Contemporary Management of Pediatric Brainstem Tumors.

Brain tumors are the second most common malignancy in childhood. Around 15-20% of pediatric brain tumors occur in the brainstem. The most common type of brainstem tumor are diffuse tumors in the ventral pons, whereas focal tumors tend to arise from the midbrain, medulla, and dorsal pons. Glioma is the most common pathological entity. Contemporary management consists of surgery, radiotherapy, chemotherapy, and other adjuvant treatment. Surgical options range from biopsy to radical excision. Biopsy can be performed for diagnostic and prognostic purposes, or in the setting of clinical trials, mainly for diffuse intrinsic pontine gliomas. For focal tumors, surgeons need to carefully balance clinical outcomes against possible neurological sequelae in order to achieve maximal safe resection. Radiotherapy is essential for control of high-grade tumors and may be applied to residual or recurrent low-grade tumors. Proton therapy may provide similar efficacy and less neurotoxicity in comparison to conventional photon therapy. Oncological treatment continues to evolve from conventional chemotherapy to targeted therapy, immunotherapy, and other novel treatment methods and holds great potential as adjuvant therapy for pediatric brainstem tumors.

Increasing Robustness of Intracortical Brain-Computer Interfaces for Recording Condition Changes via Data Augmentation.

BACKGROUND AND OBJECTIVE: Intracortical brain-computer interfaces (iBCIs) aim to help paralyzed individuals restore their motor functions by decoding neural activity into intended movement. However, changes in neural recording conditions hinder the decoding performance of iBCIs, mainly because the neural-to-kinematic mappings shift. Conventional approaches involve either training the neural decoders using large datasets before deploying the iBCI or conducting frequent calibrations during its operation. However, collecting data for extended periods can cause user fatigue, negatively impacting the quality and consistency of neural signals. Furthermore, frequent calibration imposes a substantial computational load. METHODS: This study proposes a novel approach to increase iBCIs' robustness against changing recording conditions. The approach uses three neural augmentation operators to generate augmented neural activity that mimics common recording conditions. Then, contrastive learning is used to learn latent factors by maximizing the similarity between the augmented neural activities. The learned factors are expected to remain stable despite varying recording conditions and maintain a consistent correlation with the intended movement. RESULTS: Experimental results demonstrate that the proposed iBCI outperformed the state-of-the-art iBCIs and was robust to changing recording conditions across days for long-term use on one publicly available nonhuman primate dataset. It achieved satisfactory offline decoding performance, even when a large training dataset was unavailable. CONCLUSIONS: This study paves the way for reducing the need for frequent calibration of iBCIs and collecting a large amount of annotated training data. Potential future works aim to improve offline decoding performance with an ultra-small training dataset and improve the iBCIs' robustness to severely disabled electrodes.

Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

Perfluorooctanesulfonic Acid Alters the Plant's Phosphate Transport Gene Network and Exhibits Antagonistic Effects on the Phosphate Uptake.

Per- and polyfluoroalkyl substances (PFASs), with significant health risks to humans and wildlife, bioaccumulate in plants. However, the mechanisms underlying plant uptake remain poorly understood. This study deployed transcriptomic analysis coupled with genetic and physiological studies using Arabidopsis to investigate how plants respond to perfluorooctanesulfonic acid (PFOS), a long-chain PFAS. We observed increased expressions of genes involved in plant uptake and transport of phosphorus, an essential plant nutrient, suggesting intertwined uptake and transport processes of phosphorus and PFOS. Furthermore, PFOS-altered response differed from the phosphorus deficiency response, disrupting phosphorus metabolism to increase phosphate transporter (PHT) transcript. Interestingly, pht1;2 and pht1;8 mutants showed reduced sensitivity to PFOS compared to that of the wild type, implying an important role of phosphate transporters in PFOS sensing. Furthermore, PFOS accumulated less in the shoots of the pht1;8 mutant, indicating the involvement of PHT1;8 protein in translocating PFOS from roots to shoots. Supplementing phosphate improved plant's tolerance to PFOS and reduced PFOS uptake, suggesting that manipulating the phosphate source in PFOS-contaminated soils may be a promising strategy for minimizing PFOS uptake by edible crops or promoting PFOS uptake during phytoremediation. This study highlighted the critical role of phosphate sensing and transport system in the uptake and translocation of PFOS in plants.

Root exudates enhanced 6:2 FTOH defluorination, altered metabolite profiles and shifted soil microbiome dynamics.

6:2 Fluorotelomer alcohol (FTOH), one of per- and polyfluoroalkyl substances (PFAS), is widely used as a raw material in synthesizing surfactants and fluorinated polymers. However, little is known about the role of root exudates on 6:2 FTOH biodegradation in the rhizosphere. This study examined the effects of root exudates produced from dicot (Arabidopsis thaliana) and monocot (Brachypodium distachyon) grown under different nutrient conditions (nutrient-rich, sulfur-free, and potassium-free) on 6:2 FTOH biotransformation with or without bioaugmentating agent Rhodococcus jostii RHA1. All the exudates enhanced defluorination of 6:2 FTOH by glucose-grown RHA1. Amendment of dicot or monocot root exudates, regardless of the plant growth conditions, also enhanced 6:2 FTOH biotransformation in soil microcosms. Interestingly, high levels of humic-like substances in the root exudates are linked to high extents of 6:2 FTOH defluorination. Bioaugmenting strain RHA1 along with root exudates facilitated 6:2 FTOH transformation with a production of more diverse metabolites. Microbial community analysis revealed that Rhodococcus was predominant in all strain RHA1 spiked treatments. Different root exudates changed the soil microbiome dynamics. This study provided new insight into 6:2 FTOH biotransformation with different root exudates, suggesting that root exudates amendment and bioaugmentation are promising approaches to promote rhizoremediation for PFAS-contaminated soil.

Engineering stable and non-immunogenic immunoenzymes for cancer therapy via in situ generated prodrugs.

Engineering human enzymes for therapeutic applications is attractive but introducing new amino acids may adversely affect enzyme stability and immunogenicity. Here we used a mammalian membrane-tethered screening system (ECSTASY) to evolve human lysosomal beta-glucuronidase (hBG) to hydrolyze a glucuronide metabolite (SN-38G) of the anticancer drug irinotecan (CPT-11). Three human beta-glucuronidase variants (hBG3, hBG10 and hBG19) with 3, 10 and 19 amino acid substitutions were identified that display up to 40-fold enhanced enzymatic activity, higher stability than E. coli beta-glucuronidase in human serum, and similar pharmacokinetics in mice as wild-type hBG. The hBG variants were two to three orders of magnitude less immunogenic than E. coli beta-glucuronidase in hBG transgenic mice. Intravenous administration of an immunoenzyme (hcc49-hBG10) targeting a sialyl-Tn tumor-associated antigen to mice bearing human colon xenografts significantly enhanced the anticancer activity of CPT-11 as measured by tumor suppression and mouse survival. Our results suggest that genetically-modified human enzymes represent a good alternative to microbially-derived enzymes for therapeutic applications.

Remediation of PFAS-impacted soils using magnetic activated carbon (MAC) and hydrothermal alkaline treatment (HALT).

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic pollutants that are bioaccumulative, toxic, and persistent. One long-term source for PFAS release is PFAS-contaminated soil. Addition of activated carbon (AC) to soil has shown the potential to immobilize PFAS and reduce PFAS bioavailability, but PFAS-loaded spent AC remaining in the treated soil could lead to remobilization. Here we report a novel approach to address this challenge. By applying magnetic activated carbon (MAC) to remediate PFAS-impacted soil, the PFAS-loaded MAC can be retrieved from the treated soil and sorbed PFAS in the spent MAC can be destroyed using hydrothermal alkaline treatment (HALT). Effective MAC recovery was observed when water/soil ratios (w/w) were either <0.07 or > 1. Soil organic content and pH affected PFAS adsorption by the MAC added to soil. After three months of incubation with MAC, high PFAS removals [PFOS (87.6 %), PFOA (83.8 %), and 6:2 FTSA (81.5 %)] were observed for acidic environmental sandy soils with low organic content. In contrast, PFAS removal by MAC was poor for garden soils with high organic matter content. MAC was also used to remediate aqueous film-forming foam (AFFF)-impacted and PFAS-contaminated aged soils with varying PFAS removal performance. HALT technology was able to destroy and defluorinate PFAS adsorbed to the spent MAC. Additionally, the HALT-treated MAC retained its magnetic properties and PFOS sorption capacity, suggesting the potential reusability of HALT-treated MAC. Considering the low energy footprint of HALT compared to conventional PFAS thermal destruction techniques, the combination of MAC and HALT could be a promising treatment train for PFAS-contaminated soils.

Metastatic spinal cord compression as the first manifestation of malignancy: A retrospective study of surgical outcome from single institution.

BACKGROUND: Given the limited studies addressing the issue about the effect of different surgical modalities for metastatic spinal cord compression (MSCC) as the first malignancy manifestation, we conducted a retrospective case-control study to evaluate the surgical outcome of MSCC as the first malignancy manifestation. METHODS: A total of 128 patients who were suspected of having metastatic spinal cord compression and underwent surgery from 2008 to 2021 were enrolled in the study. All patients were categorized into either 'debulking group' or 'palliative group'. RESULTS: The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), Frankel scale, and Karnofsky scores. All the outcomes were analyzed with a data cutoff of December 31, 2021. There was a significant difference between groups in progression-free survival (PFS) (p = 0.0094). However, there was no significant difference between groups in the overall survival (OS) (p = 0.0746). Age of onset, gender, duration of symptoms, and location of spinal metastasis, initial Frankel, initial Tomita scores, and initial Karnofsky performance scale showed no significant differences between groups. CONCLUSION: In conclusion, debulking surgery was shown to provide better neurological recoveries and could be considered first in patients with metastatic spinal cord compression as the first malignancy manifestation.

Spinal metastases from non-small cell lung cancer - Is surgical extent enough by following suggestions of the Tomita and Tokuhashi scores?

BACKGROUND/OBJECTIVE: The Tomita, revised Tokuhashi and Tokuhashi lung scores are commonly used tools to predict the survival of patients with spinal metastases and to guide decisions regarding surgical treatment. These prognostic scores, however, tend to underestimate the prognosis of patients with lung cancer. We examined surgical outcome and hopefully provide a more accurate reference for management. METHODS: The consistency between predicted and actual survival was examined using the Tomita and Tokuhashi scores. Various factors that may influence survival were analyzed. Primary outcomes were overall survival (OS) and progression-free survival (PFS), defined as the ambulatory time after the initial surgery. Secondary outcomes included reoperation events, blood loss, and hospitalization days. RESULTS: One hundred seventy-two patients were enrolled. Correct survival predictions were made for 28%, 42%, and 56% with the Tomita, revised Tokuhashi, and Tokuhashi lung scores, respectively. The Tokuhashi lung scores underestimated OS by 35%-40%. Body mass index ≥20, systemic treatment-naïve, good general condition, the use of denosumab, and adenocarcinoma were found to positively affect OS and PFS. There was no significant difference between palliative decompression and excisional surgery regarding OS and PFS. CONCLUSION: Patients with spinal metastases from lung cancer had better prognosis than that predicted by the Tomita and Tokuhashi scores. Spine surgeons should acknowledge this discrepancy and treat these patients with at least the aggressiveness suggested. Patients with adenocarcinoma, amenable to target therapy, denosumab, good general condition, systemic treatment-naïve are better candidates for surgery. Those with cachexic status and unresectable visceral metastases are worse candidates.

Enhancing Prediction of Forelimb Movement Trajectory through a Calibrating-Feedback Paradigm Incorporating RAT Primary Motor and Agranular Cortical Ensemble Activity in the Goal-Directed Reaching Task.

Complete reaching movements involve target sensing, motor planning, and arm movement execution, and this process requires the integration and communication of various brain regions. Previously, reaching movements have been decoded successfully from the motor cortex (M1) and applied to prosthetic control. However, most studies attempted to decode neural activities from a single brain region, resulting in reduced decoding accuracy during visually guided reaching motions. To enhance the decoding accuracy of visually guided forelimb reaching movements, we propose a parallel computing neural network using both M1 and medial agranular cortex (AGm) neural activities of rats to predict forelimb-reaching movements. The proposed network decodes M1 neural activities into the primary components of the forelimb movement and decodes AGm neural activities into internal feedforward information to calibrate the forelimb movement in a goal-reaching movement. We demonstrate that using AGm neural activity to calibrate M1 predicted forelimb movement can improve decoding performance significantly compared to neural decoders without calibration. We also show that the M1 and AGm neural activities contribute to controlling forelimb movement during goal-reaching movements, and we report an increase in the power of the local field potential (LFP) in beta and gamma bands over AGm in response to a change in the target distance, which may involve sensorimotor transformation and communication between the visual cortex and AGm when preparing for an upcoming reaching movement. The proposed parallel computing neural network with the internal feedback model improves prediction accuracy for goal-reaching movements.

Traits of Patients With Pituitary Tumors in Multiple Endocrine Neoplasia Type 1 and Comparing Different Mutation Status.

CONTEXT: Recent studies suggest that the clinical characteristics and biological behavior of pituitary tumors (PITs) in patients with multiple endocrine neoplasia type 1 (MEN1) may not be as aggressive as previously reported. Increased imaging of the pituitary as recommended by screening guidelines identifies more tumors, potentially at an earlier stage. However, it is unknown if these tumors have different clinical characteristics in different MEN1 mutations. OBJECTIVE: To assess characteristics of patients with MEN1 with and without PITs, and compare among different MEN1 mutations. METHODS: Data of patients with MEN1 in a tertiary referral center from 2010 to 2023 were retrospectively analyzed. RESULTS: Forty-two patients with MEN1 were included. Twenty-four patients had PITs, 3 of which were invasive and managed with transsphenoidal surgery. One PIT enlarged during follow-up. Patients with PITs had a higher median age at MEN1 diagnosis than those without PITs. MEN1 mutations were identified in 57.1% of patients, including 5 novel mutations. In patients with PITs, those with MEN1 mutations (mutation+/PIT+ group) had more additional MEN1-associated tumors than those without (mutation-/PIT+ group). The mutation+/PIT+ group had a higher incidence of adrenal tumors and a lower median age at initial manifestation of MEN1 than the mutation-/PIT+ group. The most common neuroendocrine neoplasm was nonfunctional in the mutation+/PIT+ group and insulin-secreting in the mutation-/PIT+ group. CONCLUSION: This is the first study comparing characteristics of patients with MEN1 with and without PITs harboring different mutations. Patients without MEN1 mutations tended to have less organ involvement and it might be reasonable for them to receive less intensive follow-up.

Real-World Data Validation of NAPOLI-1 Nomogram for the Prediction of Overall Survival in Metastatic Pancreatic Cancer.

BACKGROUND: The nomogram derived from the pivotal phase III NAPOLI-1 study demonstrated a significant ability to predict median overall survival (OS) in gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) treated with liposomal irinotecan plus fluorouracil and leucovorin (nal-IRI+5-FU/LV). However, the NAPOLI-1 nomogram has not been validated in a real-world setting and therefore the applicability of the NAPOLI-1 nomogram in daily practice remains unknown. This study aims to evaluate the NAPOLI-1 nomogram in a multicenter real-world cohort. METHODS: The NAPOLI-1 nomogram was applied to a previously established cohort of metastatic PDAC patients treated with nal-IRI+5-FU/LV in nine participating centers in Taiwan. Patients were divided into three risk groups according to the NAPOLI-1 nomogram. The survival impact of relative dose intensity at 6 weeks (RDI at 6 weeks) in different risk groups was also investigated. RESULTS: Of the 473 included patients, the median OSs of patients classified as low (n = 156), medium (n = 186), and high (n = 131) risk were 10.9, 6.3, and 4.3 months, respectively (p < 0.0001). The survival impact of RDI at 6 weeks remained significant after stratification by risk groups, adjustment with Cox regression, inverse probability weighting, or propensity score matching. CONCLUSIONS: Our results support the usefulness of the NAPOLI-1 nomogram for risk stratification in gemcitabine-refractory metastatic PDAC treated with nal-IRI+5-FU/LV in daily practice. We further showed that the RDI at 6 weeks is an independent prognostic factor beyond the NAPOLI-1 nomogram.

Systemic treatments in pancreatic cancer: Taiwan pancreas society recommendation.

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis. Over the past decade, significant therapeutic advancements have improved the survival rates of patients with pancreatic cancer. One of the primary factors contributing to these positive outcomes is the evolution of chemotherapy, from monotherapy to doublet or triplet regimens, and the integration of multimodal approaches. Additionally, targeted agents tailored to patients with specific genetic alterations and the development of cell therapies show promise in benefiting certain subpopulations. This article focuses on examining pivotal studies that explore the role of chemotherapy in neoadjuvant, adjuvant, maintenance, and salvage settings; highlights interesting findings related to cell therapy; and provides an overview of ongoing trials concerning metastatic settings. This review primarily aimed to offer recommendations based on therapeutic evidence, recent advancements in new treatment combinations, and the most innovative approaches. A unique aspect of this review is the inclusion of published papers on clinical trials and real-world data in Taiwan, thus adding a valuable perspective to the overall analysis.

Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes.

OBJECTIVE: The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. METHODS: The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. RESULTS: A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). CONCLUSION: The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.

Maintenance therapy of low-dose nivolumab, S-1, and leucovorin in metastatic pancreatic adenocarcinoma with a germline mutation of MSH6: A case report.

Immune checkpoint inhibitors (ICIs) provide substantial benefits to a small subset of patients with advanced cancer with mismatch repair deficiency (MMRD) or microsatellite instability (MSI), including patients with pancreatic ductal adenocarcinoma (PDAC). However, the long duration of ICI treatment presents a considerable financial burden. We present the case of a 63-year-old woman with metastatic PDAC refractory to conventional chemotherapy. Genetic analyses identified an MSH6 germline mutation and a high tumor mutation burden (TMB). Complete response (CR) was achieved after a short course of low-dose nivolumab (20 mg once every 2 weeks) with chemotherapy. CR was maintained for over 1 year with low-dose nivolumab and de-escalated chemotherapy without any immune-related adverse events. This case supports the further exploration of low-dose, affordable ICI-containing regimens in patients with advanced MSI-high/TMB-high cancer.

Improved nasal recovery and intact olfactory function after a transseptal approach for endoscopic endonasal transsphenoidal adenomectomy: A retrospective analysis.

Objectives: Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery, and researchers have recently focused on preserving nasal function. The endoscopic transseptal approach is a promising procedure due to its reduced injury to the nasal mucosa; however, there are no studies comparing rhinological and neurosurgical outcomes concurrently with the standard endoscopic transnasal approach. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Methods: We retrospectively reviewed 25 patients who underwent endoscopic endonasal transseptal TSA for pituitary adenoma without encasement of internal carotid artery from January 2019 to December 2020. Another 25 patients who received transnasal approach from January 2017 to December 2018 were selected as controls. Patients with diseases affecting the nasal cavity/olfaction or usage of a nasoseptal flap were excluded for a better comparison of the two procedures. We collected data from radiological studies, endocrine studies, endoscopic evaluations, 22-item sinonasal outcome tests (SNOT-22) and Top International Biotech Smell Identification Test (TIBSIT) for comparison. Results: Lower postoperative SNOT-22 and Lund-Kennedy endoscopic scores were observed in the transseptal group. The effect size of differences were classified as large effect (The absolute value of Cohen's d > 0.8). Nevertheless, the TIBSIT scores were not significantly different. The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. After controlling possible confounding factors using multivariate analysis, the endoscopic transseptal approach remained an independent factor for lower SNOT-22 scores and Lund-Kennedy endoscopic scores. Conclusions: The endoscopic transseptal approach provides improved recovery of nasal mucosa and intact olfaction without compromising neurosurgical outcomes. Level of Evidence: 2b.

The impact of starting dose with or without subsequent dose escalation of liposomal irinotecan on treatment outcomes in patients with metastatic pancreatic ductal adenocarcinoma.

Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) improves survival in patients with pancreatic ductal adenocarcinoma (PDAC) after progression to gemcitabine-based therapy. Few studies have examined whether the starting dose and dose escalation of nal-IRI in subsequent treatment cycles may influence patient outcomes and toxicity profiles. A total of 667 patients who received nal-IRI + 5-FU/LV for PDAC treatment between August 2018 and November 2020 at nine medical centers in Taiwan were included and retrospectively analyzed. Patients were allocated to the standard starting dose (SD), reduced starting dose (RD) without escalation, and RD with escalation of nal-IRI groups for comparison of survival outcome and safety. Propensity score matching (PSM) was performed to adjust for possible confounding variables. Nal-IRI was prescribed at SD, RD without escalation, and RD with escalation in 465 (69.7%), 147 (22.0), and 55 (8.2%), respectively. RD with escalation patients had significantly longer treatment cycles (6, range 2-25) than SD (5, range 1-42, P<0.001) and RD without escalation patients (4, range 1-26, P<0.001). The median overall survival (OS) of the patients were as follows: SD, 6.2 months (95% confidence interval [CI], 5.7-6.7); RD with escalation, 7.6 months (95% CI, 6.1-9.2); and RD without escalation, 3.6 months (95% CI, 2.6-4.5). After PSM to adjust for potential confounders, RD without escalation patients still had the poorest OS compared to the other two groups (P<0.001), while the OS difference between SD and RD with escalation patients was insignificant (P=0.10). SD patients had higher incidences of ≥ grade 3 neutropenia and febrile neutropenia than the other two groups. Administering nal-IRI at RD followed by dose escalation in subsequent treatment cycles is safe and does not compromise survival outcomes in selected patients with PDAC receiving nal-IRI plus 5-FU/LV.

Predictive value of albumin combined with neutrophil-to-lymphocyte ratio for efficacy and safety profiles in patients with pancreatic ductal adenocarcinoma receiving liposomal irinotecan plus 5-fluorouracil and leucovorin.

Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) treatment has demonstrated survival benefits but noticeable side effects in patients with pancreatic ductal adenocarcinoma (PDAC) that is refractory to gemcitabine-based therapy. This study aimed to explore whether combining albumin with the neutrophil-to-lymphocyte ratio (NLR), herein known as the albumin and neutrophil-to-lymphocyte ratio score (ANS), could be utilized as a simple tool to predict survival and safety profiles in such patient groups. We retrospectively enrolled 434 consecutive PDAC patients treated with nal-IRI + 5-FU/LV between 2018 and 2020 at nine medical centers in Taiwan. Patients were divided into three groups: ANS 0 (high albumin and low NLR), ANS 1 (low albumin or high NLR), and ANS 2 (low albumin and high NLR), for comparison. The median overall survival times for the ANS 0, 1, and 2 groups were 8.7 months (95% confidence interval (CI), 7.0-10.3 months), 5.2 months (95% CI, 4.3-6.0 months), and 2.6 months (95% CI, 1.9-3.3 months), respectively. The ANS was found to be an independent variable for overall survival and time-to-treatment failure in multivariate analyses. Patients in the ANS 2 group had significantly higher incidences of grade 3 or higher treatment-related adverse events than those in the other two groups. The present study showed that the ANS was an independent prognosticator in PDAC patients receiving nal-IRI + 5-FU/LV therapy. The ANS can be a simple predictor of survival outcome and safety profiles in PDAC patients treated with nal-IRI + 5-FU/LV.

Neuro-Inspired Reinforcement Learning to Improve Trajectory Prediction in Reward-Guided Behavior.

Hippocampal pyramidal cells and interneurons play a key role in spatial navigation. In goal-directed behavior associated with rewards, the spatial firing pattern of pyramidal cells is modulated by the animal's moving direction toward a reward, with a dependence on auditory, olfactory, and somatosensory stimuli for head orientation. Additionally, interneurons in the CA1 region of the hippocampus monosynaptically connected to CA1 pyramidal cells are modulated by a complex set of interacting brain regions related to reward and recall. The computational method of reinforcement learning (RL) has been widely used to investigate spatial navigation, which in turn has been increasingly used to study rodent learning associated with the reward. The rewards in RL are used for discovering a desired behavior through the integration of two streams of neural activity: trial-and-error interactions with the external environment to achieve a goal, and the intrinsic motivation primarily driven by brain reward system to accelerate learning. Recognizing the potential benefit of the neural representation of this reward design for novel RL architectures, we propose a RL algorithm based on [Formula: see text]-learning with a perspective on biomimetics (neuro-inspired RL) to decode rodent movement trajectories. The reward function, inspired by the neuronal information processing uncovered in the hippocampus, combines the preferred direction of pyramidal cell firing as the extrinsic reward signal with the coupling between pyramidal cell-interneuron pairs as the intrinsic reward signal. Our experimental results demonstrate that the neuro-inspired RL, with a combined use of extrinsic and intrinsic rewards, outperforms other spatial decoding algorithms, including RL methods that use a single reward function. The new RL algorithm could help accelerate learning convergence rates and improve the prediction accuracy for moving trajectories.