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1.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
2.
Timothy J. Cordingley Mark A.G. Wilson Kathryn M. Weston 《Health & social care in the community》2022,30(1):353-359
Vaccination is a vital health care initiative to prevent individual and population infection. To increase vaccination rates the federal government implemented the ‘No Jab, No Pay’ policy, where eligibility for several government benefits required children to be fully vaccinated by removing ‘conscientious objections’ and expanding the age range of children whose families receive benefits. This study assesses the impact of this policy at a local area within a single medical practice community in NSW, Australia. A retrospective clinical audit was performed between 2012 and 2017 on a single general practice's vaccination records for children ≤19 years. Catch-up vaccinations were assessed based on age at vaccination. Incidence of catch-up vaccinations was assessed for each of four years before and two years after the implementation of the ‘No Jab, No Pay’ policy in January 2016, along with the age of children and vaccination(s) given. Catch-up vaccinations were assessed temporally either side of implementation of ‘No Jab, No Pay’. Comparing the average annual vaccination catch-up incidence rate of 6.2% pre-implementation (2012–2015), there was an increase to 9.2% in 2016 (p < .001) and 7.8% in 2017 (p = .027). Secondary outcome measurement of catch-up vaccination incidence rates before (2012–2015) and after (2016–2017) ‘No Jab, No Pay’ implementation showed statistically significant increases for children aged 8–11 years (3.2%–5.6%, p = .038), 12–15 years (7.5%–14.7%, p < .001) and 16–19 years (3.3%–10.2%, p < .001) along with a statistically significant reduction in children aged 1–3 years (11.4%–6.2%, p = .015). Also, catch-up rates for DTPa significantly increased after program implementation. This study demonstrates that the Australian federal government vaccination policy ‘No Jab, No Pay’ was coincident with an increase in catch-up vaccinations within a rural NSW community served by one medical practice, especially for older children. 相似文献
3.
James A. Akingbasote Alison J. Foster Ian Wilson Sunil Sarda Huw B. Jones J. Gerry Kenna 《Archives of toxicology》2016,90(4):853-862
Hepatic NADPH-cytochrome P450 oxidoreductase null (HRN?) mice exhibit normal hepatic and extrahepatic biotransformation enzyme activities when compared to wild-type (WT) mice, but express no functional hepatic cytochrome P450 activities. When incubated in vitro with [14C]-diclofenac, liver microsomes from WT mice exhibited extensive biotransformation to oxidative and glucuronide metabolites and covalent binding to proteins was also observed. In contrast, whereas glucuronide conjugates and a quinone-imine metabolite were formed when [14C]-diclofenac was incubated with HRN? mouse liver, only small quantities of P450-derived oxidative metabolites were produced in these samples and covalent binding to proteins was not observed. Livers from vehicle-treated HRN? mice exhibited enhanced lipid accumulation, bile duct proliferation, hepatocellular degeneration and necrosis and inflammatory cell infiltration, which were not present in livers from WT mice. Elevated liver-derived alanine aminotransferase, glutamate dehydrogenase and alkaline phosphatase activities were also observed in plasma from HRN? mice. When treated orally with diclofenac for 7 days, at 30 mg/kg/day, the severities of the abnormal liver histopathology and plasma liver enzyme findings in HRN? mice were reduced markedly. Oral diclofenac administration did not alter the liver histopathology or elevate plasma enzyme activities of WT mice. These findings indicate that HRN? mice are valuable for exploration of the role played by hepatic P450s in drug biotransformation, but poorly suited to investigations of drug-induced liver toxicity. Nevertheless, studies in HRN? mice could provide novel insights into the role played by inflammation in liver injury and may aid the evaluation of new strategies for its treatment. 相似文献
4.
5.
Rocha Déborah Ribeiro Nery Jaqueline Freire Furini Leonardo Negri Constantino Carlos José Leopoldo Eller Lizziane Kretli Winkelströter Nai Gisele Alborghetti Nakagaki Wilson Romero 《Lasers in medical science》2020,35(8):1703-1709
Lasers in Medical Science - Studies reported the harmful effects of 2,4-D on body tissues, provoking changes in the anatomy and physiology of the kidneys, liver, and testicles. Thus, the objective... 相似文献
6.
7.
Michelle E. Wilson Charles Kim Jacqueline Carrasco 《Orbit (Amsterdam, Netherlands)》2016,35(5):288-291
A 48-year-old smoker with a history of hyperthyroidism treated 10 years prior to presentation with radioactive iodine ablation of the thyroid gland presented to his ophthalmologist with a 2-week history of transient loss of vision in the right eye occurring for 1 to 2 hours each morning. He denied ocular pain, diplopia or change in the prominence of one or both eyes. Examination revealed 2 mm of relative proptosis on the right, bilateral temporal flare and lower lid retraction. There was minimal upper lid retraction and no evidence of lid lag. Ocular motility was full. Dilated fundoscopic examination revealed bilateral optic nerve edema, right more than left. CT of the orbit demonstrated enlargement of the extraocular muscles bilaterally with marked enlargement of the right medial rectus and left inferior rectus muscles resulting in crowding at the orbital apex bilaterally. Laboratory testing revealed the patient to be hyperthyroid. The patient was treated with high dose oral steroids followed by orbital radiation. Hyperthyroidism was managed by the patient’s primary care physician. Visual symptoms rapidly improved with oral steroids and orbital radiation. Optic nerve edema completely resolved. Repeat CT imaging demonstrated a reduction in the enlargement of the extraocular muscles with relief of bilateral optic nerve compression. 相似文献
8.
Claire Letournel François Babinet Bénédicte Allard Vincent Montecot 《Néphrologie & thérapeutique》2019,15(1):51-58
Objective
The “Centre Hospitalier Francois Dunan” is located on an isolated island and ensures patients care in hemodialysis thanks to telemedicine support. Many research studies have demonstrated the importance of hemodialysis fluids composition to reduce morbidity in patients on chronic hemodialysis. The aim of this study was to identify the risks inherent in the production of dialysis fluids in a particular context, in order to set up an improvement action plan to improve risk control on the production of dialysis fluids.Methods
The risk analysis was conducted with the FMECA methodology (Failure Mode, Effects and Criticality Analysis) by a multi professional work group. Three types of risk have been reviewed: technical risks that may impact the production of hemodialysis fluids, health risks linked with chemical composition and health risks due to microbiological contamination of hemodialysis fluids.Results
The work group, in close cooperation with the expert staff of the dialysis center providing telemedicine assistance, has developed an action plan in order to improve the control of the main risks brought to light by the risk analysis.Conclusion
The exhaustive analysis of the risks and their prioritisation have permitted to establish a relevant action plan in this improving quality of dialysis fluids approach. The risk control of dialysis fluids is necessary for the security of dialysis sessions for patients, even more when these sessions are realized by telemedicine in Saint-Pierre-et-Miquelon. 相似文献9.
10.
Leyi Wang Saraswathi Lanka Debbie Cassout Nohra E. Mateus‐Pinilla Ganwu Li William C. Wilson Dongwan Yoo Paul Shelton Richard L. Fredrickson 《Transboundary and Emerging Diseases》2019,66(5):1809-1820
First described in 1955 in New Jersey, epizootic haemorrhagic disease (EHD) causes a severe clinical disease in wild and domestic ruminants worldwide. Epizootic haemorrhagic disease outbreaks occur in deer populations each year from summer to late autumn. The etiological agent is EHD virus (EHDV) which is a double‐stranded segmented icosahedral RNA virus. EHD virus utilizes point mutations and reassortment strategies to maintain viral fitness during infection. In 2018, EHDV serotype 2 was predominantly detected in deer in Illinois. Whole genome sequencing was conducted for two 2018 EHDV2 isolates (IL41747 and IL42218) and the sequence analyses indicated that IL42218 was a reassortant between different serotypes whereas IL41747 was a genetically stable strain. Our data suggest that multiple strains contribute to outbreaks each year. 相似文献