 and 1.5. Further, ZOL treatment resulted in radiosensitisation of PC tumours in an allograft mouse model.
Unbiased pathway analysis of radioresistance allowed for the discovery of novel pathways associated with resistance to ionising radiation in PC. Specifically, our analysis indicates the importance of the cholesterol synthesis pathway in PC radioresistance. Further, a novel radiosensitiser, ZOL, showed promising results and warrants further study into the universality of these findings in PC, as well as the true potential of this drug as a clinical radiosensitiser.
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Materials made of synthetic vitreous mineral fibers, such as stone wool, are widely used in construction, in functional composites and as thermal and acoustic insulation. Chemical ...stability is an important parameter in assessing long term durability of the products. Stability is determined by fiber resistivity to dissolution, where the controlling parameters are solid surface area to solution volume ratio (S/V), pH and composition of the fibers and organic compounds used as binders. We investigated stone wool dissolution under flow through conditions, far from equilibrium, at pH range of 2 to 13, as well as under batch conditions, close to equilibrium, for up to 28 days, where S/V ranged from 100 to 10000 m−1. The dissolution rate of stone wool shows minimum at pH 8.5 and increases significantly at pH < 4.5 and pH > 12. In close to equilibrium conditions, S/V defines the steady state concentration for the leached components. Decreased dissolution rate could result from evolution of a surface leached layer or the formation of secondary surface phases or both. We suggested three dissolution rate controlling mechanisms, which depend on pH. That is, dissolution is controlled by: a SiO2 rich surface layer at pH < 4.5; by adsorption of an Al and Al-Si mixed surface layer at 5 < pH < 11 and by divalent cation adsorption and formation of secondary phases (silicates, hydroxides) at pH ∼ 13. The organic compounds, used to treat the stone wool fibers during manufacture, had no influence on their dissolution properties.
The large bloom-forming flagellate Gonyostomum semen has been hypothesized to be inedible to naturally occurring zooplankton due to its large cell size and ejection of long slimy threads ...(trichocysts) induced by physical stimulation. In a grazing experiment using radiolabelled algae and zooplankton collected from lakes with recurring blooms of G. semen and lakes that rarely experience blooms, we found that Eudiaptomus gracilis and Holopedium gibberum fed on G. semen at high rates, whereas Daphnia cristata and Ceriodaphnia spp. did not. Grazing rates of E. gracilis were similar between bloom-lakes and lakes with low biomass of G. semen, indicating that the ability to feed on G. semen was not a result of local adaptation. The high grazing rates of two of the taxa in our experiment imply that some of the nutrients and energy taken up by G. semen can be transferred directly to higher trophic levels, although the predominance of small cladocerans during blooms may limit the importance of G. semen as a food resource. Based on grazing rates and previous observations on abundances of E. gracilis and H. gibberum, we conclude that there is a potential for grazer control of G. semen and discuss why blooms of G. semen still occur.
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