bluuebunny/crossref_metadata_2025 huggingface dataset:
m6A methylation regulators as predictors for treatment of advanced urothelial carcinoma with anti-PDL1 agent
Authors: Kong Jianqiu , Lu Sihong , Zhang Long , Yao Yuhui , Zhang Jie , Shen Zefeng , Luo Mingli , Liu Bin , Zheng Junjiong , Lin Tianxin
Published: September 2022

Purpose

Immune checkpoint blockade agents were shown to provide a survival advantage in urothelial carcinoma, while some patients got minimal benefit or side effects. Therefore, we aimed to investigate the prognostic value of m6A methylation regulators, and developed a nomogram for predicting the response to atezolizumab in urothelial carcinoma patients.

Methods

A total of 298 advanced urothelial carcinoma patients with response data in the IMvigor210 cohort were included. Differential expressions of 23 m6A methylation regulators in different treatment outcomes were conducted. Subsequently, a gene signature was developed in the training set using the least absolute shrinkage and selection operator (LASSO) regression. Based on the multivariable logistic regression, a nomogram was constructed by incorporating the gene signature and independent clinicopathological predictors. The performance of the nomogram was assessed by its discrimination, calibration, and clinical utility with internal validation.

Results

Six m6A methylation regulators, including IGF2BP1, IGF2BP3, YTHDF2, HNRNPA2B1, FMR1, and FTO, were significantly differentially expressed between the responders and non-responders. These six regulators were also significantly correlated with the treatment outcomes. Based on the LASSO regression analysis, the gene signature consisting of two selected m6A methylation regulators (FMR1 and HNRNPA2B1) was constructed and showed favorable discrimination. The nomogram integrating the gene signature, TMB, and PD-L1 expression on immune cells, showed favorable calibration and discrimination in the training set (AUC 0.768), which was confirmed in the validation set (AUC 0.755). Decision curve analysis confirmed the potential clinical usefulness of the nomogram.

Conclusions

This study confirmed the prognostic value of FMR1 and HNRNPA2B1, and constructed a nomogram for individualized prediction of the response to atezolizumab in patients with urothelial carcinoma, which may aid in making treatment strategies.
Association between SII and hepatic steatosis and liver fibrosis: A population-based study
Authors: Xie Ruijie , Xiao Mengde , Li Lihong , Ma Nengqian , Liu Mingjiang , Huang Xiongjie , Liu Qianlong , Zhang Ya
Published: September 2022

Background

The systemic immune-inflammation index (SII) is a novel marker of inflammation, and hepatic steatosis and fibrosis are associated with inflammation. This study aimed to investigate the possible relationship between SII and hepatic steatosis and fibrosis.

Methods

The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between SII and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship.

Results

This population-based study included a total of 6,792 adults aged 18–80 years. In a multivariate linear regression analysis, a significant positive association between SII and CAP was shown [0.006 (0.001, 0.010)]. This positive association in a subgroup analysis was maintained in men [0.011 (0.004, 0.018)] but not in women. Furthermore, the association between SII and CAP was nonlinear; using a two-segment linear regression model, we found an inverted U-shaped relationship between SII and CAP with an inflection point of 687.059 (1,000 cells/µl). The results of the multiple regression analysis showed that the relationship between SII and LSM was not significant (P = 0.263).

Conclusions

Our findings imply that increased SII levels are linked to hepatic steatosis, but SII is not linked to liver fibrosis. To confirm our findings, more large-scale prospective investigations are needed.
Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus
Authors: Chen Ding-Ping , Lin Wei-Tzu , Yu Kuang-Hui
Published: September 2022

Human leukocyte antigen genes have been shown to have the strongest association with autoimmune disease (AD). However, non-HLA genes would be risk factors of AD. Many genes encoding proteins that are related to T- and B-cell function have been identified as susceptibility genes of systemic lupus erythematosus (SLE). In this study, we explored the correlation between SLE and the genetic polymorphisms of co-stimulatory/co-inhibitory molecules, including CTLA4, CD28, ICOS, PDCD1, and TNFSF4. We found that there were nine single-nucleotide polymorphisms (SNPs) associated with SLE, namely, rs11571315 (TT vs. CT vs. CC: p < 0.001; TT vs. CT: p = 0.001; p = 0.005; TT vs. CT +CC: p < 0.001; TT+CT vs. CC: p = 0.032), rs733618 (CC vs. CT vs. TT: p = 0.002; CC vs. CT: p = 0.001; CC vs. TT: p = 0.018; CC vs. CT + TT: p = 0.001), rs4553808 (AA vs. AG: p < 0.001), rs62182595 (GG vs. AG vs. AA: p < 0.001; GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs16840252 (CC vs. CT vs. TT: p < 0.001; CC vs. CT: p < 0.001; CC vs. CT + TT: p < 0.001), rs5742909 (CC vs. CT: p = 0.027; CC vs. CT + TT: p = 0.044), rs11571319 (GG vs. AG vs. AA: p < 0.001, GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs36084323 (CC vs. CT vs. TT: p = 0.013, CC vs. TT: p = 0.004; CC vs. CT + TT: p = 0.015; CC +CT vs. TT: p = 0.015), and rs1234314 (CC vs. CG vs. GG: p = 0.005; CC vs. GG: p=0.004; CC+ CG vs. GG: p=0.001), but not in CD28 and ICOS by using the chi-square test. Additionally, rs62182595 and rs16840252 of CTLA and rs1234314 and rs45454293 of TNFSF4 were also associated with SLE in haplotypes. These SLE-related SNPs also had an association with several diseases. It was indicated that these SNPs may play an important role in immune regulation and pathogenic mechanisms.
Activation and regulation mechanisms of NOD-like receptors based on structural biology
Authors: Ohto Umeharu
Published: September 2022

Innate immunity is a primary defense system against microbial infections. Innate immune pattern recognition receptors (PRRs) play pivotal roles in detection of invading pathogens. When pathogens, such as bacteria and viruses, invade our bodies, their components are recognized by PRRs as pathogen-associated molecular patterns (PAMPs), activating the innate immune system. Cellular components such as DNA and RNA, acting as damage-associated molecular patterns (DAMPs), also activate innate immunity through PRRs under certain conditions. Activation of PRRs triggers inflammatory responses, interferon-mediated antiviral responses, and the activation of acquired immunity. Research on innate immune receptors is progressing rapidly. A variety of these receptors has been identified, and their regulatory mechanisms have been elucidated. Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) constitute a major family of intracellular PRRs and are involved in not only combating pathogen invasion but also maintaining normal homeostasis. Some NLRs are known to form multi-protein complexes called inflammasomes, a process that ultimately leads to the production of inflammatory cytokines and induces pyroptosis through the proteolytic cascade. The aberrant activation of NLRs has been found to be associated with autoimmune diseases. Therefore, NLRs are considered targets for drug discovery, such as for antiviral drugs, immunostimulants, antiallergic drugs, and autoimmune disease drugs. This review summarizes our recent understanding of the activation and regulation mechanisms of NLRs, with a particular focus on their structural biology. These include NOD2, neuronal apoptosis inhibitory protein (NAIP)/NLRC4, NLR family pyrin domain containing 1 (NLRP1), NLRP3, NLRP6, and NLRP9. NLRs are involved in a variety of diseases, and their detailed activation mechanisms based on structural biology can aid in developing therapeutic agents in the future.
Instantaneous death risk, conditional survival and optimal surgery timing in cervical fracture patients with ankylosing spondylitis: A national multicentre retrospective study
Authors: Huang Jinfeng , Bai Hao , Tan Quanchang , Hao Dingjun , Wu Aimin , Wang Qingde , Wang Bing , Wang Linfeng , Liu Hao , Chen Xiongsheng , Jiang Zhengsong , Ma Xiaoming , Liu Xinyu , Liu Peng , Cai Weihua , Lu Ming , Mao Ningfang , Wang Yong , Fu Suochao , Zhao Shuai , Zang Xiaofang , Xie Youzhuan , Yu Haiyang , Song Ruixian , Sun Jiangbo , Xiang Liangbi , Liu Xiang , Li Songkai , Liao Bo , Wu Zixiang
Published: September 2022

Background

The mortality rate in patients with ankylosing spondylitis (AS) and cervical fracture is relatively high.

Objectives

This study aimed to investigate the instantaneous death risk and conditional survival (CS) in patients with AS and cervical fracture. We also studied the relationship between surgical timing and the incidence of complications.

Methods

This national multicentre retrospective study included 459 patients with AS and cervical fractures between 2003 and 2019. The hazard function was used to determine the risk of instantaneous death. The five-year CS was calculated to show the dynamic changes in prognosis.

Results

The instantaneous death risk was relatively high in the first 6 months and gradually decreased over time in patients with AS and cervical fracture. For patients who did not undergo surgery, the instantaneous risk of death was relatively high in the first 15 months and gradually decreased over time. For patients with American Spinal Injury Association impairment scale (ASIA) A and B, the 5-year CS was 55.3% at baseline, and improved steadily to 88.4% at 2 years. Odds ratios (ORs) for pneumonia, electrolyte disturbance, respiratory insufficiency, and phlebothrombosis decreased as the surgery timing increased.

Conclusion

Deaths occurred mainly in the first 6 months after injury and gradually decreased over time. Our study highlights the need for continued surveillance and care in patients with AS with cervical fractures and provides useful survival estimates for both surgeons and patients. We also observed that early surgery can significantly increase functional recovery, and decrease the incidence of complications and rehospitalisation.
Regulatory T-cells-related signature for identifying a prognostic subtype of hepatocellular carcinoma with an exhausted tumor microenvironment
Authors: Zhang Genhao
Published: September 2022

Regulatory T-Cells (Tregs) are important in the progression of hepatocellular cancer (HCC). The goal of this work was to look into Tregs-related genes and develop a Tregs-related prognostic model. We used the weighted gene co-expression network analysis (WGCNA) to look for Tregs-related genes in the TCGA, ICGC, and GSE14520 cohorts and then used the non-negative matrix factorization (NMF) algorithm to find Tregs-related subpopulations. The LASSO-Cox regression approach was used to determine Tregs-related genes, which were then condensed into a risk score. A total of 153 overlapping genes among the three cohorts were considered Tregs-related genes. Based on these genes, two Tregs-associated clusters that varied in both prognostic and biological characteristics were identified. When compared with Cluster 1, Cluster 2 was a TME-exhausted HCC subpopulation with substantial immune cell infiltration but a poor prognosis. Five Tregs-related genes including HMOX1, MMP9, CTSC, SDC3, and TNFRSF11B were finally used to construct a prognostic model, which could accurately predict the prognosis of HCC patients in the three datasets. Patients in the high-risk scores group with bad survival outcomes were replete with immune/inflammatory responses, but exhausted T cells and elevated PD-1 and PD-L1 expression. The results of qRT-PCR and immunohistochemical staining (IHC) analysis in clinical tissue samples confirmed the above findings. Moreover, the signature also accurately predicted anti-PD-L1 antibody responses in the IMvigor210 dataset. Finally, HMOX1, MMP9, and TNFRSF11B were expressed differently in Hep3B and Huh7 cells after being treated with a PD1/PD-L1 inhibitor. In conclusion, our study uncovered a Tregs-related prognostic model that could identify TME- exhausted subpopulations and revealed that PD1/PD-L1 inhibitors could alter the expression levels of HMOX1, MMP9, and TNFRSF11B in Hep3B and Huh7 cells, which might help us better understand Tregs infiltration and develop personalized immunotherapy treatments for HCC patients.
Radiotherapy improves the outcomes of immunotherapy with Sintilimab in non-small-cell lung cancer: A real-world analysis
Authors: Li Shuling , Chen Kuifei , Yang Meiwen , Hlaing Swe Swe , Chen Meng , Gu Pinjun , Meng Yinnan , Yang Haihua
Published: September 2022

Introduction

Radiotherapy may augment systemic antitumor responses to immunotherapy. We did a retrospective study to infer whether radiotherapy improves outcomes to immunotherapy in patients with stage III and IV non-small-cell lung cancer (NSCLC).

Methods

This retrospective study conducted at Enze Medical Center enrolled 259 patients with histopathology confirmed NSCLC from December 2018 to December 31, 2021. All were treated with Sintilimab, some patients received radiotherapy at an appropriate time point. Radiation type includes conventional radiotherapy and stereotactic body radiotherapy. The progression-free survival (PFS), and overall survival (OS) were the primary endpoint.

Results

A retrospective analysis was performed on 259 patients, of whom 140 had been treated with immunotherapy lonely and 119 had been remedied with immunotherapy plus radiotherapy. Baseline variables were well balanced between the two groups, including gender, age, smoking status, TNM staging, number of metastases, ECOG score, pathological type and lines of previous systemic therapy. The median PFS in the immunotherapy alone group was 5.00 months (95%CI 4.38-5.62) versus immunotherapy plus radiotherapy was 9.00 months (5.95-12.05; p<0.001). The median OS in the immunotherapy alone group was 16.00 months (12.59-19.42) versus immunotherapy plus radiotherapy was 30.00 months (20.75-39.25; p=0.027). PFS was finer in the radiotherapy plus immunotherapy group than the immunotherapy group alone in both stage III(P=0.0069) and Stage IV(P=0.006) patients. In the univariate analysis, radiotherapy, male, ECOG=0 and <2 lines of previous systemic therapy were connected with an observably better PFS (P<0.001; P=0.03; P=0.002;P=0.021). In a multivariate analysis, radiotherapy, ECOG=0 and <2 lines of previous systemic therapy were independent prognostic factors with a markedly better PFS (P<0.001; P=0.006;P=0.009). An univariate analysis, radiotherapy, male, stage III, non-metastasis, ECOG=0 and squamous carcinoma were associated with a significantly better OS (P=0.032, P=0.036,P=0.002,P<0.001,P=0.002,P=0.025). A multivariate analysis, non-metastasis was a standalone prognostic indicator with a significantly better OS (P=0.006). However, radiotherapy was a tendency indicator with a better OS (HR0.70 95% CI 0.47-1.06). There were also no obvious increases in adverse events in the combination group.

Conclusions

Radiotherapy with addition of immunotherapy was observably linked to a better outcome in patients with III and IV staging NSCLC.
Bifidobacterium animalis KV9 and Lactobacillus vaginalis FN3 alleviated β-lactoglobulin-induced allergy by modulating dendritic cells in mice
Authors: Tian Xiaoying , Fan Rongbo , He Hong , Cui Qingyu , Liang Xi , Liu Qiqi , Liu Tongjie , Lin Kai , Zhang Zhe , Yi Huaxi , Gong Piming , Zhang Lanwei
Published: September 2022

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, β-lactoglobulin (β-LG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of β-LG-specific immunoglobulins E (β-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-γ+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce β-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.
Biomarkers of related driver genes predict anti-tumor efficacy of immune checkpoint inhibitors
Authors: Jiang Shuai , Geng Shuai , Luo Xinyu , Zhang Can , Yu Yang , Cheng Mengfei , Zhang Shuo , Shi Ning , Dong Mei
Published: September 2022

Cancer is a disease with high morbidity and mortality in the world. In the past, the main treatment methods for cancer patients were surgery, radiotherapy and chemotherapy. However, with early treatment, the recurrence rate of cancer is higher, and the drug resistance of cancer cells is faster. In recent years, with the discovery of immune escape mechanism of cancer cells, Immunotherapy, especially Immune Checkpoint Inhibitors (ICIs), has made a breakthrough in the treatment of solid tumors, significantly prolonging the overall survival time and disease-free progression in some solid tumors, and its clinical benefits are more prominent than those of traditional anti-tumor drugs, which has become the hope of cancer patients after the failure of multi-line therapy. More and more studies have shown that there is a correlation between cancer driving genes and the clinical benefits of ICIs treatment, and the therapeutic effects and adverse reactions of ICIs can be predicted by the status of driving genes. Therefore, screening potential biomarkers of people who may benefit from immunotherapy in order to maximize the therapeutic benefits is a top priority. This review systematically summarizes the cancer driving genes that may affect the clinical benefits of immune checkpoint inhibitors, and provides accurate scientific basis for clinical practice.
Case report: Pneumonia with clinical symptoms precedes imaging evidence after immune checkpoint inhibitors combined with radiotherapy in lung squamous cell cancer
Authors: Wang Yao , Wang Yimeng , Yu Jinming , Meng Xiangjiao
Published: September 2022

Immune-checkpoint inhibitors (ICI) targeting programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) have quickly changed the treatment landscape in advanced non-small cell lung cancer. However, any patient treated with an immune checkpoint inhibitor is at risk for immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) is a rare but potentially severe pulmonary toxicity of immunotherapy. Since the imaging features and symptoms are not specific, the diagnosis of CIP is challenging. In addition, CIP may mimic other lung diseases. Due to these characteristics, proper patient management may be delayed. So, a comprehensive understanding of imaging features is essential for a prompt detection and correct management of these drug-induced lung diseases. We presented a patient with lung squamous cell cancer who has clinical symptoms preceding imaging evidence of pneumonitis after immunotherapy and radiotherapy. We also discussed the safety of immunotherapy, the complexity and management of immune pneumonitis.
Placoid scales in bioluminescent sharks: Scaling their evolution using morphology and elemental composition
Authors: Lourtie Alexia , Duchatelet Laurent , Straube Nicolas , Puozzo Nathan , Grace Mark A. , Naylor Gavin J. P. , Delroisse Jérôme
Published: September 2022

Elasmobranchs are characterised by the presence of placoid scales on their skin. These scales, structurally homologous to gnathostome teeth, are thought to have various ecological functions related to drag reduction, predator defense or abrasion reduction. Some scales, particularly those present in the ventral area, are also thought to be functionally involved in the transmission of bioluminescent light in deep-sea environments. In the deep parts of the oceans, elasmobranchs are mainly represented by squaliform sharks. This study compares ventral placoid scale morphology and elemental composition of more than thirty deep-sea squaliform species. Scanning Electron Microscopy and Energy Dispersive X-ray spectrometry, associated with morphometric and elemental composition measurements were used to characterise differences among species. A maximum likelihood molecular phylogeny was computed for 43 shark species incuding all known families of Squaliformes. Character mapping was based on this phylogeny to estimate ancestral character states among the squaliform lineages. Our results highlight a conserved and stereotypical elemental composition of the external layer among the examined species. Phosphorus-calcium proportion ratios (Ca/P) slightly vary from 1.8-1.9, and fluorine is typically found in the placoid scale. By contrast, there is striking variation in shape in ventral placoid scales among the investigated families. Character-mapping reconstructions indicated that the shield-shaped placoid scale morphotype is likely to be ancestral among squaliform taxa. The skin surface occupied by scales appears to be reduced in luminous clades which reflects a relationship between scale coverage and the ability to emit light. In luminous species, the placoid scale morphotypes are restricted to pavement, bristle- and spine-shaped except for the only luminescent somniosid,Zameus squamulosus, and the dalatiidMollisquama mississippiensis. These results, deriving from an unprecedented sampling, show extensive morphological diversity in placoid scale shape but little variation in elemental composition among Squaliformes.
In-situ electro-stimulation enhanced branching but not massive scleractinian coral growth
Authors: Samidon Munandar , Razi Nanda Muhammad , Agustiar Muhammad , Harahap Puad Batari , Najmi Nurul , Bahri Samsul , Liu Shang Yin Vanson
Published: September 2022

Calcium carbonate (CaCO3) is the main component of the skeleton of scleractinian corals and is a preferable substrate for attachment and growth. An electro-stimulation method based on the electrolysis of seawater, which generates calcium and magnesium minerals as a crystalline coating over artificial metal structures, was used to boost coral growth during the 1970s. Few studies have attempted to compare survival and growth between electro-stimulated corals and non-electro-stimulated corals in situ. In this study, we used 2D image analysis to quantify the growth of branching and massive corals on electro-stimulated structures. Among four metallic structures that were deployed in Sabang, Aceh, Indonesia, three were electro-stimulated (12 V) and one was used as a control. Two branching corals (Acropora gemmifera and Pocillopora verrucosa) and two massive coral species (Porites murrayensis and Porites lobata) were selected. A total of 256 fragments, comprising 128 fragments derived from two branching species and 128 fragments derived from two massive species, were randomly dispatched to each structure. Underwater photographs were taken at three intervals from August 2019 to December 2020. The results showed that the survival rates (excluding lost fragments) of branching corals under electro-stimulation were approximately 19% higher than massive. However, no significant difference was found between the survival rates of the treatment and control groups for both branching and massive corals. Furthermore, we found that under electro-stimulation, branching corals grew faster than controls but not massive. Our study provides pieces of evidence for the potential use of electrochemical processes in stimulating the growth of branching corals.
Study on the seasonal variations of dimethyl sulfide, its precursors and their impact factors in the Bohai Sea and North Yellow Sea
Authors: Guo Yu , Peng Liying , Liu Zishi , Fu Xiaoting , Zhang Guicheng , Gu Ting , Li Danyang , Sun Jun
Published: September 2022

Dimethyl sulfide (DMS) is one of the most important volatile biogenic sulfur compounds and plays a significant role in global climate change. Studying the seasonal variations and the environmental factors that affect the concentration of DMS would aid in understanding the biogeochemical cycle of sulfur compounds. Using benzene-assisted photoionization positive ion mobility spectrometry (BAPI-PIMS), the seasonal distribution and the key impact factors of DMS and dimethylsulfoniopropionate (DMSP) in the Bohai Sea and North Yellow Sea were investigated in the summer and autumn of 2019. The concentrations of DMS and its precursors, DMSPp and DMSPd, in the surface seawater were 0.11–23.90, 0.67–41.38, and 0.03–12.28 nmol/L, respectively, in summer, and 0.10–20.79, 0.39–13.51, and 0.18–20.58 nmol/L, respectively, in autumn. The air-to-sea exchange flux of DMS was 43.05 ± 44.52 and 34.06 ± 63.38 μmol/(m·d), respectively, in summer and autumn. The results demonstrated that the temperature was the most dominant environmental factor, and the abundance of dinoflagellates was the most dominant biological factor that affected the distribution of DMS and DMSP in summer. The abundance of diatoms was the most dominant biological factor, and the levels of PO43-, NO2-, NO3-, and SiO32- were the dominant environmental factors that affected the distribution of DMS and DMSP in autumn. These results of this study would be of great significance in understanding the biochemical cycle of DMS in BS and NYS.
Effect of different volume fraction of steel fiber/graphite on thermal conductivity and compressive properties of concrete
Authors: Ren Xiang , Ding Yunxiang , Liu Qunfeng , Chen Shaojie , Song Fei
Published: September 2022

The enhancement of the thermal conductivity can be utilized to reduce the temperature difference between the internal and external structural surfaces and thus the thermal induced stresses in concrete. This study investigated the compressive strength and thermal conductivity in concrete structures enhanced by the steel fiber and graphite at different volume fractions. First, the cubic and the cylinder concrete samples were fabricated by adding different volume fractions of the steel fibers, such as 0%, 0.5%, 1.0%, 1.5%, 2.0%, and 2.5%, to the concrete mixture. The fiber enhanced samples were tested following the standard procedures, and the optimal compressive strength and thermal conductivity can be obtained in the sample with the volume fraction of steel fiber at 1.5%. Moreover, graphite powders with different volume proportions at 5%, 10%, and 15% were added to the fiber enhanced concrete samples with identical size. The compressive strength and thermal conductivity tests were also performed and the optimal content of steel fiber was 1.5%, and the graphite was 5%. These results could not only meet the design requirements of the compressive strength of the concrete, but also improve the thermal conductivity of the concrete. The research could provide some reference for the design of the high thermal conductivity concrete.
Study of performance of aerostat envelope materials on the coast
Authors: Lv Jing , Zhou Yan , Zhang Yuanping , Nie Ying , Wang Qian
Published: September 2022

In this article, the performance of several naturally aged envelope materials in Hainan, China, was studied. The results show that the outer layer contributes to the properties of the envelope materials, where PVF and PVDF are better candidates for a weathering layer than TPU and aluminum. Due to the superior water and mildew resistance of PVF and PVDF, the loss of tensile strength for 3216LV and FV1175 was slight, whose value reduced from 101.43 ± 5.45 Kgf/cm and 76.15 ± 3.81 Kgf/cm to 79.73 ± 6.40 Kgf/cm and 70.20 ± 6.57 Kgf/cm, respectively, when aging for 24 months with the helium permeability reduction from 0.8818 L/m2•day•atm and 0.6360 L/m2•day•atm to 0.2047 L/m2•day•atm and 0.2169 L/m2•day•atm aging for 18 months, in the case of FV1175 showed leakage after aging for 24 months due to delamination. However, the tensile strength of HV150 dropped from 82.13 ± 3.61 Kgf/cm to 15.22 ± 2.16 Kgf/cm at 24 months with helium leakage, owing to heavy mildew and degradation. Meanwhile, ETAV150 also exhibited a decreased tensile strength of 57.92 ± 1.32 Kgf/cm after 6 months aging, 32.8% lower than that of the original sample, and showed leakage when aging for 12 months. This research provides a theoretical guidance for the structural design and screen of envelope materials for aerostat used along the coast.
Piloting a systems level intervention to improve cervical cancer screening, treatment and follow up in Kenya
Authors: Mabachi Natabhona M. , Wexler Catherine , Acharya Harshdeep , Maloba May , Oyowe Kevin , Goggin Kathy , Finocchario-Kessler Sarah
Published: September 2022

Although preventable, Cervical Cancer (CC) is the leading cause of cancer deaths among women in Sub-Saharan Africa with the highest incidence in East Africa. Kenyan guidelines recommend an immediate screen and treat approach using either Pap smear or visual screening methods. However, system (e.g., inadequate infrastructure, weak treatment, referral and tracking systems) and patient (e.g., stigma, limited accessibility, finance) barriers to comprehensive country wide screening continue to exist creating gaps in the pathways of care. These gaps result in low rates of eligible women being screened for CC and a high loss to follow up rate for treatment. The long-term goal of 70% CC screening and treatment coverage can partly be achieved by leveraging electronic health (eHealth, defined here as systems using Internet, computer, or mobile applications to support the provision of health services) to support service efficiency and client retention. To help address system level barriers to CC screening treatment and follow up, our team developed an eHealth tool—the Cancer Tracking System (CATSystem), to support CC screening, treatment, and on-site and external referrals for reproductive age women in Kenya. Preliminary data showed a higher proportion of women enrolled in the CATSystem receiving clinically adequate (patients tested positive were treated or rescreened to confirm negative within 3 months) follow up after a positive/suspicious screening, compared to women in the retrospective arm.
Bibliometric-analysis visualization and review of non-invasive methods for monitoring and managing the portal hypertension
Authors: Sun XiaoHan , Ni Hong Bo , Xue Jian , Wang Shuai , Aljbri Afaf , Wang Liuchun , Ren Tian Hang , Li Xiao , Niu Meng
Published: September 2022

Background

Portal hypertension monitoring is important throughout the natural course of cirrhosis. Hepatic venous pressure gradient (HVPG), regarded as the golden standard, is limited by invasiveness and technical difficulties. Portal hypertension is increasingly being assessed non-invasively, and hematological indices, imaging data, and statistical or computational models are studied to surrogate HVPG. This paper discusses the existing non-invasive methods based on measurement principles and reviews the methodological developments in the last 20 years.

Methods

First, we used VOSviewer to learn the architecture of this field. The publications about the non-invasive assessment of portal hypertension were retrieved from the Web of Science Core Collection (WoSCC). VOSviewer 1.6.17.0 was used to analyze and visualize these publications, including the annual trend, the study hotspots, the significant articles, authors, journals, and organizations in this field. Next, according to the cluster analysis result of the keywords, we further retrieved and classified the related studies to discuss.

Results

A total of 1,088 articles or review articles about our topic were retrieved from WoSCC. From 2000 to 2022, the number of publications is generally growing. “World Journal of Gastroenterology” published the most articles (n = 43), while “Journal of Hepatology” had the highest citations. “Liver fibrosis” published in 2005 was the most influential manuscript. Among the 20,558 cited references of 1,088 retrieved manuscripts, the most cited was a study on liver stiffness measurement from 2007. The highest-yielding country was the United States, followed by China and Italy. “Berzigotti, Annalisa” was the most prolific author and had the most cooperation partners. Four study directions emerged from the keyword clustering: (1) the evaluation based on fibrosis; (2) the evaluation based on hemodynamic factors; (3) the evaluation through elastography; and (4) the evaluation of variceal bleeding.

Conclusion

The non-invasive assessment of portal hypertension is mainly based on two principles: fibrosis and hemodynamics. Liver fibrosis is the major initiator of cirrhotic PH, while hemodynamic factors reflect secondary alteration of splanchnic blood flow. Blood tests, US (including DUS and CEUS), CT, and magnetic resonance imaging (MRI) support the non-invasive assessment of PH by providing both hemodynamic and fibrotic information. Elastography, mainly USE, is the most important method of PH monitoring.
Long-term trends of alanine aminotransferase levels among persons living with human immunodeficiency virus/hepatitis B virus with and without hepatitis delta coinfection
Authors: Begré Lorin , Béguelin Charles , Boyd Anders , Peters Lars , Rockstroh Jürgen , Günthard Huldrych F. , Bernasconi Enos , Cavassini Matthias , Lacombe Karine , Mocroft Amanda , Wandeler Gilles , Rauch Andri
Published: September 2022

Background

Hepatitis delta virus (HDV) infection accelerates the progression of liver disease in persons living with HIV and hepatitis B virus (HBV) coinfection. We explored the association between HDV infection and alanine aminotransferase (ALT) elevation during tenofovir-containing antiretroviral treatment among persons living with HIV/HBV.

Materials and methods

We included persons living with HIV/HBV with and without HDV starting tenofovir-containing antiretroviral therapy (ART) in three European cohorts with at least 18 months of follow-up. We defined HDV infection as a positive anti-HDV antibody test. We assessed risk factors for ALT elevation ≥ 1.25x upper limit of normal after 5 years of tenofovir-treatment using multivariate logistic regression models. The difference in ALT trends between individuals with and without HDV was evaluated using linear mixed effects models.

Results

61/518 (11.8%) participants had an HDV infection. Among individuals with HDV, 63.9% had ALT elevation after 2 years and 55.6% after 5 years of tenofovir, whereas the estimates were 34.1% after two and 27.0% after 5 years in those without HDV. HDV coinfection (adjusted odds ratio 2.8, 95% confidence interval 1.4–5.8) and obesity at baseline (adjusted odds ratio 3.2, 95% confidence interval 1.2–8.0) were associated with ALT elevation after 5 years of tenofovir therapy. Mean ALT levels were consistently higher during follow-up in participants with HDV compared to those without HDV.

Conclusion

Persistent ALT elevation is common in persons living with HIV/HBV in Europe despite adequate HBV therapy. HDV coinfection and obesity are independent risk factors for persistent ALT elevation during long-term tenofovir treatment.
Endogenous advanced glycation end products in the pathogenesis of chronic diabetic complications
Authors: Mengstie Misganaw Asmamaw , Chekol Abebe Endeshaw , Behaile Teklemariam Awgichew , Tilahun Mulu Anemut , Agidew Melaku Mekonnen , Teshome Azezew Muluken , Zewde Edgeit Abebe , Agegnehu Teshome Assefa
Published: September 2022

Diabetes is a common metabolic illness characterized by hyperglycemia and is linked to long-term vascular problems that can impair the kidney, eyes, nerves, and blood vessels. By increasing protein glycation and gradually accumulating advanced glycation end products in the tissues, hyperglycemia plays a significant role in the pathogenesis of diabetic complications. Advanced glycation end products are heterogeneous molecules generated from non-enzymatic interactions of sugars with proteins, lipids, or nucleic acids via the glycation process. Protein glycation and the buildup of advanced glycation end products are important in the etiology of diabetes sequelae such as retinopathy, nephropathy, neuropathy, and atherosclerosis. Their contribution to diabetes complications occurs via a receptor-mediated signaling cascade or direct extracellular matrix destruction. According to recent research, the interaction of advanced glycation end products with their transmembrane receptor results in intracellular signaling, gene expression, the release of pro-inflammatory molecules, and the production of free radicals, all of which contribute to the pathology of diabetes complications. The primary aim of this paper was to discuss the chemical reactions and formation of advanced glycation end products, the interaction of advanced glycation end products with their receptor and downstream signaling cascade, and molecular mechanisms triggered by advanced glycation end products in the pathogenesis of both micro and macrovascular complications of diabetes mellitus.
The long-term trend of Parkinson’s disease incidence and mortality in China and a Bayesian projection from 2020 to 2030
Authors: Chen Fangyao , Chen Shiyu , Si Aima , Luo Yaqi , Hu Weiwei , Zhang Yuxiang , Ma Jiaojiao
Published: September 2022

Background: Parkinson’s disease is a disabling degenerative disease of the central nervous system that occurs mainly in elderly people. The changes in the incidence and mortality of Parkinson’s disease at the national level in China over the past three decades have not been fully explored.

Methods: Research data were obtained from the Global Burden of Disease 2019 study. The trends of crude and age-standardized incidence and mortality rates by gender of Parkinson’s disease in China were analyzed with the age-period-cohort model and the Joinpoint regression analysis. The effects of age, time period, and birth cohort on the incidence and mortality of Parkinson’s disease were estimated. The gender- and age-specific incidence and mortality rates of Parkinson’s disease from 2020 to 2030 were projected using the Bayesian age-period-cohort model with integrated nested Laplace approximations.

Results: From 1990 to 2019, the annual percentage change of the age-standardized incidence rate was 0.8% (95% CI: 0.7%–0.8%) for males and 0.2% (95% CI, 0.2–0.2%) for females. And the age-standardized mortality rate for males was 2.9% (95% CI: 2.6%–3.2%) and 1.8% (95% CI: 1.5%–2.1%) for females. The results of the age-period-cohort analysis suggested that the risk and burden of Parkinson’s disease continued to increase for the last several decades. Projection analysis suggested that the overall Parkinson’s disease incidence will continue to increase for the next decades. It was projected that China would have 4.787 million Parkinson’s patients by the year 2030, however, the mortality of Parkinson’s disease for both genders in China may keep decreasing.

Conclusion: Though the mortality risk may decrease, Parkinson’s disease continues to become more common for both genders in China, especially in the senior-aged population. The burden associated with Parkinson’s disease would continue to grow. Urgent interventions should be implemented to reduce the burden of Parkinson’s disease in China.
Testing technology for tensile properties of metal materials based on deep learning model
Authors: Chen Xuewen , Fan Weizhong
Published: September 2022

The properties of metallic materials have been extensively studied, and nowadays the tensile properties testing techniques of metallic materials still have not found a suitable research method. In this paper, the neural Turing machine model is first applied to explore the tensile properties of metallic materials and its usability is demonstrated. Then the neural Turing machine model was improved. The model is then improved so that the required results can be obtained faster and more explicitly. Based on the improved Neural Turing Machine model in the exploration of tensile properties of metal materials, it was found that both H-NTM and AH-NTM have less training time than NTM. A-NTM takes more training time than AH-NTM. The improvement reduces the training time of the model. In replication, addition, and multiplication, the training time is reduced by 6.0, 8.8, and 7.3%, respectively. When the indentation interval is 0.5–0.7 mm, the error of the initial indentation data is large. The error of the tensile properties of the material obtained after removing the data at this time is significantly reduced. When the indentation interval is 0.8–1.5 mm, the stress is closer to the real value of tensile test yield strength 219.9 Mpa and tensile test tensile strength 258.8 Mpa. this paper will improve the neural Turing machine model in the exploration of metal material tensile properties testing technology has some application value.
Palmitoylation of A-kinase anchoring protein 79/150 modulates its nanoscale organization, trafficking, and mobility in postsynaptic spines
Authors: Chen Xiaobing , Crosby Kevin C. , Feng Austin , Purkey Alicia M. , Aronova Maria A. , Winters Christine A. , Crocker Virginia T. , Leapman Richard D. , Reese Thomas S. , Dell’Acqua Mark L.
Published: September 2022

A-kinase anchoring protein 79-human/150-rodent (AKAP79/150) organizes signaling proteins to control synaptic plasticity. AKAP79/150 associates with the plasma membrane and endosomes through its N-terminal domain that contains three polybasic regions and two Cys residues that are reversibly palmitoylated. Mutations abolishing palmitoylation (AKAP79/150 CS) reduce its endosomal localization and association with the postsynaptic density (PSD). Here we combined advanced light and electron microscopy (EM) to characterize the effects of AKAP79/150 palmitoylation on its postsynaptic nanoscale organization, trafficking, and mobility in hippocampal neurons. Immunogold EM revealed prominent extrasynaptic membrane AKAP150 labeling with less labeling at the PSD. The label was at greater distances from the spine membrane for AKAP150 CS than WT in the PSD but not in extra-synaptic locations. Immunogold EM of GFP-tagged AKAP79 WT showed that AKAP79 adopts a vertical, extended conformation at the PSD with its N-terminus at the membrane, in contrast to extrasynaptic locations where it adopts a compact or open configurations of its N- and C-termini with parallel orientation to the membrane. In contrast, GFP-tagged AKAP79 CS was displaced from the PSD coincident with disruption of its vertical orientation, while proximity and orientation with respect to the extra-synaptic membrane was less impacted. Single-molecule localization microscopy (SMLM) revealed a heterogeneous distribution of AKAP150 with distinct high-density, nano-scale regions (HDRs) overlapping the PSD but more prominently located in the extrasynaptic membrane for WT and the CS mutant. Thick section scanning transmission electron microscopy (STEM) tomography revealed AKAP150 immunogold clusters similar in size to HDRs seen by SMLM and more AKAP150 labeled endosomes in spines for WT than for CS, consistent with the requirement for AKAP palmitoylation in endosomal trafficking. Hidden Markov modeling of single molecule tracking data revealed a bound/immobile fraction and two mobile fractions for AKAP79 in spines, with the CS mutant having shorter dwell times and faster transition rates between states than WT, suggesting that palmitoylation stabilizes individual AKAP molecules in various spine subpopulations. These data demonstrate that palmitoylation fine tunes the nanoscale localization, mobility, and trafficking of AKAP79/150 in dendritic spines, which might have profound effects on its regulation of synaptic plasticity.
Laparoscopic repeat hepatectomy versus conventional open repeat hepatectomy for recurrent hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Hao Fulong , Li Hancong , Li Nan , Li Jiaxin , Wu Hong
Published: September 2022

Background

Repeat hepatectomy has been proven to be an effective treatment in patients with recurrent hepatocellular carcinoma (RHCC). However, for RHCC, it is still controversial whether laparoscopic hepatectomy is superior to conventional ones. The present meta-analysis was carried out to investigate the safety and overall effect of laparoscopic repeat hepatectomy (LRH) to open repeat hepatectomy (ORH) for patients with RHCC.

Methods

A meta-analysis was registered at PROSPERO, and the registration number is CRD42021257569. PubMed, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before 25 April 2022. Data on operative times, bleeding volume, overall complications, 90-day mortality, blood transfusion, length of stay, overall survival rate, and long-term recurrence-free survival rate were subjected to meta-analysis.

Results

Overall, we identified nine studies of LRH versus ORH enrolling a total of 945 patients (460 and 485 underwent LRH and ORH, respectively). The present meta-analysis revealed non-significant differences in operative time, blood transfusion, overall complications, 90-day mortality, 3-year overall survival rate, 5-year overall survival rate, and long-term recurrence-free survival rate between the two groups. Alternatively, comparing LRH with ORH, LRH has less bleeding volume (p < 0.001) and a shorter length of stay (p = 0.005).

Conclusion

LRH is a feasible and effective treatment strategy for RHCC.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42021257569.