Financial toxicity and its risk factors among patients with cancer in China: A nationwide multisite study.

Objective: We assessed financial toxicity (FT) among Chinese patients with cancer and investigated associated risk factors guided by a multilevel conceptual framework. Methods: Applying multistage stratified sampling, we selected six tertiary and six secondary hospitals across three economically diverse provinces in China. From February to October 2022, 1208 patients with cancer participated. FT was measured using the COmprehensive Score for financial Toxicity (COST), with 28 potential risk factors identified at multilevel. Multiple regression analysis was used for risk factor identification. Results: FT prevalence was 82.6% (95% confidence interval [CI]: 80.5%, 84.8%), with high FT (COST score ≤ 18.5) observed in 40.9% of participants (95% CI: 38.1%, 43.7%). Significant risk factors included younger age at cancer diagnosis, unmarried status, low annual household income, negative impact of cancer on participants' or family caregiver's work, advanced cancer stage, longer hospital stay for cancer treatment or treatment-related side effects, high perceived stress, poor emotional/informational support, lack of social medical insurance or having urban and rural resident basic medical insurance, lack of commercial medical insurance, tertiary hospital treatment, and inadequate cost discussions with healthcare providers (all P < 0.05). Conclusions: Cancer-related FT is prevalent in China, contributing to disparities in cancer care access and health-related outcomes. The risk factors associated with cancer-related FT encompasses multilevel, including patient/family, provider/practice, and payer/policy levels. There is an urgent need for collective efforts by patients, healthcare providers, policymakers, and insurers to safeguard the financial security and well-being of individuals affected by cancer, promoting health equities in the realm of cancer care.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

BACKGROUND: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. METHODS: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (- 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. CONCLUSION: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

INGEsT: An Open-Source Behavioral Setup for Studying Self-motivated Ingestive Behavior and Learned Operant Behavior.

Ingestive behavior is driven by negative internal hunger and thirst states, as well as by positive expected rewards. Although the neural substrates underlying feeding and drinking behaviors have been widely investigated, they have primarily been studied in isolation, even though eating can also trigger thirst, and vice versa. Thus, it is still unclear how the brain encodes body states, recalls the memory of food and water reward outcomes, generates feeding/drinking motivation, and triggers ingestive behavior. Here, we developed an INstrument for Gauging Eating and Thirst (INGEsT), a custom-made behavioral chamber which allows for precise measurement of both feeding and drinking by combining a FED3 food dispenser, lickometers for dispensing liquid, a camera for behavioral tracking, LED light for optogenetics, and calcium imaging miniscope. In addition, in vivo calcium imaging, optogenetics, and video recordings are well synchronized with animal behaviors, e.g., nose pokes, pellet retrieval, and water licking, by using a Bpod microprocessor and timestamping behavioral and imaging data. The INGEsT behavioral chamber enables many types of experiments, including free feeding/drinking, operant behavior to obtain food or water, and food/water choice behavior. Here, we tracked activity of insular cortex and mPFC Htr3a neurons using miniscopes and demonstrate that these neurons encode many aspects of ingestive behavior during operant learning and food/water choice and that their activity can be tuned by internal state. Overall, we have built a platform, consisting of both hardware and software, to precisely monitor innate ingestive, and learned operant, behaviors and to investigate the neural correlates of self-motivated and learned feeding/drinking behaviors.

Intern-Nursing Students' Knowledge of Vascular Catheter-Associated Infections and Its Associated Factors: A Cross-Sectional Survey in China.

Background: Medical personnel contact with the patient closely, and their knowledge of vascular catheter-associated infections (VCAIs) is closely related to the prevention of VCAIs. Researchers mainly pay attention to the VCAIs knowledge of doctors and nurses but rarely pay attention to the nursing students in the hospital internship stage. Purpose: To investigate the current situation of knowledge of intern-nursing students in VCAIs, and analyze its influencing factors. Patients and Methods: 843 intern-nursing students were selected from 10 hospitals in five regions of eastern, western, southern, northern, and central China from June 26 to July 31, 2023, using a two-stage random sampling method. A self-designed questionnaire with good reliability and validity was used to investigate their knowledge of VCAIs, and t-test, multiple linear regression analysis, and Welch t-test were used to analyze the collected data by using SPSS Statistics 26.0 (IBM Corp., Armonk, NY). Results: Intern nursing students' mean score of VCAIs knowledge was 48.66 (SD=15.77), with a score below 60 (unqualified) accounting for 75.4%, a score of 60-79 (qualified) accounting for 19.7%, a score of 80-89 (good) accounting for 3.6%, and a score of above 90 accounting for 1.3%. Students who attended VCAIs training three or more times had higher scores than those who did not attend training (B: 4.706, p=0.001), knowledge scores of students with a bachelor's degree or above were higher than those with junior college degree or below (B: 8.479, p<0.001), students who interned in tertiary hospitals had higher scores than those practicing in secondary hospitals (B:12.381, p<0.001) and scores of students in hospital training were significantly higher than study independently (B:4.116, p=0.007). Conclusion: Intern-nursing students have a relatively low level of knowledge about VCAIs. It is recommended to strengthen clinical systematic and standardized training, improve the knowledge mastery level of intern-nursing students, and enhance their ability to handle VCAIs.

Evaluation of perineal wound healing and pain outcomes after low-angle mediolateral episiotomy in women undergoing vaginal childbirth: A systematic review and meta-analysis.

The efficacy of episiotomy, particularly the angle of incision in mediolateral episiotomies, remains a significant area of inquiry in obstetrics. This meta-analysis aimed to evaluate the impact of low-angle mediolateral episiotomy on perineal wound healing and pain outcomes in women undergoing vaginal childbirth. Adhering to PRISMA guidelines, a systematic review was conducted using the PICO framework. Studies were selected based on predefined inclusion and exclusion criteria, focusing on randomised controlled trials (RCTs) involving low-angle mediolateral episiotomies. Comprehensive literature searches were performed across major electronic databases including PubMed, Embase, Web of Science and Cochrane Library. Data extraction and quality assessments were meticulously carried out by independent reviewers, employing the Cochrane Collaboration's risk of bias tool. A total of 1246 articles were initially identified, with 8 articles meeting the strict inclusion criteria for the final analysis. The meta-analysis revealed significant heterogeneity among studies regarding postoperative pain (p < 0.0001, I2 = 77.5%), and employed a random-effects model. Results showed that low-angle episiotomies significantly reduced postoperative pain (OR = 0.27, 95% CI: 0.17-0.42, p < 0.001), and increased first-degree healing rates (OR = 2.95, 95% CI: 2.20-3.96, p < 0.001) compared to traditional angles. Sensitivity analyses confirmed the stability of these findings, and no significant publication bias was detected. The analysis suggests that low-angle episiotomies can potentially reduce postoperative perineal pain and enhance wound healing. However, the limited number and varying quality of the included studies warrant cautious interpretation of these results. Further well-designed studies are needed to corroborate these findings and guide clinical practice.

Self-assembly of amphiphilic asymmetric comb-like copolymers with responsive rigid side chains.

Amphiphilic asymmetric comb-like copolymers (AACCs) exhibit distinct self-assembly behaviours due to their unique architecture. However, the synthetic difficulties of well-defined AACCs have prohibited a systematic understanding of the architecture-morphology relationship. In this work, we conducted dissipative particle dynamics simulations to investigate the self-assembly behaviours of AACCs with responsive rigid side chains in selective solvents. The effects of side chain length, number of branches, and spacers on the morphology of aggregates were investigated by mapping out morphology diagrams. Besides, the numbers and surface areas of aggregates clearly depicted the morphological transitions during the self-assembly process. Moreover, the rod-to-coil conformation transitions were simulated to explore the stimuli-responsive behaviour of the AACCs with responsive rigid side chains by adjusting the bond angle parameter of the rigid chains. The results indicated that without the support of the rigid chains, the assembly structure collapsed, leading to the tube-to-channelized micelles and one-compartment-to-multicompartment vesicle morphology transformations. The simulation results are consistent with earlier experimental results, which can provide theoretical guidance for assembly toward desired nanostructures.

Study on the Relationship Between Uncertainty Tolerance and Positive Acceptance in Postoperative Patients With Cervical Cancer.

OBJECTIVE: The objective of this study is to clarify the correlation between uncertainty tolerance (UT) and positive acceptance (PA) in patients with cervical cancer (CC) after surgical treatment. METHODS: A total of 233 patients with CC who had undergone surgery were included and were scored on the UT Scale and Positive Acceptance Scale. In addition, patients were classified according to the length of stay ≥1 week and length of stay <1 week, and the UT score and satisfaction and enterprising score of the two groups were compared. This was performed in order to analyze the effect of length of hospital stay on UT and PA. RESULTS: The mean UT score of 233 patients was 3.74±0.34 and the mean PA score was 1.96±0.20, with a negative correlation and a significant correlation coefficient (r=-0.342, P 0.05). The UT score of post-operative CC patients with length of stay ≥1 week was significantly higher than that of patients with length of stay <1 week, P<0.05. The score of PA in patients with post-operative CC whose hospital stay was ≥1 week was significantly lower than for patients with hospital stays <1 week (P<0.05). UT was negatively correlated with PA in patients with hospital stays < 1 week (r=-0.358, P<0.05). There was a significant negative correlation between UT and PA in patients with hospital stay ≥1 week (r =-0.493, P<0.05). Increased hospitalization time correlated with increased scores of UT, with reductions in scores of PA. CONCLUSION: Post-operative patients with CC had higher scores of UT and lower scores of PA, which were negatively correlated. Increased hospitalization time was linked to a detriment in patient UT and reduced PA. Targeted interventions to improve the level of UT and PA within postoperative CC cases should be developed.

Clinical efficacy of metformin in familial adenomatous polyposis and the effect of intestinal flora.

BACKGROUND AND AIMS: Metformin has been reported to inhibit the occurrence and development of colorectal cancer (CRC) by mediating changes in intestinal flora. Studies have also indicated that the occurence of familial adenomatous polyposis (FAP) may also be associated with changes in the intestinal flora. Therefore, we investigated the efficacy and safety of metformin in treating FAP and the association with intestinal flora. RESULTS: Compared with the baseline, the mean number and load of polyps in the areas of nanocarbon labeling and postoperative residuals in the test group were lower than those in the placebo group, while the diversity of intestinal flora species was increased. At the genus level, the relative abundance of g_Ruminococcus in the test group was lower than that at baseline, whereas the relative abundance of g_Lactobacillus was higher. These changes were statistically significant (P < 0.05). CONCLUSION: One-year metformin therapy for FAP is safe and effective, potentially mediated by modulating the intestinal flora. This study provides new insights and strategies for preventing adenomatous polyp carcinogenesis in FAP and explores possible preventive action.

Prognostic value of preoperative sarcopenia in gastric cancer: A 10-year follow-up study.

BACKGROUND: Preoperative sarcopenia is associated with prognosis in patients with gastric cancer (GC); however, studies with 10-year survival follow-up are lacking. METHODS: Consecutive patients with GC who underwent radical gastrectomy between December 2009-2012 were included retrospectively. Preoperative sarcopenia was diagnosed using computed tomography skeletal muscle index. The Kaplan-Meier method estimated overall survival (OS) and relapse-free survival (RFS). Cox proportional hazard regression analysis determined the prognostic factors for OS and RFS. RESULTS: In total, 781 patients with GC were included; among these, 207 (26.5%) had preoperative sarcopenia. Patients with sarcopenia had significantly lower 10-year OS and RFS than patients without sarcopenia (39.61% vs. 58.71% and 39.61% vs. 57.84%, respectively). Further, preoperative sarcopenia was an independent risk factor for 10-year OS (HR = 1.467; 95% confidence interval [CI]: 1.169-1.839) and RFS (HR = 1.450; 95% CI: 1.157-1.819). Patients with sarcopenia had a higher risk of death and recurrence in the first 10 years postoperatively than patients without sarcopenia. Additionally, the risk of death (HR = 2.62; 95% CI:1.581-4.332) and recurrence (HR = 2.34; 95% CI:1.516-3.606) was the highest in the 1st postoperative year and remained relatively stable thereafter. Further, postoperative adjuvant chemotherapy significantly improved 10-year OS (p = 0.006; HR = 0.558) and RFS (p = 0.008; HR = 0.573) in patients with TNM stage II-III GC that presented with sarcopenia. CONCLUSION: Preoperative sarcopenia remained an independent risk factor for postoperative very long-term prognosis of GC. Postoperative adjuvant chemotherapy improved the long-term outcomes of stage II-III patients with sarcopenia.

Revealing the Heterogeneous Bubble Nucleation at Individual Silica Nanoparticles.

Deep understanding of the bubble nucleation process is universally important in systems, from chemical engineering to materials. However, due to its nanoscale and transient nature, effective probing of nucleation behavior with a high spatiotemporal resolution is prohibitively challenging. We previously reported the measurement of a single nanobubble nucleation at a nanoparticle using scanning electrochemical cell microscopy, where the bubble nucleation and formation were inferred from the voltammetric responses. Here, we continue the study of heterogeneous bubble nucleation at interfaces by regulating the local nanostructures using silica nanoparticles with a distinct surface morphology. It is demonstrated that, compared to the smooth spherical silica nanoparticles, the raspberry-like nanoparticles can further significantly reduce the nucleation energy barrier, with a critical peak current about 23% of the bare carbon surfaces. This study advances our understanding of how surface nanostructures direct the heterogeneous nucleation process and may offer a new strategy for surface engineering in gas involved energy conversion systems.

Computational Chemistry in Structure-Based Solute Carrier Transporter Drug Design: Recent Advances and Future Perspectives.

Solute carrier transporters (SLCs) are a class of important transmembrane proteins that are involved in the transportation of diverse solute ions and small molecules into cells. There are approximately 450 SLCs within the human body, and more than a quarter of them are emerging as attractive therapeutic targets for multiple complex diseases, e.g., depression, cancer, and diabetes. However, only 44 unique transporters (∼9.8% of the SLC superfamily) with 3D structures and specific binding sites have been reported. To design innovative and effective drugs targeting diverse SLCs, there are a number of obstacles that need to be overcome. However, computational chemistry, including physics-based molecular modeling and machine learning- and deep learning-based artificial intelligence (AI), provides an alternative and complementary way to the classical drug discovery approach. Here, we present a comprehensive overview on recent advances and existing challenges of the computational techniques in structure-based drug design of SLCs from three main aspects: (i) characterizing multiple conformations of the proteins during the functional process of transportation, (ii) identifying druggability sites especially the cryptic allosteric ones on the transporters for substrates and drugs binding, and (iii) discovering diverse small molecules or synthetic protein binders targeting the binding sites. This work is expected to provide guidelines for a deep understanding of the structure and function of the SLC superfamily to facilitate rational design of novel modulators of the transporters with the aid of state-of-the-art computational chemistry technologies including artificial intelligence.

Determination of a cut-off COmprehensive Score for financial Toxicity (COST) for identifying cost-related treatment nonadherence and impaired health-related quality of life among Chinese patients with cancer.

PURPOSE: This study aimed to determine a cut-off for the simplified Chinese version of the COmprehensive Score for financial Toxicity (COST) that could identify cost-related treatment nonadherence among Chinese patients with cancer. The study also sought to validate this cut-off score by using it to assess impaired health-related quality of life (HRQoL) in the same population. METHODS: A secondary analysis was conducted using data from a cross-sectional survey of 1208 Chinese patients with cancer who were recruited from 12 hospitals in six cities across three provinces of the Chinese mainland. Sociodemographic information and data on financial toxicity (FT), cost-related treatment nonadherence, and HRQoL were used in the analysis. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off for the simplified Chinese version of the COST. RESULTS: The ROC analysis identified a COST cut-off of 18.5 for identifying cost-related treatment nonadherence, yielding a sensitivity of 76.5% and specificity of 71.4%. In the validation study, this cut-off score yielded a sensitivity of 64.2% and a specificity of 67.1% for identifying impaired HRQoL. CONCLUSION: Early and dynamic assessment of cancer-related FT in routine clinical practice may play a crucial role in the early identification and management of FT. Accordingly, a COST cut-off of 18.5 was identified to indicate cost-related treatment nonadherence and impaired HRQoL in a population of patients with cancer from the Chinese mainland. This finding may facilitate the implementation of universal FT screening among patients with cancer in specific settings such as the Chinese mainland.

Comparison of Short-Term Outcomes After Robotic Versus Laparoscopic Radical Gastrectomy for Advanced Gastric Cancer in Elderly Individuals: A Propensity Score-Matching Study.

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.

Characterization changes and research waste in randomized controlled trials of global bariatric surgery over the past 20 years: cross-sectional study.

BACKGROUND: The results of several large randomized controlled trials (RCTs) have changed the clinical practice of bariatric surgery. However, the characteristics of global RCTs of bariatric surgery have not been reported internationally and whether there was research waste in these RCTs is unknown. METHODS: Search ClinicalTrials.gov for bariatric surgery RCTs registered between January 2000 and December 2022 with the keywords 'Roux-en-Y gastric-bypass' and 'Sleeve Gastrectomy'. The above analysis was conducted in January 2023. RESULTS: A total of 326 RCTs were included in this study. The number of RCTs registered for sleeve gastrectomy and gastric bypass surgery increased year by year globally. Europe has always accounted for the largest proportion, Asia has gradually increased, and North America has decreased. A total of 171 RCTs were included in the analysis of waste, of which 74 (43.8%) were published. Of the 74 published RCTs, 37 (37/74, 50.0%) were judged to be adequately reported and 36 (36/74, 48.6%) were judged to have avoidable design defects. In the end, 143 RCTs (143/171, 83.6%) had at least one research waste. Body weight change as the primary endpoint (OR: 0.266, 95% CI: 0.103-0.687, P =0.006) and enrolment greater than 100 (OR: 0.349, 95% CI: 0.146-0.832, P =0.018) were independent protective factors for research waste. CONCLUSIONS: This study for the first time describes the characteristic changes of the mainstream RCT of bariatric surgery globally in the last 20 years and identifies a high research waste burden and predictive factor in this area, which provides reference evidence for carrying out bariatric surgery RCTs more rationally.

STING promotes invasion and migration of uveal melanoma through p38­MAPK signaling.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults, with a lack of effective treatment for metastasis and a poor prognosis. Stimulator of interferon genes (STING, also known as TMEM173) plays an important role in tumor development by regulating cell proliferation, metastasis and other cellular processes. However, the function of STING in UM remains unclear and requires further investigation. The present study analyzed the expression status of STING to elucidate the mechanisms underlying UM. The correlation between STING and the prognosis of UM was evaluated based on UM RNA­seq data and clinical information extracted from The Cancer Genome Atlas database. Quantification of STING in UM cell lines and tissues was performed using the Wes Separation protein immunoassay. The effects of STING on the proliferation, migration and invasion of UM cells were investigated using Cell Counting Kit­8, Transwell and wound healing experiments. Survival analysis demonstrated that high levels of STING in UM tissues indicated a poor prognosis. The expression of STING in UM tissues was higher than that in the choroid membranes. Furthermore, it was found that downregulation of STING expression in UM cells suppressed migration and invasion, whereas overexpression of STING significantly promoted migration and invasion. Notably, STING had no significant effect on UM cell proliferation. It was also identified that STING positively upregulated the phosphorylation of p38 mitogen­activated protein kinase (p38­MAPK) in UM cells, enhancing cell migration and invasion, which the p38­MAPK inhibitor SB203580 reversed. Finally, the results of the present study demonstrated that high STING expression in UM indicates a poor prognosis. STING was revealed to promote the migration and invasion of UM cells through p38­MAPK signaling.

Morphologically Tunable Rectangular Platelets Self-Assembled from Diblock Molecular Brushes Containing Azopyridine Pendants.

Two-dimensional (2D) platelet structures are of growing importance as building blocks for the preparation of optical and electrical devices. However, the creation of morphologically tunable rectangular platelets through polymer self-assembly still remains a challenge. Herein, we describe a rational strategy for the fabrication of 2D rectangular platelets by stacking azopyridine-containing diblock molecular brushes in two dimensions in a selective solvent. Amphiphilic PEG-co-(PtBA-g-PAzoPy) DMBs with poly(ethylene glycol) (PEG) block, poly(t-butyl acrylate) (PtBA) backbone, and poly(6-(4-(4-pyridyazo)phenoxy)-hexyl methacrylate) (PAzoPy) brush were synthesized by sequential reversible addition-fragmentation chain transfer polymerization and atom transfer radical polymerization. Various rectangular platelets were obtained via the solution self-assembly of PEG-co-(PtBA-g-PAzoPy) through a heating-cooling-aging process in which the morphology and size of platelets could be controlled by adjusting the composition of DMBs as well as the solvent polarity. In addition, we investigated the metal chelation ability and H-bonding-assisted co-assembly capability of PEG-co-(PtBA-g-PAzoPy). The results displayed that 2D hybrids and flower-like platelets were formed, respectively. Our study presents an efficient method to fabricate rectangular platelets with tunable morphologies.

SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway.

Interferon-gamma (IFN-γ) signaling is necessary for the proinflammatory activation of macrophages but IFN-γ-independent pathways, for which the initiating stimuli and downstream mechanisms are lesser known, also contribute. Here we identify, by high-content screening, SEPTIN2 (SEPT2) as a negative regulation of IFN-γ-independent macrophage autoactivation. Mechanistically, endoplasmic reticulum (ER) stress induces the expression of SEPT2, which balances the competition between acetylation and ubiquitination of heat shock protein 5 at position Lysine 327, thereby alleviating ER stress and constraining M1-like polarization and proinflammatory cytokine release. Disruption of this negative feedback regulation leads to the accumulation of unfolded proteins, resulting in accelerated M1-like polarization, excessive inflammation and tissue damage. Our study thus uncovers an IFN-γ-independent macrophage proinflammatory autoactivation pathway and suggests that SEPT2 may play a role in the prevention or resolution of inflammation during infection.

An international multi-institution real-world study of the optimal surveillance frequency for stage II/III gastric cancer: the more, the better?

BACKGROUND: Due to lacking evidence on surveillance for gastric cancer (GC), this study aimed to determine the optimal postsurgical surveillance strategy for pathological stage (pStage) II/III GC patients and compare its cost-effectiveness with traditional surveillance strategies. METHODS: Prospectively collected data from stage II/III GC patients ( n =1661) who underwent upfront surgery at a large-volume tertiary cancer center in China (FJMUUH cohort) between January 2010 and October 2015. For external validation, two independent cohorts were included, which were composed of 380 stage II/III GC patients at an tertiary cancer center in U.S.A (Mayo cohort) between July 1991 and July 2012 and 270 stage II/III GC patients at another tertiary cancer center in China (QUAH cohort) between May 2010 and October 2014. Random forest models were used to predict dynamic recurrence hazards and to construct individual surveillance strategies for stage II/III GC. Cost-effectiveness was assessed by the Markov model. RESULTS: The median follow-up period of the FJMUUH, the Mayo, and QUAH cohorts were 55, 158, and 70 months, respectively. In the FJMUUH cohort, the 5-year recurrence risk was higher in pStage III compared with pStage II GC patients ( P <0.001). Our novel individual surveillance strategy achieved optimal cost-effectiveness for pStage II GC patients (ICER =$490/QALY). The most intensive NCCN surveillance guideline was more cost-effective (ICER =$983/QALY) for pStage III GC patients. The external validations confirmed our results. CONCLUSION: For patients with pStage II GC, individualized risk-based surveillance outperformed the JGCTG and NCCN surveillance guidelines. However, the NCCN surveillance guideline may be more suitable for patients with pStage III GC. Even though our results are limited by the retrospective study design, the authors believe that our findings should be considered when recommending postoperative surveillance for stage II/III GC with upfront surgery in the absence of a randomized clinical trial.

Using shallow neural networks with functional connectivity from EEG signals for early diagnosis of Alzheimer's and frontotemporal dementia.

Introduction: Dementia is a neurological disorder associated with aging that can cause a loss of cognitive functions, impacting daily life. Alzheimer's disease (AD) is the most common cause of dementia, accounting for 50-70% of cases, while frontotemporal dementia (FTD) affects social skills and personality. Electroencephalography (EEG) provides an effective tool to study the effects of AD on the brain. Methods: In this study, we propose to use shallow neural networks applied to two sets of features: spectral-temporal and functional connectivity using four methods. We compare three supervised machine learning techniques to the CNN models to classify EEG signals of AD / FTD and control cases. We also evaluate different measures of functional connectivity from common EEG frequency bands considering multiple thresholds. Results and discussion: Results showed that the shallow CNN-based models achieved the highest accuracy of 94.54% with AEC in test dataset when considering all connections, outperforming conventional methods and providing potentially an additional early dementia diagnosis tool.

Evaluation of dynamic recurrence risk for locally advanced gastric cancer in the clinical setting of adjuvant chemotherapy: a real-world study with IPTW-based conditional recurrence analysis.

BACKGROUND: The long-term dynamic recurrence hazard of locally advanced gastric cancer (LAGC) in the clinical setting of adjuvant chemotherapy (ACT) remains unclear. PURPOSE: This study aimed to investigate the dynamic recurrence risk of LAGC in patients who received ACT or not. METHODS: The study assessed data from patients with LAGC who underwent radical gastrectomy between January, 2010 and October, 2015. Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias between the ACT and observational (OBS) groups. Conditional recurrence-free survival (cRFS) and restricted mean survival time (RMST) were used to assess the survival differences. RESULTS: In total, 1,661 LAGC patients were included (ACT group, n = 1,236 and OBS group, n = 425). The recurrence hazard gradually declined; in contrast, cRFS increased with RFS already accrued. Following IPTW adjustment, the cRFS rates were higher in the ACT group than those in the OBS group for patients at baseline or with accrued RFS of 1 and 2 years (p˂0.05). However, the cRFS rates of the ACT group were comparable with those of the OBS group for patients with accrued RFS of 3 or more years (p > 0.05). Likewise, the 5-year △RMST between the ACT and OBS groups demonstrated a similar trend. Moreover, the hematological metastasis rate of the ACT group was significantly lower than that of the OBS group for patients at baseline or with accrued RFS of 1 and 2 years, respectively (p˂0.05). CONCLUSIONS: Although ACT could provide substantial benefits for patients with LAGC, the differences in recurrence hazard between the ACT and OBS groups may attenuate over time, which could help guide surveillance and alleviate patients' anxiety. Further prospective large-scale studies are warranted.