bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic characteristics and clinical response to immunotherapy targeting programmed cell death 1 for patients with advanced gastric cancer with liver metastases
Authors: Liang Huayuan , Li Zhiwei , Huang Zhicheng , Wu Chaorui , Qiu Yaopeng , Liang Yanrui , Chen Xinhua , Li Fengping , Xu Zhou , Li Guoxin , Liu Hao , Zhao Liying
Published: September 2022

Background

The specific efficacy of immunotherapy for patients with liver metastases of gastric cancer is unclear. This study set out to explore the treatment response and related prognostic factors for patients with liver metastases of gastric cancer treated with immunotherapy.

Patients and methods

This retrospective cohort study included 135 patients with unresectable advanced gastric cancer. According to the presence of liver metastases and/or first-line treatment with immunotherapy, patients were divided into the following three groups: I-LM(-) group(patients without liver metastases treated with immunotherapy, n=66), I-LM(+) group(patients with liver metastases treated with immunotherapy, n=36), C-LM(+) group(patients with liver metastases treated with chemotherapy and/or target therapy, n=33). Cox regression analyses were used to identify factors associated with survival in all patients and the three groups, respectively.

Results

For the patients with liver metastases treated with immunotherapy, multivariate analysis showed that only the presence of peritoneal metastases was significantly associated with shorter PFS [hazard ratios (HR), 3.23; 95% CI, 1.12-9.32; P=0.030] and the patients with peritoneal metastases had shorter median PFS than patients without peritoneal metastases(3.1 vs 18.4 months; P=0.004), while the objective response rate was 100% in patients with HER2-positive (2 complete radiographic responses and 2 partial responses; 3 of 4 patients were still ongoing benefits [median follow-up time, 15.3 months ; interquartile range(IQR), 6.3-17.9 months]).

Conclusions

The findings suggest that patients with various types of gastric cancer liver metastases respond differently to immune checkpoint inhibitors, HER2-positive patients may derive clinical benefits from immune checkpoint inhibitors, while the presence of peritoneal metastases is associated with resistance.
Prognostic value of TIGIT in East Asian patients with solid cancers: A systematic review, meta-analysis and pancancer analysis
Authors: Li Sicong , Li Lanxing , Pan Tianyan , Li Xiaoqun , Tong Yujia , Jin Yongdong
Published: September 2022

Background

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) participates in tumor immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the prognostic value of TIGIT and its immunological function in solid cancers.

Methods

Three databases were searched for relevant articles. The main endpoints were overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Hazard ratios (HR) were pooled by using fixed-effects or random-effects models. Pancancer analysis of TIGIT was performed based on public online databases, mainly The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UCSC Xena. The possible relationships between TIGIT expression and the tumor microenvironment (TME), infiltration of immune cells, immune-related genes, tumor mutation burden (TMB), and microsatellite instability (MSI) were revealed in this article.

Results

Sixteen studies met the inclusion criteria. High expression of TIGIT was associated with worse OS [HR= 1.73, 95% confidence interval (CI) 1.50, 1.99], PFS (HR = 1.53, 95% CI [1.25, 1.88]), RFS (HR = 2.40, 95% CI [1.97, 2.93]), and DFS (HR= 6.57, 95% CI [0.73, 59.16]) in East Asian patients with solid cancers. TIGIT expression was positively correlated with immune infiltration scores and infiltration of CD8 T lymphocytes in all of the cancers included. TIGIT was found to be coexpressed with the genes encoding immunostimulators, immunoinhibitors, chemokines, chemokine receptors, and major histocompatibility complex (MHC), especially in gastroesophageal cancer. TMB and MSI were also associated with TIGIT upregulation in diverse kinds of cancers.

Conclusion

High expression of TIGIT is associated with poorer prognosis in East Asian patients with solid cancers. TIGIT is a novel prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumorigenesis.
Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice
Authors: Li Hanglin , Ma Linyan , Li Wenjian , Zheng Boyang , Wang Junhai , Chen Shunyan , Wang Yang , Ge Fei , Qin Beibei , Zheng Xiaoqing , Deng Yuqing , Zeng Ruihong
Published: September 2022

Background

Infants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma.

Objective

To address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma.

Methods

Neonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma.

Results

PVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma.

Conclusion

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood.
Case report: Immunoadsorption therapy for anti-caspr1 antibody-associated nodopathy
Authors: Liu Lili , Chen Juanjuan , Zhang Yue , Wu Jun , Hu Jun , Lin Zhijian
Published: September 2022

Background and objectives

Several autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) in the last few years. Then a new concept, autoimmune nodo-paranodopathies was proposed. Cases of Caspr1 autoantibodies are the most rare. Here we describe an anti-Caspr1 nodopathy patient, summarized his clinical, physiological and pathological features.

Case presentation

We present the case of a 56-year-old male patient with proprioceptive loss, ataxia, coarse tremor and distal limb weakness without any painess and cranial involvement. Electrophysiological studies showed prolonged distal motor latencies, conduction slowing and reduced amplitude distal compound muscle action potential (CMAP) amplitude. Antibodies against the nodes of Ranvier in serum samples revealed a positive finding for the anti-Caspr1 antibody (1:10).Myelinated fiber loss could be revealed in nerve biopsy. Longitudinal ultrathin sections of the nodal region was discovered in electron microscope, the paranodal/nodal architecture was destructed. It was lack of transverse bands and enlargement of the space between the axon and the paranodal loops was seen. The patient improved obviously after three times immunoadsorption(IA) therapy.

Conclusion

Anti-Caspr1 nodopathy patient may present atypical symptoms without any neuropathic pain and cranial palsy. The destruction of paranodal/nodal architecture could be observed in nerve biopsy, which may be caused by the lost of axoglial complex formed by NF155, CNTN1 and Caspr1. Antibodies detection is important for the diagnosis, while IA therapy could be regarded as an option for the patients allergic to rituximab (RTX).
Effect of long-term manganese exposure on oxidative stress, liver damage and apoptosis in grouper Epinephelus moara ♀ × Epinephelus lanceolatus ♂
Authors: Wang Xi , Liu Bao-Liang , Gao Xiao-Qiang , Fang Ying-Ying , Zhang Xian-Hong , Cao Shu-Quan , Zhao Kui-Feng , Wang Feng
Published: September 2022

Manganese is an indispensable trace element, however, it may be present at high concentrations in water and sediments of aquatic ecosystems due to natural and anthropogenic activities, and can interfere with physiological and biochemical mechanisms in fish. This study was conducted to determine the toxic effects associated with exposure to Mn2+ (0, 0.5, 1, 2, and 4 mg/L) for 30 d, regarding liver damage and apoptosis in Yunlong grouper (Epinephelus moara♀×E. lanceolatus♂). Expression of superoxide dismutase (sod) and catalase (cat) genes in the liver was significantly increased on days 10 and 20 following Mn2+ exposure (4 mg/L), but was reduced on day 30. Similarly, expression of glutathione peroxidase (gpx) and glutathione reductase (gr) genes was elevated after 10 d of exposure to 2 and 4 mg/L Mn2+, but decreased after 20 and 30 d. After 30 d of exposure to high concentrations (2 and 4 mg/L) of Mn2+, liver tissue showed hepatic sinusoidal gap congestion, dilatation, cell vacuolation, and necrosis. In addition, the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) as well as 8-hydroxydeoxyguanosine (8-OHdG) levels were significantly increased after Mn2+ exposure. Moreover, Mn2+ exposure altered the expression pattern of some pivotal genes associated to apoptosis (p53, bax, bcl-2, apaf-1, caspase-9, and caspase-3), which suggested that Mn2+ exposure induces apoptosis through the mitochondrial pathway. The above results showed that excessive Mn2+ induced apoptosis and liver damage in grouper through elicitation of oxidative stress. These insights help elucidate the mechanism by which Mn2+ induces toxicity in marine fish, and provide a new perspective regarding the detrimental effects of heavy metals in fish.
Associated benefits of manatee watching in the Costa dos Corais Environmental Protection Area
Authors: Izidoro Flávia Bonfietti , Schiavetti Alexandre
Published: September 2022

Marine mammals provide diverse and interconnected ecosystem services. According to the literature, the use of these services is associated with human needs related to provision, ecosystem regulation, education, culture, spirituality, and recreation. Tourism with marine animals can provide psychological benefits, emotional connection, fun, and learning, in addition to generating high income in local communities. This study aimed to determine the willingness to pay of the community and visitors for the conservation of the West Indian manatee (Trichechus manatus), identify the revenue from manatee watching, and evaluate well-being according to the participants of this attraction. The study was conducted from January 2020 to February 2021, in the Costa dos Corais Environmental Protection Area, Brazil. Data were collected using questionnaires and specific forms for the seven categories of social actors involved with manatee watching. The contingent valuation method was used to evaluate the willingness to pay of the respondents for the conservation of the manatee. The willingness of individuals to conduct voluntary work was also considered and subsequently converted into monetary values. Revenue from manatee watching was calculated through the direct costs of acquiring tour tickets and indirect expenditure on accommodation, food, transportation, and souvenirs. The feelings of the tourists who completed the trip were determined using a semi-structured question and their level of satisfaction was established using a five-point Likert scale. A total of 761 interviews were conducted. Most of the survey respondents were female, with a high level of education, and with a median monthly income of USD 1 800 dollars. The average mean value declared for willingness to pay was USD 3.6 dollars per month. The median hours devoted to volunteer work were 60 hours per year, which is the equivalent of USD 2.59 dollars per month. Direct revenue from this form of tourism was USD 125 595 dollars and total projected revenue was USD 15 392 225.45 dollars in the studied period. The vast majority of tourists managed to see the manatee and declared positive feelings after the trip. We believe that more elaborate promotion of manatee-watching would attract a higher number of tourists to the protected area.
China’s policy for the marine engineering equipment industry and potential challenges: An appraisal of the new developments under the 14th five-year plans
Authors: Zhang Hu , Wang Qiuwen , Huang Jiabei
Published: September 2022

The Five-Year Plans are China’s most important macroeconomic and social management tool, setting goals and directions for the national economic and social development vision. To date, China has implemented 13 periods of Five-Year Plans. On March 12, 2021, the Chinese government adopted its 14th Five-Year Plan, which requires breakthrough the key core technologies of marine engineering and cultivating and expanding the marine engineering equipment industry. This research conducts a policy analysis to comprehensively examine the development plans for the marine engineering equipment industry in these 14th Five-Year Plans issued by China’s central level and local level governments. By summarizing and analyzing these policies pertaining to the marine engineering equipment industry, it aims to show a holistic picture for the new policy developments in China’s new five-year period. This paper also highlights the challenges and pressures that might be faced by the Chinese authorities in the policy implementation stage.
Contribution of allergy in the acquisition of uncontrolled severe asthma
Authors: Delgado Dolset María Isabel , Obeso David , Rodriguez-Coira Juan , Villaseñor Alma , González Cuervo Heleia , Arjona Ana , Barbas Coral , Barber Domingo , Carrillo Teresa , Escribese María M.
Published: September 2022

Asthma is a multifactorial, heterogeneous disease that has a challenging management. It can be divided in non-allergic and allergic (usually associated with house dust mites (HDM) sensitization). There are several treatments options for asthma (corticosteroids, bronchodilators, antileukotrienes, anticholinergics,…); however, there is a subset of patients that do not respond to any of the treatments, who can display either a T2 or a non-T2 phenotype. A deeper understanding of the differential mechanisms underlying each phenotype will help to decipher the contribution of allergy to the acquisition of this uncontrolled severe phenotype. Here, we aim to elucidate the biological pathways associated to allergy in the uncontrolled severe asthmatic phenotype. To do so, twenty-three severe uncontrolled asthmatic patients both with and without HDM-allergy were recruited from Hospital Universitario de Gran Canaria Dr. Negrin. A metabolomic fingerprint was obtained through liquid chromatography coupled to mass spectrometry, and identified metabolites were associated with their pathways. 9/23 patients had uncontrolled HDM-allergic asthma (UCA), whereas 14 had uncontrolled, non-allergic asthma (UCNA). 7/14 (50%) of the UCNA patients had Aspirin Exacerbated Respiratory Disease. There were no significant differences regarding gender or body mass index; but there were significant differences in age and onset age, which were higher in UCNA patients; and in total IgE, which was higher in UCA. The metabolic fingerprint revealed that 103 features were significantly different between UCNA and UCA (p < 0.05), with 97 being increased in UCA and 6 being decreased. We identified lysophosphocholines (LPC) 18:2, 18:3 and 20:4 (increased in UCA patients); and deoxycholic acid and palmitoleoylcarnitine (decreased in UCA). These metabolites were related with a higher activation of phospholipase A2 (PLA2) and other phospholipid metabolism pathways. Our results show that allergy induces the activation of specific inflammatory pathways, such as the PLA2 pathway, which supports its role in the development of an uncontrolled asthma phenotype. There are also clinical differences, such as higher levels of IgE and earlier onset ages for the allergic asthmatic group, as expected. These results provide evidences to better understand the contribution of allergy to the establishment of a severe uncontrolled phenotype.
Cutaneous vasculitis; An algorithmic approach to diagnosis
Authors: Alpsoy Erkan
Published: September 2022

Vasculitides, characterized by inflammation and damage of blood vessels, encompass a broad spectrum of diseases. They can occur with different pathophysiological mechanisms and have a rich clinical heterogeneity depending on the vessel diameters they affect. Vasculitides may also present with a broad spectrum of severity, ranging from a mild self-limiting to a potentially life-threatening disease. The high prevalence of skin involvement in vasculitis, visible character and, finally, the easy accessibility of the skin for both physical examination and biopsy offers important advantages for prompt disease recognition and diagnosis. Thus, dermatologists are privileged to diagnose the disease earlier and more effectively than any other discipline. As a consequence, a detailed clinical and histopathological evaluation of the skin is one of the most critical steps in diagnosing vasculitis. Besides obtaining a good medical history, laboratory and radiological evaluation methods are used in the diagnosis. In this review, a practical and algorithmic approach is aimed to assist in the diagnosis of vasculitis. However, this approach should not be seen as strict rules. This stepwise algorithmic diagnostic approach for vasculitis was developed by combining the current literature knowledge and the author's experience in this field to provide a rational framework for selecting the most appropriate among various diagnostic approaches.
Negative impact of SARS-CoV-2 infection in acute coronary syndrome mortality in a Latin American cohort study
Authors: Junior Wenderval Borges Carvalho , Ferreia Neila Nunes , Santos Luciano de Moura , Borges Patrícia Brito de Almeida , Albuquerque Cleandro Pires de , Espindola Laila Salmen , Nóbrega Otávio de Toledo , Gomes Ciro Martins , Mota Licia Maria Henrique da , Soares Alexandre Anderson de Sousa Munhoz
Published: September 2022

Purpose

COVID-19 infection has been associated with a high risk of complications and death among patients with acute coronary syndrome (ACS). However, there is little information on the simultaneous involvement in Latin American countries.

Methods

In the period between May 2020 and February 2021, an observational, longitudinal, prospective cohort study with two parallel branches was conducted in private and public hospitals in Brasilia, Brazil, including patients with ACS with and without a positive SARS-CoV-2 test result during hospitalization.

Results

A total of 149 patients with ACS were included (75 with COVID-19 and 74 controls). Patients with COVID-19 exhibited an average of 62 years of age, 57% men, 40% diabetics, 67% hypertensive, 48% had an ACS with ST-segment elevation, Killip I was predominant, a low Syntax Score in 72%, with an average Grace Score of 117, and a length of hospitalization of 43 days in average. The control branch was similar in clinical characteristics, except for a lower proportion of ST-segment elevation ACS (16%, p < 0.01) and a higher incidence of arrhythmias (8 vs. 20 %, p = 0.03). Using the Cox regression method of analysis of covariates collected in the study, it was identified that patients with COVID-19 had a risk of death 2.34 times higher than patients without COVID-19 (p = 0.049).

Conclusion

In this study conducted in a Latin American capital, SARS-CoV-2 infection predicted a higher chance of death in patients admitted with ACS, which is a finding that reinforces the need for greater care when diseases develop in overlapping ways.
Exploitation of wasted bread as substrate for polyhydroxyalkanoates production through the use of Haloferax mediterranei and seawater
Authors: Montemurro Marco , Salvatori Gaia , Alfano Sara , Martinelli Andrea , Verni Michela , Pontonio Erica , Villano Marianna , Rizzello Carlo Giuseppe
Published: September 2022

The use of the halophile microorganism Haloferax mediterranei, able to synthesize poly(hydroxybutyrate-hydroxyvalerate) (PHBV), is considered as a promising tool for the industrial production of bioplastic through bioprocessing. A consistent supplementation of the growth substrate in carbohydrates and minerals is overall necessary to allow its PHBV production. In this work, wasted bread was used as substrate for bioplastic production by microbial fermentation. Instead of the consistent and expensive minerals supplement required for Hfx. mediterranei DSM1411 growth, microfiltered seawater was added to the wasted bread-derived substrate. The suitable ratio of wasted bread homogenate and seawater, corresponding to 40:60, was selected. The addition of proteases and amylase to the bread homogenate promoted the microbial growth but it did not correspond to the increase of bioplastic production by the microorganism, that reach, under the experimental conditions, 1.53 g/L. An extraction procedure of the PHBV from cells, based on repeated washing with water, followed or not by a purification through ethanol precipitation, was applied instead of the conventional extraction with chloroform. Yield of PHBV obtained using the different extraction methods were 21.6 ± 3.6 (standard extraction/purification procedure with CHCl3:H2O mixture), 24.8 ± 3.0 (water-based extraction), and 19.8 ± 3.3 mg PHAs/g of wasted bread (water-based extraction followed by ethanol purification). Slightly higher hydroxyvalerate content (12.95 vs 10.78%, w/w) was found in PHBV obtained through the water-based extraction compared to the conventional one, moreover, the former was characterized by purity of 100% (w/w). Results demonstrated the suitability of wasted bread, supplemented with seawater, to be used as substrate for bioplastic production through fermentation. Results moreover demonstrated that a solvent-free extraction, exclusively based on osmotic shock, could be used to recover the bioplastic from cells.
Mouse feeding study and microbiome analysis of sourdough bread for evaluation of its health effects
Authors: Kwon Joon-Gi , Park Sung-Hoon , Kwak Jeong-Eun , Cho Jae Hyoung , Kim Gooyoun , Lee Deukbuhm , Kim Dong Hyun , Kim Hyeun Bum , Lee Ju-Hoon
Published: September 2022

Sourdough bread fermented with yeast and lactic acid bacteria (LAB) is thought to have various beneficial health effects. However, its beneficial effects were not fully evaluated with in vivo mouse model. To evaluate these effects in vivo, a mouse feeding study and microbiome analysis of white bread containing 40% sourdough (WBS) and yeast-leavened white bread (WB) were performed. Although feed consumption and body weight increased with WBS, the glycemic index was reduced, suggesting a diabetes-lowering effect, probably due to the presence of dietary fiber and short-chain fatty acids (SCFA). In addition, a mineral absorption test showed that WBS increased magnesium absorption owing to phytate degradation during fermentation. Interestingly, WBS decreased total cholesterol and triglycerides, probably due to the dietary fiber and SCFA in LAB. In addition, the ratio of low- and high-density lipoprotein was decreased in WBS, implying potential risk reduction for cardiovascular disease. An immunomodulatory assay of WBS revealed that pro-inflammatory cytokines TNF-α and IL-6 were decreased, suggesting anti-inflammatory activity. Gluten degradation by fermentation and antioxidation activity of menaquinol/ubiquinol by gut microbiota also supported the anti-inflammatory activity of sourdough bread. Furthermore, some beneficial gut bacteria, including Akkermansia, Bifidobacterium, and Lactobacillus, were increased in WBS. In particular, Akkermansia has been associated with anti-inflammatory properties. Consequently, WBS has beneficial effects on health, including decreased glycemic index and cholesterol, increased mineral availability and absorption, anti-inflammatory properties, and establishment of healthy gut microbiota.
Endocytosis at extremes: Formation and internalization of giant clathrin-coated pits under elevated membrane tension
Authors: Akatay Ahmet Ata , Wu Tianyao , Djakbarova Umidahan , Thompson Cristopher , Cocucci Emanuele , Zandi Roya , Rudnick Joseph , Kural Comert
Published: September 2022

Internalization of clathrin-coated vesicles from the plasma membrane constitutes the major endocytic route for receptors and their ligands. Dynamic and structural properties of endocytic clathrin coats are regulated by the mechanical properties of the plasma membrane. Here, we used conventional fluorescence imaging and multiple modes of structured illumination microscopy (SIM) to image formation of endocytic clathrin coats within live cells and tissues of developing fruit fly embryos. High resolution in both spatial and temporal domains allowed us to detect and characterize distinct classes of clathrin-coated structures. Aside from the clathrin pits and plaques detected in distinct embryonic tissues, we report, for the first time, formation of giant coated pits (GCPs) that can be up to two orders of magnitude larger than the canonical pits. In cultured cells, we show that GCP formation is induced by increased membrane tension. GCPs take longer to grow but their mechanism of curvature generation is the same as the canonical pits. We also demonstrate that GCPs split into smaller fragments during internalization. Considering the supporting roles played by actin filament dynamics under mechanically stringent conditions that slow down completion of clathrin coats, we suggest that local changes in the coat curvature driven by actin machinery can drive splitting and internalization of GCPs.
Inhibition of the integrated stress response reverses oxidative stress damage-induced postoperative cognitive dysfunction
Authors: Jiang Linhao , Dong Rui , Xu Minhui , Liu Yujia , Xu Jiyan , Ma Zhengliang , Xia Tianjiao , Gu Xiaoping
Published: September 2022

Postoperative cognitive dysfunction (POCD) is a common complication following anesthesia and surgery that might lead to a decline in learning and memory. Oxidative stress damage is one of the pathogenic mechanisms underlying POCD. Recent studies had shown that the integrated stress response (ISR) is closely related to oxidative stress. The core response of the ISR is phosphorylation of eIF2α. Various cellular stress stimuli trigger activation of eIF2α kinases, thus causing phosphorylation of eIF2α. ISR is associated with many neurodegenerative diseases; however, the relationship between POCD and ISR has not been defined. In the present study, the tibias in 4-month-old male C57BL/6 mice were fractured under isoflurane anesthesia to establish the POCD animal model. Cognitive function was assessed by fear conditioning tests and the Y-maze from 3 to 14 days post-surgery. Western blot was used to determine the levels of PeIF2α, eIF2α, ATF4, GADD34, CHOP, BDNF, proBDNF, and p-NR2B expression. The levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to determine oxidative stress in hippocampal tissues. After tibial fracture surgery in mice, the hippocampus had increased levels of PeIF2α, ATF4, GADD34, and CHOP protein, ROS-positive cells, and average fluorescence intensity, SOD activity was decreased, and the MDA level was increased. The ISR inhibitor, ISRIB, reduced the levels of PeIF2α, ATF4, GADD34, and CHOP protein, and alleviated oxidative stress in the hippocampus of POCD mice. Moreover, ISRIB ameliorated cognitive dysfunction in POCD mice. Our findings suggested that targeting ISR may represent an effective approach to combat POCD.
Outcome and risk factors of complications after cranioplasty with polyetheretherketone and titanium mesh: A single-center retrospective study
Authors: Yao Shun , Zhang Qiyu , Mai Yiying , Yang Hongyi , Li Yilin , Zhang Minglin , Zhang Run
Published: September 2022

Background

To compare the incidence of complications and constructive effects of cranioplasty with polyetheretherketone (PEEK) and titanium mesh after decompressive craniectomy, and to further explore potential risk factors of postoperative and post-discharge complications.

Methods

A retrospective study was conducted on 211 patients who underwent PEEK or titanium mesh cranioplasty in the Department of Neurosurgery of Zhujiang Hospital, Southern Medical University, between July 2017 and September 2021. Demographic data, imaging data, and postoperative complications were recorded and statistically analyzed. Long-term effects and satisfaction degree were evaluated based on following-up telephone survey. Univariate and multivariate logistic regression models were used to analyze risk factors of postoperative and post-discharge complications of PEEK and titanium cranioplasty.

Results

The total postoperative complication rates of the PEEK and titanium mesh groups were 38.7 and 51.4% (p = 0.063), and post-discharge complication rates were 34.7 and 36.0% (p = 0.703), respectively. The incidence of pneumocephalus during hospitalization (33.3% vs. 6.6%, p < 0.001) and epidural effusion in the titanium mesh group were significantly higher than that in the PEEK group (18.0 vs. 6.6%, p = 0.011). Patients in PEEK group were less likely to occur subcutaneous effusion after discharge than in TI group (2.0 vs. 10.5%, p = 0.013). Multivariate logistic regression analysis revealed a history of ventriculoperitoneal shunt (VPS) before CP was an independent risk factor for postoperative overall complications (p = 0.023). Either superficial (p < 0.001) or intracranial infection (p = 0.001) was a risk factor for implant failure. Depressed skull defects (p = 0.024) and cranioplasty with titanium cranioplasty (p < 0.001) were associated with increased incidence of early pneumocephalus.

Conclusion

There were no differences in overall postoperative and post-discharge complication rates between the titanium mesh and PEEK. A history of VPS before cranioplasty was an independent risk factor for postoperative overall complications, and infection was a risk factor for implant failure. Finally, depression skull defects and titanium mesh implants increased the incidence of postoperative pneumocephalus. Our results aim to promote a better understanding of PEEK and titanium cranioplasty and to help both clinicians and patients make better choices on implant materials.
Recognition ability of untrained neural networks to symbolic numbers
Authors: Zhou Yiwei , Chen Huanwen , Wang Yijun
Published: September 2022

Although animals can learn to use abstract numbers to represent the number of items, whether untrained animals could distinguish between different abstract numbers is not clear. A two-layer spiking neural network with lateral inhibition was built from the perspective of biological interpretability. The network connection weight was set randomly without adjustment. On the basis of this model, experiments were carried out on the symbolic number dataset MNIST and non-symbolic numerosity dataset. Results showed that the model has abilities to distinguish symbolic numbers. However, compared with number sense, tuning curves of symbolic numbers could not reproduce size and distance effects. The preference distribution also could not show high distribution characteristics at both ends and low distribution characteristics in the middle. More than half of the network units prefer the symbolic numbers 0 and 5. The average goodness-of-fit of the Gaussian fitting of tuning curves increases with the increase in abscissa non-linearity. These results revealed that the concept of human symbolic number is trained on the basis of number sense.
Studying food entrainment: Models, methods, and musings
Authors: Trzeciak Jacqueline R. , Steele Andrew D.
Published: September 2022

The ability to tell time relative to predictable feeding opportunities has a long history of research, going back more than 100 years with behavioral observations of honeybees and rats. Animals that have access to food at a particular time of day exhibit “food anticipatory activity” (FAA), which is a preprandial increase in activity and arousal thought to be driven by food entrained circadian oscillator(s). However, the mechanisms behind adaptation of behavior to timed feeding continue to elude our grasp. Methods used to study circadian entrainment by food vary depending on the model system and the laboratory conducting the experiments. Most studies have relied on rodent model systems due to neuroanatomical tools and genetic tractability, but even among studies of laboratory mice, methods vary considerably. A lack of consistency within the field in experimental design, reporting, and definition of food entrainment, or even FAA, makes it difficult to compare results across studies or even within the same mutant mouse strain, hindering interpretation of replication studies. Here we examine the conditions used to study food as a time cue and make recommendations for study design and reporting.
LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer
Authors: Song Zhengwei , Wang Xiaoguang , Chen Fei , Chen Qiuli , Liu Wenjun , Yang Xiaodan , Zhu Xun , Liu Xiaorong , Wang Peter
Published: September 2022

Pancreatic cancer is the fourth leading cause of cancer death in the United States. The main methods of treating pancreatic cancer are surgery and chemotherapy, but the treatment efficacy is low with a poor prognosis. Immunotherapy represented by PD-1/PD-L1 has brought a milestone progress in the treatment of pancreatic cancer. However, the unique tumor microenvironment of pancreatic cancer presents challenges for immunotherapy. In addition, m6A is a common RNA modification and a potential molecular target in tumor therapy. The expression pattern of m6A in pancreatic cancer is still unclear. LncRNAs also play an essential role in pancreatic cancer development and treatment. In this study, we found that some m6A regulators were significantly elevated in pancreatic cancer and associated with the expression of PD-1/PD-L1. Moreover, we observed that METTL3 can increase the expression of PD-L1. Notably, METTL3 positively regulates the expression of lncRNA MALAT1 in pancreatic cancer cells. Strikingly, lncRNA MALAT1 increased the expression of PD-L1 in pancreatic cancer cells. This finding indicated that METTL3 regulated the expression of PD-L1 possibly via targeting lncRNA MALAT1 in pancreatic cancer cells. Lastly, MALAT1 governed the viability of pancreatic cancer cells. Taken together, lncRNA MALAT1 is involved in METTL3-mediated promotion of PD-L1 expression in pancreatic cancer.
Immunotherapy improved cancer related pain management in patients with advanced Hepato-Pancreatic Biliary Cancers: A propensity score-matched (PSM) analysis
Authors: Wu Xiufang , Qin Fei , Zhang Qiangze , Qiao Jianling , Qi Yulian , Liu Bing
Published: September 2022

Background

Hepato-pancreato-biliary (HPB) cancer is a serious form of cancer. in many HPB cancers, including cholangiocarcinoma (also known as bile duct cancer), pancreatic cancer, hepatocellular carcinoma, gallbladder cancer and ampullary cancer, although several treatment options are developed during these decades, the prognosis is still poor.

Methods

A total of 356 HPB cancers patients in advanced stage received different kinds of treatments including adjuvant chemotherapy, radiotherapy, targeted therapy and immunotherapy. Among these patients with advanced HPB cancers, 135 patients have received standard opioid treatment for pain controlling.

Results

We performed a PSM analysis to minimize differences between groups. Before PSM, 135 patients received standard opioid treatment for pain controlling were enrolled in this study and divided into 4 groups, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. Relevant clinical variables that were available at the time of initial diagnosis were used for 1:1 matching between the two groups. After PSM, the cohort consisted of 18 patients in each group. Prior to PSM, patients received targeted therapy and immunotherapy exhibited shorter median OSs than their counterparts for patients received chemotherapy and radiotherapy (p<0.001). there were so survival differences among all the four different treatments for these patients with HPB cancers (p>0.05). We found the OMED (mg) q/day and NRS scores decreased significantly when patients received immunotherapy treatment. Fewer adverse events were showed between immunotherapy group and other three treatment groups, which was consistent with our previous reports.

Conclusion

In conclusion, we found that given the same survival benefit, immunotherapy reduced opioid consumption in HPB cancers patients and improved the pain management. Moreover, immunotherapy results in fewer other adverse effects.
Symptom burden and surgical outcome in non-skull base meningiomas
Authors: Mederer Tobias , Schachinger Sebastian , Rosengarth Katharina , Brosig Anja , Schebesch Karl-Michael , Doenitz Christian , Schmidt Nils-Ole , Proescholdt Martin Andreas
Published: September 2022

Purpose

Non-skull base meningiomas (NSBM) are a distinct entity and frequently present with focal neurological deficits. This study was designed to analyze functional and oncological outcome following microsurgical tumor resection in patients with NSBM.

Patients and methods

An analysis of 300 patients that underwent NSBM resection between 2003 and 2013 was performed. Assessment measures for functional outcome were Karnofsky Performance Scale (KPS), Medical Research Council - Neurological Performance Scale (MRC-NPS), and improvement rates of focal deficits and seizures. The extent of resection; recurrence-free survival (RFS) and tumor-specific survival (TSS) were also determined.

Results

Impaired KPS and MRC-NPS were present in 73.3% and 45.7%, respectively. Focal neurological deficits were recorded in 123 patients (41.0%), with hemiparesis (21.7%) and aphasia (9.3%) the most prevalent form of impairment. Most meningiomas were localized at the convexity (64.0%), followed by falcine tumors (20.3%). Both KPI and MRC-NPS scores were significantly improved by surgical resection. Postoperative improvement rates of 96.6%, 89.3%, 72.3%, 57.9%, and 27.3% were observed for aphasia, epilepsy, hemiparesis, cranial nerve, and visual field deficits, respectively. Long-term improvement was achieved in 83.2%, 89.3%, 80.0%, 68.4% and 54.6% of patients, respectively. Gross total resection (GTR) over subtotal resection (STR) significantly improved preoperative seizures and visual field deficits and correlated with reduced risk of new postoperative hemiparesis. Poor Simpson grade was the only significant prognostic factor in multivariate analysis for long-term functional deficit, which occurred in 7.3%. Median RFS was 45.9 months (6.0 - 151.5 months), while median TSS was 53.7 months (3.1 – 153.2 months). Both WHO grade (p= 0.001) and Simpson classification (p= 0.014 and p= 0.031) were independent significant prognostic factors for decreased RFS and TSS by multivariate analysis, respectively. Furthermore, tumor diameter > 50 mm (p= 0.039) significantly correlated with decreased TSS in multivariate analysis.

Conclusion

Surgical resection significantly and stably improves neurological deficits in patients with NSBM.
The impact of parenting stress on parents of school-age children with drug-resistant epilepsy
Authors: Lu Hsin-Hui , Tsai Chun-Yu , Chou I-Ching , Tsai Jeng-Dau
Published: September 2022

Background

Psychological burdens can affect the quality of life among parents of children with epilepsy, especially parents of children with poor seizure control. The impact of stress on the parents of children with epilepsy is significantly comorbid with their children’s cognitive dysfunction and the severity of epilepsy. The aim of this study was to assess the stress levels of parents of school-age children with drug-resistant epilepsy (DRE) and controlled-epilepsy after considering the children’s cognitive ability.

Methods

The study participants consisted of 35 children with typical development in the control group, 25 in the controlled-epilepsy group, 26 in the DRE group, and their parents. We used the Chinese version of the Parenting Stress Index (PSI) to measure the stress levels of all parents; and the Wechsler intelligence scale for children-fourth edition (WISC-IV) Chinese version to assess the children’s cognition levels.

Results

Parenting stress was significantly higher among the parents of children with DRE than of those in the control and controlled-epilepsy group. The PSI’s child domain showed statistically significant subscales of adaptability, acceptability, demandingness, and distractibility/hyperactivity. Moreover, the high-risk ratio on the acceptability, adaptability, demandingness, and distractibility/hyperactivity subscales were also higher for the DRE group than for the controlled-epilepsy group and for the control group.

Conclusion

Seizure severity significantly influences parenting stress after considering cognitive dysfunction in children with epilepsy. Therefore, pediatricians and clinicians should consider epilepsy-specific stress in parents of children with DRE.
Diagnostic accuracy of SARS-CoV-2 rapid antigen test from self-collected anterior nasal swabs in children compared to rapid antigen test and RT-PCR from nasopharyngeal swabs collected by healthcare workers: A multicentric prospective study
Authors: Cohen Robert , Aupiais Camille , Filleron Anne , Cahn-Sellem Fabienne , Romain Olivier , Béchet Stéphane , Auvrignon Anne , Batard Christophe , Virey Brigitte , Jung Camille , Rybak Alexis , Levy Corinne
Published: September 2022

Testing for SARS-CoV-2 is central to COVID-19 management. Rapid antigen test from self-collected anterior nasal swabs (SCANS-RAT) are often used in children but their performance have not been assessed in real-life. We aimed to compare this testing method to the two methods usually used: reverse transcription polymerase chain reaction from nasopharyngeal swabs collected by healthcare workers (HCW-PCR) and rapid antigen test from nasopharyngeal swabs collected by healthcare workers (HCW-RAT), estimating the accuracy and acceptance, in a pediatric real-life study. From September 2021 to January 2022, we performed a manufacturer-independent cross-sectional, prospective, multicenter study involving 74 pediatric ambulatory centers and 5 emergency units throughout France. Children ≥6 months to 15 years old with suggestive symptoms of COVID-19 or children in contact with a COVID-19–positive patient were prospectively enrolled. We included 836 children (median 4 years), 774 (92.6%) were symptomatic. The comparators were HCW-PCR for 267 children, and HCW-RAT for 593 children. The sensitivity of the SCANS-RAT test compared to HCW-RAT was 91.3% (95%CI 82.8; 96.4). Sensitivity was 70.4% (95%CI 59.2; 80.0) compared to all HCW-PCR and 84.6% (95%CI 71.9; 93.1) when considering cycle threshold <33. The specificity was always >97%. Among children aged ≥6 years, 90.9% of SCANS-RAT were self-collected without adult intervention. On appreciation rating (from 1, very pleasant, to 10, very unpleasant), 77.9% of children chose a score ≤3. SCANS-RAT have good sensitivity and specificity and are well accepted by children. A repeated screening strategy using these tests can play a major role in controlling the pandemic.
Exploration of the regulatory mechanisms of regeneration, anti-oxidation, anti-aging and the immune response at the post-molt stage of Eriocheir sinensis
Authors: Wang Meiyao , Ge Jiachun , Ma Xingkong , Su Shengyan , Tian Can , Li Jianlin , Yu Fan , Li Hongxia , Song Changyou , Gao Jiancao , Xu Pao , Tang Yongkai , Xu Gangchun
Published: September 2022

Eriocheir sinensisis widely appreciated by the surrounding population due to its culinary delicacy and rich nutrients. TheE. sinensisbreeding industry is very prosperous and molting is one of the important growth characteristics. Research on the regulation of molting inE. sinensisis still in the initial stages. There is currently no relevant information on the regulatory mechanisms of heart development following molting. Comparative transcriptome analysis was used to study developmental regulation mechanisms in the heart ofE. sinensisat the post-molt and inter-molt stages. The results indicated that many regulatory pathways and genes involved in regeneration, anti-oxidation, anti-aging and the immune response were significantly upregulated after molting inE. sinensis. Aside from cardiac development, the differentially expressed genes (DEGs) were relevant to myocardial movement and neuronal signal transduction. DEGs were also related to the regulation of glutathione homeostasis and biological rhythms in regard to anti-oxidation and anti-aging, and to the regulation of immune cell development and the immune response. This study provides a theoretical framework for understanding the regulation of molting inE. sinensisand in other economically important crustaceans.