Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

BACKGROUND: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. METHODS: In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. RESULTS: Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. CONCLUSIONS: Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

Sugar-coated bullets: Unveiling the enigmatic mystery 'sweet arsenal' in osteoarthritis.

Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, a series of enzymes are involved in adding, modifying, or removing sugar residues. This process plays a pivotal role in various biological functions, influencing the structure, stability, and functionality of the modified molecules. Glycosylation is essential in numerous biological processes, including cell adhesion, signal transduction, immune response, and biomolecular recognition. Dysregulation of glycosylation is associated with various diseases. Glycation, a post-translational modification characterized by the non-enzymatic attachment of sugar molecules to proteins, has also emerged as a crucial factor in various diseases. This review comprehensively explores the multifaceted role of glycation in disease pathogenesis, with a specific focus on its implications in osteoarthritis (OA). Glycosylation and glycation alterations wield a profound influence on OA pathogenesis, intertwining with disease onset and progression. Diverse studies underscore the multifaceted role of aberrant glycosylation in OA, particularly emphasizing its intricate relationship with joint tissue degradation and inflammatory cascades. Distinct glycosylation patterns, including N-glycans and O-glycans, showcase correlations with inflammatory cytokines, matrix metalloproteinases, and cellular senescence pathways, amplifying the degenerative processes within cartilage. Furthermore, the impact of advanced glycation end-products (AGEs) formation in OA pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior and extracellular matrix remodeling. These findings illuminate potential therapeutic targets and diagnostic markers, signaling a promising avenue for targeted interventions in OA management. In this comprehensive review, we aim to thoroughly examine the significant impact of glycosylation or AGEs in OA and explore its varied effects on other related conditions, such as liver-related diseases, immune system disorders, and cancers, among others. By emphasizing glycosylation's role beyond OA and its implications in other diseases, we uncover insights that extend beyond the immediate focus on OA, potentially revealing novel perspectives for diagnosing and treating OA.

Tailoring d-band center of high-valent metal-oxo species for pollutant removal via complete polymerization.

Polymerization-driven removal of pollutants in advanced oxidation processes (AOPs) offers a sustainable way for the simultaneous achievement of contamination abatement and resource recovery, supporting a low-carbon water purification approach. However, regulating such a process remains a great challenge due to the insufficient microscopic understanding of electronic structure-dependent reaction mechanisms. Herein, this work probes the origin of catalytic pollutant polymerization using a series of transition metal (Cu, Ni, Co, and Fe) single-atom catalysts and identifies the d-band center of active site as the key driver for polymerization transfer of pollutants. The high-valent metal-oxo species, produced via peroxymonosulfate activation, are found to trigger the pollutant removal via polymerization transfer. Phenoxyl radicals, identified by the innovative spin-trapping and quenching approaches, act as the key intermediate in the polymerization reactions. More importantly, the oxidation capacity of high-valent metal-oxo species can be facilely tuned by regulating their binding strength for peroxymonosulfate through d-band center modulation. A 100% polymerization transfer ratio is achieved by lowering the d-band center. This work presents a paradigm to dynamically modulate the electronic structure of high-valent metal-oxo species and optimize pollutant removal from wastewater via polymerization.

A multicenter propensity score analysis of significance of hepatic resection type for early-stage hepatocellular carcinoma.

BACKGROUND: The impact of hepatic resection type on long-term oncological prognosis of patients with early-stage hepatocellular carcinoma (HCC) has not been systematically investigated. We sought to determine risk factors, recurrence patterns, and survival outcomes after anatomical resection (AR) versus non-anatomical resection (NAR) for early-stage HCC. METHODS: From a prospectively collected multicenter database, consecutive patients undergoing curative hepatectomy for early-stage HCC were identified. Recurrence patterns, overall survival (OS), recurrence-free survival (RFS), and risk factors were investigated in patients undergoing AR versus NAR using propensity score matching (PSM), subgroup analysis, and COX regression analysis. RESULTS: A total of 3585 patients with early-stage HCC were enrolled, including 1287 and 2298 in the AR and NAR groups, respectively. After PSM, the OS and RFS of patients in the AR group were 58.8% and 42.7%, which were higher than those in the NAR group (52.2% and 30.6%, both p < 0.01). The benefits of AR were consistent across most subgroup analyses of OS and RFS. Multivariable COX regression analysis showed that AR was independently associated with better OS and RFS. Notably, although recurrence patterns were comparable, the risk factors for recurrence were not identical for AR versus NAR. Microvascular invasion and narrow resection margin were only associated with a higher recurrence rate after NAR. CONCLUSIONS: This study demonstrated that AR decreases the risk of tumor recurrence and improves OS and RFS in patients with early-stage HCC. AR should be adopted as long as such a surgical maneuver is feasible for initial treatment of early-stage HCC.

Impact of Hepatic Pedicle Clamping on Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma: Stratified Analysis Based on Intraoperative Blood Transfusion Status.

BACKGROUND: Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered. PATIENTS AND METHODS: Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses. RESULTS: Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT. CONCLUSIONS: The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.

The effect of incentives on intertemporal choice: Choice, confidence, and eye movements.

Despite various studies examining intertemporal choice with hypothetical rewards due to problematic real reward delivery, there remains no substantial evidence on the effect of the incentives on the decision confidence and cognitive process in intertemporal choice and no comprehensive exploration on the loss domain. Hence, this study conducts an eye-tracking experiment to examine the effect of incentive approach and measure participants' decision confidence using a between-subject design in both gain and loss domains. Results replicated previous findings which show incentives do not affect intertemporal choice in the gain domain. In contrast, in the loss domain, participants in the incentivized group were more likely to choose the larger-later options than those in the non-incentivized group. Furthermore, the decision confidence and the mean fixation duration differed between the incentivized and non-incentivized groups in both gain and loss domains. These findings allow for a better understanding of the effect of incentives on intertemporal choice and provide valuable information for the design of incentives in future intertemporal experiments.

Cognitive process underlying ultimatum game: An eye-tracking study from a dual-system perspective.

According to the dual-system theories, the decisions in an ultimatum game (UG) are governed by the automatic System 1 and the controlled System 2. The former drives the preference for fairness, whereas the latter drives the self-interest motive. However, the association between the contributions of the two systems in UG and the cognitive process needs more direct evidence. In the present study, we used the process dissociation procedure to estimate the contributions of the two systems and recorded participants eye movements to examine the cognitive processes underlying UG decisions. Results showed that the estimated contributions of the two systems are uncorrelated and that they demonstrate a dissociated pattern of associations with third variables, such as reaction time (RT) and mean fixation duration (MFD). Furthermore, the relative time advantage (RTA) and the transitions between the two payoffs can predict the final UG decisions. Our findings provide evidence for the independent contributions of preference for fairness (System 1) and self-interest maximizing (System 2) inclinations to UG and shed light on the underlying processes.

Evaluation Scale or Output Format: The Attentional Mechanism Underpinning Time Preference Reversal.

Time preference reversals refers to systematic inconsistencies between preferences and valuations in intertemporal choice. When faced with a pair of intertemporal options, people preferred the smaller-sooner option but assign a higher price to the larger-later one. Different hypotheses postulate that the differences in evaluation scale or output format between the choice and the bid tasks cause the preference reversal. However, these hypotheses have not been distinguished. In the present study, we conducted a hybrid task, which shares the same evaluation scale with the bid task and shares the same output format with the choice task. By comparing these three tasks, we can figure out the key reason for time preference reversal. The eye-tracking measures reflecting attention allocation, cognitive effort and information search pattern were examined. Results showed that participants' time preference and eye-tracking measures in the hybrid task were similar to those in the choice task, but different from those in the bid task. Our findings suggest that the output format is the core reason for time preference reversal and may deepen our understanding of the mechanisms that underlie time preference reversal.

The Clinical Efficacy of Minimally Invasive Clamp-Assisted Reduction and Open Reduction with Wire Cerclage for Unstable Subtrochanteric Fractures.

The purpose of this study was to compare the clinical effectiveness of minimally invasive clamp-assisted reduction and open reduction with wire cerclage and intramedullary nails for unstable subtrochanteric fractures. Between January 2016 and October 2019, 68 patients who had unstable subtrochanteric fractures experienced intramedullary nail surgery in this retrospective study. There were 41 cases in the minimally invasive clamp or closed reduction group (group A) and 27 cases in the open reduction with wire cerclage group (group B). There were 3 cases of complications in group A and 2 cases of complications in group B. Remarkable distinction was observed between the two groups in the operation time (p < 0.05), quality of reduction (p < 0.05), and union time (p < 0.05). For the successful surgical treatment of unstable femoral subtrochanteric fractures, an anatomical reduction is crucial. Reduction and wire cerclage are cut to give medial support for the anatomical reduction, which has a positive effect on fracture healing.

Influence of the Manner of Information Presentation on Risky Choice.

We are constantly faced with decisive situations in which the options are not presented simultaneously. How the information of options is presented might influence the subsequent decision-making. For instance, presenting the information of options in an alternative- or dimension-wise manner may affect searching patterns and thus lead to different choices. In this study, the effects of this manner of information presentation on risky choice according to two experiments (Experiment 1, N = 45; Experiment 2, N = 50) are systematically examined. Specifically, two tasks with different presentation are conducted. Participants could search the information of one option (alternative-wise task) or dimension (dimension-wise task) for each time. Results revealed that the participants assigned in the alternative-wise task exhibited more choices consistent with expected value theory and took a longer decision time than those in the dimension-wise task. Moreover, the effect of task on choice was mediated by the direction of information search. These findings suggest a relationship between information search pattern and risky choice and allow for a better understanding of the mechanisms and processes involved in risky choice.

Measurement of Spin Chern Numbers in Quantum Simulated Topological Insulators.

The topology of quantum systems has become a topic of great interest since the discovery of topological insulators. However, as a hallmark of the topological insulators, the spin Chern number has not yet been experimentally detected. The challenge to directly measure this topological invariant lies in the fact that this spin Chern number is defined based on artificially constructed wave functions. Here we experimentally mimic the celebrated Bernevig-Hughes-Zhang model with cold atoms, and then measure the spin Chern number with the linear response theory. We observe that, although the Chern number for each spin component is ill defined, the spin Chern number measured by their difference is still well defined when both energy and spin gaps are nonvanished.

Efficacy and Safety Aiming at the Combined-Modality Therapy of External Beam Radiotherapy (40Gy) and Iodine-125 Seed Implantation for Locally Advanced NSCLC in the Elderly.

PURPOSE: To evaluate the efficacy and safety of combined-modality therapy for elderly patients with locally advanced non-small-cell lung cancer (NSCLC) invading the chest wall. PATIENTS AND METHODS: We retrospectively enrolled 21 elderly patients (aged ≥60 years) with locally advanced NSCLC invading the chest wall. For external beam radiotherapy (EBRT) of the primary tumor, 40Gy was applied and supplemented with iodine-125 seed implantation while 60Gy was applied to the lymph nodes of the mediastinum. Follow-up was conducted every 3 months postoperatively. The related analytic parameters were change in tumor size, the objective response rate (ORR), the disease control rate (DCR), the degree of pain relief, the improvement of physical status, and toxicity. RESULTS: The combined-modality therapy significantly inhibited local growth of the tumor (from 7.84±1.20 to 4.69±1.90 cm) (P <0.0001), with 71.4% ORR and 90.5% DCR at 1 year. The cancer-related pain was significantly relieved (P <0.05) and physical status was significantly improved (P <0.05). No procedure-associated death or grade > 2 irradiation-related adverse effects were reported in this study. CONCLUSION: The combined-modality therapy of EBRT with 40Gy and permanent iodine-125 seed implantation is an efficacious and safe treatment option for elderly patients with locally advanced NSCLC invading the chest wall.

Validation of the Chinese version of the Short-Form Health Literacy in Dentistry (HeLD) scale.

OBJECTIVES: As an important part of health literacy, oral health literacy has been adapted to dental practice and research. The 14-item short version of the Health Literacy in Dentistry (HeLD) scale demonstrated excellent reliability, validity and precision when tested among English-speaking populations. However, an appropriate and reliable assessment of this scale in other language contexts remains lacking. The reliability and validity of the Chinese version of HeLD (HeLD-C) for the Chinese population must therefore be examined. METHODS: The short version of HeLD was translated into Chinese, and one item was deleted because of its unsuitability for the Chinese healthcare system. The psychometric properties of HeLD-C were evaluated in a sample of 404 Chinese participants aged from 19 to 72 years. The item selection analyses were performed by comparing the difference of each item between the high- and low-score groups. The internal consistency reliability was assessed using the Cronbach's alpha coefficient. Construct validity was assessed using exploratory structural equation modelling. For the criterion validity, correlations between the HeLD-C and the criterion validity scales, including the eHealth Literacy Scale (eHEALS), oral hygiene maintenance habits, and oral health status were tested using Pearson's correlation. RESULTS: Results of item selection reveal significant differences among all items between the high- and low-score groups (Ps < .001). The internal consistency reliability of HeLD-C was measured using Cronbach's α (0.92), whereas its construct validity was measured using χ2 [df] (3.30), comparative fit index (0.95), Tucker-Lewis index (0.94), root mean square error of approximation (0.08), and standardized root mean square residual (0.05). The criterion validity analyses show that HeLD-C is correlated with the criterion validity scales, including eHEALS, oral hygiene maintenance habits and oral health status (Ps < .001). CONCLUSIONS: Chinese version of HeLD is a reliable and valid instrument for measuring the oral health literacy of the Chinese adult population.

[Cortical 5-hydroxytryptamine receptor 3A (Htr3a) positive inhibitory neurons: diversity in type and function].

Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a+ inhibitory neurons are mainly derived from the caudal ganglionic eminence (CGE). This highly heterogeneous group of inhibitory neurons are comprised of many different subtypes with distinct molecular signatures, morphological and electrophysiological properties and connectivity patterns. In this review, we summarized recent research progress regarding cortical Htr3a+ inhibitory neurons, focusing on their molecular, morphological and electrophysiological diversity, and introduced some genetic mouse tools that were used to study Htr3a+ inhibitory neurons.

The power of last fixation: Biasing simple choices by gaze-contingent manipulation.

Among the established findings in eye movement during decision-making, decision-makers are likely to choose the last fixated option, and this phenomenon has proven robust. However, the causal link between last fixation and choices requires further examination. In Study 1 (N = 40), a gaze-contingent manipulation paradigm was developed by controlling the timing of decision prompts to manipulate the last fixation. The results showed that participants' value-based choices were biased toward the last fixated option. However, the manipulation in Study 1 may disturb their decision process, leading to an unnatural decision environment. In Study 2 (N = 40), the gaze-contingent paradigm was further developed to manipulate the last fixation by directing an additional fixation on the target option after the participants' decision prompts. The results showed that participants' choices were also biased in the uninterrupted decisions. Our findings suggest a causal link between last fixation and value-based choices.

The timing of gaze-contingent decision prompts influences risky choice.

Risky decisions are ubiquitous in daily life and are central to human behavior, but little attention has been devoted to exploring whether risky choice can be influenced by gaze direction. In the current study, we used gaze-contingent manipulation to manipulate an individual's gaze while he/she decided between two risky options, and we examined whether risky decisions could be biased toward a randomly determined target. We found that participants' risky choices were biased toward a randomly determined target when they were manipulated to gaze longer at the target option (Study 1, N=37; Study 3, N=40) or at the target outcome dimension (Study 2, N=37). We also found that both the relative time advantage and the location of the last fixation mediated the effect of the gaze-contingent manipulation on risky choice in the valid trials. However, the mediation effects of the relative time advantage and the location of the last fixation were not significant when timed-out trials were included in Studies 2 and 3, indicating that the gaze-contingent manipulation did not effectively enforce a bias toward attending to a particular stimulus through eye gaze in all trials. Future work is needed to improve the effectiveness of the gaze-contingent prompt procedure.

Strategies for the AFM-based manipulation of silver nanowires on a flat surface.

Silver nanowires (Ag NWs) are a promising material for building various sensors and devices at the nanoscale. However, the fast and precise placement of individual Ag NWs is still a challenge today. Atomic force microscopy (AFM) has been widely used to manipulate nanoparticles, yet this technology encounters many difficulties when being applied to the movement of Ag NWs as well as other soft one-dimensional (1D) materials, since the samples are easily distorted or even broken due to friction and adhesion on the substrate. In this paper, two novel manipulation strategies based on the parallel pushing method are presented. This method applies a group of short parallel pushing vectors (PPVs) to the Ag NW along its longitudinal direction. Identical and proportional vectors are respectively proposed to translate and rotate the Ag NWs with a straight-line configuration. The rotation strategy is also applied to straighten flexed Ag NWs. The finite element method simulation is introduced to analyse the behaviour of the Ag NWs as well as to optimize the parameter setting of the PPVs. Experiments are carried out to confirm the efficiency of the presented strategies. By comprehensive application of the new strategies, four Ag NWs are continuously assembled in a rectangular pattern. This study improves the controllability of the position and configuration of Ag NWs on a flat substrate. It also indicates the practicability of automatic nanofabrication using common AFMs.

Visualization of Protein in Peanut Using Hyperspectral Image with Chemometrics.

The study aims to explore the potential of hyperspectral imaging (HSI) with chemometrics for rapidly and non-invasively visualizing the spatial distribution of protein content which can affect the quality of peanut products as a critical component of peanut. Spectral data contained in the region of interest (ROI) of the corrected hyperspectral images of peanut were extracted and protein contents were measured with conventional chemical method. By comparing different pretreatments and modeling algorithms, the second-order derivatives (2nd-der) on spectra is optimal pretreatment, and partial ceast square (PLS) is the best regression method. Based on the pretreatment spectra and the measured protein content model, a good performance model (RC=0.91, SEC=0.86; RP=0.86, SEP=0.69) was built with full wavelengths. The fourteen optimal wavelengths were carried out based on the regression coefficients (RC) of the established PLS model. Then, using optimal wavelengths built RC-PLS model which show resembling performance (RC=0.86, SEC=1.03; RP=0.80, SEP=0.77). At last, an imaging processing algorithm was developed to transfer each pixel in peanut to protein content with the 2nd-der-RC-PLS model. There was no significant difference between Kjeldahl and HSI method by the paired test. The result demonstrated the capacity of HSI in combination with chemometrics for fast and non- destructively determining protein content in peanut.

Identification of chemical ingredients of peanut stems and leaves extracts using UPLC-QTOF-MS coupled with novel informatics UNIFI platform.

Peanut stems and leaves have been used traditionally as both herbal medicines and special food in Asia. In this study, the main functional compounds of peanut stems and leaves extracts were identified using UPLC separation coupled to high resolution mass spectrometry (QTOF-MS), and a traditional medicine library. Three different extraction solvents (ethyl acetate, petroleum ether and n-butanol) were evaluated to prepare the extracts of peanut stems and leaves. A total of 283 chemical compounds were identified in peanut stems and leaves extracts, of which 207 compounds are tentatively new identifications in Genus Arachis. The integration of data acquisition and processing with the traditional medicine library provides a simple, efficient process to effectively facilitate the identification of chemical ingredients in complex natural product extracts. The integrated workflow for separation, detection and identification of functional compounds in natural products using UPLC/QTOF-MS greatly improves productivity for development of traditional herbal medicines. Copyright © 2016 John Wiley & Sons, Ltd.

Preparation of nanoliposome loaded with peanut peptide fraction: stability and bioavailability.

Nanoliposome loaded with peanut peptide fraction (PPF) prepared by high pressure microfluidization (HPM) treatment was investigated as well as its stability and bioavailability. PPF showed hydrophilicity character with a solubility of 97.50 ± 2.31 mg mL(-1) in aqueous solution. HPM treatment can prepare nanoliposome but decreased encapsulation efficiency (EE). A pressure of 120 MPa was the appropriate parameter where the particle size and EE of nanolipsome was 79.67 ± 1.85 nm and 65.12 ± 2.96%, respectively. Crude liposome and nanoliposome both showed good stability under different pH conditions, even at pH value of 2.0. Nanoliposome behaved better in vitro controlled release than crude liposome. Most important of all, nanoliposome had the highest angiotension converting enzyme (ACE) inhibitory activity after simulated gastrointestinal tract (GIT) digestion. Morphology of digested liposome proved that nanoliposome can keep relative integrity in structure although it suffered a lot of attack.