LBA5500 Background: Optimal timing of cytoreduction in non-frail patients (pts) with seemingly resectable stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma (OC) remains controversial. Methods: TRUST is an international randomized multicenter phase III trial in pts with stage IIIB-IVB OC and good performance status (ECOG 0/1) comparing primary cytoreductive surgery (PCS) followed by 6 cycles of intravenous (iv) chemotherapy to 3 cycles of neoadjuvant iv chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) and 3 further iv cycles. Maintenance treatment with bevacizumab and/or PARP inhibitors was allowed if selection criteria was similar for both arms. Pts were eligible for the study if preoperative clinical and radiologic assessment identified them as potential candidates for PCS. To ensure surgical quality, participating centers complied with an onsite surgery quality assurance audit, had adequate infrastructure, surgical proficiency (complete resection rates ≥50% in PCS) and sufficient volume (≥36 PCS/year). The intent to treat analysis population included all eligible pts with confirmed stage IIIB-IVB disease. The primary endpoint was overall survival (OS). Superiority was tested using a two-sided stratified log-rank test with significance level 0.05. Secondary endpoints were progression-free survival (PFS) and surgical complications. Results: A total of 688 eligible pts (median age: 63y; range: 32-83) underwent randomization: 345 were assigned to PCS and 343 to NACT/ICS. 91% had high-grade serous histology. Complete resection was achieved in 61.7%/62.9% of all randomized/all operated pts in the PCS group and 72%/76.6% in the ICS group. Median PFS was 22.2 months in the PCS group, and 19.7 months in the ICS group (HR 0.80 95%CI: 0.66-0.96; p=0.02). Median OS was 54.3 months in the PCS group and 48.3 months in the ICS group (HR 0.89 95%CI: 0.74-1.08; p=0.24). Pts with complete cytoreduction after PCS had the most favorable outcome, with a median PFS and OS of 27.9 and 67.0 months, respectively. A long-term benefit from PCS was seen in all analyzed subgroups. The benefit of PCS was most prominent in stage III pts (n=468): median PFS for PCS vs ICS, 26.3 vs 21.4 mos; median OS for PCS vs ICS, 63.7 vs 53.2 months. Major postoperative complication rates were acceptable, with a 30-day postoperative mortality rate of < 1% in both groups. Conclusions: In expert centers with proven surgical quality, PCS followed by iv chemotherapy resulted in a significantly longer median PFS and a numerically longer OS compared to NACT/ICS in non-frail OC pts. Although statistical significance in the primary endpoint was not reached, this is the first randomized trial to show a benefit of PCS over ICS. This benefit is likely to be associated with the high complete resection rate, reinforcing PCS as a standard of care in non-frail pts with seemingly resectable advanced OC. Clinical trial information: NCT02828618 .
Accurate measurement of membrane potential dynamics is essential for understanding cellular excitability and signaling. While electrophysiological methods provide high temporal resolution, their invasiveness and low throughput limit their applicability in complex biological systems. Voltage-sensing dyes (VSDs) offer a powerful optical alternative, yet achieving near-infrared (NIR) emission, high sensitivity, and rapid response remains challenging. Here, we report the design, synthesis, and characterization of a novel phosphorus-rhodamine-based VSD (VSD 1) incorporating a phenyl substituent on the phosphorus atom. This modification enhances σ*–π* conjugation and electron-withdrawing effects, leading to a pronounced bathochromic shift with absorption and emission maxima at 715 and 744 nm, respectively—the most red-shifted spectral profile among reported rhodamine VSDs. VSD 1 shows strong fluorescence quenching in the resting state, suggesting efficient nonradiative deactivation, although the exact mechanism was not experimentally determined. Voltage-clamp fluorometry in Xenopus laevis oocytes demonstrates robust voltage sensitivity, with a linear fluorescence–voltage relationship and a ΔF/F of 4.7±1.4
Recent studies suggest that the deeper layers of Large Language Models (LLMs) contribute little to representation learning and can often be removed without significant performance loss. However, such claims are typically drawn from narrow evaluations and may overlook important aspects of model behavior. In this work, we present a systematic study of depth utilization across diverse dimensions, including evaluation protocols, task categories, and model architectures. Our analysis confirms that very deep layers are generally less effective than earlier ones, but their contributions vary substantially with the evaluation setting. Under likelihood-based metrics without generation, pruning most layers preserves performance, with only the initial few being critical. By contrast, generation-based evaluation uncovers indispensable roles for middle and deeper layers in enabling reasoning and maintaining long-range coherence. We further find that knowledge and retrieval are concentrated in shallow components, whereas reasoning accuracy relies heavily on deeper layers -- yet can be reshaped through distillation. These results highlight that depth usage in LLMs is highly heterogeneous and context-dependent, underscoring the need for task-, metric-, and model-aware perspectives in both interpreting and compressing large models.
Introduction Low back pain is a global health issue causing disability and missed work days. Commonly used MRI scans including T1-weighted and T2-weighted images provide detailed information of the spine and surrounding tissues. Artificial intelligence showed promise in improving image quality and simultaneously reducing scan time. This study evaluates the performance of deep learning (DL)-based T2 turbo spin-echo (TSE, T2 DLR ) and T1 TSE (T1 DLR ) in lumbar spine imaging regarding acquisition time, image quality, artifact resistance, and diagnostic confidence. Material and methods This retrospective monocentric study included 60 patients with lower back pain who underwent lumbar spinal MRI between February and April 2023. MRI parameters and DL reconstruction (DLR) techniques were utilized to acquire images. Two neuroradiologists independently evaluated image datasets based on various parameters using a 4-point Likert scale. Results Accelerated imaging showed significantly less image noise and artifacts, as well as better image sharpness, compared to standard imaging. Overall image quality and diagnostic confidence were higher in accelerated imaging. Relevant disk herniations and spinal fractures were detected in both DLR and conventional images. Both readers favored accelerated imaging in the majority of examinations. The lumbar spine examination time was cut by 61% in accelerated imaging compared to standard imaging. Conclusion In conclusion, the utilization of deep learning-based image reconstruction techniques in lumbar spinal imaging resulted in significant time savings of up to 61% compared to standard imaging, while also improving image quality and diagnostic confidence. These findings highlight the potential of these techniques to enhance efficiency and accuracy in clinical practice for patients with lower back pain.
