Assessing the influence of parameters on tissue welding in small bowel end-to-end anastomosis in vitro and in vivo.

BACKGROUND: The use of high-frequency electric welding technology for intestinal end-to-end anastomosis holds significant promise. Past studies have focused on in vitro, and the safety and efficacy of this technology is uncertain, severely limiting the clinical application of this technology. This study investigates the impact of compression pressure, energy dosage, and duration on anastomotic quality using a homemade anastomosis device in both in vitro and in vivo settings. METHODS: Two hundred eighty intestines and 5 experimental pigs were used for in vitro and in vivo experiments, respectively. The in vitro experiments were conducted to study the effects of initial pressure (50-400 kpa), voltage (40-60 V), and time (10-20 s) on burst pressure, breaking strength, thermal damage, and histopathological microstructure of the anastomosis. Optimal parameters were then inlaid into a homemade anastomosis and used for in vivo experiments to study the postoperative porcine survival rate and the pathological structure of the tissues at the anastomosis and the characteristics of the collagen fibers. RESULTS: The anastomotic strength was highest when the compression pressure was 250 kPa, the voltage was 60 V, and the time was 15 s. The degree of thermal damage to the surrounding tissues was the lowest. The experimental pigs had no adverse reactions after the operation, and the survival rate was 100%. 30 days after the operation, the surgical site healed well, and the tissues at the anastomosis changed from immediate adhesions to permanent connections. CONCLUSION: High-frequency electric welding technology has a certain degree of safety and effectiveness. It has the potential to replace the stapler anastomosis in future and become the next generation of new anastomosis device.

LncRNA MALAT1 suppresses monocyte-endothelial cell interactions by targeting miR-30b-5p and enhancing ATG5-mediated autophagy.

Background: Monocyte-endothelial cell (EC) interactions are one of the earliest events in the development of atherosclerosis and play a crucial role in atherosclerotic plaque formation. Although attempts have been made to modulate this interaction, the underlying molecular signalling mechanisms remain unclear. This study aimed to investigate the role of long non-coding RNA MALAT1 in monocyte-EC interactions. Methods: The expression of MALAT1, ICAM-1, VCAM-1, P-selectin, CCL2 and CXCL1 was evaluated in ApoE-/- mouse aortic tissues and inflamed human umbilical vein endothelial cells (HUVECs). The regulatory impact of MALAT1 on cell adhesion molecules, monocyte-EC adhesion, and autophagy was assessed. The interactions between MALAT1 and microRNAs (miRNAs) were evaluated using dual-luciferase reporter and RNA pull-down assays. Results: MALAT1 expression decreased in ApoE-/- mouse aortic tissues and inflammatory HUVECs. MALAT1 overexpression suppressed the expression of ICAM-1, VCAM-1 and CXCL1, and reduced the migration and adhesion of monocytes to ECs. Inhibition of MALAT1 promoted cell adhesion molecule expression and monocyte-EC interactions. Mechanistically, MALAT1 binds directly to miR-30b-5p and decreases its effective expression by functioning as an endogenous sponge, thereby increasing the expression of autophagy-related gene 5 (ATG5) and stimulates endothelial autophagy. Conclusions: Our findings suggest that MALAT1 suppresses monocyte-EC interactions by targeting miR-30b-5p and enhancing ATG5-mediated endothelial autophagy. These data imply that MALAT1 may play a protective role at the early stages of the atherosclerotic process.

Prognostic Implication of Lymphovascular Invasion in Early Gastric Cancer Meeting Endoscopic Submucosal Dissection Criteria: Insights from Radical Surgery Outcomes.

BACKGROUND: The management of early gastric cancer (EGC) has witnessed a rise in the utilization of endoscopic submucosal dissection (ESD) as a treatment modality, although prognostic markers are needed to guide management strategies. This study investigates the prognostic implications of lymphovascular invasion (LVI) in ESD-eligible EGC patients, specifically its implications for subsequent radical surgery. MATERIAL AND METHODS: A retrospective, multicenter study from two primary hospitals analyzed clinicopathological data from 1369 EGC patients eligible for ESD, who underwent gastrectomy at Shanghai Cancer Center and Huashan Hospital between 2009 and 2018. We evaluated the relationship between LVI and lymph node metastasis (LNM), as well as the influence of LVI on recurrence-free survival (RFS) and overall survival (OS). RESULTS: We found a strong association between LVI and LNM (p < 0.001). Advanced machine learning approaches, including Random Forest, Gradient Boosting Machine, and eXtreme Gradient Boosting, confirmed the pivotal role of LVI in forecasting LNM from both centers. Multivariate analysis identified LVI as an independent negative prognostic factor for both RFS and OS, with hazard ratios of 4.5 (95% CI: 2.4-8.5, p < 0.001) and 4.4 (95% CI: 2.1-8.9, p < 0.001), respectively. CONCLUSIONS: LVI is crucial for risk stratification in ESD-eligible EGC patients, underscoring the necessity for radical gastrectomy. Future research should explore the potential incorporation of LVI status into existing TNM staging systems and novel therapeutic strategies.

Structure-based discovery of potent CARM1 inhibitors for colorectal cancer therapy.

Coactivator-associated arginine methyltransferase 1 (CARM1) plays an important role in cell proliferation and gene expression, and is highly expressed in a variety of tumor tissues. Guided by our previous reported structure of DCPR049_12, we focused on designing and evaluating selective CARM1 inhibitors, resulting in the identification of compound 11f as a promising lead candidate. Compound 11f displayed potent inhibition of CARM1 (IC50 = 9 nM). Comprehensive evaluations, including in vitro metabolic stability assessments, molecular modelling, cellular studies, and in vivo anti-tumor studies, confirmed that it induced cancer cell apoptosis and specifically inhibited CARM1's methylation function. Notably, compound 11f displayed significant anti-proliferative effects on colorectal cancer cell lines, showcasing its potential for targeted therapies against CARM1-related diseases. This study provides valuable insights for the future development of specific and effective CARM1 inhibitors.

Measuring ecosystem services and ecological sensitivity for comprehensive conservation in Giant Panda National Park.

China announced the development of its first 5 national parks in 2021, the primary objective of which is to conserve the natural state and integrity of natural ecosystems. As such, ecosystem services and biodiversity levels are crucial assessment factors for the parks. For Giant Panda National Park (GPNP), we evaluated ecological sensitivity based on water and soil erosion and rocky desertification; ecosystem services based on headwater conservation, soil and water conservation, and biodiversity conservation; and presence of giant panda (Ailuropoda melanoleuca) and sympatric species (e.g., takin [Budorcas taxicolor], Asiatic black bear [Ursus thibetanus]) habitat suitability derived from niche modeling to identify the ecosystem status and assess ecological problems within the park. From our results, we proposed ecologically critical areas to target to meet the park's goals. The suitable habitat for pandas and sympatric species encompassed 62.98% of the park and occurred mainly in the Minshan Mountains. One quarter of the total area (25.67%) contained areas important for ecosystem services. Ecologically sensitive and extremely sensitive areas covered 88.78% of the park and were distributed mainly in Qionglaishan and Minshan Mountains. This coverage indicated that there was much habitat for pandas and sympatric species but that the ecosystems in GPNP are vulnerable. Therefore, ecologically critical areas encompassed all suitable habitats for all the species examined and areas important and extremely important to ecosystem service provision,ecologically sensitive and extremely sensitive areas, encompassed 15.17% of panda habitat, accounted for 16.37% of the GPNP area, and were distributed mainly in the Minshan Mountains. Our results indicated where conservation efforts should be focused in the park and that by identifying ecologically critical areas managers can provide targeted protection for wildlife habitat and ecosystems and effectively and efficiently protect the composite ecosystem. Additionally, our methods can be used to inform development of new national parks.

Medición de los servicios ambientales y la sensibilidad ecológica para una conservación integral en el Parque Nacional del Panda Gigante Resumen China anunció el crecimiento de sus primeros cinco parques nacionales en 2021, con el objetivo principal de conservar el estado natural y la integridad de los ecosistemas naturales. Para ello, los servicios ambientales y los niveles de biodiversidad son factores cruciales de evaluación para los parques. Para poder identificar el estado del ecosistema y evaluar los problemas ecológicos dentro del Parque Nacional del Panda Gigante (PNPG), analizamos la sensibilidad ecológica con base en la erosión del agua y del suelo y la desertificación rocosa; los servicios ambientales con base en el suministro de conservación del agua, del agua y del suelo y de la biodiversidad; y la idoneidad de hábitat del panda gigante (Ailuropoda melanoleuca) y de especies simpátricas (takín [Budorcas taxicolor], oso negro asiático [Ursus thibetanus]) derivada del modelo de nichos. A partir de nuestros resultados proponemos enfocarnos en áreas ecológicamente críticas para lograr los objetivos del parque. El hábitat idóneo para los pandas y las especies simpátricas englobó el 62.98% del parque y se ubicó principalmente en las montañas Minshan. Un cuarto del área total (25.67%) albergó áreas importantes para los servicios ambientales. Las áreas ecológicamente sensibles y extremadamente sensibles cubrieron el 88.78% del parque y se distribuyeron en las montañas Minshan y Qionglaishan. Esta cobertura indica que hay bastante hábitat para los pandas y las especies simpátricas pero que los ecosistemas en el PNPG son vulnerables. Por lo tanto, las áreas ecológicamente críticas englobaron todos los hábitats para todas las especies analizadas y todas las áreas importantes y extremadamente importantes para el suministro de servicios ambientales. Las áreas ecológicamente sensibles y extremadamente sensibles englobaron el 15.17% del hábitat del panda, representaron el 16.37% del área del PNPG y se localizaron principalmente en las montañas Minshan. Nuestros resultados indican en dónde se deben enfocar los esfuerzos de conservación dentro del parque y que, si identificamos las áreas ecológicamente críticas, los gestores pueden proporcionar una protección focalizada para el hábitat y los ecosistemas y así proteger efectiva y eficientemente el ecosistema compuesto. Además, nuestro método puede usarse para guiar el desarrollo de nuevos parques nacionales.

大熊猫国家公园能实现物种和生态完整性的多重保护 中国在2021年宣布设立首批5个国家公园, 保护自然生态系统的真实性和完整性是其优先目标, 而生态系统服务和生物多样性水平是关键的评估要素。大熊猫国家公园作为首批唯一以单一物种命名的国家公园, 通过评估其生态系统服务、生态敏感性, 同时结合大熊猫及同域分布物种(羚牛、亚洲黑熊)的栖息地适宜性, 以揭示其国家公园内生态系统的状态及其面临的问题, 明确其生态关键区以实现多重保护的目标。我们发现大熊猫国家公园包含了超过62.98%的大熊猫和同域物种的适宜栖息地, 主要分布在岷山山系;其次, 大熊猫国家公园包含了25.67%的生态系统服务重要区域和高达88.78%的生态敏感区域, 主要分布在岷山山系和邛崃山山系。这表明尽管大熊猫国家公园内包含了大熊猫及同域物种所需的大面积适宜栖息地, 但是其生态系统具有较强的脆弱性。若将同时包含大熊猫及同域物种的适宜栖息地、生态系统服务重要和极重要区、生态敏感和极敏感的区域定义为生态关键区, 其面积占比为16.37%, 覆盖了15.17%的大熊猫栖息地, 主要分布在岷山山系。因此, 基于生态关键区制定新的科学的、针对性的保护措施, 不仅可以更好的来保护野生动物栖息地和应对生态系统的威胁, 而且也有效且高效地保护多重生态系统。.

Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

The effectiveness of using giant panda as a surrogate for protecting sympatric species.

The use of umbrella species to promote biodiversity conservation is practiced worldwide. The giant panda (Ailuropoda melanoleuca) an iconic species for world wildlife conservation, that inhabits regions with significant biodiversity. Given that the functions at wildlife of different trophic levels and in different body size groups are different within the ecosystem, it is unknown whether those groups of wildlife co-occurring with giant pandas are each likewise protected. To examine the umbrella effect of giant pandas on sympatric species, we used an extensive dataset of wildlife from more than 78% of giant panda habitats. We analysed the changes in distribution for four wildlife categories (large carnivores, large herbivores, medium carnivores and medium herbivores) using a generalized linear mixed model, and the underlying driving factors using binomial logistic regression models. Changes in forests in giant panda habitats were evaluated using Fragstats. The results have shown that the counts of herbivores and medium carnivores increased significantly during the decade. However, those of large carnivores significantly declined. Forest cover and nature reserves showed significant and positive effects on wildlife in 2001 and 2011, while the human population had significant and negative impacts on the herbivores and carnivores. Our results have also suggested that there has been a slight alleviation in forest fragmentation in areas unaffected by earthquakes. We concluded that the umbrella strategy of using the giant panda as an umbrella species achieved partial success by promoting the recovery of herbivores and medium carnivores. Meanwhile, this has indicated that the strategy was not sufficient for large carnivores, and therefore not enough for local ecosystems, given the critical role of large carnivores. We have suggested integrating habitat patches, controlling human disturbance, and preparing for potential human-wildlife conflict management in the Giant Panda National Park to restore large carnivore populations and maintain ecosystem functioning.

Association of niacin intake with constipation in adult: result from the National Health and Nutrition Examination.

BACKGROUND: Although dietary intake is believed to be associated with constipation, there is currently a lack of research exploring the relationship between niacin intake and constipation. Therefore, the aim of this study is to investigate the association between niacin intake in adults and constipation using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study included 5170 participants (aged ≥ 20 years) from the NHANES survey conducted between 2009 and 2010. Participants who reported experiencing constipation "always", "most of the time", or "sometimes" in the past 12 months were defined as constipation cases. The daily niacin intake was obtained from dietary recall and dietary supplement recalls of the patients. Weighted multivariate logistic regression analysis, restricted cubic spline regression, subgroup analysis, and interaction analysis were used to assess the correlation between niacin intake and constipation. RESULTS: After adjustment for covariates, the multivariate logistic regression model showed that low niacin intake was associated with a higher risk of constipation (Model 1: OR: 0.917, 95% CI 0.854-0.985, P = 0.023; Model 2: OR: 0.871, 95% CI 0.794-0.955, P = 0.01). After dividing niacin intake into four groups, a daily intake of 0-18 mg niacin was associated with a higher risk of constipation (Model 1: OR: 1.059, 95% CI 1.012-1.106, P = 0.019; Model 2: OR: 1.073, 95% CI 1.025-1.123, P = 0.013). The restricted cubic spline regression analysis also showed a non-linear relationship between niacin intake and the risk of constipation. CONCLUSION: The findings of this study suggested that daily intake of 0-18 mg of niacin was associated with a higher risk of constipation compared to a daily intake of 18-27 mg of niacin.

Prevalence of risk factors associated with rupture of abdominal aortic aneurysm (AAA): a single center retrospective study.

Background: Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease. The mortality rate for an AAA rupture is very high. Understanding the risk factors for AAA rupture would help AAA management, but little is known about these risk factors in the Chinese population. Methods: This retrospective study included patients that were diagnosed with AAA during the last 5 years in a large national hospital in southern China. AAA patients were divided into a rupture and non-rupture group. Clinical data were extracted from the hospital medical record system. Clinical features were compared between the rupture and non-rupture groups. The associations between potential risk factors and rupture risk were evaluated using a multivariate logistic regression analysis. Results: A total of 337 AAA patients were included for analysis in the present study. AAA diameter was significantly larger, and high-sensitivity C-reactive protein (hs-CRP) and serum creatinine levels were both significantly higher in AAA rupture patients. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels were significantly lower in AAA rupture patients. After adjustment, the multivariate logistic analysis found that AAA diameter and hs-CRP were independently positively associated with AAA rupture, and HDL-C level was adversely associated with AAA rupture. Conclusions: Our data suggests that larger AAA diameter and higher hs-CRP level are associated with a higher risk of AAA rupture, and higher HDL-C level is associated with a lower risk of AAA rupture. The results of this study may be helpful for the management of AAA patients in southern China.

Identifying priority protection areas of key food resources of the giant panda.

Animals that live in seasonal environments adjust their reproduction cycle to optimize seasonal forage quality. Giant pandas ( Ailuropoda melanoleuca) are seasonal altitudinal migrants that feed on bamboo shoots and leaves with different nutritional quality. However, the importance of bamboo shoots to giant pandas, especially small and isolated populations, is not fully appreciated. Here, we explored whether mating time of giant pandas is shaped by bamboo shoot phenology. We also assessed the intensity of ongoing bamboo shoot harvesting by local communities in 42 giant panda reserves based on questionnaire surveys. Varying intensity and protection levels of bamboo shoot harvesting were found. From these data, we developed a priority ranking scheme of protection areas for this key food resource. Our study showed that pandas time their mating behavior to coincide with bamboo shoot phenology due to the high nutritional demands associated with mating and pregnancy. We also found that bamboo shoots were not well protected in many places. Liangshan, Daxiangling, and Xiaoxiangling, containing the most isolated panda populations, were identified as the areas with the most urgent need of protection. Furthermore, equal attention should be paid to the QiongL-B population, as this region holds considerable potential to serve as a corridor between the Minshan and Qionglai populations. To address the challenges posed by bamboo shoot harvesting, we recommend establishing more practical bamboo shoot management policies, increasing public awareness of bamboo shoot protection, and providing alternative sources of income for local communities.

Construction and validation of a prognostic nomogram for locally recurrent rectal cancer: a population-based study.

Background: Postoperative recurrence was a life-threatening condition for patients with rectal cancer. Due to the heterogeneity of locally recurrent rectal cancer (LRRC) and controversy of the optimal treatment for patients, it was difficult to predict the prognosis of LRRC. This study aimed to develop and validate a nomogram that could accurately predict the survival probability of LRRC. Methods: Patients diagnosed with LRRC between 2004 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were included in the analysis. Multiple imputations with chained equations were used for missing values. These patients were further randomized into training set and testing set. Cox regression was used for univariate and multivariate analysis. Potential predictors were screened by the least absolute shrinkage and selection operator (LASSO). The Cox hazards regression model was constructed and it was visualized by nomogram. C-index, calibration curve, and decision curve were used to evaluate the model's predictive ability. Then X-tile was used to calculate the optimal cut-off values for all patients and the cohort was divided into three groups. Results: A total of 744 LRRC patients were enrolled and allocated to the training set (n=503) and the testing set (n=241). Cox regression analysis of the training set yielded meaningfully clinicopathological variables. A survival nomogram was created based on the identification of ten clinicopathological features in the LASSO regression analyses of the training set. The C-index of 3-, 5-year survival probabilities were 0.756, 0.747 in training set, and 0.719, 0.726 in testing set, respectively. The calibration curve and decision curve both demonstrated the satisfactory performance of the nomogram for prognosis prediction. Moreover, the prognosis of LRRC could be well distinguished according to the grouping of risk scores (P<0.001 in three groups). Conclusions: This nomogram was the first prediction model to preliminarily evaluate the survival of LRRC patients, which could provide more accurate and efficient treatment in clinical practice.

Prognostic value of TIMM50 expression in colorectal cancer.

Introduction: Translocase of the inner mitochondrial membrane 50 (TIMM50) is universally considered to play a key role in several malignancies. However, its role in predicting colorectal cancer (CRC) patient prognosis remains unclear. Material and methods: A total of 192 CRC patients (123 men and 69 women) who underwent radical resection participated in this study. The patients were followed up every 3 months after surgery for 5 years. TIMM50 expression in tumour tissues was measured by quantitative real-time PCR, Western blotting and immunohistochemistry. TIMM50 expression was studied to assess correlations with clinicopathological factors and survival time. Results: TIMM50 expression increased significantly in CRC tumour tissues. Moreover, high TIMM50 expression was related to pathologic stage (p = 0.043), N stage (p = 0.048) and distant metastasis (p = 0.015), but TIMM50 expression was not related to other clinical factors. A Kaplan-Meier survival analysis indicated that patients with low TIMM50 expression had a longer overall survival than those with high TIMM50 expression (p = 0.002). Furthermore, distant metastasis and high TIMM50 expression were confirmed as independent prognostic factors for the overall survival of CRC patients in a multivariate analysis (p = 0.003). Conclusions: TIMM50 may be a key factor for monitoring CRC and a new prognosis indicator for CRC patients.

Survival nomogram for patients with thymic squamous cell carcinoma, based on the SEER database and an external validation cohort.

OBJECTIVE: This study aimed to construct a nomogram to effectively predict the 3 years and 5 years overall survival of patients with thymic squamous cell carcinoma (TSCC). METHOD: From 2000 to 2019, a total of 355 patients with TSCC were enrolled in our research from the Surveillance, Epidemiology, and End Results (SEER) database and used as the training cohort. 106 patients were included from the Zhejiang Cancer Hospital, for the external validation cohort. A nomogram was constructed based on the risk factors affecting prognosis using a Cox proportional hazards regression model. The discrimination and calibration of the nomogram were evaluated by C-index and curve of calibration. The two cohorts were divided into low-risk and high-risk subgroups based on the median risk score. RESULTS: Age (p = 0.002), stage (p = 0.003), surgery therapy (p < 0.001), and radiotherapy (p = 0.030) were the independent prognostic factors for overall survival and were incorporated in the prognostic model. The discrimination of the nomogram revealed a good prognostic accuracy and clinical applicability as indicated by C-index values of 0.696 (95% confidence interval [CI] 0.676-0.716) and 0.717 (95% CI 0.640-0.794) for the training cohort and external validation cohort, respectively. In addition, the two cohorts were divided into a high-risk group and a low-risk group according to the median risk score. Significant differences in overall survival were observed between the high-risk and low-risk groups in the training (p < 0.0001) and external validation cohort (p < 0.0001). CONCLUSION: We developed a nomogram to predict 3- and 5 year survival rate for TSCC. This nomogram provides a convenient and reliable tool for assessing the condition of patients with TSCC and assisting clinicians in making decisions.

Few Shot Class Incremental Learning via Efficient Prototype Replay and Calibration.

Few shot class incremental learning (FSCIL) is an extremely challenging but valuable problem in real-world applications. When faced with novel few shot tasks in each incremental stage, it should take into account both catastrophic forgetting of old knowledge and overfitting of new categories with limited training data. In this paper, we propose an efficient prototype replay and calibration (EPRC) method with three stages to improve classification performance. We first perform effective pre-training with rotation and mix-up augmentations in order to obtain a strong backbone. Then a series of pseudo few shot tasks are sampled to perform meta-training, which enhances the generalization ability of both the feature extractor and projection layer and then helps mitigate the over-fitting problem of few shot learning. Furthermore, an even nonlinear transformation function is incorporated into the similarity computation to implicitly calibrate the generated prototypes of different categories and alleviate correlations among them. Finally, we replay the stored prototypes to relieve catastrophic forgetting and rectify prototypes to be more discriminative in the incremental-training stage via an explicit regularization within the loss function. The experimental results on CIFAR-100 and miniImageNet demonstrate that our EPRC significantly boosts the classification performance compared with existing mainstream FSCIL methods.

Joint Correlation and Attention Based Feature Fusion Network for Accurate Visual Tracking.

Correlation operation and attention mechanism are two popular feature fusion approaches which play an important role in visual object tracking. However, the correlation-based tracking networks are sensitive to location information but loss some context semantics, while the attention-based tracking networks can make full use of rich semantic information but ignore the position distribution of the tracked object. Therefore, in this paper, we propose a novel tracking framework based on joint correlation and attention networks, termed as JCAT, which can effectively combine the advantages of these two complementary feature fusion approaches. Concretely, the proposed JCAT approach adopts parallel correlation and attention branches to generate position and semantic features. Then the fusion features are obtained by directly adding the location feature and semantic feature. Finally, the fused features are fed into the segmentation network to generate the pixel-wise state estimation of the object. Furthermore, we develop a segmentation memory bank and an online sample filtering mechanism for robust segmentation and tracking. The extensive experimental results on eight challenging visual tracking benchmarks show that the proposed JCAT tracker achieves very promising tracking performance and sets a new state-of-the-art on the VOT2018 benchmark.

Novel WFS1 mutations in patients with low-to-middle frequency hearing loss.

BACKGROUND: Hearing loss (HL) is the most common sensorineural disorder in human. It is estimated that genetic factors contribute to over 50% of prelingual hearing loss. Most of dominant HHL patients manifest postlingual progressive hearing loss that mainly affect high frequencies. However, mutations in a few dominant HL genes, such as WFS1, TECTA and DIAPH1, cause distinct audiogram that primarily affects the low and middle frequencies. METHODS: We recruited twelve independent HL families with worse low or middle frequency audiograms. Each proband of these families was excluded for pathogenic mutations in GJB2, SLC26A4, and MT-RNR1 genes. Mutation screening was performed by whole exome sequencing. Next, candidate variants were validated in each family by sanger sequencing. RESULTS: Six heterozygous WFS1 variants were identified in six families, including three novel mutations (c.2519T > G, p.F840C; c.2048T > G, p.M683R and c.2419A > C, p.S807R) and three previously reported variants (c.2005T > C, p.Y669H; c.2590G > A, p.E864K and c.G2389A, p.D797 N). All the novel mutations were absent in 100 ethnically matched controls and were predicted to be deleterious by multiple algorithms. CONCLUSIONS: We identified three novel and three previously reported WFS1 mutations in six unrelated Chinese families. Our findings enriched the genotype-phenotype spectrum of WFS1 related NSHL. Additional genotype-phenotype correlation study will clarify the detailed phenotypic range caused by WFS1 mutations.

Clinical outcomes of immune checkpoint inhibitor therapy for advanced lung adenosquamous carcinoma.

Background: Primary adenosquamous carcinoma (ASC) of the lung is a rare and aggressive disease and limited information is available on the efficacy of immune checkpoint inhibitors (ICIs) for this disease. Here, we evaluated the expression status of programmed death-1 ligand 1 (PD-L1) and efficacy of ICIs in patients with pulmonary ASC. Methods: The efficacy and toxicity of ICIs were examined in 38 patients with previously treated lung ASC from November 2017 to October 2021 in Zhejiang Cancer Hospital (Hangzhou, China). Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. Results: A total of 38 patients with ASC were included in this retrospective study. ICI treatment induced an objective response rate (ORR) of 23.7% and a disease control rate (DCR) of 86.8%. The median progression-free survival (PFS) and median overall survival (OS) were 5.47 and 24.10 months, respectively. Seventeen patients were successfully evaluated for PD-L1 expression status, with 11 (64.7%) identified as PD-L1-positive. ORR and DCR for PD-L1-positive patients were 36.4% (4/11) and 100% (11/11) and the corresponding values for PD-L1-negative patients were 0 (0/6) and 50% (3/6), respectively. The median PFS of PD-L1-positive and PD-L1-negative patient groups was 5.00 and 1.90 months (P=0.166) while the median OS was 11.30 months and not reached, respectively (P=0.966). The incidence rate of immune-related adverse events (irAEs) was 52.6%, with 13.2% grade 3-4 irAEs. The most common irAEs were malaise and pneumonitis. One patient died of pneumonitis during the study. Conclusions: ICIs show considerable potential as a treatment option for lung ASC. PFS and OS rates are similar for PD-L1-positive and PD-L1-negative patients. Further large-scale studies are required to establish the relationship between PD-L1 expression and response to ICIs in ASC.

Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis.

The efficacy of immune checkpoint inhibitors (ICIs) on KRAS-mutant advanced non-small cell lung cancer (NSCLC) remains controversial. This retrospective study compared the effects of ICIs treatment and chemotherapy on the prognosis of patients with KRAS-mutant advanced NSCLC and different mutant subtypes in the real world. The study included 95 patients with KRAS-mutant advanced NSCLC. Patients treated with first-line ICIs plus platinum-containing chemotherapy had better progression-free survival (PFS) (7.4 vs 4.5 months, P = 0.035) and overall survival (OS) (24.1 vs 13.2 months, P = 0.007) than those receiving platinum-containing chemotherapy alone, and second-line ICI monotherapy was associated with better PFS (4.8 vs 3.0 months, P = 0.043) and OS (18.0 vs 13.8 months, P = 0.013) than chemotherapy monotherapy. There was no significant difference in PFS (5.267 vs 6.734 months, P = 0.969) and OS (19.933 vs 20.933 months, P = 0.808) between patients with KRAS-mutant and KRAS-wild-type NSCLC treated with ICIs or between KRAS G12C and KRAS non-G12C patients (PFS: 8.1 vs 4.8 months, P = 0.307; OS: 21.3 vs 21.8 months, P = 0.434). In summary, patients with advanced NSCLC with KRAS mutations can benefit from ICIs, but no difference between KRAS mutant subtypes was observed.

Loss of ndrg2 Function Is Involved in Notch Activation in Neuromast Hair Cell Regeneration in Zebrafish.

The regeneration of hair cells in zebrafish is a complex process involving the precise regulation of multiple signaling pathways, but this complicated regulatory network is not fully understood. Current research has primarily focused on finding molecules and pathways that can regulate hair cell regeneration and restore hair cell functions. Here, we show the role of N-Myc downstream regulated gene 2 (ndrg2) in zebrafish hair cell regeneration. We first found that ndrg2 was dynamically expressed in neuromasts of the developing zebrafish, and this expression was increased after neomycin-induced hair cell damage. Then, ndrg2 loss-of-function larvae showed reduced numbers of regenerated hair cells but increased numbers of supporting cells after neomycin exposure. By in situ hybridization, we further observed that ndrg2 loss of function resulted in the activation of Notch signaling and downregulation of atoh1a during hair cell regeneration in vivo. Additionally, blocking Notch signaling rescued the number of regenerated hair cells in ndrg2-deficient larvae. Together, this study provides evidence for the role of ndrg2 in regulating hair cell regeneration in zebrafish neuromasts.