Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited.
We analysed clinical ...data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions.
Median age at diagnosis of BMs was 56 years (22–90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)–positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000–2009 with 2010–2015 (51%–44%), whereas the percentage of patients with luminal-like tumours increased (28%–34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval CI: 6.7–8.0 months). One-year survival rate was 37.7% (95% CI: 35.2–40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0–13.4) compared with 5.9 months (95% CI: 5.0–7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9–5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001).
Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.
•The first analysis of 1712 patients of breast cancer patients with brain metastases (BMs) is presented.•Localisation of BMs was different depending on tumour subtypes.•Survival times differ depending on the subtype and localisation of BMs.•A change in the incidence of BMs over time was observed.
Multifunctional polymer nanomedical platforms make simultaneous cancer‐targeted MRI or optical imaging together with efficient drug delivery in vitro possible. In addition, clusters of Fe3O4 ...nanoparticles loaded in the polymer nanoparticles endow the magnetic guiding of the polymer particles, providing synergetic targeting efficiency.
We present a theoretical analysis of Raman intensities for a molecule that bridges a current carrying junction. Experimental data is used to estimate parameters for the theoretical model. The ...recently reported staircase of Raman intensities observed during the fusion of nanodumbbell is reproduced.
Aims
Experiments were designed to determine the effects of different chemical inhibitors of lysozyme and peptidases on rumen protozoa and the associated prokaryotes, and in vitro fermentation using ...Entodinium caudatum as a model protozoan species.
Methods and Results
Imidazole (a lysozyme inhibitor), phenylmethylsulphonyl fluoride (PMSF, a serine peptidase inhibitor) and iodoacetamide (IOD, a cysteine peptidase inhibitor) were evaluated in vitro both individually and in two‐ and three‐way combinations using E. caudatum monocultures with respect to their ability to inhibit the protozoan and their effect on feed digestion, fermentation and the microbiota. All the three inhibitors, both individually and in combination, decreased E. caudatum counts (P < 0·001), and IOD and its combinations with the other inhibitors significantly (P < 0·01) decreased ammonia concentration, with the two‐ and three‐way combinations showing additive effective. Feed digestion was not affected, but fermentation and microbial diversity were affected mostly by PMSF, IOD and their combinatorial treatments potentially due to the overgrowth of Streptococcus luteciae accompanying with the disappearance of host ciliates.
Conclusions
Entodinium caudatum depends on lysozyme and peptidase for digestion and utilization of the engulfed microbes and specific inhibition of these enzymes can inhibition E. caudatum without adversely affecting feed digestion or fermentation even though they changed the microbiota composition in the cultures.
Significance and Impact of the Study
The peptidase inhibitors may have the potential to be used in controlling rumen protozoa to improve ruminal nitrogen utilization efficiency.
Nuclear physics research at CENS Ahn, S.; Ahn, D. S.; Kim, S. ...
Journal of the Korean Physical Society,
03/2023, Volume:
82, Issue:
6
Journal Article
Peer reviewed
Understanding fundamental interactions of elementary particles is a long sought goal of nuclear physics study. Nuclear theorists recently estimated about 4000 nuclei are still unknown and their ...structures and reaction mechanisms need to be studied by both experiment and theory. The nuclear properties are also important to find the origin of elements in the Universe. The Center for Exotic Nuclear Studies (CENS) at the Institute for Basic Science was founded to address such fundamental problems in astrophysics and nuclear physics. In this paper, the latest research activities at CENS is highlighted and the status of experimental device developments performed by the center is reported.
Recent rapid thinning of West Antarctic ice shelves are believed to be caused by intrusions of warm deep water that induce basal melting and seaward meltwater export. This study uses data from three ...bottom-mounted mooring arrays to show seasonal variability and local forcing for the currents moving into and out of the Dotson ice shelf cavity. A southward flow of warm, salty water had maximum current velocities along the eastern channel slope, while northward outflows of freshened ice shelf meltwater spread at intermediate depth above the western slope. The inflow correlated with the local ocean surface stress curl. At the western slope, meltwater outflows followed the warm influx along the eastern slope with a ~2-3 month delay. Ocean circulation near Dotson Ice Shelf, affected by sea ice distribution and wind, appears to significantly control the inflow of warm water and subsequent ice shelf melting on seasonal time-scales.
Background
Classifications of intraductal papillary mucinous neoplasm (IPMN) remain ambiguous, especially for the mixed type. Factors predicting malignancy remain unclear. The aim of this study was ...to evaluate the usefulness of factors predicting malignancy in the new international consensus guidelines for resection of branch duct‐type (BD)‐IPMN and to compare them with those in the previous version.
Methods
A prospectively collected database of patients with biopsy‐proven BD‐IPMN was analysed to compare factors between the first and second consensus guidelines, particularly as predictors of malignancy.
Results
Of 350 patients with BD‐IPMN, sensitivity (0·724) and balanced accuracy (0·751) of the second guidelines were superior to those (0·639 and 0·730) in the first version at the expense of slightly reduced specificity (0·779 versus 0·822 for the first version) by random forest models. Multiple logistic regression analysis showed that main pancreatic duct dilatation greater than 5 mm (hazard ratio (HR) 4·54, 95 per cent confidence interval 2·45 to 8·41; P < 0·001), mural nodules (HR 6·27, 3·27 to 12·01; P < 0·001) and carbohydrate antigen 19–9 level above 37 units/ml (HR 4·03, 1·83 to 8·90; P = 0·001) were independent predictors of BD‐IPMN malignancy.
Conclusion
The new consensus guidelines provide better sensitivity, performance of factors predicting malignancy, and balanced accuracy in the diagnosis of BD‐IPMN malignancy. Size alone was limited in predicting malignancy. Variability in clinical significance of the individual factors associated with a risk of malignancy indicates the need for a tailored approach in the management of patients with BD‐IPMN.
Cyst size alone is not useful
A single, subanesthetic dose of (R,S)-ketamine (ketamine) exerts rapid and robust antidepressant effects. Several groups previously reported that (2S,6S;2R,6R)-hydroxynorketamine (HNK) had ...antidepressant effects in rodents, and that (2R,6R)-HNK increased cortical electroencephalographic gamma power. This exploratory study examined the relationship between ketamine metabolites, clinical response, psychotomimetic symptoms, and gamma power changes in 34 individuals (ages 18-65) with treatment-resistant depression (TRD) who received a single ketamine infusion (0.5 mg/kg) over 40 min. Plasma concentrations of ketamine, norketamine, and HNKs were measured at 40, 80, 120, and 230 min and at 1, 2, and 3 days post-infusion. Linear mixed models evaluated ketamine metabolites as mediators of antidepressant and psychotomimetic effects and their relationship to resting-state whole-brain magnetoencephalography (MEG) gamma power 6-9 h post-infusion. Three salient findings emerged. First, ketamine concentration positively predicted distal antidepressant response at Day 11 post-infusion, and an inverse relationship was observed between (2S,6S;2R,6R)-HNK concentration and antidepressant response at 3 and 7 days post-infusion. Norketamine concentration was not associated with antidepressant response. Second, ketamine, norketamine, and (2S,6S;2R,6R)-HNK concentrations at 40 min were positively associated with contemporaneous psychotomimetic symptoms; post-hoc analysis revealed that ketamine was the predominant contributor. Third, increased (2S,6S;2R,6R)-HNK maximum observed concentration (C
) was associated with increased MEG gamma power. While contrary to preclinical observations and our a priori hypotheses, these exploratory results replicate those of a recently published study documenting a relationship between higher (2S,6S;2R,6R)-HNK concentrations and weaker antidepressant response in humans and provide further rationale for studying gamma power changes as potential biomarkers of antidepressant response.
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