Neoadjuvant Carboplatin/Paclitaxel versus 5-Fluorouracil/Cisplatin in Combination with Radiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma:A Multicenter Comparative Study

SIMPLE SUMMARY: The most beneficial neoadjuvant chemoradiotherapy for Asian patients with esophageal squamous cell carcinoma remains uncertain. Using propensity score matching by inverse probability of treatment weighting to balance the baseline variables, the neoadjuvant carboplatin/paclitaxel (CROSS) regimen versus the cisplatin/5-fluorouracil (PF) regimen in combination with 41.4–50.4 Gy of radiotherapy were compared. We found that Taiwanese patients treated with the CROSS regimen (Carboplatin + Paclitaxel + 41.4–45.0 Gy) had less treatment-related complications and more favorable survival figures. Collectively, these results suggest that CROSS is safe and effective. ABSTRACT: Background: The most beneficial neoadjuvant chemoradiotherapy (nCRT) combination for esophageal squamous cell carcinoma (ESCC) in Asia remains uncertain. Herein, we compared the neoadjuvant carboplatin/paclitaxel (CROSS) regimen versus the cisplatin/5-fluorouracil (PF) regimen in combination with 41.4–50.4 Gy of radiotherapy. Methods: Patients were stratified according to their nCRT regimen: CROSS + 41.4–45.0 Gy (CROSS), PF + 45.0 Gy (PF4500) or PF + 50.4 Gy (PF5040). Propensity score matching by inverse probability of treatment weighting (IPTW) was used to balance the baseline variables. Results: Before IPTW, a total of 334 patients were included. The lowest chemotherapy completion rate was observed in the PF5040 group (76.2% versus 89.4% and 92.0% in the remaining two groups, respectively). Compared with CROSS, both PF groups showed more severe weight loss during nCRT and a higher frequency of post-esophagectomy anastomotic leaks. The use of PF5040 was associated with the highest rate of pathological complete response (45.3%). While CROSS conferred a significant overall survival benefit over PF4500 (hazard ratio [HR] = 1.30, 95% CI = 1.05 to 1.62, p = 0.018), similar survival figures were observed when compared with PF5040 (HR = 1.17, 95% CI = 0.94 to 1.45, p = 0.166). Conclusions: The CROSS regimen conferred a significant survival benefit over PF4500, although the similar survival figures were similar to those observed with PF5040. Considering the lower incidences of severe weight loss and post-esophagectomy anastomotic leaks, CROSS represents a safe and effective neoadjuvant treatment for Taiwanese patients with ESCC

Prompting and Adapter Tuning for Self-supervised Encoder-Decoder Speech Model

Prompting and adapter tuning have emerged as efficient alternatives to fine-tuning (FT) methods. However, existing studies on speech prompting focused on classification tasks and failed on more complex sequence generation tasks. Besides, adapter tuning is primarily applied with a focus on encoder-only self-supervised models. Our experiments show that prompting on Wav2Seq, a self-supervised encoder-decoder model, surpasses previous works in sequence generation tasks. It achieves a remarkable 53% relative improvement in word error rate for ASR and a 27% in F1 score for slot filling. Additionally, prompting competes with the FT method in the low-resource scenario. Moreover, we show the transferability of prompting and adapter tuning on Wav2Seq in cross-lingual ASR. When limited trainable parameters are involved, prompting and adapter tuning consistently outperform conventional FT across 7 languages. Notably, in the low-resource scenario, prompting consistently outperforms adapter tuning.Comment: Accepted to IEEE ASRU 202

IKKβ Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway

SummaryTNFα has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKKβ, a major downstream kinase in the TNFα signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKKβ-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKKβ is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR

Origin, Transport, and Vertical Distribution of Atmospheric Polluntants over the Northern Sourth China Sea During the 7-SEAS-Dongsha Experiment

During the spring of 2010, comprehensive in situ measurements were made for the first time on a small atoll (Dongsha Island) in the northern South China Sea (SCS), a key region of the 7-SEAS (the Seven South East Asian Studies) program. This paper focuses on characterizing the source origins, transport processes, and vertical distributions of the Asian continental outflows over the region, using measurements including mass concentration, optical properties, hygroscopicity, and vertical distribution of the aerosol particles, as well as the trace gas composition. Cluster analysis of backward trajectories classified 52% of the air masses arriving at ground level of Dongsha Island as having a continental origin, mainly from northern China to the northern SCS, passing the coastal area and being confined in the marine boundary layer (0-0.5 km). Compared to aerosols of oceanic origin, the fine mode continental aerosols have a higher concentration, extinction coefficient, and single-scattering albedo at 550 nm (i.e., 19 vs. 14 microg per cubic meter in PM(sub 2.5); 77 vs. 59 M per meter in beta(sub e); and 0.94 vs. 0.90 in omega, respectively). These aerosols have a higher hygroscopicity (f at 85% RH = 2.1) than those in the upwind inland regions, suggesting that the aerosols transported to the northern SCS were modified by the marine environment. In addition to the near-surface aerosol transport, a significant upper-layer (3-4 km) transport of biomass-burning aerosols was observed. Our results suggest that emissions from both China and Southeast Asia could have a significant impact on the aerosol loading and other aerosol properties over the SCS. Furthermore, the complex vertical distribution of aerosols-coinciding-with-clouds has implications for remote-sensing observations and aerosol-cloud-radiation interactions

The Efficacy of Endoscopic Papillary Balloon Dilation for Patients with Acute Biliary Pancreatitis

Background. No study investigated the efficacy and safety of endoscopic papillary balloon dilation (EPBD) for the treatment of acute biliary pancreatitis (ABP). Method. We retrospectively reviewed the effects of EPBD on patients with ABP from February 2003 to December 2012. The general data, findings of image studies, details of the procedure, and outcomes after EPBD were analyzed. Result. Total 183 patients (male/female: 110/73) were enrolled. The mean age was 65.9 years. Among them, 155 patients had mild pancreatitis. The meantime from admission to EPBD was 3.3 days. Cholangiogram revealed filling defects inside the common bile duct (CBD) in 149 patients. The mean dilating balloon size was 10.5 mm and mean duration of the dilating procedure was 4.3 minutes. Overall, 124 patients had gross stones retrieved from CBD. Four (2.2%) adverse events and 2 (1.1%) intraprocedure bleeding incidents but no procedure-related mortality were noted. Bilirubin and amylase levels significantly decreased after EPBD. On average, patients resumed oral intake within 1.4 days. The clinical parameters and outcomes were similar in patients with different severity of pancreatitis. Conclusion. EPBD can be effective and safe for the treatment of ABP, even in patients presenting with severe disease