We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC).
A total of 379 eligible women with estrogen ...receptor positive (ER+), HER2-negative EBC and 0–3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded.
Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice.
RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.
Laparoscopic partial nephrectomy for localized renal tumors is an upcoming standard minimally invasive surgical procedure. However, a single-site laparoscopic approach would be even more preferable ...in terms of invasiveness. While the manual approach offers rigid curved tools, robotic single-site systems provide high degrees of freedom manipulators. However, they either provide only a straight deployment port, lack of instrument integration, or cannot be reconfigured. Therefore, the current main shortcomings of single-site surgery approaches include limited tool dexterity, visualization, and intuitive use by the surgeons. For partial nephrectomy in particular, the accessibility of the tumors remains limited and requires invasive kidney mobilization (separation of the kidney from the surrounding tissue), resulting in patient stress and prolonged surgery. We address these limitations by introducing a flexible, robotic, variable stiffness port with several working channels, which consists of a two-segment tendon-driven continuum robot with integrated granular and layer jamming for stabilizing the pose and shape. We investigate biocompatible granules for granular jamming and demonstrate the stiffening capabilities in terms of pose and shape accuracy with experimental evaluations. Additionally, we conduct
in vitro
experiments on a phantom and prove that the visualization of tumors at various sites is increased up to 38% in comparison to straight endoscopes.
Mucolipidosis II is a neurometabolic lysosomal trafficking disorder of infancy caused by loss of mannose 6-phosphate targeting signals on lysosomal proteins, leading to lysosomal dysfunction and ...accumulation of non-degraded material. However, the identity of storage material and mechanisms of neurodegeneration in mucolipidosis II are unknown. We have generated 'knock-in' mice with a common mucolipidosis II patient mutation that show growth retardation, progressive brain atrophy, skeletal abnormalities, elevated lysosomal enzyme activities in serum, lysosomal storage in fibroblasts and brain and premature death, closely mimicking the mucolipidosis II disease in humans. The examination of affected mouse brains at different ages by immunohistochemistry, ultrastructural analysis, immunoblotting and mass spectrometric analyses of glycans and anionic lipids revealed that the expression and proteolytic processing of distinct lysosomal proteins such as α-l-fucosidase, β-hexosaminidase, α-mannosidase or Niemann-Pick C2 protein are more significantly impacted by the loss of mannose 6-phosphate residues than enzymes reaching lysosomes independently of this targeting mechanism. As a consequence, fucosylated N-glycans, GM2 and GM3 gangliosides, cholesterol and bis(monoacylglycero)phosphate accumulate progressively in the brain of mucolipidosis II mice. Prominent astrogliosis and the accumulation of organelles and storage material in focally swollen axons were observed in the cerebellum and were accompanied by a loss of Purkinje cells. Moreover, an increased neuronal level of the microtubule-associated protein 1 light chain 3 and the formation of p62-positive neuronal aggregates indicate an impairment of constitutive autophagy in the mucolipidosis II brain. Our findings demonstrate the essential role of mannose 6-phosphate for selected lysosomal proteins to maintain the capability for degradation of sequestered components in lysosomes and autophagolysosomes and prevent neurodegeneration. These lysosomal proteins might be a potential target for a valid therapeutic approach for mucolipidosis II disease.
1 Introduction The implementation of new monoclonal antibodies in treatment algorithms for malignant diseases offers the possibility of powerful and targeted intervention while avoiding numerous ...well-known adverse effects of classical cytotoxic agents 1. Data from experimental studies seem to indicate an essential role of tyrosine-kinases in axonal growth, function, repair and survival, which might serve as a first hint to the pathophysiological mechanisms underlying the described adverse effects on the peripheral nervous system 5.
Purpose
The management of high-risk endometrial cancer (HREC) remains controversial. We conducted a prospective multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy (CT) with ...sequential radiotherapy (RT) in patients with HREC.
Methods
Patients with HREC from 8 institutions in Germany were enrolled. After surgery, patients received four cycles of paclitaxel 175 mg/m² (P) and carboplatin AUC5 (C) (d1, q21d) and subsequent external pelvic radiation therapy (1.8 Gy/d, d1-5) at a total dose of 45 Gy with vaginal brachytherapy (3 × 5 Gy). Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Primary endpoints were tolerability, toxicity and QoL. Progression-free survival (PFS) was defined as secondary endpoint.
Results
Thirty-five patients were enrolled from 2004 through 2008. Median follow-up was 24 months (range 3–24 months). All patients received 4 cycles of P and C and completed RT. Overall, grade 3/4 haematological toxicity was 25.6 %. Three cycles were delayed because of leukopenia. Grade 3/4 non-haematologic toxicities were rare (≤3 %). No overall change in QoL occurred during treatment. Two-year median PFS and OS rates were both 75.8 %.
Conclusions
Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC. Subsequent phase-III trials are warranted.
In this work, by combining an asymmetric Silicon immersion lens configuration and a complementary resonator design, far-field transmission measurement of a single subwavelength split-ring resonator, ...ultra-strongly coupled to inter Landau level transitions in a single quantum well, is resolved. The highest coupling is 60%, achieved for only ~2000 coupled electrons for a single resonator on an InSb quantum well. This technique can be useful to characterize the complex conductivity of micron-sized samples, such as exfoliated graphene or transition metal dichalcogenide flakes, in the THz domain.
Unilateral ovarian agenesis is a rare event and only a few case have been reported.
We present three additional cases, where patients presented with diffuse lower abdominal pain. During laparoscopy, ...an unilateral ovarian agenesis was observed in the three cases.
There are two possible explanations of a unilateral ovarian absence, involving an asymptomatic adnexal torsion or congenital absence. Unknown environmental factors or genetic predisposition could contribute to this kind of anomaly.
2D - THz-Spectroscopy on a Quantum Cascade Structure Markmann, S.; Franckie, M.; Pal, S. ...
2020 45th International Conference on Infrared, Millimeter, and Terahertz Waves (IRMMW-THz),
2020-Nov.-8
Conference Proceeding
We use two-dimensional (2D) THz-spectroscopy to study the \chi^{(3)} non-linearities originating from four-wave mixing (FWM) in a quantum cascade structure (QCS), embedded in a single-plasmon ...waveguide. This approach allows us to extract the strength of all system non-linearities, study time-resolved system properties such as population and coherence lifetimes, as well as identify the dominant scattering mechanisms of the unbiased QCS at 10K.
We investigate the strong light-matter interactions of intersubband resonances (ISRs) in a triangular quantum well to a THz metamaterial. The large tuning possibility of ISRs with a high quality ...epitaxial gate enables the device to be electrically driven in-and-out of the coupling regime.
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